Neural sciences Flashcards

Question

A 24-year-old patient is admitted to a head injury unit following a road traffi c accident. He recovers well from acute neurological defi cits but is diagnosed with post-concussion syndrome. Which of the following statements pertaining to his condition is true? A. There is a consistent relationship between severity of injury and the presence of postconcussion syndrome. B. Diplopia is an early symptom of post-concussion syndrome. C. CT scans show brain lesions in up to 50% of patients in the fi rst week. D. Psychological factors are more likely to play a role in illnesses of shorter duration. E. There is no association between the presence of symptoms and compensatory claims

Answer 1

B. The term post-concussion syndrome (PCS) is used to describe a cluster of symptoms that results in severe disability following mild head injury. There is no consistent relationship between the prevalence of PCS and the severity of head injury. Sometimes a similar constellation of symptoms may be seen in moderate and severe injury, where it is more likely to be attributed to the actual brain damage. Symptoms are usually vague, but early symptoms may include neurological complaints such as diplopia, dizziness, etc. Additional symptoms include cognitive impairment, fatigue, anxiety, depression, and irritability. In general, most neurological symptoms will have resolved by 2 to 6 months. Several observations support an organic basis, for example diffuse microscopic axonal injury on post mortem, macroscopic brain lesions evident in 8–10% of individuals on CT scan, subtle abnormalities on EEG, etc. Psychosocial factors play a part in the syndrome, especially in those lasting longer than 1 year. This is greatest in those with very mild head injuries and very chronic symptoms. There is an association between severity of post-concussion symptoms and seeking compensation, but very few improve even after the compensation.

Answer 2

E. Anticonvulsants are not indicated at this point in time, especially since the patient has no symptoms suggestive of seizures. About 2 to 5% of all patients with mild, closed head injury tend to develop long-term seizure disorder. This rises to about 10 to 20% in patients with severe, closed head injury. A higher incidence of seizures has been seen in patients with depressed skull fractures (15%), haematomas (30%), and penetrating brain wounds (50%). Early seizures, within the fi rst week, are relatively benign and are only weak predictors of later epilepsy. This patient has a mild, closed injury, and he is at a low risk for developing seizures, despite positive family history. Randomized controlled studies have shown that the use of anticonvulsants does not prevent the development of post-traumatic epilepsy beyond the fi rst week after injury. There is a limited role for genetic predisposition in developing post-traumatic epilepsy. Those with the ApoE-ε4 allele may be at higher risk for post-traumatic epilepsy

Answer 3

D. This patient is most probably suffering from multiple sclerosis. The lifetime prevalence of major depression in multiple sclerosis (MS) is around 50%. It is three to 10 times the rate in the general population. Suicidal intent occurs in up to 30% of MS patients. This is linked to the presence and severity of depression and degree of social isolation. Suicide rates in MS patients are up to seven times higher than rates in the general population. Depression and suicide rates are higher in MS than in most other neurologic disorders. In MS patients, the lifetime prevalence of bipolar affective disorder is twice the prevalence in the general population. Pathological laughing and crying is a syndrome that presents with inappropriate laughter without associated happiness and inappropriate tears without associated sadness. Approximately 10% of MS patients are affected, with varying degrees of severity. ECT is generally well tolerated by patients with MS, but carries a risk of neurological relapse and exacerbation of the illness

Answer 4

C. Around 50% of patients with MS have cognitive defi cits. Aphasia, apraxia, and agnosia, which are characteristic of predominantly cortical diseases, are generally absent in MS, where pathology is largely confi ned to subcortical white matter. Although patients with long-lasting and advanced physical disability may also have severe cognitive impairment, the correlation between cognitive dysfunction and disease characteristics (type and duration of MS) is usually weak or modest. Cognitive defi cits are also independent of mood symptoms in MS. Defi cits in working, semantic, and episodic memories have been reported. MS patients have diffi culty both in acquiring and in retrieving information (although performance on recognition tests is better than recall). Procedural memory is usually unaffected. Impaired attention and slowness of thinking is another feature of MS. Frontal lobe defi cits may take the form of defi cits in conceptualization and abstract thinking. At least one study has shown that donepezil is effective in improving cognitive defi cits in MS.

Answer 5

D. Pathological laughter and crying is a symptom seen in MS, where approximately 10% of MS patients are affected, with varying degrees of severity. This is similar to descriptions of the pseudobulbar affect, although this symptom can be present without pseudobulbar palsy. Patients are more likely to have frontally mediated cognitive defi cits. Commonly used scales to identify and characterize this syndrome include the Pathological Laughter and Crying Scale and the Centre for Neurologic Study–Lability Scale. The most common differential diagnosis is a mood disorder, but patients with pathological crying exhibit the emotional display in the absence of a pervasive and sustained elation or depressed mood. But when mood disorder and pathological laughter and crying coexist, differentiation can be very diffi cult. TCAs and SSRIs have been found to be effective in the treatment even if no depression is noted

Answer 6

B. Epilepsy is a common disorder, affecting approximately 1% of the population and may involve individuals of any age. Seizures are convulsions that may be produced by a wide variety of events, including alcohol and drug withdrawal syndromes, hypoglycaemia, transient cerebral anoxia, and epileptic syndromes. Epilepsies are characterized by recurrent seizures and their classifi cation is based on seizure type, age of onset, intellectual development, fi ndings on neurological examination, and results of neuroimaging studies. Seizures are broadly classifi ed into partial and general forms. Partial seizures are further divided into simple and complex. In simple partial seizures consciousness is preserved; complex seizures are characterized by disturbances in consciousness. Partial seizures pertain to one half or one particular area of the brain. Generalized seizures involve both hemispheres from the beginning of the seizure but, at times, they may be secondary to spread from a partial seizure. Tonic–clonic seizures and absence seizures are examples of primary generalized seizures. They are usually associated with a loss of conscious awareness.

Answer 7

D. Left-sided foci are associated with an increased risk of depression and right-sided foci with an increased risk of mania. Mood disorders are the most common type of psychopathology encountered in patients with epilepsy. Prevalence rates of depression range from 30 to 50% in patients with epilepsy. With intractable disorders, up to 60% have lifetime histories of depressive syndromes. In contrast to the incidence of depression in epilepsy, the incidence of mania and bipolar disorder are at normal or near-normal levels. Some retrospective chart reviews state a lifetime prevalence of 20%. The incidence of suicide in epilepsy patients is fi ve to 10-fold greater than in the general population. In those with temporal lobe epilepsy, suicide rates are around 25 times that of the general population

Answer 8

B. Geschwind’s syndrome is an eponymous syndrome of interictal behaviour/personality disorder which has been described in temporal lobe epilepsy (TLE). Clinical features of this syndrome include preoccupation with philosophical and religious concerns, anger, excessive emotionality, viscosity (noted especially in speech), circumstantiality, altered sexuality, and hypergraphia. Recent reviews state that personality traits, rather than a personality disorder per se, seems more likely in these disorders and they tend to resemble the cluster C category of disorders in DSM-IV

Answer 9

E. Psychogenic non-epileptic seizures were previously referred to as ‘pseudoseizures’. They are seizure-like behavioural events that occur in the absence of abnormal electrical discharge in the brain. The gold standard for diagnosis is video-EEG monitoring. People who present with non-epileptic seizures commonly have comorbid epilepsy. Nearly 30 to 50% of patients who have non-epileptic seizures have epilepsy and 20 to 60% of patients who have epilepsy have non-epileptic seizures. The average age of onset is between 20 and 30 years and it is three times more common in women than men. Prevalence rates of a history of sexual abuse in non-epileptic seizures range from 25 to 75%. An elevated prolactin level (usually two times baseline or three standard deviations above normal) could be due to seizures or any neurological event, such as syncope. Some patients with pseudoseizures may have modest elevations in prolactin levels. A normal prolactin may not always be diagnostic of pseudoseizures, since it is frequently normal in partial seizures and sampling may be mistimed following convulsions

Answer 10

C. Historically, left anterior stroke has been associated with depression. This has been questioned in more recent times—including a few meta-analyses that did not show such a relationship. The laterality hypothesis of poststroke depression may hold true only in the acute stage of illness of less than 2 months’ duration. As time passes, the chance of getting a depressive episode is equal in all kinds of stroke. Major depression occurs in approximately 10–25% of patients. Anxiety occurs without depression in up to 10%. Apathy occurs in 20% of patients. Anosognosia with denial of illness is present in 25–45% of patients, particularly those with right posterior lesions. Catastrophic reactions appear in approximately 20% and emotional lability is present in 20%. The mean duration of major depression appears to be about 9 months, but can be chronic, lasting for years in hospitalized patients.

Answer 11

C. Goldstein instigated the term ‘catastrophic reaction’ to describe a cluster of symptoms characterized by aggressive outbursts in patients with brain injury. It was ascribed to the inability of the person to cope with the physical/cognitive defi cit. An important study with respect to catastrophic reaction was conducted by Starkstein et al. in 1993. The major fi ndings of this study are as follows. Catastrophic reaction occurs in around 20% of stroke patients. It is associated with a personal and family history of psychiatric illness. It is also signifi cantly associated with the presence of poststroke depression. It is more common in anterior subcortical lesions and lesions involving the basal ganglia. The reaction is not merely a frustration reaction to the presence of aphasia or cognitive defi cits; it could be present as a symptom on its own or as a behavioural symptom in a subgroup of depressed patients with anterior subcortical damage.

Answer 12

B. On the basis of the fact that not all patients with a left anterior or a right posterior lesion develop depression, other premorbid factors were studied by Starkstein et al. Along with the presence of family history of affective disorders in those who developed poststroke depression, they also found that there was no signifi cant relationship between the presence of depression and demographic variables such as age, sex, education, socioeconomic status, etc. Presence of premorbid cortical atrophy was found to be a risk factor for depression. Similarly, cortical atrophy also predicts mania.

Answer 13

B. The middle cerebral artery supplies most of the cortical grey matter, including the parietal cortex. The inferior parietal lobe includes the upper part of the optic radiation which carries fi bres from upper half of the retina and hence lesions of this area produce inferior quadrantanopia. Parietal lobe damage also explains the hemineglect, mild hemiparesis, and dressing apraxia. Carotid artery syndrome usually presents with amaurosis fugax, the feature distinguishing it from the middle cerebral artery syndrome. Amaurosis fugax is transient, painless monocular blindness, usually due to emboli either from the large arteries or the heart itself. Occlusions of the coronaries usually occur at the bifurcation of the common carotid.

Answer 14

D. Stage 4 NREM sleep is characterized by more than 50% delta activity. When the delta activity ranges from 20 to 50%, the person is in stage 3 NREM sleep. K complexes and sleep spindles along with delta waves of less than 20% is noted in stage 2. Stage 2 is also the longest sleep stage through the night, comprising almost 50% of adult sleep. Stage 1 is characterized by gradual slowing of the alpha wave (less than 50% alpha activity). This is the sleep onset. Stage W (wakefulness) is characterized by predominantly alpha waves posteriorly with low voltage mixed frequency beta waves anteriorly. REM sleep constitutes around 20–25%. Normally, much less time is spent in stage W and stage 1.

Answer 15

A. Characteristics of REM sleep include variable heart and breathing rate, high oxygen consumption and cerebral blood fl ow, penile erections (morning erections due to high levels of REMs), increased vaginal blood fl ow and uterine activity, absent electrodermal activity, poikilothermic state, and dream-like mental activity. In contrast, NREM sleep is characterized by regular, slow heart and breathing rate, low cerebral blood fl ow and O2 consumption, absent penile blood fl ow, and thought-like mental activity. Muscular tone is maintained in NREM sleep and atonia is seen in REM.

Answer 16

A. Characteristics of REM sleep include variable heart and breathing rate, high oxygen consumption and cerebral blood fl ow, penile erections (morning erections due to high levels of REMs), increased vaginal blood fl ow and uterine activity, absent electrodermal activity, poikilothermic state, and dream-like mental activity. In contrast, NREM sleep is characterized by regular, slow heart and breathing rate, low cerebral blood fl ow and O2 consumption, absent penile blood fl ow, and thought-like mental activity. Muscular tone is maintained in NREM sleep and atonia is seen in REM. Sleep terrors occur in slow-wave sleep (stage 3 and 4) unlike nightmares which occur in REM sleep. Sleep terrors are characterized by a sudden arousal with intense fearfulness, often associated with a sharp scream. The subject may sit up in bed, may vocalize unintelligibly, and waking the individual leads to confusion. There is amnesia for the episode and unlike nightmares it is very rarely associated with vividly recalled dreams and images. A familial pattern has been reported. In children, night terrors may be transient but in adults they may be associated with other psychopathology.

Answer 17

D. This patient is likely to have narcolepsy. Narcolepsy is a disorder of unknown aetiology. It consists of the tetrad of excessive day time sleepiness, cataplexy, sleep paralysis, and hypnagogic hallucinations. Polysomnography typically shows sleep-onset REM stage. Cataplexy refers to sudden loss of muscular tone, often seen in association with emotional reactions in those with narcolepsy. An abnormality in the hypocretin neurones in the lateral hypothalamus has been noted in those with narcolepsy. Hypocretin (orexin) is a highly excitatory peptide hormone secreted from the hypothalamus. This is necessary to maintain wakefulness and it also increases appetite. Narcolepsy, especially cataplexy, is considered to be a hypocretin defi ciency syndrome. SSRIs and TCAs remain the treatment of choice currently. Modafi nil is also being tried as a treatment

Answer 18

D. Dementia is estimated to occur in 27% of patients with Parkinson’s disease (PD). Dementia has been associated with older age, greater PD severity, hallucinations, longer duration of PD, greater disability, and male gender. Causes of dementia in PD include Lewy body pathology, dopamine depletion, coexisting AD, and other conditions. Reduced fl uorodopa uptake in the frontal cortex and caudate nucleus, and in mesolimbic pathways are predictors of cognitive impairment. Temporoparietal cortical hypometabolism also predicts cognitive impairment. Donepezil has been found to be useful in two separate double-blind trials in patients with PD.

Answer 19

C. Progressive supranuclear palsy is considered as a Parkinson plus syndrome. It is distinguished from Parkinson’s disease by the presence of early broad-based and stiff gait disorder (axial greater than limb rigidity in extension) with backward falls, and supranuclear gaze palsy with slow vertical saccades and diffi culty looking down (and hence the falls). Falls are very common in these patients and are an important cause of morbidity. Patients are prone to develop various psychiatric complications, including cognitive dysfunction and mood disorders. Cholinesterase inhibitors have not been particularly useful in treating patients with progressive supranuclear palsy associated dementia. Other Parkinson plus syndromes include multisystem atrophy (called Shy–Drager syndrome when associated with autonomic failure), olivopontocerebellar atrophy, and corticobasal degeneration.

Answer 20

C. In this case the origin of emboli must be at the internal carotid artery. The ophthalmic artery, a branch of the internal carotid artery, is blocked transiently, producing the symptoms described in the question. This is called as amaurosis fugax which translates to ‘fl eeting darkness’. It is related to transient but sudden monocular visual loss as a result of decreased retinal circulation. It is a type of transient ischaemic attack and could be a harbinger of a cerebrovascular accident. Compromise of posterior circulation usually leads to cortical blindness, often with macular sparing.

Answer 21

A. The given history is consistent with dissociative fugue. Fugue states are associated with stressful life events wherein total amnesia for the recent past can be seen. More often the amnesia related to dissociation is circumscribed to events of personal importance. During the fugue, the patient may retain normal functional activities and may even learn new verbal and nonverbal materials. Following recovery from the fugue, one may not remember the activities carried out during the fugue state.

Answer 22

C. This is an example of utilization behaviour. A patient with utilization behaviour will be forced to ‘utilize’ objects presented to him despite the absence of obvious need for such usage. An extreme form of this is seen in ‘environmental dependence syndrome’—the patient becomes compelled to make use of all that is seen in his immediate environment resulting in an array of serial complex behaviour. Klüver–Bucy syndrome occurs in the context of bilateral temporal lobe damage. It is associated with hyperorality, inappropriate sexuality, and increased exploratory behaviour (hypermetamorphosis). Alien hand syndrome refers to loss of control of limb movements resulting in ‘automatic’ coordinated hand movements. The patient is usually aware of this and may try to exercise control using the other hand. Balint’s syndrome is characterized by oculomotor apraxia, optic ataxia, and simultanagnosia

Answer 23

A. Utilization behaviour is seen in patients with frontal lobe damage. Dominant parietal lobe lesions result in apraxia, right–left confusion, acalculia, and fi nger agnosia. Balint’s syndrome occurs in bilateral parieto-occipital damage.

Answer 24

D. Temporal lobe is the most common site of origin of complex partial seizures; in very few cases parietal focus has been demonstrated. When accompanied by hallucinations, intense emotional reactions may be seen during the seizure. Fear is the most common emotion noted. Curiously, patients are often aware of the unreal nature of their hallucinatory experiences, but this awareness is not specifi c to complex seizures. Pathology of familiarity characterized by déjà vu and jamais vu are commonly reported in temporal lobe epilepsy.

Answer 25

B. Progressive fl uent aphasia early in the course of a dementing illness is a feature of semantic dementia. Semantic dementia is a type of frontotemporal degenerative disorder. The pathological fi nding is predominantly frontotemporal degeneration with ubiquitin inclusions. Motor neurone disease type inclusions may also be noted. Semantic memory refers to representation of meanings, understanding concepts, and knowledge unrelated to temporal events (cf. episodic memory). Focal cortical defi cits, especially progressive aphasia, can be presenting features of Alzheimer’s disease but this is uncommon.

Answer 26

A. The National Adult Reading Test (NART) has been widely used as a measure of premorbid IQ. The usefulness of NART as a measure of premorbid IQ is based on two assumptions: 1. Reading ability is relatively independent of brain damage. 2. Ability to read irregular words from a list is a strong predictor of intelligence in the normal population. Hence in those with brain damage, irrespective of the diagnosis, NART can be used to estimate the most probable IQ level before becoming ill. However, the notion that the NART score is relatively independent of brain damage has come under scrutiny of late. Studies in Alzheimer’s dementia and Korsakoff ’s syndrome have indicated deterioration in reading ability, leading to an underestimated premorbid IQ.

Answer 27

D. This history is consistent with transient global amnesia (TGA). Sudden-onset amnesia with inability to form new memories of current events and a variable degree of retrograde amnesia is seen. The entire episode lasts for hours to days and on recovery the extent of retrograde amnesia shrinks and almost intact memory for events that happened before the episode is restored, but a dense amnesia persists for the events during the episode (24 hours in this case) even after full recovery. During the episode itself, the procedural memory, visuospatial functions, and problem-solving ability are intact; the patients may even be able to drive during the episode.

Answer 28

C. TGA is thought to be vascular in origin. Posterior cerebral circulation (vertebrobasilar insuffi ciency) is implicated, which supplies signifi cant part of hippocampal and other medial temporal regions. Migrainous or epileptic aetiology has not been entirely disproved. Obstruction to cortical sinuses may be related to idiopathic intracranial hypertension in some cases. The middle meningeal artery may be injured in skull fractures, often becoming a source of extradural haematoma.

Answer 29

C. The anterior spinothalamic tract is supplied by the anterior spinal artery. The spinothalamic tract carries pain and temperature sensations. Posterior tracts such as dorsal columns of gracilis and cuneatus carry joint sense, light touch, proprioception, and vibration sensations. Infarction of the spinal cord usually involves the territory of the anterior spinal artery—the ventral two-thirds of the spinal cord.

Answer 30

A. The cerebellum has an external cortical grey matter and the deep cerebellar nuclei. There are four deep nuclei: dentate, globose, emboli-form, and fastigial nuclei. Mossy fi bres and climbing fi bres provide the major input into the cerebellum. Substantia nigra and subthalamic nucleus are part of basal ganglia. Red nucleus is an upper brainstem nucleus seen at the level of tegmentum. Similar to substantia nigra, red nucleus also contains iron pigments. It is involved in motor coordination

Answer 31

C. Pseudobulbar palsy is also known as spastic bulbar palsy. It usually results from bilateral frontal damage. This may be due to vascular, demyelinating, or motor neurone disease (amyotrophic lateral sclerosis). Diffuse brainstem damage (bulb) will produce lesions in the cranial nerve nuclei, causing bulbar palsy. Pseudobulbar palsy is an upper motor neurone type of lesion. Bulbar palsy produces lower motor neurone damage. Hence increased tone (producing spastic tongue), exaggerated tendon refl exes (brisk jaw jerk), and lack of fasciculations are notable. Diffuse frontal damage may produce frontal release signs. Poliomyelitis, diptheria, and Guillain–Barré syndrome are known causes. The most common cause of progressive bulbar palsy is motor neurone disease

Answer 32

B. Lesions of the subthalamic nucleus are associated with hemiballismus. Lesions of the caudate nucleus are associated with chorea. Disturbances in the GABA system of caudate nucleus are noted in Huntington’s disease. Similarly, damage to the caudate nucleus is implicated in Sydenham’s chorea seen in streptococcal infection. Parkinsonian movement disturbances, especially bradykinesia, are associated with damage to the substantia nigra

Answer 33

C. Set shifting is an executive function. In the Wisconsin Card Sorting Test, abstract reasoning and fl exibility in problem solving are tested. In this test, cards of different colour, form, and number are available. Patients are asked to sort the cards into groups according to varying categories (colour only, form only, or number only) as requested by the examiner. This measures the capacity for abstract thinking and set-shifting ability (cognitive fl exibility). Tower of London is a problem-solving test; it involves frontal and basal ganglia function but does not directly test set-shifting ability. Rey Osterrieth fi gure is a test of visual memory wherein a complex geometric fi gure is given to be copied, followed by immediate reproduction from memory and reproduction after a delay.

Answer 34

C. Anomic (or nominal) aphasia presents with inability to name objects and body parts. Patients have fl uent speech, intact repetition, intact comprehension, reading, and writing. Nominal aphasia often presents together with, or may follow, recovery from other forms of aphasia. Nominal aphasia is not very useful for lesion localization. It is also noted in early Alzheimer’s disease.

Answer 35

D. The blood supply to the rostral third of the hippocampus comes from the anterior choroidal artery, which is a direct branch of the internal carotid artery. It does not take part in the circle of Willis anastamosis. The occipital two-thirds are supplied by hippocampal branches, the posteromedial choroidal artery, and the inferior temporal branches of the posterior cerebral artery.

Answer 36

D. Early in the Alzheimer’s disease neuronal loss is most pronounced in layer II of the entorhinal cortex of the hippocampus. The parahippocampal gyri and subiculum are also affected. This extends to anterior nuclei of the thalamus, septal nuclei, amygdala, and monoaminergic systems of the brainstem are also depleted. The cholinergic neurones of the nucleus basalis of Meynert are also reduced. In cerebral cortex, most pronounced loss occurs with respect to pyramidal neurones and astrocytic proliferation follows as a compensatory or reparative process, most prominently in layers III and V.

Answer 37

A. Excessive stimulation of glutamate receptors leads to an increase in intraneuronal calcium and nitric oxide. Calcium activates proteases that could destroy the neurone from within. Memantine is an NMDA antagonist used in the treatment of Alzheimer’s disease, based on the excitotoxicity hypothesis. This mechanism may be applicable for Parkinson’s disease too. In Huntington’s disease, an expansion of the polyglutamine region of huntingtin takes place due to the disease-causing mutation. Hence the mutant huntingtin protein accumulates in the nuclei of neurones, preferentially in striatum and cortex. These aggregates may be directly toxic to some extent, but predominant striatal loss, as opposed to cortical loss, may be due to glutamate-mediated excitotoxicity. Huntingtin accumulation may render cells unusually sensitive to glutamate-mediated damage

Answer 38

D. Posterior inferior cerebellar artery occlusion leads to Wallenberg’s syndrome. The resulting signs and symptoms are attributed to infarction of a wedge of lateral medulla that contains vestibular nuclei, descending sympathetic tract, spoinothalamic system (carrying pain and temperature from contralateral side of body), descending fi fth nerve tract and nucleus, and ninth and tenth nerve fi bres of same side. This leads to ipsilateral Horner’s syndrome (miopsis, anhidrosis, and ptosis due to sympathetic damage), ipsilateral loss of face sensation (fi fth nerve damage), dysphagia, hoarseness, loss of gag refl ex (ninth/tenth nerve damage), and contralateral loss of pain and temperature over half of the body.

Answer 39

A. The age of the patient, the triad of memory diffi culties, loss of balance, and urinary incontinence, and the neuroimaging fi ndings suggest normal-pressure hydrocephalus (NPH). NPH is not a hydrocephalus in the true sense—there is no increase in intracranial pressure when lumbar puncture is carried out. Following certain meningeal insults, secondary to subarachnoid haemorrhage, head trauma, or resolved meningitis, an increase in intracranial pressure may develop but reach a stable stage where formation of CSF diminishes and equilibrates with absorption, which increases proportionate to the pressure. Once this equilibrium is reached there must be a gradual fall in pressure, although at a high normal level. In some patients, this high normal intracranial pressure of 150 to 200 mm H2O leads to manifestation of NPH.

Answer 40

B. The presence of low heart rate, muscle tone, and blood pressure is suggestive of NREM sleep. At this stage of sleep if a person is awakened, he will be confused. He may not recollect the instance of awakening in the morning. A normal adult spends nearly 75% of sleep in various NREM stages, while the remaining 25% is REM sleep. Penile erection, high cerebral blood fl ow, and vividly recalled dreams are features of REM stage

Answer 41

B. Alpha, beta, delta, and theta are four important wavelets in EEG when awake. Alpha waves are predominant, especially posteriorly when the eyes are closed; they occur at a frequency of 8 to 13 Hz. Beta waves are sometimes seen in normal EEG over central, anterior regions; they occur at a frequency higher than 13 Hz. Theta activity is seen infrequently when awake but often when a subject is drowsy or sleeping. Excessive theta when awake is abnormal. Delta waves (frequency less than 3.5 Hz) are normally seen only in deep sleep and are pathological if noted in adult waking EEG. With ageing, slow waves become more common in EEG.

Answer 42

A. Huntington’s disease is characterized by diffuse fl attening or loss of alpha waves in EEG. In a study conducted in a group of 95 patients with Huntington’s chorea, 31 showed little activity of any kind (fl at trace EEG) and in particular no alpha rhythm above 10 μV in amplitude was seen. There was a statistically signifi cant association between cortical atrophy, especially the frontal lobe, and a ‘low voltage’ EEG in the same study. Such low-voltage records, though not specifi c for Huntington’s chorea, are rare in other neurological disorders

Answer 43

E. Two types of cannabinoid receptors, central (CB1) and peripheral (CB2), have been identifi ed. Both receptors bind to exogenously administered tetrahydrocannabinol (THC), present in marijuana. Anandamide (from the Sanskrit word ‘ananda’ for bliss) is chemically N-arachidonoylethanolamine (arachidonic acid and ethanolamine derivative). It is a weak endogenous cannabinoid ligand. 2-arachnidonylglycerol is a strong endogenous ligand for the cannabinoid receptor. Endogenous cannabinoids exhibit intraocular pressure-lowering effects. They also decrease motor activity level and relieve pain. Anandamides are demonstrated in the thalamus, with a putative role in pain-related neurotransmission.

Answer 44

D. Bitemporal hemianopia is secondary to chiasmatic lesions. Pituitary tumours characteristically cause bitemporal hemianopia. Craniopharyngioma is a benign epithelioid tumour arising from remnants of Rathke’s pouch at the junction of the infundibular stem and pituitary. It lies above the sella turcica and so exerts pressure effects on the optic chiasm leading to bitemporal hemianopia. Tunnel vision is a result of extensive peripheral fi eld defects. Quadrantanopias usually result from damage to the optic radiation beyond the chiasma. Parietal lesions result in inferior, while temporal lesions result in superior, quadrantanopia.

Answer 45

C. Priapism is defi ned as a persistent penile erection greater than 4 hours in duration, which is unrelated to sexual stimulation or desire. Roughly 40 to 50% of patients who develop priapism become impotent, even after surgical treatment. Drug-induced priapism accounts for 15–40% of all cases. Psychotropics associated with priapism include trazodone, phenothiazines, butyrophenones, risperidone, and clozapine. Priapism results from decreased venous outfl ow from the corpora cavernosa of the penis. This can be caused by obstruction of the venous system, for example by blood dyscrasias such as sickle cell anaemia or by blocking the sympathetically mediated (α1 receptor) detumescence. Hence the ability of a drug to block α1 receptors correlates with its risk of priapism. This is especially true if the antiadrenergic effect is unopposed by an equally strong anticholinergic effect. Sympathetic tone is related to detumescence while parasympathetic tone is related to erection. For drugs with combined antiadrenergic and anticholinergic activity, when antiadrenergic activity negates detumescence, the anticholinergic activity will negate erection and so priapism will be rare.

Answer 46

B. Metacognition refers to one’s knowledge concerning one’s own cognitive processes and products of such processes. Metacognition is predominantly a function of prefrontal cortex. Prefrontal damage leads to overestimation of abilities, lack of awareness of defi cits, and inability to use feedback to change behaviour.

Answer 47

A. ‘N back’ test is a popular experimental paradigms for functional neuroimaging studies of working memory. In this test subjects are asked to monitor a series of verbal or non-verbal stimuli and to indicate when the currently presented stimulus is the same as the one presented n trials previously. Using quantitative meta-analysis technique of normative functional imaging studies, a broadly consistent activation of frontal and parietal cortical regions by various versions of the n-back working memory paradigm has been demonstrated

Answer 48

B. MPTP occurred as an impurity when illicit synthesis of opioids was attempted by a chemistry graduate student. He developed acute parkinsonian disease. Following detailed investigations, animal models of Parkinson’s disease have been developed using MPTP as a neurotoxin. VMA is a metabolite of epinephrine; 5HIAA is a metabolite of serotonin. MDMA is the chemical name for ecstasy. Ketamine is a dissociative anaesthetic that stimulates sigma receptors in brain. It is being increasingly used as a street drug.

Answer 49

D. Human neocortex consists of a six-layered laminar structure. This cytoarchitectural division has been largely adapted from Brodmann’s pioneering work. These six layers are numbered from the top, that is the pial surface to the underlying white matter. In order, these are: 1. Molecular (or plexiform) 2. External granular layer 3. External pyramidal 4. Internal granular 5. Internal pyramidal (or ganglionic) 6. Multiform (or fusiform) layer. The layers vary mostly in the size and density of pyramidal and stellate cells

Answer 50

E. Lateral geniculate nucleus is the junction where axons of retinal ganglion cells terminate after passing through uninterrupted via the optic nerve, optic chiasm, and optic tract. The medial geniculate body is involved in auditory processing.

Answer 51

D. Granule cells are the only excitatory neurones in the cerebellum. The cerebellar cortex is a three-layered structure with the outermost layer containing two types of inhibitory neurones, the stellate cells and basket cells. The middle layer has cell bodies of Purkinje cells (main output) which are GABA-mediated and so are inhibitory in function. The innermost layer contains granule cells, which are excitatory, and Golgi cells, which are inhibitory

Answer 52

A. Working memory can be tested using digit span tasks. Using digit repetition forward, a patient’s working memory capacity can be tested. Usually, a list of numbers (in no specifi c pattern) is read aloud by the examiner and the patient is asked to repeat it immediately in same order (forward span) or reverse order (backward span). Gradually, the length of the numeric string is increased. Consistent error at a particular length is an indication for test termination. The normal forward digit span is 7±2 for most adults. Backward span is more diffi cult and averages around 5±2.

Answer 53

C. Sensory ataxia is due to posterior column disease, resulting from spinal cord lesions. In this condition, loss of joint position sense and loss of tendon refl exes are seen. In cerebellar ataxia, associated cerebellar signs such as dysarthria or nystagmus may be present. The corrective effects of vision on balance and posture are seen in sensory ataxia. This is elicited by Romberg’s test wherein swaying, which is almost absent when eyes are open and feet together, becomes prominent on eye closure. In cerebellar ataxia, the patient may sway even with eyes open, which worsens on eye closure

Answer 54

C. Long-term potentiation (LTP) is conceptualized as a more or less permanent increase in synaptic effi cacy following high-frequency activity across the synapse. Glutamate via NMDA receptor activation infl uences LTP. This may underlie changes in synaptic plasticity observed in learning- and memory-related processes. LTP is proposed to be the cellular biological correlate of long-term memory.

Answer 55

B. Most neurones from the ventral tegmental area of midbrain ascend in the medial forebrain bundle and the nigrostriatal pathway. These neurones are rich in dopamine. The dopamine neurones of the ventral tegmental area (VTA) are thought to play a central role in reward, motivation, and drug addiction. Nucleus basalis of Meynert is a major cholinergic site. Dorsal raphe nucleus is predominantly a serotonergic site. Locus coeruleus contains noradrenergic neurones

Answer 56

A. Nucleus basalis of Meynert contains a majority of cholinergic neurones. Apart from hippocampal (entorhinal cortex) neuronal loss, selective loss of neurones in the nucleus basalis has led to the pursuit of cholinergic theories of memory impairment in dementia. Currently available pharmacological interventions largely target cholinergic defi ciency in Alzheimer’s disease.

Answer 57

C. SM, a patient with rare bilateral amygdala damage, was initially reported to lack the ability to recognize fear from facial expressions. Since the report of her case, a number of lesion and functional imaging studies have demonstrated the role of the amygdala in fear processing. It is possible that the amygdala mediates spontaneous fi xations on the eyes when viewing expressions of faces. Lack of such fi xation may lead to failure of spontaneous processing of fearful emotions

Answer 58

A. Pyridoxine (vitamin B6) when phosphorylated to pyridoxal phosphate acts as a coenzyme in the conversion of glutamic acid to GABA, mediated by the rate-limiting enzyme glutamate decarboxylase. The pivotal role of this chemical interaction is evident from pyridoxine-dependent seizures, which can occur in relation to mutations of chromosome 5q31. Dysfunction of this enzyme leads to glutamate accumulation and excitatory damage via NMDA receptors

Answer 59

C. The circumventricular organs are midline structures around the third and fourth ventricles. Pineal gland, median eminence, neurohypophysis, subfornical organ, area postrema, subcommissural organ, organum vasculosum of the lamina terminalis, and the choroid plexus are considered as circumventricular organs. These structures lack the blood–brain barrier seen in other regions of brain. These areas enable the brain’s direct response to chemical challenges in blood.

Answer 60

C. A neuromodulator is a substance that enhances or diminishes the effect of neurotransmitters but does not usually result in neuronal conduction changes on its own. Substance P, enkephalin, cholecystokinin, somatostatin, and neuropeptide Y are examples of neuromodulators. Neurotrophin is a substance produced to infl uence neuronal growth. Neurohormones are substances released by neurones into the blood stream to infl uence effector organs at distant sites, for example corticotrophin-releasing hormone.

Answer 61

D. Norepinephrine acts as physiological antagonist for acetylcholine. Physiological antagonism is defi ned as the process wherein two chemical molecules that act through two different receptor systems result in opposing actions in the body that tend to negate each other’s physiological effect. Insulin and glucagon can be considered as physiological antagonists, to some extent.

Answer 62

E. Muscarinic receptors act via the G protein-coupled second messenger system. Nicotinic cholinergic receptors operate via ligand gated channels that are permeable to Na+, K+ and sometimes Ca2+. GABAA receptors are also ligand-gated ion channels that allow Cl– ions to pass through, resulting in inhibitory activity. Glycine receptors are strychnine-sensitive ligand-gated ion channels with inhibitory activity. Metabotropic receptors aside, most glutamate receptors (NMDA, AMPA, and kainate) are ionotropic and allow Ca2+ transit (NMDA, AMPA) or Na+, K+ transit (kainate) via ligand-gated channels

Answer 63

D. 11C raclopride is used to identify postsynaptic dopamine receptors (D2/D3). Raclopride is related to the antipsychotic sulpride and amisulpride (substituted benzamide); hence it acts as a D2/D3 inhibitor

Answer 64

D. Adipose tissues are the major source of leptin. The amount of leptin in plasma is directly proportional to degree of adiposity in one’s body. Leptin enters the brain, by an unknown mechanism, to reduce appetite via a central mechanism. In obesity, a certain degree of leptin resistance exists, leading to high circulating levels of leptin

Answer 65

E. Thyroid hormone acts in a similar manner to steroid hormone. Receptors for these hormones are not present in the cell membrane but, upon cellular entry, they bind to nuclear receptors to directly affect cellular processes. These nuclear receptors act as hormone-activated transcription factors that modulate gene expression

Answer 66

B. The patient described in the question is most likely to have a diagnosis of Alzheimer’s dementia. Diffuse and neuritic plaques with amyloid deposits in cortex and hippocampus are highly suggestive of Alzheimer’s disease. Ballooning of cells with intraneuronal accumulations suggests Pick’s disease. Diffuse amyloid deposition restricted to blood vessels is seen in amyloid angiopathy. Eosinophilic rod-shaped inclusions of actin fi laments are Hirano bodies, seen sometimes in Alzheimer’s disease

Answer 67

A. 5-HT1B receptors are present as presynaptic autoreceptors. On stimulation, these receptors can decrease further serotonin release. Postsynaptic 5-HT1B receptors may have a role in locomotor activity and aggression. 5-HT1A receptors are associated with antidepressant activity. 5-HT2A receptors are implicated in hallucinogenic properties of LSD-like drugs and blockade is associated with antipsychotic activity. 5-HT3 is the only ligand-gated ion channel among serotonin receptors; it is present in gut in large numbers and may mediate emesis

Answer 68

B. Dopamine exerts its action via one of two families of dopamine receptors. After receptor stimulation, dopamine can either be taken back into the presynaptic neurone and destroyed or repackaged as a neurotransmitter. Among those dopamines that are taken back, some are metabolized by monoamine oxidase (MAO). MAOB selectively metabolizes dopamine. Catechol-O-methyltransferase (COMT) is localized in the postsynaptic neuronal cytoplasm and is involved in secondary metabolism of dopamine. The primary metabolite of dopamine is homovanillic acid (HVA)

Answer 69

B. In depression, hypercortisolism is seen in a subgroup of patients. This can be demonstrated by the dexamethasone suppression test wherein exogenously administered steroid dexamethasone fails to activate the negative feedback loop to reduce endogenous cortisol. Depressed patients also show blunted TSH response when thyrotrophin-releasing hormone (TRH) is injected. A brisk GH release seen on apomorphine/levodopa challenge is absent in some patients with depression. This suggests dopaminergic dysfunction in a subgroup. Clomipramine challenge in normal subjects leads to increased serotonergic activation and prolactin release. This prolactin response to clomipramine-mediated via serotonin is blunted in depression. Psychotic depression shows more HPA axis disturbance than non-psychotic depression. Melancholic (somatic syndrome) depression increases the chance of fi nding endocrine disturbances among depressed patients.

Answer 70

D. P300 is a positive component that occurs 250–500 ms after stimulus onset. Amplitude and latency of P300 is altered in schizophrenia. These changes refl ect a trait rather than being related to psychotic state, but these are not specifi c to schizophrenia; for instance Alzheimer’s disease patients show similar defi cits. The reduction in amplitude is more pronounced in earlieronset and paranoid subgroups. P300 is not affected by medication status, disease duration, or severity of psychopathology.

Answer 71

C. Fluid intelligence includes non-verbal intellectual functions such as problem solving and reasoning; these are not infl uenced by one’s cultural experience or education. Crystallized intelligence includes acquired knowledge, which is heavily infl uenced by culture, formal education, and opportunities. Kaufman Adolescent and Adult Intelligence Test measures both ‘fl uid’ and ‘crystallized’ intelligence. The Wechsler Intelligence Scale for Children and the Wechsler Adult Intelligence Scale measure IQ and are infl uenced by cultural differences and formal educational attainment. Stanford–Binet Scale is one of the earliest intelligence scales and is infl uenced by school education. Raven’s Progressive Matrix is a measure of ability to form perceptual relations and analogical reason; it is independent of language and formal schooling. It can be used for anyone above age 6.

Answer 72

C. Pro-opiomelanocortin (POMC) is a polypeptide precursor protein. It produces many biologically active peptides including the melanocyte-stimulating hormones (MSH), corticotrophin (ACTH), and β-endorphin. MSH and ACTH are collectively known as melanocortins and a family of specifi c receptors has been described for them. In the CNS, POMC-producing neurones are located in the arcuate nucleus of the hypothalamus and the nucleus tractus solitarius of the brainstem. The CNS POMC system regulates feeding behaviour, sexual behaviour, lactation, the reproductive cycle, and possibly central cardiovascular control.

Answer 73

B. GABA does not directly mediate working memory. Prefrontal dopamine via D1 receptors is thought to heavily infl uence working memory capacity. GABAA activation has sedative properties. GABAA activation leads to an increase in seizure threshold via inhibitory activity. GABAA also plays a role in memory consolidation. GABA agonists prevent formation of long-term memory, though the process of learning itself may not be affected. GABAB activation mediates central muscle relaxation via spinal cord and brain receptors

Answer 74

D. Several neuroanatomical differences between homosexuals and heterosexuals have been reported from human studies. The suprachiasmatic nucleus (SCN) has been noted to be larger and more elongated in homosexual males (and females in general). The third interstitial nucleus of the anterior hypothalamus (INAH-3) was noted to be smaller among homosexuals. Anterior commissure is larger in homosexual men than in heterosexual men. No sexual-orientation differences have been reported in the sexually dimorphic nuclei of the preoptic area in humans. LeVay S.

Answer 75

E. Lewy bodies contain ubiquitin (non-specifi c) and alpha synuclein. Synucleiopathies refer to a set of disorders in which aggregates of synculein accumulation is noted. Lewy bodies are demonstrated pathologically in these disorders, but unlike the Lewy bodies in the substantia nigra seen in Parkinson’s disease, cortical Lewy bodies are not surrounded by a distinct halo that enables their identifi cation. Recently, the development of immunostaining for ubiquitin and synuclein have increased the accuracy of visualizing Lewy bodies

Answer 76

E. Wilson’s disease is also known as hepatolenticular degeneration. It is an autosomal recessive disorder of copper metabolism. The abnormal gene (ATP7B) is located in chromosome 13. Ceruloplasmin is an α2 globulin that normally carries 90% of the copper present in the plasma. In Wilson’s disease, ceruloplasmin fails to bind copper and its excretion by the liver is impaired. The excess copper accumulates fi rst in the liver and then in the brain (especially putamen and pallidus) and other tissues. In the early stages of the disease, proliferation of large protoplasmic astrocytes, such as Opalski cells and Alzheimer cells, occurs. Deposition of copper in Descemet’s membrane in the cornea leads to the appearance of the golden-brown ‘Kayser–Fleischer’ (KF) ring. The main neurological abnormalities are rigidity, dystonia, chorea, athetosis, dysarthria, and tremor. It is considered that a pure psychiatric presentation occurs in 20–25% of cases. Around 50% of patients will have mental disturbances at some point during the course of the disease. Psychiatric manifestations tend to occur more commonly with neurological forms of Wilson’s disease than with the hepatic form of the clinical syndrome. Cognitive impairment occurs in up to 25% of patients. The dementia is usually subcortical type with frontal defi cits. Depression occurs in 30% of cases and suicidal behaviour may occur in between 4 and 16%.

Answer 77

E. It has been postulated that exposure of the brain to alcohol during the period of rapid synaptogenesis (third trimester) leads to apoptosis and neuronal loss, especially in thalamic and basal ganglia area. Since this change is apoptotic, it does not lead to fi brous scarring. This apoptotic cell death has been postulated to be due to the action of alcohol on the NMDA and GABA receptors. Apparently, large quantities of alcohol taken during a short period of time, even once, as in a binge episode, can lead to these changes. The cluster of symptoms also depends on the timing of alcohol exposure, so if the exposure occurred during the fi rst trimester it would lead to facial abnormalities. In addition to developing hyperactivity/attention defi cit disorder and varying degrees of learning impairment in children, a high percentage have adult-onset neuropsychiatric disturbances, including major depression and psychosis. There is no evidence to suggest that thiamine defi ciency mediates neuronal damage in fetal alcohol syndrome

Answer 78

C. Cauda equina syndrome is characterized by low back pain (radicular pain), asymmetric weakness, arefl exia, and sensory loss in the legs, and relative sparing of bowel and bladder function. The syndrome usually results from injury of multiple lumbosacral nerve roots within the spinal canal. Most commonly, this is due to a ruptured lumbosacral intervertebral disc (disc prolapse). Less common causes include lumbosacral spine fracture, haematoma within the spinal canal, and compressive tumours. Cauda equine must be differentiated from conus medullaris syndrome, which includes compression of the lower sacral and coccygeal segments. This results in bilateral saddle anaesthesia, prominent bladder and bowel dysfunction, and impotence. Cutaneous refl exes are absent, but the muscle strength is usually preserved in conus medullaris syndrome. Kasper DL

Answer 79

D. During embryonic development, gastrulation leads to the formation of the germ layers—ectoderm, mesoderm, and endoderm. Skin and nervous system develops from the ectoderm, the gut from the endoderm, and all other visceral organs from the mesoderm. After gastrulation, the notochord is formed from mesodermal cells. This notochord lies rostro caudally and it sends signals to the ectoderm lying adjacent to it, transforming them into neurectoderm. This forms the neuronal stem cells in the embryo. This strip of ectoderm is otherwise called the neuronal plate. By the third week of gestation, a groove develops on the dorsal aspect of the neural plate and this groove gradually deepens, forming neuronal folds. These folds gradually close bidirectionally by the end of the fourth week, forming the neural tube. Closure of the neural tube is susceptible to teratogenic infl uences operating in fi rst trimester (e.g. valproate).

Answer 80

E. Sphincter disturbance is not a feature of isolated cerebellar lesions. Unilateral lesions of the cerebellum affect ipsilateral limbs. Symptoms of cerebellar damage include asynergia (loss of coordination between muscles leading to jerky movements), dysmetria (defects in reaching targets via crude motor movements, for example past pointing on fi nger–nose test), intention tremor, dysarthria, disturbed balance including gait ataxia (produces wide-based, staggering gait prone to shuffl e or fall), hypotonia, dysdiadochokinesia (inability to do rapid alternate movements), and nystagmus. The cerebellum has been suggested to be a seat of cognitive function, especially working memory

Answer 81

E. The vestibulocochlear nerve is purely sensory. It has two components, the vestibular and the cochlear, both of which are sensory. The vestibular component transmits information on position and balance received from the semicircular canals and the cochlear component serves the sense of hearing. The hypoglossal nerve innervates the ipsilateral side of the tongue. It is a purely motor efferent nerve. In unilateral lower motor neurone palsy of the eight nerve, when protruded, the tongue deviates toward the side of weakness. The trochlear nerve is unique among cranial nerves in that it decussates to the contralateral side and its point of exit is through the dorsal surface of the brain. The trochlear nerve thus innervates the superior oblique muscle of the contralateral eye. It is a purely efferent nerve. The facial nerve innervates the muscles of the face. It has a sensory component, innervating the anterior two-thirds of the tongue, via the chorda tympani. Facial nerve palsy causes deviation of the angle of mouth to the normal side. As a mnemonic, ‘the rule of 17’ applies to deviations in cranial nerve palsies. Palsy of tenth (vagus and hence palate) and seventh (facial) nerve leads to deviation to the normal side. Palsy of the fi fth (trigeminal and hence the jaw muscles) and twelfth (hypoglossal, tongue) nerve leads to deviation to the paralytic side.

Answer 82

C. The pathway that enables normal vision starts from rods and cones in the retina, which are receptors of the ganglion cells. The axons of ganglion cells extend as the optic nerve, through the optic chiasma, via the optic tract, and synapse at the lateral geniculate body of thalamus. From the lateral geniculate body, second-order neurones go through the optic radiation to the visual cortex in the occipital lobe. In contrast, the pathway constituting the papillary light refl ex digresses from the visual pathway before it joins the lateral geniculate body to reach the dorsal midbrain. They synapse at the pretectal nuclei, from where second-order neurones go to the Edinger–Westphal nucleus on both sides. Edinger–Westphal nuclei, via the third nerve, control the pupillary constrictors that constitute the response to light. So, pupillary light refl ex do not involve the occipital cortex. Hence even in those with cortical blindness due to bilateral occipital cortex damage, light refl ex may be intact

Answer 83

C. The hypoglossal nerve is a purely somatic motor nerve. The autonomic nervous system has two parts, the sympathetic and parasympathetic. Sympathetic output from the CNS is mainly through thoracic and lumbar spinal nerves. Sympathetic preganglionic nerves are short and form synapses in paired ganglia adjacent to the spinal cord. The parasympathetic system has a craniosacral output, that is it operates through some cranial nerves and sacral spinal nerves. These have long preganglionic nerves which form synapses at ganglia near or on the organ innervated. Among the cranial nerves, the vagus is the chief parasympathetic nerve. It supplies parasympathetic efferents to heart and most of the abdominal viscera and the gastrointestinal tract, but oculomotor (III), facial (VII), and glossopharyngeal nerves (IX) also carry parasympathetic fi bres. The neurotransmitter at the preganglionic nerve ending is acetylcholine in both sympathetic and parasympathetic systems. At the post ganglionic nerve ending, the neurotransmitter is acetylcholine in the parasympathetic system and mostly norepinephrine in the sympathetic system.

Answer 84

D. The sympathetic system is responsible for the ‘fl ight and fi ght’ and the parasympathetic system for the ‘rest and digest’ reactions. Generally, they are considered to have opposing actions. The sympathetic system is activated in emergency situations, where the body requires more energy. This response includes increased cardiac output, dilatation of bronchioles, routing blood to the muscles, glycogen and fat breakdown leading to a rise in the blood glucose and fatty acids, and slowing down of digestion and renal fi ltration. This also leads to a decrease in gastrointestinal secretion and motility (leading to dryness of the mouth). In addition, sympathetic activity causes constriction of bladder and bowel sphincters and relaxation of the smooth muscles of the viscera. The pupils dilate due to action on the dilators. In contrast, parasympathetic stimulation leads to pupillary constriction and accommodation for close vision, reduces heart rate, constricts bronchioles, and increases gastrointestinal secretions with relaxation of sphincters. Parasympathetic stimulation is necessary for erection and sympathetic stimulation for ejaculation. Ganong WF.

Answer 85

D. The posterior column is responsible for transmission of proprioception, light touch, tactile localization, and vibration senses. Posterior column dysfunction can result in disturbances in the knowledge of extremity movement and position. This presents as sensory ataxia (noted fi rst in the dark as visual input does not compensate for the lost position sense) and a positive Romberg’s sign. Pain and temperature is transmitted to the central nervous system through the spinothalamic tract. Spinothalamic tracts cross over two segments above the level of entry of the root at the spinal cord. Posterior column tracts cross over only at the midbrain level, where they synapse with the cuneate and gracilis nuclei. Hence, if hemisection of the cord takes place, ipsilateral posterior column senses are lost below the level of section; contralateral spinothalamic sensations are lost from two levels below the site of section.

Answer 86

A. The term basal ganglia traditionally applied to fi ve large, subcortical nuclear masses on each side of the brain: the caudate nucleus, putamen, and globus pallidus, subthalamic nucleus, and substantia nigra. The globus pallidus is further divided into an external and an internal segment, and the substantia nigra is divided into a pars compacta and a pars reticulata. The caudate nucleus and the putamen are frequently called the striatum; the putamen and the globus pallidus are sometimes called the lenticular nucleus. The nucleus accumbens is the region where the putamen and the caudate merge anteriorly. What structures comprise the basal ganglia has been a debate over the years. More recently, an additional term, ‘ventral striatum’ has been introduced to describe those parts of the striatum (caudate and putamen) closest to limbic structures and that are involved in cognitive and behavioural functions. The ventral striatum includes the nucleus accumbens, which plays a major role in motivational and reward-related behaviour. Amygdala is closely related to the basal ganglia due to its functional and structural proximity. The amygdala complex develops from the same tissue mass as the caudate nucleus

Answer 87

C. Horner’s syndrome is caused by sympathetic dysfunction at the craniocervical output. Clinical features include ipsilateral mild (usually <2 mm) ptosis, anisocoria (unequal pupils) due to ipsilateral miosis, enophthalmos, loss of ciliospinal refl ex, and ipsilateral facial anhidrosis (mnemonic ‘PAMELA’). Nystagmus is generally not seen. Nystagmus is a rhythmical oscillation of the eyes, occurring pathologically in a wide variety of diseases. Abnormalities of the eyes or optic nerves, especially when the onset is in childhood, may present with nystagmus (pendular or jerk nystagmus). Jerk nystagmus is characterized by a slow drift off the target, followed by a fast corrective saccade. Jerk nystagmus can be downbeat, upbeat, or horizontal (left or right) with the names being given according to the direction of the fast phase. Gaze-evoked nystagmus is the most common form of jerk nystagmus, where the subject is asked to look to the corner of the eye. Exaggerated gaze-evoked nystagmus can be seen in: drug intake/toxicity (sedatives, anticonvulsants, alcohol); muscle paresis; myasthenia gravis; demyelinating disease; and cerebellopontine angle, brainstem, and cerebellar lesions. Downbeat nystagmus usually occurs from lesions near the craniocervical junction, while upbeat nystagmus is associated with damage to the pontine tegmentum, from stroke, demyelination, or tumour. Vestibular system dysfunction also leads to nystagmus. This occurs in discrete attacks, usually associated with sudden movements of the head and is accompanied by symptoms of nausea, tinnitus, hearing loss, and vertigo.

Answer 88

A. Ageing results in declines in a variety of cognitive domains, but some abilities appear to be relatively preserved. The relatively unaffected faculties include general intellectual knowledge, vocabulary and comprehension, attention processes, language abilities related to phonologic, lexical, and syntactic knowledge, motor skills that are learned early in life and repeatedly used, and immediate and implicit memory, including some aspects of short-term memory. Signifi cant age-associated decline is seen in processing speed, ability to reason and solve problems, fl uid intelligence, dividing attention between two tasks, executive function domains (mental fl exibility, abstraction, and concept formation), visuospatial skills (drawing, construction, and maze learning), language skills involving semantic knowledge needed for naming and verbal fl uency, motor skills that require speed, and ability to learn and retain new information for long-term access

Answer 89

A. Gelastic seizures are characterized by shallow laughter occurring in fi ts. The laughter usually lasts less than 1 minute and is then followed by signs of complex partial or focal seizures, such as eye and head movement, automatisms such as lip-smacking, and altered awareness. In many cases, these associated features may be absent, resulting in delayed diagnosis. The most common areas of the brain associated with gelastic seizures are the hypothalamus, the temporal lobes, and the frontal lobes. A combination of gelastic seizures and precocious puberty is often noted and can be attributed to hamartoma of the hypothalamus

Answer 90

C. The cholinergic nicotinic receptor forms the prototypical model for ionotropic receptors. It is a heteromeric pentameric protein, and each subunit is a transmembrane protein with four transmembrane domains (in total 20 transmembrane domains compared to seven in the case of metabotropic receptors). Binding of a neurotransmitter to the extracellular domain of the ionic receptor results in the brief opening of a transmembrane ionic pore. This leads to an infl ux of certain ions, which produces a brief modifi cation of the resting membrane potential. This results in a postsynaptic action potential. Muscarinic acetyl choline receptors are not ionotropic; they are G-protein coupled and act via second messengers. GABAA not GABAB is an ion channel receptor. Norepinephrine receptors are largely G-protein coupled; they are not ion channels.

Answer 91

A. The presence of spiked red blood cells (RBCs) together with ataxia, progressive weakness, and cognitive impairment is suggestive of neuroacanthocytosis. Patients with neuroacanthocytosis may also show personality changes characterized by impulsivity, distractibility, and compulsivity. Neuropathological fi ndings include severe atrophy of the caudate and putamen with loss of neurones and an associated astrocytic reaction. Less severe changes are seen in the pallidum, thalamus, substantia nigra, and anterior horn cells of spinal cord. Acanthocytes are spiked RBCs seen in peripheral blood smears. Acanthocytosis is also seen in patients with abetalipoproteinaemia or hypobetalipoproteinaemia, where serum vitamin E and lipoprotein levels are abnormal.

Answer 92

D. The exact mechanisms of action of LSD and other hallucinogens are not completely understood as yet, but there is substantial evidence pointing towards serotonergic systems in the brain. Receptor-binding studies have shown that radiolabelled LSD binds to 5-HT2A and 5-HT1C receptors. Hallucinogens have agonist actions at the 5-HT2A receptor. The psychoactive and behavioural effects of hallucinogens are blocked by 5-HT2A antagonists. Tolerance/tachyphylaxis of hallucinogenic effect is related to down-regulation of 5-HT2A receptors. There may be a role for 5-HT2C receptors too in mediating the actions of hallucinogens. LSD is only a partial agonist at 5-HT2A, in contrast to the full agonist actions of other hallucinogens. The 5-HT2A receptor potentiates glutamatergic and dopaminergic neurotransmission when activated, while activating the inhibitory GABA interneurone system

Answer 93

B. The acute administration of all addictive drugs (except benzodiazepines) stimulates dopamine transmission in the projection from the ventral mesencephalon to the nucleus accumbens. This projection is generally referred to as the mesolimbic dopamine system. The site of action by which different street drugs activate dopamine can be classifi ed into three distinct types: 1. Increasing the presynaptic release of dopamine without directly altering the activity of dopamine neurones, for example stimulants acting via dopamine reuptake channels 2 Stimulation of dopamine neurones via receptors on dopaminergic neuronal membrane, for example marijuana via cannabinoid receptors 3. Via decrease of inhibitory input into dopaminergic cells leading to disinhibition of dopamine activity, for example opioids and alcohol

Answer 94

A. Neurotrophins comprise a family of proteins including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophins (NT)-3, -4/5, and -6. Proneurotrophins are enzymatically processed to create mature neurotrophins. Neurotrophins bind to specifi c tyrosine kinase receptors. Neurotrophins promote neuronal growth, differentiation, and survival, and modulate synaptic plasticity. These growth-related effects result from the interaction of neurotrophins with mitogen-activated protein kinase (MAPK) signalling pathway and the phosphatidylinositol-3 kinase pathway. In addition, the neurotrophins can inhibit cell death cascades. Reduced expression of neurotrophins such as BDNF has been proposed to underlie defi cits in hippocampal neurogenesis seen in animal models of depression. Chronic antidepressant treatments are shown to upregulate neurotrophin expression, mediating relief from depression. Neurotrophin-mediated proliferation of hippocampal cells may be one of the fi nal common pathways of antidepressant effects

Answer 95

D. L-tyrosine is an amino acid derived from food proteins. It is also derived from the catabolism of phenylalanine in the liver by phenylalanine hydroxylase. L-tyrosine forms the precursor for the catecholamine neurotransmitters. Dopamine is the major initial product derived from L-tyrosine. Dopamine hydroxylase further converts dopamine into norepinephrine. In cells that contain phenylethanolamine N-methyltransferase (PNMT), norepinephrine undergoes further processing via methylation to produce epinephrine. Epinephrine is formed in trivial amounts in the CNS but is a major product in the adrenal medulla. Any drug that enhances the action of tyrosine hydroxylase and dopamine hydroxylase is likely to enhance noradrenergic transmission. Catecholamines are metabolized by two enzymes: monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT).

Answer 96

C. The majority of distributed serotonin in human body is located in the intestines. Due to the wide distribution of serotonin receptors, side-effects of serotonergic drugs may be variable; for example 5-HT3 receptors in the area postrema or the hypothalamus are associated with nausea and vomiting. The receptors in the basal ganglia are associated with akathisia and agitation. Limbic receptors are associated with an anxiety response when serotonergic drugs are administered initially. The serotonin receptors in spinal cord may produce sexual dysfunction. The intestinal receptors constitute nearly 90% of the body’s serotonin receptors. Hence the common side-effects with most serotonergic drugs are gastrointestinal upset and diarrhoea.

Answer 97

E. The neurotransmitter that brings a signal to a neurone is considered to be the ‘fi rst messenger’. For the signal to get across to the postsynaptic neurone, it must be transformed into an intraneuronal message. This is enabled via formation of the ‘second-messenger’ molecules. Second messengers generally do not act outside the cell of origin. The most commonly encountered second messengers include cAMP and cGMP, the calcium ion (Ca2+), and the phosphoinositol metabolites such as inositol triphosphate (IP3) and diacylglycerol (DAG). Gases such as nitric oxide and carbon monoxide also act as intraneuronal second-messenger molecules. The second messengers are not hormones as they do not reach tissues via the blood stream. Unlike receptor proteins, they do not combine with the neurotransmitter molecules directly. They are present throughout the CNS.

Answer 98

A. This patient’s presentation is suggestive of Bell’s palsy. It is the most common cause of facial paralysis, usually occurring on one side only. The lifetime prevalence is about 1 in 60 in the UK. It is most commonly seen between the ages of 15 and 45, in both men and women. Pregnancy and diabetes may increase the risk of Bell’s palsy substantially. Though the exact cause is not known, a viral aetiology is suspected (herpesvirus). The symptoms usually develop overnight. Most patients present with diffi culty closing the eye, drooling of saliva, and sagging of the eyebrow on one side. Less commonly, patients may have heightened sensitivity to loud noise on the affected side. Most patients (nearly 80%) recover completely within 3 weeks. Almost all patients recover within 6 months. Patients with Bell’s palsy exhibit Bell’s phenomenon. Bell’s phenomenon is a normal defence refl ex present in about 75% of the population. It results in elevation of the globes when shutting eyes closed or when the eyes are directly threatened by external agents. Such upward movement helps to protect the most important structures (cornea and lens) of one’s eyes. This elevation becomes noticeable when the orbicularis muscle becomes weak as in Bell’s palsy. Bilateral Bell’s phenomenon is found in myasthenia gravis, sarcoidosis, bilateral Bell’s palsies, congenital facial diplegia, some rare forms of muscular dystrophy, motor neurone disease, and Guillain–Barré syndrome.

Answer 99

C. Serotonergic cells are localized in the brainstem in a group of nuclei called the raphe nuclei. In contrast to the more circumscribed dopaminergic pathways, almost all parts of the brain receive serotonergic input. This probably explains the multiple effects of serotonin receptors on mood and behaviour. All serotonin receptors are G-protein linked, except 5-HT3 which is ligand gated. Serotonin does not cross the blood–brain barrier and thus the brain synthesizes its own serotonin. This is in turn determined by concentrations of free plasma tryptophan and transport across the blood–brain barrier. This forms the basis of the rapid tryptophan depletion test. Tryptophan hydroxylase hydroxylates tryptophan to 5-hydroxy tryptophan (5-HTP), which is further decarboxylated to serotonin (5-HT) by aromatic-L-amino acid decarboxylase (AADC) in the presence of vitamin B6 as coenzyme. The rate-limiting step in serotonin synthesis is considered to be the availability of 5-HTP. In parallel with dopamine and norepinephrine, following release into the synaptic cleft, 5-HT is either metabolized or actively transported back into the neurone by a high-affi nity transporter, the serotonin reuptake transporter (SERT). SERT is encoded by a single gene on chromosome 17. The SERT gene has been recently postulated to play an important role in gene–environment interaction in disorders such as depression.

Answer 100

C. Prion protein (PrP) is a glycoprotein anchored to neuronal cell membranes. The normal function of prion protein is not known. Bovine spongiform encephalopathy (‘mad cow disease’) and Crutzfeldt–Jakob disease are associated with altered prion proteins. In prion diseases, the normal cellular form of PrP (called PrPC) undergoes transformation to an altered version (called scrapie-associated prion protein PrPSc). The latter accumulates in the brain to form insoluble aggregates, leading to neuronal dysfunction, but unlike other neurodegenerative diseases, prion diseases are transmissible. This is made possible because PrPSc imprints its pathological conformation onto other, normal PrPC molecules, thus ‘converting’ them to be abnormal. PrPC and PrPSc do not differ in their amino acid sequences

Answer 101

D. The establishment and maintenance of a wakeful state is called arousal. In humans, arousal activity requires at least three brain regions. The most important of these is the ascending reticular activating system (ARAS). ARAS may have a role in setting the level of consciousness. ARAS, via the intralaminar nuclei of the thalamus, project widely throughout the cerebral cortex. A synchronized, rhythmic burst of neuronal activity (20–40 Hz frequency) results from ARAS and thalamic coordination. The degree of synchronization varies directly with the level of wakefulness. During sleep the synchronicity is lost. The third most important region in arousal state is the right frontal lobe. The right frontal lobe is essential for the ‘maintenance’ of attention; this is evident when testing letter-cancellation tasks or trail-making tasks in patients with right frontal lesions. Sadock BJ

Answer 102

E. Hodgkin and Huxley showed that the inside of a cell, such as a neurone, is negatively charged compared to the outside. This is called the resting membrane potential and its value ranges between −40 mV and −90 mV (average −70 mV), depending on the type of cell. This negative resting membrane potential arises due to the membranes of the resting neurone being more permeable to potassium ions than to any other ions. There are more potassium ions inside the cell than outside it, which is due to a constant outward leak creating a negative potential inside the cell. An action potential is initiated in the axon hillock when the synaptic signals received by the dendrites and soma are suffi cient to raise the intracellular potential from −70 mV to the threshold potential of −55 mV. When this potential is reached, the Na+ channels, which are dormant at rest, will open. This Na+ infl ux causes rapid reversal of the membrane potential from −70 to +40 mV.

Answer 103

D. Glycine is an inhibitory transmitter, predominantly found in the spinal cord; it has relatively insignifi cant effects in the brain compared to the spinal cord. Glycine acts on a chloride channel that is different from GABAA receptors, called the strychnine-sensitive glycine receptor. On activation, the transmembrane glycine receptors facilitate entry of chloride ion into the cell, leading to hyperpolarization of the cell. Glycine is synthesized from serine; this conversion is mediated by rate-limiting steps via serine trans-hydroxymethylase and glycerate dehydrogenase. Glycine also serves as an obligatory neurotransmitter adjunct for glutamate activity on the NMDA glutamate receptors (non-strychnine-sensitive glycine site). Some clinical trials have shown a reduction in the negative symptoms of schizophrenia using D-serine or glycine mediated via NMDA receptors, though this has not been widely replicated

Answer 104

C. Positron emission tomography (PET) is considered as the gold standard of functional neuroimaging modalities. Among other available techniques, only PET can measure cerebral glucose metabolism directly. In addition, a large number of radioligands for receptor characterization are available for PET. Despite these advantages, PET is not widely available due to the expensive nature of the equipment; it requires relatively rapid access to a cyclotron to produce the positron-emitting radionuclides.

Answer 105

C. Most hormones show a diurnal–nocturnal variation in their plasma levels. This is partly related to circadian mechanisms and hypothalamic functions. Level of physical activity and diurnal change in metabolic requirements may also infl uence the hormonal levels in blood. Growth hormone regulates carbohydrate and lipid metabolism. There is a nocturnal surge of growth hormone seen during slow wave sleep (stage 3 and 4 NREM sleep). Speculative association of growth hormone surge and memory consolidation has not been borne out by experimental results.

Answer 106

C. The presentation here is consistent with craniopharyngioma. It is a benign, slowgrowing tumour involving the pituitary gland. The clinical presentation is usually insidious with the most common presenting symptoms being headache, endocrine dysfunction, and visual fi eld disturbances. The headache may be positional and slowly progressive. Hypothyroidism, adrenal failure, and diabetes insipidus are the common endocrine disturbances noted. Young patients may have growth failure and/or delayed puberty. Visual fi eld defects are due to pressure effects on the optic nerve route. Bitemporal hemianopia is the most common problem due to pressure at the chiasma. The anatomic location of the craniopharyngioma may be classifi ed into prechiasmal (associated with optic atrophy), retrochiasmal (associated with signs of increased intracranial pressure such as papilledema), or intrasellar (associated with headache and endocrine dysfunction). The diagnosis is strongly suggested by imaging studies. The appearance of a suprasellar or intrasellar calcifi ed cyst is considered to be the radiological hallmark. CT scan is the most sensitive method as calcifi cations are easily picked up as high-density areas. MRI is very helpful for neurosurgeons to plan a surgical approach.

Answer 107

E. The embryogenetic theory of craniopharyngioma suggests the involvement of Rathke’s pouch. The infundibulum is a downward projection of diencephalon; the Rathke’s pouch is an upward elongation of the primitive oral cavity. Rathke’s pouch and the infundibulum develop during the fourth week of gestation and grow towards each other until they unite to form the hypophysis of the pituitary gland during the second month. The remnants of Rathke’s pouch involute into a cleft and disappear completely in normal conditions. In some cases, this Rathke’s cleft remnant can become the site of origin of craniopharyngiomas. Alar plate is related to development of the spinal cord. Isthumus of thyroid is related to thyroglossal duct.

Answer 108

D. The patient described in Question 133 has an acute onset of fl inging movements of one side of the body. This is called hemiballism. Movements are usually involuntary, wide amplitude, and irregular with no pattern or rhythm. They commonly involve the arm and leg together; facial involvement has been reported in about half of the cases. Movements are increased with action, decreased with relaxation, and absent during sleep. In some patients the movements can cause physical exhaustion or injury of the affected limb. Hemiballism is considered to be primarily a disorder of the contralateral subthalamic nuclei (STN), but recently lesions outside STN have been demonstrated in patients with hemiballism. It is noted that the hemiballism caused by lesions of the STN is more severe than that caused by lesions elsewhere.

Answer 109

C. The cardinal function of prefrontal cortex is planning and organization of behaviour (executive function) in addition to functions of short-term memory, motor attention, and inhibitory control. The change in Gage’s personality would be consistent with damage to the orbitofrontal cortex of the ventral aspect of his frontal lobe, affecting affect and emotion. A pseudopsychopathic syndrome, characterized by impulsivity and socially inappropriate behaviour, is recognized in orbitofrontal damage. Inferior parietal cortex may play a role in attention and body image function. The primary function of superior temporal cortex is auditory processing. The hippocampus is the seat of episodic memory; lesions can result in amnesia. The hypothalamus is involved in appetitive behaviours such as hunger, thirst, and sex.

Answer 110

A. Mononeuritis multiplex is a form of peripheral neuropathy wherein axonal destruction occurs in different sites leading to sensory and motor defi cits. The nerves involved are generally multiple and random with no predictability of progression. This acute or subacute involvement of multiple individual nerves may be serial or even simultaneous. It is not a single disease but a syndrome caused by various disorders; often the fi nal common pathway includes vascular damage to neurones. Nearly one-third of cases are idiopathic. The most common identifi able cause in adults is diabetes mellitus, followed by vasculitis syndromes such as polyarteritis nodosa and connective tissue diseases such as rheumatoid arthritis or systemic lupus erythematosus. In children and adolescents, the most common cause of mononeuritis multiplex is connective tissue disease. Mononeuritis multiplex can mimic conversion disorder and present to psychiatric units.

Answer 111

E. The question describes the classic form of the Stroop Colour–Word Test. In this test the subject is initially required to read names of some basic colours. Later the subject is asked to name the colours of geometrical shapes. Following this, the test of interference is applied. Looking at a colour name written in a different colour produces a confl ict; this makes the subject read the name instead of saying the colour in which it is written, for example if the word ‘blue’ is written in green the subject tends to say blue, even when asked to name the displayed colour. The classic form of the Stroop Colour–Word Test is the most commonly used, though variations such as Emotional Stroop are now available. Rorschach’s is a projective test which uses ink-blot images. The Continuous Performance Test measures sustained/selective attention and impulsivity. Goldfarb L

Answer 112

A. Dopamine is synthesized from the amino acid tyrosine. Initially, tyrosine is converted to L-dihydroxyphenylalanine (L-DOPA) by tyrosine hydroxylase (the rate-limiting step). L-DOPA is rapidly converted to dopamine by dopa decarboxylase. Dopamine is stored in vesicles and 80% of the released dopamine is rapidly transported back into the nerve terminal by a dopamine-specifi c transporter (DAT). This intracellular extravesicular dopamine is metabolized by monoamine oxidase (MAO) to dihydroxyphenylacetic acid (DOPAC). Twenty percent of the released dopamine is sequentially degraded extracellularly by catechol-O-methyltransferase (COMT) and MAO to 3-methoxytyramine (3-MT) and homovanillic acid (HVA). Dopaminergic cell bodies in the brain are mainly localized in the ventral tegmental area in the brainstem. There are predominantly four pathways that are considered to be dopaminergic in the brain: mesocortical and mesolimbic axons originate from the VTA and project to the prefrontal cortex and limbic structures, respectively; the tuberoinfundibular pathway mediates release of prolactin from the pituitary; and the nigrostriate pathway forms an integral part of the basal ganglion extrapyramidal system.

Answer 113

C. Parkinsonian tremor is usually of large amplitude with a frequency of 4 to 6 cycles per second. It is a resting tremor which persists even during action. Parkinsonian tremor is not reduced by alcohol but is exaggerated in stressful situations. In contrast, benign essential tremor is usually of smaller amplitude and higher frequency (10 to 12 cycles per second). It is often seen during action and may be unnoticeable during rest. It is exacerbated by stress, similar to Parkinsonian tremor. Clinically, essential tremor is similar to exaggerated physiological tremor.

Answer 114

D. The patient described here has acute, severe headache, photophobia, and meningism. These features are highly suggestive of subarachnoid haemorrhage (SAH). A CT scan is not 100% sensitive in ruling out possible intracranial bleed. Given the high clinical suspicion, the gold standard test for SAH, lumbar puncture, must be carried out. Presence of depression must not distract one from considering acute medical causes of somatic complaints such as headaches. Haloperidol is not indicated in this scenario. Please note that if the CT scan discloses a subarachnoid haemorrhage, lumbar puncture need not be carried out as a routine

Answer 115

C. This patient is having an infarct of the thalamus. Thalamic infarcts affecting ventral posterolateral nucleus and posteromedial nucleus result in a severe sensory syndrome characterized by intense burning pain, hyperaesthesia, or hemianaesthesia affecting the contralateral body. Cold thermal stimuli, emotional stress, and loud sounds may aggravate the painful state. Despite this apparent hypersensitivity, the patient shows an elevated pain threshold requiring a stronger than usual stimulus to produce a sensation of pain (hypoalgesia with hyperpathia). This thalamic pain syndrome is also called Dejerine–Roussy syndrome. Some patients may develop hemiataxia and choreoathetosis

Answer 116

parietal cortex

Answer 117

cerebellum

Answer 118

occipital cortex

Answer 119

temporal cortex

Answer 120

brain stem

Answer 121

area postrema medulla subfornical organ neurohypophysis

Answer 122

Primary->secondary->contents 1. Rhobencephalon->myelencephalon & metencephalon-> caudal medulla oblongata & pons, part of medulla and cerebellum 2. Mesencephalon->mesencephalon->tectum (inf sup colliculi), basis pedunculi, tegmentum (red nucleus, fibre tracts) 3. Prosencephalon->diencephalon (to thalamus, epithalamus hypothalamus, subthalamus) & telencephalon (to hemispheres, olfactor, corpus striatum, medullary centre, pallium

Answer 123

1. pyramid - consists of corticospinal fibres (a.k.a. pyramidal tract) 2. the olive - marks the position of the inferior olivary nucleus 3. fasciculi gracilis and cuneatus 4. cranial nerves: a) abducens (VI) b) facial (VII) c) vestibulocochlear (VIII) d) glossopharyngeal (IX) e) vagus (X) f) accessory (XI) g) hypoglossal (XII)

Answer 124

The Pons · consists of a basal portion (a relay station between the cortex of a cerebral hemisphere and the opposite cerebellar hemisphere - involved in voluntary movement) and a dorsal portion (contains ascending and descending tracts) · contents: 1. trigeminal (V) nerve nucleus 2. motor nucleus of facial (VII) nerve 3. vestibular (VIII) nuclei 4. abducens (VI) nerve nucleus 5. isthmus of brain stem - contains the lateral lemniscus which is the main auditory tract of the brain stem 6. reticular formation 7. locus coeruleus – lies at the rostral end of the fourth ventricle 8. trapezoid body - contains acoustic fibres 9. medial longitudinal fasciculus

Answer 125

Midbrain · extends from the pons to the mammillary bodies of the diencephalon · contents: 1. inferior and superior colliculi a) the inferior colliculus is a relay nucleus on the auditory pathway to the thalamus and thence to the cerebral cortex b) the superior colliculus is involved in the voluntary control of ocular movements, and in movements of the eyes and head in response to visual and other stimuli 2. oculomotor (III) nerve 3. trochlear (IV) nerve 4. raphe nuclei 5. red nucleus a) motor nucleus; has afferents from cerebellum and cerebral cortex 6. substantia nigra 7. ventral tegmental area 8. crus cerebri

Answer 126

``` Afferent pathways: · corpus striatum · subthalamic nucleus · raphe nuclei of midbrain · pontine reticular formation Efferent pathways: · neostriatum (caudate nucleus) · amygdaloid body in the temporal lobe ```

Answer 127

Medial medullary syndrome · results from occlusion of the medullary branch of the vertebral artery · results in: · contralateral hemiparesis · contralateral disturbance of the sensations of position and movement · paralysis of the tongue is ipsilateral, and deviation is towards the affected side

Answer 128

Lateral medullary (Wallenberg’s) syndrome · due to occlusion of a vessel supplying the lateral area of the medulla · results in: · ipsilateral loss of pain and temperature in the area of distribution of the trigeminal nerve · contralateral sensory loss - touch sensation is diminished rather than abolished (since the medial lemniscus is intact)

Answer 129

Raphe nuclei · the neurones of the raphe produce serotonin and use this as a neurotransmitter Afferents: · spinal cord · primary motor cortex of the frontal lobe · parietal lobe · vestibular nuclei · cerebellar nuclei · periaqueductal grey matter Efferents: · thalamus · spinal cord · activity of the raphe nuclei induces sleep, due to release of serotonin in more rostral parts of the brain · electrical stimulation of the periaqueductal grey matter or the nucleus raphe magnus results in loss of pain sensation · encephalins are released at synapses in the periaqueductal grey matter, the raphe nuclei, and the substantia gelatinosa in the spinal cord - the analgesic effects of these chemicals requires integrity of the raphe spinal tract

Answer 130

The Reticular Activating System (RAS) · sensory data conveyed by the lemniscal system (medial, spinal, and trigeminal lemnisci) when projected from the thalamus to the somaesthetic cortical area, is interpreted in a specific manner with respect to the nature of the stimulus · much of the cortex is stimulated, with an effect on levels of consciousness and on alerting reactions to sensory stimuli · impulses from the trigeminal area of distribution have a significant effect on consciousness · some general anaesthetics are thought to suppress transmission through the RAS, although conduction continues along lemniscal routes · prolonged coma results from damage to the pontine or mesencephalic reticular formation

Answer 131

``` The Locus coeruleus · cells contain large quantities of noradrenaline · Afferents: · some raphe nuclei · hypothalamus · amygdala and cingulate gyrus · Efferents: · cerebral cortex · diencephalon · brain stem · cerebellum · spinal cord ```

Answer 132

Structure · consists of 4 components on each side: 1. thalamus: a) subdivided into nuclei which have different afferent and efferent connections 2. subthalamus: a) consists of the subthalamic nucleus, and also parts of the reticular formation and substantia nigra 3. epithalamus: a) includes the pineal gland, and structures concerned with autonomic responses to emotional changes 4. hypothalamus: a) the main cerebral centre for integrative control of the autonomic nervous system and of several endocrine glands b) the neurohypophysis which includes part of the pituitary gland is an outgrowth of the hypothalamus

Answer 133

Thalamus · there are a number of thalamic nuclei, all of which except the reticular nucleus sends axons to the cerebral cortex · there are few if any connections between the nuclei of the thalamus Intralaminar Nuclei 1. centromedian nucleus 2. parafascicular nucleus Ventral Group of Nuclei 1. Medial geniculate body a) involved in discriminative aspects of hearing 2. Lateral geniculate body/ nucleus (LGN) a) contains a detailed point-to-point projection of the retina b) involved in awareness of visual stimuli and the discriminative and mnemonic aspects of vision 3. Ventral Posterior Nucleus a) part of the pathway for conscious appreciation of sensations arising from skin, muscles, and internal parts of the body b) contains a topographical projection of the contralateral half of the body 4. Ventral Lateral Nucleus 5. Ventral Anterior Nucleus 6. Ventral Medial Nuclei Posterior group of nuclei 1. part of the pulvinar 2. part of the medial geniculate body 3. suprageniculate nucleus 4. nucleus limitans Lateral group of nuclei 1. Lateral Dorsal Nucleus a) part of the limbic system 2. Lateral Posterior Nucleus a) projects to the somatosensory association cortex of the parietal lobe 3. Pulvinar Medial group of nuclei 1. Mediodorsal Nucleus a) part of the limbic system and contributes to those aspects of emotions considered as ‘moods’ b) lesions around the third ventricle involving the mediodorsal nucleus are seen in Korsakoff’s syndrome and this area probably has a role in memory c) memory deficits have been reported following surgical destruction of the mediodorsal thalamic nuclei 2. Medioventral Nucleus a) part of the limbic system Anterior group of nuclei 1. consists of three nuclei which are considered to be part of the limbic system

Answer 134

Subthalamus 1. sensory fasciculi 2. rostral extensions of midbrain nuclei 3. fibre bundles from the cerebellum and globus pallidus 4. subthalamic nucleus a) a motor nucleus b) a lesion in this nucleus results in hemiballismus

Answer 135

Hypothalamus · surrounds the third ventricle · functions: · autonomic control of basic body functions, e.g., heart, bowel, blood pressure · regulation of body temperature · regulation of food and water intake · experience of pleasure · rage and aversion · the amygdala and hypothalamus have sex-specific patterns of neuronal and dendritic development · the anterior hypothalamus is involved in the relaxation response · the posterior hypothalamus is involved in the fight-or-fright response

Answer 136

uncontrolled laughter (sham mirth) occurs in hypophyseal and hypothalamic tumours · hypothalamic rage (sham rage) due to stimulation of hypothalamic nucleus

Answer 137

1. Supraoptic nucleus 2. Paraventricular nucleus a) involved in the eating of certain types of food 3. Suprachiasmatic nucleus a) forms the brain’s timepiece; keeps an approximate 24 hr clock 4. Ventromedial nucleus a) satiety centre which inhibits food intake b) controls parasympathetic activities 5. Dorsomedial nucleus 6. Infundibular nucleus 7. Premammillary nucleus 8. Mammillary body and posterior nucleus 9. Lateral nucleus a) involved in the stimulation of eating and control of drinking b) controls sympathetic activities, and is involved in the somatic correlates of heightened emotionality

Answer 138

Efferent pathways 1. periventricular fibres 2. dorsal longitudinal fasciculus 3. mamillothalamic fasciculus

Answer 139

``` Amygdala · ‘the seat of social and emotional intelligence’ · consists of two main nuclei - medial and lateral Medial amygdala · has afferents from olfactory tract · rich in encephalin-containing cells Lateral amygdala · able to modify output from hypothalamus and initiate appropriate higher functions, i.e. hypothalamus signals hunger and the amygdala signals the correct response from the body Afferents · the contralateral amygdala · dopaminergic brain stem nuclei · frontal association area · lateral olfactory stria · noradrenergic brain stem nuclei · serotonergic brain stem nuclei · septal nucleus · temporal association area Efferents · hypothalamus · septal nucleus · corpus striatum · frontal association area · lateral olfactory stria · temporal association area · thalamus ```

Answer 140

Functions · main role is that of attention, information processing, memory, new learning, cognitive mapping of the environment · prevents extremes of arousal by maintaining a state of quiet alertness · most complex organically-produced hallucinations are caused by tumours of the most anterior part of the temporal lobe (including the amygdala and hippocampus) · left sided lesions affect verbal memory · right sided lesions affect visual memory

Answer 141

associated with processing and modulating the expression of emotional nuances, emotional learning and vocalization, formation of long term attachments, and maternal behaviour

Answer 142

The first evidence that the limbic system was responsible for the cortical representation of emotions was discovered in 1939, by Heinrich Kluver and Paul Bucy. Kluver and Bucy, after much research, demonstrated that the bilateral removal of the temporal lobes in monkeys created an extreme behavioral syndrome.

Answer 143

Paul Pierre Broca in 1878 spoke of 'le grand lobe limbique' or the great limbic lobe and applied the term “limbic” (from the Latin limbus for border) to the curved rim of the cortex which incudes the cingulate and the parahippocampal gyri.

Answer 144

Primary nuclei 1. hypothalamic nuclei 2. amygdaloid nucleus 3. hippocampus 4. septal nuclei 5. thalamic nuclei: a) anterior, lateral dorsal, and medioventral nuclei 6. mamilllary bodies 7. superior central nucleus 8. ventral tegmental area 9. raphe nucleus

Answer 145

Cortical areas 1. cingulate gyrus 2. hippocampal formation: a) dendate nucleus b) hippocampus c) parahippocampal gyrus 3. olfactory tubercle 4. secondary olfactory area 5. subcallosal gyrus 6. indusium griseum 7. paraterminal gyrus

Answer 146

Connecting tracts 1. cingulum a) hippocampus to cingulate gyrus 2. anterior commissure 3. dorsal longitudinal fasciculus 4. stria terminalis a) hypothalamus to amygdala 5. stria medullaris thalami 6. amygdalofugal bundle a) hypothalamus to amygdala 7. fornix a) hypothalamus to hippocampus 8. medial forebrain bundle a) hypothalamus to septal nuclei b) involved in the positive reinforcement of behaviours 9. mamillothalamic tract a) mamillary bodies (hypothalamus) to anterior thalamic nucleus

Answer 147

``` Circuits of the limbic system · the largest components contain a ring of interconnected neurons called the circuit of Papez, which links the neocortex to the limbic system via the cingulate gyrus · hippocampus · mammillary body · thalamus · cingulate gyrus · input: · neocortex · thalamus · septal area · raphe nuclei · ventral tegmental area · catecholamine nuclei of the reticular formation · output: · neocortex · regions of the reticular formation that influence the autonomic system indirectly ```

Answer 148

Functional considerations · bilateral removal of the temporal lobes (including the hippocampal formations and amygdaloid bodies) is followed by docility and lack of emotional responses such as fear or anger · there is increased sexual activity, often perverted · lesions to the amygdala produce similar changes, although the sexual behaviour is less affected · electrical stimulation of the amygdala in humans induces feelings of fear or anger · summary of functions: · strong affective responses such as fear, anger, and sexual behaviour · changes in visceral function: · changes in gastrointestinal movements and secretion · piloerection · pupillary dilatation · changes in respiratory movements · role in memory (especially the hippocampus) · the hippocampus may also have a role in the sleep-wake cycle

Answer 149

``` · memory disturbance occurs in damage to: · mammillary bodies · hippocampus · fornix · substantia innominata ```

Answer 150

The Corpus Striatum · a substantial region of grey matter near the base of each cerebral hemisphere · the term ‘basal ganglia’ refers to the corpus striatum, subthalamic nucleus, and substantia nigra · consists of: 1. caudate nucleus 2. lentiform nucleus a) putamen b) globus pallidus · the paleostriatum (a.k.a. pallidum) refers to the globus pallidus in mammals · the neostriatum (a.k.a. striatum) refers to the putamen and the caudate nucleus

Answer 151

Functions · the striatum inhibits the pallidum · the pallidum inhibits the thalamocortical neurons · GABA is the inhibitory transmitter · when no movements are being made, the cells of the striatum are quiet and the cells of the pallidum are active · shortly before a movement, the above situation is reversed · removal of pallidal inhibition allows the ventral thalamic nuclei to be stimulated by other afferent fibres, most of which come from the premotor area of cortex · the nigrostriatal dopaminergic neurons are active all the time

Answer 152

· Huntington’s chorea: · neuronal degeneration in the corpus striatum, most marked in the neostriatum

Answer 153

Functional anatomy 1. vestibulocerebellum a) consists of the flocculonodular node and a region of the vermis known as the uvula b) receives input from the vestibular nerve and nuclei c) influences motor neurons through the vestibulospinal tract, the medial longitudinal fasciculus, and reticulospinal fibres d) involved in adjustment of muscle tone and maintenance of equilibrium 2. spinocerebellum a) consists of parts of the vermis and adjacent parts of the hemispheres b) site of termination of the spinocerebellar tracts, which convey proprioceptive and other sensory information c) receives information from all three sensory nuclei of the trigeminal nerve, and also the red nucleus d) involved in the control of muscle tonus and synergy of collaborating muscles 3. pontocerebellum a) the lateral parts of the hemispheres and the superior vermis in the posterior lobe; also the dentate nucleus b) fibres pass through the red nucleus c) ensures a smooth and orderly sequence of muscular contractions and the intended precision in the force, direction, and extent of volitional movements d) connections are ipsilateral

Answer 154

``` Cells of the cerebellum · glomerulus: · mossy fibre · dendrites of granule cells · axon of Golgi cell · Purkinje cells: · use GABA as neurotransmitter · axons are the only cells leaving the cortex · terminate in central nuclei of cerebellum · also send efferents to: · thalamus · Golgi cells · reticular neurones · intracortical circuits are inhibitory · most input to the cortex is excitatory ```

Answer 155

``` The Extrapyramidal System · includes: · basal ganglia (caudate and lentiform nucleus) · cerebellum: · dentate nucleus · brain stem nuclei: · substantia nigra · midbrain nuclei · tectal nuclei · lateral vestibular nucleus (Reiter’s nucleus) ```

Answer 156

``` The Pyramidal System · originates in the motor cortex · descends through: · corona radiata · internal capsule · ventral midbrain · medulla oblongata (forms the pyramids) · 85 % of the fibres decussate in the medulla to form the lateral corticospinal tract · 15 % of the fibres form the ventral corticospinal tract · sends fibres to: · red nucleus · reticular formation · pontine nuclei · terminates in: · interneurones of dorsal horn (laminae IV, V, and VI) · ventral horn (lamina VII) – contains Renshaw cells (interneurones) ```

Answer 157

``` Clinical considerations · degeneration leads to: 1. ataxia 2. wide-based gait 3. loss of vibration sense 4. loss of deep pain sensation 5. positive Romberg’s sign ```

Answer 158

``` The Frontal Lobes Frontal Operculum · consists of areas 44, 45, and 47 · Broca’s area – on the dominant side, and consists of areas 44 and 45 · a lesion in this area can lead to Broca’s/ Expressive nonfluent aphasia · lesions in the non-dominant frontal operculum can lead to dysprosody Superior mesial region 1. supplementary motor area (SMA) 2. anterior cingulate cortex · lesions of the left or right superior mesial region can lead to akinetic mutism Inferior mesial region 1. orbital cortex a) functions include: i) social behaviour ii) personality b) lesions of the orbital cortex (either side) can lead to a form of acquired sociopathy 2. basal forebrain: a) contains the following nuclei: i) diagonal band of Broca ii) nucleus accumbens iii) septal nuclei iv) substantia innominata b) lesions of the basal forebrain (either side) can lead to amnesia (retrograde and anterograde) and confabulation Dorsolateral prefrontal cortex (DLPFC) · functions include: · problem-solving · perceptual judgement · memory · programming and planning sequences of behaviour · verbal regulation · level of response emission · adaptability of response pattern · tertiary level of motor control · lesions in this region can cause: · abnormal cognitive executive functions · impairment of verbal (left) or non-verbal (right) intellectual functions · memory impairment affecting recency and frequency judgements · poor organization · poor planning · poor abstraction · disturbances in motor programming · impaired verbal fluency (left-sided lesions) · impaired design fluency (right-sided lesions) ```

Answer 159

``` Frontal lobe syndrome · personality change: · disinhibition · reduced social and ethical control · sexual indiscretions · poor judgement · elevated mood (fatuous euphoria) · perseveration · contralateral spastic paresis · ‘Utilization syndrome’ · palilalia · impairment of attention, concentration, and initiative · motor Jacksonian fits · Witzelsucht (inappropriate jocularity) · aphasia · primary motor aphasia · motor agraphia · ipsilateral optic atrophy · anosmia · magnetism (ask pt. to draw a clock face) · grasp reflex, and other primitive reflexes · urinary incontinence if the lesion is lateral ```

Answer 160

The Parietal lobes Temporoparietal junction · left-sided lesions: · receptive aphasia · right-sided lesions: · phonagnosia (inability to recognise familiar voices) · amusia (inability to recognise and process music) Inferior parietal lobule 1. angular gyrus 2. supramarginal gyrus · left-sided lesions (affecting the arcuate fasciculus): · conduction aphasia – patient cannot repeat what is said to them · tactile agnosia · dysphasia · right-left disorientation · finger agnosia (can be elicited by the ‘In-Between Test’) · agraphia · body image disorders · sensory extinction · astereoagnosia (inability to recognise objects by palpation) · alexia · dysgraphaesthesia (inability to recognise letters or numbers written on the hand) · right-sided lesions: · anosognosia (lack of awareness of disease, particularly of hemiplegia) · neglect · tactile agnosia · asomatognosia (inability to recognize parts of the body) · constructional dyspraxia · Angular gyrus: · inability to read · inability to write

Answer 161

``` Gerstmann’s syndrome · lesion of dominant parietal lobe: 1. right-left disorientation 2. finger agnosia 3. dysgraphia 4. dyscalculia ```

Answer 162

The Temporal lobes Superior temporal gyrus · area 22, forms, on the left, Wernicke’s area · lesions here can cause a receptive aphasia Posterior Inferolateral region 1. post. portion of the middle temporal gyrus 2. post. portion of the inferior temporal gyrus 3. post. portion of the fourth temporal gyrus · lesions in this region can lead to: · prosopagnosia · impaired object recognition Anterior Inferolateral region 1. ant. portion of the middle temporal gyrus 2. ant. portion of the inferior temporal gyrus 3. ant. portion of the fourth temporal gyrus 4. temporal pole · left-sided lesions can lead to: · anomia · defects in accessing the reference lexicon · right-sided lesions may lead to: · inability to name facial expressions · bilateral lesions lead to: · retrograde amnesia The Mesial Temporal Region 1. parahippocampal gyrus (areas 27 and 28) 2. amygdala 3. entorhinal cortex 4. hippocampus · left-sided lesions: · anterograde amnesia affecting verbal information · right-sided lesions: · anterograde amnesia affecting non-verbal information · bilateral lesions: · verbal and non-verbal anterograde amnesia

Answer 163

· Kluver-Bucy (due to bilateral damage of amygdala, uncus, and hippocampus) · social and emotional agnosia (unable to discern the meaning or significance of common objects) hypermetamorphosis/ hyperorality (perseverative oral exploration) · sexual indiscretion · loss of fear, leading to aggression · affective blunting · visual agnosia

Answer 164

The Occipital lobes 1. primary visual cortex 2. visual association cortices · lesions of the dorsal region and adjoining parietal region can lead to partial (unilateral) or full-blown (bilateral) Balint’s syndrome: 1. simultanagnosia (the ability to understand individual details of a scene, but is unable to recognize the full meaning) 2. ocular apraxia or psychic gaze paralysis 3. optic ataxia · bilateral dorsal lesions: · astereopsis · impaired visual motion perception · depending on site of lesion, the following can occur: · achromatopsia (loss of colour perception) – due to damage to the lingual gyri · hemiachromatopsia · acquired dyslexia · apperceptive visual agnosia · visual agnosia · prosopagnosia (unable to recognize familiar faces) - can occur with bilateral inferior occipital lesions · disturbances of visual recognition · complex visual hallucinations · visual field defects · visual disorientation

Answer 165

Anton’s syndrome - denial of visual disability and confabulation of visual detail

Answer 166

``` The Basal Ganglia Components 1. corpus striatum a) caudate nucleus b) lentiform nucleus i) globus pallidus ii) putamen 2. amygdaloid nucleus 3. claustrum Connections 1. Afferents: a) caudate nucleus b) cerebral cortex c) putamen d) substantia nigra 2. Efferents: a) globus pallidus b) hypothalamus c) reticular formation d) substantia nigra e) subthalamus f) thalamic nuclei Fronto-subcortical circuits · Alexander et al. (1986) · connect the frontal cortex with the basal ganglia and the thalamus · involved in: · motor activity · eye movements · behaviour · the overall structure is: · frontal lobe cortex Ë caudate nucleus Ë globus pallidus/ substantia nigra Ë thalamus Ë frontal lobe cortex ```

Answer 167

``` Somatosensory systems Spinothalamic system · carries information from: 1. mechanoreceptors (crude touch, pressure, tickle and itch, sexual sensation) 2. thermoreceptors (warm and cold sensation) 3. pain receptors Dorsal column system · carries information only from mechanoreceptors: 1. fine, precisely localised touch 2. vibration 3. kinaesthetic sensation 4. fine pressure sensation · contains thick myelinated fibres ```

Answer 168

Lower motor neuron lesions · features include: 1. flaccid paresis or paralysis 2. weak or absent tendon reflexes 3. muscle atrophy 4. fibrillation potentials, detected on electromyography 5. sprouting at nodes of Ranvier and at motor end plates (on biopsy)

Answer 169

``` Upper motor neuron lesions · features include: 1. weak or absent voluntary movements 2. atrophy does not occur 3. spasticity, due to the continuous operation of the stretch reflex 4. exaggerated tendon reflexes 5. upgoing plantar reflex 6. superficial reflexes are suppressed or absent (e.g. abdominal & cremasteric reflexes) ```

Answer 170

``` The Light and Accommodation reflexes · involves: 1. Short ciliary nerves 2. Ciliary ganglion 3. Oculomotor nerve 4. Pre-tectal area 5. Edinger-Westphal nucleus 6. Posterior commissure 7. Optic tract 8. Lateral Geniculate nucleu ```

Answer 171

The corneal reflex · involves: 1. afferent fibres are in the ophthalmic nerve 2. efferent fibres are in the facial nerve 3. spinal nucleus of the trigeminal nerve

Answer 172

``` Alzheimer’s disease Macroscopic neuropathology · global brain atrophy (most marked in the frontal and temporal lobes) · ventricular enlargement · sulcal widening Histopathology · neuronal loss · shrinking of dendritic branching · reactive astrocytosis · neurofibrillary tangles · neuritic (senile) plaques · histological changes commonly seen in the hippocampus include: · granulovacuolar degeneration · Hirano bodies · neurofibrillary tangles · neuritic (senile) plaques Ultrastructural pathology · neuritic plaques contain a core of amyloid · scattered deposits of beta-amyloid have been found to localize to active microglia ```

Answer 173

``` Neurochemical pathology · decreased: · Acetylcholinesterase · Choline acetyltransferase · GABA · noradrenaline ```

Answer 174

``` Pick’s disease Macroscopic · selective asymmetrical atrophy of the anterior temporal lobes and frontal lobes · knife-blade gyri · ventricular enlargement Histopathology · Pick’s bodies · neuronal loss · reactive astrocytosis · these changes are seen in: · cerebral cortex · basal ganglia · locus coeruleus · substantia nigra Ultrastructural · Pick’s bodies consist of: · straight neurofilaments · paired helical filaments ```

Answer 175

``` Lewy body disease Histopathology · Lewy bodies · neuronal loss · neurofibrillary tangles · neuritic (senile) plaques · compared to Parkinson’s disease, the density of Lewy bodies is much higher in: · cingulate gyrus · parahippocampal gyrus · temporal cortex Ultrastructural · Lewy bodies contain: · protein neurofilaments · granular material · dense core vesicles · microtubule assembly protein · ubiquitin · tau protein ```

Answer 176

``` Parkinson’s disease Macroscopic · depigmentation of the substantia nigra, especially in the zona compacta · depigmentation of the locus coeruleus · diffuse cortical atrophy can take place Histopathology · neuronal loss · reactive astrocytosis · Lewy bodies in: · substantia nigra · dorsal motor nucleus of the vagus · hypothalamus · nucleus basalis of Meynert · locus coeruleus · Edinger-Westphal nucleus · raphe nuclei · cerebral cortex · olfactory bulb · presence of melanin-containing macrophages Neurochemical · reduced inhibitory dopaminergic action of the nigrostriatal pathway on striatal cholinergic neurones ```

Answer 177

``` Huntington’s disease Macroscopic · small brain with reduced mass · marked atrophy of the corpus striatum, particularly the caudate nucleus · marked atrophy of the cerebral cortex, particularly the frontal lobe gyri · dilatation of the lateral and third ventricles Histopathology · neuronal loss in the cerebral cortex, especially the frontal cortex · neuronal loss in the corpus striatum, particularly neurones using as neurotransmitters: · GABA and enkephalin · GABA and substance P · astrocytosis in affected regions · sparing of: · diaphorase-positive neurones containing nitric oxide synthase · large cholinesterase-positive neurones Neurochemical · Í GABA · Í Glutamic acid decarboxylase · Í Acetylcholine · Í Substance P · Í CRF · È somatostatin · dopamine hypersensitivity ```

Answer 178

Dopamine hypersensitivity hypothesis Proposed mechanism Long- term treatment ‡ chronic dopamine receptor blockade ‡ D2 receptor hypersensitivity in the nigrostriatal pathway ‡ tardive dyskinesia Evidence in favour · studies of denervation-induced hypersensitivity in muscles · animal experiments in which, following the discontinuation of antipsychotic drugs, acute dopamine agonist challenges ‡ increased oral stereotyped behaviour · animal experiments in which repeated antipsychotic treatment may lead to increased D2 receptor levels Problems with the theory · differences in the chronology of onset of symptoms in animal and human models · PM studies in humans have not shown significant differences in schizophrenic brains with or without TD · blood biochemical assays have not shown significant differences between patients with TD and patients without TD with respect to: · prolactin · somatotrophin · dopamine agonists do not strikingly exacerbate tardive dyskinesia · dopamine antagonist antipsychotics may sometimes worsen TD

Answer 179

Dopamine hypersensitivity Free radical induced neurotoxicity GABA insufficiency Noradrenergic dysfunction

Answer 180

Proposed mechanism Long- term treatment ‡ increased catecholamine turnover ‡ free radical byproducts ‡ membrane lipid peroxidation in the basal ganglia ‡ tardive dyskinesia Evidence in favour · vitamin E is of benefit in rodent models of TD · some studies have shown increased blood or CSF levels of lipid peroxidation byproducts in patients with TD compared to those without TD Problems · Vitamin E treatment of TD does not work

Answer 181

Proposed mechanism Long-term treatment ‡ destruction of GABAergic neurones in the striatum ‡ reduced feedback inhibition ‡ TD or Long-term treatment ‡ reduced GABAergic activity in the pars reticulata of the substantia nigra ‡ reduced inhibition of involuntary movements ‡ TD Evidence in favour · antipsychotic-treated dyskinetic monkeys have a decrease in glutamic acid decarboxylase in the basal ganglia · patients with TD have been found, on PM, to have a reduced level of in glutamic acid decarboxylase in the subthalamic nucleus · GABAergic agonists such as BZDs, baclofen, and gamma-vinyl GABA have shown promise as therapeutic agents Problems · rodent models do not show consistent changes in GABA function with neuroleptic treatment · GABA agonists are not yet effective treatments

Answer 182

Mechanism · noradrenergic overactivity contributes to the pathphysiology of TD Evidence in favour · patients with TD have significantly higher dopamine b-hydroxylase activity · platelet alpha-2 adrenoceptor binding and CSF noradrenaline have been correlated with the severity of TD Problems · TD cannot be treated with noradrenergic drugs

Answer 183

Delta - slow wave sleep - up to 3hz - babies - pathologically in metabolic encephalopathy, subcritical lesions, hydrocephalus, deep midline lesions Theta - 4-7hz - young children - pathological in focal subcortical, deep midline, metabolic encephalopathy, some instances of hydrocephalus Alpha - 8-12hz - in closing eyes - path in coma Beta - active - 12-30hz - path with benzodiazepines - some antidepressants may increase

Answer 184

Absence seziure

Answer 185

Focal lesion

Answer 186

Huntington’s

Answer 187

Allows measurements of blood flow, oxygen extraction, blood volume and glucose metabolic rate Can be used to determine neurotransmitter turnover Can be used to assess the receptor occupancy by different medications- using raclopride to estimate dopamine receptor occupancy Useful to diagnose FTD and VaD

Answer 188

Sensitive to pathology with altered blood flow and metabolism such as epilepsy and AV malformations Can the differential diagnosis of dementia Can differentiate between dementia and depression of old age

Answer 189

It can detect metabolic and hemodynamic changes secondary to alterations in neuronal activity

Answer 190

Initiation Elongation Conformational change

Answer 191

Missense changes the amino acid coded for | No sense results in a stop signal

Answer 192

``` 1. Analysis of segregation to establish mode of transmission Adoption studies Parent as proband Adoptee as proband Cross fostering design ``` 2. Twin studies Measures concordance rates, similarity of phenotype between twins MZ and DZ 3. Gene mapping Positional- identify location Functional- selection of candidate genes 4. Linkage analysis Performed in families with more than one affected Cosegregation of polymorphic DNA markers with diseases in families 6. Association studies Frequency of marker in populations of patients and healthy controls 7. Cytogenetic studies Cloning disrupted genes