Flashcards in Nervous System, Opthamology, Psychiatry Deck (494):
What type of receptors are mu opioid receptors and what types of second messenger pathways do they activate?
G-protein linked receptors; activate and regulate many 2nd messenger pathways- one involves K+ conductance: upon binding to mu receptors, morphine causes G-protein coupled activation of K+ channels to increase K+ efflux from the cell. This causes hyperpolarization of the post synaptic neurons and termination of pain transmission. Other pathways induce inhibition of adenlyl cyclase, calcium conductance, and inhibition of NT release.
In the neuromuscular junction, Ach release from presynaptic terminal vesicles depends on the inflow of what ion?
Inflow of extracellular calcium into the presynaptic terminal; this occurs following neuronal depolarization and opening of voltage gated Ca2+ channels.
What type of receptors are found on postsynaptic skeletal muscle end plates?
Ligand gated sodium and potassium ion channels.
What microscopic changes are seen in brain tissue 12-48 hours post ischemic injury?
Red neurons- eosinophilic cytoplasm, pyknotic nuclei, loss of Nissl substance
When does liquefactive necrosis of brain tissue appear macroscopically after injury?
1-2 weeks after injury.
What is a pyknotic nucleus?
A small and deeply basophilic nucleus.
What embryological process gone wrong is responsible for neural tube defects?
Failure of fusion of the neural tube during the fourth week of fetal development. This occurs in the region of the neuropores, at the cranial or caudal end of the neural tube. This leads to a persistent communication between the spinal canal and amniotic cavity.
Amniotic fluid of a fetus with a neural tube defect will show what diagnostic markers?
a-fetoprotein and Acetylcholinesterase. AFP will also be elevated in maternal serum.
What are two anterior neural tube defects?
What are three posterior neural tube defects?
Spina bifida occulta, meningiocele, meningomyelocele. Posterior NTDs are more common than anterior NTDs
What is encephalocele?
Herniation of the brain tissue through a cranial defect.
What is anencephaly?
Total absence of the brain and calvarium.
To what drug class does Thiopental belong?
Short acting, IV barbiturate anesthetic
What is Thiopental used for?
Induction of anesthesia due to its rapid onset
How is mutated huntingtin protein thought to cause Huntington's disease?
Transcriptional repression (silencing) due to histone deacetylation
What is the result of histone acetylation?
Weakening of the DNA histone bond that makes DNA segments more accessible for transcription factors and RNA polymerases enhancing gene transcription.
An isolated right nasal hemianopia is caused by a lesion in what location?
Right peri-chiasmal lesion.
What is a possible cause of an isolated right nasal hemianopia?
Calcification or aneurysm of the internal carotid artery impinging on uncrossed lateral retinal fibers.
What may cause monocular scotoma?
Macular degeneration, optic neuritis.
What type of lesion may cause left homonymous superior quadrantanopia?
Right temporal lobe- meyers loop region
What type of lesion may cause left homononymous inferior quadrantanopia?
Right parietal lobe (dorsal optic radiation)
What type of lesion would cause left homonymous hemianopia with macular sparing?
Lesion to the right primary visual cortex (occipital lobe)
What structures does the posterior cerebral artery supply?
Thalamus, medial temporal lobe, splenium of the corpus callosum, parahippocampal gyrus, fusiform gyrus, occipital lobe. It also supplies CN III and IV
What is the most common finding of PCA infarction?
Contralateral hemianopia often with macular sparing. Contralateral paresthesias and numbness affecting the face, trunk, and limbs occur if the lateral thalamus is also affected.
How do you distinguish between schizoaffective disorder and bipolar disorder/ major depression with psychotic features?
Temporal relationship of psychotic symptoms to mood symptoms- in bipolar disorder and major depression with psychotic features, psychotic sx occur exclusively during manic or depressive episodes. When the patient's mood is euthymic, there are no psychotic sx.
Describe the positional relationship between the caudate, globus pallidus and putamen.
Head of the caudate lies in the inferolateral wall of the anterior horn of the lateral ventricle. It is separated from the globus pallidus and putamen by the internal capsule.
What is the site called where the frontal, parietal, temporal, and sphenoid bones meet in the skull?
Why is the pterion relevant?
Skull is thin here and the middle meningeal artery courses within the skull deep to this point- fractures to this region can cause an epidural.
The middle meningeal is a branch of what artery?
The maxillary artery (which is a branch of the external carotid).
Korsakoff syndrome is associated with damage to what regions of the brain?
Anterior and dorsomedial thalamic nuclei.
What nervous system defects are associated with Vitamin E deficiency?
Degeneration of the spinocerebellar tracts, dorsal column of the spinal cord, and peripheral nerves.
Vitamin E deficiency closely resembles what genetic condition?
Freiderich ataxia- degeneration of the spinocerebellar tracts, dorsal column of the spinal cord, and peripheral nerves; ataxia, dysarthria, loss of position and vibration sensation.
Poliomyelitis causes damage to what region of the spinal cord?
Anterior horn cells.
What is myotonia?
Abnormally slow relaxation of muscles.
What are classic symptoms of myotonic muscular dystrophy?
Difficulty loosening one's grip after a handshake, inability to release the doorknob. Cataracts, frontal balding, gonadal atrophy. Type 1 muscle fibers are more affected; NO fibrofatty replacement.
Describe the inheritance of myotonic dystrophy.
Autosomal dominant trinucleotide expansion of CTG in the gene coding for myotonia protein kinase. Anticipation occurs.
What is the mechanism of action of cocaine?
Indirect sympathomimetic- Prevents the reuptake of monoamines (NE, D, 5-HT) resulting in sympathetic stimulation and CNS activation.
What drugs are used to treat generalized anxiety disorder?
Benzodiazapines and antidepressants.
On light microscopy, what is seen in temporal arteritis?
Granulomas in the media of the arteries consisting of mononuclear infiltrates and multinucleated giant cells. These changes are segmental.
What condition occurs in more than half of patients with temporal arteritis?
What is polymyalgia rheumetica?
Neck, torso, shoulder, pelvic girdle pain and morning stiffness. Fatigue, fever, weight loss may also occur.
What causes central pontine myelinolysis?
Rapid correction of chronic hyponatremia
What are the manifestations of central pontine myelinolysis?
Spastic quadriplegia and pseudobulbar palsy.(CN Ix, X, and XI are demyelinated)
What is pseudobulbar palsy?
Head and neck muscle weakness, dysphagia, dysarthria
Deficiencies in what vitamins are common in patients with cystic fibrosis?
Fat soluble (A, D, E, K)
What are the most common clinical manifestations of vitamin E deficiency?
Neuromuscular disease (skeletal myopathy, spinocerebellar ataxia, pigmented retinopathy) and hemolytic anemia (increased susceptibility of neuronal and erythrocyte membranes to oxidative stress). Involvement of the dorsal column of the spinal cord causes loss of proprioception and vibratory sense; spinocerebellar involvement causes ataxia.
What is one of the principle functions of vitamin E?
Protection of fatty acids from oxidation; deficiency disposes cell membranes with high fatty acid content to oxidative injury.
Cholinomimetics are indicated in what three conditions?
Paralytic ileus, urinary retention, glaucoma.
What is Lamotrigine used to treat and what is its principle side effect?
Anticonvulsant for partial seizures; may cause life threatening skin rash.
What two genetic conditions are associated with berry (saccular) aneurysms?
ADPKD, Ehlers-Danlos syndrome.
In SAH, where does blood accumulate?
Between the arachnoid and pia mater
What does LP reveal in a patient with SAH?
Gross blood or xanthochromia (yellow discolouration of CSF)
What are Charcot-Bouchard aneurysms?
Small aneurysms that occur in patients with long standing hypertension. They are found in the arterioles that supply the basal ganglia, internal capsule, and deep white matter. They can cause intercerebral hemorrhage, but not SAH.
What is DRESS syndrome?
Drug reaction with eosinophilia and systemic symptoms that typically occurs 2-8 weeks after exposure to high risk drugs such as anticonvulsants, allopurinol, sulfonamides, and antibiotics.
What are the symptoms of DRESS syndrome?
Fever, generalized lymphadenopathy, facial edema, diffuse skin rash, eosinophilia, organ dysfunction.
What lab values are associated with DRESS syndrome?
eosinophilia, atypical lymphocytosis, elevated ALTs.
What is mixed cryoglobulinemia?
Small to medium vasculitis caused by circulating immunoglobin-complement complexes that precipitate on refrigeration. It is typically associated with chronic inflammatory states and may present with systemic findings- fatigue, arthralgias, myalgias, and palpaple purpura in the lower extremities.
What deposits stain congo red and are seen with apple-green birefringence under polarized light?
Where does amyloid angiopathy occur?
Deposits in the media and adventitia of cerebral vessels that cause thickening of the basal membrane, stenosis of the vessel lumen, and fragmentation of the elastic lamina.
What composes senile plaques?
Parenchymal, extracellular deposits of amyloid. These are seen in many elderly people and are not pathologic.
What types of effects can tricyclic anti-depressants have on the cardiac conduction system?
Quinidine like effects- can cause QRS and QT prolongation and cardiac dysrhythmias. These effects are due to inhibition of fast sodium channels
What is the most effective intervention for TCA overdose?
Hypertonic Sodium Bicarbonate- it can correct QRS prolongation, reverse hypotension, and treat ventricular dysrhythmias.
Where is the body's satiety center?
The ventromedial nucleus of the hypothalamus.
What symptoms are noted with bilateral lesions to the ventromedial nuclei?
Hyperphagia, obesity, rage/ savage behaviour.
What is the most common cause of lesions to the ventromedial nuclei?
Tumor- namely craniopharyngioma.
What is synaptophysin?
A transmembrane glycoprotein found in the presynaptic vesicles of neurons, neuroectodermal, and neuroendocrine cells.
Immunoreactivity of a CNS tumor for synaptophysin indicates a tumor of what origin?
Where are primary brain tumors most commonly located in adults and in children?
Adults- supratentorial; children- infratenrotial
What brain tumors stain positive for GFAP?
Gliomas- astrocytomas, oligodendrogliomas, ependymomas, peripheral neural sheath tumors.
Which benzodiazapines are short acting and typically used before bedtime?
Triazolam and alprazolam.
Name four intermediate to long acting benzodiazepines.
Lorazepam, flurazepam, diazepam, chlordiazepoxide
Name the three types of glial cells.
Astrocytes, oligodendrocytes, microglia.
From what tissue type are astroctyes derived?
From what tissue type are oligodendrocytes derived?
From what tissue type are microglia derived?
Monocytes in the bone marrow
What are the functions of astrocytes?
Repair, structural support, BBB support, metabolic.
What is the function of oligodendrocytes?
Production of myelin.
What compensates for volume loss that occurs after neuronal cell death?
A glial scar.
What is the thalamic syndrome?
Total sensory loss on the contralateral side of the body. There are no motor deficits and proprioception is often profoundly affected and may lead to difficulty ambulating and falls.
Damage to what nuclei cause complete contralateral sensory loss?
The thalamic VPL and VPM nuclei.
What are lacunar infarctions?
Small cavities located within the basal ganglia, posterior limb of the internal capsule, pons, and cerebellum. They are caused by occlusion of the small penetrating arteries that supply these structures.
What are the primary mechanistic causes of lacunar infarcts?
Lipohyalinosis and microatheromas
What is lipohyalinosis?
A destructive vessel lesion characterized by loss of normal arterial architecture, mural foam cells, and in acute cases, evidence of fibrinoid vessel wall necrosis.
What causes microatheromas?
Accumulation of lipid laden macrophages within the intimal layer of a vessel.
Damage to what area causes hemiballism?
Contralateral subthalamic nucleus (most commonly from a lacunar stroke).
What is hemiballism?
wild, flinging movements of the extremities on one side of the body.
The subthalamic nucleus is part of what region?
Basal ganglia. It is ventral to the thalamus and superior to the internal capsule.
What is kinesin?
A microtubule associated motor protein whose function is anterograde transport of intracellular vesicles and organelles towards the growing end of microtubules down axons to synaptic terminals. It is powered by ATP.
What is seen on light microscopy of peripheral nerves in a patient with Guillain Barré?
Segmental demyelination and endoneural inflammatory infiltrate.
What is the function of cranial nerve VII?
Motor output to the facial muscles, parasympathetic innervation to the lacrimal, submandibular, and sublingual salivary glands, special afferent fibers for taste from the anterior 2/3 of the tongue, somatic afferents from the pinna and external auditory canal.
What findings are specific to Bell's palsy?
Sudden onset of unilateral facial paralysis. Specific findings include impaired eye closure, eyebrow sagging, inability to smile and frown, disappearance of the nasolabial fold, and the mouth being drawn to the non-affected side. Patients may also have decreased tearing, hyperacusis, and/or loss of taste sensation over the anterior two thirds of the tongue.
Why is atropine administered prior to bronchoscopy?
To decrease respiratory mucous secretions and promote bronchodilation.
What symptoms are associated with atropine toxicity?
Dry and flushed skin, hyperthermia, mydriasis, cycloplegia, bronchodilation, tachycardia, constipation, urinary retention.
What is the mechanism of action of physostigmine?
Acetylcholinesterase inhibitor both peripherally and centrally (it is a tertiary amine so is capable of crossing the BBB).
Which acetylcholinesterase agents have quaternary ammonium structures and this can't penetrate the CNS?
Neostigmine and edrophonium.
What is the mechanism of Buspirone?
Selective 5HT1A receptor agonist that has no hypnotic, sedative, or euphoric effects. Dependence does not occur and there is minimal potential for abuse.
What clinical findings are associated with tabes dorsalis due to Treponema pallidum (syphilis) infection?
Sensory ataxia (may cause wide based gait), lancinating pains, neurogenic urinary incontinence, Argyll robertson pupils.
What is tabes dorsalis?
A late form of neurosyphilis that usually manifests 5-20 years after primary infection.
What are Argyll Robertson pupils?
Small, irregularly shaped pupils that fail to constrict in response to light but constrict normally in response to accommodation. They are thought to be caused by spirochetes invading and damaging the midbrain tectum.
What tracts of the spinal cord are affected by Tabes dorsalis?
Dorsal columns and dorsal roots of the spinal cord, resulting in loss of position and vibration sense and severe lancinating pains. Peripheral reflexes may also be absent.
What are the primary symptoms of cryptococcal infection in HIV patients?
Subacute meningitis- fever, malaise, headache.
What are the primary symptoms of Herpesvirus type 1 encephalitis?
Encephalitis where the temporal lobe is primarily affected- symptoms include fever, headache, confusion, personality changes.
What causes progressive multifocal leukoencephalopathy?
Reactivation of the JC virus (polyomavirus). Symptoms include progressive dementia, motor deficits, and visual impairment.
What is subacute sclerosing panencephalitis?
Rare complication of measles occuring years after infection. It is caused by continuous replicating viral particles which cause a persistent, nonproductive infection that evades host immune mechanisms. Accumulation of viral nucleocapsids within neurons and oligodendrocytes results in formation of intranuclear inclusions and inflammation, demyelination, and gliosis in several cerebral areas.
What type of virus is measles?
Enveloped, single-stranded RNA virus that is a member of the paramyxovirus family. Its genome codes for hemagglutin and matrix protein.
What is seen in the CSF of patients with subacute sclerosing panencephalitis?
Oligoclonal bands (antibodies) of measles virus.
What is progressive supranuclear palsy?
A form of parkinsonism resulting from neurodegeneration of the midbrain and frontal subcortical white matter. It presents with rapidly progressive gait dysfunction and falls, executive function loss, vertical gaze palsy. Biopsy usually shows deposits of abnormal p-tau.
What are the diagnostic criteria for bullemia nervosa?
Recurrent binge eating with compensatory behaviours to prevent weight gain. These behaviours must occur at least twice a week for at least 3 months. Compensatory responses are typically purging or nonpurging (excessive excercise, dieting, fasting).
What distinguishes binge purge anorexia from binge purge bulemia?
Anorexia entails low body weight (<85% of ideal or BMI of 17.5) and amenorrhea.
How does hydrocephalus in early infancy present?
With macrocephaly, irritability, poor feeding, muscle hypertonicity, hyperreflexia. Hypertonity and hyperreflexia result from upper motor damage caused by stretching of the periventricular pyramidal tracts.
What nerve innervates the posterior part of the external auditory canal? What innervates the remainder of the canal?
The small auricular branch of the vagus nerve. Mandibular division of the trigeminal nerve (auriculotemporal branch) innervates the rest. The inner surface of the tympanic membrane is innervated by the CN IX tympanic branch.
Name five medications that may cause seizures.
Bupropion, clozapine (at high doses), isoniazid, ciprofloxacin, imipenem (antibiotic).
Describe the symptoms of lithium toxicity.
Neuromuscular excitability, irregular coarse tremors, fascicular twitching, agitation, ataxia, delirium. Hemodialysis is the most effective way to reduce blood levels of Li.
What can lead to lithium toxicity?
Renal injury toxins and drugs that alter GFR as it is almost exclusively excreted by the kidneys.
Name four classes of drugs that lead to increased lithium levels.
Thiazide diuretics, ACE-Is, NSAIDs, nondihydropyridine Ca2+ channel blockers (verapamil, diltiazem).
What is clasp knife spasticity?
Initial resistance to passive extension followed by a sudden release of resistance. It is seen in UMN lesions.
What symptoms are associated with internal capsule stroke?
Pure motor weakness affecting the contralateral arm, leg, and lower face. Contralateral spasticity or increased tone, hyperreflexia, and a positive Babinski sign are also present.
What is the function of the insula?
The insular cortex is involved in integrating body states with emotions (limbic system), ANS control, and conscious experience of visceral sensations.
What is the function of the putamen?
Part of the basal ganglia; plays a role in the initation of movement. Lesions in this area can cause contralateral tremor, bradykinesia, and rigidity.
What symptoms result from damage to the external and internal segments of the globus pallidus?
Part of the basal ganglia/ extrapyramidal motor system. Damage to the external segment results in decreased motion/ movement; damage to the internal segment results in excessive motion/ movement
UMN lesions can affect what regions?
Any part of the pyramidal motor nervous system including the corticospinal tracts of the spinal cord, the medulla, pons and midbrain, the internal capsule, and the precentral gyrus (primary motor cortex).
Prolactinomas are derived from what embryologic layer?
Ectoderm gives rise to what three layers?
Surface ectoderm, neural tube, and neural crest.
Blotchy red muscle fibers on Gomori trichrome stain are characteristic of what condition?
Mitochondrial myopathies- "Red ragged fiber diseases"
Name the three most common mitochondrial myopathies.
Myoclonic epilepsy with red ragged fibers (MERRF), Leber optic neuropathy (blindness), mitochondrial encephalopathy with stroke like episodes and lactic acidosis (MELAS).
From what embryologic layers are neurofibromas derived?
Tumors of schwann cells derived from the neural crest.
Describe the two most important mechanisms of the development of diabetic neuropathy.
1. Non-enzymatic glycosylation of proteins leads to increased thickness, hyalinization, and narrowing of the arterial walls. These changes cause diabetic mucroangiopathy of endoneural arterioles; ischemic damage follows.
2. Intracellular hyperglycemia occurs in peripheral nerves- accumulating glucose is converted into sorbitol and fructose by aldose reductase. Sorbitol increases cell osmolarity and facilitates water influx into the cell. This causes osmotic damage to axons and schwann cells.
Name five effects of volatile anesthetics.
Increased cerebral blood flow, myocardial depression, hypotension, respiratory depression, decreased renal function.
What is the most common cause of acute and painless monocular vision loss?
Central retinal artery occlusion (CRAO).
What fundoscopic findings are characteristic of central retinal artery occlusion?
Pale retina with cherry red macula.
Describe the blood supply to the macula and to the retine.
Macula is supplied by the choroid artery; the remainder of the retina is supplied by the central retinal artery.
From where is the central retinal artery derived?
The opthalmic artery which is a branch of the internal carotid.
What symptoms are associated with diabetic retinopathy?
Blurry vision, poor night vision, floaters, decreased peripheral vision. Fundoscopy reveals aneurysms, cotton wool exudates, dot and blot retinal hemorrhages and new retinal vessel formation.
What target organs are innervated by alpha-1 receptors?
Peripheral vasculature, bladder, eye.
What target organs are innervated by beta-2 receptors?
Peripheral vasculature (skeletal muscle), bronchi, uterus.
Alpha 1 stimulation of the eye causes contraction of what muscle?
The ocular pupillary dilator muscle.
What should not be taken if a patient is prescribed levodopa?
B6 (or most over the counter vitamins that have B6) B6 increases peripheral metabolism of levodopa and less drug enters the CNS.
What is a common physiologic change associated with Cimetidine?
What is 'reaction formation'?
A behaviour pattern in which a person does the opposite of what he/she feels or desires. Ex- when a person uses excessive behaviour to cover up how he/she really feels because that feeling may be perceived as unacceptable.
What is 'projection'?
Transplantation of ones unacceptable impulses or behaviours onto another person or situation.
What is the difference between 'repression' and 'suppression'?
Suppression is voluntary withholding of unpleasant thoughts, repression is relatively unconscious.
What is 'displacement'?
The transfer of an impulse or desire toward a safer and less distressful object.
Lateral horns of the spinal cord are present in what spinal segments?
T1-L2 (sympathetic preganglionic neurons).
What regions does the dorsal column system contain?
Gracile fasciculus, cuneate fasciculus.
What symptoms result from demyelination of the axons within the dorsal columns of the spinal cord?
Lancinating pains, paresthesias, loss of vibratory and position sensation. Sensory ataxia also prevails in the dark.
Brain atrophy in advanced alzheimer's disease is associated with what regions?
Temporoparietal lobes and hippocampus. The greatest degeneration occurs in the hippocampus and hippocampal atrophy on MRI is highly suggestive of AD.
What four histologic changes are characteristic of active (acute) MS plaques?
Demyelination with relative preservation of axons, accumulation of lipid-laden macrophages (containing products of myelin breakdown), astrocytosis (injury proliferation response), infiltration by lymphocytes and mononuclear cells.
What are the early and late manifestations of oculomotor nerve compression by an aneurysm?
Early: dilated pupil and loss of acomodation; Late: ptosis and opthalmoplegia.
What are the clinical symptoms of diabetic opthalmoplegia?
Down and out position with normal sized reactive pupil and ptosis.
What ocular motor never is most commonly involved in diabetic opthalmoplegia?
CN III- mononeuropathy will present with acute onset diplopia. It is caused predominately by central ischemia.
Describe the pathway of aqueous humor production and transport in the eye.
It is produced by epithelial cells of the ciliary body and excreted into the posterior eye chamber and transferred through the pupil into the anterior eye chamber. The anterior chamber angle contains a trabecular meshwork through which the aqueous humor diffuses into Schlemm's canal (scleral venous sinus). Schlemm's canal drains into the episcleral and conjunctival veins.
What is glaucoma and how does it develop?
Chronic eye disease characterized by increased IOP. It develops due to diminished outflow or increased secretion of aqueous humor.
When does narrow angle glaucoma occur?
When the anterior chamber narrows obstructing the trabecular meshwork. It is often precipitated by anticholinergic medications and manifests with an acute attack of headache and eye pain.
What types of drugs are used to treat glaucoma?
Drugs to decrease production of aqueous humor or to increase its outflow- non selective beta blockers like Timolol work by diminishing secretion of aqueous humor by the ciliary epithelium. Acetazolamide is a carbonic anhydrase inhibitor that decreases aqueous humor secretion by the ciliary epithelium; PG F2a and cholinomimetics (pilocarpine, carbachol) decrease IOP by increasing outflow.
When is clozapine used to treat schitzophrenia?
In treatment resistant patients for both positive psychotic symptoms (delusions and hallucinations) and negative symptoms of social withdrawal, anhedonia, blunted affect, and poor initiative.
What is the mechanism of action of clozapine and how does it differ from other traditional antipsychotics?
Clozapine acts on D4 receptors; traditional drugs act on D2 receptors.
What side effects are avoided with Clozapine?
Dopaminergic side effects- pseudoparkinsonism, tardive dyskinesia, hyperprolactinemia.
What is the greatest side effect associated with clozapine?
Life threatening agranulocytosis. WBC monitoring during treatment is required. Another important side effect is seizures.
Where is Wernicke's area?
Posterior portion of the superior temporal gyrus in the dominant temporal lobe. It is supplied by the MCA (as is the superior division of Broca's area)
Name four conditions that carpal tunnel syndrome is associated with.
Hypothyroidism, DM, RA, dialysis associated amyloidosis.
What cranial nerve is associated with the first branchial arch?
What bones are associated with the first branchial arch?
Maxilla, zygoma, mandible, vomer, palatine, incus, and malleus.
Muscles of mastication, the anterior belly of the digastric, the mylohyoid, the tensor tympani, and the tensor veli palatini are derived from what tissue?
What atypical antipsychotic is most likely to cause extrapyramidal symptoms and which is least likely?
Most likely- Risperidone; least likely- Clozapine.
When does acute dystonia manifest after treatment with antipsychotics?
Between four hours and four days after receiving medication
What is treatment for acute dystonia?
Antihistamines or anticholinergics.
What is akathisia and when can it occur after treatment with antipsychotics?
Subjective feeling of restlessness that compels patients to move around; it can occur at any time during treatment.
What symptoms are associated with neuroleptic malignant syndrome?
Delirium, fever, muscle rigidity, autonomic instability.
What is the typical viral pattern of CSF composition?
Lymphocytic pleocytosis, normal glucose, elevated protein. A few RBCs may also be present due to hemorrhagic destruction of the temporal lobes.
What condition most commonly causes retinitis in HIV positive patients with a CD4+ count less than 50?
CMV retinitis- caused by hematogenous spread of CMV to the eye.
What is the most common complication of CMV retinitis?
What is used to treat CMV retinitis?
Name three locations of possible brain herniation due to compression.
Falx cerebri, tentorium cerebelli, foramen magnum
What is transtentorial (uncal) herniation?
Medial temporal lobe (uncus) herniates through the gap between the crus cerebri and tentorium
What is subfalcine herniation?
Cingulate gyrus herniation under the falx cerebri. It may potentially compress the anterior cerebral artery.
What is tonsillar herniation?
Cerebellar tonsils displace through foramen magnum and compress medulla.
Transtentorial herniation may cause compression of which of the following structures?
Ipsilateral CN III, ipsilateral PCA, compression of contralateral cerebral peduncle against tentorium
What symptoms are caused by damage to CN III?
A fixed and dilated pupil followed by paralysis of the occulomotor muscles which leads to ptosis and a down and out position of the ipsilateral eye
What visual symptoms are associated with compression to the posterior cerebral artery?
Contralateral homonymous hemianopsia with macular sparing.
Compression of the cerebral peduncle against the tentorium causes what symptoms?
What is typically the first sign of uncal herniation?
A fixed and dilated pupil on the side of the lesion. Ipsilateral paralysis of oculomotor muscles, contralateral or ipsilateral hemiparesis, and contralateral homonymous hemianopsia with macular sparing may also occur.
What is cataplexy?
Brief loss of muscle tone precipitated by strong emotion.
What CSF levels are low in patients with narcolepsy?
What effects does narcolepsy have on latency to REM sleep?
Shorter latency to REM sleep
What type of drug is primidone?
An antiepileptic that is metabolized to phenobarbital and phenylethylmalonamide (PEMA). It has anti-seizure effects also.
What drug characteristically causes elevated phenobarbital levels?
Primidone- it is metabolized to phenobarbital
What are the somatic motor functions of CN IX?
Innervation of stylopharyngeus muscle.
What are the parasympathetic functions of CN IX?
Innervation of the inferior salivatory nucleus
What nerve innervates parotid gland secretion?
What are the general sensory functions of CN IX?
Inner surface of tympanic membrane, eustacian tube, posterior 1/3 of tongue, tonsillar region, upper pharynx (affects portion of the gag reflex), carotid body, carotid sinus.
What clinical features result from a lesion to the glossopharyngeal nerve?
Loss of gag reflex, loss of sensation to upper pharynx, posterior tongue, tonsils, and middle ear cavity; loss of taste sensation on posterior 1/3 of tongue.
What nerve innervates taste sensation for the anterior two thirds of the tongue?
Chorda tympani branch of the facial nerve (CN VII).
A calcified cystic mass seen on MRI is likely what type of tumor?
What structure shares a common origin with a craniopharyngioma?
Describe the appearance of craniopharyngiomas on light microscopy.
Cysts lined by stratified squamous epithelium. Keratin pearls may be seen. They are usually filled with a yellow, viscous fluid rich in cholesterol crystals.
From where are craniopharyngiomas derived?
Remnants of Rathke's pouch.
What is Rathke's pouch?
Envagination of the ectoderm that lines the fetal oral cavity..
From where are the anterior and posterior lobes of the pituitary derived?
Posterior- neuroectoderm; anterior- rathkes pouch.
What symptoms are caused by craniopharyngiomas?
Headaches, growth failure, bitemporal hemianopia.
Name the three symptoms, one of which is required for diganosis of schitzophrenia.
1. disorganized speech; 2. delusions; 3. hallucinations. Patients must have at least one of the above.
During the first week after an acute stroke, what is shown on CT imaging?
Hypodense ischemic area that is poorly deliniated from surrounding tissue. Edema and loss of the grey-white matter junction are also seen.
When do microglia begin to phagocytose dead tissue after ischemic cerebral infarct? When do astrocytes appear?
3-5 days after onset of ischemia. Astrocytes then form a glial scar around periphery of necrosed area of macrophage infiltration.
What deposits are located in the cytoplasm of microglia that enter ischemic tissue following infarct?
Lipids due to extensive myelin breakdown.
What is the difference between a simple and complex seizure?
Simple seizures have no associated impairment of consciousness; complex seizures are characterized by loss of memory during the event and a postictal state.
What drug effectively treats both simple and complex seizures?
What are the uses for carbamazepine?
Management of tonic-clonic seizures, mood stabilizer in bipolar disorder, treatment of trigeminal neuralgia, treatment of simple and complex seizures.
What is the mechanism of action of carbamazepine?
Blocks voltage gated sodium channels in cortical neurons. It stabilizes these channels in an inactivated state which cause fewer Na channels to propagate an AP.
What are the three most important adverse affects associated with use of Carbamazepine?
Bone marrow suppression (anemia, agranulocytosis, thrombocytopenia, low Hb, leukopenia, thrombocytopenia); hepatotoxicity (must monitor LFTs), SIADH.
Where does the spinal cord terminate at the conus medullaris?
At approximately the L2 vertebral level.
A lesion at what level causes conus medullaris syndrome?
Lesion at L2.
What are the symptoms of conus medullaris syndrome?
Flaccid paralysis of the bladder and rectum, impotence, and saddle (S3-S5 roots) anesthesia.
What is cauda equina syndrome?
Typically results from massive rupture of an intervertebral disk that is capable of causing compression of more than 2 of the cauda equina spinal nerve roots.
What symptoms are associated with cauda equina syndrome?
Low back pain radiating to one or both legs, saddle anesthesia, loss of anocutaneous reflex, bowel and blaffer dysfunction, loss of ankle jerk reflex with plantar flexion weakness of the feet.
Lesions to what spinal nerve roots will cause cauda equina syndrome?
Lesions involving S2 through S4.
What is the immediate precursor of dopamine?
Why is levodopa instead of dopamine given to patients with Parkinsons?
Levodopa can cross the BBB, dopamine can not.
Why is levodopa administered with carbidopa?
To increase amount of levodopa that enters the brain
What type of drug is entacapone?
A COMT inhibitor that primarily serves to increase bioavailability of levodopa by inhibiting peripheral methylation. COMT inhibitors must be administered in combination with levodopa as they are otherwise ineffective.
What causes Charcot Bouchard pseudoaneurysms?
Increased blood pressure induces hyaline arteriolosclerosis of tiny arterioles (usually in the basal ganglia). This causes weakening of the vascular walls and dilatation which may cause them to rupture. They can produce a small amount of bleeding or may cause a large hematoma.
What types of deficits are seen with charcot bouchard pseudoaneurysms?
What consequences are associated with deficiency in thiamine?
Thiamine is a key enzyme for pyruvate dehydrogenase in glucose metabolism. Deficiency thus results in inability to metabolize glucose into energy.
What is the Papez circuit?
A neural pathway of the limbic system that is involved in cortical control of emotion and memory.
How is phenytoin metabolized?
Dose dependent hydroxylation in hepatocytes. It is an inducer of P450 oxidase.
What complications are associated with SAH?
Arterial vasospasm which may cause cerebral ischemia and can present with new onset symptoms 4-12 days after the initial insult. Rebleeding and hydrocephalus are also possible.
What is the genetic mutation and mode of inheritance of Friedreich ataxia?
Autosomal recessive; caused by a mutation on chromosome 9 which codes for frataxin which is essential for normal mitochondrial function. Mutation causes increased numbers of trinucleotide repeats which causes diminished levels of frataxin in these patients.
What neural tracts and peripheral nerves are commonly degenerated in friedreich ataxia?
Ascending and descending spinocerebellar tracts, dorsal columns and dorsal root ganglia
What symptom results from degeneration of the ascending and descending spinocerebellar tracts?
What symptoms result from degeneration of the dorsal columns and dorsal root ganglia?
Loss of position and vibration sense.
Name five symptoms associated with Friedreich ataxia.
Gait ataxia, loss of position and vibration sensation, kyphoscoliosis and foot abnormalities, hypertrophic cardiomyopathy and CHF, DM.
What neurotransmitter is deficient in Huntington disease?
Where does atrophy occur in patients with Huntington disease?
Caudate nucleus and putamen bilaterally (striatum).
What is heteroplasmy?
Random distribution of normal and mutated maternal mitochondria causes variable expression and severity of disease.
Name three conditions associated with heteroplasmy.
Leber hereditary optic neuropathy; myoclonic epilepsy with ragged red fibers; mitochondrial encephalomyopathy with lactic acidosis and stroke like episodes.
What neuropeptides produced in the lateral hypothalamus function to promote wakefullness and to inhibit REM sleep related phenomena?
Hypocretin-1 (orexin A) and hypocretin-2 (orexin B). (orexin A is usually undetectable in CSF of patients with narcolepsy.)
What are the two classes of dopamine agonists?
Ergot compounds (bromocriptine, pergolide); nonergot compounds (pramipexole and ropinirole).
What receptors are stimulated by dopamine agonists?
What type of drug is pramipexole?
A dopamine agonist that stimulates dopamine receptors.
What conditions is bromocriptine used to treat?
Parkinsons and hyperprolactinemia.
What progressive neurological disorder is associated with cystic degeneration of the putamen?
What anti-seizure drug is preferred in patients with both absence and tonic clonic seizures?
Which three anticonvulsants are also used as mood stabilizing agents in bipolar disorder?
Valproate, carbamazepine, lamotrigine.
Rupture of a berry aneurysm causes what type of hemorrhage?
SAH (sudden onset)
Arnold Chiari malformations are caused by what impaired development?
Impaired development of the posterior fossa.
What are the three indications for benzodiazepine use?
Hypnotics to treat insomnia, anxiolytics for panic attacks/ anxiety, anticonvulsants.
Name the four long acting benzodiazepines.
Chlordiazepoxide, Clorazepate, Diazepam, Flurazepam,
Name the three short acting benzodiazepines.
Alprazolam, triazolam, oxazepam
What is transference?
The unconscious shifting of emotions or desires associated with one person to another.
How does syringomyelia present?
With disproportionate loss of pain and temperature sensation involving the arms and hands. It is caused by the formation of a syrinx (cavity) in the cervical region of the spinal cord. IF the syrinx extends to destroy the motor neurons in the ventral horns, flaccid paralysis and atrophy of the intrinsic muscles of the hand occur.
What areas are most commonly damaged by syringomyelia?
Ventral white commissure and ventral horns..
What symptoms arise from destruction of the ventral white commissure?
Loss of pain and temperature sensation bilaterally over all affected dermatomes.
How does brain tissue react to ischemic cerebral infarction or vascular occlusion soon after and weeks after injury?
Soon after- soft and edematous; in a few weeks the lesion turns into a cystic space surrounded by scar tissue. The size of the necrotic area depends on the diameter of the occluded blood vessel.
Name four specific syndromes caused by lacunar infarction and their symptoms.
1. Pure motor hemiparesis- injury to posterior limb of the internal capsule; 2. Pure sensory stroke - ventroposterolateral or ventroposteromedial thalamus; 3. Ataxia-hemiplegia syndrome- base of the pons; 4. Dysarthria-clumsy hand syndrome- base of the pons or the genu of the internal capsule.
What is the most likely cause of lacunar infarcts?
Hypertensive arteriolosclerosis of small, penetrating arterioles.
What is the difference between a lacunar infarct and a Charcot-Bouchard aneurysm?
Charcot Bouchard aneurysms are less than 1 mm in diameter. Lacunar infarcts are small ischemic infarcts less than 15 mm in diameter.
What areas of the brain are most susceptible to lacunar infarcts?
Basal ganglia, pons, internal capsule, deep white matter of the brain.
What is hydrocephalus ex vacuo?
Ventricular enlargement that occurs due to brain atrophy and is not accompanied by an increase in CSF pressure.
What symptoms may be caused by lesions in the temporal lobe?
Disruption to Meyer's loop, causing a contralateral superior quadrantanopia, aphasia, memory deficits, seizures, hallucinations.
Injury to what area causes contralateral superior quadrantanopia?
Meyers loop in the temporal lobe.
What liver toxicity is associated with halothane?
Massive hepatic necrosis- widespread centrilobular hepatic necrosis.
What causes halothane induced liver damage?
Halothane metabolites and formation of autoantibodies against liver proteins.
What is the effect on the blood gas coefficient in poorly soluble gasses?
Low blood/ gas partition coefficient.
How does highly soluble gas diffuse into the bloodstream?
Slowly leading to delayed rise in partial pressure.
Does nitrous oxide have a high or low blood/gas partition coefficient?
Low- partial pressure rises rapidly indicating that the blood quickly becomes saturated.
The amount of gas needed to saturate the blood is large or small in poorly soluble gasses and in highly soluble gasses?
In poorly soluble gasses- small amount needed; highly soluble- large amount needed
Name a highly soluble gas.
Describe the rise in blood partial pressure of a poorly soluble gas vs a highly soluble gas.
Rapid rise in poorly soluble; slow rise in highly soluble.
Describe the equilibration with the brain of poorly soluble gasses and highly soluble gasses.
Poorly soluble- rapid equilibriation; highly soluble- slow equilibriation.
Describe the onset of action of poorly soluble gasses vs highly soluble gasses.
Poorly soluble- rapid onset; highly soluble- slow onset.
What effect does increased acetylcholine concentration due to organophosphate poisoning have on nicotinic synapses of the NMJ?
Muscle fasciculations followed by paralysis. Atropine does not have an effect on the nicotinic receptors.
Which drug reverses both muscarinic and nicotinic effects of organophosphates by restoring cholinesterase?
Ampicillin should be added to Ceftriaxone in empiric treatment of infants (and immunocompromised adults) for meningitis to cover what organism?
What drug is most commonly associated with neuroleptic malignant syndrome?
Name the four primary presenting features of neuroleptic malignant syndrome.
Hyperthermia, extreme generalized rigidity, autonomic instability, altered mental status.
What clinically distinguishes neuroleptic malignant syndrome from serotonin syndrome?
Absence of myoclonus and presence of rigidity in NMS.
What two drug classes are often used to attenuate symptoms/ decrease mortality in neuroleptic malignant syndrome?
Dopamine agonists (bromocriptine), muscle relaxants (dantrolene).
What are pyramidal signs?
Signs of upper motor neuron lesions.
What is the pathophysiology associated with Meniere's disease?
Disorder of the inner ear characterized by an increased volume of endolymph due to defective resorption.
What triad of symptoms characterizes Meniere's disease?
Tinnitus, vertigo, sensorineural hearing loss.
Name the three important dopaminergic systems.
Mesolimbic-mesocortical pathway, nigrostriatal pathway, tuberoinfundibular pathway.
What is the function of the mesolimbic-mesocortical pathway and what disease is associated with its dysfunction?
Function is to regulate behaviour; dysfunction in schitzophrenia.
What is the function of the nigrostriatal pathway and what disease is associated with its dysfunction?
Coordination of voluntary movements; dysfunction in parkinsonism.
What is the function of the tuberoinfundibular pathway and what disease is associated with its dysfunction?
Controls prolactin secretion; dysfunction causes hyperprolactinemia.
Where in the cell cycle does Rb inhibit the pathway?
It prevents cells from proceeding from the G1 to S stage of the cell cycle.
What are the motor functions of the superior oblique nerve of the eye and what findings are associated with a lesion?
Function is internal rotation, depression, abduction. Lesion causes upward deviation and vertical/ torsional diplopia.
What findings are associated with a lesion to CN VI?
Eye deviated medially with horizontal diplopia.
What findings are associated with a lesion to CN III?
Eye deviated downwards and laterally, diagonal diplopia, dilation of pupil and loss of accommodation, ptosis.
How do Schwannomas present histologically?
Biphasic pattern of cellularity (Antoni A and B areas) and are S-100 positive.
Name two tumor types that are S-100 positive and the embryonal origin of their cells.
Melanoma, scwannoma; both are derived from neural crest.
Where are meningiomas typically located?
Adjacent to the falx cerebri and compressing the medial surface of the hemisphere. This causes compression of the parasagittal cortex and contralateral spastic paralysis of the leg. Focal seizures may also occur.
Which areas of the brain are most vulnerable to global cerebral ischemia?
Pyramidal cells of the hippocampus and neocortex and the Purkinje cells of the cerebellum.
What is the first area damaged during global cerebral ischemia?
What nerve is responsible for the afferent limb of the pupillary reflex and what nerve is responsible for the efferent limb?
Afferent- CN II; efferent- CN III.
Paralysis of what muscle causes ptosis?
What types of nerve fibers innervate the iris sphincter and ciliary muscles?
Parasympathetic fibers of CN III. Paralysis causes a fixed, dilated pupil and loss of accommodation.
PCP abuse induces what type of behaviour?
What is the most common cause of death in PCP intoxication?
Violence and subsequent trauma.
What symptoms are associated with PCP intoxication?
Violent behaviour, loss of coordination, nystagmus, acute brain syndrome (disorientation, poor judgement, memory loss).
How are the adrenal glands innervated sympathetically?
Directly by preganglionic sympathetic neurons that use Ach as a neurotransmitter.
Paralysis of upward gaze (Parinaud syndrome or dorsal midbrain syndrome) is consistent with what finding?
Tumor of the pineal region.
What is the most common tumor of the pineal gland?
What triad of symptoms are associated with pineal germinomas?
Precocious puberty in males (caused by b-hCG production); aqueductal compression by the tumor may lead to obstructive hydrocephalus, parinaud syndrome- paralysis of upward gaze and of convergence.
What pharmaceutical intervention may be used to treat restless leg syndrome?
Dopamine agonists (ex. ropinirole, pramipexole)
What is holoprosencephaly?
Incomplete division of the forebrain into two hemispheres.
What conditions are associated with holoprosencephaly?
Trisomy 13 and trisomy 18. It may also occur as a consequence of fetal alcohol syndrome.
What causes holoprosencephaly?
Failure of forebrain cleavage into cerebral hemispheres.
Anticholinergic medications are contraindicated in what condition?
What affect does atropine have on bradycardia?
It increases HR by decreasing vagal influence on SA and AV nodes.
What is a common side effect of atropine?
Increased IOP and acute closed angle glaucoma.
Phenytoin causes what oral abnormality?
Gingival hyperplasia. Phenytoin may also cause ataxia and nystagmus.
What causes gingival hyperplasia?
Increased expression of PDGF.
What is delusional disorder?
Characterized by one or more delusions in the absence of other psychotic symptoms. Behaviour is not obviously bizarre and functioning is not significantly impaired apart from the direct impact of delusions. Usually delusions have a specific theme.
Stimulation of kappa opioid receptors have what effects?
Miosis, dysphoria, sedation.
Stimulation of delta opioid receptors have what effects?
ALS causes loss of neurons in what areas of the spinal cord?
Loss of neurons in the anterior horns (LMN lesion) causes weakness and atrophy; demyelination of the lateral corticospinal tract (UMN lesion) leads to spasticity and hyperreflexia.
What is the difference between ALS and Poliomyelitis in terms of motor damage?
Polio is a LMN disease only; ALS is UMN and LMN
Describe the sensory innervation of the tongue.
Anterior 2/3- mandibular branch of CN V; Posterior 1/3- glossopharyngeal; posterior area of the tongue root- CN X.
Describe the gustatory innervation of the tongue.
Anterior 2/3- chorda tympani branch of CN VII; posterior 1/3- CN IX; posterior area of the tongue root and taste buds of the larynx and upper esophagus- CN X.
What structure delineates the anterior 2/3 of the tongue from the posterior 1/3?
The terminal sulcus.
Where is the foramen cecum located?
Along the terminal sulcus at the midline.
What are transpeptidases?
A form of penicillin binding protein that functions to cross-link peptidoglycan in the bacterial cell wall.
How does ceftriaxone lead to cell wall instability and bacteriolysis?
By inhibiting transpeptidases
Name a mechanism of bacterial resistance to cephalosporins.
Change in the structure of Penicillin binding proteins prevents cephalosporin binding.
Describe the symptoms of paraneoplastic cerebellar degeneration.
Progressively worsening dizziness, limb and truncal ataxia, dysarthria, visual disturbances.
What process causes paraneoplastic cerebellar degeneration?
Immune response against tumor cells that cross react with Purkinje neuron antigens leading to acute onset rapid degeneration of the cerebellum.
Paraneoplastic cerebellar degeneration is associated with which cancers?
Breast, ovarian, uterine, and small cell lung cancer.
Define classical conditioning.
It involves a neutral stimulus that is repeatedly paired with a non neutral stimulus that elicits a reflexive, unconditioned response.
Describe the histological appearance of pilocytic astrocytomas.
Well differentiated neoplasms of the cerebellum, brainstem, hypothalamic region or optic pathways in children. They are comprised of spindle cells with hair-like glial processes that are associated with microcysts. These cells are mixed with Rosenthal fibers and granular eosinophilic bodies.
Non specific muscarinic agonist action on peripheral blood vessels would have what effect?
Cholinomimetic agents would bind to endothelial muscarinic receptors promoting release of NO (also called EDRF).
What is another name for NO?
Endothelium derived relaxation factor.
What symptoms are associated with drug induced parkinsonism?
Prominent rigidity and bradykinesia, tremor, masked facies. Caused by D2 receptor blockade in the nigrostriatal pathway.
What drugs are used to treat drug induced parkinsonism?
Anticholinergics (trihexyphenidyl, benzotropine), Amantadine.
What drug class most commonly causes drug induced parkinsonism?
First generation antipsychotics.
Describe treatment for status epilepticus.
1. Benzodiazepines; 2. Phenytoin. If this does not stop seizures, phenobarbital is indicated. Inhaled anesthetics may cause a state of general anesthesia.
What is the mechanism of action of Phenytoin?
It inhibits neuronal high frequency firing by reducing the ability of sodium channels to recover from inactivation. At high frequency firing rates, it renders neurons refractory.
What is the genetic mechanism underlying Fragile X syndrome?
Increase in the number of trinucleotide repeats with the FMR1 gene on the X chromosome.
What characterizes the gross brain changes in Creutzfelt-Jakob disease?
Spongiform encepalopathy with vacuoles that form in the cytoplasm of the neutrophils and neurons. As the disease progresses, the vacuolated areas transform into cysts. No inflammatory change is present.
What characterizes the gross brain changes in Progressive Multifocal leukoencephalopathy?
Patches of demyelination due to preferential infection of oligodendrocytes.
What is subacute sclerosing panencephalitis?
Linked to an abnormal measles virus that persists in the CNS of patients years after recovery from infection. It causes progressive dementia, spasticity, seizures. Microscopic examination shows myelin degeneration and viral inclusions.
What is projection?
Attributing one's own feelings to others.
What is displacement?
Transferring feelings to a more acceptable object.
Where are intracranial schwannomas most commonly located?
At the cerebellopontine angle (between the cerebellum and lateral pons).
Other than CN VIII, which other CNs may be affected due to proximity in an acoustic neuroma (schwannoma)?
CN V, CN VII
Damage to what CN causes loss of corneal reflex?
Damage to CN V.
Describe the temporal pattern of cluster headaches.
Rapid onset, severe nonpulsatile pain that generally last from 30 mins to 2 hours and occur around the same time of day for consecutive days or weeks. Patients often have a pain free interval of about a year between attacks.
Diagnosis of syringomyelia is consistent with what symptoms?
Chronic loss of upper extremity pain and temperature sensation, upper extremity weakness and hyperreflexia, lower extremity weakness and hyperreflexia, kyphoscoliosis.
What areas of the spinal cord are damaged by syringomyelia?
Damage to the ventral white commissure and anterior horns.
Administration of what drugs causes malignant hyperthermia in susceptible individuals?
Succinylcholine and/or inhalation anesthetics.
All benzodiazepines should be excluded from use in conjunction with what other drugs?
Alcohol, barbiturates, neuroleptics, or first generation antihistamines.
What type of drug is chlorpheniramie and what is its mechanism of action?
1st generation antihistamine that blocks both central and peripheral H1 receptors.
What is the most common location of a medulloblastoma and what are the most common presenting symptoms?
Cerebellar vermis; cerebellar dysfunction, increased ICP are most common signs.
What can be detected in the CSF of a patient with MS?
Oligoclonal bands of IgG.
Describe the mechanism of action of methadone.
Mu receptor agonist. Potent, long acting opiate with good PO bioavailabilty. Its long halflife allows for continuous suppression of withdrawal symptoms in heroin dependent patients.
Psammoma bodies are characteristic of what type of brain neoplasm?
Name three types of tumors that form psammoma bodies.
Papillary thyroid carcinoma, serous papillary ovarian adenocarcinoma, meningioma.
From what types of cells do meningiomas arise?
Arachnoid villi cells.
What are the most common presenting symptoms in meningioma?
Personality changes due to compression of the frontal lobe, presence of new onset seizures in an adult. They are benign.
Describe the cellular changes associated with Wallerian degeneration.
Swelling and irregularity are seen in the distal segment of the axon. Within a week the axon is destroyed and its fragments are digested by Schwann cells and macrophages. Similar degenerative changes occur in the segment proximal; degeneration of the proximal segment continues to the nearest node of Ranvier.
What is an axonal reaction?
Change in neuronal bodies after an axon is severed. Cell body shows signs of cellular edema, becomes swollen and rounded with nucleus displaced to the periphery, Nissl substance becomes fine, granular, and dispersed throughout the cytoplasm. This occurs 24-48 hrs after injury. These changes reflect increased protein to facilitate axon repair.
What neurotransmitters are decreased in the caudate nucleus and putamen of patients with Huntington's?
Decrease in GABA, ACh, and Substance P.
Recurrent lobar hemorrhages in an elderly patient most likely result from what condition?
Cerebral amyloid angiopathy.
What is the pathology of cerebral amyloid angiopathy?
B amyloid deposition into the arterial wall resulting in weakening of the wall. The most common presentation is recurrent hemorrhagic stroke.
Compare the ares of the brain affected in hypertensive hemorrhagic strokes vs cerebral amyloid angiopathy strokes.
Basal ganglia- hypertensive; small areas of the cerebral hemisphere- amyloid angiopathy.
In trigeminal neuralgia, what triggers episodes?
Any stimulus to CN V- chewing, teeth brushing, shaving, washing the face, swallowing, exposure to hot or cold temperatures.
What is the drug of choice for treatment of trigeminal neuralgia?
What is the mechanism of action of Carbamazepine?
Inhibits neuronal high frequency firing by reducing the ability of sodium channels to recover from inactivation.
A CN III palsy can be caused by compression of what artery?
What types of drugs cause acute urinary retention?
Anticholinergics and TCAs
Name four drugs that belong to the TCA class.
Imipramine, doxepin, amitriptyline, clomipramine.
Name four first generation antihistamines.
Hydroxyzine, promethazine, chlorpheniramine, diphenhydramine, promethazine.
To what drug class does fexofenadine belong?
Second generation antihistamine.
B12 deficiency involves degeneration of what spinal tracts?
Posterior columns and lateral cortical spinal tracts. Also causes axonal degeneration of peripheral nerves.
Damage to what areas of the spinal cord is characteristic of tabes dorsalis?
Dorsal columns and dorsal roots.
Damage to what spinal tracts is seen in ALS?
Lateral corticospinal tracts, anterior horns.
Damage to the lateral corticospinal tracts causes what symptoms?
Spasticity and hyperreflexia.
Damage to the anterior horns of the spinal cord causes what symptoms?
Flaccid paralysis, atrophy, fasciculations
Patients with anterior spinal artery syndrome have what symptoms?
Loss of strength below the level of injury with loss of pain and temperature sensation; Preserved vibratory senses.
What is hyperacusis and what causes it?
Increased sensitivity to everyday sounds. It is caused by injury to the stapedius nerve (which innervates the stapes) and is a branch of CN VII.
What is the function of the tensor tympani muscle and what innervates it?
Functions to dampen sound transmission; it is innervated by the mandibular branch of CN V.
What amino acid is the precursor to serotonin?
What is the treatment for serotonin syndrome?
Supportive care, airway maintenance, hydration, temperature maintenance. Severe cases will involve treatment with a serotonin antagonist such as cyproheptadine.
What type of drug is cyproheptadine?
A serotonin antagoinst; it is a first generation histamine antagonist with non specific serotonin antagonistic properties.
What side effect of trazodone makes it contraindicated in adolescent boys?
'Splitting' is a hallmark of what disorder?
Borderline personality disorder.
What is 'splitting'?
The unconscious belief that all people are either wholly good or wholly bad.
What causes the pain associated with migraine?
Activation of trigeminal afferents that innervate the meninges, causing release of vasoactive neuropeptides which result in neurogenic inflammation and vasodilation due to plasma protein extravasation. Neuronal sensitization also occurs.
What is the mechanism of action of triptans?
Serotonin 5HTab/5HT1D agonists used for abortive therapy of migraines. They initiate postsynaptic serotonin receptor stimulation.
Name three types of drugs prescribed for migraine prophylaxis.
Beta blockers, antidepressants, anticonvulsants.
Compare and contrast Lambert-Eaton myasthenic syndrome to Myasthenia Gravis
L.E: Weakness improves with exercise/ stimulation; weakness of proximal muscles; antibodies are directed against PRE SYNAPTIC CALCIUM CHANNELS. It is often caused by a pre-existing malignancy and there is no improvement in tensilon (edrophonium) test. MYASTHENIA GRAVIS: weakness is worse with exertion; extraocular muscles are effected first (ptosis and diplopia); associated with risk of thymoma; antibodies generated against acetylcholine receptors; improvement with tensilon test.
Which drug binds to the same GABA receptor site as benzodiazepines?
What types of receptors are GABAa, b, and c respectively.
A and C are ion channels; B is linked to a G protein.
To what GABA subunit do benzodiazepines, barbiturates, and alcohol bind?
To different components of the GABAa receptor to facilitate the inhibitory action of GABA in the CNS.
Where are serotonergic neurons found?
They are only found in the raphe nuclei of the brainstem.
Where are the raphe nuclei located?
Midbrain, pons, medulla. Axons from these nuclei project widely however.
What is the function of serotoninergic neurons?
Play a role in the sleep wake cycle and in level of arousal
Lesions to the raphe nuclei cause what symptoms?
What is the mechanism of action of TCAs?
They inhibit reuptake of norepinephrine and serotonin
What is the most common cause of death in patients taking TCAs and what is its mechanism of action?
Arrhythmias (v-fib or cardiogenic shock) due to inhibition of fast sodium channel conduction. This causes decreased conduction and a prolonged QRS. Decreased cardiac contractility can also cause direct peripheral vasodilation and refractory hypotension.
What is the best treatment for TCA overdose?
Fluid resuscitation- normal saline and hypertonic sodium bicarbonate.
What type of drug is Pentazocine?
An opioid narcotic with partial agonist activity and weak antagoinst activity at mu receptors. It is designed to provide little to no abuse potential.
What opioid drug when used in combination with morphine or other opioids that are selective mu receptor agonists produce antagonistic effects which reduce morphine analgesia?
Pentazocine due to competitive inhibition of mu receptors. It may also generate withdrawal symptoms secondary to antagonistic effects.
Name six opioid narcotics that are selective mu receptor agonists.
Methadone, Codeine, Meperidine, Fentanyl, Levorphanol, Oxymorphone.
What is Jimson Weed poisioning?
Condition which causes strong anticholinergic effects. Effects and symptoms very similar to atropine poisoning.
What drugs are used to treat atropine poisioning?
Cholinesterase inhibitors- physostigmine.
What information travels to the VPL of the thalamus and where is information transmitted to?
Spinothalamic and medial leminiscus pathway information; transmitted to the primary somatosensory cortex (BA 1, 2, 3)
What information travels to the VPM of the thalamus and where is information transmitted to?
Trigeminal and gustatory pathways; transmitted to primary somatosensory cortex (BA 1, 2, 3)
What information is relayed through the lateral geniculate body of the thalamus and where is information transmitted to?
Visual information from the optic nerve; transmits via optic radiations to the visual cortex (calcarine sulcus)
What information is relayed through the medial geniculate body of the thalamus and where is information transmitted to?
Auditory information received from superior olivary nucleus and inferior colliculus of the pons; travels to auditory cortex of the temporal lobe (BA 41, 42)
Which antidepressants have the greatest risk of inducing mania in susceptible individuals?
TCAs and venlafaxine.
To what drug class does venlafaxine belong?
Serotonin- Norepinephrine reuptake inhibitor.
What is the most common cause of sporadic encephalitis?
HSV-1 encaphalitis targets what area of the brain?
Temporal lobe causing aphasia, olfactory hallucinations, personality changes (amygdala involvement)
Macroscopic examination of a brain with HSV-1 encaphalitis shows what?
Edema and hemorrhagic necrosis of the temporal lobes. Eosinophilic intranuclear inclusions (Cowdry type A) are present in glial cells and neurons. Multinucleated giant cells may also be found.
What is the CSF pattern in herpetic encephalitis?
Lymphocytic pleocytosis, normal glucose, elevated protein levels.
Where is the sacral micturition center and what is its function?
S2-S4 levels; responsible for bladder contraction. Parasympathetic nerves travel from ventral white matter within pelvic nerves and stimulate cholinergic receptors on the bladder wall.
What is the pontine micturition center and where exactly is it located?
Pontine reticular formation; it coordinates relaxation of external urethral sphincter with bladder contraction during voiding.
What is the role of the cerebral cortex in micturition?
It inhibits the sacral micturition center.
What pathways are disrupted in normal pressure hydrocephalus?
Expanded ventriculi place traction on cortical efferent and afferent fibers (corona radiata) which disrupts the periventricular pathways that transmit impulses from the cortex to the sacral micturition center. This causes lack of inhibition.
What areas of the brain are most distorted in normal pressure hydrocephalus?
Periventricular white matter.
What type of cells line the ependymal layer of the choroid plexus?
Simple ciliated columnar epithelium with tight junctions between cells.
What connects the lateral ventricles to the third ventricle?
The interventricular foramina of Monro.
What connects the third ventricle to the fourth ventricle?
The Cerebral aqueduct of Sylvius
Through what three foramina can CSF exit the fourth ventricle into the subarachnoid space?
2 lateral foramina of Luschka; 1 midline foramen of Magendie.
How is CSF returned to the venous circulation?
What is pseudotumor cerebri?
Presents in young overweight women with elevated ICP and is thought to be associated with venous outflow abnormalities due to elevated ICPs.
Broca's area is located in what lobe?
What is the principle difference in presentation between a patient with Pick's Disease and one with AD?
AD presents with memory loss, Pick's manifests with personality changes which progresses to a more global dementia.
What tumor is the most common extracranial chilhood cancer?
From what cells does neuroblastoma develop?
Neuroblasts of the adrenal medulla.
What is associated with opsoclonus-myoclonus syndrome?
Neuroblastoma when seen in young children. This is a paraneoplastic syndrome.
What genetic mutation is associated with neuroblastoma?
Increased copies of the N-myc gene.
What is the microscopic appearance of a neuroblastoma?
Solid sheets of small cells with dark nuclei and scant cytoplasm.
What is the clinical presentation of neuroblastoma?
Retroperitoneal mass (displaces the kidney), hypertension, anorexia/ weight loss.
What UA abnormalities are seen with neuroblastoma?
Increased excretion of catecholamines.
What makes for a better prognosis in neuroblastoma?
Younger age, best if patient is less than 1 year.
Describe the changes in ACh in patients with AD?
Decreased ACh levels in the hippocampus and nucleus basalis of Meynert.
What causes the decrease in acetylcholine levels in AD?
Deficiency of choline acetyltransferase, most notable in the basal nucleus of Meynert which participates in memory and cognition.
What are Nissl substance?
Basophillic granules in the cell bodies of neurons. It represents RER and is responsible for protein synthesis.
What histopathologic changes are associated with acute neuronal injury (red neuron)?
Shrinkage of the cell body, pyknosis of the nucleus, loss of Nissl substance, eosinophillic cytoplasm. These changes become evident about 12-24 hrs after injury. Microglia then phagocytose dead neurons and astrocytes proliferate to form a glial scar.
What histopathologic changes are associated with an axonal reaction and loss of axons?
Enlargement of the cell body with an eccentric nucleus and enlargement of the nucleolus and dispersion of the nissl substance.
What histopathologic changes are associated with neuronal atrophy as in degenerative disease?
Loss of neurons and functional groups of neurons, reactive gliosis.
Name two low potency first generation antipsychotics.
What are the side effects of low potency first generation antipsychotics?
Sedation, anticholinergic effects, orthostatic hypotension.
Name two high potency first generation antipsychotics.
What side effects are associated with high potency first generation antipsychotics?
Extrapyramidal symptoms (acute dystonia, akathisia, parkinsonism) due to potent D2 antagonism in the nigrostriatal pathway.
Hyperglycemia is associated with what antipsychotics?
Second generation (atypicals)
What cell type participates in walling off a cystic cavity after injury?
Astrocytes form the glial scar.
Deficits in grip, whistling, and swallowing would be caused by infarction of what artery?
How would occlusion of the anterior cerebral artery affect motor function? Sensory deficits?
Of the contralateral leg and foot; sensory deficits of teh contralateral legs, trunk, and genitals
How does an infarct in the MCA affect the upper body vs lower body?
Hemiparesis is more affected in upper body.
What antipsychotic may cause retinal deposits that resemble retinitis pigmentosa?
What is a prominent side effect of thioridazine?
Retinal deposits that resemeble retinits pigmentosa
What is a prominent side effect of Chlorpromazine?
What is classified as hyperpyrexia?
Body temperature greater than 40 deg C (43+ is incompatible with life)
What brain cells are most susceptible to heat damage?
Purkinje cells of the cerebellum.
In hyperpyrexia, what cooling mechanisms are employed?
Cooling blankets, application of cool saline bags, cold water enemas in addition to oral antipyretics (NSAIDS and acetaminophen).
What is reaction formation?
Responding in a manner opposite to ones feelings.
Define the alturistic defense mechanism?
Avoiding negative feelings by helping others.
Name the four mature defense mechanisms.
Alturism, humor, sublimination, suppression.
What is the major factor that determines the AV concentration gradient of a gas anesthetic in arterial and venous blood?
Solubility of the anesthetic in the peripheral tissues
Inhaled anesthetics with high peripheral tissue solubility are fast or slow onset?
What are the symptoms of sciatica?
Weakness of the posterior thigh muscles as well as weakness of all muscles below the knee. Ankle reflex is diminished but the patellar reflex is unaffected (L2-L4)
The sciatic nerve provides sensory innervation to what areas?
Posterior thigh and calf as well as plantar surface of the foot.
Transection of the sciatic nerve would result in what muscular deficiencies?
Inability to flex the leg at the knee and paralysis of the muscles below the knee.
The sciatic nerve is derived from what roots?
Sciatica most commonly involves what nerve roots?
What is the typical difference in presentation between a patient with L5 sciatics vs S1 sciatica?
L5: posterior and lateral thigh and leg pain shooting to the inner foot; S1: pain strictly in the posterior thigh and leg, shooting to the foot accompanied by weakness of plantar flexion and ankle jerk reflex.
What is the ideal three drug regimen for Parkinson's until they can no longer control symptoms?
Selegiline, anticholinergics, amantadine.
What is the mechanism of action of H1 receptor blockers?
Decrease activity of this receptor by increasing the proportion of inactive H1 receptors (reverse blockade).
Blockade of what neurotransmitters causes most of the side effects of first generation antihistaminics?
Antimuscarinic, anti-alpha adrenergic, anti-serotinergic.
What are the anticholinergic side effects associated with first generation antihistaminics?
Pupillary dilation, dry mouth, urinary retention, constipation. This can cause blurry vision.
What symptoms are characteristic of acute opioid withdrawal?
Pupillary dilatation, rhinorrhea, sneezing, nasal stuffiness, diarrhea, nausea, vomiting. Sometimes seizures may be present.
What is the treatment of choice for acute opioid withdrawal in neonates?
Opium solution (tincture of opium)
What nerve provides innervation to the muscles of mastication?
CN V3 mandibular nerve.
Which three muscles close the jaw?
Masseter, medial pterygoid, temporalis.
Which muscle opens the jaw?
From what foramina does CN V3 exit the skull?
What exits the skull through foramen ovale?
CN V3, lesser petrosal nerve, accessory meningeal artery, emissary veins.
Where does CN V2 exit the skull?
What exits the skull in foramen spinosum?
Middle meningeal artery and middle meningeal vein and meningeal branch of CN V3
What structures leave the skull through the jugular foramen?
CN IX, X, XI, inferior petrosal and sigmoid sinuses, posterior meningeal artery.
What drug is first line treatment for myoclonic seizures?
For both simple and complex partial seizures, what drug is first line?
Which three drugs are indicated for tonic-clonic seizure?
Phenytoin, carbamazepine, valproate.
What is first line treatment for absence seizures?
1st line: ethosuxamide, second line- valproate.
What type of receptors are nicotinic cholinergic receptors?
Ligand gated ion channel receptors.
Generation of the end plate potential involves movement of which ions?
Influx: sodium and calcium; Outflux: potassium
Describe an unpredictable and dose-independent characteristic of advanced Parkinsons disease?
The on-off phenomenon.
What is the typical presentation of botulism?
Descending paralysis that first manifests with CN abnormalities (diplopia, dysphagia, difficulty speaking) and antimuscarinic sx.
What is the difference in mechanism of action of anticholinergic poisoning between muscarinic antagonists and botulinum neurotoxin?
Muscaranic antagonists inhibit the post-synaptic action of ACh; botulinum blocks the presynaptic exocytosis of ACh vessicles. (Organophosphates prevent degradation of ACh in the synaptic cleft)
What is conversion disorder?
The unconscious manifestation of neurologic symptoms (symptoms/ deficits of voluntary motor and/or sensory function) when pathophysiological explanations for the symptoms cannot be found. The symptoms cannot be limited to pain or sexual dysfunction and symptoms cannot be produced intentionally
What is somatization disorder?
Refers to patients with numerous physical complaints over the course of years for which no physical explanation can be found. The sx must have started before age 30 and must have impacted social or occupational functioning. Patients must have all of the following: four pain sx, 2 GI sx, one sexual sx, one pseudoneurologic sx.
What is the mechanism of action of memantine?
NMDA receptor antagonist.
What is first line treatment for acute mania?
Mood stabilizers (lithium, valproate, carbamazepine) plus an atypical antipsychotic.