Neurology Lectures Flashcards
(174 cards)
1
Q
Describe the physiology of consciousness
A
Anatomically consciousness is dependent on the reticular activating system in the brain stem and the cerebral cortex. Biochemically this is dependent on GABA-type A receptors, NMDA and noradrenaline receptors.
2
Q
Define Coma
A
Coma is defined as the total absence of awareness of both self and the external environment. It is a state of hypnosis, amnesia, areflexia, and analgesia. The patient will not open their eyes to the pain, do not move spontaneously, and do not utter recognizable words.
3
Q
Describe the causes of loss of consciousness
A
Loss of consciousness can be caused by a vast array of conditions. These can be remembered by:
Units of Insulin
Narcotics
Convulsions
Oxygen
Non-organic
Stroke
Cocktail
ICP
Organism (infection)
Urea
Shock
CO2 and CO excess
Overdose
Metabolic
Apoplexy
4
Q
How should an unconscious patient by assessed?
A
When assessing an unconscious patient, always start with the airway. Reduced level of consciousness is the number one cause of airway obstruction. This may require airway manoeuvres, airway adjuncts or intubation. This may present as snoring.
Breathing should be assessed as always for increased or reduced effort of breathing. Always considered whether oxygen or ventilation support is required. This may also indicate the cause of LOC such as overdose or CO poisoning.
Circulation assessment should be assessed for inadequacies or arrhythmias.
GCS or AVPU score should be used for disability. Pupils should be assessed here:
- Small reactive pupils: Metabolic encephalopathy or midbrain herniation
- PP/Fixed: Pontine lesion, opiates or organophosphates
- Dilated/reactive: Metabolic, midbrain, ecstasy or amphet’s
- Dilated/Fixed: Ictal, hypoxia, ischaemia, hypothermia, or anticholinergics
- Unequal: Horner’s, III nerve palsy or Uncal herniation
Everything else should assess rash, pyrexia, evidence of trauma, PMH and even what is in their pockets.
5
Q
What investigations should be done for the unconscious patient?
A
Investigations should include blood gases, bloods, BMs, urine dip, or other special tests.
6
Q
Describe some specialist treatments for the unconscious patient when the cause is hypoglycemia or opiate overdose
A
Hypoglycemia should be treated with 10% glucose if unconscious. Pabanex should be given alongside this if there is evidence of alcohol abuse to avoid Wernicke’s Korsakoff’s. Opiate overdose should be treated with naloxone 200 or 200mcg IV.
7
Q
How does SAH present?
A
Subarachnoid hemorrhage shows a star sign of CT. 50% will have a warning bleed which presents as a sudden onset severe headache, this will go away. 1/3 develop during exercise. Risk factors include a FMx, smoking, hypertension, and connective tissue disease. They may have a III or VI nerve palsy, papilledema, or signs of meningism. Subarachnoid Haemorrhage is assessed with the Hunt and Hess score or the World Federation of Neurosurgeons score.
8
Q
How should SAH be managed?
A
Subarachnoid heamorrhage patients should be transferred to a specialist neurological centre, given analgesia + antiemetics, surgical clipping, ICP monitoring, BP management and Nimodipine po 60mg/ 4hrly (within 48 hours of the bleed).
Rebleeding occurs in 4% within 48 hours and 20% within 2 weeks. This is associated with a high mortality. SH is also associated with subdural haemorrhage, global cerebral ischaemia, vasospasm (hence nimodipine), hydrocephalus, seizures and SIADH/cerebral salt wasting syndrome.
9
Q
Describe the epidemiology of brain tumours
A
Primary brain tumours are uncommon at 12,000 a year but they are increasing in the UK. Brain tumours are second most common tumour in children behind haematological malignancy.
10
Q
What are the causes of brain tumours?
A
Causes of brain tumours can include hereditary syndromes such as neurofibromatosis or tuberous sclerosis, immunosuppression (HIV/AIDS) leading to cerebral lymphoma, and therapeutic ionizing radiation. There is no correlation with a head injury, power lines, smoking, or air pollution.
11
Q
What are the most common brain tumours and how are they graded?
A
The three most common brain tumours are meningioma (benign), glioblastoma (primary malignancy) and metastases which are often solitary with surrounding oedema. WHO classification of brain tumours is based on the appearance of the cell such as glia – glioma. Gliomas can include astrocytoma, oligodendroglioma and ependymoma.
Grading is based on the WHO classification:
1. Pilocytic astrocytoma (most common in children)
2. Diffuse astrocytoma
3. Anaplastic astrocytoma
4. Glioblastoma (most aggressive primary)
Oligodendromas can only be classified as type 2 or 3 (anaplastic). These have a fried egg appearance. Patients respond well to treatment.
Meningiomas have three grades:
1. Meningioma
2. Atypical
3. Anaplastic (malignant)
Resection is usually curative.
Once the tumour has been named and graded, genetics should be considered:
- 1p 19q deletion = Oligodendroglioma (better prognosis)
- IDH1 mutation = Astrocytoma (better prognosis with mutation)
- MGMT promotor methylation = Glioblastoma which respond to chemotherapy
- P53 mutation = Gliomas
12
Q
Describe the behaviour of benign brain tumours
A
Benign brain tumours behave differently in the brain. Some invade surrounding brain/blood vessels/tissues. Therefore, patients still die of benign tumours so they should be called pre-malignant.
13
Q
Describe primary malignant brain tumours and metastases to the brain
A
Primary malignant tumours of the brain tend to spread throughout the brain and rarely to other parts of the body. Metastases to the brain are from lung (small cell most common), breast, melanoma, renal and colorectal. 1/3 will be solitary metastases, 1/3 up to 4 and 1/3 numerous. Metastases usually spread to the cerebrum (80%), cerebellum (15%) and the brain stem (5%).
14
Q
How do brain tumours present?
A
Presenting symptoms include headache, nausea and vomiting, blurred vision (papilledema), fits, dysphagia, progressive weakness or numbness, sudden deterioration from a bleed or it may be an incidental finding. Always check for signs of a metastases from elsewhere in the history.
15
Q
How should patients with a suspected brain tumour be assessed initially?
A
Assess the performance score to understand what the aim of treatment is for each individual patient. Patients who are able to care for themselves are most likely to benefit from treatment. 1% of patients are diagnosed on 2 week wait. Most patients present through ED.
Consider an urgent direct access MRI in adults with progressive subacute loss of CNS function – NICE
In children – consider a very urgent referral (48 hours) with newly abnormal cerebellar or other central neurological function.
16
Q
What investigations should be ordered for a suspected brain tumour?
A
Bloods: FBC, U&Es, LFTs, Clotting, CEA, PSA, aFP, prolactin and IGF1. These should all be normal.
Imaging:
- CT will show an abnormal lesion
- MR is the best imaging as it shows anatomy better and spectroscopy can be done to assess cell turnover. Blood flow can also be assessed as angiogenesis is an indicator of neoplasia. Surgical planning can also be done with MR as speech tracts can be viewed.
- Functional MR looks at primary cortical areas which light up when movement are instigated. This is assess by blood oxygen level dependent as blood moves to the area of the brain which is in use. This allows for the damage of resection to be determined.
- Positron Emission Tomography (PET) can help assess new tumour growth vs response to treatment.
Histology is the ultimate determining investigation.
17
Q
How should brain tumours be treated?
A
Biopsy should be done if operation is not possible. This is then discussed at MDT. Surgery may not always be curative but will assist with prognosis and quality of life in most cases. It can also help improve the outcome of chemotherapy or radiotherapy.
Gliomas produce migrating cells which may proliferate in years to come. Further, some cells may respond to chemotherapy whereas others don’t in the same tumour.
Metastases to the brain should be treated depending on the assessment of performance. The type of metastases is rarely important.
Awake surgery is useful when tumours are near speech areas as this allows surgeons to improve outcomes. 5 ALA is a drink given before operation which lights up tumour tissue under UV light so more can be resected.
Gliadel is chemotherapy in wafers that can be inserted during surgery near the tumour resection site.
The mainstay of tumour treatment is radiotherapy and radiosurgery. Radiotherapy is with fractionated treatment over 6 weeks every day. This is prognostically beneficial for all patients (temozolamide). Radiosurgery is a single dose treatment is excellent for metastases and meningiomas.
18
Q
What are the prognostic factors for brain tumours?
A
Prognostic factors include age, radiotherapy, surgery, and chemotherapy. Many patients take cannabis oil, laser therapy, ketogenic diet and tumour treating fields (electric fields) are all unknown options.
19
Q
What is the DVLA guidance for those with brain tumours?
A
DVLA guidance is that brain tumour patients are not allowed to drive. This is a 2 year ban for grade III or IV (malignant), 1 year for low grade and 6 months for symptomatic meningioma. No ban for asymptomatic meningioma.
20
Q
Define meningitis and how does it present?
A
Meningitis is inflammation of the meninges and presents with headache, vomiting, photophobia, neck stiffness and Kernig’s sign
21
Q
What is encephalitis and how does it present?
A
Encephalitis is a viral invasion/inflammation of brain tissue. This presents with behavioural change, psychiatric illness, confusion, coma, focal signs and convulsions
22
Q
What is an brain abscess and how does it present?
A
An abscess is a space-occupying lesion and thus presents with focal neurology
23
Q
Define myelitis and how does it present?
A
Myelitis is inflammation of the anterior horn cells in the spinal cord. This can present with flaccid limb paralysis and absent reflexes.
24
Q
What is encephalopathy?
A
Encephalopathy is a clinical syndrome of altered mental status manifesting as reduced consciousness or altered cognition, personality, or behaviour. This has many causes including systemic infection, toxins, hypoxia, trauma, vasculitis, or CNS infection.
25
How is encephalitis diagnosed and how can the cause be determined?
Encephalitis is inflammation of the brain. This is strictly a pathological diagnosis, but clinical markers are used such as CSF inflammatory change or changes in neuroimaging. Causes include viruses, small intracellular bacteria and some parasites. Rarely it can be caused by disseminated encephalitis myelitis (ADEM) or antibody-associated encephalitis.
When assessing cognitive status you can use assessment tools such as MOCA (Montreal cognitive assessment) or ACE (Addenbrooke’s cognitive assessment).
Movement disorders in encephalitis suggest an autoimmune cause, especially orofacial movements or chorea. If a rash is present consider shingles or if purpura it may be meningococcus. Animal or insect bites may suggest rabies or malaria.
26
How should a patient with a suspected brain infection be investigated?
Any patient with a suspected brain infection should have an LP and CSF analysis. This is essential for distinguishing brain infection from systemic infection. If there is evidence of ‘brain shift’ then a CT should be done before LP. Signs of ‘brain shift’ include focal neurology other than cranial nerves, papilledema, recent onset seizures, moderate-severe impairment of consciousness, hypertension with bradycardia, or immunocompromise. Other contraindications for an LP include bleeding disorders, anticoagulant treatment and sepsis over the spine.
‘Brain shift’ is a concern because it pushes the brain down and an LP will cause herniation and coning. On CT a brain shift will present with loss of normal sulcal patterns and reduced space around the basal cisterns.
The CSF should then be sent for PCR
27
How is epilepsy defined?
A transient occurrence of signs and/or symptoms due to abnormal, excessive or synchronous neuronal activity in the brain.
Seizures can be classified as focal onset, generalised onset, or unknown onset.
This is a disorder of the brain characterised by an enduring predisposition to generate epileptic seizures and by the neurobiological, cognitive, psychological, and social consequences of this condition.
28
How is epilepsy diagnosed?
Diagnosis of epilepsy:
- At least two unprovoked seizures occurring greater than 24 hours apart
- One unprovoked seizure and a probability of further seizures similar to the general recurrence risk (greater than 60%) after two unprovoked seizures, occurring over the next 10 years – e.g one seizure with structural abnormality or abnormal EEG.
- Diagnosis of epilepsy can be given concurrently to the diagnosis of an epilepsy syndrome
Epilepsy classification is based on seizure type (focal, generalised or unknown), epilepsy type (focal, generalised, combined or unknown), Epilepsy syndrome (clusters of features such as generic generalised epilepsies) and aetiology (structural, generic, infectious, metabolic, immune or unknown).
29
What are the causes of epilepsy?
Birth trauma, genetic (cerebral dysgenesis, tuberous sclerosis, and storage diseases), congenital infections, cerebral tumours, intracranial infections, febrile seizures, head injuries, hypoglycaemia, hypocalcaemia, pyridoxine dependency, drugs and alcohol and cerebrovascular degeneration.
It is important to establish whether there are primary brain tumours, metastases, AV malformations, and infarction.
30
Describe the onset of epilepsy and its prognosis
Generalized onset epilepsies are usually present in childhood whereas focal/partial epilepsies present later in life (usually acquired causes). The prognosis for epilepsy is that 70% will become seizure-free with antiepileptics whereas 40% will be without treatment. Epilepsy which is not controlled by anti-epileptics is refractory.
31
How should convulsions be assessed in a clinical setting?
1. Differentiate between seizures and seizure mimics (syncope, sleep disorders, migraine, paroxysmal movement disorders, and psychological disorders)
2. Differentiate between acute symptomatic seizures and unprovoked (spontaneous) seizures
3. Classify seizure type and epilepsy type. Basic history and examination, ECG, bloods, and glucose. If focal consider MRI and then EEG whereas generalised should have EEG.
Convulsions can be caused by seizures, concussive convulsions, syncope, and dissociative seizures.
32
How should syncope and seizures be differentiated?
Syncope: Upright posture, pallor and sweating, gradual onset, no injury, can have convulsive jerks, rarely incontinent, unconsciousness lasting for a few seconds, recovery is rapid, no post-ictal confusion, occur infrequently and are often preceded by lack of food or unpleasant circumstances
Seizures: Any posture, no pallor or sweating, sudden onset (sometimes with aura), can have an injury, convulsive jerks, commonly incontinent, unconsciousness lasting minutes, recovery is slow, post-ictal confusion, frequent seizures and rarely any precipitating factors
Acute symptomatic seizures are almost always tonic-clonic. They can be:
- Metabolic disturbance such as uraemic/hepatic encephalopathy, electrolyte disturbance, DKA, severe illness, drugs, or alcohol (withdrawal or intoxication)
- CNS disorders such as trauma, surgery, haemorrhage, infection, and cerebral hypoxia
33
What advice should be given to new-onset epilepsy patients?
All patients should be offered a diagnosis and explanation, discuss triggers (poor sleep and alcohol), safety, status epilepticus, and SUDEP risk, driving advice, and consider discussions around pregnancy and breastfeeding.
34
What is status epilepticus?
Status epilepticus is a seizure that lasts longer than 5 minutes or having more than 1 seizure within a 5 minute period without returning to normal level of consciousness.
35
What is SUDEP?
SUDEP stands for Sudden, Unexpected Death in Epilepsy
36
What are the medical options for epilepsy treatment?
1.Focal epilepsy – generally give Lamotrigine
2.Generalised epilepsy – Sodium Valproate (never in pregnancy) or lamotrigine in women of childbearing age
Epilepsy should be treated with monotherapy. Rational polytherapy means prescribing drugs with different mechanisms of action if one is not sufficient.
Refractory epilepsy is defined as the failure of adequate trials of two appropriate and adequately tolerated AEDs, either as monotherapy or polytherapy. These patients may be considered for epilepsy surgery.
37
What are the surgical options for epilepsy management?
Epilepsy surgery is indicated in patients with focal epilepsy that is medically refractive, non-eloquent cortex, no significant medical/psychiatric co-morbidities and fully counselled.
Surgical options include focal resection (temporal lobe resection or extratemporal resections of the frontal, parietal or occipital lobe), lesionectomy, multiple subpial transections, laser interstitial thermal therapy, anatomical or functional hemispherectomy/hemispherotomy, corpus callosotomy or stereotactic radiosurgery.
38
What are the non-pharmacological options for managing epilepsy?
Nonpharmacological management includes vagal nerve stimulation (modest degree of benefit) or ketogenic diet (high fat, low carb diet to induce ketosis) is most effective in patients with epilepsy syndromes and refractory seizures.
39
How should epilepsy be managed in women of childbearing age
Women of childbearing age (15-45) – All must be on folic acid supplementation
AEDs have teratogenic risks and neurocognitive risks, but this should be measured against the dangers of uncontrolled seizures. Focal seizures are unlikely to have major impact on mother/fetus however generalised seizures can cause hypoxia, lactic acidosis, blunt trauma, reduction of IQ of child, and an increased risk of SUDEP.
AEDs, especially sodium valproate, has an increased risk (10%) of major congenital malformations. This risk is increased with polytherapy. There is also a significant reduction in IQ for children exposed to valproate in utero where lamotrigine and levetiracetam have less/no impact.
40
How do AEDs affect breastfeeding?
In breastfeeding there is no adverse effects for taking AEDs when breastfeeding. Lamotrigine metabolism is affected by pregnancy and the dose may need to be increased during pregnancy.
41
Describe a primary and secondary headache
Primary headache has no underlying physical abnormality
Secondary headaches are due to an underlying abnormality or an external factor. These account for less than 1% of presentations to GP. They present with a sudden onset severe headache (thunderclap). Other red flags are signs of CNS infection, raised or low cranial pressure, new onset neurological deficit, alteration of consciousness, elderly, known malignancy, immunocompromised, head injury, anticoagulated, glaucoma, or temporal arteritis
42
Describe a typical history for a thunderclap headache
Thunderclap headache is defined as a new sudden onset headache which is severe right from the onset. There will not be any build up to the symptoms. Associated symptoms such as syncope or vomiting are relevant. There may be ophthalmoplegia or true neurological weakness. The location of the pain is not always relevant unless behind the eye or back of the neck.
43
What are the causes of a thunderclap headache?
Causes include subarachnoid haemorrhage (usually berry aneurysm), other intracranial haemorrhages such as pituitary apoplexy, dissection of cerebral blood vessels, cerebral vasculitis, reversible cerebral vasoconstriction syndrome, cerebral venous thrombosis, and idiopathic causes.
44
How should a thunderclap headache be investigated and treated?
A CT brain scan must be done immediately. If CT does not show a reason for thunderclap headache, then 12 hours later an LP and CSF examination should be done. The 12-hour gap is so that blood not picked up on CT can break down into bilirubin and then be detected on the xanthochromia test.
Subarachnoid hemorrhage should be treated with IV or enteral nimodipine, a short course of tranexamic acid, VTE assessment, fluid therapy, and potentially surgical review of the ruptured aneurysm.
45
How does a CNS infection with thunderclap headache present?
Cardinal features are raised temperature, neck stiffness, seizures, and alteration in consciousness. Causes include meningitis, encephalitis, cerebral abscess, subdural empyema, paraspinal collections, unusual organisms, and systemic infection with associated headache.
46
How should a thunderclap headache caused by CNS infection be managed?
Management is to start antibiotics/antivirals, CT brain, DO NOT delay an LP if there are no contraindications and MR brain if suspecting encephalitis for temporal lobe changes or haemorrhage.
47
What would a thunderclap headache with raised CSF present with?
There will be headaches AND papilledema/loss of visual acuity/visual field defect/ new IV or VI nerve palsy. Headache which are worse on lying down or waking up, and those brought on by Valsalva manoeuvres (not worsened) should be considered worrying. A feeling of pressure or tightness is not relevant. Visual obscurations are loss/clouding of vision with valsalva and they may also have pulsatile tinnitus.
48
What are the causes of raised CSF headaches?
Causes of raised CSF headaches include tumours, cerebral venous sinus thrombosis, malignant meningitis (cancer cells), and significant Chiari malformations. IIH is a diagnosis and should only be considered in appropriate young overweight individuals. They may have papilledema, normal CT, MRU and venogram, CSF analysis normal but CSF opening pressure high.
49
How should raised CSF headaches be investigated?
When suspecting raised ICP, CT brain with contrast and venogram or MRI brain and venogram. This will pick up most of the secondary causes of papilledema.
50
Describe the features of a cerebral venous sinus thrombosis
Cerebral venous sinus thrombosis presents with headache, papilledema, seizures, focal deficit, reduced GCS, cranial nerve palsies, bilateral cortical signs, and rarely cerebellar signs. Precipitating causes include trauma, intracranial tumour, infection, abscess, meningitis, post-partum, oral contraceptive pill, polycythaemia, systemic infection and severe dehydration. The headache can be progressive over days or be thunderclap. These patients require a CT with venogram or MRI with venogram.
51
How does a low CSF headache present?
Low CSF pressure occurs post lumbar or dural puncture. Rarely they are spontaneous. They will not have a headache on lying down but within 5-15 minutes of sitting up or standing they will have severe (throbbing), bilateral severe headache which is incapaciting. Orthostatic headaches. The positional element is lost in chronic cases.
52
How should low CSF pressure headaches be treated?
Treatment is to lie flat (symptomatic relief) for days-week and let the tear heal. This will heal in around a week but will worsen if they try to go about their daily activities. Patient should have IV fluids 8 hourly or 2-3 litres of oral fluids every 24 hours. If spontaneous in origin then a MR brain with contrast is needed to look for a cause and if patients are worsening despite medical treatment for 72 hours then epidural blood patch is required.
53
Describe some other headache red flags
1.New headache with neurological deficit/immunocompromised/known malignancy/elderly/anticoagulated/pregnancy
2.Temporal arteritis which presents with jaw claudication, stroke like features, and raised inflammatory markers. These patients should be started on steroids and a temporal artery biopsy should be arrived within 2-7 days. Jaw claudication is pain on chewing caused by temporal ischaemia to the temporalis and masseter. Usually in patients over 50.
3.Glaucoma presents with loss of vision and halo effect. They require emergency ophthalmology assessment.
All of these patients with new sudden onset headache have a high risk of persistent headaches which behaviour like chronic migraine.
54
Describe migraine
Migraine is a form of sensory processing disturbance with manifestations within and outside the CNS function. The trigemino-cervical complex is currently the accepted pathway of migraine genesis. Pain is only one of the symptoms. The TCC pathophysiology involves a variety of neuropeptides in a cascade. There is a genetic predisposition with genetic types with aura such as FMH and CADASIL. Frequent migraines is a tendency rather than a disease.
55
What are episodic migraines?
Episodic migraine is episodes of headaches that can be unilateral or bilateral (1-4 days) which are moderate-severe intensity and involve the face, scalp and neck. The pain may be aching/throbbing/stabbing/pressure-like. Patients may have nausea, photophobia, noise sensitivity and olfactory sensitivity. It affects the patient’s capacity to function as they will prefer to lie down, sleep, and keep away from noise. In between episodes they will function well and be free of symptoms.
Diagnostic criteria is at least 5 headaches fulfilling:
1. Duration 4-72 hours
2. Headache has two of the following: Unilateral, pulsatile, moderate/severe pain and avoidance of routine activity
3. One of the following during the headache: Nausea or vomiting or photophobia or phonophobia
Aura occurs in 20%. This is a spreading neurological deficit that can affect visual, sensory, and speech but will completely reverse after coming on over 5 minutes. Black spots in front of the eyes is not aura.
56
What are the phases of migraine?
Phases:
1. Premonitory (days): yawning, craving, mood changes and hypothalamic
2. Aura phase (2-60 mins) with cortical spreading dysfunction
3. Headache phase (up to 3 days) with the TCC firing
4. Postdrome (days) with a dull persistent headache, TCC firing and central sensitisation.
57
How should acute migraine be treated?
Acute episodes should be treated with triptans AND/OR aspirin OR NSAIDs as first line. Ensure adequate hydration, aim to reduce pain by 50%, do not use opiates and advise patient to recuperate at home with rest and use pain medications sparingly. Migraine sufferers should be evaluated for use of preventative therapy if they are getting more than 2-3 episodes a month or if the episodes are severe.
Very severe attacks should be treated with triptans, NSAIDs and antiemetics. Avoid opiates and codeine.
58
What is chronic migraine?
Chronic migraine occurs after many years of episodic migraine with progression. It is defined as headache occurring on 15 or more days/month for more than three months or 8 days a month with features of migraine. Triggers include stress, fatigue, sleep disturbance, dehydration, hormones and missing meals.
If patients use analgesia for more than 10 days in a month that will make the migraines worse.
59
How should chronic migraine be managed?
Management of chronic migraine:
-Explain that this is a long process which may take 6-9 months
-Try to get patients off regular analgesia and start them on preventatives
-Use short courses of naproxen to help patients come off codeine
-Rest, hydration and avoiding triggers
-Refer to neurology if not benefitting from adequate trials of three or more preventatives
Preventative options include propranolol, topiramate, pregabalin and candesartan. Doses should start small and work up. Make take 3-4 months to work. Other options are calcium antagonists, SSRIs, occipital nerve injections and acupuncture. Rarely botulinum toxin can be used.
60
What are trigeminal autonomic cephalgias?
Trigeminal autonomic cephalagias are always unilateral. The have prominent autonomic features because there is parasympathetic involvement due to being parallel to the trigeminal nerve. These symptoms include congestion or watering of the eye, eyelid drooping/swelling, blocked or runny nose. The patient will be restless and agitated. The headaches are episodic. The attacks are stereotyped as in they occur in exactly the same way every time (especially cluster). They are categorised by duration of attacks and frequency. Cluster is 1-8 attacks in 24 hours with each attack 1-4 hours, hemicrania are 30-minute attacks up to 20 times a day whereas SUNCT lasts for a few seconds for 100s times a day.
61
What are cluster headaches?
Cluster headaches are unilateral, side locked, headaches with extreme pain. They present with autonomic features such as streaming of the eye and nostril, conjunctival congestion, and swelling of the eyelids or face. Usually have night-time attacks which wake the patient up between 2-6am. There will be severe agitation and restlessness. There is periodicity as in they occur for a few weeks then go away.
62
How should cluster headaches be treated?
This is an emergency. Acute treatment is with sumatriptan (injection or nasal spray) and high flow oxygen (15 litres) through tight non-re-breathable mask via a HOOD form. Short term prevention is with greater occipital nerve blocks, prednisolone 60-80mg/day for 5 days and then taper off. This should not be done more than twice a year. Long term prevention is with verapamil (high doses of 480mg and ECG monitoring), topiramate, lithium and gammacore device. These patients should be referred to neurology.
63
What is trigeminal neuralgia?
This is a primary headache which affects the 2nd and 3rd trigeminal branches whereas cluster and migraine affect the 1st division. All headache pains are mediated by the trigeminal nerve. There will be recurrent paroxysms (jabs) of pain with triggers, a refractory phase and then remissions. Persistent dull ache of the face is not trigeminal neuralgia.
64
What are the causes of trigeminal neuralgia?
Trigeminal neuralgia can be caused by compression of the vascular loop/ tumours/ MS plaques. MRI will find a secondary cause in 5%. Vascular compression at the root of entry zone of the nerve can be demonstrated in 50% of idiopathic TNs.
65
How should trigeminal neuralgia be treated?
TN responds very well to Carbamazepine, but facial pain will not. Other options include phenytoin, gabapentin, pregabalin, lamotrigine, baclofen, and levetiracetam.
66
Define multiple sclerosis
Multiple sclerosis is defined as a multifocal UMN disorder, disseminating in time and space which can either be relapsing or progressive.
67
What is the pathophysiology of MS?
The pathophysiology of the inflammation is that there is focal demyelination which causes perivascular inflammation. On CT they are described as dawson’s fingers with white lesions spreading out from the ventricles. The position of the inflammatory lesion determines the symptoms which are experienced. For example:
-Weakness of both legs = spinal cord
-Numbness down the whole left arm = (right) cerebrum
-Dizziness, slurred speech, falls and left sided incoordination = brainstem (left cerebrum)
-Blurred vision in the left eye with painful eye movements = Cerebrum (left optic nerve). This is the only pain felt in MS.
68
How is MS diagnosed?
A diagnosis is made from 2 attacks with objective clinical evidence. This cannot be the same symptom as that would not be disseminated in space (of the brain).
69
What are the other risk factors for developing MS?
There is an increased risk with a family history of MS. There is also an association with low vitamin D, especially below the age of 14. EBV also has a small increased risk. Weight, salt and smoking may have a role
70
Generally what are the symptoms of MS?
Symptoms include balance/vertigo, gait disturbance, fatigue, bladder dysfunction, spasticity, sensory dysfunction, hand problems, pain, heat sensitivity, sexual dysfunction, poor memory, and vision problems. 2/3 of patients will recover fully from a relapse. Relapse frequency decreases with time (17% over 5 years).
Progressive MS is not increasing frequency of relapses but progressive disability. Primary progressive MS will never have a relapse but progressive disability from onset. 20% will have benign MS without any progression.
The cause of progression is that there is axonal loss and diffuse inflammation/cortical demyelination. Essentially progression is related to atrophy. There is a strong correlation between early disease activity and late atrophy.
71
What is the prognosis for MS?
This is mainly a disease or morbidity and not mortality with only a slight reduction in life expectancy. Progressive MS will require walking stick in around 7 years and wheelchair in 13 whereas relapsing will be 23 years and 33 years respectively.
72
How should MS be treated?
Treatment of acute relapse: Methylprednisolone 500mg PO for 5/7 – these accelerate the speed of recovery but do not improve outcomes.
There is debate about how to treat progressive MS. It is an incurable condition, but we can help with symptom management.
73
What is the pathophysiology of Parkinson's disease?
There is Lewy body depositions (composed of alpha synuclein protein) in the substantia nigra and midbrain. These develop and envelope the rest of the brain. As the disease progresses, so do the Lewy body deposits.
The deposition of protein causes cell death through a combination of inflammation, oxidative stress, mitochondrial dysfunction, and excitotoxicity. The alpha Synuclein gene has been associated with PD. Other genetic factors include GBA, ATP13A2, VPS3s, kinase alterations (LRRK2), impaired mitophagy (Parkin/PINK1) and oxidative stress gene DJ1.
74
How is Parkinsonism defined?
Parkinsonism can be divided into:
1. Neurodegenerative Parkinson’s disease such as idiopathic (sporadic or genetic) and atypical Parkinson’s disorders
2. Symptomatic parkinsonism which can be drug-induced, vascular, basal ganglia lesions, toxic (MPTP and CO), encephalitis and frontal meningiomas.
75
What is the clinical presentation of Parkinson's disease?
To diagnose Parkinson’s disease there must be bradykinesia with at least one of the following:
- Muscle rigidity
- 4-6hz resting tremor
- Postural instability not caused by a primary visual, vestibular, cerebellar or proprioceptive dysfunction
Signs include hypomimia (masked face), hypophonia/bradyphrenia, micrographia, small-stepped gait, reduced arm swing and difficulties rising from a chair or turning in bed. Other diagnostic criteria include:
- Unilateral onset
- Excellent response to levodopa
- Presence of levodopa-induced dyskinesia
- Resting tremor
- Progressive disorder
- Persistent asymmetry affecting side of onset most
- L-Dopa response for over 5 years
- Clinical course of over 10 years
There are other feature of PD which are non-motor due to the spread of Lewy body deposits. Common extra-motor symptoms include REM sleep disorder or REM without atonia, neuropsychiatric features of cognitive dysfunction and mood, autonomic dysfunction, sensory symptoms, pain, and olfactory dysfunction. These non-motor symptoms have a significant impact on the quality of life.
76
What are the differentials for Parkinson's disease?
Differentials to consider are essential tremor, atypical Parkinson’s disorders (multiple systems atrophy or progressive supranuclear palsy) and vascular Parkinsonism.
In a Parkinson’s history, these RED FLAGs should make you consider other conditions: Rapid progression of gait impairment, strictly unilateral features after three years, history of repeated strokes with stepwise progression, repeated head injury, history of encephalitis, severe dysphonia/dysarthria/dysphagia for over 5 years, inspiratory stridor, severe autonomic failure within 5 years, recurrent falls (3 years), neuroleptic treatment at onset, more than one affected relative, supranuclear gaze palsy, early severe dementia, positive Babinski sign, presence of brain tumour/hydrocephalus, cerebellar signs, MTPT exposure and negative L-dopa response.
77
How should Parkinson's disease be investigated?
Parkinson’s is a clinical diagnosis and investigations are rare. Investigative options can include L-dopa trial, olfactory testing, MRI imaging (which should be normal if PD), DAT-spect is very sensitive but expensive, TCUS and genetic testing.
78
What is the relationship between L-dopa treated and disease progression?
The honeymoon period is the initiation of L-dopa which will make the patient very happy. However, this will wear off and progression ensue. As the disease progresses there will be motor features that are resistant to L-dopa such as axial and limb deformities (camptocormia, antecollis, lateral trunk flexion and striatal limb deformities), postural instability, falls, freezing gait, dysarthria, and dysphagia.
79
How should Parkinson's disease be managed?
On initial presentation the aim is to replace dopamine, usually with levodopa. L-dopa can pass through the blood brain barrier where it is decarboxylated by Dopa-decarboxylase to dopamine which can then act on the D2 receptors. However, this also occurs in the blood so there is dopamine in the blood and methydopa is produced in the brain and blood as well. This means only 10% of the dose will reach the D2 receptors. This is why dopa-decarboxylase inhibitors are prescribed with L-dopa such as co-careldopa or co-beneldopa. This maintains as much dopamine as possible so it can reach the D2 receptors.
Other enzyme inhibitors used in PD include rasagiline and safinamide which are monoamine oxidase inhibitors which also inhibit the breakdown of dopamine. COMT inhibitors can be peripherally acting or central and these work to reduce the conversion of L-dopa to by-products such as methyldopa.
As the disease progresses the motor symptoms will worsen, and L-dopa will become less effective. This will be experienced as motor fluctuations and requires careful optimisation of levodopa such as modified release and adherence. Long acting dopamine agonists are often required. When Parkinson’s disease is end stage then MDT is required to maximise quality of life as therapy is as important as medication. Exercise is important throughout management.
Late-stage PD will cause falls, dementia, hallucinations, choking, speech problems, postural hypotension and incontinence. This should be managed with a reduction of L-dopa, treatment of non-motor symptoms and MDT. 50% are living in a care home 20 years after diagnosis.
80
What are the characteristics of Parksinonism?
Parkinsonism is characterised by slowness of initiating and executing movements (bradykinesia). The cardinal symptoms are TRAP (Tremor, rigidity, akinesia/bradykinesia and postural instability). It is caused by degeneration of the basal ganglia, especially the substantia nigra (dopamine secreting neurones).
81
What are the causes of Parkinsonism?
Parkinsonism can be caused by toxins (MPTP, carbon monoxide and manganese), head trauma (boxing), structural brain lesions (tumour), metabolic disorders (Wilson’s disease), infections (encephalitis lethargica), CVD (vascular Parkinsonism), drugs, and idiopathic Parkinson’s disease. Drugs And IPD are the most common causes.
Drug-induced Parkinsonism is caused by dopamine receptor blocking agents such as typical neuroleptics (haloperidol), anti-emetics (metoclopramide) and atypical neuroleptics (clozapine). Treatment is to discontinue the drug and use anticholinergics such as procyclidine.
Other drug induced movement disorders include Akathisia (motor restlessness and compelling urge to move) and Tardive dyskinesia (smacking lips, choreoathetoid movements of the tongue), lateral jaw movements, choreiform movements and dystonias.
82
What is the mechanism of action of Levodopa?
Dopamine does not cross the blood-brain barrier, but the precursor L-dopa does. In the brain, DOPA decarboxylase decarboxylates levodopa to dopamine. Only 1% reaches the brain with the rest being metabolised peripherally. Therefore, levodopa is combined with a peripheral DOPA decarboxylase inhibitor such as carbidopa or benserazide.
83
What are the side effects of Levodopa?
Side effects include nausea, hallucinations, confusion, postural hypotension, dizziness and sleepiness. Long-induced complications include dyskinesias which should be managed by reducing the L-dopa dose and amantadine (inhibits the NMDA receptors), and motor fluctuations due to progressive degeneration of the nigrostriatal terminals which is managed by shortening
84
How do dopamine agonists work in the treatment of Parkinson's disease?
Dopamine agonists have a direct action on postsynaptic dopamine receptors. These are broadly divided into Ergot-based (pergolide + cabergoline) and non-ergot based (pramipexole and ropinirole). Adverse effects include pulmonary/pericardial/retroperitoneal fibrosis, sudden onset of sleep and impulse control disorders such as gambling and hypersexuality.
85
Give an overview of monoamine oxidase inhibitors
Monoamine oxidase inhibitors are modestly effective in symptomatic PD and examples include Selegiline and Rasagiline. Caution when used with tricyclics or SSRIs due to risk of serotonin syndrome
86
How is essential tremor treated?
Essential tremor is treated with beta blockers such as propranolol
87
How are dyskinesias treated?
Amantadine has a very modest anti-Parkinson’s effect so is no longer used for PD but is used for dyskinesias.
88
How is dystonia treated?
Dystonia is treated with botulinum toxin injections
89
Define a seizure
A paroxysmal attack of transient signs and symptoms
90
Define an epileptic seizure
A transient occurrence of signs and symptoms due to abnormal, excessive or synchronous neuronal activity in the brain.
91
How is epilepsy defined?
This is a disease of the brain defined by any of the following:
- At least two unprovoked (or reflex) seizures occurring more than 24 hours apart
- One unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years
92
What is the aetiology of epilepsy?
1. Structural: Tuberous sclerosis, lissencephaly, neuronal migration disorder, and brain injury from stroke or trauma
2. Genetic: Angelman syndrome, tuberous sclerosis, SCN1a, SCN2a, and KCNQ2
3. Metabolic: Nonketotic hyperglycinaemia and pyridoxine-dependent epilepsy
4. Infectious: HSV encephalitis, cerebral abscess, and meningitis
5. Immune: Autoimmune encephalitis (NMDA/VGKC)
6. Unknown
93
How are AEDs decided?
Transmembrane ion pumps maintain the concentration gradient. These pumps are ATPase dependent, pumping sodium out and potassium into the cells. Anti-epileptic drugs work by decreasing the excitation or enhancing the inhibition. They can act on Na+/K+, Cl- and Ca2+ pumps to alter the membrane excitability. Others act on neurotransmitter receptors such as GABA, NMDA, and glycine which upregulates/downregulates the membrane excitability.
The choice of AED depends on the seizure type and the underlying cause of epilepsy. It is also important to consider the tolerability and side effects.
SCN1a – Avoid CBZ and phenytoin
POLG1 – avoid Sodium Valproate
The time scale by which therapeutic levels can be achieved should also be considered. For example, Levetiracetam can be loaded via IV whereas Carbamazepine/Lamotrigine will need to be titrated over weeks.
94
How should AEDs be chosen for women of childbearing age?
Sodium valproate must not be used in women of childbearing age because of the risk of foetal valproate syndrome. This is characterised by facial features (epicanthal folds, short nose, anteverted nostrils, long philtrum and small mouth), spina bifida, congenital heart defects, cleft lip and palate, genital abnormalities, skeletal abnormalities, developmental delay and learning/behavioural difficulties.
However, uncontrolled epilepsy in a pregnant woman can cause status epilepticus, hypoxia and endanger the lives of mother and child. Therefore, for some women low dose sodium valproate may be the lesser of two evils. Women on sodium valproate of childbearing age should attempt to prevent pregnancy.
95
What are the common side effects of AEDs?
- Levetiracetam – behavioral problems
- Carbamazepine – Rash (steven-Johnson) and behavioral problems
- Nitrazepam – drowsiness
- Vigabatrin – visual field defects
- Topiramate – weight loss
96
Name some IV AEDs
Examples of IV AEDs are phenytoin, benzodiazepines, levetiracetam, sodium valproate, phenobarbitone, lacosamide, and topiramate. These should be used when enteral is not available or in emergency situations. They can also be used when a patient is nil by mouth.
97
What options for AEDs are there in children?
Children often prefer syrup formulations, and most AEDs are available as syrups. Some come in granule forms such as levetiracetam and sodium valproate which can be hidden in other foods.
98
What are P450 hepatic enzyme inducers?
These inducers include Carbamazepine, phenytoin and phenobarbitone so extra care should be taken when considering what other medications, a patient has been prescribed.
99
What are category one AEDs?
These should not be switched between brand names. Examples include Phenytoin, carbamazepine, phenobarbitol and primidone
100
What are category two AEDs?
Clinical judgment should be used regarding whether to switch brands.
Examples include sodium valproate, lamotrigine, perampanel, retigabine, rufinamide, clobazam, clonazepam, oxcarbazepine, eslicarbezapine acetate, topiramate, and zonisamide
101
What are category three AEDs?
Can switch freely between brands.
Examples include Levetiracetam, lacosamide, tiagabine, gabapentin, pregabalin, ethosuximide and vigabatrin.
102
What is status epilepticus?
Status epilepticus is a condition resulting either from the failure of the mechanisms responsible for seizure termination, or from the initiation mechanisms which lead to abnormally prolonged seizures. It is commonly defined as generalised tonic-clonic seizure lasting for longer than 5 minutes or repetitive seizures with no intervening recovery of consciousness.
This is a medical emergency because it can cause hypoxia. Further, a seizure lasting longer than 30 minutes can cause cytotoxic brain damage.
103
What are the causes of status epilepticus?
The causes of prolonged seizures include epilepsy syndromes, hypoglycaemia, infection (meningitis/encephalitis), intracranial haemorrhage, electrolyte imbalance (sodium or calcium) and drug related withdrawal (benzodiazepines or opioids)/toxicity (tricyclic antidepressants).
104
How should premonitory status epilepticus be managed?
Diazepam 10-20mg given rectally and repeated once 15 mins later if status continues to threaten, or 10mg midazolam given buccally.
105
How should early status epilepticus be managed?
IV lorazepam 0.1 mg/Kg (usually a 4mg bolus repeated once after 10 mins).
106
How should established status be managed?
Phenytoin infusion at a dose of 15-18mg/Kg at a rate of 50mg/min
107
How should refractory status epilepticus be managed?
General anaesthesia should be induced with propafol/midazolam/ thiopental sodium. GA should be continued for 24 hours after the last seizure.
108
Define refractory status?
Refractory status is reached 60/90 minutes after the initial therapy.
109
How should status epilepticus be managed in children?
Management in children is very similar except for the addition of Paraldehyde and consideration of phenobarbitone. Guidelines have now changed which say that second line AEDs should be levetiracetam, phenytoin or sodium valproate and not phenobarbital. Phenobarbital can now be considered as a third line alongside general anaesthesia.
110
What is the impact of trauma on the brain?
Trauma can cause cerebral oedema, cerebral contusions, and haemorrhage such as extra-Dural (middle meningeal artery), subdural (venous sinuses) and subarachnoid (arterial rupture).
111
Categorise space occupying lesions
Space occupying lesions can be localised or generalised: Localised such as haemorrhage, neoplasm, abscess, and other infections. Generalised such as cerebral oedema and hydrocephalus.
112
What are the causes of cerebral oedema and why is it dangerous?
Cerebral oedema is increased fluid within the brain and it is problematic because there is a fixed volume within the skull without a lymphatic system and there is limited CSF space. Cerebral oedema occurs in response to TBI, stroke, infection, and neoplasia but can also occur in DKA, altitude sickness, CO poisoning, some drugs and venomous bites.
113
Describe the pathological findings of meningitis
Meningitis produces an exudate on the surface of the brain which is the physical sign of meningism. Viral causes are the most common and the least serious. Bacterial is rare but serious. Viral causes include enteroviruses, mumps and HSV whereas bacterial causes include Haemophilus influenza B, meningococcal and pneumococcal bacteria.
114
Describe the pathological findings of neurological tumours
Tumours clinically present as SOLs or as epilepsy. They are the second most common cancer in children. Glial cells produce gliomas (astrocytoma has a better prognosis than a glioblastoma). Primitive neuroectodermal cells produce medulloblastomas, meninges produce meningiomas and lymphoid cells can become lymphoma.
115
Describe the pathological findings in dementia
Cortical atrophy histologically presents with markedly reduced sulci with expansion. In Alzheimer’s there is progressive destruction of the brain tissue, especially in memory and language centres. At a cellular level there is deposition of Aß peptide which are highly prone to aggression and are neurotoxic. These become neuritic plaques of extracellular amyloid deposition whereas neurofibrillary tangles are caused by the accumulation of Tau protein.
116
Describe the pathological findings of Parkinson's disease
Parkinson’s disease is caused by the accumulation of a-synuclein in the substantia nigra. This causes impaired function of the mitochondria, lysosomes and other organelles which eventually leads to neuron loss in the substantia nigra. These are known as Lewy bodies.
117
What are the main types of primary headache?
90% are migraine but others include tension type headache and trigeminal autonomic cephalalgias such as cluster and hemicrania continua.
118
How are secondary headaches classified?
The HIS classification says these are due to trauma, cranial or cervical vascular disorders, non-vascular intracranial disorders, use or withdrawal of substances, infection, disorder of homeostasis, disorders of the cranium, and psychiatric disorders.
119
What are the red flag symptoms of headaches?
Thunderclap, refractory pain, progressive or persistent daily headache, papilledema, features of raised ICP, visual loss, scalp tenderness, atypical aura or duration, progressive neurological deficit, unexplained cognitive or behavioural change, cancer history and immunosuppression.
SNOOP: Systemic symptoms, Neurological symptoms, Onset, Older (>50) and Pattern
120
How should migraine be managed?
Conservative management is with sleep, fluids, caffeine, stress, exercise, and diet.
Acute medical management is with aspirin 900 mg as a one off dose, ibuprofen 400-600 mg and triptans and antiemetics.
Migraine prevention is with propranolol, topiramate, tricyclic antidepressants or candesartan.
121
When should medication overuse headaches be diagnosed?
This should be suspected if a headache develops or worsens in someone who is taking regular medication for an already established primary headache and the headache occurs 15 days or more per month and the patient has been using regular acute medications for 3 months and there is no other diagnosis which is more appropriate.
122
How should medication overuse headaches be managed?
Management is to ensure no red flags, educate on primary headaches, supported medication withdrawal with aim to end within one month, warning about initial worsening of headache symptoms and address any co-morbidities such as depression. They should be followed up in 4-8 weeks, ongoing support with relapse prevention and refer to neurology is problematic.
123
What is the definition of fibromyalgia?
This is chronic, widespread pain, which moves from site to site and often has a burning quality. It is associated with fatigue, sleep disturbance (unrefreshed), cognitive change (fibro-fog), mood disturbance and various somatic symptoms. Fibromyalgia has a prevalence of around 2%.
Diagnosis is with severe pain in 3-6 different areas or milder pain in 7 or more areas of the body. This is a clinical diagnosis and should only be made when there is no other reason for the symptoms and symptoms are consistent for 3 or more months.
124
What are the causes of fibromyalgia?
Causes are unknown but there may be a change in neurotransmitters such as substance P increase or lack of serotonin. There may also be disordered sensory processing. Triggers include trauma, viral infections, emotional events, and sleep issues.
125
How should fibromyalgia be managed?
Management is with realistic expectations, individualised management plans with psychological and physical interventions, and refer to pain management clinics promptly. Pain should not be managed with the WHO analgesia ladder. Pain management programmes have been shown to be effective.
Pharmacological management can include amitriptyline 25-125mg PO, Pregabalin 300-600mg, Duloxetine 60mg PO, paracetamol + Tramadol combination, or fluoxetine 20-80mg PO.
126
How can epilepsy and dissociative seizures be distinguished?
This can this be distinguished between with EEG pattern during seizure activity. Seizures should be filmed and shown to a specialist. Epilepsy will appear blue when seizing (involuntary restriction of breathing), epileptics will not be conscious during the attack (they will not resist eye opening), and tongue biting (side of the tongue whereas non-epilepsy bites the tip). Finally, the movements may indicate epilepsy if the jerks are more rhythmic whereas non-epileptic will present with flailing movements. So, assess: Movement, cardio-respiratory status, and level of consciousness.
The movements correspond to the representation on the motor homunculus. So limbs have a lot of representation whereas the trunk doesn’t so movements of the trunk is unlikely to be epilepsy. Patients with non-epileptic attacks may be tearful.
127
Describe PNEAD
PNEAD stands for psychologically derived non-epileptic attack disorder. It is more common in younger women, childhood trauma, history of abuse or other psychological co-morbidities. PNEAD and IBS are caused by psychological autonomic dysfunction. Management is with psychiatry.
128
Describe late-onset psychogenic non-epileptic attacks
This is an older man which is unusual for non-epileptic attacks. However, the description of the attack in non-epileptic. A recent life-threatening event (AF and MI) increases the likelihood of developing non-epileptic attacks as this is a psychogenic insult.
129
How should status epilepticus be managed?
Management of status epilepticus
- Provide ABCDE with resuscitation
- Give a benzodiazepine (buccal midazolam or rectal diazepam) or IV lorazepam
- Assess for underlying causes such as hypoglycaemia, eclampsia, or alcohol withdrawal which may require different medical management
- Consider dissociative seizures
- If no response to two benzodiazepines, then give levetiracetam, phenytoin, or sodium valproate (levetiracetam is quickest to administer and has the least side effects).
- If this fails then consider an alternative second line treatment
- Third line management is with phenobarbital or general anaesthesia
5-15mins 1st line treatment, 15+ 2nd line and 30+ 3rd line treatment
Bloods should include calcium, magnesium, sodium, and potassium as these can cause seizures. LFTS, FBC and inflammatory markers. Sepsis can cause seizures, alongside meningitis and encephalitis.
130
What are the causes of a first fit?
Cerebrovascular disease (13%), alcohol/drugs/toxins/metabolic (9%), drug reduction/withdrawal (9%), acute CNS infection (13%), acute CNS anoxia (11%), head trauma (4%), cerebral tumour (4%), idiopathic (20%), and others (17%).
131
What is Guillain-Barre syndrome?
Guillain-Barre is an autoimmune polyradiculoneuropathy. It is an acute inflammatory condition of the peripheral nerves whereby autoimmune attack on the myelin causes demyelination of the peripheral nerves, moving proximally. The chronic form can cause degeneration of the whole nerve fibre and is called Chronic inflammatory demyelinating polyneuropathy.
132
What can cause an elevated cell count in CSF?
Lyme disease can cause meningitis affecting the spine and HIV seroconversion and cause elevated cell count. Malignant tumours metastasing to the meninges. Sarcoidosis and amyloidosis can also cause elevated cell count.
133
How is chronic inflammatory demyelinating polyneuropathy managed?
Given that this is an autoimmune disease it makes sense that this is treated with IV immunoglobulins or plasma exchange. CIDP can be treated with steroids.
Cardiac instability and distended abdomen are likely due to autonomic dysfunction. This may cause an inability to control heart rate, and blood pressure and impair the enteric nervous system of the GI tract leading to gastroparesis and thus a distended abdomen.
Priority should be ventilation as this is a neurological emergency for respiratory arrest and thus at risk of death. The disease-modifying treatment could be provided once the patient was stable.
134
How can GBS and locked-in syndrome be differentiated?
Locked-in syndrome is characterised by quadriplegia and the inability to speak in otherwise cognitively intact individuals. They may be able to communicate through blinking. They are conscious and aware with no loss of cognitive function. Occasionally they retain some sensation and proprioception. They can almost always use the extra-ocular muscles whereas severe GBS would not be able to do this.
135
What are the neurological causes of loss of consciousness?
AEIOU-TIPS (Alcohol/abuse of substances/acidosis, ecstasy/epilepsy/electrolytes/encephalopathy/endocrine, Infection, Overdose/Oxygen deficiency, uraemia, trauma/tumour, Insulin, psychogenic/poisons, and stroke/shock
The brain requires adequate blood supply, CSF, oxygen, sensory input and electrolytes.
VITAMIN E (Vascular, Infective, Trauma, Autoimmune, Metabolic, Iatrogenic, Neoplastic, and Environment.
136
What are the hyper-acute causes of neurological loss of consciousness?
Electrical, vascular, arterial haemorrhage, hypoperfusion (shock) and trauma
137
What are the acute causes of neurological loss of consciousness?
Systemic metabolic, CNS infections, and venous haemorrhage (acute subdural)
138
What are the sub-acute causes of neurological loss of consciousness?
Tumours, hydrocephalus, and chronic subdural collections
139
Summarise subarachnoid hemorrhage?
Subarachnoid haemorrhage is an uncommon and severe subtype of stroke affecting patients at a mean age of 55 years, leading to loss of many years of productive life. The rupture of an intracranial aneurysm is the underlining cause in 85% of cases. Nevertheless, survivors commonly have cognitive impairments, which in turn affect patients' daily functionality, working capacity, and quality of life. Additionally, those deficits are frequently accompanied by mood disorders, fatigue, and sleep disturbances.
140
How should sub-arachnoid haemorrhage be managed?
Management is with ABCDE approach, treat acute hypertension, surgical repair of the aneurysm, and administering anti-fibrolytic drugs. Endovascular repair is the mainstay of surgical treatment but stents can be used. Antiemetic, reverse warfarin and assess analgesia requirement. There is a risk of raised ICP due to the blood blocking the CSF aqueduct which is a non-communicating hydrocephalus. Some can be treated with an LP while others can be treated with an EDV.
The increased intracranial pressure can cause global central ischaemia, global cerebral oedema, and thus early brain injury within 72 hours of aSAH. There will be a loss of gray-white differentiation on CT which shows oedema.
If DCI develops then rescue therapies such as induced hypertension and intraarterial balloon angioplasty or infusion of vasodilator drugs are recommended.
141
How is central perfusion pressure measured?
Cerebral perfusion pressure = mean arterial pressure -- intracranial pressure
142
What is the Monro-Kellie doctrine?
The Monro-Kellie doctrine states that the head is a fixed box and everything within it is incompressible.
143
How is extra-dural haematoma seen on CT?
lens shape on axial CT head.
144
Explain and describe the GCS breakdown
EYE OPENING:
1: No response
2: Pain
3: Speech
4: Spontaneous
VERBAL RESPONSE:
1: No response
2: Incomprehensible sounds
3: Inappropriate words
4: Confused
5: Orientated to time, place, and person
MOTOR RESPONSE:
1: No response
2: Abnormal extension
3: Abnormal flexion
4: Flexion withdrawal to pain
5: Moves in response to localised pain
6: Obeys commands
For GCS – localisation is flexion above the clavicle for localisation whereas flexion is below the clavicle.
145
What is the lucid interval characteristic of?
Extra dural haemorrhage
146
What is consciousness?
Consciousness requires both wakefulness and awareness. Consciousness is maintained by the reticular activating system which maintains behavioural arousal and consciousness. Consciousness therefore requires the ability to sense to the environment and the ability to process this information. Oxygen and glucose is therefore required.
147
What are the symptoms of extra-dural hemorrhage?
Drowsiness, severe headache, nausea, vomiting, confusion, weakness, dysphasia, and seizures. There is a lucid interval between initial trauma which cause LOC and then transient recovery before collapse and death.
148
How can brain herniation be managed?
Uncal herniation presents with a characteristic ipsilateral pupillary dilation. This is due to direct compression to the 3rd cranial nerve by the herniated temporal lobe. This compression impairs the parasympathetic supply to the eye (as the parasympathetic supply is located the surface of the CNIII and vulnerable to compression) and thence a loss of normal pupillary constriction function. Unopposed sympathetic function leads to a relatively dilated pupil.
In a clinical context, a blown pupil is a barometer in to the intracranial pressure and it portends a life threatening deterioration; A herniation syndrome is a neurosurgical emergency. The patient should have urgent intubation, osmotherapy and CT scan
Rationale 1: Intubation as GCS3 for airway protection but also sedation is neuroprotective. General anaesthesia reduces the depolarisation of neurones so reduces the energy demand in a situation where oxygen might be limited. Also as the blood supply to the brain is matched to its activity reducing the metabolic activity with anaesthesia reduces the demand for blood flow and reduces the intracranial blood volume, which reduces the ICP.
Rationale 2: Osmotherapy: Mannitol or hypertonic saline. These agents both transiently reduce intracranial pressure. The exact mechanism is unknown but possibilities include an improvement in the blood rheology (flow characteristics).
Importantly these agents may stimulate the normal cerebral autoregulation mechanisms to cause relative vasoconstriction. This vasoconstriction again reduces intracranial blood volume, and therefore reduces ICP. This treatment is readily available to give and can be instigated during the set up for intubation.
149
What should be done before prescribing carbamazepine?
Patients of Asian descent should be tested for HLA B1502 allele due to the increased risk of Steven-Johnson syndrome and TEN.
The medication should be considered in terms of mechanism of action, bioavailability, half-life, drug interactions and the side effect profile as these will often determine patient adherence. Reducing the dose frequency through extended-release mechanisms should be used where possible. Also consider whether a liquid or solid is better for taking medication.
150
Which AEDs can be interact with the COCP?
Carbamazepine and Topiramate RED. Lamotrigine AMBER
151
Which AEDs can be used for focal temporal epilepsy?
Carbamazepine, oxcarbazepine, levetiracetam, lamotrigine, and topiramate
152
Which AED is not allowed in pregnancy?
Sodium valproate should not be used in women of childbearing age because of the risk of teratogenic effects on the featus. Any women on SV should be on highly protective contraception.
153
Which AEDs should patients stay on the same brand of medication?
Phenytoin, carbamazepine, phenobarbital, and primidone
154
What is the importance of AEDs in breastfeeding?
Breastfeeding for most AEDs is generally safe and should be encouraged. With lamotrigine it is present in breast milk but there is no evidence that it causes any harm.
155
What is the function of CSF and what are its constituents?
CSF is a clear, colourless fluid surrounding the brain and spinal cord. It functions to protect the brain from injury, deliver nutrients and remove waste. If there is a disease or injury process this can change the composition in the CSF.
80% of the protein in CSF comes from blood, which has been filtered across the capillary endothelium into the CSF. The other 20% is synthesised in neural cells. If the endothelium is damaged or the flow of CSF is disrupted this will cause the protein concentration in CSF to increase. Causes of raised CSF protein include tumours, infection, trauma, infarction, autoimmune conditions, and inflammation. Normal range is 0.15-0.45. The amount of protein in a sample is tested for with turbidometry which assesses the cloudiness.
It is important to remember that a traumatic tap can introduced blood (not due to SAH) and therefore Hb into the CSF. This will likely give a falsely elevated CSF protein concentration. Further, protein should be interpreted in conjunction with CSF glucose for diagnosis of bacterial meningitis.
Glucose concentration is normally 2/3 of the glucose concentration in the blood. Bacteria use up glucose so if CSF glucose is low compared to plasma glucose, then this could indicate a bacterial infection in the nervous system. Viruses do not use glucose so will not affect the glucose concentration. This is measured with conversion into a coloured compound.
156
What are oligoclonal bands?
We can separate the protein in CSF by size using electrophoresis. Large protein (albumin) stays at the top and small proteins (immunoglobulins) fall to the bottom. Proteins that are the same size will form a band that can be visualised. Immunoglobulins are produced by the immune system in response to an infection so oligoclonal bands may indicate meningitis. Immunoglobulins are also produced in autoimmune conditions such as MS where autoantibodies are attacking the myelin sheath of the neurons.
157
What is the significance of Beta-Transferrin (Tau protein)?
Beta-2-Transferrin (Tau protein) is almost exclusively found in the CSF. This can be used to determine whether a fluid is CSF or not. CSF leaks can occur if the dura have become perforated through trauma or surgery. It is important that CSF leaks are quickly identified. A paired sample should be sent to exclude false positives from rare metabolic glycoprotein disorders, genetic variants of transferring or excess alcohol use.
158
What are xanthochromia tests?
Xanthochromia tests are used to diagnose SAH. Red blood cells are released in the bleed which degrade in the CSF and produce bilirubin. Since bilirubin is yellow it changes the colour of the CSF which can then be measured. This test should only be performed if the CT scan was normal but the symptoms fit.
159
What is cervical myelopathy?
This is defined as a clinical syndrome caused by compression to the spinal cord, often beginning with numb, clumsy hands. Differentials should include primary cerebral disorders, primary movements disorders and peripheral neuropathies.
160
How is cervical myelopathy investigated?
Imaging is with a T2 sagittal MRI. This is the best scan for imaging compression. The myelopathy scoring system is mJOA and the score is based on UMN, LMN, Upper extremity sensory and urinary function.
161
How is cervical myelopathy treated?
Treatment can be conservative, medical, and surgical. Conservative is with physiotherapy, coping strategies, occupational therapy, and psychological support. Medical management is with analgesia but there is no medication cure. Gabapenanoids should be used. However, if the compression symptoms are worsening then decompression should be considered.
Surgical decompression of the cervical spine does not have an excellent prognosis. 2/3s of patients will not get worse afterwards, they will likely have the same symptoms for the rest of their lives. Risks of surgical decompression include spinal cord damage so quadriplegia and even death through respiratory arrest (C3,4,5 keep the diaphragm alive). Removing the spinous process can cause kyphosis but this is only seen when the surgery is attempted posteriorly. If approached anteriorly there is a risk of damage to the oesophagus, trachea, and recurrent laryngeal nerve. There is always a risk of infection and bleeding and with any neurosurgery there is a risk of CSF leak.
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Define Coma
Coma is a neurological system failure. This is a state of impaired consciousness and arousal. Arousal is the brainstem’s reticular activating system whereas consciousness is awareness and responsiveness which are neuro-anatomically mediated by the cerebrum.
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How should a focal abscess causing seizures be managed?
Management is with phenytoin infusion, craniotomy + evacuation of infected collection and cranialisation of air sinus. Remember cranial sepsis is life threatening.
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What are the symptoms of a raised ICP headache?
Raised ICP headache is associated with blurred optic margins, failure of eye aBduction (VI palsy) which is a false localising sign due to the fragility of the VI nerve path.
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How should diplopia be categorized as neurological or ophthalmological?
Diplopia which is corrected when one eye is covered is a neurological problem (binocular) whereas monocular diplopia is due to ophthalmological dysfunction.
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What is the Frankel classification?
This is the classification system used for spinal injuries.
A: Absence of motor or sensory function below the level of the lesion
B: Absence of motor function, but with some degree of sensitivity preserved below the level of the lesion.
C: Some degree of motor function without practical usefulness
D: Useful motor function below the level of the lesion
E: Normal sensory and motor function, although there may be some abnormality of reflexes.
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What is neurogenic and spinal shock?
Neurogenic shock is when the sympathetic system is damage which causes vasodilation due to autonomic dysfunction. Spinal shock is hypoperfusion of the spinal cord which causes transient neurological symptoms.
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What imaging is used for spinal imaging?
The GOLD standard for spinal imaging is MR but CT is often more readily available and provides information on haemorrhage and fractures.
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Describe the posterior musculature of the spine
1. Superficial: Trapezius and latissimus dorsi
2. Intermediate: Serratus posterior
3. Deep: Errector spinae
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Describe the anterior musculature of the spine
1. Superficial: Cervical Scalenes and lumbar rectus abdominis
2. Deep: Cervical longus coli and lumbar psoas
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Describe the pattern of injury in Brown-Sequard
Weakness or paralysis on one side of the body and a loss of sensation on the opposite side.
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Describe the pattern of injury in anterior cord syndrome
Anterior cord syndrome is an incomplete cord syndrome that predominantly affects the anterior 2/3 of the spinal cord, characteristically resulting in motor paralysis below the level of the lesion as well as the loss of pain and temperature at and below the level of the lesion
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Describe the pattern of injury in central cord syndrome
Patients typically complain of weakness in the upper extremities (arms) and less severe weakness of the lower extremities (legs) because the arms are located in the centre of the spinal cord tracts.
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How are spinal injuries managed?
Treatment is with targeted secondary prevention or primary prevention. CT and MR scan is always required for spinal injuries and collar to prevent movement of the spine which may cause another primary injury. Secondary prevention is adequate ventilation and observations. Prevent VTE and PE is also a major priority. Avoid hypoxia, hypotension (neurogenic shock), infection and steroids.
When taking the history, the timing, mechanism of injury and movement at the scene are very important. Further, spinal conditions and conditions which may impact surgery are important. Always ask about allergies and anticoagulants. Examination should be ABCDE followed by complete neurological examination. A PR and bladder function are vital in the assessment.
Investigations are CT, MR, and X ray ABG, and bloods (Glucose, FBC, CRP and G&S). Rarely an EMG may be required.
