Neurosciences Flashcards
USMLE
Define focal and generalised seizures
Focal seizures = Electrical discharge restricted to a limited part of the cortex of one cerebral hemisphere
Generalised seizures = Simultaneous involvement of both hemispheres, always associated with loss of consciousness
Give the three types of focal seizures
Aware
Impaired awareness
Focal to bilateral tonic-clonic seizure
Give localising features of focal seizures at frontal, temporal, parietal, and occipital lobes
Frontal
* Head/leg movements
* Posturing
* Jacksonian march (progressive clonic movements travelling from distal to proximal)
* Postictal Todd’s palsy
Temporal
* Aura
- rising epigastric sensation
- psychic/experiential phenomena, déjà vu, jamais vu
- hallucinations (auditory / gustatory / olfactory)
* Automatisms
* Seizures typically last around one minute
Parietal
* Paraesthesia/numbness
* Tingling
Occipital - Spots / lines / flashes
List the motor and non-motor onset seizures
Motor onset
* automatisms
* clonic
* tonic
* atonic
* epileptic spasms
* hyperkinetic
* myoclonic
Non-motor onset
* autonomic
* behavioural arrest
* cognitive
* emotional
* sensory
Give the first line management for seizures in community
Buccal midazolam
Give the first line management for focal seizures
Lamotrigine / levetiracetam
Give the first and second line managements for generalised seizures:
Absence seizures
Generalised tonic-clonic seizures
Myoclonic seizures
Tonic/atonic seizures
Absence seizures
1. ethosuximide
2. sodium valproate
Generalised tonic-clonic seizures
1. sodium valproate
2. lamotrigine / levetiracetam (women of childbearing age, girls)
Myoclonic seizures
1. sodium valproate
2. levetiracetam (women of childbearing age, girls)
Tonic/atonic seizures
1. sodium valproate
2. lamotrigine (women of childbearing age, girls)
Name two teratogenic effects associated with phenytoin
cleft palate
congenital heart disease
Give the clinical definition for epilepsy
Any of:
* At least two unprovoked seizures occurring > 24 hours apart
* One unprovoked 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
* Diagnosis of epilepsy syndrome
Define psychogenic non-epileptic seizures
emotionally triggered attacks not associated with any paroxysmal epileptic activity in the brain
List the causes for epilepsy
(Only identified in ~⅓)
Structural
* Traumatic brain injury
* Hippocampal sclerosis
* Intracranial mass lesions
Vascular (most common cause of epilepsy in age > 60)
* Stroke
* Cavernous haemangiomas (cavernomas)
* Arteriovenous malformation
* Venous sinus thrombosis
Developmental - Cortical dysplasia
Primary generalised epilepsy - Juvenile myoclonic epilepsy
Genetic - Dravet syndrome
Infectious
* Viral encephalitis
* Meningitis
* Cerebral TB, malaria, toxoplasmosis
* HIV
* Neurocysticercosis
Metabolic abnormalities
* Hyponatraemia, hypocalcaemia, hypoglycaemia
* Acute hypoxia
* Porphyria
* Uraemia, hepatic encephalopathy
* Pyridoxine deficiency
Auto-immune CNS inflammation
* anti-NMDA receptor encephalitis
* anti-LG11 encephalitis
List the laboratory studies indicated for epileptic seizures
12-lead ECG - identify cardiac-related conditions that could mimic an epileptic seizure
Electrolyte panel (Na+, Mg2+, Ca2+)
Blood glucose
FBC - signs of systemic / CNS infection
Toxicology screen
Lumbar puncture - If fever / CNS infection suspected
EEG in all patients with suspected seizure
- focal cortical spikes or generalised spike-and-wave activity (in PGE)
Video/EEG long-term monitoring
Neuroimaging
Define status epilepticus
Prolonged convulsive seizure lasting for 5 minutes or longer, or recurrent seizures one after the other without recovery in between
List the causes for status epilepticus
Hypoxia
Trauma
Tumour
Stroke
Metabolic abnormalities
Drug/alcohol intoxication/withdrawal
Inadequate anticonvulsants in a known epileptic
Infection
Give managements for status epilepticus during the stages:
0 to 5 minutes: immediate management (stabilisation)
5 to 20 minutes: early status epilepticus
20 to 40 minutes: established status epilepticus
40 to 60 minutes: refractory status epilepticus
0 to 5 minutes: immediate management (stabilisation)
* Airway, Breathing, Circulation
* Give glucose if hypoglycaemia
* Thiamine (vitamine B1) before / at the same time as glucose if alcohol abuse or impaired nutrition
5 to 20 minutes: early status epilepticus
* IV lorazepam
20 to 40 minutes: established status epilepticus
* Second line IV anticonvulsant (levetiracetam / sodium valproate)
40 to 60 minutes: refractory status epilepticus
* Transfer to intensive care
Describe the characteristics of dysarthrias in:
Pseudobulbar palsy
Cerebellar lesions
Parkinson’s
Myasthenia gravis
Pseudobulbar palsy - gravelly speech
Cerebellar lesions - jerky ataxic speech
Parkinson’s - hypophonic monotone
Myasthenia gravis - fatigued speech, dies away
Locate the lesions on the optic tract:
(1) Mononuclear field loss
(2) Bitemporal hemianopia
(3) Homonymous hemianopia
(4) Superior homonymous quadrantanopia
(5) Inferior homonymous quadrantanopia
(6) Homonymous hemianopia with macular sparing
(7) Hemiscotoma
(1) Mononuclear field loss – complete optic nerve lesion.
(2) Bitemporal hemianopia – chiasmal lesion.
(3) Homonymous hemianopia – optic tract lesion.
(4) Superior homonymous quadrantanopia – temporal lesion (Meyer’s loop).
(5) Inferior homonymous quadrantanopia – parietal lesion.
(6) Homonymous hemianopia with macular sparing – occipital cortex or optic radiation.
(7) Hemiscotoma – occipital pole lesion.
List the triad in Horner syndrome
Partial ptosis
Unilateral miosis
Facial anhidrosis
List the causes of Horner syndrome
(Damage to sympathetic nervous supply to the eye)
Hypothalamus - infarction
Brainstem
* Brainstem demyelination
* Lateral medullary infarction
Cervical cord
* Syringomyelia
* Tumours
T1 root
* Apical lung tumour
* Tuberculosis
* Cervical rib trauma
* Brachial plexus trauma
Sympathetic chain and carotid artery
* Thyroid/laryngeal/carotid surgery
* Carotid artery dissection
* Neoplastic infiltration
* Cervical sympathectomy
Locate the lesion and list the causes when there is:
Anhidrosis of the face, arm and trunk
Anhidrosis of the face
No anhidrosis
Central lesions: anhidrosis of the face, arm and trunk
* Stroke
* Syringomyelia
* Multiple sclerosis
* Tumour
* Encephalitis
Preganglionic lesions: anhidrosis of the face
* Pancoast’s tumour
* Thyroidectomy
* Trauma
* Cervical rib
Postganglionic lesions: No anhidrosis
* Carotid artery dissection
* Carotid aneurysm
* Cavernous sinus thrombosis
* Cluster headache
Where does the vestibular schwannoma develop from
Develops from the vestibular divisions of the vestibulocochlear nerve within the internal auditory canal
List the presentations for vestibular schwannoma
Progressive unilateral sensorineural hearing loss
Tinnitus
Intermittent dizziness
Vertigo
List the causes for cerebellar syndromes
Tumours
* Hemangioblastoma
* Medulloblastoma
* Metastasis
* Compression by vestibular schwannoma
Vascular
* Haemorrhage/Infarction
* Arteriovenous malformation
Infection
* Abscess
* HIV
* Prion diseases
* Encephalitis
Developmental
* Arnold–Chiari malformation
* Cerebral palsy
Toxic and metabolic
* Antiepileptic drugs
* Chronic alcohol use
* Carbon monoxide poisoning
* Lead poisoning
* Solvent misuse
Inherited
* Friedreich’s and other spinocerebellar ataxias
* Ataxia telangiectasia
Others
* Multiple sclerosis
* Hydrocephalus
* Hypothyroidism
* Paraneoplastic syndromes (rapidly progressive)
* Multiple system atrophy
List the presentations by lateral cerebellar hemisphere lesions
Broad, ataxic gait faltering towards the side of the lesion
Rebound upward overshoot when the limb is pressed downwards and released
Dysmetria, dysdiadochokinesia
Intention tremor
Preserved speed of fine movement
Coarse horizontal nystagmus, the fast component is always towards the side of the lesion
Scanning dysarthria
Titubation
Hypotonia
Slow, pendular reflexes
List the presentations by cerebellar vermis lesions
Truncal ataxia (difficulty standing and sitting unsupported)
Broad-based, ataxic gait
List the presentations by Flocculonodular region lesions
Vertigo and vomiting
Gait ataxia
List the causes for an ischaemic stroke (85% cases)
Thrombus (atherosclerosis)
Embolus (atrial fibrillation, atherosclerosis of the carotid arteries)
Intra/extracranial vessels diseases:
* Carotid artery dissection
* Vasculitis
* Cerebral venous thrombosis
Haematological condition:
* Sickle cell anaemia
* Antiphospholipid syndrome
List the causes for an haemorrhagic stroke (15% cases)
Intracerebral haemorrhage - Hypertension
Subarachnoid haemorrhage
* Intracranial aneurysm rupture
* Arteriovenous malformations
* Arterial dissections
* Anticoagulant use
List the complications in the early period following stroke
Hemorrhagic transformation of ischaemic stroke
Cerebral oedema
Delirium
Seizures
Pulmonary embolism
Cardiac complications
* Myocardial ischemia
* Congestive heart failure
* Atrial fibrillation
* Arrhythmias
Infection
* Aspiration pneumonia
* Urinary tract infection
* Cellulitis from infected pressure sores
Describe the presentations of a TIA
Neurological dysfunction < 24 hours
Unilateral weakness/sensory loss
Dysphasia
Ataxia, vertigo, loss of balance
Syncope
Amaurosis fugax, diplopia, homonymous hemianopia
Cranial nerve deficits
List the risk factors for stroke
Lifestyle factors
* Smoking.
* Alcohol misuse and drug abuse (cocaine, methamphetamine).
* Physical inactivity.
* Poor diet.
Cardiovascular diseases:
* Hypertension
* Atrial fibrillation
* Infective endocarditis
* Valvular disease
* Carotid artery disease
* Congestive heart failure
* History of myocardial infarction
* Congenital / structural heart disease
Other medical conditions:
* Migraine.
* Hyperlipidaemia.
* Diabetes mellitus.
* Sickle cell disease.
* Haemophilia.
* Antiphospholipid syndrome and other hypercoagulable disorders.
* Chronic kidney disease.
* Ehlers-Danlos syndrome.
* Marfan syndrome.
* Pseudoxanthoma elasticum.
* Polycystic kidney disease.
* Neurofibromatosis type I.
* Obstructive sleep apnoea.
* Vascular malformations
Other factors:
* Older age
* Gender
Male sex - more likely to have a stroke at a younger age
Female sex
* Anticoagulation
* Previous TIA/stroke, family history of stroke
What increases the risk of stroke in female population
Combined oral contraceptives
Immediate postpartum period
Pre-eclampsia
List 4 risk factors for cerebral venous thrombosis
Pregnancy
Infection
Dehydration
Malignancy
List the components of the Glasgow Coma Scale
Best motor response
6 - obeys commands
5 - localising pain
4 - withdrawal from pain
3 - flexion to pain
2- extension to pain
1 - no motor response
Best verbal response
5 - oriented
4 - confused
3 - inappropriate words
2 - incomprehensible sounds
1 - no verbal response
Best eye response
4 - open spontaneously
3 - open to verbal command
2 - open to pain
1 - no eye opening
List the immediate examinations performed in stroke
The level of consciousness using Glasgow Coma Scale
Airway, breathing, and circulation
Vital signs
* Blood pressure
* Heart rate
* Respiratory rate
* Oxygen saturation
* Temperature
Focused neurological examination - Face Arm Speech Test (FAST)
The cardiovascular system
* Arrhythmia (atrial fibrillation)
* Murmurs
* Pulmonary oedema
* Heart failure
Give the immediate management of a suspected TIA
Aspirin 300 mg immediately
* PPI cover if dyspepsia
* Clopidogrel if aspirin contraindicated
Give the management for secondary prevention of stroke
No AF - Antiplatelet therapy
* clopidogrel 75 mg
* Intolerance - Aspirin 75 mg daily with modified-release dipyridamole 200 mg twice daily
AF - Anticoagulant drugs
* Valvular AF - Adjusted-dose warfarin
* Non-valvular AF - Direct thrombin (Dabigatran) / factor Xa inhibitor (Apixaban, Betrixaban, Edoxaban, Rivaroxaban)
High-intensity statin - Atorvastatin 20-80 mg daily
Antihypertensive drugs
In which patients non-contrast head CT should be performed within 1 hour?
To exclude intracranial haemorrhage:
Indicated for thrombolysis or thrombectomy
On anticoagulant treatment
Known bleeding tendency
Depressed level of consciousness (GCS scale score <13)
Unexplained progressive / fluctuating symptoms
Papilloedema, neck stiffness, fever
Severe headache at onset of stroke symptoms
Uncertain diagnosis
Give features on a non-contrast CT head for an ischaemic stroke
hypoattenuation (darkness) of the brain parenchyma
loss of grey-white matter differentiation, sulcal effacement
hyperattenuation (brightness) in an artery indicates clot
What laboratory studies should be indicated in an ischaemic stroke
Serum glucose - hypo/hyperglycaemia (before thrombolysis)
Serum electrolytes - electrolyte disturbance
Serum urea and creatinine - renal failure
Cardiac enzymes - concomitant myocardial infarction
ECG - cardiac arrhythmia/ischaemia
FBC - anaemia/thrombocytopenia before thrombolysis, anticoagulants, or antithrombotics.
PT and aPTT (with INR) - coagulopathy.
Give the managements in an ischaemic stroke
IV alteplase / tenecteplase within 4.5 hours of known onset
Manage ABC
* Endotracheal intubation if unable to protect their airway or GCS score ≤8
* Supplemental oxygen if sat < 93%
Mechanical thrombectomy if confirmed occlusion of the proximal anterior circulation (ICA/M1) or the proximal posterior circulation (basilar/PCA).
Give the most common cause of intracerebral haemorrhage
Chronic hypertension resulting in
* Rupture of microaneurysms (Charcot–Bouchard aneurysms)
* Degeneration of small, deep, penetrating arteries
List the Nonhypertensive Causes of Intracerebral Haemorrhage
Cerebral amyloid angiopathy
Vascular malformations
* Saccular/mycotic aneurysms
* Arteriovenous malformations
* Cavernous angiomas
* Moyamoya disease
Intracranial tumours
Bleeding disorders, anticoagulant and fibrinolytic treatment
Vasculitides
* Granulomatous angiitis of the central nervous system
* Polyarteritis nodosa
Sympathomimetic agents
* Amphetamine
* Cocaine
Hemorrhagic infarction
Head trauma
Septic emboli/arteritis in the setting of infective endocarditis
Give the non-contrast CT imaging features for an intracerebral haemorrhage
hyperattenuation (brightness), suggesting acute blood, often with surrounding hypoattenuation (darkness) due to oedema
List 4 causes for a nontraumatic subarachnoid haemorrhage
Aneurysm rupture (80%)
Arteriovenous malformations
Arterial dissections
Anticoagulant use
List the symptoms for a subarachnoid haemorrhage
Thunderclap headache
Neck stiffness
Nausea and Vomiting
Photophobia
Loss of consciousness
Seizures (7%)
Diplopia (CN VI), eyelid drooping, mydriasis, orbital pain (CN III)
Visual loss (Intraocular haemorrhage from increased ICP)
Agitation
Focal neurological deficits
* Unilateral loss of motor function
* Loss of visual field
* Aphasia
Give the non-contrast CT imaging features for a subarachnoid haemorrhage
Presence of hyperdense appearance of blood in the subarachnoid space / basal cisterns
List two differentials for a sudden onset of severe headache and an elevated CSF opening pressure
cerebral venous sinus thrombosis
idiopathic intracranial hypertension
What may a sudden onset of severe headache and a reduced CSF opening pressure suggest
low pressure headache
List two cardiac complications from an aneurysm rupture
Left ventricular subendocardial injury
Takotsubo cardiomyopathy
List the investigations and findings after a subarachnoid haemorrhage
Full blood count - Leukocytosis (independent risk factor for cerebral vasospasm)
Serum electrolytes - Hyponatremia (associated with SIADH)
Serum glucose - Hyperglycemia (Present in ⅓. Feature of any acute brain injury)
Clotting profile - coagulopathy (elevated INR, prolonged PTT)
Serum troponin I - Elevated (acute myocardial injury due to autonomic dysregulation with sympathetic stimulation)
ECG
* Arrhythmias and ischaemic changes
* Prolonged QT
* ST segment / T wave abnormalities
Give the immediate medical management for SAH
Oral nimodipine
List the management approaches towards an intracerebral haemorrhage
IV mannitol - reduce ICP
Stop / reverse anticoagulation
BP control < 140 mmHg systolic
Surgical eg. EVD
List the signs of rebleeding after SAH
Sudden drop in conscious level
Spike in blood pressure
Tonic/extensor posturing
Pupillary changes
List the management approaches for rebleeding after SAH
Early aneurysm repair
Short-term Tranexamic acid
What are the short term complications after SAH
Rebleeding
Acute hydrocephalus
Seizures
Vasospasm and delayed cerebral ischaemia
Give signs of an acute hydrocephalus after SAH
A gradually worsening level of arousal with relative preservation of deliberate motor responses
Severe headache/vomiting/agitation
Give a management approach for acute hydrocephalus after SAH
CSF drainage or diversion
Give signs for a vasospasm and delayed cerebral ischaemia after SAH
≥ 2 drop in GCS score
New focal neurological deficit (e.g., unilateral motor or sensory loss, speech disturbance, visual field loss)
List the management approaches in vasospasm and delayed cerebral ischaemia after SAH
Triple-H (uses hypertension, hypervolaemia, and haemodilution)
Endovascular strategies (balloon angioplasty / intra-arterial vasodilators)
List the risk factors for cerebral aneurysms
Hereditary connective tissue diseases:
* ADPKD
* Neurofibromatosis type 1
* Ehlers-Danlos syndrome type IV
* Marfan’s syndrome
Hypertension
Arteriovenous malformations/fistulas
Smoking, Alcohol, Drug abuse
List the causes for subdural haematoma
Trauma (most common)
Rupture of a cerebral aneurysm
Vascular malformation
* AVM
* Dural fistula
What does acute SDH typically result from?
torsional / shear forces causing disruption of bridging cortical veins
List the CT appearances in SDH
Acute - <3 days old, diffusely hyperdense
Subacute - 3~21 days old, heterogeneously hyperdense/isodense
Chronic - >21 days old, diffusely hypodense
Acute-on-chronic - areas of hyperdensity within hypodense haematoma
List the signs of a skull base fracture
Raccoon eyes
CSF rhinorrhea
CSF otorrhea
Haemotympanum
Give the typical time line in extradural haemorrhage
Head injury with a brief duration of unconsciousness
Followed by improvement (lucid interval)
Then becomes stuporose
* Ipsilateral dilated pupil
* Contralateral hemiparesis
* Transtentorial coning
Followed by
* Bilateral fixed, dilated pupils
* Tetraplegia
* Respiratory arrest
List the differential diagnoses for dementia syndrome
Normal-age related memory changes
Mild cognitive impairment
Depression
Delirium
Thiamine deficiency (Wernicke-Korsakoff’s syndrome)
Hypothyroidism
Normal pressure hydrocephalus
List the risk factors for dementia syndrome
Age
Mild cognitive impairment (MCI)
Learning disability
Genetics
Cardiovascular disease
Cerebrovascular disease
Parkinson’s disease (PD)
List the causes for dementia syndrome
Alzheimer’s disease (50–75% of cases)
Vascular dementia (up to 20% of cases)
Dementia with Lewy bodies (DLB) (10–15% of cases)
Frontotemporal dementia (FTD) (2% of cases)
Other causes of dementia:
Parkinson’s disease (PD) dementia
Progressive supranuclear palsy
Huntington’s disease
Cretzfeldt-Jakob disease (Prion disease)
Normal pressure hydrocephalus
Chronic subdural haematoma
Benign tumours
Metabolic and endocrine disorders
* Chronic hypothyroidism
* Addison’s disease
* Hypopituitarism
Vitamin deficiencies (B12, thiamine)
Infections (HIV, syphilis)
Inflammatory and autoimmune disorders
Transient epileptic amnesia
Name two pathological findings in Alzheimer’s disease
extracellular plaques composed primarily of amyloid
intraneuronal neurofibrillary tangles composed primarily of hyperphosphorylated tau
List the specific features for Alzheimer’s disease
Loss of recent memory first
Difficulty with executive function / nominal dysphasia
Loss of episodic memory
Cognitive deficits - aphasia, apraxia, agnosia
List the management for Alzheimer’s disease
Acetylcholinesterase (AChE) inhibitors - mild to moderate AD
* Donepezil
* Rivastigmine
* Galantamine
Memantine (N-methyl-D-aspartic acid receptor antagonist) - moderate to severe AD
List the causes for vascular dementia
Large / multiple small infarcts
Haemorrhage
Cerebral amyloid angiopathy
Subcortical leukoencephalopathy
List the specific features in vascular dementia
Stepwise increase in severity of symptoms
Focal neurological signs eg. hemiparesis / visual field defects
List the specific features for Dementia with Lewy Bodies
REM sleep behaviour disorder
Fluctuating cognition
Recurrent visual hallucinations
One or more symptoms of Parkinsonism - bradykinesia, rest tremor, rigidity, postural instability
Memory impairment in later stages
Give the first line management in Dementia with Lewy Bodies
donepezil or rivastigmine
List four conditions which Frontotemporal dementia maybe associated with
Amyotrophic lateral sclerosis (ALS)
Parkinsonism
Corticobasal degeneration
Progressive supranuclear palsy
What drugs should FTD not be offered with
AChEi
Memantine
List the diagnostic criteria for delirium
Evident disturbance in attention
Cognitive change
Develops over a short period of time
Evident physiological disturbance
Give three clinical subtypes of delirium
Hyperactive
Hypoactive
Mixed
List the common causes of delirium
PINCHME:
Pain
Infection
Nutrition
Constipation
deHydration
Medication
Environment
Give the pathophysiology of migraine
Headache of migraine results from neurogenic inflammation of CNV1 sensory neurons (Innervates the large vessels and meninges of the brain)
CNV neurons release substances that cause dilation of the meningeal blood vessels, leakage of plasma proteins into surrounding tissues, and platelet activation.
This peripheral sensitisation results in increased nociceptive inputs into CNV sensory nucleus and ultimately central sensitisation. Therefore, non-painful stimuli (eg. light touch) are interpreted as pain.
Give key features of migraine
Intermittent Headache
Visual disturbance
Nausea and vomiting
Photophobia and phonophobia
Reduced ability to function
List the management approaches to migraine
aspirin (900 mg)
sumatriptan
List the medication for prophylaxis in migraine
propanolol
List the triggers for tension type headache
Psychological stress (most common)
Disturbed sleep patterns (episodic)
Insomnia and other sleep disorders (chronic)
Describe the clinical features in tension headache
Dull, non-pulsatile pain (typically expressed as being a ‘tight band’ around the head)
list the medication for an acute attack of tension headache
Aspirin
What may cluster headache be precipitated by?
Alcohol
Volatile smells
Warm temperatures
Sleep
List three cardinal features in cluster headache
Trigeminal distribution of the pain
Ipsilateral cranial autonomic symptoms
Circadian/circannual pattern of attacks
Give the International Headache Society (IHS) diagnostic criteria for cluster headache
Severe unilateral orbital, supra-orbital, and/or temporal pain lasting 15 to 180 minutes
At least one of the following symptoms or signs, ipsilateral to the headache:
* Conjunctival injection, lacrimation
* Nasal congestion, Rhinorrhoea
* Eyelid oedema, Facial and forehead sweating
* Miosis, Ptosis
* Sense of restlessness or agitation.
Give the acute attack therapy in cluster headaches
subcutaneous sumatriptan / nasal zolmitriptan
High flow oxygen
Give the preventative therapy in cluster headaches
Verapamil
Give the symptom in trigeminal neuralgia
Unilateral paroxysms of facial pain lasting seconds to minutes in a distribution along ≥1 divisions of the CNV
Describe the pathophysiology in trigeminal neuralgia
Neuropathic pain due to focal demyelination and resultant conduction aberration
List the triggers for trigeminal neuralgia
Tooth brushing
Eating
Cold
Touch
Give the medical management in trigeminal neuralgia
Carbamazepine
Oxcarbazepine
Give one complications for giant cell arteritis
irreversible vision loss due to optic nerve ischaemia
List the presentations in giant cell arteritis
Age >50 yrs
New onset headache
Limb, jaw, tongue claudication
Scalp tenderness
Acute visual symptoms (amaurosis fugax)
Unexplained raised ESR/CRP
Constitutional symptoms:
* Fever
* Fatigue
* Night sweats
* Weight loss
Give the medical management in giant cell arteritis
IV high-dose methylprednisolone
Give the histological features in giant cell arteritis
Granulomatous inflammation of the intima and media
Breaking up of the internal elastic lamina
Giant cells, lymphocytes and plasma cells in the internal elastic lamina
List the spinal reflex arcs and their levels
S1-2 Ankle
L3-4 Knee jerk
C5-6 Biceps
C7-8 Triceps
Describe the patterns of sensory loss in the following lesions
(A) Thalamic lesion (rare)
(B) Brainstem lesion
(C) Central cord lesion
(D) Hemisection of cord/unilateral cord lesion
(E) Transverse cord lesion
(F) Dorsal column lesion
(G) Individual sensory root lesions
(H) Polyneuropathy
(A) Thalamic - sensory loss throughout the opposite side.
(B) Brainstem - contralateral sensory loss below face and ipsilateral loss on face.
(C) Central cord - ‘suspended’ areas of loss, often asymmetrical and ‘dissociated’: i.e. pain and temperature lost but light touch intact.
syrinx
(D) Hemisection of cord/unilateral cord lesion - Brown–Séquard syndrome: contralateral spinothalamic (pain and temperature) loss with ipsilateral weakness and dorsal column loss below lesion.
(E) Transverse cord - loss of all modalities, including motor, below lesion.
(F) Dorsal column - loss of proprioception, vibration and light touch. (multiple sclerosis)
(G) Individual sensory root lesions, e.g. C6, T5, L4.
(H) Polyneuropathy - distal sensory loss. UMN, upper motor neuron.
List the presentations in central cord syndromes
Weakness in the upper extremities greater than the lower
Pain and temperature loss 2/3 levels caudal to the lesion
Loss of bladder control
If lesion expands:
* bilateral spastic paraparesis of the lower extremities
* asymmetric upper extremity paraparesis
List the presentations in anterior cord syndromes
(Involve the anterior two-thirds of the spinal cord)
Pain, temperature, and motor function below the level of the lesion lost
Vibration, proprioception, and fine touch sensation intact
List the presentations in posterior column syndrome
Loss of vibration and proprioception
Spastic paraparesis and brisk reflexes
Urgency and incontinence
Retained pain and temperature sensation
List the presentations in syringomyelia
‘Suspended’ area of dissociated sensory loss (cape like distribution)
Loss of upper limb reflexes
Hand and forearm muscle wasting
Spastic paraparesis (initially mild)
Brainstem signs (syringobulbia)
* Tongue atrophy and fasciculation
* Bulbar palsy
* Horner’s syndrome
* Impairment of facial sensation
List the causes for spinal cord compression
Spinal cord tumours
* Extramedullary - meningioma, neurofibroma
* Intramedullary - ependymoma, glioma
Bony metastases (vertebral body destruction)
Disc and vertebral lesions:
* Chronic degenerative
* Acute central disc prolapse
* Trauma
Inflammatory:
* Epidural abscess
* Tuberculosis
* Granulomatous
Epidural haemorrhage / haematoma
List the signs for cervical spondylotic radiculopathy
Radiating arm pain
Mild weakness in the muscles
Reflex changes
List the signs for degenerative cervical myelopathy
Loss of hand coordination
Hand intrinsic muscles weakness eg. interossei
Mild gait ataxia (impaired position sense)
Bowel and bladder difficulties in severe cases
List the metastatic causes for malignant spinal cord compression
Prostate
Breast
Lung
Renal
Thyroid
List the lab tests ordered in malignant spinal cord compression
serum calcium levels - hypercalcaemia
serum ALP - elevated
cancer-specific laboratory testing
* prostate specific antigen (PSA)
* breast cancer genes 1 and 2 (BRCA1 and 2)
* carcinoembryonic antigen (CEA)
* serum and urine protein electrophoresis
List the afferent and efferent pupillary light reflex pathway
Afferent pathway:
1. Light activates optic nerve axons.
2. Axons (some decussating at the chiasm) pass through each lateral geniculate body
3. Synapse at pretectal nuclei.
Efferent pathway:
4. Action potentials pass to Edinger–Westphal nuclei of the CN III
5. Via parasympathetic neurons in CN III to cause
6. Pupil constriction
List the signs of a left APD
Absent direct and consensual reflex
Intact consensual reflex of the right eye
What does an incomplete damage to one optic nerve relative to the other cause?
Relative afferent pupillary defect
What is internuclear ophthalmoplegia caused by
lesion of the medial longitudinal fasciculus
List the major cause of internuclear ophthalmoplegia
Multiple sclerosis
List the signs of internuclear ophthalmoplegia
Ipsilesional adduction deficit
Contralateral, horizontal abducting nystagmus on attempted gaze to the contralesional side
List the signs of large vestibular schwannoma
Headache
CN5 compression
* Hemifacial hypo/paraesthesia
* Trigeminal neuralgia
CN7 compression - Facial spasm/weakness
4th ventricle compression - Obstructive hydrocephalus
Cerebellar displacement
* Nystagmus
* Ataxia
List the central and peripheral causes of vertigo
Peripheral
* Benign paroxysmal positional vertigo
* Meniere’s disease
* Labyrinthitis
* Labyrinthine concussion
* Vestibular neuronitis
* Vestibular ototoxicity
* Perilymphatic fistula
* Semicircular canal dehiscence syndrome
* Syphilis
Central
* Migraine
* Stroke
* Cerebellar tumour
* Vestibular schwannoma
* Multiple sclerosis
List the vestibular migraine features
vertigo
visual disorders
occipital pressure
nausea and vomiting
Give the major mechanisms of all subtypes of BPPV
Canalithiasis
Give the major mechanism of lateral canal BPPV
Cupulolithiasis
List the secondary causes of BPPV
Head trauma
Labyrinthitis
Vestibular neuronitis
Meniere’s disease (endolymphatic hydrops)
Migraines
Ischaemia
Iatrogenic
List the subtypes of BPPV
Posterior canal
Lateral canal
Superior canal
Give the presentation of BPPV
Sensation that the environment is spinning around relative to oneself
Sudden onset and intense vertigo
Precipitated by head movements
Short duration
Episodic and recurrent
What does the Dix-Hallpike manoeuvre test for?
Posterior canal BPPV
Describe the Dix-Hallpike manoeuvre
- The patient sits on the examination table
- their head is turned 45° to one side
- then they are laid back into a supine position, with the head hanging back but supported by the examiner and the neck extended by about 30°
Describe the Dix-Hallpike manoeuvre findings in right sided BPPV
Eyes rotate in an anticlockwise manner during the fast phase of nystagmus
With a slight up-beating vertical component (towards the forehead)
Describe the Dix-Hallpike manoeuvre findings in left sided BPPV
Eyes rotate in a clockwise manner during the fast phase of nystagmus
With a slight up-beating vertical component (towards the forehead)
What does supine lateral head turns test for
lateral canal BPPV
Give the hallmark feature in lateral canal BPPV, when tested by supine lateral head turns
pure horizontal nystagmus without a torsional (rotatory) component
List the signs of canalithiasis, when tested by supine lateral head turns
horizontal nystagmus with the fast phase beating towards the ground (geotropic)
the side with the stronger response is the affected side
List the signs of cupulolithiasis, when tested by supine lateral head turns
the fast phase beats away from the ground (apogeotropic)
the side with the weaker response is the affected side
Give the management for BPPV
Particle repositioning manoeuvre
Define Meniere’s disease
Endolymphatic hydrops - overproduction or impaired absorption of endolymph
Give the classic presentation in Meniere’s disease
Episodic sudden onset of vertigo, hearing loss, tinnitus, and sensation of fullness in the affected ear.
List the signs in Meniere’s disease
Positive Romberg’s test
Inability to walk tandem (heel to toe) in a straight line
Fukuda stepping test (march in place with eyes closed) - unable to maintain position and turn towards the affected side
List the management options in Meniere’s disease
Salt restriction to 1500~2300 mg/day - prevent Na+ related water retention and re-distribution into the endolymphatic system
Thiazide diuretics
Lifestyle:
* Limit caffeine
* Reduce alcohol
* Ceasing smoking
* Managing stress
Define Labyrinthitis
Inflammation of the otic capsule:
* Cochlea
* Three orthogonal semi-circular canals
* Otolith organs (utricle, saccule)
What does suppurative (bacterial) labyrinthitis present with
severe to profound hearing loss (typically irreversible) and vertigo
What is suppurative (bacterial) labyrinthitis associated with?
(Direct microbial invasion of the inner ear)
Acute/chronic otitis media
Cholesteatoma
Meningitis
List the potential bacterial causes in suppurative (bacterial) labyrinthitis
Treponema pallidum
Haemophilus influenzae
Streptococcus species
Staphylococcus species
Neisseria meningitidis
What does serous (viral) labyrinthitis present with
less severe hearing loss (often reversible) and vertigo than suppurative labyrinthitis.
Is suppurative (bacterial) labyrinthitis more common in adults or children
adults
What is serous (viral) labyrinthitis associated with
Preceding URTI
Autoimmune inner ear disease
* Cogan’s syndrome
* Behçet’s disease
List the viral agents involved in serous (viral) labyrinthitis
Varicella zoster virus
Cytomegalovirus
Mumps, measles, rubella
HIV
List the presentations in labyrinthitis
Unilateral sensorineural hearing loss
Tinnitus
Vertigo with nausea and vomiting
List the signs in labyrinthitis
Spontaneous horizontal-rotary nystagmus - fast phase beating towards the normal ear
Significant difficulty walking
Unable to perform tandem gait
Fall with Romberg’s testing
List the causes of vestibular neuronitis
Inflammation of the vestibular nerve (after a viral infection)
Secondary to ischaemia of the anterior vestibular artery
How to differentiate vestibular neuronitis with labyrinthitis
hearing is not affected in vestibular neuronitis.
List the complications in vestibular neuronitis
BPPV
Persistent postural perceptual dizziness (PPPD)
Oscilloposia
List the presentations in vestibular neuronitis
Spontaneous vertigo
* Exacerbated by changes of head position
* Acute symptoms settle in a few days and recovery over 2–6 weeks.
Imbalance (veer to the affected side)
Nausea and vomiting
Autonomic symptoms
* Malaise
* Pallor
* Sweating
Give the ocular sign in vestibular neuronitis
Nystagmus with the fast phase away from the affected ear
Give the symptomatic managements for nausea, vomiting, vertigo in vestibular neuronitis
Buccal prochlorperazine
Intramuscular prochlorperazine / cyclizine
List the four characteristic features of Parkinsonism
Bradykinesia
Tremor
Rigidity
Postural instability
List the causes of Parkinsonism
Parkinson’s disease
Vascular Parkinsonism
Drug induced
Parkinson-plus syndromes
* Lewy body dementia
* Multiple system atrophy
* Progressive supranuclear palsy
* Corticobasal degeneration
Wilson’s disease
Repeated head injury
List the drugs that may cause Parkinsonism
First generation antipsychotics (fluphenazine, trifluoperazine, haloperidol, chlorpromazine, flupentixol, zuclopenthixol)
Antiemetics (prochlorperazine, metoclopramide)
List the symptoms in multiple system atrophy
Parkinsonism
Severe early autonomic dysfunction:
* Symptomatic hypotension
* Constipation / Urinary retention
* Faecal / Urinary urge incontinence
* Persistent erectile dysfunction
Speech/bulbar dysfunction
Pyramidal/cerebellar dysfunction
Poor response to levodopa
List the symptoms of progressive supranuclear palsy
Parkinsonism
Early dysphagia
Vertical gaze palsy
Recurrent falls (postural instability)
List the symptoms of corticobasal degeneration
Parkinsonism
Asymmetric rigidity and dystonia
Cortical sensory loss
Progressive aphasia
Apraxia
Cognitive impairment
Alien limb phenomenon
List the symptoms of Wilson’s disease
Kayser-Fleischer rings
Variable neurological signs including tremor, ataxia, dystonia
Non-specific liver disease
List the symptoms in Parkinson’s disease
Tremor at rest
Rigidity
Bradykinesia
Postural instability
Autonomic dysfunction
* Orthostatic hypotension
* Swallowing problems
* Excessive salivation
* Weight loss
* Urinary symptoms
* Constipation
* Sexual problems
Non-motor symptoms
* Depression, anxiety, and fatigue
* Anosmia
* Cognitive impairment
* REM sleep behaviour disorder
* Pain
List the pathologies in Parkinson’s disease
Selective loss of nigrostriatal dopaminergic neurons in the substantia nigra pars compacta (SNc)
Intracytoplasmic eosinophilic inclusions (Lewy bodies) and neurites, composed of alpha-synuclein
Give the pathophysiology in Parkinson’s disease
- Decreased activity of the direct pathway and increased activity of the indirect pathway
- Increased inhibitory activity from the GPi/SNr to the thalamus
- Reduced output to the cortex
List the symptomatic management options in Parkinson’s
Levodopa
Monoamine oxidase-B (MAO-B) inhibitors
* Selegiline
* Rasagiline
* Safinamide
Dopamine agonists
* Pramipexole (oral)
* Ropinirole (oral)
* Rotigotine (transdermal)
List the side effects of levodopa
Dyskinesia
Excessive sleepiness
Hallucinations
Impulse control disorders
List the causes of tremor
Essential tremor
Postural and action tremor
* Dystonic tremor
* Hyperthyroidism
* Drugs eg. beta2-agonists
Intention tremor - cerebellar disorder
List the presentations in essential tremor
Postural tremor - worse if arms outstretched
Bilateral and symmetrical
Involves the head, neck, voice, and limbs
Worsen with
* stress
* caffeine
* sleep deprivation
Improves
* alcohol
* beta-blockers
List the presentations in Huntington’s disease
Chorea
Incoordination
Cognitive decline
Personality changes
Psychiatric symptoms
List the causes of chorea
Systemic disease
* Thyrotoxicosis
* SLE
* Antiphospholipid syndrome
* Polycythaemia vera
Genetics
* Huntington’s disease
* Neuroacanthocytosis
* Benign hereditary chorea
Structural and vascular disorders of the basal ganglia
Drugs
* Levodopa
* Oral contraceptives
Post-infectious (Sydenham’s chorea)
Pregnancy
List the management options for depression in Huntington’s disease
Fluoxetine (SSRI)
Buspirone
Benzodiazepines
Give the inheritance and genetic mechanism in myoclonic dystonia
Autosomal dominant disorder
Mutation in ε-sarcoglycan gene
List the characteristics in Tourette’s syndrome
Childhood onset
Motor and vocal tics
Psychiatric disorders (OCD, ADHD)
Give the first line management for tics in Tourette’s syndrome
Comprehensive behavioural intervention for tics
List the pharmacological therapies in Tourette’s syndrome
Alpha-2 agonist (monotherapy at minimal dosage)
* Clonidine
* Guanfacine
Antipsychotics
* Aripiprazole
* Risperidone
* Ziprasidone
Botulinum toxin
Define geste antagoniste
Dystonia may improve with simple ‘sensory tricks’ such as lightly touching the affected body part
List the presentations in focal dystonia
Axial
* Blepharospasm
* Cervical torticollis
Limb
* Task related (writer’s cramp)
* Foot
* Orofacial/mandibular
Give one cause of early-onset (<26 years) dystonia
TOR1A gene mutations
List the management options of generalised dystonias
Levodopa
Trihexyphenidyl (anticholinergic)
Pallidal deep brain stimulation
List the four clinical patterns of motor neurone disease
Amyotrophic lateral sclerosis
Progressive muscular atrophy
Progressive bulbar and pseudobulbar palsy
Primary lateral sclerosis
List the presentations in progressive muscular atrophy
Pure LMN presentation
Weakness
Muscle wasting
Fasciculations
Usually starting in one limb and gradually spreading to involve other adjacent spinal segments
List the presentations of primary lateral sclerosis
UMN disorder
Slowly progressive tetraparesis and pseudobulbar palsy
List the UMN signs
Mild weakness
Spasticity
Hyperreflexia and clonus
Pathological reflexes:
* Babinski
* Hoffmann sign
* Loss of abdominal reflexes
List the LMN signs
Moderate to severe weakness
Atrophy
Hyporeflexia
Flaccidity
Fasciculations
List the aetiologies in ALS
Sporadic (mostly)
Genetic
* free radical scavenging enzyme superoxide dismutase (SOD-1) - missense mutations
* C9orf72
* TDP-43
* FUS
List the initial symptoms in ALS
Isolated dysarthria
Hand weakness
Foot drop
Gait changes
Shortness of breath
What is familial ALS associated with
FTD
List the physical examination findings in ALS
Typical UMN findings:
Loss of coordinated movement
Spasticity
Muscle spasms
Pronator drift
Hyperreflexia
* Babinski’s sign
* Hoffmann’s reflex
* Crossed adductors
* Exaggerated jaw jerk
* Primitive reflexes: palmomental/snout reflex
Typical LMN findings:
Weakness
Atrophy
Fasciculations
Split-hand phenomenon - severe changes in the thenar eminence but relative sparing of the hypothenar eminence
Give the diagnostic criteria in ALS
(El Escorial Diagnostic Criteria)
Definite ALS - UMN and LMN signs in at least 3 regions
Probable ALS - UMN and LMN signs in 2 regions, with some UMN signs rostral to LMN signs
List the investigations for ALS
Nerve conduction studies
* Diminished CMAP
* Normal sensory nerve conduction study
Electromyography
* Fasciculation potentials
* Acute (positive sharp waves and fibrillation potentials) + chronic (reduced neurogenic firing pattern, polyphasic motor unit potentials) changes
List other tests to exclude in ALS
Nerve conduction studies - Rule out peripheral nerve disease mimicking ALS eg. multifocal motor neuropathy
If NCS suggests possible peripheral nerve disease, blood tests to assess:
* Vitamin B₁₂ level
* Specific antibodies (anti-GM1, acetylcholine receptor, muscle-specific tyrosine kinase, voltage-gated calcium-channel antibodies)
Neuroimaging - Exclude structural, inflammatory, or infiltrative disorders
Lumbar puncture - Exclude infectious diseases
Give the 1st line and alternative Disease-modifying pharmacological therapies for ALS
1st line: Riluzole
Edaravone (antioxidant)
Sodium phenylbutyrate / tauroursodeoxycholic acid
Give the mechanism of Riluzole
Glutamate inhibitor, reduces excitotoxicity
Give two adverse effects associated with riluzole
Hepatotoxicity and neutropenia (rare)
LFT and FBC monthly for first 3 months, then every 3 months
Give the mutation in DMD and Becker muscular dystrophy
Dystrophin - exon deletions
Give the inheritance of DMD
X-linked recessive
What do the mutations in Emery-Dreifuss muscular dystrophy affect
Nuclear envelope proteins
* Emerin (X-linked recessive)
* Lamin A/C (autosomal dominant)
Give the mutations in Facioscapulohumeral muscular dystrophy
Small deletion on chromosome 4 affecting
D4Z4 region in FSHD1 (95%)
SMCHD1 region in FSHD2
Give the inheritance in Facioscapulohumeral muscular dystrophy
Autosomal dominant
Spontaneous mutations (up to 30%)
Give the mutation in Myotonic dystrophy type 1 (DM1)
CTG triplet repeat expansion in the 3’ non-coding region of DMPK
Give the onset age for Limb-girdle muscular dystrophies
10~20 years
Give the onset age for Facioscapulohumeral muscular dystrophy
10–40 years
What muscles are predominantly affected in Limb-girdle muscular dystrophies
Proximal: shoulders, pelvic girdle
What muscles are predominantly affected in facioscapulohumeral muscular dystrophies
Face, shoulders, scapular winging, upper arms, foot drop.
Typically asymmetric
What are the associated features in facioscapulohumeral muscular dystrophies
deafness and retinal abnormalities
Give the prognosis in Limb-girdle muscular dystrophies
Severe disability <25 years
Give the prognosis in facioscapulohumeral muscular dystrophies
Life expectancy normal, slow progression
Give the pathophysiology in DMD
Xp21 defect / deletion results in the absence of dystrophin (sarcolemma-associated protein)
Provides structural stability to the dystroglycan complex in cell membranes
Results in ongoing cell membrane depolarisation due to calcium entering the cell
Causes ongoing degeneration and regeneration of muscle fibres
Degeneration is faster than regeneration, and muscle fibres undergo necrosis
Muscle fibres are replaced by adipose and connective tissue, causing the muscles to progressively weaken
List the classic presentation in Duchenne muscular dystrophy
Toddler with
* Delayed motor milestones
* Calf hypertrophy
* Proximal hip girdle muscle weakness
* Marked elevation of serum creatine kinase
List the physical examination findings in Duchenne muscular dystrophy
Imbalance of strength at all lower extremity pivots
Relatively weaker hip extensors, knee extensors, and ankle dorsiflexors
Physical signs:
* Gowers’ sign
* Musculotendinous contractures - imbalance of lower body strength
* Increased lumbar lordosis and heel cord contractures
List the management options for DMD
Corticosteroid therapy - Preserve muscle strength
Prevention/reduction of musculotendinous contractures
Physiotherapy
List the novel oral direct factor Xa inhibitors
Apixaban
Betrixaban
Edoxaban
Rivaroxaban
List the novel oral direct factor IIa inhibitors
Dabigatran
List the presentations in Anterior cerebral artery syndrome
Contralateral hemiparesis and sensory loss of lower limbs
Anosmia
Anterior corpus callosum involvement - alien hand syndrome
Pericallosal branch involvement - apraxia, agraphia, tactile anomia of the left hand
List the presentations in infarction of the Inferior division of dominant MCA
Contralateral homonymous hemianopia or upper quadrant anopsia
Receptive aphasia (Wernicke)
List the presentations in infarction of the superior division of dominant MCA
Contralateral weakness (affects the lower face and arm more than the leg)
Contralateral sensory loss (including the face)
Contralateral hemineglect
Expressive aphasia (Broca)
List the presentations in infarction of the Whole of the dominant MCA
(Gerstmann syndrome)
Agraphia, Acalculia, Finger agnosia
Right-left disorientation
Contralateral weakness, sensory loss
Contralateral hemineglect
Contralateral homonymous hemianopia
Global aphasia (receptive and expressive)
List the signs of elevated ICP
Reducing level of consciousness
Severe headache
Nausea/vomiting
Sudden increase in blood pressure
Give the presentations in occlusion of one of the paramedian branches of the basilar artery
Weber syndrome (Ventromedial midbrain)
* Ipsilateral oculomotor nerve palsy
* Contralateral hemiplegia
Give the presentations in Anterior inferior cerebellar artery (AICA) infarction
(Lateral pontine syndrome (Marie-Foix Syndrome))
Ipsilateral cerebellar ataxia (arm and leg)
Ipsilateral facial weakness
Ipsilateral deafness, vertigo, nystagmus (CN VIII palsy)
Contralateral weakness (corticospinal tract)
Contralateral pain and temperature loss (spinothalamic tract)
List the presentations in Posterior inferior cerebellar artery (PICA) infarction
(Lateral medullary syndrome (Wallenberg Syndrome))
Ipsilateral
* Loss of gag reflex
* Facial sensory loss
* Horner’s syndrome
* Nystagmus
* Ataxia
Contralateral - Pain and temperature sensory loss in the extremities
Generally
* Vertigo
* Nausea
* Dysphagia
Give the transitional therapy options in cluster headache
Prednisolone
IV dihydroergotamine (Contraindicated in patients with CV risk factors (CAD, HTN))
Greater occipital nerve block
List the severity grading and mortality in TBI
Mild TBI: GCS 13-15; mortality 0.1%
Moderate TBI: GCS 9-12; mortality 10%
Severe TBI: GCS <9; mortality 40%
List the aetiologies for TBI
Blunt TBI
* Falls (48%)
* Motor vehicle-related injury (17%)
* Crush injuries
* Physical altercations
Penetrating TBI
* Gunshot
* Stabbing
Blast TBI - combination of contact and inertial forces, overpressure, and acoustic waves
What is Diffuse axonal injury
Rapid rotational/deceleration force that causes stretching and tearing of neurons, followed by focal areas of haemorrhage and oedema.
List the CT grading for Diffuse axonal injury
Petechial haemorrhages and oedema located at the:
Grey-white matter junction (Grade 1)
Corpus callosum (Grade 2)
Brainstem (Grade 3)
List the primary interventions to elevated intracranial pressure
Raising the head of the bed to 30°
Analgesics and sedation - reduce metabolic demands
Inducing hypocapnia by hyperventilation - reduces pCO₂, which provokes cerebral vasoconstriction, and lowers ICP
* Hyperventilation should be limited to <30 minutes to treat acute cerebral herniation.
List the secondary interventions to elevated intracranial pressure
Osmosis: hypertonic saline, mannitol
High-dose barbiturate
ICP monitoring
Decompressive hemicraniectomy
List the six cognitive domains
attention
executive function
memory and learning
language
perceptual motor
social cognition
Give the DSM5 diagnostic criteria for Major Neurocognitive Disorder/Dementia
Significant cognitive decline in one or more cognitive domains, based on:
1. Concern about significant decline, expressed by individual/reliable informant/observed by clinician.
2. Substantial impairment, documented by objective cognitive assessment.
Interference with independence in everyday activities.
Not exclusively during delirium.
Not better explained by another mental disorder.
Specify one or more etiologic subtypes
Define Idiopathic intracranial hypertension
Increased intracranial pressure in an alert and oriented patient
In what population does Idiopathic intracranial hypertension predominantly occur?
overweight women of childbearing years, often in the setting of weight gain.
Give the pathophysiology in Idiopathic intracranial hypertension
CSF absorption occurs both via the arachnoid granulations and along nerve root sheaths, especially along the olfactory nerve through the cribriform plate.
Abnormalities of the absorption pathways.
Papilloedema and loss of vision are usually due to intraneuronal ischaemia related to increased CSF pressure transmitted along the optic nerve sheath.
List the symptoms and signs of Idiopathic intracranial hypertension
Symptoms
* Headaches
* Pulse-synchronous tinnitus
* Transient visual obscurations, visual loss, diplopia
* Neck and back pain
Signs
* Papilloedema
* CN6 paresis
* Sensory visual disturbances
List the secondary causes of intracranial hypertension
Decreased flow through arachnoid granulations due to scarring from previous inflammation
* Meningitis
* Sequel to subarachnoid haemorrhage
Obstruction to venous drainage
* Venous sinus thrombosis
* Bilateral radical neck dissection
* Superior vena cava syndrome
* Increased right heart pressure
Endocrine disorders
* Addison’s disease
* Hypoparathyroidism
* Corticosteroid withdrawal
Hypervitaminosis A (vitamin, liver, or isotretinoin intake)
Arteriovenous malformations and dural shunts
List the investigations and findings in Idiopathic intracranial hypertension
Lumbar puncture - opening pressure >250 mm H2O
MRI
* Transverse sinus stenosis
* Empty sella
* Posterior globe flattening
* Pituitary stalk displacement
* Meningoceles
* Abnormalities of the optic nerve
* Slit like ventricles
* Tight subarachnoid spaces
Inferior position of cerebellar tonsils
List the non-medical management options for Idiopathic intracranial hypertension
Weight-reduction
Low-sodium diet
List the medical management options for Idiopathic intracranial hypertension
Acetazolamide
Furosemide
Topiramate
List the mechanisms of Acetazolamide in treating Idiopathic intracranial hypertension
Inhibit carbonic anhydrase, reduces sodium ion transport across the choroid plexus epithelium
Acetazolamide decreases CSF production in humans by 6~50%
List the contents in cavernous sinus
CN III, IV, V1, V2, VI
Internal carotid artery
List the sources of cavernous sinus
Superior and Inferior ophthalmic vein
Superficial middle cerebral vein
Middle meningeal vein
Hypophyseal veins
Where does cavernous sinus drain to
Superior and inferior petrosal sinuses
List the septic causes of Cavernous sinus thrombosis
Sinusitis
Facial infection (folliculitis)
Periorbital infection.
Mucormycosis (highly invasive fungal infection, usually occurs in immunocompromised)
Otitis media, mastoiditis
Petrous apicitis (infection of the medial portion of the temporal bone at the base of the skull)
Odontogenic infection
Bacterial meningitis
List the aseptic causes of Cavernous sinus thrombosis
Trauma
Post-surgery
Hypercoagulable states
Malignancy
* Rhabdomyosarcoma
* Nasopharyngeal carcinoma
Vascular abnormalities
List the Hypercoagulable states
Polycythaemia vera
Sickle cell disease
Acute lymphocytic leukaemia
Deficiencies of antithrombin III, protein C, or protein S
Resistance to activated protein C
Antiphospholipid syndrome
Thrombocytosis
Elevated IgM
Nephrotic syndrome
Oral contraceptives
What is the most common causative organism for septic Cavernous sinus thrombosis
Staphylococcus aureus
List the causative organisms in septic Cavernous sinus thrombosis
Staphylococcus aureus (most common)
Fusobacterium necrophorum
Streptococci
List the presentations in Cavernous sinus thrombosis
Headache - unilateral, V1/2 regions (retro-orbital or frontal areas)
Fever (septic CST)
Ocular manifestations
* Chemosis (conjunctival oedema)
* Periorbital oedema
* Proptosis.
* Painful ophthalmoplegia
* Ptosis
* Mydriasis
* External ophthalmoplegia (restriction of extraocular muscles)
Give the investigation and finding in Cavernous sinus thrombosis
CT with contrast - abnormal filling defects with lateral convexity of the cavernous sinuses
List the managements in Cavernous sinus thrombosis
Empirical antibiotics: vancomycin with/without rifampicin
Linezolid
Trimethoprim/sulfamethoxazole
Give the level of motor lesion in bulbar palsy and pseudobulbar palsy
Bulbar - LMN
Pseudobulbar - UMN
List the clinical features in bulbar palsy
Tongue - wasted, fasciculations
Absent palatal movement
Absent gag reflex
Absent jaw jerk
Nasal speech (flaccid dysarthria)
Normal emotions
List the causes of bulbar palsy
Motor neurone disease
Syringobulbia
Guillain-Barre syndrome
Poliomyelitis
Subacute menignitis (carcinoma, lymphoma)
Neurosyphilis
Brainstem cerebrovascular accident
What is the most common cause for pseudobulbar palsy
Bilateral cerebrovascular accidents affecting the internal capsule
List the causes for pseudobulbar palsy
Cerebrovascular accidents
Multiple sclerosis
Motor neurone disease
High brainstem tumours
Head injury
List the clinical features in pseudobulbar palsy
Spastic tongue, slow moving
Absent palatal movement
Increased gag reflex
Increased jaw jerk
Spastic speech, ‘Donald Duck’ dysarthria
Labile emotions
Describe the gait in Parkinson’s disease and other Parkinsonian syndromes
Stooped posture
Shuffling (reduced stride length)
Loss of arm swing
Postural instability
Freezing
Describe the gait in muscular dystrophies and acquired myopathies
(Myopathic gait)
Waddling (proximal weakness)
Bilateral Trendelenburg signs
Describe the gait in common peroneal nerve palsy
Foot drop
Describe the gait in cerebellar disease
(Central ataxia)
Wide-based, ‘drunken’
Tandem gait poor
Describe the gait in sensory ataxia
Wide-based
Positive Romberg sign
List the causes of positive Romberg sign
Sensory ataxia
Bilateral vestibular failure
Describe the gait in Hemiplegia
The foot on the affected side is plantar flexed and describes a semicircle as the patient walks
The upper limb may be flexed
Describe the gait in bilateral UMN damage
Scissor-like gait (spasticity)
List the drugs commonly causing tremor
Sodium valproate
Glucocorticoids
Lithium
Describe the tremor in Parkinson’s disease
slow (3 to 7 Hz), coarse, ‘pill-rolling’ tremor, worse at rest but reduced with voluntary movement
Describe Physiological tremor
fine (low-amplitude), fast (high-frequency, 3 to 30 Hz) postural tremor
List the Medical Research Council grading of muscle power
0 - No muscle contraction visible
1 - Flicker of contraction but no movement
2 - Joint movement when effect of gravity eliminated
3 - Movement against gravity but not against resistance
4 - Movement against resistance but weaker than normal
5 - Normal power
List the nerve and muscle supplies of shoulder abduction
Deltoid - Axillary C5
List the nerve and muscle supplies of:
Elbow flexion
Elbow extension
Elbow flexion
* Biceps - Musculocutaneous C5/6
* Brachioradialis (supinator reflex) - Radial C6
Elbow extension
* Triceps - Radial C7
List the nerve and muscle supplies of:
Wrist extension
Extensor carpi radialis longus - Radial (posterior interosseous branch) C6
List the nerve and muscle supplies of:
Finger extension
Finger flexion
Finger extension
* Extensor digitorum communis - Radial (posterior interosseous branch) C7
Finger flexion
* Flexor pollicis longus/Flexor digitorum profundus - Median (anterior interosseous branch) C8
* Flexor digitorum profundus - Ulnar C8
List the nerve and muscle supplies of:
Finger abduction
Thumb abduction
Finger abduction
* First dorsal interosseous - Ulnar T1
Thumb abduction
* Abductor pollicis brevis - Median T1
List the nerve and muscle supplies of:
Hip flexion
Hip extension
Hip flexion
* Iliopsoas - Iliofemoral nerve L1/2
Hip extension
* Gluteus maximus - Sciatic L5/S1
List the nerve and muscle supplies of:
Knee flexion
Knee extension
Knee flexion
* Hamstrings - Sciatic S1
Knee extension
* Quadriceps - Femoral L3/4
List the nerve and muscle supplies of:
Ankle dorsiflexion
Ankle plantar flexion
Ankle dorsiflexion
* Tibialis anterior - Common peroneal L4/5
Ankle plantar flexion
* Gastrocnemius and soleus - Tibial S1/2
List the nerve and muscle supplies of:
Great toe extension (dorsiflexion)
Extensor hallucis longus - Common peroneal L5
List the nerve and muscle supplies of:
Ankle eversion
Ankle inversion
Ankle eversion
* Peronei - Common peroneal L5/S1
Ankle inversion
* Tibialis posterior - Tibial nerve L4/5
What may isolated loss of a reflex suggest
mononeuropathy
radiculopathy
What may unilateral grasp and palmomental reflexes suggest
Contralateral frontal lobe pathology
List the causes of Bell’s palsy
Ramsay Hunt syndrome (herpes zoster infection of the geniculate (facial) ganglion)
Vestibular schwannoma (cerebellopontine angle compression)
Parotid tumours
Trauma
List the features in Bell’s palsy
(LMN CN7 paralysis)
Weakness of both upper and lower facial muscles
Taste impairment
Hyperacusis
What is anterior cord syndrome caused by
Anterior vertebral artery injury eg. flexion injury
What is the most common cause of central recurrent attacks of vertigo
Migraine
Give the pathophysiology in cervical spondylotic radiculopathy
Mechanical compression/chemical irritation of a specific nerve root by
* degenerative disc
* degenerative joint changes, narrowing the root exit at the foraminal level
Give the pathophysiology in degenerative cervical myelopathy
Posterior disc protrusion
Congenital spinal canal narrowing
Osteophytic bars
Ligamentous thickening
Ischaemia
Give the managements in malignant spinal cord compression
Corticosteroid - dexamethasone sodium phosphate
Radiotherapy
Surgery
Give the landmark for conus medullaris
T12-L1
Contrast the presentations in cauda equina syndrome vs conus medullaris syndrome
CES (LMN involvement)
* Usually bilateral, severe radicular pain
* Saddle anaesthesia
* Asymmetric motor weakness
* Hypo/areflexia
* Late-onset bowel/bladder dysfunction
CMS (Mixed UMN and LMN involvement)
* Sudden-onset severe back pain
* Perianal anaesthesia
* Symmetric motor weakness
* Hyperreflexia
* Early-onset bowel/bladder dysfunction
List the clinical presentations in cauda equina syndrome
Low back pain
Bilateral / unilateral sciatica
Saddle anaesthesia / paraesthesia
Sexual dysfunction
Bladder dysfunction
* Difficulty starting/stopping urination
* Impaired sensation of urinary flow
* Urgency
* Urinary retention with overflow urinary incontinence
Bowel dysfunction
* Loss of sensation of rectal fullness
* Faecal incontinence
* Laxity of the anal sphincter
Give the investigation for cauda equina syndrome
MRI lumbar spine without IV contrast
What diseases may affect the anterior horn cells?
Anterior poliomyelitis
Motor neuron disease
What may axonal degeneration be caused by
Systemic metabolic disorders
Toxin exposure
Vasculitis
Inherited neuropathies
What does axonal degeneration present as
Stocking and glove sensory loss
Muscle weakness and atrophy
Loss of distal limb myotatic reflexes
Give the presentation when anterior horn cells are affected
Focal weakness without sensory loss
Give the presentation when dorsal root ganglion neurons are affected
Sensory ataxia
Sensory loss
Diffuse areflexia
What diseases may affect the dorsal root ganglion neuron?
Toxins
* organic mercury compounds
* doxorubicin
* high-dose pyridoxine
Vitamin E deficiency
Immune-mediated
* paraneoplastic sensory neuronopathy
* Sjögren syndrome
List the types of nerve fibres
Sensory - large myelinated
Motor - small myelinated
Autonomic - small unmyelinated
List the presentations in L5 Radiculopathy
Foot drop
Weak ankle inversion
List the presentations in Sciatic nerve L4~S3 palsy
Paralysis of knee flexion and all movements below knee
Sensory loss below knee
Reflexes
* ankle and plantar reflex lost
* knee jerk intact
List the presentations in Tibial nerve L4~S3 palsy
Inability to
* Stand on tiptoe (plantar flexion)
* Invert the foot
* Flex the toe
* Sensory loss over the sole
Give the Median nerve root
C6-T1
What other conditions may be carpal tunnel syndrome be seen in
Hypothyroidism
Pregnancy (third trimester)
Rheumatoid disease
Acromegaly
Amyloidosis, including dialysis
List the risk factors for carpal tunnel syndrome
variations in the anatomy of the carpal tunnel
age over 30 years
high BMI
pregnancy
occupations involving repetitive movements of the wrist
List the clinical presentations for carpal tunnel syndrome
Gradual onset, intermittent, bilateral hand numbness and pain
Numbness typically confined to the palmar aspect of the thumb and radial fingers
Sensory loss in the radial 3.5 fingers.
Thenar muscle wasting
Waking up at night-time
Difficulty finger extension / flexion on awakening
Relived by shaking or flicking the wrist
Give the gold standard investigation in carpal tunnel syndrome and findings
Electromyography
* conduction velocity slowing in the median sensory nerves across the carpal tunnel
* median distal motor latency prolongation
* decreased amplitude of median sensory/motor nerves
Give the ulnar nerve root and list the ulnar neuropathy presentation
Ulnar nerve root = C8-T1
Claw hand
Wasting of interossei and hypothenar muscles
Weakness of interossei and medial two lumbricals
Sensory loss in the little finger and splitting of the ring finger
Give the radial nerve root and list the radial neuropathy presentation
Radial nerve root = C5-T1
Wrist drop
Weakness of brachioradialis and finger extension
What is meralgia paraesthetica caused by? Give its presentation
Compression of the lateral femoral cutaneous nerve (L2-3)
Anterio-lateral burning thigh pain
Give the common peroneal nerve root and list the common peroneal neuropathy presentation
Common peroneal nerve root = L4-S2
Foot drop
Intact ankle jerk (S1)
Weakness of
* ankle eversion
* foot dorsiflexion
Sensory loss over the dorsum of the foot and the lower lateral part of the leg
Wasting of the anterior tibial and peroneal muscles
Name two branches of the sciatic nerve
Divides into tibial and common peroneal nerves
In what conditions may mononeuritis multiplex occur in
Vasculitis
Diabetes mellitus
Malignancy
Neurofibromatosis
HIV and hepatitis C infection
Leprosy
Multifocal motor neuropathy with conduction block.
Give the presentation in mononeuritis multiplex
Painful, acute to subacute sensory and motor deficits that may be limited to one nerve or multifocal.
Give the typical presentations in polyneuropathies
Symmetric numbness, paraesthesias, and dysesthesias in the feet and distal lower extremities.
Stocking-glove sensory symptoms in severe cases
List the specific etiologies for demyelinating polyneuropathy
Guillain–Barré syndrome
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)
Monoclonal gammopathies
Hereditary neuropathies
List the neuropathies with Autonomic Nervous System Involvement
Acute
* Acute pandysautonomic neuropathy (autoimmune, paraneoplastic)
* Guillain-Barré syndrome
* Porphyria
* Toxic: vincristine
Chronic
* Diabetes mellitus
* Amyloid neuropathy
* Paraneoplastic sensory neuronopathy (malignant inflammatory sensory polyganglionopathy)
* HIV-related autonomic neuropathy
* Hereditary sensory and autonomic neuropathy
Give the aetiology for Guillain–Barré syndrome
Infections in the 6 weeks before symptom onset
Campylobacter jejuni
Cytomegalovirus
Epstein–Barr virus
Mycoplasma pneumoniae
List the symptoms and signs in Guillain–Barré syndrome
Paraesthesias in hands and feet
Pain (typically begins in the back and legs)
Hyporeflexia/areflexia
Facial, oropharyngeal, and extraocular weakness (cranial nerve deficits)
Dysautonomia
* Sinus tachycardia, Cardiac arrhythmias
* Hypertension, postural hypotension
* Urinary retention, Ileus
Respiratory muscle weakness
* Dyspnoea on exertion
* Shortness of breath
List the investigations and findings in Guillain–Barré syndrome
Lumbar puncture - Increased CSF albumin with a normal cell count (albuminocytological dissociation)
Nerve conduction studies
* Prolonged distal and F-wave latencies
* Reduced conduction velocities
LFT - Elevated AST, ALT
Spirometry - reduced:
* Vital capacity
* Maximal inspiratory/expiratory pressure
List the management options for Guillain–Barré syndrome
high-dose intravenous immunoglobulin (IVIG)
plasma exchange
List the causes for Wernicke–Korsakoff’s syndrome
(Thiamine (vitamin B1) deficiency)
Alcohol (most common)
Anorexia nervosa
Vomiting of pregnancy
List the physical examination findings in Charcot-Marie-Tooth disease
Sensory ataxia
Reduced strength in the distal muscles with associated atrophy and weakened foot eversion
Reduction in pinprick and vibration sensation, more pronounced distally than proximally
Areflexia/hyporeflexia
High-arched feet and hammer toes (pes cavus)
Steppage gait
List the presentations in Wernicke–Korsakoff’s syndrome
Eye signs
* Nystagmus
* Bilateral lateral rectus palsies
* Conjugate gaze palsies
Ataxia
* Broad-gait based gait
* Cerebellar signs
* Vestibular paralysis
Cognitive change
* Stupor and coma (acute)
* Amnestic syndrome with confabulation (chronic)
List the key features in Charcot-Marie-Tooth disease
Clumsiness as a child
Weak ankles
Steppage gait
Pes cavus (high foot arches with hammer toes)
Distal atrophy of the hands and legs (inverted champagne bottle legs)
Abnormal sensations typically begin distally and proceed proximally over time
Kyphoscoliosis
Symmetrical nerve conduction changes
Name the most common type of Charcot-Marie-Tooth disease, inheritance, and genetic mechanisms
CMT 1A - most common
Autosomal dominant
PMP22 gene duplication
Define CMT type 1 and CMT2
CMT type 1 (CMT1) - demyelinating conductions and dominant inheritance
CMT2 - axonal conductions and dominant inheritance
What does dietary deficiency of Thiamine (vitamin B1) cause
beriberi
* Polyneuropathy
* Cardiac failure
Give the typical presentation in Pyridoxine (vitamin B6) deficiency
limb numbness developing during anti-tuberculosis therapy with slow isoniazid acetylators
How is Pyridoxine (vitamin B6) deficiency prevented
Prophylactic pyridoxine 10 mg daily is given with isoniazid
List the presentations of Vitamin B12 (cobalamin) deficiency
Subacute combined degeneration of the cord (SACD)
* spastic paraparesis
* loss of vibration sense, proprioception, and two-point discrimination
* ataxic gait
* reduced sensation
Give the pathologies in multiple sclerosis
Plaques of demyelination 2~10mm in size, commonly in
* Optic nerves
* Periventricular region
* Corpus callosum
* Brainstem and cerebellar connections
* Cervical cord (corticospinal tracts and posterior columns)
List the four main clinical patterns of MS
Relapsing-remitting MS
* Onset over days and typically recovery (partial/complete) over weeks.
* Average one relapse per year.
* May accumulate disability over time if they do not recover fully after relapses.
Secondary progressive MS
* Late stage MS
* Gradually worsening disability progressing slowly over years
* ~75% of patients with relapsing–remitting MS will eventually evolve into a secondary progressive phase by 35 years after onset.
Primary progressive MS
* Gradually worsening disability without relapses or remissions
* Typically presents later
* Associated with fewer inflammatory changes on MRI
Relapsing–progressive MS
* Similar to PPMS but with occasional supra-added relapses on a background of progressive disability from the outset.
List the common presenting symptoms in multiple sclerosis
Optic neuritis
* Partial / total unilateral visual loss
* Pain behind the eye
* Loss of colour discrimination (particularly reds)
* Relative afferent pupillary defect - paradoxical dilation of the pupil when light is rapidly shifted from the unaffected eye to the affected eye
Transverse myelitis
* Paresthesia
* Weakness (initial flaccid paralysis, followed by spastic paralysis with hyperreflexia)
* Tight band sensation around the trunk at the level of the inflammation
* Lhermittes’ phenomenon - Shock-like sensation radiating radiating down the spine induced by neck flexion
Cerebellar syndromes - Ataxia, Vertigo, Clumsiness, Dysmetria
Brainstem syndromes
* Ataxia
* Eye movement abnormalities- Diplopia, Oscillopsia, Nystagmus, Internuclear ophthalmoplegia
Bilateral trigeminal neuralgia
Uhthoff phenomenon: symptoms worsening with increased body temperature
Urinary frequency
Bowel dysfunction (constipation)
List the neurological signs in multiple sclerosis
Internuclear ophthalmoplegia - nystagmus of the abducting eye with absent adduction of the other eye
UMN signs
* Spasticity
* Hyperreflexia
Gait
* Mild dragging of the foot
* Spasticity
* Balance problems
Give the first line investigation and findings in multiple sclerosis
MRI brain (high field magnet with IV gadolinium contrast)
* Hyperintensities in the periventricular white matter
* Demyelinating lesions in the spinal cord, particularly cervical
List the LP findings in MS
Oligoclonal bands
CSF IgG
Give the management for acute MS relapse
Oral methylprednisolone 0.5 g for 5 days
Plasma exchange
Give the management for Secondary progressive MS
1st line: Siponimod or IV methylprednisolone
2nd line: Cladribine
Give the management for Primary progressive MS
Ocrelizumab
List the antibodies for neuromyelitis optica spectrum disorders (NMOSD)
Anti-aquaporin 4
Anti-myelin oligodendrocyte glycoprotein
List the NMOSD adult presentations
Optic neuritis
Acute myelitis
Area postrema syndrome (unexplained hiccups, nausea, or vomiting)
Acute brainstem syndrome
Symptomatic narcolepsy
Symptomatic cerebral syndrome with NMOSD-typical brain lesions
List the typical presentations in transverse myelitis
Typically bilateral
Progressive paraparesis/quadriparesis
Sensory loss/paraesthesias below the lesion
Autonomic (bowel and bladder) dysfunction
Evolution of signs over several days.
Radicular or segmental pain at the level of the spinal lesion
Back pain
L’hermitte’s sign
Paroxysmal tonic spasms
List the treatment for Transverse myelitis
IV methylprednisolone
Define Progressive Multifocal Leukoencephalopathy
Demyelinating disease preferentially affecting the CNS
Areas commonly involved
* subcortical white matter
* periventricular areas
* cerebellar peduncles
In most cases, the optic nerve and the spinal cord are unaffected.
List the causes for Progressive Multifocal Leukoencephalopathy
Reactivation of John Cunningham virus (JC virus) infecting oligodendrocytes in patients with compromised immune systems.
* AIDS
* Post solid organ/bone marrow transplant recipients
* Malignancies
* Chronic inflammatory conditions
(Progressive and fatal disease)
List the presentations for Progressive Multifocal Leukoencephalopathy
New-onset neurological symptoms in a patient with immunosuppression
Cognitive impairment
Limb, gait ataxia
Hemiparesis
Hemianopia
Aphasia
Give the CT findings in Progressive Multifocal Leukoencephalopathy
hypodense confluent lesions without mass effect
List the risk factors of essential tremor
Ageing
Genetics
Environmental toxins
* Organochlorine pesticides
* Lead
* Mercury
* Beta-carboline alkaloids (harmane, harmaline)
List the management options for essential tremor
Propranolol
Primidone
Small amounts of alcohol
Benzodiazepines - clonazepam
DBS
* ventralis intermedius nucleus (VIM) of the thalamus
* caudal zona incerta (posterior subthalamic area)
Ultrasound thalamotomy
* refractory ET ineligible for DBS
Give the inheritance and genetic mechanism in Huntington’s disease
Autosomal dominant
Expanded CAG repeats at the N-terminus of the HTT gene that codes for huntingtin protein.
Individuals with ≥40 CAG repeats are certain to develop Huntingon’s disease.
Reduced penetrance is observed in those with 36 to 39 repeats.
Give the pathology in Huntington’s disease
Degeneration of cholinergic and GABAergic neurons in the striatum of the basal ganglia
Define Posthypoxic myoclonus
A form of secondary myoclonus following cardiac arrest, divided into acute and chronic
Myoclonus status epilepticus - acute, within 24 hrs
* Generalised myoclonus
* Intermittent eye opening, upward gaze deviation, swallowing movements
Lance-Adams syndrome - chronic, days to weeks
* Focal in nature and exacerbated by action
* Negative (relaxation) myoclonus also occurs - drop objects or fall
List the primary and secondary causes of myoclonus
Primary
* Physiological
* Myoclonic dystonia
* Epilepsy
Secondary
* Metabolic disorders (hepatic and renal failure, asterixis)
* Alzheimer’s
* Encephalitis
Give the natural history in Tourette’s syndrome
Symptoms typically begin in childhood, peak prior to puberty, attenuate later in adolescence
List the causes for restless legs syndrome
Primary - familial, autosomal dominant
Secondary
* Iron deficiency
* Pregnancy (26%, third trimester)
* Uraemia
* Renal dialysis/ESRD (20%)
What is restless legs syndrome associated with
Obesity
Diabetes
Multiple sclerosis
Parkinson’s disease
Neuropathy
What medicines can cause or worsen restless leg symptoms
TCAs, SSRIs
Sedating antihistamines
Metoclopramide (DPA antagonist)
Neuroleptics
List the presentations for restless legs syndrome
Symptoms are nocturnal
The urge to move with dysaesthesia symptoms (creeping, crawling, tingling, cramping, aching)
Symptoms worse at rest, relieved temporarily with movement
Lower extremities are more commonly affected
Give the McDonald diagnostic criteria for multiple sclerosis
(Dissemination in both time and space)
2 or more attacks + 2 or more lesions on MRI
What population does MS classically present in
White women aged between 20 and 40 years.
List the risk factors for MS
EBV infection
Female, caucasian, HLA-DRB1
Environmental factors
* Location (USA, europe)
* Cold climate
Low vitamin D
Smoking
List the differential diagnoses in MS
Thyroid disease
Vitamin B12 deficiency
Diabetes mellitus
List the antibodies positive in myasthenia gravis
Anti-AChR (80-90%)
Anti-muscle-specific tyrosine kinase (MuSK) (3-7%)
Give the pathophysiology in myasthenia gravis
Circulating antibodies against the nicotinic acetylcholine receptor (AChR) or associated proteins impair neuromuscular transmission.
List the clinical features in myasthenia gravis
Muscle weakness that increases with exercise (fatigue) and improves on rest.
* Ptosis, Diplopia
* Dysarthria, Dysphagia
* Facial paresis
* Proximal limb weakness
* Shortness of breath
Define myasthenic crisis
An MG exacerbation requiring mechanical ventilation
* forced vital capacity ≤ 15 (normal ≥60 mL/kg)
* negative inspiratory force ≤ 20 (normal ≥70 cm H₂O)
What may myasthenic crisis be provoked by
Infections (particularly respiratory infections)
Aspiration
Medicines including high-dose corticosteroids
Medications that are contraindicated in MG
Failure to adhere to medications
Administration of immune checkpoint inhibitors eg cancer therapy
Surgery
Trauma
Give the management in myasthenic crisis
Intubation and mechanical ventilation
Plasma exchange / IVIG
List the management options for myasthenic crisis
1st line: Pyridostigmine (cholinesterase inhibitor)
Prednisolone
Azathioprine
Rituximab (MuSK-MG)
Thymectomy
When may thymectomy be considered in MS
Early in disease course for aged 18~50 to minimise the need for immunosuppressants
Ocular AChR-MG with insufficient response to cholinesterase inhibitors
Severe disease
What conditions are associated with Lambert Eaton syndrome
Small cell lung cancer
Autoimmune thyroid disease
Vitamin B12 deficiency
Rheumatoid arthritis
Inflammatory myopathy
Systemic vasculitis
What is Lambert Eaton syndrome associated with
Small cell lung cancer (CA-LEMS)
Autoimmune (NCA-LEMS)
* Autoimmune thyroid disease
* Vitamin B12 deficiency
* Rheumatoid arthritis
* Inflammatory myopathy
* Systemic vasculitis
List the differences between LEMS and MG
MG
* Antibody against AChR Antibody
* Associated with thymic tumour
* Weakness worsen on prolonged exercise
* Normal deep tendon reflex
* Autonomic dysfunction absent
* On repeated nerve stimulation, there is decremental response
LEMS
* Antibody against voltage gated calcium channel
* Associated with small cell lung cancer
* Weakness improves on prolonged exercise
* Decreased/absent deep tendon reflex
* Autonomic dysfunction present
* On repeated nerve stimulation, there is incremental response
Give the pathophysiology in LEMS
Disruption of neurotransmission due to depletion of voltage-gated calcium channels (VGCCs)
In normal neurotransmission, depolarisation of the presynaptic nerve terminal triggers calcium influx at VGCC that ultimately results in quantal release of ACh into the synaptic cleft.
This produces localised depolarisation of the adjacent peri-endplate muscle membrane.
List the symptoms in LEMS
Generalised fatigue
Proximal leg weakness
Dry mouth (xerostomia), Dysarthria, Dysphagia
Prominent ocular weakness with ptosis and binocular diplopia
Autonomic features
* Pupillary dilation
* Orthostatic hypotension
List the signs in LEMS
Proximal muscle weakness in hip girdle and thigh muscles
Absent/reduced tendon reflexes
Dilated, poorly reactive pupils
List the investigations in LEMS
Auto-antibody serology - serum P/Q-type VGCC antibodies +ve
NCS
* Typically low initial CMAP
* Decremental responses to low-frequency repetitive nerve stimulation
List the treatment approaches to LEMS
Treat malignancy
Symptomatic
* Amifampridine
* Pyridostigmine
Give the hall mark in Prion diseases
Progressive dementia and motor dysfunction
List 3 types of prion diseases
Sporadic Creutzfeldt-Jakob disease (sCJD)
Genetic prion diseases
* Familial CJD
* Gerstmann-Straussler-Scheinker
* Fatal familial insomnia
Acquired prion diseases
* Iatrogenic CJD
* Variant CJD
List the investigations in prion diseases
MRI (FLAIR)
* hyperintensity in the cerebral cortex grey matter gyri, basal ganglia, thalamus
* bilateral pulvinar hyperintensity (vCJD)
EEG - generalised slowing, focal or diffuse, and periodic polyspike-wave complexes and sharp waves
CSF testing
List the common metastatic brain tumours
Lung
Breast
Melanoma
Kidney
Stomach
Prostate
Thyroid
List the primary malignant tumours of neuroepithelial tissue
Astrocytoma
Oligodendroglioma
Oligoastrocytoma
Ependymoma
Lymphoma
Medulloblastoma
List the benign brain tumours
Meningioma
Neurofibroma
List the etiological risk factors for glioma
Ionising radiation
Genetic syndromes
* Neurofibromatosis type 1
* Tuberous sclerosis complex
* Li-Fraumeni syndrome
* Turcot syndrome
List the investigations and findings for meningioma
MRI head/spine with/without contrast
* Contrast-enhancing tumour
* Surrounding cerebral oedema
* Enhancing dural tail
CT head/spine
* Bony changes (hyperostosis)
* Calcification (25%) (slower growing tumour)
* Contrast-enhancing tumour
* Surrounding oedema, enhancing dural tail
List the meningitis causative organisms by age group
Neonates
* E. coli
* Group B streptococcus (S. agalactiae)
* L. monocytogenes
Infant
* N. meningitidis
* H. influenzae
* S. pneumoniae
Young adult
* N. meningitidis
* S. pneumoniae
Elderly
* S. pneumoniae
* N. meningitidis
* L. monocytogenes
Where does meningioma arise from
Meningothelial cells of the arachnoid layer (arachnoid-cap cells)
Compare CSF features of bacterial vs viral meningitis
Bacterial
* Opening pressure: raised
* Appearance: turbid, cloudy, purulent
* CSF WBC count: raised (typically >100)
* Predominant cell type: neutrophils
* CSF protein: raised
* CSF glucose: very low
* CSF/plasma glucose ratio: very low
Viral
* Opening pressure: normal/mildly raised
* Appearance: clear
* CSF WBC count: raised (typically 5 to 1000)
* Predominant cell type: lymphocytes
* CSF protein: normal/mildly raised
* CSF glucose: normal
* CSF/plasma glucose ratio: normal
Give the meningococcal disease antibiotic prophylaxis
oral ciprofloxacin single dose
List the symptoms for meningitis
Headache
Neck stiffness
Photophobia
Fever
Altered consciousness
Rash
Seizures
Shock
Describe Kernig’s and Brudzinski’s sign
Kernig’s sign (present in only 11%)
Pain in the lower back or back of thigh on extension of knee when hip is flexed to a 90° right angle
Brudzinski’s sign (present in only 9%)
Forced flexion of the neck elicits a reflex flexion of the hip
Give the first line investigation in meningitis
Blood culture
List the serum electrolyte features in meningitis
Acidosis
Hypokalaemia
Hypocalcaemia
Hypomagnesaemia
Low sodium (TB meningitis)
List the contraindications for lumbar puncture
Signs suggesting raised ICP
Shock
Extensive or spreading purpura
After convulsions, until stabilised
Coagulation abnormalities
Local infection at the lumbar puncture site
Respiratory insufficiency
Give the antibiotics in meningitis
IM/IV benzylpenicillin (children, adults)
IV ceftriaxone/cefotaxime (adults)
List the causes of encephalitis
(Viruses)
Herpes viruses
* Herpes simplex virus
* Varicella zoster virus
* Cytomegalovirus
* Epstein-Barr virus
West Nile virus
Picornaviridae / enteroviruses
* Coxsackievirus
* Poliovirus
Bacterial
* Neisseria meningitidis (meningoencephalitis)
* Syphilis
* Listeria
* Bartonella (cat-scratch disease)
* Borrelia burgdorferi (Lyme disease)
Autoimmune
* Anti-NMDA encephalitis
* Acute hemorrhagic leukoencephalitis
Give the signs and symptoms in encephalitis
Acute/subacute onset of a febrile illness
Altered mental status
Focal neurological abnormalities
Seizures
Give the diagnostic criteria for encephalitis
Major criteria (required):
Altered mental status lasting ≥24 hours with no alternative cause identified
* Altered level of consciousness
* Lethargy
* Personality change
Minor criteria (2 required for possible, ≥3 required for probable/confirmed encephalitis)
* Documented fever ≥38°C within the 72 hours before/after presentation
* Generalised/partial seizures not fully attributable to a pre-existing seizure disorder
* New onset of focal neurological findings
* CSF WBC count ≥5/mm³
* Abnormality of brain parenchyma on neuroimaging suggestive of encephalitis
* Abnormality on EEG consistent with encephalitis and not attributable to another cause.
Give the empirical treatment for encephalitis
Immunocompetent - Aciclovir
Immunocompromised - Aciclovir AND ganciclovir AND foscarnet
List the symptoms and signs in brain abscess
Symptoms
* Recent unexplained fever with neurological deficit
* Headache
* Fever
* New-onset neurological deficits
Signs
* Nuchal rigidity, and Kernig and Brudzinski signs in the presence of neurological deficits
* Increased intracranial pressure and impending cerebral herniation:
* CN3 / 6 palsies
* Anisocoria
* Papilloedema
List the most common aetiology for brain abscess by age
Neonates - Proteus mirabilis and Citrobacter species
Children - Streptococcus species in combination with cyanotic heart disease
Adults - Streptococcus and Staphylococcus species
Give the antibiotic of choice in brain abscess
Vancomycin + Metronidazole/clindamycin + third generation cephalosporin (ceftriaxone, cefotaxime)
Give the neuroimaging sign in brain abscess
1 or more ring-enhancing lesions
Give the triad in normal pressure hydrocephalus
Clinical features of hydrocephalus without significantly elevated CSF
* levodopa-unresponsive gait apraxia
* urinary incontinence
* cognitive impairment
List the cardinal features of levodopa-unresponsive gait apraxia
A slow, cautious gait
Gait initiation failure
Unsteadiness
Reduced stride length
Shuffling gait
Falls
Freezing
How much CSF is produced by the choroid plexus and is reabsorbed at the arachnoid granulations every minute.
0.5 mL
List the investigations for normal pressure hydrocephalus
MRI/CT without contrast
* May be normal
* Moderate dilation of the ventricles and periventricular leukomalacia
* Disproportionate central atrophy, resulting in larger ventricles with relative preservation of cortical sulci
Levodopa challenge - unresponsive
Lumbar puncture - Normal CSF pressure
Give the management for normal pressure hydrocephalus
Ventriculoperitoneal shunt surgery
List the complications of ventriculoperitoneal shunt surgery
subdural haematoma
mechanical obstruction
infection
What features of migraine is more common in children?
Nausea, vomiting and abdominal pain
What are the first-line treatments for spasticity in multiple sclerosis
Baclofen and gabapentin
Give the diagnosis for seizure after acute sinusitis PLUS:
* Focal Neurology
* Cranial Nerve Palsy, Ophthalmoplegia
* Neck Stiffness, Photophobia, Kernig’s/Brudzinski’s positive
* Painful Ophthalmoplegia, Proptosis, Eye swelling
* Staph. Aureus
Focal Neurology - Cerebral Abscess
Cranial Nerve Palsy, Ophthalmoplegia - Cavernous Sinus Thrombosis
Neck Stiffness, Photophobia, Kernig’s/Brudzinski’s positive - Meningitis
Painful Ophthalmoplegia, Proptosis, Eye swelling - Orbital Cellulitis
Staph. Aureus - Frontal bone osteomyelitis
What is a contraindication to triptan use
Cardiovascular disease
List the adverse effects of Lamotrigine
Stevens-Johnson syndrome and toxic epidermal necrolysis
Drug reaction with eosinophilia and systemic symptoms (DRESS)
Give the presentation of Stevens-Johnson syndrome after lamotrigine
Develops up to 2 months after starting an anti-convulsant.
Usually prodromal illness which resembles a viral upper respiratory tract infection
Followed by rapid onset of painful red skin rash which starts on the trunks and extends abruptly onto the face and limbs.
Rash rarely affects the scalp, palms or soles.
When is carotid endarterectomy considered for TIA
carotid artery stenosis >50% (NASCET criteria) on the side contralateral to the symptoms
What does DVLA say about epilepsy
The person with epilepsy may qualify for a driving licence if they have been free from any seizure for 1 year.
What drug is used to prevent vasospasm in aneurysmal subarachnoid haemorrhages
Nimodipine
What is Ondansetron selective for
5-HT1 antagonist
What is the first line management in pituitary apoplexy
IV hydrocortisone
List the order of drugs to give in status epilepticus
- Buccal midazolam/IV lorazepam
- IV lorazepam
- IV phenytoin/levetiracetam/sodium valproate
- Rapid sequence induction of anaesthesia using thiopental sodium
What can be used to differentiate a general tonic-clonic/partial seizure from a non-epileptic pseudo seizure
Elevated serum prolactin 10 to 20 minutes after an episode
Give the first line treatments for neuropathic pain
amitriptyline, duloxetine, gabapentin, pregabalin
List the causes for neuropathic pain
diabetic neuropathy
post-herpetic neuralgia
trigeminal neuralgia
prolapsed intervertebral disc
