Neurology Flashcards
Inheritance pattern of Huntington’s disease
Autosomal Dominant
Contents of the cavernous sinus
OTOMCAT: OTOM = lateral wall CA = within sinus, joining to T Occulomotor n Trochlear n Ophthalmic division of CNV Maxillary division of CNV internal Carotid artery Abducent n
Ramsay Hunt syndrome
Herpes zoster otitis - reactivation of VZV in geniculate ganglion
Ipsilateral facial paralysis, ear pain and vesicles in auditory canal
Ipsilateral facial paralysis, ear pain and vesicles in auditory canal
Ramsay Hunt syndrome
VZV reactivation in geniculate ganglion
Cause of myasthenia gravis
Antibodies to anticholine receptor at post synaptic membrane
Regulators of cerebral blood flow
Partial pressure of CO2 and O2
- hypercapnia increases flow
- hypoxia increases flow
Definition of Parkinson’s disease
Progressive neurodegenerative disorder characterised by rigidity, tremor, postural instability and bradykinesia due to a loss of dopamine in the neostriatal pathway
Pathophysiology of Parkinson’s disease
Abnormal aggregation of alpha synuclein (Lewy body constituent)
Loss of pigmented dopaminergic neurons in substantia nigra pars compacta of midbrain
-loss of DA in neostriatal pathway (esp putamen)
60% of these neurons have degenerated before clinical features develop
Clinical features of Parkinson’s disease
Tremor (resting)
Rigidity (cogwheel/leadpipe)
Akinesia/bradykinesia
Postural instability
+/- autonomic features (bowel, bladder, orthostatic dizziness)
+/- anosmia
+/- fatigue and nonspecific discomfort
+/- neuropsychiatric (anxiety, depression, sleep disruption)
Insidious onset
Parkinsonian gait features (9)
Hesitation in starting Shuffling Freezing Propulsion Retropulsion Reduced arm swing Festination (short, accelerating steps) Difficulty stoping Difficulty turning (multi point turn)
Pharmacological management options for PD
Dopamine replacement Dopamine D2 receptor agonists Combination dopaminergic/antiCh COMT inhibitors MAOB inhibitors ACh inhibitors
Dopamine replacement therapy in PD
Levo-dopa crosses BBB, converted to DA within CNS by dopa decarboxylase (DDC)
DDC inhibition to prevent L-dopa being converted in periphery
(carbidopa, benserazide) - cannot cross BBB
Standard treatment = L-dopa + peripheral DDC inhibitor
DDC inhibitors
Carbidopa, beserazide
Adverse effects of L-dopa
Nausea, vomiting
Postural hypotension
Dyskinesia
Hallucination
In long term, shorter duration of benefit and reduced efficacy as disease progresses
Benefits of L-dopa
Improves tremor, bradykinesia and rigidity
Types of dopamine D2 receptor agonists
Non-ergot derivatives: - pramipexole Ergot-derivatives: - cabergoline - pergolide - bromocriptine
Mechanism of dopamine D2 agonists in Parkinson’s disease
mimics action of DA at D2 receptors in striatum
less marked benefit than L-dopa
Benefits of D2 agonists in PD
Longer duration of action than L-dopa
Can be first-line in younger patients to delay L-dopa use OR in combination with L-dopa in late stage disease when need additional response
Adverse effects of DA D2 agonists
Nausea, vomiting
Postural hypotension
More likely to cause hallucinations and confusion than L-dopa
ergot-derivatives lead to fibrosis (especially heart valve disease)
Combined preparations for Parkinson’s
Sinemet = L-dopa + carbidopa Madopar = L-dopa + benserazide
Example of a COMT inibitor
Entacapone
Mechanism of COMT inhibitors
(catechol-O-methyltransferase - responsible for breakdown of catecholamines)
Inhibition leads to reduced peripheral breakdown of L-dopa, increasing amount delivered to CNS
Short-half life therefore administered with each dose of L-dopa
Used in late disease with “wearing off” phenomenon of L-dopa
Adverse effects of COMT inhibitors
dyskinesia
Nausea and vomiting
Dry mouth
Diarrhoea
Example of a MAOB inhibitor
selegiline
Mechanism of MAOB inhibitors in PD
inhibits MAOB - reduces breakdown of dopamine - prolongs effect of L-dopa
Used in late stage disease (wearing off phenomenon)
Adverse effects of MAOB inhibitors
Insomnia
Exaggeration of L-dopa side effects
ACh inhibition in PD
Benzotropine (e.g.)
blocks muscarinic receptors - improvement of tremor and rigidity (little effect on bradykinesia)
Mainly used in drug induced parkinsonism
Adverse effects of benzotropine
Drowsiness Confusion Restlessness Dry mouth Blurred vision Urinary retention
Drugs to consider adding to patient with PD suffering from “wearing off” phenomenon of L-dopa
MAOB inhibitor (selegiline) OR ACh inhibitor (benzotropine)
Symptoms of PD likely to respond or not to deep brain stimulation
Gait changes and freezing (especially if respond well to medications)
Severe balance problems less likely to respond to DBS
Patients in which to consider deep brain stimulation
Significant motor fluctuations difficult to control with drug therapy
Patients with early PD, who have been responding well to drugs, but having increasing difficulties threatening social/work
Definition of multiple sclerosis
A chronic autoimmune demyelinating disease of the CNS characterised by subacute neurological impairment correlated with CNS lesions separated in time and space that cannot be explained by another disease
Patterns of MS
Relapsing-Remitting (80%): relapses followed by (near)complete recovery… 50-80% will later transition to secondary progressive
Secondary progressive: progression of disability with few or no relapses
Primary progressive (20%): progression from onset of disease, typically without relapses
Pathophysiology of MS
autoimmune destruction of myelin sheaths in the CNS
Effect of pregnancy on MS
Child birth is likely to trigger a relapse/flare-up
breastfeeding offers some protection to relapse
Presentations of MS
Optic neuritis (visual blurring +/- pain)
Weakness or sensory disturbances
Incoordination, dysarthria and intention tremor
Trigeminal neuralgia
Bladder or bowel symptoms (urgency or incontinence)
Diagnosis of MS
MRI brain and spinal cord
- more than 3 lesions greater than 6mm diameter
- oval shaped
- located in periventricular area, corpus callosum and posterior fossa
- gadalonium-enhancing lesions indicate new attacks
Lumbar puncture in MS
Non-specific, rarely used if MRI positive
- lymphocytic raised WCC
- oligoclonal bands
- raised IgG/albumin index
Primary and secondary prevention of MS
Vitamin D - reduces risk of development in susceptible individuals (e.g. family history) by 70% and reduces relapse
Management of acute exacerbation for MS
high-dose IV methlyprednisolone 5 days
(followed by oral corticosteroids if optic neuritis)
Plasmapheresis sometimes indicated (ask neurologist)
Disease modifying therapy in MS
First line: IFN beta OR galatiramer
Second-line natalizumab
Fingolimod
Causes of resting tremor
Parkinson disease/syndromes
Midbrain (rubral) tremor
Wilson’s disease
Severe essential tremor
Causes of postural-action tremor
Enhanced physiological tremor Essential tremor Primary writing tremor Extrapyradimal disorders (PD, Wilson's, dystonia) Cerebellar disease Peripheral neuropathy
Causes of intention tremor
(Cerebellar outflow)
- Cerebellar disease
- Multiple sclerosis
- Midbrain stroke
- Midbrain trauma
Causes of stroke
Ischaemic - 90%
- Cardioembolic - 30%
- Artery-artery embolism (atherosclerotic plaques)
- In situ thrombosis
Haemorrhagic (10%) - SAH or ICH
- hypertensive small vessel disease
- amyloid angiopathy
- congenital vascular malformations (young people)
Haemodynamic (hypovolaemic)
- circulatory failure (hypotension, cardiac arrest)
Cerebral vein thrombosis - inc. pressure into brain due to congestion - swollen - haemorrhage
Investigations to perform in stroke
General:
- CXR
- ECG ?AF
- CBE - ?hypercoagulable state
- ESR - ? vascultis
CT MRI Diffusion weighted MRI or FLAIR Cardiac imaging (TOE) Imaging of cerebral vessels (Carotid doppler, CTA, MRA, catheter angiogram)
CT findings in stroke
Not very sensitive in first few hours
- Normally should see “cortical ribbon (line running around brain between gyri) - lost early after stroke
- Loss of grey-white differentiation
Infarction = hypodense (DARK)
Acute haemorrhage = hyperdense (WHITE)
What is a FLAIR scan and what is it’s role?
Fluid attenuation inversion recovery MRI
Shows all cerebral damage (post-traumatic, scarring, demyelination etc.)
Non specific
Does not differentiate acute from chronic ischaemia
Role of diffusion weighted imaging in stroke
MRI scan
Measures acute cytotoxic oedema
Circulation of water particules through an area of damage - accumulated in acute damage (appears bright on scan!)
Is able to differentiate acute from chronic damage
Imaging for lacunar or brainstem infarcts
MRI - much more sensitive than CT
General supportive care following a stroke
- Fever
- hyperthermia increases infarct size
- treat fever over 37.5 with antipyretics - Blood pressure
- treat only if diastolic 120+ or systolic 220+ (180+ if using thrombolysis)
- oral captopril or sublingual GTN
- Avoid nifedipine - Hyperglycaemia
- associated with poorer outcome
- monitor BGLs, consider insulin if 10mmol/L+ - Admission to stroke unit!
- reduces risk of death and disability
- medical expertise, nursing expertise, allied health expertise
4 interventions proven to improve outcome after acute ischaemic stroke
- Manage in stroke unit
- Give aspirin within 48h of ischaemic stroke
- IV alteplase (thrombolysis)
- treat within 4.5h of symptom onset
- risk of haemorrhagic transformation (6% will be asymptomatic, some fatal) - Hemicraniectomy
Contraindications of thrombolysis with alteplase in patient suffering ischaemic stroke
- Over 4.5h since onset of symptoms
- severe HTN (over 180 systolic)
- Recent surgery
- anticoagulation
Indications for hemicraniectomy following acute ischaemic stroke
- under 60y
- infarction over 50% MCA territory
- Able to perform procedure within 48h of symptom onset
- deterioration in conscious state from time of admission
Primary prevention of stroke
Blood pressure detection and management!!!
AF - detection and management (CHADS) - 2+ - warfarin or NOACs
Lifestyle: smoking, hyperlipidaemia
Early detection and investigation of patients experiencing TIAs
Secondary prevention of stroke
- *15% of ischaemic strokes are preceded by a TIA, highest risk in first days - week after initial TIA**
- start anti-platelet therapy (aspirin 100mg/day)
- Cerebral imaging (exclude differentials)
- establish ASAP if eligible for carotid endarterectomy (within 14 days)
- treat even normotensive patients with ACEi
- Statin regardless of cholesterol
- ABCD2 score to determine risk of stroke
ABCD2 score
Estimated the risk of a stroke after a TIA
- Age over 60
- Blood pressure over 140/90
- Clinical features (weakness = 2, speech only = 1)
- Duration of symptoms (10-59min = 1, 60+ = 2)
- Diabetes history
Over 4 = high risk - investigate within 24h
Less than 4, investigate within 72h
Clinical features of intracerebral haemorrhage
Neck stiffness Seizures Diastolic BP over 110 Vomiting Headache Focal neurological changes
Differentiating intracerebral haemorrhage from subarachnoid haemorrhage
ICH forms “blobs” of bleeding
SAH forms lines etc. following meninges - not a large pool of blood
Management of intracerebral haemorrhage
Supportive care
- maintain airway
- oxygenation
- prevention of secondary complications
Medical care:
- IV recombinant factor VIIa (Novo7) within 4h (reduced volume of haemorrhage and surrounding oedema, no improvement in clinical outcomes)
Surgical therapy:
- evacuate intracerebral haematoma - no better than medical therapy
- Aim to remove cause (e.g. AV malformation) and prevent hydrocephalus
Causes of subarachnoid haemorrhage
Most common = trauma
Most common spontaneous cause = ruptured saccular aneurysm
Other causes: AV malformations, bleeding into pre-existing tumours, vasculitis, cerebral artery dissection
Clinical features of subarachnoid haemorrhage
Thunderclap headache (97%)
- worst headache of life
- lateralised toward the side of the haemorrhage in 30%
- only 10% presenting with this headache will have SAH
- ONLY symptoms in 30% of SAH patients
Loss of consciousness Seizures - poor prognosis Focal neurological deficits Photophobia/meningism Vomiting Sudden death (10-15% before reaching hospital)
Sympathetic storm
- raised BP
- Neurogenic pulmonary oedema
- arrhythmias/arrest (3%)
- ECG changes (may resemble acute MI) + increased troponin
Acute v subacute haemorrhage on CT
Acute = hyperdense (white)
Subacute (over5d) = isodense to brain (around the same colour as surrounding tissue)
Imaging in acute CNS bleed
CT more sensitive acutely, MRI for sensitive few days later
Investigations in subarachnoid haemorrhage
CT head Lumbar puncture - raised opening pressure - raised RBC, not diminishing from tube 1-4 - Xanthochromia (yellowish/pink colour)
CT angiography brain
- determine location, accessibility and shape of aneurysm
- ?coil-able
CBE, INR, coag studies etc.
Management of subarachnoid haemorrhage
- Prevent re-bleeding
- clipping or coiling (cannot coil if aneurysm has broad base, only used if saccular) - Identify/treat hydrocephalus
- over 10-15mmHg, may have Cushing’s triad
- Hyperventilation
- elevate head
- osmotherapy (IV mannitol)
- diuretics
- hypothermia
- Novo 7 - Identify/treat vasospasm
- vasodilators (nimodipine)
- HHH therapy: induce hypervolaemia, hyperdilution, hypertension (if aneurysm is secured)
- balloon or chemical angioplasty (local Ca release via catheter)
Complications of subarachnoid haemorrhage
Re-bleed Communicating hydrocephalus Cerebral oedema Seizures Cerebral vasospasm - most common cause of late death (post day 7)
Causes of extradural haemorrhage
Trauma (fall, assault, MVA, sports) Complications of neurosurgery Coagulopathy Vascular malformations Bleed is USUALLY arterial (can be venous or mixed)
Extradural haemorrhage on imaging
CT:
Lens/lentiform shape that does not cross suture lines (dura is welded at suture lines)
Clinical features of extradural haemorrhage
Headache - may be gradual and present weeks after traumatic event Vomiting Drowsiness Lucid intervals between LOC Reduced GCS Confusion Speech difficulties Seizures Focal neurologic deficits Cushing's triad (raised ICP)
Management of extradural haemorrhage
ABC principles
C-spine protection if unconscious
Treatment of underlying coagulopathy/correction of medication induced anticoagulation
Immediate neurosurg consultation once confirmed (for evacuation of haematoma)
Mannitol to reduce ICP while being transferred if acute deterioration
Definition of subdural haemorrhage
A collection of blood or blood products between the arachnoid mater and the dura mater of the brain. May be acute or chronic
Cause of subdural haemorrhage
Shearing and trauma of a bridging VEIN between brain parenchyma and dura mater
(slow bleed therefore presentation can be delayed by days to weeks)
Trauma
Antithrombotic therapy
Brain atrophy secondary to age, alcoholism (incr. stretch of bridging vessels)
investigations in subdural haemorrhage
Coagulation studies
CBE: PLT
LFT (esp if history of alcoholism)
CT: crescent shape hyperdensity, extends over suture lines
Management of of subdural haemorrhage
Correction of underlying coagulopathy
Majority of awake patients can be managed without surgery
Surgical evacuation indications:
- Acute: over 10mm with midline shift over 5mm
- Chronic: mass effect, clear change in neuro examination from baseline, enlargement of haematoma size
Normal pressure hydrocephalus clinical triad
Syndrome of enlarged lateral ventricles in elderly patients with triad of:
- A gait apraxia
- dementia
- Urinary incontinence
Types of brain herniations
SUPRATENTORIAL:
Uncal/transtentorial:
- medial temporal lobe from middle into posterior fossa across the tentorial opening
- CNIII palsy, PCA infarct
Central:
- diencephalon and parts of temporal lobes squeezed through a notch in tentorium cerebelli
Cingulate/subflacine (most common)
- cingulate gyrus to contralateral hemisphere under falx cerebri
Transcalvarial/external
- brain squeezes through a fracture or surgical site in the skull
INFRATENTORIAL
Upward:
- midbrain moves from posterior fossa through tentorial notch
Cerebellar tonsillar:
- displacement of cerebellar tonsils into foramen magnum
- neck stiffness, cardiorespiratory arrest
Classifications of peripheral neuropathies
- Axonal degeneration
- reduced amplitude on nerve conduction studies +/- reduced conduction velocity - demyelination
- reduced internodal conduction, reduced conduction velocity in affected segment - neuronopathies
Axonal degeneration causes
Systemic illness: - DM - sepsis/critical illness - uraemia - Vit B12 deficiency - HIV Drugs/toxins: - Amiodarone - Disulfuram - Phenytoin - Arsenic
Secondary demyelination can occur making nerve conduction studies difficult to interpret
Types of demyelination neuropathies
- uniform - all segments in all nerves (e.g. hereditary and sensory type 1 disorders)
- multifocal -some segments in some nerves but not all (e.g. acute/chronic inflammation)
- Monofocal - 1 nerve, 1 site (e.g. carpal tunnel, usually compressive syndromes)
Causes of demyelination
Systemic illness - DM - chronic liver disease - mulitple myeloma Drugs/toxins: - amiodarone - diphtheria toxin
Definition of Guillain-Barre syndrome
Acute immune-medicated peripheral polyneuropathy
Clinical features of Guillain-Barre syndrome
Progressive, symmetrical muscle weakness + areflexia
Usually begins in legs and moves upwards
+/- paraesthesia in hands and feet
Dysautonomia in 70% (tachycardia, urinary retention, alternating BP, orthostatic hypotension, bradycardia, arrhythmias, loss of sweating)
Laboratory features of Guillain-Barre syndrome
Lumbar puncture (CSF)
- increased protein
- normal WCC
Neurophysiology studies (electromyogram or NCS)
- acute polyneuropathy
- predominantly demyelinating features
Glycolipid antibodies
Natural history of Guillain Barre syndrome
Usually lasts a few weeks, symptoms then improve slowly over weeks to months
Most recover with no long-term weakness
2% will develop relapsing weakness of chronic inflammatory demyelinating polyneuropathy
management of Guillain Barre Syndrome
Supportive care:
- O2, intubation/ventilation as indicated
- autonomic function monitoring
- bowel and bladder care
- pain control (CBZ or gabapentin)
- Rehab
Disease modifying treatment:
- if non-ambulatory presenting within 4w of symptom onset
- Plasma exchange (removes circulating antibodies, complement and soluble biological response modifiersd)
- IVIG (if more severe clinical disease, usually preferred treatment based on administration and availability)
NO ROLE OF CORTICOSTEROIDS
Complications of plasma exchange
Hypotension
Sepsis
Problems with IV access
Complications of IVIG
Aseptic meningitis
Rash
Acute renal failure
Poor prognostic factors for Guillain-Barre syndrome
- older age
- rapid onset (less than 7d) prior to presentation
- Severe weakness on admission
- need for ventilator support
- preceding diarrhoeal illness
Triggers commonly identified for Guillain-Barre syndrome
Campylobacter HIV CMV Influenza-like illness EBV
Immunisation (esp flu and meningococcal)
Trauma
Bone marrow transplant
Management of migraines
- Avoid identified triggers
ACUTE ATTACK - simple analgesics (paracetamol, NSAIDs, aspirin)
+ triptans (serotoning agonists, inhibit release of vasoactive peptides - promote vasoconstriction and block pain pathways in the brainstem)
PROPHYLACTIC TREATMENT
- indicated if more than 1/week or symptomatic treatments ineffective or contraindicated
- Anti-HTN (Propanolol, Ca-channel blockers, ACEi)
- Antidepressants (TCAs)
- AEDs (valproate, topiramate)
- Domperidone (motillium)
- Gabapentin
Definition of motor neurone disease
Progressive, incurable degenerative disorder of motor neurons of the CNS related to excitotoxicity due to elevated levels of glutamate
Most commonly sporadic but can be familial in 5-10%
Clinical features of motor neuron disease
INITIAL PRESENTATION:
- Asymmetric limb weakness is most common presentation (commonly foot drop and hand weakness)
- bulbar segment onset (dysarthria or dysphagia)
- respiratory muscle weakness
- generalised weakness in limbs and bulbar muscles
COGNITIVE - frontotemporal dementia
AUTONOMIC
- constipation
- dysphagia
- early satiety and bloating
- urinary urgency
- diaphoresis
Progression:
- variable rate
- symptoms initially spread within the segment of onset then to other regions in relatively predictable pattern (e.g. unilateral arm onset - contralateral arm - ipsilateral leg - contralateral leg - bulbar muscles)
Life threatening features of motor neuron disease
Neuromuscular respiratory failure
- diaphragm generally spared, therefore easier to breathe while sitting upright
- often experience nocturnal hypoventilation if lying flat
Progressive dysphagia
- aspiration of foods, liquids or secretions - pneumonia
- malnutrition and dehydration
- minimise risk early with PEG feeding
Good prognostic factors in motor neuron disease
- Riluzole
- glutamate antagonist - red. excitation
- increase survival by 3-6m - Early PEG feeding
- reduces risk of aspiration pneumonia
- improves nutrition, general health - Non-invasive ventilation
- prevents respiratory failure overnight especially and improves drowsiness etc. during the day - Referral to a multi-disciplinary MND clinic
Features of frontotemporal dementia
Medial syndrome:
- apathy
- lack of energy
- introverted
- reduction in speech, potentially progressing to mutism
Lateral syndrome:
- loss of empathy, especially towards spouse (usually on non-dominant side of the brain)
- disinhibition
- lack of judgement/insight - impulsivity
- Wrong use of words
- perseveration of motor movements and speech
Most cases originate from the R frontal lobe
Loss of MMSE points per year with dementia
3-4
If declining slower, probably just age related
Brainstem 4 rules of 4s
- There are 4 structures in the midline, beginning with M
- motor pathway (Corticospinal tract)
- medial lemniscus
- medial longitudinal fasculus
- motor nuclei (3, 4, 6, 12) - There are 4 structures to the Side (lateral) beginning with S
- Spinothalamic tract
- Spinocerebellar tract
- Sensory nucleus of CN V
- Sympathetic pathway - There are 4 CN above the pons, 4 CN in the pons and 4 CN in the medulla
- The 4 motor nuclei that are in the midline are dose that divide into 12, others are lateral brainstem (i.e. 3, 4, 6, 12)
Clinical features of medial brainstem syndromes
Motor nuclei - ipsilateral loss of CN affected (3 = dow’n n’ out, 4, 6, 12 = deviation of tongue towards side of lesion)
Motor pathway - contralateral weakness of arm or leg
Medial lemniscus - contralateral loss of vibration and proprioception affecting arm and leg
Medial longitudinal fasciculus - failure of adduction of ipsilateral eye + nystagmus of contralateral eye as it looks laterally
Clinical features of lateral brain stem syndromes
Spinocerebellar - ipsilateral ataxia of arm and leg
Spinothalamic - contralateral alteration of pain and temperature affecting arm and leg
Sensory nucleus of CNV - ipsilateral alteration of pain and temperature on the face in distribution of CNV
Sympathetic pathway - ipsilateral horner’s syndrome
+ Cranial neuropathies of lateral CN in affected area (pons v medulla)
Vascular supply to the brainstem
Paramedian branches - medial structures
Long circumferential branches - lateral structures
(Superior cerebellar artery, anterior inferior cerebellar artery and posterior inferior cerebellar artery)
Lateral medullary syndromes can also be secondary to unilateral vertebral occlusion
Features of lacunar/subcortical strokes
PURE motor hemiparesis or PURE sensory loss affecting contralteral arm and leg EQUALLY
is NOT associated with:
- dysphagia
- visual field loss
- visual inattention
Features of anterior cerebral artery stroke
Leg weakness more than arm
Personality change
Oculomotor palsy
Urinary incontinence
Features of middle cerebral artery stroke
Arm weakness more than leg Dysphasia Dyspraxias Agnosia (inability to recognise things) Neglect Poor two-point discrimination Dysgraphaesthesia
Features of posterior cerebral artery stroke
Cortical blindness = contralateral homonymous hemianopia with normal fundoscopy and normal pupil reaction to light
Can also have subcortical signs to confuse things
Features and cause of Gerstmann’s syndrome
RAAF (like the air force) right-left confusion Agraphia Acalculia Finger agnosia
Caused by infarct to DOMINANT parietal lobe
Features of vertebrobasilar territory ischaemia
Bilateral weakness or sensory disturbance
Diplopia
Vertigo
+/- nausea, vomiting and inability to stand
Risk factors for brainstem infarcts
SYSTEMIC HYPERTENSION Diabetes mellitus Smoking Inc. age High LDL and cholesterol Chiropractic manipulation
Aetiology of lateral v medial medullary infarcts
Lateral medullary syndrome: - atherothrombosis 58% - arterial dissection 31% - cardioembolic 10.3% Tend to be more associated with younger patients with head trauma
Medial medullary syndrome:
- atherothrombosis 87%
- arterial dissection 12.5%
Investigations in brainstem infarcts
Must have a high index of clinical suspicion, as very small infarcts which may not be visible on MRI can cause significant clinical symptoms!
MRI misses 37% and 13% of medial and lateral syndromes respectively
Therefore MRI does not change management in a classical medullary presentation, but excludes other causes
Poor visibility of posterior circulation on CT due to the skull
Definition of myasthenia gravis
An autoimmune disorder in which antibodies form against acetylcholine nicotinic postsynaptic receptors at the neuromuscular junction of skeletal muscles, causing weakness of those muscles involved
Epidemiology of myasthenia gravis (incidence, who does it affect, risk factors)
1-2/100,000 per year
Occurs at any age
Bimodal distribution: early peak in teens-20s with female predominance, late peak in 50-70s with male predominance
Neonatal myasthenia gravis is transient form in neonates as a result of transplacental passage of maternal antibodies interfering with neuromuscular junction
May be associated with other AI disorders (e.g. RA, SLE, scleroderma)
Pathophysiology of mysasthenia gravis
Anti-acetylcholine receptor autoantibodies attack AChR, reduce number of receptors over time
Autoantibodies thought to originate in hyperplastic germinal centres in the thymus
- 60-70% have thymic hyperplasia
- 10-12% have thymoma
Presenting symptoms of myasthenia gravis
FLUCTUATING SKELETAL MUSCLE WEAKNESS
- specific muscles, not generalised muscle fatigue
- most commonly worse in late day/evening or after exercise
Occular (over 50%):
- ptosis and or diplopia
- may switch from one eye to the other etc
- PUPILS ALWAYS SPARED
Bulbar (15%):
- fatigable chewing occurring half-way through meal
- dysarthria (nasal or hypophonic, worsens with prolonged speech)
- dysphagia
- nasal regurgitation of liquids (palatal weakness)
Proximal limb weakness alone (5%)
- arms more than legs
Clinical signs in myasthenia gravis
Curtain sign: ptosis increases by holding up the opposite eyelid with examiner’s finger
Myasthenic sneer: mid-lip rises when try to smile but outer corners of mouth fail to move
Orbicularis oculi weakness - prying eyes open on forced closure
Dropped head syndrome: weight of head overcomes neck extensors, especially late in day
Investigations for myasthenia gravis
Bedside test:
- Tensilon/Edrophonium test: readily reversible acetycholinesterase inhibitor prevents breakdown of ACh at NM junction - reduces weakness or ptosis in patients with myasthenia gravis
- Ice pack test: cover eye for 1-2 minutes with ice pack and examine for improvement of ptosis when remove
Laboratory tests:
- serologic tests for autoantibodies
- repetitive nerve stimulation studies and single-fibre EMG
Management of myasthenia gravis
Symptomatic treatment:
- oral anticholinesterases (pryidostigmine, neostigmine)
- 15-30 min onset of action, duration 3-4h
- S/E cholinergic crisis (rare) but mimics worsening of myasthenia gravis
Chronic immunotherapies
- if patients have significant symptoms on pyridostigmine
- high dose glucocorticoids (preferred in child-bearing age patients)
- AZA, mycophenolate mofetil, cyclosporine
Rapid immunotherapies:
- Used in myasthenic crisis, preop before thymemctomy or other surgery, as a bridge to slower acting immunotherapies
- Plasmapheresis or IVIG
Surgical:
- thymectomy
- mainstay if thymoma is present
Lifestyle:
- avoid drugs which worsen MG
- annual influenza vaccine if on immunosuppressive therapy
Medications to avoid in myasthenia gravis
Aminoglycoside antibiotics Beta blockers Procainamide Quinidine Quinine Phenytoin
Prognosis of myasthenia gravis
Symptoms start as transient early on
typically worsen and become more persistent
Progression peaks within 2-3y
Active phase 5-7y, stable phase, remission phase
Myasthenic crisis
Life threatening condition characterised by neuromuscular respiratory failure
Severe bulbar weakness - dysphagia - aspiration often complicated respiratory failure
Typically experience generalised weakness as a warning
Treat with hospitalisation and rapid immunotherapy (IVIG or plasmapheresis)
Definition of CJD
Creutzfeldt-Jakob disease is the most frequently occurring human prion disease, classified into 5 different types, each of which cause neurodegenerative disease which progress inexorably after a long incubation period
Types of CJD
Sporadic: 85-95%
- family history
- personal history of psychosis
- multiple surgical procedures
- spent over 10y on a farm
Familial: 5-15%
Variant - much younger age
- related to mad cow disease
Iatrogenic: less than 1%
- following administration of cadaveric human pituitary hormones (GH and gonadotrophin), dual graft transplants, corneal orliver transplants, contaminated neurosurgical instruments
Symptoms of CJD
RAPIDLY PROGRESSIVE MENTAL DETERIORATION AND MYOCLONUS Mental deterioration: - dementia - behavioural abnormalities - deficits of higher cortical function - concentration, memory and judgement difficulties are frequent early signs - mood changes (apathy and depression) - hypersomnia or sleep disturbances
Myoclonus - 90% of patients will develop at some point, especially provoked by startle
Extrapyramidal and cerebellar: - hypokinesia - nystagmus - ataxia Corticospinal tract involvement - hyperreflexia - extensor Babinski - spasticity
Psych symptoms are more prominent in younger patients and clinical course is often more prolonged
CRANIAL AND PERIPHERAL NERVES ARE NOT INVOLVED. SENSORY ABNORMALITIES ARE RARE
Diagnostic criteria for CJD
Progressive dementia AND At least 2 of the following - myoclonus - visual or cerebellar disturbance - pyramidal/extrapyramidal dysfunction - akinetic mutism AND 1 of: - atypical EEG during an illness - a positive 14-3-3 CSF assay with a clinical duration to death less than 2y - MRI high signal abnormalities in caudate nucleus and/or putamen on DWI or FLAIR AND Routine investigations do not suggest alternative diagnosis
Protein marker for CJD
14-3-3 in CSF fluid
Prognosis of CJD
No effective treatment
Supportive care
Death usually occurs within 1 year of symptom onset
Median disease duration of 6 months
Definition of syringomyelia
The formation of fluid-filled, gliosis-lined cavity (syrinx) in the spinal cord
