Myasthenia Gravis
Neurology | Neuromuscular Disorders | Neuromuscular Junction Disorders
Overview
Third most common cause of death worldwide and most common cause of neurological disability. It is subdivided into ischaemic stroke (caused by vascular occlusion or stenosis) and haemorrhagic stroke (caused by vascular rupture, resulting in intra-parenchymal and/or subarachnoid haemorrhage).
Definition
Stroke: Acute onset of a focal neurologic deficit due to a cerebral infarction or hemorrhage.
Transient Ischaemic Attack (TIA): Transient episode of neurological dysfunction caused by focal brain or retinal ischaemia, without infarction. When there is evidence of brain infarction, the episode is considered to be a mild stroke (if symptoms are minor or disappear).
Amaurosis Fugax: Transient monocular blindness that often is described as a gray shade being pulled down over the eye caused by ischemia to the retinal artery.
Anatomy and Phsyiology
Cerebral anatomy and blood supply
Sensory Pathways
Motor Pathways
Watch Video
Aetiology and Risk Factors
Aetiology
- Ischaemic stroke (80%)
- Cerebral haemorrhage
- Subarachnoid haemorrhage
Risk Factors
Non-Modiafiable Risk Factors
- Age
- Family history
- Diabetes mellitus
- Chronic kidney disease
- Sleep apnea
- Infective endocarditis
Modifiable risk factors
- Hypertension
- Atrial fibrillation
- Smoking
- Symptomatic carotid artery disease
- Sickle cell disease
- Physical inactivity
- Regular consumption of sweetened beverages
- Low daily consumption of fish, fruits, or vegetables
In Women
- Oral contraceptives
- Migraine with aura
- Immediate postpartum period
- Pre-eclampsia
Remember
The highest- risk patients for stroke are those with previous ischemic events such as TIA.
Classification
Types of stroke
- Ischaemic
- Large vessels disease
- Embolism
- Small vessels (lacunar)
- Uncertain
- Rare – dissection, venus infarction
- Haemorrhage
- Primary intracerebral haemorrhage
- Subarachnoid haemorrhage
Side note
Although traditionally included as a type of stroke, subarachnoid haemorrhage is quite distinct. It presents with acute onset of severe headache or sudden loss of consciousness, is diagnosed by CT scan and managed by the neurosurgeon.
| Anatomical classification – Oxford territorial classification |
| Total anterior circulation infarct |
| Partial anterior circulation infarct |
| Posterior circulation infarct |
| Lacunar infarct |
| Pathophysiological classification – TOAST |
| Large-artery atherosclerosis (embolus/thrombosis) |
| Cardioembolism (high-risk/medium-risk)Atrial fibrillationValvular heart diseaseValvular prosthesisPost MIDilated cardiomyopathyPatent foramen ovale |
| Small-vessel occlusion (lacune) |
| Stroke of determined aetiologyArterial dissectionHypercoagulable stateHaematological disorders |
| Stroke of undertermined aetiology |
Think
cardioembolism can cause multiple infarcts, often in different vascular territories. Whereas large artery atherosclerosis is a single area of infarct.
Clinical Manifestation
Remember
FAST – acute signs and symptoms of stroke
Face: unilateral drooping
Arms: these may feel weak and numb. Patient may not be able to lift them
Speech: slurring of speech
Time: time for emergency medical attention
Symptoms
- Acute onset
- Arm weakness
- Leg weakness
- Self-reported speech disturbance
- Facial weakness
- Arm paresthesia
- Leg paresthesia
- Headache
- Nonorthostatic dizziness
Signs
- Arm paresis
- Leg paresis
- Dysphasia or dysarthria
- Hemiparetic/ataxic gait
- Facial paresis
- Eye movement abnormality
- Visual field defect
Clinical Presentation based on location of “stroke” using the Anatomical classification – Oxford territorial classification:
- Anterior circulation infarct
- Posterior circulation infarct
- Lacunar infarct
| Anterior circulation (carotid territory) |
| Amaurosis fugax/retinal infarction. |
| Hemiparesis |
| Hemisensory loss |
| Hemianopia (optic tract and radiation) |
| Dysphasia |
| Sensory inattention |
| Visual inattention |
| Posterior circulation (vertebrobasilar) |
| Ataxia |
| Cranial nerve involvement:diplopiafacial sensory lossdysphagiadysarthria |
| Hemiparesis (may be bilateral) |
| Hemisensory loss (may be bilateral) |
| Hemianopia (occipital lobe) |
| Cortical blindness—basilar artery occlusion |
| Lacunar |
| Pure motor strokes (face, arm, and leg) in the posterior limb of internal capsule |
| Pure sensory stroke (thalamus) |
| Ataxic hemiparesis (weakness and ataxia affecting the same side) due to a pontine lesion |
| Clumsy hand/dysarthria due to a lesion in the pons or in its internal capsule. |
Investigations
Imaging
- CT brain non-contrast to rule out haemorrhagic stroke
- CT show 50% of lesions only however is most available and is fast
- CT angiogram from aorta to circle of willis (COW)
- MRI Brain
Infarcts best detected by MRI (but not in first few hours) > CT
Remember
Imaging should be performed within 24 hours to exclude haemorrhagic stroke and other causes, e.g. tumours.
General
- FBC
- ESR
- Ca2+ (hypo- or hypercalcaemia may be a cause of focal deficit).
- EUC
- LFT
- Glucose
- Thyroid function test
- Lipid Profile
- Coagulation profile
Other blood investigations to consider
- Thrombophilia screen
- Protein C, S, and antithrombin III defects
- Factor V Leiden mutation
- Antiphospholipid antibody
- Lactate
- Cardiac enzymes
Other investigation
- Urine analysis – diabetes, haematuria in BE or vasculitis, toxicology screen
- ECG – AF, MI
- Echocardiogram and TOE.
Differential Diagnosis
| CONDITION | CLINICAL MANIFESTATION |
| Brain tumor | Severe unilateral headache with nausea and vomiting |
| Central nervous system infection (e.g., meningitis, encephalitis) | Fever, headache, confusion, neck stiffness, nausea, vomiting, photophobia, change in mental status |
| Falls/trauma | Headache, confusion, bruising |
| Hypoglycemia | Confusion, weakness, diaphoresis |
| Migraines | Severe headaches with or without photophobia, younger age |
| Multiple sclerosis | Diplopia, limb weakness, paresthesia, urinary retention, optic neuritis |
| Seizure | Confusion with or without loss of consciousness, urinary incontinence, tongue biting, tonic-clonic movements |
| Subarachnoid hemorrhage | Severe headache with sudden onset and photophobia |
| Vertigo (central or peripheral) | Generalized dizziness and diaphoresis with or without hearing loss |
Remember
TIA is more likely with sudden onset, unilateral paresis, speech disturbance, or transient monocular blindness.
Treatment
The development of an acute stroke or transient ischaemic attack is a medical emergency.
| INDICATION FOR CT/MRI |
| Patient on anticoagulants or with abnormal coagulation |
| Plan to give thrombolysis or immediate anticoagulants |
| Deteriorating conscious level or rapidly progressing deficits |
| Suspected cerebellar haematoma, to exclude hydrocephalus |
General management
- CT – to rule out Haemorrhagic cause
- Admission to stroke unit
Remember
Urgent brain imaging is required. Computerised tomography (CT) can help to exclude a stroke mimic and to differentiate haemorrhagic to ichaemic stroke.
Acute ischaemic stroke
- Thrombolysis – alteplase (within 4.5 hours. >4.5 hours is not recommended)
- If thrombolysis is not possible then antithrombotic therapy should be commenced
- Antiplatelet drugs
- Contraindicated in haemorrhagic stroke (CT)
- Within 48 hours reduces mortality and recurrent stroke
- Surgery
- Neurosurgical hemicraniectomy – if cerebral oedema (cerebral oedema has 80% mortality)
Pharmacology
Alteplase is a recombinant tissue plasminogen activator.
Long term interventions following a stroke or TIA are aimed at preventing a future episodes (secondary prevention)
- Education and rehabilitation
- Antiplatelet therapy – aspirin + dipyridamole
- Anticoagulant – warfarin if has Atrial fibrillation
- Treat hypertension
- Treat dyslipidaemia with statin
- Treat Diabetes mellitus
- Treat Atrial fibrillation
- Smoking cessation
- Alcohol cessation
- Weight loss
- Increase physical activity
- Hormone Replacement Therapy should be stopped
- Carotid endarterectomy or stenting
Side note
Eligible stable patients should undergo carotid endarterectomy as soon as possible after the stroke event (ideally within two weeks).
Acute Haemorrhagic Stroke
- Brain imaging with CT
- Neurosurgical and neurocritical care evaluation
- ICU admission
- Supportive care – airway protection, aspiration protection
- DVT/PE prophylaxis
- Anti-pyretic measures – Fever has been associated with worse outcome after intracranial haemorrhage, and hypothermia is neuroprotective in animal models.
Remember
Some patients with an intracerebral haemorrhage will be on warfarin therapy. Warfarin therapy must be urgently reversed with a combination of prothrombin complex concentrate, fresh frozen plasma and vitamin K.
Complications and Prognosis
Complications
Prognosis Ischaemic Stroke
- Mortality following ischaemic stroke is 8% to 12%.
- Long-term significant disability, sufficient to impair or prevent return to work, is seen in another 15% to 30%
- Advanced age, female sex, and medical comorbidities have also been associated with worse outcomes
Prognosis Haemorrhagic Stroke
- Mortality is significantly higher than for ischaemic stroke, in the range of 35% to 40%
- Haemorrhage volume is the strongest predictor of outcome.
References
AAFP – Diagnosis of Acute Stroke 2015
Best Practice
UpToDate
Discussion