Neurology Flashcards
Describe the corticospinal tracts
Descending pathway for motor control
Located in the white mater of the spinal cord, laterally or ventrally (anterior)
The UMN travels from the primary motor cortex through the internal capsule, the 85% of the fibres decussate at the medulla to from the lateral corticospinal tract (remainder form the ventral tract)
They synapse with the LMN in the ventral grey horn and the axons leave in the spinal nerve
What does a lesion of the corticospinal tract cause?
Ipsilateral weakness of muscles
Describe the dorsal column pathway
An ascending tract for touch, proprioception, and vibration
Located in the dorsal white matter of the spinal cord
The cuneate fasciculus (more lateral) carries information from the upper limbs, and the gracile fasciculus (more medial) carries information from the lower limbs
Primary sensory neurons ascend in the ipsilateral dorsal columns and synapse with the 2nd neuron at the cuneate/gracile nucleus (in medulla)
The 2nd neuron decussates in the medulla then ascends to the thalamus, where is synapses with the 3rd neuron, which then projects to the somatosensory cortex
What does a lesion of the dorsal column pathway cause?
Ipsilateral impairment/loss of fine touch, proprioception, and vibration
Describe the spinothalamic tract
An ascending tract for pain and temperature
Located in the ventrolateral white matter of the spinal cord
The primary sensory neuron synapses with the 2nd neuron in the grey horn, and this decussates then ascends
It synapses with the 3rd neuron in the thalamus which then projects to the somatosensory cortex
What does a lesion in the spinothalamic tract cause?
Contralateral impairment/loss of pain and temperature sensation
Define cerebrovascular event (stroke)
A clinical syndrome caused by disruption of blood supply to the brain (due to infarction or haemorrhage), characterised by rapidly developing signs of focal or global disturbance of cerebral functions, lasting for more than 24 hours or leading to death
Define ischemic stroke
An episode of neurological dysfunction caused by focal cerebral, spinal, or retinal infarction (cell death due to lack of blood supply)
What are the 5 types of ischemic stroke?
Large vessel disease (atherosclerosis/thrombosis)
Small vessel disease (microathermoma, lacunes)
Cardioembolic (caused by AF, endocarditis, mural thrombus)
Other (rare causes e.g. vasculitis, venous thrombosis, carotid dissection)
Undefined
Define stroke due to primary intracerebral haemorrhage
Rapidly developing clinical signs of neurological dysfunction because of a focal collection of blood within the brain parenchyma or ventricular system, which is not caused by trauma
*secondary intracerebral haemorrhage = due to trauma, blood thinners etc.
Define stroke due to subarachnoid haemorrhage
Rapidly developing signs of neurological dysfunction and/or headache (thunderclap) because of bleeding into the subarachnoid space, which is not caused by trauma
What are the risk factors for strokes?
Lifestyle factors:
- smoking
- alcohol misuse
- physical inactivity
- poor diet
Established CVD:
- hypertension
- AF
- infective endocarditis
- IHD
- congestive heart failure
- structural defects
Other medical conditions:
- migraine
- hyperlipidaemia
- diabetes mellitus
- hypercoagulable disorders
- connective tissue disorders
Non-modifiable factors:
- older age
- male sex
- personal/family history of stroke/TIA
- lower level of education
What are the signs/symptoms of a stroke in the anterior circulation?
Either hemisphere (symptoms contralateral):
- hemiparesis (upper limb = MCA, lower limb = ACA)
- hemisensory loss (upper limb = MCA, lower limb = ACA)
- visual field defect
Dominant hemisphere (usually LEFT hemisphere)
- language dysfunction (expressive/receptive dysphasia, dyslexia, dysgraphia)
Non-dominant hemisphere (usually RIGHT hemisphere)
- visuospatial dysfunction (geographical agnosia, dressing apraxia, constructional apraxia)
- anosognosia (impaired understanding of their illness, neglect of paralysed limb, denial of weakness)
What are the signs/symptoms of a stroke in the posterior circulation?
Unsteadiness
Visual disturbance
Slurred speech
Disorder of perception
Headache
Vomiting
Others e.g. memory loss, confusion
What investigations are needed for a stroke?
CT head (1ST LINE, without contrast, ideally within 1 hour)
MRI brain with diffusion weighted imaging (GOLDSTANDARD)
Blood tests (FBC, U&E, ESR, TFTs, glucose, lipids to asses general health and exclude other causes)
ECG (look for arrhythmias and cardiac causes)
ECHO (may show mural thrombus, valvular lesions)
Carotid Doppler ultrasound, or CT/MRI angiogram (asses carotid artery stenosis)
What are the treatments for an ischemic stroke?
ABCDE
Oxygen as needed
Maintain blood pressure and glucose
Antiplatelets (e.g. aspirin) - only once haemorrhagic stroke is ruled out
Thrombolysis - only within 4.5 hours of onset, and if haemorrhagic stroke is ruled out, most effective in 1st 90 mins
Thrombectomy - for larger arterial occlusions
What is the primary prevention for strokes?
Control risk factors:
- asses and treat hypertension, DM, hyperlipidaemia, cardiac disease
- smoking cessation
- exercise
Long term anticoagulants
- e.g. warfarin/DOAC
- in AF or prosthetic heart valves
What is the secondary prevention for a stroke?
Antiplatelets: short-term = aspirin, long-term = clopidogrel
Anticoagulants if cardiac cause (warfarin/DOAC)
Investigate and treat risk factors: hypertension, hyperlipidaemia, cardiac disease, carotid artery stenosis, etc.
Define TIA
Transient ischemic attack:
Transient (less than 24 hours) neurological dysfunction caused by focal cerebral, spinal, or retinal infarction
What are the signs/symptoms of TIA?
*symptoms come on suddenly and usually resolve after 1 hour but can persist up to 24 hours
Focal neurological defects:
- unilateral weakness/sensory loss
- dysphasia
- ataxia, vertigo, loss of balance
Cranial nerve defects
Amaurosis fugax (sudden transient loss of vision in one eye
What are the treatments for a TIA?
Control cardiovascular risk factors (blood pressure, lipids, glucose)
Antiplatelets: short-term aspirin, long-term (secondary-prevention) = clopidogrel
Anticoagulants (warfarin/DOAC) is cardiac cause
Carotid endarterectomy (reduce stenosis)
How is the risk of having a stroke after a TIA assessed
ABCD2 =
Age (>60)
Blood pressure (>140/90)
Clinical features (weakness, speech disturbance)
Duration of symptoms
Diabetes
Higher score = higher risk = urgent referral
Describe the epidemiology of brain tumours
Mostly affects younger patients
55% malignant
How are brain tumours categorised?
Cell type: gliomas (most common - e.g. astrocytoma, ependymoma, oligodendrocytoma)
Location: meninges, sellar region, germ cell tumours (pituitary/pineal region)
Cranial nerve involvement (schwannoma)
Secondary/metastatic
Molecular markers
Genetic factors
Describe the grades of brain tumour
Grade 1: slow growing, non-malignant, and associated with long-term survival
Grade 2: have cytological atypia, slow growing but recur as higher-grade tumours
Grade 3: malignant, have anaplasia and mitotic activity
Grade 4: aggressive malignant tumours, reproduce rapidly, anaplasia, mitotic activity with microvascular proliferation
What are the causes of brain tumours?
Majority no cause found
Ionising radiation
5% family history (associated genetic syndromes)
Immunosuppression (increased risk of CNS lymphoma)
What are the signs/symptoms of brain tumours?
Varied - depends on tumour type, grade and site
Headache (due to raised intracranial pressure)
Seizures (new onset)
Focal neurological symptoms (e.g. limb weakness, sensory loss, visual/speech disturbances, ataxia)
Other non-focal symptoms (e.g. behavioural/cognitive change)
What are the red flags for brain tumours?
Headache + other symptoms
New/changed headache
Headache always on one side
New onset focal seizure
Rapidly progressive focal neurology
Previous history of cancer
What investigations are needed for brain tumours?
CT (1st line, with contrast)
MRI (better detail especially for pituitary lesions)
Functional MRI
Biopsy
What are the treatments for brain cancer?
Depends on tumour type, grade and site
Treatment is non-curative (except for grade I)
High grade:
- steroids - reduces oedema
- surgery - biopsy, relief of raised ICP, debulking for radiotherapy, resection
- chemotherapy + radiotherapy
Low grade:
- early surgery
- early radiotherapy + chemotherapy
Define epileptic seizures
Paroxysmal event in which changes of
behaviour, sensation or cognitive processes are caused by excessive, hypersynchronous neuronal discharges in the brain
Define epilepsy
A chronic neurological disorder of recurrent epileptic seizures
Describe the epidemiology of epilepsy
Affects 1 in 100 (UK)
Highest risk are infants and over 50s
What are the causes of epilepsy?
Idiopathic (2/3)
Structural abnormalities (developmental, or after injury/stroke/infection)
Genetic mutation
Space occupying lesion
What are the characteristics of an epileptic seizure?
Vary varied depending on the type of seizure
Duration: 30-120s
“Positive” ictal symptoms (during in seizures, e.g. excessive limb movements)
“Negative” postictal symptoms (after seizure, paralysis, amnesia)
May occur from sleep
May be associated with other brain dysfunction
Patients can have different types of seizures, but these will stay the same
Describe focal epileptic seizures
Originating from one hemisphere, associated with structural damage
Focal aware seizures: consciousness is not impaired, no post-ictal symptoms
Focal impaired awareness: consciousness is impaired, most commonly in temporal lobe which causes post-ictal confusion
Focal to bilateral convulsive seizure: occurs in 2/3 of patients, electrical disturbance starts focally and spreads widely causing a generalised seizure
Describe generalised epileptic seizures
Electrical disturbance rapidly affecting both hemispheres, with no associated structural abnormality
Tonic-clonic seizures: muscle stiffening (tonic), then jerking (clonic), lasting <5mins, LOC, post-ictal confusion/drowsiness
Absence seizures: brief pauses (<10s) in activity, can happen in clusters, worse with coming in/out of sleep, presents in childhood
Myoclonic seizures: sudden jerking of limb, face and/of trunk, can be thrown to floor but can get up straight away
Tonic seizures: all muscles stiffen, may cause fall, extended neck, open eyes, stop breathing
Atonic seizures: all muscles relax, may cause falls, head drops forwards, knees sag, but no LOC, muscle tone returns quickly after
What investigations are needed for epilepsy?
Look for risk factors and provoking cause
EEG (records electrical activity, can’t exclude diagnosis, can be false +ve in syncope)
MRI (look for structural causes)
ECG (rule out cardiac conditions mimicking epileptic seizures)
Lumbar puncture (if infection is suspected)
Neuropsychiatric assessment
Genetic testing
What are the treatments for epilepsy?
Anti-seizure medication (ASMs):
- focal seizures: carbamazepine or lamotrigine
- generalised seizures: sodium valproate (teratogenic) or lamotrigine
- monotherapy, rarely dual therapy
- withdrawal: only under supervision of specialist, done slowly, only if >2 years seizure free
Phycological therapies:
- relaxation, CBT (don’t improve seizure frequency, so only an adjunct not alternative)
Surgical intervention:
- only if single focus is identified
Others:
- vagal nerve stimulation
- deep brain stimulation
Describe syncope
A paroxysmal event in which changes in behaviour, sensation and cognitive processes are caused by an insufficient blood or oxygen supply to the brain
Symptoms: loss of consciousness, may have clonic jerking of limbs, with nausea, pallor, sweating and narrowing of visual field occurring before
Often situational, lasting less than 2 mins, and does not occur when lying down/sleeping
Describe non-epileptic seizures
A paroxysmal event in which changes in behaviour, sensation and cognitive function caused by mental processes associated with psychosocial distress
Also called functional/dissociative seizures
Characteristics: situational, duration of 1-20 mins, can have motor symptoms of atonia, eyes closed, history of psychiatric illness
Define an extradural haemorrhage
Bleeding (arterial) between the skull and the dura
What are the causes of an extradural haemorrhage?
Usually traumatic - fractured temporal or parietal bone causing laceration of the middle meningeal artery
What are the clinical features of an extradural haemorrhage?
May present with traumatic injuries
Can have a ‘lucid period’ lasting hours-days
Rising ICP causes decreasing GCS
Symptoms include headache and drowsiness
Can cause coma and death if not treated rapidly
How does an extradural haemorrhage appear on a CT scan
Acute (fresh) blood appearing hyperdense (bright wight)
Convex - does not conform to surface of the brain, limited by dural attachments
Involves compression of the brain (midline shift of falx cerebri, compression of lateral ventricles)
Skull fracture may be seen (or picked up on X-ray)
How is an extradural haemorrhage managed?
Palin X-ray of skull
CT head
ABC management
Oxygen if needed
IV fluids to maintain circulation
Mannitol (to reduce ICP)
Surgery
Define subdural haemorrhage
Bleeding (venous) between the dura and arachnoid
What are the causes of a subdural haemorrhage?
Usually trauma - a fall or minor event causing bleeding from dural bridging veins
Could be due to low ICP or dural metastases
More likely in patients with brain atrophy (elderly, dementia, alcoholics, epilepsy)
What are the clinical features of subdural haemorrhage?
Gradual/insidious physical or intellectual slowing
Fluctuating level of consciousness
History of fall (can be minor, up to 9 months ago)
Raised ICP
Other symptoms include sleepiness, headache, personality changes, unsteadiness
Localised neurological symptoms (e.g. unequal pupils, hemiparesis) occur late
How does a subdural haemorrhage appear on a CT scan?
Chronic (old) bleed appears hypodense (dark)
Concave - conforms to surface of the brain as bleeding is not limited by dural attachments
Involves compression of the brain (midline shift of falx cerebri, compression of lateral ventricles)
A clot may be seen on CT or MRI
How is a subdural haemorrhage managed?
Bloods: check for bleeding disorders and other causes of impaired consciousness
Urgent CT
ABC management
Intubation/ventilation if unconscious
Mannitol (to reduce ICP)
Surgery
Define a subarachnoid haemorrhage
Bleeding (arterial) between the arachnoid and pia (arachnoid space)
What are the causes of a subarachnoid haemorrhage?
Usually spontaneous rupture of a berry aneurysm, or due to arterio-venous malformations
Can be traumatic but rarely
What are the clinical features of a subarachnoid haemorrhage?
Sudden-onset excruciating headache (thunder-clap)
May have vomiting, collapse, seizures, neck stiffness, or focal neurology (pupil changes, hemiparesis)
Could be conscious, reduced GCS, or unconscious
How does a subarachnoid haemorrhage appear on CT?
Acute (fresh) bleed is hyperdense (bright white)
Blood seen in fissures and cisterns +/- ventricles
How is a subarachnoid haemorrhage managed?
Urgent CT head scan
CT angiography
Nimodipine (calcium antagonist, reduces vasospasm)
Control blood pressure
Surgery (endovascular coiling or surgical clipping)
What are the complications of a subarachnoid haemorrhage?
Irritation to the meninges
Hypoxic injury (due to vasospasm of the cerebral vessels)
Hydrocephalus (due to blockage of the ventricular system)
Describe an intracerebral haemorrhage
Bleeding into the brain parenchyma
Caused by spontaneous rupture of aneurysm/vessel
Occurring in small perforating vessels prone to rupture, especially if hypertensive
Clinical features: determined by size and location of bleed - weakness (facial/limbs), seizure, coma
CT: acute hyperdense blood, within substance of brain, with mass effect (midline shift) if large
Define meningitis
Inflammation of the meninges
What are the causes of meningitis?
Infective:
- bacteria
- viral
- fungal
- parasitic
Non-infective:
- paraneoplastic
- drug side effects
- autoimmune (e.g. vasculitis/SLE)
Which pathogens cause acute meningitis?
Bacterial:
- Neisseria meningitidis (gram -ve cocci)
- Streptococcus pneumoniae (gram +ve cocci)
- Haemophilus influenzae B, E.coli (gram -ve bacilli)
- Listeria monocytogenes (gram +ve bacilli)
Viral:
- Herpes Simplex Virus (HSV)
- Varicella Zoster Virus (VZV)
- Enterovirus
Describe the transmission of meningitis
The most common organism causing meningitis (Neisseria meningitidis and Streptococcus pneumoniae) are normal commensals of the nasopharynx
These are spread by aerosol, droplets, or direct contact with secretions
Which pathogens cause chronic meningitis?
Bacterial:
- Mycobacteria tuberculosis
- Syphilis
Fungal:
- Cryptococcal
Other:
- non-infective
- parasitic
- Lyme disease
What are the signs/symptoms of meningitis?
Fever
Headache
Photophobia (eye discomfort in bright light)
Neck stiffness (“meningism”)
Non-blanching purpuric rash
Later/rare:
- shock (hypotension, prolonged capillary refill time)
- reduced GCS or coma
- seizures
What are the investigations needed for meningitis?
Blood cultures
Nose and throat swabs: for culture and PCR
Lumbar puncture (microscopy and culture of CSF):
- bacterial = cloudy, neutrophils, high protein, low glucose
- viral = clear, lymphocytes, high protein, normal glucose
CT (if aged >60, immunocompromised, history of CNS disease, seizures)
Bloods: FBC, U&E, glucose, coagulation (asses general health, rule out differentials)
What are the treatments for meningitis?
Broad spectrum antibiotics (e.g. ceftriaxone unless contraindicated in penicillin allergy, immunocompromised, recent travel, expect listeria = amoxicillin)
Steroids (IV dexamethasone)
Oxygen support, fluid resuscitation, analgesia, metabolic correction (as needed)
What is given to close contacts of those diagnosed with bacterial meningitis?
Prophylactic ciprofloxacin
Define encephalitis
Inflammation of the brain
What are the causes of encephalitis?
Viral (most common):
- herpes simplex
- varicella zoster
- HIV
Bacteria:
- listeria
- TB
- any cause of bacterial meningitis
Fungal:
- cryptococcus
Non-infective:
- autoimmune
- paraneoplastic
Tropical:
- tick borne
Describe the epidemiology of encephalitis
More common in children and the elderly
What are the signs/symptoms of encephalitis?
Initial flu-like illness (headache, fever)
Altered GCS - confusion, drowsiness, coma)
Seizures
Focal neurological signs
What are the investigations needed for encephalitis?
Blood cultures + serum for PCR
Nose and throat swabs: for culture and PCR
Contrast CT: identify raised ICP, rule out space-occupying lesion, stroke etc.
MRI: more detail, shows oedematous changes
Lumbar puncture: high proteins and lymphocytes, low glucose
EEG: abnormal, can help to determine localisation
What are the treatments for encephalitis?
Aciclovir (treats viral causes)
Supportive treatments: fluids, sedatives, ventilation
Describe meningoencephalitis
Encephalitis + meningitis
Inflammation of the brain and meninges
Clinical symptoms = lethargy, decreased GCS, fever + meningism (stiff neck, photophobia, headache)
Describe cranial nerve I
Name = olfactory
Function = smell
Fibres = sensory
Test = smelling
Its receptors are in the nasal cavity, and the axons travel through the cribriform plate to olfactory bulbs, which travel as tracts to the olfactory centres in the temporal lobe
There are connections with the limbic system
Lesion present as anosmia
Describe cranial nerve II
Name = optic
Function = vision, afferent limb of pupillary light reflex
Fibres = sensory
Test = visual acuity, fields, pupillary light reflex
Fibres travel from the retina through optic canal as the optic nerve, via the optic chiasm, and then as the optic tracts to the primary visual cortex (in the calcarine sulcus, medial aspect of occipital lobe)
Lesions present as visual field defects, pupillary light reflex = no response in either eye when shone in affected side, normal response when shone in unaffected side
Describe cranial nerve III
Name = oculomotor
Function = movement of MR, SR, IR, IO, LPS, efferent limb of pupillary light reflex
Fibres = motor, parasympathetic
Nerve root = between midbrain and pons
Test = eye movements, pupillary light reflex
Lesion presents as ptosis, lack of certain eye movements, pupil dilation, pupillary light reflex = no response in eye of affected side, but response in other
Describe cranial nerve IV
Name = trochlear
Function = movement of SO
Fibres = motor
Nerve root = midbrain, exists dorsally and its course is anterior
Test = eye movements (look laterally and down)
Lesion presents as diplopia when looking down
Describe cranial nerve V
Name = trigeminal (1 - ophthalmic, 2 - maxillary, 3 - mandibular)
Function = 1- general sensation to the forehead, cornea, anterior nose, 2 -general sensation to cheeks, lower eyelid, nasal cavity, upper lip, 3 - general sensation to external ear, lower lip, chin, anterior 2/3 of tongue + motor to muscle of mastication
Fibres = sensory (+ muscles of mastication in 3)
Nerve root = pons
Test = general sensation over face, corneal reflex, movement of jaw
Lesion presents as loss of sensation, weakness/paralysis of jaw
Describe cranial nerve VI
Name = abducens
Function = motor to LR
Fibres = motor
Nerve root = pons (pontomedullary junction)
Test = eye movement (looking laterally and down)
Lesion presents as medial deviation when looking forwards, unable to look laterally
Describe cranial nerve VII
Name = facial
Function = muscles of facial expression, taste to anterior 2/3 tongue, stimulation of lacrimal, submandibular, and sublingual salivary glad secretion
Fibres = motor, sensory, parasympathetic
Nerve root = pons (cerebellopontine angle)
Fibres travel through the internal acoustic meatus and innervate the upper face bilaterally and the lower face contralaterally
Test = taste (anterior 2/3), muscles of facial expressions (frown, screw up eyes, smile etc), corneal reflex (efferent limb)
Lesion presents as ipsilateral facial weakness (upper and lower face)
Describe cranial nerve VIII
Name = vestibulocochlear
Function = hearing and balance
Fibres = sensory
Nerve root = pons (cerebellopontine angle, more lateral)
Test = hearing, balance, gait, caloric test
Lesion presents as hearing loss, balance issues
Describe cranial nerve IX
Name = glossopharyngeal
Function = motor to stylopharyngeus, sensation to pharynx and posterior 1/3 tongue (+taste), stimulation of parotid salivary gland secretion
Fibres = motor, sensory, parasympathetic
Nerve root = medulla (more superior, several small rootlets)
Test = gag reflex (afferent limb), taste posterior 1/3 tongue
Describe cranial nerve X
Name = vagus
Function = sensation to pharynx, larynx, oesophagus, motor to soft palate, pharynx, larynx, parasympathetic to thoracic and abdominal viscera
Fibres = sensory, motor, parasympathetic
Nerve root = medulla (several small rootlets)
Test = swallowing, gag reflex (efferent limb), hoarseness of voice, elevation of palate
Lesion present as difficulty swallowing, hoarse voice, deviation of uvula and palate away from lesion
Describe cranial nerve XI
Name = accessory
Function = movement of sternocleidomastoid and trapezius
Fibres = motor
Nerve root = cranial - medulla (more posterior, several small rootlets), spinal - ventral horn of spinal cord
Test = shrugging of shoulders, turning head
Lesion presents as weakness/paralysis of these movements
Describe cranial nerve XII
Name = hypoglossal
Function = movement of tongue
Fibres = motor
Nerve root = medulla (more medial, several small rootlets)
Test = stick out tongue
Lesion presents as atrophy, deviation towards the side of the lesion
Define Parkinson’s disease
A chronic and progressive neurodegenerative disorder resulting from dopamine deficiency in the basal ganglia which leads to a movement disorder with classical parkinsonian motor symptoms (bradykinesia + tremor/rigidity/postural instability)
Describe the epidemiology of Parkinson’s disease
Prevalence increases with age
Mean onset is 60 y/o
More common in men
What are the causes of Parkinson’s disease?
Cell loss in the substantia nigra due to…
- inherited factors (genes and susceptibility)
- environmental factors (risk factors or toxin induced)
What are the signs/symptoms of Parkinson’s disease?
Brady/akinesia:
- problems with fine finger movements (e.g. doing up buttons, writing)
- deteriorated walking (small steps, dragging one foot, reduced arm swing)
- onset is unilateral
- progressive reduction in speed/amplitude of repetitive actions
Tremor:
- at rest
- often asymmetrical but may be unilateral
Rigidity:
- pain
- problems turning in bed
Postural instability:
- balance problems
What are the investigations needed for Parkinson’s disease?
Diagnosis is clinical
MRI - rule out other structural pathology
DaTscan - functional neuroimaging
What are the treatments for Parkinson’s disease?
Pharmacological:
- L-DOPA (e.g. levodopa)
- dopamine agonists (e.g. ropinirole)
- catechol-O-methyl/COMT (e.g. entacapone)
- monoamine oxidase-B/MAO-B inhibitors e.g. rasagiline)
Non-pharmacological:
- deep brain stimulation (thalamus)
- surgical ablation of overactive basal ganglia circuits (e.g. subthalamic nuclei)
What are the complications of Parkinson’s disease?
Motor:
- deteriorating function
- loss of drug effect
- motor fluctuations
- dyskinesia (involuntary erratic movements)
- freezing of gait
- falls
Non-motor:
- depression and other psychiatric problems
- dementia
- autonomic problems (constipation, incontinence, dysphagia, excessive salivation, postural hypotension)
- sleep disturbances
Define ataxia
A group of disorders that affect coordination, balance and speech (cerebellar dysfunction)
What are the types of ataxia?
Inherited (most commonly autosomal dominant or autosomal recessive - Friedreich’s ataxia)
Acquired:
- toxic/metabolic (alcohol, drugs)
- immune mediated (paraneoplastic, gluten related)
- infective (post infection e.g. encephalitis)
- degenerative
- structural
What are the sings/symptoms of cerebellar dysfunction?
Dizzy – unsteady/wobbly/clumsy
Falls, stumbles
Difficulty focusing/double vision/‘oscillopsia’
Slurred speech
Problems with swallowing
Tremor (intention)
Problems with dexterity/fine motor skills
Nystagmus
Dysdiadochokinesia, dysmetria (struggle touching finger to nose)
Gait/trunk/limb ataxia (wide base gait, struggle sitting/standing unsupported etc.)
What are the investigations needed for ataxia?
Bloods: autoimmune screen, gluten serology
MRI: shows cerebellar atrophy, excludes structural causes
Describe the management for ataxia
Depends on the underlying cause
Requires input from multidisciplinary teams (physio/occupational therapy) and ataxia specialists
Define motor neuron disease
A neurodegenerative disorder that affects the brain and spinal cord (upper and lower motor neurons), characterised by selective loss of neurons in the motor cortex, cranial nerve nuclei, and/or anterior horn cells, leading to progressive paralysis and eventual death
Describe the different types of motor neuron disease
Amyotrophic lateral sclerosis - most common, loss of neurons in motor cortex and anterior horn, UMN and LMN symptoms
Progressive bulbar palsy - affects cranial nerves IX-XII
Primary lateral sclerosis - loss of neurons from the motor cortex, UMN symptoms
Progressive muscular atrophy - anterior horn cell lesion, LMN symptoms
Describe the epidemiology of motor neuron disease
More common in men
Onset usually in 50-60s
Life expectancy = 2-4 yeas post-onset
What causes motor neuron disease?
Causes is unknown
5-10% are inherited due to a specific gene mutation
A possible theory is due to abnormal mitochondrial function causing oxidative stress in motor neurons
What are the signs/symptoms of motor neuron disease?
Limb symptoms:
- UMN = spastic weakness
- LMN = flaccid weakness, wasting, fasciculations
- wrist drop, stiffness, weakness or cramping of the hands
- foot drop, gait disturbances, difficulty standing from chair/climbing stairs
- functional effects of weakness e.g. loss of dexterity or falls
Bulbar symptoms:
- dysarthria (speech problems due to weakness of muscles)
- dysphagia
- wasting/fasciculations of the tongue
Respiratory failure:
- appetite reduced
- sleep disturbance, unrefreshing sleep, morning headaches
- fatigue
- shortness of breath on exertion/lying down
Extra-motor features:
- frontotemporal dementia
- cognitive problems (behavioural/emotional
- parkinsonism
What investigations are needed for motor neuron disease?
Diagnosis is clinical
Brain/cord MRI: exclude structural causes
Lumbar puncture: exclude infectious causes
Muscle biopsy: exclude myopathic conditions
EMG: detect subclinical denervation
What are the treatments for motor neuron disease?
Riluzole (neuroprotective glutamate-release inhibitor)
Non-pharmacological:
- physio/occupational therapists
- speech therapists
- dietitian
- non-invasive ventilation (positive airway pressure, mask used overnight)
Symptomatic/supportive treatments
Define multiple sclerosis
A chronic, relapsing/remitting, and progressive disorder, characterised by immune-mediated inflammation causing demyelination of the central nervous system (brain + spinal cord)
Describe the epidemiology of multiple sclerosis
Usually begins between 20-40 y/o
More common in women
Mostly affects Caucasians
Incidence increases with geographical latitude (more common away from equator)
What is the cause of multiple sclerosis?
Unknown
Interaction between environment and genetics causing activated autoreactive T-lymphocytes, resulting in demyelination and eventual axonal loss
What are the risk factors for multiple sclerosis?
Genetics
Female
Vitamin D deficiency
Latitude
Smoking
Diet and obesity in early life
EBV
What are the signs/symptoms of multiple sclerosis?
Motor: spasticity, weakness, tremor, ataxia
Sensory: paraesthesia, neuralgia,
Visual symptoms: optic neuritis (impaired vision, pain), diplopia, nystagmus, vertigo
Autonomic: bladder, bowel, and sexual dysfunction
Behavioural: cognitive problems, depression
Non-specific: fatigue
What are the investigations needed for multiple sclerosis?
MRI (sensitive but not specific, can exclude other causes)
Lumbar puncture: electrophoresis shows oligoclonal bands of IgG (not present in serum)
Visual evoked potential studies (electrophysiology)
What are the treatments for multiple sclerosis?
Disease-modifying drugs:
- beta interferon
- dimethyl fumarate (mild disease)
- alemtuzumab (active disease)
Relapse treatment:
- methylprednisolone
- plasma exchange (for acute relapses)
Non-pharmacological:
- lifestyle advice (exercise, stop smoking, avoid stress)
- physio/occupational/speech therapy
- counselling
Management of symptoms/complications
What signs are seen in an upper motor neuron lesion?
Spastic paralysis (muscles are tight and may jerk)
DTR = hyperreflexia
Hypertonia
Disuse atrophy
Positive Babinski sign
No fasciculations
What signs are seen in a lower motor neuron lesion?
Flaccid paralysis (muscles are relaxed)
DTR = hyporeflexia
Hypotonia
Wasting atrophy
Absent Babinski sign
Fasciculations
Define headache
A common symptom associated with many clinical conditions, categorised as…
- primary (no underlying cause) = migraine, cluster, tension
- secondary (precipitated by local or systemic condition) = meningitis, subarachnoid haemorrhage, giant cell arteritis, idiopathic intracranial hypertension, medication overuse
- other = trigeminal neuralgia
Describe the epidemiology of headaches
Lifetime prevalence of more than 90%
More common in females
Most common type is tension headache, then migraine
What are the associated signs/symptoms of headaches?
Migraine:
- aura (visual/sensory disturbance)
- nausea/vomiting
- light/motion/noise intolerance
- preference to staying still
Cluster:
- autonomic features ipsilateral to pain (e.g. lacrimation, eyelid swelling/drooping, nasal congestion)
- agitation/restlessness
Tension:
- normally no associated symptoms
What other symptoms with a headache need urgent referral?
New-onset, age >50 (GCA, space-occupying lesion)
Changing personality/cognitive dysfunction/focal neurological defect (stroke/TIA)
Vomiting (associated with migraine, but can be lesion)
Jaw claudication or visual loss (GCA)
Sudden onset/thunderclap headache (SAH)
Fever/neck stiffness (meningitis)
Red eye/severe eye pain (acute glaucoma)
Pregnant (venous sinus thrombosis)
Papilloedema (space-occupying lesion)
What investigations are needed for headaches?
Diagnosis made using ICHD criteria
Fundoscopy
Blood/CSF cultures: exclude CNS infection
CT/MRI: exclude SAH, stroke, space-occupying lesion
ESR/CRP, biopsy: exclude GCA
What are the treatments for migraines?
Avoid identified triggers
Drug treatment during attack:
- oral triptan + NSIAD/paracetamol
- high dose aspirin
- anti-emetic
Prophylactic drug treatment:
- propranolol
- topiramate (teratogenic)
- amitriptyline
- last resort = botulinum toxin type A injections
What are the treatments of cluster headaches?
Avoid identified triggers
Acute attack:
- sumatriptan (s/c or nasal spray)
- high flow oxygen in short bursts
Prophylaxis:
- verapamil (calcium channel blocker)
What are the treatments for tension headaches?
Over-the-counter simple analgesia (paracetamol, NSAIDs)
Prophylactic amitriptyline
What are the treatments for trigeminal neuralgia?
Carbamazepine
- initial high dose, then reduce for maintenance
Microvascular decompression (if medication fails)
Define dementia
A neurodegenerative syndrome with a range of behavioural and cognitive symptoms which cause significant functional decline in usual activities or work
Describe the epidemiology of dementia
Incidence increase with age
1 in 20 are aged under 65 (early-onset dementia)
What are the causes of the different types of dementia?
- Alzheimer’s disease: atrophy of the cerebral cortex, and formation of amyloid plaques and neurofibrillary tangles
- Vascular dementia: reduced blood supply to the brain
- Lewy body dementia: abnormal deposition of intracytoplasmic protein in brainstem and neoplasm
- Frontotemporal dementia: progressive atrophy in the frontal and/or temporal lobes
- Other: Parkinson’s, Huntington’s, CJD, infections (HIV, syphilis), repeated head trauma, substance misuse, hypothyroidism
What are the risk factors for dementia?
Age
Mild cognitive impairment
Learning disability (e.g. Down’s syndrome)
Genetics
Cardio/cerebrovascular disease
Parkinson’s disease
Modifiable:
- hypertension/obesity/diabetes
- smoking/alcohol
- depression
- lack of physical activity
- low social engagement/support
- lower educational attainment
- traumatic brain injury
- air pollution
What are the signs/symptoms of dementia?
Cognitive symptoms:
- memory loss
- problems with reasoning/making decisions
- dysphasia/communication problems
- difficulty carrying out coordinated movements
- disorientation (time and place)
- impairment of executive function (planning, judgement, problem-solving, initiative)
Behavioural symptoms:
- psychosis/delusions/hallucinations
- agitation and emotional liability
- depression and anxiety
- withdrawal/apathy
- sleep disturbance/insomnia
- inappropriate social/sexual behaviour
Difficulty with daily activities:
- early stages = carrying out household tasks
- later stages = bathing, eating, walking
What signs/symptoms are related to the specific subtypes of dementia?
- Alzheimer’s disease: usually presents with memory loss, difficulty with executive function, and/or nominal dysphasia
- Vascular dementia: stepwise increases in the severity of symptoms, may present with insidious gait and attention problems, and changes in personality
- Lewy body dementia: fluctuating cognition, visual hallucinations, parkinsonism
- Frontotemporal dementia: personality changes and behavioural disturbance (e.g. apathy, social/sexual disinhibition)
What investigations are needed for dementia?
Bloods: FBC, ESR/CRP, U&E, glucose, LFTs, TFTs, B12, folate (exclude reversible/organic causes of cognitive decline)
Cognitive testing:
- mini mental state examination
- six item cognitive impairment test
MRI: detect underlying vascular/structural damage
Functional imaging: PET scan
What are the treatments for dementia?
Non-pharmacological:
- cognitive stimulation programmes
- social activities
- music/art/animal/massage/aromatherapy
- control vascular risk factors
Pharmacological:
- acetylcholinesterase inhibitors (e.g. rivastigmine/donepezil)
- NMDA antagonists (memantine)
- avoid drugs which impair cognition (tricyclic antidepressants, sedatives, antihistamines, analgesics)
Define Huntington’s disease
A progressive neurodegenerative disorder, characterised by chorea and neuropsychiatric problems
Describe the epidemiology or Huntington’s disease
Mean age of onset is 30-50 years
Most common hereditary neurodegenerative disorder
What causes Huntington’s disease?
Autosomal dominant inheritance of the Huntington’s gene on chromosome 4 (CAG repeat)
Associated with cell loss within the basal ganglia and cortex
What are the signs/symptoms of Huntington’s disease?
Early signs:
- personality changes
- apathy/depression
- clumsiness/incoordination
- fidgeting
- behavioural problems
- irritability
Later signs:
- chorea (can become severe and cause uncontrollable limb movements)
- dystonia (replaces chorea)
- spasticity, clonus
- dysarthria/dysphasia
- abnormal eye movement
- cognitive decline (dementia)
What investigations are needed for Huntington’s disease?
MRI/CT scans: show loss of striatal volume and increased size of the frontal horns of the lateral ventricles in moderate/severe disease
Genetic testing (with counselling)
What are the treatments for Huntington’s disease?
Symptomatic treatment only - no effect on progression of disability
Neuroleptics (Tetrabenazine)- for chorea
Levodopa - for bradykinesia
SSRI (fluoxetine)/SNRI (duloxetine) - for depression
Antipsychotics
Deep brain stimulation
Speech and language, physio, occupational, psychological therapy, dietician advice
Define Guillain-Barre syndrome
An acute autoimmune, inflammatory polyneuropathy that causes axonal degradation and demyelination of peripheral nerves and roots, characterised by weakness, paraesthesia and hyporeflexia
What are the causes of Guillain-Barre syndrome?
75% of patients have a history of viral or bacterial infection usually of the respiratory and GI tract, such as…
- campylobacter jejuni
- EBV
- HIV
Antibodies to the infectious organism (or vaccinations) also attack antigens in peripheral nerve tissue, through molecular mimicry.
Describe the epidemiology of Guillain-Barre syndrome
Higher incidence in males, increases with age
Peak ages are 15-35 years and 50-75 years
What are the signs/symptoms of Guillain-Barre syndrome?
Weakness (symmetrical, ascending, progressive, severe cases = paralysis, respiratory failure)
Neuropathic pain (legs/back)
Reduced/absent reflexes
Paraesthesia/sensory loss (starting in lower extremities)
Autonomic symptoms:
- sweating
- changes to heart rate/rhythm, and blood pressure
- urinary hesitance
What investigations are needed for Guillain-Barre syndrome?
Nerve conduction studies (can be normal in early stages)
Lumbar puncture: high protein, normal cell count
ECG: asses arrythmias
Spirometry: asses FVC
Blood tests: FBC, LFT, U&E, glucose: exclude other causes
What are the treatments for Guillain-Barre syndrome?
IV immunoglobulin
Plasma exchange
Analgesia
Intubation/ventilation
DVT prophylaxis
What are the complications of Guillain-Barre syndrome?
Persistent paralysis
Respiratory failure
Arrhythmias
Urinary retention
Psychiatric problems - depression/anxiety
Define myasthenia gravis
An autoimmune disorder of the neuromuscular junction, leading to muscle weakness and fatiguability
Describe the epidemiology of myasthenia gravis
Can onset at any age
Peak onset is bimodal:
- 20-30 = women
- 50-60 = men
What are the associations of myasthenia gravis?
Other autoimmune diseases (especially rheumatoid arthritis and SLE)
Associated with thymic hyperplasia (mostly commonly females <50), or atrophy or tumour (mostly males >50)
What is the causes of myasthenia gravis?
In 85% = IgG antibodies to acetylcholine receptors on the post-synaptic membrane of NMJ
In the rest= antibodies to muscle-specific tyrosine kinase (MuSK)
What are the signs/symptoms of myasthenia gravis?
Extra-ocular weakness:
- ptosis
- diplopia
Bulbar weakness:
- swallowing difficulties
- weak chewing
- dysarthria (worse after continued speech)
- nasal/slurred speech
Limb weakness:
- fatigued after exercise
- proximal is more effected, usually symmetrical
- normal tone, reflexes, and sensation
Severe symptoms:
- weakness of muscles of ventilation can cause acute respiratory distress
- seizures
What things trigger the symptoms of myasthenia gravis?
Pregnancy
Infection
Over-treatment
Change of climate
Emotion
Exercise
Hypokalaemia
Drugs (gentamicin, opiates, tetracycline, beta-blockers)
What are the investigations needed for myasthenia gravis?
Antibodies: anti-acetylcholine receptor or MuSK antibodies
TFTs
Nerve conduction studies
EMG: decremental muscle response to repetitive nerve stimulation, and many have increased single-fibre jitter
CT/MRI of thymus
MRI of brain: exclude structural brain disease
Ice pack test: >2mm improvement of ptosis after 2mins
What are the treatments for myasthenia gravis?
Acetylcholine-esterase inhibitors - for symptom control (e.g. pyridostigmine)
Steroids - for immunosuppression/relapses (e.g. prednisolone, or azathioprine)
Thymectomy - improves symptoms, reduces need for immunosuppression
Describe Lambert-Eaton myasthenic syndrome
A disorder of neuromuscular transmission caused by autoantibodies to pre-synaptic calcium channels which impairs the release of acetylcholine
Causes: paraneoplastic (particularly associated with small-cell lung cancer), or autoimmune
Presentation: same as myasthenia gravis, but reduced/absent reflexes
Define mononeuropathy
A nerve disorder resulting from focal involvement of a single periphery or cranial nerve trunk, usually caused by local lesions
What do the following mononeuropathies cause:
Median nerve
Radial nerve
Ulnar nerve
Common peroneal nerve
Sciatic nerve
Median nerve = carpal tunnel syndrome
Radial nerve = wrist/finger drop
Ulnar nerve = claw hand
Common peroneal nerve = foot drop
Sciatic nerve = sciatica/foot drop
Describe mononeuritis multiplex
Mononeuropathy of two or more peripheral nerves occurring simultaneously in different areas
Systemic causes: DM, connective tissue disorders (RA, SLE), vasculitis, sarcoidosis
Define polyneuropathy
Motor and/or sensory disorder of multiple peripheral or cranial nerves, usually symmetrical and widespread, and classified as acute or chronic
What are the causes of peripheral neuropathy?
Metabolic (DM, chronic alcohol abuse)
Rheumatological (RA, SLE, vasculitis)
Malignancy
Infection (HIV, leprosy)
Nutritional (vitamin deficiencies)
Congenital (Charcot-Marie-Tooth syndrome)
Inflammation (Guillain-Barre syndrome)
What are the signs/symptoms of polyneuropathies?
Sensory:
- paraesthesia, numbness, burning pain, loss of vibration sense and proprioception
- often worse distally (glove and stocking distribution)
Motor:
- weak or clumsy hands
- difficulty walking/falls
- difficulty breathing
- muscle wasting
- often progressive and worse distally
Autonomic:
- constipation
- urinary/faecal incontinence
- postural hypotension
- pale/dry skin
- sexual dysfunction
What are the treatments of polyneuropathies?
Treat the cause
Non-pharmacological:
- foot care
- walking aids
- physio/occupational therapy
Pharmacological:
- depends on cause
- autoimmune causes respond to IV immunoglobulin therapy
- vasculitic causes respond to steroids
- neuropathic pain = amitriptyline
Define tremor
An involuntary, rhythmic, oscillatory movement of a body part
Define essential tremor
Most common type of postural tremor
Absent at rest but present on maintained posture, so seen when carrying cup, writing, holding book
Has a family history and improves with alcohol
Define functional tremor
A tremor which shows distractibility and entrainability, with a variable frequency/amplitude, and an unusual pattern
Define dystonia
A movement disorder characterised by sustained or intermittent muscle contractions causing abnormal, repetitive movements/postures
The can be generalised or focal
Subtypes include idiopathic and functional
Define chorea
Abnormal involuntary movement which is non-rhythmic (flowing), jerky, and moves from one place to another, most commonly caused by Huntington’s disease
Define tic
Brief stereotyped movements or vocalisations, that are repetitive and inopportune to social context, and involuntary but can be suppressed for a while
Seen in Tourette’s syndrome
Define myoclonus
Sudden, brief, involuntary jerks of a muscle or group of muscles, caused by muscle contraction (positive jerk) or interruption to muscle activity (negative jerk)
