Neurology Flashcards
Causes of a 6th nerve (abducens) palsy?
Causes of mononeuritis multiplex
Vascular lesion
Malignancy
Demyelination
Infection (Lyme disease, syphilis)
Raised IC pressure (false localising sign)
Wernicke’s encephalopathy (if bilateral)
Causes of mononeuritis multiplex? WARDS PLC
Wegener’s granulomatosis
Amyloidosis
Rheumatoid arthritis
Diabetes mellitus
Sarcoidosis
Polyarteritis nodosa
Leprosy
Cancer
Define and give causes of an internuclear ophthalmoplegia?
INO is a disorder of conjugate gaze, where the eye ipsilateral to the lesion will fail to adduct, and the contralateral eye will exhibit nystagmus. It is caused by a lesion of the median longitudinal fasciculus (MLF).
Causes of an INO include:
Vascular lesion and MS.
Clinical findings of a 3rd (oculomotor) nerve palsy?
Ptosis
Eye ‘down and out’
Pupil may be unreactive + dilated depending on cause
Clinical findings of a 4th (trochlear) nerve palsy?
Weakness of downward movement of the eye, causing vertical diplopia
Clinical findings of a 6th (abducens) nerve palsy?
Cannot abduct affected eye
Causes of a complex ophthalmoplegia?
Nerve lesions: mononeuritis, demyelination
Myasthenia gravis
Graves’ disease
Mitochondrial diseases
Surgical causes of a 3rd nerve palsy?
SURGICAL causes affect the pupil (dilated and unreactive).
Posterior communicating artery aneurysm.
SOL.
ICH.
Medical causes of a 3rd nerve palsy?
MEDICAL causes do not affect the pupil.
Causes of mononeuritis multiplex.
Demyelination (MS).
Infarction.
Investigations in an ocular palsy?
MRI of brainstem and posterior fossa
Investigations for causes of mononeuritis multiplex
Investigations for myasthenia gravis and thyroid disease
Bamford classification of a TACS (total anterior circulation stroke)
Hemiplegia (contralateral to lesion)
Homonymous hemianopia (contralateral to lesion)
Higher cortical dysfunction (dysphasia, dyspraxia, neglect)
Bamford classification of a PACS (partial anterior circulation stroke)
2/3 of TACS criteria
Bamford classification of a LACS (lacunar stroke)
Pure hemi-motor or sensory loss
What is the NIHSS?
The NIHSS is a stroke severity scale, a systematic assessment to measure the neurological deficits seen with acute stroke.
Designed to standardise and document an easy to perform, reliable and valid neurological assessment.
Can be used to determine eligibility for thrombectomy, and to assess treatment success. Can be used before and after thrombolysis or thrombectomy.
How would you assess speech in a patient you suspect has had a stroke?
Give simple, then 2-step commands.
Ask to repeat phrases ‘42 West Register Street’.
Test naming objects: hold up and ask them to name what you’re holding.
What is used to consider eligibility for thrombectomy?
Patient’s overall clinical status
NIHSS (score >5)
Modified Rankin Scale (score >3)
Territories of infarction on brain imaging
How is a POCS (posterior circulation stroke) defined? cerebellum + brainstem
Need ONE of:
Cranial nerve palsy + contralateral motor or sensory deficit.
Bilateral motor / sensory deficit.
Gaze palsy.
Cerebellar dysfunction.
Isolated homonymous hemianopia.
Investigations and management of suspected acute stroke?
Bedside: A-E assessment, observations, GCS, blood glucose (stroke mimics), ECG (AF), urine dip (infection). Obtain collateral history to determine sx onset for thrombolysis eligibility.
Bloods: FBC, CRP/ESR (young stroke - arteritis), UE, TFTs, cholesterol / lipid profile.
Imaging: CT head to rule out haemorrhage. MR brain.
Acute management is either thrombolytic or endovascular:
- Thrombolysis with alteplase (tPA) if <4.5 of sx onset and no ICH.
- If outside thrombolysis window, consider whether eligible for thrombectomy (6-12h sx onset)
- If not eligible, give aspirin 300mg OD for 2 weeks then 75mg clopidogrel lifelong
Longer-term management:
- Consider: echo, carotid doppler, CT venogram (to rule out CVST in young pt), clotting screen (thrombophilia), vasculitis screen (young stroke).
- Referral to HASU
- MDT input: SLT, PT, OT, dietetics (consider NG feeding)
- Secondary prevention: statin, HTN management, smoking cessation, consider anticoagulation if AF
- DVT prophylaxis with IPCs
Differential diagnosis for hemiparesis?
Anterior circulation vascular event affecting R or L cortex or lacunar infarct.
SOL (tumour, SDH, abscess).
Hemiplegic cerebral palsy.
Less common: Todd’s paresis following seizure, hemiplegic migraine, stroke mimic (sepsis, hypoglycaemia, demyelination).
Clinical features of a patient with myotonic dystrophy?
Face:
- long, thin, expressionless face
- wasting of facial muscles
- bilateral ptosis + cataracts
- frontal balding
- dysarthria (myotonia of tongue)
Hands:
- grip myotonia (grip my hand and let go)
- percussion myotonia (percuss thenar eminence + watch for thumb flexion)
Chest:
- cardiomyopathy / pacemaker due to brady and tachyarrhythmias
Limbs:
- wasting and weakness of distal muscles
- areflexia
Other features:
- diabetes - look for libre monitor
- testicular atrophy
- dysphagia
Investigations to perform in myotonic dystrophy?
EMG: ‘dive bomber’ action potentials.
Genetic testing.
Muscle biopsy: fibre atrophy type 1.
Management of complications of myotonic dystrophy?
Affected individuals die prematurely due to respiratory complications.
Weakness is a problem without treatment options.
Phenytoin may help myotonia.
Advise against general anaesthetic.
What are the genetics of myotonic dystrophy?
Type 1: expansion of the trinucleotide repeat sequence on chromosome 19.
Type 2: expansion of the tetranucleotide repeat sequence on chromosome 3.
Shows genetic anticipation (worsening severity + earlier age of presentation with successive generations).
Autosomal dominant condition.
Usually presents in 20-40s.
List the different types of muscular dystrophy.
Duchenne’s muscular dystrophy.
Becker’s muscular dystrophy.
Fascioscapulohumeral muscular dystrophy (affects arms + shoulders).
Limb-girdle muscular dystrophy.
Myotonic dystrophy.
Oculopharyngeal muscular dystrophy.
What are the features of limb-girdle muscular dystrophy?
Inherited muscular dystrophy, characterised by progressive weakness of the shoulders and pelvic girdle muscles. It has a variable phenotypic presentation depending on the specific type of dystrophy.
Unilateral and bilateral causes of ptosis?
Unilateral: 3rd nerve palsy, Horner’s syndrome.
Bilateral: myotonic dystrophy, myasthenia gravis, congenital.
Side effects of Parkinson’s disease treatment?
Impulsivity + disinhibition can be associated with dopaminergic therapies.
Levodopa is associated with on/off phenomena and dose-related dyskinesia.
Management of Parkinson’s disease?
L-dopa (Madopar) with peripheral inhibitor
Dopamine agonists (Apomorphine)
MAO-B inhibitor (Selegeline)
Anticholinergics
COMT inhibitors (Entacapone)
Amantadine
Surgery: deep brain stimulation
MDT approach: PT/OT/SLT
What is the pathophysiology of Parkinson’s disease?
Degeneration of the dopaminergic neurones between the substantia nigra and basal ganglia.
List some causes of tremor.
Rest tremor: Parkinson’s disease
Postural tremor: anxiety, essential tremor, hyperthyroidism, hepatic encephalopathy, co2 retention, alcohol
Intention tremor: cerebellar disease
List some causes of Parkinsonism.
Idiopathic Parkinson’s disease
Parkinson’s plus syndromes: multisystem atrophy, progressive supranuclear palsy, corticobasal degeneration
Drug-induced Parkinsonism (phenothiazines)
Hypoxic brain injury
Post-encephalitis
MPTP toxicity
Clinical findings expected in a patient with Parkinson’s disease?
Expressionless face
Coarse, pill-rolling, 4-6 Hz tremor, classically asymmetrical
Bradykinesia (‘snap test’ on each thumb)
Cogwheel rigidity at wrists (exaggerated by synkinesis)
Gait: slow, shuffling and festinant. Absence of arm swing, often asymmetrical
Speech: slow, faint, monotonous
Additional things to request at the end of a Parkinsonism exam (thinking about Parkinson’s plus syndromes)
BP looking for evidence of MSA (Parkinsonism with postural hypotension, cerebellar and pyramidal signs)
Test vertical eye movements (for evidence of PSP)
Test cognition (LBD)
Take a medication history (phenothiazines)
Assess patient’s handwriting (micrographia) and ask to draw an Archimedes’ spiral
What is the classical triad of features of idiopathic Parkinson’s disease?
‘BRR’
Bradykinesia
Rigidity
Rest tremor
Non-motor symptoms of Parkinson’s disease?
Anosmia
Cognitive effects
Mood disorders
Pain
REM sleep disorder
Why do a carotid doppler following stroke?
To look for evidence of stenosis, to see if it could be the cause of stroke. If suitable for carotid endarterectomy, could arrange that.
What other investigations could you consider if a patient has a normal ECG and carotid doppler following a stroke?
Look more closely for paroxysmal AF using a 24h or 5-day Holter monitor.
Consider a TTE looking for structural cause (PFO - paradoxical embolism).
How does the nature of a visual field defect help you localise the lesion?
In an MCA stroke - would expect sensory changes.
Homonymous hemianopia can result from lesions of the optic tract, lateral geniculate body or optic radiation.
A left HH would signify a right-sided lesion.
In a posterior cerebral artery stroke, would expect macular sparing of the visual field defect (due to supply from the MCA)
Signs of a dominant parietal lobe cortical infarct?
Dysphasia
Gerstmann’s syndrome: dyslexia, dyscalculia, finger agnosia, left and right disorientation
‘Dominant side - D’s’
Signs of a non-dominant parietal lobe infarct?
Dressing and constructional apraxia
Spatial neglect
List the corresponding lesions for the following visual field defects:
unilateral field loss, bitemporal hemianopia, homonymous hemianopia, superior homonymous quadrantanopia, inferior homonymous quadrantanopia
Unilateral field loss: lesion at ipsilateral optic nerve.
Bitemporal hemianopia: lesion at optic chiasm.
Homonymous hemianopia: lesion at contralateral optic tract.
Superior homonymous quadrantanopia: lesion at contralateral temporal lobe of optic radiation.
Inferior homonymous quadrantanopia: lesion at contralateral parietal lobe of optic radiation.
Management of MS?
MDT approach: nursing, PT, OT, social worker, doctor.
Disease-modifying treatments: interferon beta and glatiramer. MAB therapy (natalizumab).
Symptomatic treatments:
IV methylprednisolone for acute attacks.
Antispasmodics (baclofen).
Carbamazepine (neuropathic pain).
Laxatives / intermittent catheterisation for bladder and bowel symptoms.
What are the different types of MS?
Relapsing-remitting
Primary progressive
Secondary progressive
Clinically isolated syndrome
Define multiple sclerosis?
CNS demyelination causing neurological impairment that is disseminated in time and space.
Investigations to perform in suspected MS?
CSF: oligoclonal IgG bands
MRI brain/spinal cord: periventricular white matter plaques
Visual evoked potentials (VEPs): delayed velocity but normal amplitude (evidence of previous optic neuritis)
Differential diagnosis for MS?
If acute onset, consider vascular cause.
Disc prolapse.
Demyelination (MS) is more likely if there are other features such as RAPD, pale optic disc (optic neuritis), and INO.
Clinical signs present in MS?
Mobility aids
Cranial nerves: bilateral INO, optic atrophy, reduced visual acuity, cranial nerve palsies
UL/LL exam: UMN spasticity, weakness, brisk reflexes, altered sensation
Cerebellar: dysdiadochokinesia, ataxia, nystagmus, intention tremor, hypotonia
Other clinical features include: depression, autonomic (urinary retention + bowel problems), Uthoff’s phenomenon (worsening of sx after hot bath or exercise), L’hermitte’s sign: lightening pain down spine on flexion of neck
Signs of cerebellar syndrome to elicit on examination and the corresponding conditions that can cause cerebellar syndrome?
INO/RAPD/UMN weakness/sensory disturbance - demyelination
Cachexia/clubbing/tar staining - paraneoplastic cause
Weakness/visual field defects - stroke / SOL
CN 5, 7, 8 lesion pathology - cerebellopontine angle lesion
Parkinsonism - MSA
Gum hypertrophy - phenytoin use
Stigmata of CLD - alcohol
Ophthalmoplegia - Miller-Fisher syndrome
Pes cavus - Freidreich’s ataxia
Horner’s syndrome - lateral medullary syndrome
List some causes of a bilateral cerebellar syndrome
Demyelination (MS)
Paraneoplastic conditions
Bilateral posterior strokes / SOL
List some causes of a unilateral cerebellar syndrome
Demyelination
Posterior ischaemic stroke / haemorrhage
SOL in the posterior fossa
Differentials for a spastic paraparesis and cerebellar signs?
Demyelination
Freidreich’s ataxia
Spinocerebellar ataxia
Arnold-Chiari malformation
Syringomyelia
How do you differentiate between a cerebellar and a sensory ataxia?
Cerebellar: nystagmus and dysarthria.
Sensory: impaired sensation (joint position / vibration), pseudoathetosis, finger-nose testing ok with eyes open but struggles with eyes closed.
If sensory ataxia, need to decide if CENTRAL or PERIPHERAL. Spinal cord pathology, neuropathy, or both (B12 deficiency)
What investigations are appropriate to request in cerebellar syndrome?
Bloods: TFTs, copper studies, paraneoplastic screen, coeliac screen, infective screen, autoimmune screen, FBC, LFTs, B12, drug levels (lithium / phenytoin / carbamazepine).
Imaging: MRI brain + spinal cord (superior to CT for imaging the posterior fossa).
Special: LP (oligoclonal bands - MS), EMG + nerve conduction studies, genetic testing.
What is a Charcot joint?
A neuropathic joint where impaired joint position and pain sense leads to chronic damage to ankle and midfoot, resulting in deformity.
Which medications cause neuropathy?
Sensory: isoniazid
Sensorimotor: vincristine, amiodarone
Motor: dapsone
How would you distinguish between a neuropathy and a myopathy on examination?
A myopathy has a proximal pattern of weakness, absence of fasciculations, preserved reflexes and contractures.
A neuropathy has sensory signs.
NB if thinking myopathy, impt to consider cardiac involvement.
Differential diagnosis for a sensory polyneuropathy?
Most common = diabetes.
Metabolic: uraemia, hyperthyroidism, B12 deficiency.
Toxic: chemotherapy, nitrofurantoin, isoniazid.
Inflammatory: CIDP, sarcoid, vasculitis.
Paraneoplastic: lung cancer / paraproteinaemia
What is the purpose of doing nerve conduction studies in a peripheral neuropathy?
To determine whether the neuropathy is demyelinating or axonal in nature.
Demyelinating neuropathy is more likely to be due to an underlying inflammatory condition such as CIDP.
Can also figure out whether it is length-dependent. If length-dependent, it is more likely to be inflammatory.
Investigations to request in a case of peripheral neuropathy?
Bedside: CBG, urinalysis (glucose), fundoscopy (diabetic retinopathy).
Bloods: FBC (macrocytic anaemia), UEs (urea), LFTs (alcohol use), TFTs, B12, AI screen with ESR. HbA1c, immunoglobulins and serum electrophoresis.
Special: nerve conduction studies and EMG.
Why do we do Romberg’s test on examination?
To determine whether unsteadiness is due to a sensory ataxia. Often, it is positive in peripheral neuropathy.
Differential diagnosis for a peripheral motor and sensory neuropathy?
Diabetic neuropathy
Hereditary neuropathy with pressure palsy (HNPP)
Metabolic: B12, porphyria
Drugs / toxins: platinum chemo, lead, alcohol, isoniazid, dapsone
Inflammatory: AIDP, CIDP, GBS, sarcoid, vasculitis causing mononeuritis multiplex
Infections: HIV, Lyme, leprosy
Paraneoplastic phenomenon
Inheritance and pathophysiology of Charcot Marie Tooth disease?
Caused by genetic mutations that affect the myelin sheath, but occasonally the axons of neurones.
Inherited in autosomal dominant, autosomal recessive, and x-linked patterns.
How would you go about investigating a mononeuropathy?
Need to arrange neurophysiological studies.
Nerve conduction studies - to localise the lesion.
EMG would help provide prognosis in terms of recovery.
MRI neck to rule out cervical radiculopathy.
How would you treat neuropathic pain associated with neuropathy?
Amitriptyline is 1st line.
Gabapentin / pregabalin - 2nd line
Duloxetine - 3rd line
Topical therapies if tablets not tolerated (capsacium)
How can you differentiate between an ulnar neuropathy and a C8/T1 nerve root lesion?
The power in abductor pollicis brevis would be strong in ulnar neuropathy.
Sensation in T1 dermatome would be normal in an ulnar neuropathy.
How would you rule out a lesion of the other major upper limb peripheral nerves in a suspected ulnar nerve palsy?
Wrist extension - motor aspect of radial nerve.
Finger extension - motor function of posterior interroseus nerve.
Thumb abduction - motor function of median nerve (abductor pollicis brevis).
Sensation would only be affected in the distribution of the ulnar nerve in an ulnar neuropathy.
Clinical signs of an isolated ulnar neuropathy?
Resting flexion of interphalangeal joints of 4th and 5th digits ‘ulnar claw’.
Wasting of the first dorsal interrosei and hypothenar eminence.
Scars may give clue as to MOI.
Weakness of finger abduction.
Altered sensation in the region of the ulnar nerve.
NB ulnar lesions are often caused by trauma or a surgical procedure.
How would you differentiate a mononeuropathy from a more generalised neurological disorder such as mononeuritis multiplex?
Reflexes would be normal in mononeuropathy.
In a generalised inflammatory neurological condition, you would expect some degree of areflexia.
Differential diagnosis of chorea?
Immune-mediated inflammatory causes (Sydenham’s chorea or SLE-associated chorea).
Hyperglycaemia.
Vascular causes.
Genetic: Huntington’s disease.
Management of Huntington’s disease?
No disease-modifying therapy.
MDT approach focused on symptom management: neurology, neuropsych, dietician.
OT/PT for work/home adaptations.
Support groups: Huntington’s Disease Association
What is the inheritance of Huntington’s disease?
Trinucleotide repeat disorder.
Inherited from affected parent who carries a mutation in the Hungtintin gene. 10% de novo mutations.
Autosomal dominant condition - 50% chance of passing on.
Shows ‘genetic anticipation’ - where subsequent generations are often affected earlier or have more severe phenotype.
Clinical signs of tuberous sclerosis?
Skin: perinasal butterfly rash, angiofibromata. Periungual fibromas. Shagreen patch (roughened skin over lumbar region), ash-leaf macules (depigmented macules on trunk).
Respiratory: cystic lung disease.
Abdo: renal enlargement, transplanted kidney, dialysis fistulae.
Eyes: retinal phakomas (dense white patches).
CNS: mental retardation, seizures, signs of antiepileptic treatment.
Pathophysiology of tuberous sclerosis?
Autosomal dominant inheritance with variable penetrance.
Caused by a mutation in either of two genes: TSC1 or TSC2 (tumour suppressor genes)
80% have epilepsy (most present in childhood).
Cognitive defects in 50%.
Renal manifestations of tuberous sclerosis?
Renal angiomyolipomas, renal cysts, RCC
The genes for TS and ADPKD are contiguous on chromosome 16, hence some mutations lead to both conditions
Renal failure may result from cystic disease or parenchymal destruction
Investigations for a patient with suspected tuberous sclerosis?
Skull films: ‘railroad track’ calcification
CT/MR head: tuberous masses in cerebral cortex
Echo and abdominal USS: hamartomas and renal cysts
Causes of a spastic paraparesis?
Demyelination (MS)
Cord compression / cervical myelopathy
Trauma
Motor neuron disease
Causes of a spastic paraparesis + sensory level
Cord compression
Cord infarction
Transverse myelitis (infection / autoimmune / paraneoplastic / sarcoid / NMO)
Causes of a spastic paraparesis + dorsal column loss (joint position / vibration sense)
Demyelination
Freidreich’s ataxia
SACD of the spinal cord
Syphilis
Cervical myelopathy
Causes of a spastic paraparesis + spinothalamic loss
Syringomyelia
Anterior spinal artery infarction
Causes of a spastic paraparesis + cerebellar signs
Demyelination
Freidreich’s ataxia
Spinocerebellar ataxia
Arnold-Chiari malformation
Syringomyelia
Spastic paraparesis + small muscle of the hand wasting
Cervical myelopathy
MND
Syringomyelia
Other causes of spastic paraparesis
Hereditary spastic paraparesis
Tropical spastic paraparesis due to HTLV-1
Cerebral palsy
Investigations to do in a suspected spastic paraparesis?
Bloods: FBC, UE, bone, CRP, HIV, syphilis, HTLV-1, autoimmune panel, AQP4 antibodies (NMO), paraneoplastic screen, serum electrophoresis, B12 (SACD of the cord)
Other: NCS + EMG, LP (MS), visual evoked potentials (MS), MR brain and spine (cord compression / tumour / MS)
Causes of flaccid paraparesis?
ACL MNM
Anterior horn cell disease: MND, polio
Cauda equina syndrome: disc herniation, mets, abscess
Lumbosacral plexopathy: tumour, trauma, abscess
Motor neuropathies: inflammatory, toxins, drugs, metabolic, infectious, congenital (CMT, HMSN)
NMJ disorders: MG, LEMS, botulism
Myopathies: inflamm (SLE), CTD (RA), cancer (paraneoplastic), infection (HIV / CMV / EBV), toxins (alcohol), endocrine (Cushings’, Addison’s, thyroid)
Features of Guillain-Barre syndrome?
An acute, inflammatory, demyelinating polyneuropathy.
Onset over days to weeks, usually secondary to infection (mycoplasma / campylobacter).
Ascending flaccid limb weakness, areflexia, fatigue, distal parasthesia, patchy sensory loss, spinal pain.
CNS: ptosis, ophthalmoplegia, facial nerve, bulbar weakness.
Autonomic: tachycardia / labile BP, bladder and bowel dysfunction.
Resp: SOB + fatigue.
Investigations to do in suspected Guillain-Barre syndrome?
LP: albuminocytological dissociation of CSF.
Reduced velocity + conduction block on NCS.
Antibodies to gangliosides.
FVC
ECG
Management of Guillain-Barre syndrome?
ICU if FVC <1.3L or bulbar dysfunction.
IVIG +/- methylprednisolone.
Consider plasma exchange.
Causes of foot drop?
Myopathy of anterior tibialis muscle.
Common peroneal nerve palsy: trauma / surgery / compression / mononeuritis multiplex.
Sciatic nerve palsy.
Lumbosacral plexopathy: trauma / tumour.
L5 root lesion: prolapsed disc.
How to differentiate between a CPN palsy, sciatic nerve lesion and an L5 lesion?
CPN palsy: lose plantarflexion and foot eversion. inversion and ankle reflex intact.
Sciatic nerve lesion: lose plantarflexion and eversion. Lose dorsiflexion and inversion too. Weak knee flexion and lose ankle reflex.
L5 lesion: ankle jerk preserved. Lose inversion, eversion, dorsiflexion. Also lose sensation on sole + dorsum of foot, and anterolateral shin.
Investigations to request in a foot drop of unknown cause?
Urine dip (blood / protein)
Bloods: screen for causes of neuropathy / mononeuritis multiplex (autoimmune, infectious, inflammatory, endocrine causes)
Imaging: XR fibula, EMG + NCS, MR spine and sacrum.
Management of a foot drop?
Conservative: splint / calliper, avoid leg crossing, PT/OT, DVLA considerations
Medical: analgesia, treat cause
Surgical: repair fracture / severed nerve
Clinical features of a patient presenting with a foot drop?
Wasting of the lower leg, fasciculations and reduced tone.
Weak ankle dorsiflexion and eversion.
Ankle reflex may or may not be intact. Inversion and plantarflexion may be intact.
Distribution of sensory loss: lateral lower leg, foot dorsum, webspace between 1-2nd toes, sole of foot.
High-stepping gait, walking aid, splint, insoles.
Scars in fibula area / back.
Clinical signs of syringomyelia?
Weakness + wasting of small muscles of the hands
Loss of reflexes in ULs
Dissociated sensory loss in ULs and chest: loss of pain / temperature sensation but preserved joint position / vibration sense (spares dorsal columns).
Scars from painless burns.
Charcot joints: shoulder and elbow.
Which sensory modalities are affected in syringomyelia?
Spinothalamic - pain + temperature loss at level of syrinx.
Anterior horn cells - LMN weakness at level of syrinx.
Corticospinal tract - UMN weakness - below level of syrinx.
Usually spares dorsal columns - proprioception.
Define syringomyelia.
Syringomyelia is caused by a progressively expanding fluid-filled cavity within the cervical cord, typically spanning several levels.
It is associated with spina bifida and Arnold-Chiari malformation. Investigation of choice is an MRI spine.
Causes of charcot’s joint?
Tabes dorsalis (hip and knee)
Diabetes (foot and ankle)
Syringomyelia (elbow and shoulder)
Signs of lateral medullary syndrome?
‘Crossed findings’
Ipsilateral:
- cerebellar signs
- nystagmus
- Horner’s syndrome
- palatal paralysis + decreased gag reflex
- loss of trigeminal pain / temp sensation
Contralateral:
- loss of pain and temp sensation
Which artery is commonly occluded to cause lateral medullary syndrome?
The posterior inferior cerebellar artery (PICA).
Clinical findings expected in post-polio syndrome?
Orthoses / walking aids at bedside
Inspection: scars, wasting, leg length discrepancy
Tone: hypotonia, more pronounced in affected leg
Power: areflexic, mute plantars
Sensation: preserved in both dermatomal and length-dependent pattern
Coordination: preserved in good limb
Bilateral, but asymmetrical LL weakness
The presence of pes cavus suggests a chronic neuromuscular disease (one that usually started in childhood)
What is the pathophysiology of poliomyelitis?
The virus enters via respiratory or faeco-oral route.
Infects CNS and destroys anterior horn cells.
This causes paralysis, an asymmetrical weakness which affects LLs more than ULs.
What is post-polio syndrome?
After a period of prolonged stability following infection, individuals who have been infected and recovered begin to experience new signs and symptoms: muscle atrophy, weakness, pain, fatigue.
This can occur in limbs that were originally affected or limbs that did not seem to be affected at the initial time of the polio illness.
Clinical signs of cervical myelopathy?
Asymmetric spastic paraparesis
Ataxic, broad-based gait
Romberg’s positive
Increased tone / clonus
Brisk reflexes + upgoing plantars
Weakness
Sensory modalities preserved
What is Brown-Sequard syndrome?
Caused by damage to one half of the spinal cord.
Results in paralysis + loss of proprioception on IPSILATERAL side to the lesion.
Loss of pain + temperature sensation on CONTRALATERAL side to the lesion.
In a myelopathy, why the need to examine CNs and limbs, and look for a sensory level?
- To work out the level of the lesion
- To look for signs of other lesions (i.e., in MS)
Differential diagnosis of a myelopathy?
Compressive: disc herniation, tumours, spinal stenosis
Autoimmune: MS, SLE, sarcoid
Infective: HIV, varicella
Nutritional: vitamin B12, copper
Genetic: hereditary spastic paraparesis
Clinical findings in a patient with Freidreich’s ataxia?
Young adult, wheelchair, ataxic gait
Pes cavus
Bilateral cerebellar ataxia (ataxic handshake, past-pointing, intention tremor, dysdiadochokinesis)
Leg wasting with absent reflexes and upgoing plantars, clonus
Loss of vibration / joint position sense
Other signs: kyphoscoliosis, optic atrophy, high-arched palate, +ve Romberg’s, sensorineural deafness, murmur / pacemaker, signs of diabetes
Which tracts are affected in Freidreich’s ataxia?
Spinocerebellar: proprioception
Corticospinal: motor control of body / limbs
Dorsal columns: fine touch and vibration
Differential diagnosis for Freidreich’s ataxia?
Demyelination (but would have brisk reflexes)
Other causes of mixed UMN+LMN signs: SCD, MND, taboparesis, cervical myelopathy
Vitamin E deficiency - rare FA mimic
Conus medullaris lesion
Tell me about Freidreich’s ataxia.
A progressive, neurodegenerative disorder.
Most common inherited ataxia in UK.
Onset usually <20y. Autosomal recessive.
Frataxin gene on chromosome 9, trinucleotide repeat disorder.
There is an association with HOCM and mild dementia.
Causes of flaccid paraparesis?
‘ACL MNM’
Anterior horn cell disease: MND, polio
Cauda equina syndrome: secondary to disc herniation, epidural abscess, mets, haematoma
Lumbosacral plexopathy: secondary to trauma, tumour, abscess
Motor neuropathies: inflammatory, toxins, drugs, metabolic, infectious, congenital (CMT, HSMN)
Neuromuscular junction disorders: myasthenia gravis, LEMS, botulism
Myopathies: ‘DICC TE’
– drugs: statins / steroids
- infective: HIV, EBV, CMV
- CTD: SLE, vasculitis, RA
- cancer: paraneoplastic
- toxins: alcohol
- endocrine: thyroid, Addison’s, Cushing’s
Features of hereditary motor sensory neuropathies (HMSNs)?
High stepping / stamping gait
Wasting of distal muscles and preservation of proximal (champagne-bottle legs)
Pes cavus (agonist / antagonist mismatch)
Palpable lateral popliteal + ulnar
Weakness of ankle dorsiflexion and toe extension
Absent ankle jerks
Mild stocking sensory loss
What are the different types of HMSNs?
Most common types are demyelinating and axonal.
- Demyelinating:
- AD, 70%, due to duplication of PMP22
- AD, mutations of P0
- Mutation on EGR gene - Axonal:
- May present later, fewer genes identified
Features of hereditary neuropathy with liability to pressure palsies (HNPP)?
Slowly progressive, autosomal dominant disorder limited to peripheral nerves
Painless weakness and sensory loss
Deletion of PMP22 (in contrast to HMSN, addition of PMP22)
Susceptible to nerve injury from trivial pressure, stretch or use, results in demyelinations
Can progress to more generalised HMSN
Signs and additional features of Freidreich’s ataxia?
Signs:
- young adult in wheelchair
- pes cavus
- kyphoscoliosis
- bilateral cerebellar signs
- pyramidal weakness
- upgoing plantars but absent ankle reflexes
- dorsal column signs
Additional:
- sensorineural deafness (bilateral hearing aids) (10%)
- optic atrophy (30%)
- murmur of HOCM
- diabetes mellitus (10%)
FA is autosomal recessive (unusual, as most ‘structural’ diseases are AD)
Features of CIDP?
- relapsing-remitting AIDP / GBS
- predominantly motor
- symmetrical proximal and distal weakness out of proportion to wasting
- areflexia
- 10% pure motor, 10% pure sensory
- CSF shows raised protein / normal lymphs
- managed with IVIg or plasma exchange acutely
Features of brachial neuritis?
Whole or branches of brachial plexus affected
Young / middle-aged adults
Acute onset of pain, followed by flaccid / areflexic / hyporeflexic paralysis
Thought to be immune-mediated
Rarely inherited: AD SEPT gene
Bilateral in 10-20%
Differential diagnosis for bilateral 7th cranial nerve palsy?
Myopathy: inclusion-body myositis, muscular dystrophy
NMJ: myasthenia
Peripheral nerve: bilateral Bell’s, bilateral Ramsay-Hunt, Lyme, GBS, neck / parotid trauma
AHC: MND
Brainstem: listeria, malignancy, sarcoid
Idiopathic intracranial hypertension features?
Younger female, high BMI, COCP use
Exclude mass lesion / hydrocephalus
Presents with headaches: postural, vomiting, vasalva, visual obscurations, 6th nerve palsy (false localising sign)
Investigations in idiopathic intracranial hypertension?
Need to exclude secondary causes of raised ICP first.
- MRI and MR venogram (rule out stroke and CVST)
- LP (rule out hydrocephalus) with opening pressure
- Formal visual fields assessment
Management of IIH?
Acetazolamide
Weight loss
If visual loss present:
- LP
- optic nerve fenestration
- VP shunt
Features of hereditary spastic paraparesis?
Any age of onset (tend to be more rapidly progressive if start >35y)
Circumduction gait (scissor)
Progressive LL pyramidal weakness (UMN)
Mild dorsal column disturbance
1/3rd have pes cavus
Corticobulbar involvement
Features of chronic progressive external ophthalmoplegia (CPEO)?
Present in 2/3rds of mitochondrial myopathies
Slowly progressive
Bilateral ptosis with frontalis overactivity
Ophthalmoplegia (complex - all gazes affected)
May have retinitis pigmentosa if Kearns-Sayre syndrome
Facial + limb weakness in 25%
What investigations would you do in a case of CPEO?
Muscle biopsy with Gomori stain: shows ‘ragged red fibres’ and enlarged mitochondria
PCR for mutations:
Mitochondrial disorder
- maternal inheritance: MELAS, MERFF, LHON
- sporadic pattern: KSS, CPEO
Ddx for cerebellar disorders?
(PASTRIES)
PASTRIES
Posterior fossa neoplasia
Alcohol
Sclerosis (demyelination)
Trauma
Rare (spinocerebellar ataxias)
Inherited (Freidreich’s ataxia)
Epilepsy meds (phenytoin)
Stroke
Ddx for retinitis pigmentosa associations?
Mitochondrial cytopathies: Kearns-Sayre
Refsum’s disease: recessive, cerebellar ataxia, optic atrophy, deafness, cardiomyopathy, ichthyosis
Laurence-Moon-Biedl syndrome: recessive, obesity, mental retardation, dwarfism, polydactyly
Hereditary neuropathies and ataxias
Ddx for muscular disorders? (no sensory features, no fatiguability, patterns of wasting and weakness)
Inclusion body myositis
Myotonic dystrophy
Dermato/polymyositis
Facio-scapulo-humeral muscular dystrophy
Duchenne’s muscular dystrophy
Becker’s muscular dystrophy
Limb-girdle muscular dystrophy
Features of dermato/polymositis?
Heliotrope purple rash on eyelids + Gottron’s papules.
Can be paraneoplastic phenomenon.
Features of facio-scapulo-humeral muscular dystrophy?
Face + shoulder girdle weakness
Unable to whistle, dysarthric, can’t close eyes, winging of scapula when tested
AD condition, CK elevated
Features of Duchenne’s and Becker’s muscular dystrophies?
Duchenne’s:
- x-linked, absence of dystrophin
- calf hypertrophy
- respiratory complications + cardiomyopathy
- CK >10,000
Becker’s:
- x-linked, milder but still have cardiomyopathy
- calf hypertrophy
- CK >10,000
Features of limb-girdle muscular dystrophy?
Autosomal recessive inheritance
No facial involvement
Variable cardiac / resp involvement
Features of inclusion body myositis?
Usually proximal UL, distal LL, asymmetrical
Early involvement of knee extensors, ankle dorsiflexors, wrist flexors, finger flexors
Reflexes normal / reduced
Dysphagia is v common
Classical features of myotonic dystrophy?
‘Myopathy + myotonia’
Myopathic facies: long, thin face with reduced expression, bilateral ptosis. Wasting temporalis, masseter and sternocleidomastoid. Frontal balding, dysarthria
Hands: grip myotonia, percussion myotonia, wasting and weakness distally, areflexic
Other features:
- cataracts
- cardiomyopathy / arrhythmias (look for pacemaker)
- diabetes mellitus
- testicular atrophy
Ddx for myotonic dystrophy if none of the extra features are present?
Myotonica congenita.
What investigations would you like to perform if you suspect myotonic dystrophy?
CK - likely increased
Genetic testing:
- AD inheritance pattern
- onset in 20s, M > F preponderance
- trinucleotide repeat disorder with genetic anticipation
EMG - shows ‘dive bomber’ action potentials
Management options in myotonic dystrophy?
MDT input!
Carbamazepine
Mexilitine (if normal OTc)
Advise against general anaesthesia
Genetic counselling
What are the two anterior horn cell disorders to be aware of?
Old poliomyelitis
Motor neuron disease
Differential diagnosis for fasciculations?
Polio
MND
Cervical disc disease
Syrinx
Neuralgic amyotrophy
Thyrotoxicosis
Neuromyotonia
Multifocal motor neuropathy (MMN) with conduction block
Features and management of old polio? (AHC disorder)
Signs:
- shortened limbs
- signs of previous surgery / scars
- walking aids
- fasciculations ++ suggest post-polio syndrome
About:
- poliovirus is a neurotropic virus acquired via the faeco-oral route
- results in aseptic meningitis or paralytic disease
- attacks anterior horn cells
Management:
- MDT approach: orthotics, PT, OT, nurse, home modifications, orthopaedic surgery for limb fusion
- analgesia
- rehab
Investigations when suspecting anterior horn cell disorder?
Voltage-gated calcium channel and ganglioside antibodies
TFTs
MRI whole spine
NCS / EMG
Types and management options for MND
Types:
- progressive muscular atrophy (muscle wasting + hyperreflexia)
- amyotrophic lateral sclerosis (spastic weakness in legs)
- progressive bulbar palsy (speech, palate, tongue)
Management:
- MDT approach
- Riluzole increases life expectancy by 3 months
- Carbamazepine
- Citalopram
- PT / OT / orthotics / SLT / dietician
- NIV
- PEG feeding
Ddx for peripheral neuropathy?
‘MTV DID IIT’
Metabolic: diabetes
Trauma / compressive
Vitamin: B12, thiamine
Demyelination: GBS, CIDP
Inflammatiory: vasculitis, RA, SLE, sarcoid
Drugs: cisplatin
Inherited: HMSN (CMT, HNPP)
Infection: HIV, leprosy, Lyme
Toxins: lead poisoning
Investigations for a patient presenting with peripheral neuropathy?
Fasting glucose, HbA1c, B12, thiamine
ESR, ANCA, ANA, ENA
Urinalysis
NCS / EMG (demyelination)
Autonomic tests
Causes of absent ankle jerks but extensor plantars?
MND
Conus medullaris lesion
Freidreich’s ataxia
SACD spinal cord
Taboparesis
(1 pathology affecting 2 areas)
Cervical myelopathy + peripheral neuropathy (2 pathologies)
Ddx for a monocular visual defect?
Constricted field: papilloedema, glaucoma
Tunnel vision + poor night vision: retinitis pigmentosa
Central scotoma: optic nerve / macular degeneration
Altitudinal defect: anterior ischaemic optic neuropathy
Ddx for a bitemporal hemianopia visual defect?
Indicates a lesion at the optic chiasm. This is likely to be either a pituitary tumour or a craniopharyngioma.
Bitemporal superior quadrantanopia = pituitary tumour
Bitemporal inferior quadrantanopia = craniopharyngioma
Ddx for homonymous hemianopia?
Caused by lesions of the retro-chiasmal visual pathways:
- optic tract
- optic radiation
- occipital lobe (macular sparing)
Homonymous superior quadrantanopia = retrochiasmal in temporal lobe
Homonymous inferior quadrantanopia = retrochiasmal in parietal lobe
‘PITS’
Ddx of unilateral ptosis?
3rd nerve (complete ptosis)
- Surgical (ie compressive), involves pupil: ICH, SOL
- Medical (doesn’t involve pupil): diabetes, vasculitis
Horner’s (incomplete)
- Brainstem / cord: demyelination, syrinx
- C8 / T1 root: disc prolapse, Pancoast’s tumour
- Cervical chain: carotid dissection
Ddx of bilateral ptosis?
Myasthenia gravis
Myotonic dystrophy
Congenital
Tabes dorsalis
Mitochondrial disorder with chronic progressive external ophthalmoplegia (CPEO)
Investigations for a patient with unknown cause of bilateral ptosis?
Ice / edrephonium test
Ach receptor + MUSK antibodies
CT thorax (thymoma)
Muscle biopsy for ragged red fibres
Treponemal antibody
Investigations for a patient with unknown cause of unilateral ptosis?
Bedside: fasting glucose
Bloods: HbA1c, ESR, ANA, ENA, ANCA
Imaging: MRI brain / spinal cord, CT thorax, angiography
Asked to examine a patient with a tremor, and they are displaying features of Parkinsonism. What other things would you test during the exam?
At rest, asymmetric, coarse, 4-6 Hz pill-rolling tremor, worse with distraction (waving opposite hand).
Gait: reduced armswing, slow turn, axial rigidity
Hypomimia
Bradykinesia (tap fingers together)
Rigidity: test tone in ULs (leadpipe, cogwheel)
Micrographia: write sentence, draw Archimedes’ spiral if pen / paper
How would you do a Parkinson’s plus features screen at the end of a Parkinsonism case?
PSP: supranuclear gaze palsy, retropulsion, axial rigidity
MSA: falls, postural hypotension, autonomic features (dry mouth, urinary incontinence)
DLB: hallucinations, cognitive function tests (MMSE)
Corticobasal degeneration: ask about phantom limb
Hemi-parkinsonism: stepwise decline, atherosclerotic risk factors
Drug-related: metoclopramide and atypical antipsychotics (clozapine, olanzapine)
Non-motor features of PD: anosmia, depression, REM sleep disorder, dysautonomia
If a young patient presents with signs of Parkinsonism, what additional screening would you like to do?
Wilson’s screen (copper + caeruloplasmin)
PTH screen (calcium, PTH)
Stiff-Man Syndrome (anti-GAD antibodies, EMG)
Possible polio mimics / ddx for polio?
MND (other anterior horn cell disorder)
Polio-like syndromes: acute flaccid myelitis, aresnic and organophosphate poisoning
Features of a cerebellar gait?
Broad-based
Falls towards side of lesion
DANISH features
Features of an extrapyramidal gait?
Shuffling, festinant
Slow turning circle + axial rigidity
Bradykinesia, bradyphrenia (slowness of thought)
Rest tremor (uni / bilateral)
Features of a sensory pathology gait?
Stamping / high-stepping gait
Romberg’s positive
Features of a gait indicating proximal weakness?
Difficulty rising from a chair
Gower’s sign
Features of a gait with foot drop?
High-stepping gait
Cannot stand on heels or toes
Features of a paraplegic gait?
Spastic leg extension
‘Like walking through mud’
Look for a sensory level!
Features of a hemiplegic gait?
Spastic arm flexion and leg extension
Circumduction of leg
Toe walking
Areas that can we can localise a lesion within the CNS to, and expected signs
Brain: pure UMN signs, hemiparesis or hemisensory, cerebellar signs
Brainstem: UMN signs with cranial nerve palsies, crossed signs
Cord: sensory level, spastic paraparesis, bladder + bowel dysfunction, isolated / mixed dorsal / spinothalamic signs
Causes and features of an anterior horn cell lesion?
Expect either LMN only, or mixed UMN and LMN signs with fasciculations.
Narrow differential: only old polio or motor neuron disease.
Areas that can we can localise a lesion within the PNS to, and expected signs
Root: LMN and sensory signs, 1 or more nerve roots in a myo/dermatomal pattern
Plexus: LMN and sensory signs, affecting >1 nerve root (eg whole limb)
Nerve: either sensory > LMN signs (length-dependent) OR sensory + LMN signs (mononeuropathy)
Muscle: no sensory features, no fatiguability (IBM, myotonic dystrophy, dermato/polymyositis, facio-scapulo-humeral MD, Beckers, Duchenne’s, limb-girdle MD
NMJ: myasthenia gravis, LEMS
Ddx for a lesion within the CNS? (UMN signs)
‘TVN DID’
Traumatic (TBI / SC injury)
Vascular (haemorrhage, thrombotic, embolic)
Neoplastic / paraneoplastic
Demyelination (MS)
Infection
Degeneration
Ddx for an anterior horn cell lesion? (pure LMN or LMN + UMN with fasciculations)
Narrow differential, either:
- Old polio / post-polio syndrome
or
- Motor neuron disease
Ddx for a PNS lesion (LMN signs)
‘MTV DID IIT’
Metabolic: diabetes, porphyria
Trauma / compression
Vitamin: B12, thiamine
Demyelination: GBS, CIDP
Inflammatory: vasculitis, RA, sarcoid, SLE
Drugs: cisplatin
Inherited: hereditary sensorimotor neuropathies (CMT, HNPP)
Infections: HIV, syphilis, lyme disease
Toxins: lead poisoning
Motor tracts and their corresponding modalities?
Pyramidal tracts (motor tracts, damage causes UMN signs)
Extrapyramidal tracts (damage leads to hypo and hyper-kinetic movement disorders - PD and HD)
Sensory tracts and their corresponding modalities?
Dorsal columns: fine touch, proprioception, vibration
Spinocerebellar tracts: proprioception
Spinothalamic tracts: pain and temperature
In the exam: do
FINE TOUCH - dorsal columns
PINPRICK - spinothalamic
TOE UP AND DOWN - dorsal + spinocerebellar
Myotomes for biceps, triceps and brachioradialis reflexes?
Biceps and brachioradialis: C5-C6
Triceps: C7-C8
Myotomes for shoulder abduction, elbow flexion and elbow extension?
Shoulder abduction: C5, deltoid
Elbow flexion: C6, biceps, brachioradialis
Elbow extension: C7, triceps
Myotomes for wrist flexion and finger abduction?
Wrist flexion: C8, flexor carpi radialis
Finger abduction: T1, dorsal interrosei
Myotomes for hip flexion and knee extension?
Hip flexion: L2, iliopsoas
Knee extension: L4, quad fem
Myotomes for foot dorsiflexion and plantarflexion?
Foot dorsiflexion: L5, tibialis anterior
Foot plantarflexion: S1, gastrocnemius
Dermatomal areas for C5, C6, C7, C8 dermatomes?
C5 - lateral shoulder
C6 - thumb
C7 - middle finger
C8 - pinky finger
Dermatomal areas for T4, T7, T10?
T4 - nipple line ‘teet pore’
T7 - xiphoid
T10 - umbilicus (belly butTEN)
Dermatomal areas for L1, L4, L5 and S1?
L1 - inguinal LIgament
L4 - medial malleolus
L5 - top of foot
S1 - heel (stand on S1)
What are the contra-indications for thrombolysis?
Absolute contraindications:
Intra-cranial haemorrhage
Seizure at onset
Stroke/TBI <3m
LP <7d
GI bleed <3w
Active bleeding
Pregnancy
Varices
Uncontrolled HTN
What makes up the Modified Rankin Score?
Modified Rankin Score (MRS) of DISABILITY not frailty.
0 = nil
1 = symptoms without disability
2 = Can look after own self for 1 week
3 = Cannot look after own self for 1 week
4 = Needs help with ADL’s
5 = Bed-bound
What do you do if a patient is on a DOAC and needs thrombolysis?
Contra-indicated if received DOAC within 24 hours of stroke (move towards 48 hours)
How do you manage blood pressure control in a candidate for thrombolysis?
No clear evidence that high blood pressure is a risk - there is a theoretical risk of bleeding.
Blood pressure is a protective mechanism in stroke.
If thrombolysing, - need to bring the blood pressure down
In thrombolysis - Labetolol boluses then infusion (provided HR>60)
Can you ever thrombolyse a wake up stroke?
Can thrombolyse if you can get an urgent MRI to look at the T2/DWI mismatch to assess penumbra.
What are the indications for thrombectomy?
- Ischaemic stroke
- Large vessel occlusion - intra-cranial carotid, MCA (M1, M2), basilar, and most recently posterior circulation strokes.
- Need CTA!!!! Not just non-contrast CT. Need the scan BEFORE you refer.
- MRS 0-1 (latest guidelines)
- NIHSS >6 (or >10 for basilar)
Patients will get thrombolysis + thrombectomy together.
After 12 hours - need CT or MR perfusion scan to assess flow to brain and salvageable brain.
Even the larger strokes with large cores will now get thrombolysed - there isn’t actually as big a risk of bleeding as we predicted, so if there is a potentially salvageable penumbra - thrombolysis is on the table (based on data from 2023 trials)
What do you know about HMSN?
2 types
Type 1: demyelinating
Type 2: axonal pathology
Type 1 is more common and inherited in an AD pattern
Defect in PMP 22 gene
Motor symptoms predominate
Distal muscle wasting
What are some causes for demyelinating polyneuropathies?
CIDP
Multiple myeloma
MGUS
HSMN
HIV
Talk to me about nerve conduction and EMG studies
NCS -** N**erve conduction - problem with nerve
EMG - problem with muscle response to nerve stimulus
Nerve conduction studies
Axon problem or myelin problem and evaluation of conduction blocks
Axon problem:
Reduced amplitude of conduction
Trauma, toxin, ischaemia, metabolic, genetic
Myelin problem (usually immune mediated)
Slow conduction velocity
GBS, CIDP
What are the clinical signs of Friedrich’s Ataxia?
Brain:
Cerebellar syndrome
Cord:
Upgoing plantars
Dorsal column signs
Pyramidal pattern of weakness that affects the lower limbs more than upper limbs
Peripheral nerves:
Depressed DTR’s
Muscle weakness
Non-neuro:
Diabetes
Optic atrophy
Sensorineuronal deafness
HOCM
Conduction defects
What do you know about Friedrich’s ataxia’s genetic inheritence and pathophysiology?
AR trinucleotide repeat disorder that does not demonstrate anticipation
Mutation in the Frataxin gene that regulates iron and oxidative phosphorylation
Particularly affects the spinocerebellar tract and peripheral nerves
What types of inherited cerebellar ataxias do you know?
Friedreich’s
AD Cerebellar ataxia
AR Ataxic telangiectasia
AR Ataxia with Vitamin E deficiency
AR Ataxia with Occulomotor apraxia
AR Mitochondrial recessive ataxic syndrome
Are there any treatments for Myotonic Dystrophy?
Phenytoin
Maxilitine (however concern due to cardiac safety profile)
MDT to address home, work, and transport environments and make adaptations.
What other causes of myotonia do you know?
Startle myotonia
Paramyotonia congenita
Hyperkalaemic periodic paralysis
What are the clinical signs of fascio-scapulo-humeral dystrophy?
Facial weakness
NO ptosis/balding
Weakness in upper limb girdle - shoulder weakness, winging of scapula. Forearms spared.
Weakness and protuberance of abdomen
Weakness in foot dorsiflexion with foot drop
Sensosineuronal deafness
Retinal telangiectasia
What do you know about Duchenne’s?
More severe than Becker’s
X-lined recessive inactivating mutation in the dystrophin gene that leads to muscle loss in skeletal, cardiac, smooth muscle, and brain tissue
Proximal to distal weakness
Calf pseudohypertrophy with wasting in anterior shin
Contractures
Loss of DTRs
Kyphoscoliosis
Non-cardaic
Dilated cardiomyopathy
Pulmonary hypertension
Resp failure
How do you differentiate a C8/T1 radiculopathy vs. ulnar nerve lesion?
- Both with have weakness in ulnar innervated muscles
- In C8/T1 there will be weakness of thumb abduction, and finger extension
- There will be more diffuse sensory loss with a C8/T1 radiculopathy
What do you know about Kennedy’s disease?
X linked recessive
Chronic and insidious onset
Peri-oral fasciculations
What is the pathophys of idiopathic PD?
Disruption of dopaminergic transmission in basal ganglia.
Loss of melanin containing dopaminergic neurons in the substantia nigra that are replaced by Lewy bodies.
Predominantly affects the ventrolateral substantia nigra
How do you localise a problem to the NMJ / muscle?
Weakness
Normal sensation
Normal reflexes
Do you know of any drugs that cause a predominently sensory neuropathy?
Isoniazid
Metronidazole
Hydralazine
What is the pattern of disease in facio-scapulo-humeral muscular dystrophy?
Weakness of upper limb and upper arms, preserved forearm strength
Visible scapula due to weakness
Abdominal weakness (Beevor’s sign)
50% of patients will develop lower limb weakness
Sensorineuronal deafness
Retinal telangiectasia
What are the clinical findings of Becker’s and Duchenne’s muscular dystrophy?
Beckers has a ‘better’ prognosis
Proximal to distal pattern of weakness
Legs > neck > arms > distal
Waddling gait
Hyper-lordoisis
Calf pseudohypertrophy (more so in Duchenne’s)
Dilated cardiomyopathy
Pul HTN
Respiratory failure
What is Devic’s disease? (NMO)
Now considered distinct from MS
More frequently seen in Asian populations
Central cord lesions (cervical) and optic tract
Vomiting is a frequent presenting complaint
IgG Aquaporin-4 positive
Acute attacks treated with steroids, plasmapharesis and immune supression (rituximab)
What treatments for MS do you know?
Acute flares are treated with steroids. These do not affect the degree of RECOVERY, but do shorten the length of the relapse.
DMARD’s are started in
- Relapsing-remitting with 2 relapses in 2 years
- Secondary progressive disease
Anti-CD20 Ocrelizumab
Anti-α4β1 Natalizumab
S1P modulator Fingolimod
Fatigue: Amantadine
Others: Glatiramer, dimethyl fumarate, interferon beta
How do you differentiate an INO from a III palsy?
INO is a problem with the ipsilateral MLF that prevents eye adduction on conjugate gaze.
If you cover the abducting eye, the pathological eye will now adduct.
This will not be the case in a III palsy.
What is a RAPD?
Defect in AFFERENT side
Shining light in the normal eye will result in bilateral constriction. When you swing the light to the affected side, there will be bilateral dilation
If there is a RAPD with no visual loss, the problem is in the tectal midbrain (dorsal midbrain)
If there is visual loss + RAPD = problem is in the retina or the optic nerve
What is the genetics of Huntington’s?
Autosomal dominant
CAG trinucleotide repeat on chromosome 4
What are the clinical features of Huntington’s?
Presents in 3-4th decade
Degeneration of motor cortex and striatum (caudate + putamen) with early caudate atrophy seen on MRI
Manifests are chorea
In younger patients, may be rigid with PD signs and slow saccadic eye movements
Fronto-cortical cognitive impairment leads to behavioural disturbances
What is your differential diagnosis for chorea?
Inherited
Huntingtons (AD)
Wilson’s (AR)
Spinocerebellar ataxia (AD)
Acquired
SLE
PRV
Levodopa
Syndenham’s chorea (late feature of Strep pyogens rheumatic fever)
What is the gene implicated in Wilson’s disease and how is it inherited?
ATP 7B
Autosomal recessive
Failure of biliary copper excretion
What is macular sparing?
Central field representation in the occipital cortex receives blood supply from MCA and PCA. So if PCA is interrupted, the central field portion is still supplied by the MCA and you get ‘macular sparing’.
Causes for an upgaze palsy?
Miller Fisher variant of GBS
Parinaud syndrome (pineal tumour)
PSP
MG
Graves
Are there any conditions associated with Myasthenia?
Thymomas
Thymic hyperplasia
Pernicious anaemia
Autoimmune thyroid disorders
RA
SLE
How do you treat Myasthenia?
Long-acting acetylcholinesterase inhibitors
The majority of patients eventually require immunosuppression - pred, then aza, cyclo, myco, ciclo
When starting pred - admit - might worsen symptoms and precipitate a crisis
Thymectomy
Crisis: Immunoglobulins, plasmapharesis
Lamotrigine counselling
‘Slows electrical signals down’
Comes as a tablet
Can take up to 6 weeks to work
Common side effects - skin rashes (SJS), headaches, mood changes, sleep, GI
Rashes are most common in the first 8 weeks and at dose changes, especially when dose increased too quickly
Long-term risk of osteoporosis
Need to check kidney and liver function
Safe in pregnancy
Advise 5mg folic acid for 3 months before conception
Safe in breastfeeding (can be found in breastmilk and can lead to drowsiness)
Might stop the COMBINED pill working - advise changing contraception or using condoms
Valproate counselling
Epilem
Comes as tablets or liquid
Side effects - GI, oral ulcers, tremors, sleepy, weight gain. Rare - hepatic, suicidal thoughts, pancreatitis
CONTRAINDICATED in pregnancy
Safe in breastfeeding
No effect on contraception
Reduces fertility
Leviteracetam counselling
Keppra
Takes a few weeks
Headaches, blocked nose, feeling sleepy
Safe in pregnancy
Usual folic acid 5mg 3/12 before
Does NOT affect contraception
Safe in pregnancy
What are the features of a Parkinsonian gait?
Stooped posture
Reduced arm swing
Short shuffling steps (bradykinesia)
Postural instability
Difficulty turning ‘turning on block’
What are the causes of Parkinsonism?
Idiopathic PD
Drug-induced Parkinsonism
Wilson’s disease
Normal pressure hydrocephalus
Parkinson’s plus syndromes: progressive supranuclear palsy, the multisystem atrophy syndromes and LBD.
What are the classical features of Parkinson’s disease?
Bradykinesia
Rigidity
Rest tremor
(+ postural instability)
What is a key differentiating feature between idiopathic PD and Parkinsonism?
A differentiating feature of Parkinsonism is the symmetrical distribution of signs.
Differentiating features between cerebellar and sensory ataxia?
Cerebellar ataxia: accompanied by nystagmus and dysarthria.
Sensory ataxia: impaired sensation, especially joint position and vibration. Struggle with putting feet together on Romberg’s testing, and heel-to-shin walking. Signs made worse by removing pt’s visual input.
If you identify sensory ataxia - must elicit whether the cause is central or peripheral.
Central causes - dorsal column pathology / SC pathology
Peripheral causes - neuropathy (large myelinated sensory fibres affected)
Occasionally due to both central and peripheral causes - B12 deficiency
DDx for motor neuron disease?
Spinal muscular atrophy
Kennedy’s disease (spinal and bulbar muscular atrophy)
Primary lateral sclerosis (PLS) - presents mainly with UMN features
Tell me about Kennedy’s disease.
Spino bulbar muscular atrophy.
Only lower motor neurones affected.
Perioral fasciculations are almost pathognomonic.
X-linked recessive disorder associated with androgen insensitivity.
Very slow rate of progression, differentiating it from ALS.
Talk about the different types of muscular dystrophy
Muscular dystrophies are a large group of weakness of skeletal muscles.
- Duchenne’s muscular dystrophy
- Becker’s muscular dystrophy
- Oculopharyngeal MD
- Myotonic dystrophy
- Fascio-scapulo-humeral muscular dystrophy
- Limb-girdle muscular dystrophy (weakness of shoulder + pelvic girdle muscles)
Investigations to do in cases of suspected muscular dystrophy?
Bloods: CK (raised), genetic testing (obviates need for muscle biopsy)
Imaging: MR brain can be useful
EMG: myopathic changes are seen
Echo: regular screening for cardiac complications is usually required
Important differentials to include when suspecting motor neurone disease?
Spinal muscular atrophy
Kennedy’s disease
Multifocal motor neuropathy with conduction block (treatable)
Suggested investigations in suspected motor neurone disease?
Neurophysiology: on EMG would be looking for fibrillations, fasciculations and an absence of sensory signs
In multifocal motor neuropathy - would find demyelinating features and a conduction block
If the diagnosis is not straightforward, would proceed with an MRI scan for structural imaging
How would you distinguish between motor neurone disease, Kennedy’s disease and multifocal motor neuropathy with conduction block?
MND - asymmetrical disease process, rapid and aggressive in disease course. Signs/symptoms of frontotemporal dementia.
Multifocal motor neuropathy with conduction block - more pronounced distal weakness early on in the disease process, and pt may complain of clumsiness.
Kennedy’s disease - check the pt’s family history. Ask about other family members. There are familial causes of MND.
Management of MND / ALS?
MDT approach: dieticians, doctors, sp. nurses, psychologists, SLT, PT/OT
Refer to specialist neurology clinic - MND specialist
Only drug is Riluzole - 3 month improved survival
Consider nutrition and PEG feeding
Consider respiratory function: measure early morning blood gas and FVC (may need NIV / cough assist devices)
Screen for cognitive and behavioural changes - may indicate frontotemporal dementia
Do you know of any inherited forms of motor neurone disease?
X-linked spinobulbar muscular atrophy (Kennedy’s disease)
ALS associated with the C9orf72 hexanucleotide repeat expansion
How would you confirm a diagnosis of Freidreich’s ataxia?
Other conditions can present in very similar ways. Therefore it is important to:
* Rule out treatable causes: B12 and vitamin E bloods
* Exclude compressive pathology (MRI brain and spinal cord)
* NCS and EMG
* Ultimately the diagnosis would be made with genetic testing
What do you know about the management of Freidreich’s ataxia?
- Regular echo + ECGs: high risk of arrhythmias and cardiomyopathy with Freidreich’s
- MDT approach: OT / PT / neurology / orthotics / SALT / genetics counselling team
Tell me about the genetics of Freidreich’s ataxia
Trinucleotide repeat disorder
AR inheritance, mutation of the frataxin gene
What are the non-motor symptoms of Parkinson’s disease?
Anosmia
Cognitive defects
Mood disorders
Pain
REM sleep disorder
Name some causes of tremor
Rest tremor: Parkinson’s disease
Postural tremor: essential tremor, anxiety, hyperthyroidism, hepatic encephalopathy, co2 retention, alcohol
Intention tremor: cerebellar disease
Causes of Parkinsonism?
Idiopathic PD
Parkinson plus syndromes: MSA, PSP, corticobasal degeneration
Drug-induced (phenothiazines)
Hypoxic brain injury
Post-encephalitis
MPTP toxicity
Parkinson’s disease management options?
L-dopa + dopa decarboxylase inhibitor
Apomorphine (dopamine agonist)
Selegiline (MAO-B inhibitors)
Anticholinergics
Entacapone (COMT inhibitors)
Amantadine
Surgery: DBS
MDT approach required: PT/OT/SLT
Assess non-motor symptoms using the ‘non-motor symptoms questionnaire’
Classical presentation of a patient with myelopathy?
Usually presents with asymmetric spastic paraparesis.
Onset + progression of disease:
- 1-2 days: trauma / disc herniation
- days-weeks: MS / lupus
- weeks-months: nutritional or tumour
- months-years: genetic
Any previous episodes of neurologic dysfunction (thinking of MS)
Full systems enquiry (think malignancy and autoimmune causes)
Family history
ASK ABOUT bladder and bowel control, saddle anaesthesia and leg weakness (CES)
Differential diagnosis for myelopathic cause of spastic paraparesis?
Broad differential, and can be differentiated by time of onset:
- If very acute, consider vascular cause such as spinal stroke (but you would expect ‘spinal shock’ here which presents with hypotonia)
- If acute cause with back pain and red flags associated with back pain, consider compressive pathology (need urgent MR spine)
- Over a period of days: consider inflammatory or infective cause (MS, transverse myelitis, VZV, HIV, HTLV-1)
- If come on over a period of time, consider vitamin B12 deficiency as cause
- Over longer term: consider neurodegenerative conditions (primary lateral sclerosis) or hereditary causes such as HSP.
MRC muscle power scale?
0 - no contraction
1 - flicker
2 - active movement with gravity eliminated
3 - active movement against gravity
4 - active movement against gravity and resistance
5 - normal power
Ddx for unilateral foot drop?
- Sciatic nerve lesion: hip trauma / surgery, obstetric injury
- L4/L5 nerve root lesion: prolapsed disc
- CPN palsy: fracture / pressure on neck of fibula
- Peripheral neuropathy (uni or bilateral): GBS, CIDP, diabetes, lead toxicity, porphyria, congenital (CMT)
