Neurology Flashcards
Neurological examples of trinucleotide repeat disorders?
Huntington’s Disease (CAG)
Spinocerebellar Ataxia Disorders (CAG)
Friedrich’s Ataxia (GAA)
Myotonic Dystrophy (CTG)
MRC Grading of Power
5 = full power against resistance
4 = reduced power, able to move against some resistance
3 = able to move against gravity; NOT against resistance
2 = unable to move against gravity; some movement if gravity eliminated
1 = visible flicker of muscle contraction
0 = no muscle contraction or movement
UMN Features
?Contractures
Increased tone
+/- Clonus
Brisk reflexes
Upgoing (extensor) plantar reflexes
Localisation of UMN
Brain (including parasagittal sinus) to spinal cord (terminates at L1-L2, conus medullaris)
Spasticity vs Rigidity
SPASTICITY = increased tone, velocity dependent (faster you move the limb, the greater increase in tone)
= lesion of pyramidal tract
RIGIDITY = increased tone; velocity INDEPENDENT (same increased tone whether you move the limb fast or slow)
= lesion of extrapyramidal tract
Pyramidal vs Extrapyramidal Tracts
PYRAMIDAL TRACT = Cerebral cortex to spinal cord via medullary pyramids = conscious control of muscles from the cerebral cortex
EXTRAPYRAMIDAL TRACT = Originate in the brainstem, carrying motor fibres to the spinal cord = involved in the control of movement and coordination
Differentials for UMN pattern of limb weakness
Differential will be guided by timing of onset of symptoms
Vascular - ischaemic stroke, haemorrhage
Infection - Encephalitis, meningitis, cerebral abscess, spinal abscess, transverse myelitis
Trauma
Demyelinating - MS, NMO
Compressive lesion e.g. malignancy, prolapsed vertebral disc
Cerebral palsy
Hereditary e.g. hereditary spastic paraparesis
Autoimmune e.g. AI encephalitis
Differentials for SPASTIC HEMIPARESIS
Contralateral stroke
- ACA affects legs > arms (face often spared)
- MCA affects arms > legs
Space-occupying lesion
Cord Compression e.g. Tumour
Intrinsic cord disease e.g. MS, tumour, vascular
Brown-Sequard syndrome
Presenting SPASTIC HEMIPARESIS
If acute onset - concerned presenting as a stroke
To complete my examination I would like to…
1) Fundoscopy
2) Full cranial nerve examination and neurological examination
3) Cardiovascular examination
4) Speech and swallow assessment
5) Check the BP and blood glucose
Investigating SPASTIC HEMIPARESIS
If acute onset = urgent CT head (esp if <4.5 hours onset, may be candidate for thrombolysis)
BP, BM
12-lead ECG
FBC, ESR, baseline renal and liver function
Coagulation studies
Lipid profile, HbA1c (ischaemic stroke RFs)
Neuroimaging
Further investigations for Ischaemic Stroke
Carotid dopplers (if anterior circulation stroke suspected)
24 - 72 hour tape
Echo
MRI with diffusion weighted imaging +/- MRA (dissection, aneurysm, AVM, venous sinus thrombosis, posterior fossa lesion suspected)
Vasculitic and thrombophilia screen = ANA, ANCA, antiphospholipid antibodies, lupus anticoagulant, factor V leiden, protein C and S, antithrombin III
HIV and syphilis serology
?Bubble echo (if young patient and want to exclude PFO,VSD etc)
Management of Ischaemic Stroke
ABCDE assessment
Rule out mimics e.g. hypoglycaemia
Urgent CT head (esp if <4.5 hours onset)
Discuss with stroke team
NBM until swallow assessed
Admit to hyperacute stroke unit, with BP monitoring and regular neuro obs
Aspirin 300mg PO/NG/PR for 2 weeks with PPI
Atorvastatin 80mg ON
MDT approach - PTs/OTs/SLT
Secondary prevention e.g. stop smoking
Driving advice
Contraindications to Thrombolysis
Seizure at onset of stroke
Stroke/HI < 3 months
Active bleeding
History of UGIB<3 weeks
Major surgery/trauma < 2 weeks
Intracranial neoplasm
Uncontrolled HTN (>200/120)
LP < 7 days
Oesophageal varices
Pregnancy
Complications of Stroke
ACUTE
Haemorrhagic transformation
Aspiration pneumonia
Raised intracranial pressure –> herniation
Death
CHRONIC
Pneumonia (HAP/Asp)
DVT –> PE
Pressure sores
Swallow impairment
Depression
Hosp Acquired Infections
Long term morbidity & disability
Haemorrhagic Stroke
15-20% of all strokes
CAUSES/RFs
- HTN
- Anticoagulation
- Trauma
- Tumour (1 or 2)
- Aneurysm (e.g. berry aneurysms in ADPKD)
- AVMs
- Infective endocarditis (haem transformation of septic emboli)
- Amyloid Angiopathy
DVLA Advice TIA vs Stroke vs Seizure (Category 1)
TIA = stop driving until seen in TIA clinic. If TIA confirmed, stop driving for 1 month
Stroke = stop driving for 1 month, review with doctor
Seizure = cannot drive until 1 year seizure free
DVLA Advice TIA vs Stroke vs Seizure (Category 2 - HGV)
TIA = stop driving until seen in TIA clinic. If confirmed, then cannot drive cat 2. for at least 1 year, review with doctor
Stroke = stop driving for at least 1 year, review with doctor
Seizure = cannot drive until seizure free>5 years and seizure free without AEDs for 5 years.
>2 seizures = STOP
Differentials for SPASTIC PARAPARESIS
- bilateral lower limb UMN
- Spastic gait
PARASAGITTAL Causes
- Meningioma
SPINAL CORD Causes
- Trauma
- Compressive e.g. SCC, tumour, prolapsed disc
- Demyelinating e.g. MS, NMO
- Infective e.g. transverse myelitis (HSV, VZV, HIV), tropical spastic paraparesis
- Ischaemic e.g. anterior spinal artery occlusion
CONGENITAL Causes
- Hereditary Spastic Paraparesis
- Cerebral palsy
- Friedrich’s Ataxia
Presenting SPASTIC PARAPARESIS
If acute onset - MRI to exclude spinal cord compression
1) Take a full history - ?back pain/bladder or bowel disturbance/visual problems
2) Perform a PR (anal tone, saddle anaesthesia)
3) Examine upper limbs and cranial nerves in full as well as speech
Investigating SPASTIC PARAPARESIS
If acute onset - need to exclude SCC = Urgent MRI Spine
Bloods
- FBC, renal profile, bone profile
- Myeloma screen (immunoGs, serum electrophoresis)
- Serum oligoclonal bands
- AQ4 antibiodies (?NMO)
- B12
- ANA (vasculitis screen)
- HIV
Imaging - MRI spine
?LP - particularly if history concerning for MS/NMO
? Visual evoked potentials
Multiple Sclerosis
= inflammatory demyelinating disease of CNS
RFs = FHx, female > male, increasing latitude
“>2 relapses with evidence of >2 lesions”
Most common form is relapsing-remitting (85%)
Visual Features of MS
Optic neuritis
= pain on eye movements, reduced red colour spectrum
Pulrich’s Effect
= reduced depth perception
Internuclear Ophthalmoplegia
= adduction deficit in affected eye and nystagmus in other eye (lesion in MLF)
What is Uhthoff’s phenomenon?
Symptoms worsen as temperature increases
- temperature sensitive Na+ channels in demyelinated neurones
Diagnosing/Investigating MS
McDonald Criteria
Expanded Disability Status Scale (EDSS)
“Evidence of lesions disseminated in time and space”
MRI (High signal T2, FLAIR sequence)
LP - oligoclonal bands
Visual/Auditory Evoked potential
Positive Prognostic Factors for MS
“Typical MS patient”
- Young age at onset (20-30s)
- Female
- Relasping-remitting type
- Sensory symptoms only
- Long intervals between relapses/Complete recovery between relapses
How would you manage a patient with MS?
MDT approach - PT/OT/SLT
SYMPTOMATIC RX
- Antispasmodics e.g. baclofen
- Anticholinergics/ISC or LTC if bladder issues
ACUTE RX
- High dose steroids for 5-7 days (e.g. PO pred or IV methylpred
DISEASE-MODIFYING THERAPIES (immunomodulatory)
- Beta-Interferon
- Glatiramer
- Natalizumab
What is Neuromyelitis Optica?
Autoimmune demyelinating disorder
90% relapsing-remitting
Aquaporin 4 +ve antibodies
= Bilateral optic neuritis + myelitis with 2 of the following:
1) Spinal cord lesion > 3 levels
2) Normal MRI brain
3) AQ4 positive serum antibody
Features of Parkinsonism
1) Rigidity
- Unilateral increased tone
- Cogwheeling
- Synkinesia
2) Bradykinesia
- Shuffling gait
- Hypomimia
- Quiet, slow speech
- “Finger tapping” or “Heel tapping”
3) Tremor
- Resting, rotational element
- Usually asymmetrical esp at first
- Synkinesia
Differentials for Parkinsonism
*Idiopathic Parkinson’s Disease
*Vascular Parkinsonism (e.g. Basal Ganglia strokes)
*Drug-Induced Parkinsonism e.g. metoclopramide, haloperidol, and risperidone
*Wilson’s Disease
PARKINSON’S PLUS
*Lewy Body Disease
- Hallucinations
- Faster progression, less responsive to medication
*Supranuclear Palsy
- Falls, reduced vertical gaze, poor response to L-dopa
*MSA Type P
- Autonomic and cerebellar dysfunction
*Corticobasal degeneration
Investigating Parkinsonism Features
MMSE/MOCA
L+S BP
Routine bloods - vascular RFs
Neuroimaging
- CT head
- MRI head (vasculature of basal ganglia)
- DAT scan (looks at levels of presynaptic dopamine)
Assess response to treatment
Medical Management of Parkinson’s Disease
DISEASE MODIFYING MEDICATIONS
- Dopamine replacement = L-dopa + decarboxylase inhibitors = Carbidopa
- Dopamine Receptor Agonists e.g. Ropirinole, Pramipexole, Rotigotine (PATCH!), Apomorphine (LATE) - IMPULSE CONTROL DISORDERS!!!!!!
- COMT inhibitors e.g. Entacapone
- MAO-B inhibitors e.g. selegiline
SYMPTOM CONTROL
- Tremor = Antimuscarinics e.g procyclidine
- Dementia = Rivastigmine
- L-dopa dyskinesias - Amantidine
Management of Parkinson’s Disease
MDT Approach - neurologists, PT, OT, SLT, Nutrition team, psychology
MEDICAL
- Dopamine replacement therapies/agents to help reduce breakdown of dopamine
- Symptom control e.g. tremor
SURGICAL
- Deep Brain Stimulation (indicated if on medication >5x day, nil cognitive imp and suitable surgical candidate)
Types of Tremor
ESSENTIAL
- Postural/on action (kinetic)
- FHx
- Alcohol/beta blockers help
PARKINSONIAN
- Present at rest
- Low frequency, rolling
- Asymmetrical (at first)
- Increased with distraction
DRUG INDUCED
- Fine tremor, usually bilateral
- E.g. salbutamol, tacrolimus, ciclosporin
CEREBELLAR
- Absent at rest, present with movement, getting worse closer towards target = INTENTION
- Low frequency
Differentials for Chorea
Chorea = d2 damage to Basal Ganglia (esp caudate nucleus)
ST VITUS DANCE + Wilson’s
S - Sydenham’s chorea (Rheum fever)
T - Trauma
V - Vascular (stroke)
I - Increased RBC (Polycythaemia)
T - Thyrotoxicosis
U - Uraemia
S - SLE
D - Drugs e.g. L-dopa, antipsychotics. COCP
A - APS
N - Neurodegenerative e.g Huntington’s, Prion disease
C - Chorea Gravidarum
E - Exposure to toxins
LMN Features
Wasting/muscle fasciculations
Reduced tone
Reduced/absent reflexes
Normal or downgoing plantar reflexes
Localisation of LMN
Anterior horn cell –> nerve root –> plexus –> peripheral nerve –> NMJ –> muscle
Differentials of LMN pattern of limb weakness
ANTERIOR HORN CELL
- MND (Nil sensory!!)
- Poliomyelitis
CAUDA EQUINA
- Disc prolapse/abscess/malignancy
LUMBOSACRAL PLEXOPATHY
- Trauma/tumour/abscess
(Usually unilateral)
PERIPHERAL NEUROPATHY
(See separate flashcards)
- Metabolic vs Inflamm vs Infective vs Congenital vs Toxic
NEUROMUSCULAR JUNCTION
- Myasthenia Gravis, LEMS
MYOPATHIES
(See separate flashcards)
Differentials for FLACCID PARAPARESIS
ANTERIOR HORN CELL
- MND (No sensory features!!!!!!!!!!!!)
- Poliomyelitis
CAUDA EQUINA
- Disc prolapse
- Abscess
- Malignancy
(Predominantly MOTOR) PERIPHERAL NEUROPATHY
- Inflam = GBS, CIDP, sarcoid
- Infective = HIV
- Toxic = Lead
- Diabetic amyotrophy
- HSMN
NMJ
- Myasthenia, LEMS
MYOPATHIES
- Polymyositis, dermatomyositis
- Muscular dystrophies
- Myotonia
Presenting FLACCID PARAPARESIS
If acute onset - MRI to exclude spinal cord compression
1) Take a full history - ?back pain/bladder or bowel disturbance/visual problems
2) Perform a PR (anal tone, saddle anaesthesia)
3) Examine upper limbs and cranial nerves in full as well as speech
Investigations for FLACCID PARAPARESIS
BP, L+S BP, ECG
?Spirometry (FVC), ABG
Bloods
- Routine
- Peripheral neuropathy screen (see other flashcards)
- Anti-AChR antibodies
- CK
Neuro imaging
Special Extra Tests (guided by history)
* LP - ?GBS (raised protein)
* EMG/NCS
* Nerve biopsy or Muscle biopsy
* Genetic testing
MND (Anterior Horn Cell Disorder)
Progressive degenerative disease of UMN and LMN
Affects Anterior Horn Cells and Motor Cranial Nuclei
Progressive disease (50% die within 2 years of diagnosis)
Mixture of UMN and LMN signs
- Brisk reflexes, upgoing plantars
- Wasting and fasciculations
NO SENSORY DEFICIT
Average age at diagnosis 65
Most common type Amyotrophic Lateral Sclerosis (ALS)
Investigation and Management of MND
Clinical diagnosis of exclusion - exclude peripheral neuropathy, myopathies
EMG may show active denervation
MDT approach - PT/OT/SLT/nutrition
Riluzole only disease modifying therapy - slows progression by 3 months
NIV - can prolong life by 7 months
Advanced care planning and palliative team involvement
What is Kennedy’s disease?
= rare, X-linked slowly progressive neuromuscular disorder
Trinucleotide CAG repeat expansions in androgen receptor (AR) gene
Typically an adult-onset disease (20 - 50s)
Limb and facial weakness
Fasciculations of the tongue / face (perioral)
Decreased or absent deep tendon reflexes
Dysphagia, Dysarthria
Androgen insensitivity –> gynaecomastia, erectile dysfunction, reduced fertility, testicular atrophy
MANAGEMENT
Symptomatic and supportive
Life expectancy is normal - ~10% die from swallowing complications d2 bulbar weakness.
Poliomyelitis (Anterior Horn Cell Disorder)
Caused by the poliovirus
Mainly affects children under 5 years of age.
1 in 200 infections leads to irreversible paralysis.
Flaccid paralysis - usually of one limb, with wasting
Typically no sensory features
Peripheral Neuropathies
Which peripheral nerves are myelinated?
Motor Nerves = Myelinated
Sensory Nerves = Mixture of myelinated and unmyelinated
Autonomic nerves = Unmyelinated
Peripheral Neuropathies
Demyelinating vs axonal loss
DEMYELINATING LOSS
- Mainly motor fibres first
- NCS = reduced velocity
AXONAL LOSS
- Sensory loss first
- Affects longest nerve fibres first (feet before hands)
- NCS = reduced Amplitude
Peripheral Neuropathies
Causes of predominantly SENSORY peripheral neuropathy
A - Alcohol
B - B12 or B1 deficiency
C - CKD, CTD, Cancer (e.g. myeloma), Chemotherapy agents (e.g. vincristine, cisplatin)
D - Diabetes (NUMBER 1 CAUSE)
- Drugs (amiodarone, isoniazid etc)
E - Endocrine causes (Hypothyroid)
F - Folate deficiency
G - Granulomatous disease e.g. sarcoidosis
H - Hereditary e.g. HSMN
I - Infection (HIV, leprosy)
Peripheral Neuropathies
Causes of predominantly MOTOR peripheral neuropathy
- Acute inflammatory demyelinating polyradiculopathy (GBS)
- Chronic IDP
- Porphyria
- Heavy Metal toxins e.g Lead
- HSMN - Charcot-Marie-Tooth disease
- Diabetes (diabetic amyotrophy)
Investigation of Peripheral Neuropathy
Urine dip - glucose, protein
BM
Bloods
- Routine FBC, U&Es, LFTs
- B12 and folate
- HbA1C, fasting glucose
- TFTs
Nerve Conduction Studies and EMG
- reduced Amplitude = Axonal
EXTRA TESTS (if initial N)
- Electrophoresis & Immunoglobulins
- Vasculitis screen
- HIV/syphilis serology
- LP
- Genetic testing ?HSMN
Hereditary Sensorimotor Neuropathy
Encompasses Charcot-Marie-Tooth disease
HSMN Type 1
- Autosomal Dominant
- Includes CMT 1 = defect in PMP-22 gene (myelin)
- Symptoms start in puberty
- MOTOR features predominate e.g. distal muscle wasting (inverted champagne bottle legs, clawed hands), pes cavus, hammer toes
- Areflexia common
- Sensory loss also common (can have sensory ataxia with positive Rhombergs)
- Bilateral foot drop with high-stepping gait.
Demyelinating = reduced velocity on NCS
Rx = Supportive; MDT approach with PT/OT/orthotics/orthopaedics; Analgesia
Differentials for Pes Cavus
Charcot Marie Tooth disease
Spina bifida
Polio
Friedreich’s ataxia
Syringomyelia
Cerebral palsy
Muscular dystrophy
Hereditary Neuropathy with Liability to Pressure Palsy (HNPP)
Trivial trauma to peripheral nerves = mononeuropathy
Auto Dominant (PMP 22 gene on chromo 17)
20-30 year olds
Reduced velocity on NCS (demyelinating)
Rx = supportive (splints, padding, orthoses)
What is Guillian Barre Syndrome (GBS)?
= acute inflammatory demyelinating polyneuropathy (AIDP)
Onset over days- weeks.
Often preceeded by resp infection or diarrhoeal illness (e.g. campylobacter)
FEATURES
Ascending flaccid limb weakness
Distal paraesthesiae - sensory deficits usually mild/patchy
Areflexia.
Can also affect autonomic system = tachycardiac, labile BP, arrhythmias, bladder/bowel issues
Can also affect cranial nerves: ptosis, opthalmoplegia, facial nerve palsy, bulbar weakness
Becomes chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) if doesn’t cease by 6 weeks.
What is Miller Fischer syndrome?
= form of acute inflammatory demyelinating polyneuropathy (AIDP)
Miller-fischer syndrome is a proximal variant of GBS causing ataxia, opthalmoplegia, areflexia
Anti-GQ1b antibodies!
How would you investigate for and manage Acute Inflammatory Demyelinating Polyneuropathy?
Spirometry
Bedside ECG (risk of arrhythmias)
Bloods
- Routine (FBC, renal function, liver function, inflam markers)
- Antibodies to gangliosides (anti-GM1)
Lumbar Puncture
- Raised CSF protein, normal WCC
Management = mainly supportive, MDT approach
- Refer to ITU if vital capacity <1.3L/bulbar dysfunction. May need tracheostomy
- Give IVIG +/- methylprednisolone, or plasma exchange (liaise with neurology)
- SLT & nutrition team esp if bulbar involvement
Ulnar Nerve Palsy
Ulnar nerve root = C8-T1
Elbow key site for injury/compression
Wasting of dorsal interossei and hypothenar eminance
Clawing of 4th and 5th fingers
MOTOR =
- Small muscles of hand (excluding LOAF) e.g. palmar and dorsal interossei (PAD/DAB) = palmar ADduct, dorsal ABduct
- Flexor carpi ulnaris
- Adductor pollicis
SENSORY =
- Dorsal and palmar surface of hand over 5th and half of 4th finger
FROMENT’S sign = weak adductor pollicis brevis
Median Nerve Palsy
Median nerve root = C6-T1
Wrist (carpal tunnel) key site for injury/compression
Wasting of thenar eminence
MOTOR =
- LOAF muscles of hands = mainly affects thumb movement
- Weak thumb abduction, flexion and opposition
- Wrist and finger flexion
SENSORY =
-Palmar surface of hand from thumb to half of 4th digit
- Dorsal surface of digits 1-4 (not on back of hand)
PHALEN’S test = numbness on upside down prayer sign
TINEL’s test = numbness whilst tapping over flexor retinaculum
Causes of Carpal Tunnel Syndrome
= median nerve compression between flexor retinaculum and carpal bones
Idiopathic
Work-related repetitive strain
MSK
- RA
- Gouty tophi
- OA
- Wrist fractures
Endocrine
- Pregnancy
- Acromegaly
- DM
- Hypothyroidism
CKD
Myeloma
Amyloidosis
Vasculitides
Radial Nerve Palsy
Radial nerve root = C5-T1
Site for injury/compression can occur in axillary, humeral and elbow regions
Wrist drop! Finger drop!
MOTOR =
- Extensors of forearm, wrist and fingers & triceps brachii
- Weak wrist and elbow extension
- Unable to straighten fingers
- Weakness of finger adduction and abduction (can be overcome if hand placed on flat surface)
SENSORY =
- Palmar base of thumb, dorsal surface of radial side of hand (does not innervate any finger sensation)
Differentials for Foot Drop
Charcot-Marie-Tooth Disease
Common Peroneal Nerve palsy
MND
L4/L5 root lesion
Differentials for Foot Drop
Think anterior horn cell—nerve root—plexus—peripheral nerve—NMJ—muscle
Muscle (weak anterior tibialis): any cause of myopathy
Peripheral Nerve:
** Common peroneal nerve palsy (mono/polyneuropathy) eg. trauma to fibular head, surgery on leg, compression of fibula neck, mononeuritis multiplex of any cause, Charcot Marie Tooth disease
** Sciatic nerve palsy eg. trauma
Plexus: Lumbosacral plexopathy
Nerve Root: L5 root lesion eg. prolapsed disc
Anterior horn cell eg. MND (NB: no sensory deficit)
Common Peroneal Nerve Palsy
FEATURES
Weak ankle dorsiflexion
INversion is INtact, EVersion “EVicted”
Ankle reflex intact
If Deep branch only: preserved eversion and sensory loss only in webspace between 1st and 2nd toes and not lateral lower leg or foot dorsum
Sciatic Nerve Palsy
L4 - S3
FEATURES
Weak knee flexion
Weak plantarflexion and dorsiflexion
Weak eversion and inversion
Widespread lower limb sensory loss
L5 Lesion
L5 lesion:
Cannot straight leg raise
Weak inversion and eversion
Weak dorsiflexion
Reduced sensation on sole of foot as well as anterolateral shin and foot dorsum
Ankle jerk preserved
Causes of Mononeuritis Multiplex
Diabetes! (Top cause)
(CALVS)
C - Cancer
A - Amyloidosis
L - Lyme disease/Leprosy
V - vasculitides e.g. EPGA, GW, RhA, SLE
S - Sarcoidosis
Types of Diabetic Neuropathy
1) “Glove and Stocking” Polyneuropathy
- Distal, symmetrical
- Progressive (distal to proximal)
- Axonal loss
2) Autonomic Neuropathy
- Postural hypotension
- Gastroparesis
- Gustatory sweating
3) Diabetic Amyotrophy
- Microvasculitis
- Asymmetrical, proximal weakness
- Hair loss, poor vascular supply
Myasthenia Gravis
Autoimmune disease of Acetylcholine receptors at NMJ (IgG antibodies to AChR in 85%)
Associated with thymomas (15%) and other AI conditions e.g. pernicious anaemia
Muscle fatiguability!
Proximal muscle weakness
Extraocular muscle weakness –> diplopia, ptosis
Reflexes normal but reduce with repeated testing
3 Forms
- Ocular (85%)
- Oropharyngeal
- Generalised
Investigations for Myasthenia Gravis
Spirometry (FVC)
Bloods
- Routine, including TFTs
- CK (exclude myopathy)
- Anti AChR antibodies
Single fibre EMG (jitter)
CT thorax (exclude thymoma)
{Sussman Guidelines}
Management of Myasthenia Gravis
MDT Approach - neuro, PT, OT, SLT, respiratory team
Assess respiratory function
Avoid precipitating medications
Pyridostigmine (inhibits anticholinesterase)
Immunosuppression e.g. steroids (risk of paradoxical reaction in first 2 weeks = inpatient), AZA/MTX
?Thymectomy
What is a Myasthenic Crisis? How would you manage it?
Exacerbation requiring mechanical ventilation (FVC < 1.5L)
Rx = mainly supportive, consider early referral to ICU for ventilatory support
- Remove trigger
- IVIg or Plasma exchange
Drugs which can trigger a Myasthenic Crisis
Gentamicin
Macrolides
Tetracyclines
Quinolones
Procainamide
Beta blockers
Lithium
Phenytoin
Mixed UMN and LMN Signs
Differentials of ABSENT ankle jerk and EXTENSOR plantar reflexes
MND
Subacute combined degeneration of the cord (vit B12)
Friedrich’s Ataxia
Syphilis
Mixed UMN/LMN Signs - Differentials
Most likely = dual pathology e.g. cervical myelopathy (UMN) and peripheral neuropathy (LMN)
MND (nil sensory signs)
Subacute Combined degeneration of the Cord (B12)
Syringomyelia
= cyst in central canal of spinal cord = UMN signs initially
- As expands, starts to damage Anterior Horn Cells = LMN signs
What is Subacute Combined Degeneration of the Cord?
Vitamin B12 deficiency results in damage to:
1) Doral columns (UMN)
- Symmetrical distal sensory neuropathy (legs > arms)
- Loss of light touch, proprio and vibration
2) Lateral corticospinal tract (UMN)
- Muscle weakness and spasycity
- Hyper-reflexia
- Upgoing plantars
3) Spinocerebellar tract (UMN)
- Sensory ataxia
4) Peripheral nerves (LMN)
- Glove and stocking distribution
- Absent ankle reflexes
Rx = B12 supplementation (neuropathy recovers better than myelopathy)
Investigate cause - ?malnutrition ?malabsorption ?pernicious anaemia ?Nitrous oxide abuse
Causes of Syringomyelia
Syringomyelia = fluid filled cyst in central canal of spinal cord
CAUSES/ASSOCIATIONS
- Chiari malformations
- Spinal cord tumour
- Trauma
- Idiopathic
Features of Syringomyelia
Reduced pain and temp sensation in “cape-like distribution”
Light touch/vibration/proprio preserved
LMN signs of upper limbs = wasting and fasciculations
UMN signs of lower limbs = brisk reflexes, upgoing plantars
Bladder and bowel dysfunction
Differentials for Myopathies
Autoimmune
- Dermatomyositis, polymyositis, inclusion body myositis
Connective Tissue Disease
- SLE, Vasculitides, RA, systemic sclerosis
Metabolic
- Mitochondrial disease, glycogen storage disorders (e.g. McArdle’s)
Endocrine
- Thyroid disorders, Cushing’s, Addison’s, Acromegaly, Diabetes
Dystrophies
- Myotonic Dystrophy, Duchenne’s, Becker’s , FSHD
Drugs
- Alcohol, heroin, statins, steroids, amiodarone
Investigations for Myopathies
Urine dip & PCR (dip for blood could be myoglobin)
Bloods
- Routine
- CK, AST, ALT, LDH
- TFTs, HbA1c, cortisol
- Rheum screen including ACE
- Immunoglobulins
- Myositis antibodies
NCS and EMG
?MRI muscle
Muscle biopsy
Systemic screen = ECG, PFTs, CXR, echocardiogram
Malignancy screen (if dermato/polymyositis) = FOB, mammogram, tumour markers, CT, endoscopy
What are Duchenne’s and Becker’s muscular dystrophy?
Inherited degenerative condition of muscle
X-linked, mutations on dystrophin gene on X chromosome
Typically occurs in childhood (can have later onset in Becker’s)
Progressive proximal muscle weakness
Calf pseudohypertrophy
Risk of cardiomyopathy (less in Becker’s)
Raised CK, deranged transaminases
Muscle biopsy
Genetic testing
What is Facioscapulohumeral dystrophy?
Inherited degenerative myopathy
Autosomal dominant
Slowly progressive disease of facial muscles and shoulder girdle
FEATURES
- Facial weakness –> difficulty closing eyes, asymmetric smile, can’t whistle, dysarthria
- Difficulty raising arms above head
- Winging scapulae
- Triceps more wasted than biceps (deltoid spared)
- Waddling gait (pelvic girdle involvement)
- Preserved IQ
- Lung/cardiac involvement rare
What are the genetics of Myotonic Dystrophy?
Autosomal dominant (trinucl rep disorder)
- >50 repeats = full penetrance
Most common mutation = DMPK gene on chromosome 19
Genetic anticipation
What is Myotonic Dystrophy?
Most common adult muscular dystrophy
FEATURES
- Myotonia = failure of relaxation of voluntary contraction
- Frontal balding
- Partial ptosis
- Facial muscle wasting “Hatchet facies”
- Distal muscle weakness
- Dysarthria
- Dysphagia
Usually wheelchair dependent within 15-20 years of onset
NORMAL CK (in comparison to Duchenne’s & Beckers)
Name some associated conditions of Myotonic Dystrophy
Diabetes mellitus
Testicular atrophy
Cardiomyopathy
Conduction disorders
Cholecystitis and biliary spasm
Constipation
Slow gastric emptying
Hypersomnolence (?cause)
Name 2 types of inherited neurocutaneous disorders? What is their mode of inheritance?
Neurofibromatosis & Tuberous Sclerosis
Both Autosomal dominant!
Features of Neurofibromatosis 1
Autosomal dominant (chromosome 17)
Cafe au Lait spots (>6)
Peripheral neurofibromas (>2)
Iris hamartomas (>2)
Axillary/groin freckles
Scoliosis
Phaeochromocytomas
Features of Neurofibromatosis 2
Autosomal dominant (Chromosome 22)
Bilateral acoustic neuromas/vestibular schwannomas
Multiple intracranial tumours e.g. schwannomas, meningiomas
Tuberous Sclerosis
Majority autosomal dominant (TsC2 gene on chromosome 16 = most severe form)
CUTANEOUS FEATURES
Ash-leaf spots (fluoresce under UV)
Shagreen patches (rough patches over spine)
Angiofibromas (butterfly over nose)
Subungual fibromata
NEURO FEATURES
Developmental delay
Lower IQ
Epilepsy
ASSOCIATED FEATURES
Retinal hamartomas
Cardiac rhabdomyomas
Polycystic kidney disease
Lung cysts
Differentials for Ataxic Syndromes
V - Stroke, ICH
I - Multisystem Atrophy C
T - Traumatic brain injury, Alcohol, Carbamazepine, phenytoin
A - MS, Miller-Fisher Syndrome
M - B12 deficiency, Copper deficiency
I - Spinocerebellar Ataxia, Friedrich’s Ataxia, Ataxia Telangiectasia, VHL
N - Cerebellar space occupying lesion, paraneoplastic (small cell lung cancer, breast, gynae, testicular)
Outline cerebellar signs
D - Dysdiadochokinesis
A - Ataxic (gait, limb or truncal)
N - Nystagmus (gaze-evoked)
I - Intention tremor
S - Slurred or staccato speech
(dysarthria)
H - Hypotonia
Also - Rebound phenomenon!
Name 3 inherited ataxia syndromes?
What is their mode of inheritance?
Spinocerebellar Ataxias - group of conditions, autosomal dominant trinucleotide repeats
Ataxic telangiectasia - autosomal recessive
Friedrich’s Ataxia - autosomal recessive
Friedrich’s
Autosomal recessive disorder (trinucleotide repeat, FRATAXIN gene on chromosome 9)
Most common hereditary ataxia in UK
Combination of spinocerebellar signs, corticospinal tract signs and dorsal column loss
FEATURES
Onset in adolescence
Gait ataxia
Kyphoscoliosis
Mix of UMN and LMN - absent ankle reflexes, upgoing plantars
Spasticity
Loss of proprioceptive and vibration sensation
ASSOCIATED FEATURES
HOCM (90%, common cause of death)
Diabetes
High arched palate
High arched feet
Preserved IQ
{Vitamin E deficiency = rare mimic!}
Ataxia Telangiectasia
Autosomal recessive disorder (ATM gene)
Inherited Combined Immunodeficiency disorder - 10% risk of development malignancy (esp Leukaemias, lymphoma)
FEATURES
Typically presents in childhood as abnormal movements
Cerebellar ataxia
Skin & eye telangiectasia
Recurrent LRTIs (due to IgA deficiency)
Dystonia
Chorea
Spinocerebellar Ataxia
Group of autosomal dominant disorders - majority trinucleotide repeats
FEATURES
Usually develops in 30-40s
Progressive cerebellar signs
UMN and extrapyramidal signs
Peripheral neuropathy
Ophthalmoplegia
