Pastest - Neuro Flashcards
What are the causes of anosmia/ reduced olfaction?
-Upper respiratory tract infection
-Smoking
-Nasal polyps
-Older Age
-Tumours: ethmoid sinus, meningioma of the olfactory groove, frontal lobe tumours
-Trauma: basal or frontal skull fracture
-Congenital: Kallman syndrome
-Degenerative: Parkinson’s and alzheimers dementia
What are the sites of lesions causing reduced visual acuity?
Cornea: chlamydia trachomatis
Aqueous humour, eg aberrant drainage in glaucoma
Lens, eg cataract
Vitreous, eg preretinal haemorrhage
Retina, eg retinitis pigmentosa or macular degeneration
Optic nerve, eg optic neuritis
Intracerebral eg tumour or stroke
What are the causes of a small pupil?
Horner’s syndrome: includes meiosis, ptosis, anhidrosis and enophthalmos
Argyll-Robertson pupil: a small irregular pupil which accommodates but does not react to light
What are the causes of a large pupil?
Third nerve palsy: pupil fixed and dilated, eye in down and out position and ptosis
Holmes-Adie pupil: the pupil is large and irregular and accommodates but reacts only slowly to light
-This is a tonic pupil because, once constricted, it is slow to dilate. If associated with absent deep tendon reflexes, it is known as Holmes-Adie syndrome. This is a normal variant.
What 3 rules can you use to further locate the issue in a gaze palsy?
Ask the patient to report if he or she sees double at any point. If the patient does see double there are 3 rules:
- If the images are side by side, only the lateral or medial recti can be responsible
- Separation of the two images is greatest in the direction of movement of the affected muscle (or direction in which it has the purest action)
- Using the cover test, the eye that gives the outer or most peripheral image is the affected eye.
If the ophthalmoplegia is complex, then always consider Graves’ disease or myasthenia gravis. Look for fatiguability in eye movements particularly in upwards gaze.
What will a left sided INO give you?
A left sided INO from a lesion affecting the left medial longitudinal fasciculus will give failure of left eye adduction on gaze to the right, but intact adduction with accommodation. All other eye movements will be normal.
What are the types of gait?
Parkinsonism
Hemiparetic
Ataxic
Paraparetic
Spastic
Choreoathetoid
High stepping
Waddling
Shuffling (march a petit pas)
What neurological conditions cause a leg length discrepancy?
Old polio and infantile hemiplegia may cause shortening of one limb.
What are the causes of pes cavus?
Unilateral: poliomyelitis, spinal cord tumour, spinal trauma
Bilateral: idiopathic (20%), cerebral palsy, CMT/HMSN, Friedreich’s ataxia, muscular dystrophies, syringomyelia
What is pes cavus and how does it arise?
Describes a high arches foot with fixed plantar flexion that does not flatten on weight bearing.
It is thought to arise from imbalance between the stronger plantar flexors, posterior tibialis and peroneus longus, and the weaker dorsiflexor, anterior tibialis.
What are the differentials for MS patients?
Neuromyelitis optics (Devic’s disease):
-Presents acutely with optic neuritis and spinal cord myelitis with spastic paraparesis/ tetraparesis.
-It is very rare to get brainstem or cerebellar involvement
Myelopathy from cervical spondylosis
-Signs and symptoms are all below the neck. -Gradual onset not separated by time and space
B12 deficiency with subacute combined degeneration of the cord
-Tend to be more symmetrical than MS.
-Low B12, high methylmalonic acid and homocyteine without MS MRI findings would differentiate
Ischaemic stroke
Peripheral neuropathy
Guillian-Barre syndrome
-Progressive bilateral flaccid paralysis and hypo-/areflexia with distal sensory symptoms (sensory symptoms are unusual in MS)
Amyotrophic lateral sclerosis
-There will be UMN and LMN signs in the same muscle groups with no sensory signs or visual changes.
What is the pathogenesis of neuromyelitis optica?
Antibody mediated autoimmune pathology, with IgG antibodies (NMO antibodies) against the aquaporin-4 water channel in astrocytes surrounding the blood brain barrier.
It is not known how this leads to the demylination process that follows.
What is the differential diagnosis of optic neuritis?
Ischaemic optic neuropathy
-Hyperacute onset with no other cranial nerve or peripheral signs
Rhinogenous optic neuritis:
-Extension of disease from sinuses causes exophthalmos, ophthalmoplegia and optic neuritis
-Often there are surprisingly few rhinological symptoms
Lyme borreliosis optic neuropathy
-Has associated signs of arthritis, lymphadenopathy, constitutional upset and pathognomonic erythema migrans rash
HIV-associated optic neuropathy
-This is bilateral and tends to present late in disease so there will be other manifestations of HIV
Syphilis
-Can present with a unilateral optic neuritis often with other neurological manifestations, lymphadenopathy and a maculopapular rash of the torso or palms and soles
What is the differential diagnosis of INO or lateral gaze palsy?
The two most common causes are MS and stroke
Others include: trauma, herniation, infection (including HIV, meningitis and cystercosis), tumours (including pontine gliomas and metastases), aneurysms, vasculitides and systemic lupus erythematosus (SLE).
What are the categories of MS
Relapsing remitting (80-85%)
Secondary progressive (50% of relapse remitting become secondary progressive)
Primary progressive (15-20%)
-Tend to occur in older age patients and the F:M ratio is even unlike in relapse remitting where F>M
Relapsing progressive (5%)
-Progressive disease with occassional marked deteriorations
What are the investigations for MS?
MRI T2 imaging
-Other diagnostic tests are used only when MRI is contraindicated
Visual evoked potentials reveal asymmetrical and prolonged conduction
Lumbar puncture with CSF analysis
-Will show IgG oligocolonal bands in greater concentrations than the serum, in 80% of those with MS
-CNS analysis is needed only if there is suspicion of CNS infection
Blood tests
-FBC, biochem, TFTs and B12 should all be normal
Anti-NMO antibodies can be requested if Devic’s disease is suspected
What are the physical signs of parkinson’s disease?
Mask like facies
Advanced disease may have drooling (sialorrhoea)
Asymmetrical pill rolling tremor of 4-6Hz
-ask patient to tap knee and count back from 20
Patient may freeze on walking, stooped posture, narrow based festinant gait, little arm swing
Postural instability with propulsion (tendency to fall forward) and retropulsion (falling backward)
Quiet, monotonous speech
Lead pipe rigidity and cogwheel rigidity
Micrographia
What features should you try to ellicit to determine between Parkinson’s disease and parkinson’s plus syndromes?
Ask to measure a lying standing blood pressure (autonomic dysfunction)
Fully assess eye movements for any supranuclear gaze palsy
Examine for pyramidal tract or cerebellar signs
Ask to assess cognition with simple screening tool
Request a drug history to rule out parkinsonism secondary to medications (although this would commonly give rise to symmetrical symptoms)
What are the differentials for a rest tremor?
Parkinson’s disease
Parkinsonian disorders
Severe essential tremor
Wilson’s disease
What are the differentials for a postural tremor?
Essential tremor
Physiological tremor
What are the differentials for an action tremor (includes intention tremor)?
Essential tremor
Cerebellar disease
Midbrain stroke/ trauma
MS
What are the differential diagnoses of parkinsonism?
Parkinson’s disease (most common cause)
Drug induced (second most common cause)
Cerebral anoxia
-bilateral basal ganglia infarction (eg after cardiac arrest
Normal pressure hydrocephalus
Infections
-Post encephalitis, AIDS and prior disease
Toxicity
-MPTP (narcotic street impurity), carbon monoxide, manganese, Paraquat and mercury poisoning
Parkinson-plus syndromes
-Dealt with elsewhere
What are the parkinson-plus syndromes?
Progressive supranuclear palsy (Steele-Richardson-Olzewski syndrome)
Multiple system atrophy
-MSA-A, formerly Shy-Drager syndrome
-MSA-P striatonigral degeneration
-MSA-C olivopontocerebellar atrophy
Corticobasal ganglionic degeneration
Diffuse lewy body disease
What is the investigation of parkinson’s disease?
No specific tests. Clinical and improvement on treatment confirms diagnosis
MRI brain with or without contrast if atypical features such as rapid onset, early dementia, symmetrical features, UMN signs or additional signs of a vascular aetiology
Functional neuroimaging with SPECT not used routinely but can be helpful in distinguishing cerebrovascular disease, essential tremor and psychogenic causes
Formal psychometric testing is indicated if any symptoms of cognitive impairment are present.
What is the management of Parkinson’s disease?
OT, PT, SALT and dietician services
National support groups
Inform DVLA and insurance at diagnosis
Dopamine agonists
-Pramipexole, ropinirole, cabergoline
-Can be used in younger patients who are more susceptible to dyskinesias
-SEs include nausea, constipation, hypotension, drowsiness, confusion and hallucinations
MAO-B inhibitors (rasagiline)
-Can be used as monotherapy early in disease (not selegiline)
-SEs constipation, depression and hallucinations
Levodopa
-preferred in older adults who are more likely to have orthostasis or hallucinations with dopamine agonists
-SEs N+V, arrhythmias, postural hypotension, depression, insomnia, psychosis, cognitive impairment
Anticholinergics (benzhexol, benzatropine, pro-cyclidine)
-Can be used in refractory tremor but can worsen cognitive function
COMT inhibitors
-Avoid in hepatic impairment or ischaemic heart disease
-SEs confusion, dizziness, insomnia, hallucinations, dyskesias
Apomorphine (injectable form of dopamine)
-Can be useful in mornings for freezing or dysphagia in advanced PD or when oral cannot be taken
Amantadine
-Improves dyskinesias associated with increasing levodopa
-SEs GI upset, mood changes, postural instability, confusion, hallucinations
DBS
Non-motor symptoms
-Nausea from drugs (domperidone), constipation, dementia, Depression
Palliative care
What are the physical signs of motor neurone disease?
General appearance
-Wheelchair, walking aids or foot supports for foot drop
-Wasting and contractures are characteristics of severe disease
-FASCICULATIONS
Cranial nerve examination
-Wasting of temporalis and masseters may be present
-Oculomotor muscles are spared!
-Bulbar palsy (LMN IX, X, XI, XII)
-Slurred, quiet, nasal speech
-Pseudobulbar palsy
Upper and lower limbs
-LMN signs and UMN signs
-No sensory signs
Mention you would like to assess
-Respiratory function with examination and FVC both standing and supine
-Formal SALT and swallow assessment
-MMSE
What are the features of bulbar palsy on examination (LMN)?
Weakness of the muscles of mastication
Absent jaw reflex
Upper and lower facial muscle weakness
Palatal weakness
Reduced gag reflex
Flaccid and wasted tongue with fasciculation
Weak sternocleidomastoid and trapezius
What are the features of a pseudobulbar palsy (UMN)?
Emotional lability, with spontaneous laughing or crying
Pronounced gag reflex
Small stiff tongue that is difficult to protrude and has slowed rotational or sideways movements
Brisk jaw reflex
Speech is slow, thick and indistinct, and due to the tongue moving little (sometimes described as ‘hot potato speech’
What are the types of MND?
Amyotrophic lateral sclerosis (most common)
-UMN and LMN signs
Primary lateral sclerosis
-Initially UMN signs but eventually progresses to include LMN
Progressive muscular atrophy
-Initially LLMN but progresses to UMN
Progressive bulbar palsy
-LMN (bulbar) or IMN (pseudobulbar) signs involving bulbar muscles
What are the MND mimic disorders that should be included in differentials?
Cervical spondylosis with myelopathy and radiculopathy
-UMN and LMN (only UMN below lesion)
-No bulbar, cranial nerve involvement
-Usually sensory signs and symptoms of pain
Dual pathology (e.g. cervical myelopathy with peripheral neuropathy)
Syringomyelia/ syringobulbia
-At level of lesion UMN and dissociated sensory loss
-Below level LMN signs
-Dissociated sensory loss results from decussating spinothalamic pathways (loss of temp and pain) but preserve dorsal columns (normal pressure, proprioception and vibration)
Multifocal motor neuropathy with conduction block
Benign cramp fasciculation syndrome
-This presents only with cramps and fasciculations, usually of large limb muscles, made worse after exercise or sleep deprivation.
-There are no other LMN or any UMN signs and no disease progression
Inclusion body myositis
Monomelic amyotrophy (benign focal amyotrophy)
Chronic inflammatory demyelinating polyneuropathy (CIDP)
Spinal muscular atrophy
Myasthenia gravis
Post poliomyelitis syndrome.
What is multifocal motor neuropathy with conduction block?
Rare disease usually presenting in young or middle aged men and its onset and progression are slower than that of MND.
It is an acquired autoimmune demyelinating disease that is progressive and gives rise to LMN signs, such as weakness, wasting anf fasciculations, with little or no sensory involvement.
Clinically it can be difficult to distinguish from MND in the initial stages, except that there are until much later.
Nerve conduction studies can show multiple sites of conduction block and CSF analysis might be positive for anti-GM1 ganglioside antibody. The patients condition may improve with IVIG.
What is inclusion body myositis?
Inflammatory myopathy that presents with slowly progressive weakness and wasting in distal and proximal muscle groups in the limbs without sensory symptoms .
There are no UMN signs.
It tends to affect older age groups
Diagnosis is by electromyography and muscle biopsy.
It tends to have a more benign course than MND.
What is monomelic amyotrophy )benign focal amyotrophy)?
This is a focal LMN disease characterised by weakness and wasting of a single limb, usually a hand or arm rather than foot or leg. There will be no UMN or sensory signs.
Typically it affects young Asiatic males (aged 15-25 years), most commonly in India or Japan. It plateaus after 2-5 years with no improvement or progression.
There is no treatment beyond physiotherapy
What is the management of MND?
Riluzole (only DMARD)
-Prolongs life by 3-4 months and should be offered to all patients at diagnosis
PT, dietician, respiratory therapist, SALT, OT, social work and primary care team
Respiratory
-PT, suction, NIV
Pharyngeal and GI
-Dietician, PEG feeding, anticholinergics
MSK
-PT and OT, baclofen, quinine for cramps
Psychological:
-CBT, SSRI
What is the prognosis of MND?
MND progresses without relapses, remission or any stabilisation. The clinical time course varies with a median life expectancy of 3-5 years. Of patients 10% may survive >10 years
Good prognostic indicators include: younger age at onset, onset of disease in limbs and FVC >75% at baseline
Poor prognostic factors include older age at onset, bulbar symptoms at onset, co-morbidity, frontotemporal dementia and FVC <75% at baseline.
What specific sign should you always remember to check in suspected pyramidal weakness?
Pronator drift
What are the differential diagnoses in a hemiparesis?
TIA
Demyelinating conditions such as MS
Space occupying lesions
Post-ictal hemiparesis
-Commonly 1 limb rather than 1 side
-Can be gaze palsy towards hemiparesis rather than stroke which is usually away from side of paresis
Complex migraine
Somatisation/ conversion disorders
What are the cardinal signs of a spastic paraparesis?
Pyramidal pattern of weakness in the lower limbs and a sensory level representing spinal cord pathology.
Full diagnosis involves examination of the cranial nerves and upper limbs to help describe the pattern and level of pathology
(the instruction is usually to examine gait and/or lower limbs)
What are the differentials for a spastic paraparesis?
Can be broadly divided into compressive and non-compressive. Further dichotomy can include whether onset was (sub-)acute or chronic. (patients with compressive lesions will mostly be spared signs above the level of the lesion.
Compressive disease:
-Trauma, Tumours, TB or other abscesses
Non-compressive disease
-MS, MND, Parasagittal tumour (meningiomas),
-Hereditary spastic paraparesis (Strumpell-Lorrain syndrome)
-Friedreich’s ataxia
-Syringomyelia
-Transverse myelitis
-Vascular (spinal stroke)
-Subacute combined degeneration of the cord
What is hereditary spastic paraparesis?
Usually dominantly inherited (X-linked and recessive forms also exist), and leadds to progressive stiffness and UMN weakness of the lower limbs from axonal degeneration.
It can be associated with other neurological features such as cerebellar signs, peripheral neuropathy, epilepsy and cognitive changes.
It may be associated with cataracts and optic neuropathy.
Diagnosis is usually from typical presentation with a family history and after genetic testing.
There are no sensory signs and upper limbs tend not to be involved
What are the causes of transverse myelitis?
MS (most common), SLE, sarcoid, paraneoplastic syndromes, antecedent viral infection including HSV, VZV, HIV, HTLV-1 (tropical spastic paraparesis), CMV and EBV, or antecedent bacterial infection including syphilis and lyme borreliosis
What are the investigations for a spastic paraparesis?
Acute onset must focus on ruling out remediable spinal cord compression as sphincter dysfunction is irreversible if present for >24hrs.
Acute: FBC, ESR, chest radiograph, MRI spine
non-acute
-Blood tests: ESR/CRP, autoantibody screening, B12 and folate
-Infection screen: serological testing for HIV, HTLV-1 and syphilis; blood culture, sputum culture, early morning urine
-Lumbar puncture with CSF analysis: oligoclonal bands, bacterial culture, ACE and cell count
-MRI of CNS
-Biopsy of identified cord masses
-EMG and NCS
What are the physical signs of cervical myelopathy?
Mixture of LMN and UMN signs in upper limbs most commonly C5-7 where spinal canal is narrowest
Midcervical reflex pattern
Inverted reflexes
-contraction of triceps with bicep reflex testing and finger flexion with supinator testing
sensory loss in dermatomal pattern
Pseudoathetosis
-damage to the cervical dorsal columns causes loss of proprioception, so with eyes closed and arms held out the fingers writhe unconsciously
Hoffman’s reflex
Myelopathy hand sign
What is a midcervical reflex pattern
Describes the loss of biceps and supinator reflexes (C5-C6) and a brisk triceps reflex (C7) and is almost pathognomonic of a cord lesion due to pathology at C5-C6. e.g. cervical myelopathy
What is myelopathy hand sign?
Has two components
-Finger escape sign: with the patient holding the forearms out and hands pronated, the little finger can be seen to abduct (‘escape’) and there may be difficulty with full finger extension. This phenomenon can spread to the ring and middle fingers with more severe cervical lesions. The little finger can abduct and flex normally, differentiating this from an ulnar nerve lesion
-Grip and release testing; the patient remains in the same position as above and is asked to grip and then fully extend the hand and fingers as fast as possible for 10 seconds. There is a slowed response with difficulty in fully extending fingers on release with fewer than the 20 repetitions seen in healthy individuals.
What is the differential diagnosis of cervical myelopathy?
MND
MS
Friedreich’s ataxia
Syringomyelia
Subacute combined degeneration of the cord
Transverse myelitis
What are the features of syringomyelia/ syringobulbia?
Characterised by LMN signs in the upper limbs (and more rarely bulbar muscles) with dissociated sensory loss affecting pain and temperature, but preserving vibration, proprioception and light touch in the upper limbs. This is occasionally associated with autonomic signs including Horner’s syndrome and/or long-tract signs in the lower limbs with UMN weakness.
Cranial nerve nuclei IX-XII (syringobulbia) gives signs of palatal weakness, reduced gag reflex, and a hoarse and nasal voice with weak, wasted and fasiculating tongue. Bilateral weakness of sternocleidomastoid and trapezius also observed
Balaclava/ Onion skin sensory loss in face which slowly progresses inwards
Nystagmus. INO. Horner’s syndrome
What is the differential diagnosis in syringomyelia?
CSF blockage (most common >50%)
-Arnold-Chiari malformation, other hindbrain malformations, spina bifida, tumours near foramen magnum, scarring of meninges or meningeal carcinomatosis
Spinal cord injury
-traumatic, haemorrhage, infection, infarction
Intramedullary tumours
-Most commonly associated are ependymomas and haemangioblastomas
Idiopathic
Other differentials:
-CIDP
-Peripheral neuropathy
-Amyotrophic lateral sclerosis (MND)
-MS
-Cervical spondylosis
-Anterior spinal artery syndrome
What are the physical signs of myotonic dystrophy?
General appearance
-Myopathic facies (long, thin face and neck)
-Bilateral ptosis and cataracts
-Frontal balding
-Myotonia on shaking patients hand
Gait
-Bilateral foot drop with high steppage gait
-As disease progresses waddling gait
-Romberg’s negative
Upper and lower limb examination
-Tone is normal
-Symmetrical distal wasting and weakness (advances proximally)
-Wasting of the small muscles of the hands
-Myotonia
-Deep tendon reflexes will be reduced
-Coordination will be normal
-No sensory impairment
Cranial nerve examination
-Patient may have difficulty opening eyes after tight closure
-Red reflex will demonstrate cataracts
-Nasal quality to speech
Additional
-To end exam state you would like to test blood glucose, perform cardiovascular examination (arrhythmia/ pacemaker), thyroid nodules, genital exam (testicular atrophy), MMSE
How do you formally test for myotonia?
Can be demonstrated by tapping on the thenar eminence, which will cause dimpling and adduction of the thumb with slow relaxation.
Alternatively you could ask the patient to grip you hand tightly for 5 seconds and let go quickly, and there will be delayed release.
On repeating the hand-grip exercise several times the myotonia phenomenon can reduce, described as the ‘warm up’ effect (contrast this with the fatigability seen in myasthenia gravis). The phenomenon of myotonia can disappear with disease progression as muscle weakness increases.
What is the differential diagnosis of myotonia?
Myotonia congenita
Paramyotonia (PM/Eulenberg’s disease)
Hyperkalaemic periodic paralysis (HPP)
Mild tetanus
Stiff person syndrome
What is myotonia congenita?
This is a chloride ion channelopathy affecting skeletal muscle. Thomsen’s disease (autosomal dominant) presents in the first few years of life with non-progressive muscle stiffness and hypertrophy.
Becker’s disease (autosomal recessive) presents a bit later but with more severe stiffness.
What is paramyotonia (PM/Eulenberg’s disease)?
Sodium channelopathy (autosomal dominant). This presents in the first decade of life with paradoxical myotonia that is worse after exercise and triggered by cold.
What is hyperkalaemic periodic paralysis (HPP)?
Sodium channelopathy (autosomal dominant) affecting the same sodium channel gene (SCN4A) as PM, but thought to be clinically distinct.
It is characterised by transient but frequent episodes of paralysis starting in infancy, associated with raised serum potassium and triggered by fasting or rest after exercise.
How does mild tetanus cause myotonia?
Caused by neurotoxin from Gram-positive Clostridium tetani. Local or mild tetanus can occur in the area local to the initial injury causing spasms and stiffness, although severe generalised tetanus is the most common presentation.
What is Stiff person syndrome?
Rare syndrome of unknoen cause associated with autoimmune anti-GAD (anti-glutamic acid decarboxylase) antibodies and diabetes.
The syndrome can occur at any age and in both sexes. It starts as axial muscle spasms and progresses to generalised proximal stiffness that can cause skeletal fracture and muscle rupture.
It is either self limiting or progressive.
What is the differential diagnosis for symmetrical LMN muscle weakness?
Distal spinal muscular atrophy
-Variant of SMA, presenting similarly to Charcot-Marie Tooth disease
Peripheral neuropathies
-Tend to cause wasting, and include sensory signs, reduced reflexes and distal-proximal progression
Neuromuscular junction pathology
-Manifests as diffuse weakness in the absence of wasting, sensory signs or abnormal reflexes. There is fatigability, and ocular, bulbar and respiratory muscles are involved. Diseases include myasthenia gravis and Lambert-Eaton myasthenic syndrome.
Myopathies
-Manifest as wasting with no sensory signs, normal or reduced reflexes and no fatigability. The myotonic phenomenon may occur in a proximal pattern.
What are the types of myopathies?
Myopathies can be inherited or acquired.
Inherited:
-Muscular dystrophies
–Duchene, becker, scapuloperoneal (Emery-Dreifuss), distal, facioscapulohumeral, limb girdle, oculopharyngeal
-Congenital myopathy
–Nemaline, myotubular, central core and hyaline body myopathy
-Mitochondrial myopathies
–Kearns-Sayre syndrome
-Metabolic myopathies
–Glycogen storage diseases (e.g. McArdle’s disease), Lipid storage disease and disorders or purine nucleotide metabolism.
Acquired
-Drug induced
–Corticosteroids, fibrates, statins, colchicine, D-penicillamine, zidovudine, B-blockers, ciclosporin
-Toxins: alcohol, organophosphates, snake venom
-Endocrine
–Diabetes, hypo-/hyperthyroidism, Cushing syndrome, hypo-hyperparathyroidism, pituitary disfunction
-Inflammatory
–Polymyositis, dermatomyositis, inclusion body myositis
What is the investigation of MND?
Focus on confirming diagnosis, classifying type and identifying multisystem involvement
Genetic testing
Other tests
-Blood testes: GGT and CK raised, IgG, FSH (raised), testosterone (low/normal), fasting glucose, HbA1c
-EMG: myotonic discharges
-ECG: conduction defects or arrhythmias
-ECHO: cardiomyopathy
-Genetic testing
-Muscle biopsy: infrequently used in diagnosis now
What are the types of myotonic dystrophy?
-MD Type 1: autosomal dominant mutation DMPK (dystrophia myotonica protein kinase) chromosome 19. CTG repeat above upper limit 35
–Congenital MD >2000 repeats, presents at birth, life expectancy 30-40 years
–Classic MD 100-1500 repeats; presents 10-30 years, life expectancy 45-55
–Mild MD: 50-150 repeats; presents age 20-70 years. Normal life span
MD Type 2 (proximal myotonic myopathy (PROMM):
-Also autosomal dominant. Trinucleotide CCTG, in ZNF9 (zinc finger protein 9) gene on chromosome 2
-Shares much of the clinical features but less distal limb, facial and bulbar weakness, no cognitive impairment and does not have a severe congenital form.
What is the management of Myotonic dystrophy?
No cure
Patient support groups
Muscle weakness: Physiotherapy, splints, orthoses
Myotonia: procainamide or phenytoin
SALT: communication or swallow
GI symptoms: metoclopramide
Cataracts: ophthalmology
Cardiology: ECG monitoring and pacemaker
Avoid: statins (myopathy), opiates (resp drive), anaesthesia (malignant hyperthermia)
What are the physical signs of myasthenia gravis?
General appearance:
-Expressionless face
-Asymmetrical ptosis
Gait:
-Proximal muscle weakness
Upper and lower limb examination
-Normal muscle bulk and tone
-Proximal muscle weakness (upper > lower limbs)
-Fatiguability (test by assessing power before and after performed repeated shoulder abduction)
Cranial nerve examination
-Bilateral facial weakness
-Asymmetrical ptosis
-Weak jaw opening/closing against resistance
-Complex opthalmoplegia
-Diplopia on lateral gaze (pupils normal)
-Fatiguability demonstrated by sustained upward gaze (eyes will eventually begin to close)
-Pseudo INO due to weakness medial rectus
-Weakness bulbar muscles
Additional features. Tell examiner you would like to look for:
-Thymectomy scar (sternotomy)
-Autoimmune disease: diabetes, RA, thyroid dysfunction, SLE
-Evidence of steroid use
-FVC for resp compromise
-Drug history
What is the differential diagnosis of myasthenia gravis?
Lambert-Eaton myasthenic syndrome
Primary Myopathies
Miller-Fisher syndrome
Thyroid disease
Multiple sclerosis
Amyotrophic lateral sclerosis
Drug induced myasthenia-like syndrome
What agents cause drug induced myasthenia-like syndrome?
D-penicillamine
Interferon alpha
Antibiotics: aminoglycosides, fluoroquinolones, macrolides, penicillins and sulfonamides
B-blockers: propranolol, atenolol, timolol
CCB: verapamil
Anticonvulsants: phenytoin, carbamazepine, benzodiazepines
Psychiatric drugs: lithium, phenothiazines
Anaesthetic agents: propanediol ether, methoxyflurane, lidocaine, procainamide, vecuronium
Snake venom toxins
Botulinum toxin
What are the investigations for myasthenia gravis?
Serology:
-80-90% nAChR autoantibodies
-3-7% MuSK antibodies
Other:
-Tensilon test (IV edrophonium and see if improvement)
-Ice pack test (if tensilon contraindicated, place on eye and see if improvement)
-Electrophysiology: repetitive nerve stimulation and single fibre EMG
-CT chest thymoma
What is the treatment for myasthenia gravis?
Cholinesterase inhibitors:
-Pyridostigmine (SEs include bradycardia, hypotension, bronchoconstriction, salivation, increased resp secretions, lacrimation, etc etc)
Immunosuppressants (corticosteroids):
-Used in moderate disease not responsive to cholinesterase inhibitors alone
-Start low and go slow until symptoms improved (high dose can cause myasthenic crisis)
-Steroid sparing agents: azathioprine, mycophenolate, ciclosporin, tacrolimus
Plasmaphoresis and IVIG
-Used in crisis
Thymectomy
-Only absolute indication is presence of thymoma but all myasthenia gravis patients aged <55 usually treated with thymectomy, regardless of thymoma disease
-Less evidence for >55 and decisions on case to case basis.
What are types of muscular dystrophy?
Comprise a group of progressive, non-inflammatory muscle diseases characterised by ongoing degeneration and aberrant regeneration of damaged muscle tissue:
-Facioscapulohumeral dystrophy
-Duchene muscular dystrophy
-Becker muscular dystrophy
-Oculopharyngodistal myopathy
What are the physical signs of facioscapulohumeral dystrophy?
General appearance:
-Myopathic facies (thin and long)
-NO frontotemporal balding or cataracts
Gait:
-Exaggerated lumbar lordosis
-Myopathic/waddling gait
-Foot slapping/drag/circumduction if there is foot droop
Upper and lower limb examination:
-Tone will be normal
-Weakness of the shoulder girdle muscles causing winging scapulae
-Weakness in proximal muscle groups but deltoid may be spared
-Lower limbs may show no abnormality, or minor wasting of anterior tibialis with weak ankle dorsiflexion and foot drop
-Deep tendon reflexes may be reduced or absent
-Plantars normal
-Coordination normal within confines of reduced power
-Sensation normal
Cranial nerves:
-No ptosis of ophthalmoplegia (contrast with myotonic dystrophy or myasthenia which look similar in face)
-Facial muscle weakness
-Hearing aids (associated sensorineural deafness)
-Fundoscopy: retinal telangiectasias
Additional:
-Look for pulse, pacemaker insertion and cardiovascular exam for dilated cardiomyopathy
What is the differential diagnosis for fascioscapulohumeral muscular dystrophy?
DMD and BMD
-Patients tend to be younger and symptoms more severe. Calf hypertrophy. No facial weakness
Limb girdle muscular dystrophy
-Similar to DMD or BMD with cardiomyopathy and calf hypertrophy but later onset. More lower limb. No facial muscle weakness
Emery-Dreifuss muscular dystrophy:
-Winging of scapulae but presents early with contractures even before muscle weakness. No facial muscle weakness
What are the investigations for facioscapulohumeral dystrophy?
CK is raised
EMG shows myopathic potentials
Genetic testing: FSHD is an autosomal dominant condition in up to 90% and sporadic in the remainder with the mutations localised to chromosome 4 but the related genes remain unidentified
Muscle biopsy
What is the management for facioscapulohumeral dystrophy?
Physiotherapy to delay/ prevent contractures
Surgery to the scapulothoracic area to fixate the scapulae and improve shoulder girdle function
Eye protection and lubrication for incomplete eye closure
What is the prognosis of facioscapulohumeral dystrophy?
Approximately 20% will require wheelchair assistance in their lifetime and life expectancy is normal.
What are the physical signs of duchenne muscular dystrophy and becker muscular dystophy?
General appearance
-Will be walking aids or wheelchair
-NORMAL facies
-Kyphoscoliosis
Gait
-Myopathic/waddling gait
Upper and lower limb examination
-Normal tone
-Contractures
-Wasting and weakness of proximal upper and lower limbs and neck muscles
-Pseudohypertrophy of calves
-Preferential weakness of extensor muscle groups
-Deep tendon reflexes are reduced or absent (plantars normal)
-Coordination and sensation normal
Additional
-Cardiomyopathy and pulmonary hypertension
-Spirometry for FVC
How do you differentiate DMD and BMD?
These forms of muscular dystrophy affect the same muscle groups but the age of onset is younger and disease progression is more rapid in DMD
Adult patients presenting to the examination with DMD may be younger and wheelchair dependent, with severe weakness, contractures and kyphoscoliosis, and marked calf muscle hypertrophy.
What are the investigations for DMD and BMD?
CK levels high
EMG: Myopathic picture
Muscle biopsy: muscle cell proteins become replaced by adipose and connective tissue
Genetic testing:
-Both are x linked recessive disorders caused by mutations in dystrophin gene on short arm of x chromosome at Xp21
Echocardiography: dilated cardiomyopathy
