Muscle Disorder Flashcards
What are general clinical features of myopathies?
Usually proximal weakness
Loss of tone secondary to disease of muscle
Loss of muscle bulk from proximal wasting
Preserved reflexes
When do you get enlarged muscles?
Pseudohypertrophy from muscle infiltration of fat in muscular dystrophies - exacerbates the weakness
What do you see on EMG with myotonia?
Sustained contraction/slow relaxation - for a few seconds often during attempted relaxation
Rhythmic discharges, high frequency, elicited by a sharp tap on muscle belly
When do you get pain in muscle disease
Rare presentation
Can get it in severe inflammatory myopathy
What is elevated in many dystophies
CK - marker of muscle fibre damage
What do you see on EMG with myopathies?
Short-duration spiky polyphasic muscle action potentials
Occasionally spontaneous fibrillation
What are polymyositis and dermatomyositis?
Chronic inflammation of muscles
Inflammation of muscles and of the skin
Causes of polymyositis?
Unknown - may involve viruses and autoimmune factors (autoantibodies found in 25% of patients)
25% associated with connective tissue disease
10% underlying carcinoma - especially in dermatomyositis
Clinical features of polymyositis
Usually presents in 40-50 s
Proximal muscle weakness!!
Pain and tenderness in less than half of patients
Clinical features of dermatomyositis
Muscle weakness, pain etc
Macular erythema on face
Gottron’s papules - over dorsal aspects of fingers
Nail-fold haemorrhages
Photosensitivity
What will muscle biopsy show in polymyositis
Muscle fibre necrosis with inflammatory infiltrate
Treatment of polymyositis
Corticosteroids and other immunosuppressive drugs
Treat carcinoma and associated connective tissue disease
Prevalence of Duchennes Muscular Dystrophy
1/3000 male infants - x-linked recessive condition
Pathology of duchennes muscular dystrophy
Absence of dystrophin -skeletal muscle protein
Affects skeletal and cardiac muscle
Presentation of DMD
No abnormality at birth - obvious by age 4, wheelchair bound by 10 years old
Initially proximal weakness with calf pseudohypertrophy
Normally death by age 20 from respiratory failure or cardiomyopathy
Sign present in DMD
Gower’s sign - child needs to use hands to stand up
Investigations for DMD
Often done clinically
CK grossly elevated
EMG = myopathic
Muscle biopsy shows fatty infiltration and lack of staining for dystrophin
Management of DMD
No cure
Physiotherapy to prevent contractures
Respiratory support - portable
Features of Becker’s Muscular dystrophy
X-linked recessive
Similar to DMD but much milder and dystrophin is depleted rather than absent
Presentation of Beckers MD
Weakness only becomes apparent in young adults - cramps with exercise
Cardiomyopathy problems are worse than skeletal muscle problems and predispose to arrhythmias
Cardiac problems lead to death
Features of facioscapulohumeral dystrophy
Autosominal dominant Onset age 10-40 Affects face, shoulder and pelvic girdle Winged scapular and foot drop Muscle hypertrophy is rare 20% require wheelchair
What do myotonic dystrophies present with?
Tonic muscle spasm/delayed relaxation (myotonia)
Features of Myotonic dystrophy
Dystrophia Myotonica
Onset in 20s
Progressive distal-onset muscle weakness
Weakness and thinning of facial muscles and sternocleidomastoid muscles
Associated features of myotonic dystrophy
Male frontal baldness Gynaecomastia and testicular atrophy Cataracts Cardiomyopathy and conduction defects Mild intellectual impairment and sleep disturbance DM Bronchiectasis
What is McArdle’s Syndrome?
Deficiency of myophosphorylase in skeletal muscle
Symptoms begin in teens
Fatigue and severe pain during exercise
Continued exercise causes contractures
DX - absence of rise in venous lactate during forearm exercise test
Diseases/deficits associated with myopathy
Cushings (proximal)
Thryrotoxicosis (severe proximal shoulder>pelvic)
Hypothyroidism (muscle pain and stiffness)
Calcium and vit D deficiency - proximal myopathy
Acute and chronic hypokalaemia
Drugs which cause myopathies
Steroids (cushings) Lithium Fibrates AZT Vincristine Cholorquine Statins Alcohol
What is malignant hyperpyrexia?
Widespread skeletal muscle rigidity with hyperpyrexia
Following general anaesthesia or other neuroleptic drugs
Due to a defect in SR calcium-release channel
Young woman with opthalmoplegia + bilateral ptosis
MG
Young woman with opthalmoplegia + proptosis
Thyroid eye disease
Young woman with opthalmoplegia + brainstem symptoms
MS
EMG incremental increase after repetitive stimulation
LEMS - Lambert-Eaton Myasthenic Syndrome
EMG incremental decrease after repetitive stimulation
MG - Myasthenia Gravis
What is myasthenia gravis?
An acquired autoimmune disorder
Producing antibodies against post-synaptic acetylcholine receptor
How does MG present?
Proximal weakness and fatiguability of skeletal muscles (therefore worst after use and at the end of the day)
Most frequently affects proximal limbs, ocular and bulbar muscles
Muscle wasting rare and sensory exam is normal
What abnormality is found in many MG patients?
Thymus dysfunction
Hyperplasia found in 70% of patients
Two groups of MG patients?
Young women, 20-35years - acute, severely fluctuating - more generalised, HLA-68 and HLA-DR3 association
Older men 60-75 years - more ocularbulbar presentation
Ocular symptoms in MG
Ptosis and diplopia
Other important weakness symptoms
Neck and trunk axial weakness
Respiratory muscle weakness
Other head problems
Weak jaw and face
Dysarthria
Dysphonia
Dysphagia
Cranial muscles affected
Diagnosis test in MG
Tensilon/Edrophonium Test
Fast-acting anti-cholinesterase
IV bolus with atropine (prevent cardiac side effects)
Weakness improves within seconds and only lasts for 2-3minutes
Now only used after other clinical tests if confirmation still needed
Investigations in MG x5
1) Acetylcholine receptor antibodies - 85% of patients
2) EMG - incremental decrease after repetitive stimulation
3) Muscle autoantibodies
4) Thymus imaging - CT or MRI
5) Spirometry to check VC due to ventilation failure
Prognosis of MG
Can have fluctuating course
Can get acute respiratory exacerbations following infection or drugs - ventilation needed
Can remit permanently after thymus removal or with immunosuppressive treatment
Medical management of MG x4
Oral acetylcholinesterases - pyridostigmine - lasts about 3-5 hours - only symptomatic
Immunosuppression - corticosteroids (prednisolone) - excellent response in 70% of patients
IV - immunoglobulin - in acute exacerbation or if resp involvement
Azathioprine - steroid sparing agent
Surgical treatment of MG
Thymectomy - in patients with thymic hyperplasia this improves prognosis
In thymoma - remove a possibly malignant tumour - will not improve MG
Intervention treatment of MG
Plasmapheresis - acute exacerbation or resp. involvement
Only lasts a few days therefore needs repeating
What is Lambert-Eaton Myasthenic Syndrome?
Rare
Antibodies to presynaptic voltage-gated calcium channels at NMJ
Therefore failure of Ach release
What is the cause of LEMS in many cases?
Non-metastatic manifestation of malignancy especially small cell carcinoma of lung
Presentation of LEMS
Proximal limb weakness, especially lower limbs
Ocular and Cranial muscles typically spared
Initial improvement in power following exercise
Reflexes absent
Sometimes autonomic involvement
Treatment of LEMS
Try and treat primary tumour
Guanethidine hydrocholride and 4AP - may enhance Ach release
Steroids and plasmapheresis may help
3 rarer types of Myasthenia
Congenital MG - weakness as newborns - often problems with Ach release
Neonatal MG - antibodies across placenta - resolves after delivery
Penicillamine-induced myasthenia
What toxin can damage NMJ?
Botulinum toxin from clostridium botulinum
Condition similar to v.severe MG
What is MND
A neurodegenerative condition causing progressive weakness and eventually death - within 1-5years
Death usually from respiratory failure or aspiration
Annual incidence of MND
Overall incidence
2/100,000
6/100,000
Usual age of presentation of MND
50-75 years
Which presentation has shorter life expectancy?
Bulbar involvement - aspiration pneumonia more common
Pathogenesis of MND
Neurodegeneration of UMN, LMN and cranial nerve motor nuclei and nerves
Prevalence of frontal symptoms in MND
5% have frontotemporal dementia
40% have some measurable frontal lobe impairment
Pathology of MND - cellularly
Protein aggregation may be involved
RNA processing proteins in cytoplasmic inclusions - TDP-43 and FUS
Oxidative neuronal damage and glutamate mediated excitotoxicity have been implicated
Causes of MND
5-10% are familial (mutations in SOD-1, TDP-43 and FUS)
Usually sporadic
Guam incidence is higher may be due to environment (Cycad nut) or familial
4 clinical patterns seen in MND
1) Amyotrophic Lateral Sclerosis
2) Progressive Muscular Atrophy
3) Progressive Bulbar or pseudobulbar palsy
4) Primary Lateral Sclerosis
Features of ALS
UMN and LMN involvement
Therefore weakness, UMN signs (hyperreflexia, spasticity) and LMN signs (fasciculations, wasting)
One limb and then gradually to other
LMN signs usually develop after the presentation of asymmetric spastic paraparesis
Features of Progressive Muscular Atrophy
Purely LMN
Therefore weakness, wasting, fasciculations
Usually starts in one limb and spreads to involve adjacent spinal segments
Features of progressive bulbar or pseudobulbar palsy (corticobulbar palsy)
20%
Initially just CN involvement until MND merges
talking and swallowing affected
Bulbar = LMN - wasting and tongue fasciculation, absent jaw jerk and gag reflex, quiet/hoarse/nasal voice
Pseudobulbar = UMN - slow tongue movements, slow deliberate speech, increased reflexes, pseudobulbar affect (mood incongruent weeping or giggling)
Features of primary lateral sclerosis
Rare 1-2% Only UMN affected Loss of Betz cells in cortex Legs usually affected first Progressive tetraparesis and PBP Cognition not affected
Features not present in MND which distinguish it from MS
No sensory loss
No sphincter dysfunction
Features not present in MND which distinguish it from MG
No opthalmoplegia
DX of MND
No diagnostic test
Tests to exclude other pathology - eg. MRI
DDX of ALS
Cervical spondylosis - as combination of UMN from radiculopathy and anterior horn cell loss - LMN
Spinal tumours, LMN at level of pathology and UMN below lesion
Hyperthyroidism - wasted fasciculating muscles but secondary to myopathy with brisk reflexes
DDX of Progressive muscular atrophy
Only LMN
Poliomyelitis
Post-polio syndrome
Neuropathy
DDX of PBP
Cerebrovascular disease can cause PSP as well as UMN limb signs
MS - usually pseudobulbar palsy but also eye and other brainstem syndromes
DDX of BP
MG
Tumours causing lower cranial nerve lesions
Medical treatment of MND
No curing treatment
Riluzole (antiglutamergic) prolongs life by 3 months - side effects = raised LFT (mainly in ALS)
Drooling - propantheline and amitriptyline
Baclofen or Tizanidine - for spasticity
Management of MND
Blended food, NG tube, percutaneous catheter gastrostomy
Analgesia for pain
Non-invasive ventilation for respiratory failure - shown to improve survival by about 7months
Do you get cerebellar symptoms in MS
yes
When do you use gadolinium enhancement with neuromuscular stuff
Shows active lesion in MRI for MS
DNA cause of myotonic dystrophy
trinucelotide CTG triplet repeat in UTR of DMPK genen
