Approach to the patient with

proximal weakness
GENERALIZED

Neuromuscular
Myopathy junction disease
•MG

PROXIMAL
WEAKNESS
 Ocular Bulbar
Fatiguability
GENERALIZED weakness weakness

Neuromuscular
Myopathy junction disease
•MG

PROXIMAL
WEAKNESS
 Ocular Bulbar
Fatiguability
GENERALIZED weakness weakness

Neuromuscular
Myopathy junction disease
•MG

PROXIMAL
WEAKNESS
LOCALIZED

•Diabetic amyotrophy
Plexopathy
•Brachial neuritis
 Disorders of the
neuromuscular junction
Myasthenia Gravis
 Incidence
 15-30 yr old females > males
 60-75 yr old males > females

 Clinical
 Ocular features (60% early, further 30% later)
 Bulbar weakness

 Facial weakness

 Weakness prox > distal

 Fatiguability

 Myasthenic crisis
Myasthenia Gravis
 Provocative tests
 Shoulder abduction
 Sustained upgaze

 Speech fatiguability

 Ice pack test

 Pathogenesis

Ab against post-synaptic
acetylcholine receptor
 Ach binding
•Degradation of receptors
Myasthenia Gravis
 Diagnostic workup
 Confirm diagnosis
 Tensilon / Neostigmine test
Myasthenia Gravis
 Diagnostic workup
 Confirm diagnosis
 Tensilon / Neostigmine
test
Myasthenia Gravis
 Diagnostic workup
 Confirm diagnosis
 Tensilon / Neostigmine test
 Electrophysiology

 Repetitive stimulation
 Single fiber EMG
 Anti-Achetylcholine Receptor antibodies
 Exclude thymoma / thymic hyperplasia
Myasthenia Gravis
Treatment
Myasthenia Gravis
Chronic Symptomatic
Treatment
Pyridostigmine

Disease modifying
Corticosteroids

Azathioprine

Thymectomy
Myasthenia Gravis
Chronic Symptomatic
Treatment
Pyridostigmine

Disease modifying
Acute Corticosteroids

Azathioprine

Thymectomy

Myasthenic crisis
Treat precipitating
factors
Plasma exchange

IVIg
The thymus in MG
 Normal thymus serves as primary organ
for lymphocytes
 MG: % of mature B- and T-cells
 Active AchR Ab production
The thymus in MG

10-15%
Myasthenia Gravis

Thymoma
The thymus in MG

40%
Myasthenia Gravis

Thymoma
MG
The thymus in MG

40%
Myasthenia Gravis

Thymoma
MG

Thymoma
•90% benign
•Severe generalized myasthenia
•Pure ocular disease rare
Other disorders of NMJ
 Lambert-Eaton Myasthenic syndrome
(LEMS)
 Weakness of proximal leg muscles >>
shoulder girdle muscles
 Ocular & bulbar symptoms rare and mild
 Autonomic dysfunction
 Examination:
 Weakness
 Post-tetanic facilitation of reflexes
LEMS
 Pathogenesis
 Ab against pre-synaptic voltage gated calcium
channels (85-90% of LEMS)
 Calcium mediates release of Ach
 Ab initially arise against similar tumor antigens
LEMS
 Pathogenesis
 Ab against pre-synaptic voltage gated calcium
channels (85-90% of LEMS)
 Calcium mediates release of Ach
 Ab initially arise against similar tumor antigens

 ± 50% of LEMS have underlying malignancy

 >90% of these = SCLC
 Pt’s with cancer and LEMS have better prognosis
 Facilitation of NM
transmission
 Treatment •Pyridostigmine
•Diaminopyridine
(blocks K channels
 prolongs AP)
•Guanidine (?MOA)
 Facilitation of NM
transmission
 Treatment •Pyridostigmine
•Diaminopyridine
(blocks K channels
 prolongs AP)
•Guanidine (?MOA)

Suppression of Ab
production
•Prednisone
•Azathioprine
 Facilitation of NM
transmission
 Treatment •Pyridostigmine
•Diaminopyridine
(blocks K channels
 prolongs AP)
•Guanidine (?MOA)

Suppression of Ab
production
•Prednisone
Removal of antibodies
•Azathioprine
•IVIg
•Plasma exchange
 Facilitation of NM
transmission
 Treatment •Pyridostigmine
•Diaminopyridine
(blocks K channels
 prolongs AP)
•Guanidine (?MOA)

Suppression of Ab
production
•Prednisone
Treatment of Removal of antibodies
underlying •Azathioprine
•IVIg
malignancy
•Plasma exchange
Other disorders of NMJ
 Drug-induced myasthenia gravis
 D-penicillamine
Drugs associated with
myasthenic syndromes
Antibiotics Aminoglycosides, quinolones,
tetracyclines, ampicillin
ß-blockers Propranolol, timolol

Calcium channel blockers Verapamil

Anticonvulsants Phenytoin, phenobarb,

carbamazepine, gabapentin
Antirheumatics D-penicillamine, chloroquine

Psychiatric drugs Phenothiazines, lithium

Hormonal medications Corticosteroids, estrogen

Anti-arrhythmics Quinidine, quinine, procainamide,

Other Diazepam, iodinated radiographic

contrast, Mg sulphate
Myopathies
Myopathies
 Inflammatory myopathies
 Polymyositis
 Dermatomyositis

 Inclusion body myositis

 Eosinophylic myositis
Inflammatory myopathies
 DM vs PM
 Pathogenesis
 Clinical
 Age groups
 Skin lesions
Inflammatory myopathies
 DM vs PM
 Pathogenesis
 Clinical
 Age groups
 Skin lesions

 Cancer
Inflammatory myopathies
 Associations
 DM - often occurs alone
 Connective tissue disorders
 Systemic sclerosis
 MCTD
 PM – uncommon as stand-alone entity
 Viral infections
 Systemic autoimmune diseases

 Connective tissue disorders

 SLE
 Sjögren syndrome
 RA
Myopathies
 Inflammatory myopathies
 Infections
 Viral
Myopathies associated with viral
infections
 Retroviral infection
 Induces polymyositis via “molecular mimicry”
 HIV
 HTLV-1
 Coxsackie
 Influenza
 Post-viral myositis
Myopathies
 Inflammatory myopathies
 Infections
 Drugs
Drug-induced myopathies
 Cholesterol-lowering agents
 Statins
 Fibrates
 Corticosteroids
 ?up to 60% of patients
 Anti-rheumatic agents
 Chloroquin, D-penicillamine
 ARVs
 AZT
 Colchicine
 Amiodarone
Myopathies
 Inflammatory myopathies
 Infections
 Drugs
 Alcohol
Alcoholic myopathy
Acute Chronic

Precipitated by: Binge Years of daily abuse

Rhabdomyolysis Yes No

CK Elevated Often normal

Associated Delirium tremens, Peripheral neuropathy,

disorders withdrawal Korsakoff’s
Course Rapid onset and Slower onset and
recovery recovery ( if at all)
Myopathies (…cont)
 Endocrinopathies
 Thyroid disease – due to metabolic derangements
leading to  eficiency
 Hypothyroidism
 Thyrotoxicosis
 Parathyroid disease – due to Ca and P abnormalities
 Hyperparathyroidism
 Hypoparathyroidism (rare)
 Cushing’s disease
 Addison disease
 Acromegaly
Myopathies (…cont)
 Endocrinopathies
 Dystrophies
 Duchenne / Becker
 Fascioscapulohumeral dystrophy

 Limb-girdle muscular dystrophies

 Myotonic muscular dystrophies

FSHD
Duchenne’s

Becker’s
Myotonic muscular dystrophy
Myotonic muscular dystrophy
Associated disorders:
•DM / Insulin resistance
•Cataracts
•Premature balding
•Cardiac conduction
disturbances
•Mental retardation
•Testicular atrophy,
impotence
Myopathies (…cont)
 Endocrinopathies
 Dystrophies
 Other