I. Be Able to Recognize the Major Types of Neuromuscular Disorders
These include diseases of the anterior horn cells, also known as motor neuron diseases
(polio, ALS, or Lou Gehrig’s disease).
Diseases of the peripheral nerves (polyneuropathies and mononeuropathies):
Think Distal Weakness with Neuropathies
Stocking-Glove Sensory Loss- Numbness in Hands and Feet
Diseases of muscle (dystrophies, myopathies):
Think Proximal Weakness with Myopathies
Diseases of the neuromuscular junction (myasthenia gravis):
Diseases of nerve roots (radiculopathies) and plexuses (plexopathies).
II. Know the Clinical and Lab Findings of the Major Types of NM disorders (SEE Tables
Major Clinical Neuromuscular Presentations
Topography Weakness distribution
Symmetric or Proximal Distal Bulbar Syndrome Sensory loss
Myopathy Symmetric +++ Rare occ’l no
Polyneur. symmetric rare +++ rare yes
Motor neuro disease asymmetric late ++ no +++
Neurom transm. (MG) symmetric rare +++ no +++
Lab Findings in Neuromuscular Diseases
Syndrome CPK EMG Nerve bx Muscle bx Other
Myop +++ +++ -- +++
Polyn --- +++ +++ ---
MND + +++ --- den'n
N-M transm --- +++ --- +/- AchRAb
Key Test for Assessing Neuromuscular Diseases: Electromyography/nerve conduction velocity testing
Frequency of Polyneuropathy Syndromes
CPK EMG Biopsy Other
Atrophic norm +/- Type 2 atr. None
Dystrophic +/+++ ++ Characteristic Selective
Inflammatory/necrotic +++ +++ Inflamm. Necr Rash in some
Metabolic variable var Characteristic Cramps,myalgia,
Congenital norm +/- Characteristic Static weakn
III. Be Familiar with the Path-physiological Mechanisms of these Disorders and their TX A. Anterior horn cell diseases:
The cause is unknown. About 10% of cases are inherited, usually in an autosomal
It generally starts insidiously with atrophy and weakness of a hand, a distal leg or the
facial and, especially, the tongue-pharyngeal muscles. It is slowly and inexorably
progressive and gradually spreads to other parts of the body until virtually all skeletal
muscles are affected
DX: It is the combination of both upper and lower motor neuron signs that is the key to
TX: There is currently no treatment of the disorder and the disease runs its course in
anywhere from a few months to several years.
B. Myopathies: Myopathies are diseases which affect muscles directly. They can be
primary to muscles (dystrophies) or secondary to changes elsewhere in the body (toxic
myopathies). For purposes of general discussion, myopathies can be divided into 5
categories (Table): atrophic, dystrophic, inflammatory-necrotic, metabolic, and
1) Atrophic myopathies present with proximal weakness (shoulder girdle, hip
girdle and neck flexors). As in all myopathies, sensation is unaffected and
reflexes are reduced in proportion to the weakness of the muscle tested. These
are generally chronic, slowly progressive disorders and are generally not
Causes include steroids, inactivity (especially in the elderly), metabolic and
hormonal imbalances (dysthyroidism) and other diseases causing disuse
Treatment consists of correction of the underlying abnormality and exercise.
2) Necrotic-inflammatory: These patients usually experience subacute proximal
weakness with or without muscle discomfort and swelling. They may have a
skin rash (dermatomyositis) and may have an underlying collagen vascular
disease or malignancy.
Causes include autoimmune disease (poly and dermatomysitis), underlying
malignancies or infections (HIV) or toxins (mevacor, AZT).
Treatment usually consists of immunosupression or removal of toxin.
3) Dystrophies are genetically determined diseases if muscles that are each
relatively characteristic clinically and morphologically and are due to
unknown (for the most part) abnormalities of muscle.
All have more or less symmetrical weakness that is often highly selective and
involves characteristics muscles in each entity.
TX: There is currently no effective treatment for any of these disorders.
Genetic research and counseling offers the best hope.
4) Metabolic myopathies are generally inherited disorders of fuel metabolism of
muscle cells. They may present in several ways. Disorders which affect the
glycolytic pathways (McArdle’s Disease) present with cramps and myalgias
with exercise. Disorders which result in storage of material in myocytes
(carnitine deficiency with lipid storage) cause a progressive myopathy with
exercise intolerance. Myopathies with mitochondrial defects (mitochondrial
myopathies) cause multisystemic disease with combinations of CNS and PNS
disease often associated with lactic acidosis.
5) Congenital myopathies are myopathies, which are present from birth. These
myopathies are generally relatively mild and lifelong. Children are often born
with joint contractures (arthrogryposis congenita) and their motor
development is poor and delayed. Muscles are small and poorly formed. The
disease is relatively nonprogressive.
TX: These are largely inherited disorders with no effective treatment.
C. Neuromuscular transmission disorders:
These are disorders, which affect the presynaptic or postsynaptic neuromuscular
junction. They are closest in character to myopathies but have rather unique
features. The prototype is myasthenia gravis
Myasthenia gravis is due to autoantibodies directed at the post-synaptic
acetylcholine receptor. LEMS is due to antibodies directed at the calcium
channel, which controls acetylcholine release, on the presynaptic nerve terminal.
Botulism is due to a toxin produced by Clostridium botulinum, which also
affects the presynaptic nerve terminal and prevents acetylcholine relsease.
Treatment consists of two approaches: symptomatic and definitive.
Symptomatic involves uses of chemicals (ie, acetylcholinesterase inhibitors) to
potentiate N-M transmission. Definitve attacks the primary defect (ie.
immunosuppression). The outlook, with modern treatment, is generally good
for most of these patients.
Summary of MG:
Post-Synaptic Problem with ACH receptors
Classic Auto-immune with ant-ACHR antibodies
Treated with ACH-E inhibitors, Thymectomy, IgG, Plasma Exchange
Diseases of peripheral nerves include disorders that affect nerve roots as they
exit the spinal foramina (disks, tumors), diseases of plexuses (inflammation,
tumors), diseases of single nerves in the limbs (compression, infaracts) and
disorders that affect multiple nerves all over the body (polyneuropathies due to
One of the most important determinants of etiology is the nature of the nerve damage that is whether primarily directed at the axon itself (axonopathy) or the myelin sheath (demyelinating neuropathy) since certain etiologies tend to do one or the other. Nerve conduction studies are excellent at making this determination so that early study of unknown cases with careful nerve conduction studies is often the most helpful part of the evaluation.
This is the most common form of polyneuropathy in this country, accounting for about 30% of all cases. The polyneuropathy, in genera, parallels length and severity of diabetes and is more common in the elderly. It also parallels the presence of other complications of diabetes, such as nephropathy and retinopathy. The etiology is thought to be a vasculopathy affecting small arterioles and capillaries, perhaps brought on by the metabolic changes of diabetes.
Except for spontaneous there is no effective treatment for these disorders.
Accounts for about 20% of all cases. Charcot-Marie-Tooth Disease is the prototype of these disorders
The only available treatment at present consists of physical therapy and bracing.
These are acquired, autoimmune neuropathies which account for about 10% of all polyneuropathies and are due to antibody or T-cell activity against peripheral nerve, most commonly myelin. The most common is the Guillan-Barre Syndrome, which is the acute variety. These patients present with the rapid onset of generalized weakness, areflexia and mild sensory loss, usually following the flu but also associated with other antecedent factors, e.g. surgical procedures. They peak in 3-4 weeks, then slowly improve. Treatment consists of medical and, especially, respiratory support and plasmapheresis. 80-90% make a more or less complete recovery. The chronic form, called for lack of a better term chronic inflammatory demyelinating
Summary of GB Syndrome (AIDP)
Ascending Paralysis: Starts in the toes and goes up
Respiratory Compromise and Autonomic dysfunction
Treat with IV IgG, plasma exchange and NOT STEROIDS
The other 40% or so have multiple causes from toxins and drugs to internal metabolic and neoplastic conditions and HIV infection. About 15% remain undiagnosed despite extensive testing and prolonged follow up.