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Neuromuscular Diseases

By Ann Washington,2014-04-26 19:41
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Neuromuscular Diseases

    Neuromuscular Diseases

    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):

    Think Fatigability

    Diseases of nerve roots (radiculopathies) and plexuses (plexopathies).

    II. Know the Clinical and Lab Findings of the Major Types of NM disorders (SEE Tables

    Below)

    Table 1

    Major Clinical Neuromuscular Presentations

     Topography Weakness distribution

    Symmetric or Proximal Distal Bulbar Syndrome Sensory loss

    asymmetric

    Myopathy Symmetric +++ Rare occ’l no

    Polyneur. symmetric rare +++ rare yes

    Motor neuro disease asymmetric late ++ no +++

    (ALS)

    Neurom transm. (MG) symmetric rare +++ no +++

    Table 2

    Lab Findings in Neuromuscular Diseases

Syndrome CPK EMG Nerve bx Muscle bx Other

Myop +++ +++ -- +++

    Polyn --- +++ +++ ---

    MND + +++ --- den'n

    N-M transm --- +++ --- +/- AchRAb

    antibodies

Key Test for Assessing Neuromuscular Diseases: Electromyography/nerve conduction velocity testing

     Table 3

    Frequency of Polyneuropathy Syndromes

    Diabetic----------------30%

    Inherited---------------20%

     Inflammatory-

     Demyelinating--------10%

     Dysproteinemic--------5%

     Other-------------------20%

     Undiagnosed----------15%

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    Table 4

    Myopathy Syndromes

     CPK EMG Biopsy Other

    Atrophic norm +/- Type 2 atr. None

    Dystrophic +/+++ ++ Characteristic Selective

    Weakness

    Inflammatory/necrotic +++ +++ Inflamm. Necr Rash in some

    Metabolic variable var Characteristic Cramps,myalgia,

    fatigue, CNS

    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

    dominant fashion.

    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

    the diagnosis.

    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

    congenital.

    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

    severe.

    Causes include steroids, inactivity (especially in the elderly), metabolic and

    hormonal imbalances (dysthyroidism) and other diseases causing disuse

    (rheumatoid arthritis).

    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.

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    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

     And immunomodulators

    D. Neuropathies:

    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

    multiple causes).

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    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.

    Diabetes:

    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.

    Inherited:

    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.

    Inflammatory-demyelinating polyneuropathies:

    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

    polyradiculoneuropathy (CIDP)

Summary of GB Syndrome (AIDP)

     Ascending Paralysis: Starts in the toes and goes up

     Respiratory Compromise and Autonomic dysfunction

     Life-threatening

     Treat with IV IgG, plasma exchange and NOT STEROIDS

    Other:

    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.

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