WEAKNESS; Myopathy, Anterior horn cell
disease, Neuropathies, Neuromuscular transmission disease
4) Biochemical studies
Numerous studies are available but only neuromuscular transmission defects
and primary muscle diseases (myopathies) will be discussed.
Neuromuscular transmission defects. In myasthenia gravis, acetylcholine
receptor antibodies destroy the post synaptic acetylcholine receptors and they
are detectable in blood samples.
Primary muscle diseases - With muscle breakdown of any kind, creatine
phosphokinase (CK) is released into the blood where it can be measured.
5) Genetic studies
The genetic defects of many neuromuscular diseases are now known and can be
detected in peripheral blood or in muscle.
put this all together
1. Anterior horn cell diseases
Common causes of anterior horn cell diseases are poliomyelitis, motor
neuron disease and spinal muscular atrophy. Only spinal muscular atrophy will be
discussed further. This is usually an autosomal recessively inherited disease
with onset at any time from infancy to adulthood. The primary pathology is the
progressive loss of anterior horn cells until the patients become so weak that
they die - usually from an associated lung infection. The reason for the
progressive loss of anterior horn cells is not clear, but the disease is
associated with an abnormality on chromosome 4.
EMG findings: Normal nerve conduction velocities, normal SNAP amplitudes, low
CMAP amplitudes, large MUPs on needle examination, fasciculations.
Histology: Type grouping and group atrophy.
Biochemistry: Defect on chromosome 4.
2. Peripheral nerve diseases
This encompasses a vast number of diseases and only a cursory overview will
Damage to the peripheral nervous system results in motor, sensory and
autonomic dysfunction. A neuropathy is any disease of the nerves.
There are a number of different classes of neuropathies, but we will consider
only one of them here.
Distal polyneuropathy: All the nerves are affected distally in the
extremities. Clinically the patients have sensory loss in a glove and
stocking distribution, weakness and absent tendon reflexes in distal extremity
muscles (e.g. ankle jerk). Longer nerves are affected more severely and
thus the changes predominate in the legs. Most distal polyneuropathies are
purely sensory or affect the sensory and motor nerves together. Pure motor
distal neuropathies are rare. Depending on the etiology, the neuropathies
can be axonal (axis cylinder), demyelinating, or show features of both.
Diseases that cause distal polyneuropathies include diabetes, toxins, and
vitamin deficiency/alcohol abuse. Many of these neuropathies are
a) Predominantly axonal disease: Normal motor and sensory nerve conduction
velocities with low or absent CMAP and SNAP amplitudes. Needle examination
shows large MUPs that result from denervation and subsequent re-innervation.
b) Predominantly demyelinating disease: Relatively normal CMAP and SNAP
amplitudes with slowed nerve conduction velocities. Needle examination
reveals normal MUPs as the axons are not damaged and the muscle fibers are not
denervated. In practice pure demyelination is rare and some associated
axonal damage is common.
Type grouping and group atrophy only if there is axonal (axis cylinder)
3. Neuromuscular transmission defects
Only myasthenia gravis will be discussed further. This disease is
characterized by abnormal fatigue with exercise. Myasthenia gravis
commonly affects young woman and has a predilection for ocular, facial,
masticator and proximal upper extremity muscles. Typically the patients
recover to some degree after rest. Thus they feel much better in the
morning, but become weaker as the day progresses. When the extraocular eye
muscles are affected, diplopia (double vision) and ptosis (drooping of upper
eyelid) are common and bothersome signs. This is an auto-immune disease
with antibodies destroying the acetylcholine receptors (a postsynaptic defect).
continued to Neuromuscular