The Neuromuscular Junction in Health and Disease

 

CASE 1: MOTOR NEURONE DISEASE (ALS)

 

A 38-year-old man noticed a slowly progressive weakness of his right lower extremity beginning 6 months prior to this examination. Although he was weaker after effort, this quickly subsided. The patient also noted muscle twitching in upper and lower extremities. He had occasional cramps, especially in his gastrocnemius muscles. He denied sensory abnormalities or bladder symptoms and experienced no change in speech or swallowing difficulties. His medical history was negative.

Physical examination: Fasciculations were apparent in the upper and lower extremities. Weakness was isolated to the right tibialis anterior and peroneus longus muscles. Deep tendon reflexes were hyperactive and symmetrical, including the jaw jerk. Plantar responses were extensor.

 

A — Questions

1. What are fasciculations? What is their clinical significance?

2. What clinical observations are indicative of the patient’s pathology?

3. Comment on the absence of sensory symptoms and signs.

 

A — Answers

1. Fasciculations are visible spontaneous twitchings of muscle, probably caused by random contractions of motor units. It probably originates from regions of the nerve that have changes in myelinations, such as near the cell body, at the axon terminal branches, or at areas of abonormal demyelination. Ectopic discharges from these regions may be propagated to the cell body, causing generation of a MUP, which is a fasciculation.

Although they are a frequent feature of motor neuron disease (MND), they are by no means pathognomonic of this disease, occurring in many conditions and in normal people. These include Creutzfeldt-Jakob disease, spinal cord disease (hematomyelia, syringomyelia, cervical spondylosis), a root lesion, polyneuropathy, myopathies (polymyositis, thyrotoxic), and a condition associated with cramps, myokymia, and increased sweating. Most commonly, they are observed in normal individuals, especially after exercies.

2. In view of the concurrent hyperreflexia, extensor plantar responses (Babinski’s sign), and weakness of the tibialis anterior and peroneus longus muscles, the fasciculations in this patient take on pathologic significants. These findings indicate upper motor neuron pathology and possible involvement of the lower motor neuron as well. This combination is typical of MND. It is also common for patients with this condition to complain of cramps. Although MND eventually involves bulbar muscles, they can be spared early in the disease. At that stage, however, the examiner must consider a different, potentially treatable condition, namely cervical cord compression (caused by disc, tumor, or spondylosis) or multiple sclerosis. (In this case, though, the hyperactive jaw jerk suggests pathology above the cervical level.)

3. The absence of any sensory symptoms (except for the pain associated with muscle cramping) is characteristic of MND.

 

CASE 1: ELECTRODIAGNOSTIC EXAMINATION

Motor Conduction

Latency

(msec)

Conduction

Velocity

(M/sec)

Amplitude

Right median wrist/abductor pollicis brevis

3.2 Normal

Elbow/Wrist 57 Normal

Normal

Right ulnar wrist/abductor dig V

2.4 Normal

Axilla/elbow 57 Normal

Across elbow 55 Normal

Elbow/wrist 55 Normal

Normal

Sensory Nerve Action Potentials

Latency

Amplitude

Right median wrist/second digit

2.9 Normal

Normal

Right ulnar wrist/fifth digit

2.7 Normal

Normal

Electromyography

Right quadriceps

Right deltoid

Right brachioradialis

Fasciculation potentials at rest.

Normal and long-duration polyphasic MUPs on volition. No variability noted.

Right and left tibialis anterior

Right and left gastrocnemius

Right soleus

Right peroneus longus

Right extensor digitorum brevis

Right first dorsal interosseous

Fibrillation potentials and positive sharp waves at rest. Normal and long-duration polyphasic MUPs on volition.

Right tongue

Right mentalis

Right orbicularis oris

Silent at rest. Normal MUPs on volition

B — Questions

1. If fasciculation potentials were the only electrical findings, what would be the conclusion?

2. What do the other EMG findings tell us?

3. Are the electrodiagnostic findings specific for MND?

4. This patient was examined in 1974. What other tests would add information?

B — Answers

1. Fasciculation potentials, as discussed above, may be benign or malignant. Analysis of the duration, amplitude, or polyphasic qualities of the fasciculations does not distinguish between them. Slower frequency of firing, however, may correlate with the malignant variety, although exceptions can occur. In summary, the presence of fasciculations alone is not diagnostic of any one condition. A myotomal distribution would suggest a radicular process. But lacking a localised pattern, the examiner must look for additional abnormalities (such as fibrillation potentials and positive sharp waves) before drawing conclusions from the fasciculations.

2. Muscles sampled in both upper and lower extremities reveal fibrillation potentials and positive sharp waves. This rules out benign fasciculations. It also indicates that the problem is widespread. The characteristics of the MUPs also change in MND. As the disease evolves, a MUP or fasciculation, if observed with repetitive discharges, shows instability, probably reflecting transmission abnormalities. At a later stage, the MUPs have increased in amplitude and duration and often have late components.

3. The diffuse EMG abnormalities and the normal conduction studies should not be equated automatically with a diagnosis of MND. One must rmember that an axonal polyneuropathy or multiple root lesions may also produce similar electrical findings. It is the associated clinical features (and bulbar involvement, when present) that permit the diagnosis of MND to be made.

4. More extensive screening for a polyneuropathy is in order. This would include sural SNAPs, F waves, and H reflexes.

The prognosis of MND can be assessed by measuring the CMAP amplitudes, following the spread of the fibrillation potentials, quantitating the pattern of recruitment, and looking for a decrement on repetitive supramaximal stimulation.

 

ELECTRODIAGNOSTIC INTERPRETATION

Diffuse abnormalities in both upper and lower extremities consistent with MND.

 

FOLLOW-UP

During the following two years, the patient’s weakness progressed to near quadriplegia. In addition he developed marked swallowing and respiratory difficulties.

 

SIGNIFICANCE

This is a patient with MND seen at a stage without bulbar involvement.

 

(All cases are abstracted from Liveson, JA (1979)Peripheral Neurology: Case studies in electrodiagnosis. 2nd edn. Pub: FA Davis.)