Case 24

Case 24

HISTORY AND PHYSICAL EXAMINATION

A 36-year-old white man awoke with binocular diplopia; later that day, he noted blurred vision and lid ptosis. The next morning, he had nausea and vomited twice, and then he had slurred speech and difficulty swallowing. He was admitted to the hospital where magnetic resonance imaging (MRI) of the brain and cerebral angiography were normal. By the third day, he had developed complete ophthalmoplegia, severe dysarthria and dysphagia, and upper extremity weakness. Respiratory failure followed; the patient had to be intubated and required assisted ventilation. The Tensilon test was equivocal.

On examination on day 4, the patient was alert and intubated, and followed commands well. He had bilateral complete ophthalmoplegia to all gaze directions with bilateral ptosis (Figure C24-1). Pupils were dilated and unreactive to light or attempted accommodation. Corneal reflexes were depressed. The patient had bilateral peripheral facial weakness. His tongue was extremely weak, with no fasciculations. His palate did not move volitionally or to gagging. Neck flexors and extensors were weak (Medical Research Council [MRC] 3/5), as were proximal pelvic and shoulder girdle muscles (4/5). However, distal muscles were normal. Deep tendon reflexes were depressed (1/4). Sensation was normal. Cerebellar function also was normal.

Figure C24-1 Pupillary dilatation and ptosis in this patient at the time of diagnosis. The patient also had a complete ophthalmoplegia (not shown).

An electrodiagnostic (EDX) examination was requested.

Please now review the Nerve Conduction Studies and Needle EMG tables.

QUESTIONS

2. The most common type of botulism in the United States is:

A. Food-borne botulism.

B. Wound botulism.

C. Infantile botulism.

5. The following are correct statements regarding botulism and Lambert-Eaton myasthenic syndrome (LEMS), except:

A. Ocular manifestations are prominent in botulism but subtle in Lambert-Eaton Myasthenic syndrome.

B. After 50 Hz stimulation of motor nerves, the increment of CMAP amplitude generally is more prominent in botulism than in LEMS.

C. The CMAP increment is present in all motor nerves in LEMS but may be restricted to the affected muscles in botulism.

D. In both disorders, there is impairment of ACH release from the presynaptic terminal.

EDX FINDINGS AND INTERPRETATION OF DATA

The relevant EDX findings in this case are:

1. Normal sensory nerve action potentials (SNAPs).

2. Borderline or low-amplitude CMAPs.

3. Increment of the median CMAP recording abductor pollicis brevis, after a short period (10 seconds) of exercise measuring 90% (Figure C24-2).

4. Decrement of the median and spinal accessory CMAP after slow repetitive stimulation at rest (13%), with significant postexercise (post-tetanic) facilitation (Figure C24-3).

5. Increment of the CMAP amplitude after rapid, repetitive stimulation (50 Hz) measuring 100% (Figure C24-4).

Figure C24-2 Median compound muscle action potential (CMAP) at rest (waveform 1), and after a brief (10 seconds) period of exercise (waveform 2). Note the significant (90%) facilitation following exercise. Sensitivity = 2 mV/division.

Figure C24-3 Slow repetitive stimulation (2 Hz) of the median nerve. Train 1 is at rest, and Trains 2 through 5 are after 1 minute of exercise. The upper tracing shows all five stimulations. Although a decrement of the compound muscle action potential (CMAP) was evident at rest (13%), there is a dramatic facilitation of CMAP immediately after exercise (compare Train 1 to Train 2), with a subsequent return to baseline.

Figure C24-4 Increment of compound muscle action potential (CMAP) (100%) after rapid (50 Hz) repetitive stimulation of the spinal accessory nerve (sensitivity = 1 mV).

The EDX findings are consistent with a neuromuscular junction disorder of the presynaptic type, as supported by the borderline or low-amplitude baseline CMAPs, and the significant increment (>50%) of the CMAP amplitude after brief exercise and rapid repetitive stimulation of motor nerves. This case is consistent with botulism based on subacute progression of a descending muscle paralysis (ocular to bulbar to limbs), the muscarinic involvement (pupillary dilatation), and the EDX findings (presynaptic blockade). It is not consistent with Lambert-Eaton myasthenic syndrome because of the rapid evolution of symptoms, the prominent oculobulbar muscle weakness, and the relatively modest increment on rapid repetitive stimulation and after brief exercise (see electrodiagnosis).

DISCUSSION

Physiology and Pathophysiology

Botulinum toxin is produced by the anaerobic bacterium Clostridium botulinum. Eight immunologically distinct subtypes of the toxin have been identified (A, B, C1, C2, D, E, F, and G). Five serotypes are associated with human disease, with types A and B being the most common. Botulinum toxin type A is the most common in the United States, accounting for 60% of reported cases; it is the predominant type west of the Mississippi and is the most toxic of all subtypes. Type B serotype causes 30% of US cases and is the most common in Europe. It is the major type east of the Mississippi and tends to cause a milder illness.

Botulinum toxin is an extremely potent toxin with doses as small as 0.05 to 0.1 μg causing death in humans. The toxin has significant affinity to both muscarinic and nicotinic cholinergic nerve terminals resulting in autonomic failure and skeletal muscle paralysis. The toxin results in failure of ACH release from the presynaptic terminal and ultimately leads to destruction of the presynaptic terminal. Botulinum toxin first attaches irreversibly to the axonal terminal, and enters via endocytosis without interfering with the calcium channel (calcium entry is not blocked by botulinum toxin). The toxin then interferes with the calcium-dependent intracellular cascade that is responsible for ACH release, by cleaving proteins essential for docking and fusion of the presynaptic vesicles at the presynaptic active zones. Electron microscopy of nerve endings exposed to the toxin reveal a “log jam” of vesicles in the presynaptic terminals. It is now known that various serotypes bind to different presynaptic proteins: botulinum toxin A and E hydrolyze synaptosomal-associated protein-25 (SNAP-25), a protein of the presynaptic membrane; botulinum toxins B, D, F, and G specifically cleave synaptobrevin, a membrane protein of the neurotransmitter-containing vesicles; botulinum toxin C cleaves both SNAP-25 and syntaxin, a nerve plasmalemma protein (Figure C24-5). Because the ultimate result of this intoxication is interference with neurotransmitter release (exocytosis of synaptic vesicles) and destruction of the nerve terminals, recovery of neurologic function is protracted since it is dependent on the regrowth of sprouts from the injured nerve terminal.

Figure C24-5 Neuromuscular junction demonstrating the action of botulinum toxin. After entering the axon terminal by means of the botulinum toxin and endocytosis, the protease action of the toxin cleaves synaptic proteins leading to the compromise of synaptic vesicle release. Botulinum toxins A, C, and E cleave synaptosomal-associated protein (SNAP-25), shown in this illustration. Types B, D, F, and G cleave a synaptobrevin vesicle-associated membrane protein (VAMP), and type C cleaves syntaxin.

(Reprinted from Hallet M. One man’s poison: clinical applications of botulinum toxin. N Engl J Med 1999;341:118–120, with permission. Copyright © 1999 Massachusetts Medical Society.)

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Aug 12, 2016 | Posted by admin in CARDIOLOGY | Comments Off

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