Clinical evidence of extraocular muscle fiber-type specificity of botulinum toxin.
OBJECTIVE
To compare the effects of botulinum toxin on static and dynamic aspects of eye movements, and thereby elucidate the mechanisms of its action on eye muscles.


BACKGROUND
Laboratory evidence indicates that static alignment and saccades are subserved by different extraocular muscle fiber types, and botulinum toxin may cause specific dysfunction of the fibers controlling static alignment. Diplopia is a well-known side effect of periorbital botulinum toxin injections in humans, and may be a clinical correlate of the laboratory findings.


METHODS
Search coil recording of eye movements was performed in one patient with systemic botulism, and in three patients with diplopia following periorbital injection of botulinum toxin A.


RESULTS
In the patient with acute botulism, eye movement alignment, range, and saccadic velocity profiles were abnormal. In three patients with iatrogenic diplopia, static alignment was abnormal but movement range and saccadic velocities were within normal limits. Edrophonium improved the range of movements and saccadic velocities in the patient with systemic botulism but was ineffective in reversing ocular misalignment in the one iatrogenic patient to whom it was administered.


CONCLUSIONS
Precise alignment is subserved by orbital singly innervated muscle fibers, and the effects of botulinum toxin are greatest on these fibers. This predilection is apparent when the toxin dose is very small, as must have been the case in our patients with iatrogenic diplopia. The lack of a response to edrophonium probably reflects structural damage to muscle fibers. In contrast, larger doses of toxin produce an acute dysfunction of all extraocular muscle fiber types, which is responsive to edrophonium and consequently reflects partial blockade at the neuromuscular junction.
Department of Neurology, University Hospitals of Cleveland and Cleveland Veterans Affairs Medical Center, Case Western Reserve University, OH 44106, USA.
J S
JS
Stahl
L
L
Averbuch-Heller
B F
BF
Remler
R J
RJ
Leigh
D000328:Adult; D000368:Aged; D018726:Anti-Dyskinesia Agents / Q000009:adverse effects* / Q000378:metabolism; D001905:Botulinum Toxins / Q000009:adverse effects* / Q000378:metabolism; D001906:Botulism / Q000503:physiopathology*; D004172:Diplopia / Q000139:chemically induced / Q000382:microbiology / Q000503:physiopathology; D004491:Edrophonium; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000382:microbiology; D009801:Oculomotor Muscles / Q000166:cytology / Q000382:microbiology* / Q000503:physiopathology*; D009886:Ophthalmoplegia / Q000139:chemically induced / Q000382:microbiology / Q000503:physiopathology; D010277:Parasympathomimetics; D011698:Pursuit, Smooth / Q000187:drug effects / Q000502:physiology; D012438:Saccades / Q000187:drug effects / Q000502:physiology
D018726:Anti-Dyskinesia Agents; D010277:Parasympathomimetics; D004491:Edrophonium; D001905:Botulinum Toxins