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Botulinum toxin-A improves the rigidity of progressive supranuclear palsy.

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in some motor, axonal disorders 13, 11, 121. However,
it is notable that IgG anti-GM1 antibodies were found
in only a minority of patients with axonal neuropathies.
Thus, other antigenic targets must be involved as well.
Two factors now seem to be strongly related to acute
motor neuropathies, i.e., serum IgG anti-GM1 antibodies and preceding Campylobacter jejlcni infection
C.3-61. Although it has been postulated that anti-GM1
antibodies might cross-react with Campylobacter antigens, some Chinese patients had titers of IgG antiGM 1 antibodies without serologic evidence of Campylobacterjejuni infection. Further study, possibly utilizing
stool PCR, will be required to clarify this relationship
The association of high titers of IgM anti-GM1 antibodies with chronic motor neuropathies is now well
established [1, 21. These IgM antibodies are especially
common in MMN El, 2). O u r data suggest that selective serum I@ anti-GM1 antibody reactivity is rarely
associated with MMN. The chronic LMN syndromes
with selective 1 6 antibodies do not generally have
conduction block or other findings consistent with demyelination. The mechanism by which anti-GM1 antibodies may produce disease is unknown, but differences in clinical LMN syndromes [I, 2) might be the
result of different sites of action, specificities, and
cross-reactivity of antibodies as well as accessibility to
target tissue {lS]. As there is little binding of human
IgG or IgM anti-GM 1 antibodies to dorsal root ganglia,
this may possibly explain the lack of sensory involvement in these disorders [l?]. Whatever their role in
producing disease, our data provide evidence that selective, high-titer, serum IgG antibody reactivity to
G M 1 ganglioside is a rather specific marker for peripheral nervous system disorders with predominantly motor, usually axonal, involvement.
1. Pestronk A. Invited review: motor neuropathies, motor neuron
disorders, and antiglycolipid antibodies. Muscle Nerve 1991;14:
2. Pestronk A, Chaudhiy V, Feldman EL, et al. Lower motor neuron syndromes defined by patterns of weakness, nerve conduction abnormalities, and high titers of antiglycolipid antibodies.
Ann Neurol 1990;27:316-326
3. Yuki N , Yoshino 14, Sato S,Miydtake T. Acute axonal polyneuropathy associated with anti-GM1 antibodies following Cumpylobacter enteritis. Neurology 1990;40:1900-1902
4. Yuki N, Sato S, lnuzuka T, e t al. Axonal degeneration in the
Guillain-Bard syndrome and anti-GM I ganglioside antibodies.
Muscle Nerve 1332;15:116
5. McKhann GM, Cornblath DR, Ho T, et al. Clinical and electrophysiological aspects of acute paralytic disease of children and
young adults in northern China. Lancet 1991;338:593-597
6. McKhann GM, Cornblath DR, Griffin JW, et al. Acute motor
axonal neuropathy: a frequent cause of acute flaccid paralysis in
China. Ann Neurol 1993;33:333-342
7. Cornblath DR. Electrophysiology in Guillain-Barre syndrome.
Ann Neurol 1990;27(suppl):S1 7 4 2 0
8. Asbury AK, Cornblath DR. Assessment of current diagnostic
criteria for Guillain-Barre syndrome. Ann Neurol 1990;27
9. Feasby TE, Gilbert JJ, Brown WF, et al. An acute axonal form
of Guillain-Barri. polyneuropathy. Brain 1986;109:111>-1126
10. Sovilla J-Y, Regli F, Francioli PB. Guillain-Rarre syndrome following Campylubac-twjejuni enteritis: report of three cases and
review of the literature. Arch Intern Med 1988;148:739-741
11. Nobiie-Orazio E, Carpo M, Meucci N, et al. Guillain-Barre
syndrome associated with high titers of anti-GM1 antibodies. J
Neurol Sci 1992;109:200-206
12. van den Berg LH, Marrink J, de Jager AE, et at. Anti-GM1
antibodies in patients with Guillain-Barrt. syndrome. J Neurol
Neurosurg Psychiatry 1992;55:&-11
13. Ilyas AA, Mithen FA, Dalakas MC, et al. Antibodies to acidic
glycolipids in Guillain-Barre syndrome and chronic inffammatory demyelinating polyneuropathy. J Neurol Sci 1992;107:
14. Thomas PK. The Guillain-Barri syndrome: no longer a simple
concept. J Neurol 1992;239.361-362
15. Corbo M, Quattrini A, Lugaresi A, et al. Patterns of reactivity
of human anti-GM1 antibodies with spinal cord and motor neurons. Ann Neurol 1992;32:487-493
Botulinum Toxin-A
Improves the Rigidity of
Progressive Supranuclear
Kathleen €3. Polo, ML)," and Bahman Jabbari, MD*I
Botulinum toxin-A (botox) can improve spasticity and
decrease painful spasms in the affected limbs of patients
with multiple sclerosis. We report significant improvement of muscle rigidity in the upper limbs after focal
administration of botulinum toxin A to 2 patients with
progressive supranuclear palsy.
Polo KB, Jabbari B. Botulinum toxin-A improves
the rigidity of progressive supranuclear palsy.
Ann N e u r o l 1?944;3Y237-2 39
Botulinum toxin-A (botox) blocks calcium-mediated
release of acetylcholine from presynaptic vesicles. The
The opinions or assertions expressed herein are those of the authors
and are not to be construed as reflecting the views of the United
States Army, Department of Defense, o r Uniformed Services University of the Health Sciences.
From 'Neurology Service, Walter Reed Army Medical Center,
Washington, DC, and ?Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD.
Received May 14, 19'93, and in revised form Jul 26. Accepted for
publication Aug 4 , 1993.
Address correspondence to Dr Jabbari, Neurology Service, Walter
Reed Army Medical Center, Washington DC 20307.
Copyright @I 1994 by the American Neurological Association
drug is now considered the treatment of choice for
blepharospasm [1], hemifacial spasm [2], torticollis [3 } ,
and laryngeal adductor dystonia (spastic dysphonia)
141, and also has been used to treat spasticity [ S , 61,
focal limb dystonias [7], anismus, detrusorsphincter
dyssynergia, 6th nerve palsy and nystagmus {8]. We
have investigated in a double blind manner the effectiveness of botox against rigidity in 2 severely affected
patients with progressive supranuclear palsy (PSP).
Materials and Methods
Patients were evaluated for severity of rigidity based on the
Unified Parkinson’s Disease Rating Scale (UPDRS) “91.
Treatment consisted of botox (10 UiO. 1 ml) or an equivalent
volume of normal saline, administered intramuscularly in random order, with both the administering physician (also the
rater) and the patient blinded to the order of the injections.
The patients were examined and scored by the same physician at all evaluations and improvement was considered significant if the baseline rigidity score improved by two or
more grades.
Patient 1, a 59-year-old man, experienced progressive slurring of speech and increasing difficulty with ambulation leading to multiple falls and use of a cane over a period of 9
months. H e also noticed trouble swallowing liquids and solid
foods. H e had previously been in excellent health and was
on no medications. O n neurological examination he showed
impaired short-term memory and concrete thinking, had diminished voluntary eye movements in all directions (most
prominent in the vertical plane) and normal oculocephalic
reflexes and saccadic pursuits. There was a marked dysarthria,
involving most notably labial sounds. Muscle tone was increased throughout and in all directions of motion, and was
unaffected by the velocity of passive movement. There was
no tremor or clasp-knife phenomenon. Muscle strength was
4 + / 5 throughout. Abduction of the left arm was limited and
painful due to an old rotator cuff injury. There was axial
rigidity in extension. The left forearm could not be extended
voluntarily and could be passively extended only to 150 degrees. hgidity was rated as grade 3 (marked but with full
range of motion easily achieved). The gait was slow and wide
based with circumduction of the left foot. Magnetic resonance imaging revealed diffuse cortical atrophy with normal
ventricular size.
Patient 2, a 69-year-old man, had noted gait imbalance and
mild slowing of speech approximately 7 years previously. He
had otherwise been in good health, except for mild spinal
trauma and a left knee reconstruction. The symptoms progressed slowly for 2 years, when he came to medical attention
because of a backwards fall. The neurological exmination
revealed limited voluntary gaze in all directions, most pronounced on up-gaze. He had normal oculocephalic reflexes
and slow saccadic pursuits. Strength was normal. There was
generalized velocity-independent hypertonia, equivalent in
flexors and extensors, without clasp-knife phenomenon.
There was mild cogwheeling in both wrists. Deep tendon
reflexes were increased with extensor plantar responses.
Magnetic resonance imaging revealed diffuse cortical atrophy
and a small hypodense lesion in the left frontal region consis-
238 Annals of Neurology
Vol 35
No 2
February 1994
tent with an old infarct. An electroencephalogram was normal. Gait instability and hypertonia continued to progress,
resulting in the use of a cane for 2 years and decreased spontaneous speech. Baclofen and bromocriptine produced minimal improvement. By the time of the present study, he was
wheelchair or bed bound, with no spontaneous speech and
total external ophthalmoplegia, but was alert and oriented
and communicated clearly with opening and closing of his
eyes. There was marked diffuse bilateral rigidity, more prominent on the left. There were no voluntary movements of
the forearms, which were kept forcefully flexed. The forearms could be extended passively to 120 degrees, although
this produced discomfort. Rigidity was rated as grade 4 (severe, range of motion achieved with difficulty).
Patient 1 first received saline in the left biceps and
brachioradialis muscles. The patient and his family
noted no change after 1 and 2 weeks and the blinded
rater recorded no improvement. After 2 weeks, 100
units of botox was injected in the left biceps and 60
units in the left brachioradialis muscle. One week
later, the patient could voluntarily flex and extend the
left forearm. The rater noted decreased tone in the left
flexors and that the patient could fully extend the left
arm. Repeat rating at 2 weeks disclosed no change.
The left flexor rigidity was rated 1 (slight or detectable
only when activated by mirror or other movements).
Patient 2 received botox in the left biceps (80 units)
and brachioradialis (40 units) muscles and saline in the
right biceps and brachioradialis. A few days after injection, both the patients’s wife and his physical therapist
reported an “obvious” improvement in his ability to
flex the left forearm but no change on the right. The
physical therapist was able to fit a splint for the left
forearm 1 week after this injection. The rater noted
decreased tone and rated the rigidity as grade 2 (mild
to moderate). The forearm could now be extended to
150 degrees.
Our patient’s symptoms and signs-progressive ophthalmoparesis, diffuse rigidity, postural instability, frequent falls, and profound dysarthria-conform with
the diagnosis of PSP {lo}. Both patients were significantly handicapped by the degree of their rigidity.
A variety of medications have been tried in PSP
with minimal success. These include anticholinergics,
levodopa, dopamine receptor agonists, tricyclic antidepressants, and serotonin receptor agonists Ell). Patient
2 took baclofen and bromocriptine without benefit.
In both patients, local injection of botulinum toxin
in the upper limb muscles resulted in appreciable improvement within 72 hours. The patients moved their
“frozen” limbs at will and Patient 2 could be fitted for
a forearm splint by the physical therapist.
Although our observation applies only to the rigidity
of PSP, it suggests that botulinum toxin might also be
of use for rigidity in other neurodegenerative disorders, especially those with more focal features. A rigid
dominant hand or forearm can be a major handicap for
such patients. By allowing increased voluntary movements, early reduction of rigidity in strategic limbs may
minimize the risk of contractures, lead to improved
hygiene, and extend the period of independence.
Prognostic Value of
Mvoclonus Status in
cdrnatose survivors of
Cardiac Arrest
The patients discussed in this report were a parr of an approved
ongoing protocol, number 7150, through the Department of Clinical
Investigations at Walter Reed Army Medical Center.
Generalized myoclonus status is common in comatose
patients after cardiac resuscitation, but its prognostic
value is uncertain. We studied the clinical, radiologic,
and pathologic findings in 107 consecutive patients who
remained comatose after cardiac resuscitation. Myoclonus status was present in 40 patients (3796). Features
more prevalent in patients with myoclonus status were
burst suppression on electroencephalograms, cerebral
edema or cerebral infarcts on computed tomography
scans, and acute ischemic neuronal change in all cortical
laminae. All patients with myoclonus status died. Of 67
patients without myoclonus, 20 awakened. We conclude
that myoclonus status in postanoxic coma should be considered an agonal phenomenon that indicates devastating neocortical damage. Its presence in comatose patients after cardiac arrest must strongly influence the
decision to withdraw life support.
1. Scott AB, Kennedy RA, Stuhbs HA. Botulinum A toxin injections as a treatment for blepharospasm. Arch Ophthalmol 1985;
2. Yoshimura DM, Aminoff MJ, Tami TA, Scott AB. Treatment
of hemifacial spasm with botulinum toxin. Muscle Nerve 1992;
3. Blackie JD, Lees AJ. Botulinum toxin treatment in spasmodic
torricollis. J Neurol Neurosurg Psychiatry 1990;53:640-643
4.Jankovic J. Schwartz K, Donovan DT. Botulinum toxin treatment of cranial-cervical dystonia, spasmodic dysphonia. other
focal dystonias, and hemifidcid spasm. J Neurol Neurosurg Psychiatry 1%O;> 3:633-639
5. Snow BJ, Tsui JKC, Bhatt MH, et al. Treatment of spasticity
with botulinum toxin: a double blind study. Ann Neurol 1990;
28:512-5 15
6. Das TK, Park Dh4. Effect of treatment with botulinum toxin
on spaticity. Postgrad Med J 1989;65:208-210
7 . Tsui JKC, Bhatt M, Calne S, Calne DB. Botulinum toxin in the
treatment of writer's cramp: a double blind study. Neurology
8. Jankovic J, Brin MF. Therapeutic uses of botulinum toxin. N
EnglJ Med 1991; 324:1186-1194
9. Fahn S, Elton RL.,Members of the UPDRS Development Committee. In: Koller WC, erl. Handbook of Parlunson's disease.
New York: Marcel Dekker, 1987:482-488
10. Steele JC, Richardson JC, Olszewski J. Progressive supranuclear
palsy: a hererogenous degeneration involving the brainstem,
basal gangliaand cerebellum with vertical gaze and pseudobulbar
palsy, nuchal dystonia and dementia. Arch Neurol 1964;lO:
11. Barr AN. Progressive supranuclear palsy. In: Vinken PJ, Bruyn
GW, Klawans HL, eds. Handbook of clinical neurology. New
York: Elsevier Science, 1986:239-254
Eelco F. M. Wijdicks, MD,"+ Joseph E. Parisi, MD,t
and Frank W. Sharbrough, MD"
Wijdicks EFM, Parisi JE, Sharbrough Fw.
Prognosis value of myoclonus status in
comatose survivors of cardiac arrest.
Ann Neurol 1794;35:239-243
Prognostication in comatose survivors after cardiac resuscitation has several limitations. Numerous studies
have indicated the shortcomings of neurologic assessment in the first postresuscitation days. For example,
it is recognized that even in patients with early absent
motor response, full recovery is possible {I, 21.
Myoclonus status has recently been noted as a possible early prognosticator for poor outcome 13, 41. In a
pathologic study of 11 patients, Young and colleagues
[4]found that myoclonus status in comatose patients
after cardiac arrest is a measure of severe anoxic damage and dismissed the possibility of a potentially treatable seizure disorder [ S ] . Whether myoclonus is an
important predictive factor in comparison with other
clinical variables remains unclear.
From the 'Department of Neurology ($Neurology Critical Care Service) and ?Division of Anatomic Pathology, Mayo Clinic and Mayo
Foundation, Rochester, MN.
Received Jun 4 , 1993. Accepted for publication Aug 4,1993.
Address correspondence to Dr Wijdicks, Mayo Clinic, 200 First
Street SW?Rochester, M N 55905.
Copyright 0 1994 by the American Neurological Association
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botulinum, progressive, palsy, improve, rigidity, toxic, supranuclear
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