Zusammenfassung
Der klinische Effekt von Botulinumtoxin A kann hauptsächlich durch die Wirkung auf
die neuromuskuläre Synapse erklärt werden. Dennoch wird eine zusätzliche zentrale
Wirkung diskutiert. Aus diesem Grund haben wir elf Patienten mit einem Torticollis
spasmodicus und drei Patienten mit einem Graphospasmus vor sowie eine und fünf Wochen
nach Erstinjektion von Botulinumtoxin A mittels Elektroneurographie und transkranieller
Magnetstimulation untersucht. Gemessen wurden die Muskelsummenaktionspotenziale, Nervenleitgeschwindigkeiten,
kürzeste F-Wellen-Latenzen, F-Wellen-Persistenz von 30 aufeinander folgenden Reizen
und motorisch evozierte Potenziale (MEP) von unbehandelten Muskeln beider Seiten (N.
ulnaris - M. abductor digiti minimi, N. peroneus - M. tibialis anterior). Die Parameter
der M-Antworten und die motorischen Nervenleitgeschwindigkeiten zeigten keine signifikanten
Veränderungen. Die F-Wellen-Latenzen beider Nerven verlängerten sich leicht eine Woche
nach Erstinjektion (t-test, p < 0,05), und erholten sich nach fünf Wochen wieder.
Die F-Wellen-Persistenz des rechten N. ulnaris und beider N. peronei war eine Woche
nach Behandlung reduziert (t-test, p < 0,05). Die motorische Gesamtleitungszeit und
die errechnete periphere Leitzeit des rechten N. ulnaris und beider N. peronei waren
eine Woche nach Behandlung verlängert und kehrten nach fünf Wochen zum Ausgangswert
zurück (t-test, p < 0,05). Die relative MEP-Amplitude und die motorische Schwelle
änderte sich nicht signifikant. Die Ergebnisse sprechen für eine verminderte Erregbarkeit
der α-Motoneurone nicht behandelter Muskeln. Supraspinale Effekte konnten nicht nachgewiesen
werden.
Abstract
The therapeutic effect of botulinum toxin type A can be explained mainly by its action
at the neuromuscular junction. However, an additional central effect has also been
proposed. Therefore eleven patients with torticollis spasmodicus and three patients
with writer's cramp were investigated using electroneurography and transcranial magnetic
stimulation (TMS) before and one and five weeks after first treatment with botulinum
toxin type A. We measured compound muscle action potentials (CMAPs), motor conduction
velocities (MCVs), the shortest (SFL) F-wave latencies, wave persistence of 30 consecutive
trials, and motor evoked potentials (MEP) of untreated muscles for each side (ulnar
nerve-abductor digiti minimi muscle, peroneal nerve-tibialis anterior muscle). CMAPs
and MCVs showed no significant changes. However, SFL for both nerves were prolonged
slightly one week after treatment and recovered after five weeks (t-test, p < 0.05).
The F-wave persistence was reduced one week after treatment for the right ulnar and
both peroneal nerves (t-test, p < 0.05). Total motor conduction time and calculated
PCT were increased one week after BoNT/A for the right ulnar and both peroneal nerves
and returned to baseline after five weeks (t-test, p < 0.05). Relative MEP amplitude
and motor threshold did not change significantly. Our results indicate a decreased
excitability of alpha motoneurons supplying untreated muscles. Supraspinal effects
could not be detected.
Key words
Botulinum toxin type A - central effects, alpha motoneuron - F-wave - transcranial
magnetic stimulation
Literatur
- 1
Dengler R, Neyer U, Wohlfarth K, Bettig U, Janzik H H.
Local botulinum toxin in the treatment of spastic drop foot.
J Neurol.
1992;
239
375-378
- 2
Jankovic J, Brin M F.
Therapeutic uses of botulinum toxin.
N Engl J Med.
1991;
324
1186-1194
- 3
Jankovic J, Schwartz K.
Botulinum toxin treatment of tremors.
Neurology.
1991;
41
1185-1188
- 4
Jankovic J, Schwartz K, Donovan D T.
Botulinum toxin treatment of cranial-cervical dystonia, spasmodic dysphonia, other
focal dystonias and hemifacial spasm.
J Neurol Neurosurg Psychiatry.
1990;
53
633-639
- 5
Valls-Sole J, Tolosa E S, Ribera G.
Neurophysiological observations on the effects of botulinum toxin treatment in patients
with dystonic blepharospasm.
J Neurol Neurosurg Psychiatry.
1991;
54
310-313
- 6
Ahnert-Hilger G, Bigalke H.
Molecular aspects of tetanus and botulinum neurotoxin poisoning.
Progress Neurobiol.
1995;
46
83-96
- 7
Blasi J, Chapman E R, Link E, Binz T, Yamasaki S, De Camilli P, Sudhof T C, Niemann H,
Jahn R.
Botulinum neurotoxin A selectively cleaves the synaptic protein SNAP-25.
Nature.
1993;
365
160-163
- 8
Wohlfarth K, Göschel H, Frevert J, Dengler R, Bigalke H.
Botulinum A toxins: units versus units.
Naunyn Schmiedebergs Arch Pharmacol.
1997;
355
335-340
- 9
Garner C G, Straube A, Witt T N, Gasser T, Oertel W H.
Time course of distant-effects of local injections of botulinum toxin.
Mov Disord.
1993;
8
33-37
- 10
Girlanda P, Vita G, Nicolosi C, Milone S, Messina C.
Botulinum toxin therapy: distant effects on neuromuscular transmission and autonomic
nervous system.
J Neurol Neurosurg Psychiatry.
1992;
55
844-845
- 11
Lange D J, Rubin M, Greene P E, Kang U J, Moskowitz C B, Brin M F, Lovelace R E, Fahn S.
Distant effects of locally injected botulinum toxin: a double-blind study of single
fiber EMG changes.
Muscle Nerve.
1991;
14
672-675
- 12
Olney R K, Aminoff M J, Gelb D J, Lowenstein D H.
Neuromuscular effects distant from the site of botulinum neurotoxin injections.
Neurology.
1988;
38
1780-1783
- 13
Jahanshahi M, Marsden C D.
Psychological functioning before and after treatment of torticollis with botulinum
toxin.
J Neurol Neurosurg Psychiatry.
1992;
55
229-231
- 14
Mikhailov V V.
Electrophysiological analysis of disturbances in reflex activity of the spinal cord
in experimental botulism.
Bull exp Biol Med.
1958;
46
1188-1192
- 15
Wiegand H, Erdmann G, Wellhöner H H.
125 I-labelled botulinum A neurotoxin: pharmacokinetics in cats after intramuscular
injection.
Arch Pharmacol.
1976;
292
161-165
- 16
Wiegand H, Wellhöner H H.
The action of botulinum neurotoxin on the inhibition by antidromic stimulation of
the lumbar monosynaptic reflex.
Arch Pharmacol.
1977;
298
235-238
- 17
Dengler R, Kossev A, Wohlfarth K, Schubert M, Elek J, Wolf W.
F-waves and motor unit size.
Muscle Nerve.
1992;
15
1138-1142
- 18
Dressnandt J, Auer C, Conrad B.
Influence of baclofen upon the alpha-motoneuron in spasticity by means of F-wave analysis.
Muscle Nerve.
1995;
18
103-107
- 19
Drory V E, Neufeld M Y, Korczyn A D.
F-wave characteristics following acute and chronic upper motor neuron lesions.
Electromyogr clin Neurophysiol.
1993;
33
441-446
- 20
Rossini P M, Berardelli A, Deuschl G, Hallett M, Maertens de Noordhout A M, Paulus W,
Pauri F.
Applications of magnetic cortical stimulation.
Electroencephalogr Clin Neurophysiol.
1999;
Suppl, 52
171-185
- 21
Gelb D J, Yoshimura D M, Olney R K, Lowenstein D H, Aminoff M J.
Change in pattern of muscle activity following botulinum toxin injections for torticollis.
Ann Neurol.
1991;
29
370-376
- 22
Fisher M A.
AAEM minimonograph # 13: H-reflexes and F-waves: physiology and clinical indications.
Muscle Nerve.
1992;
15
1223-1233
- 23
Kernell D.
Input resistance, electrical excitability and size of ventral horn cells in cat spinal
cord.
Science.
1966;
152
1637-1640
- 24
Kimura J.
Clinical value and limitations of F-wave determination. A comment.
Muscle Nerve.
1978;
1
250-252
- 25
Zappia M, Valentino P, Marchello L P, Paniccia M, Montagna P.
F-wave normative studies in different nerves of healthy subjects.
Electroencephal clin Neurophysiol.
1993;
89
67-72
- 26
Milanov I G.
A comparison of methods to assess the excitability of lower motoneurones.
Can J Neurol Sci.
1992;
19
64-68
- 27
Milanov I G.
F-wave for assessment of segmental motoneurone excitability.
Electromyogr clin Neurophysiol.
1992;
32
11-15
- 28
Fierro B, Raimondo D, Modica A.
Analysis of F response in upper motoneurone lesions.
Acta Neurol Scand.
1990;
82
329-334
- 29
Fraser J L, Olney R K.
The relative diagnostic sensitivity of different F-wave parameters in various polyneuropathies.
Muscle Nerve.
1992;
15
912-918
- 30
Bischoff C, Schoenle P W, Conrad B.
Increased F-wave duration in patients with spasticity.
Electromyogr clin Neurophysiol.
1992;
32
449-453
- 31
Byrnes M L, Thickbroom G W, Wilson S A, Sacco P, Shipman J M, Stell R, Mastaglia F L.
The corticomotor representation of upper limb muscles in writer's cramp and changes
following botulinum toxin injection.
Brain.
1998;
121
977-988
- 32
Gilio F, Currà A, Lorenzano C, Modugno N, Manfredi M, Berardelli A.
Effects of botulinum toxin type A on intracortical inhibition in patients with dystonia.
Ann Neurol.
2000;
48
20-26
- 33
Dengler R, Kossev A, Wohlfahrt K, Schubert M, Elek J, Wolf W.
F-waves and motor unit size.
Muscle Nerve.
1992;
15
1138-1142
Dr. med. Michael de Groot
Klinik und Poliklinik für Neurologie · Universitätsklinikum Leipzig
Liebigstraße 22 a
04103 Leipzig
Email: grootm@medizin.uni-leipzig.de