Zusammenfassung
Einleitung: Ziel der Studie war die Untersuchung therapeutischer Effekte repetitiver transkranieller Magnetstimulation (rTMS) bei Patienten mit zervikaler Dystonie. Methodik: 15 Patienten mit Torticollis spasmodicus (mittleres Alter 46,5 Jahre) wurden zufällig entweder einer aktiven (1 Hz rTMS, 90 % der motorischen Schwelle, 15 min Reizdauer, Stimulationsort motorischer Kortex kontralateral zur Seite der Kopfrotation) oder Plazebobehandlung (Abhalten der Spule im Winkel von 45°) zugeordnet. Therapieeffekte wurden klinisch mit dem Toronto Western Spasmodic Torticollis Rating Scale (TWSTR) und dem Tsui-Score bestimmt. Zusätzlich wurden motorisch evozierte Potenziale (MEPs) vom M. flexor carpi radialis (FCR) durch Einzel- und Doppelpulsmagnetstimulation (Interstimulusintervall 3 und 13 ms) abgeleitet. Die Doppelpulsstimulation diente der Beurteilung von Mechanismen intrakortikaler Inhibition (ICI) bzw. Fazilitierung (ICF). Ergebnisse: Während die aktive rTMS keinen signifikanten Einfluss auf klinische Symptome hatte (im TWSTR zeigte sich lediglich ein Trend zur Verbesserung, p < 0,10), waren die MEPs nach einer fazilitierenden Doppelpulsmagnetstimulation (13 ms) unter aktiver rTMS supprimiert. Des Weiteren zeigten die MEP-Latenzen einen Trend zur Verlängerung unter aktiver Behandlung. Diskussion: Eine inhibierende rTMS des motorischen Kortex zeigte keine signifikanten therapeutischen Effekte. Allerdings kam es unter aktiver Behandlung zu einer Verminderung der kortikalen Exzitabilität. Dieses Ergebnis könnte dafür sprechen, dass weniger kortikale als vielmehr subkortikale Störungen zur klinischen Symptomatik bei zervikaler Dystonie führen.
Abstract
Objective: To study therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) in patients with cervical dystonia (CD). Method: 15 torticollis patients (mean age 46.5 years) were randomly assigned to active treatment (1 Hz inhibiting rTMS, intensity 90 % of motor threshold, 15 min train, stimulation site motor cortex contralateral to the direction of head rotation) or sham treatment (angle of the coil 45° off the skull). Clinical outcome was determined using a Toronto Western Spasmodic Torticollis Rating Scale (TWSTR) and a Tsui-score. In addition, motor-evoked potentials (MEPs) were obtained from the flexor carpi radialis (FCR) muscle, using single-pulse transcranial magnetic stimulation (TMS), and paired-pulse TMS (inter-stimulus intervals 3 vs. 13 ms) to test for intracortical inhibition (ICI) and facilitation (ICF). Results: While clinical symptoms did not change significantly (there was only a trend for the TWSTR to improve, p < 0.10), MEPs after facilitating paired-pulse TMS (13 ms) were significantly reduced after active rTMS treatment (p < 0.05). Further, MEP latency (with 3 ms ISI) tended to increase under active treatment (p < 0.10). Discussion: Inhibiting rTMS of the motor cortex in CD patients failed to induce beneficial therapeutic effects. However, cortical excitability decreased under active rTMS. This finding may indicate that subcortical dysfunction in CD does account for clinical features of CD to a higher degree than cortical mechanisms.
Key words
Repetitive transcranial magnetic stimulation (rTMS) - cervical dystonia - paired-pulse TMS - intracortical inhibition - intracortical facilitation
Literatur
1
Berardelli A, Rothwell J C, Hallett M, Thompson P D, Manfredi M, Marsden C D.
The pathophysiology of primary dystonia.
Brain.
1998;
121
1195-1212
2
Ridding M C, Sheean G, Rothwell J C, Inzelberg R, Kujirai T.
Changes in the balance between motor cortical excitation and inhibition in focal, task specific dystonia.
J Neurol Neurosurg Psychiatry.
1995;
59
493-498
3
Däuper J, Peschel T, Kohlmetz C, Joppich G, Schrader C, Nager W, Dengler R, Rollnik J D.
Effects of subthalamic nucleus (STN) stimulation on motor cortex excitability.
Neurology.
2002;
59
700-706
4
Ikoma K, Samii A, Mercuri B, Wassermann E M, Hallett M.
Abnormal cortical motor excitability in dystonia.
Neurology.
1996;
46
1371-1376
5
Mavroudakis N, Caroyer J M, Brunko E, Zegers-de-Beyl D.
Abnormal motor evoked responses to transcranial magnetic stimulation in focal dystonia.
Neurology.
1995;
45
1671-1677
6
Curra A, Romaniello A, Berardelli A, Cruccu G, Manfredi M.
Shortened cortical silent period in facial muscles of patients with cranial dystonia.
Neurology.
2000;
54
130-135
7
Siggelkow S, Kossev A, Moll C, Dengler R, Rollnik J D.
Impaired sensorimotor integration in cervical dystonia - a study using TMS and muscle vibration.
J Clin Neurophysiol.
2002;
19
32-239
8
Amadio S, Panizza M, Pisano F, Maderna L, Miscio C, Nilsson J, Volonte M A, Comi G, Galardi G.
Transcranial magnetic stimulation and silent period in spasmodic torticollis.
Am J Phys Med Rehabil.
2000;
79
361-368
9
Gilio F, Curra 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
10
Rollnik J D, Kohlmetz C, Rodríguez-Fornells A, Kurzbuch A R, Däuper J, Möller J, Münte T F.
Functional lesions and human action monitoring: combining repetitive transcranial magnetic stimulation and event-related brain potentials.
Clin Neurophysiol.
2004;
115
145-153
11
Chen R, Classen J, Gerloff C, Celnik P, Wassermann E M, Hallett M, Cohen L G.
Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation.
Neurology.
1997;
48
1398-1403
12
Rollnik J D, Düsterhöft A, Däuper J, Kossev A, Weissenborn K, Dengler R.
Decrease of middle cerebral artery blood flow velocity after low-frequency repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex.
Clin Neurophysiol.
2002;
113
951-955
13
Berardelli A, Inghilleri M, Rothwell J C, Romeo S, Curra A, Gilio F, Modugno N, Manfredi M.
Facilitation of muscle evoked responses after repetitive cortical stimulation in man.
Exp Brain Res.
1998;
122
79-84
14
Rollnik J D, Siggelkow S, Schubert M, Schneider U, Dengler R.
Muscle vibration and prefrontal repetitive transcranial magnetic stimulation.
Muscle Nerve.
2001;
24
112-115
15
Rollnik J D, Schubert M, Dengler R.
Subthreshold prefrontal repetitive transcranial magnetic stimulation reduces motor cortex excitability.
Muscle Nerve.
2000;
23
112-114
16
Rollnik J D, Huber T J, Mogk H, Siggelkow S, Kropp S, Dengler R, Emrich H M, Schneider U.
High-frequency repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex in schizophrenic patients.
Neuroreport.
2000;
11
4013-4015
17
Siebner H R, Tormos J M, Ceballos-Baumann A O, Auer C, Catala M D, Conrad B, Pascual-Leone A.
Low-frequency repetitive transcranial magnetic stimulation of the motor cortex in writer's cramp.
Neurology.
1999;
52
529-537
18
Tsui J K, Eisen A, Stoessl A J, Calne S, Calne D B.
Double-blind study of botulinum toxin in spasmodic torticollis.
Lancet.
1986;
2
245-247
19
Consky E, Basinski A, Belle L, Ranawaya R, Lang A E.
The Toronto Western Spasmodic Torticollis Rating Scale (TWSTR): assessment of validity and interrater reliability.
Neurology.
1990;
40, Suppl 1
445
20 Consky E S, Lang A E. Clinical assessments of patients with cervical dystonia. In: Jankovic J, Hallett M (eds) Therapy with botulinum toxin. New York; Marcel Dekker 1994: 211-237
21
Kossev A R, Schrader C, Däuper J, Dengler R, Rollnik J D.
Increased intracortical inhibition in middle-aged humans - a study using paired- pulse TMS.
Neurosci Lett.
2002;
333
83-86
22
Kossev A R, Siggelkow S, Dengler R, Rollnik J D.
Intracortical inhibition and facilitation in paired transcranial magnetic stimulation: effect of conditioning stimulus intensity on sizes and latencies of motor evoked potentials.
J Clin Neurophysiol.
2003;
20
54-58
Prof. Dr. Jens D. Rollnik
Neurologische Klinik Hessisch-Oldendorf
Greitstraße 18 - 28
31840 Hessisch-Oldendorf
Email: prof.rollnik@nkho.de