Neurology -- Correspondence for Kessler et al., 59 (7) 1028-1033

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Correspondence published:

Reply to Letter to the Editor: Kirn R. Kessler, Alfons Schnitzler, Joseph Classen, and Reiner Benecke (18 November 2002)

Reduced inhibition within primary motor cortex in patients with poststroke focal motor seizures: Massimo Cincotta, Alessandra Borgheresi, Fabrizio Balestrieri, and Gaetano Zaccara (18 November 2002)

Reply to Letter to the Editor 18 November 2002

Kirn R. Kessler
J. W. Goethe Universitat Frankfurt Germany,
Alfons Schnitzler, Joseph Classen, and Reiner Benecke
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Re: Reply to Letter to the Editor

Kim.Kessler{at}kgu.de Kirn R. Kessler, et al.

We appreciate the comments made by Cincotta et al. who are pointing out some essential aspects of our study. Regarding their first main point, the intraindividual variability of the cortical silent period (CSP) determined in 10 single trials was fairly low, while the interindividual variation of CSP duration was indeed quite high, as has been reported previously in the literature. [1] Unfortunately, group comparisons in either the fist dorsal interosseus (FDI) or tibialis anterior (TA) as suggested by Cincotta et al. was impossible due to the small sample sizes (n=3). Nevertheless, there was a significant group difference in CSP duration when comparing the means of all affected muscles vs. their unaffected counterpart (n=6, W=-21.0, p<0.03; Wilcoxon signed rank test). Furthermore, to determine the potential of this method for assessing the individual risk for a stroke patient to develop post-stroke seizures, it seemed appropriate to show significant differences of CSP duration individually than to merely demonstrate a group effect.
We are of course aware of the investigations cited by Cincotta et al. extending and underscoring an important issue also raised in our paper, namely the obviously conflicting results brought forth by previous noninvasive investigations of cortical excitability in patients with epilepsy. There are a number of potential clinical (e.g. type and duration of epilepsy, antiepileptic therapy) and methodological (e.g. threshold, CSP, paired pulse technique) reasons as to why this issue is still unresolved. Furthermore, the exact physiology of the CSP is hitherto not completely understood, but our assumption that a reduced CSP indicates impaired intracortical inhibition is certainly in line with earlier findings of a reduced intracortical inhibition using paired pulse paradigms in patients with focal epilepsies. [2, 3] We were able to show an association of a markedly reduced CSP and the occurrence of post-stroke seizures. This may indeed suggest that symptomatic post-stroke epilepsy be characterized by a pathophysiological mechanism that is quite distinct from that in cryptogenic motor cortex epilepsy. Along with Cincotta et al. we hope that this case series will stimulate further investigations along this line.
References:
1. Fritz C, Braune HJ, Pylatiuk C, et al. Silent period following transcranial magnetic stimulation: a study of intra- and inter-examiner reliability. Eletrocencaphalogr Clin Neurophysiol 1997;105:235-241.
2. Fong JKY, Werhahn KJ, Rothwell JC et al. Motor cortex excitability during the silent period in focal and generalized epilepsy. J Physiol (Lon) 1993; 459: 468P.
3. Inghilleri M, Mattia D, Berardelli A, Manfredi M. Asymmetry of cortical excitability revealed by transcranial stimulation in a patient with focal motor epilepsy and cortical myoclonus. Electroencephalogr Clin Neurophysiol 1998;109:70-72.

Reduced inhibition within primary motor cortex in patients with poststroke focal motor seizures 18 November 2002

Massimo Cincotta
Santa Maria Nuova Hospital Florence Italy,
Alessandra Borgheresi, Fabrizio Balestrieri, and Gaetano Zaccara
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Re: Reduced inhibition within primary motor cortex in patients with poststroke focal motor seizures

massimo.cinotta{at}unifi.it Massimo Cincotta, et al.

We read with interest the article by Kessler et al., [1] who selected a subgroup of six patients with ischemic stroke in which the cortical silent period (CSP) following transcranial magnetic stimulation (TMS) was shortened by at least 25% in either the upper or the lower affected limb compared with the unaffected side. Focal motor seizures occurred in five of these patients, whereas none of 76 control patients with normal or prolonged CSP developed poststroke seizures. As the CSP likely reflects GABAB-mediated inhibitory mechanisms within the primary motor cortex, [2] the authors suggest that seizures following ischemic stroke may be due to a selective impairment of GABAergic interneurons at the epileptic focus. There are, however, some weaknesses in these findings. (i) From Table 2 it seems that significant intraindividual differences of the CSP duration were found by using single trials as samples of data. In contrast, no significant difference between the affected and the unaffected side would had been observed in either the first dorsal interosseous (FDI) or tibialis anterior if one had used the mean CSP duration of each subject to perform conventional parametric (paired sample t-test) or nonparametric (Wilcoxon signed rank test) statistic analysis within the whole group of six patients. Moreover, in Patient 1, who suffered from focal motor seizures in the left arm, the CSP was prolonged in the affected FDI compared with the right one. (ii) In two out of five patients, the time lag between stroke and first seizure was longer than the follow-up period for the control patients with normal or prolonged CSP after the stroke.
A number of previous papers, which are not cited by Kessler et al., showed that the CSP could be prolonged in patients with partial seizures involving the motor cortex or generalized epilepsy. [3, 4, 5, 6, 7] Epileptic conditions are characterized by pathophysiological mechanisms leading to seizures and interictal compensatory phenomena. [8] As a given epileptic syndrome can be due to different processes, we hypothesize that the CSP can be either reduced or prolonged, if the underlying neural circuits are involved in the epileptogenesis or in the interictal compensatory mechanisms, respectively. Although the present data do not allow to draw conclusions, the findings reported by Kessler et al. suggest that further studies using likewise homogeneous case series may help to clarify this point.
REFERENCES
1. Kessler KR, Schnitzler A, Classen J, Benecke R. Reduced inhibition within primary motor cortex in patients with poststroke focal motor seizures. Neurology 2002;59:1028-1033.
2. Siebner HR, Dressnandt J, Auer C, Conrad B. Continuous intrathecal baclofen infusions induced a marked increase of the transcranially evoked silent period in a patient with generalized dystonia. Muscle Nerve 1998;21:1209-1215.
3. Classen J, Witte OW, Schlaug G, et al. Epileptic seizures triggered directly by focal transcranial magnetic stimulation. Electroenceph Clin Neurophysiol 1995;94:19-25.
4. Cincotta M, Borgheresi A, Lori S, Fabbri M, Zaccara G. Interictal inhibitory mechanisms in patients with cryptogenic motor cortex epilepsy: a study of the silent period following transcranial magnetic stimulation. Electroencephalogr Clin Neurophysiol 1998;107:1-7.
5. Ertas NK, Gul G, Altunhalka A, Kirbas D. Cortical silent period following transcranial magnetic stimulation in epileptic patients. Epileptic Disord 2000;2:137-140.
6. Macdonell RA, King MA, Newton MR, et al. Prolonged cortical silent period after transcranial magnetic stimulation in generalized epilepsy. Neurology 2001;57:706-708.
7. Cincotta M, Borgheresi A, Benvenuti F, et al. Cortical silent period in two patients with meningioma and preoperative seizures: a pre- and postsurgical follow-up study. Clin Neurophysiol 2002;113:597-603.
8. Engel J Jr. Inhibitory mechanisms of epileptic seizure generation. In: Fahn S, Hallett M, L�ders HO, Marsden CD, eds. Advances in Neurology. Vol 67. Negative Motor Phenomena. Philadelphia: Lippincott- Raven Publishers, 1995:157-171.