Recruitment of motor cortex inhibition differentiates between generalized and focal epilepsy

Intracortical disinhibitory mechanisms play a crucial role in epilepsy. Therefore, the recruitment of motor cortical excitability was evaluated to distinct between focal and generalized epileptic syndromes. Twenty-five untreated patients with epilepsy and 20 controls were enrolled. Classification into focal (FE, n=10) or idiopathic generalized (IGE, n=15) epilepsy was based on seizure semiology, EEG and MRI. The recruitment of motor cortical inhibition and facilitation was measured by varying the stimulus intensity (SI) of the first conditioning stimulus in a paired-pulse transcranial magnetic stimulation (TMS) paradigm producing stimulus-response (S-R) curves of intracortical excitability. S-R curves were then compared with other commonly used TMS measures of cortical excitability [cortical silent period (CSP) and motor threshold (MT)]. In patients with IGE, inhibition occurred only at higher conditioning SIs compared to patients with focal epilepsy and controls. Recruitment of inhibition was unchanged in patients with focal epilepsy compared to controls. Recruitment of facilitation (ICF), CSP duration and MT, were not different between patients with FE or IGE or between patients and controls. These results suggest that the recruitment for motor cortical inhibition in patients with IGE is less effective. This may reflect a disturbed access to or an increased threshold of inhibitory neurons within the motor cortex. Impaired recruitment of inhibition might be a helpful parameter to access cortical excitability in newly diagnosed patients with generalized or focal epilepsy.

[1]  J Valls-Solé,et al.  Topography of the inhibitory and excitatory responses to transcranial magnetic stimulation in a hand muscle. , 1993, Electroencephalography and clinical neurophysiology.

[2]  Diane Ruge,et al.  Short‐interval paired‐pulse inhibition and facilitation of human motor cortex: the dimension of stimulus intensity , 2002, The Journal of physiology.

[3]  Mark Newton,et al.  Changes in cortical excitability differentiate generalized and focal epilepsy , 2007, Annals of neurology.

[4]  F. Awiszus TMS and threshold hunting. , 2003, Supplements to Clinical neurophysiology.

[5]  R. Cantello,et al.  Prolonged cortical silent period after transcranial magnetic stimulation in generalized epilepsy. , 2002, Neurology.

[6]  C. Schönfeldt-Lecuona,et al.  Epileptic seizure following 1Hz repetitive transcranial magnetic stimulation , 2006, Clinical Neurophysiology.

[7]  P J Delwaide,et al.  Reduced excitability of the motor cortex in untreated patients with de novo idiopathic “grand mal” seizures , 2001, Journal of neurology, neurosurgery, and psychiatry.

[8]  R. Mattson,et al.  Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against Epilepsy. , 1989, Epilepsia.

[9]  Ulf Ziemann,et al.  TMS and drugs , 2004, Clinical Neurophysiology.

[10]  B. Bourgeois,et al.  Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new onset epilepsy , 2004, Neurology.

[11]  W. Oertel,et al.  Motor cortex excitability in focal epilepsies not including the primary motor area--a TMS study. , 2005, Brain : a journal of neurology.

[12]  Jing Shen,et al.  The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial , 2007, The Lancet.

[13]  J. Bartko,et al.  New graphical method to measure silent periods evoked by transcranial magnetic stimulation , 2001, Clinical Neurophysiology.

[14]  G. Krauss Efficacy and tolerability of the new antiepileptic drugs I: treatment of new onset epilepsy: report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. , 2005, Neurology.

[15]  P Ryvlin,et al.  Comparison of levetiracetam and controlled-release carbamazepine in newly diagnosed epilepsy , 2007, Neurology.

[16]  Tracy Glauser,et al.  ILAE Treatment Guidelines: Evidence‐based Analysis of Antiepileptic Drug Efficacy and Effectiveness as Initial Monotherapy for Epileptic Seizures and Syndromes , 2006, Epilepsia.

[17]  D. Contreras,et al.  Spike-wave complexes and fast components of cortically generated seizures. I. Role of neocortex and thalamus. , 1998, Journal of neurophysiology.

[18]  B. Meldrum,et al.  GABAergic mechanisms in the pathogenesis and treatment of epilepsy. , 1989, British journal of clinical pharmacology.

[19]  K. R. Mills,et al.  Silent period to transcranial magnetic stimulation: construction and properties of stimulus–response curves in healthy volunteers , 2005, Experimental Brain Research.

[20]  B. Day,et al.  MOTOR CORTEX EXCITABILITY IN FOCAL AND GENERALIZED EPILEPSY , 1993 .

[21]  J. Cramer,et al.  Prognosis for total control of complex partial and secondarily generalized tonic clonic seizures , 1996, Neurology.

[22]  Graeme D Jackson,et al.  Epileptology of the first-seizure presentation: a clinical, electroencephalographic, and magnetic resonance imaging study of 300 consecutive patients , 1998, The Lancet.

[23]  J. Olsen,et al.  Validation of epilepsy diagnoses in the Danish National Hospital Register , 2007, Epilepsy Research.

[24]  S. Berkovic,et al.  Cortical excitability and recovery curve analysis in generalized epilepsy , 1999, Neurology.

[25]  J. Rothwell,et al.  The physiological basis of transcranial motor cortex stimulation in conscious humans , 2004, Clinical Neurophysiology.

[26]  L. Cohen,et al.  Mechanisms influencing stimulus-response properties of the human corticospinal system , 2001, Clinical Neurophysiology.

[27]  Paolo Manganotti,et al.  Motor Responses to Afferent Stimulation in Juvenile Myoclonic Epilepsy , 2004, Epilepsia.

[28]  G Zanette,et al.  Early and Late Intracortical Inhibition in Juvenile Myoclonic Epilepsy , 2000, Epilepsia.

[29]  D C Reutens,et al.  Prolonged cortical silent period after transcranial magnetic stimulation in generalized epilepsy , 2001, Neurology.

[30]  S Noachtar,et al.  Motor cortex excitability in patients with focal epilepsy , 2000, Epilepsy Research.

[31]  M. Morrell,et al.  Treatment of epilepsy in adults: expert opinion, 2005 , 2005, Epilepsy & Behavior.

[32]  K. Werhahn,et al.  Does the Recruitment of Excitation and Inhibition in the Motor Cortex Differ? , 2007, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[33]  J. Rothwell,et al.  Transcranial magnetic stimulation: new insights into representational cortical plasticity , 2002, Experimental Brain Research.

[34]  Janine Reis,et al.  Topiramate Selectively Decreases Intracortical Excitability in Human Motor Cortex , 2002, Epilepsia.

[35]  鯨井 隆 Corticocortical inhibition in human motor cortex , 1994 .

[36]  M G Marciani,et al.  Transcranial magnetic stimulation reveals an interhemispheric asymmetry of cortical inhibition in focal epilepsy , 2000, Neuroreport.

[37]  R. C. Oldfield The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[38]  S. Shorvon,et al.  Prognosis of chronic and newly diagnosed epilepsy: revisiting temporal aspects , 2007, Current opinion in neurology.

[39]  J C Rothwell,et al.  Physiological studies of electric and magnetic stimulation of the human brain. , 1991, Electroencephalography and clinical neurophysiology. Supplement.

[40]  E. Perucca NICE guidance on newer drugs for epilepsy in adults , 2004, BMJ : British Medical Journal.

[41]  J. Cramer,et al.  Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonic-clonic seizures. , 1985, The New England journal of medicine.

[42]  C. Capaday,et al.  Input-output properties and gain changes in the human corticospinal pathway , 1997, Experimental Brain Research.

[43]  D. McCormick,et al.  On the cellular and network bases of epileptic seizures. , 2001, Annual review of physiology.

[44]  M. Hallett Transcranial magnetic stimulation and the human brain , 2000, Nature.