title: Decreased cortical inhibition and yet cerebellar pathology in 'familial cortical myoclonic tremor with epilepsy'.
abstract: Cortical hyperexcitability is a feature of "familial cortical myoclonic tremor with epilepsy" (FCMTE). However, neuropathological investigations in a single FCMTE patient showed isolated cerebellar pathology. Pathological investigations in a second FCMTE patient, reported here, confirmed cerebellar Purkinje cell degeneration and a normal sensorimotor cortex. Subsequently, we sought to explore the nature of cerebellar and motor system pathophysiology in FCMTE. Eye movement recordings and transcranial magnetic stimulation performed in six related FCMTE patients showed impaired saccades and smooth pursuit and downbeat nystagmus upon hyperventilation, as in patients with spinocerebellar ataxia type 6. In FCMTE patients short-interval intracortical inhibition (SICI) was significantly reduced. Resting motor threshold, recruitment curve, silent period, and intracortical facilitation were normal. The neuropathological and ocular motor abnormalities indicate cerebellar involvement in FCMTE patients. Decreased SICI is compatible with intracortical GABA(A)-ergic dysfunction. Cerebellar and intracortical functional changes could result from a common mechanism such as a channelopathy. Alternatively, decreased cortical inhibition may be caused by dysfunction of the cerebello-thalamo-cortical loop as a result of primary cerebellar pathology.
authors: Department of Neurology and Clinical Neurophysiology, University of Amsterdam, Amsterdam, the Netherlands. a.f.vanrootselaar@amc.uva.nl
authors: Anne-Fleur
authors: AF
authors: van Rootselaar
authors: Sandra M A
authors: SM
authors: van der Salm
authors: Lo J
authors: LJ
authors: Bour
authors: Mark J
authors: MJ
authors: Edwards
authors: Peter
authors: P
authors: Brown
authors: Eleonora
authors: E
authors: Aronica
authors: Johanna M
authors: JM
authors: Rozemuller-Kwakkel
authors: Peter J
authors: PJ
authors: Koehler
authors: Johannes H T M
authors: JH
authors: Koelman
authors: John C
authors: JC
authors: Rothwell
authors: Marina A J
authors: MA
authors: Tijssen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000627:therapeutic use; D002526:Cerebellar Diseases / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D002540:Cerebral Cortex / Q000473:pathology* / Q000503:physiopathology; D004594:Electrophysiology; D004831:Epilepsies, Myoclonic / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D019054:Evoked Potentials, Motor / Q000502:physiology; D005133:Eye Movements / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009759:Nystagmus, Pathologic / Q000209:etiology; D010375:Pedigree; D011698:Pursuit, Smooth / Q000502:physiology; D012438:Saccades / Q000502:physiology; D050781:Transcranial Magnetic Stimulation; D014202:Tremor / Q000473:pathology* / Q000503:physiopathology
chemical_list: D000927:Anticonvulsants