Familial cortical tremor with epilepsy and cerebellar pathological findings

Abstract

The clinical and neuropathological findings in a patient with familial cortical tremor with epilepsy (FCTE) are described. Clinically, the patient showed cortical myoclonus, tremor, and generalized seizures. Pathological investigation showed cerebellar degeneration and somal sprouting and loss of dendritic tree in Purkinje cells. Striking similarities were found in diseases caused by channelopathies such as spinocerebellar ataxia subtype 6.

Simultaneous EMG‐functional MRI recordings can directly relate hyperkinetic movements to brain activity

“…The FCMTE patients belonged to a Dutch pedigree, described in detail previously [van Rootselaar et al, 2002[van Rootselaar et al, , 2004[van Rootselaar et al, , 2006. All patients were affected according to research criteria; they suffered from distal action myoclonus (clinically resembling essential tremor) and had a history of generalized tonic-clonic seizures (GTCS) or features of cortical reflex myoclonus [van Rootselaar et al, 2002].…”

“…Corticomuscular coherence studies in FCMTE patients point to a pathological cortical drive of the tremulous movements originating in the pre-or primary motor cortical areas [Grosse et al, 2003;van Rootselaar et al, 2006]. Postmortem investigations show typical cerebellar Purkinje cell degeneration in FCMTE patients [van Rootselaar et al, 2004]. It has been speculated that the cerebellar Purkinje cell degeneration leads to decreased cortical inhibition and thus to cortical hyperexcitability, as is described in other diseases characterized by cortical myoclonus of variable etiology [Hunt, 1921;Tijssen et al, 2000].…”

Autosomal dominant cortical tremor, myoclonus, and epilepsy: is the origin in the cerebellum? Editorial

“…Cortical tremor was then recognized to occur in Japanese families often in association with tonicclonic seizures, and this observation led to the definition of an autosomal dominant trait named Benign Adult Familial Myoclonic Epilepsy (BAFME), which was mapped on chromosome 8q [2,3]. Over the past decade, several European kindreds with overlapping clinical features have been reported under different acronyms, such as autosomal dominant cortical myoclonus and epilepsy and familial cortical myoclonic tremor with epilepsy (FCMTE) [4][5][6][7]. The available literature now suggests a worldwide distribution (more than 60 families have been reported) and genetic heterogeneity, yet with evidence that 2p11.1-q12.2 is a major locus for the kindreds of European origin [8].…”

“…Mutations in genes encoding ion channels have been excluded by several authors [3][4][5][6][7]. Patients typically show giant somatosensory evoked potentials and strong cortico-and intermuscular coherence in the 8-to 30-Hz range, thus suggesting an underlying cortical hyperexcitability, which can be the result of a decreased cortical inhibition by the cerebellum via its cerebello-thalamocortical projections [6].…”

“…Patients typically show giant somatosensory evoked potentials and strong cortico-and intermuscular coherence in the 8-to 30-Hz range, thus suggesting an underlying cortical hyperexcitability, which can be the result of a decreased cortical inhibition by the cerebellum via its cerebello-thalamocortical projections [6]. Indeed, rare post-mortem histological studies have shown evidence of cerebellar pathology reminiscent of SCA type 6 [3,5], and although there is no evident underlying structural brain abnormality at conventional MRI studies [3,6], proton MR spectroscopy demonstrated an elevated choline/creatine ratio, suggestive of changes in the white matter-in the cerebellar cortex [10]. Notably, imaging and pathological studies suggest involvement of the cerebellum and its projection areas, even in another different and much more common condition, i.e., essential tremor (ET).…”