A case-control proton magnetic resonance spectroscopy study confirms cerebellar dysfunction in benign adult familial myoclonic epilepsy

Abstract

BackgroundBenign adult familial myoclonic epilepsy (BAFME) is a rare form of epilepsy syndrome. The pathogenesis of BAFME remains unclear, though it seems to involve dysfunction of the cerebellum.ObjectivesThe purpose of this study was to use proton magnetic resonance spectroscopy (1H-MRS) to investigate whether neurochemical changes underlie abnormal brain function in BAFME.MethodsTwelve BAFME patients from one family and 12 age- and sex-matched healthy controls were enrolled in this study. The ratios of NAA/Cr, NAA/Cho, Cho/Cr, and NAA/(Cr+Cho) were analyzed.ResultsThe BAFME patients exhibited a decreased N-acetylaspartate (NAA)/choline (Cho) ratio in the cerebellar cortex, whereas there were no significant differences in the NAA/creatine (Cr), Cho/Cr, and NAA/(Cr+Cho) ratios compared with healthy controls. There were no significant differences in 1H-MRS values in the frontal cortex or thalamus between the BAFME patients and controls. No correlation was detected between the NAA/Cho ratio in the cerebellar cortex and disease duration, myoclonus severity, or tremor severity.ConclusionOur results indicate clear cerebellar dysfunction in BAFME. 1H-MRS is a useful tool for the diagnosis of BAFME in combination with family history and electrophysiological examination.

Gray Matter Loss and Related Functional Connectivity Alterations in A Chinese Family With Benign Adult Familial Myoclonic Epilepsy

“… 13 1 H-MR spectroscopy was used to demonstrate prominent cerebellar dysfunction in BAFME. 14 , 15 A diffusion tensor imaging study reported decreased cerebellar fiber density in BAFME, 16 and a case study found fronto-striatal dysfunction in type 3 BAFME during aging using single photon emission computed tomography. 17 It seems that cerebellar atrophy is a convergent finding in BAFME patients.…”

Familial Cortical Myoclonic Tremor and Epilepsy, an Enigmatic Disorder: From Phenotypes to Pathophysiology and Genetics. A Systematic Review

“…- Cerebellar findings include in French pedigrees mild ataxia and gait instability, 17 , 37 , 38 , 62 (downbeat) nystagmus increasing with hyperventilation in a Dutch pedigree, 14 and dysarthria in South African/French pedigrees. 10 , 38 Ataxia is not a feature of FCMTE 16 , 17 , 27 , 47 , 57 , 58 , 60 , 65 but subtle cerebellar signs have not explicitly been ruled out.…”

“…Valproate is the drug most often reported to be effective with or without clonazepam. 13 , 16 , 17 , 27 , 43 , 47 , 48 , 56 , 58 , 60 , 65 , 74 Because of teratogenicity, this should not be prescribed to women of childbearing age. Newer AEDs with a good effect are levetiracetam 13 , 17 , 37 , 38 , 43 , 46 , 48 , 58 , 74 , 75 and lamotrigine.…”

“… Long et al 52 Chinese, excl. 2p, 8q RS fMRI (BOLD) 11 FCMTE, 15 HS DN: R crus I with L frontal + R lobule IX ⬇ n.d. Functional connectivity AN: L lobule VIII with temporal, R putamen and L crus I ⬆ CN: L lobule VIIb and R frontal ⬆ Long et al 65 Chinese, excl. 2p, 8q 1 H-MRS 12 FCMTE, 12 HS, Neurochemical ratios NAA/Cho ratio ⬇ n.a.…”

“… 39 Moreover, imaging findings in the same pedigree showed decreased cerebellar fiber density 51 and gray matter loss in the cerebellar motor area. 53 In a Chinese pedigree in which 8q and 2p linkage was excluded, MRS indicated cerebellar dysfunction 65 and a fMRI study indicated alterations between the cerebellum and supratentorial structures after network analysis. 52 A South African pathology case, from a pedigree in which 8q and 2p linkage was excluded, revealed focal Purkinje cell loss, neuronal atrophy in the dentate nucleus, and neuronal loss with gliosis in the olives and pallidum.…”