Altered cerebellar‐cerebral functional connectivity in benign adult familial myoclonic epilepsy

Abstract

SUMMARYObjective: The pathogenesis of benign adult familial myoclonic epilepsy (BAFME) remains unknown, although cerebellar pathologic changes and brain hyperexcitability have been reported. We used resting-state functional magnetic resonance imaging (fMRI) to examine the functional connectivity between the cerebellum and cerebrum in a Chinese family with BAFME for the first time. Methods: Eleven adults with BAFME and 15 matched healthy controls underwent resting-state blood oxygen level-dependent (BOLD) fMRI scanning. The cerebellar seeds, including the bilateral crus I, lobule VIII, lobule VIIb, and lobule IV&V, were defined a priori. Next, regional time courses were obtained for each individual by averaging the BOLD time series over all voxels in each seed region. Then, seed-based functional connectivity z-maps were produced by computing Pearson's correlation coefficients (converted to z-scores by Fisher transformation) between each seed signal and the time series from all other voxels within the entire brain. Finally, a second-level randomeffect two-sample t-test was performed on the individual z-maps in a voxel-wise manner. Results: Reduced functional connectivity of the right cerebellar crus I with the left middle frontal gyrus and right cerebellar lobule IX was observed in the default network of BAFME. Enhanced functional connectivity of the left cerebellar lobule VIII with the bilateral middle temporal gyri, right putamen, and left cerebellar crus I was found in the dorsal attention network of BAFME. Enhanced functional connectivity between the left cerebellar lobule VIIb and right frontal pole was found in the control network of BAFME. Significance: Altered cerebellar-cerebral functional connectivity may contribute to the understanding of the nosogenesis of BAFME and explain the cognitive dysfunction in this Chinese family with BAFME.

TTTCA Repeat Expansion of SAMD12 in a New Benign Adult Familial Myoclonic Epilepsy Pedigree

“…First, there were only five (5/12) individuals presenting cortical tremor earlier than seizure, which was different from the conclusion that tremor was usually the first symptom (12). Besides, cognitive impairment was found by MMSE and VFT, which was basically consistent with our previous research (13). In addition, maternal clinical anticipation was observed in six mother/child pair.…”

“…According to previous studies, BAFME patients showed elevated choline/creatine ratio in the cerebellar cortex (22). The existence of cerebellar dysfunction was then proved in a Chinese BAFME pedigree along with altered cerebellarcerebral functional connectivity (13,23). In the report of the Japanese BAFME pedigrees, there were no obvious alterations in SAMD12 transcript 1 levels observed in patient's brain, but RNA lesions were observed in cortical neurons and Purkinje cells, which was consistent with MRI findings, suggesting that RNA-mediated toxicity might be the basis of the pathogenesis in BAFME.…”

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

“…- Other findings include migraine, 15 – 18 ophthalmic migraine, 37 headaches, 40 logopenic syndrome, 67 visual intolerance, 61 frontal dysfunction, 61 night blindness, 68 motionless state, 69 absence seizures, 18 parkinsonism, 48 reduced verbal fluency, 70 sensitivity to glucose deprivation or vibration as an aggravating factor, 37 , 38 and visuospatial impairment. 9 , 52 …”

“… 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. 10 …”

“… 14 Pathology findings in a Dutch FCMTE pedigree indicate Purkinje cell changes, resembling the abnormal neuronal morphology in Ctnnd2 mutant mice. 1 , 39 , 50 Congruent imaging findings include decreased fiber density, 51 functional connectivity alterations 52 and gray matter loss in the cerebellar motor area. 53 It has been hypothesized that, via the cerebello-thalamo-cortical loop, reduced input from the cerebellum can lead to cortical hyperexcitability.…”