Article
Clinical Neurology
Christel Depienne, Arn M. J. M. van den Maagdenberg, Theresa Kuehnel, Hiroyuki Ishiura, Mark A. Corbett, Shoji Tsuji
Summary: Familial adult myoclonus epilepsy (FAME) is caused by the same TTTTA/TTTCA pentanucleotide repeat expansion in six different genes. The expansion affects proteins with different functions and subcellular locations, leading to neurobiological disturbances and clinical symptoms in FAME subjects. Current hypotheses propose that the expansion's pathophysiological mechanism is independent of the gene and its function, possibly involving toxicity of RNA molecules or polypeptides encoded by the repeats.
Review
Cell Biology
Claudia Cuccurullo, Pasquale Striano, Antonietta Coppola
Summary: Familial adult myoclonus epilepsy (FAME) is a non-coding repeat expansion disorder that is associated with expansions of pentanucleotide repeats in different genes. FAME is characterized by cortical tremor and myoclonus, with infrequent seizures. The underlying mechanism of FAME is thought to involve decreased sensorimotor cortical inhibition and dysfunction of the cerebellar-thalamic-cortical loop.
Article
Clinical Neurology
Samuel F. Berkovic, Pasquale Striano, Shoji Tsuji
Summary: Familial adult myoclonus epilepsy/benign adult familial myoclonic epilepsy (FAME/BAFME) is a specific and recognizable epilepsy syndrome with autosomal dominant inheritance. Initially, it was confused with other familial myoclonus epilepsies but was later recognized as a distinct syndrome in Japan. Families with this syndrome were subsequently identified worldwide, and it was found to be caused by pentanucleotide expansions in at least six genes. The phenotype varies within and between families, mainly due to expansion size.
Article
Clinical Neurology
Betul Baykan, Silvana Franceschetti, Laura Canafoglia, Gianpiero L. Cavalleri, Roberto Michelucci, Ingrid E. Scheffer
Summary: Familial adult myoclonic epilepsy (FAME) is a under-recognized disorder characterized by cortical myoclonus, generalized tonic-clonic seizures, and additional clinical symptoms, which vary depending on the FAME subtype. FAME is caused by pentanucleotide repeat expansions of intronic TTTCA/TTTTA in different genes.
Article
Clinical Neurology
Radha Mahadevan, Rahul C. Bhoyar, Natarajan Viswanathan, Raskin Erusan Rajagopal, Bobby Essaki, Varun Suroliya, Rachel Chelladurai, Saravanan Sankaralingam, Ganesan Shanmugam, Sriramakrishnan Vayanakkan, Uzma Shamim, Aradhana Mathur, Abhinav Jain, Mohamed Imran, Mohammed Faruq, Vinod Scaria, Sridhar Sivasubbu, Shantaraman Kalyanaraman
Summary: Autosomal Dominant Cortical Tremor, Myoclonus and Epilepsy is a non-progressive disorder characterized by distal tremors. A large cohort of families in south India were reported to have this condition, with no identified genetic defect. Whole-genome sequencing and repeat-primed PCR analysis revealed repeat expansions in the SAMD12 gene intron 4 in affected individuals. All patients belong to the Nadar community with unique genetic characteristics. This study represents the largest and most comprehensive report on this disorder in a specific ethnic group worldwide.
BRAIN COMMUNICATIONS
(2021)
Article
Clinical Neurology
S. Franceschetti, E. Visani, D. Rossi Sebastiano, D. Duran, T. Granata, R. Solazzi, G. Varotto, L. Canafoglia, F. Panzica
Summary: The study found that Perampanel can reduce the severity of action myoclonus by decreasing cortico-muscular coherence and restoring the leadership of cortical regions. This highlights mechanisms suitable for treating myoclonus and emphasizes the role of reduced local synchronization and better control of distant synaptic effects.
CLINICAL NEUROPHYSIOLOGY
(2021)
Article
Clinical Neurology
Anne-Fleur van Rootselaar, Sirio Cocozza, Eleonora Aronica, Pasquale Striano
Summary: Familial adult myoclonus epilepsy (FAME) is a condition characterized by cortical myoclonus and epileptic seizures. This review examines the neuroimaging and neuropathological findings in FAME, suggesting a cortical origin of the tremulous movements and indicating cerebellar functional changes. The decreased cortical inhibition via the cerebellothalamocortical loop may result in cortical hyperexcitability and clinical symptoms. Further research is needed to determine the genetic implications in FAME.
Article
Clinical Neurology
Maya Tojima, Takefumi Hitomi, Masao Matsuhashi, Shuichiro Neshige, Kiyohide Usami, Kazuki Oi, Katsuya Kobayashi, Hirofumi Takeyama, Akihiro Shimotake, Ryosuke Takahashi, Akio Ikeda
Summary: BAFME is a rare disease that causes cortical myoclonus with giant somatosensory evoked potentials (SEPs). This study aimed to establish reliable biomarkers, including high-frequency oscillations (HFOs) with giant SEPs, for the diagnosis of BAFME. Results showed that P25-HFOs with giant SEPs could be a potential biomarker for BAFME diagnosis.
MOVEMENT DISORDERS
(2021)
Review
Clinical Neurology
Caihong Ji, Jiajia Zhao, Jianfang Zhang, Kang Wang
Summary: This study reports a novel de novo NUS1 missense variant causing progressive myoclonus epilepsy (PME) and reviews the current literature on NUS1-associated PME. Only five cases of NUS1 variants and PME have been reported so far. The relationship between NUS1 variants and PME is not well-established due to limited cases reported.
NEUROLOGICAL SCIENCES
(2023)
Review
Clinical Neurology
Yun Su, Liyuan Fan, Changhe Shi, Tai Wang, Huimin Zheng, Haiyang Luo, Shuo Zhang, Zhengwei Hu, Yu Fan, Yali Dong, Jing Yang, Chengyuan Mao, Yuming Xu
Summary: The emergence of long-read single-molecule DNA sequencing technologies has opened up new possibilities for studying neurodegenerative diseases, aiding in the discovery of novel pathogenic mutations and resolving unresolved disorders. Comparing the two prevailing long-read sequencing technologies, Pacific Biosciences and Oxford Nanopore Technologies, and discussing their applications in neurodegenerative diseases.
Article
Clinical Neurology
Hyo M. Lee, Seok-Jun Hong, Ravnoor Gill, Benoit Caldairou, Irene Wang, Jian-guo Zhang, Francesco Deleo, Dewi Schrader, Fabrice Bartolomei, Maxime Guye, Kyoo Ho Cho, Carmen Barba, Sanjay Sisodiya, Graeme Jackson, R. Edward Hogan, Lily Wong-Kisiel, Gregory D. Cascino, Andreas Schulze-Bonhage, Iscia Lopes-Cendes, Fernando Cendes, Renzo Guerrini, Boris Bernhardt, Neda Bernasconi, Andrea Bernasconi
Summary: This study explores the associations between Focal cortical dysplasia (FCD) and cytoarchitecture, gene expression, and axes of cortical organization. The findings suggest that the vulnerability of the frontal lobe to FCD may be due to early termination of prenatal neurogenesis and aberrant postnatal synaptogenesis.
Review
Genetics & Heredity
Yu Fan, Yuming Xu, Changhe Shi
Summary: GGC repeat expansion in NOTCH2NLC is the most common causative factor in neuronal intranuclear inclusion disease in Asians. This expansion has been identified in various other diseases as well, suggesting a link with clinical phenotype.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Clinical Neurology
Dehao Yang, Zhidong Cen, Lebo Wang, Xinhui Chen, Peng Liu, Haotian Wang, Zhiyuan Ouyang, You Chen, Fan Zhang, Fei Xie, Bo Wang, Sheng Wu, Houmin Yin, Biao Jiang, Zhiping Wang, Junfeng Ji, Wei Luo
Summary: Patients with the GGC repeat expansion in the NOTCH2NLC gene, initially diagnosed with essential tremor (ET), may actually have neuronal intranuclear inclusion disease (NIID). Systemic areflexia could be a key clinical clue in differentiating NIID from ET.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Clinical Neurology
Xun Zhou, Hongyan Huang, Runcheng He, Sheng Zeng, Zhenhua Liu, Qian Xu, Jifeng Guo, Xinxiang Yan, Ranhui Duan, Jinchen Li, Beisha Tang, Yanming Xu, Qiying Sun
Summary: This study confirmed the association between NOTCH2NLC GGC repeat expansions and ET, and patients with pathogenic GGC repeats exhibited more severe symptoms. Further long-term follow-up and subtype studies will contribute to a better understanding of the role of NOTCH2NLC in ET.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Editorial Material
Clinical Neurology
Eduardo Benarroch
Summary: Emerging evidence suggests that different types of potassium channels play a significant role in shaping the electrophysiological properties of Purkinje cells, with potassium channel mutations being a recognized cause of SCAs and episodic ataxia. These findings point to potassium channels as potential therapeutic targets in these disorders.