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Journal of Medical Genetics Mar 202022q11.2 deletion syndrome (22q11.2DS) is considered as the genetic model of schizophrenia. However, its polymorphic nature has led researchers to further investigate its...
BACKGROUND
22q11.2 deletion syndrome (22q11.2DS) is considered as the genetic model of schizophrenia. However, its polymorphic nature has led researchers to further investigate its neuropsychiatric manifestations.
METHODS
We enrolled 56 adults (38 men, 18 women) diagnosed with 22q11.2DS. All subjects were evaluated by a multidisciplinary team. The neuropsychiatric features were investigated by means of clinical and neurophysiological evaluation (video-EEG).
RESULTS
Thirty per cent of our patients were left-handed. Fifty-eight per cent had a low IQ, and 22 of 56 subjects had psychotic disorders (13 of 22 with schizophrenia). Eighteen patients reported at least one seizure in their lifetime, and ten were diagnosed with epilepsy; among them, seven had genetic generalised epilepsy (GGE), and five of seven showed features suggestive of juvenile myoclonic epilepsy (JME). Video-EEG recordings revealed generalised epileptiform abnormalities in 24 of 56 cases. Besides, only one patient with epilepsy had a cardiac malformation. Lastly, 31 of 56 subjects presented with parkinsonism, 16 of whom were taking neuroleptics. None of the 15 patients with parkinsonism not related to neuroleptic therapy was diagnosed with epilepsy, compared with 6 of those taking antipsychotics.
CONCLUSIONS
22q11.2DS is characterised by left-handedness and neuropsychiatric features such as cognitive impairment, schizophrenia, epilepsy and parkinsonism. GGE, mostly the JME phenotype, is the predominant epilepsy type. The significant association between 22q11.2DS and parkinsonian features confirms these patients' genetic susceptibility to parkinsonism. Despite the lack of any conclusive evidence, our study suggests a possible relationship between the analysed clinical variables: (1) an inverse correlation between low IQ/psychosis/epilepsy and major cardiac diseases; (2) a direct association between psychosis and both mental delay and epilepsy; and (3) an inverse correlation between parkinsonism and epilepsy.
Topics: Adolescent; Adult; DiGeorge Syndrome; Epilepsies, Myoclonic; Female; Functional Laterality; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Parkinsonian Disorders; Phenotype; Schizophrenia; Young Adult
PubMed: 31506323
DOI: 10.1136/jmedgenet-2019-106223 -
Epileptic Disorders : International... Apr 2021The aim of the study was to describe the electroclinical features of visual sensitivity in patients with familial cortical myoclonic tremor and epilepsy. We searched the...
The aim of the study was to describe the electroclinical features of visual sensitivity in patients with familial cortical myoclonic tremor and epilepsy. We searched the EEG database using the terms "familial cortical myoclonic tremor and epilepsy" and "visual sensitivity" over a seven-year period from March 2013 to April 2020 in the Xijing hospital, Xi'an, China. The inclusion criteria were demonstrable electroclinical visual sensitivity in the form of eye-opening sensitivity, eye-closure sensitivity, eyes-closed sensitivity and photosensitivity. Clinical, EEG and imaging records of patients were screened, and subsequently, detailed analysis of their data was undertaken. We enrolled six patients with visual sensitivity, five of whom suffered with rare generalized tonic-clonic seizures. Neuroimaging was negative in all cases. All patients demonstrated photosensitivity; eye-opening sensitivity associated with cortical myoclonic in one patient, eyes-closed sensitivity associated with cortical myoclonic tremor status in three patients, and eye-closure sensitivity in two patients. At the last follow-up visit, cortical myoclonic tremor and epilepsy in all patients was well controlled with first-line treatment. Visual sensitivity is therefore likely to be an important reflex trait in some patients with familial cortical myoclonic tremor and epilepsy, and should be routinely evaluated in order to better define the electroclinical features in FCMTE syndrome. [Published with video sequences].
Topics: Electroencephalography; Epilepsies, Myoclonic; Humans; Pedigree; Photosensitivity Disorders; Tremor
PubMed: 33935025
DOI: 10.1684/epd.2021.1278 -
Journal of Clinical Neurophysiology :... Sep 2019Smartphones and other personal electronic devices present novel cortical processing tasks with potential for identification of novel EEG waveforms. A 17-year-old patient...
Smartphones and other personal electronic devices present novel cortical processing tasks with potential for identification of novel EEG waveforms. A 17-year-old patient with epilepsy manifested as recurrent myoclonic seizures, absence seizures, and a single generalized tonic-clonic seizure was hospitalized to undergo video-EEG monitoring for seizure quantification and classification of the epilepsy syndrome. During the monitoring session, a frontocentral predominant 5 to 6 Hz theta rhythm was identified only when the patient was actively texting or playing a video game on his smartphone. Previously, patients with focal epilepsy have been found to have a frontocentral theta rhythm on EEG while texting on mobile devices. We report similar EEG findings in a patient with genetic generalized epilepsy during smartphone gaming to expand the population and triggers for this theta waveform. Given the young age and type of epilepsy, we suggest that the waveform represents the EEG manifestation of the attention-visuomotor pathway that is stimulus independent.
Topics: Adolescent; Electroencephalography; Epilepsies, Myoclonic; Humans; Male; Smartphone; Text Messaging; Theta Rhythm; Video Games
PubMed: 31490453
DOI: 10.1097/WNP.0000000000000575 -
Medicine Sep 2022Myoclonic epilepsy in infancy (MEI) is a rare syndrome characterized by generalized myoclonic seizures (MS) that occur within the first 3 years of life. In the present...
Myoclonic epilepsy in infancy (MEI) is a rare syndrome characterized by generalized myoclonic seizures (MS) that occur within the first 3 years of life. In the present study, the form of onset, and clinical and electroencephalogram (EEG) features were analyzed. A retrospective chart review was conducted for 16 MEI patients between March 2009 and July 2022 in Peking Union Medical College. The clinical and video EEG (VEEG) characteristics, treatment strategy, and follow-up information were analyzed. Four cases presented with afebrile generalized tonic-clonic seizures (GTCS) at the onset of MEI (GTCS at onset or atypical MEI), while 12 cases presented with MS at onset (MS at onset or typical MEI). The 24-hour VEEG revealed a generalized discharge of polyspike (or spike)-and-wave complexes that lasted for 1-3 seconds in the ictal phase. All patients were treated with valproic acid monotherapy, and none of the patients experienced seizure recurrence. Furthermore, all patients had normal psychomotor development at the end of the follow up period. Typical MEI (MS at onset) and atypical MEI (GTCS at onset) were described in the present study. These 2 groups differed in form of onset, but there were no significant differences in clinical or EEG features.
Topics: Electroencephalography; Epilepsies, Myoclonic; Humans; Retrospective Studies; Seizures; Valproic Acid
PubMed: 36197249
DOI: 10.1097/MD.0000000000030512 -
Medicina 2023Juvenile myoclonic epilepsy (JME) is an epileptic syndrome with onset in childhood and adolescence with myoclonus, absences, and generalized tonic-clonic seizures....
INTRODUCTION
Juvenile myoclonic epilepsy (JME) is an epileptic syndrome with onset in childhood and adolescence with myoclonus, absences, and generalized tonic-clonic seizures. Reflex stimuli such as sensitivity to light or photosensitivity, eyelid opening and closing, and praxis induction produce epileptiform discharges and seizures. These reflex triggers are not all systematically studied.
OBJECTIVE
Examine reflex features in patients with JME.
METHODS
One hundred adolescents and adults with JME who received different anti-seizure treatments were evaluated consecutively. A standard electroencephalogram was performed with an intermittent light stimulation (SLI) protocol and another for the evaluation of praxias through neurocognitive activity (CNA). The statistical analysis was descriptive and of correlation with a p > 0.05.
RESULTS
Current age was 28±11 (14-67). The seizure began at 15 years ±3 (Range 8-25 years). They presented myoclonus and generalized tonic-clonic seizures in 58%. 50% received valproic acid and 31% continued with seizures. Epileptiform discharges at rest 20%; hyperventilation 30%; eyelid opening and closing 12%; photoparoxysmal response in SLI 40%; CNA 23%. Higher percentage of discharges and delay in performing CNA in those who presented seizures. Valproic acid compared to other drugs did not demonstrate superiority in seizure control.
CONCLUSIONS
These findings confirm the importance of studying reflex traits for diagnosis, follow-up, and therapeutic control.
Topics: Adult; Adolescent; Humans; Myoclonic Epilepsy, Juvenile; Valproic Acid; Myoclonus; Electroencephalography; Reflex; Seizures; Epilepsies, Myoclonic
PubMed: 38117708
DOI: No ID Found -
Neurobiology of Disease Sep 2023The progressive myoclonic epilepsies (PMEs) are a group of rare neurodegenerative diseases characterized by myoclonus, epileptic seizures, and progressive neurological... (Review)
Review
The progressive myoclonic epilepsies (PMEs) are a group of rare neurodegenerative diseases characterized by myoclonus, epileptic seizures, and progressive neurological deterioration with cerebellar involvement. They include storage diseases like Gaucher disease, Lafora disease, and forms of neuronal ceroid lipofuscinosis (NCL). To date, 13 NCLs have been reported (CLN1-CLN8, CLN10-CLN14), associated with mutations in different genes. These forms, which affect both children and adults, are characterized by seizures, cognitive and motor impairments, and in most cases visual loss. In NCLs, as in other PMEs, central nervous system (CNS) neurodegeneration is widespread and involves different subpopulations of neurons. One of the most affected regions is the cerebellar cortex, where motor and non-motor information is processed and transmitted to deep cerebellar nuclei through the axons of Purkinje cells (PCs). PCs, being GABAergic, have an inhibitory effect on their target neurons, and provide the only inhibitory output of the cerebellum. Degeneration of PCs has been linked to motor impairments and epileptic seizures. Seizures occur when some insult upsets the normal balance in the CNS between excitatory and inhibitory impulses, causing hyperexcitability. Here we review the role of PCs in epilepsy onset and progression following their PME-related loss. In particular, we focus on the involvement of PCs in seizure phenotype in NCLs, highlighting findings from case reports and studies of animal models in which epilepsy can be linked to PC loss.
Topics: Animals; Neuronal Ceroid-Lipofuscinoses; Purkinje Cells; Myoclonic Epilepsies, Progressive; Epilepsy; Seizures
PubMed: 37573956
DOI: 10.1016/j.nbd.2023.106258 -
Epilepsy & Behavior : E&B Jun 2022Dravet syndrome is a well-established electro-clinical condition first described in 1978. A main genetic cause was identified with the discovery of a loss-of-function... (Review)
Review
Dravet syndrome is a well-established electro-clinical condition first described in 1978. A main genetic cause was identified with the discovery of a loss-of-function SCN1A variant in 2001. Mechanisms underlying the phenotypic variations have subsequently been a main topic of research. Various genetic modifiers of clinical severities have been elucidated through many rigorous studies on genotype-phenotype correlations and the recent advances in next generation sequencing technology. Furthermore, a deeper understanding of the regulation of gene expression and remarkable progress on genome-editing technology using the CRISPR-Cas9 system provide significant opportunities to overcome hurdles of gene therapy, such as enhancing Na1.1 expression. This article reviews the current understanding of genetic pathology and the status of research toward the development of gene therapy for Dravet syndrome. This article is part of the Special Issue "Severe Infantile Epilepsies".
Topics: Epilepsies, Myoclonic; Epilepsy; Epileptic Syndromes; Genetic Therapy; Humans; NAV1.1 Voltage-Gated Sodium Channel; Spasms, Infantile
PubMed: 34053869
DOI: 10.1016/j.yebeh.2021.108043 -
Neurologia I Neurochirurgia Polska 2022Cannabis sativa has been cultivated for human use for about 5,000 years, and has likewise been used in the treatment of epilepsy for thousands of years.
INTRODUCTION
Cannabis sativa has been cultivated for human use for about 5,000 years, and has likewise been used in the treatment of epilepsy for thousands of years.
STATE OF THE ART
Cannabidiol (CBD), which was isolated from cannabis sativa in 1940, has an anti-seizure effect and no psychoactive activity. Its effectiveness in reducing various types of seizures has been proven in animal seizure and epilepsy models. Recent randomised, placebo-controlled trials have confirmed its effectiveness in patients with drug-resistant epilepsy.
CLINICAL IMPLICATIONS
The aim of this position paper was to present the specific mechanism of CBD's anti-seizure action and current indications for CBD's use in epilepsy. The only cannabis-derived drug that has successfully passed clinical trials and has obtained United States Food and Drug Administration and European Medicines Agency approval for epilepsy is Epidiolex®. This paper presents the outcomes of the completed clinical trials with the use of this drug.
FUTURE DIRECTIONS
CBD may be an effective drug in drug-resistant epilepsy, particularly in Dravet Syndrome, Lennox- Gastaut Syndrome and seizures associated with tuberous sclerosis complex. Additional randomised, placebo-controlled studies with CBD are needed.
Topics: Animals; Anticonvulsants; Cannabidiol; Epilepsies, Myoclonic; Epilepsy; Humans; Lennox Gastaut Syndrome
PubMed: 35211946
DOI: 10.5603/PJNNS.a2022.0020 -
Biomolecules Feb 2023Farber disease (FD) and spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) are ultra-rare, autosomal-recessive, acid ceramidase (ACDase) deficiency... (Review)
Review
Farber disease (FD) and spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) are ultra-rare, autosomal-recessive, acid ceramidase (ACDase) deficiency disorders caused by gene mutations. Currently, 73 different mutations in the gene have been described in humans. These mutations lead to reduced ACDase activity and ceramide (Cer) accumulation in many tissues. Presenting as divergent clinical phenotypes, the symptoms of FD vary depending on central nervous system (CNS) involvement and severity. Classic signs of FD include, but are not limited to, a hoarse voice, distended joints, and lipogranulomas found subcutaneously and in other tissues. Patients with SMA-PME lack the most prominent clinical signs seen in FD. Instead, they demonstrate muscle weakness, tremors, and myoclonic epilepsy. Several ACDase-deficient mouse models have been developed to help elucidate the complex consequences of Cer accumulation. In this review, we compare clinical reports on FD patients and experimental descriptions of ACDase-deficient mouse models. We also discuss clinical presentations, potential therapeutic strategies, and future directions for the study of FD and SMA-PME.
Topics: Mice; Animals; Humans; Farber Lipogranulomatosis; Ceramides; Myoclonic Epilepsies, Progressive; Muscular Atrophy, Spinal; Mutation
PubMed: 36830643
DOI: 10.3390/biom13020274 -
Progressive Myoclonus Epilepsy: A Scoping Review of Diagnostic, Phenotypic and Therapeutic Advances.Genes Jan 2024The progressive myoclonus epilepsies (PME) are a diverse group of disorders that feature both myoclonus and seizures that worsen gradually over a variable timeframe.... (Review)
Review
The progressive myoclonus epilepsies (PME) are a diverse group of disorders that feature both myoclonus and seizures that worsen gradually over a variable timeframe. While each of the disorders is individually rare, they collectively make up a non-trivial portion of the complex epilepsy and myoclonus cases that are seen in tertiary care centers. The last decade has seen substantial progress in our understanding of the pathophysiology, diagnosis, prognosis, and, in select disorders, therapies of these diseases. In this scoping review, we examine English language publications from the past decade that address diagnostic, phenotypic, and therapeutic advances in all PMEs. We then highlight the major lessons that have been learned and point out avenues for future investigation that seem promising.
Topics: Humans; Myoclonus; Myoclonic Epilepsies, Progressive
PubMed: 38397161
DOI: 10.3390/genes15020171