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Seizure Jun 2024Sleep disturbances significantly impact the lives of individuals with Juvenile Myoclonic Epilepsy (JME). This study aimed to investigate sleep studies, disturbances, and... (Review)
Review
Sleep disturbances significantly impact the lives of individuals with Juvenile Myoclonic Epilepsy (JME). This study aimed to investigate sleep studies, disturbances, and the impact of anti-seizure drugs on sleep in JME patients. Relevant studies were retrieved from the National Library of Medicine (Pubmed) database and the Cochrane Library utilizing the search terms "Juvenile Myoclonic Epilepsy" and "sleep". A total of 160 papers' review, data extraction, and resolution of discrepancies were performed independently by two reviewers according to the PRISMA protocol and were registered in PROSPERO (CRD42023472439). A systematic review of 31 studies was conducted, encompassing various methodologies, including sleep questionnaires (Pittsburgh Sleep Quality Index (n = 13), Epworth Sleepiness Scale (n = 10)), polysomnography (n = 8), EEG (n = 9), actigraphy (n = 1), and transcranial magnetic stimulation (n = 1). Most studies were hospital-based (n = 31), cross-sectional (n = 11), and prospective (n = 25). Patients with JME exhibit a higher prevalence of sleep disturbances, worse quality of sleep (n = 4), daytime sleepiness (n = 2), sleep efficiency (n = 7), and increased sleep latency (n = 1) compared to controls. These disruptions are characterized by increased wakefulness (n = 3), frequent arousals (n = 3), decreased REM sleep (n = 2), and conflicting NREM sleep findings (n = 3). Additional sleep-related issues observed in JME patients include insomnia (n = 1) and increased prevalence of parasomnias such as nightmares and sleep talking. Periodic limb movement and obstructive sleep apnea are similar or less frequent (3/28). REM behavioral disorders and sleepwalking were not seen. Valproate showed conflicting effects on sleep (n = 7), while levetiracetam did not impact sleep (n = 1). These findings underlined the need for more sufficient evidence of sleep studies in JME. Future research should prioritize understanding the nature of sleep in JME and its impact on management.
PubMed: 38908143
DOI: 10.1016/j.seizure.2024.05.014 -
Epilepsy & Behavior : E&B Jun 2024In this study, patients with epilepsy with eyelid myoclonia (E-EM) were evaluated according to their EEG findings, seizure outcomes, and their consistency with the final...
PURPOSE
In this study, patients with epilepsy with eyelid myoclonia (E-EM) were evaluated according to their EEG findings, seizure outcomes, and their consistency with the final ictal EEG findings. We also investigated the possible prognostic factors.
METHODS
Patients with E-EM and at least two years of follow-up in our clinic were included in the study. We analyzed the presence of eyelid myoclonia, absence and myoclonic seizures, and generalized tonic-clonic seizures for the prior two years and then verified with the latest ictal EEG features. Video-EEGs were analyzed according to the background activity, the existence of generalized spike-wave discharge or polyspike-wave complexes, focal spike-wave discharge, photoparoxysmal responses, and fast activity.
RESULTS
21 patients were involved in this study. In six patients, the seizures were undetected on the first EEGs, whereas they were detected on subsequent ones. The seizures were captured on the first EEGs of six patients; however, they disappeared on subsequent ones. Only one patient had seizures detected on every EEG. The consistency of the seizures was variable in eight patients. At the final follow-up, seizures were reported as being under control for more than two years in 12 patients, according to patients and their parents' reports. However, ictal EEG findings were detected in six of these patients. No electroclinical feature was associated with seizure freedom.
CONCLUSION
This study provides further evidence that seizure freedom in E-EM patients is overestimated. The patients and their parents may not be aware of the seizures. Therefore, video-EEG monitorization is essential during follow-up.
PubMed: 38905913
DOI: 10.1016/j.yebeh.2024.109895 -
Frontiers in Neurology 2024To investigate whether changes occur in the dynamic functional connectivity (dFC) of motor cerebellum with cerebral cortex in juvenile myoclonic epilepsy (JME).
OBJECTIVE
To investigate whether changes occur in the dynamic functional connectivity (dFC) of motor cerebellum with cerebral cortex in juvenile myoclonic epilepsy (JME).
METHODS
We adopted resting-state electroencephalography-functional magnetic resonance imaging (EEG-fMRI) and a sliding-window approach to explore the dFC of motor cerebellum with cortex in 36 JME patients compared with 30 and age-matched health controls (HCs). The motor cerebellum was divided into five lobules (I-V, VI, VIIb, VIIIa, and VIIIb). Additionally, correlation analyses were conducted between the variability of dFC and clinical variables in the Juvenile Myoclonic Epilepsy (JME) group, such as disease duration, age at disease onset, and frequency score of myoclonic seizures.
RESULTS
Compared to HCs, the JME group presented increased dFC between the motor cerebellum with SMN and DMN. Specifically, connectivity between lobule VIIb and left precentral gyrus and right inferior parietal lobule (IPL); between lobule VIIIa and right inferior frontal gyrus (IFG) and left IPL; and between lobule VIIIb and left middle frontal gyrus (MFG), bilateral superior parietal gyrus (SPG), and left precuneus. In addition, within the JME group, the strength of dFC between lobule VIIIb and left precuneus was negatively ( = -0.424, = 0.025, Bonferroni correction) related with the frequency score of myoclonic seizures.
CONCLUSION
In patients with JME, there is a functional dysregulation between the motor cerebellum with DMN and SMN, and the variability of dynamic functional connectivity may be closely associated with the occurrence of motor symptoms in JME.
PubMed: 38903166
DOI: 10.3389/fneur.2024.1373125 -
ACS Pharmacology & Translational Science Jun 2024Drug-resistant epilepsy is a prominent challenge in chronic neurological disorders. Valproate, commonly used to treat epilepsy, can fail due to various side effects and...
Unlocking the Therapeutic Potential: Sitagliptin's Multifaceted Approach in Drug-Resistant Epilepsy through a Novel Mechanism Inhibiting Protein Kinase C-γ and a Long-Term Potentiation Pathway.
Drug-resistant epilepsy is a prominent challenge in chronic neurological disorders. Valproate, commonly used to treat epilepsy, can fail due to various side effects and interactions, necessitating the exploration of alternative treatments. Our study primarily investigated sitagliptin's potential as a therapeutic agent for drug-resistant epilepsy. Employing computational modeling and enzyme assay testing, three lead compounds, emixustat, sitagliptin, and distigmine bromide, were evaluated against the target enzyme protein kinase C-γ. , experiments on a pentylenetetrazolium-induced lamotrigine-resistant epilepsy model were conducted to test sitagliptin's antiseizure effects, compared with the standard phenobarbital treatment. Emixustat and sitagliptin showcased strong inhibitory properties, while distigmine bromide was less effective in the enzyme assay. Mechanistic insights revealed sitagliptin's ability to modulate the seizure grade and first myoclonic jerk latency via oxidative stress markers, like reduced glutathione and glutathione peroxidase emphasizing its antioxidative role in epilepsy. Additionally, it demonstrated anti-inflammatory effects by significantly reducing proinflammatory markers interleukin-1β and interleukin-6. The modulation of key genes of the long-term potentiation pathway, particularly protein kinase C-γ and metabotropic glutamate receptor 5, was evident through mRNA expression levels. Finally, sitagliptin showed potential neuroprotective properties, limiting pentylenetetrazolium-induced neuronal loss in the hippocampal region. Collectively, our findings suggest sitagliptin's multidimensional therapeutic potential for drug-resistant epilepsy specifically via a long-term potentiation pathway by inhibiting protein kinase C-γ.
PubMed: 38898950
DOI: 10.1021/acsptsci.4c00073 -
The Neurohospitalist Jul 202422q11.2 microdeletion is the most common microdeletion syndrome in humans with a prevalence of 13 per 100 000 live births, and it is a multisystem condition with...
BACKGROUND
22q11.2 microdeletion is the most common microdeletion syndrome in humans with a prevalence of 13 per 100 000 live births, and it is a multisystem condition with variable phenotypic presentations.
METHODS
We present a case of an adult patient with Dandy-Walker syndrome who presented to our epilepsy clinic with 2 years of new-onset seizures and cognitive decline and 1 year of psychotic symptoms.
RESULTS
Patient had a non-revealing autoimmune and malignancy work-up. Continuous scalp vEEG study showed bursts of 1-2 Hz generalized fronto-centrally predominant spike or polyspike and slow wave discharges. Several myoclonic jerks were time-locked with the generalized discharges indicative of cortical myoclonus. MRI brain revealed periventricular nodular heterotopia in addition to findings suggestive of Dandy-Walker syndrome. Array-based comparative genomic hybridization demonstrated a 22q11.2 microdeletion seen in 22q11.2 deletion syndrome.
CONCLUSION
Our case illustrates the challenges of diagnosing genetic disorders in adults especially when the initial diagnosis is dependent on a number of factors, including the patient's age, the severity of the phenotypic features, and the awareness of the physician.
PubMed: 38895014
DOI: 10.1177/19418744241228618 -
International Journal of Molecular... May 2024, the gene encoding for the Nav1.1 channel, exhibits dominant interneuron-specific expression, whereby variants disrupting the channel's function affect the initiation...
, the gene encoding for the Nav1.1 channel, exhibits dominant interneuron-specific expression, whereby variants disrupting the channel's function affect the initiation and propagation of action potentials and neuronal excitability causing various types of epilepsy. Dravet syndrome (DS), the first described clinical presentation of SCN1A channelopathy, is characterized by severe myoclonic epilepsy in infancy (SMEI). Variants' characteristics and other genetic or epigenetic factors lead to extreme clinical heterogeneity, ranging from non-epileptic conditions to developmental and epileptic encephalopathy (DEE). This current study reports on findings from 343 patients referred by physicians in hospitals and tertiary care centers in Greece between 2017 and 2023. Positive family history for specific neurologic disorders was disclosed in 89 cases and the one common clinical feature was the onset of seizures, at a mean age of 17 months (range from birth to 15 years old). Most patients were specifically referred for investigation (Sanger Sequencing and MLPA) and only five for next generation sequencing. Twenty-six variants were detected, including nine novel causative variants (c.4567A>Τ, c.5564C>A, c.2176+2T>C, c.3646G>C, c.4331C>A, c.1130_1131delGAinsAC, c.1574_1580delCTGAGGA, c.4620A>G and c.5462A>C), and are herein presented, along with subsequent genotype-phenotype associations. The identification of novel variants complements SCN1A databases extending our expertise on genetic counseling and patient and family management including gene-based personalized interventions.
Topics: Humans; NAV1.1 Voltage-Gated Sodium Channel; Male; Female; Child; Adolescent; Infant; Phenotype; Child, Preschool; Epilepsy; Infant, Newborn; Mutation; Adult; Young Adult
PubMed: 38891831
DOI: 10.3390/ijms25115644 -
Frontiers in Pharmacology 2024In recent years, with the continuous expansion of the application scope of Tranexamic acid (TXA), its usage has surged. Despite numerous studies demonstrating its...
BACKGROUND
In recent years, with the continuous expansion of the application scope of Tranexamic acid (TXA), its usage has surged. Despite numerous studies demonstrating its powerful efficacy, concerns regarding its adverse reactions persist, necessitating comprehensive safety assessment. This study analyzed real-world data from the U.S. Food and Drug Administration to investigate TXA-related adverse events, aiming to elucidate its safety and optimize patient treatment.
METHODS
The adverse drug event data concerning TXA from 2004 Q1 to 2023 Q3 were collected. Following data standardization, a variety of signal quantification techniques, including the reporting odds ratios, proportional reporting ratios, Bayesian confidence propagation neural network, and empirical Bayes geometric mean were used for analysis.
RESULTS
After analyzing 16,692,026 adverse event reports, a total of 1,574 cases of adverse events related to TXA were identified, spanning 23 system organ classes and 307 preferred terms. In addition to the common thrombosis-related Vascular disorders ( = 386) and Cardiac disorders ( = 377), adverse reactions in the Nervous system disorders category were also observed ( = 785), including Myoclonus ( = 70), Status epilepticus ( = 43), and Myoclonic epilepsy ( = 17). Furthermore, this study uncovered adverse effects such as Renal cortical necrosis, Hepatic cyst rupture, and Vascular stent stenosis, which were not previously mentioned in the instructions. Although these occurred infrequently, they exhibited high signal strength. Both Retinal artery occlusion and Vascular stent thrombosis disorder were frequent and exhibited high signal strength as well. It is worth noting that 78 cases of adverse reactions were caused by confusion between incorrect product administration.
CONCLUSION
Our research suggests that TXA has some adverse reactions that are being overlooked. As a cornerstone medication in hemorrhage treatment, it's crucial to monitor, identify, and address these adverse reactions effectively.
PubMed: 38863974
DOI: 10.3389/fphar.2024.1388138 -
Seizure Jul 2024Epilepsy is a hallmark of IQSEC2-related encephalopathy within a phenotypic variability ranging between early onset epileptic and developmental encephalopathy and...
BACKGROUND
Epilepsy is a hallmark of IQSEC2-related encephalopathy within a phenotypic variability ranging between early onset epileptic and developmental encephalopathy and X-linked intellectual disability with epilepsy.
PATIENTS AND METHODS
Data including demographic aspects, gene variants, seizure semiology and timing, EEG features, neuroimaging and response to therapy were retrospectively collected in patients with IQSEC2-related epilepsy referring to 8 Italian tertiary centres.
RESULTS
The reported cohort included 11 patients (8 males and 3 females). Mean age at the onset of epilepsy was 3.90±2.80 years. No cases were reported in the first year of life. No specific epileptic syndromes were recognized. Predominant seizure-types in the age range 12-36 months included focal onset tonic seizures with impaired awareness, myoclonic seizures, and late onset spasms. Generalized motor seizures were predominant in patients between 3 and 6 years and between 12 and 18 years while focal motor seizures with impaired awareness were the most represented types between 6 and 12 years. No patients experienced status epilepticus. EEG patterns included a delayed maturation of EEG organization, irregular focal or diffuse slow activity, multifocal or diffuse epileptiform abnormalities. No structural epileptogenic lesions were detected at MRI. Valproate, lamotrigine, clobazam, topiramate and levetiracetam were the most used antiseizure medication. Complete seizure freedom was achieved only in 2 patients.
CONCLUSIONS
Onset of epilepsy after the first year of age, predominance of focal seizures with impaired awareness and generalized motor seizures, no pathognomonic underlying epileptic syndrome and infrequent occurrence of status epilepticus emerged as the main features of IQSEC2-related epilepsy phenotype.
Topics: Humans; Male; Female; Child; Child, Preschool; Adolescent; Retrospective Studies; Italy; Phenotype; Electroencephalography; Epilepsy; Guanine Nucleotide Exchange Factors; Infant; Anticonvulsants; Age of Onset
PubMed: 38851096
DOI: 10.1016/j.seizure.2024.06.002 -
Neuroradiology Jun 2024We conducted a multilayer network analysis in patients with juvenile myoclonic epilepsy (JME) and healthy controls, to investigate the gray matter layer using a...
INTRODUCTION
We conducted a multilayer network analysis in patients with juvenile myoclonic epilepsy (JME) and healthy controls, to investigate the gray matter layer using a morphometric similarity network and analyze the white matter layer using structural connectivity.
METHODS
We enrolled 42 patients with newly diagnosed JME and 53 healthy controls. Brain magnetic resonance imaging (MRI) using a three-tesla MRI scanner, including T1-weighted imaging and diffusion tensor imaging (DTI) were performed. We created a gray matter layer matrix with a morphometric similarity network using T1-weighted imaging, and a white matter layer matrix with structural connectivity using the DTI. Subsequently, we performed a multilayer network analysis by applying graph theory.
RESULTS
There were significant differences in network at the global level in the multilayer network analysis between the groups. The average multiplex participation of patients with JME was lower than that of healthy controls (0.858 vs. 0.878, p = 0.007). In addition, several regions showed significant differences in multiplex participation at the nodal level in the multilayer network analysis. Multiplex participation in the right entorhinal cortex was lower, whereas multiplex participation in the right supramarginal gyrus was higher at the nodal level in the multilayer network analysis of patients with JME compared to healthy controls.
CONCLUSION
We demonstrated differences in network at the global and nodal levels in the multilayer network analysis between patients with JME and healthy controls. These features may be associated with the pathophysiology of JME and could help us understand the complex brain network in patients with JME.
PubMed: 38847850
DOI: 10.1007/s00234-024-03390-3 -
Neurobiology of Disease Jun 2024Progressive myoclonus ataxia (PMA) is a rare clinical syndrome characterized by the presence of progressive myoclonus and ataxia, and can be accompanied by mild...
Progressive myoclonus ataxia (PMA) is a rare clinical syndrome characterized by the presence of progressive myoclonus and ataxia, and can be accompanied by mild cognitive impairment and infrequent epileptic seizures. This is the first study to describe the natural history of PMA and identify clinical, electrophysiological, and genetic features explaining the variability in disease progression. A Dutch cohort of consecutive patients meeting the criteria of the refined definition of PMA was included. The current phenotype was assessed during in-person consultation by movement disorders experts, and retrospective data was collected to describe disease presentation and progression, including brain imaging and therapy efficacy. Extensive genetic and electrophysiological tests were performed. The presence of cortical hyperexcitability was determined, by either the identification of a cortical correlate of myoclonic jerks with simultaneous electromyography-electroencephalography or a giant somatosensory evoked potential. We included 34 patients with PMA with a median disease duration of 15 years and a clear progressive course in most patients (76%). A molecular etiology was identified in 82% patients: ATM, CAMTA1, DHDDS, EBF3, GOSR2, ITPR1, KCNC3, NUS1, POLR1A, PRKCG, SEMA6B, SPTBN2, TPP1, ZMYND11, and a 12p13.32 deletion. The natural history is a rather homogenous onset of ataxia in the first two years of life followed by myoclonus in the first 5 years of life. Main accompanying neurological dysfunctions included cognitive impairment (62%), epilepsy (38%), autism spectrum disorder (27%), and behavioral problems (18%). Disease progression showed large variability ranging from an epilepsy free PMA phenotype (62%) to evolution towards a progressive myoclonus epilepsy (PME) phenotype (18%): the existence of a PMA-PME spectrum. Cortical hyperexcitability could be tested in 17 patients, and was present in 11 patients and supported cortical myoclonus. Interestingly, post-hoc analysis showed that an absence of cortical hyperexcitability, suggesting non-cortical myoclonus, was associated with the PMA-end of the spectrum with no epilepsy and milder myoclonus, independent of disease duration. An association between the underlying genetic defects and progression on the PMA-PME spectrum was observed. By describing the natural history of the largest cohort of published patients with PMA so far, we see a homogeneous onset with variable disease progression, in which phenotypic evolution to PME occurs in the minority. Genetic and electrophysiological features may be of prognostic value, especially the determination of cortical hyperexcitability. Furthermore, the identification of cortical and non-cortical myoclonus in PMA helps us gain insight in the underlying pathophysiology of myoclonus.
PubMed: 38844245
DOI: 10.1016/j.nbd.2024.106555