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The Neuroscientist : a Review Journal... Jun 2024The current study investigates the intricate connection between neurology and islands shedding light on the historical, epidemiological, and genetic aspects. Based on an...
The current study investigates the intricate connection between neurology and islands shedding light on the historical, epidemiological, and genetic aspects. Based on an elaborate literature review, we identified neurological conditions having a significant clustering in an island(s), confined to a particular island(s), named after an island, and described first in an island. The genetic factors played a crucial role, uncovering disorders like Cayman ataxia, Machado Joseph disease, SGCE-mediated dystonia-myoclonus syndrome, X-linked dystonia parkinsonism, hereditary transthyretinrelated amyloidosis, Charcot Marie Tooth 4F, and progressive myoclonic epilepsy syndromes, that exhibited remarkable clustering in diverse islands. Local customs also left enduring imprints. Practices such as cannibalism in Papua New Guinea led to Kuru, while cycad seed consumption in Guam triggered Lytico-Bodig disease. Toxin-mediated neurologic disorders exhibited intricate island connections, exemplified by Minamata disease in Kyushu islands and atypical parkinsonism in French Caribbean islands. Additionally, the Cuban epidemic of amblyopia and neuropathy was associated with severe nutritional deficiencies. This study pioneers a comprehensive review narrating the genetic, environmental, and cultural factors highlighting the spectrum of neurological disorders in island settings. It enriches the medical literature with a unique understanding of the diverse influences shaping neurological health in island environments.
PubMed: 38842035
DOI: 10.1177/10738584241257927 -
Cureus Apr 2024The objective of this case report is to describe and document a case of respiratory syncytial virus (RSV) in a pediatric patient with Dravet syndrome (DS), also known as...
The objective of this case report is to describe and document a case of respiratory syncytial virus (RSV) in a pediatric patient with Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy. Febrile seizures are often a complication in a patient with DS and can lead to status epilepticus, necessitating measures to prevent triggers such as fever, electrolyte imbalance, or dehydration. An increased awareness and understanding of DS can facilitate the identification of warning signs. A two-year-old female with a past medical history of DS with focal and generalized features presented to the pediatric emergency department (ED) with a five-day history of cough, fever, and decreased oral intake. The patient's parents accompanied her and expressed concerns regarding the risk of seizures associated with a rise in body temperature, as they had been alternating between acetaminophen and ibuprofen to manage her fever with a maximum recorded temperature of 101.5℉. She exhibited signs of increased work of breathing, necessitating the administration of supplemental oxygen via nasal cannula. Blood samples were obtained and resulted in the development of metabolic acidosis. A respiratory panel confirmed the presence of an RSV infection, promoting the administration of breathing treatment with albuterol and ipratropium bromide. The patient was admitted for dehydration and was started on ½ normal saline/potassium chloride 20 mEq at 40 mL/hr. Additionally, her home medication regimen was resumed to minimize the risk of seizures. Given the patient's complications and increased risk of seizure, she was transferred to higher-level care where her status improved after the placement of a percutaneous endoscopic gastrostomy (PEG). This case underscores the complexities involved in managing patients with DS, particularly when complicated by respiratory illness and electrolyte imbalances that can lower the seizure threshold. This patient received a combination of diet and medications to prevent seizures, as well as allow for recovery and correction of the underlying metabolic acidosis. The transfer to a higher level of care in this case was necessary to allow for the specialized resources and expertise needed to handle this case.
PubMed: 38826591
DOI: 10.7759/cureus.59405 -
Clinical Neurophysiology : Official... Apr 2024To test the hypothesis that myoclonic seizures can evolve to tonic seizures, we documented the electroclinical features of this under-recognized seizure type.
BACKGROUND AND PURPOSE
To test the hypothesis that myoclonic seizures can evolve to tonic seizures, we documented the electroclinical features of this under-recognized seizure type.
METHODS
We observed a distinct seizure pattern starting with myoclonus without returning to an interictal state, which subsequently evolved into generalized tonic seizures. The detailed symptomatic and electroencephalographic characteristics of this seizure were extracted, and the clinical manifestations, drug curative responses in patients with this seizure were reviewed and analyzed.
RESULTS
The onset of all seizures was characterized by a preceding period of myoclonus and bursts of generalized spike or poly-spike slow wave discharges with high amplitude. This was closely followed by the occurrence of tonic seizures, which were distinguished by bursts of generalized fast activity at 10 Hz or higher frequency. This under-recognized seizure type has been designated as myoclonic-to-tonic (MT) seizure. The number of patients identified with MT seizures in this study was 34. The prevalence rate of MT seizures was found to be higher in males. While MT seizures typically included a tonic component, it should be noted that some patients experiencing this seizure type never presented with isolated tonic seizures. Generalized Epilepsy not further defined (GE) accounted for approximately one-third of the diagnosed cases, followed by Lennox-Gastaut syndrome and Epilepsy with Myoclonic-Atonic seizures. In comparison to other types of epilepsy, GE with MT seizures demonstrated a more favorable prognosis.
CONCLUSIONS
The classification of myoclonic-to-tonic seizure represents a novel approach in comprehending the ictogenesis of generalized seizures and can provide valuable assistance to clinicians in epilepsy diagnosis.
PubMed: 38823261
DOI: 10.1016/j.clinph.2024.04.011 -
Epilepsy & Behavior : E&B May 2024Previous research has demonstrated that neuroinflammation is a key element in the progress of epilepsy. Nevertheless, it is currently unidentified which inflammatory...
BACKGROUND
Previous research has demonstrated that neuroinflammation is a key element in the progress of epilepsy. Nevertheless, it is currently unidentified which inflammatory factors and proteins increase or decrease the risk of epilepsy.
METHODS
We adopted Mendelian randomization techniques to explore the causal relationship between circulating inflammatory factors and proteins and various epilepsy. Our principal approach was inverse variance weighting, supplemented by several sensitivity analyses to guarantee the robustness of our findings.
RESULTS
Studies have identified associations between epilepsy and specific inflammatory factors and proteins: three inflammatory factors and six proteins are linked to epilepsy in general; one inflammatory factor and four proteins are associated with focal epilepsy with no documented lesions; two inflammatory factors and three proteins are related to focal epilepsy, excluding cases with hippocampal sclerosis; two inflammatory factors and two proteins are connected to juvenile myoclonic epilepsy; two inflammatory factors and five proteins are linked to juvenile absence epilepsy; four inflammatory proteins are associated with childhood absence epilepsy; two inflammatory factors are related to focal epilepsy overall; two inflammatory factors and two proteins are connected to generalized epilepsy; and two inflammatory proteins are linked to generalized epilepsy with tonic-clonic seizures. Additionally, six inflammatory factors may play a downstream role in focal epilepsy.
CONCLUSION
Our study uncovers various inflammatory factors and proteins that influence the risk of epilepsy, offering instructive insights to the diagnosis and therapy of the condition.
PubMed: 38823075
DOI: 10.1016/j.yebeh.2024.109868 -
Neurology. Genetics Jun 2024Epilepsies are associated with differences in cortical thickness (TH) and surface area (SA). However, the mechanisms underlying these relationships remain elusive. We...
BACKGROUND AND OBJECTIVES
Epilepsies are associated with differences in cortical thickness (TH) and surface area (SA). However, the mechanisms underlying these relationships remain elusive. We investigated the extent to which these phenotypes share genetic influences.
METHODS
We analyzed genome-wide association study data on common epilepsies (n = 69,995) and TH and SA (n = 32,877) using Gaussian mixture modeling MiXeR and conjunctional false discovery rate (conjFDR) analysis to quantify their shared genetic architecture and identify overlapping loci. We biologically interrogated the loci using a variety of resources and validated in independent samples.
RESULTS
The epilepsies (2.4 k-2.9 k variants) were more polygenic than both SA (1.8 k variants) and TH (1.3 k variants). Despite absent genome-wide genetic correlations, there was a substantial genetic overlap between SA and genetic generalized epilepsy (GGE) (1.1 k), all epilepsies (1.1 k), and juvenile myoclonic epilepsy (JME) (0.7 k), as well as between TH and GGE (0.8 k), all epilepsies (0.7 k), and JME (0.8 k), estimated with MiXeR. Furthermore, conjFDR analysis identified 15 GGE loci jointly associated with SA and 15 with TH, 3 loci shared between SA and childhood absence epilepsy, and 6 loci overlapping between SA and JME. 23 loci were novel for epilepsies and 11 for cortical morphology. We observed a high degree of sign concordance in the independent samples.
DISCUSSION
Our findings show extensive genetic overlap between generalized epilepsies and cortical morphology, indicating a complex genetic relationship with mixed-effect directions. The results suggest that shared genetic influences may contribute to cortical abnormalities in epilepsies.
PubMed: 38817246
DOI: 10.1212/NXG.0000000000200143 -
Journal of Integrative Neuroscience May 2024To explore the time-frequency structure and cross-scale coupling of electroencephalography (EEG) signals during seizure in juvenile myoclonic epilepsy (JME),...
BACKGROUND
To explore the time-frequency structure and cross-scale coupling of electroencephalography (EEG) signals during seizure in juvenile myoclonic epilepsy (JME), correlations between different leads, as well as dynamic evolution in epileptic discharge, progression and end of seizure were examined.
METHODS
EEG data were obtained for 10 subjects with JME and 10 normal controls and were decomposed using gauss continuous wavelet transform (CWT). The phase amplitude coupling (PAC) relationship between the 11th (4.57 Hz) and 17th (0.4 Hz) scale was investigated. Correlations were examined between the 11th and 17th scale EEG signals in different leads during seizure, using multi-scale cross correlation analysis.
RESULTS
The time-frequency structure of JME subjects showed strong rhythmic activity in the 11th and 17th scales and a close PAC was identified. Correlation analysis revealed that the ictal JME correlation first increased in the anterior head early in seizure and gradually expanded to the posterior head.
CONCLUSION
PAC was exhibited between the 11th and 17th scales during JME seizure. The results revealed that the correlation in the anterior leads was higher than the posterior leads. In the perictal period, the 17th scale EEG signal preceded the 11th scale signal and remained for some time after a seizure. This suggests that the 17th scale signal may play an important role in JME seizure.
Topics: Humans; Myoclonic Epilepsy, Juvenile; Electroencephalography; Male; Female; Young Adult; Adult; Adolescent; Wavelet Analysis; Brain; Brain Waves; Signal Processing, Computer-Assisted
PubMed: 38812390
DOI: 10.31083/j.jin2305097 -
Proceedings of the National Academy of... Jun 2024Epilepsies have numerous specific mechanisms. The understanding of neural dynamics leading to seizures is important for disclosing pathological mechanisms and developing...
Epilepsies have numerous specific mechanisms. The understanding of neural dynamics leading to seizures is important for disclosing pathological mechanisms and developing therapeutic approaches. We investigated electrographic activities and neural dynamics leading to convulsive seizures in patients and mouse models of Dravet syndrome (DS), a developmental and epileptic encephalopathy in which hypoexcitability of GABAergic neurons is considered to be the main dysfunction. We analyzed EEGs from DS patients carrying a pathogenic variant, as well as epidural electrocorticograms, hippocampal local field potentials, and hippocampal single-unit neuronal activities in and DS mice. Strikingly, most seizures had low-voltage-fast onset in both patients and mice, which is thought to be generated by hyperactivity of GABAergic interneurons, the opposite of the main pathological mechanism of DS. Analyzing single-unit recordings, we observed that temporal disorganization of the firing of putative interneurons in the period immediately before the seizure (preictal) precedes the increase of their activity at seizure onset, together with the entire neuronal network. Moreover, we found early signatures of the preictal period in the spectral features of hippocampal and cortical field potential of mice and of patients' EEG, which are consistent with the dysfunctions that we observed in single neurons and that allowed seizure prediction. Therefore, the perturbed preictal activity of interneurons leads to their hyperactivity at the onset of generalized seizures, which have low-voltage-fast features that are similar to those observed in other epilepsies and are triggered by hyperactivity of GABAergic neurons. Preictal spectral features may be used as predictive seizure biomarkers.
Topics: Animals; Epilepsies, Myoclonic; Interneurons; Mice; NAV1.1 Voltage-Gated Sodium Channel; Seizures; Humans; GABAergic Neurons; Male; Hippocampus; Female; Disease Models, Animal; Electroencephalography; Child
PubMed: 38809712
DOI: 10.1073/pnas.2316364121 -
Frontiers in Psychiatry 2024Epileptologists and psychiatrists have long observed a correlation between epilepsy and personality disorders (PDs) in their clinical practice. We conducted a... (Review)
Review
Epileptologists and psychiatrists have long observed a correlation between epilepsy and personality disorders (PDs) in their clinical practice. We conducted a comprehensive PubMed search looking for evidence on PDs in people with epilepsy (PwE). Out of over 600 results obtained without applying any time restriction, we selected only relevant studies (both analytical and descriptive) limited to English, Italian, French and Spanish languages, with a specific focus on PDs, rather than traits or symptoms, thus narrowing our search down to 23 eligible studies. PDs have been investigated in focal epilepsy (predominantly temporal lobe epilepsy - TLE), juvenile myoclonic epilepsy (JME) and psychogenic non-epileptic seizures (PNES), with heterogeneous methodology. Prevalence rates of PDs in focal epilepsy ranged from 18 to 42% in surgical candidates or post-surgical individuals, with Cluster C personality disorders or related traits and symptoms being most common. In JME, prevalence rates ranged from 8 to 23%, with no strong correlation with any specific PDs subtype. In PNES, prevalence rates ranged from 30 to 60%, with a notable association with Cluster B personality disorders, particularly borderline personality disorder. The presence of a PD in PwE, irrespective of subtype, complicates treatment management. However, substantial gaps of knowledge exist concerning the neurobiological substrate, effects of antiseizure medications and epilepsy surgery on concomitant PDs, all of which are indeed potential paths for future research.
PubMed: 38800062
DOI: 10.3389/fpsyt.2024.1404856 -
BioRxiv : the Preprint Server For... May 2024Mutations in human (ciliogenesis associated kinase 1) are linked to ciliopathies and epilepsy. Homozygous point and nonsense mutations that extinguish kinase activity...
Mutations in human (ciliogenesis associated kinase 1) are linked to ciliopathies and epilepsy. Homozygous point and nonsense mutations that extinguish kinase activity impair primary cilia function, whereas mutations outside the kinase domain are not well understood. Here, we produced a knock-in mouse equivalent of the human A615T variant identified in juvenile myoclonic epilepsy (JME). This residue is in the C-terminal region of CILK1 separate from the kinase domain. Mouse embryo fibroblasts (MEF) with either heterozygous or homozygous A612T mutant alleles exhibited a higher ciliation rate, shorter individual cilia and up-regulation of ciliary Hedgehog signaling. Thus, a single A612T mutant allele was sufficient to impair primary cilia and ciliary signaling in MEFs. Gene expression profiles of wild type versus mutant MEFs revealed profound changes in cilia-related molecular functions and biological processes. CILK1 A615T mutant protein was not increased to the same level as the wild type protein when co-expressed with scaffold protein KATNIP (katanin-interacting protein). Our data show that KATNIP regulation of a JME-associated single residue variant of CILK1 is compromised and this impairs the maintenance of primary cilia and Hedgehog signaling.
PubMed: 38798407
DOI: 10.1101/2024.05.14.594243 -
Molecular Therapy : the Journal of the... May 2024Lafora disease is a rare and fatal form of progressive myoclonic epilepsy typically occurring early in adolescence. The disease results from mutations in the EPM2A gene,...
Lafora disease is a rare and fatal form of progressive myoclonic epilepsy typically occurring early in adolescence. The disease results from mutations in the EPM2A gene, encoding laforin, or the EPM2B gene, encoding malin. Laforin and malin work together in a complex to control glycogen synthesis and prevent the toxicity produced by misfolded proteins via the ubiquitin-proteasome system. Disruptions in either protein cause alterations in this complex, leading to the formation of Lafora bodies containing abnormal, insoluble, and hyperphosphorylated forms of glycogen. We used the Epm2a knockout mouse model of Lafora disease to apply gene therapy by administering intracerebroventricular injections of a recombinant adeno-associated virus carrying the human EPM2A gene. We evaluated the effects of this treatment through neuropathological studies, behavioral tests, video-electroencephalography, electrophysiological recordings, and proteomic/phosphoproteomic analysis. Gene therapy ameliorated neurological and histopathological alterations, reduced epileptic activity and neuronal hyperexcitability, and decreased the formation of Lafora bodies. Moreover, differential quantitative proteomics and phosphoproteomics revealed beneficial changes in various molecular pathways altered in Lafora disease. Our results represent proof of principle for gene therapy with the coding region of the human EPM2A gene as a treatment for EPM2A-related Lafora disease.
PubMed: 38796707
DOI: 10.1016/j.ymthe.2024.05.032