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Neurosurgical Review Jul 2024Trigonal meningiomas are rare intraventricular tumours that present a surgical challenge. There is no consensus on the optimal surgical approach to these lesions, though...
Trigonal meningiomas are rare intraventricular tumours that present a surgical challenge. There is no consensus on the optimal surgical approach to these lesions, though the transtemporal and transparietal approaches are most frequently employed. We aimed to examine the approach-related morbidity and surgical nuances in treating trigonal meningiomas. This retrospective review assimilated data from 64 trigonal meningiomas operated over 15 years. Details of clinicoradiological presentation, surgical approach and intraoperative impression, pathology and incidence of various postoperative deficits were recorded. In our study, Trigonal meningiomas most frequently presented with headache and visual deterioration. The median volume of tumours was 63.6cc. Thirty-one meningiomas each (48.4%) were WHO Grade 1 and WHO Grade 2, while 2 were WHO Grade 3. The most frequent approach employed was transtemporal (38 patients, 59.4%), followed by transparietal (22 patients, 34.4%). After surgery features of raised ICP and altered mental status resolved in all patients, while contralateral limb weakness resolved in 80%, aphasia in 60%, seizures in 70%, and vision loss in 46.2%. Eighteen patients (28.13%) developed transient postoperative neurological deficits, with one patient (1.5%) developing permanent morbidity. Surgery for IVMs results in rapid improvement of neurological status, though visual outcomes are poorer in patients with low vision prior to surgery, longer duration of complaints and optic atrophy. The new postoperative deficits in some patients tend to improve on follow up. Transtemporal and transparietal approaches may be employed, based on multiple factors like tumour extension, loculation of temporal horn, size of lesion with no significant difference in their safety profile.
Topics: Humans; Meningioma; Female; Male; Middle Aged; Adult; Aged; Treatment Outcome; Retrospective Studies; Meningeal Neoplasms; Neurosurgical Procedures; Postoperative Complications; Cerebral Ventricle Neoplasms; Young Adult
PubMed: 38965148
DOI: 10.1007/s10143-024-02542-6 -
European Journal of Pediatrics Jul 2024Developmental and epileptic encephalopathies (DEEs) cause disability and dependence affecting both children and the family. The aim of the study was to describe the...
Developmental and epileptic encephalopathies (DEEs) cause disability and dependence affecting both children and the family. The aim of the study was to describe the perspective of parents of children with DEEs regarding the impact of the disease on the family. We carried out a qualitative study based on the interpretivist paradigm. Twenty-one participants were selected using purposive sampling. Parents of children with DEEs of SCN1A, KCNQ2, CDKL5, PCDH19, and GNAO1 variants were included. In-depth interviews and researcher notes were used for data collection. A thematic analysis was performed on the data. Three themes were identified in the results: (a) Assuming conflicts and changes within the couple, causing them to distance themselves, reducing their time and intimacy and leading them to reconsider having more children; (b) impact of the disorder on siblings and grandparents, where siblings perceived DEE as a burden in their lives, felt neglected, and needed to grow and mature alone; conversely, the grandparents suffered for their grandchildren and the parents, in addition to perceiving that their health worsened, and (c) reconciling the care of the child with family life and work; this led the parents to share tasks, abandon or reduce working hours and ask for help.Conclusions: Caring for a child with DEE can result in neglect of social, psychological, emotional, recreational, educational, or occupational needs and obligations that ultimately impact all family members. What is Known: • Children with DEE may develop seizures and experience developmental and cognitive problems. • Caring for a child with DEE has a social and psychological impact on the entire family.
Caring for a child with DEE has a social and psychological impact on the entire family.What is New: • Within the couple, there are tensions due to a lack of time, which could be alleviated by alternating childcare duties. • It is necessary to implement programs that address the physical and mental needs of the couple, as well as cater to the needs of siblings and alleviate the suffering of grandparents.PubMed: 38965081
DOI: 10.1007/s00431-024-05677-2 -
Journal of Medical Genetics Jul 2024variants have been reported to be associated with immune-related disorders with/without seizures. It is unknown whether variants are associated with common epilepsy...
BACKGROUND
variants have been reported to be associated with immune-related disorders with/without seizures. It is unknown whether variants are associated with common epilepsy without acquired causes and the mechanism underlying phenotypic variation remains elusive.
METHODS
Trio-based whole-exome sequencing was performed on patients with febrile seizures or epilepsy with antecedent febrile seizures. Previously reported variants were systematically reviewed to investigate genotype-phenotype associations.
RESULTS
Two de novo heterozygous and three biallelic missense variants were identified in five patients with generalised epilepsy with antecedent febrile seizures. The variants were predicted to be damaging by in silico tools and were associated with hydrogen bonding changes to neighbouring amino acids or decreased protein stability. Patients exhibited an early onset age and became seizure-free with favourable outcome. Further analysis revealed that de novo missense variants located in the Hel region resulted in seizures with multiple neurological abnormalities, while those in the pincer domain or C-terminal domain led to seizures with normal neurodevelopment, suggesting a sub-molecular effect. Biallelic missense variants, which were inherited from unaffected parents and presented low allele frequencies in general populations, were associated with seizures without neurological abnormalities. Truncation variants were related to refractory epilepsy and severe developmental delay, suggesting a genotype-phenotype correlation. is predominantly expressed in the neonatal stage and decreases dramatically in the adulthood, which is consistent with the early onset age and favourable outcome of the patients.
CONCLUSIONS
variants are potentially associated with generalised epilepsy with antecedent febrile seizures. The sub-molecular implication and genotype-phenotype association help explain phenotype variations of variants.
PubMed: 38964834
DOI: 10.1136/jmg-2024-109950 -
Seminars in Pediatric Neurology Jul 2024Previously known as Munchausen syndrome by proxy, medical child abuse is a form of child maltreatment whereby the caregiver creates an environment in which medical care... (Review)
Review
Previously known as Munchausen syndrome by proxy, medical child abuse is a form of child maltreatment whereby the caregiver creates an environment in which medical care harms or threatens the wellbeing of a child. Approximately 40-50 % of medical child abuse cases involve neurological symptoms, with fabricated or induced seizures accounting for a significant proportion. Identifying fictitious seizures is often difficult even for the most experienced clinicians. Therefore, having a low threshold for clinical suspicion is essential in the timely diagnosis of medical child abuse. This article provides a review of the epidemiology, diagnosis, and management of medical child abuse when it involves seizures.
Topics: Humans; Seizures; Child Abuse; Child; Neurologists; Munchausen Syndrome by Proxy; Pediatricians; Pediatrics
PubMed: 38964818
DOI: 10.1016/j.spen.2024.101137 -
Seminars in Pediatric Neurology Jul 2024Child abuse is a major cause of morbidity and mortality in the United States. The leading cause of child physical abuse related deaths is abusive head trauma, formerly... (Review)
Review
Child abuse is a major cause of morbidity and mortality in the United States. The leading cause of child physical abuse related deaths is abusive head trauma, formerly known as shaken baby syndrome, making the rapid identification and assessment of these children critical. The clinical presentation of cases of abusive head trauma ranges from neurological complaints, such as seizures, to vague or subtle symptoms, such as vomiting. This results in frequent missed diagnoses of abusive head trauma. The identification of abusive head trauma relies on a thorough medical history and physical examination, followed by lab evaluation and imaging. The goal of the evaluation is to discover further injury and identify possible underlying non-traumatic etiologies of the patient's symptoms. In this article we present a framework for the assessment of abusive head trauma and provide information on common presentations and injuries, as well as differential diagnoses. A strong foundational knowledge of abusive head trauma will lead to greater recognition and improved safety planning for victims of this unfortunate diagnosis.
Topics: Humans; Child Abuse; Craniocerebral Trauma; Infant; Diagnosis, Differential; Shaken Baby Syndrome
PubMed: 38964810
DOI: 10.1016/j.spen.2024.101135 -
Genes To Cells : Devoted To Molecular &... Jul 2024An autism-associated gene Shank3 encodes multiple splicing isoforms, Shank3a-f. We have recently reported that Shank3a/b-knockout mice were more susceptible to kainic...
An autism-associated gene Shank3 encodes multiple splicing isoforms, Shank3a-f. We have recently reported that Shank3a/b-knockout mice were more susceptible to kainic acid-induced seizures than wild-type mice at 4 weeks of age. Little is known, however, about how the N-terminal and ankyrin repeat domains (NT-Ank) of Shank3a/b regulate multiple molecular signals in the developing brain. To explore the functional roles of Shank3a/b, we performed a mass spectrometry-based proteomic search for proteins interacting with GFP-tagged NT-Ank. In this study, NT-Ank was predicted to form a variety of complexes with a total of 348 proteins, in which RNA-binding (n = 102), spliceosome (n = 22), and ribosome-associated molecules (n = 9) were significantly enriched. Among them, an X-linked intellectual disability-associated protein, Nono, was identified as a NT-Ank-binding protein. Coimmunoprecipitation assays validated the interaction of Shank3 with Nono in the mouse brain. In agreement with these data, the thalamus of Shank3a/b-knockout mice aberrantly expressed splicing isoforms of autism-associated genes, Nrxn1 and Eif4G1, before and after seizures with kainic acid treatment. These data indicate that Shank3 interacts with multiple RNA-binding proteins in the postnatal brain, thereby regulating the homeostatic expression of splicing isoforms for autism-associated genes after birth.
PubMed: 38964745
DOI: 10.1111/gtc.13142 -
Epilepsy & Behavior : E&B Jul 2024Variants in sodium channel genes (SCN) are strongly associated with epilepsy phenotypes. Our aim in this study to evaluate the genotype and phenotype correlation of...
BACKGROUND
Variants in sodium channel genes (SCN) are strongly associated with epilepsy phenotypes. Our aim in this study to evaluate the genotype and phenotype correlation of patients with SCN variants in our tertiary care center.
METHODS
In this retrospective study, patients with SCN variants and epilepsy who were followed up at our clinic between 2018 and 2022 were evaluated. Our study discussed the demographics of the patients, the seizure types, the age of seizure onset, the SCN variants, the domains and the functions of the variants, the magnetic resonance imaging findings, the motor, cognitive, and psychiatric comorbidities, and the response to anti-seizure medication. Genetic testing was conducted using a next-generation sequencing gene panel (epilepsy panel) or a whole-exome sequencing. For evaluating variant function, we used a prediction tool (https://funnc.shinyapps.io/shinyappweb/ site). To assess protein domains, we used the PER viewer (http://per.broadinstitute.org/).
RESULTS
Twenty-three patients with SCN variants and epilepsy have been identified. Sixteen patients had variants in the SCN1A, six patients had variants in the SCN2A, and one patient had a variant in the SCN3A. Two novel SCN1A variants and two novel SCN2A variants were identified. The analysis revealed 14/23 missense, 6/23 nonsense, 2/23 frameshift, and 1/23 splice site variants in the SCN. There are seven variants predicted to be gain-of-function and 13 predicted to be loss-of-function. Among 23 patients; 11 had Dravet Syndrome, 6 had early infantile developmental and epileptic encephalopathy, three had genetic epilepsy with febrile seizures plus spectrum disorder, one had self-limited familial neonatal-infantile epilepsy, one had self-limited infantile epilepsy and one had infantile childhood development epileptic encephalopathy.
CONCLUSION
Our cohort consists of mainly SCN1 variants, most of them were predicted to be loss of function. Dravet syndrome was the most common phenotype. The prediction tool used in our study demonstrated overall compatibility with clinical findings. Due to the diverse clinical manifestations of variant functions, it may assist in guiding medication selection and predicting outcomes. We believe that such a tool will help the clinician in both prognosis prediction and solving therapeutic challenges in this group where refractory seizures are common.
PubMed: 38964184
DOI: 10.1016/j.yebeh.2024.109930 -
Epilepsy & Behavior : E&B Jul 2024Evaluate the performance of a custom application developed for tonic-clonic seizure (TCS) monitoring on a consumer-wearable (Apple Watch) device.
OBJECTIVE
Evaluate the performance of a custom application developed for tonic-clonic seizure (TCS) monitoring on a consumer-wearable (Apple Watch) device.
METHODS
Participants with a history of convulsive epileptic seizures were recruited for either Epilepsy Monitoring Unit (EMU) or ambulatory (AMB) monitoring; participants without epilepsy (normal controls [NC]) were also enrolled in the AMB group. Both EMU and AMB participants wore an Apple Watch with a research app that continuously recorded accelerometer and photoplethysmography (PPG) signals, and ran a fixed-and-frozen tonic-clonic seizure detection algorithm during the testing period. This algorithm had been previously developed and validated using a separate training dataset. All EMU convulsive events were validated by video-electroencephalography (video-EEG); AMB events were validated by caregiver reporting and follow-ups. Device performance was characterized and compared to prior monitoring devices through sensitivity, false alarm rate (FAR; false-alarms per 24 h), precision, and detection delay (latency).
RESULTS
The EMU group had 85 participants (4,279 h, 19 TCS from 15 participants) enrolled across four EMUs; the AMB group had 21 participants (13 outpatient, 8 NC, 6,735 h, 10 TCS from 3 participants). All but one AMB participant completed the study. Device performance in the EMU group included a sensitivity of 100 % [95 % confidence interval (CI) 79-100 %]; an FAR of 0.05 [0.02, 0.08] per 24 h; a precision of 68 % [48 %, 83 %]; and a latency of 32.07 s [standard deviation (std) 10.22 s]. The AMB group had a sensitivity of 100 % [66-100 %]; an FAR of 0.13 [0.08, 0.24] per 24 h; a precision of 22 % [11 %, 37 %]; and a latency of 37.38 s [13.24 s]. Notably, a single AMB participant was responsible for 8 of 31 false alarms. The AMB FAR excluding this participant was 0.10 [0.07, 0.14] per 24 h.
DISCUSSION
This study demonstrates the practicability of TCS monitoring on a popular consumer wearable (Apple Watch) in daily use for people with epilepsy. The monitoring app had a high sensitivity and a substantially lower FAR than previously reported in both EMU and AMB environments.
PubMed: 38964183
DOI: 10.1016/j.yebeh.2024.109908 -
Neuro-oncology Jul 2024Treatment of childhood medulloblastoma has evolved to reduce neurotoxicity while improving survival. However, the impact of evolving therapies on late neurocognitive...
BACKGROUND
Treatment of childhood medulloblastoma has evolved to reduce neurotoxicity while improving survival. However, the impact of evolving therapies on late neurocognitive outcomes and adult functional independence remains unknown.
METHODS
Adult survivors of childhood medulloblastoma (n=505; median[minimum-maximum] age, 29[18-46] years) and sibling controls (n=727; 32[18-58] years) from the Childhood Cancer Survivor Study completed surveys assessing neurocognitive problems and chronic health conditions (CHCs). Treatment exposures were categorized as historical (craniospinal irradiation [CSI]≥30 Gy, no chemotherapy), standard-risk (CSI>0 to <30 Gy +chemotherapy) and high-risk (CSI≥30 Gy +chemotherapy) therapy. Latent class analysis identified patterns of functional independence using employment, independent living, assistance with routine/personal care needs, driver's license, marital/partner status. Multivariable models estimated risk of neurocognitive impairment in survivors versus siblings and by treatment exposure group, and associations between neurocognitive impairment, CHCs, and functional independence.
RESULTS
Survivors in each treatment exposure group had 4- to 5-fold elevated risk of impaired memory and task efficiency compared to siblings. Contemporary risk-based therapies did not confer lower risk compared to historical therapy. Survivors treated in the 1990s had higher risk of memory impairment (relative risk [RR] 2.24, 95% confidence interval [CI] 1.39-3.60) compared to survivors treated in the 1970s. Sensorimotor, hearing problems and seizures were associated with 33%-34%, 25-26% and 21%-42% elevated risk of task efficiency and memory impairment, respectively. Treatment-related CHCs and neurocognitive impairment were associated with non-independence.
CONCLUSIONS
Despite treatment changes, long-term survivors of childhood medulloblastoma remain at risk for neurocognitive impairment, which was associated with CHCs. Neurocognitive surveillance after contemporary regimens is imperative.
PubMed: 38963825
DOI: 10.1093/neuonc/noae119 -
Epilepsia Open Jul 2024To examine the efficacy and safety of perampanel (PER) in patients with post-stroke epilepsy (PSE), brain tumor-related epilepsy (BTRE), and post-traumatic epilepsy...
OBJECTIVE
To examine the efficacy and safety of perampanel (PER) in patients with post-stroke epilepsy (PSE), brain tumor-related epilepsy (BTRE), and post-traumatic epilepsy (PTE) using Japanese real-world data.
METHODS
The prospective post-marketing observational study included patients with focal seizures with or without focal to bilateral tonic-clonic seizures who received PER combination therapy. The observation period was 24 or 52 weeks after the initial PER administration. The safety and efficacy analysis included 3716 and 3272 patients, respectively. This post hoc analysis examined responder rate (50% reduction in seizure frequency), seizure-free rate (proportion of patients who achieved seizure-free), and safety in patients included in the post-marketing study who had PSE, BTRE, and PTE in the 4 weeks prior to the last observation.
RESULTS
Overall, 402, 272, and 186 patients were included in the PSE, BTRE, and PTE subpopulations, and 2867 controls in the "Other" population (etiologies other than PSE, BTRE, or PTE). Mean modal dose (the most frequently administered dose) values at 52 weeks were 3.38, 3.36, 3.64, and 4.04 mg/day for PSE, BTRE, PTE, and "Other," respectively; PER retention rates were 56.2%, 54.0%, 52.6%, and 59.7%, respectively. Responder rates (% [95% confidence interval]) were 82% (76.3%-86.5%), 78% (70.8%-83.7%), 67% (56.8%-75.6%), and 50% (47.9%-52.7%) for PSE, BTRE, PTE, and "Other," respectively, and seizure-free rates were 71% (64.5%-76.5%), 62% (54.1%-69.0%), 50% (40.6%-60.4%), and 28% (25.8%-30.1%), respectively. Adverse drug reactions tended to occur less frequently in the PSE (14.7%), BTRE (16.5%), and PTE (16.7%) subpopulations than in the "Other" population (26.3%).
SIGNIFICANCE
In real-world clinical conditions, efficacy and tolerability for PER combination therapy were observed at low PER doses for the PSE, BTRE, and PTE subpopulations.
PLAIN LANGUAGE SUMMARY
To find out how well the medication perampanel works and whether it is safe for people who have epilepsy after having had a stroke, brain tumor, or head injury, we used information from real-life medical situations in Japan. We looked at the data of about 3700 Japanese patients with epilepsy who were treated with perampanel. We found that perampanel was used at lower doses and better at controlling seizures, and had fewer side effects for patients with epilepsy caused by these etiologies than the control group.
PubMed: 38963336
DOI: 10.1002/epi4.13002