Summary Objective To investigate the clinical features and outcome of epilepsy in children under 3 years of age with supratentorial brain tumors. Methods Patients under 3 years with primary ...supratentorial hemispheric brain tumors were collected during a 10-year period through a database including demographic and clinical features, neuroimaging, tumor location, developmental outcome, pharmacological and surgical treatment, and tumor histology. Postoperative outcome was assessed according to Engel classification. Results Among 28 children evaluated, twenty (71.4%) suffered from epilepsy. Mean age at seizure onset was 18.7 months (range: 1–60). In fifteen (75%) children, epilepsy was an early manifestation or the presenting symptom of the tumor; seizures were focal in 8 (53.3%) and generalized in 7 (46.7%) individuals. Three (15%) children presented with an epileptic encephalopathy and continuous spike-waves during sleep. Of the five children with epilepsy onset after surgery, four had focal seizures. Post-surgical follow-up ranged from 4 to 10 years (mean: 7.6 ± 3.74). The outcome of epilepsy was generally good, with most children (76.4%) being seizure free (Engel I) or showing >90% improvement in seizure frequency (Engel II) after surgery. However, in about 20% of the cases, epilepsy persisted despite surgery and different AEDs regimen. Best epilepsy outcome was observed in patients with low-grade tumors ( p < 0.01) and without neurological deficits after surgery ( p < 0.001). Conclusions Epilepsy is a common and early symptom in infants with brain tumors. Its outcome is negatively influenced by high tumor malignancy and by the persistence of neurological deficits after surgery. Treatment of these patients needs a multidisciplinary approach.
In the last few months, some pediatric cases with neurological and neuroradiological pictures related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been reported, ...often associated with multisystem inflammatory syndrome (MIS-C). The most frequently encountered pediatric neurological complications seem to be postinfectious immune-mediated acute disseminated encephalomyelitis (ADEM)-like changes of the brain, myelitis, neural enhancement, and splenial lesions. Concomitant neurological and cardiac involvement has been reported only in MIS-C, although specific clinical details are often not fully available.
In this case report, a very young child infected with SARs-CoV-2 and diagnosed as longitudinal extensive transverse myelitis with concomitant myo-pericarditis is presented.
A previously healthy 7-month-old girl presented with abrupt onset of generalized weakness with inability to sit up. She had had mild respiratory symptoms 1 week earlier. Spinal magnetic resonance imaging (MRI) showed a T2-hyperintense intramedullary lesion extending from C4 to T2, compatible with acute longitudinally extensive transverse myelitis (LETM). Cerebrospinal fluid analysis was negative.Echocardiography and blood tests were suggestive for myo-pericarditis. Real time polymerase chain reaction for SARS-CoV-2 on nasopharyngeal swab sample tested positive. She was promptly treated with high dose of steroids and immunoglobulin with satisfactory clinical response.
To the evolving literature of neurological complications of SARs-CoV-2 infection, we add the youngest patient described to date with isolated LETM and concomitant cardiac involvement. Our case suggests that clinicians should be aware of this association, although difficult to recognize in infants. Practitioners are encouraged to consider aggressive first-line immunotherapies with the final aim to prevent permanent disability.
Sleep disorders (SD) are very common in childhood, especially in certain genetic syndromes. Tuberous Sclerosis Complex (TSC) is a genetic syndromesassociated with a high rate of SD, although these ...are still under-recognized. The aim of this study was to assess the prevalence of SD in TSC, and to evaluate the relationship between sleep, epilepsy and TSC-associated neuropsychiatric disorders (TAND).
We administered the Sleep Disturbance Scale for Children (SDSC) and the Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD) to parents of 177 children with TSC referring to different Italian centers. We also collected information on epilepsy and TAND.
SDSC score was positive in 59.3% of patients, being positive in 30.4% of patients without and in 63.6% of those with epilepsy (p = 0.005). However, in a multivariate logistic model considering antiseizure medications and nocturnal seizures, epilepsy ceased to be a significant risk factor for positive SDSC (OR = 2.4; p = 0.17). As for TAND, SDSC was positive in 67.9% of patients with and in 32.5% of those without TAND (p < 0.001). After adding in a multivariate logistic model active epilepsy, age, and pharmacotherapies, TAND continued to be a significant risk factor for positive SDSC (p = 0.01, OR = 1.11).
Our results revealed a high prevalence of SD in children with TSC. Epilepsy didn't increase the risk for SD, while a very strong association was found with TAND. An early detection of SD is of utmost importance in order to plan an individualized treatment, that in some cases might also ameliorate behavior and attention.
•59.3% of children and adolescents with TSC presented a pathologic SDSC total score.•Sleep disorders are more frequent in patients with neuropsychiatric disorders.•Significantly higher prevalence of sleep disorders in ASD and intellectual disability.•Sleep disorders exacerbate cognitive and behavioral difficulties.•High prevalence and burden, so SD are a significant focus for clinical intervention.
Background
Periventricular nodular heterotopia (PVNH) is a congenital brain malformation often associated with seizures. We aimed to clarify the spectrum of epilepsy phenotypes in PVNH and the ...significance of specific brain malformation patterns.
Methods
In this retrospective cohort study, we recruited people with PVNH and a history of seizures, and collected data via medical record review and a standardized questionnaire.
Results
One hundred individuals were included, aged 1 month to 61 years. Mean seizure onset age was 7.9 years. Ten patients had a self-limited epilepsy course and 35 more were pharmacoresponsive. Fifty-five had ongoing seizures, of whom 23 met criteria for drug resistance. Patients were subdivided as follows: isolated PVNH (“PVNH-Only”) single nodule (18) or multiple nodules (21) and PVNH with additional brain malformations (“PVNH-Plus”) single nodule (8) or multiple nodules (53). Of PVNH-Only single nodule, none had drug-resistant seizures. Amongst PVNH-Plus, 55% with multiple unilateral nodules were pharmacoresponsive, compared to only 21% with bilateral nodules. PVNH-Plus with bilateral nodules demonstrated the highest proportion of drug resistance (39%). A review of genetic testing results revealed eight patients with pathogenic or likely pathogenic single-gene variants, two of which were
FLNA
. Five had copy number variants, two of which were pathogenic.
Conclusions
The spectrum of epilepsy phenotypes in PVNH is broad, and seizure patterns are variable; however, epilepsy course may be predicted to an extent by the pattern of malformation. Overall, drug-resistant epilepsy occurs in approximately one quarter of affected individuals. When identified, genetic etiologies are very heterogeneous.
•Children with acute CNS complication during HCT have higher epilepsy risk.•Epilepsy rate is 9.6 %, 5-year cumulative incidence is 13.3 %.•Status epilepticus as CNS complication correlates with ...epilepsy development (OR=14).•Need for tailored neuro follow-up post-HCT in children with acute CNS complication.
Acute central nervous system (CNS) complications are common and well described among pediatric patients undergoing haematopoietic cell transplantation (HCT). However, their long-term outcomes are not known. The aim of this study is to describe the incidence, characteristics, and risk factors of long-term epilepsy in pediatric patients with acute CNS complications of HCT.
This retrospective study included pediatric patients who developed acute CNS complications from autologous or allogeneic HCT between 2000 and 2022. Clinical, therapeutic and prognostic data including long-term outcomes were analyzed. A diagnosis of epilepsy was provided if unprovoked seizures occurred during follow-up.
Ninety-four patients (63 males, 31 females, median age 10 years, range 1–21 years) were included. The most common acute CNS complications were posterior reversible encephalopathy syndrome (n = 43, 46 %) and infections (n = 15, 16 %). Sixty-five patients (69 %) had acute symptomatic seizures, with 14 (16 %) having one or more episodes of status epilepticus (SE). Nine patients (9.6 %) were diagnosed with long-term focal epilepsy during the follow-up (5-year cumulative incidence from the acute complication, 13.3 %). Acute symptomatic SE during neurological complications of HCT was associated with an increased risk of long-term epilepsy (OR=14, 95 % CI 2.87–68.97).
A higher occurrence of epilepsy has been observed in our cohort compared to the general population. Acute symptomatic SE during HCT was associated with a higher risk of long-term epilepsy. Pediatric patients with CNS complications during HCT could benefit from specific neurological follow-up. Further studies are needed to characterize mechanisms of epileptogenesis in pediatric patients undergoing HCT.
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Purpose: The role of the familial background in severe myoclonic epilepsy of infancy (SMEI) has been traditionally emphasized in literature, with 25–70% of the patients having a family history of ...febrile seizures (FS) or epilepsy. We explored the genetic background of SMEI patients carrying SCN1A mutations to further shed light on the genetics of this disorder.
Methods: We analyzed the occurrence of FS and epilepsy among first‐ and second‐degree relatives (N = 867) of 74 SMEI probands with SCN1A mutations (70 de novo, four inherited) and compared data with age‐matched and ethnically matched control families. Familial clustering and syndromic concordance within the affected relatives in both groups were investigated.
Results: The frequency of FS or epilepsy in relatives of SMEI patients did not significantly differ from that in controls (FS: 13 of 867 vs. 12 of 674, p = 0.66; epilepsy: 15 of 867 vs. six of 674, p = 0.16). Different forms of epilepsy were identified in both relatives of SMEI probands and controls. Twenty‐eight relatives with FS and epilepsy were distributed in 20 (27%) of 74 SMEI families; among the controls, 18 affected relatives were clustered in 13 (18.5%) of 70 families. No pedigree showed several affected members, including the four with inherited mutations.
Conclusions: A substantial epileptic family background is not present in our SMEI patients with SCN1A mutations. These data do not confirm previous observations and would not support polygenic inheritance in SMEI. The investigation of the family background in additional series of SMEI patients will further shed light on the genetics of this syndrome.
The KCNQ5 gene, widely expressed in the brain, encodes a voltage-gated potassium channel (Kv7.5) important for neuronal function. Here, we report a novel KCNQ5 intragenic duplication at 6q13 spanning ...about 239 Kb of genomic DNA, identified by array comparative genomic hybridization (array-CGH). The duplication was found in heterozygosity in an adult patient affected by mild intellectual disability with history of absence epilepsy in adolescence, with no EEG nor MRI alterations. By in vitro analyses we demonstrated that this copy number variation (CNV) led to an aberrant transcript with exon 2–11 skipping and a premature stop codon causing, most likely, haploinsufficiency.
The Kv7.5 channel plays an important role in the regulation of M-type current and afterhyperpolarization conductances which contribute to neuronal excitability. A recently published paper described KCNQ5 missense mutations in individuals with intellectual disability and treatment-resistant epilepsy that were thought to act through either loss-of-function or gain-of-function mechanisms, associated in both cases with altered neuronal excitability.
In the case reported here, we showed that no functional protein can be produced from the allele involved by the intragenic duplication. This evidence strongly supports the hypothesis of KCNQ5 haploinsufficiency, which could lead to altered neuronal excitability, thus contributing to seizure susceptibility and intellectual disability.
Abstract Studies of epilepsy associated with chromosomal abnormalities may provide information about clinical and EEG phenotypes and possibly to identify new epilepsy genes. We describe a female ...patient with intractable focal epilepsy, borderline intellectual functioning, and facial dysmorphisms, in whom genetic study (i.e., karyotype and array-CGH analysis) revealed a distal trisomy 4p and distal monosomy Xq. Although any genetic hypothesis remains speculative, several genes are located in the 4p chromosome segment involved in the rearrangement, some of which may be related to epilepsy.
Introduction
Variants in the CACNA1A gene on chromosome 19p13 result in a spectrum of neurological phenotypes ranging from familial or sporadic hemiplegic migraine to congenital or progressive ...encephalopathies. Patients with CACNA1A variants often show acute attacks with ataxia or hemiplegia till coma, sometimes related to unilateral brain oedema. No guidelines for the medical management of these attacks are available since treatment is empiric, and many cases do not respond to common antimigraine drugs.
Case description
We report on the emergency personalized treatment protocol used in an 11 year-old girl with CACNA1A-related encephalopathy for the management of acute attacks of headache, hemiconvulsions and hemiplegia with coma.
Discussion
Combined corticosteroid pulses and hypertonic solution led to a reduction in severity and duration of acute attacks when administered in the early stages, characterized by migraine, seizure, fever, vomiting and impairment of consciousness associated to hemispheric slowing on the EEG.
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