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Epilepsy & Behavior : E&B Jul 2020Dravet syndrome (DS) is a developmental and epileptic encephalopathy with onset in the first year of life. At onset, the child displays normal development, but during...
BACKGROUND
Dravet syndrome (DS) is a developmental and epileptic encephalopathy with onset in the first year of life. At onset, the child displays normal development, but during the second year of life, stagnation/slowing of neurodevelopment is seen. In addition to difficulties with intellectual development, many children display behavioral problems including autistic features, and difficulties with attention and hyperactivity.
AIM
The aim of the present study was to systematically review studies that have focused on the prevalence of cognitive/developmental quotients (DQs) consistent with intellectual disability (ID), deficits in adaptive behavior, autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and behavioral difficulties. A secondary aim was to consider possible factors associated with intellectual and behavioral outcomes in individuals with DS.
METHOD
A systematic review using PubMed and Scopus following the Preferred Reporting Items for Systematic Review (PRISMA) guidelines was conducted on the 24th of September 2019. Study quality was rated by two researchers using the National Institutes of Health (NIH) Quality assessment tools.
RESULT
Twenty-nine studies met inclusion criteria. The pooled prevalence of ID was 86% (range across studies: 50%-100%). The pooled prevalence for ASD was 31%. The mean level of adaptive behavior was more than 2 standard deviations (SDs) below average. The prevalence of behavioral difficulties on standardized instruments ranged between 37% and 100%. The only factor consistently associated with lower cognitive scores was age with older children having significantly lower cognitive scores than younger children. For behavioral difficulties, the most consistent association was with low health-related quality of life (HRQoL) with better HRQoL associated with fewer behavioral difficulties. Study quality was almost universally poor or fair - 15/29 studies were rated 'poor', 13/29 studies were 'fair', and 1 was 'good'.
DISCUSSION
The prevalence of cognitive scores consistent with ID is very high in DS. Many patients also have significant deficits in adaptive behavior highlighting that the majority of patients with DS will meet criteria for ID. The prevalence of ASD would also appear to be higher than the general population but studies show a wide range. Behavioral difficulties are common, but most studies have not used instruments adapted to patients with low intelligence quotient/DQ (IQ/DQ). No study used standardized instruments to assess ADHD. Few studies have used comprehensive statistical methods to evaluate possible factors associated with worse cognitive and behavioral outcome.
CONCLUSION
It should be routine to screen for cognitive and behavioral difficulties for all patients with DS. There is a need for more robust studies regarding intellectual and behavioral disorders in patients with DS. These should be large population-based or multinational studies that employ standardized instruments.
Topics: Adaptation, Psychological; Adolescent; Attention; Child; Cognition; Epilepsies, Myoclonic; Female; Humans; Intellectual Disability; Male; Prevalence; Problem Behavior; Quality of Life
PubMed: 32334365
DOI: 10.1016/j.yebeh.2020.107079 -
Seizure Jan 2024Epilepsy is one of the most frequent neurological comorbidities in patients with Down Syndrome (DS). Young patients and adults are the most affected, the latter mostly... (Review)
Review
INTRODUCTION
Epilepsy is one of the most frequent neurological comorbidities in patients with Down Syndrome (DS). Young patients and adults are the most affected, the latter mostly showing a phenotype labeled as "Late-onset myoclonic epilepsy" (LOMEDS). Status epilepticus (SE) is a life-threatening complication in patients with epilepsy. In this study, we described a non-convulsive SE (NCSE) case in a patient diagnosed with LOMEDS. We also performed a systematic review of the literature on SE diagnosis and treatment in patients with Down Syndrome.
METHODS
Clinical and demographic characteristics of a DS patient diagnosed with NCSE were described. The systematic literature search dissected the diagnostic and therapeutic management of SE in patients with DS. The following databases were used: PubMed, EMBASE, and Google Scholar.
RESULTS
5 DS individuals (4 from the past literature + 1 novel case report) with SE have been identified. The median age at SE onset was 42 years (IQR: 21-60.5 years). The most common SE type was myoclonic SE (MSE), followed by NCSE. Two cases of acute symptomatic etiology were described, whereas a progressive symptomatic etiology was otherwise reported. Ictal EEG recording information was available in two patients who showed generalized spike waves and polyspike and wave discharges. In 3 cases, SE was treated with intravenous antiseizure medications that produced a complete resolution.
CONCLUSION
SE may represent a rare complication in patients with DS. Although no definitive conclusions may be achieved due to the lack of evidence, treatment with valproic acid seems effective, especially in MSE. NCSE management is more challenging. It requires low doses of anesthetics, which should be used cautiously due to the high rate of complications.
Topics: Adult; Humans; Middle Aged; Young Adult; Down Syndrome; Electroencephalography; Epilepsy; Status Epilepticus; Valproic Acid
PubMed: 38101201
DOI: 10.1016/j.seizure.2023.11.009 -
European Journal of Nuclear Medicine... Jun 2020To describe cerebral glucose metabolism pattern as assessed by F-fluorodeoxyglucose positron emission tomography (FDG-PET) in Lafora disease (LD), a rare, lethal form of...
PURPOSE
To describe cerebral glucose metabolism pattern as assessed by F-fluorodeoxyglucose positron emission tomography (FDG-PET) in Lafora disease (LD), a rare, lethal form of progressive myoclonus epilepsy caused by biallelic mutations in EPM2A or NHLRC1.
METHODS
We retrospectively included patients with genetically confirmed LD who underwent FDG-PET scan referred to three Italian epilepsy centers. FDG-PET images were evaluated both visually and using SPM12 software. Subgroup analysis was performed on the basis of genetic and clinical features employing SPM. Moreover, we performed a systematic literature review of LD cases that underwent FDG-PET assessment.
RESULTS
Eight Italian patients (3M/5F, 3 EPM2A/5 NHLRC1) underwent FDG-PET examination after a mean of 6 years from disease onset (range 1-12 years). All patients showed bilateral hypometabolic areas, more diffuse and pronounced in advanced disease stages. Most frequently, the hypometabolic regions were the temporal (8/8), parietal (7/8), and frontal lobes (7/8), as well as the thalamus (6/8). In three cases, the FDG-PET repeated after a mean of 17 months (range 7-36 months) showed a metabolic worsening compared with the baseline examination. The SPM subgroup analysis found no significant differences based on genetics, whereas it showed a more significant temporoparietal hypometabolism in patients with visual symptoms compared with those without. In nine additional cases identified from eight publications, FDG-PET showed heterogeneous findings, ranging from diffusely decreased cerebral glucose metabolism to unremarkable examinations in two cases.
CONCLUSIONS
FDG-PET seems highly sensitive to evaluate LD at any stage and may correlate with disease progression. Areas of decreased glucose metabolism in LD are extensive, often involving multiple cortical and subcortical regions, with thalamus, temporal, frontal, and parietal lobes being the most severely affected. Prospective longitudinal collaborative studies are needed to validate our findings.
Topics: Brain; Fluorodeoxyglucose F18; Humans; Lafora Disease; Positron-Emission Tomography; Prospective Studies; Retrospective Studies; Ubiquitin-Protein Ligases
PubMed: 31858178
DOI: 10.1007/s00259-019-04647-3 -
Seizure Oct 2021Rufinamide is an antiseizure medication that acts through sodium channels and is found to be efficacious in patients with Lennox Gastaut syndrome (LGS). However, no... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Rufinamide is an antiseizure medication that acts through sodium channels and is found to be efficacious in patients with Lennox Gastaut syndrome (LGS). However, no systematic review has been conducted in LGS patients to provide an estimate of the efficacy and safety of rufinamide.
METHODS
Different electronic databases were searched for articles describing the use of rufinamide in patients with LGS. For determining primary efficacy outcomes as compared to placebo, we included only studies comparing the efficacy of rufinamide with placebo in LGS patients. We performed an additional analysis to include other uncontrolled studies with a minimum sample size of 20 to provide a more comprehensive estimate of efficacy.
RESULTS
A total of ten studies included 557 patients. Out of them, five studies were placebo-controlled, enrolling a total of 265 patients in the rufinamide group and 203 patients in the placebo group. The average percentage reduction in total seizure frequency per 28 days during the double-blind phase was 29.3% in the rufinamide group compared with 8.3% in the placebo group (difference between the two groups was 20.9%, 95%CI-14.4%-27.3%, p <0.00001). Even for individual seizure types like tonic-clonic seizures, atypical absence seizures, atonic seizures, focal seizures, and myoclonic seizures, rufinamide was more efficacious than placebo(p<0.00001). The number of patients with at least one treatment-emergent adverse effects was significantly higher in rufinamide treated patients (60.2%vs50.7%, p=0.02, RR-1.24(1.03,1.51).
CONCLUSION
Rufinamide is efficacious as adjunctive therapy in patients with LGS in terms of reduction in total seizure frequency and has mild adverse reaction.
Topics: Anticonvulsants; Humans; Lennox Gastaut Syndrome; Randomized Controlled Trials as Topic; Seizures; Triazoles
PubMed: 34273668
DOI: 10.1016/j.seizure.2021.07.004