1,720,975 research outputs found
Very early pattern of movement disorders in sepiapterin reductase deficiency.
No full text[No abstract available
The burden of epilepsy on long-term outcome of genetic developmental and epileptic encephalopathies: A single tertiary center longitudinal retrospective cohort study
Full text linkBackground: This retrospective cohort analysis highlighted neurodevelopmental outcome predictors of genetic developmental and epileptic encephalopathies (DEE). Patients and methods: Patients' demographic, clinical and molecular genetics data were collected. All patients underwent clinical, developmental, and neuropsychological assessments. Results: We recruited 100 participants (53 males, 47 females) with a mean follow-up lasting 10.46 ± 8.37 years. Age at epilepsy-onset was predictive of poor adaptive and cognitive functions (VABS-II score, r = 0.350, p = 0.001; BRIEF control subscale, r = -0.253; p = 0.031). Duration of epilepsy correlated negatively with IQ (r = -0.234, p = 0.019) and VABS-II score (r = -0.367, p = 0.001). Correlations were found between delayed/lacking EEG maturation/organization and IQ (r = 0.587, p = 0.001), VABS-II score (r = 0.658, p = 0.001), BRIEF-MI and BRIEF-GEC scores (r = -0.375, p = 0.001; r = -0.236, p = 0.033), ASEBA anxiety (r = -0.220, p = 0.047) and ADHD (r = -0.233, p = 0.035) scores. The number of antiseizure medications (ASMs) correlated with IQ (r = -0.414, p = 0.001), VABS-II (r = -0.496, p = 0.001), and BRIEF-MI (r = 0.294, p = 0.012) scores; while age at the beginning of therapy with ASEBA anxiety score (r = 0.272, p = 0.013). The occurrence of status epilepticus was associated with worse adaptive performances. The linear regression analysis model showed that delayed/lacking EEG maturation/organization had a significant influence on the IQ (R2 = 0.252, p < 0.001) and the BRIEF-GEC variability (R2 = 0.042, p = 0.036). The delayed/lacking EEG maturation/organization and the duration of epilepsy also had a significant influence on the VABS-II score (R2 = 0.455, p = 0.005). Conclusions: Age at seizure-onset, EEG maturation/organization, duration of epilepsy, occurrence of status epilepticus, age at the introduction and number of ASMs used are reliable predictors of long-term outcomes in patients with genetic DEE
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The diagnostic and prognostic role of cerebrospinal fluid biomarkers in glucose transporter 1 deficiency: a systematic review
Full text link: The purpose of this study is to investigate the diagnostic and prognostic role of cerebrospinal fluid (CSF) biomarkers in the diagnostic work-up of glucose transporter 1 (GLUT1) deficiency. Reported here is a systematic review according to PRISMA guidelines collecting clinical and biochemical data about all published patients who underwent CSF analysis. Clinical phenotypes were compared between groups defined by the levels of CSF glucose (≤ 2.2 mmol/L versus > 2.2 mmol/L), CSF/blood glucose ratio (≤ 0.45 versus > 0.45), and CSF lactate (≤ 1 mmol/L versus > 1 mmol/L). Five hundred sixty-two patients fulfilled the inclusion criteria with a mean age at the diagnosis of 8.6 ± 6.7 years. Patients with CSF glucose ≤ 2.2 mmol/L and CSF/blood glucose ratio ≤ 0.45 presented with an earlier onset of symptoms (16.4 ± 22.0 versus 54.4 ± 45.9 months, p < 0.01; 15.7 ± 23.8 versus 40.9 ± 38.0 months, p < 0.01) and received an earlier molecular genetic confirmation (92.1 ± 72.8 versus 157.1 ± 106.2 months, p < 0.01). CSF glucose ≤ 2.2 mmol/L was consistently associated with response to ketogenic diet (p = 0.018) and antiseizure medications (p = 0.025). CSF/blood glucose ratio ≤ 0.45 was significantly associated with absence seizures (p = 0.048), paroxysmal exercise-induced dyskinesia (p = 0.046), and intellectual disability (p = 0.016) while CSF lactate > 1 mmol/L was associated with a response to antiseizure medications (p = 0.026) but not to ketogenic diet.Conclusions:This systematic review supported the diagnostic usefulness of lumbar puncture for the early identification of patients with GLUT1 deficiency responsive to treatments especially if they present with co-occurring epilepsy, movement, and neurodevelopmental disorders. What is Known: • Phenotypes of GLUT1 deficiency syndrome range between early epileptic and developmental encephalopathy to paroxysmal movement disorders and developmental impairment What is New: • CSF blood/glucose ratio may predict better than CSF glucose the diagnosis in children presenting with early onset absences • CSF blood/glucose ratio may predict better than CSF glucose the diagnosis in children presenting with paroxysmal exercise induced dyskinesia and intellectual disability. • CSF glucose may predict better than CSF blood/glucose and lactate the response to ketogenic diet and antiseizure medications
Long-term neurological and psychiatric outcomes in patients with aromatic l-amino acid decarboxylase deficiency
No full textbiogenic amine synthesis that presents with early-onset encephalopathy progressing to severe neurological
impairment and intellectual disability. We aimed to explore neurocognitive and behavioral profiles associated
with AADCD and possible factors predicting outcome in more detail.
Methods: Nine AADCD patients (23.2 ± 10.3 years; range 8–40) underwent systematic clinical and neuropsychological
assessment. Diagnostic levels of CSF 5-hydroxyindolacetic acid (5-HIAA) and homovanillic acid
(HVA), and DDC genotype (as ascertained by American College of Medical Genetics and Genomics grading) were
included in the data analysis.
Results: All AADCD patients were affected by intellectual disability and psychiatric disorders. Movement disorders
included parkinsonism-dystonia, dysarthria, and oculogyric crises. CSF 5-HIAA and HVA levels at diagnosis
had a significant influence on adaptive behavior and executive function performance. Patients homozygous for
DDC pathogenetic variants showed lower CSF 5-HIAA and HVA levels and higher Unified Parkinson’s Disease
Rating Scale scores. The disease showed a self-limiting clinical course with partial improvement under pharmacological
treatment (B6 and dopamine mimetic drugs).
Conclusions: Patients with AADCD suffer from neuropsychological and psychopathological impairment, which
may be improved but not reversed under the present therapeutic approach. However, cognitive functioning
should be specifically examined in order to avoid its underestimation on the basis of movement disorder severity.
Genotype and biogenic amine level at diagnosis have an important prognostic value
KCND3-Related Neurological Disorders: From Old to Emerging Clinical Phenotypes
Full text linkAbstract: KCND3 encodes the voltage-gated potassium ion channel subfamily D member 3, a six
trans-membrane protein (Kv4.3), involved in the transient outward K+ current. KCND3 defect
causes both cardiological and neurological syndromes. From a neurological perspective, Kv4.3
defect has been associated to SCA type 19/22, a complex neurological disorder encompassing a
wide spectrum of clinical features beside ataxia. To better define the phenotypic spectrum and
course of KCND3-related neurological disorder, we review the clinical presentation and evolution
in 68 reported cases. We delineated two main clinical phenotypes according to the age of onset.
Neurodevelopmental disorder with epilepsy and/or movement disorders with ataxia later in the
disease course characterized the early onset forms, while a prominent ataxic syndrome with possible
cognitive decline, movement disorders, and peripheral neuropathy were observed in the late onset
forms. Furthermore, we described a 37-year-old patient with a de novo KCND3 variant [c.901T>C
(p.Ser301Pro)], previously reported in dbSNP as rs79821338, and a clinical phenotype paradigmatic
of the early onset forms with neurodevelopmental disorder, epilepsy, parkinsonism-dystonia, and
ataxia in adulthood, further expanding the clinical spectrum of this conditio
A new case of malonic aciduria with a presymptomatic diagnosis and an early treatment
No full textMalonyl-CoA decarboxylase deficiency (MLYCD) is a rare autosomal recessive inborn error of metabolism presenting a variable clinical phenotype. We report an affected Italian male receiving an early diagnosis (8days after birth) and a timely dietary therapy (high carbohydrate, low long chain fatty acid and medium chain triglyceride supplemented diet with l-carnitine supplementation). The boy was born at term and presented normal function of the heart (except for a tricuspid Ebstein-like dysplasia) and neurodevelopmental status. Genomic sequencing of MLYCD gene revealed two point mutations (c.672G>A, c.869C>T) not listed in the Human MLYCD Allelic Variant Database nor in Human Gene Mutation Database, responsible for a deleterious effect on protein structure and function according to a computational analysis (MuPro, SIFT, ConSEQ v1.1). At the age of 2years he only showed a mild language and psychomotor delay, while heart functioning became normal. Brain MRI examination was normal. Thirty-five cases, including our patient, have been described to date. This is the first report concerning a malonic aciduria patient diagnosed on newborn screening and treated in a presymptomatic stage of the disease
Outcome in short chain acyl-CoA dehydrogenase deficiency (SCADD) detected by newborn screening (NBS)
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