The lack of influence of IVS5-91 G>A polymorphism of the SCN1A gene on efficacy of lamotrigine in patients with focal epilepsy

ABSTRACT

Background: IVS5-91G>A (rs3812718) polymorphism of the sodium voltage-gated channel alpha subunit 1 (SCN1A) gene has been associated with inadequate responsiveness to common antiepileptic drugs which act as sodium channel blockers. This study was performed to investigate the effect of IVS5-91G>A (rs3812718) polymorphism on lamotrigine (LTG) efficacy in a cohort of patients with non-lesional focal epilepsy taking LTG as monotherapy.

Methods: A total of 100 of patients with non-lesional focal epilepsy on LTG monotherapy was included in this prospective interventional study. After reaching a stable dose of LTG patients were followed-up for 12 consecutive months. LTG responsiveness was defined as a 75% or more reduction in seizure frequency on a stable dose of LTG. Genotyping was performed at the end of the study using standard procedures and data were correlated with clinical data.

Results: There were no significant differences in the prevalence of responsiveness to LTG between carriers of different genotypes. Average maintenance LTG doses in the responder group differed by genotype in the order AA>GA>GG, but these differences did not reach statistical significance.

Conclusion: Our data suggest lack of association between SCN1A IVS5-91G>A (rs3812718) polymorphism and response to LTG.     

Delay in the diagnosis of multiple sclerosis in Croatia

BackgroundThe National Institute for Health and Clinical Excellence (NICE) guidelines for multiple sclerosis (MS) recommend the time from initial presentation to first neurological evaluation to be no longer than 6 weeks, and a further 6 weeks until any necessary investigations are completed. The aim of this study was to evaluate how many patients with MS are diagnosed within the NICE timelines in two settings specific for Croatia.Patients and methodsAll patients with the final diagnosis of clinically isolated syndrome (CIS) or MS in a 6 months period were retrospectively reviewed. We calculated time from first symptom to first neurological evaluation, time from first symptom to MRI scan, time from first neurological evaluation to MRI scan, time from first neurological evaluation to lumbar puncture (LP), time from first symptom to diagnosis and time from first neurological evaluation to diagnosis. We also calculated the percentage of patients fulfilling the NICE timelines.ResultsThis study showed that only 61.5% of MS patients in Croatia see neurologist within 6 weeks of first symptoms, and 64.1% are diagnosed within next 6 weeks. However, 80% and 100% of patients presented to the emergency room of our hospital (where a visit to a MS clinic can be automatically made) met the NICE guidelines for time from first symptom to first neurological evaluation and time from first neurological evaluation to diagnosis, respectively.ConclusionA specifically designed demyelinating disease diagnostic clinic offers a better service than other existing models in the diagnosis and management of MS patients.     

A common polymorphism in the brain-derived neurotrophic factor gene in patients with adult-onset primary focal and segmental dystonia

Brain-derived neurotrophic factor (BDNF) modulates neuroplasticity. A functional polymorphism [Val66Met (G196A)] in BDNF has been reported to modify cortical plasticity in humans. Physiologic investigations have revealed that dystonia might be a consequence of the pathologic plasticity of the sensorimotor cortex. We aimed to investigate the role of the Val66Met polymorphism in a cohort of Serbian patients with adult-onset primary focal and segmental dystonia (PTD). One hundred and forty-nine patients with primary adult-onset PTD, 194 patients with Parkinson’s disease (PD), and 366 healthy control subjects were recruited for the study. Patients with PTD and PD, as well as healthy controls had a similar distribution of genotypes and allele frequencies. There was no any significant difference in the allelic distribution at the Val66Met SNP of the BDNF gene among patients with adult-onset PTD, PD, and healthy volunteers from the same geographic areas. In addition, the presence of the Met allele did not influence the clinical characteristics of PTD patients. Patients with the Met variant did not differ by age at onset, number of affected regions, and efficacy of a sensory trick. Met66Met is not associated with an increased risk of dystonia.     

Cardiologic predictors of sudden death in patients with myotonic dystrophy type 1

The aim of this study was to analyze survival, causes of death and cardiologic predictors of sudden death in a large cohort of patients with myotonic dystrophy type 1 (DM1). The study was comprised of 171 adult DM1 patients hospitalized at the Neurology Clinic in a 20-year period. Severe electrocardiographic (ECG) abnormality included at least one of the following: rhythm other than sinus, PR interval of ?240 ms, QRS complex duration of 120 ms or more, and second-degree or third-degree atrioventricular (AV) block. Survival data were analyzed by the Kaplan–Meier test, log–rank test and Cox regression analysis. During the mean follow-up period of 9.4 ± 5.4 years, a pacemaker was implanted in 5.8% of DM1 patients and 14% of patients died. The mean age at death was 55.6 ± 12.5 years. The most common causes of death in our cohort were sudden death (41.7%) and respiratory failure (29.2%). The presence of palpitations (hazard ratio [HR] = 4.7, p < 0.05) and increased systolic blood pressure (HR = 9.8, p < 0.05) were significant predictors of sudden death. Among ECG parameters, severe ECG abnormality (HR = 4.7, p < 0.05), right bundle branch block (RBBB; HR = 3.9, p < 0.05) and bifascicular block (HR = 5.8, p < 0.05) were significant predictors of sudden death.     

Episodic ataxia and severe infantile phenotype in spinocerebellar ataxia type 14: expansion of the phenotype and novel mutations

Journal of Neurology - Spinocerebellar ataxia type 14 (SCA14) is a dominantly inherited neurological disorder characterized by slowly progressive cerebellar ataxia. SCA14 is caused by mutations in...     

POLR3A variants in hereditary spastic paraparesis and ataxia: clinical,genetic, and neuroradiological findings in a cohort of Italian patients

Neurological Sciences - Mutations in POLR3A are characterized by high phenotypic heterogeneity, with manifestations ranging from severe childhood-onset hypomyelinating leukodystrophic syndromes to...