Journal of neurology, neurosurgery, and psychiatry
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J. Neurol. Neurosurg. Psychiatr. · Dec 2018
Age at onset of genetic (E200K) and sporadic Creutzfeldt-Jakob diseases is modulated by the CYP4X1 gene.
The Glu to Lys change at codon 200 (E200K) of the PRNP gene is the most frequent mutation associated to genetic Creutzfeldt-Jakob disease (CJD) and the only one responsible for geographical clusters. Patients carrying this mutation develop disease at different ages and show variable clinical phenotypes that are not affected by the methione/valine polymorphism at codon 129 of the PRNP gene suggesting the influence of other factors. The objective of this study is to look for genes other than PRNP that might be responsible of this variability. ⋯ We identified two single nucleotide polymorphisms on the CYP4X1 gene locus as candidate disease modifiers in patients with E200K CJD of the cluster area and confirmed this finding in 32 patients with E200K CJD from non-cluster areas and 259 patients with sporadic CJD. Our results indicate that the CYP4X1 gene modulates the onset of disease in patients with E200K genetic and sporadic CJD. This finding improves our understanding on the pathogenesis of CJD, suggests new targets for developing novel therapeutic strategies and might be useful for the stratification of patients in future preventive treatment trials.
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J. Neurol. Neurosurg. Psychiatr. · Dec 2018
Regional thalamic MRI as a marker of widespread cortical pathology and progressive frontotemporal involvement in amyotrophic lateral sclerosis.
The thalamus is a major neural hub, with selective connections to virtually all cortical regions of the brain. The multisystem neurodegenerative syndrome amyotrophic lateral sclerosis (ALS) has pathogenic overlap with frontotemporal dementia, and objective in vivo markers of extra-motor pathological spread are lacking. To better consider the role of the thalamus in neurodegeneration, the present study assessed the integrity of the thalamus and its connectivity to major cortical regions of the brain in a longitudinal manner. ⋯ Regional thalamic connectivity changes mirror the progressive frontotemporal cortical involvement associated with the motor functional decline in ALS. Longitudinal MRI thalamic parcellation has potential as a non-invasive surrogate marker of cortical dysfunction in ALS.
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J. Neurol. Neurosurg. Psychiatr. · Dec 2018
In utero exposure to antiepileptic drugs is associated with learning disabilities among offspring.
In utero exposure to antiepileptic drugs has previously been associated with adverse outcome among offspring, but evidence on longer term milestone development remains limited. We investigated the association between in utero exposure to antiepileptic drugs and learning disabilities in the first year of compulsory education among offspring and assessed which antiepileptic drugs carried the highest risk. ⋯ In utero exposure to antiepileptic drugs was significantly associated with learning disabilities among offspring. Lamotrigine should preferentially be considered over, for example, valproate if clinically feasible.
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J. Neurol. Neurosurg. Psychiatr. · Dec 2018
Transcranial magnetic stimulation predicts cognitive decline in patients with Alzheimer's disease.
To determine the ability of transcranial magnetic stimulation (TMS) in detecting synaptic impairment in patients with Alzheimer's disease (AD) and predicting cognitive decline since the early phases of the disease. ⋯ TMS-based assessment of LTP-like cortical plasticity could be a viable biomarker to assess synaptic impairment and predict subsequent cognitive decline progression in patients with ADs.