Journal of neurology, neurosurgery, and psychiatry
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J. Neurol. Neurosurg. Psychiatr. · Dec 2024
Fewer relapses and worse outcomes of patients with late-onset myelin oligodendrocyte glycoprotein antibody-associated disease.
To delineate the clinical characteristics and outcomes of late-onset myelin oligodendrocyte glycoprotein antibody-associated disease (LO-MOGAD) and compare them with those of early-onset MOGAD (EO-MOGAD). ⋯ Compared with patients with EO-MOGAD, patients with LO-MOGAD exhibited fewer relapsing courses but worse disability outcomes and should be actively treated.
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J. Neurol. Neurosurg. Psychiatr. · Dec 2024
Analysis of GFAP variants in UK Biobank suggests underdiagnosis or incomplete penetrance of adult-onset Alexander disease.
Alexander disease is an autosomal dominant leukodystrophy caused by heterozygous pathogenic variants in the glial fibrillar acidic protein (GFAP) gene. Although increasingly recognised, there is evidence that Alexander disease, particularly later-onset disease, is significantly underdiagnosed and its true prevalence is unknown (the only population-based prevalence was estimated at one in 2.7 million). Using the extensive UK Biobank dataset, we analysed the frequency of pathogenic and likely pathogenic variants, GFAP variants, within the UK population and identified clinical and radiological phenotypes linked to these variants. ⋯ Pathogenic and likely pathogenic GFAP variants are more prevalent in the general population than previously expected and are associated with clinical and radiological characteristics of Alexander disease. This study indicates that Alexander disease may be under-reported, misdiagnosed, or exhibit reduced penetrance.
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J. Neurol. Neurosurg. Psychiatr. · Dec 2024
ReviewFunctional pathology of neuroleptic-induced dystonia based on the striatal striosome-matrix dopamine system in humans.
Neuroleptic-induced dystonia is a source of great concern in clinical practice because of its iatrogenic nature which can potentially lead to life-threatening conditions. Since all neuroleptics (antipsychotics) share the ability to block the dopamine D2-type receptors (D2Rs) that are highly enriched in the striatum, this drug-induced dystonia is thought to be caused by decreased striatal D2R activity. However, how associations of striatal D2R inactivation with dystonia are formed remains elusive. ⋯ The article proposes a functional pathology of the striosome-matrix dopamine system for neuroleptic-induced acute dystonia or neuroleptic-withdrawal dystonia. A rationale for the effectiveness of dopaminergic or cholinergic pharmacotherapy is also provided for treating dystonias. This narrative review covers various aspects of the relevant field and provides a detailed discussion of the mechanisms of neuroleptic-induced dystonia.
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J. Neurol. Neurosurg. Psychiatr. · Nov 2024
Cutaneous phosphorylated-synuclein: an early diagnostic biomarker for pure autonomic failure.
Pure autonomic failure (PAF) presents with progressive autonomic failure without other neurological features. Atypical presentations may lead to diagnostic uncertainty. We studied whether cutaneous phosphorylated-alpha-synuclein (p-syn) could distinguish between PAF, multiple system atrophy (MSA) and non-synucleinopathy-related autonomic failure, and examined its relationship with quantitative markers of cardiovascular autonomic failure. ⋯ Cutaneous p-syn was abundant in PAF, a predominantly peripheral alpha-synucleinopathy. It is a promising biomarker to help distinguish between PAF, MSA and non-synucleinopathy-related autonomic failure to aid early diagnosis and recruitment to future clinical trials. P-syn deposition on autonomic nerves may impair control of total peripheral resistance giving rise to symptomatic orthostatic hypotension.