KIF1C-related disorders: spastic ataxia or hypomyelinating leukodystrophy? A paradigm of classification ambiguity.

A 40-year-old man with adult-onset spastic-ataxia and tremor showed a leukoencephalopathy with a hypomyelinating pattern on brain MRI. Whole-exome sequencing identified two novel likely pathogenic variants in KIF1C, a gene associated with spastic-ataxia type 2 (SPAX2). This case supports including KIF1C among the causes of adult-onset hypomyelinating leukodystrophies and highlights the diagnostic overlap between spastic-ataxia, hereditary spastic paraplegia, and hypomyelinating leukodystrophies, underscoring the limitations of current nomenclature.

Genetic diseases misdiagnosed as multiple sclerosis: Observational study and review of literature.

Background: Adult-onset neurogenetic diseases (NGDs) with white matter abnormalities are rare and often misdiagnosed as Multiple Sclerosis (MS) due to overlapping clinical and radiological features. Misdiagnosis can lead to unnecessary immunosuppressive treatments and delayed genetic counseling. This study combines a retrospective multicenter analysis with a systematic review of the literature to assess the characteristics of patients with NGDs misdiagnosed as MS (Mis-MS) or with coexisting MS (NGD-MS), with the goal of improving diagnostic accuracy.

Utility and limitations of homemade videos in differentiating functional seizures from other paroxysmal events: An Italian cohort study.

Objectives: The gold standard for distinguishing epileptic seizures (ES) from non-epileptic events is video-EEG monitoring. In some cases, video alone might suffice, leading to increased utilization of home videos, to support the diagnosis. This study aimed to assess the feasibility of such practice and its accuracy compared to video-EEG, to identify key signs and symptoms of functional seizure (FS) and to establish if self-reported questionnaires would improve diagnostic accuracy.

A systematic review and meta-analysis of GFAP gene variants in Alexander disease.

Alexander disease (ALXDRD) is a rare neurodegenerative disorder of astrocytes resulting from pathogenic variants in the GFAP gene. The genotype-phenotype correlation remains elusive due to the variable expressivity of clinical manifestations. In an attempt to clarify the effects of GFAP variants in ALXDRD, numerous studies were collected and analyzed.

Dysregulation of FLVCR1a-dependent mitochondrial calcium handling in neural progenitors causes congenital hydrocephalus.

Congenital hydrocephalus (CH), occurring in approximately 1/1,000 live births, represents an important clinical challenge due to the limited knowledge of underlying molecular mechanisms. The discovery of novel CH genes is thus essential to shed light on the intricate processes responsible for ventricular dilatation in CH. Here, we identify FLVCR1 (feline leukemia virus subgroup C receptor 1) as a gene responsible for a severe form of CH in humans and mice.

Brainstem Chipmunk Sign: A Diagnostic Imaging Clue across All Subtypes of Alexander Disease.

Background And Purpose: While classic brain MR imaging features of Alexander disease have been well-documented, lesional patterns can overlap with other leukodystrophies, especially in the early stages of the disease or in milder phenotypes. We aimed to assess the utility of a new neuroimaging sign to help increase the diagnostic specificity of Alexander disease.

Materials And Methods: A peculiar bilateral symmetric hyperintense signal on T2-weighted images affecting the medulla oblongata was identified in an index patient with type I Alexander disease.

Serum Neurofilament Light Chain in Replication Factor Complex Subunit 1 CANVAS and Disease Spectrum.

Background: Biallelic intronic AAGGG repeat expansions in the replication factor complex subunit 1 (RFC1) gene were identified as the leading cause of cerebellar ataxia, neuropathy, vestibular areflexia syndrome. Patients exhibit significant clinical heterogeneity and variable disease course, but no potential biomarker has been identified to date.

Objectives: In this multicenter cross-sectional study, we aimed to evaluate neurofilament light (NfL) chain serum levels in a cohort of RFC1 disease patients and to correlate NfL serum concentrations with clinical phenotype and disease severity.

Interval between contrast administration and T1-weighted MRI for cerebral adrenoleukodystrophy: a single-case observation.

In adrenoleukodystrophy (ALD), contrast enhancement (CE) is a disease activity marker, but there is uncertainty about the optimal delay, if any, between contrast injection and magnetic resonance imaging (MRI) acquisition to avoid false-negative results. We acquired axial two-dimensional (2D) and three-dimensional (3D) T1-weighted gradient-echo every 6 min from 0 to 36 min after contrast administration (gadobutrol 0.1 mmol/kg) in an ALD patient with enlarging white matter lesions and progressive neuropsychological symptoms, using a 3-T magnet.

Adult-onset leukodystrophy with vanishing white matter: a case series of 19 patients.

Background: Leukodystrophy with vanishing white matter (LVWM) is an autosomal recessive disease with typical pediatric-onset caused by mutations in one of the five EIF2B genes. Adult-onset (AO) cases are rare.

Methods: In this observational study, we reviewed clinical and laboratory information of the patients with AO-LVWM assessed at two referral centers in Italy and Portugal from Jan-2007 to Dec-2019.

Safety and efficacy of leriglitazone for preventing disease progression in men with adrenomyeloneuropathy (ADVANCE): a randomised, double-blind, multi-centre, placebo-controlled phase 2-3 trial.

Background: Adult patients with adrenoleukodystrophy have a poor prognosis owing to development of adrenomyeloneuropathy. Additionally, a large proportion of patients with adrenomyeloneuropathy develop life-threatening progressive cerebral adrenoleukodystrophy. Leriglitazone is a novel selective peroxisome proliferator-activated receptor gamma agonist that regulates expression of key genes that contribute to neuroinflammatory and neurodegenerative processes implicated in adrenoleukodystrophy disease progression.

International Recommendations for the Diagnosis and Management of Patients With Adrenoleukodystrophy: A Consensus-Based Approach.

Pathogenic variants in the gene cause adrenoleukodystrophy (ALD), a progressive metabolic disorder characterized by 3 core clinical syndromes: a slowly progressive myeloneuropathy, a rapidly progressive inflammatory leukodystrophy (cerebral ALD), and primary adrenal insufficiency. These syndromes are not present in all individuals and are not related to genotype. Cerebral ALD and adrenal insufficiency require early detection and intervention and warrant clinical surveillance because of variable penetrance and age at onset.

Significance and clinical suggestions for the somatosensory evoked potentials increased in amplitude revealed by a large sample of neurological patients.

Objectives: To investigate the relationship between N20-P25 peak-to-peak amplitude (N20p-P25p) of somatosensory evoked potentials (SEPs) and the occurrence of abnormalities of the peripheral and/or central sensory pathways and of myoclonus/epilepsy, in 308 patients with increased SEPs amplitude from upper limb stimulation.

Methods: We compared cortical response (N20p-P25p) in different groups of patients identified by demographic, clinical, and neurophysiological factors and performed a cluster analysis for classifying the natural occurrence of subgroups of patients.

Results: No significant differences of N20p-P25p were found among different age-dependent groups, and in patients with or without PNS/CNS abnormalities of sensory pathways, while myoclonic/epileptic patients showed higher N20p-P25p than other groups.

Novel deep intronic mutation in PLA2G6 causing early-onset Parkinson's disease with brain iron accumulation through pseudo-exon activation.

PLA2G6 is the causative gene for a group of autosomal recessive neurodegenerative disorders known as PLA2G6-associated neurodegeneration (PLAN). We present a case with early-onset parkinsonism, ataxia, cognitive decline, cerebellar atrophy, and brain iron accumulation. Sequencing of PLA2G6 coding regions identified only a heterozygous nonsense variant, but mRNA analysis revealed the presence of an aberrant transcript isoform due to a novel deep intronic variant (c.

A cross-sectional, prospective ocular motor study in 72 patients with Niemann-Pick disease type C.

Objective: To characterize ocular motor function in patients with Niemann-Pick disease type C (NPC).

Methods: In a multicontinental, cross-sectional study we characterized ocular-motor function in 72 patients from 12 countries by video-oculography. Interlinking with disease severity, we also searched for ocular motor biomarkers.