Hereditary transthyretin amyloidosis caused by the Val142Ile variant in Spain.

Introduction And Objectives: In recent years, several cases of hereditary transthyretin amyloidosis (ATTRv) due to the p.Val142Ile variant have been described in patients without African ancestry. The aim of this study was to analyze the impact of ATTRv caused by p.

Use of non-specific immunoglobulins in Catalonia in three third-level hospitals: a descriptive analysis of a hospital-prescribed medication registry.

Background: The increasing use of non-specific immunoglobulins (NSIGs) and their current shortage show a need for NSIGs' use prioritization. Data from a clinical perspective are necessary, mainly for pediatric patients.

Objectives: The aim of the study was to assess the level of clinical evidence (LoE) of the indications that NSIGs are used for, the reasons for discontinuation, and the costs invested.

Epilepsy and Myasthenia Gravis: A Case Series.

The association between epilepsy and myasthenia gravis has rarely been reported, and when it has been reported, it has only been in a small case series. The aim of the present study was to report the frequency of epilepsy and myasthenia gravis and to describe a case series of patients with myasthenia gravis and epilepsy, focusing on their clinical characteristics and searching for a possible physiopathological mechanism. A retrospective, observational, adult center study was conducted in 2022.

Identification and characterisation of pathogenic and non-pathogenic FGF14 repeat expansions.

Repeat expansions in FGF14 cause autosomal dominant late-onset cerebellar ataxia (SCA27B) with estimated pathogenic thresholds of 250 (incomplete penetrance) and 300 AAG repeats (full penetrance), but the sequence of pathogenic and non-pathogenic expansions remains unexplored. Here, we demonstrate that STRling and ExpansionHunter accurately detect FGF14 expansions from short-read genome data using outlier approaches. By combining long-range PCR and nanopore sequencing in 169 patients with cerebellar ataxia and 802 controls, we compare FGF14 expansion alleles, including interruptions and flanking regions.

Safety, Tolerability, and Outcomes of Tafamidis for the Treatment of Acquired Amyloid Neuropathy in Domino Liver Transplant Recipients.

Introduction: Acquired amyloid neuropathy is an iatrogenic disease that appears years after a domino liver transplant. The objectives of our study are to analyze the efficacy and tolerability of tafamidis for the treatment of acquired amyloid neuropathy in domino liver transplant recipients. This post-authorization, prospective, longitudinal study included seven domino liver transplant recipients with acquired amyloid neuropathy who received treatment with tafamidis for 18 months.

Clinical practice guidelines for the diagnosis and management of Charcot-Marie-Tooth disease.

Introduction: Charcot-Marie-Tooth disease (CMT) is classified according to neurophysiological and histological findings, the inheritance pattern, and the underlying genetic defect. The objective of these guidelines is to offer recommendations for the diagnosis, prognosis, follow-up, and treatment of this disease in Spain.

Material And Methods: These consensus guidelines were developed through collaboration by a multidisciplinary panel encompassing a broad group of experts on the subject, including neurologists, paediatric neurologists, geneticists, physiatrists, and orthopaedic surgeons.

Novel intragenic deletion within the FXN gene in a patient with typical phenotype of Friedreich ataxia: may be more prevalent than we think?

Background: Friedreich ataxia is the most common inherited ataxia in Europe and is mainly caused by biallelic pathogenic expansions of the GAA trinucleotide repeat in intron 1 of the FXN gene that lead to a decrease in frataxin protein levels. Rarely, affected individuals carry either a large intragenic deletion or whole-gene deletion of FXN on one allele and a full-penetrance expanded GAA repeat on the other allele.

Case Presentation: We report here a patient that presented the typical clinical features of FRDA and genetic analysis of FXN intron 1 led to the assumption that the patient carried the common biallelic expansion.

Biomarker-based risk prediction for the onset of neuroinflammation in X-linked adrenoleukodystrophy.

Background: X-linked adrenoleukodystrophy (X-ALD) is highly variable, ranging from slowly progressive adrenomyeloneuropathy to severe brain demyelination and inflammation (cerebral ALD, CALD) affecting males with childhood peak onset. Risk models integrating blood-based biomarkers to indicate CALD onset, enabling timely interventions, are lacking. Therefore, we evaluated the prognostic value of blood biomarkers in addition to current neuroimaging predictors for early detection of CALD.

ClinPrior: an algorithm for diagnosis and novel gene discovery by network-based prioritization.

Background: Whole-exome sequencing (WES) and whole-genome sequencing (WGS) have become indispensable tools to solve rare Mendelian genetic conditions. Nevertheless, there is still an urgent need for sensitive, fast algorithms to maximise WES/WGS diagnostic yield in rare disease patients. Most tools devoted to this aim take advantage of patient phenotype information for prioritization of genomic data, although are often limited by incomplete gene-phenotype knowledge stored in biomedical databases and a lack of proper benchmarking on real-world patient cohorts.

A narrative review and expert recommendations on the assessment of the clinical manifestations, follow-up, and management of post-OLT patients with ATTRv amyloidosis.

Orthotopic liver transplantation (OLT) was the first treatment able to modify the natural course of hereditary transthyretin (ATTRv) amyloidosis, which is a rare and fatal disorder caused by the accumulation of misfolded transthyretin (TTR) variants in different organs and tissues and which leads to a progressive and multisystem dysfunction. Because the liver is the main source of TTR, OLT dramatically reduces the production of the pathogenic TTR variant, which should prevent amyloid formation and halt disease progression. However, amyloidosis progression may occur after OLT due to wild-type TTR deposition, especially in the nerves and heart.

Diagnosis of Wernicke's Encephalopathy in Patients With a Psychiatric History: A Case Series and Literature Review.

To review the literature on diagnostic criteria and management of Wernicke's encephalopathy (WE) and its application in psychiatric populations. A PubMed MEDLINE search was conducted in February 2022 and updated in April 2022 for articles published in English between 2012 and 2022 describing clinical findings and treatment of WE. Reference lists of included articles and treatment guidelines were reviewed.

RINT1 deficiency disrupts lipid metabolism and underlies a complex hereditary spastic paraplegia.

The Rad50 interacting protein 1 (Rint1) is a key player in vesicular trafficking between the ER and Golgi apparatus. Biallelic variants in RINT1 cause infantile-onset episodic acute liver failure (ALF). Here, we describe 3 individuals from 2 unrelated families with novel biallelic RINT1 loss-of-function variants who presented with early onset spastic paraplegia, ataxia, optic nerve hypoplasia, and dysmorphic features, broadening the previously described phenotype.

CSF Findings in Relation to Clinical Characteristics, Subtype, and Disease Course in Patients With Guillain-Barré Syndrome.

Background And Objectives: To investigate CSF findings in relation to clinical and electrodiagnostic subtypes, severity, and outcome of Guillain-Barré syndrome (GBS) based on 1,500 patients in the International GBS Outcome Study.

Methods: Albuminocytologic dissociation (ACD) was defined as an increased protein level (>0.45 g/L) in the absence of elevated white cell count (<50 cells/μL).

Sphingolipid desaturase DEGS1 is essential for mitochondria-associated membrane integrity.

Sphingolipids function as membrane constituents and signaling molecules, with crucial roles in human diseases, from neurodevelopmental disorders to cancer, best exemplified in the inborn errors of sphingolipid metabolism in lysosomes. The dihydroceramide desaturase Δ4-dihydroceramide desaturase 1 (DEGS1) acts in the last step of a sector of the sphingolipid pathway, de novo ceramide biosynthesis. Defects in DEGS1 cause the recently described hypomyelinating leukodystrophy-18 (HLD18) (OMIM #618404).

Myasthenia Gravis Induced by Immune Checkpoint Inhibitors: An Emerging Neurotoxicity in Neuro-Oncology Practice: Case Series.

Immunotherapy with immune checkpoint inhibitors (ICIs) have been reported to induce de novo or exacerbate pre-existing Myasthenia Gravis (MG). We present a single center case series of patients who developed an immune-related myasthenia gravis (irMG) related with ICIs. We performed a retrospective chart review of the electronic medical records between 1 September 2017 and 2022.

Hereditary Transthyretin Amyloidosis with Polyneuropathy: Monitoring and Management.

Our aim in this review is to discuss current treatments and investigational products and their effect on patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) and provide suggestions for monitoring disease progression and treatment efficacy.

Phenotype and clinical outcomes of Glu89Lys hereditary transthyretin amyloidosis: a new endemic variant in Spain.

Background: The p.Glu109Lys variant (Glu89Lys) is a rare cause of hereditary transthyretin amyloidosis (ATTRv) for which clinical spectrum remains unresolved. We sought to describe the clinical characteristics and outcomes of ATTR Glu89Lys amyloidosis and assess a potential founder effect in Spain.

Loss of seryl-tRNA synthetase () causes complex spastic paraplegia and cellular senescence.

Background: Aminoacyl-tRNA synthetases (ARS) are key enzymes catalysing the first reactions in protein synthesis, with increasingly recognised pleiotropic roles in tumourgenesis, angiogenesis, immune response and lifespan. Germline mutations in several ARS genes have been associated with both recessive and dominant neurological diseases. Recently, patients affected with microcephaly, intellectual disability and ataxia harbouring biallelic variants in the seryl-tRNA synthetase encoded by seryl-tRNA synthetase 1 () were reported.

An International Perspective on Preceding Infections in Guillain-Barré Syndrome: The IGOS-1000 Cohort.

Background And Objectives: Infections play a key role in the development of Guillain-Barré syndrome (GBS) and have been associated with specific clinical features and disease severity. The clinical variation of GBS across geographical regions has been suggested to be related to differences in the distribution of preceding infections, but this has not been studied on a large scale.

Methods: We analyzed the first 1,000 patients included in the International GBS Outcome Study with available biosamples (n = 768) for the presence of a recent infection with , hepatitis E virus, , cytomegalovirus, and Epstein-Barr virus.

Activating cannabinoid receptor 2 preserves axonal health through GSK-3β/NRF2 axis in adrenoleukodystrophy.

Aberrant endocannabinoid signaling accompanies several neurodegenerative disorders, including multiple sclerosis. Here, we report altered endocannabinoid signaling in X-linked adrenoleukodystrophy (X-ALD), a rare neurometabolic demyelinating syndrome caused by malfunction of the peroxisomal ABCD1 transporter, resulting in the accumulation of very long-chain fatty acids (VLCFAs). We found abnormal levels of cannabinoid receptor 2 (CB2r) and related endocannabinoid enzymes in the brain and peripheral blood mononuclear cells (PBMCs) of X-ALD patients and in the spinal cord of a murine model of X-ALD.

Treatment With Diflunisal in Domino Liver Transplant Recipients With Acquired Amyloid Neuropathy.

To analyze the efficacy and tolerability of diflunisal for the treatment of acquired amyloid neuropathy in domino liver transplant recipients. We performed a retrospective longitudinal study of prospectively collected data for all domino liver transplant recipients with acquired amyloid neuropathy who received diflunisal at our hospital. Neurological deterioration was defined as an score increase of ≥2 points from baseline on the Neurological Impairment Scale/Neurological Impairment Scale-Lower Limbs.

Quality of Life in Myasthenia Gravis and Correlation of MG-QOL15 with Other Functional Scales.

Health-related quality of life (HRQOL) in myasthenia gravis (MG) is frequently decreased. Further, there are many validated clinical scales and questionnaires to evaluate the clinical status in MG. We aimed to determine if there was an improvement in HRQOL following an intensive treatment for MG, identify which demographic and clinical features influenced patients' HRQOL, and investigate if the questionnaire MG-QOL15 correlated with other evaluation scales.

Drug-refractory myasthenia gravis: Clinical characteristics, treatments, and outcome.

Objective: To describe the clinical characteristics and outcomes in patients with refractory myasthenia gravis (MG) and to determine the effectiveness and side effects of the drugs used for their treatment.

Methods: This observational retrospective cross-sectional multicenter study was based on data from the Spanish MG Registry (NMD-ES). Patients were considered refractory when their MG Foundation of America post-interventional status (MGFA-PIS) was unchanged or worse after corticosteroids and two or more other immunosuppressive agents.