Publications by authors named "Juan F Vazquez-Costa"
Background: Distal myopathies (MPDs) are heterogeneous diseases of complex diagnosis whose prevalence and distribution in specific populations are unknown.
Methods: Demographic, clinical, genetic, neurophysiological, histopathological and muscle imaging characteristics of a MPDs cohort from a neuromuscular reference center were analyzed to study their epidemiology, features, genetic distribution and factors related to diagnosis.
Results: The series included 219 patients (61% were men, 94% Spanish and 41% sporadic cases).
Background And Purpose: The purpose was to describe the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hospitalization for coronavirus disease 2019 (COVID-19) and related death and to assess the impact of the pandemic in the survival of amyotrophic lateral sclerosis (ALS) patients.
Methods: The risk of SARS-CoV-2 infection, hospitalization for COVID-19 and related death was assessed in ALS patients alive between March 2020 and July 2022. To evaluate its impact in the overall survival of ALS patients, the survival of patients who died before and during the pandemic was compared.
Background And Purpose: Pathogenic variants of the glycyl-tRNA synthetase 1 (GARS1) gene have been described as a cause of Charcot-Marie-Tooth disease type 2D, motor axonal neuropathy with upper limb predominance (distal hereditary motor neuropathy [dHMN] type V), and infantile spinal muscular atrophy.
Methods: This cross-sectional, retrospective, observational study was carried out on 12 patients harboring the c.794C>T (p.
Article Synopsis
- Spinal muscular atrophy (SMA) is a genetic disorder caused by mutations in the survival motor neuron 1 gene, leading to progressive muscle degeneration, prompting a need to update diagnosis best practices post-treatment advancements and newborn screening implementation.
- A systematic review and expert consensus from healthcare professionals in the U.S. and Europe emphasized the critical role of newborn screening (NBS) for SMA and established new recommendations for characterizing NBS-identified infants and enhancing specialty care services.
- The working group highlighted the necessity of involving individuals with SMA and their caregivers in the process to better support and provide resources for those diagnosed through NBS, while noting limited data on adult-onset SMA diagnosis.
The objective of this study is to evaluate biomarkers for neurodegenerative disorders in adult SMA patients and their potential for monitoring the response to nusinersen. Biomarkers for neurodegenerative disorders were assessed in plasma and CSF samples obtained from a total of 30 healthy older adult controls and 31 patients with adult SMA type 2 and 3. The samples were collected before and during nusinersen treatment at various time points, approximately at 2, 6, 10, and 22 months.
View Article and Find Full Text PDFIntermediate CAG expansions in the gene ataxin-2 () are a known risk factor for ALS, but little is known about their role in FTD risk. Moreover, their contribution to the risk and phenotype of patients might vary in populations with different genetic backgrounds. The aim of this study was to assess the relationship of intermediate CAG expansions in with the risk and phenotype of ALS and FTD in the Spanish population.
View Article and Find Full Text PDFIntroduction: The objective of this study is to develop a clinical tool for the evaluation and follow-up of adolescent and adult patients with 5q spinal muscular atrophy (SMA) and to design its validation.
Methods: This prospective, non-interventional study will be carried out at five centres in Spain and will include patients aged 16 years or older with a confirmed diagnosis of 5q SMA (biallelic mutation of the survival motor neuron 1 [SMN1] gene). A panel of experts made up of neurologists, physiatrists and Spanish patients' association (FundAME), participated in the design of the clinical tool.
Article Synopsis
- Spinal muscular atrophy (SMA) is a serious neurodegenerative disorder that has seen significant treatment advancements, allowing many patients to lead normal lives, particularly with therapies like Nusinersen, risdiplam, and onasemnogene abeparvovec-xioi now approved.
- A qualitative study surveyed healthcare providers in 21 countries to explore the availability and implementation of SMA treatments, revealing inconsistencies in drug access, newborn screening, and significant economic barriers to care.
- The findings emphasize the global inequalities in SMA management and highlight the need for expanded newborn screening to ensure better treatment access and address future challenges in genetic disease therapies.
Do we really need to calculate a minimal important difference for ALSFRS-R?: A letter in response to 'Clinically meaningful change: evaluation of the Rasch-built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS) and the ALSFRS-R' published in Vol. 24(3-4), pp. 311-316.
Amyotroph Lateral Scler Frontotemporal Degener
February 2024
Background And Objectives: Most patients with amyotrophic lateral sclerosis (ALS) lack a monogenic mutation. This study evaluates ALS cumulative genetic risk in an independent Michigan and Spanish replication cohort using polygenic scores.
Methods: Participant samples from University of Michigan were genotyped and assayed for the chromosome 9 open reading frame 72 hexanucleotide expansion.
Introduction/aims: Risdiplam has been approved for the treatment of patients with 5q spinal muscular atrophy (SMA), but data from type 2 non-sitter patients are lacking. In this study we describe our experience regarding the use of risdiplam in a series of type 2 non-sitter patients.
Methods: Type 2 SMA patients over 16 years of age were administered risdiplam through the expanded access program (NCT04256265).
Background And Objectives: To determine the diagnostic efficacy of clinical exome-targeted sequencing (CES) and spinocerebellar ataxia 36 (SCA36) screening in a real-life cohort of patients with cerebellar ataxia (CA) from Eastern Spain.
Methods: A total of 130 unrelated patients with CA, negative for common trinucleotide repeat expansions (SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA12, SCA17, dentatorubral pallidoluysian atrophy [DRPLA], and Friedreich ataxia), were studied with CES. Bioinformatic and genotype-phenotype analyses were performed to assess the pathogenicity of the variants encountered.
Article Synopsis
- * Data was collected from 17 centers, revealing 29 mutations in 144 patients, with the most common being p.Gly38Arg, and showing significant regional variations and the presence of novel mutations.
- * Older age at onset and female sex were linked to faster progression and shorter survival, indicating the need for targeted treatment approaches for SOD1 mutations in ALS.
Article Synopsis
- Traditional outcome measures for spinal muscular atrophy (SMA) clinical trials are insufficient for capturing the complete severity of the disease, prompting a study to evaluate the psychometric properties of various questionnaires addressing patient and caregiver insights.
- Conducted as a multicenter, prospective, noninterventional study, it included 113 SMA patients aged 2 to 17 years and utilized a range of assessments, including existing scales and newly developed items to evaluate domains such as fatigue and vulnerability.
- The results demonstrated high reliability and construct validity for most measured domains, with perceived fatigability being notably affected and the SMA Independence Scale (SMAIS) showing sensitivity to changes, highlighting the need for improved assessment tools in SMA.
Background And Purpose: Mos scales currently used to evaluate spinal muscular atrophy (SMA) patients have only been validated in children. The aim of this study was to assess the construct validity and responsiveness of several outcome measures in adult SMA patients.
Methods: Patients older than 15 years and followed up in five referral centres for at least 6 months, between October 2015 and August 2020, with a motor function scale score (Hammersmith Functional Motor Scale Expanded [HFMSE], Revised Upper Limb module [RULM]) were included.
Article Synopsis
- The study aimed to evaluate the safety and effectiveness of nusinersen in adult patients with 5q spinal muscular atrophy (SMA), involving a cohort of patients over 15 years old who were followed for at least 6 months.
- Results showed that treated patients had significant improvements in motor function and overall health assessments compared to untreated patients, particularly noting a 2-point improvement in the Revised Upper Limb Module (RULM) score after 6 months.
- Despite most treated patients experiencing some adverse effects, primarily mild, the findings suggest that nusinersen could provide functional benefits, particularly for those on treatment for longer periods, although severely affected patients may face a less favorable risk-benefit outcome.
Introduction: amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. Its symptoms include dysphagia that may make it necessary to place a percutaneous endoscopic gastrostomy (PEG) for feeding. The administration of drugs by PEG can obstruct it, decrease the effectiveness of treatment, and increase the risk of toxicity by altering the original pharmaceutical form.
View Article and Find Full Text PDFAims: We aim to present data obtained from three patients belonging to three unrelated families with an infantile onset demyelinating neuropathy associated to somatic and neurodevelopmental delay and to describe the underlying genetic changes.
Methods: We performed whole-exome sequencing on genomic DNA from the patients and their parents and reviewed the clinical, muscle and nerve data, the serial neurophysiological studies, brain and muscle MRIs, as well as the respiratory chain complex activity in the muscle of the three index patients. Computer modelling was used to characterise the new missense variant detected.
Clinical trials in pediatric ALS: a TRICALS feasibility study.
Amyotroph Lateral Scler Frontotemporal Degener
November 2022
Pediatric investigation plans (PIPs) describe how adult drugs can be studied in children. In 2015, PIPs for Amyotrophic Lateral Sclerosis (ALS) became mandatory for European marketing-authorization of adult treatments, unless a waiver is granted by the European Medicines Agency (EMA). To assess the feasibility of clinical studies on the effect of therapy in children (<18 years) with ALS in Europe.
View Article and Find Full Text PDFArticle Synopsis
- The study aimed to explore the outcomes and natural history of spontaneous amyloid-related imaging abnormalities (ARIA)-like cases in patients with cerebral amyloid angiopathy-related inflammation (CAA-ri).
- It involved a multicenter, observational approach, tracking patients through systematic data collection and MRI scans at multiple follow-up points over 24 months.
- Results showed that a significant majority of patients experienced clinical recovery by 12 months, although some were at high risk for intracerebral hemorrhage and recurrence of CAA-ri, especially if they had baseline cortical superficial siderosis.
Article Synopsis
- Primary lateral sclerosis (PLS) is a progressive upper motor neuron disorder that may be related to amyotrophic lateral sclerosis (ALS) or represent a distinct group of neurodegenerative conditions, with new diagnostic criteria recently established.
- Four patients, aged 25-45, diagnosed with definite PLS showed progressive motor symptoms, mild cognitive issues initially, and results from various diagnostic tests indicating changes in the motor cortex and amyloid deposition.
- The findings suggest that PLS may be a collection of different neurodegenerative diseases, and next-generation sequencing (NGS) testing should be incorporated into diagnosis, particularly for patients with early signs or genetic predispositions.
Spastic paraplegia type 7 (SPG7) is one of the most common hereditary spastic paraplegias. SPG7 mutations most often lead to spastic paraparesis (HSP) and/or hereditary cerebellar ataxia (HCA), frequently with mixed phenotypes. We sought to clinically and genetically characterize a Spanish cohort of SPG7 patients.
View Article and Find Full Text PDFIntroduction: The absence of nigrosome 1 on brain MRI and the hyperechogenicity of substantia nigra (SNh) by transcranial sonography are two useful biomarkers in the diagnosis of parkinsonisms. We aimed to evaluate the absence of nigrosome 1 in amyotrophic lateral sclerosis (ALS) and to address its meaning.
Methods: 136 ALS patients were recruited, including 16 progressive muscular atrophy (PMA) and 22 primary lateral sclerosis (PLS) patients.