Autosomal recessive spinocerebellar ataxia SCAR8/ARCA1: first families detected in Spain.

Introduction: Autosomal recessive spinocerebellar ataxia type 8 (ARCA1/SCAR8) is caused by mutations of the SYNE1 gene. The disease was initially described in families from Quebec (Canada) with a phenotype of pure cerebellar syndrome, but in recent years has been reported with a more variable clinical phenotype in other countries. Cases have recently been described of muscular dystrophy, arthrogryposis, and cardiomyopathy due to SYNE1 mutations.

Onset features and time to diagnosis in Friedreich's Ataxia.

Background: In rare disorders diagnosis may be delayed due to limited awareness and unspecific presenting symptoms. Herein, we address the issue of diagnostic delay in Friedreich's Ataxia (FRDA), a genetic disorder usually caused by homozygous GAA-repeat expansions.

Methods: Six hundred eleven genetically confirmed FRDA patients were recruited within a multicentric natural history study conducted by the EFACTS (European FRDA Consortium for Translational Studies, ClinicalTrials.

Autosomal recessive spinocerebellar ataxia SCAR8/ARCA1: First families detected in Spain.

Introduction: Autosomal recessive spinocerebellar ataxia type 8 (ARCA1/SCAR8) is caused by mutations of the SYNE1 gene. The disease was initially described in families from Quebec (Canada) with a phenotype of pure cerebellar syndrome, but in recent years has been reported with a more variable clinical phenotype in other countries. Cases have recently been described of muscular dystrophy, arthrogryposis, and cardiomyopathy due to SYNE1 mutations.

Friedreich and dominant ataxias: quantitative differences in cerebellar dysfunction measurements.

Background: Sensitive outcome measures for clinical trials on cerebellar ataxias are lacking. Most cerebellar ataxias progress very slowly and quantitative measurements are required to evaluate cerebellar dysfunction.

Methods: We evaluated two scales for rating cerebellar ataxias: the Composite Cerebellar Functional Severity (CCFS) Scale and Scale for the Assessment and Rating of Ataxia (SARA), in patients with spinocerebellar ataxia (SCA) and controls.

Accelerated atherosclerosis in ANCA-associated vasculitis.

Objectives: Cardiovascular disease, including myocardial infarction and stroke, is a major cause of mortality in ANCA-associated vasculitis (AAV). Although AAV affects small vessels, an accelerated atherosclerosis not explained by traditional cardiovascular risk factors (CVRF) has been demonstrated. We aimed to investigate the association of atherosclerosis measured by carotid intima-media thickness (CIMT) and cerebral small vessel disease in AAV-patients.

Evaluating the Calling Performance of a Rare Disease NGS Panel for Single Nucleotide and Copy Number Variants.

Introduction: Variant detection protocols for clinical next-generation sequencing (NGS) need application-specific optimization. Our aim was to analyze the performance of single nucleotide variant (SNV) and copy number (CNV) detection programs on an NGS panel for a rare disease.

Methods: Thirty genes were sequenced in 83 patients with hereditary spastic paraplegia.

Patterns of motor signs in spinocerebellar ataxia type 3 at the start of follow-up in a reference unit.

Background: Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder that affects the cerebellar system and other subcortical regions of the brain. As for other cerebellar diseases, the severity of this type of ataxia can be assessed with the Scale for Assessment and Rating of Ataxia (SARA) which gives a total score that reflects functional impairment out of 8 cerebellar function tests. SCA3 patients score profile is heterogeneous on at the start of follow up.

Brain Microvasculature Involvement in ANCA Positive Vasculitis.

Objective: Endothelial dysfunction is associated with arterial stiffness, a factor that is increasingly recognised as an important determinant of cardiovascular risk. High-flow organs such as the brain and kidneys are particularly sensitive to excessive pressure and flow pulsatility. High, local blood flow is associated with low microvascular impedance, which facilitates the penetration of excessive pulsatile energy into the microvascular bed leading to tissue damage.

Long-term outcomes of adult chronic idiopathic hydrocephalus treated with a ventriculo-peritoneal shunt.

Introduction: Adult chronic idiopathic hydrocephalus (ACIH) is a cause of dementia that can be treated by implanting a ventriculo-peritoneal shunt (VPS). We aim to study clinical and functional outcomes in patients with ACIH corrected with a VPS.

Subjects And Methods: Observational cohort study of patients diagnosed with probable ACIH (Japan Neurosurgical Society guidelines) and undergoing shunt placement between 2008 and 2013 in a centre of reference for neurosurgery in Spain.

Paraneoplastic Neurological Syndromes and Glutamic Acid Decarboxylase Antibodies.

Importance: Little is known of glutamic acid decarboxylase antibodies (GAD-abs) in the paraneoplastic context. Clinical recognition of such cases will lead to prompt tumor diagnosis and appropriate treatment.

Objective: To report the clinical and immunological features of patients with paraneoplastic neurological syndromes (PNS) and GAD-abs.

Targeted screening for the detection of Pompe disease in patients with unclassified limb-girdle muscular dystrophy or asymptomatic hyperCKemia using dried blood: A Spanish cohort.

We aimed to screen for Pompe disease in patients with unclassified limb-girdle muscular dystrophy (LGMD) or asymptomatic hyperCKemia using dried blood spot (DBS) assays. Subsequently, we aimed to calculate the diagnostic delay between initial symptom presentation and the diagnosis. A prospective, multicenter, observational study was conducted in 348 patients: 146 with unclassified LGMD and 202 with asymptomatic or paucisymptomatic hyperCKemia.

Substantia nigra echogenicity in hereditary ataxias with and without nigrostriatal pathology: a pilot study.

Our objective was to determine whether substantia nigra (SN) hyperechogenicity is greater in spinocerebellar ataxias (SCA) with nigrostriatal affectation than in ataxias without it. A cross-sectional case-control study analyzing four groups of patients was conducted: 1) nigrostriatal ataxias (SCA3 and SCA6), 2) nigrostriatal healthy controls matched by age and sex, 3) non-nigrostriatal ataxias (FRDA and SCA7), and 4) non-nigrostriatal healthy controls matched by age and sex. All the patients underwent a transcranial ultrasound performed by an experienced sonographer blinded to the clinical, genetic, and neuroimaging data.

Biological and clinical characteristics of the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) cohort: a cross-sectional analysis of baseline data.

Background: Friedreich's ataxia is a rare autosomal recessive neurodegenerative disorder. Here we report cross-sectional baseline data to establish the biological and clinical characteristics for a prospective, international, European Friedreich's ataxia database registry.

Methods: Within the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) framework, we assessed a cohort of patients with genetically confirmed Friedreich's ataxia.

Deferiprone in Friedreich ataxia: a 6-month randomized controlled trial.

Objective: We conducted a 6-month, randomized, double-blind, placebo-controlled study to assess safety, tolerability, and efficacy of deferiprone in Friedreich ataxia (FRDA).

Methods: Seventy-two patients were treated with deferiprone 20, 40, or 60mg/kg/day or placebo, divided into 2 daily doses. Safety was the primary objective; secondary objectives included standardized neurological assessments (Friedreich Ataxia Rating Scale [FARS], International Cooperative Ataxia Rating Scale [ICARS], 9-Hole Peg Test [9HPT], Timed 25-Foot Walk, Low-Contrast Letter Acuity), general functional status (Activities of Daily Living), and cardiac assessments.

A novel locus for a hereditary recurrent neuropathy on chromosome 21q21.

Hereditary recurrent neuropathies are uncommon. Disorders with a known molecular basis falling within this group include hereditary neuropathy with liability to pressure palsies (HNPP) due to the deletion of the PMP22 gene or to mutations in this same gene, and hereditary neuralgic amyotrophy (HNA) caused by mutations in the SEPT9 gene. We report a three-generation family presenting a hereditary recurrent neuropathy without pathological changes in either PMP22 or SEPT9 genes.

IGF-1 in autosomal dominant cerebellar ataxia - open-label trial.

Background: The objective of this clinical open-label trial was to test the safety, tolerability and efficacy of IGF-1 therapy for autosomal dominant cerebellar ataxia (ADCA) patients.

Results: A total of 19 molecularly confirmed patients with SCA3, 1 patient with SCA6 and 6 patients with SCA7 completed our study. They were 8 females and 18 males, 28 to 74 years of age (average ± SD: 49.

IGF-1 in Friedreich's Ataxia - proof-of-concept trial.

Background: Friedreich's ataxia is an autosomal recessive, severely incapacitating disorder. There is little objective evidence regarding FRDA management. Abnormalities in the insulin/insulin-like growth factor 1 (IGF-1) system (IIS) signalling pathway were thought to play a role in the physiopathological processes of various neurodegenerative disorders, including spinocerebellar ataxias.

Leukoencephalopathy due to oral methotrexate.

Methotrexate (MTX) is considered the main agent for the treatment of rheumatoid arthritis (RA). Neurotoxicity is often mild, but severe encephalopathy can develop, especially with intrathecal or intravenous administration. In rare cases, this syndrome has been observed in patients on long-term low-dose oral administration.

Guillain-Barré syndrome: natural history and prognostic factors: a retrospective review of 106 cases.

Background: Guillain-Barre syndrome (GBS) is characterized by acute onset and progressive course, and is usually associated with a good prognosis. However, there are forms of poor prognosis, needing ventilatory support and major deficits at discharge. With this study we try to identify the factors associated with a worse outcome.

Triple therapy with deferiprone, idebenone and riboflavin in Friedreich's ataxia - open-label trial.

Objectives: The objective of the study was to test the efficacy, safety and tolerability of triple therapy with deferiprone, idebenone and riboflavin in Friedreich's ataxia (FRDA) patients in a clinical pilot study.

Patients And Methods: Patients included in this study were 10 males and three females, 14-61 years of age (average 30.2 ± 12.

Triple therapy with darbepoetin alfa, idebenone, and riboflavin in Friedreich's ataxia: an open-label trial.

Minimal objective evidence exists regarding management of Friedreich's ataxia (FRDA). Antioxidant and recombinant human erythropoietin therapies have been considered potential treatments to slow progression of FRDA in a small number of studies. The primary objective of the current study was to test the efficacy, safety, and tolerability of triple therapy-darbepoetin alfa, idebenone, and riboflavin-in FRDA in a clinical pilot study.

Ophthalmic features of Friedreich ataxia.

Purpose: To describe ocular abnormalities in patients with Friedreich ataxia (FRDA).

Methods: Patients diagnosed with FRDA by genetic analysis were invited to participate in a prospective cohort. The patients included underwent an extensive ophthalmologic examination, including low-contrast Sloan letter charts test and retinal nerve fiber layer (RNFL) thickness analysis by optical coherence tomography (OCT).

Screening for mutations in Spanish families with myotonia. Functional analysis of novel mutations in CLCN1 gene.

Myotonia congenita is an inherited muscle disorder caused by mutations in the CLCN1 gene, a voltage-gated chloride channel of skeletal muscle. We have studied 48 families with myotonia, 32 out of them carrying mutations in CLCN1 gene and eight carry mutations in SCN4A gene. We have found 26 different mutations in CLCN1 gene, including 13 not reported previously.