Juan F. Vázquez-Costa

Analysis of the CHCHD10 gene in patients with frontotemporal dementia and amyotrophic lateral sclerosis from Spain

Sir, Recently, a study identified a mutation (c.176C>T, p.S59L) in the CHCHD10 gene as a cause of amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD) in a large pedigree with mixed phenotypes encompassing ALS, FTD, cerebellar ataxia and mitochondrial myopathy (Bannwarth et al. , 2014).The same mutation was also found in a second kindred suffering from ALS, FTD and/or parkinsonian signs by the same authors. Additional mutations (p.R15L, p.P34S, p.G66V and p.P80L) have been subsequently reported in ALS and FTD with motor neuron disease (FTD-MND) patients (Chaussenot et al. , 2014; Johnson et al. , 2014; Muller et al. , 2014; Kurzwelly et al. , 2015; Ronchi et al. 2015; Chio et al. , 2015). More recently, exon 2 of the CHCHD10 gene has been sequenced in a cohort of ALS, FTD, Parkinsons disease and Alzheimer’s dementia, revealing two novel mutations (p.P23T and p.A35D) in two patients with FTD (Zhang et al. , 2015). Importantly, some of these screenings have not included neurologically healthy individuals from the same geographic origin (Bannwarth et al. , 2014; Johnson et al. , 2014; Muller et al. , 2014; Kurzwelly et al. , 2015) and therefore, the real allele diversity within CHCHD10 might have been missed. This could have important consequences in terms of establishing firm …

Urodynamic findings in amyotrophic lateral sclerosis patients with lower urinary tract symptoms: Results from a pilot study

To determine lower urinary tract symptoms (LUTS) prevalence and urodynamic findings in amyotrophic lateral sclerosis (ALS) patients treated in our hospital.

Brain signal intensity changes as biomarkers in amyotrophic lateral sclerosis

To evaluate the contribution of the demographical, clinical, analytical and genetic factors to brain signal intensity changes in T2‐weighted MR images in amyotrophic lateral sclerosis (ALS) patients and controls.

Quantitative Muscle Ultrasonography Using Textural Analysis in Amyotrophic Lateral Sclerosis

The purpose of this study was to analyze differences in gray-level co-occurrence matrix (GLCM) parameters, as assessed by muscle ultrasound (MUS), between amyotrophic lateral sclerosis (ALS) patients and healthy controls, and to compare the diagnostic accuracy of these GLCM parameters with first-order MUS parameters (echointensity [EI], echovariation [EV], and muscle thickness [MTh]) in different muscle groups. Twenty-six patients with ALS and 26 healthy subjects underwent bilateral and transverse ultrasound of the biceps/brachialis, forearm flexor, quadriceps femoris, and tibialis anterior muscle groups. MTh was measured with electronic calipers, and EI, EV, and GLCM were obtained using Image J (v.1.48) software. Sensitivity, specificity, likelihood ratios, and area under the curve (AUC) were performed by logistic regression models and receiver operating characteristic curves. GLCM parameters showed reduced granularity in the muscles of ALS patients compared with the controls. Regarding the discrimination capacity, the best single diagnostic parameter in forearm flexors and quadriceps was GLCM and in biceps brachialis and tibialis anterior was EV. The respective combination of these two parameters with MTh resulted in the best AUC (over 90% in all muscle groups and close to the maximum combination model). The use of new textural parameters (EV and GLCM) combined with usual quantitative MUS variables is a promising biomarker in ALS.

Genetic and constitutional factors are major contributors to substantia nigra hyperechogenicity

Hyperechogenicity of substantia nigra (SNh) is a frequent finding in amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD) and other movement disorders (MD) patients, but its meaning is unclear. To ascertain the contribution of different factors to SNh area, we measured it in 108 ALS, 102 PD, 91 other MD patients and 91 healthy controls. Demographical data were collected in all patients and controls. In ALS patients, we also recorded clinical variables, performed genetic analysis and measured baseline levels of ferritin. After family history and genetic testing, ALS patients were classified as familial (15) or sporadic (93). ALS, PD and other MD patients had a larger SNh area than controls. Left SNh and male gender, but not age, associated with larger SNh area in both patients and controls. Familial ALS patients showed larger SNh area than sporadic ones and familial ALS was the only clinical variable in the multivariate analysis to be associated with larger SNh area in ALS patients. Our results suggest that SNh associates with genetic and constitutional factors (male gender, handedness), some of which predispose to certain neurodegenerative diseases. This evidence supports the idea of SNh as an inborn marker of unspecific neuronal vulnerability.

Clinical and neuroimaging characterization of two C9orf72-positive siblings with amyotrophic lateral sclerosis and schizophrenia

Neuromuscular Research Unit, Instituto de Investigación Sanitaria la Fe (IIS La Fe), Valencia, Department of Neurology, Hospital Universitario y Politécnico La Fe, Valencia, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Laboratory of Molecular Genetics, Institut de Biomedicina de València-CSIC, Valencia, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Unidad Mixta de Investigación en Neurologı́a y Genética Molecular, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Nuclear Medicine Department, Hospital Universitario y Politécnico La Fe, Valencia, Department of Psychiatry, Hospital Universitario y Politécnico La Fe, Valencia, and Department of Medicine, University of Valencia, Valencia, Spain

Sonoelastography for the Assessment of Muscle Changes in Amyotrophic Lateral Sclerosis: Results of a Pilot Study

The purpose of this study was to assess the sonoelastographic features of four different muscles in patients with amyotrophic lateral sclerosis compared with healthy controls and to evaluate the relationship of these features to muscle strength and other ultrasonographic variables. Fourteen patients with amyotrophic lateral sclerosis and 20 controls were examined using strain sonoelastography scanning. The RGB channel fraction ratio was analyzed with ImageJ software (Version 1.48). Two main sonoelastographic patterns could be distinguished in the controls: a clear predominance of the blue channel (hard areas) and a more heterogeneous pattern with predominance of the green channel (intermediate stiffness). These patterns were also observed in patients, although a higher green channel score was observed in mildly impaired muscles, whereas a higher blue channel score was observed in the most severely impaired muscle. Sonoelastography may be a good complementary biomarker in the detection and monitoring of muscle changes in amyotrophic lateral sclerosis.

Monitoring Progression of Amyotrophic Lateral Sclerosis Using Ultrasound Morpho-Textural Muscle Biomarkers: A Pilot Study

The need is increasing for progression biomarkers that allow the loss of motor neurons in amyotrophic lateral sclerosis (ALS) to be monitored in clinical trials. In this prospective longitudinal study, muscle thickness, echointensity, echovariation and gray level co-occurrence matrix textural features are examined as possible progression ultrasound biomarkers in ALS patients during a 5-mo follow-up period. We subjected 13 patients to 3 measurements for 20 wk. They showed a significant loss of muscle, an evident tendency to loss of thickness and increased echointensity and echovariation. In regard to textural parameters, muscle heterogeneity tended to increase as a result of the neoformation of non-contractile tissue through denervation. Considering some limitations of the study, the quantitative muscle ultrasound biomarkers evaluated showed a promising ability to monitor patients affected by ALS.

Phenotypical features of two patients diagnosed with PHARC syndrome and carriers of a new homozygous mutation in the ABHD12 gene

PHARC (Polyneuropathy, Hearing loss, Ataxia, Retinitis pigmentosa and Cataracts) (MIM# 612674) is an autosomal recessive neurodegenerative disease caused by mutations in the ABHD12 gene. We evaluated two Spanish siblings affected with pes cavus, sensorimotor neuropathy, hearing loss, retinitis pigmentosa and juvenile cataracts in whom the genetic test of ABHD12 revealed a novel homozygous frameshift mutation, c.211_223del (p.Arg71Tyrfs*26). The earliest clinical manifestation in these patients was a demyelinating neuropathy manifested with a Charcot-Marie-Tooth phenotype over three decades. Progressive hearing loss, cataracts and retinitis pigmentosa appeared after the age of 30. We herein describe the complete clinical picture of these two patients, and focus particularly on neuropathy characteristics. This study supports the fact that although PHARC is rare, its phenotype is very characteristic and we should include its study in patients affected with demyelinating polyneuropathy, hearing loss and retinopathy.

The width of the third ventricle associates with cognition and behaviour in motor neuron disease

An enlarged width of the third ventricle (WTV) has been described in amyotrophic lateral sclerosis (ALS) patients, although its clinical meaning is unknown. The aims of this study were to evaluate the contribution of demographical, clinical and genetic factors to the WTV in different motor neuron disease (MND) phenotypes and to assess its brain structural correlates.