Aurelio Hernandez Lain’s research while affiliated with Hospital Universitario 12 de Octubre and other places

Chitinase 3-like protein 1 (CHI3L1) is emerging as a promising biomarker for assessing intracranial lesion burden and predicting prognosis in traumatic brain injury (TBI) patients. Following experimental TBI, Chi3l1 transcripts were detected in reactive astrocytes located within the pericontusional cortex. However, the cellular sources of CHI3L1 in response to hemorrhagic contusions in human brain remain unidentified. Hence, we examined a comprehensive collection of histologically defined acute and subacute human cerebral contusions with various surgical intervals using immunohistochemistry, validated through double immunofluorescence for markers such as GFAP, NeuN, MBP, and Iba-1, along with Fluoro-Jade C histofluorescence staining. CHI3L1 was found at meningeal interfaces, showing significant thickening of subpial glial plate. Paradoxically, CHI3L1-positive astrocytes were identified in neuroanatomical locations distant from hemorrhagic foci, where numerous eosinophilic ischemic neurons also exhibited CHI3L1 immunoreactivity. CHI3L1 immunostaining extended into white matter tracts and highlighted various phagocytic or activated microglia forms after delayed surgical decompressions. Given these findings, we advise against using CHI3L1 as a reactive astrogliosis marker due to its expression in multiple cell types, including astrocytes, neurons, oligodendrocytes, ependymocytes, leptomeningeal cells, microglia, and blood vessels. This non-selective response underscores the potential for CHI3L1 elevation patterns in biofluids to reflect the overall lesion burden extent.

Intracranial ependymal cysts (ECs) are rare benign lesions. They are frequently asymptomatic and arise in the supratentorial regions. Retrocerebellar ECs is a rare location. We present a case of 3-months-old infant who developed obstructive hydrocephalus, bulging fontanel, and macrocephaly secondary to a retrocerebellar EC. Magnetic resonance imaging (MRI) showed a large retrocerebellar cyst that compressed the cerebellum and the brainstem, producing fourth ventricle outlet obstruction and supratentorial hydrocephalus. Microsurgical fenestration of the cyst to the obex of the fourth ventricle and a cystic wall biopsy were performed. The procedure improved supratentorial hydrocephalus, as well as the patient's clinical condition. A histopathological study confirmed the diagnosis of an EC. As far as we know, after a thorough review of the literature, this is the first reported case of retrocerebellar EC. It is a rare cause of hydrocephalus due to outlet obstruction of the fourth ventricle. Treatment of the cause itself has been shown to be effective.

Background The ANO5 gene encodes for anoctamin-5, a chloride channel involved in muscle cell membrane repair. Recessive mutations in ANO5 are associated with muscular diseases termed anoctaminopathies, which are characterized by proximal or distal weakness, or isolated hyperCKemia. We present the largest series of patients with asymptomatic/paucisymptomatic anoctaminopathy reported so far, highlighting their clinical and radiological characteristics.Methods Twenty subjects were recruited retrospectively from the Neuromuscular Disorders Units database of two national reference centers. All had a confirmed genetic diagnosis (mean age of diagnosis was 48 years) established between 2015 and 2019. Clinical and complementary data were evaluated through clinical records.ResultsNone of the patients complained about weakness or showed abnormal muscular balance. Among paucisymptomatic patients, the main complaints or findings were generalized myalgia, exercise intolerance and calf hypertrophy, occasionally associated with calf pain. All patients showed persistent hyperCKemia, ranging from mild-moderate to severe. Muscle biopsy revealed inflammatory changes in three cases. Muscle magnetic resonance imaging revealed typical signs (preferential involvement of adductor and gastrocnemius muscles) in all but one patient. In two cases, abnormal findings were detectable only in STIR sequences (not in T1). Three patients showed radiological progression despite remaining asymptomatic. Twelve different mutations in ANO5 were detected, of which seven are novel.Conclusions Recessive mutations in ANO5 are a frequent cause of undiagnosed asymptomatic/paucisymptomatic hyperCKemia. Patients with an apparent indolent phenotype may show muscle involvement in complementary tests (muscle biopsy and imaging), which may progress over time. Awareness of anoctaminopathy as the cause of nonspecific muscular complaints or of isolated hyperCKemia is essential to correctly diagnose affected patients.

Background Bethlem myopathy represents the milder phenotype of collagen type VI-related myopathies. However, clinical manifestations are highly variable among patients and no phenotype-genotype correlation has been described. We aim to analyse the clinical, pathological and genetic features of a series of patients with Bethlem myopathy, and we describe seven new mutations. Methods A series of 16 patients with the diagnosis of Bethlem myopathy were analyzed retrospectively from their medical records for clinical, creatine kinase (CK), muscle biopsy, and muscle magnetic resonance (MRI) data. Genetic testing was performed through next-generation sequencing of custom amplicon-based targeted genes panel of myopathies. Mutations were confirmed by Sanger sequencing. Results The most frequent phenotype consisted of proximal limb weakness associated with interphalangeal and wrists contractures. However, cases with isolated contractures or isolated myopathy were found. CK levels did not correlate with severity of the disease. The most frequent mutation was the COL6A3 variant c.7447A>G, p.Lys2486Glu, with either an homozygous or compound heterozygous presentation. Five new mutations were found in COL6A1 gene and other two in COL6A3 gene, all of them with a dominant heritability pattern. From these, a new COL6A1 mutation (c.1657G>A, p.Glu553Arg) was related to an oligosymptomatic phenotype with predominating contractures in the absence of weakness and a normal muscle MRI. Finally, the most common COL6A1 mutation reported to date that leads to an Ullrich phenotype (c. 868G>A, p.Gly290Arg), has been found here as Bethlem presentation. Conclusions Manifestations of Bethlem myopathy are quite variable, so either contractures or weakness may be lacking, and no phenotype-genotype associations can be brought.

Calf pseudohypertrophy due to radiculopathy is an exceptional phenomenon rarely described. We report a 67 year old woman with a previous history of lumbar disc surgery consulting by progressive increase for more than a year of evolution painless right calf associated loss of strength. Electromyographic findings showed chronic S1 radiculopathy and radiologically was appreciated in the medial gastrocnemius and soleus rights substitution of normal muscle tissue by adipose tissue without evidence of myopathy or sarcomatous degeneration. Copyright © 2016 Elsevier España, S.L.U. y Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

We describe a slowly progressive myopathy in seven unrelated adult patients with storage of polyglucosan in muscle fibers. Genetic investigation revealed homozygous or compound heterozygous deleterious variants in the glycogenin-1 gene (GYG1). Most patients showed depletion of glycogenin-1 in skeletal muscle whereas one showed presence of glycogenin-1 lacking the C-terminal that normally binds glycogen synthase. Our results indicate that either depletion of glycogenin-1 or impaired interaction with glycogen synthase underlies this new form of glycogen storage disease that differs from a previously reported patient with GYG1 mutations who showed profound glycogen depletion in skeletal muscle and accumulation of glycogenin-1. ANN NEUROL 2014. © 2014 American Neurological Association

Objective: To establish the clinical relevance of the histological evidence of inflammatory cell infiltrates in surgical samples of operated lumbar disc hernia. Material and method: Surgical samples, clinical, and epidemiological data were obtained from 50 patients consecutively operated on of lumbar disc herniation during 2012 were obtained. Also the MR appearance as extruded or contained hernia was recorded. All samples were processed using hematoxilin-eosin staining and different histological parameters were determined such as the presence and quantity of chondrocytes present in the disc as a sign of disc degeneration. Results: Even though the majority of samples examined showed signs of disc degeneration, such as the presence of chondrocyte proliferation, the evidence of neovascularisation or inflammatory infiltrates was scarce. The presence of inflammatory infiltrates was invariably related to the presence of neovascularisation. However, the presence of inflammatory infiltrates was not related to any radiological or clinical variable. Conclusion: There is no relation between the presence of inflammatory infiltrates and the clinical data registered. The presence of histological evidence of inflammation in herniated lumbar disc tissue is not related to disc degeneration or the presence of pain.