Assessing diabetic polyneuropathy in Spanish-speaking patients: Translation and validation of the Toronto Clinical Neuropathy Score.

BACKGROUND AND AIMS: Diabetic sensorimotor polyneuropathy (DSP) is a common complication of diabetes. The Toronto Clinical Neuropathy Score (TCNS) is a useful tool for detecting DSP. However, it is not available in Spanish. The study aimed to translate and culturally adapt the TCNS and modified (mTCNS) scales into Spanish and evaluate their measurement properties. METHODS: A multistep forward-backward method was used for translation and cultural adaptation. A panel of physicians subjected the final Spanish versions of TCNS and mTCNS (TCÑS, mTCÑS) to cognitive debriefing. Consecutive patients with diabetes mellitus and DSP were recruited from an outpatient clinic, and the TCÑS and mTCÑS were tested for construct validity, along with other measures. RESULTS: The internal consistency of both TCÑS and mTCÑS was excellent, as evidenced by Cronbach's Alpha coefficients of 0.83 and 0.85, respectively. Furthermore, there was a robust positive correlation between TCÑS and mTCÑS. In addition, TCÑS was found to exhibit a strong negative correlation with sural sensory nerve action potential amplitude (r = -0.9206) and peroneal compound motor action potential amplitude (r = -0.729), while demonstrating a positive and strong correlation with the Michigan Neuropathy Screening Instrument (r = 0.713). INTERPRETATION: The TCÑS and mTCÑS are reliable and valid translations of the original TCNS. The TCÑS and mTCÑS can be used to diagnose and measure the severity of neuropathy in Spanish-speaking patients with diabetes.

Autophagy in non-immune-mediated rhabdomyolysis: Assessment of p62 immunohistochemistry.

INTRODUCTION/AIMS: p62 immunochemistry (IHC) has been shown to aid diagnosis with distinct patterns of muscle fiber staining observed in some inflammatory, hereditary, and degenerative myopathies, such as immune-mediated necrotizing myopathy (IMNM). The pattern of p62 staining may help narrow the pathological differential diagnosis of rhabdomyolysis. However, there is a lack of information on the pattern of p62 IHC in non-immune-mediated rhabdomyolysis. In this study we aim to describe histopathological findings in non-immune-mediated rhabdomyolysis, with particular emphasis on the pattern of p62 IHC. METHODS: We retrospectively reviewed the histopathological features of patients with a confirmed diagnoses of non-immune-mediated rhabdomyolysis referred to our center. RESULTS: Five patients were identified. Rhabdomyolysis was determined to be due to statin-associated toxicity in three patients, alcohol overuse in one patient, and intensive exercise in one patient. All patients showed increased numbers of necrotic and regenerating muscle fibers. Diffuse and finely granular sarcoplasmic positive p62 staining was present in scattered non-necrotic muscle fibers in all patients. DISCUSSION: Disturbance of autophagy appears to be a common mechanism in non-immune-mediated rhabdomyolysis. Our results show p62 IHC is sensitive but lacks specificity. Therefore, the pattern of p62 staining does not distinguish non-immune-mediated rhabdomyolysis from histopathologically similar IMNM.

Diagnostic utility of transcranial magnetic stimulation for neurodegenerative disease: a critical review / Utilidade diagnóstica da estimulação magnética transcraniana para doenças neurodegenerativas: uma revisão crítica

ABSTRACT. Neurodegenerative diseases pose significant challenges due to their impact on brain structure, function, and cognition. As life expectancy rises, the prevalence of these disorders is rapidly increasing, resulting in substantial personal, familial, and societal burdens. Efforts have been made to optimize the diagnostic and therapeutic processes, primarily focusing on clinical, cognitive, and imaging characterization. However, the emergence of non-invasive brain stimulation techniques, specifically transcranial magnetic stimulation (TMS), offers unique functional insights and diagnostic potential. TMS allows direct evaluation of brain function, providing valuable information inaccessible through other methods. This review aims to summarize the current and potential diagnostic utility of TMS in investigating neurodegenerative diseases, highlighting its relevance to the field of cognitive neuroscience. The findings presented herein contribute to the growing body of research focused on improving our understanding and management of these debilitating conditions, particularly in regions with limited resources and a pressing need for innovative approaches.

RESUMO. As doenças neurodegenerativas representam desafio significativo por seu impacto na estrutura cerebral, função e cognição. À medida que a expectativa de vida aumenta, a prevalência dessas doenças cresce rapidamente, resultando em substanciais encargos pessoais, familiares e sociais. Esforços têm sido feitos para otimizar os processos diagnósticos e terapêuticos, com foco principal na caracterização clínica, cognitiva e de imagem. No entanto, o surgimento de técnicas de estimulação cerebral não invasivas, especificamente a estimulação magnética transcraniana (EMT), oferece compreensão funcional e potencial diagnóstico únicos. A TMS permite a avaliação direta da função cerebral, fornecendo informações valiosas inacessíveis por outros métodos. Esta revisão teve como objetivo resumir a utilidade diagnóstica atual e potencial da EMT na investigação de doenças neurodegenerativas, destacando sua relevância para o campo da neurociência cognitiva. As conclusões aqui apresentadas contribuem para o crescente corpo de investigação centrado na melhoria da nossa compreensão e gestão dessas condições debilitantes, particularmente em regiões com recursos limitados e necessidade premente de abordagens inovadoras.

Diagnostic utility of transcranial magnetic stimulation for neurodegenerative disease: a critical review.

Neurodegenerative diseases pose significant challenges due to their impact on brain structure, function, and cognition. As life expectancy rises, the prevalence of these disorders is rapidly increasing, resulting in substantial personal, familial, and societal burdens. Efforts have been made to optimize the diagnostic and therapeutic processes, primarily focusing on clinical, cognitive, and imaging characterization. However, the emergence of non-invasive brain stimulation techniques, specifically transcranial magnetic stimulation (TMS), offers unique functional insights and diagnostic potential. TMS allows direct evaluation of brain function, providing valuable information inaccessible through other methods. This review aims to summarize the current and potential diagnostic utility of TMS in investigating neurodegenerative diseases, highlighting its relevance to the field of cognitive neuroscience. The findings presented herein contribute to the growing body of research focused on improving our understanding and management of these debilitating conditions, particularly in regions with limited resources and a pressing need for innovative approaches.

As doenças neurodegenerativas representam desafio significativo por seu impacto na estrutura cerebral, função e cognição. À medida que a expectativa de vida aumenta, a prevalência dessas doenças cresce rapidamente, resultando em substanciais encargos pessoais, familiares e sociais. Esforços têm sido feitos para otimizar os processos diagnósticos e terapêuticos, com foco principal na caracterização clínica, cognitiva e de imagem. No entanto, o surgimento de técnicas de estimulação cerebral não invasivas, especificamente a estimulação magnética transcraniana (EMT), oferece compreensão funcional e potencial diagnóstico únicos. A TMS permite a avaliação direta da função cerebral, fornecendo informações valiosas inacessíveis por outros métodos. Esta revisão teve como objetivo resumir a utilidade diagnóstica atual e potencial da EMT na investigação de doenças neurodegenerativas, destacando sua relevância para o campo da neurociência cognitiva. As conclusões aqui apresentadas contribuem para o crescente corpo de investigação centrado na melhoria da nossa compreensão e gestão dessas condições debilitantes, particularmente em regiões com recursos limitados e necessidade premente de abordagens inovadoras.

Manejo multidisciplinario y avances terapéuticos en la esclerosis lateral amiotrófica / Multidisciplinary care and therapeutic advances in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that mainly affects the motor system, resulting in progressive weakness and muscle wasting. Despite the tremendous advances in physiopathological and clinical characterization, we do not have a curative treatment yet. The progressive and fatal course of ALS makes its management particularly complex and challenging given the diversity of symptoms presenting during the disease progression. The main goal in the treatment of ALS patients is to minimize morbidity and maximize the quality of life. Currently, a series of therapeutic interventions improve the quality of life and prolong survival, including multidisciplinary care, respiratory management, and disease-modifying therapy. Within the supportive interventions, weight maintenance through nutritional and metabolic support is critical. In addition, the management of neuropsychiatric manifestations and preservation of communicative capacity before speech loss are also crucial. Lastly, early palliative care intervention is essential to optimize symptomatic management. Anticipatory guidelines to face the inevitable patient deterioration should be devised. This article updates the main therapeutic strategies used in these patients, including evolving clinical trials with promising novel therapies.

Genetic Profile of Patients with Limb-Girdle Muscle Weakness in the Chilean Population.

Hereditary myopathies are a group of genetically determined muscle disorders comprising more than 300 entities. In Chile, there are no specific registries of the distinct forms of these myopathies. We now report the genetic findings of a series of Chilean patients presenting with limb-girdle muscle weakness of unknown etiology. Eighty-two patients were explored using high-throughput sequencing approaches with neuromuscular gene panels, establishing a definite genetic diagnosis in 49 patients (59.8%) and a highly probable genetic diagnosis in eight additional cases (9.8%). The most frequent causative genes identified were DYSF and CAPN3, accounting for 22% and 8.5% of the cases, respectively, followed by DMD (4.9%) and RYR1 (4.9%). The remaining 17 causative genes were present in one or two cases only. Twelve novel variants were identified. Five patients (6.1%) carried a variant of uncertain significance in genes partially matching the clinical phenotype. Twenty patients (24.4%) did not carry a pathogenic or likely pathogenic variant in the phenotypically related genes, including five patients (6.1%) presenting an autoimmune neuromuscular disorder. The relative frequency of the different forms of myopathy in Chile is like that of other series reported from different regions of the world with perhaps a relatively higher incidence of dysferlinopathy.

Mitochondrial dysfunction in anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) immune-mediated necrotising myopathy.

Mitochondrial dysfunction is a plausible cause of muscle fibre damage in a number of myopathies including immune-mediated necrotising myopathy. However, histopathological evidence of mitochondrial dysfunction is not often described in immune-mediated necrotising myopathy and, when present, it is often attributed to patient age. The purpose of this study was to describe features of mitochondrial dysfunction on muscle biopsy in anti-3­hydroxy-3-methylglutaryl-CoA reductase immune-mediated necrotising myopathy and explore whether these features are age-related. In this observational case control study, a statistically significant increase in the number of muscle fibres with increased lipid content (p = 0.004) and cytochrome c oxidase-negative/succinate dehydrogenase-positive fibres (p = 0.037) in anti-3­hydroxy-3-methylglutaryl-coenzyme immune-mediated necrotising myopathy was found compared to age-matched controls. Therefore, histopathological features of mitochondrial dysfunction are more frequent in anti-3­hydroxy-3-methylglutaryl-coenzyme immune-mediated necrotising myopathy than aged-matched controls and therefore, may be contributing to the pathogenesis.

[Multidisciplinary care and therapeutic advances in amyotrophic lateral sclerosis]. / Manejo multidisciplinario y avances terapéuticos en la esclerosis lateral amiotrófica.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that mainly affects the motor system, resulting in progressive weakness and muscle wasting. Despite the tremendous advances in physiopathological and clinical characterization, we do not have a curative treatment yet. The progressive and fatal course of ALS makes its management particularly complex and challenging given the diversity of symptoms presenting during the disease progression. The main goal in the treatment of ALS patients is to minimize morbidity and maximize the quality of life. Currently, a series of therapeutic interventions improve the quality of life and prolong survival, including multidisciplinary care, respiratory management, and disease-modifying therapy. Within the supportive interventions, weight maintenance through nutritional and metabolic support is critical. In addition, the management of neuropsychiatric manifestations and preservation of communicative capacity before speech loss are also crucial. Lastly, early palliative care intervention is essential to optimize symptomatic management. Anticipatory guidelines to face the inevitable patient deterioration should be devised. This article updates the main therapeutic strategies used in these patients, including evolving clinical trials with promising novel therapies.

Fasciculaciones y calambres: bases fisiológicas y enfrentamiento clínico de un fenómeno complejo

Fasciculations and cramps originate in the motor unit, a functional unit that includes the lower motor neuron and their innervated muscle fibres. Both are common complaints in outpatient practice. These symptoms can be secondary to neurological or medical pathology, presenting a broad differential diagnosis and a complex approach. Recent neurophysiological studies have increased the knowledge of their origin mainly in amyotrophic lateral sclerosis. The symptomatic management of fasciculations and cramps depends on their etiology and includes pharmacological and non-pharmacological treatments. This article aims to present an updated review of the most relevant aspects of physiopathology, clinical approach, and differential diagnosis of both phenomena.

[Fasciculations and cramps: physiological bases and clinical approach of a complex phenomenon]. / Fasciculaciones y calambres: bases fisiológicas y enfrentamiento clínico de un fenómeno complejo.

Fasciculations and cramps originate in the motor unit, a functional unit that includes the lower motor neuron and their innervated muscle fibres. Both are common complaints in outpatient practice. These symptoms can be secondary to neurological or medical pathology, presenting a broad differential diagnosis and a complex approach. Recent neurophysiological studies have increased the knowledge of their origin mainly in amyotrophic lateral sclerosis. The symptomatic management of fasciculations and cramps depends on their etiology and includes pharmacological and non-pharmacological treatments. This article aims to present an updated review of the most relevant aspects of physiopathology, clinical approach, and differential diagnosis of both phenomena.

[Idiopathic inflammatory myopathies. A review]. / Miopatías inflamatorias idiopáticas: una mirada actualizada al diagnóstico y el manejo.

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of acquired immune-mediated diseases, which typically involve the striated muscle with a variable involvement of the skin and other organs. Clinically, they are characterized by proximal muscle weakness, elevation of muscle enzymes, myopathic changes on electromyography and an abnormal muscle biopsy. The different IIM have been classified according to their distinctive histopathologic features in dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM) and immune-mediated necrotizing myopathy (IMNM). Several myositis-specific antibodies are associated with the different phenotypes, as well as with different risk of neoplastic disease and systemic complications. The basis for the treatment of DM, PM, and IMNM is immunosuppression. For IBM there are only symptomatic treatments. Steroids, associated or not with other immunosuppressant drugs, are the first line of treatment. Biologic drugs will allow future individualized therapies. The 10-year survival of DM, PM and IMNM is 62 to 90%. The leading causes of death are neoplastic, lung and cardiac complications. IBM does not impair survival, although it affects the quality of life.

Miopatías inflamatorias idiopáticas: una mirada actualizada al diagnóstico y el manejo / Idiopathic inflammatory myopathies: a review

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of acquired immune-mediated diseases, which typically involve the striated muscle with a variable involvement of the skin and other organs. Clinically, they are characterized by proximal muscle weakness, elevation of muscle enzymes, myopathic changes on electromyography and an abnormal muscle biopsy. The different IIM have been classified according to their distinctive histopathologic features in dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM) and immune-mediated necrotizing myopathy (IMNM). Several myositis-specific antibodies are associated with the different phenotypes, as well as with different risk of neoplastic disease and systemic complications. The basis for the treatment of DM, PM, and IMNM is immunosuppression. For IBM there are only symptomatic treatments. Steroids, associated or not with other immunosuppressant drugs, are the first line of treatment. Biologic drugs will allow future individualized therapies. The 10-year survival of DM, PM and IMNM is 62 to 90%. The leading causes of death are neoplastic, lung and cardiac complications. IBM does not impair survival, although it affects the quality of life.

Linfoma testicular: incidencia, descripción epidemiológica y manejo durante el período 2005-2011 / Testicular lymphoma: incidence, epidemiologic description and management during the 2005-2011 period

El linfoma testicular es una patología infrecuente, correspondiendo al 9 por ciento de los cánceres testiculares, presentándose más frecuentemente entre los 60 a 80 años (25-50 por ciento). La presentación clínica más frecuente es el aumento de volumen unilateral e indo/oro. El tipo histológico más común es linfoma difuso de células grandes B (60-90 por ciento). La orquidectomía radical asociada a quimioterapia y radioterapia es la primera línea de tratamiento para los pacientes con enfermedad limitada. Material y método: Estudio retrospectivo descriptivo. Se revisó y filtró la lista de pacientes ingresados al SIGGES como tumor testicular entre enero 2005 a abril 2011. De los pacientes con diagnóstico histológico e inmunohistoquímico compatible, se registraron las características epidemiológicas, estudio, manejo y sobrevida. Posteriormente se realizó un análisis de la base de datos con el programa estadístico SPSS 13. 0. Resultados: De un total de 299 pacientes con el diagnóstico histológico de cáncer testicular, 8 pacientes fueron diagnosticados como linfoma testicular confirmado por histología e inmunohistoquímica. El promedio y mediana de edad fue 52 años y 63 años (18-73) respectivamente. Tres casos (37,5 por ciento) correspondieron a presentaciones secundarias. En 6 de los casos (75 por ciento) el testículo afectado fue el derecho. Histológicamente, el 63 por ciento correspondió a Linfoma difuso de células grande B. Clínicamente, el todos los casos se presentaron con aumento de volumen y con marcadores en rango normal. En 7 casos (8 7, 5 por ciento) el diagnóstico y manejo inicial fue mediante orquidectomía radical, y en un caso por biopsia testicular, con orquidectomía posterior 3 casos presentaron diseminación...

esticular lymphoma is a rare disease, happening in 9 percent of testicular cancers, most commonly between the ages 60 to 80 years (25 percent-50 percent). The most common presentation is unilateral indolent testicular growth. Histology shows a diffuse big B cell lymphoma in most of the cases (60 percent-90 percent). Radical orchiectomy, chemotherapy and radiation are the first line therapy for patients with limited disease. Materials and methods: Retrospective clinical study. We included and filtered the SIGGES list of patients admitted for Testicular Tumor from January 2005 to April 2011. Patients with a compatible diagnosis were analyzed, using SPSS 13.0® as statistical software. Result: Of a total number of 299 testicular cancer patients 8 presented with a histological and inmunnohistochemical testicular lymphoma. Mean age was 52 years and the median 63 years (18-73). ln three cases (37.5 percent) it was a secondary localization. ln 6 cases ( 75 percent) the affected testicle was the right one. 63 percent corresponded to a diffuse big cell B cell Lymphoma. All patients presented normal tumor markers. ln 7 (87,5 percent) cases the initial treatment was radical orchiectomy in one patient the diagnosis was don through a testicular biopsy, and the orchidectomy was differed. 3 cases presented dissemination. In 7 patients adjuvant chemotherapy was performed. Mortal/ty was 38 percent with a 1 7-month follow-up. Conclusion: Testicular lymphoma is a rare condition with bad prognosis. Histology is fundamental for treatment, an in this sense inmunohystochemcal analysis is especially helpful...