Clinical practice guidelines for the diagnosis and management of Charcot-Marie-Tooth disease.

INTRODUCTION: Charcot-Marie-Tooth disease (CMT) is classified according to neurophysiological and histological findings, the inheritance pattern, and the underlying genetic defect. The objective of these guidelines is to offer recommendations for the diagnosis, prognosis, follow-up, and treatment of this disease in Spain. MATERIAL AND METHODS: These consensus guidelines were developed through collaboration by a multidisciplinary panel encompassing a broad group of experts on the subject, including neurologists, paediatric neurologists, geneticists, physiatrists, and orthopaedic surgeons. RECOMMENDATIONS: The diagnosis of CMT is clinical, with patients usually presenting a common or classical phenotype. Clinical assessment should be followed by an appropriate neurophysiological study; specific recommendations are established for the parameters that should be included. Genetic diagnosis should be approached sequentially; once PMP22 duplication has been ruled out, if appropriate, a next-generation sequencing study should be considered, taking into account the limitations of the available techniques. To date, no pharmacological disease-modifying treatment is available, but symptomatic management, guided by a multidiciplinary team, is important, as is proper rehabilitation and orthopaedic management. The latter should be initiated early to identify and improve the patient's functional deficits, and should include individualised exercise guidelines, orthotic adaptation, and assessment of conservative surgeries such as tendon transfer. The follow-up of patients with CMT is exclusively clinical, and ancillary testing is not necessary in routine clinical practice.

Validation of Neuromyotype: a smart keyboard for the evaluation of spinal muscular atrophy patients.

INTRODUCTION: Spinal muscular atrophy 5q (SMA) is a genetic neurodegenerative disease that affects alpha motor neurons producing progressive weakness. New outcome measures are currently required to accurately characterise the disease progression and the efficacy of new available treatments. The objective of this work is to preliminarily validate a new intelligent keyboard (Neuromyotype) measuring typing strength and speed in patients with SMA. MATERIAL AND METHODS: Twenty two SMA patients older than 15 years, and 26 healthy controls were included. Three measurements were obtained with the keyboard (maximum strength, execution time of a random typing task, execution time of a sequential typing task) together with the time to complete the Nine-Hole Peg Test (9HPT). Patients were also administered motor (Hammersmith Functional Motor Scale Expanded, HFMSE; Revised Upper Limb module, RULM), and functional scales (Egen Klassification, EK2; and the revised version of Amyotrophic Lateral Sclerosis Functional Rating Scale, ALSFRS-R). The viability and construct validity of the Neuromyotype were analysed, measuring the discriminative power between patients and controls (using ROC curves and the Bangdiwala's B statistic), between the different functional types of SMA (walker, sitter and non-sitter) and their correlation with the rest of motor scales. RESULTS: Neuromyotype measurements could be performed in all patients, unlike the rest of the scales. Its administration was quick and easy. The 3 variables on the keyboard discriminated very well between patients and controls, with strength (ROC = 0.963) being the one that best differentiates from the 3, equaling 9HPT (ROC = 0.966). They also showed a good ability to differentiate by functional type (especially non-sitters from sitters and walkers), with sequential time (B = 0.83) being the tool that best discriminates between the three groups above the rest of motor scales. All motor and functional scales showed strong or very strong correlations with each other (rs = 0.71-0.99), with strength correlating better with motor scales and timed variables with functional scales. CONCLUSION: This study shows the feasibility and validity of Neuromyotype for the evaluation of adolescent and adult patients with SMA. Data obtained with this tool could be of great clinical relevance, saving time and resources compared to the rest of the scales.

Analysis of the diagnostic pathway and delay in patients with amyotrophic lateral sclerosis in the Valencian Community.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is an insidious, clinically heterogeneous neurodegenerative disease associated with a diagnostic delay of approximately 12 months. No study conducted to date has analysed the diagnostic pathway in Spain. METHODS: We gathered data on variables related to the diagnostic pathway and delay for patients diagnosed with ALS between October 2013 and July 2017. RESULTS: The study included 143 patients with ALS (57% men; 68% spinal onset). Patients were diagnosed in public centres in 86% of cases and in private centres in 14%. The mean diagnostic delay was 13.1 months (median 11.7). Patients were examined by neurologists a mean time of 7.9 months after symptom onset, with diagnosis being made 5.2 months later. Half of all patients underwent unnecessary diagnostic tests and multiple electrophysiological studies before diagnosis was established. Diagnostic delay was longer in cases of spinal onset (P=.008) due to onset of the disease in the lower limbs. No differences were found between the public and private healthcare systems (P=.897). CONCLUSIONS: The diagnostic delay in ALS in Spain is similar to that of neighbouring countries and seems to depend on disease-related factors, not on the healthcare system. Patients with lower-limb onset ALS constitute the greatest diagnostic challenge. Misdiagnosis is frequent, and partly attributable to an incorrect approach or erroneous interpretation of electrophysiological studies. Specific training programmes for neurologists and general neurophysiologists and early referral to reference centres may help to reduce diagnostic delay.

Análisis del trayecto y retraso diagnóstico de los pacientes con esclerosis lateral amiotrófica en la Comunidad Valenciana / Analysis of the diagnostic pathway and delay in patients with amyotrophic lateral sclerosis in the Valencian Community

Introducción: La esclerosis lateral amiotrófica (ELA) es una enfermedad insidiosa y clínicamente heterogénea, lo que resulta en un retraso diagnóstico de unos 12 meses. En España el trayecto diagnóstico no ha sido analizado.MétodosSe recogieron variables relativas al trayecto y retraso diagnóstico de pacientes diagnosticados de ELA entre octubre del 2013 y julio del 2017.ResultadosSe incluyó a 143 pacientes con ELA (57% varones, 68% de inicio espinal). El 86% de ellos fueron estudiados en centros públicos y un 14% en privados. El retraso diagnóstico medio fue de 13,1 meses (mediana 11.7). El paciente tardó de media 7,9 meses en llegar al neurólogo y este, 5,2 meses más en diagnosticarlo. En la mitad de los pacientes se realizaron pruebas innecesarias y más de un estudio electrofisiológico para llegar al diagnóstico. El retraso diagnóstico fue mayor en los casos espinales (p = 0,008), atribuible a los pacientes cuyos síntomas se iniciaron en miembros inferiores, pero sin diferencias entre el sistema público y privado (p = 0,897).ConclusionesEl retraso diagnóstico de la ELA en nuestro medio es similar al de países de nuestro entorno y parece determinado por factores propios de la enfermedad e independiente del sistema sanitario. Las formas de inicio en miembros inferiores constituyen el mayor reto. Los errores diagnósticos del neurólogo son frecuentes y en parte atribuibles a una mala orientación o interpretación del estudio electrofisiológico. La formación específica del neurólogo y neurofisiólogo general y la derivación precoz a centros de referencia podrían ayudar a reducir la demora. (AU)

Introduction: Amyotrophic lateral sclerosis (ALS) is an insidious, clinically heterogeneous neurodegenerative disease associated with a diagnostic delay of approximately 12 months. No study conducted to date has analysed the diagnostic pathway in Spain.MethodsWe gathered data on variables related to the diagnostic pathway and delay for patients diagnosed with ALS between October 2013 and July 2017.ResultsThe study included 143 patients with ALS (57% men; 68% spinal onset). Patients were diagnosed in public centres in 86% of cases and in private centres in 14%.The mean diagnostic delay was 13.1 months (median 11.7). Patients were examined by neurologists a mean time of 7.9 months after symptom onset, with diagnosis being made 5.2 months later. Half of all patients underwent unnecessary diagnostic tests and multiple electrophysiological studies before diagnosis was established. Diagnostic delay was longer in cases of spinal onset (P = .008) due to onset of the disease in the lower limbs. No differences were found between the public and private healthcare systems (P = .897).ConclusionsThe diagnostic delay in ALS in Spain is similar to that of neighboring countries and seems to depend on disease-related factors, not on the healthcare system. Patients with lower-limb onset ALS constitute the greatest diagnostic challenge. Misdiagnosis is frequent, and partly attributable to an incorrect approach or erroneous interpretation of electrophysiological studies. Specific training programmes for neurologists and general neurophysiologists and early referral to reference centers may help to reduce diagnostic delay. (AU)

Incidence of and risk factors for neurologic complications after heart transplantation.

INTRODUCTION: Following heart transplantation (HT), neurologic complications occur in 50% to 70% of patients, mostly in the perioperative period. The objective of our study was to analyze the frequency and impact of factors related to the development of neurological complications after HT. MATERIALS AND METHODS: HT patients with survival greater than 1 month (November 1987 to May 2003) were included. Heart-lung transplants, retransplants, and pediatric patients were excluded. Neurologic complications were defined as a neurologic event requiring hospitalization or detected in the hospital. Groups included ischemic or hemorrhagic stroke, seizures, neurotoxicity or other complications (e.g., infections, headaches, Alzheimer's). RESULTS: We assessed 322 HT patients (87.6% men, 12.4% women) and grouped them according to the presence of neurologic complications during follow-up. There were no differences in the baseline characteristics between the two groups. Of patients the patients studied, 13.7% suffered a neurologic complication: ischemic stroke (3.5%), neurotoxicity (2.9%), seizures (1.9%), and other complications (1.6%). Only two cases of hemorrhagic stroke (0.6%) were observed. Associations with pretransplant risk factors included seizures with diabetes mellitus (OR, 6.54; 95% CI, 1.28 to 33.6, P = .024), seizures with renal failure (OR, 5.95; 95% CI, 1.03 to 34.3; P = .046), and ischemic stroke with prior valvular disease (OR, 4.96, 95% CI, 1.22 to 20.1; P = .045). Associations with pretransplant risk factors were neurologic complications with the number of infections (OR, 1.35, 95% CI, 1.05 to 1.73; P = .02). No differences were found in survival of patients with neurologic complications. CONCLUSIONS: The incidence of neurologic complications in our series was 13.7%. The most frequent neurologic complication was ischemic stroke. Valvular disease as the underlying disease was associated with ischemic stroke. Diabetes mellitus and renal failure were associated with seizures. The number of posttransplant infections was associated with neurologic complications. There were no differences in survival of patients with neurologic complications.

[Cranial hyperostosis as a metastasic adenocarcinoma presentation form]. / Hiperostosis craneal como forma de presentación de un adenocarcinoma metastásico.

Hyperostosis is a volume-unit osseous increase of very diverse etiology. We present the case of a 68-year woman with a cranial hyperostosis debuting with frontal protrusion, headache and neurologic symptoms. Image proves demonstrated a hyperostosis in the calotte and meningeal enhancement, without intracerebral lesions nor malignant cells in the cerebrospinal fluid. Analytic data were unspecific. Cranial biopsy showed huge neoplastic infiltration in bone and meninges. Primary site remained unknown after a CAT and a mammography.

Hiperostosis craneal como forma de presentación de un adenocarcinoma metastásico / Cranial hyperostosis as a metastasic adenocarcinoma presentation form

La hiperostosis es un aumento de masa ósea por unidad de volumen de etiología muy diversa. Presentamos el caso de una mujer de 68 años con hiperostosis craneal que debutó con clínica de protusión frontal derecha, cefalea y sintomatología neurológica. Las pruebas de imagen demostraron la existencia de hiperostosis de calota con afectación meníngea, sin lesiones cerebrales ni células malignas en líquido cefalorraquídeo. Los datos analíticos eran inespecíficos. La biopsia craneal mostró amplia infiltración neoplásica por adenocarcinoma metastásico tanto en hueso como en meninges. No se localizó el tumor primario tras realizarse TAC y mamografía (AU)

[Nonsystemic vasculitic neuropathy]. / Neuropatía vasculítica no sistémica.

BACKGROUND: Nonsystemic vasculitic neuropathy (NSVN) is an infrequent type of vasculitic neuropathy that evolves without manifestations of vasculitis in other organs and in the absence of serological abnormalities. There are non clarified conjectures about the pathogenesis, outcome and treatment approach. PATIENTS AND METHOD: A retrospective study of a series of six patients diagnosed of NSVN during a period of 12 years. Clinical, electrophysiological and pathological features, as well as the response to therapy and outcome are analysed. RESULTS: Four cases presented with a pattern of multiple mononeuropathy, evolving towards a symmetrical sensory and motor polyneuropathy in two of them. One patient presented with an acute sensory neuropathy and another had a subacute asymmetric sensory and motor neuropathy. No signs of accompanying systemic vasculitis were observed during the follow-up (mean 35 months) and the only outstanding serological abnormality was the presence of antibodies against hepatitis B virus in four of them. The nerve conduction studies showed typical features of axonal degeneration. The diagnostic was obtained due to the presence of a necrotizing vasculitis in the sural nerve biopsy in all cases. The mean time from symptom onset to diagnosis was 11 months. All patients were treated with immunosuppressive therapy presenting a favourable response, except the case of the sensory neuropathy that remained stable. CONCLUSIONS: NSVN is a benign type of vasculitic neuropathy with a variable clinical pattern of presentation and favourable response to immunosuppression. This neuropathy requires a high index of suspicion for diagnosis, so nerve biopsy must be carried out in all neuropathy of unknown etiology. Careful follow-up of patients is necessary, so that life-threatening systemic vasculitis neuropathy can be diagnosed early.

Neuropatía vasculítica no sistémica / Nonsystemic vasculitic neuropathy

FUNDAMENTO: La neuropatía vasculítica no sistémica (NVNS) es una forma infrecuente de neuropatía vasculítica, sin participación de otros órganos y con escasas alteraciones analíticas, existiendo conjeturas no aclaradas acerca de su patogenia, pronóstico y enfoque terapéutico. PACIENTES Y MÉTODOS: Estudio retrospectivo de una serie de 6 pacientes diagnosticados de NVNS durante un período de 12 años. Se analizan los patrones clínicos, los hallazgos electrofisiológicos y patológicos, la respuesta al tratamiento y el pronóstico. RESULTADOS: El patrón de neuropatía predominante fue el de mononeuropatía múltiple, evolucionando dos de ellos a polineuropatía simétrica sensitivomotora. Un paciente cursó como polineuropatía sensitiva pura aguda y otro como neuropatía sensitivomotora asimétrica subaguda. No se detectaron datos de participación de otros órganos durante el tiempo de evolución de los síntomas (media, 35 meses), siendo la única alteración serológica destacable la presencia de anticuerpos frente al virus hepatitis B en 4 pacientes. Los estudios electrofisiológicos fueron compatibles con degeneración axonal. El diagnóstico se estableció al detectar una vasculitis necrosante en la biopsia de nervio sural, obteniéndose tras una latencia media de 11 meses desde el inicio de los síntomas. Todos los pacientes recibieron tratamiento inmunodepresor con respuesta favorable, salvo el caso de la neuropatía sensitiva aguda, que permaneció estable. CONCLUSIONES: La NVNS es una forma benigna de neuropatía vasculítica, con un patrón clínico de presentación variado y buena respuesta a la inmunodepresión. Se requiere un alto nivel de sospecha para su diagnóstico, por lo que es obligada la biopsia de nervio en toda neuropatía cuya etiología no esté clara. No obstante, se recomienda efectuar un estrecho seguimiento durante un período razonable por si se tratase de la fase temprana de una vasculitis sistémica con neuropatía como presentación inicial (AU)