Analysis of autonomic outcomes in APOLLO, a phase III trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis.

Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive, debilitating disease often resulting in early-onset, life-impacting autonomic dysfunction. The effect of the RNAi therapeutic, patisiran, on autonomic neuropathy manifestations in patients with hATTR amyloidosis with polyneuropathy in the phase III APOLLO study is reported. Patients received patisiran 0.3 mg/kg intravenously (n = 148) or placebo (n = 77) once every 3 weeks for 18 months. Patisiran halted or reversed polyneuropathy and improved quality of life from baseline in the majority of patients. At baseline, patients in APOLLO had notable autonomic impairment, as demonstrated by the Composite Autonomic Symptom Score-31 (COMPASS-31) questionnaire and Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire autonomic neuropathy domain. At 18 months, patisiran improved autonomic neuropathy symptoms compared with placebo [COMPASS-31, least squares (LS) mean difference, - 7.5; 95% CI: - 11.9, - 3.2; Norfolk QOL-DN autonomic neuropathy domain, LS mean difference, - 1.1; - 1.8, - 0.5], nutritional status (modified body mass index, LS mean difference, 115.7; - 82.4, 149.0), and vasomotor function (postural blood pressure, LS mean difference, - 0.3; - 0.5, - 0.1). Patisiran treatment also led to improvement from baseline at 18 months for COMPASS-31 (LS mean change from baseline, - 5.3; 95% CI: - 7.9, - 2.7) and individual domains, orthostatic intolerance (- 4.6; - 6.3, - 2.9) and gastrointestinal symptoms (- 0.8; - 1.5, - 0.2). Rapid worsening of all study measures was observed with placebo, while patisiran treatment resulted in stable or improved scores compared with baseline. Patisiran demonstrates benefit across a range of burdensome autonomic neuropathy manifestations that deteriorate rapidly without early and continued treatment.

Peripheral polyneuropathy associated with Chikungunya virus infection.

The Chikungunya virus (CHIKV) is an arbovirus transmitted to humans through mosquito bites and can cause a series of symptoms ranging from a benign febrile illness to severe neurological conditions. We report the identification of CHIKV in a serum sample from an elderly woman with febrile illness and severe arthralgia in Brazil. The occurrence was found of peripheral polyneuropathy affecting the upper and lower limbs evidenced by electroneuromyographic findings. The patient was treated with a corticoid associated with methotrexate, suggesting that the pathophysiological basis of the case in question may be related to an immune-mediated response by T cells and inflammatory cytokines. This finding reinforces the need to be aware of the emergence of neuroinfections related to CHIKV and effective diagnoses for the early detection of neurological alterations, favoring the clinical management of these patients.

Tafamidis for autonomic neuropathy in hereditary transthyretin (ATTR) amyloidosis: a review.

PURPOSE: Autonomic dysfunction is a very common, early and distressing aspect of hereditary transthyretin (ATTR) amyloidosis leading to significant loss of quality of life and morbidity for patients. Although the clinical variability of ATTR has been well characterized as neuropathic, cardiac or mixed phenotype, the extent of autonomic involvement remains poorly understood. Despite the fact that the autonomic nervous system has not been specifically evaluated in any of the clinical trials of tafamidis, and that, for some primary and secondary endpoints used in these trials, the behavior cannot be separated from non-autonomic items, an attempt was made to use published material to indirectly access the efficacy of tafamidis in treating dysautonomia. METHODS: Literature review summarizing the results of primary and secondary endpoints related to the autonomic features used in the original tafamidis trials, the post hoc publications, and real-world data, on the effect of tafamidis on autonomic dysfunction in patients with ATTR amyloidosis. RESULTS: There is some evidence that indirectly demonstrates that tafamidis is safe and could slow or arrest the progression of autonomic neuropathy in patients with ATTR amyloidosis, in addition to its well-described effects to ameliorate sensory-motor peripheral neuropathy. CONCLUSION: Although the current evidence is scarce, tafamidis might be effective in arresting the progression of autonomic neuropathy in patients with ATTR amyloidosis. Tafamidis might be more effective at the early stage of the disease; however, individual responses must be monitored.

Hereditary transthyretin amyloidosis: baseline characteristics of patients in the NEURO-TTR trial.

BACKGROUND: Hereditary transthyretin (ATTRm) amyloidosis is a rare, progressive and fatal disease with a range of clinical manifestations. OBJECTIVE: This study comprehensively evaluates disease characteristics in a large, diverse cohort of patients with ATTRm amyloidosis. METHODS: Adult patients (N = 172) with Stage 1 or Stage 2 ATTRm amyloidosis who had polyneuropathy were screened and enrolled across 24 investigative sites and 10 countries in the NEURO-TTR trial ( www.clinicaltrials.gov , NCT01737398). Medical and disease history, quality of life, laboratory data, and clinical assessments were analyzed. RESULTS: The NEURO-TTR patient population was diverse in age, disease severity, TTR mutation, and organ involvement. Twenty-seven different TTR mutations were present, with Val30Met being the most common (52%). One third of patients reported early onset disease (before age 50) and the average duration of neuropathy symptoms was 5.3 years. Symptoms affected multiple organs and systems, with nearly 70% of patients exhibiting broad involvement of weakness, sensory loss, and autonomic disturbance. Over 60% of patients had cardiomyopathy, with highest prevalence in the United States (72%) and lowest in South America/Australasia (33%). Cardiac biomarker NT-proBNP correlated with left ventricular wall thickness (p<.001). Quality of life, measured by Norfolk QoL-DN and SF-36 patient-reported questionnaires, was significantly impaired and correlated with disease severity. CONCLUSIONS: Baseline data from the NEURO-TTR trial demonstrates ATTRm amyloidosis as a systemic disease with deficits in multiple organs and body systems, leading to decreased quality of life. We report concomitant presentation of polyneuropathy and cardiomyopathy in most patients, and early involvement of multiple body systems.

Eficacia y seguridad de inmunoglobulina humana en pacientes con polineuropatía desmielinizante inflamatoria crónica idiopática y respuesta inadecuada a corticoides e inmunosupresores / Efficacy and safety of human immunoglobulin in patients with idiopathic chronic inflammatory demyelinating polyneuropathy and inadequate response to corticosteroids and immunosuppressants

INTRODUCCIÓN: La presente evaluación de tecnología expone la evidencia científica encontrada acerca de eficacia y seguridad de inmunoglobulina humana en pacientes con polineuropatía desmielinizante inflamatoria crónica idiopática y respuesta inadecuada a corticoides e inmunosupresores. La polineuropatía desmielinizante inflamatoria crónica idiopática es una enfermedad heterogénea adquirida. Esta condición causa alteraciones sensitivas, síntomas de sensores positivos, así como debilidad motora debido a un proceso de desmielinización de los nervios periféricos. Usualmente las regiones involucradas son las áreas proximales y distales del sistema nervioso periférico. Dado el curso progresivo de la enfermedad, los desenlaces evaluados en los estudios publicados comprenden diversas escalas de mejora de la discapacidad y funcionalidad, las cuales constituyen desenlaces clínicamente relevantes desde la perspectiva del paciente, cuya calidad de vida se ve seriamente afectada con la progresión del tiempo. TECNOLOGIA SANITARIA DE INTERES: La inmunoglobulina humana intravenosa está compuesta por inmunoglobulina intravenosa (IgIV) que consiste de IgG, el cual es obtenido de miles de donantes de plasma sanos. Esta molécula ha sido empleada por primera vez para el manejo de púrpura trombocitopenica idiopática, tras lo cual ha sido empleada para otras enfermedades autoinmunes. METODOLOGÍA: Se llevó a cabo una búsqueda sistemática de la literatura con respecto a la eficacia y seguridad de inmunoglobulina humana en pacientes con polineuropatía desmielinizante inflamatoria crónica idiopática y respuesta inadecuada a corticoides e inmunosupresores. Para la búsqueda primaria se revisó en primer lugar la información disponible por entes reguladoras y normativas de autorización comercial como la Administración de Drogas y Alimentos (FDA) de Estados Unidos, la Agencia de Medicamentos Europea (EMA) y la Dirección General de Medicamentos y Drogas (DIGEMID) en el Perú. Seguidamente, se emplearon los motores de búsqueda de los metabuscadores Translating Research into Practice (TRIPDATABASE), Epistemonikos y Health Systems Evidence (HSE). Asimismo, se buscó información generada por grupos internacionales que realizan revisiones sistemáticas, evaluaciones de tecnologías sanitarias y guías de práctica clínica, tales como el National Institute for Health and Care Excellence (NICE) del Reino Unido, National Guideline Clearinghouse (NGC) de Estados Unidos, Canadian Agency for Drugs and Technologies in Health (CADTH) de Canadá, Scottish Medicines Consortium (SMC) de Escocia, Haute Authorité de Santé (HAS) de Francia, el Instituto de Evaluación de Tecnologías Sanitarias (IETS) de Colombia, el Instituto de Efectividad Clínica y Sanitaria (IECS) de Argentina. Finalmente, se realizó una búsqueda dentro de las bases de datos Pubmed, EMBASE, y The Web of Science que a su vez fue complementada con una búsqueda en www.clinicaltrials.gov y www.clinicaltrialsregister.eu para identificar estudios primarios en proceso que no hayan sido publicados aún, tanto en Estados Unidos como en Europa. RESULTADOS: A la fecha, no se ha evaluado la eficacia y seguridad de IgIV en pacientes refractarios a corticoides o inmunosupresores, por lo que la evidencia encontrada responde a la pregunta PICO de interés de la presente evaluación de manera indirecta. Se encontraron dos GPCs, una ETS, y dos RS de ECAs de buena calidad metodológica que sustentan la eficacia y seguridad de IgIV en pacientes recientemente diagnosticados con PDIC. La evidencia encontrada indica que la terapia con IgIV mejora el estado de paciente medido en escalas de discapacidad y funcionalidad frente a placebo. A pesar de ser evidencia indirecta, la magnitud del efecto observado (i.e. RR 2.4; 95% CI 1.72-3.36) de IgIV frente a placebo para el desenlace primario de eficacia aporta suficiente evidencia como para sugerir que IgIV pueda ser eficaz en la población de pacientes con PDIC refractarios al tratamiento con corticoides e inmunosupresores, a pesar de las limitaciones metodológicas que los estudios pudieran presentar. Las diferencias encontradas en los ECAs individuales, así De las RS evaluadas, el estudio de Hughes 2008 incluido en ambas RS, contó con una muestra representativa de pacientes y empleó una escala validada de medición de la discapacidad, la cual puede ser empleada en la práctica clínica para la evaluación de la respuesta al tratamiento. Actualmente en EsSalud, no existe alternativa de tratamiento para pacientes que no remiten con corticoides o inmunosupresores disponibles en el Petitorio Farmacológico de EsSalud. El grupo de pacientes no respondedores a corticoides e inmunosupresores que no reciban terapia alternativa sufrirían un deterioro serio en su calidad de vida por la degeneración de la percepción sensorial y función neurológica a la que la PDIC conlleva, según la opinión de los expertos en neurología mencionados en la autoría del presente Dictamen. CONCLUSIÓN: el Instituto de Evaluación de Tecnologías en Salud e Investigación ­ IETSI, aprueba el uso de inmunoglobulina humana en pacientes con polineuropatía desmielinizante inflamatoria crónica idiopática y respuesta inadecuada a corticoides e inmunosupresores. El presente Dictamen Preliminar tiene una vigencia de dos años a partir de su fecha de publicación.

Treatment with α-Lipoic Acid over 16 Weeks in Type 2 Diabetic Patients with Symptomatic Polyneuropathy Who Responded to Initial 4-Week High-Dose Loading.

Effective treatment of diabetic sensorimotor polyneuropathy remains a challenge. To assess the efficacy and safety of α-lipoic acid (ALA) over 20 weeks, we conducted a multicenter randomized withdrawal open-label study, in which 45 patients with type 2 diabetes and symptomatic polyneuropathy were initially treated with ALA (600 mg tid) for 4 weeks (phase 1). Subsequently, responders were randomized to receive ALA (600 mg qd; n = 16) or to ALA withdrawal (n = 17) for 16 weeks (phase 2). During phase 1, the Total Symptom Score (TSS) decreased from 8.9 ± 1.8 points to 3.46 ± 2.0 points. During phase 2, TSS improved from 3.7 ± 1.9 points to 2.5 ± 2.5 points in the ALA treated group (p < 0.05) and remained unchanged in the ALA withdrawal group. The use of analgesic rescue medication was higher in the ALA withdrawal group than ALA treated group (p < 0.05). In conclusion, in type 2 diabetic patients with symptomatic polyneuropathy who responded to initial 4-week high-dose (600 mg tid) administration of ALA, subsequent treatment with ALA (600 mg qd) over 16 weeks improved neuropathic symptoms, whereas ALA withdrawal was associated with a higher use of rescue analgesic drugs. This trial is registered with ClinicalTrials.gov Identifier: NCT02439879.

The effects of intraplantar and intrathecal botulinum toxin type B on tactile allodynia in mono and polyneuropathy in the mouse.

BACKGROUND: Mononeuropathies (MNs: nerve ligation) and polyneuropathies (PNs: cisplatin) produce unilateral and bilateral tactile allodynia, respectively. We examined the effects of intraplantar (IPLT) and intrathecal (IT) botulinum toxin B (BoNT-B) on this allodynia. METHODS: Mice (male c57Bl/6) were prepared with an L5 nerve ligation. Others received cisplatin (IP 2.3 mg/kg/d, every other day for 6 injections). Saline and BoNT-B were administered through the IPLT or IT route. We examined mechanical allodynia (von Frey hairs) before and at intervals after BoNT. As a control, we injected IPLT BoNT-B treated with dithiothreitol to cleave heavy chain from light chain. We measured motor function using acute thermal escape and sensorimotor tests. RESULTS: MN and PN mice showed a persistent ipsilateral and bilateral allodynia, respectively. IPLT BoNT-B resulted in an ipsilateral dorsal horn reduction in the synaptic protein target of BoNT-B (vesicle-associated membrane protein) and a long-lasting (up to approximately 17 days) reversal of allodynia in PN and MN models. The predominant effect after IPLT delivery was ipsilateral to IPLT BoNT. The effects of IPLT BoNT-B in MN mice were blocked by prior reduction of BoNT-B with dithiothreitol. IT BoNT-B in mice with PN resulted in a bilateral reversal of allodynia. With these dosing parameters, hind paw placing and stepping reflexes were unaltered, and there were no changes in thermal escape latencies. After cisplatin, dorsal root ganglions displayed increases in activation transcription factor 3, which were reduced by IT, but not IPLT BoNT-B. CONCLUSIONS: BoNT-B given IPLT and IT yields a long-lasting attenuation of the allodynia in mice displaying MN and PN allodynia.

[Oropharyngeal dysphagia associated with Chiari I malformation and syringomyelia J]. / Disfagia orofaringea asociada a malformación de Chiari tipo I y siringomielia.

BACKGROUND: Dysphagia associated with neurological disease is an important clinical manifestation in the diagnosis of injury that justifies the compression of the brainstem and lower cranial nerves. OBJECTIVE: To emphasize the study of dysphagia in a patient with Chiari I malformation associated with syringomyelia in the absence of primary gastroenterological symptoms. CLINICAL CASE: We describe the case of a 62 year-old woman with oropharyngeal dysphagia of six years of evolution, cervicobrachialgia, ptosis and facial diplexia. CONCLUSIONS: Magnetic resonance imaging is an essential element for establishing the etiologic diagnosis of neurogenic dysphagia.

Antecedentes: la disfagia con afección neurológica constituye un dato clínico significativo en el diagnóstico de lesiones que justifiquen la compresión del tronco cerebral y los nervios craneales bajos. Objetivo: destacar la importancia del estudio de la disfagia en una paciente con malformación de Chiari tipo I y siringomielia, sin síntomas gastroenterológicos primarios. Caso clínico: se comunica el caso de una mujer de 62 años de edad con disfagia orofaríngea de seis años de evolución, cervicobraquialgia, ptosis palpebral y diplejía facial. Conclusiones: el estudio por resonancia magnética constituye un elemento fundamental para establecer el diagnóstico causal de la disfagia neurogénica.

[Hypothyroid polyneuropathy in a patient with autoimmune polyglandular syndrome type 2: case report]. / Polineuropatia hipotireóidea em um paciente com síndrome poliglandular autoimune tipo 2: relato de caso.

The incidence of polyneuropathy in patients with hypothyroidism is not precisely known, but some studies report that about 25% to 42% of patients may show neuropathic clinical signs. We report a case of autoimmune poliglandular syndrome type 2 (APS-2), whose initial presentation was hypothyroid polyneuropathy. A 41-year-old man complained of slowly progressive paresthesias and weakness affecting all four limbs, and associated with frequent drowsiness, weakness, cold intolerance, dizziness, nausea, and craving for salt. General physical examination showed hyperpigmentation of skin and mucous membranes, and hypotension. Neurological examination showed global, deep, and symmetrical hyporeflexia with slight signs of superficial hypoesthesia in the limbs. Electrodiagnostic studies (ENMG) together with laboratory tests, confirmed the suspicion of Hashimoto's thyroiditis associated with Addison's disease featuring the picture of APS-2. The patient was treated with fludrocortisone 0.05 mg/day and levothyroxine 100 mcg/day, and showed gradual and complete resolution of complaints. Changes were found in general physical and neurological examinations. ENMG repeated six months later showed complete resolution of neuropathy. This report shows a rare case of APS-2 presented as polyneuropathy hypothyroidism, and reinforces the importance of dosing thyroid hormone in polyneuropathy syndromes. Levothyroxine replacement was shown to be effective in reversing clinical and electrophysiologic neuropathy.

Polineuropatia hipotireóidea em um paciente com síndrome poliglandular autoimune tipo 2: relato de caso / Hypothyroid polyneuropathy in a patient with autoimmune polyglandular syndrome type 2: case report

A incidência de polineuropatia em indivíduos com hipotireoidismo não é precisamente conhecida, mas alguns estudos relatam que cerca de 25% a 42% dos pacientes podem apresentar sinais clínicos neuropáticos. A seguir, relataremos um caso de síndrome poliglandular autoimune tipo 2 (SPA-2), cuja apresentação inicial foi uma polineuropatia hipotireóidea. Homem de 41 anos com queixas de parestesias e fraqueza lentamente progressiva acometendo os quatro membros associadas a sonolência frequente, astenia, intolerância ao frio, vertigens, náuseas e avidez por sal. O exame físico geral evidenciava hiperpigmentação de pele e mucosas, além de hipotensão. O exame neurológico demonstrou apenas hiporreflexia profunda global e simétrica com discretos sinais de hipoestesia superficial em extremidades dos membros. O estudo eletroneuromiográfico (ENMG), juntamente com a avaliação laboratorial, confirmou a suspeita de tireoidite de Hashimoto associada à doença de Addison, caracterizando o quadro de SPA-2. O paciente foi tratado com fludrocortisona 0,05 mg/dia e levotiroxina 100 mcg/dia e apresentou resolução gradual e completa das queixas e das alterações encontradas nos exames físico geral e neurológico. O ENMG, repetido após seis meses, evidenciou resolução completa do quadro neuropático. Este relato mostra um caso raro de SPA-2 apresentando-se como uma polineuropatia hipotireóidea e reforça a relevância da dosagem de hormônios tireoideanos em síndromes polineuropáticas. A reposição de levotiroxina mostrou-se efetiva em reverter o quadro clínico e eletrofisiológico da neuropatia. .

The incidence of polyneuropathy in patients with hypothyroidism is not precisely known, but some studies report that about 25% to 42% of patients may show neuropathic clinical signs. We report a case of autoimmune poliglandular syndrome type 2 (APS-2), whose initial presentation was hypothyroid polyneuropathy. A 41-year-old man complained of slowly progressive paresthesias and weakness affecting all four limbs, and associated with frequent drowsiness, weakness, cold intolerance, dizziness, nausea, and craving for salt. General physical examination showed hyperpigmentation of skin and mucous membranes, and hypotension. Neurological examination showed global, deep, and symmetrical hyporeflexia with slight signs of superficial hypoesthesia in the limbs. Electrodiagnostic studies (ENMG) together with laboratory tests, confirmed the suspicion of Hashimoto’s thyroiditis associated with Addison’s disease featuring the picture of APS-2. The patient was treated with fludrocortisone 0.05 mg/day and levothyroxine 100 mcg/day, and showed gradual and complete resolution of complaints. Changes were found in general physical and neurological examinations. ENMG repeated six months later showed complete resolution of neuropathy. This report shows a rare case of APS-2 presented as polyneuropathy hypothyroidism, and reinforces the importance of dosing thyroid hormone in polyneuropathy syndromes. Levothyroxine replacement was shown to be effective in reversing clinical and electrophysiologic neuropathy.

Efficacy of low-dose intravenous cyclophosphamide in systemic lupus erythematosus presenting with Guillain-Barre syndrome-like acute axonal neuropathies: report of two cases.

There are few cases of Guillain-Barré syndrome (GBS), particularly of atypical variants, occurring in association with systemic lupus erythematous (SLE). Reports addressing a specific therapy thus remain almost anecdotal. It is therefore challenging to determine the treatment that is best suited for this subset of patients, especially if initial conventional therapy for GBS fails. We present two cases of GBS-like acute axonal neuropathies, one with acute motor axonal neuropathy (AMAN), and another with acute motor sensory axonal neuropathy (AMSAN), presenting early in the course of SLE. The first case failed to respond to therapy with intravenous immunoglobulins (IVIG) and plasmapheresis, but achieved a favorable outcome when high-dose glucocorticoids along with low-dose intravenous (IV) cyclophosphamide pulses were given. The second case responded favorably to high-dose glucocorticoids, IVIG, and low-dose IV cyclophosphamide pulses. Both patients have remained in clinical remission and without neurologic sequelae after 10 and three years of follow-up, respectively.

Evaluación del efecto del tratamiento con ácido lipoico administrado a la rata Wistar intoxicada con el fruto de Karwinskia humboldtiana / Evaluation of the effect of treatment with lipoic acid administered to the Wistar rat intoxicated with the fruit of Karwinskia humboldtiana

La ingesta accidental de fruto de Karwinskia humboldtiana ocasiona una parálisis flácida, simétrica, progresiva y ascendente, similar al síndrome de Guillain-Barré. Evoluciona en el transcurso de 3 a 12 meses hasta su recuperación total, pero los casos graves terminan en la muerte por insuficiencia respiratoria. No existe un tratamiento específico. La lesión histopatológica descrita en nervio periférico de pacientes, y animales de experimentación corresponde a una desmielinización segmentaria acompañada de degeneración Walleriana. Una de las toxinas extraídas a partir de la semilla, la T-514, ocasiona un incremento de radicales libres in vitro. Los radicales libres se han relacionado con la desmielinización que se presenta en otros tipos de neuropatías como en la diabética. Ya que la lesión ultraestructural que se presenta en los modelos animales de diabetes es similar a la que se observa en la intoxicación experimental con fruto de K. humboldtiana, se decidió administrar un potente agente antioxidante, el ácido a-lipoico en un modelo de intoxicación crónica por fruto de K. humboldtiana. Sin embargo, no se observó mejoría sobre las manifestaciones clínicas evaluadas en los animales o sobre las lesiones histopatológicas presentes en el nervio periférico. Estos resultados sugieren que los radicales libres no son el mecanismo principal de lesión sobre el nervio periférico en la polineuropatía causada por K. humboldtiana.

The accidental ingestion of Karwinskia humboldtiana causes a flaccid, symmetrical, progressive and ascending paralysis, similar to Guillain-Barre syndrome. It evolves over the course of 3 to 12 months until full recovery, but severe cases end in death due to respiratory failure. There is no specific treatment. The histopathological lesions described in peripheral nerve of patients and in experimental animals, corresponds to segmental demyelination accompanied by Wallerian degeneration. One of the toxins extracted from the seed, T-514, causes an increase of free radicals in vitro. Free radicals have been associated to demyelination that occurs in other types of neuropathy such as diabetic neuropathy. Since the ultrastructural damage that occurs in animal models of diabetes is similar to that observed in experimental poisoning with the fruit of K. humboldtiana, we decided to administer a powerful antioxidant, a-lipoic acid, in a model of chronic poisoning due of K. humboldtiana. However, no improvement was observed on the clinical manifestations evaluated in animals or in the histopathological lesions in the peripheral nerve. These results suggest that free radicals are not the primary mechanism of injury on the peripheral nerve caused by K. humboldtiana.

Acute axonal polyneuropathy with predominant proximal involvement: an uncommon neurological complication of bariatric surgery.

Bariatric surgery is frequently indicated in the treatment of morbid obesity. Previously unreported complications have been associated to this surgery; among them, neurological complications have gained attention. We report the case of a 25-year-old man submitted to gastric surgery for treatment of morbid obesity who developed, two months after surgery, acute proximal weakness in lower limbs. The electroneuromyography revealed axonal peripheral polyneuropathy with predominant proximal involvement. After treatment with immunoglobulin and vitamin supplementation, rapid clinical and neurophysiologic recovery was observed. We describe the clinical and electroneuromyographic features of this case, stressing the difficulty of initial diagnosis, particularly in the differential diagnosis with Guillain-Barré syndrome. We discuss the importance of nutritional follow-up and the eventual indication of routine vitamin supplementation in these patients.

Acute axonal polyneuropathy with predominant proximal involvement: an uncommon neurological complication of bariatric surgery / Polineuropatia axonal aguda com acometimento proximal predominante: manifestação neurológica incomum de cirurgia bariátrica

Bariatric surgery is frequently indicated in the treatment of morbid obesity. Previously unreported complications have been associated to this surgery; among them, neurological complications have gained attention. We report the case of a 25-year-old man submitted to gastric surgery for treatment of morbid obesity who developed, two months after surgery, acute proximal weakness in lower limbs. The electroneuromyography revealed axonal peripheral polyneuropathy with predominant proximal involvement. After treatment with immunoglobulin and vitamin supplementation, rapid clinical and neurophysiologic recovery was observed. We describe the clinical and electroneuromyographic features of this case, stressing the difficulty of initial diagnosis, particularly in the differential diagnosis with Guillain-Barré syndrome. We discuss the importance of nutritional follow-up and the eventual indication of routine vitamin supplementation in these patients.

A cirurgia bariátrica é freqüentemente indicada no tratamento da obesidade mórbida. Complicações previamente não relatadas têm sido associadas a essa cirurgia; dentre estas, as complicações neurológicas têm recebido destaque. Relatamos o caso de um homem de 25 anos de idade submetido a cirurgia gástrica para tratamento de obesidade mórbida que desenvolveu, dois meses após a cirurgia, fraqueza de predomínio proximal nos membros inferiores, de instalação aguda. A eletroneuromiografia demonstrou polineuropatia periférica axonal nos membros inferiores, de predomínio proximal. Após tratamento com imunoglobulina e suplementação vitamínica, apresentou rápida melhora clínica e neurofisiológica. Descrevemos as características clínicas e eletroneuromiográficas desse caso, destacando a dificuldade diagnóstica inicial, particularmente com relação ao diagnóstico diferencial com síndrome de Guillain-Barré. Discutimos a importância de acompanhamento nutricional e a eventual indicação de suplementação vitamínica de rotina nesses pacientes.

[POEMS syndrome: report of a case and review of the literature]. / Síndrome de POEMS: presentación de un caso y revisión de la literatura.

A case of POEMS Syndrome of six years of evolution is reported. This syndrome is characterized by Raynaud phenomenon, polyneuropathy, edema, anasarca, papilledema, osteosclerosis and lymphadenopathy with the histopathology of Castleman's disease, hypothyroidism, hypogonadism, cutaneous sclerosis, hyperpigmentation, axillary alopecia and the presence of urinary lambda light chains. A bone marrow biopsy did not show plasmocytic infiltration and there was no evidence of extramedullary plasmocytoma. Methylprednisone was given at the dose of 1 mg/kg/day and subjective and objective improvement was observed. The edema and anasarca disappeared as well as the lymphadenopathies; muscle strength improved and the patient was able to walk without aid. Papilledema persisted. The pathogenesis of this syndrome remains unknown; some of the symptoms have been attributed to paraprotein deposits in peripheral nerves, high capillary permeability due to vascular alterations, accelerated conversion of androgen to estrogen, or to the production by plasma cells of a toxic substance. Mortality is related to complications of the polyneuropathy. Some patients in whom POEMS syndrome was associated, or not, with myeloma were treated with chemotherapy and/or radiotherapy with different responses; in others, corticosteroids were of short lived benefit. Our patients remains well after 42 months treatment with 20 mg methylprednisone every other day.

Steroid-responsive polyneuropathy with subacute onset in childhood.

Five pediatric patients with subacute onset polyneuropathy are presented, with electrophysiologic and pathologic data. All patients improved, the majority to resolution, with administration of prednisone. Distinguishing factors included (1) subacute onset polyneuropathy progressing gradually over weeks to months, (2) primarily motor neuropathy with little cranial nerve involvement, (3) elevated CSF protein concentration, (4) markedly delayed nerve conduction velocities, and (5) tendency toward relapse and recurrence. Although this disorder may share characteristics with the Guillain-Barré syndrome, its steroid responsiveness sets it apart clinically from the acute form of the disease. Because of the steroid responsiveness, it is important to recognize this entity.