Disability evaluation in patients with Guillain-Barre syndrome and SARS-CoV-2 infection.

Objective: Several cases of Guillain-Barre syndrome (GBS) associated with SARS-CoV-2 infection have been described. This study illustrated the demographic, clinical, and neurophysiological characteristics of patients with GBS and COVID-19, as well as associated factors with disability at discharge. Materials and methods: A retrospective analytical observational study was conducted. It included patients diagnosed with GBS admitted in a national reference center in Peru between 2019 and 2021. Epidemiological, clinical, neurophysiological, and cerebrospinal fluid data were analyzed. A multivariate analysis, using the generalized linear model, was performed, considering the presence of disability at discharge as the dependent variable. Results: Eight-one subjects diagnosed with GBS were included. The mean age was 46.8 years (SD: 15.2), with a predominance of males (61.73%). The most frequent clinical presentation was the classic sensory-motor form in 74 cases (91.36%) with AIDP (82.35%) as the most frequent neurophysiological pattern in the group with COVID-19, while AMAN pattern predominated (59.26%) in those without COVID-19 (p = <0.000). The disability prevalence ratio at discharge between subjects with COVID-19 and those without COVID-19 was 1.89 (CI 1.06-3.34), p = 0.030, adjusted for age, sex, and neurophysiological subtype. Conclusion: The neurophysiologic subtype AIDP, and a higher disability were associated with the presence of COVID-19.

Concurrence of Guillain-Barré syndrome and primary biliary cholangitis not related to SARS-CoV-2: Case report. / Concurrencia de síndrome de Guillain-Barré y colangitis biliar primaria no vinculado a SARS-CoV-2: reporte de caso.

Introduction: Guillain-Barré syndrome is a polyradiculoneuropathy of autoimmune origin, considered the most frequent cause of acute flaccid paralysis. Various associations of Guillain-Barré syndrome with other non-neurological autoimmune diseases have been reported, some of them extremely rare, such as that which occurs with primary biliary cholangitis, a chronic disease of autoimmune etiology whose diagnosis is also supported by the clinical picture. , in the alteration of liver enzymes and the presence of anti-mitochondrial antibodies. Clinical case: A 38-year-old male patient, with no history of previous comorbidities, who, after presenting with diarrheal disease two weeks prior, developed subacute onset ascending weakness associated with paresthesias in four extremities that progressed to quadriplegia and respiratory distress. Cerebrospinal fluid cytochemistry was performed, which showed albuminocytological dissociation and electromyography, which showed findings compatible with acute motor axonal neuropathy, for which he received treatment with intravenous immunoglobulin at 0.4g/kg/day, achieving improvement in the neurological condition. Since admission and during hospitalization, he presented persistent changes in liver enzymes which followed a cholestatic pattern, in addition to mild abdominal pain and generalized itching, for which he was evaluated by gastroenterology, who requested anti-mitochondrial antibodies that were positive. Concluding in the diagnosis of primary biliary cholangitis. Conclusion: The present case shows an extremely rare association of two autoimmune diseases Guillain-Barré syndrome and primary biliary cholangitis, so much so that it represents the first case reported, not linked to SARS-CoV-2.

Introducción: El síndrome de Guillain-Barré es una polirradiculoneuropatia de origen autoinmune, considerada la causa más frecuente de parálisis flácida aguda. Se han reportado diversas asociaciones del síndrome de Guillain-Barré con otras enfermedades autoinmunes no neurológicas, algunas de ellas extremadamente raras, como la que ocurre con la colangitis biliar primaria, una enfermedad crónica de etiología autoinmune cuyo diagnóstico se sustenta, además del cuadro clínico, en la alteración de las enzimas hepáticas y la presencia de anticuerpos anti-mitocondriales. Caso clínico: Paciente varón de 38 años, sin antecedente de comorbilidades previas, quien luego de presentar enfermedad diarreica dos semanas antes, desarrolló debilidad ascendente de inicio subagudo asociado a parestesias en cuatro extremidades que progresó hasta generar cuadriplejia y dificultad respiratoria. Se le realizó examen citoquímico de líquido cefalorraquídeo que evidenció disociación albumino-citológica y electromiografía que mostró hallazgos compatibles con neuropatía axonal motora aguda. Recibió tratamiento con inmunoglobulina intravenosa a dosis de 0,4 gramos por kilogramo al día, logrando mejoría del cuadro neurológico. Desde su ingreso y durante la hospitalización, presentó alteración persistente de las enzimas hepáticas que seguía un patrón colestásico. Además, se agregó dolor abdominal de leve intensidad y prurito generalizado, por lo cual fue evaluado por gastroenterología, quienes solicitaron anticuerpos anti-mitocondriales que resultaron positivos. Con esta prueba, se comprobó el diagnóstico de colangitis biliar primaria. Conclusión: El presente caso muestra una asociación extremadamente rara de dos enfermedades autoinmunes; síndrome de Guillain-Barré y colangitis biliar primaria, tanto así que representa el primer caso reportado, no vinculado a SARS-CoV-2.

Concurrencia de síndrome de Guillain-Barré y colangitis biliar primaria no vinculado a SARS-CoV-2: reporte de caso / Concurrence of Guillain-Barré syndrome and primary biliary cholangitis not related to SARS-CoV-2: Case report

Introducción El síndrome de Guillain-Barré es una polirradiculoneuropatia de origen autoinmune, considerada la causa más frecuente de parálisis flácida aguda. Se han reportado diversas asociaciones del síndrome de Guillain-Barré con otras enfermedades autoinmunes no neurológicas, algunas de ellas extremadamente raras, como la que ocurre con la colangitis biliar primaria, una enfermedad crónica de etiología autoinmune cuyo diagnóstico se sustenta, además del cuadro clínico, en la alteración de las enzimas hepáticas y la presencia de anticuerpos anti-mitocondriales. Caso clínico Paciente varón de 38 años, sin antecedente de comorbilidades previas, quien luego de presentar enfermedad diarreica dos semanas antes, desarrolló debilidad ascendente de inicio subagudo asociado a parestesias en cuatro extremidades que progresó hasta generar cuadriplejia y dificultad respiratoria. Se le realizó examen citoquímico de líquido cefalorraquídeo que evidenció disociación albumino-citológica y electromiografía que mostró hallazgos compatibles con neuropatía axonal motora aguda. Recibió tratamiento con inmunoglobulina intravenosa a dosis de 0,4 gramos por kilogramo al día, logrando mejoría del cuadro neurológico. Desde su ingreso y durante la hospitalización, presentó alteración persistente de las enzimas hepáticas que seguía un patrón colestásico. Además, se agregó dolor abdominal de leve intensidad y prurito generalizado, por lo cual fue evaluado por gastroenterología, quienes solicitaron anticuerpos anti-mitocondriales que resultaron positivos. Con esta prueba, se comprobó el diagnóstico de colangitis biliar primaria. Conclusión El presente caso muestra una asociación extremadamente rara de dos enfermedades autoinmunes; síndrome de Guillain-Barré y colangitis biliar primaria, tanto así que representa el primer caso reportado, no vinculado a SARS-CoV-2.

Introduction Guillain-Barré syndrome is a polyradiculoneuropathy of autoimmune origin, considered the most frequent cause of acute flaccid paralysis. Various associations of Guillain-Barré syndrome with other non-neurological autoimmune diseases have been reported, some of them extremely rare, such as that which occurs with primary biliary cholangitis, a chronic disease of autoimmune etiology whose diagnosis is also supported by the clinical picture. , in the alteration of liver enzymes and the presence of anti-mitochondrial antibodies. Clinical case A 38-year-old male patient, with no history of previous comorbidities, who, after presenting with diarrheal disease two weeks prior, developed subacute onset ascending weakness associated with paresthesias in four extremities that progressed to quadriplegia and respiratory distress. Cerebrospinal fluid cytochemistry was performed, which showed albuminocytological dissociation and electromyography, which showed findings compatible with acute motor axonal neuropathy, for which he received treatment with intravenous immunoglobulin at 0.4g/kg/day, achieving improvement in the neurological condition. Since admission and during hospitalization, he presented persistent changes in liver enzymes which followed a cholestatic pattern, in addition to mild abdominal pain and generalized itching, for which he was evaluated by gastroenterology, who requested anti-mitochondrial antibodies that were positive. Concluding in the diagnosis of primary biliary cholangitis. Conclusion The present case shows an extremely rare association of two autoimmune diseases Guillain-Barré syndrome and primary biliary cholangitis, so much so that it represents the first case reported, not linked to SARS-CoV-2.

Polirradiculoneuropatía desmielinizante inflamatoria crónica con anticuerpos antineurofascina-155: primer reporte de caso en Perú / Chronic inflammatory demyelinating polyradiculoneuropathy with antineurofascin-155 antibodies: A first case report in Peru

La polirradiculoneuropatía desmielinizante inflamatoria crónica, es un grupo de neuro-patías periféricas inmunomediadas clínicamente heterogéneas que comparten manifes-taciones neurofisiológicas de desmielinización y disociación albuminocitológica. Se distinguen una forma típica y variantes atípicas, algunas asociadas a anticuerpos con-tra proteínas del nodo de Ranvier, como la neurofascina- 155. Presentamos el caso de un varón de 38 años, que acudió por cuadro de ocho meses de evolución, caracterizado por parestesias y debilidad progresiva de cuatro extremidades, asociado a diplopía y disfagia. El paciente estaba despierto, con cuadriparesia flácida simétrica de predominio distal, hipotrofia en dorso y palma de ambas manos, arreflexia generalizada, temblor postural de baja frecuencia y alta amplitud en miembros superiores de predominio izquierdo, dismetría apendicular, adiadococinesia, oftalmoparesia a la dextroversión en ojo dere-cho, reflejo nauseoso ausente, marcha atáxica con aumento de base de sustentación y signo de Romberg positivo. El líquido cefalorraquideo mostró disociación albuminocitológica y la electromiografía fue compatible con polineuropatía sensitivo- motora primariamente desmielinizante. Por la sospecha clínica, solicitamos anticuerpos antineurofascina- 155, que resultaron positivos. Recibió tratamiento con metilprednisolona a dosis de un gramo al día durante cinco días, seguido de un miligramo por kilogramo durante tres meses de prednisona, con disminución progresiva con lo que mejoró la diplopía y la disfagia, sin mejoría de la fuerza en extremidades e incluso empeoramiento de la funcionabilidad. Por esta razón se inició tratamiento con rituximab en dosis de dos gramos presentando una notable mejoría en la fuerza muscular distal, el temblor, la estabilidad de la marcha, coordinación y de su funcionabilidad medida con la escala de Rankin modificado.

Chronic inflammatory demyelinating polyradiculoneuropathy is a clinically heterogeneous group of immune- mediated peripheral neuropathies that share neurophysiological manifesta-tions of demyelination and albuminocytologic dissociation. There are typical and atypical variants of this disease, some associated with antibodies against proteins of the node of Ranvier, such as neurofascin- 155. We present the case of a 38- year- old male who presented with an eight- month history of par-esthesia and progressive weakness of four limbs associated with diplopia and dysphagia. The patient was conscious, with symmetric flaccid quadriparesis of distal predominance, hyp-otrophy in the dorsum and palm of both hands, generalized areflexia, postural low frequency, and high amplitude tremor in upper limbs of left predominance, appendicular dysmetria, dys-diadochokinesia, ophthalmoparesis to dextroversion in the right eye, absent gag reflex, ataxic gait with an increased base of support and positive Romberg's sign. Cerebrospinal fluid showed albuminocytologic dissociation, and electromyography was com-patible with primarily demyelinating sensory- motor polyneuropathy. Due to clinical suspicion, we requested anti- neurofascin- 155 antibodies, which tested positive. The patient was treated with methylprednisolone at a dose of one gram per day for five days, followed by one milligram per kilogram for three months of prednisone, with progressive de-crease, which improved diplopia and dysphagia, with no effect on limb strength and even worsening of function. For this reason, treatment with rituximab was started in doses of two grams, presenting a substantial improvement in distal muscle strength, tremor, gait stability, coordination, and functionality measured with the modified Rankin scale.

Chronic inflammatory demyelinating polyradiculoneuropathy with antineurofascin-155 antibodies: A first case report in Peru. / Polirradiculoneuropatía desmielinizante inflamatoria crónica con anticuerpos antineurofascina-155: primer reporte de caso en Perú.

Chronic inflammatory demyelinating polyradiculoneuropathy is a clinically heterogeneous group of immune- mediated peripheral neuropathies that share neurophysiological manifesta-tions of demyelination and albuminocytologic dissociation. There are typical and atypical variants of this disease, some associated with antibodies against proteins of the node of Ranvier, such as neurofascin- 155. We present the case of a 38- year- old male who presented with an eight- month history of par-esthesia and progressive weakness of four limbs associated with diplopia and dysphagia. The patient was conscious, with symmetric flaccid quadriparesis of distal predominance, hyp-otrophy in the dorsum and palm of both hands, generalized areflexia, postural low frequency, and high amplitude tremor in upper limbs of left predominance, appendicular dysmetria, dys-diadochokinesia, ophthalmoparesis to dextroversion in the right eye, absent gag reflex, ataxic gait with an increased base of support and positive Romberg's sign. Cerebrospinal fluid showed albuminocytologic dissociation, and electromyography was com-patible with primarily demyelinating sensory- motor polyneuropathy. Due to clinical suspicion, we requested anti- neurofascin- 155 antibodies, which tested positive. The patient was treated with methylprednisolone at a dose of one gram per day for five days, followed by one milligram per kilogram for three months of prednisone, with progressive de-crease, which improved diplopia and dysphagia, with no effect on limb strength and even worsening of function. For this reason, treatment with rituximab was started in doses of two grams, presenting a substantial improvement in distal muscle strength, tremor, gait stability, coordination, and functionality measured with the modified Rankin scale.

La polirradiculoneuropatía desmielinizante inflamatoria crónica, es un grupo de neuro-patías periféricas inmunomediadas clínicamente heterogéneas que comparten manifes-taciones neurofisiológicas de desmielinización y disociación albuminocitológica. Se distinguen una forma típica y variantes atípicas, algunas asociadas a anticuerpos con-tra proteínas del nodo de Ranvier, como la neurofascina- 155. Presentamos el caso de un varón de 38 años, que acudió por cuadro de ocho meses de evolución, caracterizado por parestesias y debilidad progresiva de cuatro extremidades, asociado a diplopía y disfagia. El paciente estaba despierto, con cuadriparesia flácida simétrica de predominio distal, hipotrofia en dorso y palma de ambas manos, arreflexia generalizada, temblor postural de baja frecuencia y alta amplitud en miembros superiores de predominio izquierdo, dismetría apendicular, adiadococinesia, oftalmoparesia a la dextroversión en ojo dere-cho, reflejo nauseoso ausente, marcha atáxica con aumento de base de sustentación y signo de Romberg positivo. El líquido cefalorraquideo mostró disociación albuminocitológica y la electromiografía fue compatible con polineuropatía sensitivo- motora primariamente desmielinizante. Por la sospecha clínica, solicitamos anticuerpos antineurofascina- 155, que resultaron positivos. Recibió tratamiento con metilprednisolona a dosis de un gramo al día durante cinco días, seguido de un miligramo por kilogramo durante tres meses de prednisona, con disminución progresiva con lo que mejoró la diplopía y la disfagia, sin mejoría de la fuerza en extremidades e incluso empeoramiento de la funcionabilidad. Por esta razón se inició tratamiento con rituximab en dosis de dos gramos presentando una notable mejoría en la fuerza muscular distal, el temblor, la estabilidad de la marcha, coordinación y de su funcionabilidad medida con la escala de Rankin modificado.

Clinical and Laboratory Features in Anti-NF155 Autoimmune Nodopathy.

BACKGROUND AND OBJECTIVES: To study the clinical and laboratory features of antineurofascin-155 (NF155)-positive autoimmune nodopathy (AN). METHODS: Patients with anti-NF155 antibodies detected on routine immunologic testing were included. Clinical characteristics, treatment response, and functional scales (modified Rankin Scale [mRS] and Inflammatory Rasch-built Overall Disability Scale [I-RODS]) were retrospectively collected at baseline and at the follow-up. Autoantibody and neurofilament light (NfL) chain levels were analyzed at baseline and at the follow-up. RESULTS: Forty NF155+ patients with AN were included. Mean age at onset was 42.4 years. Patients presented with a progressive (75%), sensory motor (87.5%), and symmetric distal-predominant weakness in upper (97.2%) and lower extremities (94.5%), with tremor and ataxia (75%). Patients received a median of 3 (2-4) different treatments in 46 months of median follow-up. Response to IV immunoglobulin (86.8%) or steroids (72.2%) was poor in most patients, whereas 77.3% responded to rituximab. HLA-DRB1*15 was detected in 91.3% of patients. IgG4 anti-NF155 antibodies were predominant in all patients; anti-NF155 titers correlated with mRS within the same patient (r = 0.41, p = 0.004). Serum NfL (sNfL) levels were higher in anti-NF155+ AN than in healthy controls (36.47 vs 7.56 pg/mL, p < 0.001) and correlated with anti-NF155 titers (r = 0.43, p = 0.001), with I-RODS at baseline (r = -0.88, p < 0.001) and with maximum I-RODS achieved (r = -0.58, p = 0.01). Anti-NF155 titers and sNfL levels decreased in all rituximab-treated patients. DISCUSSION: Anti-NF155 AN presents a distinct clinical profile and good response to rituximab. Autoantibody titers and sNfL are useful to monitor disease status in these patients. The use of untagged-NF155 plasmids minimizes the detection of false anti-NF155+ cases. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that anti-NF155 antibodies associate with a specific phenotype and response to rituximab.

Síndrome de Guillain Barré e infección por SARS-CoV-2: reporte de dos casos en Perú / Guillain Barré syndrome and SARS-CoV-2 infection: Report of two cases in Peru

RESUMEN La enfermedad por coronavirus 2019 (COVID-19), provocada por el virus SARS-CoV-2, se manifiesta principalmente a nivel respiratorio. Sin embargo, puede afectar otros órganos y sistemas, entre ellos el sistema nervioso, generando diversas manifestaciones neurológicas en las que se incluye el síndrome de Guillain Barré (SGB). Presentamos dos casos de pacientes varones de 35 y 46 años con SGB, uno clasificado como neuropatía axonal motora aguda (AMAN) y el otro como polineuropatia inflamatoria desmielinizante aguda (AIDP), quienes mostraron serología positiva para SARS-CoV-2 y sintomatología respiratoria previa al cuadro de debilidad. En ambos casos, la reacción en cadena de polimerasa en tiempo real (RT-PCR) en secreción faríngea y liquido cefalorraquideo fue negativa. El diagnóstico de infección por SARS-CoV-2 fue confirmado por prueba de anticuerpos totales en suero, mediante inmunoensayo CLIA (Chemiluminescent Immunoassay), positiva para IgG en ambos casos. Las características de los casos presentados sustentan una posible relación posinfecciosa entre el SARS-CoV-2 y el SGB y abren, además, la posibilidad de que, a pesar de que los pacientes sean asintomáticos o presenten síntomas respiratorios leves, podrían desarrollar complicaciones posinfecciosas tales como SGB.

SUMMARY Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, shows mainly clinical manifestations at the respiratory level. It can affect, however, other organs and systems, including the central nervous system, generating neurological manifestations that include the Guillain Barré Syndrome (GBS). We present the cases of two male patients, aged 35 and 46, with GBS, one classified as AMAN and the other as AIDP. Both patients showed positive serology for SARS-CoV-2 and reported respiratory symptoms prior to the weakness condition. RT-PCR in pharyngeal secretion and CSF was negative in both cases. The infection by SARS-CoV-2 was confirmed by the total antibody test in serum through a positive CLIA immunoassay, positive for IgG in the two cases. The characteristics of the cases support a possible postinfectious relationship between SARS-CoV-2 and GBS, and open as well the possibility that despite being asymptomatic or having mild respiratory symptoms, some patients may develop post- infectious complications such as GBS.

Case Report: Anti-LGI1 Limbic Encephalitis Associated With Anti-thyroid Autoantibodies.

Anti-LGI1 encephalitis is an autoimmune encephalitis with antibodies against leucine-rich glioma-inactivated 1 (LGI1), first described in 2010. It is a non-frequent and poorly understood entity that represents the second most frequent cause of autoimmune encephalitis. This entity is characterized by the presence of limbic encephalitis, hyponatremia, and faciobrachial dystonic seizures. Herein, we present the case of a male patient with an onset of epileptic seizures (generalized tonic-clonic seizure), and involuntary dystonic movements that affect the right side of his face and right upper limb associated with mental disorder, and affectation of higher functions. The electroencephalogram showed continuous generalized slowing of the background activity. The brain magnetic resonance imaging showed signal hyperintensity at the level of both mesial temporal lobes and hippocampi and in the head of the right caudate nucleus. Anti-thyroglobulin antibodies were positive, and he was initially diagnosed as Hashimoto's encephalopathy (HE). However, the response to corticosteroids was not completed as it is usually observed in HE. For that, antibodies for autoimmune encephalitis were tested, and the anti-LGI1 antibodies were positive in serum and cerebrospinal fluid. HE is an important differential diagnosis to consider. Furthermore, the presence of Anti-thyroglobulin antibodies should not be taken as the definitive diagnostic criteria, since these antibodies could be associated with other autoimmune encephalopathies, which include in addition to anti-LGI1, anti-NMDA and anti-Caspr2.

[Autoimmune encephalitis mediated by antibodies against the N-Nethyl-N-Aspartate receptor: report of four cases in Peru]. / Encefalitis autoinmune mediada por anticuerpos contra el receptor N-Metil-N-Aspartato: reporte de cuatro casos en Perú.

Autoimmune encephalitis with antibodies against the N-methyl-D-aspartate receptor (anti-NMDAR) is a disorder mediated by antibodies against neural surface antigens, whose early diagnosis and timely treatment improve the prognosis of the disease. Four cases with the definitive diagnosis of autoimmune encephalitis by anti-NMDAR are presented, treated at the National Institute of Neurological Sciences in Lima-Peru. All patients had epileptic seizures and three cases developed a refractory epileptic state. In addition, three patients presented neuropsychiatric alterations, dyskinesias, and dysautonomia. Two cases required ventilatory support. All presented an abnormal electroencephalogram; two cases had pleocytosis in cerebrospinal fluid, and only one showed brain abnormalities on MRI. Regarding treatment, all patients received methylprednisolone immunotherapy and only two of them required plasma exchange for an ineffective response to corticosteroid treatment. After 12 months of hospital discharge, three patients were free of epileptic seizures and only one case did not achieve functional independence. These cases show that anti-NMDAR encephalitis is a treatable condition and its early recognition together with appropriate treatment (immunotherapy/plasmapheresis) are essential for a favorable evolution.

La encefalitis autoinmune por anticuerpos contra el receptor N-metil-D-aspartato (anti-NMDAR) es un desorden mediado por anticuerpos contra antígenos de superficie neuronal, cuyo diagnóstico temprano y tratamiento oportuno mejoran el pronóstico de la enfermedad. Se presentan cuatro casos con el diagnóstico definitivo de encefalitis autoinmune por anti-NMDAR, tratados en el Instituto Nacional de Ciencias Neurológicas en Lima-Perú. Todos los pacientes presentaron crisis epilépticas y tres casos desarrollaron un estado epiléptico refractario. Asimismo, tres pacientes presentaron alteraciones neuropsiquiátricas, discinesias y disautonomías. Dos casos requirieron soporte ventilatorio. Todos presentaron un electroencefalograma anormal, dos casos tuvieron pleocitosis en líquido cefalorraquídeo, y sólo uno mostró anormalidades cerebrales en la resonancia magnética. Respecto al tratamiento, todos los pacientes recibieron inmunoterapia con metilprednisolona y sólo dos de ellos requirieron plasmaféresis por respuesta ineficaz al tratamiento con corticoides. A los 12 meses del alta hospitalaria, tres pacientes quedaron libre de crisis epilépticas y sólo un caso no logró la independencia funcional. Estos casos muestran que la encefalitis anti-NMDAR es una condición tratable y su reconocimiento temprano junto con un tratamiento adecuado (inmunoterapia/plasmaféresis) son esenciales para una evolución favorable.

Encefalitis autoinmune mediada por anticuerpos contra el receptor N-Metil-N-Aspartato: reporte de cuatro casos en Perú / Autoimmune encephalitis mediated by antibodies against the N-Nethyl-N-Aspartate receptor: report of four cases in Peru

RESUMEN La encefalitis autoinmune por anticuerpos contra el receptor N-metil-D-aspartato (anti-NMDAR) es un desorden mediado por anticuerpos contra antígenos de superficie neuronal, cuyo diagnóstico temprano y tratamiento oportuno mejoran el pronóstico de la enfermedad. Se presentan cuatro casos con el diagnóstico definitivo de encefalitis autoinmune por anti-NMDAR, tratados en el Instituto Nacional de Ciencias Neurológicas en Lima-Perú. Todos los pacientes presentaron crisis epilépticas y tres casos desarrollaron un estado epiléptico refractario. Asimismo, tres pacientes presentaron alteraciones neuropsiquiátricas, discinesias y disautonomías. Dos casos requirieron soporte ventilatorio. Todos presentaron un electroencefalograma anormal, dos casos tuvieron pleocitosis en líquido cefalorraquídeo, y sólo uno mostró anormalidades cerebrales en la resonancia magnética. Respecto al tratamiento, todos los pacientes recibieron inmunoterapia con metilprednisolona y sólo dos de ellos requirieron plasmaféresis por respuesta ineficaz al tratamiento con corticoides. A los 12 meses del alta hospitalaria, tres pacientes quedaron libre de crisis epilépticas y sólo un caso no logró la independencia funcional. Estos casos muestran que la encefalitis anti-NMDAR es una condición tratable y su reconocimiento temprano junto con un tratamiento adecuado (inmunoterapia/plasmaféresis) son esenciales para una evolución favorable.

ABSTRACT Autoimmune encephalitis with antibodies against the N-methyl-D-aspartate receptor (anti-NMDAR) is a disorder mediated by antibodies against neural surface antigens, whose early diagnosis and timely treatment improve the prognosis of the disease. Four cases with the definitive diagnosis of autoimmune encephalitis by anti-NMDAR are presented, treated at the National Institute of Neurological Sciences in Lima-Peru. All patients had epileptic seizures and three cases developed a refractory epileptic state. In addition, three patients presented neuropsychiatric alterations, dyskinesias, and dysautonomia. Two cases required ventilatory support. All presented an abnormal electroencephalogram; two cases had pleocytosis in cerebrospinal fluid, and only one showed brain abnormalities on MRI. Regarding treatment, all patients received methylprednisolone immunotherapy and only two of them required plasma exchange for an ineffective response to corticosteroid treatment. After 12 months of hospital discharge, three patients were free of epileptic seizures and only one case did not achieve functional independence. These cases show that anti-NMDAR encephalitis is a treatable condition and its early recognition together with appropriate treatment (immunotherapy/plasmapheresis) are essential for a favorable evolution.

Signo de la copa de vino: A propósito de un caso con esclerosis lateral primaria y demencia frontotemporal / Wine glass sign in a patient with primary lateral sclerosis and frontotemporal dementia: a case report

La esclerosis lateral primaria es muy poco frecuente, representa 2-4 % del grupo de enfermedades de motoneurona. Se caracteriza por espasticidad corticoespinal y síndrome pseudobulbar. La resonancia magnética nuclear muestra lesiones hiperintensas de secuencias potenciadas en T2; cuando el compromiso es bilateral, la imagen da la apariencia de copa de vino . Caso clínico: Paciente varón de 56 años de edad, con un cuadro clínico de dos años de evolución, caracterizado por desinhibición, apatía, y conducta social inapropiada. La evolución clínica mostró criterios diagnósticos de esclerosis lateral primaria y de demencia frontotemporal. La resonancia magnética de encéfalo, protocolo T2, corte coronal reveló el compromiso bilateral de los haces cortico-espinales desde el centro semioval hasta las pirámides bulbares semejando la imagen en copa de vino . Aunque infrecuente, el caso muestra la posible asociación de Esclerosis Lateral Primaria (ELP) con demencia frontotemporal; la imagen en copa de vino puede estar presente en enfermedad de motoneurona y, cuando particularmente asociada a ELP, puede ser de gran ayuda en el diagnostico diferencial con otras entidades crónicas de curso clínico similar.

Primary lateral sclerosis is a very uncommon progressive disease and represents 2-4% of motor neuron diseases group. It is characterized by cortico-spinal spasticity and pseudo bulbar syndrome. Magnetic resonance shows white matter hyperintensities in T2 weight sequence. When the impairment is symmetrical, the image takes the appearance of a wine glass . Clinical case: A 56-year-old male patient with a clinical picture of 2-years duration characterized by disinhibition, apathy, and inappropriate social behavior. The clinical evolution met the diagnostic criteria of primary lateral sclerosis and frontotemporal dementia. Magnetic resonance imaging in coronal T2 weighted sequences, showed symmetrical impairment of corticospinal pathway from the semiovale centrum to the medullary pyramids showing the wine glass appearance. Although infrequent, the case shows the possible association of Primary Lateral Sclerosis (PLS) with frontotemporal dementia; the wine glass image in magnetic resonance may be present in motor neuron disease, when particularly associated with PLS may be of great help in the differential diagnosis with other chronic entities of similar clinical course.

Susac syndrome: the first case report in Peru. / Síndrome de Susac: primer reporte de caso en el Perú.

Susac Syndrome is a rare entity, characterized by a triad of subacute encephalopathy, retinal artery occlusion and sensorineural hearing loss. It is more common in women and the age of onset fluctuates between 9-58 years of age. The pathogenesis is presented as microangiopathic changes at the cerebral, retinal and cochlear levels associated with an autoimmune mechanism. We present the case of a 31-year-old woman who started with a diffuse headache, puerile behavior, bradylalia and somnolence. As the disease progressed, she had auditory deficit and arterial obstruction of the right temporal retinal branch in retinal fluorescein angiography. Brain magnetic resonance showed rounded hyperintense lesions in the corpus callosum, periventricular region and cerebellum. This is the first reported case of Susac Syndrome in Peru, presented with the classic triad, which is an infrequent presentation. However, cases that show incomplete forms should be evaluated in a timely manner to initiate timely treatment and avoid irreversible consequences.

El síndrome de Susac es una entidad rara, caracterizada por la triada clásica de encefalopatía subaguda, oclusión de la arteria retiniana e hipoacusia neurosensorial. Es más frecuente en mujeres, la edad de inicio fluctúa entre los nueve y los 58 años de edad. La patogénesis se plantea como un cuadro microangiopático a nivel cerebral, retiniano y coclear asociado a un mecanismo autoinmune. Presentamos el caso de una mujer de 31 años de edad que inició con cefalea holocraneana, conducta pueril, bradilalia y somnolencia. En la angiografía con fluoresceína de retina presentó en la evolución un déficit auditivo y obstrucción arterial de la rama temporal retiniana derecha. La resonancia magnética cerebral mostró lesiones redondeadas hiperintensas en el cuerpo calloso, región periventricular y cerebelo. Se reporta el primer caso de síndrome de Susac definido en Perú, el que se manifestó con la triada clásica, que es de presentación poco frecuente. Sin embargo, también los casos que muestran formas incompletas deben ser evaluados oportunamente para iniciar un tratamiento oportuno y evitar secuelas irreversibles.

Encefalitis por anticuerpos contra receptores de N-metil-D-aspartato y síndrome de DRESS secundario a fenitoína: Reporte de un caso / Encephalitis by anti-N-Methyl-D-Aspartate receptor antibodies and DRESS syndrome secondary to phenytoin: A case report

La encefalitis debida a anticuerpos contra receptores N-metil-D-aspartato (NMDA)es una entidad potencialmente tratable, caracterizada por síntomas neuropsiquiátricos que incluyen crisis epilépticas, alteración de conciencia, catatonía y trastornos autonómicos, y desencadenada por una respuesta inmunológica mediada por antígenos. A su vez, el síndrome DRESS (sigla en inglés de Reacción a drogas con eosinofília y síntomas sistémicos) es un cuadro de hipersensibilidad retardada mediada por células, frecuentemente asociada a fármacos antiepilépticos aromáticos. Se presenta el caso de una paciente joven que debutó con crisis epilépticas inicialmente fármaco-sensibles, desarrolló luego el síndrome de DRESS secundario a fenitoína. Cursó posteriormente con trastornos de memoria y lenguaje, alteraciones conductuales y estado catatónico y presentó anticuerpos contra receptores NMDA en el líquido cefalorraquídeo. Ambas entidades respondieron a inmunoterapia con corticoides, lo cual contribuiría a explicar una asociación fisiopatogénica entre estas dos entidades inmunomediadas.

N-Methyl-D-Aspartate receptor encephalitis is a potentially treatable entity characterized by neuropsychiatric symptoms including epileptic seizures, disruption of consciousness, catatonia, and autonomic disorders, and triggered by an immunological response mediated by an antigen. In turn, the DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) is a delayed cell-mediated hypersensitivity reaction, frequently associated with antiepileptic aromatic drugs. The case is presented of a young patient who debuted with epileptic seizures initially drug-sensitive, developedthen DRESS syndrome secondary to the use of phenytoin, and later presented disorders of memory and language, behavioral alterations and catatonic state, and presented anti- NMDA receptor antibodies in CSF. Both entities responded to corticoid immuno-therapy, which could contribute to explain a pathogenic association between these two immunomediated entities.

Cavernomatosis cerebral múltiple: primer reporte de caso en Perú / Multiple cerebral cavernous: first case report in Peru

La cavernomatosis cerebral (CC), única o múltiple, es la presencia de conductos vasculares distendidos, angiográficamente ocultos, por lo cual clásicamente eran hallazgos incidentales intraoperatorios o en autopsias. Actualmente la resonancia magnética (RM) cerebral, permite identificar éstas lesiones en un mayor número de pacientes. Las manifestaciones clínicas son hemorragias intracerebrales, crisis epilépticas y cefalea. Se reporta el caso de un varón de 55 años, sin antecedentes de importancia que ingresó por presentar cefalea y crisis de arresto del habla. El examen físico fue normal. Estudios tomográficos previos mostraron una lesión hemorrágica única, al realizarse una RM cerebral con protocolo T2-eco gradiente se evidencia múltiples imágenes compatibles con CC múltiple. Es el primer reporte de CC múltiple, entidad poco diagnosticada, que se debe sospechar en pacientes sin antecedentes de riesgo vascular que debutan con hemorragias intracerebrales, crisis epilépticas y/o cefaleas; constituyendo la RM cerebral en protocolo T2-eco gradiente, el estudio indicado para el diagnóstico.

Cerebral cavernomatosis (CC), single or multiple, is the presence of distended vascular channels, angiographically occult, for that, they are classically incidental intraoperative findings at autopsy. Currently the magnetic resonance imaging (MRI) let us identify these lesions in a larger number of patients. Clinical manifestations are intracerebral hemorrhages, seizures and headache. A male, 55, no history of significance is reported; he was admitted for headache and some months later presents speech arrest crisis. On physical examination, nothing unusual. Previous tomographic studies showed a hemorrhagic lesion, when the brain MRI with T2-eco gradient protocol was performed, multiple images observed, were compatible with multiple CC. This is the first report of multiple CC, unfrequent entity that should be suspected in patients with no history of vascular risk who present intracerebral hemorrhage, seizure and / or headache; being the brain MRI, the study indicated for diagnosis.