[Clinical characteristics and prognosis of patients with anti-glutamic acid decarboxylase antibody-related cerebellar ataxia].

The clinical data, diagnosis, treatment, and prognosis of 10 patients with anti-glutamic acid decarboxylase (GAD) antibody-related cerebellar ataxia in Department of Neurology, Peking Union Medical College Hospital, from May 2015 to November 2021 were retrospectively analyzed. There were 8 female patients with a median age of 55 years old. Patients mainly presented with gait ataxia (10/10), dizziness (8/10), diplopia (6/10), and dysarthria (5/10). Four of them were complicated with other autoimmune disease, including vitiligo (3/4), Hashimoto thyroiditis (1/4), thrombocytopenia (1/4), and small cell lung cancer (1/4). All patients received immunotherapy, 6 out of 10 exhibited a good response, and half of them had satisfied functional prognosis. Patients of anti-GAD antibody-related cerebellar ataxia may be complicated with other autoimmune diseases, but underlying tumor is rare. More than half of patients have a good response to immunotherapy and satisfied prognosis.

[Neuropsychiatric symptoms and caregivers' distress in anti-N-methyl-D-aspartate receptor encephalitis].

Objective: To explore the characteristics of psychiatric symptoms and caregivers' distress in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Methods: Seventy-two patients with anti-NMDAR encephalitis were investigated in Peking Union Medical College Hospital from 2011 to 2018. The Chinese version of the Neuropsychiatric Inventory-Questionnaire (NPI-Q) was used to assess the severity of neuropsychiatric symptoms and caregivers' distress around the treatment. Results: A highly positive correlation existed between severity scores of neuropsychiatric symptoms and caregiver distress, and pre- and post-treatment correlation coefficients was 0.872 and 0.947, respectively (all P<0.001). The frequency of 12 symptom domains was higher than 45% before treatment, however, it significantly reduced to below 45% after treatment. Irritability/lability, agitation/aggression were the most common neuropsychiatric symptoms. Irritability/lability, agitation/aggression, and nighttime behavioral disturbances occurred concurrently. Patients with severe symptoms tended to be administrated antipsychotics (Z=-2.581, P=0.01). Neuropsychiatric symptoms significantly improved after immunotherapy (Z=-6.611, P<0.001). There was no significant difference in the symptom severity and distress subscale scores between the first episode and relapse around the therapy (P>0.05). Conclusion: Patients with anti NMDAR encephalitis often present severe neuropsychiatric symptoms, which aggravate the burden on caregivers. Immunotherapy significantly improves neuropsychiatric symptoms, and thus reduces the distress of caregivers.

[Clinical observation on the overlapping syndrome of myelin oligodendrocyte glycoprotein antibody and anti-N-methyl-D aspartate receptor in children].

Objective: To investigate the clinical features, imaging findings and prognosis of children with overlapping syndrome of myelin oligodendrocyte glycoprotein (MOG) antibody disease and anti-N-methyl-D aspartate receptor (NMDAR) encephalitis (MNOS). Methods: The clinical manifestations, immunological antibodies in blood and cerebrospinal fluid, cranial image, treatment and follow-up of 11 patients diagnosed as MNOS in the Department of Neurology, Beijing Children's Hospital from January 2011 to April 2019 were analyzed retrospectively. Results: A total of 11 patients, including 4 males and 7 females were analyzed, the age of onset was (10.4±2.3) years. A total of 29 episodes occurred in 11 children. At the last follow-up, 8 cases showed relapsed remission course, the interval of recurrence was 3 to 60 months. The onset symptoms of 11 patients included convulsions (10 cases), lethargy (6 cases), psychosis (6 cases). Among 29 episodes, the common symptoms were convulsions (16 episodes), psychosis (13 episodes),and lethargy (10 episodes). According to the diagnostic criteria of anti-NMDAR encephalitis and MOG-antibody disease, 29 episodes were divided into three phenotypes, including anti-NMDAR encephalitis(4 episodes), MOG-antibody diseases (10 episodes) and overlapping types (15 episodes).Twenty-seven times of acute stage cranial magnetic resonance imaging (MRI) were available, common lesions included cortical focus (22 times), subcortical white matter (7 times), brainstem (9 times). All patients were sensitive to first-line immunotherapy. Eight patients had recurrence during glucocorticoid reduction, 6 of them were treated with additional second-line immunosuppressive therapy, including cyclophosphamide (1 case) and mycophenolate mofetil (5 cases). The follow-up time of patients were 5-99 months. At the last follow-up, all patients were in remission, the pediatric cerebral performance category (PCPC) score was 1 (10 cases) and 2 (1 cases). Conclusions: MNOS mainly affects older children. In the period of acute episodes, convulsions and psychosis are common. The cranial MRI showed extensive brain involvement and mainly in the cortex. The recurrence rates of MNOS are relatively high, patients are sensitive to first-line immunotherapy. No significant neurological dysfunction was left in the remission stage.

[Clinical approach and prognosis of continuous neurological care after intensive care for the patients with severe and refractory anti-N-methyl-D-aspartate receptor encephalitis].

Objective: To study the clinical features, continuous care and prognosis of the patients with severe and refractory anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis after intensive care unit (ICU). Methods: Clinical data of patients with severe and refractory anti-NMDAR encephalitis, who were transferred from ICU to general ward of neurology between December 2015 and October 2019, were retrospectively reviewed and analyzed in the study. Results: Twenty patients (11 females and 9 males) were enrolled in the study. The median course of disease when patients were transferred to general ward was 4.4 (2.0, 6.0) months. Six cases were alert, 6 cases were in a coma, 5 were in the early recovery phase and 3 were in the late recovery phase. Severe malnutrition, pneumonia, urinary tract infections, bedsores and leukocytopenia were common complications. Seven out of 18 patients were tested positive for cerebrospinal fluid anti-NMDAR antibodies with high titers (≥1∶100). During this continuous therapy stage,10 patients were treated with intravenous immunoglobulin (IVIg), 1 with methylprednisolone, 2 with rituximab, 1 with intrathecal methotrexate and 1 received intravenous cyclophosphamide. All Patients were prescribed a long-term immunotherapy (mycophenolate mofetil 1.5-3.0 g/d). Sixteen patients (80%) had good prognosis (modified Rankin Scale (mRS)≤2), and the mortality was 10%, with follow-up time of 17.0 (8.0, 27.0) months. Conclusions: Patients with anti-NMDAR encephalitis, who are transferred from ICU, have severely impaired neurologic function. These patients need long-term individualized immunotherapy and continuous neurological care. Good outcomes can be achieved in most patients.

[Clinical analysis of paraneoplastic neurological syndrome associated with thymoma].

Objectives: To investigate the clinical features, diagnosis and treatment of antibody mediated paraneoplastic neurological syndrome associated with thymoma. Methods: From 2012 to 2017, the paraneoplastic antibody and neuron antibody were tested from both blood and cerebrospinal fluid (CSF) in consecutive patients clinically suspected with neurological paraneoplastic syndromes/unknown encephalitis in Peking Union Medical College Hospital.The clinical data, lab results, electrophysiological examinations, imaging features, treatment and clinical prognosis were collected.In this study, the patients who met the diagnostic criteria of both thymoma and neurological paraneoplastic syndrome were retrospectively analyzed.The functional severity was assessed by modified Rankin score(mRS). Results: Six patients (4 female and 2 male) were included for the analysis.Of them, 4 patients presented with limbic encephalitis, 1 with peripheral neuropathy accompanying with myasthenia gravis and 1 with spinal and cerebella degeneration.Three patients were in severe condition (mRS=5). Positive α-amino-3-hydroxy-5-methyl-4-iso xazolepropionic acid receptor, antibody (AMPAR) was identified in 3 patients(2 in blood and CSF, 1 in blood), CV2 plus acetylcholine receptor antibody (ACH-Ab) positive in blood was seen in 1 patient and positive N-methyl-D-aspartate receptor (NMDAR) in blood and CSF in 1 patient. Brain MRI showed abnormalities in 2 patients.The CT scan revealed thymoma in all 6 patients.All patients received intravenous immunogloblin (IVIG) and/or glucocorticoid immediately after diagnosis.Furthermore, thymectomy was performed in 5 patients. All the patients were remarkably improved with mRS 0-1 at discharge.Five patients were clinical stable within follow-up of 1-2.5 years.However, one patient who refused thymectomy experienced several clinical recurrencs. Conclusions: Antibodies mediated paraneoplastic neurological syndrome/autoimmune encephalitis can occur in patients with thymoma with typical characteristics. The correlated antibody test and chest CT might be important in patients clinically suspected with neurological paraneoplastic syndrome or encephalitis with unknown reason. Surgical thymectomy combining with active immunological treatment may play a role in the favorable prognosis, even in those clinical severe patients.

[Analysis of prodromal phase and prodromal events in anti-N-methyl-D-aspartate receptor encephalitis].

Objective: To analyze prodromal phase and prodromal events of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Methods: Clinical data of 179 patients hospitalized and diagnosed during 2010-2016 including adults and children in Peking Union Medical College Hospital and Beijing Children's Hospital were collected.Patients with prodromal phase or prodromal events were selected.A retrospective analysis of clinical characteristics including prodromal phase or prodromal events, course of disease, brain imaging, laboratory results and therapeutic effect was performed. Results: Prodromal phase was presented in 31.8% (57/179) of patients.Most common symptoms included fever (73.7%) and headache (68.4%). Prodromal phase was prolonged in 6 patients, the longest being 64 days.Among those 6 patients (10.5%), headache and fever were the only symptoms throughout disease courses in 3 cases.Prodromal events were reported in 6.1% (11/179) of patients, including 5 patients after HSV1 encephalitis, 1 after Japanese encephalitis, and 2 after resection of melanocytic nevi. Conclusions: Anti-NMDAR encephalitis can be preceded with prolonged prodromal phase.In some patients prodromal symptoms are the only clinical presentation.Clinical features of those atypical cases suggest that infection may be the precipitating factor.Viral encephalitis including HSV1 encephalitis and Japanese encephalitis may be prodromal events in some cases.

[Immunotherapy strategy for 35 cases of severe anti-N-methyl-D-aspartate receptor encephalitis].

OBJECTIVE: To provide evidence for establishing standardized treatment strategy of severe anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in China, by demonstrating the clinical characteristics and comparing the treatment strategy with that adopted in foreign countries. METHODS: A total of 35 hospitalized cases who met the diagnostic criteria for severe anti-NMDAR encephalitis were retrospectively analyzed. Demographic data, clinical history, past medical history, laboratory tests, imaging studies, treatment and the follow-up information were recorded using unified forms. RESULTS: Mental and behavioral abnormalities, seizures and consciousness disturbance occurred in all cases; involuntary movements, speech disorders, memory loss, central hypoventilation and autonomic dysfunction happened in 45%-65% of cases. Sixteen patients (45.71%) required mechanical ventilation. Modified Rankin score (mRS ) arranged 4-5 (mean mRS 4.86). The percentage of patients with elevated intracranial pressure, white blood cell and protein in cerebrospinal fluid were 42.86%, 60.00%, and 14.29%, respectively. Abnormal findings in brain magnetic resonance imaging scan happened in 31.43% cases, located in frontal lobe, temporal lobe, insular lobe, hippocampus, cingulate gyrus, corpus callosum, brain stem, and cerebellum. All cases received intravenous immunoglobulin, for one to maximum seven cycles, with an average of three cycles. 91.43% of cases received glucocorticoid therapy, including 54.29% of cases received high-dose methylprednisolone. Two patients (5.71%) received plasma exchange. Five patients(14.29%) received second-line therapy including rituximab for 4 patients and intravenous cyclophosphamide (CTX) for one. Fifteen patients(42.86%) received long-term immunosuppression therapy. All cases acquired improvement after immunotherapy and were transferred out from ICU, the median ICU time was 46 days and median hospitalized duration was 72 days. The mRS were 5 for 2 cases, 1-4 for the rest patients, and no patient died during hospitalization. During a median follow-up period of 17.6 months, 30 of 35 patients (85.71%) achieved complete recovery or a good outcome (mRS 0-2). Eleven patients (31.43%) relapsed. One patient(2.90%) died 2 years after discharge. CONCLUSION: Intravenous immunoglobulin combined with high-dose methylprednisolone therapy is effective for severe anti-NMDAR encephalitis. Retrial of the first-line immunotherapy is an option for initially unresponsive cases.