神经领域-神经系统自身免疫性疾病方向

METHODS::The diagnosis of hemophagocytic lymphohistiocytosis (HLH) with cerebral involvement is challenging given the rarity of HLH and its resemblance to the much more common severe sepsis. Timely diagnosis and treatment may be lifesaving. We report two cases demonstrating different and rare forms of severe brain involvement in adult patients with HLH: acute necrotizing encephalopathy, and diffuse hemorrhagic disease due to disseminated intravascular coagulation. Severe HLH with brain involvement in adults is rare. HLH with cerebral involvement should be considered in patients presenting with severe systemic inflammatory response syndrome (SIRS) but negative cultures and unusual or unexpectedly severe clinical and/or radiologic signs of cerebral dysfunction. Similar brain injury may occur in patients with cytokine storm syndrome due to COVID-19. BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) presents with fevers, rash, organomegaly, cytopenia, and increased triglycerides and ferritin (Ramos-Casals et al., 2014) [1]. Neurologic abnormalities are reported in about one-third of patients (Cai et al., 2017), including a few cases of acute necrotizing encephalopathy (ANE) (Xiujuan et al., 2015). Coagulation abnormalities are frequent in HLH patients (Valade et al., 2015). OBJECTIVE: To raise awareness about the importance of early diagnosis and treatment of HLH with neurological involvement to prevent serious complications and demise.

METHODS:BACKGROUND:Adherence to disease-modifying therapies is determinant to attain maximal clinical benefit in multiple sclerosis (MS). RebiSmart® is an electronic auto-injector for subcutaneous delivery of interferon β-1a (INF-β1a) that monitors adherence by featuring a log of each drug administration for objective evaluation. The aim of this study was to assess long-term adherence to INF-β1a by using the RebiSmart® device in Mexican patients with relapsing MS. METHODS:This is an observational multicenter study on patients with relapsing MS treated with INF-β1a subcutaneously delivered by the RebiSmart® device. Adherence was computed as the number of injections received during the study period divided by the number of injections scheduled and expressed as percent. RESULTS:A total of 66 patients from 6 specialized MS centers were evaluated (45 females and 21 males, mean age 43.91±13.32 years). Mean adherence was 79.51±18% (median: 85.54%, range: 34.4-100%). During a median follow-up of 27.5 months (mean 33.36±29.39 months) the annualized relapse rate had a mean of 0.50±1.63. Mean initial EDSS was 1.90±1.52, and mean EDSS at the end of follow-up was 1.80±1.74. Compared with their counterparts, the mean number of relapses was significantly lower among patients with high (>80%) adherence (0.25±0.44 vs 0.67±92 relapses, respectively; P = 0.03). The proportion of relapse-free patients was 75.0% among patients with high adherence and 53.3% in low-compliant patients (P = 0.06). High adherence patients presented lower rates of EDSS worsening ≥1.0 at the end of treatment, as compared with low-compliant patients (11.1% vs 43.3%, respectively; P = 0.003). High schooling (>12 years) was the only predictor of a high adherence (OR: 2.97, 05% CI: 1.08-1.18; P = 0.03) and of being relapse-free during follow-up (OR: 3.22, 05% CI: 1.12-9.23; P = 0.03). CONCLUSION:Adherence to INF-β1a using RebiSmart® in this Mexican cohort with MS was moderate, but associated with low relapse rate and influenced by high schooling.

METHODS:RATIONALE:Guillian-Barré syndrome (GBS) is a devastating autoimmune disorder characterized by progressive ascending weakness, areflexia with or without autonomic and sensory disturbances. Hydrocephalus is a rare but well-documented complication in patients with GBS. However, due to the rarity of this condition, no treatment guideline for GBS with hydrocephalus is currently available. PATIENT CONCERNS:We describe a 23-year old woman with a history of bilateral limbs pain followed by dysarthria, dysphagia, severe quadriplegia 0/5, areflexia, loss of consciousness and dysautonomia. Neuroimaging studies revealed enlarged lateral ventricles; while Electromyography demonstrated demyelination and nerve injury. Lumbar puncture results showed elevated protein level 2.6 g/L; normal glucose and cell count. DIAGNOSIS:GBS with hydrocephalus. INTERVENTIONS:The patient was started on intravenous immunoglobulin for 5 consecutive days followed by endotracheal intubation and supportive therapy including osmotherapy and CSF drainage. OUTCOMES:At 2 months after admission, the patient stopped choking and had a significant improvement in muscles' strength (grade 4) and pain; then was discharged. On 1 year post-discharge follow-up, CT has revealed a significant improvement of hydrocephalus, and the patient has completely returned to the normal baseline. LESSONS:Respiratory failure is the strongest predictor of concurrent hydrocephalus in patients with GBS. The prognosis of hydrocephalus in patients with GBS is usually good, and it can be medically treated; thereby shunt surgery is rarely required.

METHODS:BACKGROUND:Coronavirus disease 19 (COVID-19) is a novel disease entity that is spreading throughout the world. It has been speculated that patients with comorbidities and elderly patients could be at high risk for respiratory insufficiency and death. Immunosuppression could expose infected patients to even higher risks of disease complications due to dampened immune response. However, it has been speculated that overactive immune response could drive clinical deterioration and, based on this hypothesis, several immunosuppressants are currently being tested as potential treatment for COVID-19. METHODS:In this paper we report on a patient that has been treated with ocrelizumab (a B-cell depleting monoclonal antibody) for primary progressive multiple sclerosis who developed COVID-19. RESULTS:Despite complete B cell depletion, patient symptoms abated few days after hospitalization, and he was discharged to home-quarantine. Phone interview follow-up confirmed that, after 14 days, no new symptoms occurred. DISCUSSION:This report supports the putative role of immunosuppressive therapy in COVID-19 affected patients.

METHODS:INTRODUCTION:Hyperekplexia is a rare hereditary neurological disorder; only 5 glycine receptor alpha 1 subunit gene (GLRA1) mutations have been reported in 5 Chinese patients. We report a Chinese infant with hyperekplexia and a novel mutation at c.292G > A. PATIENT CONCERNS:A Chinese infant with hyperekplexia and a novel mutation at c.292G > A. DIAGNOSIS:All exons of GLRA1 were sequenced in her parents and her, which revealed a mutation at c.1030C > T and another novel mutation at c.292G > A. Her diagnosis was confirmed as hereditary hyperekplexia with GlRA1 hybrid gene mutations based on the sequencing results. INTERVENTIONS:She was treated with clonazepam. OUTCOMES:Her muscle hypertonia recovered rapidly and the excessive startle reflex to unexpected stimuli was significantly reduced. CONCLUSION:Genetic DNA sequencing is a crucial method for diagnosing hyperekplexia-related gene mutation.

METHODS:INTRODUCTION:Complications such as severe infection may occur during the chemotherapy of malignant lymphoma. Phlegmonous gastritis (PG) is a rare acute bacterial infection associated with high mortality, requiring early diagnosis, and prompt management. In addition, Guillain-Barré syndrome (GBS) occasionally requires early treatment and intensive care management due to the occurrence of severe neuropathy and respiratory failure. PATIENT CONCERNS:A 70-year-old male was diagnosed with primary gastric diffuse large B-cell lymphoma (DLBCL) after the detection of several polypoid tumors with ulcers. The patient underwent chemotherapy for DLBCL and exhibited adverse effects (i.e., fever, vomiting, epigastric pain, and neutropenia). Computed tomography indicated widespread thickening in the gastric wall. Furthermore, approximately 2 weeks later, the patient presented with gradual symmetric lower extremity weakness and respiratory failure due to paralysis of the respiratory muscle. DIAGNOSES:DLBCL was diagnosed through a gastric tumor biopsy. On the basis of the computed tomography findings, a culture of gastric juice, nerve conduction studies, and clinical symptoms, this case of gastric lymphoma was complicated with PG and GBS. INTERVENTIONS:The patient was treated with antimicrobial therapy and administration of granulocyte colony-stimulating factor for PG, and with intravenous immunoglobulin and intensive care management for GBS. OUTCOMES:Despite the aggressive progress of the condition, the patient improved without relapse of DLBCL. CONCLUSION:PG was regarded as a precedent infection of GBS. In this article, we present the first reported case of gastric lymphoma complicated with PG and GBS.

METHODS:BACKGROUND:The novel Coronavirus SARS-CoV-2, which was identified after a recent outbreak in Wuhan, China, in December 2019, has generated a global pandemic impacting over 200 countries around the world. Recent reports suggest that ACE2, which is the target protein to invade the host, has a ubiquitous presence in human organs, including lung parenchyma, gastrointestinal tract, nasal mucosa, renal and urinary tract, airway epithelia, lymphoid tissues, reproductive organs, vascular endothelium and neurons. In this scenario, neurologists are particularly involved into considering even more specific therapeutic strategies according to the available data during the pandemic. In particular, MS patients are usually receiving disease-modifying therapies (DMTs) with immunosuppressant or immunomodulatory effects, which increase the risk of infections and morbidity, compared with the general population. Development of PML or other serious opportunistic infections during treatment with natalizumab forces to consider whether de-risking strategies are needed in this particular context and how to manage a high-efficacy treatment. METHODS:In this paper we report on a patient treated with natalizumab for relapsing MS who developed COVID-19 and recovered in a few days without complications. RESULTS:After recovery natalizumab has been administered in the window of the extended interval dosing (EID), without reporting any worsening or new symptoms. DISCUSSION:This case supports the opportunity to avoid discontinuing or delaying the retreatment over 8 weeks in patients recovered from a recent COVID-19.

METHODS::We present a case of facial diplegia after 10 days of SARS-CoV-2 confirmed infection symptoms in a 61 year old patient without prior clinically relevant background. There are few known cases of Guillain-Barré Syndrome (GBS) related to SARS-CoV-2 infection; we propose this case as a rare variant of GBS in COVID-19 infection context, due to Its chronology, clinical manifestations and cerebrospinal fluid (CSF) findings.

METHODS:BACKGROUND:Treatment decisions in patients with multiple sclerosis (MS) during the coronavirus disease 2019 (COVID-19) pandemic are challenging. It is not known whether and how various disease modifying therapies, especially immunosuppressive drugs, affect COVID-19 risk and disease course. METHODS:Case report RESULTS: We report a fingolimod-treated MS patient who developed severe COVID-19 but recovered after treatment with tocilizumab. CONCLUSION:This report suggests that a brief course of tocilizumab for the treatment of severe COVID-19 may be effective while not aggravating pre-existing MS.

METHODS:RATIONALE:Although distal nerves located at sites prone to compression are susceptible to autoimmune attack, Guillain-Barre' syndrome (GBS) with exclusive hand muscle involvement is rarely found in clinics. All reported patients presented with a special variant - finger extensor weakness, especially claw hand caused by predominant ulnar extensor involvement. Similar to typical GBS, these patients showed bilateral symmetric onset with rapid clinical progression. PATIENT CONCERNS:A 62-year-old man with GBS was admitted to our hospital with unilateral onset of claw hand. He showed relatively slow progression and did not develop bilateral symmetric claw hands until 6 weeks later. DIAGNOSES:Eventually the patient was diagnosed as having a regional variant of GBS by neuronal electrophysiology and cerebrospinal fluid examinations. INTERVENTIONS:This patient was treated with intravenous thrombolysis within 4.5 hours of onset. Eventually he was diagnosed as having a regional variant of GBS and was treated with gamma-globulin (400 mg/kg/d) for 5 consecutive days via intravenous infusion. OUTCOMES:The patient had a slow recovery with persistent mild finger extensor weakness. LESSONS:This patient presented with unilateral onset of claw hand, and the diagnosis of acute ischemic stroke could not be excluded because of a short time window; hence, he was treated with intravenous thrombolysis within 4.5 hours of onset. Eventually he was diagnosed as having a regional variant of GBS. It is important that GBS should also be considered in patients with unilateral hand weakness and unknown aetiology in the early stages of disease.