With the understanding of autoimmune encephalitis many novel types of autoimmune encephalitis and related antibodies have been identified. There are some cases of autoimmune encephalitis with autoantibody overlapping syndromes or phenotype overlapping syndromes, which bring challenges to diagnosis and treatment in practice. The relevant literature was reviewed and the clinical characteristics, pathological mechanism and treatment of overlapping syndromes associated with autoimmune encephalitis were summarized, in order to provide a reference for the management of autoimmune encephalitis with overlapping syndromes.

Objective To investigate the MR imaging findings of acute experimental allergic encephalomyelitis(EAE) in correlation with pathology. Methods An EAE model was induced by intradermal inoculation with guinea pig CNS homogenate in 6 female Lewis rats.Another 6 rats served as control.The clinical presentation and body weight of the animals were recorded daily. Routine MRI,Gd-enhanced MRI were performed when EAE animals showed the initial symptoms. Uhrasmall superparamagnetic iron oxide(USPIO) colloid solution was also administrated intravenously and MRI was performed again after 24 hours. The brain was removed instantly after the second MR imaging. The pathological exams including HE staining,myelin sheath staining and prussian staining were performed.The imaging findings were observed in correlation with pathological results. Results The EAE rats showed decrease of body weight on the 6th to 7th day after inoculation,and the clinical symptoms appeared on the 10th to 11th day after inoculation.Routine MRI did not show any definite abnormalities.The Gd-enhanced MRI found the diffuse thickening and enhancement of brain meninges.The USPIO-enhanced MRI showedareas of low signal intensity at white matter of medulla oblongata on T2WI,and high signal intensity was observed at the corresponding area on T1 WI. Gradient T2 * WI found more foci of low signal intensity in eerebellar white matter besides the lesions in the brain stem.The range of abnormal signal intensity was larger in animal with higher clinical scores than that with lower score.There were no abnormal findings in control animaL The pathological exam found "perivascular cuff" in the brain white matter in EAE animals,some accompanied with adjacent demyelinatian. The prussian staining found blue particles within the cytoplasm of the macrophages around the lesion,which corresponded to the area of low signal intensity on T2WI.Conclusion USPIO-enhanced MRI could reveal acute EAE lesions which were not capable of being shown on routine MRI and Gd-enhanced MRI.It can image the macrophages around the lesions in vivo.USPIO is important for future research and application in MS patients.

Objective To analyze the clinic and pathological features of Castleman’s disease (CD),or an angiofollicular lymph node hyperplasia(ALNH) Method Retrospectively gave a review of 6 patients with CD in recent 15 years in PUMC Hospital Results 4 patients with multicentric Castleman’s disease (MCD) had systemic symptom including fever,anemia,edema and endocrine disorders M protein presented in 3 of them 3 patients with MCD had progressive polyneuropathy,with presenting distal symmetric weakness and numbness, areflexia Nerve conduction velocity was slow and action amplitude decreased significantly.Sural nerve biopsy showed a moderate? prominent axon degeneration with minimal vasculopathy 2 patients with localized CD (LCD) had no systemic or neurological complications Histological study of lymph tissue confirmed the diagnosis of CD,showing that there were subtype of hyaline vascular (HV) in 5 cases and plasma cell (PC) in 1 case Conclusion Multicentric Castleman’s disease should be associated with systemic and neurological involvement It might present with distal symmetric motor sensory axonal polyneuropathy The clinic feature should be a PEOMS syndrome with a poor prognosis

Objective To summarize the clinical and pathological features of glycogen storage disease (GSD) type Ⅱ. Methods The clinical and pathological data of the 20 GSD type Ⅱ patients were reviewed. Results One patient with infantile-onset mainly presented hypotonia, muscle weakness, feeding difficulties, pulmonary infection and cardiomyopathy insufficiency and increase of serum creatine kinase (778 IU/L) and echographic evidence of hypertrophic cardiomyopathy were detected. Electromyography studies indicated a definite myopathy. Nineteen cases were late-onset, presenting a slowly progressive proximal myopathy with truncal involvement or with symptoms dominated by respiratory insufficiency. Not all muscles were equally affected. Increase of serum creatine kinase (208-2600 IU/L) was detected in 14 patients and normal level in 1 patient. Electromyography studies indicated a definite myopathy in 9 patients,with abnormal irritability in 1 patient and susceptible in 4 patients and myotonic discharge in 1 patient and no abnormalities in 2 patients. Echographic evidence of thickening of the interventricular septum and pulmonary hypertension were detected in 2 patients respectively. The common light microscopic feature of all case was a vacuolar myopathy with high glycogen content and acid phosphatase activity in the vacuoles. Conclusions GSD type Ⅱ often presents slowly progressive myopathy which often affect the toro and respiratory muscles.In most patients the serum creatine kinase level is elevated slightly. Muscle biopsy is of use to make the definite diagnosis of this disease.

Objective:To analyze and summarize the clinical characteristics of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis patients with cerebellar ataxia.Methods:The clinical manifestations, laboratory examinations, treatment and prognosis of anti-NMDAR encephalitis patients with cerebellar ataxia diagnosed and treated in Peking Union Medical College Hospital from 2011 to 2019 were retrospectively analyzed.Results:About 4.3% (15 cases) of a total of 347 anti-NMDAR encephalitis patients were complicated with cerebellar ataxia, of which one patient had ovarian teratoma. There were seven male cases and eight female cases, with a median age of 28 years. The average duration from the onset of encephalitis to the onset of cerebellar symptoms was 30.8 days.The average modified Rankin Scale (mRS) score was 3.73. In the acute phase, the median cerebrospinal fluid leukocyte count was 28×10 6/L. All patients received first-line immunotherapy, of which one case additionally received second-line immunotherapy with rituximab and nine patients received long-term immunotherapy with mycophenolate mofetil. The follow-up time ranged from seven to 66 months. The average mRS score of the last time was 2.73, and only six patients (6/15) had good prognosis (mRS score≤2). Conclusions:Patients with anti-NMDAR encephalitis and cerebellar ataxia are rare, and have relatively poor prognosis in terms of neurological function. Symptoms of cerebellar ataxia in anti-NMDAR encephalitis patients should be recognized in time, and standardized immunotherapy regimens and long-term immunotherapy should be adopted to improve the prognosis.

Objective To explore the clinical features and diagnostic method of primary natural killer( NK)/T cell meningeal lymphoma. Methods An unusual case of a 19-year-old male with primary NK/T cell meningeal lymphoma was reported. His clinical presentation and laboratory findings were discussed. The related literatures have been reviewed. Results The patient presented with diplopia,headache, vomiting and facial drooping at the onset, followed by progressive pain and weakness of the four limbs. Cerebrospinal fluid showed significant increase in pressure, leukocytes number, levels of protein,normal glucose and adenosine deaminase, negative tuberculosis antibody and sterile staining. In cerebrospinal fluid cytological analysis, May-Grunwald-Gimsa staining showed large number of atypical lymphocytes with irregular nucleus and nuclear fission, Ki-67 immunostaining showed extensive proliferative activity of the lymphoid cells. Flow cytometric immunophenotypic analysis of cerebrospinal fluid indicated 97. 98 percent of cells expressed surface CD3, CD7, CD56, CD2, CD5, and partially expressed CD8. This was a rare immunophenotype for NK/T-cell. Cranial MRI with gadolinium showed thickening of the trigeminal nerve with slight enhancement and diffuse leptomeningeal enhancement. CT of the chest and abdomen and bone marrow biopsies were negative. He was diagnosed as primary NK/T cell meningeal lymphoma based on the clinical features and related examination. Conclusions Primary NK/T cell meningeal lymphoma is a rare type of primary central nervous lymphomas which has special immunophenotype. The clinical features include progressive raised intra-cranial pressure, multiple cranial and spinal nerve involvements. Cerebrospinal fluid cytological analysis and flow cytometric immunophenotypic analysis are key work-up for diagnosis. It has poor response to chemotherapy and radiotherapy.

Objective To investigate the value of the cerebrospinal fluid ( CSF ) cytology in diagnosis of intracranial germinomas by reviewing the outcomes of CSF cytology of 8 patients with intracranial germinomas. Methods Eight patients with positive CSF cytology at our clinic from January 2006 to June 2009 were reviewed. Conventional cytology and immunocytochemistry of CSF were performed. The relevant literature on the subject was reviewed. Results The patients, including 7 male and 1 female, developed endocrinological or neurological symptoms at the age of 13 to 25, and the typical neurological presentation included vertigo, headache, mental and behavior disorders, double vision and weakness of legs. The CSF cell count ranged from 0 to 300 leukocytes per cubic and elevated in 7 cases, typically lymphocytic inflammation. CSF level of human chorionic gonadotropin was 3.2-1087.0 mIU/ml, higher than the individual serum level. On CSF cytology studies, typical tumor cells of germinima were found, which had positive particles in cytoplasm on periodic acid Schiff stain. All presents had lymphocyte inflammation ( small lymphocyte predominant ). On immunocytochemical studies of CSF, the tumor cells were positive on placental alkaline phosphatase and Ki-67 stains. Conclusions CSF cytology is clinically useful for diagnosis of primary intracranial germinoma. Further clinical and cytological studies will be necessary for a better understanding of the biology of these tumors.

Objective To explore the clinical significance of expressing multiple autoantibodies in patients with autoimmune encephalitis.Methods Cerebrospinal fluid and serum were tested in patients with undefined encephalitis admitted to Peking Union Medical College Hospital from May 2013 to December 2014.Indirect immunofluorescence test was firstly used to identify the antibodies to neuronal cell-surface or synaptic receptors (including N-methyl-D-aspartate receptor (NMDAR),contactin-associated protein-like 2 (CASPR2),α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR),leucine-rich glioma inactivated protein 1 (LGI1),and gamma-aminobutyric acid beta receptor (GABABR)).In those patients with positive antibodies,antibodies against intracellular neuronal antigens associated with paraneoplastic neurological symptoms were tested.Anti-aquaporin protein-4 (AQP4) antibody was tested depending on patients' clinical manifestations.Results Ten patients were detected combined with additional autoantibodies in 531 patients with positive antibodies related to autoimmune encephalitis.AntiHu antibody was positive in 5 patients with anti-GABABR encephalitis,in 1 of whom anti-NMDAR antibody was also identified;anti-AQP4 antibody was positive in 1 patient with relapsing anti-NMDAR encephalitis;anti-CASPR2 and anti-Yo antibodies were respectively positive in 2 patients with anti-LGI1 encephalitis;anti-CV2 and anti-Hu antibodies were respectively positive in 2 patients with anti-AMPAR encephalitis.Clinical presentation of all cases was consistent with typical encephalitis or limbic encephalitis.Brain stem was involved in 3 patients.Peripheral sensory neuropathy was present in 1 patient,while myalgia and fasciculation were present in 1 patient.Seven patients responded well to the immunotherapy.Tumors were pathologically or radiologically confirmed in 7 cases,including lung cancer in 5 cases,suspected thymoma in 1 case and highly suspected mediastinal tumor without pathological identification in 1 case.Conclusions Due to the pathological mechanism,co-existence of multiple autoantibodies affects clinical manifestations of patients and results in variation and overlap of them.The additional positivity of onconeuronal antibodies directs the search for occult tumor.

Objective To investigate the efficacy and safety of rituximab in the treatment of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis.Methods Three patients with anti-NMDAR antibodies in cerebrospinal fluid and serum hospitalized from May 2012 to July 2014 were retrospectively reviewed.The clinical syndrome,investigations,and therapeutic interventions by rituximab when first line immunotherapy failed were evaluated.Results All 3 patients were females with median age of 17 years (12,17,and 22 years).One patient had ovarian teratoma.All 3 patients presented with psychiatric symptoms and movement disorders,2 of which developed into a state of unresponsiveness.Brain magnetic resonance imaging of 2 patients was unremarkable,and 1 showed T2 and FLAIR hyperintensity among the areas of medulla,pons,caudex cerebri and callosum.Fluoro-2-deoxy-D-glucose-PET showed variable multifocal cortical and subcortical abnormalities that changed during the course of the disease.Electroencephalograms were abnormal in all patients,showing non-specific,slow,and disorganised activity,1 showing extreme delta brush.The cerebrospinal fluid showed lymphocytic pleocytosis.All patients showed no response to treatment with first line immunotherapy (corticosteroids,intravenous immunoglobulin (400 mg · kg-1 · d-1 × 5 d,2-3 courses of treatment)).After the administration of rituximab,1 patient responded slower,whereas the other 2 patients who recovered dramatically (375 mg/m2 every week for 3-4 weeks) continued immunosuppression with mycophenolatemofetil for 1 year.Relapse occurred in 1 patient when the immunotherapies discontinued 6 months later.During the treatment of rituximab,2 patients had grade 3 infectious adverse events (hospitalization and intravenous administration of antibiotics).Conclusions Rituximab is effective for the patients with anti-NMDAR encephalitis who fail to respond to the first line immunotherapy.However the utility of rituximab is still a challenge due to the risk of infectious complications and off-label use.

ObjectiveIn an attempt to clarify the usefulness of combined nerve and muscle biopsy in the diagnosis of neuromuscular disease when compared with traditional sural nerve biopsy.Methods Fifteen biopsies of superficial peroneal nerve (SPN) and peroneus brevis muscle ( PBM ) by one incision performed within one neurological clinic were reviewed.All patients had peripheral neuropathy while 3 of them had myopathy clinically.The diagnostic significance of SPN and PBM biopsies were classified into 3 grade: essential,helpful,no value.ResultsOf 15 SPN and PBM biopsies,7 showed essential pathological findings whichreachedthe etiologicaldiagnosis, including 5definitevasculitis, 1inflammatory demyelinating polyneuropathy and 1 amyloid neuropathy.Five biopsies are helpful for etiological diagnosis,including demyelinating neuropathy,mild inflammation,and microvascular lesion,et al.Three biopsies are of no value for etiological diagnosis which only have nonspecific change such as type 2 fiber atrophy,neurogenic atrophy and axonal degeneration et al. Finally,SPN and PBM biopsies made the definite etiological diagnosis possible in 12 patients.ConclusionsSPN and PBM biopsy improved the yield of specific pathological and etiological diagnosis of neuropathy and myopathy such as vasculitis and amyloidosis with minor trauma and side effect.Further clinical and pathological studies will be necessary for a better practice of combined nerve and muscle biopsy.