Morvan syndrome with positive anti LGI1/CASPR2 antibodies in serum/cerebrospinal fluid:a case report and literature review / 中华内科杂志

To report a typical case of Morvan syndrome with positive anti-leucine rich glioma-inactivated 1(LGI1) and contactin-associated protein 2 (CASPR2) antibodies in serum and cerebrospinal fluid. A 39-years-old female initially presented weakness of extremeties. The main symptoms included paroxysmal limb pain, wheezing, itching, muscle twitching, epilepsy, hypomnesia, dysphoria, apathy, intractable insomnia, salivation and sweating. Tests of electrolytes found hypokalemia (2.7-3.1 mmol/L) and hyponatremia (130-136 mmol/L). Arterial blood gas analysis showed hypoxemia (oxygen saturation 50%-70%). Total thyroxine (TT4) was elevated to 207 nmol/L with positive thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (TG-Ab). LGI1and CASPR2 antibodies (CBA method) were positive in both serum and cerebrospinal fluid, and the remaining antibodies related to autoimmune encephalitis and paraneoplastic syndrome were negative. Head MRI was almost normal, while mild abnormalities were found in electroencephalogram. Electromyography showed slightly increased voltage of left quadriceps motor unit potential. After treated with corticosteroids, IVIG and mycophenolate mofetil, the patient completely improved. Cognitive function scores recovered from MoCA/MMSE (16/24) to MoCA/MMSE (26/29). Positivity of LGI1/CASPR2 antibodies both in serum/cerebrospinal fluid are rarely seen in patients with Morvan syndrome. Steroids and immunosuppressants are suggested for treatment as early as possible.

Anti-metabotropic glutamate receptor 1 antibodies associated encephalitis: a case report / 中华神经科杂志

Objective:To establish a tissue based assay and in-house cell based assay combined system to screen anti-metabotropic glutamate receptor 1 antibodies in a case of previously idiopathic encephalitis with prominent cerebellar ataxia and make the final diagnosis, and to summarize and analyze clinical characteristics and treatment response of the disease.Methods:A middle-aged woman admitted to Department of Neurology, People's Liberation Army General Hospical Accredited to the Sixth Medical Center in January 9, 2020, who presented with acute dizziness, unsteady gait and developed head titubation, repeated language and calculation impairment was reported. The patient′s serum and cerebrospinal fluid were firstly tested with commercial kits for conventional neural antibodies.Then samples were incubated with rat hippocampus, cerebellum and human embryonic kidney 293 cells transfected with metabotropic glutamate receptor 1 plasmid to screen extra antibodies by indirect immunofluorescence method. By reviewing literature, physical functions of metabotropic glutamate receptor 1 and clinical features of anti-metabotropic glutamate receptor 1 antibodies associated encephalitis were summarized.Results:The patient was neural antibodies negative with commercial kits. Further investigation showed neuropil staining pattern after her serum and cerebral spinal fluid were incubated with rat brain slices. The characteristic "Medusa head" staining pattern of Purkinje cells in cerebellum was also noticed. Along with her previous head titubation symptom, an in-house cell based assay using human embryonic kidney 293 cells transfected with metabotropic glutamate receptor 1 plasmid was developed and proved the existence of anti-metabotropic glutamate receptor 1 antibodies. The final diagnosis of anti-metabotropic glutamate receptor 1 antibodies associated encephalitis was made. One-year follow-up revealed her serum antibodies titers dramatically decreased and cerebrospinal fluid antibodies were negative after using steroids and intravenous immunoglobulin, but still left prominent cerebellum atrophy and severe ataxia.Conclusions:Anti-metabotropic glutamate receptor 1 antibodies may cause acute encephalitis. Cerebellar ataxia and head titubation are characteristic symptoms of metabotropic glutamate receptor 1 autoimmunity. The response to immunotherapies is limited and patients may have severe neurological deficits.

A clinical report of five cases of central nervous system miliary tuberculomas first diagnosed by neurologists / 中华内科杂志

To explore the clinical characteristics and imaging features of miliary tuberculomas in central nervous system (CNS).A total of 5 cases diagnosed with tuberculosis in CNS first diagnosed by neurologists in Navy General Hospital of PLA were enrolled in the study.All clinical and imaging data were collected and analyzed retrospectively.The main initial symptoms were fever and headache (4/5).Multiple diffused miliary lesions were shown by brain MRI,with maximum diameter ranged from 1-4 mm and ringshape or nodular enhancement after gadolinium injection.As mycobacterium tuberculosis could seldomly be found in serum and cerebrospinal fluid,contrast MRI remains the effective method for detecting miliary tuberculomas in CNS.

Clinical manifestations and pathological features of cortical vein thrombosis / 中国脑血管病杂志

Objective To analyze the clinical,imaging and pathological features of cortical vein thrombosis (CoVT). Methods Ten patients with CoVT (4 patients with CoVT alone and 6 patients with CoVT and venous sinus thrombosis)treated at Navy General Hospital from January 2006 to Jun 2013 were collected retrospectively.Its etiology,imaging,and pathological features of brain tissue in 3 patients were analyzed. Results Of the 10 patients with CoVT,3 were female and 7 were male.Their mean age was 31 ± 15 years old.(1)Brain CT scan and MRI showed hemorrhagic cerebral infarction,and contrast-enhanced MRI showed scattered heterogeneous enhancement within lesions. DSA could find CoVT at different parts.(2)3 patients underwent brain biopsy because they were initially diagnosed as brain tumor. Pathological examination showed glial cell,endothelial proliferation and phagocytic reaction.Scattered spotty bleeding was observed,and significant expansion of small veins,A few of them had blood stasis and thrombosis. Conclusion CoVT is one kind of intracranial venous thrombosis. It is more common occurred in young and middle aged adults,and most of them were venous sinus thrombosis.It is caused by retrograde thrombosis and spread to cortical veins.CoVT is easily to be misdiagnosed as brain tumor.Combination of clinical and imaging findings is needed for accurate diagnosis.

Cortical vein thrombosis: three cases for the clinical, neuroimaging and pathological analysis / 中华神经科杂志

Objective To analyze the clinical,imaging and pathological features of cortical vein thrombosis (CoVT).Methods Three cases of cortical vein thrombosis were diagnosed in our hospital from February 2010 to October 2012.We reviewed and summarized their clinical manifestation,radiological feature and pathological characteristics.Results All patients were young with acute onset.The main clinical manifestations included headache,epilepsy or limbs weakness.Two cases had intracranial hypertension.One case had decreased activity of protein S.One had increased plasma homocysteine.Brain computed tomography scan showed hypodensity lesion with some hyperdensity inside.Cranial routine magnetic resonance imaging showed long signal in T1-weighed image and T2-weighed image,with occasional short T1 signal inside.Contrast-enhanced magnetic resonance imaging revealed heterogeneous enhancement.All of 3 cases underwent brain biopsy because of the suspected diagnosis of brain tumor.Brain pathology showed the local necrosis and hemorrhage,dilated small vein with congestion or thrombosis.Neuronal degeneration,hyperplasia of gliocyte,hyperplasia of endotheliocyte in small blood vessels with reaction of histiocytes was also displayed.Duration from initial visit to final diagnosis was from 14 days to 2 months.Conclusions CoVT has various clinical and radiological manifestations and it is easy to misdiagnose as brain tumor.Careful analysis of clinical and imaging data could improve its diagnostic accuracy.Brain biopsy would also be helpful for diagnosis.

Association of hyperhomocysteinemia and methylenetetrahydrofolate reductase gene polymorphisms with ischemic stroke in Northwest Chinese population / 中国组织工程研究

BACKGROUND: It is proposed that elevated serum homocysteine is an important independent risk factor for ischemic stroke (IS), and 5, 10-methylenetetrahydrofolate reductase (MTHFR) is the key enzyme for homocysteine metabolism. The relationship between genetic mutation of MTHFR and IS remains controversial.OBJECTIVE: To examine the association of hyperhomocysteinemia and two MTHFR gene polymorphisms with IS in Northwest Chinese population.DESIGN: Case-control study.SETTING: Department of Neurology, First Hospital Affiliated to Jilin University, and Department of Neurology, Xijing Hospital, Fourth Military Medical University of Chinese PLA.PARTICIPANTS: Ninety-seven consecutive patients with ischemic stroke (71 males and 26 females) treated between November 2001 and May 2002were recruited, who were diagnosed by CT scan or MRI in the Department of Neurology, Xijing Hospital, Fourth Military Medical University of Chinese PLA. The control group consisted of 94 subjects (58 males and 36 females) without history of ischemic stroke. All the subjects were free of intracranial hemorrhage, cancer, renal dysfunction, and none used multivitamins or estrogen.METHODS: Serum homocysteine was measured by fluorescence polarization immunoassay. Polymerase chain reaction-restriction length polymorphism (PCR-RFLP) method was employed to detect the genotype at the two sites of C677T and A1298C in MTHFR gene.MAIN OUTCOME MEASURES: Serum homocysteine levels and the genotypic frequency frequencies of the two mutations of MTHFR.RESULTS: The 677T allele frequency was 59.3% in IS patients and 44.7% in the controls, showing significant differences (P=0.006), but no difference in 1298C allele frequency was detected between the two groups (22.7% vs 19.7%, P ＞ 0.05). Homozygous 677TT genotype was closely associated with hyperhomocysteinemie (P ＜ 0.01). In multivariate logistic regression analysis,677T gene mutation and hyperhomocysteinemie were all associated with the IS, with an OR of 1.870 and 1.031 (P＜ 0.05), respectively.CONCLUSION: Hyperhomocysteinemie is a risk factor of IS, and C677T mutation significantly increases homocysteine levels, and serves also as an independent genetic risk factor of IS.