Hongzhi Guan

Temporal lobe epilepsy with amygdala enlargement: a subtype of temporal lobe epilepsy

BackgroundSome recent studies suggest that some imaging-negative temporal lobe epilepsy (TLE) had significant amygdala enlargement (AE). Contradictory data were also reported in previous studies regarding the association between AE and TLE. The present study was to investigate the clinical characters of a group of TLE with AE and compare the amygdala volume of the same patient before and after antiepileptic drugs treatment by a larger sample size.MethodsThis study recruited 33 mesial TLE patients with AE and 35 healthy volunteers. The clinical history, seizure semiology, electroencephalogram (EEG), fluorodeoxyglucose-positron emission tomography (FDG-PET) and amygdala volume were investigated. The amygdala volume were compared between ipsilateral and contralateral sides, TLE patients and 35 healthy controls, and patients at first and follow-up visit by 3.0 T MRI.ResultsAverage seizure onset age was 42.0 years (SD 14.3). All patients had complex partial seizures, fourteen had occasional generalized tonic-clonic seizures which often happened during sleep. Ninety percent patients suffered from anxiety or depression. Thirty percent patients had memory decline. Interictal epileptiform discharges appeared predominantly in the anterior or inferior temporal area ipsilateral to AE. Interictal FDG-PET showed regional glucose hypometabolism in the ipsilateral temporal lobe. No hippocampal sclerosis (HS) was suspected in all patients. 22 patients demonstrated good seizure control and significantly reduced volume of the enlarged amygdala after treatment (P < 0.01). The other 11 patients showed initial response to treatment, followed by a gradual increase in seizure frequency over time, and no volume change of the enlarged amygdala after treatment.ConclusionsTLE with AE probably represents a distinct nosological and probably less homogeneous syndrome which is most likely a subtype of TLE without ipsilateral HS. The chronic and long lasting inflammatory processes or focal cortical dysplasia could lead to amygdala enlargement possibly.

CSF findings in patients with anti-N-methyl-d-aspartate receptor-encephalitis

PURPOSE Anti-NMDAR-encephalitis is a recently described form of autoimmune encephalitis. Here, we characterize CSF changes in Chinese patients with anti-NMDAR encephalitis, and explore the relationship between CSF findings and disease outcome. METHODS The presence of NMDAR antibodies in serum or CSF samples was evaluated in patients diagnosed with encephalitis between October 1, 2010 and August 1, 2014 at the West China Hospital. All patients fulfilling our diagnostic criteria were included and CSF findings were analyzed. Patient outcome was assessed after 4, 8, 12, 16, 20, and 24 months using the modified Rankin scale (mRS). RESULTS Out of 3000 people with encephalitis screened, 43 patients were anti-NMDAR antibody positive in CSF or serum and included in this study. 62.8% of the patients identified with positive CSFs had positive serum anti-NMDAR samples, while 100% patients with positive serum had positive CSF samples. In the CSF white cell counts were elevated in 58.1% of cases; protein was increased in 18.6%; QAlb>Qlim(Alb) of the blood-CSF barrier was found in 29.3%; intrathecal immunoglobulin synthesis was detected in 17.1%, and 39.5% patients exhibited increased CSF pressures. A longer follow-up period was associated with better outcomes. There was no relationship between changes in CSF findings and outcome. CONCLUSION The sensitivity of NMDA receptor antibody testing is higher in CSF compared to serum. Other CSF abnormalities are present in some patients with Anti-NMDAR-encephalitis, however these changes do not appear to affect prognosis.

Limbic Encephalitis Associated with Anti-γ-aminobutyric Acid B Receptor Antibodies: A Case Series from China

Background:Autoimmune encephalitis associated with antibodies against &ggr;-aminobutyric acid B receptor (GABAB R) in patients with limbic encephalitis (LE) was first described in 2010. We present a series of Han Chinese patients for further clinical refinement. Methods:Serum and cerebrospinal fluid (CSF) samples from patients referred to the program of encephalitis and paraneoplastic syndrome of Peking Union Medical College Hospital were tested with indirect immunofluorescence. Clinical information of patients with anti-GABAB R antibody positivity was retrospectively reviewed, and descriptive statistical analysis was performed. Results:All eighteen anti-GABAB R antibody-positive cases had limbic syndromes, and electroencephalogram (EEG) or neuroimaging evidence fulfilled the diagnostic criteria of LE. Four patients had additional antibodies against Hu in serum and one had anti-N-methyl-d-aspartate receptor antibody in both sera and CSF. Seventeen (17/18) patients presented with new-onset refractory seizure or status epileptics. Twelve (12/18) patients had memory deficits, 11 (11/18) patients had personality change, 7 (7/18) patients had disturbance of consciousness, and 3 (3/18) patients showed cerebellar dysfunction. One patient with LE had progressive motor and sensory polyneuropathy. Lung cancer was detected in 6 (6/18) patients. Ten (10/18) patients showed abnormality in bilateral or unilateral mediotemporal region on magnetic resonance imaging. Ten (10/18) patients had temporal lobe epileptic activity with or without general slowing on EEG. Seventeen patients received immunotherapy and 15 of them showed neurological improvement. Four patients with lung cancer died within 1–12 months due to neoplastic complications. Conclusions:Our study demonstrates that most Han Chinese patients with anti-GABAB R antibody-associated LE have prominent refractory epilepsy and show neurological improvement on immunotherapy. Patients with underlying lung tumor have a relatively poor prognosis. Testing for anti-GABAB R antibodies is necessary for patients with possible LE or new-onset epilepsy with unknown etiology.

Detection of Listeria monocytogenes in CSF from Three Patients with Meningoencephalitis by Next-Generation Sequencing

Background and Purpose Encephalitis caused by Listeria monocytogenes (L. monocytogenes) is rare but sometimes fatal. Early diagnosis is difficult using routine cerebrospinal fluid (CSF) tests, while next-generation sequencing (NGS) is increasingly being used for the detection and characterization of pathogens. Methods This study set up and applied unbiased NGS to detect L. monocytogenes in CSF collected from three cases of clinically suspected listeria meningoencephalitis. Results Three cases of patients with acute/subacute meningoencephalitis are reported. Magnetic resonance imaging and blood cultures led to a suspected diagnosis of L. monocytogenes, while the CSF cultures were negative. Unbiased NGS of CSF identified and sequenced reads corresponding to L. monocytogenes in all three cases. Conclusions This is the first report highlighting the feasibility of applying NGS of CSF as a diagnostic method for central nervous system (CNS) L. monocytogenes infection. Routine application of this technology in clinical microbiology will significantly improve diagnostic methods for CNS infectious diseases.

Changing Brain Metabolism Patterns in Patients With ANMDARE: Serial 18F-FDG PET/CT Findings.

Purpose The aim of this study was to describe brain metabolic changing patterns demonstrated by serial brain FDG PET/CT scans and their relationship with the clinical course in patients with anti-N-methyl-d-aspartate receptor encephalitis (ANMDARE). Patients and Methods Eighteen serial PET scans of 8 patients with ANMDARE were reviewed. All the 18 PET scans were divided into 4 groups according to studies timing in different clinical course: group A, the acute and subacute phase; group B, early recovery phase; group C, recovery phase; and group D, relapsing phase. Antibody levels of ANMDARE of all these patients were tested at the same time. The PET images of each group were analyzed visually and also compared with 10 age- and sex-matched normal controls using voxel-wise statistical parametric mapping analysis (SPM5). Results Variable brain metabolic patterns and its association with the clinical course and the levels of NMDA antibody were demonstrated by FDG PET images. First, severe hypometabolism in bilateral occipital lobes and relatively mild hypermetabolism in the partial frontal and basal ganglia in acute and subacute phase, the level of antibody was high. Second, in early recovery phase when the symptoms was partially improved, extensive cortical hypometabolism was observed, and the level of antibody was low. Third, the patients in the recovery phase have no obvious neurological and psychiatric symptoms; PET images were nearly normal, and the antibodies tests were all negative, correspondingly. Fourth, 3 scans of relapsing phase presented heterogeneous brain metabolic abnormalities. Conclusions There existed a specific serial brain metabolic changing pattern that correlated with the clinical course and antibody level in ANMDARE.

Comparison of myelin oligodendrocyte glycoprotein (MOG)-antibody disease and AQP4-IgG-positive neuromyelitis optica spectrum disorder (NMOSD) when they co-exist with anti-NMDA (N-methyl-D-aspartate) receptor encephalitis

BACKGROUND Myelin oligodendrocyte glycoprotein (MOG)-antibody (ab) disease and AQP4-IgG-positive neuromyelitis optica spectrum disorder (NMOSD) can co-exist with anti-NMDA (N-methyl-D-aspartate) receptor encephalitis (NMDARe). OBJECTIVES To characterize MOG-ab disease and AQP4-IgG-positive NMOSD during NMDARe. METHODS We analyzed all the patients with overlapping MOG-ab disease and NMDARe (MNOS) and patients with AQP4-IgG-positive NMOSD and NMDARe (ANOS) in our hospital and compared those data with data from systematically review of previously published reports. RESULTS In our cohorts, 11.9% patients with MOG-ab disease and 0.6% patients with NMOSD had overlapping NMDARe (P < 0.01). After treatment with steroids and/or intravenous immunoglobulin (IVIg), the median modified Rankin Scale (mRS) of the MNOS group decreased significantly during attacks associated with or without NMDARe (P < 0.01 for both), while that of the ANOS group did not (attack: P < 0.05; attack associated with NMDARe: P > 0.05). Analyzed together with previously reported cases, 6% patients with MNOS and 40% patients with ANOS also used rituximab or cyclophosphamide after steroids and/or IVIg (P < 0.05) during attacks associated with NMDARe. CONCLUSION Compared with NMOSD, MOG-ab disease may more commonly co-exist with NMDARe. MNOS patients respond better to steroids and IVIg than do ANOS patients during attacks associated with NMDARe.

Cranial and lumbosacral hypertrophic pachymeningitis associated with systemic lupus erythematosus: A case report.

Background:Hypertrophic pachymeningitis (HP) is a chronic disease characterized by inflammatory hypertrophy and fibrosis of dura mater. It can be divided into cranial and spinal forms depending on the location of the lesion. HP involving 2 separate sites simultaneously is quite uncommon. Case summary:This study presents a case of a 49-year-old woman with pathologically confirmed cranial and lumbosacral hypertrophic pachymeningitis associated with systemic lupus erythematosus (SLE), which is a rare etiology of HP. She experienced persistent numbness and pain of the left lower limb, followed by headache and seizures. In laboratory tests, levels of erythrocyte sedimentation rate and C-reactive protein were elevated, and antinuclear antibodies and anti–double-strand deoxyribonucleic acid (DNA) antibodies were detected. Magnetic resonance imaging revealed dural thickening with homogenous gadolinium enhancement both at lumbosacral level and over cerebral convexities. Histology suggested chronic inflammation in spinal dura mater with extensive fibrosis, dense lymphoplasmacytic infiltrate, and focal vasculitis. Treatment with corticosteroids and cyclophosphamide was started with significant clinical and radiological improvement. Conclusion:HP is etiologically heterogeneous. Despite its rarity, SLE should be considered in the differential diagnosis of HP. Early recognition and therapy may provide an optimal outcome.

Autoimmune Encephalitis: An Expanding Frontier of Neuroimmunology

IntRoductIon Discovery of the spectrum of autoimmune encephalitis (AIE) is among the most attractive events of neurology in the past decade. AIE includes a heterogeneous group of encephalitic syndromes, which generally include two major categories: classic paraneoplastic limbic encephalitis (LE) associated with the so-called well-characterized onconeural autoantibodies against intracellular neuronal antigens (e.g., Hu, Ma2, etc.) and new-type AIE associated with autoantibodies to the neuronal surface or synaptic antigens.[1] Paraneoplastic LE occurs in the context of malignant tumors and results from an immunological response to tumor antigens, which mimic intracellular antigens expressed in neurons. The autoantibodies in this situation might not be pathogenic but can serve as diagnostic markers for paraneoplastic LE. The new-type AIE occurs in association with pathogenic autoantibodies against synaptic receptors or membrane antigens, and the binding of autoantibodies to their targets causes neuronal dysfunction, usually irreversibly. Over a dozen new-type autoantibodies have been identified since the discovery of anti-N-methyl-D-aspartate receptor (NMDAR) antibody by Dalmau et al. in 2007.[2] Most of these autoantibodies associated with specific and well-characterized symptoms and the detection of these autoantibodies confirm the diagnosis. Since the introduction and establishment of the diagnostic test for anti-NMDAR antibody in China in 2010,[3] hundreds of cases of AIE have been diagnosed and treated, which has changed our clinical approach to encephalitis management. The following sections will focus on a few recent advances as well as related clinical research on AIE in China. epIdeMIology Autoimmune encephalitis is not a rare cause of encephalitis. However, it is still difficult to estimate its incidence. Anti-NMDAR encephalitis is the major component of the disease spectrum. According to the UK-based prospective surveillance study in children, the incidence of anti-NMDAR encephalitis is 0.85 per million children annually.[4] No data about incidence in adults is available. Gable et al.[5] reported that the frequency of anti-NMDAR encephalitis surpassed that of individual viral etiologies in young individuals enrolled in the California Encephalitis Project. Increasing numbers of AIE cases have been identified in China since the autoantibody assay was introduced to some neurological centers after 2010. The frequency of AIE also surpassed that of viral encephalitis in our project in Peking Union Medical College Hospital (PUMCH). A total of 4106 cases of encephalitis of unidentified etiology were registered to PUMCH encephalitis and paraneoplastic neurological syndrome project for autoantibody assay between May, 2013 and December, 2014. A total of 531 cases (12.9%) were positive for autoantibodies, including 423 cases (10.3%) with anti-NMDAR antibodies, 68 cases (1.66%) with anti-leucine-rich glioma-inactivated 1 (LGI1) antibodies, thirty cases (0.73%) with anti-γ-aminobutyric acid B Autoimmune Encephalitis: An Expanding Frontier of Neuroimmunology

A Chinese female Morvan patient with LGI1 and CASPR2 antibodies: a case report

BackgroundMorvan syndrome is a rare disorder characterized by the combination of peripheral nerve hyperexcitability, encephalopathy and dysautonomia with marked insomnia. It was reported to have association to antibodies to voltage-gated potassium channels including contactin associated protein-like 2 antibodies (CASPR2-Ab) and leucine-rich glioma inactivated protein 1 antibodies (LGI1-Ab). LGI1-Ab was reported to associate with seizures, amnesia, confusion, hyponatraemia and a good prognosis, while CASPR2-Ab with peripheral presentations, probable risk for tumor and a poor prognosis. The vast majority of Morvan syndrome patients were male, with normal magnetic resonance imaging of the brain.Case presentationWe report a female case presenting with a combination of bilateral leg pain, widespread myokymia, memory disturbance, seizure, hyperhidrosis and insomnia. She had antibodies targeting CASPR2 and LGI1, tested by the indirect immunofluorescence test, which demonstrated the diagnosis of typical Morvan syndrome as well as classical limbic encephalitis. Cranial MRI revealed bilateral hyper-intensity of the medial temporal lobe, insular lobe and basal ganglia on T2/FLAIR and DWI sequence. As the treatment carried on, her serum LGI1-Ab disappeared and her memory loss, seizure and confusion quickly relieved. But her peripheral presentations did not relieve until serum CASPR2-Ab turned negative. Intravenous immunoglobulin treatment showed limited efficacy while she achieved almost complete remission with corticosteroids therapy.ConclusionsThis case provides a rare female resource of Morvan syndrome, which is the first patient with both CASPR2-Ab and LGI1-Ab positive Morvan syndrome in China and one of the few female patients with Morvan syndrome reported so far. Through the detailed analysis of her clinical course, the diverse and overlapping clinical phenotype of CASPR2-Ab and LGI1-Ab in patients with Morvan syndrome was obvious and interesting.

Anti-Ma2 Paraneoplastic Encephalitis Associated with Ileal Lymphoma.

To the Editor: Ma2 antibody-mediated encephalitis is a rare type of paraneoplastic neurological syndrome (PNS) present with various clinical symptoms. Lung or testicular germ-cell malignancies are the most commonly associated tumors.[1] Here, we reported a patient with a Ma2 antibody-mediated encephalitis related to ileal lymphoma. A 62-year-old male with a history of hypertension and diabetes mellitus presented with 6 months of mental and behavior change. He had memory loss and visual hallucinations since September 2013. The patient gained 12.5 kg of bodyweight increase due to increased appetite and was diagnosed as bulimia nervosa at a local hospital. He also stated dizziness, unstable walking and diplopia with ptosis of bilateral eyelids. He felt sleepy and drowsy during daytime but sleepless at night. He also experienced urinary incontinence occasionally. On admission, the patient was alert. The mini-mental state examination was 18/30, indicating moderate impairment of memory. The patient had vertical gaze paresis, unable to look upward and downward with horizontal nystagmus. His muscle power and muscle tone were normal with diminished tendon reflexes. He had unstable gait and could not walk in a straight line. Brain magnetic resonance imaging showed abnormality in medial temporal lobe and diencephale [Figure 1]. A lumbar puncture yielded clear cerebrospinal fluid (CSF) with normal open pressure. CSF exhibited a white blood cell count of 38 × 106/L, a protein level of 0.73 g/L, normal level of glucose and chloride and no detectable oligoclonal bands. The cytological analysis yielded no malignant cells. Paraneoplastic antibody testing (EUROIMMUN AG, Germany) revealed that anti-Ma2 antibodies were positive in both CSF and serum. The patient developed hypothermal episodes with bradycadia and decreased the level of consciousness which was remitted after intravenous immunoglobulin (IVIg) treatment. Positron-emission tomography revealed hypermetabolism in the right hippocampus and left parahippocampal gyrus while hypermetabolism in ileal lesions indicated malignant lesion. After the resection of his terminal ileum and the right superior colon, pathological examination confirmed the diagnosis of submucosal follicular lymphoma. The patient received chemotherapy for lymphoma but deceased 1-month later due to septic shock with leucopenia. Figure 1 Neuroimaging and pathological findings of the patient. Brain magnetic resonance imaging fluid-attenuated inversion recovery sequences showed abnormity in medial temporal lobe (a) and diencephale (b). Resected tissue of terminal ileum demonstrated a focal ... Anti-Ma2 encephalitis differs from typical paraneoplastic limbic encephalitis for most patients developed combination of the limbic system, diencephalon or brainstem encephalitis. Hypothalamus and pituitary gland could even be involved.[2] It was reported in young patients with testicular cancer or tumors of lung and breast.[3] We described the clinical and pathological findings in a patient with Ma2 antibody-mediated brain stem/limbic encephalitis associated with submucosal follicular lymphoma of the ileum. It broadens the spectrum of tumor associated with this rare PNS. The clinical manifestation and neuroimaging of this patient suggested a combined limbic, diencephalic and brainstem lesions. In fact, only 26% of the patients had classical limbic encephalitis in the literature. Excessive daytime sleepiness, as presented, in this case, affected 32% of the patients, sometimes with narcolepsy cataplexy.[1] After receiving oncological treatment and immunotherapy, including steroids, IVIg and plasma exchange, some patients have neurological improvement. But nearly half of the patients deteriorated after treatment. Anti-Ma2-associated encephalitis has a unique clinical presentation and should not be overlooked considering its remarkable involvement of the limbic system, diencephalon and brainstem. This disorder should be suspected in patients with subacute involvement of one or more of these three brain regions and CSF abnormalities suggesting an inflammatory process.