Clinical Characteristics of Autoimmune Disease with Dual Seropositive Antibodies of Leucine-rich Glioma Inactivated 1 and Contactin-associated Protein 2 / 中国医学科学院学报

Objective To explore the clinical characteristics of autoimmune disease with dual seropositive antibodies of leucine-rich glioma inactivated 1(LGI1)and contactin-associated protein 2(Caspr2).Methods The clinical data of seven patients with dual seropositive LGI1 and Caspr2 antibodies who were admitted to the Neurology Department of Peking Union Medical College Hospital from July 2014 to December 2017 were retrospectively analyzed.Results Central,peripheral and autonomic nervous systems were all involved in the seven cases;100%(7/7)presented with insomnia,myokymia,neuropahic pain and hyperhydrosis;71%(5/7)showed memory decline or psychiatric and behavioral symptoms;57%(4/7)had urinary hesitation or constipation;and 43%(3/7)had seizure.Electromyography showed 100%(6/6) of the patients had prolonged afterdischarges following normal M waves and/or abnormal spontaneous firing.Electroencephalography revealed slow waves or basic rhythm slowing in 71%(5/7)of patients.Electrocardiography showed sinus tachycardia,axis deviation,and prolonged QT intervals in 71%(5/7)of patients.One patient died from arrhythmia before immunotherapy.One died from pulmonary infection after immunotherapy.Improvement with immunotherapy was documented in the other five cases.No relapse was noted during the 1-2-year follow-up.Conclusions Autoimmune disease with dual seropositive antibodies of LGI1 and Caspr2 can diffusely affect the central,peripheral,and autonomic nervous systems.The possibility of this disease should be considered in patients with acute and subacute onset of neuropsychiatric symptoms,especially in patients with accompanying insomnia,myokymia,and hyperhydrosis.

Utility and Safety of Intrathecal Methotrexate Treatment in Severe Anti-N-methyl-D-aspartate Receptor Encephalitis: A Pilot Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a treatable autoimmune neurologic syndrome that occurs with or without tumor association. However, some severe cases are refractory to systemic immunotherapy. This pilot study aimed to evaluate the utility and safety of intrathecal methotrexate injection for severe patients with anti-NMDAR encephalitis who did not respond to first-line immunotherapy.</p><p><b>METHODS</b>Intrathecal injections with methotrexate and dexamethasone were performed weekly in four legible patients within consecutive 4 weeks. Cerebrospinal fluid (CSF) was collected at baseline and each time of intrathecal injection for identification of anti-NMDAR antibody titers.</p><p><b>RESULTS</b>Significant clinical improvement was observed in three patients associated with a stepwise decrease of CSF anti-NMDAR antibody titers (maximum: 1/320 to minimum: 1/10). After 2 months of follow-up, they were able to follow simple commands and had appropriate interactions with people (modified Rankin scale [mRS] of 0-2). At 12 months of follow-up, they all had returned to most activities of daily life (mRS of 0), and no relapses were reported. One patient showed no clinical improvement and died of neurologic complications.</p><p><b>CONCLUSIONS</b>Intrathecal treatment may be a potentially useful supplementary therapy in severely affected patients with anti-NMDAR encephalitis. Further large cohort study and animal experiment may help us elaborate the utility of intrathecal injection of methotrexate and its mechanism of action.</p>

Diagnosis of Muscular Dystrophy Using Western Blot with Micro-sample of Muscle / 中国医学科学院学报

<p><b>OBJECTIVE</b>To diagnose muscular dystrophy using Western blot (WB) by improving the method of the protein extraction.</p><p><b>METHOD</b>Firstly,we compared the effect of different sample buffer solutions and processing Methods on the extraction of muscle protein in rats,then selected the appropriate extracting method and the process of the muscular protein.</p><p><b>RESULTS</b>We put the selected sample buffer into the micro-sample,then mixed. The concentration of the extracting protein was much more,and the loss during the process was much less. We extracted enough protein in 62 cases. The protein bands were showed clearly by WB,and the abnormal protein bands were shown in some patients. Compared with the Results of immunohistochemical staining detected the severe abnormal expressions of Dys-R,Dys-C,and Dys-N in the specimens,we did not detect the corresponding target band in WB. We detected the target protein band of the specimens were abnormal position,light or normal staining in WB,while Dys were mildly expressed in immunohistochemical staining.</p><p><b>CONCLUSIONS</b>The improved protein extraction method can save the muscle tissue,and the protein bands can be used for diagnosing the muscular dystrophy. For clinically suspected patients with dystrophinopathy,if normal or mild deficiency is shown by immunohistochemistry,WB should be applied to detect the dystrophin protein band.</p>

Limbic Encephalitis Associated with Anti-γ-aminobutyric Acid B Receptor Antibodies: A Case Series from China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Autoimmune encephalitis associated with antibodies against γ-aminobutyric acid B receptor (GABA B R) in patients with limbic encephalitis (LE) was first described in 2010. We present a series of Han Chinese patients for further clinical refinement.</p><p><b>METHODS</b>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-GABA B R antibody positivity was retrospectively reviewed, and descriptive statistical analysis was performed.</p><p><b>RESULTS</b>All eighteen anti-GABA B 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.</p><p><b>CONCLUSIONS</b>Our study demonstrates that most Han Chinese patients with anti-GABA B 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-GABA B R antibodies is necessary for patients with possible LE or new-onset epilepsy with unknown etiology.</p>

Application of magnetic resonance contrast agent ultrasmall superparamagnetic iron oxide combined with magnetic transfer imaging in the animal model of experimental allergic encephalopathy / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the sensitivity of magnetic resonance contrast agent ultrasmall superparamagnetic iron oxide (USPIO) enhancement scan in detecting experimental allergic encephalopathy (EAE) lesions and the change of magnetic transfer of USPIO enhancement lesions in the animal model of EAE.</p><p><b>METHODS</b>The routine T1-weighted imaging, T2-weighted imaging, three dimensional T1 magnetic transfer, three dimensional T1 no magnetic transfer, Dimeglumine Gadopentetate injection (Gd-DTPA) enhancement, and USPIO enhancement scan were performed in 11 EAE rats and 10 control rats respectively. The sensitivity of USPIO and Gd-DTPA enhancement in detecting the lesions in EAE rats was calculated. Magnetic transfer ratio (MTR) of USPIO enhancement area for the first time in EAE rats and MTR of the same area of the last scan were calculated respectively. HE and myelin staining of brain tissues were performed.</p><p><b>RESULTS</b>No abnormally enhanced lesions were showed in EAE rats' brain in Gd-DTPA enhancement scan, while abnormally enhanced lesions were showed in 11 EAE rats' brain in USPIO enhancement scan. The MTR value of USPIO enhancement area for the first time was significantly different from MTR of the same area of the last scan in EAE rats (P < 0.05). Inflammation cells and demyelination lesions were found in USPIO enhancement area histopathologically. There were no positive findings in control rats.</p><p><b>CONCLUSIONS</b>The sensitivity of USPIO enhancement scan in detecting EAE lesions was high. Magnetic transfer imaging, together with USPIO enhancement scan, was helpful to determine the features of the EAE lesions.</p>

Biological effect of hepatocyte growth factor gene transfection to rat cerebral ischemic model:the experimental study / 中华放射学杂志

Objective To investigate hepatocyte growth factor(HGF)gene expression and biological effect after gene transfection into penumbra tissue in rat cerebral ischemic model.Methods Human HGF cDNA was ligated to pIRES2-EGFP vector.The recombinant plasmid was transfected into the penumbra tissue with liposome.Brains of treated and control animals were analyzed 7 days later.Expression of HGF protein was determined by fluorescence microscopy and immunohistochemistry.Vessel numbers were quantified.Changes of cerebral blood flow(CBF)was detected by CT perfusion.Results Enzymatic digestion and electrophoresis confirmed that HGF fragment had been correctly cloned into BamH I and Sal I sites of pIRES2-EGFP.After HGF gene transfection,expression of HGF in transfected neurocytes was observed with fluorescence microscopy and immunohistochemistry.The number of vessels was significantly increased in penumbra tissue transfected with HGF vector as compared with control vector(46.71?7.11, 20.43?3.21,18.00?3.27,respective,F = 74.447;P

Clinicopathological observation On two sensory,neuronopathy cases / 中华神经科杂志

Objective To determine the clinical features,neurophysiological characteristics and cervical magnetic resonance imaging of sensory neumnopathy,and to describe the pathology of skin nerve, sural nerve and spinal dorsal columns.Methods Two patients who died from sensory neuron disease (SND)after infection of digestive tract were discussed including clinical features and ancillary tests which included neurophysiology and pathology of peripheral nerve and spinal dorsal columns.Associated documents are reviewed.Results Early ataxia,widespread sensory symptoms and global loss of deep tendon reflex were the distinctive signs of SND,which was characterized by non-length-dependent abnormalities of sensory nerve action potentials,a hallmark of ganglionopathies.The second patient showed normal cervical magnetic resonance imaging possibly because of short course of disease,while diffuse hyperintensity in the spinal posterior columns of SND was reported.Demyelination of spinal posterior columns and loss of mostly large diameter nerve fibers without regeneration clusters were the main pathological features.Conclusions The distinctive clinical features and neurophysiological characteristics of SND indicate that peripheral sensory nerve fibers are widely damaged.Pathology of spinal posterior columns confirm that central sensory pathway are impaired which allow the localization of the pathologic site to the dorsal root ganglion neurons.Cervical spinal MRI of SND are possibly normal at early phase.