1.Transcranial magnetic stimulation at low frequency can promote the recovery of neurological functioning after a stroke
Yushu JIANG ; Wei LI ; Lingzhi QIN ; Milan ZHANG ; Xiaojuan WANG ; Rui PANG ; Huiqin LIU ; Jiewen ZHANG
Chinese Journal of Physical Medicine and Rehabilitation 2022;44(7):577-582
Objective:To explore any effect of repeated transcranial magnetic stimulation (rTMS) on the recovery of neurological functioning and the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) and inflammatory factors after ischemic stroke.Methods:Sixty-four C57BL/6J mice were randomly divided into a normal control group, a model group, a sham stimulation group and an observation group, each of 16. All mice except those of the normal control group received middle cerebral artery occlusion using the suture method to model an ischemic stroke. After the modeling the observation group was given 1Hz rTMS daily for 7 consecutive days, while the sham stimulation group was given sham rTMS. After the intervention, Zea-Longa scores were used for all of the groups, and the size of the cerebral infarct was measured using triphenyltetrazolium chloride staining. The expression of NLRP3 around the cerebral infarction was detected using immunofluorescence, while that in the brain tissue was measured using Western blotting. The expression of interleukin-1β and IL-18 in the brain tissue was detected using enzyme-linked immunosorbent assays.Results:Compared with the normal control group, a significant increase was observed in the other groups′ average neurological function impairment scores. Expression of NLRP3, IL-1β and IL-18 in the model and sham stimulation groups also increased, with large cerebral infarcts in the cortex and hippocampus. Compared with the sham stimulation and model groups, there was a significant decrease in the average neurological dysfunction scores, the area of cerebral infarction in the cortex and hippocampus, as well as the expression of NLRP3, IL-1β and IL-18 in the observation group.Conclusions:Low-frequency rTMS can promote the recovery of damaged nerve function after an ischemic stroke, at least in mice. It can reduce the size of cerebral infarction, and inhibit neuronal pyroptosis, which is closely related to the down-regulation of NLRP3, IL-1β and IL-18 expression.
2.Clinical and imaging features and prognoses of myelin oligodendrocyte glycoprotein antibody associated disorders
Huiqin LIU ; Hongpei CUI ; Milan ZHANG ; Rui PANG ; Weifeng MA ; Yongshi TENG ; Jiewen ZHANG ; Yue HUANG ; Lipin YUAN ; Wei LI
Chinese Journal of Neuromedicine 2022;21(2):164-171
Objective:To explore the clinical and imaging features and prognoses of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD).Methods:Thirty-nine MOGAD patients, admitted to our hospital from January 2018 to April 2021, were chosen in our study. The clinical and imaging data and follow-up results of these patients at acute attack period (first-onset or relapse) were collected and their features were analyzed.Results:In these 39 patients with MOGAD, 20 patients (51.3%) had non-reversing course, and 19 patients (48.7%) had relapsing course. The clinical and imaging data of 55 episodes of these 39 patients were collected. In these 55 episodes, optic neuritis was noted in 27 episodes (49.1%), encephalitis was noted in 10 episodes (18.2%), brainstem encephalitis was noted in 8 episodes (14.5%), meningoencephalitis in 2 episodes (14.5%), myelitis in 3 episodes (5.5%), encephalomyelitis in 1 episode (1.8%), optic neuromyelitis in 1 episode(1.8%), optic neuritis+meningoencephalitis in 2 episodes (3.6%), and optic neuritis+encephalitis in 1 episode (1.8%). The positive rate of antinuclear antibody (ANA) was 11.1% (4/36); the cerebrospinal fluid results of 28 samples were collected from 22 patients, and CSF pleocytosis occurred in 67.9% of the samples with value of 54.89±67.70×10 6/L. Twenty-seven brain MRIs of 19 patients at the acute episode were collected; one completely normal MRI was recorded; among the remaining 26 MRIs, 6 were with one single lesion, 5 were with 2 lesions, and 15 were with 3 or more lesions; in terms of distribution, lesions involving brainstem and its adjacent structures were found in 9 MRIs, lesions involving diencephalon and deep gray matter were found in 7 MRIs, supratentorial white matter lesions were found in 13 MRIs, and cortical lesions were found in 13 MRIs. Meningeal enhancement were found in 4 contrast-enhanced brain MRIs (4/20). Long or short segmental myelitis in the spinal MRIs was noted in spinal lesions, involving cervical spinal cord, thoracic spinal cord and conus, and the "H" sign could be seen in the cross section. All patients received steroids therapy at the acute phase and the doses of steroids were tapered down gradually. Thirty-eight patients (97.4%) had good prognosis after 3 months of treatment. Conclusions:MOGAD is a disease entity widely involving the white matter, gray matter and meninges of the central nervous system with various clinical manifestations such as optic neuritis, encephalitis, brainstem encephalitis, meningoencephalitis and myelitis or a combination of the above. Immunotherapy is effective in most patients, but the recurrence rate is high, and some patients require long-term immunotherapy.
3.Clinical characteristics of neurological syndrome associated with anti-glutamic acid decarboxylase antibodies
Huiqin LIU ; Zeqin DONG ; Jiajia XU ; Milan ZHANG ; Rui PANG ; Yushu JIANG ; Lipin YUAN ; Yue HUANG ; Wei LI
Chinese Journal of Neuromedicine 2023;22(7):683-689
Objective:To explore the clinical characteristics of neurological syndrome associated with anti-glutamic acid decarboxylase (GAD) antibodies (Abs).Methods:Six patients with neurological syndrome associated with anti-GAD-Abs admitted to Department of Neurology, Henan Provincial People's Hospital from January 2019 to October 2022 were chosen. The clinical manifestations, imaging and laboratory results, therapeutic schedules, and follow-up prognoses of these patients were collected and summarized.Results:Three females and 3 males were included, with onset age of (54.3±17.7) years. Three patients had stiff-person syndrome (SPS), 1 had limbic encephalitis+generalized epilepsy, 1 had extralimbic encephalitis+occipital epilepsy, and 1 had cerebellar ataxia who was diagnosed with paraneoplastic syndrome associated with small cell lung cancer. Four patients had elevated level of thyroid peroxidase antibodies, and 1 patient was positive for overlapping anti-gamma aminobutyric acid B receptor antibodies and Amphiphysin antibodies. Two patients with SPS had failed lumbar puncture; 1 had slightly increased white blood cells and proteins in cerebrospinal fluid (CSF); the remaining 3 patients were basically normal. Specific oligoclonal bands in CSF were observed in 2 patients. Brain MRI showed abnormal signals in the bilateral occipital lobes in 1 patient, and no specific inflammatory lesions in other patients. All patients accepted corticosteroids and intravenous immunoglobulin/plasma exchange therapies; except for the one with paraneoplastic syndrome associated with small cell lung cancer, the remaining 5 patients had improved modified Rankin scale (mRs) scores at discharge and received long-term immunotherapy. Two patients with SPS had gradually aggravated symptoms, and mRs scores reached 5 at the last follow-up (one for 3 years and the other one for 2 years).Conclusions:The clinical manifestations of patients with neurological syndrome associated with anti-GAD-Abs include SPS, limbic encephalitis, extralimbic encephalitis, epilepsy and cerebellar ataxia; some of these patients have paraneoplastic syndromes. Immunotherapies are effective except for these patients with paraneoplastic syndromes. Some patients with SPS tend to have a chronic course and a poor prognosis.
4.Influencing factors for prognoses of pulmonary adenocarcinoma patients with leptomeningeal metastases: a single-center study
Weifeng MA ; Milan ZHANG ; Tao ZHANG ; Mengge ZHANG ; Linlin JIA ; Yongshi TENG ; Shuhua DAI ; Huiqin LIU ; Yushu JIANG ; Lingzhi QIN ; Lipin YUAN ; Wei LI
Chinese Journal of Neuromedicine 2022;21(1):28-33
Objective:To investigate the prognoses of pulmonary adenocarcinoma patients with leptomeningeal metastases (LM) and explore their influencing factors.Methods:A retrospective analysis was performed. The clinical data, imaging features and treatment plans of pulmonary adenocarcinoma patients with LM admitted to our hospital from January 2010 to June 2021 were collected. Overall survival (OS) was used as the prognostic evaluation criterion and patients were divided into good prognosis group (OS≥6 months) and poor prognosis group (OS<6 months) accordingly. Logistic regression analysis was used to evaluate the influencing factors for prognoses of pulmonary adenocarcinoma patients with LM. These patients were grouped according to different Karnofsky performance status (KPS) scores and different treatment methods, and survival curves were drawn to compare their OS.Results:A total of 173 pulmonary adenocarcinoma patients with LM were enrolled in the study, including 75 with good prognosis and 87 with poor prognosis. There were significant differences in the KPS scores, pulmonary adenocarcinoma lesion controlled status, giving third generation tyrosine kinase inhibitor (TKI) therapy or not, giving systemic chemotherapy and/or whole brain radiotherapy or not between the two groups ( P<0.05). Multivariate Logistic regression analysis showed that KPS scores and pulmonary adenocarcinoma lesion controlled status were independent influencing factors for prognoses ( OR=4.186, 95%CI: 1.583-11.070, P=0.004; OR=4.198, 95%CI: 1.499-11.760, P=0.006). Survival curves showed median OS of 8.2 months for all patients ( 95%CI: 6.5-9.8). The OS in patients with low-risk(KPS scores≥60) was significantly higher than that in patients with high-risk(KPS scores<60), that in patients accepted TKI treatment was significantly higher than that in patients not accepted TKI treatment, and that in patients accepted TKI and systemic chemotherapy was significantly higher than that in patients accepted TKI alone ( P<0.05). Conclusion:Patients with high KPS scores and controlled pulmonary adenocarcinoma can have relatively good prognosis; TKI treatment and combination therapy may prolong OS of these patients.
5.Effect of Wendantang on Expression of TrKB and CREB in Hippocampus of Rats with Schizophrenia
Yuan ZHANG ; Jinhua ZHU ; Milan ZHANG ; Jing CHEN ; Hongjiao WAN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(3):26-33
ObjectiveTo study the effects of Wendantang on the expression of receptor tyrosine kinase receptors B (TrkB) and cyclic adenosine monophosphate response element binding protein (CREB) in the hippocampus of rats with schizophrenia (SCZ). MethodFifty-four rats were randomly divided into a normal group, a model group, high (40 g·kg-1), medium (20 g·kg-1), low-dose (10 g·kg-1) Wendantang groups, and a clozapine (0.02 g·kg-1) group, with 9 rats in each group. All groups of rats were given corresponding drugs by gavage for 21 d. The normal and model groups were given equal volume of normal saline. Except the normal group, the other 5 groups were given 0.6 mg·kg-1 dizocilpine maleate (MK-801) at 2 hours after the last administration for intraperitoneal injection to induce the rat model of SCZ. The level of spontaneous activity of rats was observed by open field experiment. Histomorphological changes in the hippocampal CA1 area was observed by hematoxylin-eosin (HE) staining. The protein expression levels of TrKB, phosphorylated-TrKB (p-TrKB), CREB, and phosphorylated-CREB (p-CREB) were detected by Western blot. The protein expression levels of TrKB and CREB in the hippocampal CA1 area were observed by immunohistochemistry. The mRNA expression levels of TrKB and CREB in the hippocampus were detected by real-time quantitative polymerase chain reaction (Real-time PCR). ResultAs compared with the normal group, the level of spontaneous activity in the model group was significantly increased (P<0.01). The arrangement of neuronal cells in the hippocampus CA1 area was loose and disorganized, and some neurons were denatured in the model group. The protein expression levels of TrKB, p-TrKB, CREB, and p-CREB in the hippocampus, the protein expression levels of TrKB and CREB in the hippocampal CA1 area, and the mRNA expression of TrKB and CREB in the hippocampus were significantly decreased (P<0.05, P<0.01). As compared with the model group, the level of spontaneous activity in all Wendantang groups were significantly decreased (P<0.01). The neuronal cells in the hippocampal CA1 area of rats in all Wendantang groups were relatively neatly and closely arranged, the morphology of cell body was more regular, and neurons degeneration was rarely observed. The protein expression level of TrKB in the hippocampus was significantly higher in the medium and low-dose Wendantang groups (P<0.05). The protein expression levels of p-TrKB, CREB, and p-CREB in the hippocampus were significantly higher in all Wendantang groups (P<0.05). The protein expression of TrKB in the hippocampal CA1 area was significantly increased in all Wendantang groups (P<0.05, P<0.01). The protein expression of CREB in the hippocampal CA1 area was significantly increased in the medium and low-dose Wendantang groups (P<0.01). The mRNA expression of TrKB in the hippocampus was significantly increased in the high and low-dose Wendantang groups (P<0.05, P<0.01). The mRNA expression of CREB was significantly increased in the medium and low-dose Wendantang groups (P<0.05, P<0.01). ConclusionWendantang can prevent the occurrence and development of SCZ and cognitive impairment by decreasing the level of spontaneous activity, improving the pathological damage of hippocampal neurons, and increasing the expression levels of TrKB, p-TrKB, CREB, and p-CREB.