Paraneoplastic cerebellar degeneration(PCD),which is rare in clinical practice,is closely related to autoimmunity.Cases positive for anti-Yo antibodies(anti-Purkinje cytoplasmic antibody 1)are the main subtype of PCD....Paraneoplastic cerebellar degeneration(PCD),which is rare in clinical practice,is closely related to autoimmunity.Cases positive for anti-Yo antibodies(anti-Purkinje cytoplasmic antibody 1)are the main subtype of PCD.PCD is subacute cerebellar degeneration,and while it progresses over weeks to months,its resultant deficits last much longer.Cancer patients with anti-Yo antibody-positive PCD are very rare.Most of them are breast cancer or ovarian cancer patients but also occasionally lung cancer patients.CASE SUMMARY A 61-year-old woman presented with sudden vertigo,nausea,and vomiting for approximately 10 d.The patient's neurological examination showed torsion with downbeat nystagmus and ataxia of the right limb and trunk.Laboratory examination found that the patient's cerebrospinal fluid and serum were anti-Yo antibody-positive,positron emission tomography computed tomography showed an increased metabolic rate in the retroperitoneal lymph nodes,and the pathology of lymph node punctures in the retroperitoneum and neck suggested adenocarcinoma of the pancreaticobiliary duct,which strengthens the hypothesis of paraneoplastic origin.Intravenous immunoglobulin(IVIg)0.4 g/kg/d for 5 d and methylprednisolone 160 mg for 3 d were initiated,which was reduced to 80 mg for 3 d and then to 40 mg for 7 d.After treatment with IVIg and a steroid,the patient's vertigo and ataxia alleviated.CONCLUSION The patient's vertigo and ataxia alleviated after treatment,suggesting that early immunotherapeutic intervention may have certain value in stopping neurological loss.展开更多
OBJECTIVE We have recently reported that cysteinyl leukotriene(Cys LT) signaling plays an important role in microglial interleukin(IL)-1β secretion and subsequent neurotoxicity.The present study aimed to examine micr...OBJECTIVE We have recently reported that cysteinyl leukotriene(Cys LT) signaling plays an important role in microglial interleukin(IL)-1β secretion and subsequent neurotoxicity.The present study aimed to examine microglial morphological changes and the upstream molecular underlying IL^(-1)β production in Cys LT receptor agonist leukotriene D4(LTD4)-treated BV2 microglia in vitro.METHODS Twenty-four hours after murine microglial BV2 cells were stimulated with LTD4(1-100 nmol·L^(-1)),the cell proliferation and morphology were observed.The expression level of cysteinyl aspartate-specific protease 1(CASP1) protein was measured by Western blotin BV2 cells.In addition,BV2 cells were pretreated with or without CysLT1 receptor antagonist montelukast for 1 h and the effects of monte-lukaston LTD4-stimulated microglial activation and CASP1 expression were evaluated.RESULTS The number of BV2 cells had an increasing tendency after 24 h treatment with LTD4,but no significant differences were observed between the control and LTD4-treated cells(P>0.05).Under basal and resting conditions,BV2 microglial cells displayed a ramified morphology.However,LTD4 at 100 nmool·L^(-1) drove microglial morphological changes from a ramified towards an amoeboid shape.The expression of CASP1 protein was significantly upregulated in 100 nmool·L^(-1) LTD4-treated BV2 microglia(P<0.01).Furthermore,pretreatment with CysLT1 receptor antagonist montelukast prevented cell morphological changes and suppressed the increased CASP1 expression in LTD4-treated BV2 cells(P<0.05).CONCLUSION Cys LT receptor agonist LTD4 induces morphological changes and CASP1 expressionin BV2 microglia,which can be inhibited by CysLT1 antagonist.These results suggest the involvement of Cys LT signaling in microglial morphological changes and CASP1 expression.展开更多
基金Natural Science Foundation of Zhejiang Province,No.LQ19H090006Department of Health of Zhejiang Province,No.2019KY260.
文摘Paraneoplastic cerebellar degeneration(PCD),which is rare in clinical practice,is closely related to autoimmunity.Cases positive for anti-Yo antibodies(anti-Purkinje cytoplasmic antibody 1)are the main subtype of PCD.PCD is subacute cerebellar degeneration,and while it progresses over weeks to months,its resultant deficits last much longer.Cancer patients with anti-Yo antibody-positive PCD are very rare.Most of them are breast cancer or ovarian cancer patients but also occasionally lung cancer patients.CASE SUMMARY A 61-year-old woman presented with sudden vertigo,nausea,and vomiting for approximately 10 d.The patient's neurological examination showed torsion with downbeat nystagmus and ataxia of the right limb and trunk.Laboratory examination found that the patient's cerebrospinal fluid and serum were anti-Yo antibody-positive,positron emission tomography computed tomography showed an increased metabolic rate in the retroperitoneal lymph nodes,and the pathology of lymph node punctures in the retroperitoneum and neck suggested adenocarcinoma of the pancreaticobiliary duct,which strengthens the hypothesis of paraneoplastic origin.Intravenous immunoglobulin(IVIg)0.4 g/kg/d for 5 d and methylprednisolone 160 mg for 3 d were initiated,which was reduced to 80 mg for 3 d and then to 40 mg for 7 d.After treatment with IVIg and a steroid,the patient's vertigo and ataxia alleviated.CONCLUSION The patient's vertigo and ataxia alleviated after treatment,suggesting that early immunotherapeutic intervention may have certain value in stopping neurological loss.
基金supported by National Natural Science Foundation of China(81671188)Zhejiang Provincial Natural Science Foundation of China(LY12H31010)the Key Laboratory of Hangzhou City Project(20090233T12)
文摘OBJECTIVE We have recently reported that cysteinyl leukotriene(Cys LT) signaling plays an important role in microglial interleukin(IL)-1β secretion and subsequent neurotoxicity.The present study aimed to examine microglial morphological changes and the upstream molecular underlying IL^(-1)β production in Cys LT receptor agonist leukotriene D4(LTD4)-treated BV2 microglia in vitro.METHODS Twenty-four hours after murine microglial BV2 cells were stimulated with LTD4(1-100 nmol·L^(-1)),the cell proliferation and morphology were observed.The expression level of cysteinyl aspartate-specific protease 1(CASP1) protein was measured by Western blotin BV2 cells.In addition,BV2 cells were pretreated with or without CysLT1 receptor antagonist montelukast for 1 h and the effects of monte-lukaston LTD4-stimulated microglial activation and CASP1 expression were evaluated.RESULTS The number of BV2 cells had an increasing tendency after 24 h treatment with LTD4,but no significant differences were observed between the control and LTD4-treated cells(P>0.05).Under basal and resting conditions,BV2 microglial cells displayed a ramified morphology.However,LTD4 at 100 nmool·L^(-1) drove microglial morphological changes from a ramified towards an amoeboid shape.The expression of CASP1 protein was significantly upregulated in 100 nmool·L^(-1) LTD4-treated BV2 microglia(P<0.01).Furthermore,pretreatment with CysLT1 receptor antagonist montelukast prevented cell morphological changes and suppressed the increased CASP1 expression in LTD4-treated BV2 cells(P<0.05).CONCLUSION Cys LT receptor agonist LTD4 induces morphological changes and CASP1 expressionin BV2 microglia,which can be inhibited by CysLT1 antagonist.These results suggest the involvement of Cys LT signaling in microglial morphological changes and CASP1 expression.
