Oxaliplatin is a novel platinum compound with clinical activity against several solid tumors. It has been associated with sensory neuropathies and, rarely, a neuromyotonia-like hyperexcitability syndrome;a form of per...Oxaliplatin is a novel platinum compound with clinical activity against several solid tumors. It has been associated with sensory neuropathies and, rarely, a neuromyotonia-like hyperexcitability syndrome;a form of peripheral neuropathy manifested by tremor and twitching activity of muscles. We present a case of hyperexcitability syndrome developed during the treatment of stage III appendiceal adenocarcinoma with oxaliplatin-containing regimen and was successfully treated with Pregabalin.展开更多
Neuromyotonia is a neuromuscular hyperexitability disorder characterized by muscle stiffness caused by continuous muscle fiber activity. It is an immune mediated disorder with elevated antibody level against presynapt...Neuromyotonia is a neuromuscular hyperexitability disorder characterized by muscle stiffness caused by continuous muscle fiber activity. It is an immune mediated disorder with elevated antibody level against presynaptic, voltage gated potassium channels, either as isolation or as a paraneoplastic process. Symptoms usually include muscle twitching during rest (myokymia), cramps, peudomyotonia (delayed relaxation), increased sweating, and sometimes motor weakness. In this case report, we present a seventy-two years old man who presented with pain in both thighs for one month. It gradually became worse to involve feet and chest. His brain CT scan showed features of brain atrophy. EMG showed fasciculation along neuromyotonic discharges with characteristic wave in frequency and amplitude typical of Isaacs’ syndrome. Potassium channel antibodies were very high. Diagnosis of Isaacs’ syndrome was made. He was followed up for two months with treatment by three-day course of methyl prednisolone followed by oral steroid and methotrexate with much improvement. This is the first case of Isaacs’ syndrome in Kurdistan.展开更多
Aim: Sorafenib has been shown to improve time to tumor progression (TTP) and overall survival (OS) in patients with hepatocellular carcinoma (HCC);however, post-progression survival (PPS) has not been well characteriz...Aim: Sorafenib has been shown to improve time to tumor progression (TTP) and overall survival (OS) in patients with hepatocellular carcinoma (HCC);however, post-progression survival (PPS) has not been well characterized in these patients. This study aimed to evaluate the predictors of PPS by using time-dependent and dynamic changes in radiologic progression patterns, liver function, and performance status (PS) in patients with advanced HCC receiving sorafenib treatment. Methods: We retrospectively analyzed the clinical characteristics of 128 advanced HCC patients with Child-Pugh scores ≤ 7 at the initiation of sorafenib treatment. Results: The median TTP, OS, and PPS were 3.8, 15.6, and 9.9 months, respectively. At the time of confirmation of radiologic progressive disease (PD), a total of 46 (35.6%) patients showed impairments in their PS of ≥ +1 points over time. For the Child-Pugh score, 27 (21.1%) and 26 (10.9%) patients exhibited an impairment of ≥ +1 and ≥ +2 points, respectively. Multivariate analysis identified the following independent predictors of PPS: impairment in the PS score of ≥+1 point [hazard ratio (HR) 1.81, 95% confidence interval (CI) 1.16-2.82], impairment in the Child-Pugh score of ≥ +2 points (HR 3.70, 95% CI 1.68-8.15), radiologic pattern of progression (target lesion growth and emergence of a new lesion) (HR 2.91, 95% CI 1.79-2.91), a TTP < 4 months(HR 1.87, 95% CI 1.21-2.91), second-line treatment after radiologic confirmation of PD (HR 0.16, 95% CI 0.08-0.32), and continuous sorafenib treatment after radiologic confirmation of PD (HR 1.76, 95% CI 1.06-3.00). Conclusion: PPS in patients with advanced HCC can be characterized by using time-dependent dynamic changes in clinical parameters.展开更多
Voltage-gated potassium channels(VGKCs)represent a group of tetrameric signaling proteins with several functions,including modulation of neuronal excitability and neurotransmitter release.Moreover,VGKCs give a key con...Voltage-gated potassium channels(VGKCs)represent a group of tetrameric signaling proteins with several functions,including modulation of neuronal excitability and neurotransmitter release.Moreover,VGKCs give a key contribution to the generation of the action potential.VGKCs are complexed with other neuronal proteins,and it is now widely known that serum autoantibodies directed against VGKCs are actually directed against the potassium channel subunits only in a minority of patients.By contrast,these autoantibodies more commonly target three proteins that are complexed with alpha-dendrotoxin-labeled potassium channels in brain extracts.These three proteins are contactin-associated protein-2(Caspr-2),leucine-rich,glioma inactivated 1(LGI-1)protein and the protein Tag-1/contactin-2.Neoplasms are detected only in a minority of seropositive patients for VGKC complex-IgG and do not significantly associate with Caspr-2 or LGI-1.Among all the cancers described in association with VGKC complex-IgG,lung carcinoma,thymoma,and hematologic malignancies are the most commonly detected.We will review all the major neurological conditions associated with VGKC complex-IgG.These include Isaacs’syndrome,Morvan syndrome,limbic encephalitis,facio-brachial dystonic seizures,chorea and other movement disorders,epilepsy,psychosis,gastrointestinal neuromuscular diseases,a subacute encephalopathy that mimics Creutzfeldt-Jakob prion disease both clinically and radiologically and autoimmune chronic pain.The vast majority of these conditions are reversible by immunotherapy,and it is becoming increasingly recognized that early diagnosis and detection of VGKC complex-IgG is critical in order to rapidly start the treatment.As a result,VGKC complex-IgG are now part of the investigation of patients with unexplained subacute onset of epilepsy,memory or cognitive problems,or peripheral nerve hyperexcitability syndromes.展开更多
Isaacs' syndrome is a disease characterized by nerve hyperexcitability. The patients are commonly treated with symptomatic therapies and immunomodulatory approaches, but no clinical trials are available to date. H...Isaacs' syndrome is a disease characterized by nerve hyperexcitability. The patients are commonly treated with symptomatic therapies and immunomodulatory approaches, but no clinical trials are available to date. Here, we report the case of an anti-Caspr2-positive patient, presenting with continuous muscle twitches and diffuse muscle pain. He experienced a nearly complete clinical response to intravenous high-dose steroids combined with plasma exchange, sustained for at least 1 year. Our experience suggests that methylprednisolone 1000 mg/day × 5 days and consecutive tapering followed by plasma exchange may be efficient and well tolerated in patient with Isaacs' syndrome due to anti-Caspr2 antibodies.展开更多
目的探讨1个神经性肌强直与轴索型神经病(neuromyotonia and axonal neuropathy,NMAN)家系的临床及遗传学特点。方法收集先证者及其双亲的临床资料与外周血样,应用三联重复引物PCR联合毛细管电泳检测先证者强直性肌营养不良致病基因DMPK...目的探讨1个神经性肌强直与轴索型神经病(neuromyotonia and axonal neuropathy,NMAN)家系的临床及遗传学特点。方法收集先证者及其双亲的临床资料与外周血样,应用三联重复引物PCR联合毛细管电泳检测先证者强直性肌营养不良致病基因DMPK与ZNF9的动态突变;应用高通量测序筛查神经系统遗传病致病基因的变异,用Sanger测序验证检出的基因变异;应用Sanger测序分析双亲及100名非病个体的变异位点基因型;分析基因变异的致病性。结果未发现DMPK与ZNF9基因动态突变位点的异常扩展;测序结果显示先证者HINT1基因第3外显子存在c.335C>T(p.R119W)纯合错义变异,其表型正常的双亲均为上述变异的携带者,对照群体未检出该变异。基于ACMG指南的评价提示为致病性变异。结论在NMAN患者中发现的这个新的致病变异(c.335C>T,p.R119W)为HINT1基因与NMAN的关系提供了更多的证据,填补了中国人群HINT1基因突变谱的空白。展开更多
文摘Oxaliplatin is a novel platinum compound with clinical activity against several solid tumors. It has been associated with sensory neuropathies and, rarely, a neuromyotonia-like hyperexcitability syndrome;a form of peripheral neuropathy manifested by tremor and twitching activity of muscles. We present a case of hyperexcitability syndrome developed during the treatment of stage III appendiceal adenocarcinoma with oxaliplatin-containing regimen and was successfully treated with Pregabalin.
文摘Neuromyotonia is a neuromuscular hyperexitability disorder characterized by muscle stiffness caused by continuous muscle fiber activity. It is an immune mediated disorder with elevated antibody level against presynaptic, voltage gated potassium channels, either as isolation or as a paraneoplastic process. Symptoms usually include muscle twitching during rest (myokymia), cramps, peudomyotonia (delayed relaxation), increased sweating, and sometimes motor weakness. In this case report, we present a seventy-two years old man who presented with pain in both thighs for one month. It gradually became worse to involve feet and chest. His brain CT scan showed features of brain atrophy. EMG showed fasciculation along neuromyotonic discharges with characteristic wave in frequency and amplitude typical of Isaacs’ syndrome. Potassium channel antibodies were very high. Diagnosis of Isaacs’ syndrome was made. He was followed up for two months with treatment by three-day course of methyl prednisolone followed by oral steroid and methotrexate with much improvement. This is the first case of Isaacs’ syndrome in Kurdistan.
文摘Aim: Sorafenib has been shown to improve time to tumor progression (TTP) and overall survival (OS) in patients with hepatocellular carcinoma (HCC);however, post-progression survival (PPS) has not been well characterized in these patients. This study aimed to evaluate the predictors of PPS by using time-dependent and dynamic changes in radiologic progression patterns, liver function, and performance status (PS) in patients with advanced HCC receiving sorafenib treatment. Methods: We retrospectively analyzed the clinical characteristics of 128 advanced HCC patients with Child-Pugh scores ≤ 7 at the initiation of sorafenib treatment. Results: The median TTP, OS, and PPS were 3.8, 15.6, and 9.9 months, respectively. At the time of confirmation of radiologic progressive disease (PD), a total of 46 (35.6%) patients showed impairments in their PS of ≥ +1 points over time. For the Child-Pugh score, 27 (21.1%) and 26 (10.9%) patients exhibited an impairment of ≥ +1 and ≥ +2 points, respectively. Multivariate analysis identified the following independent predictors of PPS: impairment in the PS score of ≥+1 point [hazard ratio (HR) 1.81, 95% confidence interval (CI) 1.16-2.82], impairment in the Child-Pugh score of ≥ +2 points (HR 3.70, 95% CI 1.68-8.15), radiologic pattern of progression (target lesion growth and emergence of a new lesion) (HR 2.91, 95% CI 1.79-2.91), a TTP < 4 months(HR 1.87, 95% CI 1.21-2.91), second-line treatment after radiologic confirmation of PD (HR 0.16, 95% CI 0.08-0.32), and continuous sorafenib treatment after radiologic confirmation of PD (HR 1.76, 95% CI 1.06-3.00). Conclusion: PPS in patients with advanced HCC can be characterized by using time-dependent dynamic changes in clinical parameters.
文摘Voltage-gated potassium channels(VGKCs)represent a group of tetrameric signaling proteins with several functions,including modulation of neuronal excitability and neurotransmitter release.Moreover,VGKCs give a key contribution to the generation of the action potential.VGKCs are complexed with other neuronal proteins,and it is now widely known that serum autoantibodies directed against VGKCs are actually directed against the potassium channel subunits only in a minority of patients.By contrast,these autoantibodies more commonly target three proteins that are complexed with alpha-dendrotoxin-labeled potassium channels in brain extracts.These three proteins are contactin-associated protein-2(Caspr-2),leucine-rich,glioma inactivated 1(LGI-1)protein and the protein Tag-1/contactin-2.Neoplasms are detected only in a minority of seropositive patients for VGKC complex-IgG and do not significantly associate with Caspr-2 or LGI-1.Among all the cancers described in association with VGKC complex-IgG,lung carcinoma,thymoma,and hematologic malignancies are the most commonly detected.We will review all the major neurological conditions associated with VGKC complex-IgG.These include Isaacs’syndrome,Morvan syndrome,limbic encephalitis,facio-brachial dystonic seizures,chorea and other movement disorders,epilepsy,psychosis,gastrointestinal neuromuscular diseases,a subacute encephalopathy that mimics Creutzfeldt-Jakob prion disease both clinically and radiologically and autoimmune chronic pain.The vast majority of these conditions are reversible by immunotherapy,and it is becoming increasingly recognized that early diagnosis and detection of VGKC complex-IgG is critical in order to rapidly start the treatment.As a result,VGKC complex-IgG are now part of the investigation of patients with unexplained subacute onset of epilepsy,memory or cognitive problems,or peripheral nerve hyperexcitability syndromes.
文摘Isaacs' syndrome is a disease characterized by nerve hyperexcitability. The patients are commonly treated with symptomatic therapies and immunomodulatory approaches, but no clinical trials are available to date. Here, we report the case of an anti-Caspr2-positive patient, presenting with continuous muscle twitches and diffuse muscle pain. He experienced a nearly complete clinical response to intravenous high-dose steroids combined with plasma exchange, sustained for at least 1 year. Our experience suggests that methylprednisolone 1000 mg/day × 5 days and consecutive tapering followed by plasma exchange may be efficient and well tolerated in patient with Isaacs' syndrome due to anti-Caspr2 antibodies.
文摘目的探讨1个神经性肌强直与轴索型神经病(neuromyotonia and axonal neuropathy,NMAN)家系的临床及遗传学特点。方法收集先证者及其双亲的临床资料与外周血样,应用三联重复引物PCR联合毛细管电泳检测先证者强直性肌营养不良致病基因DMPK与ZNF9的动态突变;应用高通量测序筛查神经系统遗传病致病基因的变异,用Sanger测序验证检出的基因变异;应用Sanger测序分析双亲及100名非病个体的变异位点基因型;分析基因变异的致病性。结果未发现DMPK与ZNF9基因动态突变位点的异常扩展;测序结果显示先证者HINT1基因第3外显子存在c.335C>T(p.R119W)纯合错义变异,其表型正常的双亲均为上述变异的携带者,对照群体未检出该变异。基于ACMG指南的评价提示为致病性变异。结论在NMAN患者中发现的这个新的致病变异(c.335C>T,p.R119W)为HINT1基因与NMAN的关系提供了更多的证据,填补了中国人群HINT1基因突变谱的空白。
