Anti-CASPR2 antibody-associated autoimmune encephalitis： a case report / 四川精神卫生

This paper elaborated a case of an elderly patient with anti-contactin-associated protein-like 2 （CASPR2） antibody-associated autoimmune encephalitis. It illustrated the common manifestations and diagnostic process of anti-CASPR2 antibody-associated encephalitis， and the analysis of clinical symptoms and ancillary findings had contributed to gaining insight into the diagnosis of autoimmune encephalitis in elderly patients characterized by distinct psycho-behavioral abnormalities and cognitive decline， as well as suggesting the possibility that autoimmune encephalitis in elderly may exacerbate the development of cerebrovascular disease.

Clinical analysis of skeletal muscle and small fiber involvement associated with anti-contactin-associated protein-like 2 antibodies positive Morvan syndrome / 中华神经科杂志

Objective:To analyze the clinical data of a patient with anti-contactin- associated protein-like 2 (CASPR2) antibodies-related Morvan syndrome (MoS) and the related literature, and summarize the clinical characteristics of MoS patients.Methods:Clinical data of a CASPR2 antibodies-related MoS patient who was admitted in the Department of Neurology, the First Medical Center of Chinese People′s Liberation Army General Hospital in June 2021 were collected. CASPR2 IgG was detected by cell-based assay. Positron emission tomography/computed tomography (PET/CT), skin sympathetic response (SSR) and other examinations were performed. Clinical profiles of MoS patients were summarized by database retrieval.Results:The patient was a 55-year-old man presenting with peripheral nerve hyperexcitability, autonomic dysfunctions, neuropsychiatric symptoms and pain. Physical examination showed cognitive impairment, muscle quivering and absent deep-tendon reflexes. There was no family history of MoS and poisons exposure in this patient. Auxiliary examination showed serum creatine kinase was elevated (570 U/L) and antinuclear antibodies were positive (granular-type 1∶320). Other rheumatic and immunological antibodies, erythrocyte sedimentation rate, autoantibody profile, tumor marker, thyroid function, etc, were normal. Cerebrospinal fluid (CSF) protein and immunoglobulin were slightly higher. CASPR2 antibodies were positive in both serum and CSF (serum: 1∶100, CSF: 1∶10). Needle electromyography showed myokymic discharges, motor and sensory nerve conduction velocities were normal. SSR showed no waveform was elicited from both hands and feet. Cranial magnetic resonance imaging suggested scattered ischemic changes in the brain. PET/CT showed local metabolism increased slightly in soft tissues of bilateral shoulder and back, right lumbar and back muscles and bilateral gluteus medius. A total number of 232 cases of MoS patients were found in literature reports, most of which were male. The most common clinical manifestations were sleep disorders, and cognitive deficits accounted for 32.3%. Among them, skeletal muscle involvement was found in only 1 case by PET, and 4 patients had SSR abnormalities. Most of the patients had favorable neurological outcomes after the immunotherapy.Conclusions:MoS, as an autoimmune syndrome, may present with high uptake of skeletal muscle in PET/CT examination. Skeletal muscle involvement is a rare clinical manifestation of this disease. SSR as an electrophysiological test to evaluate autonomic neuropathy, its clinical value should be further strengthened.

Clinical and electrophysiological features of peripheral nerve hyperexcitability syndromes with severe pruritus / 中风与神经疾病杂志

@#To improve the understanding of peripheral nerve hyperexcitability syndromes（PNHS）. MethodsTwo cases of PNHS with severe pruritus were analyzed retrospectively. Their clinical characteristics，diagnosis，treatment process，and follow-up outcomes were summarized and discussed in combination with the literature. ResultsCase 1，a 60-year-old male with serum contactin-associated protein-like 2（CASPR2）and leucine rich glioma inactivated 1（LGI1）antibodies. The patient presented with pain，twitches，and severe pruritus in both lower limbs，autonomic dysfunction such as hyperhidrosis and abnormal feces，mood and sleep disorders could also be observed in the course of disease. Electrical diagnosis presented as peripheral nerve excitability（PNH）and abnormal sympathetic skin response（SSR）. The final diagnosis was Morvan syndrome，CASPR2/LGI1 related autoimmune encephalitis. Case 2，a 37 year old female with positive CASPR2 antibody，presented with pain and twitches in both lower limbs，and persistent pruritus in lower abdomen and perineum. She also had hyperhidrosis，abnormal feces and sleep disorders in the course of the disease. Electromyography showed myokymic discharge and abnormal SSR. Current perception threshold（CPT）test suggested hyperesthesia of Aβ sensory nerve fibers. The final diagnosis of this patient was Isaacs syndrome. The two patients achieved clinical remission after immunotherapy and symptomatic treatment. The abnormal EMG was improved. ConclusionPruritus can be a prominent manifestation of PNHS patients with CASPR2 antibody. Identifying the clinical manifestations，carrying out serological and electromyographic detections are helpful for early diagnosis. Timely immunotherapy can effectively alleviate the disease.

Contactin-associated protein-like 2 antibody-mediated neurological disease:clinical characters analysis of 12 cases / 中风与神经疾病杂志

@#Abstract Objective　To investigate clinical features,treatment and prognosis of patients with CASPR2-Ab associated neurological disease.Methods　The clinical data of 12 patients with CASPR2-Ab in Xuanwu Hospital,Capital Medical University from September 2016 to September 2019 were analyzed.Results　The age of 12 patients was 44.42±15.541 years old,and the ratio of male to female was 1∶1.Initial presenting symptoms comprised seizures (6/12),limb pain (2/12),limb weakness (3/12) and cerebellar speech (1/12).All patients developed central nervous system problems,presenting as seizures (8/12),mental abnormality (4/12) or memory decline (4/12).Five cases suffered from peripheral nervous system impairment,including muscle cramps (3/12),limb numbness (4/12),limb weakness (1/12),and neuropathic pain (2/12).Five patients got autonomic nervous system involved,manifested as hyperhidrosis.EMG showed abnormal spontaneous firing in four patients.Diffuse slow wave activity on background of EEG was found in six patients.Brain MRI in two cases showed hyperintensity lesions in bilateral temporal lobes on T2WI/FLAIR sequences,and tumor screening of one patient revealed benign thymoma.Ten patients got remission after immunotherapy.Conclusion　CASPR2-Ab associated disease tended to be susceptible to elderly male and middle-aged female,which extensively affected various nervous system.Early immunotherapy was effective in patients,especially those with seizure as the only symptom or with limbic encephalitis.

Potential Autoepitope within the Extracellular Region of Contactin-Associated Protein-like 2 in Mice.

Aims: Implicated in autoimmune encephalitis, neuromyotonia and genetic forms of autism, here we report that contactin-associated protein-like 2 (CNTNAP2) contains a potential autoepitope within the extracellular region. Methodology: CNTNAP2 sequence-similar regions (CSSRs) from human pathogens were identified. Sera from autistic and control children were obtained and analyzed for the presence of antibodies able to bind CSSRs. One such candidate CSSR was evaluated for evidence of autoimmune responses to CNTNAP2 in a mouse model of acute infection. Results: Autistic and control children sera contained antibodies able to discrete regions of CNTNAP2. In a murine model of acute infection, a CSSR derived from the N-terminal extracellular region of CNTNAP2 resulted in anti-CNTNAP2 antibody production, proinflammatory cytokine elevation, cerebellar and cortical white matter T-cell infiltration as well as motor dysfunction. Conclusion: Taken together, these data suggest that CNTNAP2 contains a potential autoepitope within the extracellular region.

What should you know about limbic encephalitis? / O que deve saber sobre encefalites auto-imunes?

Autoimmune encephalitis is an inflammatory disorder characterized by a subacute impairment of short-term memory, psychiatric features and seizures. It is often associated with a variety of other neurological symptoms, and its differential diagnosis is wide, leading to challenges in its recognition. It used to be regarded as a rare disease, usually paraneoplastic and with poor prognosis. However, with the recent recognition of membrane-surface directed antibodies, it is now known that in a substantial proportion of cases there is no association with any malignancy and there is a good prognosis if treated. Hence, early recognition and prompt initiation of immunotherapies are of great importance.

A encefalite autoimune é uma doença inflamatória caracterizada por envolvimento subagudo da memória de curto prazo, presença de sintomas psicóticos e crises epilépticas. Dada a diversidade de sintomas na apresentação, o diagnóstico diferencial é um verdadeiro desafio. Anteriormente, era considerada uma doença rara, de etiologia paraneoplásica e com mau prognóstico. No entanto, com a recente descoberta dos anticorpos dirigidos à superfície da membrana, é atualmente reconhecido que uma grande parte dos casos não tem uma neoplasia subjacente e apresenta um ótimo prognóstico. Assim, o diagnóstico e tratamento imunoterápico precoces são de extrema importância.