Isaacs syndrome with LGI1 and CASPR2 antibodies after HPV vaccination: A case report.

RATIONALE: Isaacs syndrome is peripheral nerve hyperexcitability characterized by spontaneous muscle twitching and rigidity and is often associated with antibodies to CASPR2 (contactin-associated protein-like 2) and LGI1 (leucine-rich glioma-inactivated 1). But it is a rare Isaacs syndrome with LGI1 and CASPR2 antibodies after human papilloma virus (HPV) vaccination. PATIENT CONCERNS: The patient presented with limb pain, muscle twitching, numbness in the extremities and around the mouth, and hand rash after the second dose of HPV vaccine. DIAGNOSES: Laboratory tests indicated positive for LGI1 antibodies, CASPR2 antibodies, anti-phosphatidylserine/prothrombin antibodies and anti-sulfatide antibodies, TPO and ATG, IgG E. The patient post-M-wave discharges were seen on F-wave examination of the posterior tibial nerve in both lower limbs. We diagnosis the patient with Isaacs syndrome. INTERVENTIONS: Treatment with the intravenous immunoglobulin (IVIG) treatment, after 5 days of IVIG therapy (0.4 mg/kg/day), the rash on the hand disappeared, the pain was relieved, the sleep improved. OUTCOMES: After 3 Courses of treatment, the clinical manifestations of the nervous system disappeared and negative responsibility antibodies profile. LESSONS: This case report suggests a possible adverse reaction to HPV vaccination, which could be treated by attempting several periods of IVIG therapy. The underlying immune mechanisms need to be studied with further extensive data.

Kcna1-mutant rats dominantly display myokymia, neuromyotonia and spontaneous epileptic seizures.

Mutations in the KCNA1 gene, which encodes for the α subunit of the voltage-gated potassium channel Kv1.1, cause episodic ataxia type 1 (EA1). EA1 is a dominant human neurological disorder characterized by variable phenotypes of brief episodes of ataxia, myokymia, neuromyotonia, and associated epilepsy. Animal models for EA1 include Kcna1-deficient mice, which recessively display severe seizures and die prematurely, and V408A-knock-in mice, which dominantly exhibit stress-induced loss of motor coordination. In the present study, we have identified an N-ethyl-N-nitrosourea-mutagenized rat, named autosomal dominant myokymia and seizures (ADMS), with a missense mutation (S309T) in the voltage-sensor domain, S4, of the Kcna1 gene. ADMS rats dominantly exhibited myokymia, neuromyotonia and generalized tonic-clonic seizures. They also showed cold stress-induced tremor, neuromyotonia, and motor incoordination. Expression studies of homomeric and heteromeric Kv1.1 channels in HEK cells and Xenopus oocytes, showed that, although S309T channels are transferred to the cell membrane surface, they remained non-functional in terms of their biophysical properties, suggesting a dominant-negative effect of the S309T mutation on potassium channel function. ADMS rats provide a new model, distinct from previously reported mouse models, for studying the diverse functions of Kv1.1 in vivo, as well as for understanding the pathology of EA1.

Oxaliplatin-induced hyperexcitability syndrome in a patient with pancreatic cancer.

A recent pooled analysis and a meta-analysis suggested a survival benefit of gemcitabine-platinum doublets when compared with single agent gemcitabine in pancreatic cancer. Sensory neurotoxicity is a potentially limiting toxicity associated with oxaliplatin therapy. In this letter, we describe a case of a patient with metastatic pancreatic cancer who developed acquired neuromyotonia while receiving intravenous oxaliplatin as part of her treatment. It is a condition characterized by cramps, muscle twitching, weakness, myotonia and pseudomyotonia (slow muscle relaxation after forceful contraction). Her symptoms were ameliorated after initiation of pregabalin. We postulate that hyperexcitability syndrome associated with administration of oxaliplatin can be treated with pregabalin. Future studies will be needed to confirm this as well as to determine the long-term adverse effects associated with pregabalin.

Acute oxaliplatin-induced peripheral nerve hyperexcitability.

PURPOSE: Oxaliplatin is a novel platinum compound with clinical activity in several malignancies. Neurotoxicity is dose-limiting and occurs in two distinct forms, an acute neurologic symptom complex that occurs within hours or days of therapy and a chronic, cumulative sensory neuropathy. PATIENTS AND METHODS: Patients were treated in a phase I study designed to establish the maximum-tolerated dose of capecitabine given with oxaliplatin. Because of the unusual neurosensory toxicity of oxaliplatin, detailed neurologic examination, needle electromyography (EMG), and nerve conduction studies (NCS) were performed before and the day after oxaliplatin in a subset of 13 patients. Carbamazepine therapy was tried in 12 additional patients to determine whether the neurologic effects might be relieved. RESULTS: All patients experienced acute, reversible neurotoxicities with oxaliplatin. Symptoms included paresthesias, dysesthesias, cold hypersensitivity, jaw pain, eye pain, pain in the arm used for drug infusion, ptosis, leg cramps, and visual and voice changes. Serial EMG and NCS revealed striking signs of hyperexcitability in motor nerves after oxaliplatin. In patients who achieved therapeutic levels, carbamazepine did not alter the clinical or electromyographic abnormalities. CONCLUSION: The acute neurotoxicity seen with oxaliplatin is characterized by peripheral-nerve hyperexcitability, and the findings are similar to the clinical manifestations of neuromyotonia. Carbamezepine, which provides symptomatic relief in acquired neuromytonia, did not seem to be beneficial. Efforts to identify a successful neuroprotectant strategy would have a major impact on improving patient quality of life and the ability to deliver full doses of oxaliplatin.