SEZ6L2 Antibody–Associated Cerebellar Ataxia Responsive to Sequential Immunotherapy

ObjectivesSeizure-related 6 homolog like 2 (SEZ6L2) antibody–associated ataxia is an extremely rare disease. Six patients have been reported and none of them improved significantly with immunotherapy. Herein, we present the case of a patient with cerebellar ataxia and SEZ6L2 antibodies who benefited from immunotherapy, which dramatically altered the course of her disease.MethodsWe present a case report of a 73-year-old woman with progressive balance problems. Her condition had rapidly deteriorated in the 2 weeks before the admission to our hospital leading to repeated falls and eventually left her bed-ridden.ResultsShe presented with severe trunk ataxia, bidirectional nystagmus, dysarthric speech, and persistent nausea. With the exception of cerebellar atrophy, extensive imaging studies revealed no pathology. SEZ6L2 antibodies were found in both CSF and serum. Over a period of 9 months, our patient received immunotherapy consisting of steroid pulse therapy, IV immunoglobulin infusions, rituximab, and cyclophosphamide. Consequently, her condition improved markedly, and she was discharged home from the neurologic rehabilitation unit.DiscussionOur case report shows that intense sequential immunotherapy may considerably improve level of functioning in some patients with SEZ6L2 antibody–associated cerebellar ataxia.Classification of EvidenceThis provides Class IV evidence. It is a single observational study without controls.

Case Report: Rehabilitation for Lower Extremity Pain Due to Venous Stasis in a Patient With Multisystem Inflammatory Syndrome in Children

Recently, it was reported that children recovering from coronavirus disease (COVID-19) developed multisystem inflammatory syndrome in children (MIS-C), which causes severe inflammation in multiple organs of the body. Because MIS-C is a new disease, the pathophysiology and prognosis are unknown. Owing to a lack of studies on this subject, we herein provide information on rehabilitation for children with MIS-C. A 12-year-old male patient presented with systemic inflammatory symptoms after approximately 2 months since recovery from COVID-19. He was treated with cyclosporine and steroid pulse therapy after admission to our hospital. His general condition improved significantly within approximately 1 week. Thereafter, his lower legs turned dark purple and he experienced intense pain whenever the lower limbs hung below the heart, such as in the sitting position. The patient was referred to the rehabilitation department, as he had difficulties during standing and walking. Because the symptoms improved with elevation of the lower extremities, we considered that the pain was related to venous stasis. The pain reduced when an elastic bandage was applied for the prevention of venous stasis; therefore, exercise therapy was implemented while the patient wore the elastic bandage. The patient's lower extremity symptoms improved in 10 days. He was discharged after 16 days and could independently perform activities of daily living (ADL). The mechanism underlying the patient's pain could not be determined; however, rehabilitation was effective when combined with compression therapy using an elastic bandage.

The Combination of Nucleotide Analog Therapy and Steroid Pulse Therapy for Acute HBV Infection Effectively Promotes HBV Clearance

Acute hepatitis B virus (HBV) infection occasionally progresses to acute liver failure, often with poor prognosis. The appropriate pharmacological approach is yet to be established. Although nucleotide analogs (NA) and corticosteroids are candidates for the treatment of acute HBV infection, their therapeutic effects, especially their effect on HBV clearance, remain unclear. To clarify effects on the HBV clearance of combination therapy of NA and steroid pulse therapy (SPT) for acute HBV infection, we first analyze the effectiveness of this therapy in patients with HBV infection compared with NA monotherapy (NAM). Of the 57 consecutive patients with acute hepatitis B infection from May 2007 to December 2018, we have included 25 patients for this study, whom we followed up until HBV clearance. According to the administration of NA and SPT, we divided patients into two groups (NAM group and NA + SPT group) and compared their results. Of the 25 patients, 10 received NAM, whereas 15 received NA + SPT. There were no appreciable adverse effects related to SPT. The time required for the clearance of HBsAg (76 (43–116) days vs. 26 (14–51) days, p = 0.0418) and HBV-DNA (NAM group vs. NA + SPT group: 180 (83.5–220) vs. 69 (43–136) days, p = 0.0420) was significantly shorter in the NA + SPT group than in the NAM group. The hazard ratio of NA + SPT for the clearance of HBsAg and HBV-DNA were 0.45 (0.19–1.09) and 0.35 (0.14–0.89), respectively. In conclusion, we showed that NA + SPT promoted HBV elimination. These findings support the use of the NA + SPT combination for acute HBV infection without the concern of persistent HBV infection.

A Case of Vogt-Koyanagi-Harada Disease-Like Uveitis Induced by Nivolumab and Ipilimumab Combination Therapy

Nivolumab and ipilimumab are widely used immune checkpoint inhibitors (ICPIs) for the treatment of metastatic melanoma. ICPIs cause an array of side effects called immune-related adverse events (IRAEs) due to activation of an immune response. ICPI-uveitis can cause irreversible vision loss if untreated. There are few reports of recurrent Vogt-Koyanagi-Harada (VKH) disease-like uveitis induced by nivolumab and ipilimumab. We report a case of VKH disease-like uveitis recurrence after resuming ICPIs. A 73-year-old man with advanced melanoma was referred to our clinic with visual loss 25 days after starting nivolumab/ipilimumab. His corrected visual acuity was 0.5 in the right eye and 0.02 in the left eye. Enhanced-depth imaging optical coherence tomography (EDI-OCT) showed marked choroid thickening. The patient was diagnosed with VKH disease-like uveitis due to IRAEs. Subtenon injection of triamcinolone acetonide was performed, and nivolumab/ipilimumab was suspended, but serous retinal detachment (SRD) markedly worsened and choroidal detachment appeared. With 2 courses of steroid pulse therapy and oral steroids, SRD disappeared, and corrected visual acuity recovered in both eyes. Five months after the first injection, exacerbation of melanoma was observed, and nivolumab and oral steroids were restarted. Six weeks later, an increase in choroidal thickness was observed with EDI-OCT and diagnosed as a recurrence of VKH disease-like uveitis. Monitoring for the recurrence of VKH disease-like uveitis during the administration of ICPIs, even after uveitis is treated, is essential. Assessment of choroidal thickness with EDI-OCT may be useful for detecting early signs of VKH disease-like uveitis.

Optic neuropathy secondary to granulomatosis with polyangiitis in a patient with Graves’ disease: a case report

Background Dysthyroid optic neuropathy is the most commonly suspected diagnosis of optic neuropathy in Graves’ patients; however, other causes need to be ruled out. We present a unique case of optic neuropathy secondary to hypertrophic pachymeningitis with antineutrophil cytoplasmic antibody-associated vasculitis, which was suspected to be antithyroid drug related. Case presentation A 79-year-old Japanese male presented with acute visual loss in the left eye. He had a 24-year history of Graves’ disease and was taking methimazole. Best-corrected visual acuity was 0.8 in the right eye and light perception in the left eye, and relative afferent pupillary defect in the left eye was seen. Ocular movement was normal, and there were no findings explaining visual loss in intermediate optic media and fundus in the left eye. Contrast-enhanced magnetic resonance imaging demonstrated thickened dura mater. Tests for myeloperoxidase-antineutrophil cytoplasmic antibody, proteinuria, and hematuria were positive; pulmonary nodule lesions and a blood clot in the left lower leg were also found. After excluding the presence of diseases that could lead to hypertrophic pachymeningitis, we diagnosed optic neuropathy due to hypertrophic pachymeningitis with granulomatosis with polyangiitis—a subtype of antineutrophil cytoplasmic antibody-associated vasculitis. Since he had history of using methimazole, antineutrophil cytoplasmic antibody-associated vasculitis was considered as drug related. We started high-dosage steroid pulse therapy followed by 1 mg/kg body weight daily of oral prednisolone, and subsequently tapered. Methimazole was stopped. Best-corrected visual acuity recovered to 0.9, 2 weeks after starting treatment. Though myeloperoxidase-antineutrophil cytoplasmic antibody remained negative, the symptom relapsed 6 months after treatment initiation. We gave a second high-dose steroid pulse therapy followed by prednisolone tapered together with methotrexate. Remission remained, and using 4 mg/week methotrexate without prednisolone, myeloperoxidase-antineutrophil cytoplasmic antibody was kept within the normal limit until now, 4 years after onset. Conclusion We present a case of optic neuropathy with hypertrophic pachymeningitis related to antineutrophil cytoplasmic antibody-associated vasculitis, which was suspected to be drug related. The patient had good visual recovery after quitting the drug and receiving immunosuppressive therapy with systemic steroids. Hypertrophic pachymeningitis with antineutrophil cytoplasmic antibody-associated vasculitis related to antithyroid drugs should be considered as a differential diagnosis for optic neuropathy in Graves’ patients in whom optic nerve compression is not obvious.

Dermatomyositis Identified During Palliative Care Management for Chemotherapy-Associated Pain: A Case Report

Introduction: Skin disorders and neuropathy often occur as side effects of chemotherapy. We encountered a patient who was treated for drug-induced skin symptoms, but the symptoms did not improve, and he was eventually diagnosed as having dermatomyositis. Case presentation: A 71-year-old man underwent chemotherapy with regorafenib in February 2020 for the postoperative recurrence of sigmoid colon cancer, but treatment was discontinued after about 2 months owing to the appearance of skin symptoms, which were thought to be side effects of regorafenib. Subsequently, his symptoms further worsened, and he was hospitalized 3 weeks after the appearance of the initial skin symptoms, and a palliative care team was asked to relieve his back pain caused by the drug-induced skin symptoms. Erythema was widely observed on the lower back and limbs, and he experienced needle stick-like pain. Furthermore, the patient demonstrated difficulty in lifting both upper limbs. As acetaminophen was effective for his pain, the dose was slowly increased with careful observation. The cause of the patient’s muscle weakness was unclear, and after careful discussion of the possible causes among specialists in dermatology, neurology, and rheumatoid arthritis, a diagnosis of dermatomyositis associated with the malignant tumor was made about 10 days after his admission. The patient’s symptoms gradually improved with steroid pulse treatment (methylprednisolone 1 g/day for 3 days) followed by high-dose gamma globulin treatment (2.5 g/day for 5 days), and the patient was discharged 48 days after admission. Discussion: Because this patient was referred to a palliative care team for the purpose of relieving pain caused by skin symptoms associated with chemotherapy, a crucial point is the symptoms were treated as side effects of the chemotherapy from the beginning. As neuropathy can occur as a result of chemotherapy, the pain and muscle weakness could be explained at the time; however, the symptoms continued to worsen even after the chemotherapy was stopped. Because the symptoms were not typical of polymyositis/dermatomyositis, diagnosis of the patient was delayed, even though he was treated in each specialized department. Our present case indicates that paraneoplastic syndrome should always be kept in mind when treating cancer patients.