Switching from zonisamide to perampanel improved the frequency of seizures caused by hyperthermia in Dravet syndrome: a case report.

BACKGROUND: Dravet syndrome is a severe epilepsy disorder characterized by drug-resistant seizures and cognitive dysfunction, often caused by SCN1A gene mutations. It leads to neurodevelopmental delays and motor, behavioral, and cognitive impairments, with a high mortality rate. Treatment options include sodium valproate, clobazam, and newer agents such as cannabidiol and fenfluramine. Zonisamide, which is used in some cases, can cause hyperthermia and oligohydrosis. Herein, we present a case of a patient with Dravet syndrome whose seizures were controlled by treating infections and switching from zonisamide to perampanel. CASE PRESENTATION: A 24-year-old Japanese man with Dravet syndrome presented to our department with aspiration pneumonia. The patient had been treated with valproate, sodium bromide, and zonisamide for a long time. His seizures were triggered by hyperthermia. The patient was experiencing a sustained pattern of hyperthermia caused by infection, zonisamide, and persistent convulsions, which caused a vicious cycle of further seizures. In this case, the control of infection and switching from zonisamide to perampanel improved seizure frequency. CONCLUSION: Dravet syndrome usually begins with generalized clonic seizures in its infancy because of fever and progresses to various seizure types, often triggered by fever or seizure-induced heat due to mutations in the SCN1A gene that increases neuronal excitability. Seizures usually diminish with age, but the heat sensitivity remains. In this case, seizures were increased by repeated infections, and hyperthermia was induced by zonisamide, resulting in status epilepticus. Perampanel, an aminomethylphosphonic acid receptor antagonist, decreased seizures but caused psychiatric symptoms. It was effective in suppressing seizures of Dravet syndrome in this patient.

Lambert-Eaton Myasthenic Syndrome Complicated by anti-GABAB Receptor Encephalitis.

A 74-year-old man experienced diplopia, generalized muscle weakness, and acute respiratory failure. He was diagnosed with Lambert-Eaton myasthenic syndrome (LEMS) and treated with immunotherapy, but no improvement was observed, and additional symptoms, including central apnea and hallucinations, appeared. Subsequent serum and cerebrospinal fluid (CSF) analyses confirmed the presence of GABAB receptor antibodies, indicating the coexistence of autoimmune encephalitis. Although there were no findings of malignancy, it is highly likely that occult small-cell lung carcinoma was present. When atypical symptoms occur in patients with LEMS, it is important to consider the possibility of concomitant autoimmune encephalitis.

Dynamic transition of molecular subtypes in relapsed small cell lung cancer treated with multimodal therapy: A case report.

Several transcription factors in small cell lung cancer (SCLC), including achaete-scute homolog 1 (ASCL1) and neurogenic differentiation factor 1 (NEUROD1), contribute to rapid tumor growth and early metastatic dissemination. Recent studies suggested that these molecular subtypes represent neuroendocrine differentiation in dynamic SCLC evolution. In the present case, a 62-year-old man was diagnosed with limited disease SCLC originating from the right upper lobe. Biopsy specimens were positive for ASCL1 but negative for NEUROD1. Six months after concurrent chemoradiotherapy and prophylactic cranial irradiation, the primary tumor had regrown and salvage surgery was performed. The pathological diagnosis was recurred SCLC, and postoperative histopathology was positive for both ASCL1 and NEUROD1. The patient was subsequently followed up; however, he had multiple bone metastases 9 months after surgery. It was speculated that the shift to NEUROD1-high expression in tumor cells surviving concurrent chemoradiation therapy may be related to the poor outcome after combined modality treatment.

Atypical posterior reversible encephalopathy syndrome associated with Sjögren'|s syndrome: a case report.

Sjögren'|s syndrome (SJS) is a common autoimmune disease. Generally, posterior reversible encephalopathy syndrome (PRES) is often concomitant with autoimmune disease; however, PRES rarely complicates SJS. Thus, the detailed clinical course of cases with SJS and PRES remains unknown. We present the case of a 71-year-old female patient with primary SJS, whose magnetic resonance (MR) images showed bilateral vasogenic edema in the basal ganglia, brainstem, and cerebellum. Cerebrospinal fluid (CSF) examination revealed increased IgG index and higher interleukin-6 and anti-SSA-autoantibody levels. Management of her blood pressure combined with corticosteroid therapy improved her neurological symptoms, including abnormal CSF and MR imaging findings.

Clinical significance of MYC family protein expression in surgically resected high-grade neuroendocrine carcinoma of the lung.

OBJECTIVES: MYC family genes including MYC, MYCN, and MYCL are amplified and overexpressed as oncogenic drivers in high-grade neuroendocrine carcinoma of the lung (HGNEC), but little is known about their clinical significance. This study evaluated the prognostic impact of MYC family protein expression in patients with surgically resected HGNEC. METHODS: Immunohistochemical analyses were performed on 83 resected specimens of HGNEC using antibodies against MYC family proteins (c-MYC, n-MYC, and l-MYC). When nuclear staining of any intensity in ≥10% of tumor cells showed immunoreactivity with any one or more of c-MYC, n-MYC, or l-MYC, the specimens were defined as MYC family-positive. RESULTS: A total of 83 patients were analyzed. MYC family-positive status was observed in 33.7% (28 of 83 cases) and was not correlated with clinicopathological factors. The protein expression was mutually exclusive and no duplicate cases were observed. A log-rank test showed that MYC family-positive status was significantly associated with shorter overall survival (OS) (p = 0.003) and recurrence-free survival (RFS) (p = 0.039). According to Cox multivariate analysis, MYC family-positive status had a significant effect on shorter OS (hazard ratio [HR] = 2.217, 95% confidence interval [CI] 1.179-4.169, p = 0.014) and RFS (HR = 1.802, 95% CI 1.014-3.202, p = 0.045). In patients with pathological stage I, MYC family-positive status also showed significantly poor OS (HR = 2.847, 95% CI 1.236-6.557, p = 0.014) and RFS (HR = 2.088, 95% CI 1.006-4.332, p = 0.048) in the multivariate analysis. CONCLUSIONS: MYC family protein expression could be an independent unfavorable prognostic factor in patients with surgically resected HGNEC.

Practice of Hereditary ATTR Amyloidosis in Non-endemic Areas of Japan.

Objective Hereditary ATTR (ATTRv) amyloidosis was once an incurable disease; however, in recent years, disease-modifying therapies, such as tafamidis and patisiran, have become available. We herein report the medical care situation in an ATTRv amyloidosis non-endemic area of Japan. Methods We confirmed the information in the medical records of our department and analyzed the data retrospectively. Patients Patients with ATTRv amyloidosis who were treated in our department between 2010 and 2021 were included. Results A total of 15 ATTRv amyloidosis cases (8 men and 7 women) were treated in our department during the study period; 9 patients had a family history, and the transthyretin V30M (p.V50M) gene mutation was present in 66% of cases. The average age of the onset was 57 years old, with 73% of the initial symptoms being dysesthesia and 13% being autonomic dysfunction. Ten patients were treated with tafamidis and nine with patisiran. Although it took a long time to start treatment among our experienced cases, there were some cases in which treatment could be introduced relatively early. Conclusion ATTRv amyloidosis is treatable and should be included in the differential diagnosis of neuropathy so that it can be diagnosed early and introduced into treatment. In the near future, the presymptomatic diagnosis of ATTRv amyloidosis and genetic counseling will become more important.

Rituximab Was Effective in Relieving Symptoms of Isaacs Syndrome: A Case Report.

We presented a 23-year-old patient who had experienced neuromyotonia in his left leg. Although he tested negative for anti-LGI1 and anti-CASPR2 antibodies, we diagnosed him with Isaacs syndrome due to myokymic discharges on electromyography and symptoms being relieved by intravenous methylprednisolone (IVMP) and intravenous immunoglobulin (IVIg). IVMP, IVIg, plasma exchange, or cyclosporine treatment did not provide a long-term response; however, rituximab showed long-term improvement. Rituximab should be considered early in the treatment of patients with antibody-negative Isaacs syndrome who are responsive to immunotherapy, including IVMP, IVIg, and plasma exchange, and have long-term symptoms that are hard to control.

Prognostic impact of surgical treatment for high-grade neuroendocrine carcinoma of the lung: a multi-institutional retrospective study.

Background: High-grade neuroendocrine carcinoma (HGNEC) of the lung, which includes small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC), is an aggressive form of lung cancer. Although lobectomy followed by adjuvant chemotherapy is regarded as the standard therapy for this disease, it would be an uphill struggle for HGNEC patients to receive that multidisciplinary therapy perfectly. This study aimed to examine recurrence and survival outcomes in surgically treated patients with HGNEC of the lung. Methods: The medical records of 104 HGNEC patients who underwent surgical treatment in five institutions were retrospectively analyzed. Standard treatment (ST) was defined as lobectomy, bilobectomy, or pneumonectomy with mediastinal lymph node dissection followed by adjuvant platinum-doublet chemotherapy with more than two cycles. Results: Patients in the ST group (n=31; 30%) were younger and had fewer respiratory complications than those in the non-standard treatment (NST) group (n=73; 70%). A significantly higher proportion of patients in the NST group developed ipsilateral lymph node recurrence (21% vs. 3%; P=0.035) and ipsilateral or contralateral lung recurrence (15% vs. 0%; P=0.031). Five-year overall survival (OS) was 64.2% in the ST group and 38.3% in the NST group (P=0.038). NST was independently associated with worse OS in multivariate analysis (hazard ratio, 2.044; 95% confidence interval, 1.016-4.113; P=0.045). Conclusions: Surgically treated HGNEC patients who received ST had a more favorable outcome than those who received NST. Patients who receive NST may require additional treatment.

Pembrolizumab-induced Myasthenia Gravis Relapse after Immunosuppressive Therapy.

Myasthenia gravis (MG) is an immune-related adverse event (irAE), and as an irAE, MG (irAE-MG) generally has a monophasic course, with only a few case reports of irAE-MG flare-ups during the course of the disease. We herein report a case of pembrolizumab-induced MG with relapsing symptoms. irAE-MG is a rare disease that has not yet been fully characterized, and our case shows that MG symptoms may relapse. Therefore, regular follow-up is necessary, even after the symptoms improve with immunosuppressive therapy.

High mRNA expression of POU2F3 in small cell lung cancer cell lines predicts the effect of lurbinectedin.

BACKGROUND: Small cell lung cancer (SCLC) is a progressive disease with a poor prognosis. Recently, a method to classify SCLC by the expression status of four transcription factors, ASCL1, NEUROD1, POU2F3, and YAP1, was proposed. Here, we investigated the potential relationships between expression of these four transcription factors and the effect of lurbinectedin. METHODS: mRNA and protein expression of ASCL1, NEUROD1, POU2F3, and YAP1 were quantified in eight SCLC cell lines and analyzed for potential correlations with drug sensitivity. In addition, ASCL1, NEUROD1, POU2F3, and YAP1 expression were evaluated in 105 resected cases of high-grade neuroendocrine carcinoma of the lung, including 59 resected cases of SCLC. RESULTS: Based on the results of qRT-PCR and western blot analyses, the eight SCLC cell lines examined were classified into NEUROD1, POU2F3, and YAP1 subtypes, as well as five ASCL1 subtypes. There were no correlations between cell line subtype classification and drug sensitivity to cisplatin, etoposide, or lurbinectedin. Next, we compared relative mRNA expression levels of each transcription factor with drug sensitivity and found that the higher the mRNA expression level of POU2F3, the lower the IC50 of lurbinectedin. Evaluation of resected SCLC tissue revealed that the composition of subtypes defined by the relative dominance of ASCL1, NEUROD1, POU2F3, and YAP1 was as follows: 61% ASCL1, 15% NEUROD1, 14% POU2F3, 5% YAP1, and 5% all-negative. CONCLUSION: In our experiments, high mRNA expression of POU2F3 in SCLC cell lines correlated with the effect of lurbinectedin.

Clinical Significance of Serglycin Expression in Human Breast Cancer Patients.

BACKGROUND/AIM: Serglycin plays a crucial role in the aggressiveness of several types of malignancies, including breast cancer. In this study, we aimed to investigate the prognostic impact of serglycin expression in breast cancer patients, which has not been previously reported. PATIENTS AND METHODS: Immunohistochemical analyses were performed on 348 resected specimens of invasive carcinomas, using antibodies against serglycin. RESULTS: Low serglycin expression was observed in 23% of specimens (80/348) and significantly correlated with high histological grade (p=0.001) and negative ER (p=0.013). The log-rank test showed that low serglycin expression correlated with shorter distant metastasis-free survival (DMFS) (p=0.016) and disease-specific survival (DSS) (p=0.037) in node-positive breast cancer patients. Cox's multivariate analysis revealed that low serglycin expression was an independent factor for shorter DMFS (p=0.017) and DSS (p=0.020) in node-positive breast cancer patients. CONCLUSION: Low serglycin expression is an independent predictor of unfavorable prognosis in node-positive breast cancer patients.

Comparison between robot-assisted thoracoscopic surgery and video-assisted thoracoscopic surgery for mediastinal and hilar lymph node dissection in lung cancer surgery.

OBJECTIVES: Lymph node dissection (LND) with robot-assisted thoracoscopic surgery (RATS) in lung cancer surgery has not been fully evaluated. The aim of this study was to compare LND surgical results between video-assisted thoracoscopic surgery (VATS) and RATS. METHODS: We retrospectively compared perioperative parameters, including the incidence of LND-associated complications (chylothorax, recurrent and/or phrenic nerve paralysis and bronchopleural fistula), lymph node (LN) counts and postoperative locoregional recurrence, among 390 patients with primary lung cancer who underwent lobectomy and mediastinal LND by RATS (n = 104) or VATS (n = 286) at our institution. RESULTS: The median total dissected LN numbers significantly differed between the RATS and the VATS groups (RATS: 18, VATS: 15; P < 0.001). They also significantly differed in right upper zone and hilar (#2R + #4R + #10L) (RATS: 12, VATS: 10; P = 0.002), left lower paratracheal and hilar (#4L + #10L) (RATS: 4, VATS: 3; P = 0.019), aortopulmonary zone (#5 + #6) (RATS: 3, VATS: 2; P = 0.001) and interlobar and lobar (#11 + #12) LNs (RATS: 7, VATS: 6; P = 0.041). The groups did not significantly differ in overall nodal upstaging (P = 0.64), total blood loss (P = 0.69) or incidence of LND-associated complications (P = 0.77). CONCLUSIONS: In this comparison, it was suggested that more LNs could be dissected using RATS than VATS, especially in bilateral superior mediastinum and hilar regions. Accumulation of more cases and longer observation periods are needed to verify whether RATS can provide the acceptable quality of LND and local control of lung cancer.

A rare case of combined thymoma and a multilocular thymic cyst discovered due to chest pain.

BACKGROUND: A thymoma with chest pain and multilocular thymic cysts (MTCs) is very rare. CASE PRESENTATION: A 49-year-old man presented to another hospital complaining of an anterior chest pain. Chest computed tomography (CT) showed an anterior mediastinal tumor 60 × 30 × 55 mm in size. The boundary with the pericardium or left brachiocephalic vein seemed to be partially unclear while enhanced by the contrast medium, and so the tumor could have invaded them. No definitive diagnosis of myasthenia gravis was made although the serum anti-acetylcholine receptor antibody count was high. We performed an extended thymectomy with combined partial resection of left brachiocephalic vein, left upper lobe, and left phrenic nerve. He was discharged with no chest pain and no complications post-surgery. The tumor was pathologically type B2 thymoma with hemorrhage necrosis and MTCs, and we diagnosed Masaoka stage II because of no histological infiltration to the organs. CONCLUSIONS: We speculated that hemorrhagic necrosis due to infarction in tumor caused the inflammation to spread to the surrounding organs, which was related to the chest pain and the development of MTCs.

Inflammatory Myopathy Associated with Anti-mitochondrial Antibody Presenting Only with Respiratory Failure.

A 56-year-old woman presenting with type II respiratory failure was transferred to our hospital. She did not exhibit muscle weakness or elevated serum myogenic enzymes, but needle electromyography revealed myogenic changes in the limb muscles, and her blood tests were positive for anti-mitochondrial antibodies (AMA). Muscle histopathological findings included immune-mediated necrotizing myopathy, so she was diagnosed with inflammatory myopathy associated with AMA. After treatment with corticosteroids and noninvasive positive pressure ventilation, her symptoms improved. If a diagnosis of type II respiratory failure is difficult, inflammatory myopathy associated with AMA should be considered as a differential diagnosis.

Successful Treatment with Rituximab for Granulomatosis with Polyangiitis and Multiple Cranial Neuropathies.

We herein report a case of granulomatosis with polyangiitis in a 73-year-old man. He had experienced bilateral ptosis, redness of both eyes, right facial weakness, and hearing loss in the right ear for two months. Myeloperoxidase anti-neutrophil cytoplasmic antibody was positive. Corticosteroids and intravenous cyclophosphamide pulse therapy yielded a response. After the fourth pulse of cyclophosphamide, he developed headache, diplopia, restricted left eye movement, right facial palsy, and hearing loss in the right ear. A one-year remission period was achieved by increasing the steroid and rituximab doses. Rituximab was effective against the relapse of granulomatosis with polyangiitis and cranial neuropathy.

[Two elderly cases of transthyretin amyloid polyneuropathy without a family history].

We report two cases of transthyretin familial amyloid polyneuropathy (ATTR-FAP) from non-endemic areas. Both cases showed chronic progressive distal limb numbness and weakness. Due to nonspecific symptoms, they were not diagnosed for a long period of time. A nerve conduction study revealed axonal neuropathy in the lower limbs and carpal tunnel syndrome. An echo test showed thickness of the left ventricle, one of the red flag symptom clusters of ATTR-FAP. Genetic analysis revealed a mutation in the transthyretin gene. In cases with chronic progressive neuropathy, it is important to consider a differential diagnosis of ATTR-FAP.

Primary renal mixed tumor characterized by marked proliferation of osteoblast-like cells with osteoid formation in a swine.

Renal mixed tumor characterized by the absence of nephrogenic blastema and the presence of predominant osteoid-producing osteoblast-like cells occurred in the kidney of a 6-month-old, hybrid, female pig. At the post-mortem examination, the tumor was found as a calcified grayish-white mass at the cranial end of the left kidney. Histologically the tumor consisted of 3 growth areas of poorly differentiated spindle cells, osteoid-producing osteoblast-like cells, and luminal epithelial cells. Transition from the spindle cells to the osteoblast-like cells or the luminal epithelial cells was observed. Immunohistochemically, the spindle cells and the osteoblast-like cells were consistently positive for ß-catenin. Although the luminal epithelial cells and adjacent spindle cells were positive for cytokeratin, these 3 types of tumor cells were consistently negative for WT1. The tumor was diagnosed as primary renal mixed tumor characterized by marked proliferation of osteoblast-like cells with osteoid formation.

The laterality of stop and go processes of the motor response in left-handed and right-handed individuals.

The objective of the present study was to investigate whether the stop and go processes of the motor response are asymmetrical and whether the asymmetries are dependent on handedness and the response selection process that is engaged. Both right-handed and left-handed participants abducted either the left or right index finger in response to an imperative cue in the choice reaction time (choice RT) or the simple RT task. A stop cue was presented after the imperative cue with a probability of .25. When the stop cue was presented, the participants withheld the prepared response. On the choice RT task, left-handed participants had significantly shorter RT and stop signal reaction time (SSRT) with the left versus the right hand, whereas right-handers showed no difference between hands on either measure. In the simple RT task, the RT and SSRT were not significantly different between the groups or the response sides. These results indicate that both the stop and go processes of the prepared left-hand response are completed earlier than those of the right-hand response in left-handed individuals when the stimulus-response process involves a response selection process.