Serum perampanel levels in patients with seizures are not affected by hemodialysis.

Perampanel belongs to a novel class of antiseizure medications (ASMs). Studies examining the effect of hemodialysis on perampanel serum levels in clinical settings are lacking. We aimed to evaluate the changes in serum perampanel levels during hemodialysis. We studied patients with seizures who received oral perampanel between April 2020 and March 2023 and whose serum concentration of perampanel was measured before and after hemodialysis. We analyzed the serum concentrations of levetiracetam and lacosamide for comparison. Fourteen patients, with a mean age of 76.1 ± 7.88 years, were included. The dose of perampanel was 2.14 ± 1.27 mg. The hemodialysis clearance rate of perampanel, levetiracetam, and lacosamide was 0 ± 13%, 69 ± 11%, and 59.6 ± 8.2%, respectively. The post-dialysis CD ratio decreased significantly with levetiracetam but not with perampanel. Adverse but acceptable effects of perampanel were observed in two patients. The serum concentrations of several ASMs have been shown to be reduced during hemodialysis. Our study revealed that the serum perampanel concentration does not decrease during hemodialysis. Owing to the low rate of adverse effects and the stability of perampanel serum concentration during hemodialysis, perampanel could be a favorable choice as an ASM for patients with seizures undergoing hemodialysis. PLAIN LANGUAGE SUMMARY: Our study looked at how hemodialysis affects the serum levels of perampanel, a new type of medication for seizures. In 14 patients who started treatment between April 2020 and March 2023, perampanel serum levels did not decrease during hemodialysis, unlike other seizure medications. This shows that perampanel can be a good option for patients with seizures who need hemodialysis, with fewer side effects compared to other medications.

Bilateral Phrenic Nerve Palsy Associated With Neuralgic Amyotrophy.

Neuralgic amyotrophy (NA) is a multifocal inflammatory neuropathy accompanied by acute pain and muscle atrophy. NA commonly affects the upper extremities, but rarely affects the phrenic nerve. Here, we report a male with neck pain, orthopnea, difficulty sleeping in the supine position, and inability to slurp. His saturated oxygen level decreased from 97% to 86% in the supine position. His right shoulder showed muscle atrophy. Chest X-ray examination in the supine position and a nerve conduction study showed phrenic palsy. We diagnosed it as bilateral phrenic nerve palsy associated with NA. NA sometimes causes phrenic nerve palsy and may cause slurping difficulty.

[A case of neurosarcoidosis initially diagnosed as cervical spondylotic myelopathy, leading to diagnosis by gadolinium contrast-enhanced MRI].

A 70-year-old female presented with bilateral numbness in her upper limbs. She was diagnosed with cervical spondylotic myelopathy and underwent cervical laminoplasty. However, there was no significant improvement in sensory disturbance, and at 6 months after surgery, she developed subacute motor and gait disturbance in four extremities. Spinal MRI revealed a long lesion of the spinal cord with edema, and a part of the lesion showed gadolinium contrast enhancement. Bronchoscopy revealed an elevated CD4/8 ratio, and gallium scintigraphy demonstrated an accumulation in the hilar lymph nodes, leading to a diagnosis of neurosarcoidosis. In case of rapid deterioration during the course of cervical spondylotic myelopathy, neurosarcoidosis should be considered as a differential diagnosis, which can be assessed by contrast-enhanced MRI.

[Altered antibody titers in patients with neuromuscular diseases after high-dose intravenous immunoglobulin therapy].

We investigated the changes in antibody titers after intravenous immunoglobulin (IVIg) administration in patients with neuromuscular diseases. Among patients who received IVIg from April 1, 2020, to August 31, 2022, we retrospectively evaluated 15 patients with antibody measurements before and after IVIg administration for any rise in the following antibody levels and examined the data for subsequent changes of false positive results to negative ones. The levels of anti SS-A, anti-thyroglobulin, anti-thyroid peroxidase, anti-glutamic acid decarboxylase, HBs, and HBc antibodies transiently increased after IVIg administration and showed false-positive results. However, levels of rheumatoid factor and anti-nuclear and antineutrophil cytoplasmic antibodies were not elevated. The false-positive results became negative after 3 months. Here, we report on the changes in antibody levels before and after IVIg administration and note that levels of hepatitis B virus-related antibodies and various autoantibodies transiently rise after IVIg administration.

Serum concentrations of HGF are correlated with response to anti-PD-1 antibody therapy in patients with metastatic melanoma.

BACKGROUND: Anti-programmed cell death protein (PD)-1 antibody treatment is associated with a notable improvement in only 30%-40% of patients. Thus, a predictive and easily measured marker of the clinical benefit of anti-PD-1 antibody treatment is necessary; therefore, in this study, we focused on the serum concentration of hepatocyte growth factor (HGF). OBJECTIVES: To evaluate whether the serum concentration of HGF can be used as a biomarker for the clinical response to anti-PD-1 antibody therapy. METHODS: This study included 29 metastatic melanoma patients receiving nivolumab or pembrolizumab. Nine patients responded to anti-PD-1 antibody treatment, whereas the other 20 patients did not. The serum concentrations of HGF were analyzed by using ELISA. In 28 patients, immunohistochemical analysis of the HGF protein in patients' cancer tissues was also performed. Peripheral blood mononuclear cells (PBMCs) from healthy donors were cultured with an anti-CD3 antibody in the presence or absence of HGF and c-MET inhibitor. The expression of perforin in CD8+ T cells were evaluated by using flow cytometry. RESULTS: Among the 29 recruited patients, the non-responders displayed higher serum concentrations of HGF than the responders (P = 0.00124). Patients with low serum concentrations of HGF showed longer overall survival (N = 28, P = 0.039; HR 0.3125, 95% CI 0.1036-0.9427) and progression-free survival (N = 24, P = 0.0068; HR 0.2087, 95% CI 0.06525-0.6676) than those with high concentrations of HGF. We observed a significant correlation between the serum concentration of HGF and immunohistochemical-positive staining (P = 0.000663). In a flow cytometry analysis of PBMCs from healthy donors, HGF was found to downregulate perforin secretion. Furthermore, the addition of capmatinib, a specific inhibitor of c-MET, increased the expression of perforin in CD8+ T cells. CONCLUSIONS: HGF concentration represents a valid biomarker that can be further developed for the evaluation of anti-PD-1 therapy. Our results suggested that c-MET inhibition promotes perforin expression in CD8+ T cells. Therefore, c-MET inhibitors can activate the immune system and may play an important role in combined immunotherapy.