Kenji Isahaya

Effects of Edaravone, a Free Radical Scavenger, on Serum Levels of Inflammatory Biomarkers in Acute Brain Infarction

The potent free radical scavenger edavarone is widely used in Japan to treat acute ischemic stroke within 24 hours after onset. Recent experimental studies have shown that edavarone alleviates blood-brain barrier disruption in conjunction with suppression of the inflammatory reaction in acute brain ischemia. We investigated the effects of edaravone on circulating inflammatory biomarkers in patients with ischemic stroke. Patients with acute ischemic stroke admitted 12-36 hours after onset of symptoms were prospectively enrolled. Intravenous edaravone at 60 mg/day for 14 days was administered to patients admitted 12-24 hours after symptom onset (edaravone group; n = 29). Patients admitted 24-36 hours after onset served as controls (control group; n = 34). Venous blood samples were obtained on admission and at 48 hours, 7 days, and 14 days after symptom onset. Serum concentrations of high-sensitivity C-reactive protein, interleukin (IL)-6, IL-10, IL-18, tumor necrosis factor α, matrix metalloproteinase (MMP)-2, and MMP-9 were measured. General linear models were used to compare changes in concentrations of these biomarkers over time between the groups. In the control group, the mean MMP-9 concentration increased gradually from 3.857 ± 1.880 ng/mL to 4.538 ± 1.966 ng/mL over the 14-day period (P = .027, one-way repeated-measures analysis of variance [ANOVA]), but the edavarone group demonstrated no such increase (P = .564). A significant group-time interaction was demonstrated only for MMP-9 (P = .029, two-way repeated-measures ANOVA), and no significant differences in other biomarkers were seen between groups. Our data indicate that edaravone suppresses serum MMP-9 level in patients with acute ischemic stroke. Further studies with a larger sample size are needed to explore the relationship between circulating MMP-9 level and the protective effect of edaravone.

Association between Inflammatory Biomarkers and Progression of Intracranial Large Artery Stenosis after Ischemic Stroke

BACKGROUND Proinflammatory state has been implicated as a pathogenetic mechanism in the progression of intracranial large artery atherosclerosis (ILA). High levels of inflammatory biomarkers in healthy populations and in patients with acute stroke or acute coronary syndrome are known to be associated with subsequent stroke events. This study investigated the relationship between circulating biomarkers measured early after stroke onset and future ILA progression. METHODS In 48 patients with acute ischemic stroke, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), IL-18, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2 and MMP-9 were measured within 48 hours after onset. Baseline severity and ILA progression were assessed by serial magnetic resonance angiography (MRA). The median follow-up period for MRA was 3.1 years. Hazard ratio (HR) was calculated using the Cox proportional hazard model adjusted for traditional risk factors, and accuracy of predicted ILA progression was analyzed by receiver operating characteristic (ROC) curve analysis. RESULTS ILA progression was observed in 6 of 48 patients (12.5%). After adjusting for age, sex, and presence of hypertension, baseline ILA severity score (HR 2.814; 95% confidence interval [CI] 1.172-6.754) and IL-6 (HR 1.215; 95% CI 1.002-1.473) were significantly associated with ILA progression. Area under the ROC curve (AUC) for prediction of ILA progression by traditional risks, baseline ILA severity score and IL-6, was 0.647. When IL-6 was removed from this model, AUC remained at 0.631. CONCLUSIONS In addition to traditional risk factors and baseline radiologic findings, circulating levels of IL-6 measured soon after stroke onset are associated with future ILA progression.

A case of cerebral infarction during a hemodialysis procedure successfully treated with recombinant tissue plasminogen activator

Thrombolytic therapy is an effective treatment for acute ischemic stroke and provides benefits and improvements that lead to better neurological outcomes. However, thrombolytic therapy with recombinant tissue plasminogen activator (r-tPA) in hemodialysis (HD) patients is limited because HD patients have a higher risk of bleeding. We report a case of a 75-year-old HD patient who presented with sudden aphasia during HD treatment. She was brought to the hospital for treatment for infarction. Following thrombolytic therapy, we achieved re-opening without complications. To our knowledge, no report has been published describing the patients who had a stroke during a maintenance HD session and were treated with r-tPA successfully. Although the number of HD patients treated with r-tPA is small and requires further investigation, thrombolytic therapy can be an alternative option. After weighing the risks and benefits and assessing each patient carefully, the use of r-tPA should be considered, even in HD patients.

Mononeuritis multiplex in a patient with cutaneous arteritis diagnosed by skin biopsy

A 55-year-old man was admitted with paralysis of the left lower leg. He had purpura in the left lower extremity for three years, left calf pain for two years, and dysesthesia in the left plantar region and first toe for one year. A physical examination revealed livedo reticularis on the left leg and mononeuritis multiplex was diagnosed in the bilateral tibial and left peroneal nerve area. Anti-neutrophil cytoplasmic antibody was negative. A nerve conduction study showed decreased amplitude of compound muscle-action potential in the bilateral tibial and the left peroneal nerve, sensory nerve action potential in the bilateral sural nerve. A skin biopsy revealed inflammatory cells on blood vessel walls and cutaneous arteritis was diagnosed. Cyclophosphamide pulse therapy with steroid and anti-coagulation improved the neurological symptoms. A skin biopsy should be considered when patients present with mononeuritis multiplex in the lower extremities and cutaneous findings such as livedo reticularis in the symptomatic area.

Nonbacterial Thrombotic Endocarditis Complicated by Cerebral Infarction in a Patient with Adenomyosis with High Serum CA125 Level; A Case Report

We report a case of a 48-year-old woman with multiple cerebral infarctions caused by nonbacterial thrombotic endocarditis (NBTE) because of adenomyosis with high serum carbohydrate antigen (CA)125 level. Transesophageal echocardiography (TEE) showed a vegetation, 4 mm in diameter, adjacent to the anterior leaflet of the mitral valve on day 2. Soluble CA125 level was elevated to 901 U/mL. Intravenous infusion of unfractionated heparin sodium was started. On day 35, TEE revealed reduction of the vegetation in size, 2 mm in diameter. On day 38, she was transferred to the hospital for further rehabilitation. CA125 is a transmembrane mucin that contributes to the progression of epithelial ovarian cancer. It is important to keep in mind that adenomyosis with abnormally high serum CA125 level may be at high risk of NBTE.

Nerve conduction study of lower extremities in cutaneous arteritis patients with neurological manifestations

Some patients originally diagnosed with cutaneous arteritis (CA) could develop additional disease manifestations, including peripheral neurological involvement. We evaluated the biological neurological parameters among CA patients who underwent nerve conduction studies for neurological involvement in the lower extremities. We reviewed 164 patients who were originally diagnosed with CA at our dermatology department between 2004 and 2015. Seventeen (10.4%) of the CA patients underwent further nerve conduction studies to determine their peripheral neurological manifestations, primarily in the lower extremities, in our neurology division. The frequency of low compound muscle action potential (CMAP) was significantly higher compared with that of delayed latency in both the peroneal nerve and sural nerve based on nerve conduction studies. The frequency of low CMAP was significantly higher compared with that of prolonged distal latency in both the peroneal and sural nerves. We suggest that impairment of the nerve axon pathways in the peroneal and sural nerves could result in the peripheral neurological manifestations in the lower extremities in CA patients.

Reversible Cerebral Vasoconstriction Syndrome Presenting with Transient Global Amnesia

A 65-year-old man who had been diagnosed with transient global amnesia (TGA) 15 years previously was admitted to hospital with complaints of amnesia and headache. His symptoms improved on day-2. The initial brain MRI and electroencephalography findings were normal. He was diagnosed with a recurrence of TGA and discharged. However, he returned with right leg weakness and complained of a thunderclap headache. MRI demonstrated subarachnoid hemorrhage and multifocal segmental narrowing of the left posterior cerebral artery (PCA) and large intracranial arteries, and he was diagnosed with reversible cerebral vasoconstriction syndrome (RCVS). He was discharged on day-30 without any neurological deficits. This case suggested that TGA should be interpreted as one of the symptoms of RCVS or a prodromal symptom of RCVS.