Long-term outcomes of edaravone in amyotrophic lateral sclerosis in South Korea: 72-week observational study.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease characterized by the gradual loss of upper and lower motor neurons that leads to progressive muscle atrophy and weakness. Edaravone, a free-radical scavenger, was approved as an ALS treatment in 2015 in South Korea. METHODS: This study investigated the long-term effects and safety of edaravone by reviewing the medical records of 16 Korean patients with ALS who received extended edaravone between 2015 and 2021 in a single tertiary ALS center. RESULTS: Among sixteen patients, eleven patients underwent extended edaravone therapy for more than 18 cycles (72 weeks). The mean monthly changes in the revised ALS Functional Rating Scale (ALSFRS-R) were - 0.96 ± 0.83 (0-24 weeks), - 0.70 ± 0.76 (24-48 weeks), - 1.18 ± 1.67 (48-72 weeks), and - 0.81 ± 0.60 (0-72 weeks). The mean decline in forced vital capacity (FVC) was 17.4 ± 24.1. The changes were significant in both ALSFRS-R (p < 0.001) and FVC (p = 0.048); however, the mean change in compound muscle action potential of phrenic nerves was not. Patients experienced only minor adverse events, which were well tolerated. CONCLUSIONS: This study verifies previous reported outcomes of edaravone in 16 Korean ALS patients, indicating a modest effect with a favorable safety profile.

Preclinical safety assessment of antipyrine combined with lidocaine hydrochloride as ear drops.

This study was designed to assess the preclinical toxicity of antipyrine combined with lidocaine hydrochloride ear drops (ALED) and support the clinical trials of ALED in clinical settings in China. All the experiments including acute toxicity in rodents, skin sensitization toxicity in guinea pigs, skin irritation toxicity in rabbits and chronic toxicity in rats were performed according to China Food and Drug Administration guidelines. The maximum tolerated dose (MTD) of ALED administration for mice and rats was over (400 g antipyrine plus 100 g lidocaine hydrochloride)/kg and (240 g andtipyrine plus 60 g lidocaine hydrochloride)/kg, respectively. No obvious skin sensitization toxicity and skin irritation toxicity were observed. The main changes concentrated in chronic toxicity study in rats. For the chronic toxicity, rats were administrated once a day for 28 consecutive days, and a 14-day recovery period was followed. The side effects of ALED included decreased dietary intake in male rats, increased proportion of reticulocytes, decreased or even inversed granulocyte:erythrocyte ratio, fluctuated alanine aminotransferase and aspartate aminotransferase, and slightly increased relative weight of liver. Conclusively, blood system (especially erythrocyte system) and digestive system, including liver and gastrointestinal tract, might be the toxic targets of ALED.

Edaravone: a new hope for deadly amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a fatal motor neuron degenerative disorder leading to paralysis and eventual death. At present, we do not have any specific cure for this deadly disorder. Current drug therapy can only reduce morbidity in ALS patients. In 1995, riluzole was the first drug approved by the U.S. Food and Drug Administration (FDA) for ALS. After a long gap of 22 years, Mitsubishi Tanabe Pharma America got U.S. FDA approval for edaravone (Radicava) in May 2017 for the management of ALS. Edaravone, a novel neuroprotective agent, is indicated to slow down progression of ALS. In 2015, Mitsubishi Tanabe Pharma launched edaravone (Radicut) for the treatment of stroke and ALS in Japan. The U.S. FDA approved edaravone following clinical evidence from three clinical trials conducted in 368 ALS patients in Japan. Edaravone is awaiting approval by the European Medicines Agency (EMA) in Europe. Edaravone (60 mg) is administered by very slow intravenous infusion (60 minutes) in 28-day cycles. It has been shown to slow down the loss of physical function in ALS patients by 33% as compared to placebo. Edaravone is a strong antioxidant that prevents oxidative stress from inducing motor neuron death in ALS patients. Being a potent free radical scavenger, it has been shown to inhibit nitration of tyrosine residues in the cerebrospinal fluid and improve motor functions in mouse models of ALS. The product has been patented and the FDA has not approved any generic version of edaravone. This article discusses the preclinical pharmacology, pharmacokinetics, safety profile, clinical studies and drug interactions of edaravone (Radicava) in ALS.

Outcome of Acute Ischemic Stroke after the Treatment with Edaravone and 0.6 Mg/Kg Alteplase in Japanese Patients with Diabetes.

BACKGROUND: We investigated how diabetes mellitus (DM) affects the outcome of acute ischemic stroke (AIS), comparing with the outcomes in those who had hypertension (HT) and atrial fibrillation (AF). METHODS: This study was a sub-analysis of PROTECT4.5, which was previously performed as a large-scale, prospective observational study of edaravone with approximately 10,000 patients with AIS in Japan. The study patients treated with edaravone alone or edaravone + alteplase (recombinant tissue plasminogen activator [tPA]) were analyzed for their outcomes and explored for the risk factors of poor outcome, after being divided into 8 groups according to their affected complications of DM, HT, or AF in the groups treated with edaravone alone or edaravone + tPA. RESULTS: Among patients treated with edaravone alone and edaravone + tPA, the mean reduction in the National Institutes of Health Stroke Scale from baseline to 3 months after the onset was 2.0 and 4.4 in DM groups, respectively. The reduction was smaller in these groups compared with other groups (3.3-4.3 and 6.0-7.7, respectively). The logistic regression model revealed that DM was an independent risk factor for highly unfavorable outcome of modified Rankin Scale score 3-6 at 3 months after the onset, among both patients treated with edaravone alone and those treated with edaravone + tPA (odds ratio [OR]: 2.23, 95% confidential interval [CI]: 1.42-3.50 and OR: 2.05, 95% CI: 1.33-3.14, respectively). CONCLUSIONS: DM is suggested to adversely affect the outcome of AIS in Japanese patients.

Discussing edaravone with the ALS patient: an ethical framework from a U.S. perspective.

The recent approval of edaravone by the United States Food and Drug Administration has generated a mix of hope tempered by reality. The costs of the drug, both monetarily and with regard to intensity of treatment, are high. The benefits, while modest, will be viewed through a very different lens by individuals depending on their goals of care. By virtue of our training and experience, physicians are ideally suited to understand and explain new treatments to our patients. As healthcare providers with a fiduciary responsibility to our patients, we must make sure they are fully informed about both the costs and benefits of non-curative therapies such as edaravone, and be prepared to discuss these in the context of their goals of care and potential impact on quality of life. Respect for our patients' autonomy is critical when discussing these issues, but we should always be guided by the ethical principles of beneficence and non-maleficence.

A safety analysis of edaravone (MCI-186) during the first six cycles (24 weeks) of amyotrophic lateral sclerosis (ALS) therapy from the double-blind period in three randomized, placebo-controlled studies.

BACKGROUND: There continues to be a need for new therapies to treat ALS. OBJECTIVE: Provide an overview of safety for edaravone in ALS patients during the first six cycles of treatment. METHODS: Analysis was based on three randomised, placebo-controlled clinical trials. Endpoints included treatment-emergent adverse events (TEAEs), including AEs leading to discontinuation, serious adverse events (SAEs), and deaths. RESULTS: The analysis included a total of 368 patients (184 in the edaravone group and placebo group, respectively). Of those, 94.6% of the edaravone group and 90.2% of placebo group completed six cycles of therapy. Baseline characteristics were comparable between the two groups. TEAE incidence in the edaravone group and placebo group was 87.5% and 87.0%, respectively. TEAEs ocurring at ≥2% incidence in the edaravone group compared to placebo were contusion (14.7% vs. 8.7%), gait disturbance (12.5% vs. 9.2%), headache (8.2% vs. 5.4%), eczema (6.5% vs. 2.2%), dermatitis contact (6.0% vs. 3.3%), respiratory disorder (4.3% vs. 1.1%), and glucose urine present (3.8% vs. 1.6%). There was no imbalance in TEAEs leading to discontinuation (2.2% [edaravone], and 5.4% [placebo]). SAE incidence was 17.4% in the edaravone group and 22.3% in placebo group. Treatment-emergent deaths occurred in 2.2% in the edaravone group and 1.1% in placebo group, all respiratory in nature and attributed to worsening ALS. CONCLUSION: Data collected from three double-blind assessments found that while some TEAEs were more common in the edaravone group compared to placebo, the overall incidences of SAEs, deaths, and discontinuations due to AEs were similar or less for edaravone compared to placebo.

Open-label 24-week extension study of edaravone (MCI-186) in amyotrophic lateral sclerosis.

We aimed to explore the longer-term efficacy and safety of edaravone in an active-treatment extension period following the double-blind period of the second phase III study. Patients who met all the following criteria (scores ≥2 points on all 12 items of the revised amyotrophic lateral sclerosis functional rating scale [ALSFRS-R], forced vital capacity ≥80%, definite or probable ALS, and disease duration ≤2 years) were randomised to 60 mg intravenous edaravone or placebo for six cycles in the double-blind period, and then offered the opportunity to proceed to this 24-week open-label extension period. One hundred and twenty-three of 137 patients continued to the extension period: 65 edaravone-edaravone (E-E group) and 58 placebo-edaravone (P-E group). Change (mean ± standard deviation; SD) in the ALSFRS-R score from baseline in the double-blind period was -4.1 ± 3.4 and -6.9 ± 5.1 in the E-E group and P-E group, respectively, while it was -8.0 ± 5.6 in the E-E group and -10.9 ± 6.9 in the P-E group over the whole 48-week period. The ALSFRS-R score changed almost linearly throughout Cycles 1-12 in the E-E group. The most commonly reported adverse events were constipation, dysphagia, and contusion. There was no sudden deterioration in the ALSFRS-R score of the E-E group. No safety concerns related to edaravone were detected.

Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: In a previous phase 3 study in patients with amyotrophic lateral sclerosis (ALS), edaravone did not show a significant difference in the Revised ALS Functional Rating Scale (ALSFRS-R) score compared with placebo. Post-hoc analysis of these data revealed that patients in an early stage with definite or probable diagnosis of ALS, defined by the revised El Escorial criteria, who met a select set of inclusion criteria showed a greater magnitude of effect than did the full study population. We aimed to substantiate this post-hoc result and assess safety and efficacy of edaravone in a phase 3 trial that focused on patients with early stage ALS who met the post-hoc analysis inclusion criteria. METHODS: In this phase 3, randomised, double-blind, parallel-group study, patients aged 20-75 years with ALS of grade 1 or 2 in the Japan ALS Severity Classification, scores of at least 2 points on all 12 items of ALSFRS-R, forced vital capacity of 80% or more, definite or probable ALS according to the revised El Escorial criteria, and disease duration of 2 years or less were recruited from 31 hospitals in Japan. Eligible patients also had a decrease of 1-4 points in the ALSFRS-R score during a 12-week observation period before randomisation. Patients meeting all criteria were then randomly assigned 1:1 to receive 60 mg intravenous edaravone or intravenous saline placebo for 6 cycles (4 weeks per cycle with 2 weeks on, 2 weeks off) for a total treatment duration of 24 weeks. In cycle 1, the study drug or placebo was administered once per day for 14 days within a 14 day period, followed by the drug-free period. In cycle 2 and thereafter, the study drug or placebo was administered for 10 days within a 14 day period, followed by a 2 week drug-free period. Participants and investigators, including those assessing outcomes, were masked to treatment allocation. The primary efficacy outcome was the change in ALSFRS-R score from the baseline to 24 weeks (or at discontinuation if this was after the third cycle) after randomisation. The primary outcome was assessed in all patients who had received at least one treatment infusion, had at least one assessment post-baseline, and reached the end of cycle 3. For patients with missing values at the end of cycle 6, data were imputed by the last observation carried forward (LOCF) method, provided the patients had completed at least cycle 3. Safety was assessed in all patients who had received at least one treatment infusion and had at least one assessment post-baseline. This trial is registered with ClinicalTrials.gov, NCT01492686. FINDINGS: Between Nov 28, 2011, and Sept 3, 2014, we screened 213 patients, and enrolled 192 as potential participants. Of these, 137 patients completed the observation period: 69 were randomly assigned to receive edaravone, and 68 were randomly assigned to receive placebo. 68 patients taking edaravone and 66 taking placebo were included in the primary efficacy analysis. For the primary outcome, the change in ALSFRS-R score was -5·01 (SE 0·64) in the edavarone group and -7·50 (0·66) in the placebo group. The least-squares mean difference between groups was 2·49 (SE 0·76, 95% CI 0·99-3·98; p=0·0013) in favour of edaravone. Treatment-emergent adverse events were reported in 58 (84%) patients receiving edaravone and 57 (84%) patients receiving placebo. 11 (16%) patients taking edaravone and 16 (24%) taking placebo had serious adverse events, and one (1%) patient receiving edaravone and four (6%) patients receiving placebo had adverse events (one dysphagia in edaravone group and one dyspnoea, two respiratory disorder, and one rash in the placebo group) that led to withdrawal. INTERPRETATION: Edaravone showed efficacy in a small subset of people with ALS who met criteria identified in post-hoc analysis of a previous phase 3 study, showing a significantly smaller decline of ALSFRS-R score compared with placebo. There is no indication that edaravone might be effective in a wider population of patients with ALS who do not meet the criteria. FUNDING: Mitsubishi Tanabe Pharma Corporation.

Assessment of ototoxicity of intratympanic administration of Auralgan in a chinchilla animal model.

OBJECTIVES/HYPOTHESIS: Auralgan (benzocaine and antipyrine) is an over-the-counter otic drug commonly used for otalgia. Nevertheless, there is limited evidence about the effects of the drug on hearing function and cochlear morphology in the presence of a tympanic membrane perforation. The aim of the present study was to assess the cytotoxicity of Auralgan using cultured auditory cells (HEI-OC1) and to examine its effects on hearing function and cochlear morphology after intratympanic administration in a chinchilla model. STUDY DESIGN: Animal experiment. METHODS: Cell viability and DNA labeling assays were conducted to investigate the cytotoxic effect of the drug on cultured auditory cells (HEI-OC1). To examine the possible drug ototoxic effect in vivo, chinchillas received intratympanic injection of Auralgan in one ear, whereas the contralateral control ear received saline. Outcome measures included auditory brainstem response and postmortem cochlear morphology. RESULTS: A dose-dependent toxic effect of Auralgan was noted on cultured cells. Animal experiments showed an inflammatory reaction in the experimental ears and facial paralysis in 80% of the animals on the side receiving transtympanic injection of Auralgan (P < .05). Auditory brainstem response testing demonstrated a 30- to 50-dB hearing threshold shift across all frequencies tested (P < .05). Control ears showed no inflammation or significant threshold shift. Microscopy showed damage to the hair cells and stria vascularis with bleeding in the perilymphatic space in the experimental ears and damage to the hair cells. CONCLUSIONS: Auralgan was cytotoxic to cultured auditory cells. It promoted an inflammatory reaction and seemed to be ototoxic when given via transtympanic injection in an animal model. LEVEL OF EVIDENCE: NA

Edaravone for acute stroke: Meta-analyses of data from randomized controlled trials.

AIMS: To assess the effectiveness of edaravone for acute stroke including ischemic stroke and intracerebral hemorrhage (ICH). METHODS: We identified randomized controlled trials with comprehensive searches and performed systematic reviews according to the Cochrane methods of systematical reviews. RESULTS: Edaravone can reduce the rate of death or long-term disability significantly for acute ischemic stroke (AIS) (RR = 0.65; 95%CI, 0.48 to 0.89, p = 0.007). However, sensitivity analysis yielded a different result. Edaravone can also improve the short-term neurological impairment of AIS (MD = 7.09; 95%CI, 5.12 to 9.05, p < 0.00001), and ICH (MD = -4.32; 95%CI, -5.35 to -3.29, p < 0.00001). CONCLUSIONS: Edaravone is beneficial in improving neurological impairment resulting from AIS and ICH. However, currently there is no enough convincing evidence that edaravone reduces death or long-term disability for AIS and ICH.

[Case of cardiac tamponade during the treatment of acute cerebral infarction].

A 59-year-old man was admitted to our hospital because of sudden weakness in his left foot. He had been treated for lung cancer by chemotherapy and irradiation 3 years earlier. Brain magnetic resonance (MR) imaging revealed multiple acute cerebral infarctions in the area of the right anterior cerebral artery. MR angiography (MRA) revealed that the right anterior cerebral artery was patent, with slight irregularity in the A3 portion. He was treated by administration of aspirin (200 mg/day) and a continuous intravenous unfragmented heparin infusion (10,000 IU/day). Four days after admission, he developed dyspnea. Chest computed tomography (CT) performed 5 days after admission revealed both a marked pericardial effusion and a pleural effusion. Emergency pericardiocentesis was therefore performed. While 1,000 ml of bloody pericardial effusion were aspirated, his dyspnea ameliorated dramatically. Histological examination of the pericardial effusion revealed infiltration of lung adenocarcinoma cells in the pericardium. Intracranial 3D-CT angiography revealed the pearl and string sign in the right anterior cerebral artery 6 days after admission. Anterior cerebral artery dissection was diagnosed as the cause of his cerebral infarction. It is important to recognize the possibility of cardiac tamponade as an uncommon complication of the treatment for acute cerebral infarction.

Safety, tolerability and pharmacokinetics of MCI-186 in patients with acute ischemic stroke: new formulation and dosing regimen.

BACKGROUND AND PURPOSE: MCI-186 (edaravone) is a free radical scavenger approved in Japan since 2001 for the treatment of patients with acute ischemic stroke within 24 h from the onset of symptoms. It was recommended by the Japanese Guidelines for the Management of Stroke 2004. Our aim was to investigate the safety, tolerability and pharmacokinetics of a new formulation and dose regimen (intravenous bolus plus infusion) of MCI-186 suitable for the treatment of acute ischemic stroke in Europe because the Japanese treatment protocol includes twice-a-day intravenous infusion of MCI-186 for a maximum of 14 days. Such a treatment protocol is not very practical in Europe, where hospital stay is much shorter in acute hospitals. METHODS: In a double-blind, placebo-controlled randomized clinical trial we studied two dosing regimens, each in a cohort of 18 patients. Patients were randomized in a 2:1 ratio in both cohorts to receive MCI-186 or placebo. Review of safety and plasma concentration data from the first cohort (loading dose 0.08 mg/kg + 0.2 mg/kg/h infusion) preceded the second cohort (loading dose 0.16 mg/kg + 0.4 mg/kg/h infusion). Safety parameters included adverse events, severe adverse events, physical examinations, local reactions at infusion site, ECG, clinical chemistry and hematology, modified Total Neuropathy Score and CT scans. RESULTS: Mean age and National Institutes of Health Stroke Scale (NIHSS) score on admission of patients in cohorts 1 and 2 and the placebo group were 64, 63, and 69 years and 5, 5, and 6, respectively. The number of treatment emergent adverse events that occurred was 109, most of which were transient, mild or moderate. Both doses of the new formulation and dosing regimen were well tolerated. After the initiation of the infusion, plasma concentrations of MCI-186 reached or exceeded prespecified target levels within 24 h in both MCI-186 cohorts, which were in the putative therapeutic range in humans. Geometric mean values of MCI-186 plasma concentration at the end of the infusion in cohorts 1 and 2 were 391 and 1,595 ng/ml, respectively. CONCLUSIONS: The primary objective of the present study, safety and tolerability of the new formulation and dosing regimen, was achieved. The new formula and both dosing regimens were well tolerated and achieved intended plasma concentrations suitable for larger safety studies before pivotal trials.

Acute kidney injury and edaravone in acute ischemic stroke: the Fukuoka Stroke Registry.

BACKGROUND: A free radical scavenger, edaravone, which has been used for the treatment of ischemic stroke, was reported to cause acute kidney injury (AKI) as a fatal adverse event. The aim of the present study was to clarify whether edaravone is associated with AKI in patients with acute ischemic stroke. METHODS: From the Fukuoka Stroke Registry database, 5689 consecutive patients with acute ischemic stroke who were hospitalized within 24 hours of the onset of symptoms were included in this study. A logistic regression analysis for the Fukuoka Stroke Registry cohort was done to identify the predictors for AKI. A propensity score-matched nested case-control study was also performed to elucidate any association between AKI and edaravone. RESULTS: Acute kidney injury occurred in 128 of 5689 patients (2.2%) with acute ischemic stroke. A multivariate analysis revealed that the stroke subtype, the basal serum creatinine level, and the presence of infectious complications on admission were each predictors of developing AKI. In contrast, a free radical scavenger, edaravone, reduced the risk of developing AKI (multivariate-adjusted odds ratio [OR] .45, 95% confidence interval [CI] .30-.67). Propensity score-matched case-control study confirmed that edaravone use was negatively associated with AKI (propensity score-adjusted OR .46, 95% CI .29-.74). CONCLUSIONS: Although AKI has a significant impact on the clinical outcome of hospital inpatients, edaravone has a protective effect against the development of AKI in patients with acute ischemic stroke.

Phase I clinical study of edaravone in healthy Chinese volunteers: safety and pharmacokinetics of single or multiple intravenous infusions.

OBJECTIVE: The objective of this study was to investigate the safety and pharmacokinetics of edaravone administered by single or successive intravenous infusions in healthy Chinese volunteers. METHODS: A total of 30 subjects (15 males and 15 females) were recruited and randomly assigned to three groups receiving edaravone doses of 20, 30, and 60 mg. All subjects received a single dose of edaravone during a 30-minute period, and only the 30 mg dose group continued to receive the same dose successively by intravenous infusion twice daily for the next 5 days. Plasma concentrations of edaravone were monitored by high-performance liquid chromatography at the following times: 15, 30, 45, 60, 75, 105, 165, 225, 300, 390, 480, 600, and 720 minutes after edaravone administration. RESULTS: The area under the plasma concentration-time curve during a dosage interval (AUC(τ)) values of the single dose in the 20, 30, and 60 mg dose groups were 3.64 ± 1.37, 5.17 ± 0.93, and 11.25 ± 3.42 mg · h/L, respectively, while in the group receiving repeated dosing of 30 mg, the mean AUC(τ) value was 5.06 ± 0.89 mg · h/L. The corresponding maximum plasma drug concentration (C(max)) values were 1599.0 ± 382.6, 2378.7 ± 316.7, and 4540.1 ± 901.1 ng/mL, respectively, in the single-dose groups, and 2479.1 ± 477.9 ng/mL in the 30 mg repeated-dose group. The mean AUC(τ) and C(max) ratios between the repeated-dose group and the single-dose groups were 0.98 and 1.04. All laboratory test abnormalities (including increased alanine transaminase and triacylglycerol levels, and decreased white blood cell counts and creatinine levels) were mild and tolerable. All abnormal blood biochemical indices returned to normal levels after 7 days. CONCLUSION: Edaravone was safe and well tolerated in the volunteers and displayed linear increases in the C(max) and AUC(τ) values.

Basophil activation test for investigation of IgE-mediated mechanisms in drug hypersensitivity.

Hypersensitivity reactions against non-steroidal anti-inflammatory drugs (NSAIDs) like propyphenazone (PP) and diclofenac (DF) can manifest as Type I-like allergic reactions (1). In clinical practice, diagnosis of drug hypersensitivity is mainly performed by patient history, as skin testing is not reliable and oral provocation testing bears life-threatening risks for the patient (2). Hence, evidence for an underlying IgE-mediated pathomechanism is hard to obtain. Here, we present an in vitro method based on the use of human basophils derived from drug-hypersensitive patients that mimics the allergic effector reaction in vivo. As basophils of drug-allergic patients carry IgE molecules specific for the culprit drug, they become activated upon IgE receptor crosslinking and release allergic effector molecules. The activation of basophils can be monitored by the determination of the upregulation of CD63 surface expression using flow cytometry (3). In the case of low molecular weight drugs, conjugates are designed to enable IgE receptor crosslinking on basophils. As depicted in Figure 1, two representatives of NSAIDs, PP and DF, are covalently bound to human serum albumin (HSA) via a carboxyl group reacting with the primary amino group of lysine residues. DF carries an intrinsic carboxyl group and, thus, can be used directly (4), whereas a carboxyl group-containing derivative of PP had to be organochemically synthesized prior to the study (1). The coupling degree of the low molecular weight compounds on the protein carrier molecule and their spatial distribution is important to guarantee crosslinking of two IgE receptor molecules. The here described protocol applies high performance-size exclusion chromatography (HPSEC) equipped with a sequential refractive index (RI) and ultra violet (UV) detection system for determination of the coupling degree. As the described methodology may be applied for other drugs, the basophil activation test (BAT) bears the potential to be used for the determination of IgE-mediated mechanisms in drug hypersensitivity. Here, we determine PP hypersensitivity as IgE-mediated and DF hypersensitivity as non-IgE-mediated by BAT.

New treatment of free-radical scavenger in adrenoleukodystrophy.

WHAT IS KNOWN AND OBJECTIVE: Adrenoleukodystrophy (ALD) is an X-linked disorder and characterized by the accumulation of saturated very long-chain fatty acids. Treatment is still unsatisfactory. Our objective is to report on the effect of the free-radical scavenger, edaravone, in a patient with ALD. CASE SUMMARY: The patient was given edaravone intravenously twice. D-ROM in cerebral spinal fluid decreased dramatically, and a shortening of neuronal transmission time as estimated on somatosensory evoked potential was observed. After terminating the treatment, his symptoms progressively reappeared. WHAT IS NEW AND CONCLUSION: This is the first report of the use of edaravone in ALD. The drug is apparently effective in improving symptoms of ALD and should be evaluated more formally.

Effect of edaravone on the estimated glomerular filtration rate in patients with acute ischemic stroke and chronic kidney disease.

The oxygen free radical scavenger edaravone is used in patients with acute ischemic stroke in Japan, but adverse reactions, especially decreased renal function, have raised concerns. To examine whether a patient's estimated glomerular filtration rate (eGFR) at admission can predict renal function deterioration after edaravone treatment, we retrospectively evaluated the effect of edaravone on eGFR in Japanese patients with acute ischemic stroke and chronic kidney disease (CKD). The baseline eGFR in the edaravone-treated group (73.5±20.3 mL/min/1.73 m(2); n=408) at admission was significantly (P < .05) higher than that in the non-edaravone-treated group (51.9±25.2 mL/min/1.73 m(2); n=41). The change in eGFR after treatment was categorized into 3 grades: nonexacerbation (≤10%), 10%-30% exacerbation, and >30% exacerbation. There was no significant difference in exacerbation grade between the edaravone-treated and non-edaravone-treated groups (χ(2) =3.134; P=.21). We next subdivided the edaravone-treated group according to eGFR at admission as either CKD (eGFR <60 mL/min/1.73 m(2); n=111) and non-CKD (n=297). No significant decrease in eGFR was seen even in the edaravone-treated CKD group (most of whom were in stage 3 CKD). Decreased eGFR in stroke patients was found to be associated with stroke subtype (cardiogenic stroke), but not with infection. The present study demonstrates that eGFR at admission is not a good predictor of renal deterioration in edavarone-treated acute ischemic stroke patients, including those with stage 3 CKD.