Use of Perampanel and a Ketogenic Diet in Nonketotic Hyperglycinemia: A Case Report.

BACKGROUND: Nonketotic hyperglycinemia is a severe form of early onset epileptic encephalopathy caused by disturbances in the glycine cleavage system; the neurological damage is mainly attributed to overstimulation of the N-methyl-D-aspartate receptor. CASE: The patient presented with a severe form of nonketotic hyperglycinemia and experienced frequent epileptic spasms and focal seizures, which were resistant to vigabatrin, adrenocorticotropic hormone therapy, and combined dextromethorphan and sodium benzoate treatments. By 9 months of age, perampanel reduced epileptic spasms by >50%. At 14 months of age, the ketogenic diet markedly reduced focal seizures and glycine levels in the cerebrospinal fluid. CONCLUSION: Perampanel reduced fast excitatory neuronal activity, which was induced by an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor, followed by prolonged electrical depolarizations due to an N-methyl-D-aspartate receptor. Furthermore, the ketogenic diet may have modulated the excessive neurotoxic cascade through the N-methyl-D-aspartate receptor. Perampanel and ketogenic diet were effective for seizure control in our patient.

Comparison of adrenocorticotropic hormone efficacy between aetiologies of infantile spasms.

PURPOSE: We aimed to study the efficacy of adrenocorticotropic hormone (ACTH) treatment on infantile spasms with different aetiologies. In particular, we were interested in patients with structural-acquired aetiology. METHODS: Patients with infantile spasms, who were treated with ACTH, were divided into three groups based on the aetiologies: unknown aetiology with normal development (unknown-normal), structural-acquired, and combined-congenital aetiologies that included genetic, metabolic, structural-congenital, or unknown aetiology with developmental delay. RESULTS: Of the 107 patients included (58 males, 49 females), 25 patients had unknown-normal aetiology [median age at onset 5 months, standard deviation (SD) 3.12, range 2-16 months]; 20 patients had structural-acquired aetiology (median age at onset 6.5 months, SD 3.85 months, range 4-17 months); and 62 patients had combined-congenital aetiologies (median age at onset 5 months, SD 2.73 months, range 2-16 months). The efficacy of ACTH was 64.0 %, 65 %, and 30.6 % in the unknown-normal aetiology, structural-acquired aetiology, and combined-congenital aetiologies, respectively (p < 0.01). Multivariate analysis showed a statistically significant higher efficacy in the unknown-normal aetiology [Odds ratio (OR) 4.63, 95 % confidence interval (CI) 1.60-13.30] and structural-acquired aetiology (OR 3.41, 95 % CI 1.01-11.50) compared to that in the combined-congenital aetiologies. CONCLUSION: Infantile spasms with structural-acquired aetiology had greater response to ACTH treatment than those with combined-congenital aetiologies. The efficacy of standard therapy of infantile spasms should be considered based on aetiology.

Long-term safety and tolerability of atomoxetine in Japanese adults with attention deficit hyperactivity disorder.

INTRODUCTION: The primary aim of this study was to evaluate the long-term safety/tolerability of atomoxetine in Japanese adults with attention deficit hyperactivity disorder (ADHD). METHODS: This 48-week, open-label extension study involved participants with ADHD who completed a 10-week randomized controlled trial of atomoxetine. Participants received atomoxetine 40 mg/day, followed by step-wise titration to a maximum of 120 mg/day. The primary outcome was safety/tolerability. Secondary outcomes were symptoms of ADHD (Conners' Adult ADHD Rating Scales-Investigator Rated: Screening Version 18-item total score), quality of life (Adult Attention-Deficit/Hyperactivity Disorder Quality of Life scale), and executive function (Behavior Rating Inventory of Executive Function-Adult Version: Self-report). RESULTS: Of the 39.5% of participants overall who discontinued the study, 15.9% (37/233) of participants discontinued because of adverse events (AEs), primarily nausea (4.3%; 10/233). Overall, 93.6% (218/233) of participants experienced treatment-emergent AEs (TEAEs), most commonly nausea (56.2%; 131/233), nasopharyngitis (25.3%; 59/233), thirst (19.3%; 45/233), headache (17.2%; 40/233), and decreased appetite (16.3%; 38/233). Most TEAEs (70.8%; 165/233) were mild in intensity. Overall, 79.8% (186/233) of participants experienced ≥1 adverse drug reaction, primarily nausea (55.4%; 129/233). Five participants experienced serious AEs during the open-label extension; none was related/possibly related to treatment. There were statistically significant increases in vital signs and decreases in body weight that were not considered clinically significant. Symptoms of ADHD, quality of life, and executive function were significantly improved from baseline to endpoint (P < 0.05). DISCUSSION: Despite discontinuations due to the long-term, open-label design, AE related discontinuations were modest, suggesting that atomoxetine has acceptable long-term safety and tolerability in Japanese adults with ADHD. Symptoms of ADHD improved and remained improved throughout the study.