Hyperglycemic Crisis in Patients With Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS).

BACKGROUND: Diabetes mellitus is the most commonly encountered endocrinopathy in patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), which manifests as multisystemic organ failure. Whether the management of diabetes mellitus in MELAS requires special consideration is not fully clarified. METHODS: In this single-center study, we retrospectively reviewed the medical records of patients with MELAS to elucidate the clinical characteristics of MELAS-associated diabetes mellitus. RESULTS: Four patients among a total of 25 individuals with MELAS who were treated in the study institution developed diabetes mellitus. One patient had well-controlled diabetes mellitus, whereas the remaining three patients experienced hyperglycemic crisis as the first manifestation of diabetes mellitus. Two of the three patients were children aged four and six years. The hyperglycemic events occurred after surgery, infection, and status epilepticus, respectively. None of the three patients had diabetes mellitus previously based on randomly measured serum glucose levels that were within the normal range before the hyperglycemic crisis. Glycated hemoglobin levels measured during the hyperglycemic crisis indicated prediabetes in two patients and diabetes mellitus in one patient. Two patients recovered, whereas one patient died after developing multiorgan failure. CONCLUSIONS: Fulminant-onset diabetes mellitus occurring in patients with MELAS underscore the importance of routine measurement for glycated hemoglobin and more intense evaluation of glucose intolerance regardless of the patient age and lack of symptoms. Clinicians should be aware of the potential acute onset of hyperglycemic crisis in patients with MELAS, especially in individuals with aggravating factors.

Topiramate Blood Levels During Polytherapy for Epilepsy in Children.

BACKGROUND: The therapeutic range of topiramate (TPM) blood level is not set because the efficacy and safety are not considered to be related to the level. However, the therapeutic target without side effects is necessary, so the optimal range of TPM blood level was analyzed in this study. STUDY QUESTION: This study was conducted to evaluate the efficacy of TPM over 2 years and the utility of measuring blood levels of TPM during the follow-up of epileptic patients. STUDY DESIGN: Thirty patients (18 males, 12 females; age range, 6 months-15 years) were treated with TPM for epilepsy. The initial dosage of TPM was 1-3 mg·kg·d. If the effect proved insufficient after 2 weeks, the dosage was increased to 4-9 mg·kg·d. MEASURES AND OUTCOMES: Blood levels of TPM were measured by liquid chromatography-tandem mass spectrometry at 1, 6, 12, and 24 months after levels reached steady state. The efficacy of TPM was evaluated by the reduction in epileptic seizure rate (RR) at the time of blood sampling. Statistical analysis was performed using the Mann-Whitney U test. RESULTS: A positive correlation was seen between blood levels and maintenance dosages, but no correlation was observed between blood levels and RR. Any significant difference was not identified in TPM levels between the effective group (RR ≥50%) and the ineffective group (RR <50%; P = 0.159). In the subgroup of patients who did not use valproic acid, a significant difference in TPM levels was apparent between the effective and ineffective groups (P = 0.029). The optimal range of TPM was advocated 3.5-5.0 µg/mL. The optimal range was set, so that ranges did not overlap between the effective and ineffective groups. No patients experienced any side effects. CONCLUSIONS: Measuring blood levels of TPM based on the classification of concomitant drugs and adjusting the dosage to reach the optimal range were recommended.

Evoked potential studies for predicting functional recovery in a case of acute necrotizing encephalopathy.

Normal-appearing evoked potentials during the acute stage of the disease despite persistent coma may predict subsequent functional recovery of the brain in a pediatric case of acute necrotizing encephalopathy, indicating that evoked potential studies are useful for predicting functional outcome of the brain.

The Effectiveness of Lamotrigine and Its Blood Levels for Pediatric Epilepsy.

This study was conducted to evaluate the effectiveness of lamotrigine (LTG) over 2 years and the usefulness of measuring its blood levels during the follow-up of patients with epilepsy. We measured peak blood LTG levels of 32 patients with epilepsy (9.16 ± 3.34 years old; mean ± SD). The blood levels were measured at 6 months, 1 year, and 2 years after reaching the LTG maintenance dosage. The effectiveness of LTG was evaluated to determine the seizure reduction rate. The patients were classified as effective cases (mean of own seizure reduction rates >50%) and ineffective cases (≤50%). The results were that the dosage and blood level showed positive correlations in the case of combination use with sodium valproate (VPA) (r = 0.690), carbamazepine and/or phenobarbital (r = 0.940), and others (r = 0.548). In several groups, the blood levels and efficacies did not show any positive correlations. In the cases of combination use with VPA, the blood levels of effective cases and ineffective cases were significantly different (P = 0.001). The optimal range was 8-11.5 µg/mL based on the average and SD values in the effective cases. No patients had any side effects. In conclusion, no precise definition of the therapeutic range was possible because of the incomplete correlation between the blood level and seizure frequency. We recommend the optimal range of LTG as a therapeutic target without any side effects, and it was established that the range in the combination with VPA was 8-11.5 µg/mL.

Correlating blood and urinary concentrations of clobazam doses in Japanese children and adolescents with intractable epilepsy.

Clobazam (CLB) is an antiepileptic drug that is metabolized to the major metabolite N-desmethylclobazam (N-CLB). Our aim was to evaluate the utility of corrected urinary concentrations of CLB and N-CLB in Japanese children and adolescents with epilepsy. Blood and urinary concentrations of CLB and N-CLB were evaluated in 42 patients. The urinary and peak blood concentrations were measured 2-3 h after the last dose. The ratio of the blood and urinary creatinine concentrations was used to calculate the corrected urinary concentrations. A moderate correlation was found between the CLB dose and the CLB serum concentration, but this correlation was not found for N-CLB. Patients were dichotomized based on two regression lines, which were detected by statistical analyses with a cumulative distribution function: the lower ratio group (CLB/N-CLB < 0.275) and the higher ratio group (≥0.275). Moderate correlations were observed between the CLB dose and the serum concentration or the corrected value of CLB for the lower ratio group, and moderate to strong correlations were observed for the higher ratio group. The corrected urinary concentration of CLB correlates to the CLB dose when stratified by the CLB/N-CLB ratio and may prove practical for clinical estimation of the CLB serum concentration.

The efficacy of levetiracetam for focal seizures and its blood levels in children.

AIM: To evaluate the efficacy of levetiracetam (LEV) and the usefulness of measurement of its blood levels during the follow-up of patients with focal seizures. METHODS: Twenty-four patients (13 cases without impairment of consciousness or awareness and 11 cases with them or evolving to a bilateral, convulsive seizure) treated with LEV had their peak blood levels measured. The blood concentrations were measured at 2 weeks, 1 year and 2 years after reaching the LEV maintenance dosage. The efficacy of LEV was evaluated with repeated blood sampling to determine the seizure reduction rate. The patients were classified as effective cases (seizure reduction rate>50%) and ineffective cases (⩽50%). RESULTS: In Japanese children treated with LEV, the dosage and blood level showed positive correlations. The blood levels were higher in effective cases than in ineffective cases at all time points (p<0.05). In effective cases, the blood concentration was 23.26±6.88 µg/mL (mean±SD) 2 weeks later, 23.59±8.23 µg/mL 1 year later, and 24.46±7.57 µg/mL 2 years later. However, the blood levels and efficacies showed positive correlations only at 2 weeks and 1 year later. No patients had any side effects. CONCLUSIONS: No precise definition of the therapeutic range was possible because of the incomplete correlation between the blood level and seizure frequency. Instead of a therapeutic range, we recommend an optimal range for LEV of 20-30 µg/mL as a therapeutic target without any side effects.