Clinical features of long-term low-dose levetiracetam treatment for epilepsy.

BACKGROUND: The aim of this study was to assess the rate of response to long-term low-dose levetiracetam (LEV) treatment and the clinical factors associated with response. METHODS: The response to low-dose LEV of 43 patients with epilepsy (22 male, 21 female; age range, 5-39 years; median age, 13 years) was retrospectively assessed. Patients aged <15 years received <20 mg/kg/day LEV, whereas those aged ≥15 years received <1000 mg/day LEV. Clinical features were compared between responders to low-dose LEV, responders to the recommended dose, and non-responders. RESULTS: Of the 43 patients who received low-dose LEV, 13 (30%) showed improvement, defined as seizure cessation or >75% seizure reduction over 6 months for patients with monthly, weekly, and daily seizures; and over 1 year for patients with yearly seizures. Efficacy was maintained for >1 year in 10 (77%) of the 13 patients. Long-term response to low-dose LEV was significantly associated with older age at onset and fewer previous treatments with ineffective anti-epileptic drugs. All patients showing long-term response to low-dose LEV developed only focal seizures. CONCLUSIONS: Titration of LEV starting from a low dose may be effective in selected patients. Once patients respond to low-dose treatment, maintenance of the effective dosage may prolong response.

Hypersomnia and low cerebrospinal fluid hypocretin levels in acute disseminated encephalomyelitis.

A 7-year-old Japanese female diagnosed as having acute disseminated encephalomyelitis presented seizures, visual symptoms, and hypersomnia with bilateral lesions in the white matter, basal ganglia, and hypothalamus. Her clinical findings and demonstrated lesions in neuroimages were similar to those of Von Economo's encephalitis lethargica. Her hypocretin, the hypothalamic neuropeptide controlling sleep-awake cycle, was significantly low in the cerebrospinal fluid (146 pg/mL) on admission. Successive measures resulted in the gradual recovery of cerebrospinal fluid hypocretin to the normal range (263 pg/mL) as her excessive daytime sleepiness was reduced. Decreased hypothalamic hypocretin neurotransmission may be involved in this symptomatic case of hypersomnia associated with acute disseminated encephalomyelitis.

The safety of high-dose vitamin E supplementation in healthy Japanese male adults.

We administered high-dose vitamin E to healthy adult male volunteers and assessed the safety of such supplementation. Fourteen volunteers received daily 1,200 IU of vitamin E (800 mg of D-alpha-tocopherol) for 28 d and eight controls were also enrolled. The volunteers treated with vitamin E showed no abnormalities during the study period. The alpha-tocopherol concentrations of plasma and platelets were markedly elevated by vitamin E treatment, but there were no significant differences in platelet aggregation, coagulation, and the clinical parameters between the two groups. In conclusion, a high dose of vitamin E for 28 d had no adverse effects in healthy men.

Effect of angiotensin-converting enzyme inhibitor on matrix metalloproteinase-9 activity in patients with Kawasaki disease.

BACKGROUND: Matrix metalloproteinase (MMP)-9 is thought to be involved in coronary artery aneurysms (CAAs) in patients with Kawasaki disease (KD); however, MMP-9 inhibitors are not used clinically. This study investigated whether the angiotensin-converting enzyme (ACE) inhibitor captopril could inhibit serum MMP-9 activity using serum from KD patients in an in vitro experiment. METHODS: In 7 KD patients, serum MMP-9 activity was measured using the MMP-9 assay kit 3 times: before and after intravenous immunoglobulin (IVIG) treatment, and during the convalescent phase. The effect of captopril on MMP-9 activity was also assessed using serum obtained before IVIG treatment. RESULTS: Serum MMP-9 activity was significantly higher during the pre-treatment phase than during the post-treatment and convalescent phases. MMP-9 activity during the pre-treatment phase was dose-dependently inhibited by captopril, and the IC(50) for MMP-9 was 500nM. The potency of captopril for MMP-9 inhibition was comparable to that for ACE inhibition. CONCLUSION: ACE inhibitor may be effective for preventing CAA formation in KD patients, especially IVIG non-responders.