Nitric oxide (NO) is a free radical and a signaling molecule in several pathways, produced by nitric oxide synthase (NOS) from the conversion of l-arginine to citrulline. Supplementation of l-arginine has been used to treat MELAS (mitochondrial encephalopathy with lactic acidosis and stroke like syndrome), a mitochondrial disease caused by the m.3243A>G mutation. Low levels of serum arginine and endothelium dysfunction have been reported in MELAS and this treatment may increase NO in endothelial cells and promote vasodilation, decreasing cerebral ischemia and strokes. Although clinical benefits have been reported, little is known about NO synthesis in MELAS. In this study we found that osteosarcoma derived cybrid cells with high levels of m.3243A>G had increased nitrite, an NO metabolite, and increased intracellular NO, demonstrated by an NO fluorescent probe (DAF-FM). Muscle vessels from patients with the same mutation had increased staining in NADPH diaphorase, suggestive of increased NOS. These results indicate increased production of NO in cells harboring the m.3243A>G, however no nitrated protein was detected by Western blotting. Further studies are necessary to clarify the exact mechanisms of l-arginine effect to determine the appropriate clinical use of this drug therapy.

According to the second edition of the International Classification of Headache Disorders (ICHD-II) 1 , migrainous infarction (MI) is a complication of migraine with aura. MI is diagnosed when one or more aura symptoms last longer than 60 minutes, and neuroradiological studies demonstrate ischemic stroke that potentially explains the symptoms. Stroke should not be attributed to another disorder. The ICHD-II also defines sporadic hemiplegic migraine (SHM) as a subtype of migraine with aura associated with fully reversible motor weakness in association to the typical aura symptoms (visual, sensory or dysphasic aura). Unlike familial hemiplegic migraine (FHM), familial history of migraine with motor weakness in first-or second-degree relatives is absent. MI in childhood is very rare and epidemiological studies are scarce 2 . Reports of incidence of migrainous stroke in this group range from 0.5% 2 to 1.7% 3. A fairly and diligent review of the literature found no previous reports of MI during childhood following SHM in Brazil.Herein we report a case of MI following SHM in a child. We obtained written informed consent to publish the case, as well as the results of genetic testing. The principles outlined in the declaration of Helsinki were followed. CASEA 10-year-old boy was initially referred to our service on May of 2004, with a 2-year history of attacks of bifrontal and throbbing headache, preceded by right hemi-hypoesthesia and hemiparesis that typically lasted less than 60 minutes. Headache attacks were of moderate intensity and were associated with photophobia and phonophobia. Frequency was around 3 per month and duration ranged from 10 to 72 hours.Family reported a single episode of headache in which the associated right hemiparesis lasted about three days. Although attack was longer and clearly not suggestive of a benign migraine attack, it had not been investigated.The patient had no relevant prior medical history. Relevant familial history included mother suffering from migraine with visual aura, and brother with a past episode of transient left hemiparesis (without headache) in the context of varicella infection.Two months before the first consultation, patient suffered a partial seizure, characterized by right hemi-body hypertonia, cephalic deviation and gaze shift to the right side, during a typical attack of hemiplegic migraine. Patient recovered totally and neurological exam was normal. Magnetic resonance imaging revealed a left thalamic (pulvinar) lesion, suggestive of ischemia (Fig 1). The patient was then referred to our division for investigation and treatment.A comprehensive complementary investigation with blood tests, imaging tests, genetic tests, EEG and CSF for ischemic stroke was performed and revealed no abnormalities. Treatment with flunarizine yielded adequate control of the migraine attacks, but it was suspended due to significant drowsiness and weight gain. Patient responded well to propranolol and is free of headaches since then (headache free for 2 years). Mutation screeningScreening ...