Resveratrol improves motor function in patients with muscular dystrophies: an open-label, single-arm, phase IIa study.

Muscular dystrophies (MDs) are inherited disorders characterized by progressive muscle weakness. Previously, we have shown that resveratrol (3,5,4'-trihydroxy-trans-stilbene), an antioxidant and an activator of the protein deacetylase SIRT1, decreases muscular and cardiac oxidative damage and improves pathophysiological conditions in animal MD models. To determine whether resveratrol provides therapeutic benefits to patients with MDs, an open-label, single-arm, phase IIa trial of resveratrol was conducted in 11 patients with Duchenne, Becker or Fukuyama MD. The daily dose of resveratrol was 500 mg/day, which was increased every 8 weeks to 1000 and then 1500 mg/day. Primary outcomes were motor function, evaluated by a motor function measure (MFM) scale, muscular strength, monitored with quantitative muscle testing (QMT), and serum creatine kinase (CK) levels. Adverse effects and tolerability were evaluated as secondary outcomes. Despite the advanced medical conditions of the patients, the mean MFM scores increased significantly from 34.6 to 38.4 after 24 weeks of medication. A twofold increase was found in the mean QMT scores of scapula elevation and shoulder abduction. Mean CK levels decreased considerably by 34%. Diarrhoea and abdominal pain was noted in six and three patients, respectively. Resveratrol may provide some benefit to MD patients.

Epileptic negative myoclonus: a combined study of EEG and [123I]iomazenil (123I-IMZ) single photon emission computed tomography indicating involvement of medial frontal area.

Negative myoclonus (NM) is a sudden brief atonia in muscle that causes jerky lapses of posture. This study employed an electrophysiological technique (silent-period-locked-averaging (SPLA) electroencephalography (EEG)) and a pharmacodynamic imaging technique (123I-IMZ-SPECT) to examine epileptic NM (ENM). Delayed-phase 123I-IMZ-SPECT images, which reflect the specific binding of the tracers to GABA-A receptors, exhibited significant decrease in the left medial frontal area. The deficit in GABA-A receptors indicated that abnormal synchronization was mediated by the lack of inhibitory postsynaptic mechanism. The SPLA-EEG recorded spike-like notches superimposed on the slope of negative slow activity in the contralateral fronto-central region. The slow activity started around 100 ms before and the peak of the spike-like component was 30 ms before the onset of ENM. Since the 123I-IMZ-SPECT shows the actual distribution of the tracers, the abnormal area associated with ENM in this particular patient was supposed to be on the left medial frontal lobe. Scalp EEG, though it cannot always accurately locate the abnormal area, was highly sensitive to be able to detect electrical activities transmitted through neuronal network or volume conductor. Combined use of the two methods provided high resolution both in spatial and temporal domain.

[Valproate sodium and zonisamide associated interstitial pneumonitis in an infant].

A six month-old female infant developed dyspnea when she was treated with valproate sodium (VPA) and zonisamide (ZNS) for epileptic spasms. Two weeks after its onset, her dyspnea was exacerbated by respiratory syncytial virus (RSV) infection. We diagnosed interstitial pneumonitis (IP) based on her chest CT and high serum concentrations of KL-6 and surfactant protein D. Her dyspnea improved with the treatment which included steroids, neutrophil elastase inhibitor and discontinuation of VPA and ZNS. An allergic reaction probably explains the IP in our patient because steroids were effective. Her IP might have been exacerbated by several factors including the use of two anticonvulsants (VPA, ZNS), RSV infection, and physiological low serum IgA level of infants. Drug-induced interstitial lung disease should be remembered as a possible complication of anticonvulsant treatment, such as VPA and ZNS.

Guillain-Barre syndrome with meningoencephalitis after Campylobacter jejuni infection.

A 14-year-old boy presented with progressive ascending muscle weakness, urinary retention and disturbed consciousness. Initially his cerebrospinal fluid showed pleocytosis, and protein-cellular dissociation developed later. Campylobacter jejuni was isolated from his stool and serum anti-ganglioside antibodies were positive. Our case suggests that coexistence of meningoencephalitis at an early stage of illness does not necessarily exclude the diagnosis of Guillain-Barre syndrome.

Near-fatal cerebral edema associated with adenovirus type 2 infection in a previously healthy infant.

We report a near-fatal case of cerebral edema associated with adenovirus type 2 infection in a previously healthy 19-month-old boy. After 3 to 4 d of high fever and a series of seizures, he developed persistent loss of consciousness and irreversible respiratory arrest. Adenovirus type 2 infection was diagnosed by virus isolation from his stool and serology.

Intracranial hypertension in a boy with Mycoplasma pneumoniae infection: the first report.

We describe a 7-y-old boy who developed idiopathic intracranial hypertension (IIH) during the convalescent phase of Mycoplasma pneumoniae (M. pneumoniae) infection. Anti-M. pneumoniae antibody and cold hemagglutinin titer were extremely high during his course, and corticosteroid administration was noticeably effective. It supports an immunopathological mechanism for his intracranial hypertension.

[A case of oligodendroglioma with temporal lobe epilepsy initially suspected as having paroxymal tachycardia].

A 4-year-old girl had repetitive attacks of chest pain, palpitation and loss of consciousness, which lasted for a few minutes and occurred several times a day. Interictal and ictal EEGs revealed that these episodes were complex partial seizures with autonomic symptoms originating from the right antero-temporal area. Brain MRI depicted a tumor in the right temporal lobe, the suspected etiology of the seizures. The tumor and its surrounding area were carefully resected using electrocorticogram. Pathologically, the tumor was diagnosed as an oligodendroglioma. MR spectrometry demonstrated a definite reduction of NAA/creatine ratio in the tumor. It is reported that a probability of developing seizures in cases of oligodendroglioma is about 80-90%. The occurrence rate of seizures in oligodendroglioma is much higher than that in other brain tumors. The cause of the epileptogenesis in oligodendroglioma might be due to the pathological tissue of satellitosis and secondary degeneration of neurons.

Gelastic seizure with hypothalamic hamartoma: proton magnetic resonance spectrometry and ictal electroencephalographic findings in a 4-year-old girl.

Gelastic seizure is a rare symptom often associated with hypothalamic hamartoma. We present here a 4-year-old girl with gelastic epilepsy caused by hypothalamic hamartoma and report the magnetic resonance spectrometry and electroencephalographic (EEG) findings. At the age of 2 1/2 years, she developed brief, repetitive laughing attacks or mixed attacks with laughing and crying, which were refractory to carbamazepine. An interictal EEG showed intermittent slow waves in the left frontocentral region and sporadic positive sharp waves in the left centroparietal area. Ictal EEG demonstrated dysrhythmic theta activity in the left central area 3 seconds after the onset of laughing. Brain magnetic resonance imaging demonstrated a large sessile mass, isointense to gray matter, in the region of the hypothalamus, suggesting hypothalamic hamartoma. Proton magnetic resonance spectrometry of the hypothalamic hamartoma revealed a significant reduction of the N-acetylaspartate/serum creatinine ratio. The altered chemical shift imaging with magnetic resonance spectrometry in our patient suggests a biochemical abnormality in the tissue of the hypothalamic hamartoma. Moreover, this abnormal function of the hamartoma tissue might be closely related to epileptogenesis because the time difference between the ictal laughter and the subsequent EEG changes in the ictal EEG does not support the idea that the activated cortex is the epileptogenic focus.