Three cases of right frontal megalencephaly: Clinical characteristics and long-term outcome.

AIM: To delineate the clinical and neuroimaging characteristics of localized megalencephaly involving the right frontal lobe. METHOD: Data from three patients aged 14-16 years at the last follow-up were retrospectively reviewed. RESULTS: All the patients were normal on neurological examination with no signs of hemiparesis. Enlargement of the right frontal lobe with increased volume of subcortical and deep white matter, as well as thickening of the ipsilateral genu of the corpus callosum was common. The onset of epilepsy was 4-7 years of age, with seizure types of massive myoclonus in two and generalized tonic-clonic in two, which could be eventually controlled by antiepileptics. Interictal electroencephalography showed frontal alpha-like activity in one, and abundant spike-wave complexes resulting in diffuse continuous spike-wave activity during sleep in two patients even after suppression of clinical seizures. Psychomotor development appeared unaffected or slightly delayed before the onset of epilepsy, but became mildly disturbed during follow-up period of 7-11 years. CONCLUSION: Certain patients with right frontal megalencephaly can present with a milder epileptic and intellectual phenotype among those with localized megalencephaly and holohemispheric hemimegalencephaly, whose characteristic as epileptic encephalopathy was assumed from this study.

Unusual progression of herpes simplex encephalitis with basal ganglia and extensive white matter involvement.

We report a 51-year old male with herpes simplex encephalitis (HSE) showing unusual progression and magnetic resonance (MR) findings. The initial neurological manifestation of intractable focal seizure with low-grade fever persisted for three days, and rapidly coma, myoclonic status, and respiratory failure with high-grade fever emerged thereafter. The polymerase chain reaction (PCR) result of cerebrospinal fluid (CSF) was positive for HSV-1 DNA. In the early stage, MR images (MRI) were normal. On subsequent MR diffusion-weighted (DW) and fluid-attenuated inversion recovery (FLAIR) images, high-intensity areas first appeared in the left frontal cortex, which was purely extra-temporal involvement, and extended into the basal ganglia, then the white matter, which are relatively spared in HSE. Antiviral therapy and immunosuppressive therapy did not suppress the progression of HSE, and finally severe cerebral edema developed into cerebral herniation, which required emergency decompressive craniectomy. Histological examination of a biopsy specimen of the white matter detected perivascular infiltration and destruction of basic structure, which confirmed non specific inflammatory change without obvious edema or demyelination. The present case shows both MR and pathological findings in the white matter in the acute stage of HSE.

Ubc9 promotes the stability of Smad4 and the nuclear accumulation of Smad1 in osteoblast-like Saos-2 cells.

Bone morphogenetic proteins (BMPs) play important roles in osteoblast differentiation and maturation. In mammals, the BMP-induced receptor-regulated Smads form complexes with Smad4. These complexes translocate and accumulate within the nucleus, where they regulate the transcription of various target genes. However, the function of Smad4 remains unclear. We performed a yeast two-hybrid screen using Smad4 as bait and a cDNA library derived from human bone marrow to identify the proteins interacting with Smad4. Two full-length cDNA clones for Ubc9 were identified, and the potential functions of Ubc9 were investigated. To determine the role of Ubc9 in the BMP signaling pathway, the endogenous transcription of Ubc9 in the human osteoblast cell line Saos-2 was silenced using siRNA. The expression of BMP-induced transcription factors, including Runx2, Dlx5, Msx2, and Osterix, was examined using real-time reverse transcription polymerase chain reaction (qRT-PCR), and the protein expression of Smad4, Smad1, phosphorylated Smad1, and BMP type I receptors was determined by Western blotting. The subcellular localization of Smad1 and Smad4 was observed using immunofluorescence staining after Ubc9 silencing. To determine whether Smad4 is sumoylated in vitro, recombinant Smad4 was purified and sumoylated Smad4 was visualized using Western blotting. The mRNA expression of various transcription factors was markedly inhibited after Ubc9 silencing. The protein levels of Smad4 and phosphorylated Smad1 decreased in a dose-dependent manner according to the amount of siRNA applied. Gene silencing also decreased the nuclear accumulation of Smad1 and Smad4. The sumoylation assay showed that sumoylated Smad4 is present and dependent on Ubc9 in vitro, which was confirmed by pretreatment with Senp2, a SUMO-protease. These results suggest that Ubc9 promotes the stability of sumoylated Smad4. Furthermore, the expression of key transcription factors, phosphorylated Smad1 protein, and the nuclear accumulation of Smad1 and Smad4 are inhibited by Ubc9 silencing. Thus, Ubc9 plays an important role in the up-regulation of the BMP signaling pathway.

Steroid-responsive encephalitis lethargica syndrome with malignant catatonia.

We report a 47-year-old man who is considered to have sporadic encephalitis lethargica (EL). He presented with hyperpyrexia, lethargy, akinetic mutism, and posture of decorticate rigidity following coma and respiratory failure. Intravenous methylprednisolone pulse therapy improved his condition rapidly and remarkably. Electroencephalography (EEG) showed severe diffuse slow waves of bilateral frontal dominancy, and paralleled the clinical course. Our patient fulfilled the diagnostic criteria for malignant catatonia, so we diagnosed secondary malignant catatonia due to EL syndrome. The effect of corticosteroid treatment remains controversial in encephalitis; however, some EL syndrome patients exhibit an excellent response to corticosteroid treatment. Therefore, EL syndrome may be secondary to autoimmunity against deep grey matter. It is important to distinguish secondary catatonia due to general medical conditions from psychiatric catatonia and to choose a treatment suitable for the medical condition.

Localized lesions on MRI in a case of hypertensive brainstem encephalopathy.

We report a case of hypertensive brainstem encephalopathy (HBE) with unusual magnetic resonance imaging (MRI) findings. A 67-year-old woman presented with high blood pressure and stupor as the only symptoms. MRI revealed lesions localized in the area from the upper medulla oblongata to the lower pons with high fluid-attenuated inversion recovery (FLAIR) and T2-weighted signal intensity, but these were not seen in the whole brainstem and there were no accompanying occipital lobe changes. To our knowledge, no similar case has been reported. The lesions and symptoms dramatically improved after normalization of blood pressure. Severe hypertension that exceeded the range of autoregulation may have resulted in segmental vasodilatation and the increased vascular permeability may have lead to vasogenic edema in the localized areas of the brainstem.

An unexpected outbreak of Japanese encephalitis in the Chugoku district of Japan, 2002.

Six patients unexpectedly presented with Japanese encephalitis (JE) from early August to mid-September 2002 in the Chugoku district of Japan. The mean age was 67.5 years (range 42 - 89 years); the onset period in two patients shifted to the middle of September. The JE virus was isolated from the cerebrospinal fluid samples from two patients, and the strain isolated in the one was identified as genotype III. Neurologically, consciousness impairment, meningeal signs, rigidity, hemiparesis, tetraparesis, and convulsive seizures were commonly observed. Magnetic resonance imaging uniformly revealed high signal intensities in the bilateral thalami, brainstem (substantia nigra), hippocampi, and brain cortices. In all patients, acyclovir was used, due to the unexpected outbreak of JE. Five patients, except for one without sequelae, had a severe outcome, including one death. This report indicates that JE in Japan is still a threat to adults and the elderly with decreased or absent immunity to the JE virus.