Meng-Fai Kuo

Tourette's syndrome in Taiwan: an epidemiological study of tic disorders in an elementary school at Taipei County

We have done an epidemiological study in an elementary school with 2000 Taiwanese children aged from 6 to 12 years, and found 11 of them with Tourettes syndrome. The prevalence rate of Tourettes syndrome was around 0.56%. The ratio of male to female was 9 to 2. The comorbid rate of attention-deficit/hyperactivity disorder was 36%, self-injurious behaviors 27%, and obsessive-compulsive behaviors 18%. The familial rate of Tourettes syndrome was 27%. We also found that another 98 children had transient tic disorders. For 73% of patients with mild tics, understanding and acceptance from family, teachers, and friends are the most important things. When tics are so severe that medication is necessary, haloperidol is no longer the first or only choice. We tried clonidine, atypical neuroleptics such as risperidone or olanzapine, or pergolide. The first support group was established in 1999 for children with tics in Taiwan and transformed to Taiwan Tourette Family association in June 2001 to provide further service for Tourettes syndrome.

Pyridoxal phosphate-responsive epilepsy with resistance to pyridoxine

We present a female infant with seizures responsive to pyridoxal phosphate but that are resistant to pyridoxine. The mechanism by which pyridoxal phosphate controls seizures in this patient is unknown. Her seizures are perhaps not solely caused by pyridoxal phosphate deficiency. It is suggested that in addition to glutamic acid decarboxylase abnormality, the path from the absorption, transportation, phosphorylation, and oxidation of pyridoxine to pyridoxal phosphate in this patient might be defective. It should be considered whether pyridoxal phosphate can be the drug of choice instead of pyridoxine in treating patients suspected of pyridoxine-dependent epilepsy to reduce failure rate and further delay in seizure control.

Pyridoxal phosphate is better than pyridoxine for controlling idiopathic intractable epilepsy

Aim: To study the difference between pyridoxine (PN) and its active form, pyridoxal phosphate, (PLP) in control of idiopathic intractable epilepsy in children. Methods: Among 574 children with active epilepsy, 94 (aged 8 months to 15 years) were diagnosed with idiopathic intractable epilepsy for more than six months. All received intravenous PLP 10 mg/kg, then 10 mg/kg/day in four divided doses. If seizures recurred within 24 hours, another dose of 40 mg/kg was given, followed by 50 mg/kg/day in four divided doses. For those patients whose seizures were totally controlled, PLP was replaced by the same dose of oral PN. If the seizure recurred, intravenous PLP was infused followed by oral PLP 50 mg/kg/day. Results: Fifty seven patients had generalised seizures (of whom 13 had infantile spasms) and 37 had focal seizure. Eleven had dramatic and sustained responses to PLP; of these, five also responded to PN. Within six months of treatment with PLP or PN, five of the 11 patients were seizure free and had their previous antiepileptic medicine tapered off gradually. Two were controlled with pyridoxine and the other three needed PLP to maintain seizure freedom. The remaining six responders needed PLP exclusively for seizure control. Six of the 11 responders to PLP had infantile spasms (46%); four of them needed PLP exclusively. The other five responders were in the remaining 81 patients with other seizure type. Conclusions: PLP could replace PN in the treatment of intractable childhood epilepsy, particularly in the treatment of infantile spasms.

Clinical Significance of Posterior Circulation Changes after Revascularization in Patients with Moyamoya Disease

Objective: It has been noted that the posterior circulation serves as an important source of collateral blood supply in moyamoya disease. Since most of the literature has focused on non-operative cases and many symptomatic patients receive surgical revascularization, we evaluated the posterior circulation changes after revascularization and found that progressive posterior cerebral artery (PCA) steno-occlusive changes after revascularization caused cerebral hemodynamic compromise and clinical deterioration in a significant portion of patients. Methods: Twenty-three moyamoya disease patients with ischemic presentation who received revascularization with complete angiography and xenon CT during a minimum of 3 years’ clinical follow-up were enrolled. Revascularization was performed in 38 hemispheres. Pre- and postoperative angiography were reviewed to determine the internal carotid artery (ICA) stage, PCA stage, leptomeningeal collateral (LMC) grade, and Matsushima synangiosis grade. The postoperative regional cerebral blood flow (CBF) and cerebral vascular reserve (CVR) were recorded and correlated with angiographic findings and clinical outcome. Results: Progression of ICA staging was noted in 23 sides (55.2%), and progression of PCA staging was noted in 18 sides (47.4%). Among the 18 cases of PCA stage progression, an associated decrease in LMC grade was noted in 12 sides (66.7%). These changes were associated with decreased regional CBF and CVR, which also explained the recurrent ischemic symptoms in 27.8% of these patients. In contrast, LMC grade increased in 15 (65.2%) sides of patients with ICA progression. Conclusions: Progressive steno-occlusive change in the PCA after revascularization is associated with a reduction in LMC blood flow and cerebral ischemia in moyamoya patients. This phenomenon might cause recurrent ischemic symptoms in 27.8% of patients.

Choreoathetosis as an initial sign of relapsing of herpes simplex encephalitis

Twelve children with type 1 herpes simplex encephalitis (3 with relapse, 9 without) have been monitored during the past 7 years. Ten of the children received intravenous infusion of acyclovir (30 mg/kg/day) for 10 days, 1 child who experienced relapse received 15 mg/kg/day, and another relapsed child received no antiviral agents until relapse. Relapse occurred 20-36 days after initial onset. All relapsed patients underwent another 10 days of acyclovir treatment (30 mg/kg/day). Choreoathetosis appeared as the initial sign of relapse followed by rapidly progressive unresponsiveness in all 3 relapsed patients: in 1 nonrelapsed patient choreoathetosis occurred during the recovery period. In these 4 patients involuntary movement was remitted within 3 months to 2 years. One patient with choreoathetosis died of measles pneumonia 4 months after onset of herpes simplex encephalitis and the surviving 3 were severely retarded. Although neuroimaging sparing of basal ganglia does not indicate structural and functional abnormalities, the disturbance of the neural connection among the basal ganglia and the cerebral cortex, which manifested severe damage over frontal, temporal, and parietal mantles on CT, may be the source of movement disorders in these patients. We conclude that choreoathetosis may be the first sign of relapse of herpes simplex encephalitis in children and may be an indicator of poor prognosis. The neuropathogenesis of choreoathetosis requires further investigation.

Correlation among pathology, genetic and epigenetic profiles, and clinical outcome in oligodendroglial tumors

Recent studies have revealed a correlation between specific genetic changes, such as loss of chromosome 1p and 19q, and sensitivity of oligodendroglial neoplasm to radiotherapy and chemotherapy; epigenetic changes also play an important role in some tumors. In this retrospective study, we analyzed chromosomal alterations in 17 loci and promoter methylation status of 8 tumor‐related genes in 49 oligodendroglial tumors (29 WHO grade II and 11 WHO grade III oligodendrogliomas; 7 WHO grade II and 2 WHO grade III oligoastrocytomas) using quantitative microsatellite analysis and methylation‐specific polymerase chain reaction and correlated this information with clinical data. We also performed immunohistochemical stains for Ki‐67 and O (6)‐methyl guanine‐DNA methyl transferase. Our results showed that the frequency of deletions in regions on 1p, 9p, 10q, 17p and 19q were 71.4%, 26.5%, 6.1%, 69.4% and 89.8%, respectively. Promoter methylation was detected in p14, p15, p16, p53, p73, PTEN, MGMT and RASSF1A genes in 24.5%, 6.1%, 46.9%, 0%, 6.1%, 42.9%, 53.1% and 77.6% of tumors, respectively. Statistical analysis identified that 9p22 loss, p73 methylation and p15 methylation were independently associated with reduced overall survival, and Ki‐67 labeling index (LI) ≥ 5%, 9p22 loss, no loss of 19q, p73 methylation, p14 methylation and unmethylated MGMT predicted shorter progression‐free survival. Our findings suggest that the frequent deletion and hypermethylation of tumor‐related genes may represent a mechanism of tumor development and progression and emphasize the importance of defining new molecular markers for predicting prognosis, tumor recurrence and therapeutic response in cancer management.

Epidemiology of Moyamoya Disease in Taiwan A Nationwide Population-Based Study

Background and Purpose— Previous studies have shown regional and temporal variations in epidemiological features of moyamoya disease, but population-based studies in regions other than Japan are limited. We investigated the incidence and patients characteristics of moyamoya disease during 12 years in Taiwan using claims databases of a universal health insurance system. Methods— From the inpatient databases of the Taiwan National Health Insurance program, we identified subjects who had an initial hospitalization with moyamoya disease and had been underwent cerebral angiography as incidence cases during 2000 to 2011. The incidence and the patient characteristics were described by age and time periods of the hospitalization. Results— During the 12-year period, 422 patients were identified, representing an annual incidence of 0.15 per 100 000 person-years. Adults exhibited an upward trend in incidence with an incidence rate ratio of 1.74 (95% confidence interval [1.17–2.58]) in years 2010 to 2011 comparing with years 2000 to 2001. However, children had a decreased incidence except a slightly increase in the last 2 years. Compared with patients hospitalized during 2000 to 2005, patients identified during 2006 to 2011 had greater women-to-men ratio (1.7 versus 1.1, P=0.048). Children were more likely to have comorbid epilepsy than were adult patients (25.0% versus 3.4%, P=0.002). Hemorrhagic stroke was rare among pediatric patients but presented more frequently in adults. However, ischemic stroke was more prevalent in both groups. Conclusions— The incidence of moyamoya disease has increased in adults but not in children from 2000 to 2011 in Taiwan. Sex ratio and comorbid conditions differed by age and study period.

High expression of stathmin protein predicts a fulminant course in medulloblastoma.

OBJECT Stathmin, an important cytosolic phosphoprotein, is involved in cell proliferation and motility. This study was performed to elucidate the role of stathmin in the progression of medulloblastoma. METHODS The expression of stathmin protein was examined by immunohistochemical staining of tumor sections obtained in 17 consecutive patients with medulloblastoma who underwent resection between 1995 and 2005. Four patients were excluded because they were either lost to follow-up or underwent biopsy sampling only, leaving a total of 13 patients in the study. The stathmin expression was scored according to the immunoreactive fraction of tumor cells, and the level was correlated with various clinicopathological factors. RESULTS The expression level of stathmin protein was < or = 10% in 9 patients, 11-50% in 1, and > 50% in 3. No staining was seen in the tissues adjacent to the tumors. For comparison, the authors grouped the expression level of stathmin into high (> 50%) and low (< or = 50%). It was found that patients with high expression of stathmin had more frequent tumor dissemination at the time of resection or soon after total excision of the tumor (p = 0.0035), and hence experienced a fulminant course with lower patient survival (p < 0.0001), with an average survival period of 6.7 months (range 2-10 months). The expression level of stathmin did not correlate with patient age, sex, CSF cytological findings, use of adjuvant therapies, Ki 67 index, or risk classification of the tumors according to previously described categories in the literature. CONCLUSIONS High stathmin expression correlates with tumor dissemination, is an important prognostic factor of medulloblastoma, and may serve as a useful marker for more intensive adjuvant therapies.

Chronological Changes on Magnetic Resonance Images in a Case of Desmoplastic Infantile Ganglioglioma

Desmoplastic infantile gangliogliomas (DIGs) are rare tumors during infancy. They often occur as huge cystic tumors in the frontal and parietal lobes, with their solid component being adjacent to the leptomeningeal membrane. This report presents a patient with DIG and intractable epilepsy. Due to hesitation by the patient’s family in allowing surgery, this is the first time that the chronological changes in DIG have been observed on imaging studies. During the follow-up, the tumor changed from a pure solid tumor to a cystic one, which is a typical picture of DIG. Surgical pathology confirmed the diagnosis of DIG. However, for a patient with epilepsy, it is recommended that this condition should be treated immediately with surgery.

Cerebral oxygen transport and metabolism during graded isovolemic hemodilution in experimental global ischemia

To verify the optimal hematocrit (Hct) level in the treatment of cerebral ischemia, cerebral oxygen transport (CTO2) and cerebral oxygen metabolism (CMRO2) in graded isovolemic hemodilution were evaluated during cerebral ischemia. Isovolemic hemodilution with low molecular weight dextran to stepwise lower Hct from 43% to 36%, 31%, and 26% was carried out in 13 splenectomized dogs, 6 h after global cerebral ischemia. Global ischemia of the animals was produced by multiple intra- and extracranial ligations of cerebral arteries. Cerebral blood flow (CBF) was measured with radioisotope labeled microspheres. CTO2, CMRO2, and oxygen extraction fraction (OEF) were calculated from CBF, arterial oxygen content (CaO2), and venous oxygen content (CvO2). In dogs with global cerebral ischemia, CBF increased with graded isovolemic hemodilution (r=-0.73, P<0.05). CTO2 reached its highest value at a Hct level of 31.3%. CTO2 at Hct of 36.1% and 31.3% was statistically different from the value measured at a Hct of 43.3%, and there was a decrease when Hct was lowered to 25.9%. CMRO2 was the highest when Hct was at 31.3% and differed significantly from the value measured at a Hct of 43.3%. There was a 10% increase of OEF when Hct was at 25.9%; however this change was not statistically significant compared with the OEF at Hct of 36.1% and 31.3%, respectively. These findings indicate that CTO2 and CMRO2 were the highest when Hct was reduced to 31% in hemodilution. Hct at 31% is the optimum for cerebral metabolism in ischemic status. Uncoupling of CTO2, CMRO2 with CaO2 was also observed in this study. This phenomenon suggests that hemodilution to augment cerebral circulation may be at least partially attributed to the beneficial effects of hemorheologic improvement in the microcirculation of the ischemic brain.