DEPDC5 mutations in familial and sporadic focal epilepsy.

BACKGROUND AND AIMS: Mutations in the disheveled, Egl-10 and pleckstrin domain-containing protein 5 (DEPDC5) gene have emerged as an important cause of various familial focal epilepsy syndromes. However, the significance of DEPDC5 mutations in patients with sporadic focal epilepsy has yet to be characterized. MATERIALS AND METHODS: We studied a kindred of familial focal epilepsy with variable foci using whole-exome sequencing. We subsequently studied a cohort of 293 patients with focal epilepsy and sequenced all exons of DEPDC5 using targeted resequencing. RESULTS: We reported a Taiwanese family with a novel splice site mutation which affected mRNA splicing and activated the downstream mammalian target of rapamycin (mTOR) pathway. Among patients with focal epilepsies, the majority (220/293) of these patients had sporadic focal epilepsy without malformation of cortical development. Two (0.9%) of these patients had probably pathogenic mutations in the DEPDC5 gene. DISCUSSION AND CONCLUSIONS: Our finding suggests that DEPDC5 is not only the most common gene for familial focal epilepsy but also could be a significant gene for sporadic focal epilepsy. Since focal epilepsies account for more than 60% of all epilepsies, the effect of mTORC1 inhibitor on patients with focal epilepsy due to DEPDC5 mutations will be an important future direction of research.

¹8F-FP-(+)-DTBZ positron emission tomography detection of monoaminergic deficient network in patients with carbon monoxide related parkinsonism.

BACKGROUND AND PURPOSE: Although parkinsonism after carbon monoxide (CO) intoxication is well known, neurotransmitter deficient networks that are responsible for the severity of parkinsonism have rarely been systemically evaluated. METHODS: Eighteen patients with CO-related parkinsonism and nine age- and sex-matched controls were enrolled for detailed neurological examinations, three-dimensional T1-weighted images, diffusion tensor imaging and (18)F-9-fluoropropyl-(+)-dihydrotetrabenzazine ((18)F-FP-(+)-DTBZ) positron emission tomography (PET). The structural analysis included voxel-based morphometry to assess grey matter atrophy and tract-based spatial statistics related to white matter involvement. For presynaptic monoaminergic assessment, volume of interest analysis in six subcortical regions and non-parametric voxel-wise comparison were performed on PET images with estimation of registration parameters from magnetic resonance images. All the imaging modalities were compared between the patients and controls. For the patients, a regression model for correlation with cognitive behaviour and Unified Parkinson's Disease Rating Scale (UPDRS) score was used. RESULTS: In the patients, monoaminergic deficit networks were found in the caudate, anterior putamen, anterior insular, thalamus and anterior cingulate cortex. The UPDRS revealed significant correlations with the prefrontal white matter fractional anisotropy values and with the (18)F-FP-(+)-DTBZ uptake values in the caudate nucleus, insular, medial prefrontal and dorsomedial thalamus. The neuropsychiatric inventory score correlated with the (18)F-FP-(+)-DTBZ uptake values in the anterior cingulate cortex and dorsolateral prefrontal cortex. CONCLUSIONS: Our study demonstrated monoaminergic deficits and white matter damage networks in CO-related parkinsonism that determined the severity of parkinsonism or behaviour changes. As the substantia nigra was spared, the monoaminergic topography of involvement suggests a different pathophysiology in CO-related parkinsonism.

Impact of homocysteine on cortical perfusion and cognitive decline in mild Alzheimer's dementia.

BACKGROUND AND PURPOSE: Elevated plasma total homocysteine level (tHcy) is associated with increased risk of dementia via increased white matter changes or reduction in cortical volume. Whether tHcy has an independent impact on regional perfusion and if it can predict a more rapid cognitive decline in mild Alzheimer dementia (AD) warrants investigation. METHODS: Eighty AD patients with a clinical dementia rating of 1 were enrolled. Their Cognitive Ability Screening Instrument (CASI) scores on enrolment and after 1 year of follow-up as well as their perfusion index (PI) from single photon emission computed tomography upon enrolment were analyzed. RESULTS: In cross-sectional analysis, elevated tHcy was associated with lower frontal PI independent of cerebrovascular risk factors (ß = -0.35, P = 0.009). The CASI scores correlated with temporo-parietal PI (Pearson r range 0.3-0.39, P < 0.01) but not with tHcy or frontal PI. By longitudinal analysis, only tHcy level was related to a more rapid cognitive decline (odds ratio for executive function score 1.82; odds ratio for total CASI score 1.74). CONCLUSIONS: Cognitive performance in mild AD can be reflected by hypo-perfusion of the temporo-parietal region while frontal hypo-perfusion may be mediated by tHcy. tHcy level is an independent risk factor for rapid cognitive decline, especially in the executive function.

The value of serial plasma nuclear and mitochondrial DNA levels in acute spontaneous intra-cerebral haemorrhage.

BACKGROUND: Increased plasma nuclear and mitochondrial DNA levels may be connected to disease severity following spontaneous intra-cerebral haemorrhage (ICH). This study tested the hypothesis that plasma nuclear and mitochondrial DNA levels are substantially increased in acute ICH and can predict treatment outcomes. METHODS: Serial plasma nuclear and mitochondrial DNA levels were examined in 60 consecutive patients admitted within 24 h after onset of spontaneous ICH and in 60 volunteer control subjects. Additional samples were obtained on days 4, 7, 10, and 14 after onset of ICH regardless of clinical deterioration. RESULTS: Only plasma nuclear DNA, not plasma mitochondrial DNA, levels in patients with spontaneous ICH significantly correlated with Glasgow Coma Scale (GCS) (r = -0.467, P = 0.001) and ICH volume (r = 0.515, P ≤ 0.001) on presentation. Plasma nuclear DNA levels increased significantly from day 1 to day 7 in patients with poor outcome. Higher plasma nuclear DNA levels (cut-off value >18.7 ng/ml) on presentation were associated with poor outcomes in spontaneous ICH patients. CONCLUSION: Plasma nuclear DNA levels reflect the severity of cerebral damage such that higher levels are associated with poorer outcome. Plasma nuclear DNA level can be considered a neuropathologic marker of acute spontaneous ICH.

Cognitive deficits in multiple system atrophy correlate with frontal atrophy and disease duration.

BACKGROUND AND PURPOSE: Dementia remains an exclusion criterion in diagnosing multiple system atrophy (MSA). This study aimed to determine the cognitive changes and brain atrophy patterns in the Parkinsonian (MSA-P) and cerebellar (MSA-C) variants of MSA. METHODS: Voxel-based morphometry (VBM) of magnetic resonance imaging (MRI) and neuro-psychological tests were applied to 10 MSA-C and 13 MSA-P patients, and compared to 37 age-matched controls. Correlation analyses were performed between cognitive test results and morphometric data extracted from the VBM data. RESULTS: In neuro-psychological testing, the 23 MSA patients scored lower in the Stroop interference test and took longer in the trail-making test as compared with the controls, whereas MSA-C performed worse than MSA-P in the memory scores, Stroop test, and time to complete the trail-making test. MSA, as a group, showed atrophy in the cerebellum, insular cortex, fusiform gyrus, inferior orbito-frontal gyrus, superior temporal gyrus, and caudate nucleus. Memory scores correlated well with pre-frontal lobe atrophy but not in the insular area. CONCLUSION: In conclusion, although dementia is not a typical presenting feature of MSA and is regarded as a sub-cortical movement disorder, frontal atrophy, cognitive changes, and dementia are identifiable as MSA progresses.

Genetic interaction is associated with lower metabolic connectivity and memory impairment in clinically mild Alzheimer's disease.

Metabolic connectivity as showed by [18F] fluorodeoxyglucose (FDG) positron emission tomography (FDG-PET) reflects neuronal connectivity. The aim of this study was to investigate the genetic impact on metabolic connectivity in default mode subnetworks and its clinical-pathological relationships in patients with Alzheimer's disease (AD). We separately investigated the modulation of 2 default mode subnetworks, as identified with independent component analysis, by comparing APOE-ε4 carriers to noncarriers with AD. We further analyzed the interaction effects of APOE (APOE-ε4 carriers vs noncarriers) with PICALM (rs3851179-GG vs rs3851179-A-allele carriers) on episodic memory (EM) deficits, reduction in cerebral metabolic rate for glucose (CMRgl) and decreased metabolic connectivity in default mode subnetworks. The metabolic connectivity in the ventral default mode network (vDMN) was positively correlated with EM scores (ß =0.441, P < .001). The APOE-ε4 carriers had significantly lower metabolic connectivity in the vDMN than the APOE-ε4 carriers (t(96) = -2.233, P = .028). There was an effect of the APOE-PICALM (rs3851179) interactions on reduced CMRgl in regions of vDMN (P < .001), and on memory deficits (F3,93 =5.568, P = .020). This study identified that PICALM may modulates memory deficits, reduced CMRgl and decreased metabolic connectivity in the vDMN in APOE-ε4 carriers. [18F] FDG-PET-based metabolic connectivity may serve a useful tool to elucidate the neural networks underlying clinical-pathological relationships in AD.

The outcomes of statin therapy in patients with acute ischemic stroke in Taiwan: a nationwide epidemiologic study.

BACKGROUND: Acute stroke is the third leading cause of death in Taiwan. Although statin therapy is widely recommended for stroke prevention, little is known about the epidemiology of statin therapy after acute ischemic stroke (AIS) in Taiwan. To investigate the effects of statin therapy on recurrent stroke, intracranial hemorrhage (ICH), coronary artery disease (CAD), cost of hospitalization and mortality, we conducted a nationwide population-based epidemiologic study. METHODS: Cases of AIS were identified from the annual hospitalization discharge diagnoses of the National Health Insurance Research Database with the corresponding International Classification of Diseases, ninth revision codes from January 2001 to December 2010. We divided the AIS patients into three groups: non-statin, pre-stroke statin and post-stroke statin. RESULTS: A total of 422 671 patients with AIS (including 365 419 cases in the non-statin group, 22 716 cases in the pre-stroke statin group and 34 536 cases in the post-stroke statin group) were identified. When compared to the non-statin group, both statin groups had a lower recurrent stroke risk [pre-stroke statin: odds ratio (OR) = 0.84; 95% confidence interval (CI) = 0.82-0.87; P < 0.0001; post-stroke statin: OR = 0.89; 95% CI = 0.86-0.91; P < 0.0001], lower ICH risk (pre-statin: OR = 0.75; 95% CI = 0.69-0.82; P < 0.0001; post-stroke statin: OR = 0.75; 95% CI = 0.71-0.81; P < 0.0001), and a lower mortality rate (pre-stroke statin: OR = 0.56; 95% CI = 0.53-0.59; P < 0.0001; post-stroke statin: OR = 0.51; 95% CI = 0.48-0.53; P < 0.0001). In terms of CAD, only the post-statin group had a lower risk (OR = 0.81; 95% CI = 0.79-0.84; P < 0.0001) than the non-statin group. The post-statin group had the lowest 1-year medical costs after index discharge among the three groups. CONCLUSIONS: Statin therapy reduced the risks of recurrent stroke, CAD, ICH and the first year mortality in patients after AIS. Treatment with statin therapy after AIS is a cost-effective strategy in Taiwan.

(99m)Tc-ethyl cysteinate dimer brain SPECT findings in early stage of dementia with Lewy bodies and Parkinson's disease patients: a correlation with neuropsychological tests.

We examined clinical presentations, neuropsychological findings, and perfusion patterns of (99m)Tc-ethyl cysteinate dimer (ECD) single photon emission computed tomography (SPECT) in patients with early stage dementia with Lewy bodies (DLB) (n = 17) and Parkinson's disease (PD) (n = 16), with age-matched healthy controls (n = 10). Seven paired regions of interest (ROIs) were drawn manually including inferior frontal, temporal, parietal, occipital, parieto-occipital junction, striatum and thalamus for semiquantitative measurement. Neuropsychological tests were applied for clinical correlation. The SPECT results showed significant hypoperfusion in DLB group in frontal, parietal, thalamus, temporal ROIs compared with controls (P < 0.01) whilst signals in temporal areas was significantly reduced compared with PD group (P < 0.05). Neuropsychological tests showed that DLB patients had deficits in mental manipulation, short-term memory, abstract thinking, drawing and semantic verbal fluencies (P < 0.05, compared with control). In addition, DLB group had lower scores than those with PD in mental manipulation, drawing and semantic verbal fluency (P < 0.05). Our study showed that even in early stages of DLB, neuropsychological and perfusion patterns were evident and may be different from PD group, despite they shared certain similarities both in neuropsychological and image findings compared with age-matched controls.

Risk factors and outcome of seizures after spontaneous aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Seizures are important neurologic complications of spontaneous aneurysmal subarachnoid hemorrhage (SAH). A better understanding of the risk factors of seizures following aneurysmal SAH is needed to predict those who will require treatment. METHODS: A total of 137 adult patients were enrolled in this two-year retrospective study. Baseline prognostic variables were analyzed based on Cox's proportional hazards model after a minimum of one-year follow-up. RESULTS: Seizures occurred in 21 patients who had SAH, including acute symptomatic seizures in 11.7% (16/137) and unprovoked seizures in 3.6% (5/137). None progressed to status epilepticus during hospitalization. After a minimum of one-year follow-up, the mean Glasgow Outcome Score was 3.5 +/- 1.4 for patients with seizures and 3.1 +/- 1.1 for those without. CONCLUSIONS: Higher mean World Federation of Neurological Societies grade on presentation was predictive of seizure, but seizure itself was not a significant prognostic predictor after a minimum of one-year follow-up. Regarding potential side effects of anti-epileptic drugs, anti-epileptic therapy should be carefully administered to patients with seizures after aneurysmal SAH.

Cerebrospinal fluid 14-3-3-gamma protein level in eight HIV-negative cryptococcal meningitis adults.

The clinical data and cerebrospinal fluid (CSF) 14-3-3-gamma protein detection of eight adult HIV-negative cryptococcal meningitis (CM) cases were examined. The eight cases included six males and two females aged 35-70 years (mean = 49.8 years). The duration between the onset of CM symptoms and the first CSF study ranged from 1 to 60 days. Initial neuroimaging study was abnormal in 87.5% (7/8) of the cases. All the eight had positive initial and subsequent follow-up CSF 14-3-3-gamma protein detection. The densitometric values of CSF 14-3-3-gamma protein were not correlated with either the CSF white blood cell counts or the therapeutic results. The therapeutic results showed that three cases died and five survived. Significant neurologic deficits were shown in 60% (3/5) of the survivors. This study revealed that HIV-negative CM patients have elevated CSF 14-3-3-gamma protein levels, and that this level is not changed with a short-term treatment.

Hypokalemic thyrotoxic periodic paralysis: clinical characteristics and predictors of recurrent paralytic attacks.

BACKGROUND AND PURPOSE: To study the clinical characteristics of hypokalemic thyrotoxic periodic paralysis (hoTPP) and identify the predictors of recurrent paralytic attacks before achieving the euthyroid status. METHODS: We retrospectively analyzed 45 hoTPP patients who were admitted during the 7-year study period. RESULTS: A tendency towards male predominance was observed among the 45 patients (91.1%, 41/45). The mean onset age was 32.9 +/- 10.0 years (range: 16-54 years). No significant differences were observed in the onset age between male and female patients. Precipitating factors included rest/sleep at night, hot weather, upper respiratory tract infections (URIs), and excessive physical activities. Atypical weakness was observed in nine (20%, 9/45) patients. One patient initially diagnosed with sporadic periodic paralysis eventually developed hoTPP. DISCUSSION: In provocative tests, hypokalemia was not a consistent finding during paralytic attacks. Before achieving the euthyroid status, the rate of recurrent attacks was as high as 62.2%, and peaked in the first 3 months after hoTPP was diagnosed. Patients with URIs exhibited a higher incidence of recurrent paralytic attacks than those without (odds ratio = 13.00; 95% confidence interval = 1.08-156.08; P = 0.04).

Upregulation of nitric oxide synthase II contributes to apoptotic cell death in the hippocampal CA3 subfield via a cytochrome c/caspase-3 signaling cascade following induction of experimental temporal lobe status epilepticus in the rat.

Status epilepticus results in preferential neuronal cell loss in the hippocampus. We evaluated the hypothesis that the repertoire of intracellular events in the vulnerable hippocampal CA3 subfield after induction of experimental temporal lobe status epilepticus entails upregulation of nitric oxide synthase II (NOS II), followed by the release of mitochondrial cytochrome c that triggers the cytosolic caspase-3 cascade, leading to apoptotic cell death. In Sprague-Dawley rats, significant and temporally correlated upregulation of NOS II (3-24h), but not NOS I or II expression, enhanced cytosolic translocation of cytochrome c (days 1 and 3), augmented activated caspase-3 in cytosol (days 1, 3 and 7) and DNA fragmentation (days 1, 3 and 7) was detected bilaterally in the hippocampal CA3 subfield after elicitation of sustained seizure activity by microinjection of kainic acid into the unilateral CA3 subfield. Application bilaterally into the hippocampal CA3 subfield of a selective NOS II inhibitor, S-methylisothiourea, significantly blunted these apoptotic events; a selective NOS I inhibitor, N(omega)-propyl-l-arginine or a potent NOS III inhibitor, N(5)-(1-iminoethyl)-l-ornithine was ineffective. We conclude that upregulation of NOS II contributes to apoptotic cell death in the hippocampal CA3 subfield via a cytochrome c/caspase-3 signaling cascade following the induction of experimental temporal lobe status epilepticus.

Hepatocellular carcinoma presenting as nervous system involvement.

To analyze the clinical features of hepatocellular carcinoma (HCC) in patients with signs and symptoms of nervous system involvement as the initial presentation. Over a period of 11 years (January 1993 to December 2003), 15,008 HCC patients were identified at the Chang Gung Memorial Hospital in Kaohsiung, Taiwan. Amongst them, 42 cases had nervous system involvement, of which six had nervous system involvement as their initial presentation. These six cases were enrolled in this study and their clinical and laboratory data were analyzed. The clinical features of the other 36 HCC cases with nervous system involvement were also analyzed for comparison. The six cases were all males, aged 36-68 years old. The involved parts of the nervous system were the cerebellar hemisphere (one), the frontal lobe (one), the sphenoid sinus, sellar turcica, and cavernous sinus (one), the cervical spine (one), and the thoracic spine (two). Their corresponding neurologic presentations were back pain, headache, consciousness disturbance, visual disturbance, and limb weakness. Whilst three out of six patients presenting with nervous system manifestations were found to have concurrent systemic metastases in other expected sites (lung, bone), three had isolated nervous system involvement even after extensive work up. The associated medical conditions of the six cases included hepatitis B (three), hepatitis C (one), liver cirrhosis (two), portal vein thrombosis (three), and diabetes mellitus (two). All the six died within 9 months after the detection of nervous system involvement. The prevalence of nervous system involvement in HCC patients is 0.28% (42/15,088), with 0.04% (6/15,088) having this as their initial presentation. The prognosis of HCC with nervous system involvement is grave. Their clinical and laboratory data are not unique but the diagnosis could only be confirmed by hepatic and nervous system imaging studies, histopathologic examination, and serum alpha-fetoprotein detection. This consideration should be emphasized especially in areas that are hyperendemic for HCC and if the original focus of metastatic lesion is obscure.

Time course of cerebral hemodynamics in cryptococcal meningitis in HIV-negative adults.

To evaluate the cerebral hemodynamics in cryptococcal meningitis (CM) patients using non-invasive studies. Serial trans-cranial color-coded sonography (TCCS) and magnetic resonance angiography (MRA) studies were performed to measure the cerebral vasculopathy of 12 HIV-negative CM patients. With TCCS, 8 of the 22 middle cerebral arteries (MCAs) showed stenotic velocities, whereas the time-mean velocity (V(mean)) of the 20 anterior cerebral arteries (ACAs), 22 posterior cerebral arteries (PCAs), and 12 basilar arteries (BAs) did not. In total, five patients had stenotic velocities, three of whom had bilateral M1 stenosis (<50%), whilst two had unilateral M1 stenosis (<50%). The V(mean) of MCA increased from day 1 to day 35 and substantially decreased thereafter. The mean Pulsatility Index (PI) in the studied vessels was higher during the study period. A mismatch of the findings between TCCS and MRA studies were also demonstrated. There was a high incidence and a longer time-period of disturbed cerebral hemodynamics during the clinical course of CM. However, because of the limited case numbers for this study, further large-scale studies are needed to delineate the clinical characteristics and therapeutic influence of cerebrovascular insults in HIV-negative CM patients.

Adult Pseudomonas aeruginosa meningitis: high incidence of underlying medical and/or postneurosurgical conditions and high mortality rate.

We analyzed the clinical and laboratory characteristics, therapeutic outcome and prognostic factors of 25 cases of cerebrospinal fluid (CSF) culture-proven Pseudomonas aeruginosa adult bacterial meningitis (ABM). Twelve P. aeruginosa strains, isolated from clinical CSF specimens, were tested for antibiotic susceptibility. The 25 cases included 17 men and 8 women, aged 17 to 86 years (median=51). Of the 25 cases of P. aeruginosa ABM, 18 were the result of postneurosurgical infection and the other 7 were spontaneous infections. The latter 7 cases had serious underlying medical conditions. The antibiotic susceptibility rates of the 12 strains were as follows: ceftriaxone 16.7% (2/12), ceftazidime 91.7% (11/12), cefepime 83.3% (10/12), imipenem 83.3% (10/12), meropenem 83.3% (10/12) and ciprofloxacin 66.7% (8/12). The therapeutic results showed an overall mortality rate of 40% (10/25). The emergence of third-generation cephalosporin-resistant P. aeruginosa strains cultured from clinical CSF specimens in recent years has resulted in a therapeutic challenge in the treatment of ABM.

Neuropsychiatric symptoms in Alzheimer's disease: associations with caregiver burden and treatment outcomes.

BACKGROUND: Caregivers play a major role in providing care for patients with Alzheimer's disease (AD) and are themselves at higher risk of health comorbidities. AIM: To address the impact of neuropsychiatric symptoms of patients in different stages of AD on their caregivers' burden. DESIGN: This prospective study enrolled 260 AD patients with clinical dementia rating (CDR) of 0.5, 1 and 2 at a tertiary medical center. METHODS: All patients were tested using the mini-mental state examination (MMSE), the cognitive abilities screening instrument (CASI), the neuropsychiatric inventory (NPI) and the CDR scale. Data regarding therapeutic outcomes of anti-Alzheimer's drugs were also collected. Caregivers were tested using NPI. RESULTS: The mean follow-up interval was 25.0 ± 12.2 months, and two patients died during follow-up. NPI-burden was positively correlated with NPI-sum ( r = 0.822, P < 0.001) but negatively correlated with years of education ( r = -0.140, P = 0.024), CASI score ( r = -0.259, P < 0.001) and MMSE score ( r = -0.262, P <0.001). Multiple linear regression analysis showed that only NPI-sum was independently associated with mean NPI-burden. Both higher mean CASI and MMSE scores had better therapeutic outcome of anti-Alzheimer's drugs ( P = 0.001 and P = 0.005, respectively). CONCLUSIONS: The severity of neuropsychiatric symptoms in patients with AD was positively associated with caregiver's stress, and patients with better cognitive functions, under treatment with anti-Alzheimer's drugs, had better therapeutic outcomes. To reduce the impact of neuropsychiatric symptoms, it is crucial to detect dementia in its early phases and provide early intervention with anti-Alzheimer's drugs, which might help decrease the caregiver burden, thereby improving their quality of life.

Cerebral haemodynamics in acute bacterial meningitis in adults.

BACKGROUND: Vascular complications are an important cause of neurological sequelae among adult survivors of acute bacterial meningitis (ABM). AIM: To examine the haemodynamic changes associated with ABM. METHODS: Serial transcranial colour-coded sonography (TCCS) and magnetic resonance angiography (MRA) were used to examine cerebrovascular changes in adult ABM patients. Outcome at 3 months was categorized using a modified Barthel index. RESULTS: We recruited 24 patients, 12 men and 12 women, aged 21-68 years. Mean cerebral blood flow velocity (V(mean)) increased from day 1 to day 4 in the middle cerebral artery (MCA), anterior cerebral artery (ACA) and posterior cerebral artery (PCA). On day 4, V(mean) values in the MCA, ACA and PCA were all significantly higher than reference values in healthy volunteers. At 3 months follow-up, 16 cases had good outcomes, while the other eight had poor outcomes. Under multiple logistic regression analysis, only Glasgow coma score (GCS) at admission was independently associated with the three-month outcome. DISCUSSION: In these patient, stenosis as demonstrated by TCCS did not wholly coincide with stenosis as demonstrated by MRA, and the presence of intracranial stenosis was not predictive of a poor outcome at 3 months. Further studies are needed to delineate the characteristics and significance of cerebrovascular changes in adult ABM.

Factors predictive of fatality in massive middle cerebral artery territory infarction and clinical experience of decompressive hemicraniectomy.

To determine the factors predictive of fatality in massive middle cerebral artery (MCA) territory infarction and outcome of decompressive hemicraniectomy, 62 patients who were retrospectively verified with first event massive MCA infarctions were enrolled in this study. Amongst them, 21 received decompressive hemicraniectomy during hospitalization. Clinical data between early and late hemicraniectomy groups were also compared. Significant deterioration occurred in 40 cases, 21 of whom received decompressive hemicraniectomy. The other 19 received conservative treatment. The mortality rate of these 40 cases between decompressive hemicraniectomy and conservative treatment was 29% (six of 21) and 42% (eight of 19), respectively. Factors that predicted fatalities in our massive MCA infarction patients with or without decompressive hemicraniectomy were total scores of baseline GCS at the time of admission, associated with coronary artery diseases, and significant deterioration during hospitalization. This study confirms the lifesaving procedure of hemicraniectomy that prevents death in patients deteriorating because of cerebral edema after infarction, although it may produce severe disability with an unacceptably poor quality of life in survival. Despite high mortality and morbidity, decompressive hemicraniectomy to prevent cerebral herniation when significant deterioration is demonstrated are essential for maximizing the potential for survival.

Effect of oleamide on Ca(2+) signaling in human bladder cancer cells.

The effect of oleamide, a sleep-inducing endogenous lipid in animal models, on intracellular free levels of Ca(2+) ([Ca(2+)](i)) in non-excitable and excitable cells was examined by using fura-2 as a fluorescent dye. [Ca(2+)](i) in pheochromocytoma cells, renal tubular cells, osteoblast-like cells, and bladder cancer cells were increased on stimulation of 50 microM oleamide. The response in human bladder cancer cells (T24) was the greatest and was further explored. Oleamide (10-100 microM) increased [Ca(2+)](i) in a concentration-dependent fashion with an EC(50) of 50 microM. The [Ca(2+)](i) signal comprised an initial rise and a sustained plateau and was reduced by removing extracellular Ca(2+) by 85 +/- 5%. After pre-treatment with 10-100 microM oleamide in Ca(2+)-free medium, addition of 3 mM Ca(2+) increased [Ca(2+)](i) in a manner dependent on the concentration of oleamide. The [Ca(2+)](i) increase induced by 50 microM oleamide was reduced by 100 microM La(3+) by 40%, but was not altered by 10 microM nifedipine, 10 microM verapamil, and 50 microM Ni(2+). In Ca(2+)-free medium, pre-treatment with thapsigargin (1 microM), an endoplasmic reticulum Ca(2+) pump inhibitor, abolished 50 microM oleamide-induced [Ca(2+)](i) increases; conversely, pretreatment with 50 microM oleamide reduced 1 microM thapsigargin-induced [Ca(2+)](i) increases by 50 +/- 3%. Suppression of the activity of phospholipase C with 2 microM U73122 failed to alter 50 microM oleamide-induced Ca(2+) release. Linoleamide (10-100 microM), another sleep-inducing lipid with a structure similar to that of oleamide, also induced an increase in [Ca(2+)](i). Together, it was shown that oleamide induced significant [Ca(2+)](i) increases in cells by a phospholipase C-independent release of Ca(2+) from thapsigargin-sensitive stores and by inducing Ca(2+) entry.

Cerebral infarction in chronic meningitis: a comparison of tuberculous meningitis and cryptococcal meningitis.

Twenty-eight patients with cerebral infarction secondary to chronic meningitis were retrospectively identified at our institution over a period of 5 years. They accounted for 47% (17/36) of tuberculous meningitis (TBM) and 32% (11/34) of cryptococcal meningitis cases. Single infarctions were found in 15 patients and multiple infarctions in 13. The distribution of single infarctions was: basal ganglia 7; internal capsule 3; thalamus 1; cerebellum 1; and cortical infarct 3. Therapeutic outcomes at 3 months were determined using a modified Barthel INDEX: At follow-up of 3 months or more, 10 had good outcomes while the other 18 had poor outcomes. The 18 with poor outcomes included six who died, and 12 who had severe neurological sequelae. TBM and cryptococcal meningitis shared similar clinical features, both being frequently associated with other neurological complications, including hydrocephalus, cranial nerve palsy, and seizures in our patients. However, extracranial involvement, such as spinal and pulmonary involvement, was more commonly found in TBM patients. Cerebral infarction can occur in both the acute stage and later stages of treatment. Mortality and morbidity are high, and early diagnosis and appropriate antimicrobial treatment are essential. If hydrocephalus is demonstrated, early ventricular decompression is needed to prevent further cerebral ischaemia.