Risk factors predicting a higher grade of subarachnoid haemorrhage in small ruptured intracranial aneurysm (< 5 mm).

AIM: To identify the risk factors for clinical and radiographic grades of subarachnoid haemorrhage (SAH) in small (< 5 mm) intracranial aneurysms (SIAs). MATERIAL AND METHODS: We retrospectively analysed patients with SIAs treated in our centre between February 2009 and June 2018. The clinical status was graded using the Hunt and Hess (H&H) score and the radiological severity of SAH was graded by Fisher grades (FG). The risk factors were determined using multivariate logistic regression analysis. RESULTS: A total of 160 patients with ruptured SIAs (< 5 mm) were included. In univariate analysis, smoking (P = 0.007), alcohol use (P = 0.048), aspirin use (P = 0.001), and higher size ratio (SR) (P = 0.001) were significantly associated with a higher H&H grade (3-5) in SIAs; and smoking (P = 0.019), aspirin use (P = 0.031), inflow angle < 90 degrees (P = 0.011), and aneurysm size (P = 0.039) were significantly associated with a higher FG score (3-4). In the adjusted multivariate analysis, previous SAH (OR, 12.245, 95% CI, 2.261-66.334, P = 0.004), aspirin use (OR, 4.677, 95% CI, 1.392-15.718, P = 0.013), alcohol use (OR, 3.392, 95% CI, 1.146-10.045, P = 0.027), inflow angle < 90 (OR, 3.881, 95% CI, 1.273-11.831, P = 0.017), and higher SR (OR, 6.611, 95% CI, 2.235-19.560, P = 0.001) were independent risk factors for a higher H&H grade in ruptured SIAs; smoking (OR, 2.157, 95% CI, 1.061-4.384, P = 0.034), and inflow angle < 90 degrees (OR, 2.603, 95% CI, 1.324-5.115, P = 0.006) were independent risk factors for a higher FG (3-4). CONCLUSIONS: This study revealed that inflow angle < 90 degrees and size ratio, but not absolute size, may highly predict poorer grade of SAH in SRA. Aspirin use, previous SAH, and alcohol use were significantly associated with a higher H&H grade in ruptured SIAs, and smoking was a significant predictor of poorer FG.

High frequency oscillations for lateralizing suspected bitemporal epilepsy.

OBJECTIVE: In some cases of single focus epilepsy, conventional video electroencephalography (EEG) cannot reveal the epileptogenic focus even when intracranial electrodes are used. Here, we tested whether analyzing high frequency oscillations (HFOs) can be used to determine the ictal onset zone in suspected bitemporal epilepsy and improve seizure outcome. METHODS: We prospectively studied 13 patients with refractory temporal seizures who were treated over a 4-year period and underwent bilateral placement of intracranial electrodes. Subdural strips were used in all cases, and depth electrodes were implanted into mesial temporal lobes in 10 patients. The mean patient age was 30.92 years, and 30.7% of patients were male. Patients were monitored by conventional and wide-band frequency amplifiers. RESULTS: Conventional invasive EEG monitoring of interictal periods showed bilateral epileptiform abnormalities in 12 patients (92.3%) and unilateral epileptiform abnormalities in one (7.7%), and monitoring of ictal periods revealed unilateral seizure origins in nine patients (69.2%) and bilateral origins in four (30.8%). In contrast, high frequency invasive EEG monitoring of interictal periods showed bilateral HFOs in seven patients (53.8%) and unilateral HFOs in six (46.2%), and monitoring of ictal periods revealed unilateral HFOs in all 10 patients who were tested. Three patients were not monitored during ictal periods because of time limitations. All 13 patients subsequently underwent a standard unilateral temporal lobectomy and have been followed-up for a minimum of 12 months. Eleven (84%) had a Class I outcome, one (8%) a Class II outcome, and one a Class III outcome. SIGNIFICANCE: Bilateral placement of subdural strip and depth electrodes for seizure monitoring in patients with suspected bitemporal epilepsy is both safe and effective. Monitoring high frequency oscillations can help determine the laterality of the onset zone when localization using conventional EEG or brain MRI fails.

High-frequency Oscillations and the Seizure Onset Zones in Neocortical Epilepsy.

BACKGROUND: To study the characters of high-frequency oscillations (HFOs) in the seizure onset zones (SOZ) and the nonseizure onset zones (NSOZ) in the electrocorticography (ECoG) of patients with neocortical epilepsy. METHODS: Only patients with neocortical epilepsy who were seizure-free after surgery as determined with ECoG were included. We selected patients with normal magnetic resonance imaging before surgery in order to avoid the influence of HFOs by other lesions. Three minutes preictal and 10 min interictal ECoG as recorded in 39 channels in the SOZ and 256 channels in the NSOZ were analyzed. Ripples and fast ripples (FRs) were analyzed by Advanced Source Analysis software (ASA, The Netherlands). Average duration of HFOs was analyzed in SOZ and NSOZ separately. RESULTS: For ripples, the permillage time occupied by HFOs was 0.83 in NSOZ and 1.17 in SOZ during the interictal period. During preictal period, they were 2.02 in NSOZ and 7.93 in SOZ. For FRs, the permillage time occupied by HFOs was 0.02 in NSOZ and 0.42 in SOZ during the interictal period. During preictal period, they were 0.03 in NSOZ and 2 in SOZ. CONCLUSIONS: High-frequency oscillations are linked to SOZ in neocortical epilepsy. Our study demonstrates the prevalent occurrence of HFOs in SOZ. More and more burst of HFOs, especially FRs, means the onset of seizures.

A case of familial paroxysmal nonkinesigenic dyskinesia due to mutation of the PNKD gene in Chinese Mainland.

BACKGROUND: Paroxysmal dyskinesia is a rare neurological disorder characterized by paroxysmal movement disorders. Paroxysmal movement disorders include kinesigenic choreoathetosis, nonkinesigenic choreoathetosis or dyskinesia (PNKD), exercise-induced choreoathetosis, and hypnogenic paroxysmal dystonia. There have been some sporadic reports of PNKD occurrences in Chinese Mainland, but none has been reported on familial PNKD. Proband and methods A 32 years old male admitted to the First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China in 2009 with recurrent limb involuntary movements spanning over 30 years was diagnosed with PNKD. Family history was collected to identify if it was a case of familial or sporadic PNKD. Mutation and linkage analysis were performed to identify the pathogenic gene and the localization of the same. RESULTS: There were five generations of 26 patients, out of which 3 of these patients died. Follow-up was conducted on 17 out of the 23 patients alive and 9 normal family members. The pedigree showed autosomal dominant inheritance, whom could be divided into light, moderate, and severe group according to clinical signs, spontaneous attack and response to drugs. All patients harbored c.20C>T (p.A7V) mutation in exon 1 of the PNKD/MR-1 gene. Preliminary linkage analyses using phenocopy rates of 0.0001 and 0.1 suggested that linkage signal localizes between D2S126 and D2S377. The functional consequence of the mutation in the disease pathogenesis is pending investigation. Conclusions We report the first case of familial paroxysmal non-kinesigenic dyskinesia (PNKD) in Chinese Mainland, which coincidentally is also the largest case of familial PNKD ever reported. This article is part of a Special Issue entitled Brain and Memory.

Exposure to 1950-MHz TD-SCDMA electromagnetic fields affects the apoptosis of astrocytes via caspase-3-dependent pathway.

The usage of mobile phone increases globally. However, there is still a paucity of data about the impact of electromagnetic fields (EMF) on human health. This study investigated whether EMF radiation would alter the biology of glial cells and act as a tumor-promoting agent. We exposed rat astrocytes and C6 glioma cells to 1950-MHz TD-SCDMA for 12, 24 and 48 h respectively, and found that EMF exposure had differential effects on rat astroctyes and C6 glioma cells. A 48 h of exposure damaged the mitochondria and induced significant apoptosis of astrocytes. Moreover, caspase-3, a hallmark of apoptosis, was highlighted in astrocytes after 48 h of EMF exposure, accompanied by a significantly increased expression of bax and reduced level of bcl-2. The tumorigenicity assays demonstrated that astrocytes did not form tumors in both control and exposure groups. In contrast, the unexposed and exposed C6 glioma cells show no significant differences in both biological feature and tumor formation ability. Therefore, our results implied that exposure to the EMF of 1950-MHz TD-SCDMA may not promote the tumor formation, but continuous exposure damaged the mitochondria of astrocytes and induce apoptosis through a caspase-3-dependent pathway with the involvement of bax and bcl-2.

Magnetic paclitaxel nanoparticles inhibit glioma growth and improve the survival of rats bearing glioma xenografts.

UNLABELLED: Paclitaxel has fared poorly in clinical trials against brain glioma. We hypothesized that superparamagnetic nanocarriers may enhance its bioactivities by delivering it into the brain. MATERIALS AND METHODS: The magnetic paclitaxel nanoparticles (MPNPs) were fabricated and their cytotoxicity against glioma was tested both in vitro and in glioma-bearing rats. RESULTS: MPNPs exhibited superparamagnetism and produced an extended release of paclitaxel over 15 days in vitro. They were easily internalized into glioma cells and exerted remarkable toxicity, as free paclitaxel did. Furthermore, after intravenous injection of MPNPs to glioma-bearing rats and magnetic targeting with a 0.5 T magnet, drug content increased for 6- to 14-fold in implanted glioma and 4.6- to 12.1-fold in the normal brain compared to free paclitaxel. The survival of glioma-bearing rats was significantly prolonged after magnetic targeting therapy with MPNPs. CONCLUSION: MPNPs efficiently delivered paclitaxel into brain glioma by magnetic targeting and enhance its antitumor activity. They are promising for local chemotherapy for malignant glioma.

[Detection of O6-methylguanine-DNA methyltransferase promoter methylation in chemotherapy for glioma].

BACKGROUND AND OBJECTIVE: Epigenetic silencing of the DNA repair gene, O6-methylguanine-DNA methyltransferase (MGMT), is associated with the therapeutic response to methylating agents. This study was to assess the value of detecting the promoter methylation of MGMT gene in chemotherapy for glioma. METHODS: Methylation-specific PCR (MSP) was employed to detect MGMT promoter CpG island methylation in 39 samples of glioma taken from surgery. Western blot and immunohistochemistry were used to detect protein expression. MTT were employed to detect the sensitivity of two glioma cell lines to alkylating agents, ACNU and TMZ. The Kaplan-Meier curve was adopted to estimate the overall survival according to the methylation status of the MGMT promoter. RESULTS: Methylation of MGMT promoter CpG island was detectable in 46.2% of glioma tissues, but not in any normal tissues. The expression rate of MGMT protein was 61.5%. The status of MGMT methylation status was association with the protein level of MGMT (P<0.05). The MGMT gene was demethylated in glioma cell line SHG-44 following 5-Aza-CdR treatment; the expression of MGMT protein was restored and the resistance of SHG44 cells to alkylating agents was reversed. The overall survival was higher in patients with methylated MGMT promoter than in those with unmethylated MGMT promoter (P<0.05). CONCLUSIONS: The status of MGMT promoter CpG island methylation is closely correlated to MGMT protein expression and sensitivity of cells to alkylating agents in glioma. Detection of the methylated sequences of MGMT may be used as a predictive factor for the treatment of glioma.