Connectivity measures suggest a sub-cortical generator of myoclonus in Angelman syndrome

ObjectiveThe clinical and neurophysiological characteristics of myoclonus in Angelman syndrome (AS) have been evaluated in single case or small cohorts, with contrasting results. We evaluated the features of myoclonus in a wide cohort of AS patients.MethodsWe performed polygraphic EEG-EMG recording in 24 patients with genetically confirmed AS and myoclonus. Neurophysiological investigations included jerk-locked back-averaging (JLBA), cortico-muscular coherence (CMC) and generalised partial directed coherence (GPDC). CMC and GPDC analyses were compared to those obtained from 10 healthy controls (HC).ResultsTwenty-four patients (aged 3–35 years, median 20) were evaluated. Sequences of quasi-continuous rhythmic jerks mostly occurred at alpha frequency or just below (mean 8.4 ± 1.4 Hz), without EEG correlate. JLBA did not show any clear transient preceding the jerks. CMC showed bilateral over-threshold CMC in alpha band that was prominent on the contralateral hemisphere in the patient group as compared to HC group. GPDC showed a significantly higher alpha outflow from both hemispheres toward activated muscles in the patient group, and a significantly higher beta outflow from contralateral hemisphere in the HC group.ConclusionsThese neurophysiological findings suggest a subcortical generator of myoclonus in AS.SignificanceMyoclonus in AS has not a cortical origin as previously hypothesised.     

Evaluation of vilazodone for the treatment of depressive and anxiety disorders

Introduction: Major Depressive Disorder (MDD) and General Anxiety Disorder (GAD) significantly contribute to the global burden of disease. Vilazodone, a combined serotonin reuptake inhibitor and 5-HT1A partial agonist, is an approved therapy for the treatment of MDD and which has been further investigated for GAD.

Areas covered: This article covers the pharmacokinetics and pharmacodynamics of vilazodone and provides an evaluation of the clinical usefulness of vilazodone for the treatment of MDD and anxiety disorders. A literature search was performed using PubMed/MEDLINE, Web of Science and the Cochrane Library.

Expert opinion: Studies have shown that vilazodone is significantly superior to placebo. However, vilazodone cannot as yet be recommended as a first-line treatment option for MDD as it is unclear whether the drug’s dual mechanism of action provides greater efficacy than prevailing treatment options. Moreover, more phase IV studies are needed to establish its efficacy and long-term safety in larger and more diverse populations. Although vilazodone may have an additional advantage for the treatment of anxiety symptoms in MDD, here also additional studies are required to confirm its efficacy over and above SSRI alternatives and other antidepressant treatments. Therefore, presently, vilazodone should be considered as a second- or third-line treatment option for MDD and GAD.     

The human major histocompatibility complex class Ib molecule HLA-E binds signal sequence-derived peptides with primary anchor residues at positions 2 and 9

Human histocompatibility leukocyte antigen E (HLA-E) and mouse major histocompatibility complex (MHC) class Ib antigen, Qa-1, share the same substitutions at two normally conserved positions 143 and 147, which are likely to affect binding of the C terminus of peptides. Qa-1 is able to bind a peptide derived from the leader sequence of H-2 D and H-2 L molecules. We developed a peptide binding assay in vitro to compare the binding specificity of HLA-E with the mouse MHC class Ib molecule Qa-1. We demonstrate that HLA-E binds, although poorly, the peptide which binds to Qa-1 and that it also binds nonamer signal sequence-derived peptides from human MHC class I molecules. Using alanine and glycine substitutions, we could define primary anchor residues at positions 2 and 9 and secondary anchor residues at position 7 and possibly 3.     

高热惊厥214例临床分析

本文分析了214例高热惊厥,结果为:检出率4.35％;男女之比为1.61:1;好发年龄为6个月～6岁(93.5％);首发年龄为6个月～4岁(89.9％);惊厥发作时体温多在39℃以上(74.6％);惊厥发作多在发热后12h内(72.4％);每次热病中惊厥发作1～3次(99.5％);惊厥持续时间多在15min内(91.0％);致惊厥发作的热性疾病以上呼吸道感染为最多;214例中63例复发,其中2例转癫痫,61例尚未发现智力低下或其他异常。从2例转癫痫的临床及脑电图看,提示惊厥发作愈重,持续时间愈长,转癫痫的可能性愈大。     

Nonconvulsive Status Epilepticus: High Incidence of Complex Partial Status

Nonconvulsive status epilepticus may be subdivided into generalized (absence) status and complex partial status. The latter is regarded as a rarity, whereas the former constitutes the dominant part of the hitherto reported cases. We report 10 consecutive cases of adult patients with nonconvulsive status epilepticus, all documented by ictal electroencephalographic (EEG) recordings. Five had a complex partial status; the origin of the complex partial status appeared to be frontal in four of these patients. Three had recurrent complex partial seizures with incomplete recovery between seizures, and two had more continuous symptoms. One of the latter exhibited neither motor phenomena nor automatisms. The effect of diazepam or clonazepam was immediate in all 10 cases though transient in eight. A lasting control of the status was not achieved in six patients until i.v. phenytoin was added. The difficulties in the differentiation between complex partial status and absence status despite ictal EEG recordings are discussed, illustrated by a case with seizure discharges of a focal onset which rapidly generalized. The study indicates that complex partial status may be more common and the clinical expressions of absence status more variable than hitherto recognized.     

Exacerbation of Partial Seizures and Onset of Nonepileptic Myoclonus with Carbamazepine

A child had two to three generalized tonic-clonic (GTC) seizures per week unresponsive to phenobarbital (PB) and valproate (VPA). Interictal EEG demonstrated left occipital spikes. When carbamazepine (CBZ) therapy was started, he developed very frequent (4-6/day) complex partial seizures (CPS) characterized on ictal EEG by focal right temporal lobe discharges. The seizure exacerbation, which was associated with development of nonepileptic, multifocal myoclonus, resolved 24 h after CBZ was discontinued. The exacerbation occurred with therapeutic CBZ serum levels, but may have been related to the toxic levels of carbamazepine-10, 11-epoxide (CBZE).     

Influence of moderate hypothermia on cerebral oxygenation in pigs with intracranial hypertension

BACKGROUND: Moderate hypothermia is one of the effective therapeutic methods for head injury in recent years, there are many mechanisms of moderate hypothermia for brain protection, and its influence on cerebral oxygenation is also one of them. OBJECTIVE: To observe the influence of moderate hypothermia on cerebral oxygenation of animals with acute intracranial hypertension, and further investigate the protective mechanism of moderate hypothermia. DESIGN: A randomized controlled trial. SETTING: Department of Neurosurgery, Renji Hospital affiliated to the Medical College of Shanghai Jiao Tong University. MATERIALS: Twenty healthy little pigs, either male or female, weighing 4.5–5.5 kg, were used. Neurotrend-typed multiparameter monitoring system (Diametrics Company, British); CMA/100 micro-injection pump (Carnegie Company, Sweden). METHODS: The experiment was conducted in the Changzheng Hospital affiliated to the Second Military Medical University of Chinese PLA in November, 2001. The pigs were randomized into two groups: the normothermia group (control group, n =10) and moderate hypothermia group (n =10). ① Bilateral femoral arteries were separated, one was connected to pressometer for monitoring mean arterial pressure (MEP), and the other for analysis of blood gases [including peripheral blood pH value, arterial partial pressure of carbon dioxide (PaCO2), arterial partial pressure of carbon dioxide (PaCO2), HCO3–]. ② Rectal temperature was monitored with mercurial thermometer. ③ Intracranial pressure was monitored using Camino optic ICP probe placed in the subdural space. ④ Neurotrend multiparameter monitoring sensor was inserted into the white matter for about 4 cm to determine cerebral perfusion pressure (CPP, CPP=MAP(ICP), brain tissue partial oxygen pressure (PO2), partial pressure of carbon dioxide (PCO2), HCO3– and brain temperature. The rectal temperature of animals in the moderate hypothermia group was lowered to 34 ℃ using ice bags, and the body temperature was maintained at 33–35 ℃ for 2 hours. The changes of the parameters were observed continuously, and the pigs in the normothermia group were not treated with cooling. MAIN OUTCOME MEASURES: ① MAP, ICP, rectal temperature, CCP; Indexes of cerebral oxygenation detected with Neurotrend-typed multiparameter monitoring system; ② Results of blood gases analysis in the moderate hypothermia group. RESULTS: All the 20 pigs were involved in the analysis of results. ① MAP, ICP, rectal temperature, CCP and indexes of cerebral oxygenation: In the moderate hypothermia group, the ICP after cooling was obviously lower than that before cooling [(3.31±1.19), (5.33±0.95) kPa, P < 0.05], CCP was higher, brain tissue PCO2 [(12.03±1.73), (10.59±2.01) kPa, P < 0.05], and brain tissue pH value was higher [(7.03±1.63), (9.40±1.30) kPa, P < 0.05], whereas the brain temperature was decreased as compared with that before cooling [(34.9±0.3), (37.2±0.2) ℃, P < 0.05]. ② Results of blood gases analysis in the moderate hypothermia group: There were no significant differences in the parameters of peripheral arterial blood gases analysis before and after cooling in the moderate hypothermia group (P > 0.05) CONCLUSION: Moderate hypothermia will not impair the cerebral oxygenation, and it can reduce brain tissue CO2 and decrease brain tissue acidosis.     

对诊断PADAM的游离睾酮指数的评估

目的 评价诊断中老年男子部分雄激素缺乏综合征（PADAM）的游离睾酮指数（FTI）.方法 对129例45岁以上健康男性的FTI进行年龄相关分析.以推算的游离睾酮（CFT）值为依据,对FTI进行有效性检验.结果 男子在中老年期FTI与增龄呈明显的负相关.FTI敏感性97.78%,特异性58.33%.结论 计算简单的FTI可用于PADAM病人的筛选和随访,尤其对70岁以上男子是血清FT较为有效的参数.     

Iron deficiency down-regulates the Akt/TSC1-TSC2/mammalian Target of Rapamycin signaling pathway in rats and in COS-1 cells

Iron deficiency (ID) is one of the most commonly known forms of nutritional deficiencies. Low body iron is thought to induce neurologic defects but may also play a protective role against cancer development by cell growth arrest. Thus, ID may affect cellular pathways controlling cell growth and proliferation, the mechanism of which is still not fully understood. The serine/threonine protein kinase Akt and its downstream target, the mammalian Target of Rapamycin (mTOR), is known to play a crucial role in the regulation of cell growth and survival. Therefore, we hypothesized that Akt/mTOR pathway could be influenced by ID. Three-week-old male Wistar-strain rats were divided into 3 groups and the 2 groups had free access to a control diet (C group) or an iron-deficient diet (D group). The third group (PF group) were pair-fed the control diet to the mean intake of the D group. After 4 weeks, rats were killed and their brains were sampled. In separate experiments, COS-1 cells were cultured with or without the iron chelator deferoxamine. Western blots of brain samples and COS-1 lysates were used to analyze the expression and phosphorylation state of Akt, TSC2, mTOR, and S6 kinase proteins implicated in the Akt/mTOR pathway. Using 2 different ID models, we show for the first time that iron deficiency depresses Akt activity in rats and in COS-1 cells, leading to a decrease in mTOR activity.