Implications of Clinical Spectrum for Mechanisms of Action: ECT and Antidepressants Reconsidered

The similarities and differences between electroconvulsive therapy (ECT) and antidepressant medications are reviewed with respect to their clinical indications. The implications of the overlap and divergence in their spectra of clinical efficacy are discussed in reference to mechanisms of action. The hypothesis is offered that ECT has multiple mechanisms of action, which differ depending on the clinical syndrome being treated. From this perspective, ECT may share similar mechanisms of action with other agents that are also effective in treating the specific syndrome. Thus, although ECT may result in a plethora of neurobiological effects, depending on the clinical syndrome, specific and differing subsets of neurobiological changes are relevant to therapeutic action.     

Acute and Chronic Acetazolamide Administration in DBA and C57 Mice: Effects of Age

The clinical utility of the carbonic anhydrase (CA) inhibitor acetazolamide (ACTZ) is limited because of rapid development of tolerance to its effects. Tolerance is thought to develop as a result of glial cell proliferation and/or increased CA synthesis. DBA mice, susceptible to audiogenic seizures (AGSs) in an age-dependent manner, have increased CA activity as compared with C57 (non-audiogenic seizure susceptible) mice at 21 and 110 days of age. The present work utilized ACTZ to help determine the relationship between increased CA activity in brain and AGSs in DBA mice. Also, minimal electroshock seizure threshold (EST) was measured at various ages in DBA and C57 mice to determine age-related changes in CNS excitability. EST was significantly lower in DBA as compared with C57 mice at 18 days and between 40 and 115 days of age, suggesting that DBA mice remain hyperexcitable to electrical stimulation after they develop resistance to AGSs. ACTZ ED50s against maximal electroshock seizures (MES) were significantly higher in DBA as compared with C57 mice at 26,36, and 115 days of age. This finding correlates with higher CA activity in this strain at 110 days of age, noted previously. However, at 21 days of age, when CA activity is also higher in DBA versus C57 mice, there were no significant differences in ACTZ ED50s against MES between the strains. ACTZ ED50s against AGSs in DBA mice were considerably lower than ACTZ ED50s against MES in either strain, suggesting that a particular fraction of CA is intimately involved in the production of AGSs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical and Pathological Benefit of Twendee X in Alzheimer's Disease Transgenic Mice with Chronic Cerebral Hypoperfusion

BackgroundMultiple pathogeneses are involved in Alzheimer's disease (AD), such as amyloid-β accumulation, neuroinflammation, and oxidative stress. The pathological impact of chronic cerebral hypoperfusion on Alzheimer's disease is still poorly understood.MethodsAPP23 mice were implanted to bilateral common carotid arteries stenosis with ameroid constrictors for slowly progressive chronic cerebral hypoperfusion (CCH). The effects of the administration of Twendee X (TwX) were evaluated by behavioral analysis, immunohistochemical analysis, and immunofluorescent histochemistry.ResultsIn the present study, chronic cerebral hypoperfusion, which is commonly found in aged Alzheimer's disease, significantly exacerbated motor dysfunction of APP23 mice from 5 months and cognitive deficit from 8 months of age, as well as neuronal loss, extracellular amyloid-β plaque and intracellular oligomer formations, and amyloid angiopathy at 12 months. Severe upregulations of oxidative markers and inflammatory markers were found in the cerebral cortex, hippocampus, and thalamus at 12 months. Twendee X treatment (20 mg/kg/d, from 4.5 to 12 months) substantially rescued the cognitive deficit and reduced the above amyloid-β pathology and neuronal loss, alleviated neuroinflammation and oxidative stress.ConclusionsThe present findings suggested a potential therapeutic benefit of Twendee X for Alzheimer's disease with chronic cerebral hypoperfusion.     

Prognostic Factors and Clinical Outcomes of Acute Intracerebral Hemorrhage in Patients with Chronic Kidney Disease

Objective

We conducted a retrospective study examining the outcomes of intracerebral hemorrhage (ICH) in patients with chronic kidney disease (CKD) to identify parameters associated with prognosis.

Methods

From January 2001 to June 2008, we treated 32 ICH patients (21 men, 11 women; mean age, 62 years) with CKD. We surveyed patients age, sex, underlying disease, neurological status using Glasgow Coma Scale (GCS), ICH volume, hematoma location, accompanying intraventricular hemorrhage, anti-platelet agents, initial and 3rd day systolic blood pressure (SBP), clinical outcome using the modified Rankin Scale (mRS) and complications. The severity of renal functions was categorized using a modified glomerular filtration rate (mGFR). Multifactorial effects were identified by regression analysis.

Results

The mean GCS score on admission was 9.4±4.4 and the mean mRS was 4.3±1.8. The overall clinical outcomes showed a significant relationship on initial neurological status, hematoma volume, and mGFR. Also, the outcomes of patients with a severe renal dysfunction were significantly different from those with mild/moderate renal dysfunction (p<0.05). Particularly, initial hematoma volume and sBP on the 3rd day after ICH onset were related with mortality (p<0.05). However, the other factors showed no correlation with clinical outcome.

Conclusion

Neurological outcome was based on initial neurological status, renal function and the volume of the hematoma. In addition, hematoma volume and uncontrolled blood pressure were significantly related to mortality. Hence, the severity of renal function, initial neurological status, hematoma volume, and uncontrolled blood pressure emerged as significant prognostic factors in ICH patients with CKD.     

不同病因急性脑梗死患者静脉溶栓治疗的疗效分析

目的 比较不同病因脑梗死患者静脉溶栓早期疗效及出血转化风险,为不同病因脑梗死静脉溶 栓治疗提供参考和依据。 方法 回顾性纳入2015年9月-2019年9月在深圳市人民医院神经内科住院接受rt-PA静脉溶栓的 连续性急性脑梗死患者,收集患者的基线资料,并根据中国缺血性卒中分型（Chinese Ischemic Stroke Subclassification,CISS）标准进行病因分组。临床有效定义为溶栓后较溶栓前NIHSS评分下降≥4分或 NI HSS评分降至0分。分析不同病因患者静脉溶栓后24 h和7 d的有效率及24 h出血转化的风险。 结果 共纳入283例患者,静脉溶栓后24 h有效例数共129例（4 5.58%）,其中穿支动脉疾病 （penetrating artery disease,PAD）组35例（63.64%）、大动脉粥样硬化型（large-artery atherosclerosis, LAA）组70例（54.69%）、病因不确定（undetermined etiology,UE）组10例（45.45%）、其他病因（other etiology,OE）组3例（23.08%）、心源性（cardiogenic stroke,CS）组11例（16.92%）。组间比较,PAD组有 效率明显高于UE组、OE组、CS组,P值分别为0.015、0.008、0.004;LAA组有效率明显高于UE组、OE组、 CS组,P值分别为0.032、0.011、0.009;UE组有效率明显高于OE组、CS组,P值分别为0.031、0.019。溶 栓7 d有效例数共193例（68.20%）,其中PAD组有效率明显高于CS组（72.73% vs 58.46%,P =0.009）。 溶栓7 d后≤55岁患者有效率明显高于≥80岁患者（76.11% vs 55.56%,P =0.013）。共有23例出现出 血转化（8.13%）,PAD组出血转化率（1.82%）明显低于LAA组、OE组、UE组、CS组,P值分别为0.025、 0.018、0.004、0.001;CS组出血转化率（18.46%）明显高于LAA组、OE组、UE组,P值分别为0.005、 0.012、0.021;≥80岁患者出血转化率明显高于≤55岁患者（14.81% vs 6.19%,P =0.002）和55～79岁 患者（14.81% vs 8.39%,P =0.006）。 结论 不同病因脑梗死患者早期溶栓有效率和出血转化风险有差异,穿支动脉疾病组溶栓早期有 效率较高,出血转化风险低;心源性组患者早期有效率较低,出血转化风险相对较高;患者越年轻, 溶栓效果越好,出血转化风险越小。     

Neuromodulatory Approaches for Chronic Pain Management: Research Findings and Clinical Implications

Two lines of evidence provide preliminary support for the role that brain state, measured via electroencephalogram (EEG), may play in chronic pain. First, research has identified a link between brain EEG activity and the experience of pain. Second, there are a number of published studies documenting the beneficial effects of interventions that impact the cortical activity associated with chronic pain. These interventions include neurobehavioral treatments such as neurofeedback and hypnosis as well as invasive and non-invasive brain stimulation. Preliminary data showing the efficacy of neuromodulatory strategies for treating pain provides compelling reason to examine how cortical activity (as measured by EEG) may underlie the experience of pain. Existing data already suggest specific approaches that neurofeedback clinicians might consider when treating patients with chronic pain. Reciprocally, observations by neurofeedback practitioners could provide important case data that could foster the design of more definitive randomized clinical trials using such strategies for the treatment of chronic pain.     

Jitter of Corticospinal Neurons During Repetitive Transcranial Magnetic Stimulation. Method and Possible Clinical Implications

BackgroundRepetitive transcranial magnetic stimulation (rTMS) of the motor cortex activates corticospinal neurons mainly through the depolarization of cortico-cortical axons belonging to interneurons of superficial layers.ObjectiveWe used single-fiber electromyography (SFEMG) to estimate the “central jitter” of activation latency of interneural pools from one pulse of TMS to another.MethodsWe evaluated 10 healthy subjects and one patient with multiple sclerosis. By recording SFEMG evoked activity from the left first dorsal interosseous (FDI), we first used a standard repetitive electrical 3 Hz stimulation of the ulnar nerve at the wrist to calculate the mean consecutive difference from at least 10 different potentials. The same procedure was applied during 3 Hz repetitive TMS of the contralateral motor cortex. The corticospinal monosynaptic connection of the FDI and the selectivity of SFEMG recording physiologically justified the subtraction of the “peripheral jitter” from the whole cortico-muscular jitter, obtaining an estimation of the actual “central jitter.”ResultsAll subjects completed the study. The peripheral jitter was 28 μs ± 6 and the cortico-muscular jitter was 344 μs ± 97. The estimated central jitter was 343 ± 97 μs. In the patient the central jitter was 846 μs, a value more than twice the central jitter in healthy subjects.ConclusionCurrent results demonstrate that the evaluation of the central component of the cumulative cortico-muscular latency variability in healthy subjects is feasible with a minimally invasive approach. We present and discuss this methodology and provide a “proof of concept” of its potential clinical applicability in a patient with multiple sclerosis.     

急性颅脑损伤神经降压素含量变化及临床意义

目的和方法应用放免法动态测定51例急性颅脑损伤患者血浆及脑脊液神经降压素含量，以观察神经降压素水平在颅脑损伤组和正常对照组中的变化，并探讨其临床意义。结果颅脑损伤患者急性期血浆及脑脊液神经降压素含量显著高于对照组，且与病情轻重程度明显相关。结论神经降压素参与急性颅脑损伤后继发性病理生理过程；神经降压素受体桔抗剂成为治疗颅脑损伤的有效途径；血浆或脑脊液神经降压素动态含量，可能是判断急性颅脑损伤患者预后的重要因素。     

Antidepressants in children: indications, benefits, and limitations

The clinical applications of antidepressant drugs in childhood behavioral and emotional disorders were reviewed briefly as a means of introducing advances that have emerged over the past decade in the field of pediatric psychopharmacology. Using prepubertal major depressive disorder as a prototype, the benefits and limitations of antidepressant treatment were discussed in a conceptual way that builds on the current state of the evidence. Syndromic depression and major depression as a disorder with a distinct natural history, pattern of familial aggregation, and emerging set of psychobiological correlates can be supported by this evidence, and can be reliably diagnosed in children. Given the long duration of symptoms in depressed children, the degree of functional impairment they experience during and following recovery from an episode, and the high risk of relapse, treatment with antidepressant medication appears warranted despite attendant risks and potential disadvantages. Although psychosocial treatments are not as empirically defensible as drug treatment, there are compelling reasons why they should be used and investigated more exhaustively. Some suggestions regarding research directions and guidelines for clinical practice are offered.