Update on adrenal cortical neoplasia

The adrenal cortex gives rise to a biologically heterogenous group of neoplasms, each with a distinct morphology, antigen expression and molecular profile. Adrenal cortical adenomas have excellent prognosis and are usually cured by surgical resection alone, while adrenal cortical carcinomas are very aggressive tumors with a poor prognosis regardless of therapy. These tumors are rare and often challenging for a pathologist to diagnose, as significant overlap exists between benign and malignant lesions in some cases. In this review, we attempt to summarize most important histologic and clinical features of adrenal cortical adenomas and carcinomas, clarify the use of different grading systems, the use of special stains and the differential diagnosis for practicing pathologists. Most relevant hereditary syndromes associated with adrenal cortical tumors are listed. Updates in molecular alterations in adrenal cortical neoplasms and hyperplastic diseases as well as their clinical significance and potential therapeutic implications are also discussed.     

Enlarged high frequency oscillations of the median nerve somatosensory evoked potential and survival in amyotrophic lateral sclerosis

ObjectiveA large N20 and P25 of the median nerve somatosensory evoked potential (SEP) predicts short survival in amyotrophic lateral sclerosis (ALS). We investigated whether high frequency oscillations (HFOs) over N20 are enlarged and associated with survival in ALS.MethodsA total of 145 patients with ALS and 57 healthy subjects were studied. We recorded the median nerve SEP and measured the onset-to-peak amplitude of N20 (N20o-p), and peak-to-peak amplitude between N20 and P25 (N20p-P25p). We obtained early and late HFO potentials by filtering SEP between 500 and 1 kHz, and measured the peak-to-peak amplitude. We followed up patients until endpoints (death or tracheostomy) and analyzed the relationship between SEP or HFO amplitudes and survival using a Cox analysis.ResultsPatients showed larger N20o-p, N20p-P25p, and early and late HFO amplitudes than the control values. N20p-P25p was associated with survival periods (p = 0.0004), while early and late HFO amplitudes showed no significant association with survival (p = 0.4307, and p = 0.6858, respectively).ConclusionsThe HFO amplitude in ALS is increased, but does not predict survival.SignificanceThe enlarged HFOs in ALS might be a compensatory phenomenon to the hyperexcitability of the sensory cortex pyramidal neurons.     

Contribution of transcranial magnetic stimulation in restless legs syndrome: pathophysiological insights and therapeutical approaches

Transcranial magnetic stimulation (TMS) may offer a reliable means to characterize significant pathophysiologic and neurochemical aspects of restless legs syndrome (RLS). Namely, TMS has revealed specific patterns of changes in cortical excitability and plasticity, in particular dysfunctional inhibitory mechanisms and sensorimotor integration, which are thought to be part of the pathophysiological mechanisms of RLS rather than reflect a non-specific consequence of sleep architecture alteration.If delivered repetitively, TMS is able to transiently modulate the neural activity of the stimulated and connected areas. Some studies have begun to therapeutically use repetitive TMS (rTMS) to improve sensory and motor disturbances in RLS. High-frequency rTMS applied over the primary motor cortex or the supplementary motor cortex, as well as low-frequency rTMS over the primary somatosensory cortex, seem to have transient beneficial effects. However, further studies with larger patient samples, repeated sessions, an optimized rTMS setup, and clinical follow-up are needed in order to corroborate preliminary results.Thus, we performed a systematic search of all the studies that have used TMS and rTMS techniques in patients with RLS.     

应用锥形束CT对种植区牙槽骨质量分类方法的改良研究

目的    应用锥形束CT（cone beam CT，CBCT）测量种植区牙槽骨质量并结合Lekholm和Zarb分类法对骨质量分类方法进行改良，以期为提高牙槽骨质量分类的准确性提供指导。方法    选择2015年10月至2017年10月在呼和浩特市口腔医院种植科进行种植修复的196例患者术前CBCT影像资料，应用 Invivo5诊断设计软件测量306个种植位点的牙槽骨皮质骨厚度和松质骨密度（皮质骨与松质骨的CT值差值），以Lekholm和Zarb分类法为基础结合测量数据对骨质量进行改良后的量化分类。结果    牙槽骨皮质骨厚度为0.18 ~ 2.89 mm，中位数为0.92 mm。皮质骨与松质骨的CT值差值为88.5 ~ 667.8 HU，应用百分位数法找到33.3%和66.6%对应的数值分别为297.8 HU和356.1 HU。依据此数据结合Lekholm和Zarb分类法将196例患者的306个种植位点骨质量分为4类，其中Ⅰ类骨种植位点46个（占15.0%），Ⅱ类骨104个（占34.0%），Ⅲ类骨114个（占37.3%），Ⅳ类骨42个（占13.7%）。结论    结合Lekholm和Zarb分类法，应用CBCT测量种植区牙槽骨质量并进行分类方法的改良，可为临床医生术前评估牙槽骨质量提供一定参考。     

Simultaneously recorded intracranial and scalp high frequency oscillations help identify patients with poor postsurgical seizure outcome

ObjectiveHigh frequency oscillations (HFO) between 80–500 Hz are markers of epileptic areas in intracranial and maybe also scalp EEG. We investigate simultaneous recordings of scalp and intracranial EEG and hypothesize that scalp HFOs provide important additional clinical information in the presurgical setting.MethodsSpikes and HFOs were visually identified in all intracranial scalp EEG channels. Analysis of correlation of event location between intracranial and scalp EEG as well as relationship between events and the SOZ and zone of surgical removal was performed.Results24 patients could be included, 23 showed spikes and 19 HFOs on scalp recordings. In 15/19 patients highest scalp HFO rate was located over the implantation side, with 13 patients having the highest scalp and intracranial HFO rate over the same region. 17 patients underwent surgery, 7 became seizure free. Patients with poor post-operative outcome showed significantly more regions with HFO than those with seizure free outcome.ConclusionsScalp HFOs are mostly located over the SOZ. Widespread scalp HFOs are indicative of a larger epileptic network and associated with poor postsurgical outcome.SignificanceAnalysis of scalp HFO add clinically important information about the extent of epileptic areas during presurgical simultaneous scalp and intracranial EEG recordings.     

Interhemispheric visual competition after multisensory reversal of hemianopia

Unilateral lesions of visual cortex have the secondary consequence of suppressing visual circuits in the midbrain superior colliculus (SC), collectively producing blindness in contralesional space (“hemianopia”). Recent studies have demonstrated that SC visual responses and contralesional vision can be reinstated by a non‐invasive multisensory training procedure in which spatiotemporally concordant visual‐auditory pairs are repeatedly presented within the blind hemifield. Despite this recovery of visual responsiveness, the loss of visual cortex was expected to result in permanent deficits in that hemifield, especially when visual events in both hemifields compete for attention and access to the brain's visuomotor circuitry. This was evaluated in the present study in a visual choice paradigm in which the two visual hemifields of recovered cats were simultaneously stimulated with equally valent visual targets. Surprisingly, the expected disparity was not found, and some animals even preferred stimuli presented in the previously blind hemifield. This preference persisted across multiple stimulus intensity levels and there was no indication that animals were less aware of cues in the previously blind hemifield than in its spared counterpart. Furthermore, when auditory cues were combined with visual cues, the enhanced performance they produced on a visual task was no greater in the normal than in the previously blind hemifield. These observations suggest that the multisensory rehabilitation paradigm revealed greater inherent visual information processing potential in the previously blind hemifield than was believed possible given the loss of visual cortex.     

Deficiency of anti-inflammatory cytokine IL-4 leads to neural hyperexcitability and aggravates cerebral ischemia–reperfusion injury

Systematic administration of anti-inflammatory cytokine interleukin 4 (IL-4) has been shown to improve recovery after cerebral ischemic stroke. However, whether IL-4 affects neuronal excitability and how IL-4 improves ischemic injury remain largely unknown. Here we report the neuroprotective role of endogenous IL-4 in focal cerebral ischemia–reperfusion (I/R) injury. In multi-electrode array (MEA) recordings, IL-4 reduces spontaneous firings and network activities of mouse primary cortical neurons. IL-4 mRNA and protein expressions are upregulated after I/R injury. Genetic deletion of Il-4 gene aggravates I/R injury in vivo and exacerbates oxygen-glucose deprivation (OGD) injury in cortical neurons. Conversely, supplemental IL-4 protects Il-4^−/− cortical neurons against OGD injury. Mechanistically, cortical pyramidal and stellate neurons common for ischemic penumbra after I/R injury exhibit intrinsic hyperexcitability and enhanced excitatory synaptic transmissions in Il-4^−/− mice. Furthermore, upregulation of Nav1.1 channel, and downregulations of KCa3.1 channel and α6 subunit of GABA_A receptors are detected in the cortical tissues and primary cortical neurons from Il-4^−/− mice. Taken together, our findings demonstrate that IL-4 deficiency results in neural hyperexcitability and aggravates I/R injury, thus activation of IL-4 signaling may protect the brain against the development of permanent damage and help recover from ischemic injury after stroke.     

Confirmation of Age-dependence in the Leakage of Contrast Medium around the Cortical Veins into Cerebrospinal Fluid after Intravenous Administration of Gadolinium-based Contrast Agent

Purpose:It has been reported previously that intravenously administered gadolinium-based contrast agent (GBCA) leaks into the subarachnoid space around the cortical veins at 4 h after injection in all old people over 37 years, but not in younger people up to 37 years of age in 3D-real IR images. The purpose of this study was to investigate whether there was a strict threshold of 37 years of age for the leakage of the GBCA into the subarachnoid space.Methods:The subjects included 190 patients, that were scanned for 3D-real IR images at 4 hours after intravenous injection of GBCA as a diagnostic test for endolymphatic hydrops. The patient’s age ranged from 14 to 81 years. Two experienced neuroradiologists evaluated the images to determine whether the GBCA leakage around the cortical veins was positive or negative. Any discrepancies between the two observers were discussed and a consensus was obtained.A Mann–Whitney U test and receiver operating characteristic (ROC) curve analysis were used to compare the positive and the negative group and to set the age cut-off value for the prediction of GBCA leakage.Results:The GBCA leakage around the cortical veins was negative in 35 patients and positive in 155 patients. The average age was 33 ± 11 years in the negative group, and 55 ± 12 years in the positive group (P < 0.01). In the ROC analysis for the age and leakage of the GBCA, an area under the curve was 0.905 and the cut-off age was 37.317 years (sensitivity of 0.942 and specificity of 0.771).Conclusion:Intravenously administered GBCA leaks into the subarachnoid space around the cortical veins in most patients over 37 years of age. However, it should be noted that it can be found occasionally in patients under 37 years of age.     

皮质发育障碍模型的建立及其致痫敏感性的研究

目的:建立皮质发育障碍模型,探讨皮质发育障碍模型的敏感性。方法:在SD大鼠孕17d腹腔注入1,3-二氯乙烯-亚硝基脲(BCNU)制作皮质发育障碍模型;Nissl染色观察P60d仔鼠病理变化;选取P60d雄性仔鼠,腹腔注射氯化锂-毛果芸香碱,分别比较两组大鼠癫发生的潜伏期、持续状态时间和死亡率。结果:同龄仔鼠脑组织湿重实验组比对照组显著减轻(P<0.01);Nissl染色显示皮质变薄、皮质层次紊乱、海马区域异位细胞异常聚集;有皮质发育障碍的仔鼠注射氯化锂-毛果芸香碱后,癫发生的潜伏期显著缩短(P<0.01),癫持续状态时间延长(P<0.01),死亡率显著升高(P<0.05)。结论:BCNU致皮质发育障碍模型具有癫易感性。     

原发性肾上腺皮质腺癌的CT诊断价值

目的分析原发性肾上腺皮质腺癌（ACC）的CT表现及其动态增强特征，以提高其诊断准确性。方法回顾性分析经手术病理证实的ACC11例，术前均经CT平扫、动脉期（30S）和门静脉期（70—80S）扫描，复习CT扫描表现并和手术病理作对照。结果11例ACC中，右侧5例，左侧6例。直径4．1—16．0cm，其中，〈5．0cm者2例，5．0—10．0cm者4例，〉10．0cm5例；肿瘤境界清楚3例，邻近脂肪间隙见条索状异常密度影3例，邻近实质脏器受侵犯5例。肿瘤实质成分平扫、动脉期和门静脉期CT值分别为21．9～46．7HU（平均35．3HU）、30．5～65．8HU（平均47．1HU）和52．6～97．0HU（平均74．2HU）。肿瘤中央坏死形成假囊肿4例，网络状改变6例，实质为主伴小囊变1例；6例网络状改变者动脉期可见显著强化的不规则肿瘤血管：结论ACC具有较明显的形态学和血液动力学特征，动态增强扫描尤其是动脉期扫描有明显的诊断价值。