Altered fimbria-fornix white matter integrity in anorexia nervosa predicts harm avoidance

The eating disorder anorexia nervosa (AN) is associated with high anxiety. The brain mechanisms that drive those behaviors are unknown. In this study we wanted to test whether brain white matter (WM) integrity is altered in AN, and related to heightened anxiety. Sixteen adult women with AN (mean age 24 ± 7 years) and 17 healthy control women (CW, mean age 25 ± 4 years) underwent diffusion tensor imaging (DTI) of the brain. The DTI brain images were used to calculate the fractional anisotropy (FA) of WM tracts, which is a measure for WM integrity. AN individuals compared to CW showed clusters of significantly reduced FA (p < 0.05, corrected) in the bilateral fimbria-fornix and the fronto-occipital fasciculus, as well as the posterior cingulum WM. In the AN group, Harm Avoidance was predicted by FA in the left and right fimbria-fornix. Those findings were not due to WM volume deficits in AN. This study indicates that WM integrity is abnormal in AN in limbic and association pathways, which could contribute to disturbed feeding, emotion processing and body perception in AN. The prediction of Harm Avoidance in AN by fimbria-fornix WM integrity suggests that this pathway may be mechanistically involved in high anxiety in AN.     

Unraveling the biological mechanisms in Alzheimer's disease--lessons from genomics

Alzheimer's disease (AD) is the most common form of dementia and the most common neurodegenerative disease, with a complex genetic background. Genome-wide association studies (GWAS) have yielded important new insights into genetic mechanisms of AD pathology. Current results unequivocally confirm apolipoprotein E (APOE) as a major genetic risk factor for development of late onset AD. Additional associations of more than twenty genes have also been identified and replicated in subsequent genetic studies. Despite the exciting new GWAS data which have emerged in the last few years, it has become clear that common variants within the genome cannot fully explain the underlying genetic risk for AD. Novel approaches such as genome-wide analysis of copy number variations (CNV) or low-frequency rare functional gene variants may provide additional insight into genetic basis of AD. In this review we summarize the findings of eighteen GWAS studies in AD performed to date, with an emphasis on potential future developments in the quest for genetic risk factors of AD.     

Appreciating symptoms and deficits in schizophrenia: right posterior insula and poor insight

Poor insight is one of the most prominent clinical features of psychosis. Loss of insight in schizophrenia is characterised by abnormalities in awareness and attribution of the origin of pathological mental phenomena. Converging lines of investigations suggest that in healthy individuals, right posterior insula plays an important role in awareness and self-attribution of mental phenomena, contributing to the emergence of a sense of self (Craig, 2002; Farrer et al., 2003). In addition, neuroimaging studies investigating brain morphometry in schizophrenia have consistently reported deficits in the structure of insula (Glahn et al., 2008; Ellison-Wright and Bullmore, 2010). In the present study, we investigated the relationship between the morphometry of posterior insula and degree of insight in a sample of 57 patients in a stable phase of illness using high resolution Magnetic Resonance Imaging. We measured the cortical surface area and local white matter volume of posterior insula. A significant inverse relationship was found between right posterior insular structure and degree of insight in schizophrenia. No such relationship was noted for left posterior insula. Our results highlight the importance of a predominantly right-sided network that includes posterior insula as the neural basis of insight. Abnormalities in interoceptive awareness and self-appraisal of emotional states may contribute to the loss of insight seen in schizophrenia.     

What are the differences between younger and older patients with symptomatic small vessel disease?

Objective

Although typically linked to aging, small vessel disease (SVD) is also observed in younger adult patients, with common vascular risk factors (RF). We aimed to investigate features of SVD occurrence at an early adult age.

Patients and methods

Vascular RF, functional and cognitive status and severity of lesions on MRI expressed as total score on Age-Related White Matter Changes (ARWMC) scale were analyzed in 200 consecutive patients with cerebral SVD admitted to a tertiary neurological hospital. Variables were compared between younger (35–55 years) and older (>56 years) patients.

Results

In this study, 63 (31.5%) of patients were 55 years or younger. Both age groups had comparable RF profiles, but smoking emerged as an independent predictor for SVD at a younger age (OR 2.9; 95% CI 1.5–5.5; p = 0.002). Younger patients had better functional (OR 1.8; 95% CI 1.3–2.5; p = 0.0001) and cognitive (χ² 13.94; p = 0.0009) status compared to older patients. However, two thirds of younger patients had some degree of cognitive deficit. Total score on ARWMC scale was lower in younger patients (mean 12.3 in younger versus 15.2 in older, OR 1.11; 95% CI 1.0–1.18; p = 0.001). There was a strong correlation in both groups between functional score, cognitive status and ARWMC score (p < 0.0001).

Conclusion

In our dataset, younger patients with SVD shared common vascular RF with older patients. In the group aged ≤55, better functional and cognitive status and less severe MRI changes were noted. However, a substantial number of younger SVD patients presenting with TIA or ischemic stroke had various deficits.     

Differential impact of diabetes and hypertension in the brain: adverse effects in white matter

Humans subjected to diabetes mellitus (DM) and/or hypertension (HTN) develop cognitive decline, cerebral atrophy and white matter abnormalities, but the relative effects of DM and HTN upon myelin and axonal integrity is unknown. We studied models of Type 1 (streptozotocin-induced) and Type 2 DM (ZDF) ± HTN (ZSF-1, SHR) in adult rats using magnetic resonance imaging (MRI) and structural and molecular techniques. Type 1 or 2 DM independently led to loss of myelin associated with changes with MRI T2 and magnetization tensor ratios throughout white matter regions. HTN's effect on myelin loss was minimal. Loss of oligodendroglia and myelin proteins was only identified in either Type 1 or Type 2 DM. Activation of the signal transduction pathways initiated by the receptor for advanced glycation end products (AGEs), RAGE, including upregulation of the signal transducer nuclear factor (NF) κB only occurred with DM. Diabetes is a greater contributor to white matter loss than hypertension in the rat brain, while hypertension only plays a mild additive effect upon neurodegeneration in the presence of diabetes.     

深部电极脑电图在灰质异位相关癫痫的术中应用

目的 探讨脑深部电极脑电图在脑深部局灶性灰质异位相关癫痫的应用价值.方法 同顾性分析应用脑深部电极脑电图进行定位的4例灰质异位症和1例下丘脑错构瘤病例的资料.结果 男3例,女2例,年龄18～28岁,异位灰质分别位于左额2例、下丘脑、左顶和右枕各1例,病程5-27年.4例癫痫发作表现全面性发作,同时3例发作期脑电图表现为双侧广泛痫性放电.5例均行立体定向病灶内深部电极埋藏术,4例同时埋藏皮层电极,确定癫痫灶均为异位灰质结构,3例行病灶立体定向病灶毁损术,靶点为2～4个,温度为70℃,时间为80 s,2例行立体定向引导下直接手术切除病灶.随访时间12-23个月,下丘脑错构瘤患者癫痫发作减少80%,其他4例目前随访均无发作.无并发症出现.结论 深部电极埋藏脑电图是定位脑深部局灶性灰质异位相关癫痫致痫病灶的重要方法,局灶性病灶可能出现全面性癫痫发作和广泛性脑电图异常.

Abstract：

Objective Heterotopia gray matter (HGM) and hypothalamic hamartoma (HH ),congenital brain malformation underlied by neuronal migration disorders,are one of significant causes of epilepsy,this paper is to discuss the value of deep brain needle electrode EEG in epileptogenic zone localization in patients with nodule HGM and HH.Methods Intracranial electrodes EEG data of patient with HGM and HH was analyzed retrospectively.Methods This cohort included 5 cases (2 females and 3males) whose ages at surgery were from 18 to 28 year old.The heterotopic grey lied in left frontal lobe in 2patients,and hypothalamus,left parietal lobe and right occipital lobe in 1 case respectively.Generalized seizure attack was found in 4 cases and generalized ictal discharge in scalp EEG were presented in 3 patients.All patients underwent intracranial electrode EEG recording,and 1 case used needle electrode as exclusive intracranial electrode.3 patients were performed stereotactic lesion radiofrequency ablation with 2 -4 targets for 80 s with 70℃,and others were used lesion remove under stereotactic guiding.During 12-23 months follow up,4 patients with HGM rendered seizure free,and the patient with HH presented 80% seizure reduction without complication.Conclusion Deep brain needle electrode EEG is an important tool to epileptogenic zone localization of patients with brain heteotopic grey,and focal lesion could present generalized seizure attack and epileptiform discharge.     

Structural neuroimaging in schizophrenia: from methods to insights to treatments

Historically, Kraepelin speculated that dementia praecox resulted from damage to the cerebral cortex, most notably the frontal and temporal cortices. It is only recently, however, that tools have been available to test this hypothesis. Now, more than a century later, we know that schizophrenia is a brain disorder. This knowledge comes from critical advances in imaging technology--including computerized axial tomography, magnetic resonance imaging, and diffusion imaging--all of which provide an unprecedented view of neuroanatomical structures, in vivo. Here, we review evidence for structural neuroimaging abnormalities, beginning with evidence for focal brain abnormalities, primarily in gray matter, and proceeding to the quest to identify abnormalities in brain systems and circuits by focusing on damage to white matter connections in the brain. We then review future prospects that need to be explored and pursued in order to translate our current knowledge into an understanding of the neurobiology of schizophrenia, which can then be translated into novel treatments.     

Cerebrospinal fluid biomarkers of white matter lesions – cross‐sectional results from the LADIS study

Background and purpose: White matter lesions (WMLs) caused by small vessel disease are common in elderly people and contribute to cognitive impairment. There are no established biochemical markers for WMLs. We aimed to study the relation between degree of WMLs rated on magnetic resonance imaging of the brain and cerebrospinal fluid (CSF) levels of structural biomarkers associated with Alzheimer’s disease (AD) and subcortical vascular dementia. Methods: Fifty‐three non‐demented elderly individuals with WMLs were subjected to lumbar puncture. Degree of WMLs was rated using the Fazekas scale. Volumetric assessment of WMLs was performed. CSF samples were analyzed for the 40 and 42 amino acid fragments of amyloid β, α‐ and β‐cleaved soluble amyloid precursor protein, total tau (T‐tau), hyperphosphorylated tau (P‐tau₁₈₁), neurofilament light protein (NFL), sulfatide and CSF/Serum‐albumin ratio. Results: Fifteen subjects had mild, 23 had moderate and 15 had severe degree of WMLs. CSF‐NFL levels differed between the groups (P < 0.001) and correlated with the volume of WMLs (r = 0.477, P < 0.001). CSF sulfatide concentration displayed similar changes but less strongly. T‐tau, P‐tau₁₈₁ and the different amyloid markers as well as CSF/S‐albumin ratio did not differ significantly between the groups. Conclusions: The association of increased CSF‐NFL levels with increasing severity of WMLs in non‐demented subjects suggests that NFL is a marker for axonal damage in response to small vessel disease in the brain. This manifestation may be distinct from or earlier than the neurodegenerative process seen in AD, as reflected by the lack of association between WMLs and AD biomarkers.     

急性腔隙性脑梗死伴脑白质病变对认知功能的变化影响

目的探讨急性腔隙性脑梗死（LI）伴脑白质病变（WML）患者的认知功能障碍特点。方法收集137例患者和正常对照组30例,根据头颅MRIT2加权像及FLAIR像,将病例组分为LI组、WML组和u合并WML组,应用蒙特利尔认知评估量表（MoCA）进行认知评估。结果与对照组相比,WML组的延迟回忆与语言评分明显下降（P〈0．01）;LI组患者注意计算、语言、执行功能评分显著降低（P〈0．01）;LI合并WML组患者延迟记忆、视空间与执行功能评分显著降低（P〈0．01）。与LI组和WML组相比,执行功能障碍在LI合并WML组更明显（P〈0．01）。结论LI合并WML可导致患者认知功能障碍,主要表现为延迟记忆、视空间与执行等认知功能的受损;MoCA在皮层下缺血性脑血管病引起的血管性认知障碍的评定中具有很大的优势。