Traumatic brain injury and psychogenic nonepileptic seizures yield worse outcomes

Purpose: To investigate the relationship between traumatic brain injury (TBI) and psychogenic nonepileptic seizures (PNES). We hypothesized that PNES with TBI would be associated with more psychiatric comorbidities and disability than PNES without TBI. Methods: In this cross‐sectional study comparing patients with PNES with TBI to patients with PNES without TBI, medical records from 255 consecutive patients with electroencephalography (EEG)‐confirmed PNES were reviewed to assess variables including demographic, head injury, neurologic, psychiatry, social variables, and quality of life and symptoms scales. Parametric, analysis of covariance (ANCOVA), and logistic regression analyses were performed, to compare psychiatric and function variables between the two study groups while controlling for age and sex. Key Findings: Of the 92 patients with PNES who fulfilled inclusion/exclusion criteria, 41 (44.6%) had a history of TBI. Of the 41 patients with TBI, 30 (73%) met criteria for mild TBI (mTBI). Patients with TBI had more mood disorder diagnoses, were more likely to receive disability, and had lower global functioning than non‐TBI patients with PNES, after adjusting for age and sex. Patients with TBI and PNES had significantly increased odds for having major depression, behavioral impulsivity, posttraumatic stress disorder diagnosis, and a trauma/abuse history. Significance: TBI is a significant risk factor in patients with PNES, being associated with increased psychiatric diagnostic comorbidity, symptoms severity, poorer functioning, and increased disability. This study reveals the importance of identifying and addressing the impact of TBI in patients with seizure disorders. Addressing the sequelae of TBI in PNES may be a target to improve functioning.     

Trauma, stress, and preconscious threat processing in patients with psychogenic nonepileptic seizures

Purpose:   Psychogenic nonepileptic seizures (PNES) have long been considered as paroxysmal dissociative symptoms characterized by an alteration of attentional functions caused by severe stress or trauma. Although interpersonal trauma is common in PNES, the proposed relation between trauma and attentional functions remains under explored. We examined the attentional processing of social threat in PNES in relation to interpersonal trauma and acute psychological stress.
Methods:   A masked emotional Stroop test, comparing color-naming latencies for backwardly masked angry, neutral, and happy faces, was administered to 19 unmedicated patients with PNES and 20 matched healthy controls, at baseline and in a stress condition. Stress was induced by means of the Trier Social Stress Test and physiologic stress parameters, such as heart rate variability (HRV) and cortisol, were measured throughout the experiment.
Results:   No group differences related to the acute stress induction were found. Compared to controls, however, patients displayed a positive attentional bias for masked angry faces at baseline, which was correlated to self-reported sexual trauma. Moreover, patients showed lower HRV at baseline and during recovery.
Discussion:   These findings are suggestive of a state of hypervigilance in patients with PNES. The relation with self-reported trauma, moreover, offers the first evidence linking psychological risk factors to altered information processing in PNES.     

Juvenile mild traumatic brain injury elicits distinct spatiotemporal astrocyte responses

Mild-traumatic brain injury (mTBI) represents ~80% of all emergency room visits and increases the probability of developing long-term cognitive disorders in children. To date, molecular and cellular mechanisms underlying post-mTBI cognitive dysfunction are unknown. Astrogliosis has been shown to significantly alter astrocytes' properties following brain injury, potentially leading to significant brain dysfunction. However, such alterations have never been investigated in the context of juvenile mTBI (jmTBI). A closed-head injury model was used to study jmTBI on postnatal-day 17 mice. Astrogliosis was evaluated using glial fibrillary acidic protein (GFAP), vimentin, and nestin immunolabeling in somatosensory cortex (SSC), dentate gyrus (DG), amygdala (AMY), and infralimbic area (ILA) of prefrontal cortex in both hemispheres from 1 to 30 days postinjury (dpi). In vivo T2-weighted-imaging (T2WI) and diffusion tensor imaging (DTI) were performed at 7 and 30 dpi to examine tissue level structural alterations. Increased GFAP-labeling was observed up to 30 dpi in the ipsilateral SSC, the initial site of the impact. However, vimentin and nestin expression was not perturbed by jmTBI. The morphology of GFAP positive cells was significantly altered in the SSC, DG, AMY, and ILA up to 7 dpi that some correlated with magnetic resonance imaging changes. T2WI and DTI values were significantly altered at 30 dpi within these brain regions most prominently in regions distant from the impact site. Our data show that jmTBI triggers changes in astrocytic phenotype with a distinct spatiotemporal pattern. We speculate that the presence and time course of astrogliosis may contribute to pathophysiological processes and long-term structural alterations following jmTBI.     

Illness perceptions of health care workers in relation to epileptic and psychogenic nonepileptic seizures

Illness perceptions of health care professionals are likely to affect patient care. This study describes the illness perceptions of two groups of health care staff toward epilepsy and psychogenic nonepileptic seizures (PNES). Sixty-one health care professionals (30 emergency care [EC] and 31 neuroscience ward [NW] staff) who regularly see patients with seizures completed the adapted Illness Perception Questionnaire-Revised (IPQ-R) and the Symptom Attribution Question for epilepsy and PNES. Respondents reported a poorer understanding of PNES than of epilepsy (P<0.001), thought epilepsy was a more chronic condition (P=0.001/P<0.001) and that patients with PNES had more "personal control" of their seizures (P=0.014/P<0.001). Staff from both departments identified psychological causes as most important for PNES (P<0.001). EC staff also attributed PNES to behavioral issues or alcohol. The Illness Perception Questionnaire-Revised and Symptom Attribution Question demonstrated important differences in attitudes of health care staff toward epilepsy and PNES. The findings illustrate why some patients with PNES have traumatic encounters with health care professionals.     

Psychiatric disorders and traumatic brain injury

Psychiatric disorders after traumatic brain injury (TBI) are frequent. Researches in this area are important for the patients’ care and they may provide hints for the comprehension of primary psychiatric disorders. Here we approach epidemiology, diagnosis, associated factors and treatment of the main psychiatric disorders after TBI. Finally, the present situation of the knowledge in this field is discussed.     

The potential of neural transplantation for brain repair and regeneration following traumatic brain injury

Traumatic brain injury is a major health problem worldwide. Currently, there is no effective treatment to improve neural structural repair and functional recovery of patients in the clinic. Cell transplantation is a potential strategy to repair and regenerate the injured brain. This review article summarized recent de-velopment in cell transplantation studies for post-traumatic brain injury brain repair with varying types of cell sources. It also discussed the potential of neural transplantation to repair/promote recovery of the injured brain following traumatic brain injury.     

D-二聚体与进展性颅内出血的相关性研究

目的研究急性颅脑损伤病人早期D-二聚体（D-D）的变化,分析D-D与进展性颅内出血（PIH）的相关性,评估D-D对急性颅脑损伤的病情及预后的价值。方法检查292例急性颅脑损伤患者血浆D-D于颅脑损伤后24 h、3 d、7 d、14 d的变化。对其进行前瞻性研究,分析D-D与PIH、颅脑损伤病情及预后的关系。结果 292例患者中伤后24 h D-D异常发生率64.73%,明显高于伤后7 d、14 d（P〈0.01）,且易发生PIH。病情重者及死亡组D-D异常更显著（P〈0.01）。结论急性颅脑损伤中D-D异常发生率高,血液高凝状态与纤溶亢进并存,纤溶指标升高显著时,伤情严重,PIH发生率高,死亡率高。提示D-D可作为PIH发生的预测因素,对急性颅脑损伤病情评估及预后判断有较高价值。     

The less BOLD, the wiser: support for the latent resource hypothesis after traumatic brain injury

Previous studies of the BOLD response in the injured brain have revealed neural recruitment relative to controls during working memory tasks in several brain regions, most consistently the right prefrontal cortex and anterior cingulate cortices. We previously proposed that the recruitment observed in this literature represents auxiliary support resources, and that recruitment of PFC is not abnormal or injury specific and should reduce as novelty and challenge decrease. The current study directly tests this hypothesis in the context of practice of a working memory task. It was hypothesized that individuals with brain injury would demonstrate recruitment of previously indicated regions, behavioral improvement following task practice, and a reduction in the BOLD signal in recruited regions after practice. Individuals with traumatic brain injury and healthy controls performed the n-back during fMRI acquisition, practiced each task out of the scanner, and returned to the scanner for additional fMRI n-back acquisition. Statistical parametric maps demonstrated a number of regions of recruitment in the 1-back in individuals with brain injury and a number of corresponding regions of reduced activation in individuals with brain injury following practice in both the 1-back and 2-back. Regions of interest demonstrated reduced activation following practice, including the anterior cingulate and right prefrontal cortices. Individuals with brain injury demonstrated modest behavioral improvements following practice. These findings suggest that neural recruitment in brain injury does not represent reorganization but a natural extension of latent mechanisms that engage transiently and are contingent upon cerebral challenge.     

Functional outcome is tied to dynamic brain states after mild to moderate traumatic brain injury

The current study set out to investigate the dynamic functional connectome in relation to long‐term recovery after mild to moderate traumatic brain injury (TBI). Longitudinal resting‐state functional MRI data were collected (at 1 and 3 months postinjury) from a prospectively enrolled cohort consisting of 68 patients with TBI (92% mild TBI) and 20 healthy subjects. Patients underwent a neuropsychological assessment at 3 months postinjury. Outcome was measured using the Glasgow Outcome Scale Extended (GOS‐E) at 6 months postinjury. The 57 patients who completed the GOS‐E were classified as recovered completely (GOS‐E = 8; n = 37) or incompletely (GOS‐E < 8; n = 20). Neuropsychological test scores were similar for all groups. Patients with incomplete recovery spent less time in a segregated brain state compared to recovered patients during the second visit. Also, these patients moved less frequently from one meta‐state to another as compared to healthy controls and recovered patients. Furthermore, incomplete recovery was associated with disruptions in cyclic state transition patterns, called attractors, during both visits. This study demonstrates that poor long‐term functional recovery is associated with alterations in dynamics between brain networks, which becomes more marked as a function of time. These results could be related to psychological processes rather than injury‐effects, which is an interesting area for further work. Another natural progression of the current study is to examine whether these dynamic measures can be used to monitor treatment effects.     

Effectiveness of Japanese herbal medicine yokukansan for alleviating psychiatric symptoms after traumatic brain injury

The Japanese herbal medicine, yokukansan, has been reported to improve behavioral and psychological symptoms of dementia and activities of daily living in patients with dementia. In the present case report, the authors report the effectiveness of yokukansan in treating psychiatric symptoms after traumatic brain injury. An 85-year-old man, who underwent surgery for hepatic portal cholangiocarcinoma, sustained traumatic brain injury after falling from bed as the result of postoperative delirium. He subsequently presented with psychiatric symptoms, showing markedly impulsive and aggressive behavior. Neuroleptics did not alleviate the symptoms. Ultimately, we succeeded in controlling the symptoms, without adverse effects, by giving the patient yokukansan. Yokukansan shows the potential for reducing aggressive and impulsive behavior in dementia as well as in other psychiatric diseases.     

Subventricular zone neural precursor cell responses after traumatic brain injury and binge alcohol in male rats

Traumatic brain injury (TBI) is a major cause of disability worldwide. Additionally, many TBI patients are intoxicated with alcohol at the time of injury, but the impact of acute intoxication on recovery from brain injury is not well understood. We have previously found that binge alcohol prior to TBI impairs spontaneous functional sensorimotor recovery. However, whether alcohol administration in this setting affects reactive neurogenesis after TBI is not known. This study, therefore, sought to determine the short- and long-term effects of pre-TBI binge alcohol on neural precursor cell responses in the subventricular zone (SVZ) following brain injury in male rats. We found that TBI alone significantly increased proliferation in the SVZ as early as 24 hr after injury. Surprisingly, binge alcohol alone also significantly increased proliferation in the SVZ after 24 hr. However, a combined binge alcohol and TBI regimen resulted in decreased TBI-induced proliferation in the SVZ at 24 hr and 1 week post-TBI. Furthermore, at 6 weeks after TBI, binge alcohol administered at the time of TBI significantly decreased the TBI-induced neuroblast response in the SVZ and the rostral migratory stream (RMS). The results from this study suggest that pre-TBI binge alcohol negatively impacts reparative processes in the brain by decreasing short-term neural precursor cell proliferative responses as well as long-term neuroblasts in the SVZ and RMS.     

大鼠脑损伤后NMDAR1表达及其认知障碍变化的关系

目的同步考量脑损伤后大鼠与认知功能较为密切的脑区N-甲基-D-天冬氨酸受体1（NMDAR1）表达与认知功能的变化。方法参照Feeney法建立大鼠创伤性脑损伤模型,伤后1d,2d,4d,7d1）．2免疫组化SABC法检测大鼠额叶皮质、海马区、基底前脑区NMDAR1表达,以行走实验、平衡实验及记忆功能测定评估大鼠认知障碍变化。结果轻、中型脑损伤组大鼠于伤后2d认知障碍最严重,分别于伤后3,7d基本恢复正常。轻型、中型脑损伤组脑额叶皮质、海马区、基底前脑区NMDAR1均于伤后1d升高,于2d降至较低水平后再呈缓慢增高趋势,与认知障碍变化趋势呈同步变化,且中型脑损伤组NMDAR1表达高于假手术组与轻型脑损伤组（P〈0．05）。结论大鼠经创伤性脑损伤后,额叶皮质、海马区、基底前脑区细胞中的NMDAR1含量和损伤后认知障碍的变化趋势有相似性;创伤性脑损伤后表达增加的NMDAR1对大鼠认知功能有加重损害作用。     

Neuroendocrine function and associated mental health outcomes following mild traumatic brain injury in OEF-deployed service members

Mild traumatic brain injury (mTBI) has been linked to mental health disorders (MHDs) and pituitary function alterations. Due to the complex relationship of mTBI, the neuroendocrine system, and MHDs, we propose that neuroendocrine dysfunction (NED) may play a role in negative long-term health outcomes. The goal of this study was to determine if blast-concussed service members (SMs) have a stronger likelihood of developing NED. We hypothesized that NED either pre- or post-injury is associated with poor mental and physical health outcomes. Serum samples from the Armed Forces Health Surveillance Branch were obtained from concussed (n = 59) and non-concussed (n = 72) SMs treated at the Concussion Restoration Care Center (CRCC) in Afghanistan. Serum was collected within 2 years prior to deployment and one or two times within 3 years following their CRCC visit. Samples were analyzed for luteinizing hormone (LH), testosterone, human growth hormone, cortisol, and prolactin to assess post-injury neuroendocrine function. Results indicate that SMs who incurred an mTBI exhibited long-term LH and testosterone deficiencies 3 years following injury compared to controls. Specifically, 47.6% of head-injured SMs displayed hypofunction in at least one of five hormones at 3 years post-injury. Anxiety disorders were the most common MHD observed in concussed SMs with hypopituitarism, while there was also a trend for SMs with chronic pituitary dysfunction to have MHD diagnoses. Findings indicate blast-related mTBI may be associated with long-term health outcomes following a period of incubation. Neuroendocrine screenings may increase treatment opportunities, inform rehabilitation strategies, and improve overall quality of life for patients.     

Early nonischemic oxidative metabolic dysfunction leads to chronic brain atrophy in traumatic brain injury

Chronic brain atrophy after traumatic brain injury (TBI) is a well-known phenomenon, the causes of which are unknown. Early nonischemic reduction in oxidative metabolism is regionally associated with chronic brain atrophy after TBI. A total of 32 patients with moderate-to-severe TBI prospectively underwent positron emission tomography (PET) and volumetric magnetic resonance imaging (MRI) within the first week and at 6 months after injury. Regional lobar assessments comprised oxidative metabolism and glucose metabolism. Acute MRI showed a preponderance of hemorrhagic lesions with few irreversible ischemic lesions. Global and regional chronic brain atrophy occurred in all patients by 6 months, with the temporal and frontal lobes exhibiting the most atrophy compared with the occipital lobe. Global and regional reduction in cerebral metabolic rate of oxygen (CMRO₂), cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of glucose were observed. The extent of metabolic dysfunction was correlated with the total hemorrhage burden on initial MRI (r=0.62, P=0.01). The extent of regional brain atrophy correlated best with CMRO₂ and CBF. Lobar values of OEF were not in the ischemic range and did not correlate with chronic brain atrophy. Chronic brain atrophy is regionally specific and associated with regional reductions in oxidative brain metabolism in the absence of irreversible ischemia.