The incidence of traumatic brain injury in an adult population – how to classify mild cases?

Background: The incidence of traumatic brain injury (TBI) varies considerably between reports mainly because of variable methods used in recruiting of cases and especially in defining mild TBI. This study was carried out to evaluate the incidence in a given population according to published criteria for mild TBIs. Methods: All cases with symptoms of brain injury after a head trauma were collected from the health centres serving a defined population in South East Finland and from the one hospital taking care of all corresponding TBI cases. After reviewing the health records, the author classified the TBIs according to the guidelines of European Federation of Neurological Societies (EFNS). Results: A total of 370 patients were enrolled. The total crude annual incidence rate was 221 per 100.000 (95% CI: 176–265). A mild TBI was defined in 71% of the patients. According to the EFNS criteria, one‐third of them should be classified only with head traumas because of the lack of either loss consciousness (LOC) or post‐traumatic amnesia (PTA). This would reduce the total crude incidence rate to 137 per 100.000(95% CI: 101–172), an effect of the same magnitude as excluding mild TBIs treated out of hospital. Conclusions: The incidence rate falls within the wide range of previous published figures. Use of LOC or PTA as a criterion for mild TBI affects the incidence rate considerably as does the exclusion of mild cases treated out of hospital.     

Expression of long non-coding RNAs in complete transection spinal cord injury: a transcriptomic analysis

Long non-coding RNAs(lncRNAs)are abundantly expressed in the central nervous system and exert a critical role in gene regulation via multiple biological processes.To uncover the functional significance and molecular mechanisms of lncRNAs in spinal cord injury(SCI),the expression signatures of lncRNAs were profiled using RNA sequencing(RNA-seq)technology in a Sprague-Dawley rat model of the 10th thoracic vertebra complete transection SCI.Results showed that 116 of 14,802 detected lncRNAs were differentially expressed,among which 16—including eight up-regulated(H19,Vof16,Hmox2-ps1,LOC100910973,Ybx1-ps3,Nnat,Gcgr,LOC680254)and eight down-regulated(Rmrp,Terc,Ngrn,Ppp2r2b,Cox6a2,Rpl37a-ps1,LOC360231,Rpph1)—demonstrated fold changes>2 in response to transection SCI.A subset of these RNA-seq results was validated by quantitative real-time PCR.The levels of 821 mRNAs were also significantly altered post-SCI;592 mRNAs were up-regulated and 229 mRNAs were down-regulated by more than 2-fold.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses showed that differentially expressed mRNAs were related to GO biological processes and molecular functions such as injury and inflammation response,wound repair,and apoptosis,and were significantly enriched in 15 KEGG pathways,including cell phagocytosis,tumor necrosis factor alpha pathway,and leukocyte migration.Our results reveal the expression profiles of lncRNAs and mRNAs in the rat spinal cord of a complete transection model,and these differentially expressed lncRNAs and mRNAs represent potential novel targets for SCI treatment.We suggest that lncRNAs may play an important role in the early immuno-inflammatory response after spinal cord injury.This study was approved by the Administration Committee of Experimental Animals,Guangdong Province,China.     

Assessment of autonomic dysreflexia in patients with spinal cord injury.

OBJECTIVES AND METHODS: To assess the impairment of supraspinal control over spinal sympathetic centres and the occurrence of autonomic dysreflexia in patients with spinal cord injury. Autonomic dysreflexia is caused by the disconnection of spinal sympathetic centres from supraspinal control and is characterised by paroxysmal hypertensive episodes caused by non-specific stimuli below the level of the lesion. Therefore, patients with spinal cord injury were examined clinically and by different techniques to assess the occurrence of autonomic dysreflexia and to relate disturbances of the sympathetic nervous system to episodes of autonomic dysreflexia. RESULTS: None of the paraplegic patients, but 59% (13/22) of tetraplegic patients (91% of the complete, 27% of the incomplete patients) presented signs of autonomic dysreflexia during urodynamic examination. Only 62% of the tetraplegic patients complained about symptoms of autonomic dysreflexia. Pathological sympathetic skin responses (SSRs) of the hands were related to signs of autonomic dysreflexia in 93% of cases. No patient with preserved SSR potentials of the hands and feet showed signs of autonomic dysreflexia, either clinically or during urodynamic examination. Ambulatory blood pressure measurements (ABPMs) indicated a loss of circadian blood pressure rhythm (sympathetic control) but preserved heart rate rhythm (parasympathetic regulation) only in patients with complete tetraplegia. Pathological ABPM recordings were seen in 70% of patients with symptoms of autonomic dysreflexia. CONCLUSIONS: The urodynamic examination was more sensitive in indicating signs of autonomic dysreflexia in patients with spinal cord injury, whereas SSR allowed the assessment of the degree of disconnection of the sympathetic spinal centres from supraspinal control. Using ABPM recordings the occurrence of episodes of autonomic dysreflexia over 24 hours and the effectiveness of therapeutical treatment can be assessed.     

Non-painful sensory phenomena after spinal cord injury

OBJECTIVES: Non-painful sensory phenomena or "phantom" sensations are common after spinal cord injury. However, the physiological mechanisms responsible for these sensations are poorly understood. The aim of this study, therefore, was to document in a prospective fashion the time course, prevalence, and features of non-painful sensory phenomena after spinal cord injury, and to determine whether there was a relation between the presence of these sensations and completeness, level of injury, and type of spinal cord injury. METHODS: Patients admitted to an acute spinal injuries unit were interviewed after admission and at several time points over a 2 year period to determine the presence and characteristics of non-painful sensations. Sensations were divided into simple and complex, with complex referring to sensations that incorporated a sensation of volume, length, posture, or movement. RESULTS: The present study showed that the large majority (90%) of patients experience either type of sensation and most complex sensations (60%) are first experienced within 24 hours after the injury. Complex sensations were more common in those patients who had complete spinal cord injuries. The presence of either type of sensation did not seem to be related to the level of injury or the type of injury (cord syndrome). A relatively small proportion (22%) of patients reported that the postural sensations were related to their position at the time of injury and sensations were more commonly related to a familiar, comfortable, or often used position before the spinal cord injury. CONCLUSION: Complex sensations such as postural illusions seem to be due to functional changes in the CNS that may occur almost immediately after spinal cord injury. These sensations may be related to a strong sensory memory "imprint" that has been established before injury.     

Personality & behaviour changes following spinal cord injury: self perceptions--partner's perceptions

There has been little specific investigation of personality and behaviour changes following spinal cord injury (SCI) and only limited consideration of the possible impact of concurrent traumatic brain injury (TBI). By mail-out questionnaire, we evaluated personality and behaviour changes in a married group (n = 9) with traumatic SCI, who knew their partners prior to injury, and who had not been identified as having concurrent TBI on referral to the Canadian Paraplegic Association. Both the person with SCI (and the partner) completed the revised Adjective Checklist and by their combined report, there were significant personality and behaviour changes. Unexpectedly, five individuals described post-traumatic amnesia (PTA) > or = 3 days. Subsequently, participants' reports were further divided into two groups--"longer PTA" and "shorter PTA". The "longer PTA" group self-reported less change and more positive change than did their partners. The "longer PTA" partners described changes that are consistent with the profile of TBI. The "shorter PTA" group described themselves more negatively than did their partners. Given the size of the groups (n = 5, n = 4), these findings are presented to illustrate trends and to stimulate further research.     

One year outcome in mild to moderate head injury: the predictive value of acute injury characteristics related to complaints and return to work

OBJECTIVES: To determine the prognostic value of characteristics of acute injury and duration of post-traumatic amnesia (PTA) for long term outcome in patients with mild to moderate head injury in terms of complaints and return to work. METHODS: Patients with a Glasgow coma score (GCS) on admission of 9-14 were included. Post-traumatic amnesia was assessed prospectively. Follow up was performed at 1, 3, 6, and 12 months after injury. Outcome was determined by the Glasgow outcome scale (GOS) 1 year after injury and compared with a more detailed outcome scale (DOS) comprising cognitive and neurobehavioural aspects. RESULTS: Sixty seven patients were included, mean age 33.2 (SD 14.7) years and mean PTA 7.8 (SD 7.3) days. One year after injury, 73% of patients had resumed previous work although most (84%) still reported complaints. The most frequent complaints were headache (32%), irritability (34%), forgetfulness and poor concentration (42%), and fatigue (45%). According to the GOS good recovery (82%) or moderate disability (18%) was seen. Application of the DOS showed more cognitive (40%) and behavioural problems (48%), interfering with return to work. Correlation between the GOS and DOS was high (r=0.87, p<0.01). Outcome correlated with duration of PTA (r=-0.46) but not significantly with GCS on admission (r=0.19). In multiple regression analysis, PTA and the number of complaints 3 months after injury explained 49% of variance on outcome as assessed with the GOS, and 60% with the DOS. CONCLUSIONS: In mild to moderate head injury outcome is determined by duration of PTA and not by GCS on admission. Most patients return to work despite having complaints. The application of a more detailed outcome scale will increase accuracy in predicting outcome in this category of patients with head injury.     

Psychological distress and family burden following spinal cord injury: concurrent traumatic brain injury cannot be overlooked

Although concurrent spinal cord injury (SCI) and traumatic brain injury (TBI) are recognized, there is little acknowledgement of SCI/TBI as a contributor to psychological distress and family burden. By mail-out questionnaire, we evaluated psychological distress and family burden in a married group (n = 12) with traumatic SCI who had not been identified as having concurrent TBI on referral to the Canadian Paraplegic Association. Both the person with SCI and the partner completed the Brief Symptom Inventory (BSI), the Adjective Checklist, and a Likert strain scale to measure the perception of the partner's strain. The partner also completed the Zarit Burden Interview. Despite screening criteria designed to selectively recruit individuals without TBI, seven individuals described post-traumatic amnesia (PTA) > or = 3 days. Subsequently, participants' reports were divided into two groups--"longer PTA" and "shorter PTA". On the Brief Symptom Inventory, the two SCI groups did not differ, but the partners of individuals with "longer PTA" had significantly elevated Global Severity Index scores compared to the other partners. The "longer PTA" partner group demonstrated more strain and more burden (as measured by the Likert strain scale and the Zarit Burden Interview). Given the size of the groups (n = 7, n = 5), these findings are presented to illustrate trends and to stimulate further research.     

Spinal cord injury and health locus of control beliefs

Individual beliefs about control over their health were assessed in 53 patients with spinal cord injury. Patients who believed they exercised control over their health were less depressed than patients who were fatalistic. A significant number of patients were found to be higher in their internal attributions of health control (N = 31) than those who believed in chance (N = 5) and those who believed medical personnel were in control of their health (N = 11). The results are integrated with a past study of depression following spinal cord injury and locus of control beliefs.     

Posttraumatic amnesia and recall of a traumatic event following traumatic brain injury

The relationship between posttraumatic amnesia (PTA) and symptoms of posttraumatic stress disorder (PTSD) was examined in 282 outpatients at a mean of 53 days after traumatic brain injury (TBI). Patients were assessed for TBI severity, intrusive and avoidant PTSD-type symptoms, and psychological distress, and were stratified into four comparison groups by duration of PTA. Levels of PTSD-type symptoms and psychological distress did not differ significantly between groups. Even patients with PTA >1 week reported intrusive and avoidant PTSD-type symptoms. However, when patients were stratified into those with PTA of <1 hour or >1 hour, the former were more likely to report such symptoms. TBI patients with brief PTA are more likely to experience PTSD-type reactions, but severe TBI with prolonged PTA is not incompatible with such reactions in a subset of patients. Possible mechanisms that could account for this finding are discussed.     

Rehabilitation outcome following spinal cord injury

The rehabilitation outcome of 100 consecutive patients with a recent spinal cord injury was reviewed. On admission, 80% were predicted to become functionally independent; 70% had achieved this goal at discharge. Factors relating to success or failure of the rehabilitation effort were identified. Appropriate intervention to neutralized negative influences may increase the number of successfully rehabilitated patients who have spinal cord injuries.     

Lipid peroxidation and antioxidant potential in patients with cervical spinal cord injury

The aim of the study was to evaluate the intensity of oxygen-derived free radicals generation (expressed as the lipid peroxidation process), as well as antioxidant potential changes in patients with cervical spinal cord injury. Subjects in the study were 32 patients treated in the Neurosurgery and Neurotraumatology Clinic, Medical University in Bydgoszcz. Malondialdehyde (MDA) concentration and conjugated dienes (CD) level in the patients' blood plasma and erythrocytes, as well as their plasma antioxidant potential in reaction with a stable free radical--1.1-diphenyl-2-picryl-hydrazyl were assayed. Intensification of the lipid peroxidation process as well as a decrement of plasma antioxidant potential were found in the patients with cervical spinal cord injury. A strong correlation was also shown between severity of cervical spinal cord injury assessed using the ASIA impairment scale on the one hand and intensification of the lipid peroxidation process and plasma antioxidant potential decrease on the other hand.     

自体骨髓干细胞移植治疗脊髓损伤420例

目的：总结分析骨髓干细胞移植治疗脊髓损伤的效果。 方法：2003-09/2008-04解放军第四六三医院神经外科细胞治疗康复中心行干细胞移植的脊髓损伤患者420例,按病情分为2组：完全性脊髓损伤组42例,不完全性脊髓损伤组378例,两组患者在性别、年龄、受伤时间、损伤部位、损伤原因等方面比较差异无显著性意义(P > 0.05)。两组首先通过手术或立体定向的方法把干细胞直接移植在脊髓损伤部位,然后再根据患者病情经腰穿途径或经静脉途径移植,每次移植间隔为1周,干细胞移植量为(2~3)个×102/kg。移植过程中为促进干细胞的生长和分化,根据患者病情及身体状况给予相应的康复功能锻炼。 结果：与入院时比较,骨髓干细胞移植1,3,12个月后,不完全性脊髓损伤患者针刺觉评分、轻触觉评分、运动评分均有明显改善(P < 0.05或0.01),完全性脊髓损伤患者针刺觉评分、轻触觉评分、运动评分均无明显变化(P > 0.05),两组残损分级均无明显改善(P > 0.05)。 结论：骨髓干细胞移植治疗脊髓损伤有效可行。     

Comparison of surgical and conservative management in 208 patients with acute spinal cord injury

The role of surgery in the management of acute spinal cord or cauda equina injuries remains controversial. The present study analyzed ten admission features and three outcome variables in 208 patients treated in an Acute Spinal Cord Injury Unit, 116 (56%) of whom underwent at least one spinal operation. The surgical and non-surgical groups showed no significant differences in the following seven clinical features: age, sex, distance travelled to the Unit, time interval between trauma and admission, type of accident, severity of injuries to the spinal cord, and severity of associated injuries. However, the two groups showed significant differences in level and type of vertebral column injury, and in the frequency of pre-existing spinal abnormalities. These differences were due to management policies which selected certain injuries for surgical or non-surgical treatment. One-third of the operative procedures were performed primarily for neural decompression, one-third primarily for reduction of bony structures and one-third for fusion. However, 95% of the operative patients had a fusion at the initial operation. Operative treatment was associated with a lower overall mortality rate (6.1%) than non-operative (15.2%), despite a higher frequency of thrombo-embolic complications in the surgical group. Overall, there was no difference between operated and non-operated patients in length of stay or neurological recovery. Surgical management of patients with acute spinal cord injury appears safe in terms of mortality rate and neurological recovery, but it has not been proven to improve the latter.     

Spinal cord contusion in the rat: production of graded, reproducible, injury groups

A weight drop technique was used to produce a contusive injury of the spinal cord in the rat. A restricted laminectomy was carried out at T8 and the spinal column stabilized by clamps attached to the spinous processes of adjacent vertebrae. A 2.4-mm-diameter impounder was lowered onto the dura and a 10-g weight dropped 0.0, 2.5, 5.0, 7.5, 10.0, or 17.5 cm onto the impounder. The functional deficit was assessed for 4 weeks after injury and the spinal cord tissue processed for histopathologic analysis. The results indicated that groups of rats (N = 10) subjected to the weight dropped from increasing heights exhibited a graded final functional deficit as measured by scores on a modified Tarlov scale or the mean angle attained in the inclined plane test of Rivlin and Tator. Histopathologic results also indicated the production of graded lesions. Three groups of experimental animals were statistically distinguished corresponding to those with mild, moderate, or severe final functional deficit. The average functional deficit in these injury groups, produced by dropping the weight 2.5, 5.0, or 17.5 cm, respectively, was reproducible in replicate experiments. This model of spinal cord contusion in the rat may be useful in screening putative therapeutic drug regimens for subsequent clinical trials on different groups of patients with spinal cord injury.     

Cognitive moderators in adjustment to chronic illness: Locus of control beliefs following traumatic brain injury

Abstract

Locus of control (LOC) beliefs and quality of life outcomes were assessed in 54 male patients with moderate (n = 32) or severe (n = 22) traumatic brain injuries (TBI). There were no differences in LOC beliefs between the moderate and severe groups as measured by either the Multidimensional Health Locus of Control Scale (MHLC) or the Revised Internal-External Scale (RIES). Correlation coefficients calculated between LOC scales and multidimensional measures of quality of life ranged from -0.22 to 0.42. Multiple regression analyses, in which Glasgow Coma Scale scores and years of education were initially “forced” as the primary initial predictors, indicated that LOC beliefs were related significantly to outcome, even after removing the influence of injury severity and education. The results suggest that postinjury, cognitive factors, such as LOC beliefs, may play an important role in recovery from TBI. Furthermore, these factors may be amenable to intervention by the rehabilitation team in a way that injury-related variables are not.     

Spinal cord injury in forty-four patients with cervical spondylosis

Within a 12-year period, 44 (9.4%) of 466 patients had spinal cord injury complicating cervical spondylosis. A history of alcoholic use preceding the accident was obtained in 12 (54.5%) of 22 patients whose cord injury was due to a minor fall. The initial myelopathy was complete in 10 patients and incomplete in 34. Although neurological recovery was seen in the majority of the patients with incomplete cord lesion, complete recovery was unusual and most of the patients were partly or completely wheelchair dependent. No patient developed acute neurological deterioration after injury but seven expired. The mortality rate was much higher in the patients whose initial cord lesion was complete (50% or 5/10) than in those with incomplete myelopathy (5.9% or 2/34). There was no delayed neurological deterioration due to progressive spondylosis of the spine but three patients developed post-traumatic syringomyelia several months to several years after the injury.     

Epidural electrical stimulation for spinal cord injury

A long-standing goal of spinal cord injury research is to develop effective repair strategies, which can restore motor and sensory functions to near-normal levels. Recent advances in clinical management of spinal cord injury have significantly improved the prognosis, survival rate and quality of life in patients with spinal cord injury. In addition, a significant progress in basic science research has unraveled the underlying cellular and molecular events of spinal cord injury. Such efforts enabled the development of pharmacologic agents, biomaterials and stem-cell based therapy. Despite these efforts, there is still no standard care to regenerate axons or restore function of silent axons in the injured spinal cord. These challenges led to an increased focus on another therapeutic approach, namely neuromodulation. In multiple animal models of spinal cord injury, epidural electrical stimulation of the spinal cord has demonstrated a recovery of motor function. Emerging evidence regarding the efficacy of epidural electrical stimulation has further expanded the potential of epidural electrical stimulation for treating patients with spinal cord injury. However, most clinical studies were conducted on a very small number of patients with a wide range of spinal cord injury. Thus, subsequent studies are essential to evaluate the therapeutic potential of epidural electrical stimulation for spinal cord injury and to optimize stimulation parameters. Here, we discuss cellular and molecular events that continue to damage the injured spinal cord and impede neurological recovery following spinal cord injury. We also discuss and summarize the animal and human studies that evaluated epidural electrical stimulation in spinal cord injury.     

Implantation of neuronal suspensions into contusive injury sites in the adult rat spinal cord

Summary Implants of various types of neuronal and nonneuronal tissue have shown promise for the amelioration of certain disorders of the adult mammalian brain. Implants may also have therapeutic potential for some lesions of the spinal cord. To examine the feasibility of implantation for clinically relevant spinal cord injuries, we have implanted cells into injury sites produced by a well-characterized and standardized rat model of contusive injury. To reduce the possibility of the implantation procedure itself causing damage to the spinal cord, the tissue was dissociated and a suspension of cells introduced into the cord via a small bore needle. To test the implantation procedure, dissociated adult rat dorsal root ganglia were used because of the ease with which these neurons could be distinguished after implantation. The extent to which functional deficits were produced or exacerbated by the implantation procedure was assessed by behavioral tests of groups of rats that had been implanted (implant controls), contused (injury only) or contused and implanted (injury-implant). Survival of the implanted neurons was assessed by quantitative morphological analysis of histological sections taken through the injury/implant sites at different times following injury. In addition, the histopathology of the contusive injury sites was compared for rats that had or had not received immediate or delayed implants. Results indicated that cell suspensions could be implanted into the spinal cord without causing a functional deficit in an otherwise uninjured animal or exacerbating a standardized incomplete contusive injury. Implanted neurons survived for at least 4 weeks in all contusion sites whether implantation was performed immediately following injury or after a delay or 1 week. There was no significant difference in neuron survival among the groups at 2 h, 18 h or 1 week after implantation. The average number of surviving neurons expressed as a percentage of those counted immediately after implantation was about 90% at 2 h, 50% at 18 h and 30% at 1 week. However, at 4 weeks after implantation, significantly more neurons survived in the delayed group as compared to the immediate group. The results demonstrate the feasibility of implanting dissociated nervous tissue into the sites of clinically relevant experimental contusive injuries and lay the groundwork for investigating possible beneficial effects of implants of different types of neural or glial cell suspensions in the treatment of contusive spinal cord injuries.Suported by the Stroke and Trauma Program, NIH NINCDS, NO1-NS-2-2310 and NO1-NS-7-2301     

嗅鞘细胞移植治疗脊髓损伤的临床验证

背景: 一系列基础研究证实在动物脊髓损伤的模型中,嗅鞘细胞移植能够促进脊髓损伤的再生和恢复脊髓的部分神经功能。部分临床实验证明嗅鞘细胞的移植的确能改善脊髓损伤患者的神经功能,从而改善其生活质量。 目的：验证嗅鞘细胞移植对脊髓损伤患者神经功能修复的作用及安全性。 方法：取流产胚胎嗅球并消化成为单个嗅鞘细胞,培养纯化2周左右,制成嗅鞘细胞悬液。选择脊髓损伤患者213例,全麻下将制备好的嗅鞘细胞悬液采用区域性多靶点注射方法移植于损伤脊髓的周围。采用ASIA量表对患者移植前1d及移植后3周~2个月进行评分,评价患者脊髓恢复状况。 结果与结论：所有患者的脊髓神经功能于术后3周均有不同程度的改变,脊髓功能评分及感觉与运动功能均较移植前明显提高(P < 0.001),且随时间延长呈不断改善趋势;最长患者随访5年,未见已恢复的神经功能 减退及移植不良反应。证实嗅鞘细胞移植对脊髓损伤患者的神经功能恢复有促进作用,可以部分恢复及改善其部分脊髓神经功能,且治疗方法安全。     

Contractures complicating spinal cord injury: incidence and comparison between spinal cord centre and general hospital acute care

One hundred and eighty-one spinal cord injured patients admitted to the Rehabilitation Institute of Chicago after acute care following a spinal cord injury were studied. The presence or absence of contractures as well as significant abnormalities with loss of range of motion greater than 15% was recorded. Patients were either admitted from general hospitals or the acute care unit of our spinal centre, Northwestern Memorial Hospital. Patients treated in the general hospitals had a statistically significant increased incidence of contractures compared to spinal centre patients. Patients treated in the spinal centre were transferred to the rehabilitation hospital sooner post injury. An increased time from onset to rehabilitation admission correlated with a statistically significant increased incidence of contractures. Tetraplegic patients had a statistically significant increase over paraplegic patients and were more likely to have contractures of several upper extremity joints. Contracture development was not related to fractures of the extremities. This evidence further supports the need for spinal cord centres and provides data on the incidence of contractures in spinal cord injured patients which has not been reported previously.