Thalamic proton magnetic resonance spectroscopy in vegetative state induced by traumatic brain injury

OBJECTIVES: To determine whether proton magnetic resonance spectroscopy (MRS), a newer radiographic technology, would be useful in the evaluation of the thalamus of patients in vegetative states resulting from traumatic brain injury. METHODS: 14 victims of severe traumatic brain injury who were in the vegetative state and whose magnetic resonance images of the thalamus were normal underwent bilateral thalamic proton (MRS) studies. The N-acetyl aspartate to creatine (NAA:Cr) and choline to creatine (Cho:Cr) ratios were obtained for each patient. The proton thalamic MRS findings of patients who were in a persistent vegetative state (n = 8) and in patients who had regained awareness after being in the vegetative state (n = 6) were compared with proton thalamic MRS findings in five healthy volunteers. RESULTS: While conventional magnetic resonance imaging suggested that each patient had a normal thalamus, proton MRS indicated that the thalamus of each patient in the series was damaged. The NAA:Cr ratio was significantly lower in the thalami of both the patients who remained in a persistent vegetative state for the duration of the study and in those who regained awareness after being in the vegetative state (p < 0.001). In addition, NAA:Cr ratios were lower in the group of patients who remained in a persistent vegetative state than in the group of patients who regained awareness after being in the vegetative state (p < 0.001). CONCLUSIONS: Results suggest that the NAA:Cr ratio within the thalamus is significant and that thalamic MRS may be helpful when attempting to determine the degree of severity of neuronal and axonal injury in patients in the vegetative state.     

Awakenings from persistent vegetative state: report of three cases with parkinsonism and brain stem lesions on MRI

Three patients with a persistent vegetative state after severe head injury are reported. They recovered from a prolonged disturbance of consciousness after the administration of levodopa. These patients all had parkinsonian features. On magnetic resonance imaging, the distribution of lesions implied a diffuse axonal injury involving the substantia nigra or ventral tegmental area. The existence of patients whose dopaminergic systems may have been selectively damaged by a severe head injury should be recognised because such individuals may respond to levodopa treatment.     

Sleep abnormalities in traumatic apallic syndrome.

Sleep patterns in 10 patients with traumatic apallic syndrome were studied, together with 10 healthy controls matched for sex and age. All patients underwent neurological examination, brain CT, and polysomnographic recording within six months (mean 99 (SD 45) range 47-180 days) from the onset of symptoms. Clinical follow up was performed six months after enrollment in the study. Sleep patterns were recorded in nine out of 10 patients. In the tenth patient there was no rhythm resembling physiological sleep. This patient was the only one who remained in a persistent vegetative state and died before the six month follow up. The severity of neurological deficit at follow up was significantly related to the duration of coma. There was no significant difference between patients and controls with respect to sleep architecture. The time spent awake after sleep onset was longer in patients than controls. Our data highlight the presence of sleep fragmentation in traumatic apallic syndrome, which might be due to changes in brain structures responsible for sleep maintenance. The absence of sleep-wake cycles might indicate a poor outcome.     

The neurological assessment of patients in vegetative and minimally conscious states

Patients with serious central nervous system (CNS) injuries can enter a chronic state in which there is impaired awareness, but the presence of preserved basic vegetative functions. Such cases present formidable challenges to the medical practitioner in terms of clinical assessment and thus management. This paper presents the neurological approach to such patients highlighting the clinical clues that need to be sought to decide whether the patient is in a persistent vegetative or minimally conscious state (i.e., showing any responsiveness to external stimuli), or alternatively suffering from a locked-in syndrome. This neurological clinical formulation is then assimilated with other tests and assessments from a range of medical specialities, and by so doing helps confirm the clinical impression. This multidisciplinary approach is vital in the assessment of such patients and ideally should also include neurophysiological and functional imaging paradigms.     

Optic radiation injury following traumatic epidural hematoma: Diffusion tensor imaging study

Little is known about optic radiation (OR) injury in patients with traumatic brain injury (TBI). We report on a patient who showed an OR injury on diffusion tensor imaging (DTI) following traumatic epidural hematoma (EDH). A 38 year-old man with TBI and 7 age-matched normal subjects were enrolled in this study. The patient had fallen down stairs while in an alcohol intoxicated state. He underwent a craniotomy following diagnosis of traumatic EDH in the left temporo-parietal lobe on brain CT. He complained of right bilateral homonymous hemianopsia, which was confirmed on the Humphrey visual field test. No lesion on the left OR was observed during brain MRI. We were not able to reconstruct the fiber tractography for the left OR in this patient. We found that the left OR had been injured most severely around the midportion between the lateral geniculate body and occipital pole. We determined that DTI would be a useful technique for detection of an OR injury in patients with TBI. Therefore, we believe that DTI should be performed along with conventional brain MRI for patients with visual field defects following TBI.     

Mood change following left hemispheric brain injury

Eighteen patients with left hemispheric strokes were compared to 11 patients with traumatic brain injury for frequency and severity of depression, using several mood scales. More than 60% of the stroke patients had clinically significant depressions as compared with about 20% of the trauma patients, even though the two groups had comprable impairments in their activities of daily living and global cognitive functions. Analyses of brain CT scans revealed that the two groups had similar-sized lesions, but the areas of ischemic injury were more anterior than the traumatic lesion. When the results were controlled for lesion location, there were no significant differences in mood between the two groups. The severity of depression was directly correlated with the closeness of the lesion to the frontal pole. These results suggest that depression following left hemispheric brain injury may not be a nonspecific neurological or psychological response, but rather may be a symptom of injury to specific pathways, such as the catecholamine-containing ones, as they pass through the frontal cortex.     

Multimodality comparison of neuroimaging in pediatric traumatic brain injury

Traumatic brain injury is a common cause of death and disability in children; early neuroimaging has assumed an increasingly important role in evaluating the extent and severity of injury. Several imaging methods were assessed in a study of 40 children with traumatic brain injury: computed tomography (CT), T(2)-weighted magnetic resonance imaging (MRI), fluid-attenuated inversion recovery (FLAIR) MRI, and susceptibility-weighted imaging (SWI) MRI to determine which were most valuable in predicting 6-12 month outcomes as classified by the Pediatric Cerebral Performance Category Scale score. Patients were subdivided into three groups: (1) normal, (2) mild disability, and (3) moderate/severe disability/persistent vegetative state. T(2), FLAIR, and SWI showed no significant difference in lesion volume between normal and mild outcome groups, but did indicate significant differences between normal and poor and between mild and poor outcome groups. Computed tomography revealed no significant differences in lesion volume between any groups. The findings suggest that T(2), FLAIR, and SWI MRI sequences provide a more accurate assessment of injury severity and detection of outcome-influencing lesions than does CT in pediatric traumatic brain injury patients. Although CT was inconsistent at lesion detection/outcome prediction, it remains an essential part of the acute traumatic brain injury work-up to assess the need for neurosurgic intervention.     

Posttraumatic cerebral hemispheric disconnection syndrome

Gross and microscopic lesions of the corpus callosum and neighboring structures are common in severe closed head injury. This report is the first, to our knowledge, to confirm neuropathologically the occurrence of extensive traumatic destruction of the corpus callosum in a patient with left-sided apraxia and agraphia. It also demonstrates that large traumatic lesions of the corpus callosum may occur without prolonged posttraumatic coma, vegetative state, or death. In our patient, coexisting extracallosal hemispheric lesions may have modified the effects of callosal pathology. Cases of this type may be more common than generally appreciated, but since symptoms of hemispheric disconnection are not apparent in ordinary behavior, specific tests of callosal function must be employed if disconnection phenomena are to be detected in the posttraumatic period.     

Levodopa treatment for patients in persistent vegetative or minimally conscious states

The persistent vegetative state (PVS) and the minimally conscious state (MCS) are conditions of altered consciousness after severe brain damage due to a variety of pathologies. However, the specific pathophysiological mechanisms and a therapeutic strategy for intervention have not as yet been established. We review previous reports of levodopa treatment for patients in PVS, MCS, or other mental disorders, and have focused on five representative cases: four of PVS and one of MCS after severe brain injury. In summary, our review suggests the effectiveness of levodopa treatment is probably dependent upon the following criteria: (1) Diagnosis of PVS or MCS as distinct from other related conditions, (2) Concomitant symptoms of parkinsonism, and (3) Concomitant neuroradiological findings of high intensity lesions in the dopaminergic pathway on T2 weighted MRI. The apparent success of levodopa in the five cases described may reflect a specific subgroup of PVS and MCS patients, where the administration of levodopa is effective. However, we should not regard PVS or MCS as a single entity, since levodopa is unlikely to be effective in all cases. Therapeutic strategies should aim to identify the key pathophysiological mechanism for each patient and target interventions accordingly.     

Surgery for acute subaxial traumatic central cord syndrome without fracture or dislocation.

Twenty-two patients with subaxial acute traumatic central cord syndrome (CCS) without fracture or dislocation who underwent surgery between 1995 and 2002 were reviewed, retrospectively. There were 13 males and nine females ranging in age from 24 to 84 years (mean 61.2). Falls were the most common injury (68%), followed by motor vehicle accidents (32%). All patients had dynamic cervical lateral radiographs and magnetic resonance imaging (MRI). Cord compression was present in all cases and cervical instability in 11. Associated pathology included disc herniation in seven patients, cervical spondylosis (CS) in 11 and ossification of the posterior longitudinal ligament (OPLL) in four. Anterior decompression and fusion was performed in 12 patients with 1- or 2-level lesions. Posterior decompression and fusion was performed for multilevel lesions in 11 patients, including one patient who required re-operation. The interval between injury and surgery ranged from 1 to 37 days (mean 8.0). Postoperatively, all patients improved clinically. We conclude that surgical management of subaxial acute traumatic CCS without fracture or dislocation improved neurological status and prevented delayed neurological deterioration in our patients.     

口服华法令合并外伤性颅内出血患者的围手术期处理

目的 探讨长期口服抗凝药物华法令合并外伤性颅内出血患者的围手术期处理措施.方法 10例此类患者入院后给予维生素K、新鲜冰冻血浆和凝血酶原复合物来逆转患者的抗凝状态.9例患者接受开颅手术清除颅内血肿.3例患者术后接受预防剂量的低分子肝素的治疗.结果 术后所有患者均存活,其中5例恢复良好,3例遗留不同程度的偏瘫或失语症状,2例患者术后长期植物状态生存.结论 伤后、术前迅速纠正凝血指标参数至关重要,与患者预后密切相关.

Abstract：

Objective To study the perioperative management in the treatment of traumatic intracranial hemorrhage in patients with pretraumatic anticoagulation therapy of oral warfarin. Method 10 patients of traumatic intracranial hemorrhage with pretraumatic anticoagulation therapy of oral warfarin received vitamin K, FFP and PCC treatment to reverse the anticoagulation condition after admission. 9 patients underwent the operation for evacuation of intracranial hematoma. Low - molecular - weight heparin was administered as prophylactic dose in 3 patients. Results All patients in this group were survival. 5 of them get well recovery. 3 of them remained different degrees of hemiplegia or aphasia and 2 patient got vegetative state after operation. Conclusions Pre - operative normalization of coagulation capacity is of utmost importance in patients with head injury and plays an important role in the prognosis of patients.     

Persistent alpha-vegetative state

After briefly reviewing the concepts of "coma" and "alpha-coma", we report the case of a patient with presumable Pick's disease who spent several weeks in a vegetative state with a normal and reactive EEG in the alpha range in the later stages of her illness. We (a) emphasize some implications of the appearance of the eyes in such patients, b) stress the importance of distinguishing alpha activity from true alpha rhythm and (c) suggest the category "alpha-coma" should include only those individuals bearing evidence of disorders of the junctional tegmentum of the pons and midbrain. In a complementary way, we propose that patients in a persistent vegetative state displaying normal EEG should be separately classified as persistent "alpha-vegetative state".     

老年人重型颅脑外伤预后分析(附73例报道)

目的分析老年重型颅脑外伤患者的临床资料，总结影响老年人重型颅脑外伤预后的因素。方法回顾性分析73例急性重型颅脑外伤老年患者的临床资料，比较生存组及死亡组中各种因素的构成比，确定其对预后的影响。统计方法使用t检验、X^2检验及Logistic回归分析。结果本组生存30例，其中恢复良好5例，轻中残9例，重残13例，植物生存3例；死亡43例，死亡率为58．9％。结论老年重型颅脑外伤（TBI）患者死亡率高，预后差。年龄是影响预后的独立因素；GCS评分、瞳孔对光反射、原发性昏迷时间等指标是判断预后的重要因素。     

Neural connection between injured cingulum and pedunculopontine nucleus in a patient with traumatic brain injury

We report on a patient with traumatic brain injury who showed neural connection between injured cingulum and pedunculopontine nucleus on diffusion tensor tractography (DTT). A 74-year-old male who had suffered a traffic accident underwent conservative management for subarachnoid haemorrhage. Brain MRI which was performed 6 months after onset showed no specific lesions. On 6-month DTTs for cingulum of the patient, we observed discontinuations of both cingulums above the genu of corpus callosum. However, the left cingulum was connected to the left PPN via a neural tract that passed through the anterior corona radiata and thalamus. The neural connection between the injured cingulum and PPN seems to be a compensatory phenomenon for the destruction of cholinergic pathways from basal forebrain. We believe that this result might suggest one of recovery mechanisms of injured cingulum following brain injury.     

渐进性减压与常规减压治疗重型颅脑损伤的疗效比较

目的比较渐进性减压与常规减压治疗重型颅脑损伤的效果。方法将我科2012年1月至2016年5月共收治的148例重型颅脑损伤患者随机分为2组,80例采用渐进性减压,68例采用常规减压,术后治疗方案相同。比较2组手术前、术后GCS评分、并发症、术后3个月的格拉斯哥预后评分。结果术前,术后1天、2天、3天GCS评分2组无显著性差异,但术后7天、14天、1月GCS评分2组有显著性差异。渐进性减压组术后3个月GOS评分,良好15例,中残27例,重残16例,植物生存8例,死亡14例。常规减压组术后3个月GOS评分,良好10例,中残13例,重残15例,植物生存13例,死亡17例,两组比较差异有统计学意义(P0.05)。2组并发症发生率差异亦有统计学意义。结论渐进性减压在治疗重型颅脑损伤中术后恢复好,且并发症较少。     

Focal striatal dopamine may potentiate dyskinesias in parkinsonian monkeys

Striatal neurons convert L-dopa to dopamine (DA) following gene transfer of aromatic L-amino acid decarboxylase (AADC) via adeno-associated virus (AAV) in parkinsonian monkeys. We investigated whether AAV-AADC could reduce or eliminate L-dopa-induced dyskinesias (LIDs) and side effects in MPTP-treated monkeys. Five monkeys were made parkinsonian by bilateral MPTP lesions. The optimal therapeutic dose of L-dopa was determined using an acute dose response regimen. After 3 weeks of chronic L-dopa treatment, AAV-AADC or control vector was bilaterally injected into the striatum. Animals were assessed for 6 months with the same L-dopa dosing as presurgery as well as chronic oral L-dopa treatment. Presurgery LID was observed at doses greater than 5 mg/kg. The AAV-AADC-treated animals displayed an average 7.3-fold decrease in the therapeutic dose of L-dopa throughout the 6-month follow-up period. Only AAV-AADC-treated monkeys were susceptible to dyskinesias even at sub-clinical doses. Immunohistochemical analysis revealed well-delineated foci of AADC within the striatum. These results suggest that high levels of focal DA were generated in response to L-dopa administration and may be responsible for the exacerbation of dyskinesias. This may be similar to focal dopaminergic activity in PD patients that developed off-drug or "runaway" dyskinesias following fetal mesencephalic grafts.     

Late recovery from the minimally conscious state: ethical and policy implications

We consider the ethical and public policy implications of late recovery from the minimally conscious state in light of an Institute of Medicine exploratory meeting convened to discuss current knowledge about disorders of consciousness as well as a recently published study demonstrating axonal regrowth in a patient two decades after traumatic injury. Participants at the meeting (which included the authors) described a lack of research initiatives for basic investigations of patients in these states, the frequent warehousing of patients following a diagnosis of persistent vegetative state that limits their access to appropriate neurologic and diagnostic tests, and the breadth of public confusion about disorders of consciousness. Meeting participants encouraged the Institute to pursue a more formal study to outline both the need for research and the unique opportunities to study consciousness, now available through the use of neuroimaging and related technologies. Areas of initial focus would be to define the epidemiology of the minimally conscious state, elucidate mechanisms of recovery, and identify clinically useful diagnostic and prognostic markers that will aid decision making at the bedside.     

Long-latency components (N100, N200 and P300) of acoustic evoked potentials in prediction of mental recovery in severe traumatic brain injury

The authors analyzed correlations of amplitude and latency levels of N100, N200 and P300 components of acoustic evoked potentials (AEP) registered during sonic stimulation and counting of target-oriented stimuli in 22 patients in vegetative state and mutism as an outcome of traumatic brain injury. Results were analyzed with association of electrophysiological findings with data of diffusion-tensor MRI. 55 healthy volunteers were included into control group. It is described that patients in vegetative state with formal recovery to the level of clear consciousness develop all three components of AEP in response to target-oriented tone. The instruction "to counts" leads to their better development. Patients with restoration to minimal level of consciousness produce all components during audition of sounds and only N100 and N200 in response to standard tone after instruction "to count". It is discovered that levels of amplitude have bigger correlation according to Spearman's criterion with outcome in comparison to latency. There changes are more prominent in N100 and N200 components rather in P300. In addition, after instruction "to count sounds" the registered changes between stages of vegetative state and mutism are significant for leads of left hemisphere, and during audition of sounds--for sagittal leads. The study showed correspondence of acquired changes with MRI data. Chronic unconscious state is associated with changes in corpus callosum (degeneration fibers) and corticospinal tracts in the brainstem. The data are discussed in light of hypothesis of the role of morphofunctional disconnections (brainstem-thalamus and interhemispheric) in impairment of attention and in genesis of different forms of posttraumatic unconscious state.     

How often is the diagnosis of the permanent vegetative state incorrect? A review of the evidence

Some research suggests that 40% of people in the vegetative state are misdiagnosed. This review investigates the frequency, nature and causes of reported misdiagnosis of patients in the vegetative state, focusing on the nature of the error. It is a systematic review of all relevant literature, using references from key papers identified. The data are summarized in tables. Five clinical studies of the rate of misdiagnosis in practice were identified, encompassing 236 patients in the vegetative state of whom 80 (34%) were reclassified as having some awareness, often minimal. The studies often included patients in the recovery phase after acute injury, and were poorly reported. Five systematic reviews of signs and technologically based neurophysiological tests were identified, and they showed that most studies were small, lacked accurate or important details, and were subject to bias. Studies were not replicated. Many signs and tests did not differ between people in the vegetative state and in the minimally conscious state, and those that did were unable to diagnose an individual patient. The few single case reports suggest that failure to ensure an accurate diagnosis of the underlying neurological damage and dysfunction could, rarely, lead to significant misdiagnosis usually in patients who had brain‐stem damage with little thalamic or cortical damage. Significant misdiagnosis of awareness, with an apparently ‘vegetative’ patient having good awareness, is rare. Careful neurological assessment of the cause and routine measurement of awareness using the Coma Recovery Scale ? Revised should further reduce mistakes.     

A case of the persistent vegetative state following symmetrical peduncular infarction]

A 64-year-old woman presented with sudden onset of disequilibrium and dysarthria. Two days later she became lethargic and tetraparetic. An emergency MRI disclosed multiple infarctions in the medulla oblongata and pons. An angiogram revealed severe stenosis of the rostral basilar artery. The patient underwent a rapidly progressive course with impaired consciousness and flaccid tetraplegia. MR images 7 days after the onset disclosed a symmetrical midbrain infarction that was localized mainly in the cerebral peduncles, suggesting a distal basilar artery occlusion as the cause of this pathology. Since 4 weeks after the onset the patient was in the persistent vegetative state, which was essentially unchanged during the 1-year follow-up period. Persistent vegetative state is known to be caused by diffuse supratentorial or bilateral thalamic lesions, but in our case the lesions were restricted to the infratentorial area. We speculate a mechanism to cause the persistent vegetative state by partial impairment of the connection to the thalamic ascending system or extrathalamic ascending system, which leads to the dissociation of arousal(preserved in this case) and awareness(impaired in this case) after the ventral midbrain infarction.