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STUDY OBJECTIVES: To assess the phasic components of rapid eye movement (REM) sleep in patients in vegetative state and to evaluate the possible relationship of these activities to patient outcome. SETTING: Sleep disorders unit at a major rehabilitation hospital. DESIGN: Comparative control study. PATIENTS: Eleven patients in vegetative state (10 males and 1 female) aged 17-53 years. INTERVENTIONS: Continuous 24-hour polysomnographic recording. MEASUREMENTS AND RESULTS: All the patients had REM sleep periods during the 24-hr recording session. Mean total REM sleep time for the whole session was 66.5 +/- 34.9 min, and for the nocturnal hours only, 37.3 +/- 19.7 min. Comparison with the control group (79.2 +/- 11.5 min) yielded a significant difference only for nocturnal REM sleep time (p<0.0003). The duration of the REM sleep periods was significantly shorter in the patients than the controls for the whole 24-hr session (10.9 +/- 6.0 vs.19.6 +/- 4.9 min, p<0.008), but not for the nocturnal period alone. Compared to controls, the density of rapid eye movements (REMs) (p=0.001), chin twitches (p=0.002), and leg muscle twitches (p=0.023) was significantly lower in the patient group. The density of the sawtooth waves was also lower in the patients, but the difference did not reach significance (p=0.069). Similar results were obtained when the comparison was done only for the nocturnal period. There was no significant difference for any of the REM sleep characteristics or REM sleep phasic activities (24-hr, nocturnal and diurnal periods) between the patients who recovered consciousness and those who did not. CONCLUSIONS: The present study shows that patients in vegetative state have a significant reduction in the phasic activities of REM sleep. However, the amount of these activities is unrelated to recovery from the clinical condition. These findings may reflect possible damage to the pedunculopontine tegmentum cholinergic mechanisms in vegetative state.

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OBJECT: The aim of this prospective study was to evaluate the phagocytic, humoral, and cellular arms of the immune system in comatose patients shortly after severe brain injury and to compare the findings with those reported earlier in patients in a persistent vegetative state. The study was conducted in intensive care units and immunology laboratories of university-affiliated hospitals in central Israel. METHODS: The study group consisted of 14 men aged 16 to 65 years who were comatose as a result of acute brain injury due to mechanical trauma. All were studied within 72 hours of injury. Brain damage was severe in all cases (Glasgow Coma Scale score < 8). Healthy age- and sex-matched volunteers served as simultaneous controls. Infections arose in nine (75%) of the 12 patients in whom data were available; the cumulative mortality rate was 38% (five of 13 patients in whom outcome data were available). Every patient exhibited one or more defects in at least one arm of the immune system. Significant deficiencies were noted in neutrophil superoxide release, immunoglobulin (Ig)G, IgG1, IgM, C1q, C2, properdin, alternate C pathway, T cells, T helper cells, T suppressor cells, and natural killer cells. In an earlier series of patients examined by the authors months after the primary insult, these impairments were absent in most of the patients in the vegetative state. CONCLUSIONS: Significant deficiencies of the immune system, particularly the cellular arm, are precipitated by severe brain injury within 72 hours of the event. These impairments probably play a role in the high rate of complicating infections and multiple organ failure. Together with earlier findings, the results of this study indicate that if brain-injured patients survive these hazards, their immune system will eventually recover.

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STUDY OBJECTIVES: To determine whether sleep-related erections occur in vegetative state and if so, to investigate their relationship with rapid eye movement (REM) sleep. DESIGN: N/A. SETTING: Major rehabilitation hospital. PATIENTS: Nine male patients in vegetative state aged 17-40 years. INTERVENTIONS: Continuous 24-hour polysomnographic recordings including penile circumferencial changes. MEASUREMENTS AND RESULTS: Sleep-related erection episodes (SREe's) were noted in all nine patients, ranging in number from 1-7/24 hr (average 4.4+2.4) and lasting 6 to 50 min (average 22.0+5.7 min). The number of REM periods (REMp's) ranged from 4-11 (average 6.6+2.5) and lasted for 1.0 to 44.0 min (average 16.0+6.6 min). Ninety-five percent of the SREe's recorded were associated with REMp's, usually (76.3%) appearing simultaneously with the REMp or soon thereafter; 64.6% of the REMp's were associated with SRE's. For both the nocturnal and diurnal periods, there were more REMp's with SREe's than without, and the REMp's associated with SREe's were of longer duration (by 25.5% and 28.4%, respectively). There were no statistically significant differences for any of the REMp or SREe parameters between the recovered and nonrecovered patients. CONCLUSIONS: The sleep-related erection characteristics of patients in vegetative state are similar to those of normal individuals. These findings may have implications for the assessment of the reorganization of REM sleep during recovery from vegetative state and may further help in our understanding of the pathophysiology of vegetative state. More studies are needed in larger groups of patients.

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The aim of the present study was to examine the bladder tone in vegetative patients using urodynamic tests. The study population consisted of 17 patients, 13 men and four women, in a post-traumatic vegetative state under treatment at the Loewenstein Rehabilitation Centre. Time since injury ranged from 1 to 6 months. Cystometry results indicated that 100% of the patients had neurogenic bladder, hypertonic type, two (12%) with mild spasticity and 15 (88%) with severe spasticity. None showed detrusor-sphincter dyssynergia or unstable bladder. Based on these unequivocal findings, it is suggested that all patients in trauma-induced vegetative state be treated prophylactically from the 2nd week with anticholinergic agents.

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OBJECTIVE: To determine the ability of apolipoprotein E (APOE) genotypes to predict days of unconsciousness and a suboptimal functional outcome in traumatic brain injury (TBI) survivors. BACKGROUND: TBI is known to be associated with neuropsychological deficits and functional disability. Recent evidence indicates that APOE plays a pivotal role in CNS response to injury. METHODS: In this prospective study the authors determined the APOE genotypes and tested their ability to predict days of unconsciousness and functional outcome after at least 6 months in 69 survivors of TBI. A good functional outcome was defined as no dysarthria, behavioral abnormalities, or dysphasia; no severe cognitive abnormalities; and the ability to live independently. RESULTS: The odds ratio of more than 7 days of unconsciousness was 5.69 in those with the APOE-epsilon4 allele compared with those without the epsilon4 allele (95% CI, 1.69 to 20.0; p = 0.001). Only 1 of 27 subjects (3.7%) with the epsilon4 allele had a good functional outcome compared with 13 of 42 (31.0%) of those without the epsilon4 allele (p = 0.006). The OR of a suboptimal outcome (fair or unfavorable) was 13.93 for those with the epsilon4 allele compared with those without the allele after controlling for age and time of unconsciousness (95% CI, 1.45 to 133.97; p = 0.02). CONCLUSION: The results demonstrate a strong association between the APOE-epsilon4 allele and a poor clinical outcome, implying genetic susceptibility to the effect of brain injury. Additional studies of TBI patients are warranted to confirm their findings.

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"Cognitive" auditory event-related potentials (ERPs) were mapped to examine the putative conscious responsiveness of eight patients in a postcoma unawareness (PCU) state and of eight matched normal controls. A "passive P3" paradigm was used to evaluate waves N2, P3, and Slow Waves of the ERPs. Results showed that the signal/noise ratio of the patients' waveshapes was poorer than that of the controls. Yet, on the whole, no between-group significant differences were noted for most of the averaged characteristics of the waves. In general, in the patients, the left hemisphere was dominated by negative potentials relative to the right one, whereas in the controls, the opposite asymmetry was apparent. Thirty-eight percent of the patients had passive N2 and P3 waves, and 67% of the responders regained consciousness (versus none of the non-responders). These findings suggest that the presence of intact "cognitive" waves is compatible with a higher probability for improvement, although nondetection of certain waves at the postcoma unawareness state does not necessarily indicate the worst prognosis.

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The use of linear measurements in the analysis of CT scans of TBI patients was found to contribute to the understanding of brain damage and were correlated with outcome in severe traumatic close brain injured patients. The purpose of the present study was to analyse the data obtained by the linear measurements on CT studies of TBI patients who remained in persistent vegetative state following blunt head trauma. All 27 patients included in the study were reported to be neurologically normal prior to injury. Thirteen patients, 11 remaining in persistent vegetative state (responsive but unaware) and two who died, constituted the worst outcome group. Fourteen patients who regained consciousness, underwent multidisciplinary evaluation when their recovery reached a plateau and were ranked according to severity of residual symptoms and outcome. The degree of correlation with the overall vocational outcome parameter with the various radiological indices was calculated as the Spearman rank correlation coefficient, with correction for tied scores. Fisher's z transformation was used to combine results with those of our previous analysis. Three radiological parameters showed a statistically significant correlation with clinical outcome. These were the right and left septum-caudate distance and the cerebroventricular index 2; these showed Spearman rank coefficients of 0.52, 0.45 and 0.48; with two-tailed p-values under 0.01, 0.02 and 0.01 respectively. The width of the third ventricle suggested correlation with the clinical scoring. The findings of the present study point to the importance of loss of deep gray matter of the caudate nuclei and widening of the adjacent part of the lateral ventricles in catastrophic brain injury. This finding may highlight the role of localized ischemic changes, in addition to diffuse axonal injury. Values of over 8 mm for the width of the third ventricle and over 11 mm for septum caudate distance are suggestive of catastrophic and poor prognosis for recovery.

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Forty-eight post-traumatic brain-injured patients in postcoma-unawareness (PC-U) state, are included in this study. All recovered consciousness at least 1 month after the accident. The muscular tone and movement of all limbs was examined. At least two X-rays of the big joints were taken. Periarticular new bone formation appeared in 26 patients. This heterotopic ossification occurs in severely injured patients, primarily in proximal joints of the upper and lower extremities. Their aetiology in brain injury is unknown. Risk factors include prolonged coma, tone and movements in the involved extremity, and associated fractures. We found that the appearance of periarticular new bone formation had a close correlation with pathological movement (paresis or plegia), a borderline correlation with hypertonus, and no correlation with hypotonus or with associated fractures.

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Some patients who suffer severe traumatic brain injury (TBI) fail to recover higher brain functions in spite of giving the appearance of sleep-wake cycles. Such a state is called post-coma unawareness (PCU) and varies in type and degree. Patients may remain in this state for months or even years. This study focused on the follow-up of upper-limb somatosensory evoked potential (USEP) measurements and auditory brainstem responses (ABR), with an emphasis on dynamic changes, in 10 patients with PCU resulting from TBI. The prognostic value of USEP and ABR was evaluated. Results showed that the presence of ABR in PCU patients had no prognostic value, because ABRs were found both in patients who recovered and those who did not, even a year after the trauma. The presence of normal ABR in PCU patients may suggest that the brainstem has been spared in the pathoanatomy of the PCU condition, with the significant damage occurring above this level, in cortical and subcortical (that is, hemispheral) areas. USEP was graded using the new system of Houlden [1] for 'acute' comatose patients. It was found that USEP measurements had some prognostic value in PCU patients. Most of the patients who remained in the PCU state had grade 2 or less initially, whereas most of the patients who later recovered or achieved at least a 'reduced life' state were grade 4 or more. On initial testing (when all patients were still in the PCU state), defined cortical potential (mainly in the slope of the building NI potential) was seen in only some of the patients who later recovered.(ABSTRACT TRUNCATED AT 250 WORDS)

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Our experience with 13 patients suffering from various ventilatory disorders who received mechanical ventilation at home for periods between 1 and 12 years is presented. Seven of the 13 patients were ventilated by positive pressure via tracheostomy, 3 by negative body ventilators and 3 by exufflation belt and positive pressure. Only a few hospitalizations were required due to pulmonary complications, and there was no case of sudden death occurring at home. Costs of home care for respirator-dependent patients, including the initial investment of home equipment, are much lower than the costs of long-term hospital care. A comprehensive home care program should be the preferred choice for medically stable ventilator-dependent patients.

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Post-comatose unawareness (PCU) is one of the possible outcomes of severe brain injury. Patients with severe brain injury have an increased susceptibility to severe nosocomial infections for multifactorial reasons, including immune suppression at different levels. We studied different immunological aspects in 11 PCU patients. Impaired humoral immunity was found in 27% of them. Two patients had decreased haemolytic activity of the classical complement pathway, associated with decreased levels of the components C1q, C1r and C4. Another patient had very low levels of IgG2 and IgG4. The neutrophil killing activity was impaired in these three patients, but was completely restored with the addition of a heterologous serum, suggesting a humoral defect. Neutrophils showed normal chemotaxis and random migration, and the superoxide anion release by neutrophils was also found to be normal. Understanding the immunological events in PCU patients contributes to a better and more intensive therapeutic approach, which might accelerate the rehabilitation of these patients.

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A follow up study is reported of 100 consecutive unconscious patients admitted to an intensive care coma facility with a history of 30 days or more of unconsciousness of nontraumatic cause. Twenty recovered consciousness, all within 5 months of injury. 31 of the remaining patients died within 6 months following injury, while 49 continued unconscious until death. The mean life expectancy of these 49 was 26-34 months from that time. All 20 patients who recovered awareness continued to suffer from major disability. The prognosis for life or death and for recovery or not of consciousness was not significantly correlated with age or aetiology of the vegetative state. Among those who recovered consciousness, the younger patients showed somewhat better results in three parameters of function: locomotion, ADL and day-placement, but not in cognition, behaviour or speech accuracy and fluency. The overall results for these nontraumatic patients with postcomatose unawareness are clearly worse than those for patients with a similar period of unconsciousness following craniocerebral trauma.

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68 post-traumatic brain-injured patients in postcomatose unawareness (PCU) states were admitted during 1982-1987. 32 of them also suffered from fractures of the long bones and pelvis (total of 51 limbs). The muscle tone and force of all limbs were examined and x-rays of the large joints and of the fractures were taken periodically. Periarticular new-bone formation appeared in 32 patients. Normal callus developed in 41 fractured limbs and hypertrophic callus in 18. We found that pathological muscular tone (hypertonus and hypotonus) and pathologically decreased muscle force (paresis and plegia) were closely correlated with the appearance of periarticular new-bone formation. The extent of callus formation was not correlated with muscle tone and force.

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We have examined the epidemiological background of 134 consecutive patients admitted to our centre who suffered from post-traumatic unconsciousness of over 1 month's duration. The incidence of such unconsciousness in Israel is estimated as 4 per 1,000,000, or one case in 410 hospitalizations for head trauma. The cause of trauma was a road accident in 69% of cases. Among victims, pedestrians and cyclists were more likely than four-wheeled vehicle drivers and their passengers to suffer from prolonged unconsciousness, from which they were less likely to recover.

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Somatosensory evoked potentials (SEPs) were found by several authors to have a prognostic value in traumatically brain-injured (TBI) patients and can serve for monitoring changes in the state of TBI patients. Most of the studies were performed in the acute phase of trauma and most of reports have dealt with the short-latency components. The present study reports on seven patients (mean age 26.2 years) who suffered severe blunt TBI and were in prolonged post-comatose unawareness (PCU) state, in whom early and late SEP components were recorded at least 5 weeks after sustaining trauma. The SEPs studied could not reveal a uniform pattern apart from prolonged central conduction time (CCT), which was common to all patients. This may be due to individual non-homogeneous patterns of brain damage in our severe TBI patients. Meaningful late recovery of consciousness occurred in one patient and correlated with shortening of CCT. We suggest that the prolonged CCT found in our patients is related to diffuse subcortical axonal injury and that the shortened CCT found during the second examination in this patient actually reflects late partial recovery--either structural or functional--of affected brain regions. This patient is also an example of the possible relationship between reduction of CCT and recovery of consciousness a long time after injury.

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This study reviews the course and outcome of 130 patients who remained in a state of prolonged unawareness 30 days after severe cranio-cerebral trauma. Prognostic indicators and outcome were fitted by a logistic model. The significant prognostic factors observable in the first week after trauma were found to be ventilatory status, motor reactivity and significant extraneural trauma. The significant prognostic factors after the first month of unawareness were early ventilatory status, early motor reactivity, late epilepsy and hydrocephalus. The estimated probability of recovery of awareness (that is, consciousness) ranged from 0.94 in patients with early decorticate posturing in the absence of both extraneural trauma and ventilatory disturbance to 0.06 in patients with flaccidity, extraneural trauma and ventilatory disturbance in the first week after injury.

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Almost half of all patients with traumatic brain injury who remain unconscious for more than one month will not recover consciousness and will remain in a state of prolonged postcomatose unawareness (PC-U). The aim of this work is to present the survival rate and medical complications of such patients. The survival time of the 62 patients studied ranged from 2 to 115 months, with a median of 15.5 +/- 22 months. Cumulative mortality figures were 15% at 3 months, 40% at 6 months and 60% and the end of the first year. The figures at the end of the second, third and fifth years were 86%, 87% and 94%, respectively. This type of data may aid in decisions regarding the management of these patients. The longer survival with better treatment of patients in a state of PC-U poses severe ethical, medical, legal and economic problems with which society will have to deal.

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Seventy-two patients who were in a post-comatose unawareness state for periods longer than 1 month following traumatic brain injury recovered consciousness thereafter. The incidence of residual sequelae of brain trauma in relation to duration of unawareness was studied. The incidence of motor disability, communication disorders, cognitive disturbances and malbehaviour was studied in the patients recovering consciousness after 1, 2, 3 and 6 months. It was found that no significant differences were found in the incidence of the above-mentioned residual sequelae of brain-damaged patients in relation to duration of post-comatose unawareness. However, 76.1% (51/67) of the patients who recovered consciousness and survived the first year following injury were living at home. Most of these were patients who recovered consciousness within the first 3 months following trauma. None of the patients who were in post-comatose unawareness longer than 6 months did so, Five patients (6.9%) died during the first year. Motor disability, independence in activities of daily living, vocational outcome and place of living were significantly related to duration of prolonged unawareness state whereas the disturbances in high mental functions did not. Although the vocational outcome of patients with post-comatose unawareness is not good, the fact that most of them are still able to live at home, having an acceptable quality of survival, justifies, according to our experience, the comprehensive rehabilitation programme.

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