Outcome after decompressive craniectomy in older adults after traumatic brain injury.

Objective: Globally, many societies are experiencing an increase in the number of older adults (>65 years). However, there has been a widening gap between the chronological and biological age of older adults which trend to a more active and social participating part of the society. Concurrently, the incidence of traumatic brain injury (TBI) is increasing globally. The aim of this study was to investigate the outcome after TBI and decompressive craniectomy (DC) in older adults compared with younger patients. Methods: A retrospective, multi-centre, descriptive, observational study was conducted, including severe TBI patients who were treated with DC between 2005 and 2022. Outcome after discharge and 12 months was evaluated according to the Glasgow Outcome Scale (Sliding dichotomy based on three prognostic bands). Significance was established as p ≤ 0.05. Results: A total of 223 patients were included. The majority (N = 158, 70.9%) survived TBI and DC at discharge. However, unfavourable outcome was predominant at discharge (88%) and after 12 months (67%). There was a difference in favour of younger patients (≤65 years) between the age groups at discharge (p = 0.006) and at 12 months (p < 0.001). A subgroup analysis of the older patients (66 to ≤74 vs. ≥75 years) did not reveal any significant differences. After 12 months, 64% of the older patients had a fatal outcome. Only 10% of those >65 years old had a good or very good outcome. 25% were depending on support in everyday activities. After 12 months, the age (OR 0.937, p = 0.007, CI 95%: 0.894-0.981; univariate) and performed cranioplasty (univariate and multivariate results) were influential factors for the dichotomized GOS. For unfavourable outcome after 12 months, the thresholds were calculated for age = 55.5 years (p < 0.001), time between trauma and surgery = 8.25 h (p = 0.671) and Glasgow Coma Scale (GCS) = 4 (p = 0.429). Conclusion: Even under the current modern conditions of neuro-critical care, with significant advances in intensive care and rehabilitation medicine, the majority of patients >65 years of age following severe TBI and DC died or were dependent and usually required extensive support. This aspect should also be taken into account during decision making and counselling (inter-, intradisciplinary or with relatives) for a very mobile and active older section of society, together with the patient's will.

Outcome after Intracerebral Haemorrhage and Decompressive Craniectomy in Older Adults.

OBJECTIVE: There is a relationship between the incidence of spontaneous intracerebral haemorrhage (ICH) and age. The incidence increases with age. This study aims to facilitate the decision-making process in the treatment of ICH. It therefore investigated the outcome after ICH and decompressive craniectomy (DC) in older adults (>65 years of age). METHODS: Retrospective, multicentre, descriptive observational study including only consecutive patients who received DC as the consequence of ICH. Additive evacuation of ICH was performed after the individual decision of the neurosurgeon. Besides demographic data, clinical outcomes both at discharge and 12 months after surgery were evaluated according to the Glasgow Outcome Scale (GOS). Patients were divided into age groups of ≤65 and >65 years and cohorts with favourable outcome (GOS IV-V) and unfavourable outcome (GOS I to III). RESULTS: 56 patients were treated. Mean age was 53.3 (SD: 16.13) years. There were 41 (73.2%) patients aged ≤65 years and 15 (26.8%) patients aged >65 years. During hospital stay, 10 (24.4%) patients in the group of younger (≤65 years) and 5 (33.3%) in the group of older patients (>65 years) died. Mean time between ictus and surgery was 44.4 (SD: 70.79) hours for younger and 27.9 (SD: 41.71) hours for older patients. A disturbance of the pupillary function on admission occurred in 21 (51.2%) younger and 2 (13.3%) older patients (p = 0.014). Mean arterial pressure was 99.9 (SD: 17.00) mmHg for younger and 112.9 (21.80) mmHg in older patients. After 12 months, there was no significant difference in outcome between younger patients (≤65 years) and older patients (>65 years) after ICH and DC (p = 0.243). Nevertheless, in the group of younger patients (≤65 years), 9% had a very good and 15% had a good outcome. There was no good recovery in the group of older patients (>65 years). CONCLUSION: Patients >65 years of age treated with microsurgical haematoma evacuation and DC after ICH are likely to have a poor outcome. Furthermore, in the long term, only a few older adults have a good functional outcome with independence in daily life activities.

Collision of Priorities in Posttraumatic Coma and Suspected Multiple Injuries: A Prospective Multicenter Trial.

OBJECTIVE: The presence of multiple injuries in addition to a traumatic brain injury (TBI) is initially uncertain in most patients with posttraumatic coma. The interdisciplinary team of physicians in charge of initial treatment after hospital admission may face a collision of vital priorities. The purpose of this study was to analyze which diagnostic and surgical measures were given priority over others in comatose patients after injury and to draw conclusions from these data. METHODS: In this prospective multicenter cohort study, the outcomes of 1,003 comatose patients with suspected multiple injuries were studied. The analysis was divided into an early and a late stage. Diagnostic and surgical measures were analyzed for a 6-month period. The prognostic value of the Glasgow Coma Scale (GCS) and the World Federation of Neurosurgical Societies grading scale were investigated. RESULTS: Removal of intracranial hematomas and decompressive craniotomies were the most frequent procedures within the first 48 hours after admission to the hospital. Prognosis depends on the location and the combination of injuries. Outcome is significantly correlated to initial signs of brainstem dysfunction. The GCS did not adequately predict clinical outcome. CONCLUSION: Comatose patients with suspected multiple injuries should only be admitted to hospitals with a continuous neurosurgical service because intracranial operations are more frequent in the first 48 hours than extracranial operations. Depending on the neurologic status of the patient, an urgent surgical decompression may be essential for a good outcome. The GCS alone is not a sufficient tool for the neurologic assessment and the prognosis of patients with multiple injuries. The onset of clinical signs of brainstem dysfunction indicates a critical deterioration of the functioning of the central nervous system. The priority of surgical measures should be tailored accordingly.

PET/CT to Assess Prognosis after a Brain Injury. / Positronenemissionstomografie/Computertomografie zur Prognoseabschätzung bei Tumornachweis in der Traumaspirale: Fallbericht beim bewusstlosen Patienten.

In a comatose patient with acute subdural haematoma, the polytrauma spiral indicated pulmonary metastasising renal carcinoma, which limited therapeutic possibilities. Whole-body positron-emission tomography/computer tomography (PET/CT) was performed with fluorodesoxyglucose. Renal carcinoma with pulmonary, nodal and parotidal metastases was proved. A cerebral metastasis could not be excluded because of perifocal hypermetabolism. There were few therapeutic possibilities. PET/CT is possible and sensible in the unconscious patient to differentiate the results of polytrauma-CT.

The prognostic reliability of intracranial pressure monitoring and MRI data in severe traumatic brain injury.

OBJECTIVE: The predictive quality of intracranial pressure (ICP) monitoring has for many years been a matter of debate. We correlate ICP data comparing MRI data with the outcome after severe traumatic brain injury to evaluate their prognostic potency. METHODS: This study compares the results of ICP monitoring, MRI, coma duration and outcome according to Glasgow Outcome Scale obtained in 32 patients having suffered severe TBI. Level of significance was set to p≤0.05 in statistical tests. RESULTS: The MRI results were closely correlated with coma duration and Glasgow Outcome Scale, but the ICP measurements were not. With the exception of severe, bipontine lesions, there is no other region of the brain in which increased evidence of traumatogenic lesions emerges as the intracranial pressure rises. Just bipontine lesions that proof to be infaust correlate with elevated ICP values. CONCLUSION: ICP monitoring does not allow individual prognostic conclusions to be made. Implantation of an intracranial pressure sensor alone for making a prognostic estimate is not advisable. The use of intracranial pressure measurements in the retrospective appraisal of disease progress is highly problematic. However, MRI diagnostic in patients with severe TBI improves prognostic potency of clinical parameters.

Outcome After Decompressive Craniectomy in Different Pathologies.

BACKGROUND: We compare the outcome after decompressive craniectomy for various neurologic diseases with the final common pathway of coma, compression of the basal cisterns, a midline shift, or refractory intracranial hypertension. METHODS: Between January 2005 and June 2009, 134 patients underwent decompressive craniectomy for traumatic brain injury (n = 74), intracerebral hemorrhage (n = 21), spontaneous subarachnoid hemorrhage (n = 11), malignant cerebral infarction (n = 27), or encephalitis (n = 1). The outcome was classified at discharge and up to 12 months after treatment in accordance with the Glasgow Outcome Scale (GOS), as well as the Glasgow Coma Scale, Marshall classification, or National Institutes of Health Stroke Scale. Significance was established as P ≤ 0.05. RESULTS: Median and mean scores on the Glasgow Coma Scale at time of neurosurgical assessment in all patients were ≤7. Midline shift was reduced in each subset as a result of surgery (mean, 0.26-0.46 cm; P ≤ 0.049). Overall outcome based on the median GOS score at discharge ranged from death to severe disability. After 12 months, the median range narrowed to a range of death to persistent vegetative state. At various time points, mean GOS score was not found to differ significantly between the subsets. Unfavorable outcome after 3 months was found in a smaller group of patients after traumatic brain injury than was found in patients with other diseases (P = 0.016). CONCLUSIONS: The outcome after decompressive craniectomy does not differ significantly in different diseases once the final pathophysiologic pathway of refractory intracranial hypertension, coma, compression of the basal cisterns, or midline shift has been reached.

Clinical, Radiologic, and Legal Significance of "Extensor Response" in Posttraumatic Coma.

OBJECTIVE: The timely detection of neurologic deterioration can be critical for the survival of a neurosurgical patient following head injury. Because little reliable evidence is available on the prognostic value of the clinical sign "extensor response" in comatose posttraumatic patients, we investigated the correlation of this clinical sign with outcome and with early radiologic findings from magnetic resonance imaging (MRI). METHODS: This retrospective analysis of prospectively obtained data included 157 patients who had remained in a coma for a minimum of 24 hours after traumatic brain injury. All patients received a 1.5-T MRI within 10 days (median: 2 days) of the injury. The correlations between clinical findings 12 and 24 hours after the injury-in particular, extensor response and pupillary function, MRI findings, and outcome after 1 year-were investigated. Statistical analysis included contingency tables, Fisher exact test, odds ratios (ORs) with confidence intervals (CIs), and weighted κ values. RESULTS: There were 48 patients with extensor response within the first 24 hours after the injury. Patients with extensor response (World Federation of Neurosurgical Societies coma grade III) statistically were significantly more likely to harbor MRI lesions in the brainstem when compared with patients in a coma who had no further deficiencies (coma grade I; p = 0.0004 by Fisher exact test, OR 10.8 with 95% CI, 2.7-42.5) and patients with unilateral loss of pupil function (coma grade II; p = 0.0187, OR 2.8 with 95% CI, 1.2-6.5). The correlation of brainstem lesions as found by MRI and outcome according to the Glasgow Outcome Scale after 1 year was also highly significant (p ≤ 0.016). CONCLUSION: The correlation of extensor response and loss of pupil function with an unfavorable outcome and with brainstem lesions revealed by MRI is highly significant. Their sudden onset may be associated with the sudden onset of brainstem dysfunction and should therefore be regarded as one of the most fundamental warning signs in the clinical monitoring of comatose patients.

[Severe dyspnea by combination of cervical spondylosis and struma]. / Lebensbedrohliche Dyspnoe durch Struma und HWS-Spondylose.

UNLABELLED: CASE HISTORY PHYSICAL EXAMINATION: A 79-years-old female suffered from cervical pain for several years which radiated in both shoulders. A nodular goiter was already known and therefore a radio iodine treatment had been planned. Eight months ago the patient noticed a progressing breathlessness. Emergency admission happened due to inspiratory stridor and severe attacks of dyspnoea. Sufficient breathing was only possible by wearing a rigid cervical collar. There were no neurological deficits. EXAMINATION: Tracheoscopy showed a mass in the dorsal cervical region. The cervical x-ray, computed tomography and magnet resonance imaging conformed a distinct spondylopathy at the leading edge of the cervical vertebral bodies including ventralisation of the oesophagus and narrowing of the trachea (>50%). THERAPY AND COURSE: Simultaneously a total thyroidectomy, including neuromonitoring of the N. vagus, and ventral microsurgical resection of the spondylopathy was performed. There was no relapse of dyspnoea in the following year. CONCLUSION: The coincidence of a goiter and ventral cervical spondylopathy accompanied by significant dyspnoea is remarkable. The order of diagnostic steps in this emergency case displays a major problem. The patient was scheduled for goiter surgery and admitted as emergency due to a stridor. The cervical spondylopathy was diagnosed by tracheoscopy and cervical x-ray. This case report emphasizes the importance to think about cervical lesions in the presence of a goiter and dyspnoea. To find out quickly whether there is a cervical lesion or not a x-ray should be obtained. Missing these lesions can result in a fatal course.

Head Injury in Children: Has a Change in Circumstances Caused an Increase in Treatment Numbers?

The number of hospitalizations for head injuries in children is rising. The exact causes remain unclear. We analyzed data of children aged between 0 and 18 years who sustained a head injury between 2010 and 2011. The analysis focused on data related to demographics, trauma mechanism, clinical course, results of imaging scans, concomitant injuries, and outcome. A total of 794 inpatient cases of head injury were treated. The leading mechanism of injury was a fall (at home) primarily at the age of 1 to 4 years (46.5%), with the majority of the children sustaining a mild brain injury (764, 96.2%). Neurosurgery was performed in 21 (2.64%) cases; average hospital stay was 2.9 days (range: 0-68 days). This study is not able to confirm that children are increasingly being brought to the hospital by their parents because of new trauma mechanisms or parents' uncertainty, nor can we confirm that the number of nonaccidental injuries is rising.

Long-term health-related quality of life after spontaneous nontraumatic subarachnoid hemorrhage: self and proxy reports in a 10-year period.

BACKGROUND: This study sought to examine health-related quality of life several years after spontaneous nontraumatic subarachnoid hemorrhage. Recent studies report impairments to be improved as far as normal levels. We question such an improvement in our own patient population over a period of 10 years. METHODS: The Medical Outcomes Study 36-Item and Medical Outcomes Study 12-Item Short-Form Health Surveys on health-related quality of life were used to question 236 patients and 235 proxies. The patients were assigned to 5 groups according to the time that had elapsed since their hemorrhage: 1 year N = 22, 2 years N = 36, 5 years N = 86, 8 years N = 61, and 10 years N = 31. Analyses of variance (ANOVA, Kruskal-Wallis) and correlation (Spearman, Kendall tau) were used in an exploratory approach. Significance was established as P ≤ 0.05. RESULTS: Over a period of 10 years, health-related quality of life is found to be impaired, and is reported as such by the patients themselves and their proxies. Comparison of the mean values between the groups, ie, 1, 2, 5, and 10 years, revealed no significant differences in health-related quality of life. The calculations with a view to correlations between the group means and time since hemorrhage also produced only very weak correlations of no significance. CONCLUSIONS: Health-related quality of life is impaired over a period of 10 years. Spontaneous nontraumatic subarachnoid hemorrhage should be regarded as a chronic cerebrovascular condition.

Cognitive performance following spontaneous subarachnoid haemorrhage versus other forms of intracranial haemorrhage.

OBJECTIVE: The exact cause of cognitive deficits following intracranial haemorrhage is unclear. This prospective study examines the abilities after spontaneous subarachnoid haemorrhage (SAH), intracerebral haemorrhage (ICH) and chronic subdural haematoma (SDH) to elucidate the cognitive outcome. PATIENTS AND METHODS: Ninety-nine patients with SAH (N = 60), ICH (N = 25), and SDH (N = 14) were followed up for an average of 6 and 12 months post-haemorrhage. Cognitive tests were used to examine attention, memory, concentration, and executive function. Following were used for analysis: 1. the percentage of patients falling below the 25th percentile per test, 2. the general development from the first to second test point and 3. the incidence of significant changes between the test points. Significance was established as p ≤ 0.05. RESULTS: All three types of haemorrhage resulted in deficits as concerns abstract language (53%-75%). The processing speed was below the normal levels in more than 70% of the patients tested. The cognitive performance of SAH patients was similar to that of patients with SDH and ICH patients after 6 months. The number of patients with outcomes falling below the 25th percentile (to some extent more than 75% in patients post-SAH) is high in all patient groups and mostly decreases over the course. Nevertheless, patients with SAH reveal improvements in many more areas than with ICH and SDH (p ≤ 0.006). CONCLUSIONS: The cognitive impairments following SAH, ICH and SDH deficits appear to develop in a similar way regardless of the type of haemorrhage. Cognitive improvement is most pronounced in patients with SAH.

Desmopressin acetate in intracranial haemorrhage.

Introduction. The secondary increase in the size of intracranial haematomas as a result of spontaneous haemorrhage or trauma is of particular relevance in the event of prior intake of platelet aggregation inhibitors. We describe the effect of desmopressin acetate as a means of temporarily stabilising the platelet function. Patients and Methods. The platelet function was analysed in 10 patients who had received single (N = 4) or multiple (N = 6) doses of acetylsalicylic acid and 3 patients (control group) who had not taken acetylsalicylic acid. All subjects had suffered intracranial haemorrhage. Analysis was performed before, half an hour and three hours after administration of desmopressin acetate. Statistical analysis was performed by applying a level of significance of P ≤ 0.05. Results. (1) Platelet function returned to normal 30 minutes after administration of desmopressin acetate. (2) The platelet function worsened again after three hours. (3) There were no complications related to electrolytes or fluid balance. Conclusion. Desmopressin acetate can stabilise the platelet function in neurosurgical patients who have received acetylsalicylic acid prior to surgery without causing transfusion-related side effects or a loss of time. The effect is, however, limited and influenced by the frequency of drug intake. Further controls are needed in neurosurgical patients.

Health-related quality of life after spontaneous subarachnoid hemorrhage measured in a recent patient population.

OBJECTIVE: This study sought to determine the impact of spontaneous subarachnoid hemorrhage (SAH) on health-related quality of life (HRQOL). METHODS: Data were taken retrospectively from 601 patients (219 male, 382 female) treated between 1998 and 2008. Questionnaires concerning HRQOL were circulated prospectively, and the responses from 253 patients (81 male, 172 female) were analyzed. The questionnaires comprised the standardized Short-Form 36 (SF-36) and Short-Form 12 (SF-12) Health Surveys, a number of nonstandardized questions, and visual analogue scales. Statistical analysis of the results was exploratory, using unifactorial ANOVA (Scheffe), multivariate analyses of variance. RESULTS: The HRQOL is reduced considerably by SAH and remains so for a period of 10 years. Physical and emotional domains are primarily affected, but also cognitive functions, including memory and concentration in particular. Similarly, certain roles are affected that prove difficult to rehabilitate after acute care and cause serious debility in the long term. The Hunt and Hess Scale, Glasgow Outcome Scale, and seizures were found to have the greatest impact on HRQOL. CONCLUSIONS: Documentation of HRQOL after 6 to 12 months is useful because patients are often found to have a diminished HRQOL in the absence of a clear physical impairment. Because psychological, emotional, cognitive, and social functioning influence HRQOL in the long term, efforts at rehabilitation should focus in particular on improving such factors. Documentation of HRQOL is a useful, additive tool for consolidating and evaluating the outcome, and a treatment end point after SAH, respectively.

Which clinical variable influences health-related quality of life the most after spontaneous subarachnoid hemorrhage? Hunt and Hess scale, Fisher score, World Federation of Neurosurgeons score, Brussels coma score, and Glasgow coma score compared.

OBJECTIVE: To determine the strength of the correlation between the Hunt and Hess scale, Fisher score, Brussels coma score, World Federation of Neurosurgeons score, and Glasgow coma score and health-related quality of life. METHODS: Evaluable questionnaires from 236 patients (5.6 years [± standard deviation, 2.854 years] on average after hemorrhage) were included in the analysis. Quality of life was documented using the MOS-36 item short form health survey. Because of the ordinal nature of the variables, Kendall tau was used for calculation. Significance was established as P ≤ 0.05. RESULTS: Weak and very weak correlations were found in general (r ≤ 0.28). The strongest correlations were found between the Glasgow coma score and quality of life (r = 0.236, P = 0.0001). In particular, the "best verbal response" achieved the strongest correlations in the comparison, at r = 0.28/P = 0.0001. The Fisher score showed very weak correlations (r = -0.148/P = 0.012). The Brussels coma score (r = -0.216/P = 0.0001), Hunt and Hess scale (r = -0.197/P = 0.0001), and the World Federation of Neurosurgeons score (r = -0.185/P = 0.0001) revealed stronger correlations, especially in terms of the physical aspects of quality of life. CONCLUSIONS: The Glasgow coma scale revealed the strongest, and the Fisher score showed the weakest correlations. Thus the Fisher score, as an indicator of the severity of a hemorrhage, has little significance in terms of health-related quality of life.

Cerebral vasospasm and health-related quality of life after subarachnoid hemorrhage.

OBJECTIVE: To examine the influence of cerebral vasospasm on health-related quality of life after subarachnoid hemorrhage. An additional objective was to determine how the timing of nimodipine therapy can influence health-related quality of life. METHODS: Patients treated between 1998 and 2008 for nontraumatic subarachnoid hemorrhages were sent a standardized questionnaire for the purposes of documenting their health-related quality of life. Initially the patients were divided into two groups: those with and those without cerebral vasospasm after hemorrhage (radiologically confirmed). They were then differentiated according to four types of treatment options for vasospasm: 1) nimodipine since admission (N = 179); 2) nimodipine since diagnosis of vasospasm (N = 14); 3) no nimodipine/no vasospasm (N = 34); and 4) no nimodipine despite vasospasm (N = 5). Significance was established as P ≤ 0.05. RESULTS: Evaluable questionnaires were returned by 236 patients (68% women, mean age 56.35 ± 12.68 years; 32% men, mean age 54.57 ± 12.20 years). Health-related quality of life generally appeared to be impaired. Yet with the exception of the subscale (1 of 8) of physical role (P = 0.019), there were no differences between patients with and without vasospasm. Variations in the different treatment options revealed significant effects in terms of the component summaries and subscales: physical role and pain, general health, vitality, social functioning, emotional role, mental health, and mental component summary (P ≤ 0.04). CONCLUSIONS: Cerebral vasospasm had little influence on health-related quality of life in our patient population. Health-related quality of life cannot be used as the only argument in favor of treating cerebral vasospasm with nimodipine.

Head trauma in children, part 3: clinical and psychosocial outcome after head trauma in children.

With the aim of determining long-term outcome, the authors approached 38 families (average 2.1 years after trauma) with a questionnaire, following the acute-clinical treatment of head trauma of their children. Long-term damage was restricted almost exclusively to patients presenting with a Glasgow Coma Score < or =8. Paresis (16%), cranial nerve damage (13%), incontinence (5%), or coordinative disturbances (18%) continued. The older children stated that they influenced their life to a great extent (11%). Furthermore, many had mental and cognitive problems that occur quite frequently even in children with light head trauma and often only manifest after release from hospital. This causes problems and results in inferior performance (26%), especially at school, which is further complicated through lengthy periods of absence. The parents, especially, mentioned behavioral problems such as social withdrawal or aggressive demeanor, which led to tension also inside the family. A persistent vegetative state is rare after head trauma in children.

Head trauma in children, part 1: admission, diagnostics, and findings.

The objective of this study is to describe and to determine the preclinical situation and early in-clinical situation, diagnostic findings, and factors influencing the outcome of severe head trauma in children. Records of 48 children (0-16 years) were analyzed during a 3-year interval. Correlations with the outcome (Glasgow Outcome Scale) were determined by focusing on different scales, clinical findings, biochemistry, and clinical course features. The initial shock index had a major relevance (P = .0089). Systolic blood pressure (P = .0002) and bradycardia (P = .035) were important factors. Assessing the severity of trauma according to the Glasgow Coma Score, the most accurate parameter for outcome is based on the detailed quality of ''eye opening'' (P = .0155). Pupillary motoricity at the accident site (P = .002) and emergency room (P = .0004) are strong predictors. Preclinical measurements of stabilization and oxygenation have the same impact as the in-clinical management.

Head trauma in children, part 2: course and discharge with outcome.

To minimize the secondary brain damage, we analyzed the effect of cerebral perfusion pressure-orientated management and tried to find factors of clinical management and biochemical findings that influence clinical, cognitive, and psychosocial outcome. Management at intensive care unit was standardized. A standardized (short form 36 health survey) and nonstandardized split questionnaire explored long-term outcome. Glutamic-oxaloacetic-transaminase, creatine kinase MB or glucose are markers for bad outcome (P < .05). Patients with cerebral perfusion pressure values below the recommended standard for just a single occurrence had significantly worse outcome (P = .0132). Mean arterial pressure, central venous pressure, and heart rate alone do not correlate with outcome. At least 1 occurrence of mean arterial pressure and central venous pressure below the lower limits resulted in a poor outcome (P = .035). Cerebral perfusion pressure-guided therapy seems to prevent further brain damage and results in outcome scores that are comparable to those children with head trauma exhibiting symptoms of mild brain edema.