Functional outcome and quality of life 5 and 12.5 years after aneurysmal subarachnoid haemorrhage

Patients who recover from aneurysmal subarachnoid haemorrhage (SAH) often remain disabled or have persisting symptoms with a reduced quality of life (QoL). We assessed functional outcome and QoL 5 and 12.5 years after SAH. In a consecutive series of 64 patients with mean age at SAH of 51 years, initial outcome assessments had been performed at 4 and 18 months after SAH. At the initial and current outcome assessments, functional outcome was measured with the modified Rankin Scale (mRS) and QoL with the SF-36 and a visual analogue scale (VAS). We studied the change in outcome measurements over time. We used the non-parametric Wilcoxon test to compare differences in mRS grades and calculated differences with corresponding 95% confidence intervals in the domain scores of the SF-36 and the VAS. After 5 years, seven patients had died and five patients had missing data. Compared with the 4-month follow-up, the mRS had improved in 29 of the 52 patients, remained similar in 19 patients. The overall QoL (SF-36 domains and VAS score) was better. At 12.5 years an additional six patients had died. Compared to the 4-month study, 25 of the 46 remaining patients had improved mRS, 12 had remained the same and in nine patients the mRS had worsened. Between the 5 and the 12.5 years follow-up, the improvement in mRS had decreased but patients reported overall a better QoL. Among long-time survivors, QoL may improve more than a decade after SAH.     

Relationship Between Hemoglobin Concentrations and Outcomes Across Subgroups of Patients with Aneurysmal Subarachnoid Hemorrhage

Objective  Anemia predicts poor outcome following aneurysmal subarachnoid hemorrhage (SAH). We hypothesized that this association would be stronger among patients with more severe SAH, since these patients are likely to be more vulnerable to secondary brain injury in the form of reduced cerebral oxygen delivery. Methods  Daily nadir hemoglobin (Hb) concentrations over 2 weeks following SAH were retrieved in 245 consecutive patients, and compared between those with a favorable versus unfavorable outcome. The analysis was repeated with patients dichotomized as follows: WFNS score 4–5 vs. 1–3; modified Fisher score (MFS) 4 vs. 0–3; and vasospasm present vs. absent. Mixed effect models and multivariable analysis using the generalized estimating equation were employed to assess correlated data with repeated measures. Results  Patients with an unfavorable outcome consistently had lower Hb concentrations, especially between days 6–11 following SAH (P ranging from <0.001 to 0.009), as well as a greater fall in Hb over time (β = −0.07, P < 0.001). This was true regardless of WFNS score, MFS, or the presence or absence of vasospasm. However, the effect was somewhat more pronounced among patients with higher WFNS and modified Fisher scores. Conclusion  Lower Hb levels are associated with worse outcomes regardless of SAH severity or the development of vasospasm. This finding may imply that a lower Hb concentration is largely a marker for a greater degree of systemic illness, rather than necessarily causing direct harm. However, the association is somewhat stronger among patients with more severe SAH. Thus, if there is a benefit for maintaining higher Hb levels with transfusions or erythropoietin, it may be more pronounced among these patients. Supported in part by the Louise Nerancy endowment of The University of Virginia.     

Predictors for cognitive impairment one year after surgery for aneurysmal subarachnoid hemorrhage

OBJECTIVE: To assess predictors for cognitive impairment one year after spontaneous subarachnoid hemorrhage (SAH). Evaluated predictors were the total amount of cisternal blood seen on computed tomography (CT) in the acute phase as measured by the Fisher grade, neurological grade at admission classified according to the Hunt and Hess scale, aneurysm site and patient's age, gender and education level. METHOD: 44 patients were operated by surgical clipping within 72 hours after CT verified aneurysmal SAH. After twelve months the remaining 42 patients were assessed by neuropsychological test, Beck Depression Inventory (BDI), the Glasgow Outcome Scale (GOS) and CT. Multiple regression analysis was conducted where predictor variables were independent factors and a global impairment index calculated for each patient was the dependent factor. RESULTS: The Fisher grade was the only independent predictor for neuropsychological impairment. Most patients had good neurological outcome as measured by the GOS and at the same time suffered from some degree of cognitive impairment at follow-up. Individual analysis of cognitive test scores showed mild to moderate dysfunction across multiple cognitive domains. Most frequent impairments were found in domains of memory, executive function and speed of information processing. Age below 50 years was associated with relatively better outcome. CONCLUSION: The severity of cognitive impairment one year post SAH is predicted by the volume of blood in the subarachnoid space as measured by the Fisher score.     

Long-term neurological and neuropsychological outcome in patients with severe traumatic brain injury

Background

Severe traumatic brain injury (TBI) remains a major cause of death and disability worldwide. The aim of the study was to evaluate predictors for neurological and neuropsychological long-term outcome in patients with severe TBI treated according to an intracranial pressure (ICP-) targeted therapy.

Methods

From 08/2005 to 12/2008, 46 patients with severe TBI and more than 12 h of intensive care treatment were included in this study. Neurological outcome was assessed with the Glasgow Outcome Scale (GOS). Neuropsychological performance assessing 9 different domains was evaluated at long-term follow-up (median 20.5 months; range 10–46). Logistic regression was used to identify favourable outcomes according to the GOS and Fisher's exact tests were used to identify predictors of severe neuropsychological impairments at follow-up.

Results

Twenty-nine patients were available for neuropsychological assessment at long-term follow-up. Only 2 out of 29 patients presented normal or average neuropsychological findings throughout all 9 neuropsychological domains at long-term follow-up. The percentage of a favourable outcome (GOS 4-5) increased from 13.8% at hospital discharge to 75.8% at rehabilitation discharge to 79.3% at long-term follow-up, respectively. Age ≤40 was found to be a strong predictor of favourable outcome at follow-up (OR 5.95, 95% CI 1.41 25.00, p = 0.015). The GOS at hospital discharge was not a predictor for severe impairments in any of the 9 different neuropsychological domains (all p-values were p > 0.268). In contrast, the GOS at rehabilitation discharge was found to be a predictor of severe impairments at follow-up in all but one domain assessed (all p-values less than p < 0.038).

Conclusions

The GOS at rehabilitation discharge should be regarded as a better predictor for neuropsychological impairments at long-term follow-up than the GOS at hospital discharge. Even in patients with favourable GOS after finishing a course of rehabilitation, three quarters of these patients may have at least one severe neuropsychological deficit. Therefore, it remains of paramount importance to provide long-term neuropsychological support to further improve outcome after TBI.     

Speed performance and long-term functional and vocational outcome in a group of young patients with moderate or severe traumatic brain injury

We studied specific aspects of speed performance in neuropsychological tests and functional and vocational long-term outcome among moderate or severe traumatic brain injury (TBI) patients admitted to a rehabilitation programme. A group of 140 patients with mild, moderate or severe TBI was followed up for a minimum of 5 years in a rehabilitation programme. Severity of TBI was estimated using the Glasgow Coma Scale (GCS) scores on emergency hospital admission. The patients, grouped by age at injury into the categories: 7 or younger, 8-16 and 17 years of age or older, were tested five or more years post-injury with comprehensive neuropsychological tests, including a speed performance test with the Stroop material, the Purdue Pegboard (PB) test and simple visual and auditive reaction times. The outcome variables were functional outcome, as measured by the Glasgow Outcome Scale (GOS) score, and capacity for employment at the end of follow-up, i.e. on average 12 years post-injury. The patients with mild TBI were excluded from further analysis of outcome. The study was carried out at the Kauniala outpatient neurological clinic. In the Stroop test, patients with a GOS score of 3 and patients who were incapable of employment were slower (P = 0.0046 and P = 0.0015, respectively) than those with a GOS score of 1 or 2 and those capable of independent or subsidized employment, respectively. The PB test also differentiated significantly between the patients with a GOS score of 3 and those with a GOS score of 1 or 2 at the end of follow-up (P = 0.0413), and predicted incapacity for employment (P = 0.032), those with worse outcome being slower. Simple reaction times did not differ significantly between the GOS scores at the end of follow-up, and neither did they predict capacity or incapacity for employment. Our data suggest that the Stroop and PB tests can help estimate functional outcome, as measured by the GOS, among patients with initially moderate or severe TBI and who were referred to a rehabilitation programme. The same tests could also be useful in predicting long-term vocational outcome.     

Increased cerebrospinal fluid concentrations of asymmetric dimethylarginine correlate with adverse clinical outcome in subarachnoid hemorrhage patients

Elevated cerebrospinal fluid (CSF) concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, have been found in patients with subarachnoid hemorrhage (SAH). In addition, CSF levels of ADMA are associated with the severity of vasospasm. However, the relation between CSF ADMA levels and the clinical outcome of SAH patients is still unclear. We hypothesized that elevated ADMA levels in CSF might be related to the clinical outcome of SAH patients. CSF ADMA levels were measured in 20 SAH patients at days 3–5, days 7–9 and days 12–14 after SAH onset using high-performance liquid chromatography. Cerebral vasospasm was assessed by transcranial Doppler ultra sonography. Clinical outcome at 2 year follow-up was evaluated using the Karnofsky Performance Status scale (KPS). CSF ADMA concentrations in all SAH patients were significantly increased at days 3–5 (p = 0.002) after SAH, peaked on days 7–9 (p < 0.001) and remained elevated until days 12–14 (p < 0.001). In subgroup analysis, significant increases of CSF ADMA levels were found in patients both with and without vasospasm. The KPS scores significantly correlated with CSF levels of ADMA at days 7–9 (correlation coefficient = −0.55, p = 0.012; 95% confidence interval −0.80 to −0.14). Binary logistic regression analysis indicated that higher ADMA level at days 7–9 predicted a poor clinical outcome at 2 year follow-up after SAH (odds ratio = 1.722, p = 0.039, 95% confidence interval 1.029 to 2.882). ADMA may be directly involved in the pathological process and future adverse prognosis of SAH.     

Predicting Outcome in Subarachnoid Hemorrhage (SAH) Utilizing the Full Outline of UnResponsiveness (FOUR) Score

Background

Existing scoring systems for aneurysmal subarachnoid hemorrhage (SAH) patients fail to accurately predict patient outcome. Our goal was to prospectively study the Full Outline of UnResponsiveness (FOUR) score as applied to newly admitted aneurysmal SAH patients.

Methods

All adult patients presenting to Health Sciences Center in Winnipeg from January 2013 to July 2015 (2.5 year period) with aneurysmal SAH were prospectively enrolled in this study. All patients were followed up to 6 months. FOUR score was calculated upon admission, with repeat calculation at 7 and 14 days. The primary outcomes were: mortality, as well as dichotomized 1- and 6-month Glasgow Outcome Scale (GOS) and modified Rankin Scale (mRS) values.

Results

Sixty-four patients were included, with a mean age of 54.2 years (range 26–85 years). The mean FOUR score upon admission pre- and post-external ventricular drain (EVD) was 10.3 (range 0–16) and 11.1 (range 3–16), respectively. There was a statistically significant association between pre-EVD FOUR score (total, eye, respiratory and motor sub-scores) with mortality, 1-month GOS, and 6-month GOS/mRS (p < 0.05 in all). The day 7 total, eye, respiratory, and motor FOUR scores were associated with mortality, 1-month GOS/mRS, and 6-month GOS/mRS (p < 0.05 in all). The day 14 total, eye, respiratory, and motor FOUR scores were associated with 6-month GOS (p < 0.05 in all). The day 7 cumulative FOUR score was associated with the development of clinical vasospasm (p < 0.05).

Conclusions

The FOUR score at admission and day 7 post-SAH is associated with mortality, 1-month GOS/mRS, and 6-month GOS/mRS. The FOUR score at day 14 post-SAH is associated with 6-month GOS. The brainstem sub-score was not associated with 1- or 6-month primary outcomes.

     

Disability and quality of life in Guillain-Barré syndrome – Longitudinal study

Longitudinal health-related quality of life (QoL) data in Guillain-Barré (GBS) patients are still scarce. We, therefore, investigated health- related QoL in GBS patients from Serbia and surrounding countries during a six-month follow-up period, and analyzed its association with patients' disability. Our study comprised 74 adult patients diagnosed with GBS from May 2017 until May 2018 in seven tertiary healthcare centers. Health-related QoL was investigated using the SF-36 questionnaire, and compared with functional disability assessed by the GBS disability scale (GDS). Tests were performed at day 14, day 28, month 3 and month 6 from disease onset. GDS and SF-36 scores improved over time (p < 0.01). GDS scores were different at all four time points, while SF-36 did not differ between day 14 and day 28. Pooled SF-36 scores (especially physical ones) correlated with pooled GDS scores, except for Bodily Pain and Role Emotional scores. We found that GDS score at day 14 was an independent predictor of GDS score at month 6 (β = +0.52, p < 0.01), while SF-36 score at day 14 was an independent predictor of SF-36 score at month 6 (β = +0.51, p < 0.01). Neurologists should look not only on disability but also on QoL in GBS patients, since these two measures provide us with important complementary items of information.     

Amount of blood during the subacute phase and clot clearance rate as prognostic factors for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

Delayed cerebral ischemia (DCI) is a poorly predictable complication occurring after aneurysmal subarachnoid hemorrhage (SAH) that can have dramatic functional consequences. Identifying the patients with the highest risk of DCI may help to institute more suitable monitoring and therapy. Early brain injuries and aneurysm-securing procedure complications could be regarded as confounding factors leading to severity misjudgment. After an early resuscitation phase, a subacute assessment may be more relevant to integrate the intrinsic SAH severity.A retrospective analysis was performed upon patients prospectively included in the registry of SAH patients between July 2015 to April 2020. The amount of cisternal and intraventricular blood were assessed semi-quantitatively on acute and subacute CT scans performed after early resuscitation. A clot clearance rate was calculated from their comparison. The primary endpoint was the occurrence of a DCI.A total of 349 patients were included in the study; 80 (22.9%) experienced DCI. In those patients, higher Fisher grades were observed on acute (p = 0.026) and subacute (p = 0.003) CT scans. On the subacute CT scan, patients who experienced DCI had a higher amount of blood, either at the cisternal (median Hijdra sum score: 11 vs 5, p < 0.001) or intraventricular (median Graeb score: 4 vs 2, p < 0.001) level. There was a negative linear relationship between the cisternal clot clearance rate and the risk of DCI.The assessment of the amount of subarachnoid blood and clot clearance following resuscitation after aneurysmal SAH can be useful for the prediction of neurological outcome.     

Astheno-emotional disorder after aneurysmal SAH: reliability, symptomatology and relation to outcome

OBJECTIVES: Neuropsychiatric symptoms commonly found after aneurysmal SAH are covered in the astheno-emotional disorder (AED) of Lindqvist & Malmgrens diagnostic system for organic psychiatry. This study aims to describe the reliability and symptomatology of AED and its relationship with social outcome. MATERIAL AND METHODS: Patients referred due to aneurysmal SAH (n=78) were assessed after 1-6 months for AED inter-rater reliability (n=36) and after 12 months for AED severity grade, symptomatology and Glasgow Outcome Scale (GOS) (n=63). RESULTS: There was no systematic error in diagnosing and grading AED, and the agreement was 85% and 67% respectively (kappa=0.65 and 0.52). Fatigability, concentration difficulties and memory difficulties were the most frequent symptoms of AED. The relationship between AED and "moderate disability" of GOS was highly significant (P<0.00006). CONCLUSIONS: AED affects social outcome, and can be diagnosed with high reliability even without neuropsychological testing. Use of the AED diagnosis for evaluation of organic mental symptoms is encouraged.     

The impact of cardiac complications on outcome in the SAH population

OBJECTIVES: To determine the impact of cardiac complications (CdCs) on outcomes in patients with acute subarachnoid hemorrhage (SAH). PATIENTS AND METHODS: Eighty-one adult aneurysmal SAH patients with a fisher grade >1 and/or a Hunt and Hess grade >2 were recruited for this study. CdCs were defined as electrocardiogram (ECG) changes, myocardial necrosis, arrythmias, or pulmonary edema. Outcomes were assessed at 3, 6 and 12 months by telephone interview using the Modified Rankin Scale (MRS), Glasgow Outcome Scale (GOS), Barthel Index and Medical Outcome study Short Form-36 (SF-36). RESULTS: The CdCs occurred in 33% of patients. The most common CdCs were arrythmias and pulmonary edema (30%). There was no significant difference in mortality between the two groups. At 3 months there was a significant difference in the Barthel (P = 0.007) and the SF-36 (P = 0.014) with trends in the GOS (P = 0.049) and the MRS (P = 0.063). At 6 months a significant difference remained in the SF-36 (P = 0.028) and a trend in the Barthel (P = 0.069). CONCLUSION: Results show that CdCs may negatively impact outcomes in SAH patients up to 6 months following hemorrhage.     

Outcome measures for traumatic brain injury

Traumatic brain injury (TBI) is a major public health problem resulting in death and disabilities of young and productive people. Though the mortality of TBI has decreased substantially in recent years the disability due to TBI has not appreciably reduced. Various outcome scales have been proposed and used to assess disability after TBI. A few, commonly used are Glasgow Outcome Scale (GOS) with or without extended scores, Disability Rating Scale (DRS), Functional Independence Measure (FIM), Community Integration Questionnaire (CIQ), and the Functional Status Examination (FSE). These scales assess disability resulting from physical and cognitive impairments. For patients with good physical recovery a cognitive and neuropsychological outcome measure is required. Such measures include Neurobehavioural Function Inventory and specific neuropsychological tests like Rey Complex Figure for visuoconstruction and memory, Controlled Oral Word Association for verbal fluency, Symbol Digit Modalities (verbal) for sustained attention and Grooved Pegboard for fine motor dexterity. A more holistic and complete outcome measure is Quality of Life (QOL). Disease specific QOL measure for TBI, Quality of Life after Brain Injury (QOLIBRI) has also been recently proposed. The problems with outcome measures include poor operational definitions, lack of sensitivity or low ceiling effects, inability to evaluate patients who cannot report, lack of integration of morbidity and mortality categories, and limited domains of functioning assessed. GOSE-E satisfies most of the criteria of good outcome scale and in combination with neuropsychological tests is a near complete instrument for assessment of outcome after TBI.     

Atypical causes of nontraumatic intracranial subarachnoid hemorrhage

Background

To analyze the management and outcome of patients presenting with atypical causes of intracranial subarachnoid hemorrhage (SAH).

Methods

We performed a review of our last 820 nontraumatic-SAH patients and analyzed the management and outcome of patients where the SAH origin was not a ruptured aneurysm. The Glasgow Outcome Scale (GOS) was used to assess outcome 3 months after event.

Results

Thirty-two patients had atypical causes of SAH. In 15 patients with Hunt and Hess (H&H) scores from 1 to 3 without focal neurological deficit (FND), 8 perimesencephalic nonaneurysmatic SAH, 4 blood coagulation disorders, 1 sinus thrombosis, 1 vasculitis, and 1 unknown-origin-SAH (UOS) were diagnosed. Fourteen (93%) of these 15 patients were conservatively treated. In 17 patients with H&H scores from 3 to 5 and FND, 8 tumors, 1 cavernoma, 1 sinus thrombosis, 1 arteriovenous malformation, 1 blood coagulation disorders, 2 UOS, and 3 dural fistulas were diagnosed. Fifteen (88%) of these 17 patients were interventionally treated. The neurological condition 3 months later was good (GOS 4 and 5) in 12 of the 15 cases (80%) admitted with low-H&H scores, as well as in 13 of the 17 cases (76%) admitted with high-H&H scores. Three patients died and four developed a severe disability.

Conclusions

Patients presenting with atypical causes of SAH and high-H&H scores at admission are likely to harbor an intracranial organic process producing the bleeding. Despite this poor initial condition, their 3-month outcome can be similar to those of patients with low-H&H scores if the origin of the bleeding is properly treated.     

Acute systematic inflammatory response syndrome and serum biomarkers predict outcomes after subarachnoid hemorrhage

Subarachnoid hemorrhage (SAH) can trigger immune activation sufficient to induce systematic inflammatory response syndrome (SIRS). Serum inflammatory biomarkers and SIRS can predict a poor outcome. The relationship between surgical stress and inflammatory response is well known but described in few reports in the neurosurgical population. We aimed to ascertain whether postoperative SIRS and initial serum biomarkers were associated with outcomes and evaluate whether the postoperative SIRS score differed between those with clipping and coil embolization. We evaluated 87 patients hospitalized within 24 h from onset of nontraumatic SAH. Serum biomarkers, such as levels of C-reactive protein (CRP), white blood cells (WBC), and D-dimer, as well as stress index (SI: blood sugar/K ratio) were obtained at admission. SIRS scores 3 days after admission were derived by adding the number of variables meeting the standard criteria (heart rate [HR] >90, respiratory rate [RR] >20, temperature >38 °C or <36 °C, and WBC count <4000 or >12,000). Clinical variables were compared according to whether they were associated with poor outcomes. Coil embolization was performed in 30 patients and clipping in 57. WBC, SI, D-dimer levels, and SIRS scores were significantly higher in patients with poor-grade SAH and were associated with poor outcomes. SIRS scores were significantly higher with clipping than with coil embolization among patients with good-grade SAH without intracerebral hemorrhage. Acute SIRS and serum biomarkers predict outcomes after SAH. Moreover, our study suggests the influence of surgical invasion via clipping on SIRS after SAH.     

Serum Glucose and Potassium Ratio as Risk Factors for Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage

Objective: Cerebral vasospasm is associated with poor prognosis in patients with aneurysmal subarachnoid hemorrhage (SAH), and biomarkers for predicting poor prognosis have not yet been established. We attempted to clarify the relationship between serum glucose/potassium ratio and cerebral vasospasm in patients with aneurysmal SAH. Methods: We studied 333 of 535 aneurysmal SAH patients treated between 2006 and 2016 (123 males, 210 females; mean age 59.7 years; range 24-93). We retrospectively analyzed the relationship between cerebral vasospasm grade and clinical risk factors, including serum glucose/potassium ratio. Results: Postoperative angiography revealed cerebral vasospasm in 112 patients (33.6%). Significant correlations existed between the ischemic complication due to cerebral vasospasm and glucose/potassium ratio (P < .0001), glucose (P = .016), and potassium (P = .0017). Serum glucose/potassium ratio was elevated in the cerebral vasospasm grade dependent manner (Spearman's r = 0.1207, P = .0279). According to the Glasgow Outcome Scale (GOS) score at discharge, 185 patients (55.5%) had a poor outcome (GOS scores 1-3). Serum glucose/potassium ratio was significantly correlated between poor outcome (GOS scores 1-3) and age (P < .0001), serum glucose/potassium ratio (P < .0001), glucose (P < .0001), potassium (P = .0004), white blood cell count (P = .0012), and cerebral infarction due to cerebral vasospasm (P < .0001). Multivariate logistic regression analyzes showed significant correlations between cerebral infarction due to cerebral vasospasm and serum glucose/potassium ratio (P = .018), glucose (P = .027), and potassium (P = .052). Conclusions: Serum glucose/potassium ratio in cases of aneurysmal SAH was significantly associated with cerebral infarction due to cerebral vasospasm and GOS at discharge. Therefore, this factor was useful to predict prognosis in patients with cerebral vasospasm and aneurysmal SAH.     

The Effectiveness of Lumbar Cerebrospinal Fluid Drainage to Reduce the Cerebral Vasospasm after Surgical Clipping for Aneurysmal Subarachnoid Hemorrhage

ObjectiveRemoval of blood from subarachnoid space with a lumbar drainage (LD) may decrease development of cerebral vasospasm. We evaluated the effectiveness of a LD for a clinical vasospasm and outcomes after clipping of aneurysmal subarachnoid hemorrhage (SAH).MethodsBetween July 2008 and July 2013, 234 patients were included in this study. The LD group consisted of 126 patients, 108 patients in the non LD group. We investigated outcomes as follow : 1) clinical vasospasm, 2) angioplasty, 3) cerebral infarction, 4) Glasgow outcome scale (GOS) score at discharge, 5) GOS score at 6-month follow-up, and 6) mortality.ResultsClinical vasospasm occurred in 19% of the LD group and 42% of the non LD group (p<0.001). Angioplasty was performed in 17% of the LD group and 38% of the non LD group (p=0.001). Cerebral infarctions were detected in 29% and 54% of each group respectively (p<0.001). The proportion of GOS score 5 at 6 month follow-up in the LD group was 69%, and it was 58% in the non LD group (p=0.001). Mortality rate showed 5% and 10% in each group respectively. But, there was no difference in shunt between the two groups.ConclusionLD after aneurysmal SAH shows marked reduction of clinical vasospasm and need for angioplasty. With this technique we have shown favorable GOS score at 6 month follow-up.     

The neurobehavioural rating scale-revised: sensitivity and validity in closed head injury assessment

OBJECTIVES: To investigate the factor structure and psychometric properties of the neurobehavioural rating scale-revised (NRS-R) and to determine its usefulness in clinical trials. METHODS: A consecutive series of patients sustaining severe closed head injury were evacuated to one of 11 large regional North American trauma centres and entered into a randomised, phase III, multicentre clinical trial investigating the therapeutic use of moderate hypothermia. Acute care personnel were blinded to outcome and outcome personnel were blinded to treatment condition. The Glasgow outcome scale (GOS) was the primary outcome measure. Secondary outcome measures included the disability rating scale (DRS) and the NRS-R. RESULTS: Exploratory factor analysis of NRS-R data collected at 6 months after injury (n=210) resulted in a five factor model including: (1) executive/cognition, (2) positive symptoms, (3) negative symptoms, (4) mood/affect, and (5) oral/motor. These factors showed acceptable internal consistency (0.62 to 0.88), low to moderate interfactor correlations (0.19 to 0.61), and discriminated well between GOS defined groups. Factor validity was demonstrated by significant correlations with specific neuropsychological domains. Significant change was measured from 3 to 6 months after injury for the total score (sum of all 29 item ratings) and all factor scores except mood/affect and positive symptoms. The total score and all factor scores correlated significantly with concurrent GOS and DRS scores. CONCLUSIONS: The NRS-R is well suited as a secondary outcome measure for clinical trials as its completion rate exceeds that of neuropsychological assessment and it provides important neurobehavioural information complementary to that provided by global outcome and neuropsychological measures.     

Metaanalysis of Tirilazad Mesylate in Patients with Aneurysmal Subarachnoid Hemorrhage

Background  Tirilazad is a non-glucocorticoid, 21-aminosteriod that inhibits lipid peroxidation. It had neuroprotective effects in experimental ischemic stroke and reduced angiographic vasospasm after experimental subarachnoid hemorrhage (SAH). Five randomized clinical trials of tirilazad were conducted in patients with SAH. We performed a meta-analysis of these trials to assess the effect of tirilazad on unfavorable outcome, symptomatic vasospasm, and cerebral infarction after SAH. Methods  Data from 3,797 patients were analyzed and modeled using random effect and Mantel-Haenszel meta-analyses and multivariable logistic regression to determine the effect of tirilazad on clinical outcome, symptomatic vasospasm, and cerebral infarction. Clinical outcome was assessed 3 months after SAH using the Glasgow outcome scale, and symptomatic vasospasm was defined by clinical criteria with laboratory and radiological exclusion of other causes of neurological deterioration. Results  The five trials were randomized, double-blind, and placebo-controlled. Tirilazad did not significantly decrease unfavorable clinical outcome on the GOS (odds ratio [OR] 1.04, 95% confidence interval [CI] 0.89–1.20) or cerebral infarction (OR 1.04, 95% CI 0.89–1.22). There was a significant reduction in symptomatic vasospasm in patients treated with tirilazad (OR 0.80, 95% CI 0.69–0.93). There was no heterogeneity across the five trials. Conclusion  Tirilazad had no effect on clinical outcome but did decrease symptomatic vasospasm in five trials of aneurysmal SAH. The dissociation between clinical outcome and symptomatic vasospasm deserves further investigation.     

Acute hyponatremia after aneurysmal subarachnoid hemorrhage: Frequency,treatment, and outcome

We retrospectively examined the course of serum sodium levels in 180 patients with acute aneurysmal subarachnoid hemorrhage (SAH) who had been admitted to the anesthesiologic-neurosurgical intensive care unit of the University Medical Center Regensburg, Germany, between January 2014 and December 2018. Each patient file was analyzed regarding the frequency and intensity of hyponatremic episodes and the administered medication. At admission to the intensive care unit (ICU), 18 patients had shown initial hyponatremia (<135 mmol/L) and 4 patients hypernatremia (greater than145 mmol/L). 88 (48.9%) of the 158 patients with normal serum sodium levels developed at least one hyponatremic episode during ICU treatment. The number of hyponatremic episodes was similar between patients with higher-grade and lower-grade aneurysmal SAH (P = 0.848). At the end of ICU treatment, outcome did not differ between patients with and without hyponatremia (40/88, 45.5% vs. 38/70, 54.3%, P = 0.270). At 6 months after SAH, however, good outcome (Glasgow outcome scale, GOS 4–5) was more frequently observed in patients with hyponatremia (26/88, 29.5% vs. 32/70, 45.7%, P = 0.036). Medication with sodium chloride, fludrocortisone, or tolvaptan was initiated in 75.4% patients with mild hyponatremia (130–134 mmol/L) and in 92.9% with moderate hyponatremia (125–129 mmol/L). At 6 months after SAH, patients treated with tolvaptan had a lower rate of poor outcome than patients who had not received tolvaptan (1/14, 7.1% vs. 25/74, 33.8%, P = 0.045). In patients with acute aneurysmal SAH and hyponatremic episodes, consequent treatment of hyponatremia prevented impaired outcome. Because administration of tolvaptan rapidly normalized serum sodium levels, this therapy seems to be a promising treatment approach.     

Non-aneurysmal non-perimesencephalic subarachnoid hemorrhage: effect of rehabilitation at short-term and in a prospective study of long-term follow-up

Background: A recently published prospective study identified an impaired outcome of patients with non-perimesencephalic (NPM) subarachnoid hemorrhage (SAH). Our objective was to analyze the long-term outcome of patients with subsequent rehabilitation after NPM SAH.

Methods: A comparison of patients with NPM SAH receiving subsequent in-patient rehabilitation was done at discharge (using the modified Rankin scale (mRS)), short-term outcome after 6 months (mRS), and prospectively using a questionnaire (short-form health survey with 36 questions (SF-36)), which was sent to 66 patients.

Results: Thirty-seven patients answered the SF-36, on average 6.3 years after ictus (range 1.5–14 years). After NPM SAH, the mRS is impaired. Patients with subsequent rehabilitation had a significant better improvement until short-term follow-up. Until long-term outcome, the psychological items were non-significantly reduced, whereas all physical items (physical functioning, role limitations because of physical health problems, bodily pain, and general health perceptions) were significantly decreased compared to the standard population. In patients with subsequent rehabilitation, all items were only non-significantly reduced. About 16% of the patients developed secondary neurological and/or psychiatric diseases.

Conclusions: The quality of life (QoL) is decreased after NPM SAH. In the long-term follow-up, a significant reduction in physical items was identified. Due to subsequent in-patient rehabilitation after NPM SAH, the impairment can be improved significantly until short-term follow-up. Whereas patients with NPM SAH had a significantly decreased QoL at long-term follow-up, for patients with rehabilitation, the QoL was only slightly (non-significantly) reduced. Therefore, patients should receive subsequent rehabilitation after NPM SAH to improve the functional short-term outcome (mRS) and long-term QoL. www.clinicaltrials.gov (Identifier No. NCT02334657).