Somatosensory evoked potentials during mild hypothermia after cardiopulmonary resuscitation.

OBJECTIVE: In patients who remain in a coma after cardiopulmonary resuscitation (CPR), the bilateral absence of cortical N20 responses of median nerve somatosensory evoked potentials (SSEP) 24 hours after admission invariably correlates with a poor neurologic outcome. Nowadays, CPR patients are treated with mild hypothermia, with simultaneously administered sedative drugs, hampering clinical neurologic assessment. We investigated whether SSEP performed during hypothermia can reliably predict a poor neurologic outcome. METHODS: Between July 2006 and April 2008, this multicenter prospective cohort study included adult comatose patients admitted after CPR and treated with induced mild hypothermia (32-34 degrees C). SSEP was performed during hypothermia, and in patients who remained comatose after rewarming, a second SSEP was performed. Neurologic outcome was assessed 30 days after admission with the Glasgow Outcome Scale. RESULTS: Seventy-seven consecutive patients were included in 2 hospitals. In 13 patients (17%), the cortical N20 response during hypothermia was bilaterally absent. In 9 of these 13 patients in whom SSEP could be repeated during normothermia, the N20 response was also absent, yielding a positive predictive value of 1.00 (95% confidence interval [CI] 0.70-1.00). All 13 patients with absent SSEP during hypothermia had a poor neurologic outcome, yielding a positive predictive value of 1.00 (95% CI 0.77-1.00). CONCLUSIONS: The results of this pilot study show that bilaterally absent cortical N20 responses of median nerve somatosensory evoked potentials performed during mild hypothermia after resuscitation can predict a poor neurologic outcome. We started a larger multicenter prospective cohort study to confirm these results.

[Prognosis for patients in a coma following cardiopulmonary resuscitation]. / Bepalen van de prognose van een coma na reanimatie.

Most patients with post-anoxic coma after resuscitation have a poor prognosis. Reliable prediction of poor outcomes (death or vegetative state after 1 month; death, vegetative state or severe disability after at least 6 months) at an early stage is important for both family members and treating physicians. Poor outcome can be predicted with 100% reliability in the first 3 days after resuscitation in about 80% of patients using pupillary and corneal reflexes and motor response from the neurological examination, cortical responses from somatosensory evoked potentials and EEG. The predictive value of a status epilepticus or serum levels of neuron-specific enolase is uncertain at this time. In contrast to poor outcomes, good neurological recovery cannot be predicted reliably at this time.

SSEPs and prognosis in postanoxic coma: only short or also long latency responses?

BACKGROUND: Short latency somatosensory evoked potential (SSEP) (N20) is a good predictor of poor outcome in postanoxic coma. It has been suggested that the long latency response (N70) may increase the sensitivity of SSEPs for predicting poor outcome. METHODS: As part of a prospective cohort study in 407 adult patients unconscious 24 hours after cardiopulmonary resuscitation (CPR), N20 was recorded 24, 48, and 72 hours after CPR, and N70 was recorded at least once in 319 patients. Poor outcome was defined as death or persistent vegetative state 1 month after CPR. RESULTS: Absent N20 had a 0% false positive test rate at all time intervals, with prevalence of poor test result varying from 37 to 48%. Addition of abnormal N70 (absent or delayed > 130 msec) with present N20 as poor test result added 21 to 28% to this prevalence, but at the cost of a false positive test rate of 4 to 15%. Good outcome could not be predicted reliably with either of the tests, as only 28% of patients with normal N20 and N70 had a good outcome. CONCLUSION: Determination of presence or absence of the N70 in patients with postanoxic coma gives additional information about the likelihood of poor outcome, but it is not precise enough to base treatment decisions solely on its absence.

Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.

OBJECTIVE: To systematically review outcomes in comatose survivors after cardiac arrest and cardiopulmonary resuscitation (CPR). METHODS: The authors analyzed studies (1966 to 2006) that explored predictors of death or unconsciousness after 1 month or unconsciousness or severe disability after 6 months. RESULTS: The authors identified four class I studies, three class II studies, and five class III studies on clinical findings and circumstances. The indicators of poor outcome after CPR are absent pupillary light response or corneal reflexes, and extensor or no motor response to pain after 3 days of observation (level A), and myoclonus status epilepticus (level B). Prognosis cannot be based on circumstances of CPR (level B) or elevated body temperature (level C). The authors identified one class I, one class II, and nine class III studies on electrophysiology. Bilateral absent cortical responses on somatosensory evoked potential studies recorded 3 days after CPR predicted poor outcome (level B). Burst suppression or generalized epileptiform discharges on EEG predicted poor outcomes but with insufficient prognostic accuracy (level C). The authors identified one class I, 11 class III, and three class IV studies on biochemical markers. Serum neuron-specific enolase higher than 33 microg/L predicted poor outcome (level B). Ten class IV studies on brain monitoring and neuroimaging did not provide data to support or refute usefulness in prognostication (level U). CONCLUSION: Pupillary light response, corneal reflexes, motor responses to pain, myoclonus status epilepticus, serum neuron-specific enolase, and somatosensory evoked potential studies can reliably assist in accurately predicting poor outcome in comatose patients after cardiopulmonary resuscitation for cardiac arrest.

Interobserver variation in the interpretation of SSEPs in anoxic-ischaemic coma.

OBJECTIVE: To study interobserver variation in the interpretation of median nerve SSEPs in patients with anoxic-ischaemic coma. METHODS: SSEPs of 56 consecutive patients with anoxic-ischaemic coma were interpreted independently by 5 experienced clinical neurophysiologists using guidelines derived from a pilot study. Interobserver agreement was expressed as kappa coefficients. RESULTS: Kappa ranged from 0.20 to 0.65 (mean 0.52, SD 0.14). Disagreement was related with noise level and failure to adhere strictly to the guidelines in 15 cases. The presence or absence of N13 and cortical peaks caused disagreement in 5 cases each. For recordings with a noise level of 0.25 microV or more, mean kappa was 0.34; for recordings with a noise level below 0.25 microV mean kappa was 0.74. CONCLUSIONS: Interobserver agreement for SSEPs in anoxic-ischaemic coma was only moderate. Since the noise level strongly influenced interobserver variation, utmost attention should be given to its reduction. If an artefact level over 0.25 microV remains, absence of N20 cannot be judged with sufficient certainty and the SSEP should be repeated at a later stage. SIGNIFICANCE: Because of its moderate interobserver agreement, great care has to be given to accurate recording and interpretation of SSEPs before using the recordings for non-treatment decisions.

Prediction of poor outcome within the first 3 days of postanoxic coma.

OBJECTIVE: To determine the optimal timing of somatosensory evoked potential (SSEP) recordings and the additional value of clinical and biochemical variables for the prediction of poor outcome in patients who remain comatose after cardiopulmonary resuscitation (CPR). METHODS: A prospective cohort study was conducted in 32 intensive care units including adult patients still unconscious 24 hours after CPR. Clinical, neurophysiologic, and biochemical variables were recorded 24, 48, and 72 hours after CPR and related to death or persisting unconsciousness after 1 month. RESULTS: Of 407 included patients, 356 (87%) had a poor outcome. In 301 of 305 patients unconscious at 72 hours, at least one SSEP was recorded, and in 136 (45%), at least one recording showed bilateral absence of N20. All these patients had a poor outcome (95% CI of false positive rate 0 to 3%), irrespective of the timing of SSEP. In the same 305 patients, neuron-specific enolase (NSE) was determined at least once in 231, and all 138 (60%) with a value >33 microg/L at any time had a poor outcome (95% CI of false positive rate 0 to 3%). The test results of SSEP and NSE overlapped only partially. The performance of all clinical tests was inferior to SSEP and NSE testing, with lower prevalences of abnormal test results and wider 95% CI of false positive rates. CONCLUSION: Poor outcome in postanoxic coma can be reliably predicted with somatosensory evoked potentials and neuron-specific enolase as early as 24 hours after cardiopulmonary resuscitation in a substantial number of patients.

Lumbar puncture and the risk of herniation: when should we first perform CT?

Death following lumbar puncture (LP) is feared by physicians. Many opinions are found in literature on the question whether computed cranial tomography (CT) should be performed before LP, to prevent herniation. These opinions are mainly based on retrospective studies and pathophysiological reasoning. In this review the difficulties in the decision whether we should perform CT before LP are discussed. It is explained that the concept of "raised intracranial pressure" is confusing, and that the less ambiguous terms "brain shift" and "raised CSF pressure" should be used instead. Brain shift is a contraindication to LP, whether CSF pressure is raised or not, and whether papilloedema is present or not. Subsequently, recommendations are offered for indications to perform CT before LP, grouped according to the safety and clinical utility of LP.

Systematic review of prediction of poor outcome in anoxic-ischaemic coma with biochemical markers of brain damage.

OBJECTIVE: To investigate whether accurate prognostic rules can be derived from the combined results of studies concerning prediction of poor prognosis in anoxic-ischaemic coma with biochemical markers of brain damage in cerebrospinal fluid (CSF) or serum. DESIGN: A meta-analysis of prognostic studies in anoxic-ischaemic coma, selected from Medline and EMBASE databases, according to predefined criteria. SUBJECTS: Twenty-eight studies, with a total of 802 unselected, consecutive patients, in which tests, sampling time and outcome measures were described unequivocally and results were described using clear cut-off values or raw data. MAIN OUTCOME MEASURES: Poor outcome, defined as death or vegetative state, versus good outcome, defined as any other outcome state. ANALYSES: The overall prognostic accuracy of these variables was expressed as the 95% CIs of the pooled false-positive test rate and the pooled positive-likelihood ratios. RESULTS: Only markers in CSF (creatine kinase isoenzyme (CKBB) >204 U/l, neuron specific enolase (NSE) >33 ng/ml, lactate dehydrogenase (LDH) >82 U/l and glutamate oxaloacetate (GOT) >62 U/l) reached a 0% false-positive rate. However, due to small sample sizes, the confidence limits were wide. The accuracy of prediction of poor outcome seemed acceptably high for CSF-CKBB (pooled false-positive rate 0% [95% CI 0-2.3%]; pooled positive-likelihood ratio 33.2 [95% CI 4.8-230.2]), but this result was based on two retrospective studies without blinding of the treating physicians for the test result. CONCLUSIONS: Because of small numbers of patients studied and methodological limitations the combined results are not sufficiently accurate to provide a solid basis for non-treatment decisions.

Prediction of poor outcome in anoxic-ischemic coma.

Most patients who are comatose a few hours after a period of global cerebral ischemia have a poor prognosis. In a series of studies selected with strict criteria for study design, the median prevalence of death or survival in a vegetative state was 78% (range, 56-90%) (Zandbergen et al., 1998). Most nonsurvivors die within the first weeks, not from brain damage, but from cardiac or pulmonary complications. Uncertainty about treatment and nontreatment decisions is therefore most critical during this period. To reduce this uncertainty among caregivers, and the related anxiety among family members, early identification of patients with such a poor prognosis is desirable.

Determinants of quantitative spectral electroencephalography in early Alzheimer's disease: cognitive function, regional cerebral blood flow, and computed tomography.

Electroencephalography (EEG) bands may have different clinical or physiological correlates at initial diagnosis of Alzheimer's disease (AD). We studied 163 consecutive patients with probable (n = 105) and possible (n = 58) AD with measurements of cognitive function (CAMCOG), regional cerebral blood flow (rCBF) with single photon emission computed tomography using technetium-99m-labeled hexamethylpropylene amine oxime, and computed tomography (CT). Lower CAMCOG scores were significantly and most strongly associated with lower parieto-occipital and fronto-central alpha power. In a separate analysis of cognitive domains, disturbances in language, praxis, attention, and abstraction were also significantly and most consistently related to decrease in alpha power. Presence of cortical atrophy as measured on CT showed some statistically significant relations with EEG bands, but these associations were not consistent. Lower temporal and parietal rCBF were significantly related to lower parieto-occipital alpha activity. Presence of leukoaraiosis was significantly associated with lower beta values, but also with higher absolute theta and delta activity. The results suggest that alpha on EEG is most closely linked to cognitive function and rCBF, while beta and theta activity more likely reflect lower cortical or subcortical changes. Our study thus provides evidence that the EEG bands reflect differential pathophysiologic changes in AD.

[Vascular brain damage: an important and recognizable cause of cognitive and behavioral disorders]. / Vasculaire hersenschade: een belangrijke en te herkennen oorzaak van cognitieve stoornissen en gedragsstoornissen.

Four patients presented symptoms of a dementia syndrome. A man aged 67 showed gradual aggravation of disorders of memory and gait, as well as subcortical infarctions. A man aged 65 had disorders of concentration non compatible with the infarctions on the MRI scan, which disappeared after discontinuation of use of flunarizine. A woman aged 55 and a man aged 52 had changes of character and infarctions in the frontal lobe. Vascular dementia is, contrary to what most criteria suggest, often a subcortical syndrome. The relationship between cerebrovascular pathology on CT and MRI scans and cognitive and behavioural disorders is often hard to establish. If the criteria for vascular dementia are applied blindly, other causes of the subcortical dementia syndrome can be missed. The present criteria offer almost no room for detecting the subtle cognitive and behavioural disorders of cerebrovascular pathology. It is important to recognize the early changes of a threatened brain, because treatment and prevention might be effective in preventing further damage.

Measurement of temporal regional cerebral perfusion with single-photon emission tomography predicts rate of decline in language function and survival in early Alzheimer's disease.

We determined the relationship between regional cerebral blood flow (rCBF) measured with single-photon emission tomography (SPET) and decline in cognitive function and survival in Alzheimer's disease. In a prospective follow-up study, 69 consecutively referred patients with early probable Alzheimer's disease (NINCDS/ADRDA criteria) underwent SPET performed at the time of initial diagnosis using technetium-99m-labelled hexamethylpropylene amine oxime. Neuropsychological function was assessed at baseline and after 6 months and survival data were available on all patients, extending to 5.5 years of follow-up. Lower left temporal (P<0.01) and lower left parietal (P<0.01) rCBF were statistically significantly related to decline in language function after 6 months. The association between left temporal rCBF and survival was also statistically significant (P<0.05) using Cox proportional hazards regression analysis. Performing analysis with quartiles of the distribution, we found a threshold effect for low left temporal rCBF (rCBF<73.7%, P<0. 01) and high risk of mortality. In this lowest quartile, median survival time was 2.7 years (follow-up to 5.2 years), compared with 4.4 years in the other quartiles (follow-up to 5.5 years). Kaplan-Meier survival curves showed statistically significant (P<0. 05, log rank test) survival curves for the lowest versus other quartiles of left temporal rCBF. All results were unaffected by adjustment for age, sex, dementia severity, duration of symptoms, education and ratings of local cortical atrophy. We conclude that left temporal rCBF predicts decline in language function and survival in patients with early probable Alzheimer's disease, with a threshold effect of low rCBF and high risk of mortality.

Systematic review of early prediction of poor outcome in anoxic-ischaemic coma.

BACKGROUND: Studies to assess the prognostic value of early neurological and neurophysiological findings in patients with anoxic-ischaemic coma have not led to precise, generally accepted, prognostic rules. We did a systematic review of the relevant literature to assess whether such rules could be derived from the combined results of these studies. METHODS: From Medline and Embase databases we selected studies concerning patients older than 10 years with anoxic-ischaemic coma in which findings from early neurological examination, electroencephalogram (EEG), or somatosensory evoked potentials (SSEP) were related to poor outcome--defined as death or survival in a vegetative state. We selected variables with a specificity of 100% for poor outcome in all studies, and expressed the overall prognostic accuracy of these variables as pooled positive-likelihood ratios and as 95% CIs of the pooled false-positive test rates. FINDINGS: In 33 studies, 14 prognostic variables were studied, three of which had a specificity of 100%: absence of pupillary light reflexes on day 3 (pooled positive-likelihood ratio 10.5 [95% CI 2.1-52.4]; 95% CI pooled false-positive test rate 0-11.9%); absent motor response to pain on day 3 (16.8 [3.4-84.1]; 0-6.7%); and bilateral absence of early cortical SSEP within the first week (12.0 [5.3-27.6]; 0-2.0%). EEG recordings with an isoelectric or burst-suppression pattern had a specificity of 100% in five of six relevant studies (pooled positive-likelihood ratio 9.0 [2.5-33.1]; 95%CI pooled false-positive test rate 0.2-5.9%). These characteristics were present in 19%, 31%, 33%, and 33% of pooled patient populations, respectively. For the 11 SSEP studies, results did not significantly differ between studies in which the treating physicians were or were not masked from the test result, prospective and retrospective studies, studies with short and long follow-up periods, and studies with high or low overall poor outcome. INTERPRETATION: SSEP has the smallest CI of its pooled positive-likelihood ratio and its pooled false-positive test rate. Because evoked potentials are also the least susceptible to metabolic changes and drugs, recording of SSEP is the most useful method to predict poor outcome.

Predicting survival in patients with early Alzheimer's disease.

We investigated whether an index based on clinical features, electroencephalogram and computed tomography is useful to predict survival in early Alzheimer's disease. One hundred and sixty-three consecutively referred patients to an outpatient memory clinic and first diagnosed with Alzheimer's disease (105 'probable' and 58 'possible', NINCDS-ADRDA criteria) were studied and outcome measure was death. Cox proportional hazards regression analysis and Kaplan-Meier survival curves were used to investigate relations between baseline parameters and survival. Eighty-four patients (51. 5%) died during the follow-up period that extended to 5.8 years, with a median duration of survival after entry of 4.3 years. Baseline factors that were statistically significant and independently related to increased risk of mortality were high age, male sex, poor cognitive function as measured with the CAMCOG, low alpha and beta power on electroencephalogram, and temporoparietal atrophy on computed tomography scan. These results were independent of the diagnosis probable or possible Alzheimer's disease. Based on the coefficients from the regression equation, we computed a survival index for each patient and we constructed three groups according to tertiles of this index. After 5.2 years of follow-up, survival curves showed a low mortality group with 81.7% patients alive (median survival at least 5.7 years), an intermediate mortality group with 35.9% patients alive (median survival 3.8 years), and a high mortality group with no patients alive (median survival 2.3 years). Log rank tests were statistically significant for comparisons between all three groups. We conclude that an overall index combining demographic, cognitive, electroencephalogram and computed tomography features is a strong predictor of survival in early Alzheimer's disease.

Quantitative spectral electroencephalography in predicting survival in patients with early Alzheimer disease.

OBJECTIVE: To determine whether measures of quantitative spectral electroencephalography (EEG) can predict survival in patients with early Alzheimer disease. DESIGN: Prospective cohort study; median duration of follow-up was 4.4 years in survivors and 2.6 years in nonsurvivors. Cox proportional hazards models, with adjustment for age and sex were used to estimate relationships between EEG measures and survival. Log relative percentage values of EEG bands were used as predictors. SETTING: Outpatient university memory clinic. PARTICIPANTS: One hundred one consecutively referred patients with early probable Alzheimer disease according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria were studied with EEG at the time of diagnosis. The mean age of the patients was 79.2 years, which was higher than in previous EEG studies. MAIN OUTCOME MEASURE: Mortality. RESULTS: Fifty-one patients (50.5%) died during follow-up, with a median survival time in all patients of 4.1 years. The following EEG variables were significantly associated with increased risk of mortality: from parieto-occipital leads, higher theta (hazard ratio, 2.05; 95% confidence interval, 1.15-3.66; P<.05), lower alpha (hazard ratio, 0.43; 95% confidence interval, 0.25-0.76; P<.01), and lower beta (hazard ratio, 0.38; 95% confidence interval, 0.22-0.68; P<.001) activity; and from frontocentral leads, higher theta activity (hazard ratio, 2.07; 95% confidence interval, 1.17-3.66; P<.05). Stepwise Cox regression analysis showed that loss of parieto-occipital beta (P<.01) and alpha (P<.05) power were independent and significant predictors of mortality. Both beta (12.6-35.4 Hz) and alpha (7.5-12.5 Hz) activity remained significantly associated with mortality after adjustment for education, dementia severity, symptom duration, level of cognitive function, presence of extrapyramidal symptoms or hallucinations, presence of vascular risk factors, and presence of leukoaraiosis or local cortical atrophy. CONCLUSIONS: Decreases of beta and alpha activity on quantitative spectral EEG are independent predictors of mortality in patients with early Alzheimer disease. In the clinical context, the use of EEG technology for prediction of survival in individual patients remains to be determined.