Sleep in neurointensive care patients, and patients after brain tumor surgery.

BACKGROUND: Severely brain injured patients treated in the neuro intensive care unit (NICU) are usually sedated. Sedation may affect not only the ability to sleep, but also the EEG rhythms used to identify sleep. AIM: The aims were: To study if sleep patterns could be identified in the severely brain injured and sedated patients in the NICUTo study if sleep patterns could be identified in patients the night after brain tumor surgery in the neurointermediate care unit (NIMCU)To search for risk factors for not being able to sleep after brain tumor surgery. STUDY DESIGN: Two populations were included; one with patients affected by severe brain injury and one with patients who had undergone planned brain tumor surgery. This was a quantitative observational study using EEG. Eligible neurointensive care patients for this study had to be suffering from a neurosurgical condition (for example subarachnoid haemorrhage, acute subdural hematoma, intracerebral haemorrhage and meningitis), have affected consciousness and age over 18 years. Thirty-seven patients were included from NICU. Ninety-eight patients, with a suspected glioma (WHO grade II-IV) planned for surgery were also included. RESULTS: Neuro intensive care patients, sedated and treated in ventilator, showed no EEG sleep patterns at all. After brain tumor surgery, sleep occurred in 74% of the patients, despite frequent wake-up tests. The patients with sleep patterns were on average 8 years younger, p = 0.03. CONCLUSIONS: Patients with severe brain injury are at risk of having no sleep when treated at the NICU, whereas after brain tumor surgery, sleep occurs in three-fourths of the patients. Further studies and new methods are warranted to identify sleep and investigate how the loss of sleep affects these patients and how sleep disturbances can be managed.

Use of Antiepileptic Drugs and Risk of Prostate Cancer: A Nationwide Case-Control Study in Prostate Cancer Data Base Sweden.

An inverse association between use of antiepileptic drugs (AEDs) and prostate cancer (PCa) has been suggested, putatively due to the histone deacetylases inhibitory (HDACi) properties of the AEDs. In a case-control study in Prostate Cancer data Base Sweden (PCBaSe), PCa cases diagnosed between 2014 and 2016 were matched to five controls by year of birth and county of residence. AED prescriptions were identified in the Prescribed Drug Registry. Odds ratios (ORs) and 95% confidence intervals for risk of PCa were estimated using multivariable conditional logistic regression, adjusted for civil status, education level, Charlson comorbidity index, number of outpatient visits, and cumulative duration of hospital stay. Dose responses in different PCa risk categories and HDACi properties of specific AED substances were further explored. 1738/31591 (5.5%) cases and 9674/156802 (6.2%) controls had been exposed to AED. Overall, users of any AED had a reduced risk of PCa as compared to nonusers (OR: 0.92; 95% CI: 0.87-0.97) which was attenuated by adjustment to healthcare utilisation. A reduced risk was also observed in all models for high-risk or metastatic PCa in AED users compared to nonusers (OR: 0.89; 95% CI: 0.81-0.97). No significant findings were observed for dose response or HDACi analyses. Our findings suggest a weak inverse association between AED use and PCa risk, which was attenuated by adjustment for healthcare utilisation. Moreover, our study showed no consistent dose-response pattern and no support for a stronger reduction related to HDAC inhibition. Further studies focusing on advanced PCa and PCa treatments are needed to better analyse the association between use of AED and risk of PCa.

Time course of neurological deficits after surgery for primary brain tumours.

BACKGROUND: The postoperative course after surgery for primary brain tumours can be difficult to predict. We examined the time course of postoperative neurological deficits and analysed possible predisposing factors. METHOD: Hundred adults with a radiological suspicion of low- or high-grade glioma were prospectively included and the postoperative course analysed. Possible predictors of postoperative neurological deterioration were evaluated. RESULTS: New postoperative neurologic deficits occurred in 37% of the patients, and in 4%, there were worsening of a preoperative deficit. In 78%, the deficits occurred directly after surgery. The probable cause of deterioration was EEG-verified seizures in 7, ischemic lesion in 5 and both in 1, resection of eloquent tissue in 6, resection close to eloquent tissue including SMA in 11 and postoperative haematoma in 1 patient. Seizures were the main cause of delayed neurological deterioration. Two-thirds of patients with postoperative deterioration showed complete regression of the deficits, and in 6% of all patients, there was a slight disturbance of the function after 3 months. Remaining deficits were found in 6% and only in patients with preoperative neurological deficits and high-grade tumours with mainly eloquent locations. Eloquent tumour location was a predictor of postoperative neurological deterioration and preoperative neurological deficits of remaining deficits. CONCLUSIONS: Postoperative neurological deficits occurred in 41% and remained in 6% of patients. Remaining deficits were found in patients with preoperative neurological deficits and high-grade tumours with mainly eloquent locations. Eloquent tumour location was a predictor of neurological deterioration and preoperative neurological deficits of remaining deficits.

Continuous EEG monitoring after brain tumor surgery.

BACKGROUND: Prolonged seizures generate cerebral hypoxia and increased intracranial pressure, resulting in an increased risk of neurological deterioration, increased long-term morbidity, and shorter survival. Seizures should be recognized early and treated promptly. The aim of the study was to investigate the occurrence of postoperative seizures in patients undergoing craniotomy for primary brain tumors and to determine if non-convulsive seizures could explain some of the postoperative neurological deterioration that may occur after surgery. METHODS: A single-center prospective study of 100 patients with suspected glioma. Participants were studied with EEG and video recording for at least 24 h after surgery. RESULTS: Seven patients (7%) displayed seizure activity on EEG recording within 24 h after surgery and another two patients (2%) developed late seizures. One of the patients with early seizures also developed late seizures. In five patients (5%), there were non-convulsive seizures. Four of these patients had a combination of clinically overt and non-convulsive seizures and in one patient, all seizures were non-convulsive. The non-convulsive seizures accounted for the majority of total seizure time in those patients. Non-convulsive seizures could not explain six cases of unexpected postoperative neurological deterioration. Postoperative ischemic lesions were more common in patients with early postoperative seizures. CONCLUSIONS: Early seizures, including non-convulsive, occurred in 7% of our patients. Within this group, non-convulsive seizure activity had longer durations than clinically overt seizures, but only 1% of patients had exclusively non-convulsive seizures. Seizures were not associated with unexpected neurological deterioration.

Electroencephalographic Patterns During Common Nursing Interventions in Neurointensive Care: A Descriptive Pilot Study.

BACKGROUND: Many patients with neurological insults requiring neurointensive care have an increased risk of acute symptomatic seizures. Various nursing interventions performed when caring for these patients may elicit pathological cerebral electrical activity including seizures and stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs). The aim was to explore changes in electroencephalogram (EEG) due to neurointensive care nursing interventions. METHODS: A convenience sample was recruited between November 2015 and April 2016, consisting of 12 adult patients with impaired consciousness due to a neurosurgical condition. Continuous EEG and simultaneous video recordings of nursing interventions were collected 48 continuous hours for each patient. Two analysts categorized the video recordings for common nursing interventions, and a neurophysiologist analyzed the EEGs. RESULTS: In total, 976 nursing interventions were observed. Epileptiform activity was observed in 4 patients (33%), during 1 nursing intervention episode each (0.4%). The 4 observed episodes of epileptiform activity occurred during multiple simultaneous nursing interventions (n = 3) and hygienic interventions (n = 1). Stimulus-induced rhythmic, periodic, or ictal discharges were observed in 1 patient (8%), in 1 single nursing intervention (0.1%). The observed SIRPIDs occurred during repositioning of the patient. All patients had muscle artifacts, during 353 nursing interventions (36.3%). The duration of nursing interventions was longer for those with simultaneous muscle artifacts (median, 116 seconds) than those without muscle artifacts, epileptiform activity, or SIRPIDs (median, 89.0 seconds). With regard to epileptiform activity and SIRPIDs, the median durations of the nursing interventions were 1158 and 289 seconds, respectively. CONCLUSION: The results of this pilot study indicate that muscle artifacts seem prevalent during nursing interventions and may be a sign of stress. Nurses should be aware of the risk of inducing stress by performing regular nursing interventions in daily practice, consider shorter or fewer interventions at a time in sensitive patients, and administer sedation accordingly. Considering that this was a pilot study, more research that investigates correlations between EEG patterns and nursing interventions in larger samples is needed.

Diagnostic Utility of Repetitive Nerve Stimulation in a Large Cohort of Patients With Myasthenia Gravis.

PURPOSE: Optimizing the diagnostic utility of repetitive nerve stimulation in myasthenia gravis (MG) may include tailoring the examination to clinical phenotype. Therefore, we analyzed all available repetitive nerve stimulation parameters in a large cohort of patients with confirmed MG diagnosis. METHODS: All repetitive nerve stimulation examinations at the Uppsala University Hospital rendering an MG diagnosis during 1996 to 2014 were analyzed. The deltoid, trapezius, anconeus, nasalis, abductor digiti quinti, and frontalis muscles were examined. RESULTS: Two hundred one patients with MG were diagnosed. Abnormal amplitude decrement was found in 54% of patients with ocular MG, 77% of patients with predominantly bulbar fatigue, and in 83% of patients with predominantly limb fatigue. The deltoid muscle had the highest sensitivity in all MG subtypes, with a mean of 77% sensitivity in all clinical subtypes, and the most pronounced decrement for amplitude (P = 0.0002) and area (P < 0.0001). Technical issues were rare. CONCLUSIONS: These data contribute to further optimization of repetitive nerve stimulation strategies regarding muscle selection and technical performance in the electrodiagnostic workup of MG.

Vitamin D deficiency in patients with primary immune-mediated peripheral neuropathies.

PURPOSE: T cells are important in the immunopathology of immune-mediated peripheral neuropathies (PNP) and activated vitamin D regulates the immune response through increasing the amount of regulatory T cells. An association between vitamin D deficiency and polyneuropathy has been stipulated; hence we assessed whether patients with primary immune-mediated PNP have low vitamin D [25(OH)D] levels. METHODS: Plasma levels of 25(OH)D were analyzed in 26 patients with primary immune-mediated PNP, 50 healthy matched blood donors and 24 patients with motor neuron disease (MND). INCAT score was assessed in patients with Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy. ALSFRS-R score was applied to MND patients and the modified Rankin (mRankin) scale compared disability among patient groups. RESULTS: Mean 25(OH)D value in PNP patients was 40 ± 16 nmol/l, compared to 69 ± 21 nmol/l in healthy blood donors (p<0.001). MND patients had a higher mean 25(OH)D than PNP patients (59 ± 26 nmol/L; p=0.006) and comparable levels to healthy blood donors (p=0.15). Mean 25(OH)D value was not higher in PNP patients with pre-existing vitamin D3 supplementation of 800 IU/day (N=6; 35 ± 18 nmol/L) than in unsupplemented PNP patients (42 ± 16 nmol). INCAT score ranged from 0 to 10 (mean 3.5) and ALSFRS-R ranged from 11 to 44 (mean 31). mRankin score was more severe in MND patients (mean 3.5) compared to PNP patients (mean 2.1). CONCLUSIONS: All patients with primary immune-mediated PNP were diagnosed with vitamin D deficiency and they had significantly lower 25(OH)D values than healthy control persons and MND patients. We suggest monitoring of vitamin D status in patients with autoimmune PNP, since immune cells are responsive to the ameliorative effects of vitamin D.

Alterations in muscle proteome of patients diagnosed with amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by progressive muscle paralysis. Currently clinical tools for ALS diagnostics do not perform well enough and their improvement is needed. The objective of this study was to identify specific protein alterations related to the development of ALS using tiny muscle biopsies. We applied a shotgun proteomics and quantitative dimethyl labeling in order to analyze the global changes in human skeletal muscle proteome of ALS versus healthy subjects for the first time. 235 proteins were quantified and 11 proteins were found significantly regulated in ALS muscles. These proteins are involved in muscle development and contraction, metabolic processes, enzyme activity, regulation of apoptosis and transport activity. In order to eliminate a risk to confuse ALS with other denervations, muscle biopsies of patients with postpolio syndrome and Charcot-Marie-Tooth disease (negative controls) were compared to those of ALS and controls. Only few proteins significantly regulated in ALS patients compared to controls were affected differently in negative controls. These proteins (BTB and kelch domain-containing protein 10, myosin light chain 3, glycogen debranching enzyme, transitional endoplasmic reticulum ATPase), individually or as a panel, could be selected for estimation of ALS diagnosis and development. BIOLOGICAL SIGNIFICANCE: ALS is a devastating neurodegenerative disease, and luckily, very rare: only one to two people out of 100,000 develop ALS yearly. This fact, however, makes studies of ALS very challenging since it is very difficult to collect the representative set of clinical samples and this may take up to several years. In this study we collected the muscle biopsies from 12 ALS patients and compared the ALS muscle proteome against the one from control subjects. We suggested the efficient method for such comprehensive quantitative analysis by LC-MS and performed it for the first time using human ALS material. This gel- and antibody-free method can be widely applied for muscle proteome studies and has been used by us for revealing of the specific protein alterations associated with ALS.

Temperature disturbances in traumatic brain injury: relationship to secondary insults, barbiturate treatment and outcome.

OBJECTIVES: To describe the occurrence of spontaneous hyper- and hypothermia in patients with traumatic brain injury using a computerized data collecting system, to show how temperature correlates with other secondary insults, to describe how temperature affects outcome and to show how barbiturate treatment influences those analyses. METHODS: Patients with > or = 54 hours of valid monitoring within the first 120 hours after trauma (one value/min) for temperature, intracranial pressure, cerebral perfusion pressure, systolic blood pressure, mean blood pressure and heart rate were included. Correlation analyses were performed between temperature and other secondary insult variables. The non-linear relationship between temperature and outcome (measured by Glasgow outcome scale 6 months post-trauma) was illustrated using a neural network. RESULTS: Of the 53 patients, 44 experienced hyperthermia (>38 degrees C) and 29 experienced hypothermia (<36 degrees C). Hyperthermia correlated with occurrence of high blood pressure and high CPP. In individuals, hyperthermia also correlated with ICP and tachycardia. There was a trend towards better outcome for patients with normal temperature than those with hyper- or hypothermia (favorable outcome 64% versus 29 and 33% respectively). When patients treated with barbiturates were excluded, 60% showed favorable outcome in the hypothermia group as well. Barbiturate treatment also confounded analyses regarding temperature and other secondary insults. DISCUSSION: Patients with hyperthermia, hypertension, high CPP and tachycardia may suffer from a hyperdynamic state. This may worsen outcome and hence clinical awareness is important. Barbiturate treatment confounds several analyses which have not been shown before. We recommend those patients to be analysed separately in future studies.

Cerebral perfusion pressure between 50 and 60 mm Hg may be beneficial in head-injured patients: a computerized secondary insult monitoring study.

OBJECTIVE: To describe the occurrence of secondary insults using a computerized monitoring data collecting system and to investigate their relationship to outcome when the neurointensive care was dedicated to avoiding secondary insults. METHODS: Patients 16 to 79 years old admitted to the neurointensive care unit between August 1998 and December 2002 with traumatic brain injury and 54 hours or more of valid monitoring within the first 120 hours after trauma (one value/min) were included. Monitoring of intracranial pressure (ICP), cerebral perfusion pressure (CPP), systolic blood pressure (BPs), and mean blood pressure (BPm) was required, and insult levels were defined (ICP >25/>35, BPs <100/<90/>160/>180, BPm <80/<70/>110/>120, and CPP <60/<50/>70/>80 mm Hg). Insults were quantified as proportion of valid monitoring time at the insult level. Logistic regression analyses were performed with admission and secondary insult variables as explanatory variables and favorable outcome as dependent variable. RESULTS: Eighty-one patients, 63 men and 18 women, with a mean age of 43.0 years, fulfilled the inclusion criteria. Seventy-two patients (89%) had Glasgow Coma Scale scores of 8 or less. Thirty-one patients (38%) had diffuse injury, and 50 (62%) had mass lesions. Mean Injury Severity Score was 26.6. After 6 months, 54% of the patients had achieved a favorable outcome. Most patients spent 5% or less of the monitoring time at the insult level except for CPP greater than 70 mm Hg. Low age, high Glasgow Coma Scale motor score, low Injury Severity Score, and CPP less than 60 mm Hg insults were significant predictors of favorable outcome in the final multiple logistic regression model. CONCLUSION: Overall, the secondary insults were rare, except for high CPP. The results suggest that patients with traumatic brain injury might benefit from a CPP slightly less than 60 mm Hg.

Pressure reactivity as a guide in the treatment of cerebral perfusion pressure in patients with brain trauma.

OBJECT: The aim of this study was to compare the effects of two different treatment protocols on physiological characteristics and outcome in patients with brain trauma. One protocol was primarily oriented toward reducing intracranial pressure (ICP), and the other primarily on maintaining cerebral perfusion pressure (CPP). METHODS: A series of 67 patients in Uppsala were treated according to a protocol aimed at keeping ICP less than 20 mm Hg and, as a secondary target, CPP at approximately 60 mm Hg. Another series of 64 patients in Edinburgh were treated according to a protocol aimed primarily at maintaining CPP greater than 70 mm Hg and, secondarily, ICP less than 25 mm Hg for the first 24 hours and 30 mm Hg subsequently. The ICP and CPP insults were assessed as the percentage of monitoring time that ICP was greater than or equal to 20 mm Hg and CPP less than 60 mm Hg, respectively. Pressure reactivity in each patient was assessed based on the slope of the regression line relating mean arterial blood pressure (MABP) to ICP. Outcome was analyzed at 6 months according to the Glasgow Outcome Scale (GOS). The prognostic value of secondary insults and pressure reactivity was determined using linear methods and a neural network. In patients treated according to the CPP-oriented protocol, even short durations of CPP insults were strong predictors of death. In patients treated according to the ICP-oriented protocol, even long durations of CPP insult-mostly in the range of 50 to 60 mm Hg--were significant predictors of favorable outcome (GOS Score 4 or 5). Among those who had undergone ICP-oriented treatment, pressure-passive patients (MABP/ICP slope > or = 0.13) had a better outcome. Among those who had undergone CPP-oriented treatment, the more pressure-active (MABP/ICP slope < 0.13) patients had a better outcome. CONCLUSION: Based on data from this study, the authors concluded that ICP-oriented therapy should be used in patients whose slope of the MABP/ICP regression line is at least 0.13, that is, in pressure-passive patients. If the slope is less than 0.13, then hypertensive CPP therapy is likely to produce a better outcome.

Outcome after traumatic brain injury improved by an organized secondary insult program and standardized neurointensive care.

OBJECTIVE: To evaluate today's refined neurosurgical intensive care of patients with traumatic brain injury after implementation of an organized secondary insult program focused on the importance of avoiding secondary brain damage together with a standardized treatment protocol system. DESIGN: Clinical observational patient study. PATIENTS: A total of 154 patients 16-79 yrs of age with acute head trauma and pathologic computed tomographic findings treated between 1996 and 1997. SETTING: Neurointensive care unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Good recovery was obtained in 44% of the patients, moderate disability in 35%, severe disability in 16%, and no patient remained in a vegetative state. Six percent of the patients died, but only two of these patients (1.3%) died as direct result of their head injury. When the results for patients with Glasgow Coma Scale motor scores of >or=4 were compared with the periods 1980-1981 (preneurosurgical intensive care) and 1987-1988 (basic neurosurgical intensive care), mortality had decreased from 40% in the first period to 27% in the second period and to 2.8% in the present series. Favorable outcome in the same group of patients had increased steadily from 40% in the first period, to 68% in the second period, and finally, to 84% in the present series. CONCLUSIONS: The main observation in this hospital series of traumatic brain injury patients was a low rate of death directly caused by head injury and a high rate of favorable outcome. The comparison of patients with Glasgow Coma Scale motor scores of >or=4 with the previously reported results from the same unit indicate that substantial improvement in outcome has been achieved.