Brain Stress Test for Assessing Risk for Hemodynamic Stroke.

BACKGROUND: In patients with intracranial steno-occlusive disease (SOD), the risk of hemodynamic stroke depends on the poststenotic vasodilatory reserve. Cerebrovascular reactivity (CVR) is a test for vasodilatory reserve. We tested for vasodilatory reserve by using PETCO2 as the stressor, and Blood Oxygen Level Dependent (BOLD) MRI as a surrogate of blood flow. We correlate the CVR to the incidence of stroke after a 1-year follow-up in patients with symptomatic intracranial SOD. METHODS: In this retrospective study, 100 consecutive patients with symptomatic intracranial SOD that had undergone CVR testing were identified. CVR was measured as % BOLD MR signal intensity/mmHg PETCO2. All patients with normal CVR were treated with optimal medical therapy; those with abnormal CVR were offered revascularization where feasible. We determined the incidence of stroke at 1 year. RESULTS: 83 patients were included in the study. CVR was normal in 14 patients and impaired in 69 patients ipsilateral to the lesion. Of these, 53 underwent surgical revascularization. CVR and symptoms improved in 86% of the latter. The overall incidence of stroke was 4.8 % (4/83). All strokes occurred in patients with impaired CVR (4/69; 2/53 in the surgical group, all in the nonrevascularized hemisphere), and none in patients with normal CVR (0/14). CONCLUSION: Our study confirms that CO2-BOLD MRI CVR can be used as a brain stress test for the assessment of cerebrovascular reserve. Impaired CVR is associated with a higher incidence of stroke and normal CVR despite significant stenosis is associated with a low risk for stroke.

Predictor role of heart rate variability in subarachnoid hemorrhage: A systematic review.

Background- Subarachnoid hemorrhage (SAH) is one of the most devastating diseases with a high rate of morbidity and mortality. The heart rate variability (HRV) is a non-invasive method of monitoring various components of the autonomic nervous system activity that can be utilized to delineate autonomic dysfunctions associated with various physiological and pathological conditions. The reliability of HRV as a predictor of clinical outcome in aneurysmal subarachnoid hemorrhage (aSAH) is not yet well investigated in literature. Methods- A systematic review and in depth analysis of 10 articles on early HRV changes in SAH patients was performed. Results- This systematic review demonstrates a correlation between early changes in HRV indices (time and frequency domain) and the development of neuro-cardiogenic complications and poor neurologic outcome in patients with SAH. Conclusions- A correlation between absolute values or changes of the LF/HF ratio and neurologic and cardiovascular complications was found in multiple studies. Because of significant limitations of included studies, a large prospective study with proper handling of confounders is needed to generate high-quality recommendations regarding HRV as a predictor of post SAH complications and poor neurologic outcome.

Same-day discharge after craniotomy for tumor resection: a retrospective observational single-center study of 630 patients.

OBJECTIVE: Modern neurosurgical developments enable minimally invasive surgery with shorter operation times, faster recovery, and earlier hospital discharge. These in combination with Enhanced Recovery After Surgery (ERAS) protocols have the potential to safely shift craniotomy for tumor resection to the ambulatory setting in selected patients. The aim of this retrospective observational single-center study was to assess the success rate of planned same-day discharge from hospital in patients undergoing craniotomy for supratentorial brain tumor resection under general anesthesia or awake craniotomy as well as to explore potential associations with anesthesia techniques, complications, and readmission rates. METHODS: A retrospective analysis of all patients scheduled for same-day discharge after supratentorial craniotomy for tumor resection over 25 years (1996-2021) was performed. Patients were identified for same-day discharge based on specific inclusion and exclusion criteria. Data collected included patient demographics, comorbidities, anesthetic data, perioperative complications, and patient dispositions. Data are presented descriptively. RESULTS: A total of 630 patients (mean age 50.9 years; 311 females, 319 males) scheduled for same-day discharge were analyzed. Patients underwent either awake craniotomy (AC; n = 491) or craniotomy under general anesthesia (GA; n = 139). Successful preplanned same-day discharge occurred in 571 (90.6%). Failed same-day discharge happened in 59 patients (GA, n = 14; AC, n = 45). Reasons for failed discharge included the following: new neurological deficit (n = 28); presence of seizure (n = 8); postoperative nausea and vomiting (PONV; n = 12); excessive headache (n = 5); and/or social factors (n = 10). Nine patients (1.4%) (GA, n = 0; AC, n = 9) with same-day discharge required readmission to hospital within the first 24 hours after discharge. Reasons for readmission included headache (n = 2), seizure (n = 4), neurological deficit (n = 3), and/or PONV (n = 1); all patients were successfully discharged from hospital after 1 day with no need for reoperation. CONCLUSIONS: This retrospective, single-center analysis shows that same-day discharge after craniotomy can be safe in carefully selected patients after both GA and AC for tumor resection. Multidisciplinary involvement (surgeons, anesthesiologists, nurses, and other allied health professionals) optimizes success of same-day craniotomy programs. Future optimization of analgesia and prevention of PONV has the potential to increase the success rate.

Assessment of Cerebrovascular Reactivity Using CO2 -BOLD MRI: A 15-Year, Single Center Experience.

BACKGROUND: Cerebrovascular reactivity (CVR) is a measure of the change in cerebral blood flow (CBF) in response to a vasoactive challenge. It is a useful indicator of the brain's vascular health. PURPOSE: To evaluate the factors that influence successful and unsuccessful CVR examinations using precise arterial and end-tidal partial pressure of CO2 control during blood oxygen level-dependent (BOLD) MRI. STUDY TYPE: Retrospective. SUBJECTS: Patients that underwent a CVR between October 2005 and May 2021 were studied (total of 1162 CVR examinations). The mean (±SD) age was 46.1 (±18.8) years, and 352 patients (43%) were female. FIELD STRENGTH/SEQUENCE: 3 T; T1-weighted images, T2*-weighed two-dimensional gradient-echo sequence with standard echo-planar readout. ASSESSMENT: Measurements were obtained following precise hypercapnic stimuli using BOLD MRI as a surrogate of CBF. Successful CVR examinations were defined as those where: 1) patients were able to complete CVR testing, and 2) a clinically useful CVR map was generated. Unsuccessful examinations were defined as those where patients were not able to complete the CVR examination or the CVR maps were judged to be unreliable due to, for example, excessive head motion, and poor PET CO2 targeting. STATISTICAL ANALYSIS: Successful and unsuccessful CVR examinations between hypercapnic stimuli, and between different patterns of stimulus were compared with Chi-Square tests. Interobserver variability was determined by using the intraclass correlation coefficient (P < 0.05 is significant). RESULTS: In total 1115 CVR tests in 662 patients were included in the final analysis. The success rate of generating CVR maps was 90.8% (1012 of 1115). Among the different hypercapnic stimuli, those containing a step plus a ramp protocol was the most successful (95.18%). Among the unsuccessful examinations (9.23%), most were patient related (89.3%), the most common of which was difficulty breathing. DATA CONCLUSION: CO2 -BOLD MRI CVR studies are well tolerated with a high success rate. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 3.

Emergence Patterns from General Anesthesia after Epilepsy Surgery: An Observational Pilot Study.

Objective Emergence from anesthesia starts from the limbic structures and then spreads outwards to brainstem, reticular activating systems, and then to the cortex. Epilepsy surgery often involves resection of limbic structures and hence may disrupt the pattern of emergence. The aim of this study was to explore the pattern of emergence from anesthesia following epilepsy surgery and to determine associated variables affecting the emergence pattern. Setting and Design Tertiary care center, prospective observational study. Materials and Methods We conducted a prospective observation pilot study on adult patients undergoing anterior temporal lobectomy and amygdalohippocampectomy for epilepsy. Anesthesia management was standardized in all patients, and they were allowed to wake up with "no touch" technique. Primary outcome of the study was the pattern of emergence (normal emergence, agitated emergence, or slow emergence) from anesthesia. Secondary outcomes were to explore the differences in preoperative neuropsychological profile and limbic structure volumes between the different patterns of emergence. Quantitative variables were analyzed using Student's t -test. Qualitative variables were analyzed using chi-square test. Results Twenty-nine patients completed the study: 9 patients (31%) had agitated emergence, and 20 patients had normal emergence. Among the agitated emergence, 2 patients had Riker scale of 7 indicating violent emergence. Patient demographics, anesthetic used, neuropsychological profile, and limbic structure volumes were similar between normal emergence and agitated emergence groups. However, two patients who had severe agitation (Riker scale of 7) had the lowest intelligence quotient. Conclusion Our pilot study showed that emergence agitation is not uncommon in patients undergoing epilepsy surgery. However, due to smaller sample size, the role of preoperative neuropsychologic profile and hippocampal volumes in predicting the pattern of emergence is inconclusive.

A dual-center validation of the PIRAMD scoring system for assessing the severity of ischemic Moyamoya disease.

Background: Prior Infarcts, Reactivity, and Angiography in Moyamoya Disease (PIRAMD) is a recently proposed imaging-based scoring system that incorporates the severity of disease and its impact on parenchymal hemodynamics in order to better support clinical management and evaluate response to intervention. In particular, PIRAMD may have merit in identifying symptomatic patients that may benefit most from revascularization. Our aim was to validate the PIRAMD scoring system. Methods: Patients with ischemic Moyamoya disease, who underwent catheter angiographic [modified Suzuki Score (mSS) and collateralization status], morphological MRI and a parenchymal hemodynamic evaluation with blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) at two transatlantic centers, were retrospectively included. The primary outcome was the presence of neurological symptoms. The diagnostic capacity of each PIRAMD feature alone was evaluated, as well as combined and the inter-institutional differences of each parameter were evaluated. Results: Seventy-two hemispheres of 38 patients were considered for analysis, of which 39 (54%) were classified as symptomatic. The presence of a prior infarct had the highest odds ratio [odds ratio (OR) =24; 95% CI: 6.7-87.2] for having neurological symptoms, followed by impaired CVR (OR =17; 95% CI: 5-62). No inter-institutional differences in the odds ratios or area under the curve (AUC) were found for any study parameter. The PIRAMD score had an AUC of 0.88 (95% CI: 0.80-0.96) with a similar AUC for the PIRAMD grading score. Conclusions: Our multicentric validation of the recently published PIRAMD scoring system was highly effective in rating the severity of ischemic Moyamoya disease with excellent inter-institutional agreement. Future studies should investigate the prognostic value of this novel imaging-based score in symptomatic patients with Moyamoya disease.

Effects of Anesthetic Agents on Blood Brain Barrier Integrity: A Systematic Review.

BACKGROUND: The blood brain barrier (BBB) is a highly selective permeable barrier that separates the blood and the central nervous system. Anesthesia is an integral part of surgery, and there is little known about the impact of anesthetics on the BBB. Therefore, it is imperative to explore reversible or modifiable variables such as anesthetic agents that influence BBB integrity. We aimed to synthesize the literature pertaining to the various effects of anesthetics on the BBB. METHODS: MEDLINE, Embase, and Cochrane were searched from inception up to September 2022. RESULTS: A total of 14 articles met inclusion into the review. The articles included nine randomized control studies (64.3%) and five quasi-experimental studies (35.7%). Twelve studies used volatile anesthetics, one study used fentanyl intravenously, and one study used pentobarbital or ketamine intraperitoneally. BBB structural deficits following the administration of an anesthetic agent included ultrastructural deficits, decreases in tight junctions, and decreases in BBB components. BBB functional deficits included permeability increases following exposure to volatile anesthetics. However, two studies found decreased permeability after fentanyl, pentobarbital, or ketamine exposure. Moreover, the impact of anesthetics on the BBB seems to be related to the duration of exposure. Notably, study findings also suggest that changes following anesthetic exposure demonstrate some reversibility over the short-term. CONCLUSION: Overall, our systematic review highlights interesting findings pertaining to the impact of anesthetic agents on BBB integrity in previously healthy models. These findings and mechanisms should inspire future work to aid practitioners and healthcare teams potentially better care for patients.

Risk Factors and Characteristics of Intraoperative Seizures During Awake Craniotomy: A Retrospective Cohort Study of 562 Consecutive Patients With a Space-occupying Brain Lesion.

INTRODUCTION: Intraoperative seizures (IOSs) during awake craniotomy (AC) are associated with significant morbidity. The reported incidence of IOS is between 3% and 30%. The aim of this study was to identify risk factors for IOS during AC for elective resection or biopsy of a space-occupying brain lesion. METHODS: In this retrospective study, we reviewed the records of all awake craniotomies performed by a single neurosurgeon at a single university hospital between July 2006 and December 2018. IOS was defined as a clinically apparent seizure that occurred in the operating room and was documented in the medical records. Explanatory variables were chosen based on previously published literature on risk factors for IOS. RESULTS: Five hundred and sixty-two patients had a total of 607 AC procedures during the study period; 581 cases with complete anesthesia records were included in analysis. Twenty-nine (5.0%) IOS events were reported during 29 (5%) awake craniotomies. Most seizures (27/29; 93%) were focal in nature and did not limit planned intraoperative stimulation mapping. Variables associated with IOS at a univariate P -value <0.1 (frontal location of tumor, preoperative radiotherapy, preoperative use of antiepileptic drugs, intraoperative use of dexmedetomidine, and intraoperative stimulation mapping) were included in a multivariable logistic regression. Frontal location of tumor (adjusted odds ratio: 5.68, 95% confidence interval: 2.11-15.30) and intraoperative dexmedetomidine use (adjusted odds ratio: 2.724, 95% confidence interval: 1.24-6.00) were independently associated with IOS in the multivariable analysis. CONCLUSIONS: This study identified a low incidence (5%) of IOS during AC. The association between dexmedetomidine and IOS should be further studied in randomized trials as this is a modifiable risk factor.

Preoperative Heart Rate Variability Predicts Postinduction Hypotension in Patients with Cervical Myelopathy: A Prospective Observational Study.

Background: Autonomic dysfunction, commonly seen in patients with cervical myelopathy, may lead to a decrease in blood pressure intraoperatively. Objective: The aim of our study is to determine if changes in Heart rate variability (HRV) could predict hypotension after induction of anesthesia in patients with cervical myelopathy undergoing spine surgery. Methods and Material: In this prospective observational study, 47 patients with cervical myelopathy were included. Five-minute resting ECG (5 lead) was recorded preoperatively and HRV of very low frequency (VLF), low frequency (LF), and high frequency (HF) spectra were calculated using frequency domain analysis. Incidence of hypotension (MAP <80 mmHg, lasting >5 min) and the number of interventions (40 mcg of phenylephrine or 5 mg of ephedrine) required to treat the hypotension during the period from induction to surgical incision were recorded. HRV indices were compared between the hypotension group and the stable group. Results: The incidence of hypotension after induction was 74.4% (35/47) and the median (IQR) interventions needed to treat hypotension was 2 (0.5-6). Patients who experienced hypotension had lower HF power and higher LF-HF ratios. A LF/HF >2.5 indicated postinduction hypotension likely. There was a correlation between increasing LF-HF ratio and the number of interventions that needs to maintain the MAP above 80 mmHg. Conclusion: HF power was lower and LF-HF ratio was higher in patients with cervical myelopathy who developed postinduction hypotension. Hence, preoperative HRV analysis can be useful to identify patients with cervical myelopathy who are at risk of post-induction hypotension.

Tolerability of Repeat Awake Craniotomy: A Propensity-Score-Matched Analysis on 607 Consecutive Cases.

BACKGROUND: Awake craniotomy is used for addressing lesions adjacent to eloquent brain regions to minimize damage to neurological functions, and to expedite postoperative recovery. Redo (i.e., repeat) awake surgery is not common, but always an option, especially for recurrent tumors. This study investigated the tolerability of redo awake surgery in terms of surgical characteristics and postoperative clinical course. METHODS: Single-institution cohort study of 607 awake craniotomies by 1 surgeon at Toronto Western Hospital, 2006-2018. RESULTS: Out of 607 surgeries, 501 surgeries were first-time, and 106 surgeries were redo. Between the 2 groups, surgery time was longer in redo cases than first-time cases and the rate of reoperation was higher in the former. Matched propensity cohort analysis included 104 cases each, based on adjustments for age, sex, tumor location, malignancy, and preoperative performance status. This revealed differences again in surgery time (128.0 vs. 111.9 minutes, P = 0.0004) and the reoperation rate (7.4 vs. 1.0%, P = 0.03). The causes of reoperation were infection (3 wound infection and 3 brain abscess) and wound dehiscence (n = 1). There was no significant difference in the length of hospital stay, the rates of postoperative hemorrhage, new postoperative neurological deficits, home discharge, or readmission. CONCLUSIONS: Although redo surgery might increase the surgery time and the risk of reoperation due to postoperative infection, it was found to be well tolerated in other aspects overall. With extra care to infection and wound healing, redo awake surgery is a viable option to patients with the same surgical indication as for first-time surgery.

Barriers and facilitators in the implementation of a telemedicine-based outpatient brain tumor surgery program.

OBJECTIVE: Despite growing evidence on the benefits of outpatient oncological neurosurgery (OON), it is only performed in a few specialized centers and there are no previous descriptions of established OON programs in Europe. Moreover, increasing application of telemedicine strategies, especially after the start of the coronavirus disease 2019 (COVID-19) pandemic, is drastically changing neurosurgical management, particularly in the case of vulnerable populations such as neuro-oncological patients. In this context, the authors implemented an OON program in their hospital with telematic follow-up. Herein, they describe the protocol and qualitatively analyze the barriers and facilitators of the development process. METHODS: An OON program was developed through the following steps: assessment of hospital needs, specific OON training, multidisciplinary team organization, and OON protocol design. In addition, the implementation phase included training sessions, a pilot study, and continuous improvement sessions. Finally, barriers and facilitators of the protocol's implementation were identified from the feedback of all participants. RESULTS: An OON protocol was successfully designed and implemented for resection or biopsy of supratentorial lesions up to 3 cm in diameter. The protocol included the patient's admission to the day surgery unit, noninvasive anesthetic monitoring, same-day discharge, and admission to the hospital-at-home (HaH) unit for telematic and on-site postoperative care. After a pilot study including 10 procedures in 9 patients, the main barriers identified were healthcare provider resistance to change, lack of experience in outpatient neurosurgery, patient reluctance, and limitations in the recruitment of patients. Key facilitators of the process were the patient education program, the multidisciplinary team approach, and the HaH-based telematic postoperative care. CONCLUSIONS: Initiating an OON program with telematic follow-up in a European clinical setting is feasible. Nevertheless, it poses several barriers that can be overcome by identifying and maximizing key facilitators of the process. Among them, patient education, a multidisciplinary team approach, and HaH-based postoperative care were crucial to the success of the program. Future studies should investigate the cost-effectiveness of telemedicine to assess potential cost savings, from reduced travel and wait times, and the impact on patient satisfaction.

Benzodiazepine Sedation and Postoperative Neurological Deficits after Awake Craniotomy for Brain Tumor - An Exploratory Retrospective Cohort Study.

An awake craniotomy is a common neurosurgical procedure for excising brain tumor(s) located near or in eloquent areas. The use of benzodiazepine (BZD) for sedation in some patients with neuropathological conditions (e.g., stroke, brain tumors) has been previously linked with re-appearance of neurological deficits including limb incoordination, ataxia, and motor weakness, resulting in complications for the patient along with procedural challenges. Whether or not these findings can be extrapolated to patients undergoing brain tumor resection is largely unknown. The current work primarily sought to compare neurological outcome(s) in the immediate postoperative period between BZD-free and BZD-based sedation techniques in patients undergoing awake craniotomy. Using a database composed of awake craniotomies conducted within a single center and by a single surgeon, patients were retrospectively classified based on midazolam administration into BZD-free sedation (n=125) and BZD-based sedation (n=416) groups. Patients from each group were matched based on age, sex, tumor location, tumor grade, preoperative neurological deficits, non-operative BZD use, and Karnofsky Performance Scale scores, resulting in 108 patients within each group. Postoperative neurological deficits were recorded. Logistic regression analyses were conducted comparing postoperative neurological deficits between the matched groups. Postoperative neurological deficits were more prevalent within the BZD-based sedation group compared to the BZD-free sedation group (adjusted odds ratio (aOR)=1.903, 95% CI=1.018-3.560, p=0.044). In addition, subgroup analysis of the matched cohort showed a relationship between preoperative neurological symptoms and postoperative neurological deficits in the BZD-based sedation group (aOR=3.756, 95% CI=1.390-10.147, p=0.009). Our findings support the notion that the increased incidence of postoperative neurological deficits with BZD sedation may in part be related to the unmasking of preoperative neurological deficits. Further studies are required to confirm this phenomenon.

Perioperative Complications and Anesthesia Practices in Managing Patients With Quadriplegia Undergoing Surgery: A Systematic Review.

Quadriplegia is associated with a multitude of health complications affecting numerous organ systems. Complications during the perioperative periods are not uncommon in this patient population due to abnormal responses to surgical stressors. Such complications include autonomic dysreflexia, cardiac ischemia, and respiratory compromise. Currently, there is no clear consensus on the ideal technique for perioperative anesthesia management in this population. In addition, the relationship between the perioperative complications and anesthesia practices have not been explored in-depth. Therefore, we aimed to investigate perioperative complications in the context of anesthesia that are associated with patients with quadriplegia undergoing various surgical procedures. Our PRISMA compliant systematic review included 12 articles covering the literature from inception to January 12, 2021. The review showed complications being pulmonary, cerebral, but most importantly and commonly cardiac in nature, with many patients suffering hypertension, and many others hypotension. In addition, our review showed that autonomic dysreflexia is common and in majority of patients, it was managed successfully with good recovery. Based on our findings, the use of anesthesia, either general or spinal, can be considered. Future studies are needed to elucidate the exact mechanisms involved in perioperative complications and anesthetic management that are associated with patients with quadriplegia. This review will aid in developing general recommendations based on the information available in the literature to guide perioperative management of this vulnerable patient population.

Central Neurogenic Hyperventilation and Hyperlactatemia After Resection of a Fourth Ventricle Tumor: A Case Report.

We report a rare case of central neurogenic hyperventilation (CNH) and hyperlactatemia after resection of a fourth ventricle tumor. Our management consisted of close monitoring and exclusion of alternate causes of hyperventilation and hyperlactatemia. We hypothesize that a localized increase in tissue lactate, related to tumor metabolism, may have triggered CNH in our patient through stimulation of the brainstem respiratory centers. CNH should be considered during the differential diagnosis of perioperative hyperventilation with respiratory alkalosis in patients with posterior fossa tumors. Hyperlactatemia can trigger compensatory hyperventilation but will not result in alkalosis.

Brain and Heart Crosstalk During Neurointerventional Procedures: The Role of the Trigeminocardiac Reflex: An Updated Systematic Review.

The trigeminocardiac reflex is a well-described brainstem reflex that clinically manifests as bradycardia, hypotension, or apnea. This physiological phenomenon is extensively reported during open neurosurgical procedures, but very few data exist for trigeminocardiac reflex occurrence during neurointerventional procedures. This systematic review aims to provide aggregated information related to the trigeminocardiac reflex during neurointerventional procedures and to improve understanding of the various mechanisms that can incite this unique brain-heart crosstalk.

The Effects of Anesthetics on Glioma Progression: A Narrative Review.

There are many established factors that influence glioma progression, including patient age, grade of tumor, genetic mutations, extent of surgical resection, and chemoradiotherapy. Although the exposure time to anesthetics during glioma resection surgery is relatively brief, the hemodynamic changes involved and medications used, as well as the stress response throughout the perioperative period, may also influence postoperative outcomes in glioma patients. There are numerous studies that have demonstrated that choice of anesthesia influences non-brain cancer outcomes; of particular interest are those describing that the use of total intravenous anesthesia may yield superior outcomes compared with volatile agents in in vitro and human studies. Much remains to be discovered on the topic of anesthesia's effect on glioma progression.

Reappearance of Neurological Deficits in Pathologic Brain: Are Sedatives and Opioids Culprits? A Systematic Review.

Following a brain insult, focal neurological deficits may develop. Despite resolution of these deficits with time, the subsequent administration of sedative medications and opioids may lead to recrudescence of previous neurological deficits. Therefore, the present systematic review aims to explore the role of different sedatives and opioid analgesics at reproducing focal neurological deficits in patients with previous brain insults undergoing surgery. Our PRISMA compliant systematic review covering the literature from 1990 to 2020 showed a consistent reoccurrence of neurological deficits following administration of benzodiazepines and opioids across 12 studies. It appears that in all studies, the manifestations were transient and affected mostly middle-aged patients (45 to 67 y of age). In addition, benzodiazepines and opioid antagonism by naloxone and flumazenil reverses the unmasking of prior neurological deficits. In contrast, it is not clear based on our study whether the unmasking or worsening of neurological deficits occurs following recent injuries or an older brain insult, although for most patients it appears to be the former. Future studies are needed to elucidate the mechanisms involved in unmasking prior deficits and/or extension of prior injuries by sedative and opioid analgesics. This review will aid in developing prospective studies on individual sedative medications and their effects on unmasking neurological deficits in patients with multiple brain pathologies.