Are NIRS-derived cerebral autoregulation and ABPopt values different between hemispheres in hypoxic-ischemic brain injury patients following cardiac arrest?

PURPOSE: Near-infrared spectroscopy (NIRS) has been suggested as a non-invasive monitoring technique to set cerebral autoregulation (CA) guided ABP targets (ABPopt) in comatose patients with hypoxic-ischemic brain injury (HIBI) following cardiac arrest. We aimed to determine whether NIRS-derived CA and ABPopt values differ between left and right-sided recordings in these patients. METHODS: Bifrontal regional oxygen saturation (rSO2) was measured using INVOS or Fore-Sight devices. The Cerebral Oximetry index (COx) was determined as a CA measure. ABPopt was calculated using a published algorithm with multi-window weighted approach. A paired Wilcoxon signed rank test and intraclass correlation coefficients (ICC) were used to compare (1) systematic differences and (2) degree of agreement between left and right-sided measurements. RESULTS: Eleven patients were monitored. In one patient there was malfunctioning of the right-sided optode and in one patient not any ABPopt value was calculated. Comparison of rSO2 and COx was possible in ten patients and ABPopt in nine patients. The average recording time was 26 (IQR, 22-42) hours. The ABPopt values were not significantly different between the bifrontal recordings (80 (95%-CI 76-84) and 82 (95%-CI 75-84) mmHg) for the left and right recordings, p = 1.0). The ICC for ABPopt was high (0.95, 0.78-0.98, p < 0.001). Similar results were obtained for rSO2 and COx. CONCLUSION: We found no differences between left and right-sided NIRS recordings or CA estimation in comatose and ventilated HIBI patients. This suggests that in these patients without signs of localized pathology unilateral recordings might be sufficient to estimate CA status or provide ABPopt targets.

Association of Age and Sex With Multi-Modal Cerebral Physiology in Adult Moderate/Severe Traumatic Brain Injury: A Narrative Overview and Future Avenues for Personalized Approaches.

The impact of age and biological sex on outcome in moderate/severe traumatic brain injury (TBI) has been documented in large cohort studies, with advanced age and male sex linked to worse long-term outcomes. However, the association between age/biological sex and high-frequency continuous multi-modal monitoring (MMM) cerebral physiology is unclear, with only sparing reference made in guidelines and major literature in moderate/severe TBI. In this narrative review, we summarize some of the largest studies associating various high-frequency MMM parameters with age and biological sex in moderate/severe TBI. To start, we present this by highlighting the representative available literature on high-frequency data from Intracranial Pressure (ICP), Cerebral Perfusion Pressure (CPP), Extracellular Brain Tissue Oxygenation (PbtO2), Regional Cerebral Oxygen Saturations (rSO2), Cerebral Blood Flow (CBF), Cerebral Blood Flow Velocity (CBFV), Cerebrovascular Reactivity (CVR), Cerebral Compensatory Reserve, common Cerebral Microdialysis (CMD) Analytes and their correlation to age and sex in moderate/severe TBI cohorts. Then we present current knowledge gaps in the literature, discuss biological implications of age and sex on cerebrovascular monitoring in TBI and some future avenues for bedside research into the cerebrovascular physiome after TBI.

Cerebrovascular Autoregulation Monitoring in the Management of Adult Severe Traumatic Brain Injury: A Delphi Consensus of Clinicians.

BACKGROUND: Several methods have been proposed to measure cerebrovascular autoregulation (CA) in traumatic brain injury (TBI), but the lack of a gold standard and the absence of prospective clinical data on risks, impact on care and outcomes of implementation of CA-guided management lead to uncertainty. AIM: To formulate statements using a Delphi consensus approach employing a group of expert clinicians, that reflect current knowledge of CA, aspects that can be implemented in TBI management and CA research priorities. METHODS: A group of 25 international academic experts with clinical expertise in the management of adult severe TBI patients participated in this consensus process. Seventy-seven statements and multiple-choice questions were submitted to the group in two online surveys, followed by a face-to-face meeting and a third online survey. Participants received feedback on average scores and the rationale for resubmission or rephrasing of statements. Consensus on a statement was defined as agreement of more than 75% of participants. RESULTS: Consensus amongst participants was achieved on the importance of CA status in adult severe TBI pathophysiology, the dynamic non-binary nature of CA impairment, its association with outcome and the inadvisability of employing universal and absolute cerebral perfusion pressure targets. Consensus could not be reached on the accuracy, reliability and validation of any current CA assessment method. There was also no consensus on how to implement CA information in clinical management protocols, reflecting insufficient clinical evidence. CONCLUSION: The Delphi process resulted in 25 consensus statements addressing the pathophysiology of impaired CA, and its impact on cerebral perfusion pressure targets and outcome. A research agenda was proposed emphasizing the need for better validated CA assessment methods as well as the focused investigation of the application of CA-guided management in clinical care using prospective safety, feasibility and efficacy studies.

Sedation and cerebrovascular reactivity in traumatic brain injury: another potential avenue for personalized approaches in neurocritical care?

BACKGROUND: Impaired cerebrovascular reactivity appears to be linked to worse global outcome in adult traumatic brain injury (TBI). Literature suggests that current treatments administered in TBI care, in the intensive care unit (ICU), fail to greatly impact recorded cerebrovascular reactivity measures. In particular, the impact of sedation on cerebrovascular reactivity in traumatic brain injury (TBI) remains unclear in vivo. The goal of this study was to preliminarily assess the relationship between objectively measured depth of sedation and cerebrovascular reactivity in TBI. METHODS: Within, we describe a case series of 5 adult TBI patients with TBI, during which objective high-frequency physiology for sedation depth, using bispectral index (BIS), and both intracranial pressure (ICP) and arterial blood pressure (ABP) were recorded. Pressure reactivity index (PRx) and RAP (a metric of cerebral compensatory reserve) were derived. Relationships between cerebrovascular reactivity and compensatory reserve monitoring with BIS metrics were explored using descriptive plots. RESULTS: A total of 5 cases in our prospectively maintained database with high-frequency physiology for ICP, ABP, and BIS. Through error bar plotting, it can be seen that each patient displays a parabolic relationship between BIS and PRx. This suggests a potential "optimal" depth of sedation where cerebrovascular reactivity is the most intact. CONCLUSIONS: This small series highlights the potential impact of depth of sedation on cerebrovascular reactivity in TBI. It suggests that there may be an individual optimal depth of sedation, so as to optimize cerebrovascular reactivity. Further study of objective depth of sedation and its impact on cerebrovascular physiology in TBI is required.

Continuous and entirely non-invasive method for cerebrovascular reactivity assessment: technique and implications.

Continuous cerebrovascular reactivity assessment in traumatic brain injury (TBI) has been limited by the need for invasive monitoring of either cerebral physiology or arterial blood pressure (ABP). This restricts the application of continuous measures to the acute phase of care, typically in the intensive care unit. It remains unknown if ongoing impairment of cerebrovascular reactivity occurs in the subacute and long-term phase, and if it drives ongoing morbidity in TBI. We describe an entirely non-invasive method for continuous assessment of cerebrovascular reactivity. We describe the technique for entirely non-invasive continuous assessment of cerebrovascular reactivity utilizing near-infrared spectroscopy (NIRS) and robotic transcranial Doppler (rTCD) technology, with details provided for NIRS. Recent advances in continuous high-frequency non-invasive ABP measurement, combined with NIRS or rTCD, can be employed to derive continuous and entirely non-invasive cerebrovascular reactivity metrics. Such non-invasive measures can be obtained during any aspect of patient care post-TBI, and even during outpatient follow-up, avoiding classical intermittent techniques and costly neuroimaging based metrics obtained only at specialized centers. This combination of technology and signal analytic techniques creates avenues for future investigation of the long-term consequences of cerebrovascular reactivity, integrating high-frequency non-invasive cerebral physiology, neuroimaging, proteomics and clinical phenotype at various stages post-injury.

The Full Outline of UnResponsiveness (FOUR) Score and Its Use in Outcome Prediction: A Scoping Systematic Review of the Adult Literature.

BACKGROUND: The Full Outline of UnResponsivness (FOUR) score is a neurological assessment score. Its theoretical benefit over preexisting scores is its evaluation of brainstem reflexes and respiratory pattern which may allow better assessment of patients with severe neurologic impairment. OBJECTIVE: Our goal was to perform a scoping systematic review on the available literature for FOUR score and outcome prediction in critically ill patients. The primary outcome of interest was patient global outcome, as assessed by any of: mortality, modified Rankin Score, Glasgow Outcome Score, or any other functional or neuropsychiatric outcome. Information on interobserver reliability was also extracted. METHODS: MEDLINE and five other databases were searched. Inclusion criteria were: humans, adults, and children; prospective randomized controlled trial; prospective cohort, cohort/control, case series, prospective, and retrospective studies. Two reviewers independently screened the results. Full texts for citations passing this initial screen were obtained. Inclusion and exclusion criteria were applied to each article to obtain final articles for review. Results on adult populations are presented here. Data are reported following the preferred reporting items for systematic reviews and meta-analyses guidelines. RESULTS: The initial search yielded 1709 citations. Of those used, 49 were based on adult and 6 on pediatric populations. All but 8 retrospective adult studies were performed prospectively. Patient categories included traumatic brain injury, intraventricular hemorrhage, intracerebral hemorrhage, subarachnoid hemorrhage, ischemic stroke, general/combined neurology and neurosurgery, post-cardiac arrest, medicine/general critical illness, and patients in the emergency department. A total of 9092 adult patients were studied. Fourteen studies demonstrated good interobserver reliability of the FOUR score. Nine studies demonstrated prognostic value of the FOUR score in predicting mortality and functional outcomes. Thirty-two studies demonstrated equivalency or superiority of the FOUR score compared to Glasgow Coma Score in prediction of mortality and functional outcomes. CONCLUSIONS: The FOUR score has been shown to be a useful outcome predictor in many patients with depressed level of consciousness. It displays good inter-rater reliability among physicians and nurses.

ICP Versus Laser Doppler Cerebrovascular Reactivity Indices to Assess Brain Autoregulatory Capacity.

BACKGROUND: To explore the relationship between various autoregulatory indices in order to determine which approximate small vessel/microvascular (MV) autoregulatory capacity most accurately. METHODS: Utilizing a retrospective cohort of traumatic brain injury patients (N = 41) with: transcranial Doppler (TCD), intracranial pressure (ICP) and cortical laser Doppler flowmetry (LDF), we calculated various continuous indices of autoregulation and cerebrovascular responsiveness: A. ICP derived [pressure reactivity index (PRx)-correlation between ICP and mean arterial pressure (MAP), PAx-correlation between pulse amplitude of ICP (AMP) and MAP, RAC-correlation between AMP and cerebral perfusion pressure (CPP)], B. TCD derived (Mx-correlation between mean flow velocity (FVm) and CPP, Mx_a-correlation between FVm and MAP, Sx-correlation between systolic flow velocity (FVs) and CPP, Sx_a-correlation between FVs and MAP, Dx-correlation between diastolic flow index (FVd) and CPP, Dx_a-correlation between FVd and MAP], and LDF derived (Lx-correlation between LDF cerebral blood flow [CBF] and CPP, Lx_a-correlation between LDF-CBF and MAP). We assessed the relationship between these indices via Pearson correlation, Friedman test, principal component analysis (PCA), agglomerative hierarchal clustering (AHC), and k-means cluster analysis (KMCA). RESULTS: LDF-based autoregulatory index (Lx) was most associated with TCD-based Mx/Mx_a and Dx/Dx_a across Pearson correlation, PCA, AHC, and KMCA. Lx was only remotely associated with ICP-based indices (PRx, PAx, RAC). TCD-based Sx/Sx_a was more closely associated with ICP-derived PRx, PAx and RAC. This indicates that vascular-derived indices of autoregulatory capacity (i.e., TCD and LDF based) covary, with Sx/Sx_a being the exception, whereas indices of cerebrovascular reactivity derived from pulsatile CBV (i.e., ICP indices) appear to not be closely related to those of vascular origin. CONCLUSIONS: Transcranial Doppler Mx is the most closely associated with LDF-based Lx/Lx_a. Both Sx/Sx-a and the ICP-derived indices appear to be dissociated with LDF-based cerebrovascular reactivity, leaving Mx/Mx-a as a better surrogate for the assessment of cortical small vessel/MV cerebrovascular reactivity. Sx/Sx_a cocluster/covary with ICP-derived indices, as seen in our previous work.

Compensatory-Reserve-Weighted Intracranial Pressure and Its Association with Outcome After Traumatic Brain Injury.

OBJECTIVE: We introduced 'compensatory-reserve-weighted intracranial pressure (ICP),' named 'weightedICP' for brevity, as a variable that may better describe changes leading to mortality after traumatic brain injury (TBI) over the standard mean ICP. METHODS: ICP was monitored prospectively in over 1023 sedated and ventilated patients. The RAP coefficient (R-correlation, A-amplitude, and P-pressure) was calculated as the running correlation coefficient between slow changes in the pulse amplitude of ICP and the mean ICP. RAP has a value of 0 on the linear part of the pressure-volume curve and a value of + 1 on the ascending exponential part. Then, RAP decreases towards zero or even becomes negative when ICP increases further-a phenomenon thought to be related to the critical closing of cerebral vessels. In this study, we investigated a derived variable called weightedICP, calculated as ICP*(1 - RAP). RESULTS: Mortality after TBI was associated with both elevated ICP and weightedICP. Analysis of variance showed higher values of test statistics for weightedICP (K = 93) than for ICP (K = 64) in outcome categorization. Additionally, receiver operator curve analysis indicated greater area under the curve for weightedICP (0.71) than for ICP (0.67) with respect to associated mortality; however, the difference was not statistically significant (p = 0.12). The best threshold (maximizing sensitivity and specificity) was 19.5 mm Hg for mean ICP, and 8 mm Hg for weightedICP. Mortality rate expressed as a function of mean ICP and weightedICP showed an ascending profile in both cases. CONCLUSION: The proposed variable shows a significant association with mortality following head injury. It is sensitive to both the rising absolute ICP and to the critical deterioration of pressure-volume compensation.

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.

Intravenous immunoglobulins for refractory status epilepticus, part I: A scoping systematic review of the adult literature.

PURPOSE: Our goal was to perform a scoping systematic review of the literature on the use of intravenous immunoglobulins (IVIG) for refractory status epilepticus (RSE) in adults. METHOD: Articles from MEDLINE, BIOSIS, EMBASE, Global Health, Healthstar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to May 2016), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers. RESULTS: Twenty-four original articles were identified. A total of 33 adult patients were described as receiving IVIG for RSE. Seizure reduction/control with IVIG occurred in 15 of the 33 patients (45.4%), with 1 (3.0%) and 14 (42.4%) displaying partial and complete responses respectively. No adverse events were recorded. CONCLUSION: Oxford level 4, GRADE D evidence exists to suggest an unclear impact of IVIG therapy in adult RSE. Routine use of IVIG in adult RSE cannot be recommended at this time.

Plasmapheresis for refractory status epilepticus Part II: A scoping systematic review of the pediatric literature.

BACKGROUND: Our goal was to perform a scoping systematic review of the literature on the use of plasmapheresis or plasma exchange (PE) for refractory status epilepticus (RSE) in children. METHODS: Articles from MEDLINE, BIOSIS, EMBASE, Global Health, Healthstar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to May 2016), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers. RESULTS: Twenty-two original articles were identified, with 37 pediatric patients. The mean age of the patients was 8.3 years (age median: 8.5, range: 0.6 years-17 years). Seizure response to PE therapy occurred in 9 of the 37 patients (24.3%) included in the review, with 7 patients (18.9%) displaying resolution of seizures and 2 patients (5.4%) displaying a partial reduction in seizure volume. Twenty-eight of the 37 patients (75.7%) had no response to PE therapy. No adverse events were recorded. CONCLUSIONS: Oxford level 4, GRADE D evidence exists to suggest little to no benefit of PE in pediatric RSE. Routine application of PE for pediatric RSE cannot be recommended at this time.

Plasmapheresis for refractory status epilepticus, part I: A scoping systematic review of the adult literature.

PURPOSE: Our goal was to perform a scoping systematic review of the literature on the use of plasmapheresis or plasma exchange (PE) for refractory status epilepticus (RSE) in adults. METHODS: Articles from MEDLINE, BIOSIS, EMBASE, Global Health, Healthstar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to May 2016), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers. RESULTS: Twenty-two original articles were identified. Twenty-seven adult patients were described in these articles, with a variety of autoimmune conditions leading to RSE. Seizure response with the application of PE therapy occurred in 14 of the 27 patients (51.9%), with 1 (3.7%) and 13 (48.1%) displaying partial and complete responses respectively. Generalized RSE was the most likely seizure subtype to respond to PE therapy. One patient had recorded an adverse events related to PE therapy. CONCLUSIONS: Oxford level 4, GRADE D evidence exists to suggest an uncertain response of adult autoimmune RSE to PE therapy. Thus, the routine application of PE therapy for adult autoimmune RSE cannot be recommended at this time.

Levocarnitine induced seizures in patients on valproic acid: A negative systematic review.

OBJECTIVE: Warnings of L-carnitine induced seizures are recorded on product monographs and pharmacy databases, without any referenced literature. This medication can potentially improve the hospital course in those patients with valproic acid (VPA) induced hyperammonemic encephalopathy, but may be withheld because of this warning. The goal was to perform an extensive systematic review of the literature to document the incidence of levocarnitine (L-carnitine) induced seizures in those patients on VPA therapy. METHODS: Articles from MEDLINE, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to June 2015), and reference lists of relevant articles were searched. The strength of evidence was to be adjudicated using both the Oxford and GRADE methodology by two independent reviewers. RESULTS: We failed to identify a single study implicating L-carnitine supplementation leading to seizures in any patient on VPA therapy. This contradicts all quoted, but unsubstantiated, concerns on product monographs and pharmacy databases related to seizure induction/propagation with L-carnitine supplementation. CONCLUSION: There is no literature available to support claims of L-carnitine induced seizures during supplementation in patients on VPA therapy for seizures. This contradicts quoted, but not referenced, concerns on the product monograph. In patients suffering from hypocarnitinemia or hyperammonemic encephalopathy while on VPA, L-carnitine supplementation can be considered knowing there is no data to support seizure propagation or induction with administration of this supplement.

Electroconvulsive therapy for refractory status epilepticus: A systematic review.

BACKGROUND: Our goal was to perform an extensive systematic review of the literature on the use of electroconvulsive therapy (ECT) for refractory status epilepticus (RSE). METHODS: Articles from MEDLINE, BIOSIS, EMBASE, Healthstar, Global Health, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to August 2015), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers. RESULTS: We identified 14 original articles with a total of 19 patients receiving ECT for RSE. Of the 19 patients, 15 were adult, and 4 were pediatric. All studies were retrospective in nature. Seizure reduction/control with the application of ECT occurred in 11 of the 19 patients (57.9%), with 4 (21.0%) and 7 (36.8%) displaying partial and complete responses respectively. Seizures control lasted for variable duration, with the most commonly quoted duration ranging from 2 weeks to 3 months. Data on patient functional outcome was available in 13 patients, with 10 patients falling into the categories of dead or severely disabled. All studies were an Oxford level 4, GRADE D level of evidence. CONCLUSIONS: Oxford level 4, GRADE D evidence exists to suggest an improvement in seizure control with ECT application for RSE. Routine use of ECT cannot be recommended at this time. Further prospective study of this therapy is required in order to determine its efficacy in this setting.

Lateral plating of the temporal bone: Hemostatic technique for complex transverse fractures of the petrous temporal bone.

BACKGROUND: Transverse petrous temporal bone fractures are commonly associated with significant intracranial trauma. Diastases of these fractures can lead to issues with hemostasis in the setting of venous sinus or petrous internal carotid artery (ICA) injuries. OBJECTIVE: To describe a rare case of a severe displaced transverse petrous temporal bone fracture with impending intra-operative exsanguination, treated with fracture reduction and lateral plating in order to achieve hemostasis. METHODS: We retrospectively reviewed the records of a patient admitted to the neurosurgical department with a hyperacute epidural hematoma (EDH) secondary to a transverse petrous temporal bone fracture with venous sinus and petrous ICA injuries. RESULTS: A 22 year old male was admitted for a severe traumatic brain injury leading to a left displaced transverse petrous temporal bone fracture and a hyperacute EDH. Given the location of the fractures, injury to the venous sinus (at the area of the transverse-sigmoid junction) and petrous ICA was suspected.Intra-operatively, significant blood loss from both the venous sinus and petrous ICA was encountered. Given the displaced temporal bone fracture, packing of the areas was impaired.We performed a manual reduction of the temporal fracture, followed by lateral plating in order to achieve hemostasis from the petrous ICA and aid with packing of the venous sinus injury. CONCLUSIONS: Reduction and lateral plating of displaced transverse petrous temporal bone fractures can aid significantly with intra-operative hemostasis in the extreme case of venous sinus and/or petrous ICA injuries.

Transcranial Magnetic Stimulation for Status Epilepticus.

Background. Our goal was to perform a systematic review on the use of repetitive transcranial magnetic stimulation (rTMS) in the treatment of status epilepticus (SE) and refractory status epilepticus (RSE). Methods. MEDLINE, BIOSIS, EMBASE, Global Health, Healthstar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to August 2015), and gray literature were searched. The strength of evidence was adjudicated using Oxford and GRADE methodology. Results. We identified 11 original articles. Twenty-one patients were described, with 13 adult and 8 pediatric. All studies were retrospective. Seizure reduction/control with rTMS occurred in 15 of the 21 patients (71.4%), with 5 (23.8%) and 10 (47.6%) displaying partial and complete responses, respectively. Seizures recurred after rTMS in 73.3% of the patients who had initially responded. All studies were an Oxford level 4, GRADE D level of evidence. Conclusions. Oxford level 4, GRADE D evidence exists to suggest a potential impact on seizure control with the use of rTMS for FSE and FRSE, though durability of the therapy is short-lived. Routine use of rTMS in this context cannot be recommended at this time. Further prospective study of this intervention is warranted.

Magnesium sulfate for non-eclamptic status epilepticus.

BACKGROUND: Our goal was to perform a systematic review of the literature on the use of intravenous magnesium sulfate (MgSO4) for non-eclamptic status epilepticus (SE) and refractory status epilepticus (RSE). METHODS: Articles from MEDLINE, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to June 2015), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers. RESULTS: We identified 19 original articles. A total of 28 patients were described in these articles with 11 being adult, 9 being pediatric, and 8 of unknown age. Seizure reduction/control with IV MgSO4 occurred in 14 of the 28 patients (50.0%), with 2 (7.1%) and 12 (42.9%) displaying partial and complete responses respectively. Seizures recurred upon withdrawal of MgSO4 therapy in 50% of the patients whom had reduction/control of their SE/RSE. Three patients had recorded adverse events related to MgSO4 therapy. CONCLUSIONS: Oxford level 4, GRADE D evidence exists to suggest a trend towards improved seizure control with the use of intravenous MgSO4 for non-eclamptic RSE. Routine use of IV MgSO4 in non-eclamptic SE/RSE cannot be recommended at this time. Further prospective study of this drug is required in order to determine its efficacy as an anti-epileptic in this setting.

Early Angiographic Resolution of Cerebral Vasospasm with High Dose Intravenous Milrinone Therapy.

Background. Treatment of symptomatic delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) is difficult. Recent studies suggest intravenous (IV) high dose milrinone as a potential therapy. The timing to angiographic response with this is unclear. Methods. We reviewed the chart of one patient admitted for SAH who developed symptomatic DCI and was treated with high dose IV milrinone. Results. A 66-year-old female was admitted with a Hunt and Hess clinical grade 4, World Federation of Neurological Surgeons (WFNS) clinical grade 4, and SAH secondary to a left anterior choroidal artery aneurysm which was clipped. After bleed day 6, the patient developed symptomatic DCI. We planned for angioplasty of the proximal segments. We administered high dose IV milrinone bolus followed by continuous infusion which led to clinical improvement prior to angiography. The angiogram performed 1.5 hours after milrinone administration displayed resolution of the CT angiogram and MRI based cerebral vasospasm such that further intra-arterial therapy was aborted. She completed 6 days of continuous IV milrinone therapy, was transferred to the ward, and subsequently rehabilitated. Conclusions. High dose IV milrinone therapy for symptomatic DCI after SAH can lead to rapid neurological improvement with dramatic early angiographic improvement of cerebral vasospasm.