Thrombolytic Therapy for Central Retinal Artery Occlusion in an Academic Multi-Site Stroke Centre.

Central retinal artery occlusion (CRAO) is a subtype of acute ischaemic stroke leading to severe visual loss. A recent American Heart Association scientific statement proposed time-windows for thrombolysis in CRAO similar to acute ischaemic cerebral strokes. We aimed to review our academic multi-site stroke centre experience with intravenous (IVT) and intra-arterial thrombolysis (IAT) in CRAO between 1997 and 2022. Demographic, clinical characteristics, thrombolysis timeline, concurrent therapies, complications, and 3-month follow-up visual acuity (VA) were collected. The thrombolysed cohort follow-up VA was compared with an age, gender and baseline VA matched cohort of CRAO patients that received conservative therapies. Thrombolytic therapy was administered to 3.55% (n = 20) of CRAO admissions; 13 IVT (mean age 68, 61.5% male, 12 alteplase and 1 tenecteplase, all embolic aetiology, 1 CRAO mimic) and 7 IAT (mean age 55, 85.7% male, 3 post-operative and 3 embolic). Additional conservative CRAO-targeting therapies was received by 60%. The median time from onset of visual loss to IVT was 158 minutes (range 67-260). Improvement by at least two Snellen lines was achieved by 25% with 12.5% improving to 20/100 or better. Intracranial haemorrhage post IVT occurred in 1/13 (7.6%). The median time from onset of visual loss to IAT was 335 minutes. Improvement by at least two Snellen lines was achieved by 42%. No difference in 3-month VA was noted between patients that received thrombolysis, either alone (n = 8) or combined with other therapies, and those that received conservative therapies. Our results suggest that the management of acute CRAO remains heterogeneous. The lack of obvious benefit of thrombolysis in our small series supports the need for randomizsd clinical trials comparing thrombolysis to placebo to guide hyperacute CRAO management.

Blood pressure variability and early neurological outcomes in acute and subacute stroke in Southwestern Uganda.

Background: Greater blood pressure variability has detrimental effects on clinical outcome after a stroke; its effects are controversial and have not been evaluated in Sub-Saharan Africa (SSA). Methods: We conducted a prospective study of patients with CT head confirmed ischemic and hemorrhagic strokes admitted to a tertiary hospital within 7 days of onset of unilateral neurological deficits. Blood pressure variability indices, standard deviation (SD) and coefficient of variation (CV) of systolic and diastolic blood pressure between day 0 and day 7, were calculated with a subsequent modified Rankin Scale (mRS) score on day 14 post-stroke. Linear regression was performed to determine the exponential coefficients of mortality at 14 days post- stroke. Results: Out of 120 patients, 51.7% were female, 52.5% had ischemic stroke and the overall median age was 65 (IQR 54-80) years. Twenty (16.7%) patients died within a median survival time of 7 days, while 32 (26.7%) died by day 14 post-stroke. Patients with hemorrhagic stroke had an overall SDSBP of 16.44 mmHg while those with ischemic stroke had an overall SDSBP of 14.05 mmHg. In patients with ischemic stroke, SDSBP had adjusted coefficients of 1, p = 0.004 with C·I: 1.01-1.04 and NIHSS had adjusted coefficients of 1, p = 0.019 with C·I: 1.00-1.03 while in patients with hemorrhagic stroke, SDSBP had adjusted coefficients of 1, p = 0.045 with C·I: 1.00-1.04 and NIHSS had adjusted coefficients of 1, p ≤0.001 with C·I: 1.01-1.03. Conclusion: Exponential increase in Blood Pressure Variability (BPV) and stroke severity scale were independently associated with early mortality among all stroke patients in our study. We recommend future studies to evaluate whether controlling BPV among patients with stroke in Sub-Saharan Africa can reduce mortality.

Does Initiation of Prophylactic Antiseizure Medication Improve Neurological Outcomes in Patients With Acute Intracerebral Hemorrhage?: A Critically Appraised Topic.

OBJECTIVE: The objective of this study was to critically assess current evidence regarding the role of prophylactic antiseizure medication in patients presenting with acute intracerebral hemorrhage (ICH). METHODS: The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario with a clinical question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included resident neurologists, a medical librarian, and content experts in the fields of epilepsy, stroke neurology, neurohospitalist medicine, and neurocritical care. RESULTS: A randomized clinical trial was selected for critical appraisal. The trial assessed whether prophylactic levetiracetam (LEV) use reduced the risk of acute seizures in patients with ICH, as defined by clinical or electrographic seizure, captured by continuous electroencephalogram 72 hours after enrollment. A total of 42 patients were included in the final analysis (19 in the LEV group and 23 in the placebo group). There was a significantly higher occurrence of seizures in the placebo versus LEV group (LEV 16% vs placebo 43%, P = 0.043). There were no differences in functional outcomes between the groups at 3, 6, or 12 months (P > 0.1). CONCLUSIONS: The role of prophylactic treatment with antiseizure medication in ICH remains unclear.

Can Pyridoxine Successfully Reduce Behavioral Side Effects from Levetiracetam?: A Critically Appraised Topic.

BACKGROUND: Levetiracetam is a commonly used anti-seizure medication, with the development of neuropsychiatric symptoms being the most common side effect. Preliminary literature describes the improvement of these symptoms with pyridoxine, mostly within the pediatric population. However, randomized control trial data investigating this relationship is sparse. OBJECTIVE: The objective of this study was to critically assess evidence regarding the role of pyridoxine in the treatment of neuropsychiatric symptoms from levetiracetam. METHODS: The objective was addressed through the development of a structured, critically appraised topic. This included a clinical scenario with a clinical question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, medical librarians, clinical epidemiologists, and content experts in the field of epilepsy. RESULTS: A randomized, placebo-controlled clinical trial was selected for critical appraisal. This trial compared pyridoxine versus placebo for the treatment of neuropsychiatric symptoms from levetiracetam in a pediatric population and included 105 patients (46/105 received pyridoxine, 59/105 received placebo). It found that both groups had a significant reduction in behavioral symptoms at the 2-,4-and 6-week time points ( P <0.05). However, the authors noted that the pyridoxine group had almost double the relative reduction when compared with the placebo group at all time points: 1.9 at 2 weeks, 2.0 at 4 weeks, and 1.8 at 6 weeks ( P =0.001). CONCLUSIONS: This study suggests that pyridoxine for the treatment of levetiracetam-induced behavioral side effects may result in modest improvement, although many limitations prevent conclusive results. There remains a need for a double-blinded, randomized control trial in both the adult and pediatric populations.

Consensus Competencies for Postgraduate Fellowship Training in Global Neurology.

BACKGROUND AND OBJECTIVES: Use a modified Delphi approach to develop competencies for neurologists completing ≥1 year of advanced global neurology training. METHODS: An expert panel of 19 United States-based neurologists involved in global health was recruited from the American Academy of Neurology Global Health Section and the American Neurological Association International Outreach Committee. An extensive list of global health competencies was generated from review of global health curricula and adapted for global neurology training. Using a modified Delphi method, United States-based neurologists participated in 3 rounds of voting on a survey with potential competencies rated on a 4-point Likert scale. A final group discussion was held to reach consensus. Proposed competencies were then subjected to a formal review from a group of 7 neurologists from low- and middle-income countries (LMICs) with experience working with neurology trainees from high-income countries (HICs) who commented on potential gaps, feasibility, and local implementation challenges of the proposed competencies. This feedback was used to modify and finalize competencies. RESULTS: Three rounds of surveys, a conference call with United States-based experts, and a semistructured questionnaire and focus group discussion with LMIC experts were used to discuss and reach consensus on the final competencies. This resulted in a competency framework consisting of 47 competencies across 8 domains: (1) cultural context, social determinants of health and access to care; (2) clinical and teaching skills and neurologic medical knowledge; (3) team-based practice; (4) developing global neurology partnerships; (5) ethics; (6) approach to clinical care; (7) community neurologic health; (8) health care systems and multinational health care organizations. DISCUSSION: These proposed competencies can serve as a foundation on which future global neurology training programs can be built and trainees evaluated. It may also serve as a model for global health training programs in other medical specialties as well as a framework to expand the number of neurologists from HICs trained in global neurology.

Telemedicine for Acute Monocular Visual Loss: A Retrospective Large Telestroke Network Experience.

Introduction: Central retinal artery occlusion (CRAO) is an under-recognized stroke subtype that may benefit from hyperacute reperfusion therapies. We aimed to evaluate the ability of telestroke activations to provide CRAO diagnosis and thrombolysis. Methods: This retrospective observational study investigates all encounters conducted for acute visual loss between 2010 and 2021 in our multicentric Mayo Clinic Telestroke Network. Demographics, time from visual loss to telestroke evaluation, ocular examination, diagnostic, and therapeutic recommendations were collected for CRAO subjects. Results: Out of 9,511, 49 encounters (0.51%) were conducted for an acute ocular complaint. Five patients had possible CRAO, and 4 presented within 4.5 h from symptom onset (range 1.5-5 h). None received thrombolytic therapy. All telestroke physicians recommended ophthalmology consultation. Conclusion: Current telestroke assessment of acute visual loss is suboptimal and patients eligible for acute reperfusion therapies may not be offered treatment. Teleophthalmologic evaluations and advanced ophthalmic diagnostic tools should complement telestroke systems.

Is Intravenous Immunoglobulin Effective in Reducing the Risk of Mortality and Morbidity in Neuroinvasive West Nile Virus Infection?: A Critically Appraised Topic.

BACKGROUND: The clinical benefit of intravenous immunoglobulin (IVIG) in adult individuals with neuroinvasive West Nile virus (niWNV) infection is not well substantiated. We sought to critically assess current evidence regarding the efficacy of IVIG in treating patients with niWNV. METHODS: The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and a content expert in the field of neuro-infectious diseases. RESULTS: The appraised study enrolled 62 participants with suspected niWNV, randomized into 3 different arms [37 participants in the Omr-IgG-am group, 12 in the Polygam group, and 13 in the normal saline (NS) group]. Omr-IgG-am and Polygam are different formulations of IVIG. IVIG safety, measured as rates of serious adverse events, was the primary study outcome while IVIG efficacy, measured as rates of unfavorable outcomes, was a secondary endpoint. The estimated rates of SAE were statistically similar in all groups (51.4% Omr-IgG-am, 58.3% Polygam, and 23.1% NS groups). Unfavorable outcomes also occurred at a similar rate between all the groups (51.5% Omr-IgG-am, 54.5% Polygam, and 27.3% NS). CONCLUSIONS: The appraised trial showed that Omr-IgG-am and Polygam are as safe as NS. Data on efficacy from this trial were limited by a small sample size. Phase III clinical trials on IVIG efficacy in NiWNV infection are needed.

HIV Infection and 90-Day Stroke Outcomes in Uganda: A Prospective Observational Cohort Study.

Background and Objectives: Little is known about the impact of HIV infection on the clinical presentation and outcomes after stroke in the modern antiretroviral therapy (ART) era. We aimed to compare stroke characteristics and outcomes between persons with HIV (PWH) and without HIV (PWOH) presenting with stroke in Uganda. Methods: We conducted a matched cohort study at Mulago National Referral Hospital and Mbarara Regional Referral Hospital between January 2018 and November 2020. We enrolled consecutive PWH presenting with CT-confirmed acute or subacute stroke (symptom onset ≤14 days) and matched them by sex and stroke type to 2 consecutive available PWOH admitted to the same hospital. We obtained baseline clinical data and followed participants for 90 days from the day of clinical presentation. We compared stroke severity (defined by the NIH stroke scale [NIHSS]) and 90-day all-cause mortality and morbidity (using the modified Rankin Scale [mRS]) by HIV serostatus with and without adjustment for confounders. Results: We enrolled 105 PWH and 157 PWOH with stroke. PWH were younger (mean [SD] age 49 [14] vs 59 [16] years, p < 0.001), and nearly 80% (82/105) were on ART for a median of 5 years and a median CD4 count of 214 cells/uL (interquartile range 140, 337). Compared with PWOH, PWH presented with a 3-point lower median NIHSS (16 vs 19, p = 0.011), a 20% lower proportion of all-cause mortality at 90 days (p = 0.001), and had less disability at 90 days (median mRS 4 vs 5, p = 0.004). Age and NIHSS-adjusted odds ratio of 90-day all-cause mortality in PWH compared with PWOH was 0.45 (95% CI 0.22-0.96, p = 0.037). Discussion: In the modern ART era, PWH with acute stroke in Uganda present with modest stroke and are significantly less likely to die within 90 days than PWOH. This potentially reflects the protective effects of ART, enhanced health care access, and their younger age at stroke presentation.

Optimizing Door-to-Groin Puncture Time: The Mayo Clinic Experience.

Objectives: To provide a better understanding of methods that can be used to improve patient outcomes by reducing the door-to-groin puncture (DTP) time and present the results of a stroke quality improvement project (QIP) conducted by Mayo Clinic Arizona's stroke center. Methods: We conducted a systematic literature search of Ovid MEDLINE(R), Ovid EMBASE, Scopus, and Web of Science for studies that evaluated DTP time reduction strategies. Those determined eligible for the purpose of this analysis were assessed for quality. The strategies for DTP time reduction were categorized on the basis of modified Target: Stroke Phase III recommendations and analyzed using a meta-analysis. The Mayo Clinic QIP implemented a single-call activation system to reduce DTP times by decreasing the time from neurosurgery notification to case start. Results: Fourteen studies were selected for the analysis, consisting of 2277 patients with acute ischemic stroke secondary to large-vessel occlusions. After intervention, all the studies showed a reduction in the DTP time, with the pooled DTP improvement being the standardized mean difference (1.37; 95% confidence interval, 1.20-1.93; τ2=1.09; P<.001). The Mayo Clinic QIP similarly displayed a DTP time reduction, with the DTP time dropping from 125.1 to 82.5 minutes after strategy implementation. Conclusion: Computed tomography flow modifications produced the largest and most consistent reduction in the DTP time. However, the reduction in the DTP time across all the studies suggests that any systematic protocol aimed at reducing the DTP time can produce a beneficial effect. The relative novelty of mechanical thrombectomy and the consequential lack of research call for future investigation into the efficacy of varying DTP time reduction strategies.

In Patients With Melanoma Brain Metastases, Is Combination Immune Checkpoint Inhibition a Safe and Effective First-Line Treatment? A Critically Appraised Topic.

BACKGROUND: Combined PD-1/PD-L1 and CTLA-4 immune checkpoint inhibition for the has been shown to produce superior results in the treatment of malignant melanoma when compared to monotherapy. However, patients with intracranial disease were excluded from these studies given their poor prognosis. OBJECTIVE: The objective of this study was to critically assess current evidence supporting the co-administration of PD-1/PD-L1 and CTLA-4 inhibitors in the treatment of melanoma brain metastases. METHODS: The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and a content expert in the field of neuro-oncology. RESULTS: A recent, open-label, non-comparative randomized phase II trial was selected for critical appraisal. This trial evaluated the efficacy and safety of nivolumab alone or in combination with ipilimumab in 79 adult patients with untreated, asymptomatic melanoma brain metastases. The rates of the primary outcome (intracranial response at ≥12 wk) in the primary endpoint cohort were 46% for cohort A (combination therapy) and 20% for cohort B (nivolumab monotherapy). No treatment related deaths were observed in the study. Grade 4 adverse events occurred in 9% of patients in cohort A and none in cohort B. CONCLUSIONS: Co-administration of ipilimumab and nivolumab as first-line therapy is effective in the treatment of asymptomatic melanoma brain metastases, with an acceptable safety profile.

Current Guidelines on Management of Amaurosis Fugax and Transient Ischemic Attacks.

ABSTRACT: Transient ischemic attack (TIA) is defined as a transient episode of neurological dysfunction resulting from focal brain, spinal cord, or retinal ischemia, without associated infarction. Consequently, a TIA encompasses amaurosis fugax (AF) that is a term used to denote momentary visual loss from transient retinal ischemia. In this review, we use the word TIA to refer to both cerebral TIAs (occurring in the brain) and AF (occurring in the retina). We summarize the key components of a comprehensive evaluation and management of patients presenting with cerebral and retinal TIA.All TIAs should be treated as medical emergencies, as they may herald permanent disabling visual loss and devastating hemispheric or vertebrobasilar ischemic stroke. Patients with suspected TIA should be expeditiously evaluated in the same manner as those with an acute stroke. This should include a detailed history and examination followed by specific diagnostic studies. Imaging of the brain and extracranial and intracranial blood vessels forms the cornerstone of diagnostic workup of TIA. Cardiac investigations and serum studies to evaluate for etiological risk factors are also recommended.The management of all TIAs, whether cerebral or retinal, is similar and should focus on stroke prevention strategies, which we have categorized into general and specific measures. General measures include the initiation of appropriate antiplatelet therapy, encouraging a healthy lifestyle, and managing traditional risk factors, such as hypertension, dyslipidemia, and diabetes. Specific management measures require the identification of a specific TIA etiology, such as moderate-severe (greater than 50% of stenosis) symptomatic extracranial large vessel or intracranial steno-occlusive atherosclerotic disease, aortic arch atherosclerosis, and atrial fibrillation.

In Patients With Functional Movement Disorders, Is Specialized Physical Therapy Effective in Improving Motor Symptoms?: A Critically Appraised Topic.

BACKGROUND: Functional movement disorders (FMD, aka psychogenic movement disorders) are very common and frequently chronic and disabling. Despite this, there is a paucity of evidence-based treatment to manage and alleviate these conditions. Specialized physical therapy (PT), involving sequential motor relearning and redirecting attention, has shown promise as a therapeutic intervention for motor symptoms. METHODS: The objective of this study was to critically assess current evidence regarding specialized PT compared with usual care in improving motor symptoms among patients with FMD. This was addressed through the development of a structured critically appraised topic. This included a clinical scenario with a clinical question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, and content experts in the fields of physical medicine and rehabilitation, physical and occupational therapy, psychiatry, and psychology. RESULTS: A randomized controlled feasibility trial was identified and selected for critical appraisal. This study randomized 60 patients with FMD to a 5-day specialized outpatient PT program or to general outpatient PT referral, and measured patient-reported and clinician-measured outcomes. At 6 months, 72% of patients in the intervention group had a good outcome compared with 18% of control group patients. Patients in the specialized outpatient PT program had significantly better outcomes in 3 Short-Form 36 (SF36) domains (d=0.46 to 0.79) and multiple other scales of physical and social function as well as clinician-measured outcomes. The intervention resulted in 0.08 additional quality-adjusted life years in a cost-effective manner. CONCLUSIONS: Current evidence suggests that in patients with FMD, specialized PT improves motor symptoms in a clinically significant, sustained, and cost-effective manner. This promising intervention warrants further investigation and replication.

Stroke Features, Risk Factors, and Pathophysiology in SARS-CoV-2-Infected Patients.

OBJECTIVE: To provide a comprehensive description of stroke characteristics, risk factors, laboratory parameters, and treatment in a series of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients admitted to Mayo Clinic hospitals in Rochester, Minnesota; Jacksonville, Florida; and Phoenix, Arizona, as well as the Mayo Clinic Health System. PATIENTS AND METHODS: We retrospectively identified hospitalized patients in whom stroke and SARS-CoV-2 infection were diagnosed within the same 3-month interval between September 8, 2019, and December 31, 2020. and extracted data on all available variables of interest. We further incorporated our findings into the existing body of basic science research to present a schematic model illustrating the proposed pathogenesis of ischemic stroke in SARS-CoV-2-infected patients. RESULTS: We identified 30 cases during the study period, yielding a 0.5% stroke rate across 6381 SARS-CoV-2-infected hospitalized patients. Strokes were ischemic in 26 of 30 individuals and hemorrhagic in 4 of 30. Traditional risk factors were common including hypertension (24 of 30), hyperlipidemia (18 of 30), smoking history (13 of 30), diabetes (11 of 30), and atrial fibrillation (8 of 30). The most common ischemic stroke mechanisms were cardioembolism (9 of 26) and cryptogenic (9 of 26). Intravenous alteplase and mechanical thrombectomy were administered to 2 of 26 and 1 of 26, respectively. The median (interquartile range) serum C-reactive protein, interleukin-6, D-dimer, fibrinogen, and ferritin levels were 66 (21-210) mg/L, 116 (8-400) pg/mL, 1267 (556-4510) ng/mL, 711 (263-772) mg/dL, and 407 (170-757) mcg/L, respectively, which were elevated in individuals with available results. CONCLUSION: The high prevalence of vascular risk factors and concurrent elevation of proinflammatory and procoagulation biomarkers suggest that there is an interplay between both factors in the pathogenesis of stroke in SARS-CoV-2-infected patients.

HIV Infection Is an Independent Predictor of Mortality Among Adults with Reduced Level of Consciousness in Uganda.

The clinical epidemiology of adults admitted with reduced level of consciousness (LOC) in sub-Saharan Africa (SSA) and the impact of HIV infection on the risk of mortality in this population is unknown. We secondarily analyzed data from a cohort study that enrolled 359 consecutive adults with reduced LOC presenting to Mbarara Regional Hospital in Uganda with the aim of comparing the prognostic utility of the Full Outline of Unresponsiveness (FOUR) score to the Glasgow Coma Scale (GCS) Score. For this analysis, we included 336 individuals with known HIV serostatus, obtaining clinical, laboratory, and follow-up data. We recorded investigations and treatments deemed critical by clinicians for patient care but were unavailable. We computed mortality rates and used logistic regression to determine predictors of 30-day mortality. The median GCS was 10. Persons living with HIV infection (PLWH) accounted for 97 of 336 (29%) of the cohort. The 30-day mortality rate in the total cohort was 148 of 329 (45%), and this was significantly higher in PLWH (57% versus 40%, adjusted odds ratio [aOR] 2.39: 95% confidence interval [CI]: 1.31-4.35, P = 0.0046). Other predictors of mortality were presence of any unmet clinical need (aOR 1.72; 95% CIL 1.04-2.84, P = 0.0346), anemia (aOR 1.68; 95% CI: 1.01-2.81, P = 0.047), and admission FOUR score < 12 [aOR 4.26; 95% CI: 2.36-7.7, P < 0.0001). Presentation with reduced LOC in Uganda is associated with high mortality rates, with worse outcomes in PLWH. Improvement of existing acute care services is likely to improve outcomes.

Migrainous infarction of the eye: Two cases of monocular ischemic complications associated with retinal migraine.

BACKGROUND: Retinal migraine is defined by fully reversible monocular visual phenomena. We present two cases that were complicated by permanent monocular vision deficits. CASES: A 57-year-old man with history of retinal migraine experienced persistent monocular vision loss after one stereotypical retinal migraine, progressing to finger-count vision over 4 days. He developed paracentral acute middle maculopathy that progressed to central retinal artery occlusion. A 27-year-old man with history of retinal migraine presented with persistent right eye superotemporal scotoma after a retinal migraine. Relative afferent pupillary defect and superotemporal visual field defect were noted, consistent with ischemic optic neuropathy. CONCLUSION: Retinal migraine can complicate with permanent monocular visual loss, suggesting potential migrainous infarction of the retina or optic nerve. A thorough cerebrovascular evaluation must be completed, which was unrevealing in our cases. Acute and preventive migraine therapy may be considered in retinal migraine patients, to mitigate rare but potentially permanent visual loss.

Is Autologous Stem Cell Transplantation a Safe and Effective Alternative to Whole Brain Radiation as Consolidation Therapy in Patients With Primary Central Nervous System Lymphoma?: A Critically Appraised Topic.

BACKGROUND: High-dose chemotherapy followed by autologous stem cell transplantation (HD-ASCT) is a promising alternative to whole brain radiation therapy (WBRT) in the treatment of primary central nervous system lymphoma (PCNSL). The objective of this study was to critically assess current evidence supporting the use of HD-ASCT as first-line consolidative therapy in PCNSL. METHODS: The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and a content expert in the field of neuro-oncology. RESULTS: A recent, open-label, noncomparative randomized phase II trial was selected for critical appraisal. This trial evaluated the efficacy and toxicity of consolidative therapy with HD-ASCT and WBRT in PCNSL in 2 separate treatment arms. A total of 140 patients with newly diagnosed PCNSL between the ages of 18 and 60 years were included. The primary endpoint of 2-year progression-free survival was met in 63% of patients in the WBRT arm and 87% in the HD-ASCT arm. Notably, an overall improvement in neurocognitive scores was observed following HD-ASCT, while WBRT was associated with worsened cognitive outcomes. CONCLUSIONS: In young patients with newly diagnosed PCNSL, consolidative therapy with HD-ASCT appears to be associated with less neurocognitive toxicity and may be more effective than WBRT at preventing relapses, however, at the cost of a higher treatment-related mortality.

Prognostic Utility of Daily Changes in Glasgow Coma Scale and the Full Outline of Unresponsiveness Score Measurement in Patients with Metabolic Encephalopathy, Central Nervous System Infections and Stroke in Uganda.

BACKGROUND: Metabolic encephalopathy (ME), central nervous system (CNS) infections, and stroke are common causes of reduced level of consciousness in Uganda. However, the prognostic utility of changes in the daily measurements of the Full Outline of Unresponsiveness (FOUR) score and Glasgow Coma Scale (GCS) score in these specific disorders is not known. METHODS: We conducted secondary analyses of data from patients who presented with reduced level of consciousness due to CNS infections, stroke, or ME to a tertiary hospital in Uganda. Patients had FOUR/GCS scores at admission and at 24 and 48 h. We calculated a change in FOUR score (ΔFOUR) and change in GCS score (ΔGCS) at 24 and 48 h and used logistic regression models to determine whether these changes were predictive of 30-day mortality. In addition, we determined the prognostic utility of adding the admission score to the 24-h ΔFOUR and 24-h ΔGCS on mortality. RESULTS: We analyzed data from 230 patients (86 with ME, 79 with CNS infections, and 65 with stroke). The mean (SD) age was 50.8 (21.3) years, 27% (61 of 230) had HIV infection, and 62% (134 of 230) were peasant farmers. ΔFOUR at 24 h was predictive of mortality among those with ME (odds ratio [OR] 0.64 [95% confidence interval {CI} 0.48-0.84]; p = 0.001) and those with CNS infections (OR 0.65 [95% CI 0.48-0.87]; p = 0.004) but not in those with stroke (OR 1.0 [95% CI 0.73-1.38]; p = 0.998). However, ΔGCS at 24 h was only predictive of mortality in the ME group (OR 0.69 [95% CI 0.56-0.86]; p = 0.001) and not in the CNS or stroke group. This 24-h ΔGCS and ΔFOUR pattern was similar at 48 h in all subgroups. The addition of an admission score to either 24-h ΔFOUR or 24-h ΔGCS significantly improved the predictive ability of the scores in those with stroke and CNS infection but not in those with ME. CONCLUSIONS: Twenty-four-hour and 48-h ΔFOUR and ΔGCS are predictive of mortality in Ugandan patients with CNS infections and ME but not in those with stroke. For individuals with stroke, the admission score plays a more significant predictive role that the change in scores.

Intracerebral Hemorrhage: A Common yet Disproportionately Deadly Stroke Subtype.

Spontaneous intracerebral hemorrhage (ICH) is a medical emergency and is disproportionately associated with higher mortality and long-term disability compared with ischemic stroke. The phrase "time is brain" was derived for patients with large vessel occlusion ischemic stroke in which approximately 1.9 million neurons are lost every minute. Similarly, this statement holds true for ICH patients due to a high volume of neurons that are damaged at initial onset and during hematoma expansion. Most cases of spontaneous ICH pathophysiologically stem from chronic hypertension and rupture of small perforating vessels off of larger cerebral arteries supplying deep brain structures, with cerebral amyloid angiopathy being another cause for lobar hemorrhages in older patients. Optimal ICH medical management strategies include timely diagnosis, aggressive blood pressure control, correction of underlying coagulopathy defects if present, treatment of cerebral edema, and continuous assessment for possible surgical intervention. Current strategies in the surgical management of ICH include newly developed minimally invasive techniques for hematoma evacuation, with the goal of mitigating injury to fiber tracts while accessing the clot. We review evidence-based medical and surgical management of spontaneous ICH with the overall goal of reducing neurologic injury and optimizing functional outcome.