Neurology of Systemic Disease: Selected Topics with a Focus on Women.

Sex differences exist within the neurologic complications of systemic disease. To promote new avenues for prevention and develop novel therapeutics, we highlight the role of sex in differential outcomes to infectious disease and cardiac arrest and educate the reader in paraneoplastic presentations that may herald underlying malignancies in women.

Post-Trial Enhanced Deployment and Technical Performance with the MISTIE Procedure per Lessons Learned.

OBJECTIVE: We hypothesize that procedure deployment rates and technical performance with minimally invasive surgery and thrombolysis for intracerebral hemorrhage (ICH) evacuation (MISTIE) can be enhanced in post-trial clinical practice, per Phase III trial results and lessons learned. MATERIALS AND METHODS: We identified ICH patients and those who underwent MISTIE procedure between 2017-2021 at a single site, after completed enrollments in the Phase III trial. Deployment rates, complications and technical outcomes were compared to those observed in the trial. Initial and final hematoma volume were compared between site measurements using ABC/2, MISTIE trial reading center utilizing manual segmentation, and a novel Artificial Intelligence (AI) based volume assessment. RESULTS: Nineteen of 286 patients were eligible for MISTIE. All 19 received the procedure (6.6% enrollment to screening rate 6.6% compared to 1.6% at our center in the trial; p=0.0018). Sixteen patients (84%) achieved evaculation target < 15 mL residual ICH or > 70% removal, compared to 59.7% in the trial surgical cohort (p=0.034). No poor catheter placement occurred and no surgical protocol deviations. Limitations of ICH volume assessments using the ABC/2 method were shown, while AI based methodology of ICH volume assessments had excellent correlation with manual segmentation by experienced reading centers. CONCLUSIONS: Greater procedure deployment and higher technical success rates can be achieved in post-trial clinical practice than in the MISTIE III trial. AI based measurements can be deployed to enhance clinician estimated ICH volume. Clinical outcome implications of this enhanced technical performance cannot be surmised, and will need assessment in future trials.

Inversion of T Waves on Admission is Associated with Mortality in Spontaneous Intracerebral Hemorrhage.

INTRODUCTION: Cardiac dysfunction directly caused by spontaneous intracerebral hemorrhage (ICH) is a poorly understood phenomenon, and its impact on outcome is still uncertain. The aim of this study is to investigate the relationship between electrocardiographic (EKG) abnormalities and mortality in ICH. METHODS: This is a retrospective study analyzing EKG patterns on admission in patients admitted with ICH at a tertiary care center over an eight-year period. For each patient, demographics, medical history, clinical presentation, EKG on admission and during hospitalization, and head CT at presentation were reviewed. Mortality was noted. RESULTS: A total of 301 ICH patients were included in the study. The most prevalent EKG abnormalities were QTc prolongation in 56% of patients (n = 168) followed by inversion of T waves (TWI) in 37% of patients (n = 110). QTc prolongation was associated with ganglionic location (p = 0.03) and intraventricular hemorrhage (IVH) (p = 0.01), TWIs were associated with ganglionic location (p = 0.02), and PR prolongation was associated with IVH (p = 0.01), while QRS prolongation was associated with lobar location (p < 0.01). Volume of ICH, hemispheric laterality, and involvement of insular cortex were not correlated with specific EKG patterns. In a logistic regression model, after correcting for ICH severity and prior cardiac history, presence of TWI was independently associated with mortality (OR: 3.04, CI:1.6-5.8, p < 0.01). Adding TWI to ICH score improved its prognostic accuracy (AUC 0.81, p = 0.04). Disappearance of TWI during hospitalization did not translate into improvement of survival (p = 0.5). CONCLUSION: Presence of TWI on admission is an independent and unmodifiable factor associated with mortality in ICH. Further research is needed to elucidate the pathophysiologic mechanisms underlying electrocardiographic changes after primary intracerebral hemorrhage.

Effect of desmopressin on hematoma expansion in antiplatelet-associated intracerebral hemorrhage: A systematic review and meta-analysis.

The purpose of this study was to perform a systematic review and meta-analysis on the effect of desmopressin on hematoma expansion (HE) in antiplatelet-associated intracerebral hemorrhage (AA-ICH). Secondary outcomes examined were the rate of thrombotic complications and neurologic outcome. Three databases were searched (Pubmed, Scopus, and Cochrane) for randomized clinical trials and controlled studies comparing desmopressin versus controls in adult patients with AA-ICH. The Mantel-Haenszel method was applied to calculate an overall effect estimate for each outcome by combining stratum-specific risk ratio (RR). Risk of bias was computed using the Newcastle-Ottawa Scale. The protocol was registered in PROSPERO (42020190234). Three retrospective controlled studies involving 263 patients were included in the meta-analysis. Compared to controls, desmopressin was associated with a non-significant reduction in HE (19.1% vs. 30%; RR:0.61; 95%CI, 0.27-1.39; P = 0.24), a similar rate of thrombotic events (5.5% vs. 9.9%; RR:0.47; 95%CI, 0.17-1.31; P = 0.15), and significantly worse neurologic outcome (mRS ≥ 4) (66.3% vs. 50%; RR:1.36; 95%CI, 1.08-1.7; P = 0.008). Qualitative analysis of included studies for each outcome revealed low to moderate risk of bias. The available literature does not support the routine use of desmopressin in the setting of AA-ICH. Until larger prospective trials are performed, the administration of desmopressin should be judiciously considered on a case-by-case basis.

Rapid development of seizures and PRES in a COVID-19 patient.

Neurological dysfunction has been noted in up to 36% of patients hospitalized with COVID-19, and a variety of mechanisms of neurological injury are possible. Here we report the rapid development of PRES and acute seizures in a patient with COVID-19 infection and sickle cell disease. The combination of COVID and sickle cell disease may raise the risk of PRES and could contribute to the higher mortality rate of COVID in patients with sickle cell disease.

Neuroendocrine Dysfunction in the Acute Setting of Penetrating Brain Injury: A Systematic Review.

BACKGROUND: Data on neuroendocrine dysfunction (NED) in the acute setting of penetrating brain injury (PBI) are scarce, and the clinical approach to diagnosis and treatment remains extrapolated from the literature on blunt head trauma. METHODS: Three databases were searched (PubMed, Scopus, and Cochrane). Risk of bias was computed using the Newcastle-Ottawa Scale, or the methodological quality of case series and case reports, as indicated. This systematic review was registered in PROSPERO (42020172163). RESULTS: Six relevant studies involving 58 patients with PBI were included. Two studies were prospective cohort analyses, whereas 4 were case reports. The onset of NED was acute in all studies, by the first postinjury day. Risk factors for NED included worse injury severity and the presence of cerebral edema on imaging. Dysfunction of the anterior hypophysis involved the hypothalamic-pituitary-thyroid axis, treated with hormonal replacement, and hypocortisolism, treated with hydrocortisone. The prevalence of central diabetes insipidus was up to 41%. Most patients showed persistent NED months after injury. In separate reports, diabetes insipidus and hypocortisolism showed an association with higher mortality. The available literature for this review is poor, and the studies included had overall low quality with high risk of bias. CONCLUSIONS: NED seems to be prevalent in the acute phase of PBI, equally involving both anterior and posterior hypophysis. Despite a potential association between NED and mortality, data on the optimal management of NED are limited. This situation defines the need for prospective studies to better characterize the clinical features and optimal therapeutic interventions for NED in PBI.

Association between electrolyte levels at presentation and hematoma expansion and outcome in spontaneous intracerebral hemorrhage: A systematic review.

PURPOSE: To assess the association between specific electrolyte levels (sodium, potassium, calcium, magnesium, and phosphorus) on presentation and hematoma expansion (HE) and outcome in intracerebral hemorrhage (ICH). METHODS: This review was conducted in accordance with the PRISMA statement recommendations. Three databases were searched (Pubmed, Scopus, and Cochrane). Risk of bias was computed using the Newcastle-Ottawa Scale tool. RESULTS: 18 full-text articles were included in this systematic review including 10,385 ICH patients. Hypocalcemia was associated with worse short-term outcome in four studies, and two other studies were neutral. All studies investigating HE in hypocalcemia (n = 5) reported an association between low calcium level and HE. Hyponatremia (Na < 135 mEq/L) was shown to correlate with worse short-term outcome in two studies, and worse long-term outcome in one. There was one report showing no association between sodium level and HE. Hypomagnesemia was shown to be associated with worse short-term outcome in one study, while other reports were neutral. Studies evaluating hypophosphatemia or hypokalemia in ICH were limited, with no demonstrable significant effect on outcome. CONCLUSION: This review suggests a significant association between hypocalcemia, hyponatremia and, of lesser degree, hypomagnesemia on admission and HE or worse outcome in ICH.

Case Report: Management of Traumatic Carotid-Cavernous Fistulas in the Acute Setting of Penetrating Brain Injury.

Traumatic carotid-cavernous fistulas (tCCFs) after penetrating brain injury (PBI) have been uncommonly described in the literature with little guidance on optimal treatment. In this case series, we present two patients with PBI secondary to gunshot wounds to the head who acutely developed tCCFs, and we review the lead-up to diagnosis in addition to the treatment of this condition. We highlight the importance of early cerebrovascular imaging as the clinical manifestations may be limited by poor neurological status and possibly concomitant injury. Definitive treatment should be attempted as soon as possible with embolization of the fistula, flow diversion via stenting of the fistula site, and, finally, vessel sacrifice as possible therapeutic options.

Cerebrovascular Complications in Early Survivors of Civilian Penetrating Brain Injury.

BACKGROUND: This study investigates the presence of cerebrovascular injuries in a large sample of civilian penetrating brain injury (PBI) patients, determining the prevalence, radiographic characteristics, and impact on short-term outcome. METHODS: We retrospectively reviewed patients with PBI admitted to our institution over a 2-year period. Computed tomography head scans, computer tomography angiograms and venograms of the intracranial vessels were evaluated to determine the wound trajectory, intracranial injury characteristics, and presence of arterial (AI) and venous sinus (VSI) injuries. Demographics, clinical presentation, and treatment were also reviewed. Discharge disposition was used as surrogate of short-term outcome. RESULTS: Seventy-two patients were included in the study. The mechanism of injury was gunshot wounds in 71 patients and stab wound in one. Forty-one of the 72 patients (60%) had at least one vascular injury. Twenty-six out of 72 patients suffered an AI (36%), mostly pseudoaneurysms and occlusions, involving the anterior and middle cerebral arteries. Of the 72 patients included, 45 had dedicated computed tomography venograms, and of those 22 had VSI (49%), mainly manifesting as superior sagittal sinus occlusion. In a multivariable regression model, intraventricular hemorrhage at presentation was associated with AI (OR 9.9, p = 0.004). The same was not true for VSI. CONCLUSION: Acute traumatic cerebrovascular injury is a prevalent complication in civilian PBI, frequently involving both the arterial and venous sinus systems. Although some radiographic features might be associated with presence of vascular injury, assessment of the intracranial vasculature in the acute phase of all PBI is essential for early diagnosis. Treatment of vascular injury remains variable depending on local practice.

Early Determinants of Neurocritical Care Unit Length of Stay in Patients with Spontaneous Intracerebral Hemorrhage.

BACKGROUND: The present study considers patients with spontaneous intracerebral hemorrhage (ICH) admitted to the neurocritical care unit (NCCU) through the Emergency Department (ED). It aims to identify patient-specific clinical variables that can be assessed on presentation and that are associated with prolonged NCCU length of stay (LOS). METHODS: A cross-sectional, single-center, retrospective analysis of ICH patients directly admitted from the ED to the NCCU over an 8-year period was performed. Patients' demographics, clinical exam characteristics, serum laboratory values, intubation status, and neurosurgical procedures at presentation were recorded. Head computed tomography scans obtained on presentation were reviewed. LOS was calculated based on the number of midnights spent in the NCCU. Prolonged LOS was determined using a change point analysis, adopting the method of Taylor which utilizes CUMSUM charts and bootstrap analysis. A decision tree model was trained and validated to identify reliable variables associated with prolonged LOS. RESULTS: Two hundred and five patients with ICH were analyzed. Prolonged LOS was calculated to be a stay that exceeds 8 days; 68 patients (33%) had a prolonged LOS in NCCU. Median LOS did not differ between survivors and patients who died in hospital. Clinical variables explored through the decision tree model were intubation status, neurosurgical intervention (EVD, decompression or evacuation within 24 h from presentation), and components of the ICH score: age, GCS, hematoma volume, the presence of intraventricular hemorrhage (IVH), and infratentorial location. The model accuracy was 0.8 and AUC was 0.83 (95% CI 0.78-0.89). CONCLUSION: We propose an ICH-LOS model based on neurosurgical intervention, intubation status and GCS at presentation to predict prolonged LOS in the NCCU in patients with ICH. This simple clinical tool, if prospectively validated, could help with medical planning, contribute to patient care-directed conversations, assist in optimizing hospital resource utilization, and, more importantly, motivating patient-specific interventions aimed at optimizing outcomes and decreasing LOS.

Herpes Simplex Virus 2 Meningoencephalitis-Associated Bilateral Optic Neuritis and Radiculitis.

The most common ocular complication of herpes simplex virus (HSV) is acute retinal necrosis. We present a rare case of a patient with HSV-2 meningoencephalitis that developed severe vision-threatening optic neuritis. The patient was treated with steroids and IVIG, which allowed a rapid improvement in her vision.

BE-FAST: A Sensitive Screening Tool to Identify In-Hospital Acute Ischemic Stroke.

BACKGROUND: Development of acute ischemic stroke in hospitalized patients represents a significant proportion of all cerebral ischemia. Several prehospital stroke scales were developed to screen for acute ischemic stroke in the community. Despite the advent of inpatient stroke alert systems, there is a lack of validated screening tools for the inpatient population. This study aims to assess the validity of BE-FAST (Balance, Eyes, Face, Arm, Speech, Time) as a screening tool for acute ischemic stroke among inpatients. METHODS: We retrospectively analyzed all stroke alert activations at a single academic medical center between 2012 and 2016. We classified the triggering symptom as: focal neurologic deficit, aphasia, dysarthria, ataxia/vertigo/dizziness, alteration of consciousness, acute confusion, or headache. BE-FAST was applied retrospectively, and patients were classified as BE-FAST positive or negative. The final diagnosis was classified as acute ischemic stroke, transient ischemic attack , intracranial hemorrhage or noncerebrovascular diagnosis. RESULTS: Of 1965 stroke alerts, 489 were among inpatients. The mean age was 63 ± 16.1 years; 57% of patients were women (n = 1121). Acute ischemic stroke was diagnosed in 29% of all the activations (n = 567), transient ischemic attack in 12% (n = 232), intracranial hemorrhage in 8 % (n = 160) and noncerebrovascular in 51% (n = 1006). When comparing inpatient with community-onset stroke alerts, the sensitivity of BE-FAST for diagnosing acute ischemic stroke was 85% versus 94% (P = .005), with a specificity of 43% versus 23% (P < .001), respectively. However, when evaluating in-patients with an intact level of consciousness separately, BE-FAST sensitivity for diagnosing acute ischemic stroke was 92% compared to 94% in the community (P = .579). Among in-patients with acute ischemic stroke who were (1) candidates for reperfusion therapy and (2) diagnosed with acute large vessel occlusion, the sensitivity of BE-FAST was 83% and 94%, respectively. CONCLUSIONS: This is the first study to analyze the performance of BE-FAST among hospitalized patients evaluated through the inpatient stroke alert system. We found BE-FAST to be a very sensitive tool for screening for all in-hospital acute ischemic strokes, including inpatients that were candidates for acute reperfusion therapy.

The role of amantadine in cognitive recovery early after traumatic brain injury: A systematic review.

We conducted an updated systematic review on the safety and efficacy of amantadine in cognitive recovery after traumatic brain injury (TBI), in order to determine if the current literature justifies its use in this clinical condition. A comprehensive search strategy was applied to three databases (PubMed, Scopus, and Cochrane). Only randomized clinical trials (RCTs) that compared the effect of amantadine and placebo in adults within 3 months of TBI were included in the review. Study characteristics, outcomes, and methodological quality were synthesized. This systematic review was conducted and presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A quantitative synthesis (meta-analysis) was not feasible due to the large heterogeneity of studies identified. Three parallel RCTs and one cross-over RCT, with a total of 325 patients were included. All of the studies evaluated only severe TBI in adults. Amantadine was found to be well tolerated across the studies. Two RCTs reported improvement in the intermediate-term cognitive recovery (four to six weeks after end of treatment), using DRS (in both studies) and MMSE, GOS, and FIM-Cog (in one study). The effect of amantadine on the short-term (seven days to discharge) and long-term (six months from the injury) cognitive outcome was found not superior to placebo in two RCTs. The rate of severe adverse events was found to be consistently very low across the studies (the incidence of seizures, elevation in liver enzymes and cardiac death was 0.7 %, 1.9 %, and 0.3 %, respectively). In conclusion, amantadine seems to be well tolerated and might hasten the rate of cognitive recovery in the intermediate-term outcome. However, the long-term effect of amantadine in cognitive recovery is not well defined and further large randomized clinical trials in refined subgroups of patients are needed to better define its application.

Intracranial Hemorrhage in Hospitalized Patients: An Infrequently Studied Condition with High Mortality.

BACKGROUND: Intracranial hemorrhage (ICH) may occur in patients admitted to the hospital for unrelated medical conditions, resulting in prolonged hospitalization and worse prognosis. We aim to assess the clinical presentation and outcomes of in-hospital ICH compared to patients with ICH presenting from the community. METHODS: We conducted a retrospective analysis of all acute stroke alerts diagnosed with ICH in an urban academic hospital over a 4-year period. Demographics, clinical presentation, use of antithrombotic therapy, and presence of coagulopathy were recorded. ICH score and a sequential organ failure assessment score were calculated during the initial assessment. Initial head computed tomography was reviewed to determine ICH subtype, location, and volume of the hematoma. In-hospital mortality and discharge disposition were used as surrogate of clinical outcome. RESULTS: From the 1965 stroke alert cases analyzed over the studied years, 145 (7.4%) were diagnosed with ICH. Overall, the mean age was 62.9 ± 13.9 and 53.7% were women. Thirty-two patients (22%) developed ICH in the inpatient setting and 113 (78%) presented from the community. Systolic blood pressure at presentation was lower in the in-hospital group (p < 0.01). Inpatients who developed ICH were more likely than community ICH patients to be on combination of antiplatelet agents (21.9% vs. 5.3%, p < 0.05) or therapeutic heparinoids (21.9% vs. 0.9%, p < 0.01). Also, In-hospital ICH patients had a higher rate of spontaneous or iatrogenic coagulopathy (65.6% vs. 10.6%, p < 0.01) and thrombocytopenia (31.3% vs. 1.8%, p < 0.01). Lobar hemorrhages were more prevalent in the in-hospital group (82.6% vs. 39.1%, p < 0.01) and the mean hematoma volume was higher (40.9 ± 43.1 mL vs. 24.1 ± 30.4 mL; p < 0.02). Median ICH score in the in-hospital group was not statistically different from the emergency department group: 2 (IQR: 0-3) versus 1 (IQR: 0-3). When comparing patients with in-hospital ICH and those from the community, the short-term mortality was higher in the former group (81% vs. 31%, p < 0.01). The incidence of withdrawal of life-sustaining therapies as a proximate mechanism of death was higher, but not statistically significant, in the in-hospital group (86% vs. 61%). CONCLUSION: ICH is a critical complication in the inpatient setting, predominantly occurring in already ill patients with underlying spontaneous or iatrogenic coagulopathy. Large volume lobar intraparenchymal hemorrhage is a common radiographic finding. ICH is frequently a catastrophic event and powerfully weighs in with end-of-life discussion, resulting in high short-term mortality rate.

Clinical Characteristics and Emergent Therapeutic Interventions in Patients Evaluated through the In-hospital Stroke Alert Protocol.

BACKGROUND AND PURPOSE: Emergent evaluation of inpatients with suspected acute ischemic stroke faces difficulty of symptoms recognition, false alarms, and high rate of contraindications to reperfusion therapies. We aim to assess the clinical characteristics and therapeutic interventions implemented in patients evaluated though the in-hospital Stroke Alert Protocol. METHODS: We analyzed 4 years-worth of Stroke Alert cases at a university hospital. Demographics, clinical presentation, final diagnosis, and acute interventions were compared between inpatients and those presenting to the emergency department. FINDINGS: A total of 1965 Stroke Alert cases were included: 959 (48.8%) were acute cerebrovascular events and 1006 (51.2%) were noncerebrovascular. Hospitalized patients accounted for 489 (24.9%) of Stroke Alerts and patients in the emergency department for 1476 (75.1%). Inpatients were more likely to present with nonfocal neurological deficits (46.2% versus 32.4%, P < .0001) and be diagnosed with noncerebrovascular disorders (62.4% versus 47.5%, P < .0001). Acute interventions other than thrombolysis were delivered in 77.1% of in-hospital cases. Compared to the emergency department, inpatients were more commonly managed with rectification of metabolic abnormalities (21.5% versus 13.7%, P < .001), suspension or pharmacological reversal of drugs (11% versus 3.7%, P < .001), and initiation of respiratory support (13.5% versus 9.3%, P = .01). Inpatients with acute ischemic stroke received intravenous thrombolysis less frequently (4.9% versus 23.9%, P < .001), but the endovascular treatment rate was comparable (9.8% versus 10.3%) to the emergency department. CONCLUSION: Nonfocal neurological deficits and noncerebrovascular disorders are commonly encountered during in-hospital Stroke Alerts. In the inpatient setting, intravenous thrombolysis is rarely delivered while other time-sensitive therapeutic interventions are frequently implemented.