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.

Temporal Evolution and Outcomes of Non-Traumatic Intracerebral Hemorrhage in Hospitalized Patients.

OBJECTIVE: To investigate the radiographic features, temporal evolution, and outcome of patients who develop non-traumatic intracerebral hemorrhage (ICH) while hospitalized for other causes. METHODS: We retrospectively reviewed consecutive Emergency Department ICH (ED-ICH) and in-hospital ICH (IH-ICH) over an 8-year period. Variables including demographics, medical history, lab values, lead time to diagnosis, defined as time from last known well to first CT scan, and clinical characteristics, follow-up CT scan, as well as the frequency of withdrawal of life support were compared in the two groups. Mortality in correlation with ICH score was assessed. RESULTS: Sixty-One IH-ICH and 216 ED-ICH patients were compared. History of cardiac disease, cancer, coagulopathy and higher SOFA score at time of diagnosis were significantly higher in the IH-ICH group (all P< 0.01). Time from symptom onset to diagnosis was shorter in the IH-ICH group (median 95 versus 117 minutes, P=0.011). Thirty six percent of IH-ICH fell into a worse ICH category when recalculated 6 hours from initial scan time, compared to only 10% of the ED-ICH. ICH score was well calibrated in ED-ICH when assessed both at diagnosis and 6 hours later, but underestimated actual mortality in the IH-ICH, particularly at ICH scores 0 to 3. End of life measures were pursued in 69% of IH-ICH group compared to 19% in the ED-ICH group. CONCLUSIONS: IH-ICH, is associated with higher overall mortality rates and often times heralds withdrawal of life sustaining therapies in patients. In addition, IH-ICH in comparison to ED-ICH, significantly changes in severity metrics within the first 6 hours. ICH score is not accurate and not calibrated to reflect reasonable stratification of mortality in IH-ICH. Prospective validation and investigation of variables accounting for higher IH-ICH mortality are needed.

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.

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.

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.

Dysautonomia in Guillain-Barré Syndrome: Prevalence, Clinical Spectrum, and Outcomes.

BACKGROUND: Guillain-Barré syndrome (GBS), when severe, involves the autonomic nervous system; our objective was to assess the spectrum and predictors of dysautonomia, and how it may impact functional outcomes. METHODS: A retrospective review of patients admitted to the Mayo Clinic in Rochester, MN between January 1, 2000, and December 31, 2017, with GBS and dysautonomia was performed. Demographics, comorbidities, parameters of dysautonomia, clinical course, GBS disability score, and Erasmus GBS Outcome Score (EGOS) at discharge were recorded. RESULTS: One hundred eighty seven patients were included with 71 (38%) noted to have at least one manifestation of dysautonomia. There are 72% of patients with a demyelinating form of GBS and 36% of patients with demyelination had dysautonomia. Ileus (42%), hypertension (39%), hypotension (37%), fever (29%), tachycardia or bradycardia (27%), and urinary retention (24%) were the most common features. Quadriparesis, bulbar and neck flexor weakness, and mechanical ventilation were associated with autonomic dysfunction. Patients with dysautonomia more commonly had cardiogenic complications, syndrome of inappropriate antidiuretic hormone, posterior reversible encephalopathy syndrome, and higher GBS disability score and EGOS. Mortality was 6% in patients with dysautonomia versus 2% in the entire cohort (P = 0.02). CONCLUSIONS: Dysautonomia in GBS is a manifestation of more severe involvement of the peripheral nervous system. Accordingly, mortality and functional outcomes are worse. There is a need to investigate if more aggressive treatment is warranted in this category of GBS.

Vascular Disorders of the Spinal Cord.

PURPOSE OF REVIEW: Prompt recognition and timely management of vascular disorders of the spinal cord can improve patient outcomes. This article provides contemporary and practical knowledge about the most common vascular myelopathies. RECENT FINDINGS: New studies have provided additional information on the risk factors and impact of neurologic monitoring on perioperative spinal cord infarction. Additionally, recent publications have provided information on the impact of misdiagnosis, corticosteroid treatment, and postoperative prognosis in the treatment of spinal dural arteriovenous fistulas and have discussed the outcome of patients with spinal arteriovenous malformations treated with embolization, surgery, and stereotactic radiosurgery. Finally, recent studies have provided information on the natural history and postoperative prognosis of spinal cavernous malformations and on the risk factors and surgical outcome of patients with spinal epidural hematomas. SUMMARY: Diagnostic and therapeutic challenges are inherent in managing patients with vascular disorders of the spinal cord, and clinicians should have a thorough understanding of these disorders to facilitate optimal outcomes for patients with these potentially devastating illnesses. This article begins by reviewing functional vascular anatomy and subsequently describes the fundamental characteristics of both ischemic and hemorrhagic vascular myelopathies to equip clinicians with the knowledge to avoid common pitfalls.

Compound muscle action potential duration in critical illness neuromyopathy.

INTRODUCTION: We sought to determine the specificity of compound muscle action potential (CMAP) durations and amplitudes in a large critical illness neuromyopathy (CINM) cohort relative to controls with other neuromuscular conditions. METHODS: Fifty-eight patients with CINM who had been seen over a 17-year period were retrospectively studied. Electrodiagnostic findings of the CINM cohort were compared with patients with axonal peripheral neuropathy and myopathy due to other causes. RESULTS: Mean CMAP durations were prolonged, and mean CMAP amplitudes were severely reduced both proximally and distally in all nerves studied in the CINM cohort relative to the control groups. The specificity of prolonged CMAP durations for CINM approached 100% if they were encountered in more than 1 nerve. DISCUSSION: Prolonged, low-amplitude CMAPs occur more frequently and with greater severity in CINM patients than in neuromuscular controls with myopathy and axonal neuropathy and are highly specific for the diagnosis of CINM. Muscle Nerve 57: 395-400, 2018.

Intensive Care Unit-Acquired Weakness.

Intensive care unit-acquired weakness (ICUAW) is a substantial contributor to long-term disability in survivors of critical illness. Critical illness polyneuropathy, critical illness myopathy, and muscle atrophy from disuse contribute in various proportions to ICUAW. ICUAW is a clinical diagnosis supported by electrophysiology and newer diagnostic tests, such as muscle ultrasound. Risk factor reduction, including the aggressive treatment of sepsis and early mobilization, improves outcome. Although some patients with ICUAW experience a full recovery, for others improvement is slow and incomplete and quality of life is adversely affected. This article examines aspects of ICUAW and identifies potential areas of further study.

Refining the Association of Fever with Functional Outcome in Aneurysmal Subarachnoid Hemorrhage.

INTRODUCTION: We analyzed the impact of cause, severity, and duration of fever on functional outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Fever characteristics were analyzed in 584 consecutive patients with aSAH. Fever was defined as core body temperature ≥38.3 °C on ≥2 consecutive days. Subfebrile measurements were those between 37 and 38.2 °C. Febrile and subfebrile loads were the number of hours with fever or subfebrile measurements, respectively. Univariate and multivariate logistic regression models were developed to define predictors of outcome using various categorizations of fever cause, severity, and duration. RESULTS: Febrile measurements were observed in 281/584 (48.1 %) patients, recurring over a mean duration of 2.1 ± 3.0 days. Early fever within 24 and 72 h was encountered in 69 (11.9 %) and 110 (18.9 %) of patients, respectively. An infectious source was discovered in 126 (44.8 %) febrile patients. On univariate analysis, days of fever, febrile load, and fever onset within 24 and 72 h were associated with poor outcome (all p < 0.001); but subfebrile load was not (p = 0.56). On multivariate model constructed with all variables associated with outcome on univariate analyses, days of fever remained independently associated with poor outcome (OR 1.14 of poor outcome per day of fever, 95 % CI 1.06-1.22; p = 0.0006) displacing all other fever measures from the final model. CONCLUSIONS: Early onset of fever, number of hours with fever, and especially days of fever are associated with poor functional outcome. Conversely, subfebrile load does not influence clinical outcome. These data suggest prolonged fever should be avoided, but subfebrile temperatures may not justify intervention.

Asymptomatic Carotid Stenosis: Risk of Progression and Development of Symptoms.

BACKGROUND: The aim of this study is to evaluate the rate of progression of stenosis and development of symptoms in patients with asymptomatic carotid artery stenosis (aCAS) treated with contemporary medical therapy over a prolonged time interval. METHODS: This study is a retrospective review of consecutive patients diagnosed with moderate or severe aCAS at our institution between 2000 and 2001. Data were gathered from both carotid arteries for each patient excluding vessels operated within 1 year of diagnosis and occlusions. Multivariate analysis was performed to analyze factors associated with ipsilateral transient ischemic attack (TIA)/stroke. RESULTS: We identified 214 patients (58.8% men; median age 70 years) and collected data on 349 vessels. Degree of stenosis was severe (>70%) upon diagnosis in 92 (26.4%) vessels. Median length of follow-up was 13 years (interquartile range 10-14), and mean number of time points for follow-up imaging were 8.1 ± 3.9. Progression of stenosis was observed in 237 (67.9%) vessels, and 72 (20.6%) patients developed symptoms ipsilateral to the stenosis (TIA in 14.4%, non-disabling stroke in 4%, disabling stroke in 2.2%). Median time to appearance of first symptom was 6 years (range 1-13). On multivariate analysis, degree of baseline stenosis, intracranial stenosis >50%, plaque ulceration, silent infarction and previous history of TIA/stroke were associated with ipsilateral TIA/stroke, but progression of stenosis was not. CONCLUSIONS: There was a substantial rate of progression of stenosis in patients with aCAS over time despite adequate medical therapy, but progression of stenosis did not increase the risk of ipsilateral TIA/stroke. Over long-term follow-up, 1 in 5 patients with aCAS developed ipsilateral TIA/stroke, though most events were either transient or non-disabling.

Acute fever and seizure in a patient with recent atrial fibrillation ablation.

Patients undergoing radiofrequency ablation for treatment of atrial fibrillation may present critically ill with complications of atrial esophageal fistula, commonly manifesting as neurologic deficits and septicemia difficult to distinguish from other acute etiologies without a high index of suspicion. The temporal variability in fistula formation and symptom presentation, along with their nonspecific features, makes diagnosis often a late finding with historically high morbidity and mortality. We present a patient admitted to a medical intensive care unit with status epilepticus and recurrent positive blood cultures for organisms commonly associated with the gastrointestinal (GI) tract. Chest computed tomography (CT) without contrast, transthoracic echocardiography, and initial neurologic imaging were unhelpful. A diagnosis was ultimately made by upper endoscopy of the esophagus after hematemesis with suspicion for GI bleed, at which point surgical intervention was attempted but without success. This case reviews the clinical features of atrial esophageal fistula formation and its initial diagnosis and management.

Neurologist versus machine: is the pupillometer better than the naked eye in detecting pupillary reactivity.

BACKGROUND: A 62-year-old man with severe traumatic brain injury developed postsurgical anisocoria in which there was a discrepancy between pupillometer and manual testing. METHODS: Case report. RESULTS: The patient's larger pupil was read as unreactive by the pupillometer but constricted 1 mm over 7-9 s of continuous light stimulation. CONCLUSIONS: While pupillometry assessment is a valuable adjunct to the manual pupillary assessment, this case demonstrates that nonreactive pupils read on the pupillometer should be confirmed with the manual examination because it can miss very slowly reacting pupils.