Pilot study examining anti-factor Xa levels for heparin monitoring and outcomes in patients with cerebral venous thrombosis.

Objective: There are no studies to date that examine the association between anti-factor-Xa (AFXa)-based heparin monitoring and clinical outcomes in the setting of cerebral venous thrombosis (CVT). Methods: This pilot study included adults aged ≥18 admitted with CVT between 1 January 2018 and 1 January 2021, who were treated with unfractionated heparin (UFH) and were monitored via AFXa-based nomogram within 24 h of arrival. Comparisons were made between patients with AFXa levels within the target therapeutic range (0.25-0.5 IU/mL) and patients whose levels were not within the therapeutic range within 24 h of arrival; the time (hours) from arrival to reach the therapeutic range was also examined. Outcomes were length of stay (LOS) in the hospital, major (actionable) bleeding events, and discharge home (vs. higher acuity location). Continuous data are reported in the form of the median (interquartile range). Results: Among 45 patients, treatment with UFH was initiated 2 (1-11) h after arrival, and the majority (84%) of UFH infusions did not need dose adjustment. AFXa assays were conducted every 6 (5.5-7) h. Thirty patients (67%) fell within the therapeutic range. Outcomes were similar for patients with levels within the therapeutic range vs. not: major bleeding events, 10% vs. 0% (p = 0.54); discharge home, 77% vs. 80% (p = 1.0); LOS, 5 days in each group (p = 0.95). There was also no association between outcomes and time to reach the therapeutic range. Conclusion: Our findings demonstrate the practicability of monitoring UFH based on AFXa values in this population of patients with CVT, but reaching target AFXa levels within 24 h of arrival may not necessarily be prognostic.

Associations of Neutrophil-Lymphocyte Ratios with Reperfusion and Functional Outcomes in Ischemic Stroke after Endovascular Therapy.

OBJECTIVES: Treatment of ischemic stroke with endovascular thrombectomy (EVT) leads to improved outcomes compared to IV tPA. The neutrophil-lymphocyte ratio (NLR), a marker of inflammation, has been proposed to predict outcomes in ischemic stroke patients and may be used to identify patients at risk for poor outcomes after EVT. MATERIALS AND METHODS: This was a retrospective study of adult ischemic stroke patients undergoing EVT between 1/1/2018 and 12/31/2020. Outcomes were successful reperfusion (TICI score ≥2B), favorable discharge NIHSS (≤4), favorable discharge and 3-month mRS (≤2), and symptomatic intracranial hemorrhage (sICH). The primary exposure was NLR, measured pre- and post-EVT. Other variables collected included demographics and timing of stroke onset, arrival, groin puncture, tPA, and recanalization. RESULTS: A total of 592 patients were included. The most common vessel involved was the middle cerebral artery (73%). Lower admission NLR was associated with favorable discharge NIHSS and favorable discharge and 3-month mRS (all P < 0.01). NLRs measured after EVT were associated with all the primary outcomes. Improvements in NLR after EVT were associated with favorable discharge (P = 0.02) and 3-month mRS (P = 0.02) and lower incidence of sICH (P = 0.01). CONCLUSIONS: Because of the long-term functional deficits that can persist after ischemic stroke, it is vital to identify patients with higher probability for these outcomes. The results from this study showed that favorable NLR measures, as well as favorable trends in NLR over time, are associated with improved outcomes, indicating that NLR is a useful marker to identify patients at risk for poor functional outcomes.

Implementing the SNIS recommendations for neurointerventional emergent care in the setting of COVID-19: impact on stroke metrics and patient outcomes.

BACKGROUND: It is not clear whether the COVID-19 pandemic and subsequent Society of Neurointerventional Surgery (SNIS) recommendations affected hospital stroke metrics. METHODS: This retrospective cohort study compared stroke patients admitted to a comprehensive stroke center during the COVID-19 pandemic April 1 2020 to June 30 2020 (COVID-19) to patients admitted April 1 2019 to June 30 2019. We examined stroke admission volume and acute stroke treatment use. RESULTS: There were 637 stroke admissions, 52% in 2019 and 48% during COVID-19, with similar median admissions per day (4 vs 3, P=0.21). The proportion of admissions by stroke type was comparable (ischemic, P=0.69; hemorrhagic, P=0.39; transient ischemic stroke, P=0.10). Acute stroke treatment was similar in 2019 to COVID-19: tPA prior to arrival (18% vs, 18%, P=0.89), tPA treatment on arrival (6% vs 7%, P=0.85), and endovascular therapy (endovascular therapy (ET), 22% vs 25%, P=0.54). The door to needle time was also similar, P=0.12, however, the median time from arrival to groin puncture was significantly longer during COVID-19 (38 vs 43 min, P=0.002). A significantly higher proportion of patients receiving ET were intubated during COVID-19 due to SNIS guideline implementation (45% vs 96%, P<0.0001). There were no differences by study period in discharge mRS, P=0.84 or TICI score, P=0.26. CONCLUSIONS: The COVID-19 pandemic did not significantly affect stroke admission volume or acute stroke treatment utilization. Outcomes were not affected by implementing SNIS guidelines. Although there was a statistical increase in time to groin puncture for ET, it was not clinically meaningful. These results suggest hospitals managing patients efficiently can implement practices in response to COVID-19 without impacting outcomes.

Timing of Anticoagulation in Patients with Cerebral Venous Thrombosis Requiring Decompressive Surgery: Systematic Review of the Literature and Case Series.

OBJECTIVE: Cerebral venous thrombosis (CVT) is a rare type of stroke whose pathophysiology differs from arterial stroke. CVT is treated with systemic anticoagulant therapy even in the setting of intracerebral hemorrhage. Patients who do not respond adequately may require decompressive surgery. The study objective was to examine the timing of anticoagulation in patients with CVT who require decompressive surgery through systematic literature review and consecutive case series. METHODS: A review of the literature was performed through PubMed using key word search to identify case series and cohort studies examining timing of anticoagulation following decompressive surgery. Our case series included 4 patients who had decompressive surgery for hemorrhagic CVT between 1 January, 2015 and 31 December, 2016 at our comprehensive stroke center. RESULTS: The literature review summarizes 243 patients from 15 studies whose timing of anticoagulation varied. The review suggests anticoagulation can be safely resumed at 48 hours postoperatively based on larger series and as early as 12 hours in smaller series, especially when delivered as a half or prophylactic dose. In our case series, timing of anticoagulation varied slightly but was started or resumed within 38-44 hours postoperatively in 3 patients and was started at the time of decompressive surgery without interruption in 1 patient. No patient had worsening hemorrhage or new hemorrhage while 2 patients rethrombosed. CONCLUSIONS: Despite the lack of high-quality studies, this systematic review of patients with CVT requiring decompressive surgery indicates that anticoagulation can be safely initiated or resumed around 24-48 hours postoperatively; our series supports the existing literature.

Plasma Oxidized Albumin in Acute Ischemic Stroke Is Associated With Better Outcomes.

Introduction: Plasma oxidized human serum albumin (OxHSA) is evidence of an active antioxidant mechanism as measured by oxidized species of HSA. CXCL-10 is a pro-inflammatory chemokine associated with ischemic conditions. Accordingly, we examined the relationship of admission OxHSA and CXCL-10 with discharge mRS in acute ischemic stroke (AIS). Methods: Plasma samples and clinical data were collected prospectively at a Comprehensive Stroke Center. Admission biomarkers of oxidative stress, CXCL-10 and %OxHSA, were measured. We examined if CXCL-10 or %OxHSA correlated with age, admission NIHSS score, and discharge mRS score using Spearman's Rank correlation. Logistic regression was performed to identify independent predictors of a favorable discharge mRS (≤2). Results: In 106 consecutive AIS patients, the median age was 73 (IQR 61-84), 47% were male, and the median admission NIHSS score was 11 (IQR 5-19). %OxHSA and CXCL-10 were significantly correlated (r = 0.23, p = 0.02). Both biomarkers were significantly correlated with age: %OxHSA (r = 0.44, p < 0.001) and CXCL-10 (r = 0.32, p = 0.001). Neither biomarker was correlated with admission NIHSS. There was a borderline significant correlation with discharge mRS and %OxHSA (r = -0.17, p = 0.08), where higher %OxHSA correlated with lower discharge mRS scores. For every 1% increase in %OxHSA, the odds of a favorable discharge mRS increased 11%. The odds of a favorable discharge mRS decreased 18% for every 1-point increase in the initial NIHSS. Conclusions: OxHSA, the result of an oxidative environment and evidence of the strong antioxidant buffering capacity of HSA, correlated with CXCL-10 and discharge mRS, implying that strong antioxidant activity of albumin may confer better outcomes.

Decreased Odds for Vasospasm Treatment in Patients with Aneurysmal Subarachnoid Hemorrhage after Transitioning from Neurosurgery Led Care to a Neurology Led Multidisciplinary Approach.

INTRODUCTION: The limited research on the management of aneurysmal subarachnoid hemorrhages (aSAHs) has not assessed the efficacy of neurology-led care. Our objective was to describe aSAH patients' outcomes after transitioning from a neurosurgery-led intensive care unit (ICU) to a neurology-led multidisciplinary care neurocritical care unit (NCCU). The study hypothesis was that the neurology-led multidisciplinary care would improve patient outcomes. METHODS: This was a retrospective cohort study. We included patients (≥ 18) with aSAHs from 1/16 to 8/16 (pregroup) and from 3/17 to 11/17 (postgroup). The pregroup care was led by a neurosurgeon. The postgroup care included a neurologist, a pulmonary intensivist, a neurocritical care clinical nurse specialist, a neurosurgeon, and euvolemia protocol. The primary outcome was trips to interventional radiology (IR) for vasospasm treatment. Univariate analyses and multivariable ordinal logistic regression were used. RESULTS: There were 99 patients included: 50 in the pregroup and 49 in the postgroup. On average, postgroup patients were 7 years older than the pregroup (p = 0.05); no other demographic or clinical characteristics significantly differed. The 62% higher number of trips to IR for vasospasm treatment, when compared to the pregroup, p < 0.001. CONCLUSIONS: In aSAH patients, the neurology-led multidisciplinary care in the NCCU decreased the odds of repeated procedures for vasospasm treatment. Neurology-led multidisciplinary care could be more cost-effective than the neurosurgical-led care.

Comparing Outcomes of Patients With Idiopathic Subarachnoid Hemorrhage by Stratifying Perimesencephalic Bleeding Patterns.

BACKGROUND: To determine the clinical outcomes of perimesencephalic subarachnoid hemorrhages based on the computed tomography (CT) bleeding patterns. METHODS: This retrospective cohort study included: (1) patients (≥18 years) admitted to a comprehensive stroke center (January 2015-May 2018), (2) with angiography-negative, nontraumatic subarachnoid hemorrhage in a perimesencephalic or diffuse bleeding pattern, and (3) had CT imaging performed in ≤ 72 hours of symptom onset. Patients were stratified by location of bleeding on CT: Peri-1: focal prepontine hemorrhage; Peri-2: prepontine with suprasellar cistern +/- intraventricular extension; and diffuse. RESULTS: Of the 39 patients included, 13 were Peri-1, 11 were Peri-2, and 15 were diffuse. The majority were male (n = 26), with a mean (standard deviation) age of 55.3 (11.3) years, who often presented with headache (n = 37) and nausea (n = 28). Overall, patients in Peri-1 were significantly less likely to have hydrocephalus compared to Peri-2 and dSAH (P= .003), and 4 patients required an external ventricular drain. Five patients developed symptomatic vasospasm. Patients in Peri-1, compared to Peri-2 and diffuse, had a significantly shorter median neuro critical care unit length of stay (LOS) and hospital LOS. Most patients (n = 35) had a discharge modified Rankin Score between 0 and 2 with no significant differences found between groups. CONCLUSION: These data suggest that patients with the best clinical course were those in Peri-1, followed by Peri-2, and then diffuse. Because these patients often present with similar clinical signs, stratifying by hemorrhage pattern may help clinicians predict which patients with perimesencephalic subarachnoid hemorrhage develop complications.

Building a neuroinfectious disease consensus curriculum.

OBJECTIVE: To delineate a comprehensive curriculum for fellowship training in neuroinfectious diseases, we conducted a modified Delphi approach to reach consensus among 11 experts in the field. METHODS: The authors invited a diverse range of experts from the American Academy of Neurology Neuro-Infectious Diseases (AAN Neuro-ID) Section to participate in a consensus process using a modified Delphi technique. RESULTS: A comprehensive list of topics was generated with 101 initial items. Through 3 rounds of voting and discussion, a curriculum with 83 items reached consensus. CONCLUSIONS: The modified Delphi technique provides an efficient and rigorous means to reach consensus on topics requiring expert opinion. The AAN Neuro-ID section provided the pool of diverse experts, the infrastructure, and the community through which to accomplish the consensus project successfully. This process could be applied to other subspecialties and sections at the AAN.

PML diagnostic criteria: consensus statement from the AAN Neuroinfectious Disease Section.

OBJECTIVE: To establish criteria for the diagnosis of progressive multifocal leukoencephalopathy (PML). METHODS: We reviewed available literature to identify various diagnostic criteria employed. Several search strategies employing the terms "progressive multifocal leukoencephalopathy" with or without "JC virus" were performed with PubMed, SCOPUS, and EMBASE search engines. The articles were reviewed by a committee of individuals with expertise in the disorder in order to determine the most useful applicable criteria. RESULTS: A consensus statement was developed employing clinical, imaging, pathologic, and virologic evidence in support of the diagnosis of PML. Two separate pathways, histopathologic and clinical, for PML diagnosis are proposed. Diagnostic classification includes certain, probable, possible, and not PML. CONCLUSION: Definitive diagnosis of PML requires neuropathologic demonstration of the typical histopathologic triad (demyelination, bizarre astrocytes, and enlarged oligodendroglial nuclei) coupled with the techniques to show the presence of JC virus. The presence of clinical and imaging manifestations consistent with the diagnosis and not better explained by other disorders coupled with the demonstration of JC virus by PCR in CSF is also considered diagnostic. Algorithms for establishing the diagnosis have been recommended.

Acute bacterial and viral meningitis.

PURPOSE OF REVIEW: Most cases of acute meningitis are infectious and result from a potentially wide range of bacterial and viral pathogens. The organized approach to the patient with suspected meningitis enables the prompt administration of antibiotics, possibly corticosteroids, and diagnostic testing with neuroimaging and spinal fluid analysis. RECENT FINDINGS: Acute meningitis is infectious in most cases and caused by a potentially wide range of bacterial and viral pathogens. Shifts in the epidemiology of bacterial pathogens have been influenced by changes in vaccines and their implementation. Seasonal and environmental changes influence the likely viral and rickettsial pathogens. SUMMARY: The organized approach to the patient with suspected meningitis enables the prompt administration of antibiotics, possibly corticosteroids, and diagnostic testing with neuroimaging and spinal fluid analysis. Pertinent testing and treatment can vary with the clinical presentation, season, and possible exposures. This article reviews the epidemiology, clinical presentation, diagnosis, and treatment of acute meningitis.

White matter anisotropy and depression symptoms in patients with HIV.

HIV is associated with increased risk for depression. Normal appearing white matter (NAWM) fractional anisotropy in 15 HIV-seropositive (HIV+) adults with depressive symptoms was compared to 15 HIV+ adults without depressive symptoms. HIV+ adults with depressive symptoms showed increased NAWM fractional anisotropy within the left thalamus, the temporal, and frontal regions, as well as the right cingulate. Discrete components of depression were associated with distinct regional NAWM fractional anisotropy increases. These results demonstrate altered neural complexity in HIV+ adults with depressive symptoms and support the notion that depression is multifactorial with different morphological alterations contributing to discrete aspects of depression.

Second lumbrical muscle recordings improve localization in severe carpal tunnel syndrome.

OBJECTIVE: To determine how often the second lumbrical motor potential is present when the abductor pollicis brevis (APB) motor potential is absent in severe carpal tunnel syndrome (CTS). DESIGN: Prospective study of consecutive patients with severe CTS and an absent motor potential from the APB. SETTING: Single-center public hospital-based electromyography lab. PARTICIPANTS: Patients with a clinical diagnosis of CTS who had an absent median sensory response and an absent median motor response to APB on routine nerve conduction testing. Twenty-two hands of 19 patients were examined. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Presence and distal latency of motor potential to the second lumbrical. RESULTS: The second lumbrical potential was present in 17 hands (77%). The distal motor latency to the second lumbrical was prolonged in all (mean, 9.1ms; normative value, <4.1ms). CONCLUSIONS: Second lumbrical recordings improve localization in many patients with severe CTS when routine median sensory and motor conduction studies produce no potentials.

HIV-associated alterations in normal-appearing white matter: a voxel-wise diffusion tensor imaging study.

OBJECTIVE: There are conflicting reports of adverse HIV-associated alterations in white matter integrity as measured by diffusion tensor imaging (DTI). We sought to address these conflicting reports by assessing, on a voxel-by-voxel basis, HIV-associated regional changes in radiologically defined normal-appearing white matter (NAWM) integrity using high-resolution DTI. METHODS: 30 HIV-seropositive (SP) and 30 HIV-seronegative (SN) nondemented, community-dwelling participants underwent DTI to derive whole-brain measures of white matter integrity (fractional anisotropy [FA] and mean diffusivity [MD]). For each participant, the white matter T2 volume was thresholded to remove regions of abnormal signal, resulting in a NAWM mask, which was then applied to the FA and MD volumes to extract voxel-wise NAWM measures of white matter integrity. Voxel-wise group comparisons of FA and MD were conducted (P < 0.005, extent threshold 5 voxels) while controlling for age and substance-abuse history. RESULTS: There were no significant differences between the groups for demographic or cognitive performance variables. Summary whole-brain measures of FA and MD were equivalent between the SP and SN samples. Among the SP sample, history of substance abuse was associated with significantly increased whole-brain NAWM MD, and coinfection with hepatitis C virus (HCV) was associated with a trend for increased MD. Correlations between whole-brain NAWM FA and MD with cognitive performance measures were not significant. Regional analyses of DTI measures revealed variable differences in NAWM FA in the SP sample, with findings of both decreased and increased FA. Differences in NAWM MD were more consistent, with widespread increases noted in the SP sample compared to the SN sample. Eight of the 10 regions displaying significantly increased FA in the SP sample were also found to have significantly increased MD compared to the SN sample. CONCLUSIONS: Decreased white matter integrity is present even in radiologically defined NAWM in nondemented, community-dwelling patients with HIV. The decrease in NAWM integrity is best seen in increases in MD, a measure of generalized tissue breakdown. Indications of NAWM axonal integrity (FA) present a more complicated picture, with both decreased FA and increased FA in the SP sample. Our findings of variable HIV-associated FA changes in NAWM may account for previous conflicting reports of changes in DTI parameters in this population. The results of our study suggest that HIV infection contributes to variable changes in DTI values, reflecting both direct loss of axonal integrity and a loss of complexity to the underlying axonal matrix.

Multiple sclerosis, natalizumab therapy, and progressive multifocal leukoencephalopathy.

PURPOSE OF REVIEW: Multiple sclerosis affects many people, often in early adulthood, and causes significant disability. Natalizumab is a novel agent to be evaluated for multiple sclerosis and Crohn's disease that has demonstrated unique efficacy but has unfortunately been implicated in three cases of progressive multifocal leukoencephalopathy. This review covers the mechanism of action of natalizumab and efficacy for multiple sclerosis, the three cases of natalizumab-associated progressive multifocal leukoencephalopathy, our understanding of progressive multifocal leukoencephalopathy, and the mechanisms that may account for these events. RECENT FINDINGS: Natalizumab, an anti-alpha4-integrin antibody, binds to T-cell surface receptors to prevent migration from the circulation into the brain tissue. Phase II and III trials have been completed and demonstrate previously unseen efficacy in preventing relapses and disease progression. The cases of progressive multifocal leukoencephalopathy, two fatal and one disabling, resulted in the voluntary suspension of natalizumab and bring this entire class of agents into doubt. It is important to determine what led to the development of progressive multifocal leukoencephalopathy in the natalizumab-associated cases and to advance understanding and continue to develop therapies for the treatment of multiple sclerosis. SUMMARY: With ongoing safety evaluations, natalizumab is being reevaluated by the US Food and Drug Administration for possible reapproval and return to the market. If natalizumab is reapproved, challenging questions and issues will remain in treating patients with multiple sclerosis.

Statin-associated peripheral neuropathy: review of the literature.

Various pharmacologic agents are available for the treatment of hypercholesterolemia, including 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, commonly referred to as statins, which offer favorable lipid-lowering effects and reductions in morbidity and mortality. Statins are usually better tolerated than other lipid-lowering agents and therefore have become a mainstay of treatment for hypercholesterolemia. However, recent case reports of peripheral neuropathy in patients treated with statins may have gone unnoticed by health care professionals. To evaluate the possible link between statins and peripheral neuropathy, literature searches using MEDLINE (January 1993--November 2003) and International Pharmaceutical Abstracts (January 1970--June 2002) were performed. Key search terms were statin, neuropathy, and HMG-CoA reductase inhibitors. Based on epidemiologic studies as well as case reports, a risk of peripheral neuropathy associated with statin use may exist; however, the risk appears to be minimal. On the other hand, the benefits of statins are firmly established. These findings should alert prescribers to a potential risk of peripheral neuropathy in patients receiving any of the statins; that is, statins should be considered the cause of peripheral neuropathy when other etiologies have been excluded.

Leprosy (Hansen's Disease).

Leprosy (Hansen's disease) causes the most common treatable form of neuropathy in the world. Several endemic countries account for the majority of the world's cases and most of the cases seen in the US are amongst immigrants. However, endemic cases of leprosy occur in the US. The pathogen is Mycobacterium leprae, a slow-growing, obligate intracellular pathogen that consistently infects skin and peripheral nerves. The clinical appearance of the skin and neurologic deficits develop months to years after infection and are determined by the host's response to the infection. An individual's disease classification can change over time based on the immune status of the individual. Immune-mediated "reactional states" may also occur that require additional recognition and treatment. Varied in its manifestations, a successful treatment approach relies on proper recognition and classification of disease.