Clinical Reasoning: A 54-Year-Old Woman With Progressive Headache and Neurologic Decline.

A 54-year-old woman presented with headache and vasculopathy. She was treated for reversible cerebral vasoconstriction syndrome but continued to have clinicoradiographic decline with headache, seizures, systemic symptoms, and progression of vasculopathy on imaging. We present the diagnosis of a rare genetic disease with its various neurologic complications and systemic manifestations. Our case also illustrates the importance of differences in the metabolism of various antiseizure medications, recognition of which may avoid precipitating the disease.

MGMT Promoter Methylation: Prognostication beyond Treatment Response.

MGMT promoter methylation is related to the increased sensitivity of tumour tissue to chemotherapy with temozolomide (TMZ) and thus to improved patient survival. However, it is unclear how the extent of MGMT promoter methylation affects outcomes. In our study, a single-centre retrospective study, we explore the impact of MGMT promoter methylation in patients with glioblastoma who were operated upon with 5-ALA. Demographic, clinical and histology data, and survival rates were assessed. A total of 69 patients formed the study group (mean age 53.75 ± 15.51 years old). Positive 5-ALA fluorescence was noted in 79.41%. A higher percentage of MGMT promoter methylation was related to lower preoperative tumour volume (p = 0.003), a lower likelihood of 5-ALA positive fluorescence (p = 0.041) and a larger extent of resection EoR (p = 0.041). A higher MGMT promoter methylation rate was also related to improved progression-free survival (PFS) and overall survival (OS) (p = 0.008 and p = 0.006, respectively), even when adjusted for the extent of resection (p = 0.034 and p = 0.042, respectively). A higher number of adjuvant chemotherapy cycles was also related to longer PFS and OS (p = 0.049 and p = 0.030, respectively). Therefore, this study suggests MGMT promoter methylation should be considered as a continuous variable. It is a prognostic factor that goes beyond sensitivity to chemotherapy treatment, as a higher percentage of methylation is related not only to increased EoR and increased PFS and OS, but also to lower tumour volume at presentation and a lower likelihood of 5-ALA fluorescence intraoperatively.

Shorter Intensive Care Unit Stay (12 Hours) Post Thrombolysis Is Safe and Reduces Length of Stay for Minor Stroke Patients.

The current standard of practice for patients with acute ischemic stroke treated with intravenous tissue-type plasminogen activator (tPA) requires critical monitoring for 24-hours post-treatment due to the risk of symptomatic intracranial hemorrhage (sICH). This is a costly and resource intensive practice. In this study, we evaluated the safety and efficacy of this standard 24-hour ICU monitoring period compared with a shorter 12-hour ICU monitoring period for minor stroke patients (NIHSS 0-5) treated with tPA only. Stroke mimics and those who underwent thrombectomy were excluded. The primary outcome was length of hospital stay. Secondary outcome measures included sICH, deep venous thrombosis (DVT), pulmonary embolism (PE), pneumonia, favorable discharge to home or acute rehabilitation, readmission within 30 days, and favorable functional outcome defined as modified Rankin scale (mRS) of 0-2 at 90 days. Of the 122 patients identified, 77 were in the 24-hour protocol and 45 were in 12-hour protocol. There was significant difference in length of hospital stay for the 24-hour ICU protocol (2.8 days) compared with the 12-hour ICU protocol (1.8 days) (P < 0.001). Although not statistically significant, the 12-hour group had favorable rates of sICH, 30-day readmission rates, favorable discharge disposition and favorable functional outcome. Rates of DVT, PE and aspiration pneumonia were identical between the groups. Compared with 24-hour ICU monitoring, 12-hour ICU monitoring after thrombolysis for minor acute ischemic stroke was not associated with any increase in adverse outcomes. A randomized trial is needed to verify these findings.

Mechanical Thrombectomy for Acute Stroke: Early versus Late Time Window Outcomes.

BACKGROUND AND PURPOSE: Recent trials have shown benefit of thrombectomy in patients selected by penumbral imaging in the late (>6 hours) window. However, the role penumbral imaging is not clear in the early (0-6 hours) window. We sought to evaluate if time to treatment modifies the effect of endovascular reperfusion in stroke patients with evidence of salvageable tissue on CT perfusion (CTP). METHODS: We retrospectively analyzed consecutive patients who underwent thrombectomy in a single center. Demographics, comorbidities, National Institute of Health Stroke Scale (NIHSS), rtPA administration, ASPECTS, core infarct volume, onset to skin puncture time, recanalization (mTICI IIb/III), final infarct volume were compared between patients with good and poor 90-day outcomes (mRS 0-2 vs. 3-6). Multivariable logistic regression analyses were used to identify independent predictors of a good (mRS 0-2) 90-day outcome. RESULTS: A total of 235 patients were studied, out of which 52.3% were female. Univariate analysis showed that the groups (early vs. late) were balanced for age (P = .23), NIHSS (P = .63), vessel occlusion location (P = .78), initial core infarct volume (P = .15), and recanalization (mTICI IIb/III) rates (P = .22). Favorable outcome (mRS 0-2) at 90 days (P = .30) were similar. There was a significant difference in final infarct volume (P = .04). Shift analysis did not reveal any significant difference in 90-day outcome (P = .14). After adjustment; age (P < .001), NIHSS (P = .01), recanalization (P = .008), and final infarct volume (P < .001) were predictive of favorable outcome. CONCLUSIONS: Penumbral imaging-based selection of patients for thrombectomy is effective regardless of onset time and yields similar functional outcomes in early and late window patients.

Cohort analysis of desmopressin effect on hematoma expansion in patients with spontaneous intracerebral hemorrhage and documented pre-ictus antiplatelet use.

Antiplatelet therapy at the time of spontaneous intracerebral hemorrhage (sICH) may increase risk for hemorrhage expansion and mortality. Current guidelines recommend considering a single dose of desmopressin in sICH associated with cyclooxygenase-1 inhibitors or adenosine diphosphate receptor inhibitors. Adult subjects with sICH and concomitant antiplatelet therapy admitted to a large, tertiary care center were included. We sought to compare the risk of hematoma expansion in patients that received desmopressin for antiplatelet reversal in the setting of sICH to similar patients that did not receive desmopressin. The primary outcomes were the incidence of relative and absolute hematoma expansion. In total, 71 patients (29 received desmopressin, 42 did not receive desmopressin) were analyzed. All patients in the desmopressin group received a 0.3 mcg/kg intravenous dose prior to hematoma expansion assessment. Relative hematoma expansion occurred in 5/29 (17%) with desmopressin compared to 11/42 (26%) without desmopressin (OR 0.59 [95% CI 0.18-1.92]). Absolute hematoma expansion occurred in 9/29 (30%) with desmopressin compared to 12/42 (28%) without desmopressin (OR 1.13 [95% CI 0.40-3.16]). Multiple logistic regression controlling for significant covariates did not reveal a significant effect of desmopressin on relative or absolute hematoma expansion (OR 0.65 [95% CI 0.18-2.43] and OR 1.55 [0.48-4.99], respectively). We failed to find evidence that desmopressin administration for antiplatelet reversal in sICH reduces the incidence of hematoma expansion. Larger studies, focusing on the early phase of sICH, are needed to characterize the clinical efficacy and safety of desmopressin for antiplatelet reversal before widespread implementation.

Stroke code simulation benefits advanced practice providers similar to neurology residents.

BACKGROUND: Advanced practice providers (APPs) are important members of stroke teams. Stroke code simulations offer valuable experience in the evaluation and treatment of stroke patients without compromising patient care. We hypothesized that simulation training would increase APP confidence, comfort level, and preparedness in leading a stroke code similar to neurology residents. METHODS: This is a prospective quasi-experimental, pretest/posttest study. Nine APPs and 9 neurology residents participated in 3 standardized simulated cases to determine need for IV thrombolysis, thrombectomy, and blood pressure management for intracerebral hemorrhage. Emergency medicine physicians and neurologists were preceptors. APPs and residents completed a survey before and after the simulation. Generalized mixed modeling assuming a binomial distribution was used to evaluate change. RESULTS: On a 5-point Likert scale (1 = strongly disagree and 5 = strongly agree), confidence in leading a stroke code increased from 2.4 to 4.2 (p < 0.05) among APPs. APPs reported improved comfort level in rapidly assessing a stroke patient for thrombolytics (3.1-4.2; p < 0.05), making the decision to give thrombolytics (2.8 vs 4.2; p < 0.05), and assessing a patient for embolectomy (2.4-4.0; p < 0.05). There was no difference in the improvement observed in all the survey questions as compared to neurology residents. CONCLUSION: Simulation training is a beneficial part of medical education for APPs and should be considered in addition to traditional didactics and clinical training. Further research is needed to determine whether simulation education of APPs results in improved treatment times and outcomes of acute stroke patients.

The Reemergence of EEG Reactivity After Cardiac Arrest.

Electroencephalogram (EEG) reactivity has been increasingly utilized in prognostication after cardiac arrest. Recent studies have demonstrated a false-positive rate of 0% in predicting poor outcome with a nonreactive EEG. The reemergence of reactivity after an initial nonreactive EEG has been noted in cases of drug intoxication, rewarming after hypothermia, and after discontinuing sedation. This is the first case describing the reemergence of EEG reactivity without the confounding factors listed above. We describe a case of resuscitated cardiac arrest with initial EEG demonstrating a lack of reactivity. A repeat EEG completed 3 days later revealed a reemergence of reactivity in the setting of normothermia, a negative drug screen, and the absence of sedation. The delayed recovery of EEG reactivity without previously established confounding factors is novel. Serial EEGs may be beneficial as the available literature on reactivity and prognostication is based on an average of 24 to 48 hours of EEG tracing. Prognostication after cardiac arrest continues to require a multimodal approach.

Indicators of Subarachnoid Hemorrhage as a Cause of Sudden Cardiac Arrest.

Subarachnoid hemorrhage (SAH) may present with cardiac arrest (SAH-CA). We report a case of SAH-CA to assist providers in distinguishing SAH as an etiology of cardiac arrest despite electrocardiogram findings that may be suggestive of a cardiac etiology. SAH-CA is associated with high rates of return of spontaneous circulation, but overall poor outcome. An initially non-shockable cardiac rhythm and the absence of brain stem reflexes are important clues in indentifying SAH-CA.

IgG4-related disease causing facial nerve and optic nerve palsies: Case report and literature review.

IgG4-related disease (IgG4-RD) is increasingly being recognized as an entity effecting the head and neck region. Although most commonly seen with salivary gland or paranasal sinus involvement, IgG4-RD may also involve the temporal bone and skull base. We report a rare care of a 61-year-old female with IgG4-RD presenting as synchronous lesions of the middle ear and middle cranial fossa with polyneuropathy of cranial nerves II, VI, and VII. Initial histopathological evaluation of her resected ear mass suggested a benign inflammatory process but no specific diagnosis. Her symptoms progressed over 10months prompting re-evaluation of the specimen and consideration of the IgG4-RD diagnosis. Key pathologic features included prominent lymphoplasmacytic population, storiform fibrosis, obliterative phlebitis, and IgG4 specific staining. The patient was treated with high-dose intravenous and oral steroids but was transitioned to azathioprine secondary to steroid-induced myopathy. Radiographic studies before and after treatment reveal marked improvement of the intracranial and extracranial disease. Correspondingly, her cranial neuropathies resolved. A high degree of clinical suspicion is necessary to diagnosis IgG4-RD. The diagnosis can be supported by elevated serum IgG, elevated IgG index, and pathognomonic histopathological findings. Primary treatment is with corticosteroids. However, immunotherapy using azathioprine or rituximab can be utilized in recurrent disease or patients with steroid intolerance.

Risk of Ventriculostomy-Associated Hemorrhage in Patients with Aneurysmal Subarachnoid Hemorrhage Treated with Anticoagulant Thromboprophylaxis.

BACKGROUND: Patients with subarachnoid hemorrhage (SAH) frequently need a ventriculostomy for treatment of hydrocephalus. In some ICU practices, a ventriculostomy is considered a relative contraindication for subcutaneous heparin. We studied the risk of ventriculostomy-associated hemorrhage and deep venous thrombosis (DVT) in patients with anticoagulant prophylaxis. METHODS: This is a retrospective study of 241 consecutive patients with SAH and ventriculostomies treated at Mayo Clinic, Rochester from 2001 to 2014. DVT and pulmonary emboli (PE) prevention included subcutaneous or intravenous heparin, enoxaparin, dalteparin, and warfarin. The incidence of PE and DVT were noted within 30 days of hospital admission. Hemorrhages were classified as minor or major based on size and mass effect. RESULTS: Fifty-three (22 %) of the 241 patients were on prophylactic doses of anticoagulation while in the intensive care unit. Three of 53 patients on prophylactic anticoagulation had minor hemorrhages and none had major hemorrhages. Four (7.5 %) of 53 patients who received prophylactic anticoagulation versus 34 (18 %) of 188 patients who did not receive prophylactic anticoagulation developed DVT (p = 0.09). One of 10 patients on therapeutic anticoagulation had a major and fatal hemorrhage. CONCLUSION: In our cohort, the risk of VTE was reduced by more than half in patients receiving chemoprophylaxis. Ventriculostomy-associated hemorrhages were rare and minor. Anticoagulant thromboprophylaxis is mostly safe and required in aneurysmal SAH.