Mandrekar, Jay

Background: Cerebral cavernous angiomas with symptomatic hemorrhage (CASH) carry highest rebleed rates and are targeted for novel interventions. A multisite clinical trial readiness project (clinicaltrials.gov NCT03652181) aims to identify clinical and functional changes over time in trial eligible CASH patients. Methods: Adult patients from 5 high volume centers with a CASH in the prior year and no planned surgical intervention were enrolled. In addition to demographic, clinical, and imaging review, patients underwent baseline, 1 year and 2 year NIH-stroke scale (NIHSS), modified Rankin scale (mRS), Euro-QOL 5D-3L (EQ-5D-3L) and EQ VAS (visual analog score), and PROMIS 29 assessments. Recurrent symptomatic hemorrhages (SH) were verified. We assessed the hemorrhage rate, change in scores/scales over time, and determined which scales/scores were most affected in patients with SH. Results: 123 patients completed baseline assessments and were prospectively followed (60.9% female; mean age 44.1 years; 39.1% familial; 41.5% brainstem location). As of reporting date, 89 of 104 (86%) and 58 of 76 (76%) cases have completed assessments. There were 16 SHs during 147 patient-years of follow up (10.9% per patient year). At baseline, 111 (90.2%) of patients had NIHSS 0-2 and 77 (62.6%) patients had mRS baseline 0-1 which improved to 40 (95.2 %) and 43 (75.4%) at 2 years. At baseline, 54 (43.9%) of patients had at least one moderate to severely abnormal PROMIS-29 domain compared to 13 (26.5%) at 2 years. EQ-5D-3L baseline demonstrated a moderate proportion of patients reporting some difficulty with pain (48.8%), anxiety (41.5%), and activity (41.5%) which improved to 28%, 30%, and 34% respectively at 2 years. Patients with a prospective SH were more likely than those without recurrent SH at 2 years to display mild functional decline (0.5 SD) of most PROMIS-29 domains, a mRS of 2 or higher and an abnormal EQ- self-care (P<0.05). Other scales/scores were not significantly different between the groups. Conclusion: We report SH rate and functional outcome at baseline and rates of changes during 2 years in trial eligible CASH patients. The PROMIS-29, mRS, and EQ-self-care domains were most discriminative in patients with recurrent SH. No test was 100% specific.

Managing the complex care needs of seriously ill patients transitioning from hospital to home can have detrimental effects on family caregivers (FCG). Multi-component interventions tailored to FCG needs are most effective at reducing caregiver burden, distress, and depression. However, gaps exist in determining best methods to assess, document, and analyze intervention components for FCGs. Common methods used to capture patient data during transitions in care may not be appropriate or allowed for FCG needs. As such, we present a methodological approach for electronically capturing, reporting, and analyzing multiple intervention components. This approach uses a standardized terminology and pathway for tailoring intervention components in real time while evaluating intervention effects across time. We use examples from a randomized controlled trial to illustrate the benefits of the current approach for analyzing the effectiveness of multi-component interventions in the context of caregiving research.

Abstract Introduction/Aims Carpal and cubital tunnel syndrome (CTS, CuTS) are common among patients with hereditary neuropathy with liability to pressure‐palsies (HNPP) and Charcot–Marie‐Tooth type 1A (CMT1A) and may impact quality of life. We aimed to evaluate the utility of nerve decompression surgeries in these patients. Methods Medical records were reviewed for patients with PMP22 mutations confirmed in Mayo Clinic laboratories from January 1999 to December 2020, who had CTS and CuTS and underwent surgical decompression. Results CTS occurred in 53.3% of HNPP and 11.5% of CMT1A, while CuTS was present in 43.3% of HNPP and 5.8% of CMT1A patients. CTS decompression occurred in 10‐HNPP and 5‐CMT1A patients, and CuTS decompression with/without transposition was performed in 5‐HNPP and 1‐CMT1A patients. In HNPP, electrodiagnostic studies identified median neuropathy at the wrist in 9/10 patients and ultrasound showed focal enlargements at the carpal and cubital tunnels. In CMT1A, median and ulnar sensory responses were all absent, and the nerves were diffusely enlarged. After CTS surgery, pain, sensory loss, and strength improved in 4/5 CMT1A, and 6/10 HNPP patients. Of clinical, electrophysiologic and ultrasound findings, only activity‐provoked features significantly correlated with CTS surgical benefit in HNPP patients (odds ratio = 117.0:95% confidence interval, 1.94 > 999.99, p = 0.01). One CMT1A and one HNPP patient improved with CuTS surgery while 2 HNPP patients worsened. Discussion CTS symptom improvement post‐surgery can be seen in CMT1A and (less frequent) in HNPP patients. CuTS surgery commonly worsened course in HNPP. Activity‐provoked symptoms in HNPP best informed benefits from CTS surgery.

Background: Epidemiological studies examining associations between traumatic brain injury (TBI) and Alzheimer’s disease and related dementias (ADRD) have yielded conflicting results, which may be due to methodological differences. Objective: To examine the relationship between the presence and severity of TBI and risk of ADRD using a population-based cohort with medical record abstraction for confirmation of TBI and ADRD. Methods: All TBI events among Olmsted County, Minnesota residents aged > 40 years from 1985–1999 were confirmed by manual review and classified by severity. Each TBI case was randomly matched to two age-, sex-, and non-head injury population-based referents without TBI. For TBI events with non-head trauma, the Trauma Mortality Prediction Model was applied to assign an overall measure of non-head injury severity and corresponding referents were matched on this variable. Medical records were manually abstracted to confirm ADRD diagnosis. Cox proportional hazards models examined the relationship between TBI and severity with risk of ADRD. Results: A total of 1,418 residents had a confirmed TBI (865 Possible, 450 Probable, and 103 Definite) and were matched to 2,836 referents. When combining all TBI severities, the risk of any ADRD was significantly higher for those with a confirmed TBI compared to referents (HR = 1.32, 95% CI: 1.11, 1.58). Stratifying by TBI severity, Probable (HR = 1.42, 95% CI: 1.05, 1.92) and Possible (HR = 1.29, 95% CI: 1.02–1.62) TBI was associated with an increased risk of ADRD, but not Definite TBI (HR = 1.22, 95% CI: 0.68, 2.18). Conclusion: Our analyses support including TBI as a potential risk factor for developing ADRD.

Introduction: Patients undergoing bariatric surgery with body mass index (BMI) >50 kg/m2 are at a higher risk of surgical morbidity when compared with less obese patients, however, there is limited data correlating surgical risk and efficacy with increasing BMI in patients with severe obesity. We hypothesize that regardless of the degree above 50 kg/m2 their BMI, patients with severe obesity respond similarly to bariatric surgery. Materials and Methods: We performed a retrospective analysis of patients with BMI >50 kg/m2 who underwent biliopancreatic diversion with duodenal switch, Roux-en-Y gastric bypass, or sleeve gastrectomy at a single institution. Outcomes were compared in patients with a BMI between 50 and 60 kg/m2 to patients with a BMI >60 kg/m2 and included percent total weight loss as well as early and late complications. Statistical analyses were performed using logistic regression, univariate, and multivariate models. Results: There were 571 patients with BMI >50 kg/m2 who underwent bariatric surgery at our center, 170 (29.8%) had a BMI >60 kg/m2. Percent total weight loss was statistically significant between the BMI 50 and 60 kg/m2 and BMI >60 kg/m2 groups at 24 months (P=0.047) but not at 60 months (P=0.54). No significant difference was found in the incidence of early complications in a univariate (P=0.46) or a multivariate (P=0.06) analysis. The BMI >60 subgroup was associated with a higher rate of late complications in univariate analysis (heart rate=2.37; 1.03-5.47, P=0.04), but not in multivariate analysis (P=0.78). Conclusions: Efficacy and complication rates of bariatric surgeries are similar in patients with BMI 50 to 60 kg/m2 and >60 kg/m2, providing evidence supporting similar management of patients despite specific subgroups.

Background: Seizures are a known complication of ischemic stroke. Some studies have reported a higher risk of post-stroke seizure with cardioembolic strokes, whereas others have not. The risk of post-stroke seizure for different stroke mechanisms is unclear. Objective: To compare different stroke etiologies and the risk of post-stroke seizure in a population-based study. Methods: Utilizing the Rochester Epidemiology Project medical records linkage system, we ascertained all first ischemic strokes occurring among Rochester, MN residents from 1990-1994, and followed the patients in the comprehensive medical record through March 2014 for occurrence of seizure. TOAST stroke subtype classification was determined by a consensus of cerebrovascular neurologists. New post-stroke seizure was identified by physician diagnosis and/or EEG report. Patients with a seizure before the index stroke were not included. Pre-morbid stroke risk factors were recorded. Associations between seizure after index ischemic stroke as outcome and other variables of interest were assessed using univariate logistic regression. Results: A total of 490 patients met inclusion criteria, with median follow-up of 6.5 years. Out of 490 patients, 35 had new onset seizures (7.1%). Median age was significantly lower at index stroke for patients with seizures (73 v. 77 years, p=0.017). The most common TOAST stroke subtype was cryptogenic (46.8%) followed by cardioembolic (24.9%). There was no significant difference in TOAST stroke subtypes between patients with post-stroke seizure and those without (p=0.35). There was also no difference between the two groups when comparing combined cardioembolic and large-vessel to small-vessel (p=0.28) or cryptogenic to small-vessel (p=0.9) mechanisms. There was also no difference in pre-morbid stroke risk factors between the two groups, including hypertension (p=0.22), total cholesterol (p=0.95), type 2 diabetes mellitus (p=0.13), tobacco use (p=0.27), atrial fibrillation (p=0.9), or previous myocardial infarction (p=0.67). Conclusion: This study suggests that the long-term risk of post-stroke seizures does not differ by ischemic stroke etiology.

Background: Coronary artery disease (CAD) is a significant cause of morbidity and mortality in ischemic stroke (IS) patients. IS and CAD often coexist and share common risk factors. Absolute risk and predictors of myocardial infarction (MI) in IS and by IS etiology subtype is not well known. We determined the risk of MI and its predictors in patients with incident IS in a population based cohort. Methods: Using the Rochester Epidemiology Project (REP) medical records linkage system we identified all residents with incident IS in a 5-year period between January 1, 1990, and December 31, 1994. Comprehensive medical records were reviewed and variables of interest were retrieved and analyzed. Univariate Cox proportional hazard regression models were constructed to assess hazard ratios and 95% CI for predictors of MI occurrence after IS. Results: We identified 490 persons with IS, mean age at IS was 76.6 (SD 12.9) years, mean follow up to death or final follow-up was 6.5 (SD 6.3, range 0.0-23.8) years. There were 126 recurrent strokes and 93 MIs during followup. The 1-year actuarial risk of MI was 3.6% (95% CI, 2.2% - 5.9%), and 5-year actuarial risk of MI was 11.4% (95% CI, 8.4% - 15.3%). Univariate predictors of MI included (HR; 95% CI): age (1.02;1.0-1.04), pre-IS history of MI (1.37;1.13-1.65), CHF (1.85;1.06-3.23), CABG (2.11;1.19-3.75), left ventricular dyskinesia (2.14;1.32-3.4), peripheral vascular disease (1.32;1.18-1.49), diabetes mellitus (1.54;1.21-1.96), elevated creatinine (1.93;1.44-2.59), LDL level (1.01;1.00-1.01). Conclusion: MI is common after first IS. Several factors predicted an increased risk of MI after stroke, and should be taken into account in determining CAD screening strategies at the time of IS. Recurrent stroke was more common than MI during long-term followup.

Introduction: Studies have suggested a high incidence of dementia after stroke; however data regarding risk factors are conflicting and few studies are population-based. The aims of this population-based study are to determine the frequency of diagnosis and predictors of clinical dementia after ischemic stroke. Methods: The Rochester Epidemiology Project medical records linkage system was used to ascertain all first ischemic strokes (IS) occurring among Rochester, MN residents between 1990 -1994. Comprehensive medical records were reviewed. Patient and stroke characteristics, medical comorbidities, and the development of clinical dementia any time after IS were recorded. Dementia was defined as any reflection in the chart by a clinician of memory loss resulting in functional impairment. Patients with a pre-stroke diagnosis of dementia were excluded. Associations between new dementia after the index IS and other variables of interest were analyzed using univariate logistic regression. Results: First IS was detected in 490 people, 82 of whom had a prior history of dementia, and 119 (29%) of whom developed dementia during a mean follow-up of 6.5 years (range 0-23.8). The mean age at index stroke was 76.6 years (SD 12.9). Those who developed dementia were a mean 4 years older at the time of IS (p = 0.003). The odds of developing dementia were 1.7 higher in those who had at least one recurrent stroke. There was no effect of sex, stroke location (cortical, subcortical, brainstem), stroke mechanism, or premorbid stroke risk factors (coronary artery disease, atrial fibrillation/flutter, hypertension, diabetes mellitus, left-sided valvular disease) on the occurrence of dementia. Conclusions: Dementia is commonly diagnosed following ischemic stroke. While stroke risk factors did not impact the risk of diagnosis of dementia, recurrent stroke increased this risk. Stroke risk factors may indirectly increase the risk of dementia by increasing the risk of recurrent IS. This suggests that aggressive secondary stroke prevention measures may significantly decrease the risk of being diagnosed with dementia following IS.

Background: Current guidelines recommend that initial management of patients with an intracerebral hemorrhage (ICH) occur in a neuroscience intensive care unit (ICU). However, some patients can be safely managed without ICU care. We evaluated factors that may predict the need for ICU level of care. Methods: We reviewed the medical records of all adult patients with supratentorial ICH presenting within 72 hours of symptom onset seen from 2009-2012. Patients admitted for palliative care or ICH due to a known structural lesion were excluded. Criteria defining need for ICU level of care were: need for intubation/mechanical ventilation, hyperosmolar therapy, neurosurgical procedure, prolonged ICU admission, or significant clinical deterioration. A univariate and multivariable logistic regression analysis was performed on patient demographics, medical comorbidities, time to presentation, vital signs, GCS/FOUR score, medications, laboratory studies, and imaging to identify independent predictors of the need for ICU admission. Results: 229 patients met inclusion criteria. Based on our triage criteria, 128 patients (56%) required ICU level of care. Multivariable analysis identified five factors that best predicted the need for ICU admission: younger age, shorter time to presentation, lower FOUR score, larger hemorrhage volume, and use of anticoagulants at presentation (table). Intraventricular hemorrhage and GCS score were not significant predictors on the multivariable analysis. Conclusion: Age, time to presentation, FOUR score, hemorrhage volume, and use of anticoagulants predict the need for ICU care after ICH. These variables will be used to develop a formula to aid clinicians in appropriate initial triage of patients with ICH.

Background and Purpose: Strict maintenance of normovolemia is standard of care in treatment of aneurysmal subarachnoid hemorrhage (aSAH) and induced hypervolemia is used to treat delayed cerebral ischemia (DCI) from vasospasm. Fluid-related complications are not uncommon. We tested the hypothesis that fluid balance affected clinical outcomes in aSAH. Methods: We reviewed 307 patients with aSAH admitted to the Neuroscience Intensive Care Unit (NICU) from October 2001 to June 2011. We collected data on fluid balance during NICU stay, clinical and radiographic evidence of vasospasm, cardiopulmonary complications, and functional outcomes by modified Rankin scale (mRS) upon follow-up (mean 8 ± 8 months). Poor functional outcome was defined as mRS 3-6. Associations of variables of interest with outcome were assessed using univariable and multivariable logistic regression. Propensity scores were estimated to account for imbalances between patients with positive versus negative fluid balance and were included in multivariable models. Results: Average net fluid balance was 1153 ± 5586 mL. Results of univariate analysis are shown on the Table. On multivariate analysis, WFNS grade at nadir (p<0.001, OR=3.09, 95%CI 2.38-4.02) and positive fluid balance per liter increase (p=0.0005, OR=1.12, 95%CI 1.05-1.20) were associated with poor functional outcome. For every liter increase in positive net fluid balance, there was a 12% increased risk of a poor functional outcome on adjusted analysis (Area under ROC Curve 0.868). The association between positive net fluid balance and poor functional outcomes was confirmed using propensity score analysis to control for multiple confounding variables. Conclusions: Greater positive net fluid balance is independently associated with poorer functional outcome in patients with aSAH. This association does not appear to be solely explained by an excess of cardiopulmonary complications.