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We assessed motor function regularly for 6 months after stroke and then performed anatomical analyses. Despite reported negative association of the SNP with motor learning and acute deficits, we unexpectedly found that BDNF M/M mice displayed significantly enhanced motor/kinematic performance in the chronic phase of motor recovery, especially in ipsilesional hindlimb. The enhanced recovery was associated with significant increases in striatum volume, dendritic arbor, and elevated excitatory synaptic markers in the contralesional striatum. Transient inactivation of the contralateral striatum during recovery transiently abolished the enhanced function. This study showed an unexpected benefit of the BDNFVal66Met carriers for functional recovery, involving structural and molecular plasticity in the nonstroked hemisphere. Clinically, this study suggests a role for BDNF genotype in predicting stroke recovery and identifies a novel systems-level mechanism for enhanced motor recovery.

Purpose of Review This review provides an updated discussion on the clinical presentation, diagnosis and radiographic features, mechanisms, associations and epidemiology, treatment, and prognosis of posterior reversible encephalopathy syndrome (PRES). Headache is common in PRES, though headache associated with PRES was not identified as a separate entity in the 2018 International Classification of Headache Disorders. Here, we review the relevant literature and suggest criteria for consideration of its inclusion. Recent Findings COVID-19 has been identified as a potential risk factor for PRES, with a prevalence of 1–4% in patients with SARS-CoV-2 infection undergoing neuroimaging, thus making a discussion of its identification and treatment particularly timely given the ongoing global pandemic at the time of this writing. Summary PRES is a neuro-clinical syndrome with specific imaging findings. The clinical manifestations of PRES include headache, seizures, encephalopathy, visual disturbances, and focal neurologic deficits. Associations with PRES include renal failure, preeclampsia and eclampsia, autoimmune conditions, and immunosuppression. PRES is theorized to be a syndrome of disordered autoregulation and endothelial dysfunction resulting in preferential hyperperfusion of the posterior circulation. Treatment typically focuses on treating the underlying cause and removal of the offending agents.

Background: Posterior reversible encephalopathy syndrome (PRES) can cause short-term cerebrovascular complications, such as brain infarction and hemorrhage. We hypothesized that PRES is also associated with an increased long-term risk of stroke. Methods: We performed a retrospective cohort study in the United States using statewide all-payer claims data from 2016 to 2018 on all admissions to nonfederal hospitals in 11 states. Adults with PRES were compared with adults with renal colic (negative control) and transient ischemic attack (TIA; positive control). Any stroke and the secondary outcomes of ischemic and hemorrhagic stroke were ascertained using International Classification of Diseases, Tenth Revision, Clinical Modification codes . We excluded prevalent stroke. We used time-to-event statistics to calculate incidence rates and Cox proportional hazards analyses to evaluate the association between PRES and stroke, adjusting for demographics and stroke risk factors. In a sensitivity analysis, outcomes within 2 weeks of index admission were excluded. Results: We identified 1606 patients with PRES, 1192 with renal colic, and 38 216 with TIA. Patients with PRES had a mean age of 56±17 years; 72% were women. Over a median follow-up of 0.9 years, the stroke incidence per 100 person-years was 6.1 (95% CI, 5.0–7.4) after PRES, 1.0 (95% CI, 0.62–1.8) after renal colic, and 9.7 (95% CI, 9.4–10.0) after TIA. After statistical adjustment for patient characteristics and risk factors, patients with PRES had an elevated risk of stroke compared with renal colic (hazard ratio [HR], 2.3 [95% CI, 1.7–3.0]), but lower risk than patients with TIA (HR, 0.67 [95% CI, 0.54–0.82]). In secondary analyses, compared with TIA, PRES was associated with hemorrhagic stroke (HR, 2.0 [95% CI, 1.4–2.9]). PRES was associated with ischemic stroke when compared with renal colic (HR, 1.9 [95% CI, 1.4–2.7]) but not when compared with TIA (HR, 0.49 [95% CI, 0.38–0.63]). Results were similar with 2-week washout. Conclusions: Patients with PRES had an elevated risk of incident stroke.

Objective: Patients with posterior reversible encephalopathy syndrome (PRES) can develop seizures during the acute phase. We sought to determine the longterm risk of seizure after PRES. Methods: We performed a retrospective cohort study using statewide all-payer claims data from 2016-2018 from nonfederal hospitals in 11 US states. Adults admitted with PRES were compared to adults admitted with stroke, an acute cerebrovascular disorder associated with longterm risk of seizure. The primary outcome was seizure diagnosed during an emergency room visit or hospital admission after the index hospitalization. The secondary outcome was status epilepticus. Diagnoses were determined using previously validated ICD-10-CM codes. Patients with seizure diagnoses before or during the index admission were excluded. We used Cox regression to evaluate the association of PRES with seizure, adjusting for demographics and potential confounders. Results: We identified 2095 patients hospitalized with PRES and 341,809 with stroke. Median follow-up was 0.9 years (IQR, 0.3-1.7) in the PRES group and 1.0 years (IQR, 0.4-1.8) in the stroke group. Crude seizure incidence per 100 person-years was 9.5 after PRES and 2.5 after stroke. After adjustment for demographics and comorbidities, patients with PRES had a higher risk of seizure than patients with stroke (HR, 2.9; 95% CI, 2.6-3.4). Results were unchanged in a sensitivity analysis that applied a two-week washout period to mitigate detection bias. A similar relationship was observed for the secondary outcome of status epilepticus. Interpretation: PRES was associated with an increased long-term risk of subsequent acute care utilization for seizure compared to stroke.

Introduction: Posterior reversible encephalopathy syndrome (PRES) can cause brain infarction and hemorrhage in the acute phase. We hypothesized that PRES is also associated with an increased long-term risk of stroke. Methods: We performed a retrospective cohort study using statewide all-payer claims data from 2016-2018 for all admissions to nonfederal hospitals in 11 states. Adult patients with PRES were compared to patients with TIA (positive control) and renal colic (negative control), as done in prior studies. The primary outcome was any stroke, and secondary outcomes were ischemic and hemorrhagic stroke. Diagnoses were ascertained using ICD-10-CM codes. We excluded patients with stroke before and during index admissions for PRES and controls. We used Cox proportional hazards analyses to evaluate associations between PRES and stroke, adjusting for demographics, stroke risk factors, and factors associated with PRES (cancer, kidney disease, rheumatological disease). In a sensitivity analysis, stroke events within 4 weeks of index admissions were excluded. Results: We identified 3,086 patients with PRES, 85,189 with TIA, and 3,094 with renal colic. Patients with PRES (55±17 years) and renal colic (54±18 years) were younger than those with TIA (72±14 years). Median follow-up was 1.1 years and similar between groups. Stroke incidence was 3.2 per 100 person-years after PRES, 3.8 per 100 person-years after TIA, and 0.4 per 100 person-years after renal colic (Figure). After adjustment, patients with PRES had a similar stroke risk as patients with TIA (HR, 0.9; 95% CI, 0.8-1.2), and a higher stroke risk than patients with renal colic (HR, 2.6; 95% CI, 2.0-3.5). Compared to TIA, PRES had a higher risk of hemorrhagic stroke (HR, 2.9; 95% CI, 2.2-3.9) and a lower risk of ischemic stroke (HR, 0.7; 95% CI, 0.6-0.9). Results were similar with a 4-week washout period. Conclusions: PRES is associated with an increased risk of future stroke, specifically hemorrhagic stroke.

Background and Purpose: Genetics is one of several key factors that influence stroke recovery. A single nucleotide polymorphism (SNP) of the bdnf gene (Val66Met) is common in humans, ranging from 20-30% in Caucasians up to 70% in the Asian population. Previous studies show several disadvantages to carrying this allele in humans. However, the high rate of SNP occurrence raises the intriguing possibility of a selective advantage to carrying the Met allele, such as motor function. The current study investigates the impact of bdnf val66met SNP on long term recovery after stroke. Methods: Mice with a genetic knock-in of the human BDNF variant (val66met) were generated. Adult male BDNF +/+ (WT) and BDNF Met/Met (M/M) mice were subjected to the proximal middle cerebral artery occlusion. Motor and gait functions were assessed by rotarod and Catwalk analysis at acute phase and recovery phase. Anatomical volume analysis was evaluated by cresyl violet and Golgi staining at 6 months after stroke. Results: As previously reported (Qin et al., 2011), there was greater acute impairment in motor behavioral outcomes in M/M mice after stroke, compared to WT mice. However, M/M mice displayed significantly enhanced rotarod performance at 2 weeks and the enhancement was sustained up to 6 months post-stroke. Similarly, Catwalk gait analyses in swing speed and stride length showed that M/M mice exhibited enhanced gaits (i.e. faster and longer stride) than WT mice during long-term recovery phases, especially in the ipsilesional right hind limb. Since ipsilesional limbs are controlled by the contralesional hemisphere, sub-regional volumes in this hemisphere were assessed. M/M mice showed specifically increased striatal volume at 6 months post-ischemia. The increased striatal volume was also associated with higher dendritic complexity of medium spiny neurons in this region, which indicated that the contralesional anatomical plasticity may account for enhanced motor recovery in MM mice. Conclusions: The findings suggest that BDNF SNP may have selective advantage in enhancing motor/gait function through the contralesional hemisphere during stroke recovery. The study has clinical importance by providing a means to predict the course of stroke recovery based on an individual’s SNP.