Background and Purpose-The term symptomatic hemorrhage secondary to ischemic stroke implies a clear causal relationship between clinical deterioration and hemorrhagic transformation (HT) regardless of the type of HT. The aim of this study was to assess which type of HT independently affects clinical outcome. Methods-We used the data set of the European Cooperative Acute Stroke Study (ECASS) II for a post hoc analysis. All patients had a control CT scan after 24 to 96 hours or earlier in case of rapid and severe clinical deterioration. HT was categorized according to radiological criteria: hemorrhagic infarction type 1 and type 2 and parenchymal hematoma type 1 and type 2. The clinical course was prospectively documented with the National Institutes of Health Stroke Scale and the modified Rankin Scale. The independent risk of each type of HT was calculated for clinical deterioration at 24 hours and disability and death at 3 months after stroke onset and adjusted for possible confounding factors such as age, severity of stroke syndrome at baseline, and extent of the ischemic lesion on the initial CT. Results-Compared with absence of HT, only parenchymal hematoma type 2 was associated with an increased risk for deterioration at 24 hours after stroke onset (adjusted odds ratio, 18; 95% CI, 6 to 56) and for death at 3 months (adjusted odds ratio, 11; 95% CI, 3.7 to 36). All other types of HT did not independently increase the risk of late deterioration. Conclusions-Only parenchymal hematoma type 2 independently causes clinical deterioration and impairs prognosis. It has a distinct radiological feature: it is a dense homogeneous hematoma Ͼ30% of the ischemic lesion volume with significant space-occupying effect.

Background and Purpose-Both the administration of growth factors and physical therapy such as forced arm use (FAU) are promising approaches to enhance recovery after stroke. We explored the effects of these therapies on behavioral recovery and molecular markers of regeneration after experimental ischemia. Methods-Rats were subjected to photothrombotic ischemia: sham (no ischemia), control (ischemia), brain-derived neurotrophic factor (BDNF; ischemia plus BDNF, 20 g), and FAU (ischemia plus FAU, 1-sleeve plaster cast ipsilateral limb). Animals survived 1 or 6 weeks and underwent behavioral testing (Rotarod, beam balance, adhesive removal, plantar test, neuroscore). After the rats were killed, brain sections were immunostained for semiquantitative analysis of MAP1B, MAP2, synaptophysin, GFAP expression, and quantification of infarct volumes. Results-Infarct volumes were not different between the groups 1 or 6 weeks after ischemia. BDNF-treated animals had better functional motor recovery (Rotarod, beam balance, neuroscore) compared with all other groups (PϽ0.05). There was no significant adverse effect of early FAU treatment on motor recovery, although sensorimotor function (adhesive removal test) was impaired (PϽ0.05). There were no differences between groups as measured by nociception of the left and right forepaw (plantar test). BDNF treatment transiently induced MAP1B expression in the ischemic border zone and synaptophysin expression within the contralateral cortex 6 weeks after ischemia (PϽ0.05

We investigated levels and compositions of N-acylethanolamines (NAEs) and their precursors, N-acyl phosphatidylethanolamines (N-acyl PEs), in a rat stroke model applying striatal microdialysis for glutamate assay. Rats (n ¼ 18) were treated with either intravenous saline (control), NMDA receptor antagonist MK801 (1 mg/kg), or CB1 receptor antagonist SR141716A (1 mg/kg) 30 min after permanent middle cerebral artery occlusion (MCAO). MK801 significantly attenuated the release of glutamate in the infarcted striatum (79 ± 22 lmol/L) as compared with controls (322 ± 104 lmol/L). The administration of CB1 antagonist SR141716A had no statistically significant effect on glutamate release (340 ± 89 lmol/L), but reduced infarct volume at 5 h after MCAO significantly by approximately 40%, whereas MK801 treatment resulted in a non-significant (18%) reduction of infarct volume. In controls, striatal and cortical NAE concentrations were about 30-fold higher in the infarcted than in the non-infarcted hemisphere, whereas ipsilateral N-acyl phosphatidylethanolamine (N-acyl PE) levels exceeded contralateral levels by only a factor of two to three. Treatment with MK801 or SR141716A, or glutamate release in the infarcted tissue, had no significant effect on these levels. NAE accumulation during acute stroke may be due to increased synthesis as well as decreased degradation, possibly by inhibition of fatty acid amide hydrolase (FAAH).

Pronounced forward flexion of the trunk, often termed camptocormia, is a typical symptom of patients with Parkinson's disease. In 4 parkinsonian patients with camptocormia, paraspinal muscles were studied by electromyography (EMG) and axial computerized tomography (CT) or magnetic resonance imaging (MRI) scans and muscle biopsy. EMG of the lumbar and thoracic paravertebral muscles showed abundant fibrillations, positive sharp waves, and bizarre high-frequency discharges. Spinal CT and MRI scans revealed variable degrees of atrophy and fatty replacement of the thoracolumbar paraspinal muscles on both sides. No other signs of neuromuscular disease were found. Biopsy of the paraspinal muscles revealed end-stage myopathy with autophagic vacuoles, chronic inflammatory myopathy, unspecific myopathic changes, or mitochondrial myopathy. In parkinsonian patients with pronounced forward flexion of the trunk, myopathy confined to the erector spinae muscles must be considered.

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Objective The aim was to evaluate, in patients with atrial fibrillation (AF) and acute ischemic stroke, the association of prior anticoagulation with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) with stroke severity, utilization of intravenous thrombolysis (IVT), safety of IVT, and 3‐month outcomes. Methods This was a cohort study of consecutive patients (2014–2019) on anticoagulation versus those without (controls) with regard to stroke severity, rates of IVT/mechanical thrombectomy, symptomatic intracranial hemorrhage (sICH), and favorable outcome (modified Rankin Scale score 0–2) at 3 months. Results Of 8,179 patients (mean [SD] age, 79.8 [9.6] years; 49% women), 1,486 (18%) were on VKA treatment, 1,634 (20%) on DOAC treatment at stroke onset, and 5,059 controls. Stroke severity was lower in patients on DOACs (median National Institutes of Health Stroke Scale 4, [interquartile range 2–11]) compared with VKA (6, [2–14]) and controls (7, [3–15], p < 0.001; quantile regression: β −2.1, 95% confidence interval [CI] −2.6 to −1.7). The IVT rate in potentially eligible patients was significantly lower in patients on VKA (156 of 247 [63%]; adjusted odds ratio [aOR] 0.67; 95% CI 0.50–0.90) and particularly in patients on DOACs (69 of 464 [15%]; aOR 0.06; 95% CI 0.05–0.08) compared with controls (1,544 of 2,504 [74%]). sICH after IVT occurred in 3.6% (2.6–4.7%) of controls, 9 of 195 (4.6%; 1.9–9.2%; aOR 0.93; 95% CI 0.46–1.90) patients on VKA and 2 of 65 (3.1%; 0.4–10.8%, aOR 0.56; 95% CI 0.28–1.12) of those on DOACs. After adjustments for prognostic confounders, DOAC pretreatment was associated with a favorable 3‐month outcome (aOR 1.24; 1.01–1.51). Interpretation Prior DOAC therapy in patients with AF was associated with decreased admission stroke severity at onset and a remarkably low rate of IVT. Overall, patients on DOAC might have better functional outcome at 3 months. Further research is needed to overcome potential restrictions for IVT in patients taking DOACs. ANN NEUROL 2021;89:42–53

Background and Purpose-The objective of this study was to assess the effect of therapeutic moderate hypothermia on excitatory amino acids and metabolism by applying cerebral microdialysis in patients suffering from space-occupying middle cerebral artery infarction. Methods-This

Background-Excitotoxic insults such as stroke may induce release of fatty acid ethanolamides (FAEs), contributing to the downstream events in the ischemic cascade. We therefore studied release of FAEs such as anandamide, palmitylethanolamide (PEA), and oleylethanolamide (OEA) in the brain of a patient suffering from malignant hemispheric infarction treated with hypothermia. Case Description-A patient with life-threatening hemispheric stroke was treated with moderate hypothermia (33°C) that was maintained for 3 days, followed by a 3-day rewarming period. Microdialysis was applied to measure glutamate, lactate, and glycerol by using a microdialysis analyzer. FAEs were measured by microdialysis coupled with high-performance liquid chromatography/mass spectrometry. Release of neuroprotective fatty amides occurred within the first day after ischemia and reached high concentrations for all 3 substances in tissue surrounding the primary ischemic lesion: anandamide up to 42 pmol/mL, PEA up to 120 pmol/mL, and OEA up to 242 pmol/mL. There was a significant correlation with elevation of lactate as early marker for the hypoxic insult. Conclusions-This is the first report demonstrating release of FAEs in vivo during human stroke and may suggest contribution of the FAE signaling system to the pathophysiological events after ischemia. Key Words: amides Ⅲ cannabinoids Ⅲ cerebral ischemia Ⅲ fatty acids Ⅲ microdialysis Ⅲ stroke A mides of long-chain fatty acids with ethanolamine (fatty acid ethanolamides [FAEs]) are a family of ubiquitous signaling molecules that include the endogenous cannabinoid anandamide (arachidonylethanolamide), the analgesic and anti-inflammatory mediator palmitylethanolamide (PEA), and the anorexic mediator oleylethanolamide (OEA). [1][2][3][4][5] Though widely divergent in function, FAEs may share a common biosynthetic mechanism, which consists of 2 enzymatic reactions occurring in parallel. A phospholipase D activity may release FAEs by hydrolyzing the distal phosphodiester bond in N-acyl phosphatidylethanolamine (NAPE), a minor membrane phospholipid. Simultaneously, a Ca 2ϩ -regulated N-acyltransferase activity may resynthesize NAPE by translocating fatty acid from phosphatidylcholine to the amino group in phosphatidylethanolamine. 6 -8 Intracellular Ca 2ϩ plays a key role in initiating these reactions, and Ca 2ϩ -mobilizing stimuli such as membrane depolarization or glutamate receptor activation are potent triggers for FAE and NAPE biosynthesis in neurons. 2,[7][8][9] The finding that FAEs are produced on demand in neurons via a Ca 2ϩ -dependent mechanism suggests that these compounds may participate in neural signaling. This possibility is supported by a variety of evidence indicating a primary role for anandamide in cannabinergic neurotransmission and for other, noncannabinoid FAEs in the endogenous regulation of pain and feeding. [3][4][5]10 In addition to these physiological roles, FAEs may also contribute to the pathological response of brain tissue to postischemic damage. Results from in vitro ...