Effectiveness of computed tomography perfusion imaging in stroke management.

Objectives: Current guidelines do not support the use of computed tomography perfusion (CTP) in stroke, except when identifying the penumbra during an extended treatment window. Therefore, this study aimed to define the yield of CTP in diagnosing a stroke diagnosis beyond the imaging of the penumbra in the hyperacute phase (0-6 h) and an extended time window (6-24 h). Materials and methods: All consecutive patients with acute onset of symptoms within a 24-h window underwent CTP imaging. The diagnostic value of CTP was calculated against the clinical and radiological diagnoses of stroke. A positive CTP result was determined by the presence of either a core or penumbra on the RAPID summary. Clinical diagnoses corresponded to discharge diagnoses of stroke. A radiological diagnosis was established if early ischemic changes [Alberta Stroke Program Early CT Score (ASPECTS) <10] were observed on the baseline CT scan, acute infarction was confirmed on follow-up imaging, or symptomatic occlusion was evident on baseline CTA. Results: Between November 2018 and November 2019, 585 consecutive patients with an acute neurological deficit underwent multimodal CT imaging. A total of 500 patients (85%) were included, where 274 (55%) were within the hyperacute phase, 153 (31%) had a radiological diagnosis of stroke, and 122 (24%) had a clinical diagnosis of stroke. CTP yielded positive results only in patients with a confirmed stroke (positive predictive value and specificity of 100%). When CTP results were negative, 43% of the cases turned out to stroke mimics. Patients with stroke mimics were younger (66 ± 17 vs. 73 ± 13) and had lower scores on the National Institutes of Health Stroke Scale [median 0; interquartile range (IQR) 0-2 vs. median 4; IQR 2-6] compared to patients with CTP-negative strokes. Conclusion: In our study, CTP consistently indicated brain ischemia; therefore, in stroke management, CTP is most beneficial when it yields a positive result. A positive CTP result should prompt adequate stroke management actions without any delay. Conversely, a negative CTP result necessitates the consideration of both stroke and non-stroke diagnoses.

Case report: Susac syndrome-two ends of the spectrum, single center case reports and review of the literature.

Susac syndrome is a rare and enigmatic complex neurological disorder primarily affecting small blood vessels in the brain, retina, and inner ear. Diagnosing Susac syndrome may be extremely challenging not only due to its rarity, but also due to the variability of its clinical presentation. This paper describes two vastly different cases-one with mild symptoms and good response to therapy, the other with severe, complicated course, relapses and long-term sequelae despite multiple therapeutic interventions. Building upon the available guidelines, we highlight the utility of black blood MRI in this disease and provide a comprehensive review of available clinical experience in clinical presentation, diagnosis and therapy of this disease. Despite its rarity, the awareness of Susac syndrome may be of uttermost importance since it ultimately is a treatable condition. If diagnosed in a timely manner, early intervention can substantially improve the outcomes of our patients.

Cerebral air embolism: neurologic manifestations, prognosis, and outcome.

Background: Cerebral air embolism (CAE) is an uncommon medical emergency with a potentially fatal course. We have retrospectively analyzed a set of patients treated with CAE at our comprehensive stroke center and a hyperbaric medicine center. An overview of the pathophysiology, causes, diagnosis, and treatment of CAE is provided. Results: We retrospectively identified 11 patients with cerebral venous and arterial air emboli that highlight the diversity in etiologies, manifestations, and disease courses encountered clinically. Acute-onset stroke syndrome and a progressive impairment of consciousness were the two most common presentations in four patients each (36%). Two patients (18%) suffered from an acute-onset coma, and one (9%) was asymptomatic. Four patients (36%) were treated with hyperbaric oxygen therapy (HBTO), high-flow oxygen therapy without HBOT was started in two patients (18%), two patients (18%) were in critical care at the time of diagnosis and three (27%) received no additional treatment. CAE was fatal in five cases (46%), caused severe disability in two (18%), mild disability in three (27%), and a single patient had no lasting deficit (9%). Conclusion: Cerebral air embolism is a dangerous condition that necessitates high clinical vigilance. Due to its diverse presentation, the diagnosis can be missed or delayed in critically ill patients and result in long-lasting or fatal neurological complications. Preventative measures and a proper diagnostic and treatment approach reduce CAE's incidence and impact.

Penumbral Rescue by normobaric O = O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial.

RATIONALE: Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra until revascularization occurs. AIMS: PROOF investigates the use of normobaric oxygen (NBO) therapy within 6 h of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior-circulation occlusion. METHODS AND DESIGN: Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial. STUDY OUTCOMES: Primary outcome is ischemic core growth (mL) from baseline to 24 h (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 h, mRS at 90 days, cognitive and emotional function, and quality of life. Safety outcomes include mortality, intracranial hemorrhage, and respiratory failure. Exploratory analyses of imaging and blood biomarkers will be conducted. SAMPLE SIZE: Using an adaptive design with interim analysis at 80 patients per arm, up to 456 participants (228 per arm) would be needed for 80% power (one-sided alpha 0.05) to detect a mean reduction of ischemic core growth by 6.68 mL, assuming 21.4 mL standard deviation. DISCUSSION: By enrolling endovascular thrombectomy candidates in an early time window, the trial replicates insights from preclinical studies in which NBO showed beneficial effects, namely early initiation of near 100% inspired oxygen during short temporary ischemia. Primary outcome assessment at 24 h on follow-up imaging reduces variability due to withdrawal of care and early clinical confounders such as delayed extubation and aspiration pneumonia. TRIAL REGISTRATIONS: ClinicalTrials.gov: NCT03500939; EudraCT: 2017-001355-31.

Song-related dopamine receptor regulation in Area X of zebra finch male.

Song learning and production have many parallels with speech and the mechanisms of their control have been studied extensively. There is an increasing amount of evidence that the dopaminergic system is involved in song learning and maintenance. Dopamine receptors show distinct expression in most of the song nuclei and the highest levels in Area X of the striatum. Here we have investigated whether the mRNA expressions for D1A, D1B, and D2 receptors in Area X are associated with quantitative and/or qualitative characteristics of zebra finch song. We found that quantitative parameters of song such as the amount of songs sang, motif duration, and numbers of distinct syllables and/or notes per motif did not correlate with expression of D1A, D1B nor D2 receptors in Area X or surrounding striatum. However, the mean accuracy of the song correlated negatively with D1A receptor expression levels and the sequential match correlated positively with D2 receptor expression levels in Area X relative to the surrounding striatum. These data suggest that dopamine receptor densities in Area X are associated with song variability.

Basal ganglia function, stuttering, sequencing, and repair in adult songbirds.

A pallial-basal-ganglia-thalamic-pallial loop in songbirds is involved in vocal motor learning. Damage to its basal ganglia part, Area X, in adult zebra finches has been noted to have no strong effects on song and its function is unclear. Here we report that neurotoxic damage to adult Area X induced changes in singing tempo and global syllable sequencing in all animals, and considerably increased syllable repetition in birds whose song motifs ended with minor repetitions before lesioning. This stuttering-like behavior started at one month, and improved over six months. Unexpectedly, the lesioned region showed considerable recovery, including immigration of newly generated or repaired neurons that became active during singing. The timing of the recovery and stuttering suggest that immature recovering activity of the circuit might be associated with stuttering. These findings indicate that even after juvenile learning is complete, the adult striatum plays a role in higher level organization of learned vocalizations.