Insight Into Uncommon Territory: Exploring Internuclear Ophthalmoplegia in Artery of Percheron Infarct.

Internuclear ophthalmoplegia (INO), a neurological disorder is characterized by horizontal gaze palsy because of a lesion in the medial longitudinal fasciculus, a neural pathway that is mainly responsible for coordinating the movements of the eye. INO presents with diplopia and impaired adduction of the affected eye, accompanied by abducting eye nystagmus. The condition also arises from different etiologies which include multiple sclerosis, encephalitis, Lyme disease, HIV, and herpes zoster. Artery of Percheron (AOP) infarction is a subtype of bilateral thalamic infarction that poses a unique form of diagnostic perplexity due to its varied and often non-specific clinical manifestations such as altered responsiveness, memory disturbances, and oculomotor deficits. Here we discuss a 53-year-old female who presented with INO in the context of an AOP infarct. Under this context, the clinical finding includes some paradigms like nystagmus, anisocoria, and bilateral ptosis. Magnetic resonance imaging confirmed an acute infarct in the AOP territory, which supplies the rostral midbrain and paramedian thalami. This case emphasizes the critical importance of meticulous clinical evaluation and the utilization of advanced imaging techniques in diagnosing rare stroke syndromes like AOP infarction. Management of the patient included dual antiplatelet therapy to prevent further thromboembolic events and supportive care to address the immediate neurological deficits. Early recognition and prompt treatment are crucial for better patient outcomes. Long-term management focuses on the secondary prevention of stroke through lifestyle modifications, medical therapy, and regular monitoring. Education on uncommon stroke syndromes and continued research are essential for enhancing the accuracy of diagnosis and efficacy of treatment which ultimately leads to better patient care and prognosis.

Impact of diffusion-weighted imaging lesion volume on the success of endovascular reperfusion therapy.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) lesion volume is associated with poor outcome after thrombolysis, and it is unclear whether endovascular therapies are beneficial for large DWI lesion. Our aim was to assess the impact of pretreatment DWI lesion volume on outcomes after endovascular therapy, with a special emphasis on patients with complete recanalization. METHODS: We analyzed data collected between April 2007 and November 2011 in a prospective clinical registry. All acute ischemic stroke patients with complete occlusion of internal carotid artery or middle cerebral artery treated by endovascular therapy were included. DWI lesion volumes were measured by the RAPID software. Favorable outcome was defined by modified Rankin Scale of 0 to 2 at 90 days. RESULTS: A total of 139 acute ischemic stroke patients were included. Median DWI lesion volume was 14 cc (interquartile range, 5-43) after a median onset time to imaging of 110 minutes (interquartile range, 77-178). Higher volume was associated with less favorable outcome (adjusted odds ratio, 0.55; 95% confidence interval, 0.31-0.96). A complete recanalization was achieved in 65 (47%) patients after a median onset time of 238 minutes (interquartile range, 206-285). After adjustment for volume, complete recanalization was associated with more favorable outcome (adjusted odds ratio, 6.32; 95% confidence interval, 2.90-13.78). After stratification of volume by tertiles, complete recanalization was similarly associated with favorable outcome in the upper 2 tertiles (P<0.005). CONCLUSIONS: Our results emphasize the importance of initial DWI volume and recanalization on clinical outcome after endovascular treatment. Large DWI lesions may still benefit from recanalization in selected patients.

Diabetes mellitus, admission glucose, and outcomes after stroke thrombolysis: a registry and systematic review.

BACKGROUND AND PURPOSE: The potential detrimental effect of diabetes mellitus and admission glucose level (AGL) on outcomes after stroke thrombolysis is unclear. We evaluated outcomes of patients treated by intravenous and/or intra-arterial therapy, according to diabetes mellitus and AGL. METHODS: We analyzed data from a patient registry (n=704) and conducted a systematic review of previous observational studies. The primary study outcome was the percentage of patients who achieved a favorable outcome (modified Rankin score ≤2 at 3 months). RESULTS: We identified 54 previous reports that evaluated the effect of diabetes mellitus or AGL on outcomes after thrombolysis. In an unadjusted meta-analysis that included our registry data and previous available observational data, diabetes mellitus was associated with less favorable outcome (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.73-0.79) and more symptomatic intracranial hemorrhage (OR, 1.38; 95% CI, 1.21-1.56). However, in multivariable analysis, diabetes mellitus remained associated with less favorable outcome (OR, 0.77; 95% CI, 0.69-0.87) but not with symptomatic intracranial hemorrhage (OR, 1.11; 95% CI, 0.83-1.48). In unadjusted and in adjusted meta-analysis, higher AGL was associated with less favorable outcome and more symptomatic intracranial hemorrhage; the adjusted OR (95% CI) per 1 mmol/L increase in AGL was 0.92 (0.90-0.94) for favorable outcome, and 1.09 (1.04-1.14) for symptomatic intracranial hemorrhage. CONCLUSIONS: These results confirm that AGL and history of diabetes mellitus are associated with poor clinical outcome after thrombolysis. AGL may be a surrogate marker of brain infarction severity rather than a causal factor. However, randomized controlled evidences are needed to address the significance of a tight glucose control during thrombolysis on clinical outcome.

Predictors of congruency between clinical and radiographic Oxfordshire Community Stroke Project Classification subtypes.

BACKGROUND: The Oxfordshire Community Stroke Project (OCSP) classification has been widely used to assess ischemic stroke patients based on clinical characteristics alone. However, the correlation between the clinical presentation evaluated using OCSP and imaging findings is yet to be determined. Our study aimed to describe the baseline characteristics of the OCSP subtypes of patients admitted with ischemic stroke and evaluate the predictors of the relationship between clinical and neuroimaging findings. METHODS: Patients with a confirmed diagnosis of ischemic stroke admitted to a comprehensive stroke center in Brazil between February 2015 and October 2017 were eligible for the study. All participants underwent computed tomography (CT) at admission and follow-up neuroimaging within seven days, per the institutional protocol. Trained staff classified patients according to the OCSP at hospital admission. The radiographic OCSP classification was retrospectively assessed based on the last follow-up neuroimaging by investigators unaware of the clinical classification. RESULTS: The overall agreement rates ranged from 65.5% to 88.7%. Lower NIHSS scores, absent hyperdense MCA sign, higher ASPECTS, and absent brainstem symptoms were related to a higher risk of misclassification. Treatment with intravenous tPA was associated with reclassification in patients with total anterior circulation syndrome. For predicting radiographic posterior circulation involvement, vertigo (OR 2.9, 95% CI 1.7-5.1, p < 0.001) and brainstem symptoms (OR 35, 95% CI 20.5-60.2, p < 0.001) were directly associated with correct classification, but motor and higher cerebral function were not correlated. CONCLUSION: The clinical OCSP classification presented good congruency rates with the neuroimaging findings. However, patients with lacunar syndromes are often misclassified when radiological criteria are considered.

Cerebral venous sinus thrombosis following ChAdOx1 nCoV-19 AstraZeneca COVID-19 vaccine.

A woman in her mid-twenties was admitted with headache, ultimately leading to a diagnosis of cerebral venous sinus thrombosis 10 days after receiving a first dose of the AstraZeneca ChAdOx1 nCoV-19 vaccine (Vaxzevria). We report this case from clinical investigations to outcomes and discuss the issues raised by it regarding the ChAdOx1 nCoV-19 vaccine.

Motor sequela of adult and pediatric stroke: Imminent losses and ultimate gains.

Stroke is the leading cause of neurological disability in the United States and worldwide. Remarkable advances have been made over the past 20 years in acute vascular treatments to reduce infarct size and improve neurological outcome. Substantially less progress has been made in the understanding and clinical approaches to neurological recovery after stroke. This chapter reviews the epidemiology, bedside examination, localization approaches, and classification of stroke, with an emphasis on motor stroke presentations and management, and promising research approaches to enhancing motor aspects of stroke recovery.

Staged use of ordinal and linear disability scales: a practical approach to granular assessment of acute stroke outcome.

Background: The modified Rankin Scale (mRS) assessment of global disability is the most common primary endpoint in acute stroke trials but lacks granularity (7 broad levels) and is ordinal (scale levels unknown distances apart), which constrains study power. Disability scales that are linear and continuous may better discriminate outcomes, but computerized administration in stroke patients is challenging. We, therefore, undertook to develop a staged use of an ordinal followed by a linear scale practical to use in multicenter trials. Methods: Consecutive patients undergoing 3-month final visits in the NIH FAST-MAG phase 3 trial were assessed with the mRS followed by 15 mRS level-specific yes-no items of the Academic Medical Center Linear Disability Score (ALDS), a linear disability scale derived using item response theory. Results: Among 55 patients, aged 71.2 (SD ± 14.2), 67% were men and the entry NIHSS was 10.7 (SD ± 9.5). At 90 days, the median mRS score was 3 (IQR, 1-4), and the median ALDS score was 78.8 (IQR, 3.3-100). ALDS scores correlated strongly with 90 days outcome measures, including the Barthel Index (r = 0.92), NIHSS (r = 0.87), and mRS (r = 0.94). ALDS scores also correlated modestly with entry NIHSS (r = 0.38). At 90 days, the ALDS showed greater scale granularity than the mRS, with fewer patients with identical values, 1.9 (SD ± 3.2) vs. 8.0 (SD ± 3.6), p < 0.001. When treatment effect magnitudes were small to moderate, projected trial sample size requirements were 2-12-fold lower when the ALDS rather than the mRS was used as the primary trial endpoint. Conclusion: Among patients enrolled in an acute neuroprotective stroke trial, the ALDS showed strong convergent validity and superior discrimination characteristics compared with the modified Rankin Scale and increased projected trial power to detect clinically meaningful treatment benefits.

Corrigendum: Staged use of ordinal and linear disability scales: a practical approach to granular assessment of acute stroke outcome.

[This corrects the article DOI: 10.3389/fneur.2023.1174686.].

Chronic cerebral aspects of long COVID, post-stroke syndromes and similar states share their pathogenesis and perispinal etanercept treatment logic.

The chronic neurological aspects of traumatic brain injury, post-stroke syndromes, long COVID-19, persistent Lyme disease, and influenza encephalopathy having close pathophysiological parallels that warrant being investigated in an integrated manner. A mechanism, common to all, for this persistence of the range of symptoms common to these conditions is described. While TNF maintains cerebral homeostasis, its excessive production through either pathogen-associated molecular patterns or damage-associated molecular patterns activity associates with the persistence of the symptoms common across both infectious and non-infectious conditions. The case is made that this shared chronicity arises from a positive feedback loop causing the persistence of the activation of microglia by the TNF that these cells generate. Lowering this excess TNF is the logical way to reducing this persistent, TNF-maintained, microglial activation. While too large to negotiate the blood-brain barrier effectively, the specific anti-TNF biological, etanercept, shows promise when administered by the perispinal route, which allows it to bypass this obstruction.

Diagnosing and localizing the acute vestibular syndrome - Beyond the HINTS exam.

When assessing the acutely dizzy patient, the HINTS 'Plus' (Head Impulse, Nystagmus, Test of Skew, 'Plus' a bedside assessment of auditory function) exam is a crucial component of the bedside exam. However, there are additional ocular motor findings that can help the clinician distinguish peripheral from central etiologies and enable accurate localization, especially when the patient has acute dizziness, vertigo and/or imbalance but without spontaneous nystagmus. We will review the literature on these findings which are 'beyond HINTS' and include saccades/ocular lateropulsion, smooth pursuit, and provocative maneuvers including head-shaking and positional testing (not part of the HINTS exam). Additionally, we will expound on the localizing value of nystagmus, ocular alignment and the ocular tilt reaction (parts of the HINTS exam). The paper has been organized neuroanatomically, based on brainstem and cerebellar structures that have been reported to cause the acute vestibular syndrome.

How diseases caused by parasites allowed a wider understanding of disease in general: my encounters with parasitology in Australia and elsewhere over the last 50 years.

This is an account of how it can prove possible to carve a reasonable scientific career by following what brought most scientific thrill rather than pursue a safe, institution-directed, path. The fascination began when I noticed, quite unexpectedly, that the normal mouse immune response causes Babesia microti to die, en masse, inside circulating red cells. It eventuated that prior Bacillus Calmette Guerin infection caused the same outcome, even before the protozoal infection became patent. It also rendered mice quite immune, long term. I acquired an obsession about this telling us how little we know. Surrounded by basic immunologists, parasitologists and virologists in London, I had been given, in the days that funding was ample, the opportunity to follow any promising lead with a free hand. Through Bacillus Calmette Guerin, this meant stumbling through a set of phenomena that were in their infancies, and could be explained only through nebulous novel soluble mediators such as TNF, described the following year as causing the in vivo necrosis of tumours in mice. Beginning with malarial disease pathogenesis, I followed TNF wherever it led, into innate immunity, acute and chronic infections, neurophysiology and neurodegenerative diseases, in all of which states awareness of the role of this cytokine is still growing fast. Many of these steps can be illustrated and expanded upon in parasitic diseases. Covering the importance of TNF in the pathogenesis of neurodegenerative disease has proved to be highly illuminating, scientifically and otherwise. But the insights it has given me into understanding the temptations to which patent-owners can succumb when faced with opportunities to put money before people is not for the faint hearted. Clearly, parasitologists inhabit a much more common-good yet science-orientated, civilised, world.

Stroke Classification: Critical Role of Unusually Large von Willebrand Factor Multimers and Tissue Factor on Clinical Phenotypes Based on Novel "Two-Path Unifying Theory" of Hemostasis.

Stroke is a hemostatic disease associated with thrombosis/hemorrhage caused by intracranial vascular injury with spectrum of clinical phenotypes and variable prognostic outcomes. The genesis of different phenotypes of stroke is poorly understood due to our incomplete understanding of hemostasis and thrombosis. These shortcomings have handicapped properly recognizing each specific stroke syndrome and contributed to controversy in selecting therapeutic agents. Treatment recommendation for stroke syndromes has been exclusively derived from the result of laborious and expensive clinical trials. According to newly proposed "two-path unifying theory" of in vivo hemostasis, intracranial vascular injury would yield several unique stroke syndromes triggered by 3 distinctly different thrombogenetic mechanisms depending upon level of intracranial intravascular injury and character of formed blood clots. Five major phenotypes of stroke occur via thrombogenetic paths: (1) transient ischemic attack due to focal endothelial damage limited to endothelial cells (ECs), (2) acute ischemic stroke due to localized ECs and subendothelial tissue (SET) damage extending up to the outer vascular wall, (3) thrombo-hemorrhagic stroke due to localized vascular damage involving ECs and SET and extending beyond SET to extravascular tissue, (4) acute hemorrhagic stroke due to major localized intracranial hemorrhage/hematoma into the brain tissue or space between the coverings of the brain associated with vascular anomaly or obtuse trauma, and (5) encephalopathic stroke due to disseminated endotheliopathy leading to microthrombosis within the brain. New classification of stroke phenotypes would assist in selecting rational therapeutic regimen for each stroke syndrome and designing clinical trials to improve clinical outcome.

Large Vessel Occlusion in the Acute Stroke Patient: Identification, Treatment, and Management.

Acute ischemic stroke is a major cause of death and disability in the United States. Historically, acute stroke patients were treated with intravenous (IV) thrombolysis. Patients with large vessel occlusions (LVOs) should be offered mechanical thrombectomy, with or without IV thrombolysis, in an extended window up to 24 hours of last known well. Both treatment options are the standard of care for a patient with an LVO. It is critical that the intensive care unit nurse understand new treatment indications for LVO strokes, and the priorities of nursing care with medical and endovascular intervention.

Susac syndrome presenting with acute hemibody paraesthesia.

Susac syndrome is an orphan disease characterised by encephalopathy, branch retinal artery occlusion and sensorineural hearing loss. As the clinical triad is rarely present at symptom onset, it is often initially misdiagnosed and appropriate treatment is often delayed. Herewith, we report a case of Susac syndrome in a 47-year-old man presenting with acute hemisensory loss and highlight the challenges of early diagnosis, particularly relevant in the era of hyperacute stroke management.

Management Issues in Intensive Care Units for Infants and Children with Heart Disease.

Admission of infants and children with cardiac disease to the neonatal (NICU) and pediatric ICU (PICU) is ever increasing in India (30-50 % of all admissions). The commonest indication for admission to the NICU or PICU is acute deterioration of cardiac disease. This includes: acute heart failure, hypercyanotic spells, arrhythmias, pericardial tamponade and sick cardiac neonates who need urgent intervention. Other increasingly frequent indications for ICU admission include heart failure with concomitant chest infection and impending respiratory failure and, severe cyanotic heart disease with various stroke syndromes. It is thus essential that a pediatrician be comfortable with the ICU management of such children and that low cost ICU modalities be utilized in order to reach out to as many children as feasible. It is heartening that there is renewed interest in inexpensive therapies like noninvasive ventilation and therapeutic hypothermia.

Early Anticipation of Candidacy for Intra-Arterial Reperfusion Therapy Based on Baseline Clinical Stroke Subtypes: Comparison with Multiparametric MRI Taken within 4.5 Hours from Stroke Onset.

BACKGROUND: The decision to proceed with intra-arterial (IA) reperfusion therapy is typically made late in the course of in-hospital treatment for acute ischemic stroke. Early anticipation of candidacy for IA reperfusion therapy based on clinical stroke subtypes would be useful for guiding stroke management. The aim of this study was to investigate the relationship between the clinical Oxfordshire Community Stroke Project (OCSP) classification and MRI results taken within a 4.5-hour time window from stroke onset, with the hypothesis that the persistence of major arterial occlusion and extended ischemic penumbra, key criteria for proceeding with IA reperfusion therapy, would be distinctive between the clinical stroke subtypes. METHODS: A total of 161 patients with acute ischemic stroke in the anterior circulation were included in this study. All patients were treated with intravenous alteplase, and MRI scans were performed following alteplase initiation. Prior to treatment, the patients were categorized, based on the OCSP classification scheme, as having total anterior circulation infarcts (TACI), partial anterior circulation infarcts (PACI), or lacunar infarcts (LACI). The relationship between OCSP subtypes, MRI parameters, and clinical variables was analyzed. RESULTS: Overall, 40/161 patients (24.8%) were candidates for IA rescue reperfusion. With respect to the classification, 30/69 TACI (43.5%), 6/33 PACI (18.2%), and 4/59 LACI patients (6.8%) were candidates (p < 0.001). Major arterial occlusion was found in 56/161 patients (34.8%), and 46/69 TACI (66.7%), 6/33 PACI (18.2%), and 4/59 LACI patients (6.8%) had a major arterial occlusion (p < 0.001). A perfusion-diffusion mismatch greater than 20% was found in 85/161 patients (52.8%). More specifically, 40/69 TACI (58.0%), 25/33 PACI (75.8%), and 20/59 LACI patients (33.9%) had a perfusion-diffusion mismatch (p < 0.001). However, in terms of the total area of mismatch, 66.0% of patients with ASPECTSDWI-PWI ≥2 (Alberta Stroke Program Early CT Score) were classified as TACI patients (p < 0.001) and of the patients with ASPECTSDWI-PWI ≥3, 74.3% were classified as TACI patients (p < 0.001). Relative to candidates for IA rescue reperfusion, the clinical TACI group showed 75.0% sensitivity, 67.8% specificity, a positive predictive value of 43.5%, and a negative predictive value of 89.1%. CONCLUSIONS: In this study, patients classified as having clinical TACI were significantly more likely to be candidates for IA rescue reperfusion. Additionally, they incurred a higher incidence of persistent major arterial occlusion and had a penumbra area that was significantly larger than normal. Therefore, clinical OCSP can be used as an 'early warning system' for IA reperfusion candidacy, which can allow for advanced preparation of IA therapy and theoretically shorten treatment time and reduce infarction.