RNF213 Polymorphisms in Intracranial Artery Dissection.

The ring finger protein 213 gene (RNF213) is involved in several vascular diseases, both intracranial and systemic ones. Some variants are common in the Asian population and are reported as a risk factor for moyamoya disease, intracranial stenosis and intracranial aneurysms. Among intracranial vascular diseases, both moyamoya disease and intracranial artery dissection are more prevalent in the Asian population. We performed a systematic review of the literature, aiming to assess the rate of RNF213 variants in patients with spontaneous intracranial dissections. Four papers were identified, providing data on 53 patients with intracranial artery dissection. The rate of RNF213 variants is 10/53 (18.9%) and it increases to 10/29 (34.5%), excluding patients with vertebral artery dissection. All patients had the RNF213 p.Arg4810Lys variant. RNF213 variants seems to be involved in intracranial dissections in Asian cohorts. The small number of patients, the inclusion of only patients of Asian descent and the small but non-negligible coexistence with moyamoya disease familiarity might be limiting factors, requiring further studies to confirm these preliminary findings and the embryological interpretation.

Beyond RCTs: Short-term dual antiplatelet therapy in secondary prevention of ischemic stroke and transient ischemic attack.

BACKGROUND AND PURPOSE: Randomized controlled trials (RCTs) proved the efficacy of short-term dual antiplatelet therapy (DAPT) in secondary prevention of minor ischemic stroke or high-risk transient ischemic attack (TIA). We aimed at evaluating effectiveness and safety of short-term DAPT in real-world, where treatment use is broader than in RCTs. METHODS: READAPT (REAl-life study on short-term Dual Antiplatelet treatment in Patients with ischemic stroke or Transient ischemic attack) (NCT05476081) was an observational multicenter real-world study with a 90-day follow-up. We included patients aged 18+ receiving short-term DAPT soon after ischemic stroke or TIA. No stringent NIHSS and ABCD2 score cut-offs were applied but adherence to guidelines was recommended. Primary effectiveness outcome was stroke (ischemic or hemorrhagic) or death due to vascular causes, primary safety outcome was moderate-to-severe bleeding. Secondary outcomes were the type of ischemic and hemorrhagic events, disability, cause of death, and compliance to treatment. RESULTS: We included 1920 patients; 69.9% started DAPT after an ischemic stroke; only 8.9% strictly followed entry criteria or procedures of RCTs. Primary effectiveness outcome occurred in 3.9% and primary safety outcome in 0.6% of cases. In total, 3.3% cerebrovascular ischemic recurrences occurred, 0.2% intracerebral hemorrhages, and 2.7% bleedings; 0.2% of patients died due to vascular causes. Patients with NIHSS score ⩽5 and those without acute lesions at neuroimaging had significantly higher primary effectiveness outcomes than their counterparts. Additionally, DAPT start >24 h after symptom onset was associated with a lower likelihood of bleeding. CONCLUSIONS: In real-world, most of the patients who receive DAPT after an ischemic stroke or a TIA do not follow RCTs entry criteria and procedures. Nevertheless, short-term DAPT remains effective and safe in this population. No safety concerns are raised in patients with low-risk TIA, more severe stroke, and delayed treatment start.

Statin use and long-term risk of recurrent intracerebral haemorrhage: the MUCH-Italy.

BACKGROUND: Whether statin use after spontaneous intracerebral haemorrhage (ICH) increases the risk of recurrent ICH is uncertain. METHODS: In the setting of the Multicentric Study on Cerebral Haemorrhage in Italy we followed up a cohort of 30-day ICH survivors, consecutively admitted from January 2002 to July 2014, to assess whether the use of statins after the acute event is associated with recurrent cerebral bleeding. RESULTS: 1623 patients (mean age, 73.9±10.3 years; males, 55.9%) qualified for the analysis. After a median follow-up of 40.5 months (25th to 75th percentile, 67.7) statin use was not associated with increased risk of recurrent ICH either in the whole study group (adjusted HR, 0.99; 95% CI 0.64 to 1.53) or in the subgroups defined by haematoma location (deep ICH, adjusted HR, 0.74; 95% CI 0.35 to 1.57; lobar ICH, adjusted HR, 1.09; 95% CI 0.62 to 1.90), intensity of statins (low-moderate intensity statins, adjusted HR, 0.93; 95% CI 0.58 to 1.49; high-intensity statins, adjusted HR, 1.48; 95% CI 0.66 to 3.31) and use of statins before the index event (adjusted HR, 0.66; 95% CI 0.38 to 1.17). CONCLUSIONS: Statin use appears to be unrelated to the risk of ICH recurrence.

Cerebellar mutism syndrome caused by bilateral cerebellar hemorrhage in adults: a case report and review of the literature.

Cerebellar mutism syndrome (CMS) is a frequent complication of surgical intervention on posterior fossa in children. It has been only occasionally reported in adults and its features have not been fully characterized. In children and in young adults, medulloblastoma is the main reason for neurosurgery. A single case of postsurgical CMS is presented in an adult patient with a cerebellar hemorrhage and a systematic review of the published individual cases of CMS in adults was done. Literature review of individual cases found 30 patients, 18/30 (60%) males, from 20 to 71 years at diagnosis. All but one case was post-surgical, but in one of the post-surgical cases iatrogenic basilar artery occlusion was proposed as cause for CMS. The causes were: primary tumors of the posterior fossa in 16/22 (72.7%) metastasis in 3/30 (10%), ischemia in 3/30 (10%) cerebellar hemorrhage in 3/30 (10%), and benign lesions in 2/30 (6.7%) patients. 8/30 patients (26.7%) were reported as having persistent or incomplete resolution of CMS within 12 months. CMS is a rare occurrence in adults and spontaneous cerebellar hemorrhage has been reported in 3/30 (10%) adult patients. The generally accepted hypothesis is that CMS results from bilateral damage to the dentate nucleus or the dentate-rubro-thalamic tract, leading to cerebro-cerebellar diaschisis. Several causes might contribute in adults. The prognosis of CMS is slightly worse in adults than in children, but two thirds of cases show a complete resolution within 6 months.

Persistent intracranial steno-occlusion from calcified embolism: a treatment challenge.

INTRODUCTION: Calcified arterial cerebral embolism is a rare occurrence among large and medium vessel occlusions causing ischemic stroke and its diagnosis and treatment is a challenge. The sources of calcified embolism might be a calcific atheroma from the aortic arch and carotid artery, but also heart valve disease has been reported in the literature. Calcified embolism is frequently simultaneous on multiple vascular territories. The prognosis of patients is usually poor, including patients treated by using endovascular thrombectomy (EVT) and this diagnosis could be easily missed in the acute phase. In addition, the optimal secondary prevention has not been yet fully stated. METHODS: We are presenting two cases of acute stroke due to calcified embolism in the middle cerebral artery (MCA) coming from a complicated carotid atheroma, non-stenosing in the first case (a 49 years old man) and stenosing in the second case (a 71 years old man) without clinical indications to intravenous thrombolysis and/or EVT, extensively investigated in the acute phase and followed-up for over 12 months with a favorable clinical course and the persisting steno-occlusion in the involved MCA. In both cases, antiplatelet treatment and targeting of vascular risk factors were done without recurrences in the follow-up period. DISCUSSION: Cerebral calcified embolism has been reported in 5.9% of cases of acute ischemic stroke in a single center series and only in 1.2% of a large retrospective cohort of EVT-treated patients. In both series the prognosis was poor and only one third of EVT-treated patients had functional independence at 3-months follow-up. The natural history of these subtype of ischemic stroke is relatively poorly understood and both etiological diagnosis and treatment have not yet defined. It is possible that some cases might be underdiagnosed and underreported. CONCLUSIONS: Calcified cerebral embolism is a rare cause of stroke, but it is largely underreported and both acute phase and secondary preventive treatment have to be defined.

Early seizures and risk of epilepsy and death after intracerebral haemorrhage: The MUCH Italy.

INTRODUCTION: It is unclear which patients with non-traumatic (spontaneous) intracerebral haemorrhage (ICH) are at risk of developing acute symptomatic seizures (provoked seizures occurring within the first week after stroke onset; early seizures, ES) and whether ES predispose to the occurrence of remote symptomatic seizures (unprovoked seizures occurring more than 1 week after stroke; post-stroke epilepsy, PSE) and long-term mortality. PATIENTS AND METHODS: In the setting of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy) we examined the risk of ES and whether they predict the occurrence of PSE and all-cause mortality in a cohort of patients with first-ever spontaneous ICH and no previous history of epilepsy, consecutively hospitalized in 12 Italian neurological centers from 2002 to 2014. RESULTS: Among 2570 patients (mean age, 73.4 ± 12.5 years; males, 55.4%) 228 (8.9%) had acute ES (183 (7.1%) short seizures and 45 (1.8%) status epilepticus (SE)). Lobar location of the hematoma (OR, 1.49; 95% CI, 1.06-2.08) was independently associated with the occurrence of ES. Of the 2,037 patients who were followed-up (median follow-up time, 68.0 months (25th-75th percentile, 77.0)), 155 (7.6%) developed PSE. ES (aHR, 2.34; 95% CI, 1.42-3.85), especially when presenting as short seizures (aHR, 2.35; 95% CI, 1.38-4.00) were associated to PSE occurrence. Unlike short seizures, SE was an independent predictor of all-cause mortality (aHR, 1.50; 95% CI, 1.005-2.26). DISCUSSION AND CONCLUSION: The long-term risk of PSE and death after an ICH vary according to ES subtype. This might have implications for the design of future clinical trials targeting post-ICH epileptic seizures.

Stroke-Induced Secondary Neurodegeneration of the Corticospinal Tract-Time Course and Mechanisms Underlying Signal Changes in Conventional and Advanced Magnetic Resonance Imaging.

Secondary neurodegeneration refers to the final result of several simultaneous and sequential mechanisms leading to the loss of substance and function in brain regions connected to the site of a primary injury. Stroke is one of the most frequent primary injuries. Among the subtypes of post-stroke secondary neurodegeneration, axonal degeneration of the corticospinal tract, also known as Wallerian degeneration, is the most known, and it directly impacts motor functions, which is crucial for the motor outcome. The timing of its appearance in imaging studies is usually considered late (over 4 weeks), but some diffusion-based magnetic resonance imaging (MRI) techniques, as diffusion tensor imaging (DTI), might show alterations as early as within 7 days from the stroke. The different sequential pathological stages of secondary neurodegeneration provide an interpretation of the signal changes seen by MRI in accordance with the underlying mechanisms of axonal necrosis and repair. Depending on the employed MRI technique and on the timing of imaging, different rates and thresholds of Wallerian degeneration have been provided in the literature. In fact, three main pathological stages of Wallerian degeneration are recognizable-acute, subacute and chronic-and MRI might show different changes: respectively, hyperintensity on T2-weighted sequences with corresponding diffusion restriction (14-20 days after the injury), followed by transient hypointensity of the tract on T2-weighted sequences, and by hyperintensity and atrophy of the tract on T2-weighted sequences. This is the main reason why this review is focused on MRI signal changes underlying Wallerian degeneration. The identification of secondary neurodegeneration, and in particular Wallerian degeneration, has been proposed as a prognostic indicator for motor outcome after stroke. In this review, the main mechanisms and neuroimaging features of Wallerian degeneration in adults are addressed, focusing on the time and mechanisms of tissue damage underlying the signal changes in MRI.

The Prepetrous Segment of the Internal Carotid Artery as a Neglected Site of Symptomatic Atherosclerosis: A Single-Center Series.

(1) Background: Non-stenotic complicated plaques are a neglected cause of stroke, in particular in young patients. Atherosclerosis has some preferential sites in extracranial arteries and the prepetrous segment of the internal carotid artery has been rarely described as site of atheroma in general and of complicated atheroma in stroke patients. The aim of this study is to describe the rate of the prepetrous internal carotid artery's (ICA) involvement in a single-center case series of young stroke patients. (2) Methods: All patients < 50 years old with acute ischemic stroke admitted to a single-center Stroke Unit during two time periods (the first one from 1 January 2018 to 31 December 2019, and the second one from 1 January 2021 to 30 June 2022), were prospectively investigated as part of a screening protocol of the Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO) study [ClinicalTrials.gov ID NCT01934725], including extracranial vascular examination by using computed tomography (CT) or magnetic resonance imaging (MRI). (3) Results: Two out of ninety-three consecutive patients (2.15%) had a complicated atheroma in the prepetrous ICA as the cause of stroke and both CT angiography and high-resolution vessel wall MRI were applied to document the main features of positive remodeling, cap rupture, ulceration, intraplaque hemorrhage, and a transient thrombus superimposed on the atheroma. The two patients had a different evolution of healing in the first case and a persisting ulceration at 12 months in the second case. (4) Conclusions: The prepetrous ICA is a rarely described location of complicated atheroma in stroke patients at all ages and it represents roughly 2% of causes of acute stroke in this single-center case series in young people.

Tumor-like Lesions in Primary Angiitis of the Central Nervous System: The Role of Magnetic Resonance Imaging in Differential Diagnosis.

Primary Angiitis of the Central Nervous System (PACNS) is a rare disease and its diagnosis is a challenge for several reasons, including the lack of specificity of the main findings highlighted in the current diagnostic criteria. Among the neuroimaging pattern of PACNS, a tumefactive form (t-PACNS) is a rare subtype and its differential diagnosis mainly relies on neuroimaging. Tumor-like mass lesions in the brain are a heterogeneous category including tumors (in particular, primary brain tumors such as glial tumors and lymphoma), inflammatory (e.g., t-PACNS, tumefactive demyelinating lesions, and neurosarcoidosis), and infectious diseases (e.g., neurotoxoplasmosis). In this review, the main features of t-PACNS are addressed and the main differential diagnoses from a neuroimaging perspective (mainly Magnetic Resonance Imaging-MRI-techniques) are described, including conventional and advanced MRI.

Long-Term Risk of Arterial Thrombosis After Intracerebral Hemorrhage: MUCH-Italy.

BACKGROUND: The identification of patients surviving an acute intracerebral hemorrhage who are at a long-term risk of arterial thrombosis is a poorly defined, crucial issue for clinicians. METHODS: In the setting of the MUCH-Italy (Multicenter Study on Cerebral Haemorrhage in Italy) prospective observational cohort, we enrolled and followed up consecutive 30-day intracerebral hemorrhage survivors to assess the long-term incidence of arterial thrombotic events, to assess the impact of clinical and radiological variables on the risk of these events, and to develop a tool for estimating such a risk at the individual level. Primary end point was a composite of ischemic stroke, myocardial infarction, or other arterial thrombotic events. A point-scoring system was generated by the ß-coefficients of the variables independently associated with the long-term risk of arterial thrombosis, and the predictive MUCH score was calculated as the sum of the weighted scores. RESULTS: Overall, 1729 patients (median follow-up time, 43 months [25th to 75th percentile, 69.0]) qualified for inclusion. Arterial thrombotic events occurred in 169 (9.7%) patients. Male sex, diabetes, hypercholesterolemia, atrial fibrillation, and personal history of coronary artery disease were associated with increased long-term risk of arterial thrombosis, whereas the use of statins and antithrombotic medications after the acute intracerebral hemorrhage was associated with a reduced risk. The area under the receiver operating characteristic curve of the MUCH score predictive validity was 0.716 (95% CI, 0.56-0.81) for the 0- to 1-year score, 0.672 (95% CI, 0.58-0.73) for the 0- to 5-year score, and 0.744 (95% CI, 0.65-0.81) for the 0- to 10-year score. C statistic for the prediction of events that occur from 0 to 10 years was 0.69 (95% CI, 0.64-0.74). CONCLUSIONS: Intracerebral hemorrhage survivors are at high long-term risk of arterial thrombosis. The MUCH score may serve as a simple tool for risk estimation.

Prevalence of Fabry disease and GLA variants in young patients with acute stroke: The challenge to widen the screening. The Fabry-Stroke Italian Registry.

BACKGROUND: Fabry disease (FD) is a treatable X-linked lysosomal storage disorder caused by GLA gene variants leading to alpha-galactosidase A deficiency. FD is a rare cause of stroke, and it is still controversial whether in stroke patients FD should be searched from the beginning or at the end of the diagnostic workup (in cryptogenic strokes). METHODS: Fabry-Stroke Italian Registry is a prospective, multicentric screening involving 33 stroke units. FD was sought by measuring α-galactosidase A activity (males) and by genetic tests (males with reduced enzyme activity and females) in patients aged 18-60 years hospitalized for TIA, ischemic stroke, or intracerebral hemorrhage. We diagnosed FD in patients with 1) already known pathogenic GLA variants; 2) novel GLA variants if additional clinical, laboratory, or family-derived criteria were present. RESULTS: Out of 1906 patients, we found a GLA variant in 15 (0.79%; 95%CI 0.44-1.29) with a certain FD diagnosis in 3 (0.16%; 95%CI 0.03-0.46) patients, none of whom had hemorrhage. We identified 1 novel pathogenic GLA variant. Ischemic stroke etiologies in carriers of GLA variants were: cardioaortic embolism (33%), small artery occlusion (27%), other causes (20%), and undetermined (20%). Mild severity, recurrence, previous TIA, acroparesthesias, hearing loss, and small artery occlusion were predictors of GLA variant. CONCLUSION: In this large multicenter cohort the frequency of FD and GLA variants was consistent with previous reports. Limiting the screening for GLA variants to patients with cryptogenic stroke may miss up to 80% of diagnoses. Some easily recognizable clinical features could help select patients for FD screening.

Posterior reversible encephalopathy syndrome and acute ischemic stroke: an underreported association.

INTRODUCTION: Posterior reversible encephalopathy syndrome (PRES) is a rare and complex disorder with variable clinical presentation and a typical magnetic resonance imaging (MRI) pattern of vasogenic edema with typical and atypical locations. It is often triggered by other diseases and drugs and the most prototypical association is with persistently elevated arterial pressure values. Among the potential cerebrovascular complications, intracranial bleeding has been described, but ischemic stroke is uncommonly reported. METHODS: We are presenting a case of a male patient with prolonged and sustained arterial hypertension acutely presenting with lacunar ischemic stroke involving the right corona radiata and composite MRI findings with the association of chronic small vessel disease (SVD) markers, acute symptomatic lacunar stroke, and atypical, central variant, posterior fossa dominant PRES. In the MRI follow-up, the white matter hyperintensities in T2-fluid attenuated inversion recovery (FLAIR sequences) due to PRES. DISCUSSION: The pathophysiology of PRES is not yet fully known, but the association with markedly increased values of arterial pressure is typical. In this context, ischemic stroke has not been considered in the clinical and neuroradiological manifestations of PRES and it has been only occasionally reported in the literature. In this case, the main hypothesis is that sustained hypertension may have triggered both manifestations, PRES, and ischemic stroke and the last one allowed to diagnose the first one. CONCLUSIONS: Atypical variants of PRES are not so rare and it may also occur in typical triggering situations. The association with ischemic stroke is even rarer and it may add some clues to the pathomechanisms of PRES.

The Venular Side of Cerebral Amyloid Angiopathy: Proof of Concept of a Neglected Issue.

Small vessel diseases (SVD) is an umbrella term including several entities affecting small arteries, arterioles, capillaries, and venules in the brain. One of the most relevant and prevalent SVDs is cerebral amyloid angiopathy (CAA), whose pathological hallmark is the deposition of amyloid fragments in the walls of small cortical and leptomeningeal vessels. CAA frequently coexists with Alzheimer's Disease (AD), and both are associated with cerebrovascular events, cognitive impairment, and dementia. CAA and AD share pathophysiological, histopathological and neuroimaging issues. The venular involvement in both diseases has been neglected, although both animal models and human histopathological studies found a deposition of amyloid beta in cortical venules. This review aimed to summarize the available information about venular involvement in CAA, starting from the biological level with the putative pathomechanisms of cerebral damage, passing through the definition of the peculiar angioarchitecture of the human cortex with the functional organization and consequences of cortical arteriolar and venular occlusion, and ending to the hypothesized links between cortical venular involvement and the main neuroimaging markers of the disease.

Secondary neurodegeneration of ipsilateral substantia nigra in acute ischemic stroke.

INTRODUCTION: Secondary neurodegeneration after stroke is a complex phenomenon affecting remote and synaptically linked cerebral areas. The involvement of the substantia nigra in this process has been rarely described in infarcts involving the striatum. METHODS: We are presenting a case of ischemic stroke involving the right striatum due to atrial fibrillation and associated in a few days with the neuroimaging finding of hyperintensity of the ipsilateral substantia nigra and striatonigral tract on T2-fluid attenuated inversion recovery and diffusion-weighted imaging sequences of brain magnetic resonance imaging. This finding was not related to clinical manifestations and substantially disappeared within 3 months from stroke onset. DISCUSSION: The pathophysiology of secondary degeneration of the substantia nigra is poorly understood and it relies on animal models and autoptic studies. The main putative mechanism is not ischemic but excitotoxic with a different role of the internal and external globus pallidus and a different effect on the pars compacta and pars reticularis of the substantia nigra. In animal models, inflammatory mechanisms seem play a role only in the late phase. The main studies on humans were presented in detail. CONCLUSIONS: A better understanding of the secondary degeneration of the substantia nigra has the potentiality to offer a chance for neuroprotection in acute stroke, but further studies are needed.

Perfusion Status in Lacunar Stroke: A Pathophysiological Issue.

The pathophysiology of lacunar infarction is an evolving and debated field, where relevant information comes from histopathology, old anatomical studies and animal models. Only in the last years, have neuroimaging techniques allowed a sufficient resolution to directly or indirectly assess the dynamic evolution of small vessel occlusion and to formulate hypotheses about the tissue status and the mechanisms of damage. The core-penumbra concept was extensively explored in large vessel occlusions (LVOs) both from the experimental and clinical point of view. Then, the perfusion thresholds on one side and the neuroimaging techniques studying the perfusion of brain tissue were focused and optimized for LVOs. The presence of a perfusion deficit in the territory of a single small perforating artery was negated for years until the recent proposal of the existence of a perfusion defect in a subgroup of lacunar infarcts by using magnetic resonance imaging (MRI). This last finding opens pathophysiological hypotheses and triggers a neurovascular multidisciplinary reasoning about how to image this perfusion deficit in the acute phase in particular. The aim of this review is to summarize the pathophysiological issues and the application of the core-penumbra hypothesis to lacunar stroke.

CT Perfusion in Lacunar Stroke: A Systematic Review.

BACKGROUND: The main theory underlying the use of perfusion imaging in acute ischemic stroke is the presence of a hypoperfused volume of the brain downstream of an occluded artery. Indeed, the main purpose of perfusion imaging is to select patients for endovascular treatment. Computed Tomography Perfusion (CTP) is the more used technique because of its wide availability but lacunar infarcts are theoretically outside the purpose of CTP, and limited data are available about CTP performance in acute stroke patients with lacunar stroke. METHODS: We performed a systematic review searching in PubMed and EMBASE for CTP and lacunar stroke with a final selection of 14 papers, which were examined for data extraction and, in particular, CTP technical issues and sensitivity, specificity, PPV, and NPV values. RESULTS: A global cohort of 583 patients with lacunar stroke was identified, with a mean age ranging from 59.8 to 72 years and a female percentage ranging from 32 to 53.1%.CTP was performed with different technologies (16 to 320 rows), different post-processing software, and different maps. Sensitivity ranges from 0 to 62.5%, and specificity from 20 to 100%. CONCLUSIONS: CTP does not allow to reasonable exclude lacunar infarct if no perfusion deficit is found, but the pathophysiology of lacunar infarct is more complex than previously thought.

Intravenous Thrombolysis 4.5-9 Hours After Stroke Onset: A Cohort Study from the TRISP Collaboration.

OBJECTIVE: To investigate the safety and effectiveness of intravenous thrombolysis (IVT) >4.5-9 hours after stroke onset, and the relevance of advanced neuroimaging for patient selection. METHODS: Prospective multicenter cohort study from the ThRombolysis in Ischemic Stroke Patients (TRISP) collaboration. Outcomes were symptomatic intracranial hemorrhage, poor 3-month functional outcome (modified Rankin scale 3-6) and mortality. We compared: (i) IVT >4.5-9 hours versus 0-4.5 hours after stroke onset and (ii) within the >4.5-9 hours group baseline advanced neuroimaging (computed tomography perfusion, magnetic resonance perfusion or magnetic resonance diffusion-weighted imaging fluid-attenuated inversion recovery) versus non-advanced neuroimaging. RESULTS: Of 15,827 patients, 663 (4.2%) received IVT >4.5-9 hours and 15,164 (95.8%) within 4.5 hours after stroke onset. The main baseline characteristics were evenly distributed between both groups. Time of stroke onset was known in 74.9% of patients treated between >4.5 and 9 hours. Using propensity score weighted binary logistic regression analysis (onset-to-treatment time >4.5-9 hours vs onset-to-treatment time 0-4.5 hours), the probability of symptomatic intracranial hemorrhage (ORadjusted 0.80, 95% CI 0.53-1.17), poor functional outcome (ORadjusted 1.01, 95% CI 0.83-1.22), and mortality (ORadjusted 0.80, 95% CI 0.61-1.04) did not differ significantly between both groups. In patients treated between >4.5 and 9 hours, the use of advanced neuroimaging was associated with a 50% lower mortality compared with non-advanced imaging only (9.9% vs 19.7%; ORadjusted 0.51, 95% CI 0.33-0.79). INTERPRETATION: This study showed no evidence in difference of symptomatic intracranial hemorrhage, poor outcome, and mortality in selected stroke patients treated with IVT between >4.5 and 9 hours after stroke onset compared with those treated within 4.5 hours. Advanced neuroimaging for patient selection was associated with lower mortality. ANN NEUROL 2023;94:309-320.

Acute Onset Quadriplegia and Stroke: Look at the Brainstem, Look at the Midline.

Acute onset quadriplegia with or without facial sparing is an extremely rare vascular syndrome, and the main focus of attention is on the cervical and upper thoracic spinal cord as the putative site of the damage. Quadriplegia has been occasionally reported in brainstem strokes within well-defined lesion patterns, but these reports have gained little attention so far because of the rarity of this clinical syndrome. The clinical, neuroanatomical and neuroimaging features of ischemic stroke locations associated with quadriplegia have been collected and reviewed in a pragmatical view, which includes a detailed description of the neurological signs associated with the damage of the pyramidal pathways. Two clinical examples have been added to raise practical suggestions in neurovascular practice. Ischemic stroke sites determining quadriplegia have some main well-defined midline locations in the brainstem, involving the pyramidal pathways of both sides in a single synchronous ischemic lesion in the medulla oblongata and in the pons. Several accompanying neurological signs have been described when the ischemic lesion involves tracts and nuclei other than the pyramidal pathways, and they can be useful as localizing clues. In some cases, the typical neuroimaging appearance of the ischemic lesion on Magnetic Resonance Imaging (MRI) has been reported as being a "heart appearance sign". This last sign has been described in midbrain strokes too, but this location is not associated with quadriplegia. The main etiology is atherothrombosis involving the intradural segment of the vertebral artery (VA) and their perforating branches. Two clinical examples of these rare vascular syndromes have been chosen to support a pragmatical discussion about the management of these cases. A midline ischemic stroke in the brainstem is a very rare vascular syndrome, and the acute onset quadriplegia is a distinctive feature of it. The awareness of this cerebrovascular manifestation might help to recognize and treat these patients.

Intravenous Thrombolysis in Patients With Ischemic Stroke Aged ≥90 Years: A Cohort Study From the TRISP Collaboration.

BACKGROUND: The probability to receive intravenous thrombolysis (IVT) for treatment of acute ischemic stroke declines with increasing age and is consequently the lowest in very elderly patients. Safety concerns likely influence individual IVT treatment decisions. Using data from a large IVT registry, we aimed to provide more evidence on safety of IVT in the very elderly. METHODS: In this prospective multicenter study from the TRISP (Thrombolysis in Ischemic Stroke Patients) registry, we compared patients ≥90 years with those <90 years using symptomatic intracranial hemorrhage (ECASS [European Cooperative Acute Stroke Study]-II criteria), death, and poor functional outcome in survivors (modified Rankin Scale score 3-5 for patients with prestroke modified Rankin Scale score ≤2 and modified Rankin Scale score 4-5 for patients prestroke modified Rankin Scale ≥3) at 3 months as outcomes. We calculated adjusted odds ratio with 95% CI using logistic regression models. RESULTS: Of 16 974 eligible patients, 976 (5.7%) were ≥90 years. Patients ≥90 years had higher median National Institutes of Health Stroke Scale on admission (12 versus 8) and were more often dependent prior to the index stroke (prestroke modified Rankin Scale score of ≥3; 45.2% versus 7.4%). Occurrence of symptomatic intracranial hemorrhage (5.7% versus 4.4%, odds ratioadjusted 1.14 [0.83-1.57]) did not differ significantly between both groups. However, the probability of death (odds ratioadjusted 3.77 [3.14-4.53]) and poor functional outcome (odds ratioadjusted 2.63 [2.13-3.25]) was higher in patients aged ≥90 years. Results for the sample of centenarians (n=21) were similar. CONCLUSIONS: The probability of symptomatic intracranial hemorrhage after IVT in very elderly patients with stroke did not exceed that of their younger counterparts. The higher probability of death and poor functional outcome during follow-up in the very elderly seems not to be related to IVT treatment. Very high age itself should not be a reason to withhold IVT.

Bow hunter's syndrome successfully treated with a posterior surgical decompression approach: A case report and review of literature.

BACKGROUND: Bow hunter's syndrome (BHS) is a rare but surgically treatable cause of vertebrobasilar insufficiency due to dynamic rotational occlusion of the vertebral artery. Typically, patients present with posterior circulation transient ischaemic symptoms such as presyncope, syncope, vertigo, diplopia, and horizontal nystagmus, but irreversible deficits, including medullary and cerebellar infarctions, have also been described. CASE SUMMARY: A 70-year-old patient presented an acute onset of vertigo and gait instability triggered by right head rotation. His medical history included previous episodes of unilateral left neck and occipital pain followed by light-headedness, sweating, and blurred vision when turning his head, and these episodes were associated with severe degenerative changes in the atlanto-dens and left atlanto-axial facet joints and right rotation of the C2 cervical vertebrae. Brain magnetic resonance imaging revealed the presence of acute bilateral cerebellar ischaemic lesions, while static vascular imaging did not reveal any vertebral artery abnormalities. Dynamic ultrasonography and angiography were performed and confirmed the presence of a dynamic occlusion of the vertebral artery V3-V4 segment when the head was rotated to the right secondary to left C1-C2 bone spur compression. Surgical decompression led to complete resolution of paroxysmal symptoms without neurological sequelae. CONCLUSION: BHS should be considered in cases of repeated posterior circulation transient ischaemic attack or ischaemic stroke, particularly when associated with high cervical spine abnormalities.