Multivariate lesion symptom mapping for predicting trajectories of recovery from aphasia.

Individuals with post-stroke aphasia tend to recover their language to some extent; however, it remains challenging to reliably predict the nature and extent of recovery that will occur in the long term. The aim of this study was to quantitatively predict language outcomes in the first year of recovery from aphasia across multiple domains of language and at multiple timepoints post-stroke. We recruited 217 patients with aphasia following acute left hemisphere ischaemic or haemorrhagic stroke and evaluated their speech and language function using the Quick Aphasia Battery acutely and then acquired longitudinal follow-up data at up to three timepoints post-stroke: 1 month (n = 102), 3 months (n = 98) and 1 year (n = 74). We used support vector regression to predict language outcomes at each timepoint using acute clinical imaging data, demographic variables and initial aphasia severity as input. We found that ∼60% of the variance in long-term (1 year) aphasia severity could be predicted using these models, with detailed information about lesion location importantly contributing to these predictions. Predictions at the 1- and 3-month timepoints were somewhat less accurate based on lesion location alone, but reached comparable accuracy to predictions at the 1-year timepoint when initial aphasia severity was included in the models. Specific subdomains of language besides overall severity were predicted with varying but often similar degrees of accuracy. Our findings demonstrate the feasibility of using support vector regression models with leave-one-out cross-validation to make personalized predictions about long-term recovery from aphasia and provide a valuable neuroanatomical baseline upon which to build future models incorporating information beyond neuroanatomical and demographic predictors.

Commentary on "Consciousness as a Memory System" by Budson, Richman, and Kensinger (2022).

Consciouness is a phenomenon that has eluded explanation by generations of physicians and scientists. Many discussions, experiments, and theories about consciousness have been published, but none has adequately explained the phenomenon. In the previous issue, Budson and colleagues (2022) present a theory of consciousness based on explicit memory processes, with consciousness developing in the context of memory function. In the authors' view, consciousness accompanying other cortical processes such as language or visual-spatial function developed only later in evolution. The evidence presented for this evolutionary sequence, however, is very limited. Furthermore, no discussion is directed toward the theory that consciousness involves the intersection between external perceptions and internal bodily states. The authors also develop the concept that most of our actions, and even our personality, are conscious only after the fact; immediate decisions are taken by the unconscious mind-the "horse" rather than the "rider." There is empirical evidence that rapid decisions and responses occur before they become conscious. However, Budson and colleagues (2022) extend the concept of unconscious decision-making to virtually all actions; in so doing, not only do they minimize the phenomenon of self-conscious awareness, but their theory has disturbing ethical implications for personal responsibility, criminal law, free will, and personality.

Recovery from aphasia in the first year after stroke.

Most individuals who experience aphasia after a stroke recover to some extent, with the majority of gains taking place in the first year. The nature and time course of this recovery process is only partially understood, especially its dependence on lesion location and extent, which are the most important determinants of outcome. The aim of this study was to provide a comprehensive description of patterns of recovery from aphasia in the first year after stroke. We recruited 334 patients with acute left hemisphere supratentorial ischaemic or haemorrhagic stroke and evaluated their speech and language function within 5 days using the Quick Aphasia Battery (QAB). At this initial time point, 218 patients presented with aphasia. Individuals with aphasia were followed longitudinally, with follow-up evaluations of speech and language at 1 month, 3 months, and 1 year post-stroke, wherever possible. Lesions were manually delineated based on acute clinical MRI or CT imaging. Patients with and without aphasia were divided into 13 groups of individuals with similar, commonly occurring patterns of brain damage. Trajectories of recovery were then investigated as a function of group (i.e. lesion location and extent) and speech/language domain (overall language function, word comprehension, sentence comprehension, word finding, grammatical construction, phonological encoding, speech motor programming, speech motor execution, and reading). We found that aphasia is dynamic, multidimensional, and gradated, with little explanatory role for aphasia subtypes or binary concepts such as fluency. Patients with circumscribed frontal lesions recovered well, consistent with some previous observations. More surprisingly, most patients with larger frontal lesions extending into the parietal or temporal lobes also recovered well, as did patients with relatively circumscribed temporal, temporoparietal, or parietal lesions. Persistent moderate or severe deficits were common only in patients with extensive damage throughout the middle cerebral artery distribution or extensive temporoparietal damage. There were striking differences between speech/language domains in their rates of recovery and relationships to overall language function, suggesting that specific domains differ in the extent to which they are redundantly represented throughout the language network, as opposed to depending on specialized cortical substrates. Our findings have an immediate clinical application in that they will enable clinicians to estimate the likely course of recovery for individual patients, as well as the uncertainty of these predictions, based on acutely observable neurological factors.

Management of Intracerebral Hemorrhage: Update and Future Therapies.

PURPOSE OF REVIEW: Intracerebral hemorrhage (ICH) represents about 15% of all strokes in the USA, but almost 50% of fatal strokes. There are many causes of ICH, but the most common are hypertension and cerebral amyloid angiopathy. This review will discuss new advances in the treatment of intracerebral hemorrhage. RECENT FINDINGS: The treatment of ICH focuses on management of edema, aggressive blood pressure reduction, and correction of coagulopathy. Early initiation of supportive medical therapies, including blood pressure management, in a neurological intensive care unit reduces mortality, but at present there is no definitive, curative therapy analogous to mechanical thrombectomy for ischemic stroke. Nonetheless, new medical and surgical approaches promise more successful management of ICH patients, especially new approaches to surgical management. In this review, we focus on the current standard of care of acute ICH and discuss emerging therapies that may alter the landscape of this devastating disease.

Protocolizing the Workup for Idiopathic Normal Pressure Hydrocephalus Improves Outcomes.

BACKGROUND: The workup for idiopathic normal pressure hydrocephalus (INPH) can be difficult to coordinate, and determining appropriate patients for ventriculoperitoneal shunting can be challenging. Therefore, we hypothesized that implementing a formalized protocol can improve patient selection for a shunt. In conjunction with neurology and neurosurgery, we instituted a standardized means of assessing patients whose presentation is concerning for INPH and compared their workup with similar patients seen without the Protocol (i.e., preprotocol [PP]) regarding baseline characteristics, assessment, and outcomes. METHODS: Twenty-six PP patients were compared with 40 Protocol patients on measures, including baseline deficits, workup, neurosurgical evaluation, and response to shunt. RESULTS: Average age was similar between groups, and the percentage of patients who had a decline in gait, cognition, and/or incontinence was not statistically different (p > 0.05). Significantly more Protocol patients underwent high-volume lumbar puncture (HVLP; 97.5%; PP, 61.5%; p < 0.001) and received formalized gait assessment with the Gait Scale (90%; PP, 0%, p < 0.001) and standardized cognitive testing (95%; PP, 38.5%; p < 0.001). Significantly more Protocol patients had no improvement after HVLP (33.3%; PP, 6.25%; p < 0.045); subsequently, fewer got shunted (57.5%; PP, 84.6%; p < 0.030). More Protocol patients who were shunted reported gait improvement (100%; PP, 72.7%; p = 0.009), although there was no difference in cognition (59.2%; PP, 82.6%; p = 0.108) or incontinence (18.2%; PP, 39.1%; p = 0.189). CONCLUSIONS: Implementing an INPH Protocol leads to standardized and more extensive assessment and better patient selection for and subsequent outcomes from shunting, specifically regarding gait.

Association of asymptomatic hemorrhage after endovascular stroke treatment with outcomes.

BACKGROUND: Intracerebral hemorrhage (ICH) occurs in ~20%-30% of stroke patients undergoing endovascular therapy (EVT). However, there is conflicting evidence regarding the effect of asymptomatic ICH (aICH) on post-EVT outcomes. We sought to evaluate the effect of aICH on immediate and 90-day post-EVT neurological outcomes. METHODS: In this post-hoc analysis of the multicenter, prospective Blood Pressure after Endovascular Therapy (BEST) study we identified subjects with ICH following EVT. This population was divided into no ICH, aICH, and symptomatic ICH (sICH). Associations with 90-day modified Rankin Scale (mRS) dichotomized by functional independence (0-2 vs 3-6) and early neurological recovery (ENR) were determined using univariate/multivariate logistic regression models. RESULTS: Of 485 patients enrolled in BEST, 446 had 90-day follow-up data available. 92 (20.6%) developed aICH, and 18 (4%) developed sICH. Compared with those without ICH, aICH was not associated with worse 90-day outcome or lower ENR (OR 0.84 [0.53-1.35], P=0.55, aOR 0.84 [0.48-1.44], P=0.53 for 90-day mRS 0-2; OR 0.77 [0.48-1.23], P=0.34, aOR 0.72 [0.43-1.22] for ENR). aICH was not associated with 90-day outcome or ENR in patients with mTICI ≥2 b (OR 0.78 [0.48-1.26], P=0.33 for 90-day mRS 0-2; OR 0.89 [0.69-1.12], P=0.15 for ENR). A higher proportion of patients with aICH had mTICI ≥2 b than those without ICH (97%vs 87%, P=0.01). CONCLUSIONS: aICH was not associated with worse outcomes in patients with large-vessel stroke treated with EVT. aICH was more frequent in patients with successful recanalization. Further validation of our findings in large cohort studies of EVT-treated patients is warranted.

Left Atrial Appendage Closure for Patients with Cerebral Amyloid Angiopathy and Atrial Fibrillation: the LAA-CAA Cohort.

Anticoagulation increases the risk of intracerebral hemorrhage (ICH) in patients with cerebral amyloid angiopathy (CAA), so the management of stroke-risk in patients with both atrial fibrillation (AF) and CAA is controversial. Advances in left atrial appendage closure (LAAC) techniques provide a stroke-risk-reduction option which avoids long-term oral anticoagulation (OAC). We aimed to evaluate the safety of this intervention in patients with CAA. This is an observational cohort study of patients with severe CAA (with or without ICH) and AF who were treated with LAA closure. The Watchman™ and Amulet® LAAC devices and Lariat procedure or open surgical closure of the LAA were all considered acceptable means of closure. Patients with symptomatic ICH and those naïve to anticoagulation were placed on clopidogrel and/or aspirin for 6 weeks after the procedure; patients who previously tolerated anticoagulation remained on warfarin or a DOAC for 6 weeks post-procedure. All anticoagulation therapy was discontinued after confirmation of LAAC. All patients had aggressively optimized blood pressure and fall precautions in addition to surgical intervention. Safety, tolerability, stroke, and hemorrhage rates were documented. Twenty-six patients with a mean CHA2DS2-VASc score of 4.6 were treated, 13 with a history of symptomatic lobar hemorrhage and 13 without. All patients who completed LAAC tolerated the device implantation. There were no documented ischemic strokes or symptomatic ICH during the 30 days after device implantation. Patients were followed for an average of 25 months. One patient who underwent Lariat LAAC had an ischemic stroke in follow-up, but recovered well; there were no other thromboemboli in this cohort. This cohort study provides evidence that LAAC appears to be a safe and tolerable treatment to reduce stroke risk in patients with CAA. Because of the small size of the cohort and relatively short follow-up, the efficacy for stroke and ICH prevention is not conclusive, but the preliminary results are encouraging. LAA closure may be a good alternative to anticoagulation in patients with CAA and atrial fibrillation.

Misdiagnosis of lamotrigine toxicity as posterior circulation transient ischemic attack or stroke.

PURPOSE: Lamotrigine (LTG) is one of the most used antiseizure medications (ASMs). Titration is indicated for incomplete seizure control, but toxicity with vertigo, ataxia, and diplopia may ensue. Lamotrigine concentration would be the optimal diagnostic test. However, patients often receive a stroke evaluation when presenting to the emergency department (ED), leading to unnecessary cost and delayed management. We investigated the frequency of stroke evaluation for symptoms associated with LTG toxicity and attempted to identify factors leading to this expensive evaluation. METHODS: We identified adult patients treated with LTG who presented to an emergency room with dizziness, ataxia, or diplopia and received a negative stroke evaluation, between 2003 and 2018. They were among 972 patients treated with LTG for epilepsy. We collected age at time of occurrence, symptoms presented, imaging studies performed, LTG dose and serum concentration, and the time the result was available. As a denominator, we also identified patients who developed clinical LTG toxicity during the same time period. RESULTS: Thirteen patients with LTG toxicity had 16 negative stroke evaluations in the emergency room. Their mean age was 62 years (range: 43-79) as compared with 47 years for all patients treated with LTG (p < 0.0005). The mean daily LTG dose was 621 mg (range: 300-900 mg). A LTG serum concentration was requested on the day of evaluation in 7 instances, though the result was never available until at least the next day. In 4 instances, the LTG level was drawn 1-3 days after presentation. Five of the patients in this group were among 71 patients with clinical LTG toxicity and LTG concentration >20. CONCLUSION: Emergency departments will frequently call a stroke alert for patients taking LTG and presenting with symptoms consistent with LTG toxicity, particularly in seniors at greater risk of stroke. This adds not only expense but also radiation and contrast exposure from computed tomography (CT) studies. We recommend that a rapid LTG assay be made available and always ordered in patients receiving LTG, avoiding the considerable expense of an unnecessary stroke evaluation.

Mechanical Thrombectomy in Ischemic Stroke Patients with Severe Pre-Stroke Disability.

Frequency and outcomes of mechanical thrombectomy (MT) in clinical practice for patients with severe pre-stroke disability are largely unknown. In this case series, we aim to describe the disability make-up and outcomes of 33 patients with severe pre-stroke disability undergoing MT. Patients with a permanent, severe, pre-stroke disability (modified Rankin Score, mRS, 4-5) were identified from a prospectively-maintained database of consecutive, MT-treated, anterior circulation acute ischemic stroke patients at two comprehensive stroke centers in the United States. We present details on the cause of disability and socio-demographic status as well as procedural and functional outcomes. This study, despite the lack of inferential testing due to limited sample size, provides insight into demographics and outcomes of MT-treated patients with severe pre-stroke disability. Rate of return to functional baseline as well as rates of procedural success and complications were comparable to that reported in the literature for patients without any pre-existing disability.

Intravenous Fibrinolysis for Central Retinal Artery Occlusion: A Cohort Study and Updated Patient-Level Meta-Analysis.

BACKGROUND AND PURPOSE: Central retinal artery occlusion results in sudden, painless, usually permanent loss of vision in the affected eye. There is no proven, effective treatment to salvage visual acuity and a clear, unmet need for an effective therapy. In this work, we evaluated the efficacy of intravenous tissue-type plasminogen activator (IV alteplase) in a prospective cohort study and an updated systematic review and meta-analysis. METHODS: We enrolled consecutive patients with acute central retinal artery occlusion within 48 hours of symptoms onset and with a visual acuity of <20/200 from January 2009 until May 2019. The primary outcomes were safety and functional visual acuity recovery. We compared rates of visual recovery between those treated with alteplase within 4.5 hours of symptom onset to those who did not receive alteplase (including an analysis restricted to untreated patients presenting within the window for treatment). We incorporated these results into an updated systematic review and patient-level meta-analysis. RESULTS: We enrolled 112 patients, of whom 25 (22.3% of the cohort) were treated with IV alteplase. One patient had an asymptomatic intracerebral hemorrhage after IV alteplase treatment. Forty-four percent of alteplase-treated patients had recovery of visual acuity when treated within 4.5 hours versus 13.1% of those not treated with alteplase (P=0.003) and 11.6% of those presenting within 4 hours who did not receive alteplase (P=0.03). Our updated patient-level meta-analysis of 238 patients included 67 patients treated with alteplase within 4.5 hours since time last known well with a recovery rate of 37.3%. This favorably compares with a 17.7% recovery rate in those without treatment. In linear regression, earlier treatment correlated with a higher rate of visual recovery (P=0.01). CONCLUSIONS: This study showed that the administration of intravenous alteplase within 4.5 hours of symptom onset is associated with a higher likelihood of a favorable visual outcome for acute central retinal artery occlusion. Our results strongly support proceeding to a randomized, placebo-controlled clinical trial.