Prestroke Cognitive Impairment: Frequency and Association With Premorbid Neuropsychiatric, Functional, and Neuroimaging Features.

BACKGROUND: Some patients with stroke have prestroke cognitive impairment (pre-SCI), but its etiology is not clear. The aim of this cross-sectional study was to assess the frequency of pre-SCI and its association with premorbid neuropsychiatric, functional, and neuroimaging features. METHODS: Patients hospitalized in stroke unit with an informant who could complete IQCODE (Informant Questionnaire for Cognitive Decline in the Elderly) were included. Pre-SCI was diagnosed if the IQCODE score was >3.3. Prestroke assessment also included NPI-Q (Neuropsychiatric Inventory Questionnaire), the basic Activities of Daily Living and Instrumental Activities of Daily Living scales, and the Clinical Dementia Rating scale. A multivariate logistic regression model was used to evaluate the association of pre-SCI with age, sex, education, arterial hypertension, atrial fibrillation, white matter lesions, cerebral microbleeds, and pathological medial temporal lobe atrophy. RESULTS: IQCODE was available in 474 of 520 patients (91.2%; 45% women; mean age 75.5±13.3 years). Pre-SCI had a prevalence of 32.5% and was associated with prestroke NPI-Q (pre-SCI absent versus present, 1.7±2.3 versus 5.5±4.9; P<0.001), Activities of Daily Living scale (0.3±0.8 versus 1.8±1.9; P<0.001), Instrumental Activities of Daily Living scale (0.6±1.3 versus 3.8±4.0; P<0.001), and Clinical Dementia Rating scale score (0.7±1.7 versus 7.2±6.2; P<0.001). In the 271 patients with a magnetic resonance imaging available, the multivariate logistic regression showed that age (odds ratio [OR], 1.05 [95% CI, 1.62-9.73]), white matter lesions (OR, 1.26 [95% CI, 1.003-1.58]), and a pathological medial temporal lobe atrophy score (OR, 3.97 [95% CI, 1.62-9.73]) were independently associated with pre-SCI. In the 218 patients with ischemic stroke, white matter lesions (OR, 1.34 [95% CI, 1.04-1.72]) and medial temporal lobe atrophy (OR, 3.56 [95% CI, 1.38-9.19]), but not age, were associated with pre-SCI. CONCLUSIONS: One-third of patients admitted to a stroke unit have pre-SCI that is associated with preexisting neuropsychiatric symptoms and functional performance. White matter lesions and medial temporal lobe atrophy are associated with pre-SCI, suggesting that both small vessel disease and neurodegeneration might be involved in its etiology.

Early predictors of dysphagia in ischaemic stroke patients.

BACKGROUND AND PURPOSE: Post-stroke dysphagia affects outcome. In acute stroke patients, the aim was to evaluate clinical, cognitive and neuroimaging features associated with dysphagia and develop a predictive score for dysphagia. METHODS: Ischaemic stroke patients underwent clinical, cognitive and pre-morbid function evaluations. Dysphagia was retrospectively scored on admission and discharge with the Functional Oral Intake Scale. RESULTS: In all, 228 patients (mean age 75.8 years; 52% males) were included. On admission, 126 (55%) were dysphagic (Functional Oral Intake Scale ≤6). Age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.00-1.05), pre-event modified Rankin scale (mRS) score (OR 1.41, 95% CI 1.09-1.84), National Institutes of Health Stroke Scale (NIHSS) score (OR 1.79, 95% CI 1.49-2.14), frontal operculum lesion (OR 8.53, 95% CI 3.82-19.06) and Oxfordshire total anterior circulation infarct (TACI) (OR 1.47, 95% CI 1.05-2.04) were independently associated with dysphagia at admission. Education (OR 0.91, 95% CI 0.85-0.98) had a protective role. At discharge, 82 patients (36%) were dysphagic. Pre-event mRS (OR 1.28, 95% CI 1.04-1.56), admission NIHSS (OR 1.88, 95% CI 1.56-2.26), frontal operculum involvement (OR 15.53, 95% CI 7.44-32.43) and Oxfordshire classification TACI (OR 3.82, 95% CI 1.95-7.50) were independently associated with dysphagia at discharge. Education (OR 0.89, 95% CI 0.83-0.96) and thrombolysis (OR 0.77, 95% CI 0.23-0.95) had a protective role. The 6-point "NOTTEM" (NIHSS, opercular lesion, TACI, thrombolysis, education, mRS) score predicted dysphagia at discharge with good accuracy. Cognitive scores had no role in dysphagia risk. CONCLUSIONS: Dysphagia predictors were defined and a score was developed to evaluate dysphagia risk during stroke unit stay. In this setting, cognitive impairment is not a predictor of dysphagia. Early dysphagia assessment may help in planning future rehabilitative and nutrition strategies.

The use of dual antiplatelet therapy for ischemic cerebrovascular events.

In the last 10 years, the use of dual antiplatelet therapy (DAPT) in the neurological ambit has been explored in patients with non-cardioembolic ischemic stroke, transient ischemic attack (TIA), and intracranial atherosclerotic disease. Two clinical trials (CHANCE and POINT) showed that in patients with minor non-cardioembolic ischemic stroke or high-risk TIA, the addition of clopidogrel to aspirin reduces the risk of stroke recurrence. Another trial (THALES) evaluated the association of ticagrelor and aspirin in mild-to-moderate non-cardioembolic ischemic stroke or high-risk TIA, showing a reduced risk of subsequent stroke compared to aspirin alone. Finally, the use of DAPT has been assessed in the treatment of stroke associated with atherosclerotic intracranial stenosis in the SAMMPRIS trial, showing a favorable profile compared to percutaneous angioplasty and stenting. The aim of this article is, after a review the major trials evaluating DAPT in patients with ischemic cerebrovascular events and the ways they have been implemented in Italian, European, and USA guidelines, to provide a practical algorithm to help clinicians in their everyday clinical practice and to outline possible caveats in the practical implementation of guidelines. Possible limitations and gaps in knowledge regarding specific conditions (e.g., the use of DAPT after acute phase therapies) are also underlined.

A novel CACNA1A R2201W variant in a woman with hemiplegic migraine.

INTRODUCTION: Familial hemiplegic migraine type 1 (FHM1) is a monogenic rare disease that is characterized by migraine attacks accompanied by unilateral weakness and is caused by mutations in the CACNA1A gene. We report the case of a patient with a clinical history consistent with hemiplegic migraine who underwent genetic testing that revealed a variant in the CACNA1A gene. CASE PRESENTATION: A 68-year-old woman was evaluated for progressive postural instability and subjective cognitive decline. She had suffered from recurrent migraine episodes accompanied by fully reversible unilateral weakness that had started around the age of thirty and had fully disappeared at the time of evaluation. Magnetic resonance imaging (MRI) showed an extensive leukoencephalopathy, with features suggestive of small vessel disease, significantly progressing over the years. Exome sequencing revealed the heterozygous variant c.6601C>T (p.Arg2201Trp) in the CACNA1A gene. This variant, located in a highly conserved region, causes the substitution of arginine with tryptophan at codon 2202 of exon 47, with a high likelihood of a damaging effect on protein activity and/or structure. DISCUSSION: This is the first report describing the missense mutation c.6601C>T (p.Arg2201Trp) in heterozygosity in the CACNA1A gene in a patient with clinical features of hemiplegic migraine. The presence of a diffuse leukoencephalopathy on MRI is not typical of hemiplegic migraine and may suggest a phenotypic variant related to this mutation or result from the combined effect of the patient's comorbidities.

Restoring Quantum Communication Efficiency over High Loss Optical Fibers.

In the absence of quantum repeaters, quantum communication proved to be nearly impossible across optical fibers longer than ≳20 km due to the drop of transmissivity below the critical threshold of 1/2. However, if the signals fed into the fiber are separated by a sufficiently short time interval, memory effects must be taken into account. In this Letter, we show that by properly accounting for these effects it is possible to devise schemes that enable unassisted quantum communication across arbitrarily long optical fibers at a fixed positive qubit transmission rate. We also demonstrate how to achieve entanglement-assisted communication over arbitrarily long distances at a rate of the same order of the maximum achievable in the unassisted noiseless case.

Predictivity of the clock drawing test in the acute phase of cerebrovascular diseases on cognitive decline at a 6-month neuropsychological evaluation.

INTRODUCTION: We showed that the Clock Drawing Test (CDT) performed during the acute phase of cerebrovascular diseases predicted worsening of cognitive function defined based on a clinical judgement at a 3-month follow-up. The aim of this study was to verify the predictivity of the CDT on the worsening of cognitive status assessed with an extensive neuropsychological evaluation 6 months after the acute event. METHODS: Patients with a stroke or transient ischemic attack underwent a baseline clinical, neuroimaging, and neuropsychological assessment, including the CDT. Premorbid cognitive status was evaluated by means of the Clinical Dementia Rating scale. Between 6 and 7 months after the acute event, all patients underwent a neuropsychological evaluation that included tests for executive function, attention, language, memory, and visuospatial abilities. RESULTS: Fifty patients (29 males; mean age 72.2 years) were enrolled: 28 (56%) had no premorbid cognitive impairment, 15 (30%) had premorbid mild cognitive impairment (MCI), and 4 (8%) had premorbid dementia; for 3 patients, evaluation of premorbid status was not available. At follow-up, 11 (22%) had no cognitive impairment, 28 (56%) were diagnosed with MCI, and 11 (22%) dementia. In patients who were non-demented before the event, on regression analysis, the score obtained at CDT was predictive of decline of cognitive status at the 6-month follow-up (OR 1.65; 95% CI 1.08-2.52). DISCUSSION: Our study confirms that administering the CDT during the acute phase of cerebrovascular diseases is informative with regard to the worsening of cognitive function after 6 months.

Prediction of post-stroke cognitive impairment by Montreal Cognitive Assessment (MoCA) performances in acute stroke: comparison of three normative datasets.

BACKGROUND: Cognitive assessment in acute stroke is relevant for identifying patients at risk of persistent post-stroke cognitive impairment (PSCI). Despite preliminary evidence on MoCA accuracy, there is no consensus on its optimal score in the acute stroke setting to predict PSCI. AIMS: (1) To explore whether the application of different normative datasets to MoCA scores obtained in the acute stroke setting results in variable frequency of patients defined as cognitively impaired; (2) to assess whether the normality cut-offs provided by three normative datasets predict PSCI at 6-9 months; (3) to calculate alternative MoCA cut-offs able to predict PSCI. METHODS: Consecutive stroke patients were reassessed at 6-9 months with extensive neuropsychological and functional batteries for PSCI determination. RESULTS: Out of 207 enrolled patients, 118 (57%) were followed-up (mean 7.4 ± 1.7 months), and 77 of them (65%) received a PSCI diagnosis. The application of the normality thresholds provided by the 3 normative datasets yielded to variable (from 28.5% to 41%) rates of patients having an impaired MoCA performance, and to an inadequate accuracy in predicting PSCI, maximizing specificity instead of sensitivity. In ROC analyses, a MoCA score of 22.82, adjusted according to the most recent normative dataset, achieved a good diagnostic accuracy in predicting PSCI. CONCLUSIONS: The classification of acute stroke patients as normal/impaired based on MoCA thresholds proposed by general population normative datasets underestimated patients at risk of persistent PSCI. We calculated a new adjusted MoCA score predictive of PSCI in acute stroke patients to be further tested in larger studies.

Neuropsychological screening in the acute phase of cerebrovascular diseases.

INTRODUCTION: Cognitive impairment is a common and disabling consequence of stroke. Its prevalence, the best way to screen for it in the acute setting, and its relation with premorbid status have not been thoroughly clarified. MATERIALS AND METHODS: Ischemic and hemorrhagic stroke patients admitted to our stroke unit underwent a baseline assessment that included a clinical and neuroimaging assessment, two cognitive tests (clock-drawing test, CDT; Montreal Cognitive Assessment-Basic, MoCA-B) and measures of premorbid function (including the Clinical Dementia Rating Scale). A follow-up examination was repeated 3-4 months after the acute event. RESULTS: Two hundred and twenty-three patients (52.5% women, mean age ± SD 75.8 years ± 12.3) were evaluated. Prestroke cognitive impairment was present in 91 patients (40.8%). At follow-up, the prevalence of cognitive impairment was 49%, while its incidence among patients who did not have any prestroke cognitive impairment was 38.8%. Of the originally admitted 223 patients (71 were lost to follow-up), only 60 (26.9%) were still cognitively intact at follow-up. On regression analysis, age and baseline CDT were associated with worsening of cognitive status at follow-up. In patients without cognitive impairment at baseline, a cutoff of 23 for MoCA-B and of 8.7 for CDT scores predicted the diagnosis of post-stroke cognitive impairment with sufficient accuracy. DISCUSSION AND CONCLUSION: Prestroke and post-stroke cognitive impairment affect a large proportion of patients with stroke. Our findings suggest that a neuropsychological screening during the acute phase might be predictive of the development of post-stroke cognitive impairment.

Etiologic reclassification of cryptogenic stroke after implantable cardiac monitoring and computed tomography angiography re-assessment.

INTRODUCTION: Different mechanisms may underlie cryptogenic stroke, including subclinical atrial fibrillation (AF), nonstenotic carotid plaques (NCP), and aortic arch atherosclerosis (AAA). In a cohort of cryptogenic stroke patients, we aimed to: (1) evaluate the prevalence of subclinical AF, NCP, and AAA, and reclassify the etiology accordingly; (2) compare the clinical features of patients with reclassified etiology with those with confirmed cryptogenic stroke. METHODS: Data of patients hospitalized for cryptogenic stroke between January 2018 and February 2021 were retrospectively analyzed. Patients were included if they received implantable cardiac monitoring (ICM) to detect subclinical AF. Baseline computed tomography angiography (CTA) was re-evaluated to assess NCP and AAA. Since aortic plaques with ulceration/intraluminal thrombus were considered pathogenetic during the initial workup, only patients with milder AAA were included. Stroke etiology was reclassified as "cardioembolic", "atherosclerotic", or "mixed" based on the detection of AF and NCP/AAA. Patients with "true cryptogenic" stroke (no AF, ipsilateral NCP, or AAA detected) were compared with those with reclassified etiology. RESULTS: Among 63 patients included, 21 (33%) were diagnosed with AF (median follow-up time of 15 months), 12 (19%) had ipsilateral NCP, and 6 (10%) had AAA. Stroke etiology was reclassified in 30 patients (48%): cardioembolic in 14 (22%), atherosclerotic in 9 (14%), and mixed in 7 (11%). Patients with true cryptogenic stroke were younger compared to those with reclassified etiology (p = 0.001). DISCUSSION: One or more potential covert stroke sources can be recognized in half of the patients with a cryptogenic stroke through long-term cardiac monitoring and focused CTA re-assessment.

The Clock Drawing Test as a predictor of cognitive decline in non-demented stroke patients.

BACKGROUND: The early detection of patients at risk of post-stroke cognitive impairment (PSCI) may help planning subacute and long-term care. We aimed to determine the predictivity of two screening cognitive tests on the occurrence of mild cognitive impairment or dementia in acute stroke patients. METHODS: A cognitive assessment within a few days of ischemic or hemorrhagic stroke was performed in patients consecutively admitted to a stroke unit over 14 months by means of the Clock Drawing Test (CDT) and the Montreal Cognitive Assessment-Basic (MoCA-B). RESULTS: Out of 191 stroke survivors who were non-demented at baseline, 168 attended at least one follow-up visit. At follow-up (mean duration ± SD 12.8 ± 8.7 months), 28 (18.9%) incident cases of MCI and 27 (18%) cases of dementia were recorded. In comparison with patients who remained cognitively stable at follow-up, these patients were older, less educated, had more comorbidities, a higher score on the National Institutes of Health Stroke Scale (NIHSS) at admission, more severe cerebral atrophy, and lower MoCA-B and CDT scores at baseline. In multi-adjusted (for age, education, comorbidities score, NIHSS at admission and atrophy score) model, a pathological score on baseline CDT (< 6.55) was associated with a higher risk of PSCI at follow-up (HR 2.022; 95% CI 1.025-3.989, p < 0.05) with respect to non-pathological scores. A pathological baseline score on MoCA-B (< 24) did not predict increased risk of cognitive decline at follow-up nor increased predictivity of stand-alone CDT. CONCLUSION: A bedside cognitive screening with the CDT helps identifying patients at higher risk of PSCI.

Multi-segment rupture of the 2016 Amatrice-Visso-Norcia seismic sequence (central Italy) constrained by the first high-quality catalog of Early Aftershocks.

We present the first high-quality catalog of early aftershocks of the three mainshocks of the 2016 central Italy Amatrice-Visso-Norcia normal faulting sequence. We located 10,574 manually picked aftershocks with a robust probabilistic, non-linear method achieving a significant improvement in the solution accuracy and magnitude completeness with respect to previous studies. Aftershock distribution and relocated mainshocks give insight into the complex architecture of major causative and subsidiary faults, thus providing crucial constraints on multi-segment rupture models. We document reactivation and kinematic inversion of a WNW-dipping listric structure, referable to the inherited Mts Sibillini Thrust (MST) that controlled segmentation of the causative normal faults. Spatial partitioning of aftershocks evidences that the MST lateral ramp had a dual control on rupture propagation, behaving as a barrier for the Amatrice and Visso mainshocks, and later as an asperity for the Norcia mainshock. We hypothesize that the Visso mainshock re-activated also the deep part of an optimally oriented preexisting thrust. Aftershock patterns reveal that the Amatrice Mw5.4 aftershock and the Norcia mainshock ruptured two distinct antithetic faults 3-4 km apart. Therefore, our results suggest to consider both the MST cross structure and the subsidiary antithetic fault in the finite-fault source modelling of the Norcia earthquake.

Brain plasticity and migraine transformation: fMRI evidences.

INTRODUCTION: Chronification transforms episodic migraine into the pathologic chronic form. Biological characteristics of the migrainous brain progressively change, in predisposed subjects, under the repetition of external and internal stimuli. Modifications involve neurons, synapses, neurotransmitters, receptors, connectivity and pain control. f-MRI is a promising way to explore the still unclear biology of this progression. Areas covered: Data included were obtained from the most relevant and updated works available on PubMed about this topic. We summarized the pathophysiology of migraine chronification and of brain plasticity, and we described the different fMRI techniques and their main evidences about migraine transformation. Expert commentary: Functional-MRI has revealed many aspects regarding the peculiarity of the migrainous brain and its tendency toward chronicity but a series of questions are still open: What are the hallmarks of the predisposition to chronification? Which elements are the cause and which the consequence of this process?

Feasibility and efficacy of minimally invasive stand-alone surgical ablation of atrial fibrillation. A single-center experience.

PURPOSE: Minimally invasive surgical ablation for atrial fibrillation (AF) has shown good results and low complications incidence. Our objective was to evaluate feasibility and efficacy of this technique in our center. METHODS: The procedure included pulmonary vein isolation, ganglionic plexi ablation, ligament of Marshall resection, and left atrial appendage exclusion through beating heart minimally invasive bilateral thoracotomies. Patients were monitored daily by telemedicine during the first 4 months and then by quarterly 24-h Holter monitoring or by implantable cardiac monitor. Ablation success was defined as freedom from any atrial tachyarrhythmia recurrence lasting more than 30 s and from antiarrhythmic drugs. All patients were followed up for a minimum of 12 months. RESULTS: Twenty-two consecutive patients with AF, paroxysmal in 27% and persistent in 73%, were treated. Mean age was 63 ± 10 years, 86% were men. Seventy-three percent of patients had previously undergone to one or more catheter ablations. Median follow-up period was 22 months (25°-75° percentile, 20-27). Patients free from any arrhythmia recurrence for at least 6 consecutive months discontinued antiarrhythmic therapy. Ablation was successful in 73% of patients at 12 months. Freedom from AF recurrences independently from antiarrhythmic therapy status was 91% at 12 months. Results were consistent in patients that reached 24 months follow-up. There were no deaths. Complications were: one conversion to sternotomy owing to thoracic adherences, one pacemaker implant, and one postoperative hemothorax requiring surgical revision. CONCLUSIONS: Our results show that minimally invasive surgical ablation was feasible and gave satisfactory results at long-term term follow-up in patients with AF.