Early argatroban and antiplatelet combination therapy in acute non-lacunar single subcortical infarct associated with mild intracranial atherosclerosis

Background Patients with acute non-lacunar single subcortical infarct (SSI) associated with mild intracranial atherosclerosis (ICAS) have a relatively high incidence of early neurological deterioration (END), resulting in unfavorable functional outcomes. Whether the early administration of argatroban and aspirin or clopidogrel within 6–12 h after symptom onset is effective and safe in these patients is unknown. Methods A review of the stroke database of Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University and Qingdao Center Hospital, Qingdao University Medical College in China was undertaken from May 2017 to January 2020 to identify all patients with non-lacunar SSI caused by ICAS within 6–12 h of symptom onset based on MRI screening. Patients were divided into two groups, one comprising those who received argatroban and mono antiplatelet therapy with aspirin or clopidogrel on admission (argatroban group), and the other those who received dual antiplatelet therapy (DAPT) with aspirin and clopidogrel during hospitalization (DAPT group). The primary outcome was recovery by 90 days after stroke based on a modified Rankin scale (mRS) score (0 to 1). The secondary outcome was END incidence within 120 h of admission. Safety outcomes were intracranial hemorrhage (ICH) and major extracranial bleeding. The probability of clinical benefit (mRS score 0–1 at 90 days) was estimated using multivariable logistic regression analysis. Results A total of 304 acute non-lacunar SSI associated with mild ICAS patients were analyzed. At 90 days, 101 (74.2%) patients in the argatroban group and 80 (47.6%) in the DAPT group had an mRS score that improved from 0 to 1 (P < 0.001). The relative risk (95% credible interval) for an mRS score improving from 0 to 1 in the argatroban group was 1.50 (1.05–2.70). END occurred in 10 (7.3%) patients in the argatroban group compared with 37 (22.0%) in the DAPT group (P < 0.001). No patients experienced symptomatic hemorrhagic transformation. Conclusions Early combined administration of argatroban and an antiplatelet agent (aspirin or clopidogrel) may be beneficial for patients with non-lacunar SSI associated with mild ICAS identified by MRI screening and may attenuate progressive neurological deficits. Trial registration Our study is a retrospectively registered trial.

Total Magnetic Resonance Imaging of Cerebral Small Vessel Disease Burden Predicts Dysphagia in Patients with a Single Recent Small Subcortical Infarct

Background The study was performed to identify the association between total magnetic resonance imaging burden of small vessel disease and occurrence of post-stroke dysphagia in patients with a single recent small subcortical infarct. Methods All patients with a magnetic resonance imaging-confirmed single recent small subcortical infarct underwent the water-swallowing test and volume-viscosity swallow test within the first 24 hours following admission to assess swallowing. Demographic and clinical data were extracted from our stroke database. Based on brain magnetic resonance imaging, we independently rated the presence of cerebral microbleeds, lacunes, white matter hyperintensities and enlarged perivascular spaces. The presence of each small vessel disease feature was summed in the total small vessel disease burden, ranging from 0–4. Results In total, 308 patients with a single recent small subcortical infarct were enrolled. Overall, 54 (17.5%) were diagnosed with post-stroke dysphagia. The risk factors related to post-stroke dysphagia included the following: older age, National Institute of Health Stroke Scale, higher C-reactive protein levels and higher fibrinogen levels. Based on multiple logistic regression, two variables with the most significant associations, namely, National Institute of Health Stroke Scale and total small vessel disease burden, were combined with age, gender, history of hypertension, C-reactive protein level and fibrinogen level. Conclusions Dysphagia in patients with a single recent small subcortical infarct resulted from severe small vascular disease, which was associated with systemic inflammation. This information might provide a new anti-inflammatory treatment for post-stroke dysphagia in the future.

Macula Structure and Microvascular Changes in Recent Small Subcortical Infarct Patients

Purpose: This study aimed to assess the macula structure and capillaries in the macula and optic nerve head in recent small subcortical infarct (RSSI) patients.Methods: This observational cross-sectional study included 40 RSSI patients and 46 healthy controls. Optical coherence tomography angiography was used to image the capillaries in the macula and optic nerve head. An inbuilt algorithm was used to measure the densities in the microvasculature of the macula [superficial retinal capillary plexus (SRCP) and deep retinal capillary plexus (DRCP)] and optic nerve head [radial peripapillary capillary (RPC)] and thickness around the optic nerve head, peripapillary retinal nerve fiber layer (pRNFL).Results: Densities in RPC (P &lt; 0.001), SRCP (P = 0.001), and DRCP (P = 0.003) were reduced in RSSI patients when compared with healthy controls. The pRNFL thickness was thinner (P &lt; 0.001) in RSSI patients than healthy controls. In the RSSI group, the SRCP density significantly correlated with the DRCP density (rho = 0.381, P = 0.042). The pRNFL thickness displayed a significant relationship with the RPC density (rho = 0.482, P = 0.003) in the RSSI group.Conclusions: RSSI patients showed interrupted capillary plexuses leading to its significant impairment and neurodegeneration. Our report provides insight into the macula capillary microcirculation changes in RSSI.

A-174 Language Impairments Following Subcortical Infarct: An Aphasia Case Study

Objective Subcortical aphasia associated with internal capsule and adjacent structure lesions often involve impaired naming, grammatical but slow dysarthric speech, impaired syntactic comprehension, repetition impairments, and apraxia. Furthermore, neuropsychiatric disturbances, such as diminished motivation and emotional dysregulation are additionally expected given connections to frontal lobe circuits. Overall, the type and severity of aphasia varies following subcortical stroke and the pattern of symptoms associated with subcortical aphasia have not been fully explored. Method The present case is a 34-year-old right-handed African-American female who sustained an acute infarct involving the left splenium, thalamus, and internal capsule, who was evaluated at bedside. Results Upon initial exam, the patient was aphasic, exhibiting difficulties with expression, fluctuating comprehension and frequent paraphasic errors. Repetition and single-step command following were impaired and apraxia was evident. She demonstrated poor insight and awareness into her current deficits. She additionally demonstrated low motivation and mild emotional dysregulation with heightened anxiety and depression. During recovery she demonstrated improved comprehension, verbal output, and reduced emotionality. Conclusions Consistent with previous studies, this case demonstrates the extreme variability of subcortical lesions in their aphasic manifestations and may suggest that subcortical aphasias are generally milder than that of cortical aphasias with generally faster symptom recovery.

Selective atrophy of the connected deepest cortical layers following small subcortical infarct

ObjectiveTo explore whether in patients with chronic small subcortical infarct the cortical layers of the connected cortex are differentially affected and whether these differences correlate with clinical symptomatology.MethodsTwenty patients with a history of chronic small subcortical infarct affecting the corticospinal tracts and 15 healthy controls were included. Connected primary motor cortex was identified with tractography starting from infarct. T1-component probability maps were calculated from T1 relaxation 3T MRI, dividing the cortex into 5 laminar gaussian classes.ResultsFocal cortical thinning was observed in the connected cortex and specifically only in its deepest laminar class compared to the nonaffected mirrored cortex (p < 0.001). There was loss of microstructural integrity of the affected corticospinal tract with increased mean diffusivity and decreased fractional anisotropy compared to the contralateral nonaffected tract (p ≤ 0.002). Clinical scores were correlated with microstructural damage of the corticospinal tracts and with thinning of the cortex and specifically only its deepest laminar class (p < 0.001). No differences were found in the laminar thickness pattern of the bilateral primary motor cortices or in the microstructural integrity of the bilateral corticospinal tracts in the healthy controls.ConclusionOur results support the concept of secondary neurodegeneration of connected primary motor cortex after a small subcortical infarct affecting the corticospinal tract, with observations that the main cortical thinning occurs in the deepest cortex and that the clinical symptomatology is correlated with this cortical atrophy pattern. Our findings may contribute to a better understanding of structural reorganization and functional outcomes after stroke.

CADASIL syndrome (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) presenting as psychosis

Cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) is the most common monogenic form of cerebral small-vessel disease characterised by recurrent strokes. Behavioural disturbance also presents in a significant proportion of subjects as neurotic spectrum disorders and psychotic features are rarely reported. In this case report, we highlight a 32-year-old man with CADASIL syndrome, who had overt psychotic symptoms with neurological signs later on.

Dysphagia in supratentorial recent small subcortical infarcts results from bilateral pyramidal tract damage

Background Dysphagia occurs in up to 20% of patients with a recent small subcortical infarct, even when excluding brainstem infarcts. Aim To examine the impact of lesion topography and concomitant cerebrovascular lesions on the occurrence of dysphagia in patients with a single supratentorial recent small subcortical infarct. Methods We retrospectively identified all inpatients with magnetic resonance imaging-confirmed supratentorial recent small subcortical infarcts over a five-year period. Dysphagia was determined by speech-language therapists. Recent small subcortical infarcts were compiled into a standard brain model and compared using lesion probability maps. Furthermore, magnetic resonance imaging scans were reviewed for the combination of both acute and old cerebrovascular lesions. Results A total of 243 patients with a recent small subcortical infarct were identified (mean age 67.9 ± 12.2 years). Of those, 29 had mild and 18 moderate-to-severe dysphagia. Lesion probability maps suggested no recent small subcortical infarct location favoring the occurrence of moderate-to-severe dysphagia. However, patients with moderate-to-severe dysphagia more frequently showed combined damage to both pyramidal tracts by the recent small subcortical infarct and a contralateral old lesion (lacune: 77.8% vs. 19.9%, p < 0.001; lacune or confluent white matter hyperintensities: 100% vs. 57.7%, p < 0.001) than patients without swallowing dysfunction. Comparable results were obtained when analyzing patients with any degree of dysphagia. Conclusions Preexisting contralateral vascular pyramidal tract lesions are closely related to the occurrence of moderate-to-severe dysphagia in patients with supratentorial recent small subcortical infarcts.

Cerebral perfusion and compensatory blood supply in patients with recent small subcortical infarcts

Hypoperfusion is the typical perfusion pattern associated with recent small subcortical infarcts of the brain, but other perfusion patterns may be present in patients with these infarcts. Using CT perfusion, we studied 67 consecutive patients who had a small subcortical infarct at a follow-up MRI study to investigate the correlation between the perfusion pattern and the clinical and radiological course. On CT perfusion map analysis, 51 patients (76%) had focal hypoperfusion, 4 patients (6%) had hyperperfusion and the remaining 12 patients (18%) showed no abnormalities. On dynamic sequential imaging analysis obtained from the source perfusion images, 32 patients (48%) had a sustained hypoperfusion pattern, 11 patients (16%) had a reperfusion pattern, and 18 patients (27%) had a delayed compensation pattern. Systolic blood pressure was higher in patients with sustained hypoperfusion although the perfusion pattern was independent of the final volume of infarction. These results reinforce the notion that mechanisms other than hypoperfusion are at play in patients with small subcortical infarcts including the intervention of compensatory sources of blood flow. The ultimate clinical significance of these perfusion patterns remains to be determined in larger series of patients assessed longitudinally.