Posterior Limb of Internal Capsule Infarct Predicts Functional Outcome in Acute Terminal Internal Carotid Artery Occlusion After Thrombectomy.

PURPOSES: This study investigated the impact of posterior limb of internal capsule (PLIC) infarct on outcomes of acute internal carotid artery (ICA) occlusion after endovascular thrombectomy (EVT) and the diagnostic accuracy of pretreatment noncontrast computerized tomography (NCCT) and computerized tomography angiography (CTA) findings. METHODS: Patients who underwent EVT for acute ICA occlusion between September 2014 and August 2020 were included in the study. The patients were dichotomized as PLIC infarct or spared. The risk factors for PLIC infarct were investigated, and the association between infarct patterns and clinical outcomes were assessed using logistic regression analysis. Pretreatment NCCT and CTA findings, including PLIC hypodensity, choroid plexus enhancement (CPE), and posterior cerebral artery (PCA) flow status, were calculated for diagnosis of PLIC infarct. RESULTS: Among 72 patients, the mean age was 70.9 years, and the mean stroke scale was 19.4. PLIC infarct was identified in 15 patients (20.8%). PLIC infarct was associated with worse 90-day functional outcome (P = 0.01, shift test). Lack of CPE is the only independent predictor of PLIC infarct (odds ratio: 127.48, P = 0.001). Lack of CPE and impaired PCA flow produce greater diagnostic accuracy for PLIC infarct than does NCCT hypodensity (area under the receiver operating characteristics curve: 0.85 and 0.76, P = 0.0005 and 0.02, respectively). CONCLUSIONS: In acute ICA occlusion, PLIC infarct is an independent risk factor for worse clinical outcome at 90 days. The lack of CPE was associated with PLIC infarct, and pretreatment CTA can be useful for early diagnosis.

Functional near-infrared-spectroscopy-based measurement of changes in cortical activity in macaques during post-infarct recovery of manual dexterity.

Because compensatory changes in brain activity underlie functional recovery after brain damage, monitoring of these changes will help to improve rehabilitation effectiveness. Functional near-infrared spectroscopy (fNIRS) has the potential to measure brain activity in freely moving subjects. We recently established a macaque model of internal capsule infarcts and an fNIRS system for use in the monkey brain. Here, we used these systems to study motor recovery in two macaques, for which focal infarcts of different sizes were induced in the posterior limb of the internal capsule. Immediately after the injection, flaccid paralysis was observed in the hand contralateral to the injected hemisphere. Thereafter, dexterous hand movements gradually recovered over months. After movement recovery, task-evoked hemodynamic responses increased in the ventral premotor cortex (PMv). The response in the PMv of the infarcted (i.e., ipsilesional) hemisphere increased in the monkey that had received less damage. In contrast, the PMv of the non-infarcted (contralesional) hemisphere was recruited in the monkey with more damage. A pharmacological inactivation experiment with muscimol suggested the involvement of these areas in dexterous hand movements during recovery. These results indicate that fNIRS can be used to evaluate brain activity changes crucial for functional recovery after brain damage.

The anterior one third of the posterior limb of the internal capsule is also supplied by the anterior choroidal artery.

PURPOSE: It is universally recognized that the anterior choroidal artery (AChA) supplies the posterior two-third of the posterior limb of internal capsule (PLIC). On the other hand, the blood supply to the anterior one third of the PLIC has remained undetermined. We posit the anterior one third of the PLIC is also supplied by the AChA referring the previous microsurgical descriptions. METHODS: Ninety consecutive patients with isolated acute infarction in the PLIC were studied. We classified patients into 4 groups. 1. The anterior type that involved the anterior one-third part of the PLIC. 2. The posterior type that involved the caudal two-third part of the PLIC, 3. The combined type that located in the full length of the PLIC, 4. The dot type that restricted within PLIC up to10mm in diameter. RESULTS: Patient numbers in groups 1 through 4 were 7 (7.7%), 46 (51.1%), 9 (10.6%) and 28 (31.1%). The anterior type involved the medial part of pallidum (MPP) in 5 patients (71.4%) and none in the lateral thalamus (LT), while the posterior type involved MPP only in 6 patients (13.0%) and LT in 33 patients (71.7%). CONCLUSION: Corresponding to previous microsurgical descriptions, an occlusion of the proximal branches may cause anterior type infarct and that of the distal branches may cause posterior type infarcts. The anterior one third of the PLIC is also supplied by the branches of the AChA, albeit the low prevalence.

Structural and functional reorganization following unilateral internal capsule infarction contribute to neurological function recovery.

PURPOSE: To investigate proliferative reorganization in the bilateral corticospinal tract (CST) and functional reorganization in the sensorimotor network (SMN) after internal capsule stroke, and to examine the significance of this reorganization. METHODS: We recruited 17 patients with first-onset acute stroke (16 male, 1 female, mean age 52 ± 10 years) and 17 age- and sex-matched healthy controls. We excluded patients aged < 18 or > 65 years and those with lesions outside the unilateral internal capsule. All subjects underwent diffusion tensor imaging and resting-state functional MRI on days 7, 30, and 90 from symptom onset. We measured fractional anisotropy (FA) in the CST, interhemispheric functional connectivity (FC) within the SMN, and pre-MRI clinical scores, including the National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI), and Fugl-Meyer (FM). Correlations among the changes in FA, FC, and clinical scores were analyzed. RESULTS: From day 7 to 90 after stroke, FA in the bilateral CST increased (ipsilesional side, Pinternal capsule = 0.009, Pcentrum semiovale = 0.001; contralesional side, Pinternal capsule = 0.006, Pcentrum semiovale = 0.017), as did FC (P < 0.05); NIHSS scores decreased (P < 0.05), while FM and BI progressively increased (P < 0.05). Increased FA in bilateral CST was negatively correlated with decreased NIHSS scores. Increased FA in only the ipsilesional side was positively correlated with increased FM. Increased FC was positively correlated only with increased BI. CONCLUSION: Proliferative reorganization in the CST and functional reorganization in the SMN support and promote neurological functional recovery after internal capsule infarction.

The dynamics of revascularization after white matter infarction monitored in Flt1-tdsRed and Flk1-GFP mice.

Subcortical white matter infarction causes ischemic demyelination and loss of brain functions, as the result of disturbances of the blood flow. Although angiogenesis is one of the recovery processes after cerebral infarction, the dynamics of revascularization after white matter infarction still remains unclear. We induced white matter infarction in the internal capsule of Flk1-GFP::Flt1-tdsRed double transgenic mice by injection of endothelin-1 (ET-1), a vasoconstrictor peptide, together with N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, and followed the changes in Flk1 and Flt1 expression in the vascular system in the infarct area. Reduction of Flt1-tdsRed-positive blood vessels 1 day after the injection and increase of Flk1-GFP-strongly-positive blood vessels 3 days after the injection were apparent. PDGFRß-strongly-positive (PDGFRß+) cells appeared in the infarct area 3 days after the injection and increased their number thereafter. Three days after the injection, most of these cells were in close contact with Flk1-GFP-positive endothelial cells, indicating these cells are bona fide pericytes. Seven days after the injection, the number of PDGFRß+ cells increased dramatically, and the vast majority of these cells were not in close contact with Flk1-GFP-positive endothelial cells. Taken together, our results suggest revascularization begins early after the ischemic insult, and the emerging pericytes first ensheath blood vessels and then produce fibroblast-like cells not directly associated with blood vessels.

Thalamic Diaschisis in Acute Ischemic Stroke: Occurrence, Perfusion Characteristics, and Impact on Outcome.

BACKGROUND AND PURPOSE: Ipsilateral thalamic diaschisis (ITD) describes the reduction of thalamic function, metabolism, and perfusion resulting from a distant lesion of the ipsilateral hemisphere. Our aim was to evaluate the perfusion characteristics and clinical impact of ITD in acute middle cerebral artery stroke, which does not directly affect the thalamus. METHODS: One hundred twenty-four patients with middle cerebral artery infarction were selected from a prospectively acquired cohort of 1644 patients who underwent multiparametric computed tomography (CT), including CT perfusion for suspected stroke. Two blinded readers evaluated the occurrence of ITD, defined as ipsilateral thalamic hypoperfusion present on ≥2 CT perfusion maps. Perfusion alterations were defined according to the Alberta Stroke Program Early CT Score regions. Final infarction volume and subacute complications were assessed on follow-up imaging. Clinical outcome was quantified using the modified Rankin Scale. Multivariable linear and ordinal logistic regression analysis were applied to identify independent associations. RESULTS: ITD was present in 25/124 subjects (20.2%, ITD+). In ITD+ subjects, perfusion of the caudate nucleus, internal capsule, and lentiform nucleus was more frequently affected than in ITD- patients (each with P<0.001). In the ITD+ group, larger cerebral blood flow (P=0.002) and cerebral blood volume (P<0.001) deficit volumes, as well as smaller cerebral blood flow-cerebral blood volume mismatch (P=0.021) were observed. There was no independent association of ITD with final infarction volume or clinical outcome at discharge in treatment subgroups (each with P>0.05). ITD had no influence on the development of subacute stroke complications. CONCLUSIONS: ITD in the form of thalamic hypoperfusion is a frequent CT perfusion finding in the acute phase in middle cerebral artery stroke patients with marked involvement of subcortical areas. ITD does not result in thalamic infarction and had no independent impact on patient outcome. Notably, ITD was misclassified as part of the ischemic core by automated software, which might affect patient selection in CT perfusion-based trials.

[A 70-year-old woman presenting with restless shoulder following posterior internal capsule infarction].

A 70-year-old woman noticed difficulty in speech and weakness of the left upper and lower limb upon awakening. Neurological examination showed dysarthria and left hemiparesis. No sensory disturbance was observed. Brain MRI revealed acute infarction in the right posterior limb of the internal capsule. On the hospital day 1, she developed the abnormal sensations restricted to the bilateral shoulders, resulting in difficulty initiating sleep. On laboratory data, renal function and serum hemoglobin and ferritin levels were normal. When four essential features of restless legs syndrome (RLS) were applied to her shoulders, the patient met RLS criteria. Following low dose pramipexole treatment, the abnormal sensation of the shoulders and insomnia significantly improved. We should be aware of the possibility of RLS or its variant, including "restless shoulder" of our patient, for the cause of insomnia following acute ischemic infarction.

The Posterior Limb of the Internal Capsule as the Subcortical Transitional Zone of the Anterior and Posterior Circulations: Insights from Human 7T MRI.

BACKGROUND: In patients with cerebral infarction, identifying the distribution of infarction and the relevant artery is essential for ascertaining the underlying vascular pathophysiological mechanisms and preventing subsequent stroke. However, visualization of the basal perforating arteries (BPAs) has had limited success, and simultaneous viewing of background anatomical structures has only rarely been attempted in living human brains. Our study aimed at identifying the BPAs with 7T MRI and evaluating their distribution in the subcortical structures, thereby showing the clinical significance of the technique. METHODS: Twenty healthy subjects and 1 patient with cerebral infarction involving the posterior limb of the internal capsule (ICpost) and thalamus underwent 3-dimensional fast spoiled gradient-echo sequence as time-of-flight magnetic resonance angiography (MRA) at 7T with a submillimeter resolution. The MRA was modified to detect inflow signals from BPAs, while preserving the background anatomical signals. BPA stems and branches in the subcortical structures and their origins were identified on images, using partial maximum intensity projection in 3 dimensions. RESULTS: A branch of the left posterior cerebral artery (PCA) in the patient ran through both the infarcted thalamus and ICpost and was clearly the relevant artery. In 40 intact hemispheres in healthy subjects, 571 stems and 1,421 branches of BPAs were detected in the subcortical structures. No significant differences in the numbers of stems and branches were observed between the intact hemispheres. The numbers deviated even less across subjects. The distribution analysis showed that the subcortical structures of the telencephalon, such as the caudate nucleus, anterior limb of the internal capsule, and lenticular nucleus, were predominantly supplied by BPAs from the anterior circulation. In contrast, the thalamus, belonging to the diencephalon, was mostly fed by BPAs from the posterior circulation. However, compared with other subcortical structures, the ICpost, which marks the anatomical boundary between the telencephalon and the diencephalon, was supplied by BPAs with significantly more diverse origins. These BPAs originated from the internal carotid artery (23.1%), middle cerebral artery (38.5%), PCA (17.3%), and the posterior communicating artery (21.1%). CONCLUSIONS: The modified MRI method allowed the detection of the relevant BPA within the infarcted area in the stroke survivor as well as the BPAs in the subcortical structures of living human brains. Based on in vivo BPA distribution analyses, the ICpost is the transitional zone of the anterior and posterior cerebral circulations.

Clinical significance of blood supply to the internal capsule and basal ganglia.

Although the general vascular supply of the basal ganglia and internal capsule is well known, precise data are lacking regarding the variations of the vascular territories in the two regions. Twelve hemispheres were studied following an injection of coloured ink into the main cerebral arteries, namely the anterior cerebral (ACA), middle cerebral (MCA), anterior choroidal (AChA) and posterior cerebral artery (PCA). Serial sections of the injected hemispheres were taken in the axial or coronal plane. In 75% of the hemispheres, ACA perforators were seen to supply the inferomedial part of the head of the caudate nucleus and the anterior limb of the internal capsule, as well as the anterior and inferior portions of the putamen and globus pallidus. The MCA vessels perfused the superolateral part of the head and body of the caudate nucleus, the superior part of the entire internal capsule, most of the putamen and part of the globus pallidus. The AChA perforators perfused the medial segment of the globus pallidus, the inferior part of the posterior limb, the retrolenticular and sublenticular portions of the internal capsule, and occasionally its genu. The same segment of the globus pallidus and the inferior part of the genu of the internal capsule were most likely supplied by the perforators of the internal carotid artery. A predominance of ACA territory was noticed in one specimen (8.33%) and a predominance of MCA territory in two specimens (16.67%). The obtained anatomical data may help radiologic determination of perforators involved in ischemic events, as well as a better understanding of the neurological deficits in the same events.

Pure dysarthria and dysarthria-facial paresis syndrome due to internal capsule and/or corona radiata infarction.

BACKGROUND: Pure dysarthria (PD) and dysarthria-facial paresis syndrome (DFP) mainly result from lenticulostriate artery territory infarction. PD and DFP are rare clinical entities, often grouped without distinction. The purpose of this study was to examine clinical and radiographic differences between PD and DFP due to unilateral internal capsule and/or corona radiata infarction. METHODS: Using a database that included consecutive patients with ischemic stroke admitted to the neurological stroke units of three hospitals within 7 days from onset between September 2011 and April 2014, we retrospectively extracted first-ever stroke patient data, who presented with PD or DFP with a single ischemic lesion localized in the internal capsule and/or corona radiata. Patients with weakness, ataxia, sensory deficit, or cortical symptoms were excluded. Ischemic lesion volume was calculated by the ABC/2 method on diffusion-weighted imaging (DWI). DWI images were normalized and superimposed to the template for PD and DFP. We compared patients' characteristics between PD and DFP. RESULTS: A total of 2126 patients, including 65 patients (3.1%) with PD or DFP, were registered. Of these, 13 PD patients and 18 patients with DFP due to unilateral internal capsule and/or corona radiata infarction were included for analysis. Compared with DFP patients, PD patients had longer onset-to-door time (median 37.5 vs. 10.8 h, p = 0.031), shorter vertical length (C component) of ischemic lesions (median 12.0 vs. 18.8 mm, p = 0.007), and smaller ischemic lesion volume (median 285 vs. 828 mm(3), p = 0.023). Ischemic lesions causing PD were located more frequently in the left hemisphere than DFP (92% vs. 56%, p = 0.045). The superimposed lesion pattern indicated that DFP had lesions more medial and involving posterior portions of the putamen and the caudate body, as well as more of the genu and posterior limb of the internal capsule, than PD. Ninety days after onset, symptoms disappeared in 21 (72%) out of 29 patients. CONCLUSIONS: In cerebral infarction limited to the internal capsule and/or corona radiata, PD is derived from smaller and left-sided lesions with delay in diagnosis compared with DFP. The clinical course of those with PD and DFP might be benign.

Internal capsule stroke in the common marmoset.

White matter (WM) impairment and motor deficit after stroke are directly related. However, WM injury mechanisms and their relation to motor disturbances are still poorly understood. In humans, the anterior choroidal artery (AChA) irrigates the internal capsule (IC), and stroke to this region can induce isolated motor impairment. The goal of this study was to analyze whether AChA occlusion can injure the IC in the marmoset monkey. The vascular distribution of the marmoset brain was examined by colored latex perfusion and revealed high resemblance to the human brain anatomy. Next, a new approach to electrocoagulate the AChA was developed and chronic experiments showed infarction compromising the IC on magnetic resonance imaging (MRI) scanning (day 4) and histology (day 11). Behavioral analysis was performed using a neurologic score previously developed and our own scoring method. Marmosets showed a decreased score that was still evident at day 10 after AChA electrocoagulation. We developed a new approach able to induce damage to the marmoset IC that may be useful for the detailed study of WM impairment and behavioral changes after stroke in the nonhuman primate.

Simultaneous occurrence of internal capsule infarct and cerebellar haemorrhage in a patient with hemiplegia.

A 68-year-old woman with hypertension with no history of cerebrovascular events presented with a left-sided hemiplegia which had developed acutely 2 days ago. She was not on maintenance therapy with antiplatelets or anticoagulants. A CT scan showed acute ischaemic infarction of the right internal capsule and cerebellar haemorrhage. Cardiac evaluation was normal. Doppler ultrasonography of the extracranial carotid and vertebral arteries showed diffuse arteriosclerotic changes, but did not reveal any haemodynamic occlusion. The simultaneous development of dual strokes was considered to be an extension of the same arteriosclerotic process to the intracranial carotid and basilar arteries.

Anatomical location of the frontopontine fibers in the internal capsule in the human brain: a diffusion tensor tractography study.

The frontopontine fibers (FPFs) originate from the frontal lobe and end in the pontine nuclei. Many neuroanatomy textbooks have described the FPFs as descending through the anterior limb of the internal capsule. However, several studies have reported controversial results. In this study, using diffusion tensor tractography, we investigated the anatomical location of the FPFs in the internal capsule in the human brain. We recruited 53 healthy volunteers for this study. For reconstruction of the FPFs, the seed region of interest was given in the medial cerebral peduncle of the reconstructed corticospinal tract. The target regions of interest were placed in the three cerebral cortices, respectively: Brodmann's area (BA) BA 6, BA 8, and BA 9. The anatomical locations of the FPFs were evaluated using the highest probabilistic location in the internal capsule. We measured the relative distance of the FPFs from the middle point at the genu of the internal capsule to the most posterior point of the lenticular nucleus. The relative mean distances of the highest probabilistic location for the FPFs from BA 9, 8, and 6 were 18.18, 32.08, and 43.83% from the middle point of the genu of the internal capsule, respectively. By contrast, the highest probabilistic location for the corticospinal tract was 74.18%. According to our findings, the FPFs were located at the anterior half of the posterior limb in the internal capsule, in the following order, from the anterior direction: the FPFs from BA 9, BA 8, and BA 6.

Anterior choroidal artery territory infarction: lesions confined to versus beyond the internal capsule.

BACKGROUND: Studies investigating the clinical features and stroke mechanisms of anterior choroidal artery (AchA) infarction have reported inconsistent results. This may be partly due to different degrees of inclusion of patients with isolated posterior limb of the internal capsule (PLIC) lesions, which may be supplied by lenticulostriate arteries rather than AchA. The purpose of this study was to investigate clinical features and stroke mechanisms of AchA infarction, with particular attention to the above problem. METHODS: We evaluated patients with AchA infarction assessed with diffusion-weighted imaging and magnetic resonance angiography, who were admitted to the Asan Medical Center from July 2001 to April 2011. Probable AchA (pAchA) infarction was diagnosed when the lesions were confined to the lower part of the PLIC, while definite AchA (dAchA) infarction was diagnosed when the lateral geniculate body, the uncus, or the cerebral peduncle were concomitantly involved. We assessed imaging findings, stroke mechanisms, and clinical features, and investigated the differences between patients with dAchA infarction and those with pAchA infarction. RESULTS: We identified 127 patients with AchA infarction: 34 with dAchA infarctions, 90 with pAchA infarctions, and 3 without PLIC lesions. The most important stroke mechanism was small artery disease (SAD), followed by large artery disease (LAD). In patients with LAD, distal internal carotid artery (ICA) disease was a relatively important cause of stroke. The dAchA group, as compared with the pAchA group, was more frequently related to cardioembolism (12 vs. 2%, p = 0.03), distal ICA steno-occlusion (35 vs. 2%, p = 0.001), severe neurologic deficits (higher National Institute of Health Stroke Scale scores and more severe limb weakness), and less often associated with SAD (56 vs. 78%, p = 0.02). CONCLUSION: In general, SAD was the most important stroke mechanism for AchA infarction followed by LAD. However, dAchA infarction and pAchA infarction differ in that the former was more often associated with cardioembolism, distal ICA steno-occlusion, a worse clinical status and less often associated with SAD than the latter. The different proportion of patients with pure PLIC lesions included in previous studies may have led to inconsistent and confusing results, which should be considered to gain a proper understanding of AchA infarction.

Combined antithrombotic treatment with aspirin and clopidogrel for patients with capsular warning syndrome: a case report.

Capsular warning syndrome is characterized by recurrent transient ischemic attacks and is caused by microthrombosis or hypoperfusion of small-sized vessels. The pathophysiological basis of this syndrome is not well understood and currently a consensus has not been reached on its optimal treatment. In this study, we present 2 cases with favorable clinical outcomes after combined antithrombotic treatment with loading doses of clopidogrel and aspirin.

Arterial vascularisation of the anterior perforated substance.

INTRODUCTION: The arteries of the anterior perforated substance (APS) are important due to their role in supplying blood to important internal structures such as the internal capsule, putamen and caudate nucleus. The purpose of this study was to investigate in detail the arteries of the APS. METHODS: The arteries of the APS were investigated in 60 cerebral hemispheres from 30 adult cadaveric brains. The internal carotid arteries were cannulated and perfused with coloured latex. The branches of the middle cerebral artery (MCA) penetrating the APS were investigated. These arteries, known as the lateral lenticulostriate arteries and originating from the M1 segment, early temporal and early frontal branches of the MCA, were recorded. RESULTS: The branches of the anterior choroidal artery, which reached the APS, were seen in all specimens. We found one to three branches that arose from the A2 segment of the anterior cerebral artery (ACA) to the APS in all hemispheres, and one to three branches that originated from the A1 segment of the ACA in 48 hemispheres. In addition, two accessory MCAs that originated from the A2 segment of the ACA were recorded as variations, and perforating branches to the APS were observed. CONCLUSION: Serious complications like motor deficits can occur as a result of injury to the arteries of the APS. Hence, neurosurgeons performing operations such as aneurysm or insular tumour surgeries must be aware of the importance of preserving these arteries.

Brain MRI findings in patients with Fabry disease.

BACKGROUND: To evaluate the presence of ischemic and hemorrhagic lesions in brain MRI of patients with Fabry disease (FD). METHODS: Brain MRI studies in 46 consecutive patients were evaluated using classic sequences as well as GRE-weighted images, for ischemic lesions and chronic microbleed detection. Of the 36 adult patients (15 males, mean age 31.2 years; 21 females, mean age 41.6 years). All had signs or symptoms of FD but lacked history of stroke or TIA. RESULTS: Ten patients under 20 years of age initially presented a normal MRI. One child developed a hyperintense occipital lesion on T2-weighted imaging during control MRI. Sixteen adult patients (44.4%) had brain MRI evidence of small vessel disease in the basal ganglia, corona radiata, thalamus or brainstem, as well as in the periventricular white matter. Patients with MRI abnormalities were older (45.6 vs 30.9 years, p=0.005), with more vascular risk factors (1.2 vs 0.6 p=0.043). Three women (mean age 59.5 years) presented deep chronic microbleeds identified by GRE. Moreover, Flair and T2-weighted images revealed white matter disease and deep gray matter involvement. CONCLUSION: 44.4% of adult patients with FD without clinical history of CVA or prior dialysis had evidence of small vessel disease on MRI and 11% showed cerebral microbleeds. FD is a treatable disorder that should be routinely included in the differential diagnosis of ischemic and microhemorrhagic lesions in young adults.