Prolonged platelet hyperactivity after COVID-19 infection.

Platelet hyperactivity often occurs in patients with coronavirus disease 2019 (COVID-19). However, it remains unclear how long platelet hyperactivity lasts after the acute phase, owing to a lack of follow-up studies. To elucidate the course of platelet hyperactivity, we serially measured platelet activity in patients with COVID-19 up to 40 days after hospital admission using an easily assessable haematology analyser that semi-quantitates platelet clumps on a scattergram. Our results showed that platelet hyperactivity persisted for at least 40 days even after acute inflammation subsided in most patients with COVID-19, regardless of disease severity. Persistent platelet hyperactivity may contribute to thromboembolic complications in post-COVID-19 patients.

Complete nanopore repeat sequencing of SCA27B (GAA-FGF14 ataxia) in Japanese.

BACKGROUND: Although pure GAA expansion is considered pathogenic in SCA27B, non-GAA repeat motif is mostly mixed into longer repeat sequences. This study aimed to unravel the complete sequencing of FGF14 repeat expansion to elucidate its repeat motifs and pathogenicity. METHODS: We screened FGF14 repeat expansion in a Japanese cohort of 460 molecularly undiagnosed adult-onset cerebellar ataxia patients and 1022 controls, together with 92 non-Japanese controls, and performed nanopore sequencing of FGF14 repeat expansion. RESULTS: In the Japanese population, the GCA motif was predominantly observed as the non-GAA motif, whereas the GGA motif was frequently detected in non-Japanese controls. The 5'-common flanking variant was observed in all Japanese GAA repeat alleles within normal length, demonstrating its meiotic stability against repeat expansion. In both patients and controls, pure GAA repeat was up to 400 units in length, whereas non-pathogenic GAA-GCA repeat was larger, up to 900 units, but they evolved from different haplotypes, as rs534066520, located just upstream of the repeat sequence, completely discriminated them. Both (GAA)≥250 and (GAA)≥200 were enriched in patients, whereas (GAA-GCA)≥200 was similarly observed in patients and controls, suggesting the pathogenic threshold of (GAA)≥200 for cerebellar ataxia. We identified 14 patients with SCA27B (3.0%), but their single-nucleotide polymorphism genotype indicated different founder alleles between Japanese and Caucasians. The low prevalence of SCA27B in Japanese may be due to the lower allele frequency of (GAA)≥250 in the Japanese population than in Caucasians (0.15% vs 0.32%-1.26%). CONCLUSIONS: FGF14 repeat expansion has unique features of pathogenicity and allelic origin, as revealed by a single ethnic study.

Cerebral foreign body granulomas after mechanical thrombectomy: Two case reports and a review of the literature.

OBJECTIVES: A foreign body granuloma after an endovascular intervention is a rare complication. Some cases of foreign body granulomas, especially after coil embolization, have been reported. However, only four cases of foreign body granulomas after mechanical thrombectomy (MT) have previously been reported. The current study reports two cases of post-MT foreign body granulomas, including a biopsy-proven case. MATERIAL AND METHODS: Case 1: A 73-year-old woman presented with complete occlusion of the right middle cerebral artery. Cerebral angiography and MT were successfully performed with improvement in clinical symptoms. Left hemiparesis and a disturbance in attention appeared after discharge and progressed slowly. She was re-admitted to our hospital 120 days after cerebral infarction owing to foreign body granulomas diagnosed on biopsy. Case 2: A 78-year-old man presented with occlusion of the left cervical internal carotid artery and the left middle cerebral artery. Cerebral angiography, percutaneous transluminal angioplasty, and MT were successfully performed. On the 34th day, he experienced progressive consciousness disorder because of foreign body granulomas. Both cases were successfully treated with steroid therapy. RESULTS: MRI after steroid treatment showed the disappearance of most nodular lesions and improvement of the encephalopathy. CONCLUSIONS: The cause of the granuloma may be an allergic reaction to the hydrophilic polymers that peel from endovascular devices. Steroid therapy is an effective treatment; therefore, neurologists should consider this complication when neurological symptoms or signs on image appears or worsens. A reliable diagnosis is important for prompt treatment.

[Hypoglycemia].

Hypoglycemia may lead to acute hemiplegia. The most common diffusion-weighted MRI finding in patients with hypoglycemic hemiplegia is a hyperintense internal capsule lesion, which mimics acute ischemic stroke. In addition to the internal capsule lesion, various MRI findings have been reported in patients with hypoglycemia(including hyperintense lesions in the cerebral cortex, basal ganglia, subcortical white matter, and splenium of the corpus callosum). It has recently been reported that hypoglycemic brain damage starts in the large white matter tracts, such as the internal capsule, and spreads to the entire brain, including the gray matter. However, the mechanism underlying the development of focal signs, such as hemiplegia in metabolic disorders, which affects the entire brain, remains unclear.

Pitfall of Light Transmission Aggregometry-Based Assessment of Platelet Function in Acute Ischemic Stroke Patients.

BACKGROUND: The utility of light transmission aggregometry (LTA)-based assessment of platelet function in acute ischemic stroke patients remains controversial. This study aimed to clarify why LTA failed to estimate platelet function in acute ischemic stroke patients. METHODS: Using LTA, we evaluated the platelet aggregation abilities of citrated blood samples from 22 acute noncardiogenic ischemic stroke patients prior to treatment and compared them with those of 65 heathy volunteer controls. Platelet counts and mean platelet volumes (MPV) of citrated blood and platelet-rich plasma (PRP) prepared for LTA were evaluated simultaneously. Using a hematology analyzer, we also measured and compared the aggregation-prone properties of platelets in the hematology analysis process between patient and control samples. RESULTS: Although platelets aggregated more easily and frequently in patient samples (P < .01), the maximum aggregation rate (MA%) of LTA was paradoxically lower in patients than in controls (P < .05). The PRP/citrated blood ratio of platelet counts and MPV were significantly lower in patients than in controls (P < .05). CONCLUSIONS: Our results suggest that MA% of LTA is erroneously displayed as lower values than the actual status in patients with increased platelet aggregation ability such as acute ischemic stroke because activated large platelets are preaggregated and thus decreased in the PRP on LTA.

Influence of Platelet Aggregate Formation in Blood Samples on Light Transmission Aggregometry Results.

BACKGROUND: Light transmission aggregometry is a standard method used to evaluate platelet function. However, in clinical settings, light transmission aggregometry results sometimes fail to reflect actual platelet hyperactivity. In patients with suspected platelet hyperactivity such as thrombosis, platelet aggregates are frequently detected in citrated blood samples using a scattergram of a hematology analyzer. This study aimed to evaluate the effects of platelet aggregate formation on light transmission aggregometry results. METHODS: We used 19 citrated blood samples in which platelet aggregate formation was intentionally induced by a hematology analysis process. Employing fully automated light transmission aggregometry and agonists including adenosine diphosphate or collagen, light transmission aggregometry maximum aggregation percentage, platelet count, and mean platelet volume of platelet-rich plasma before and after platelet aggregate formation were evaluated. RESULTS: Light transmission aggregometry maximum aggregation percentage with adenosine diphosphate or collagen was significantly lower in the samples after than before platelet aggregate formation. Platelet count and mean platelet volume were both decreased by platelet aggregate formation (P < .01), suggesting that maximum aggregation percentage reduction was caused by the decrease in activated large platelets in the platelet-rich plasma. CONCLUSION: This study clarified that platelet aggregate formation in blood samples interfered with an accurate assessment of platelet hyperactivity. To ensure reliability of light transmission aggregometry results, we must confirm that platelet aggregates have not formed in the sample, especially in those of patients with platelet hyperactivity.

Anomalous anastomosis between the external carotid artery and vertebrobasilar artery via the hypoglossal canal: a case report and review of literature.

We report a case of an anomalous anastomosis formed between the external carotid artery (ECA) and the vertebrobasilar artery (VBA) and passing through the hypoglossal canal. A carotid-vertebrobasilar anastomosis of this kind is typically considered a variant of persistent primitive hypoglossal artery which usually originates from the internal carotid artery. However, the anastomotic vessel in this case had a common trunk with the occipital artery (OA), a remnant of the primitive proatlantal artery. The proximal and distal parts of the anastomotic vessel seemed to have been derived from the primitive proatlantal artery and the primitive hypoglossal artery, respectively. Thus, we propose that this ECA-VBA anastomosis, which passed through the hypoglossal canal and had a common trunk with the OA, be referred to as a dilated primitive hypoglossal-proatlantal anastomosis; that is, a dilated ascending pharyngeal artery rather than a variant of persistent primitive hypoglossal artery.

Adduction-Abduction Asymmetry in Saccades During Video-Oculographic Monocular Recording: A Word of Caution.

In eye movement examination, video-oculographic monocular recording has become more popular than electro-oculographic binocular recording. The aim of this study was to examine the characteristics of monocular movements recorded using video-oculography. In 66 healthy subjects, the horizontal saccades and smooth pursuit eye movements of the right eye within a range of 30º were evaluated using a video-oculographic eye movement recording system. Saccade latency, velocity, accuracy, and smooth pursuit gain were measured and analysed by age and direction. Saccade parameters (latency, velocity, and amplitude) and smooth pursuit gain deteriorated with age in healthy subjects. Saccade velocity and accuracy were significantly larger during adduction than during abduction. The smooth pursuit gain did not differ between adduction and abduction. In conclusion, unlike smooth pursuit eye movements, saccadic eye movements have adduction-abduction asymmetry. In video-oculographic monocular recording of saccades, it is necessary to recognise the possibility of the existence of adduction-abduction asymmetry.

D-Dimer versus International Normalized Ratio of Prothrombin Time in Ischemic Stroke Patients Treated with Sufficient Warfarin.

BACKGROUND: In patients receiving chronic warfarin therapy, the international normalized ratio of prothrombin time (PT-INR) reportedly correlates with the incidence, size, severity, and outcome of ischemic stroke, and thus there are guidelines for the optimal PT-INR range that is to be maintained during secondary or primary prevention of ischemic stroke. However, the details of ischemic stroke in patients in whom an optimal PT-INR is maintained by warfarin therapy have not been thoroughly investigated. We conducted a retrospective study to determine the predictors of the size, severity, and outcome of ischemic stroke occurring in patients under chronic warfarin therapy and maintenance of an optimum PT-INR. METHODS: The study group comprised 22 consecutive acute ischemic stroke patients who were receiving warfarin and whose PT-INR was within the optimal range on admission. The PT-INR and plasma D-dimer level of these patients on admission were analyzed in relation to infarction volume, National Institutes of Health Stroke Scale score on admission, and modified Rankin Scale score at discharge. RESULTS: PT-INR did not correlate with infarction volume, severity, or outcome. The D-dimer level correlated positively and significantly with the volume (r = .49, P < .05), severity (r = .54, P < .05), and outcome of ischemic stroke (r = .61, P < .01) and did not correlate with the PT-INR (r = -.27, P = .23). CONCLUSIONS: When the PT-INR is within optimal range in patients receiving chronic warfarin therapy but who suffer an ischemic stroke, the admission D-dimer level, but not PT-INR, correlates with the size, severity, and outcome of the stroke. Thus, monitoring the D-dimer level in patients receiving long-term warfarin therapy is important, regardless of whether the optimal PT-INR is maintained.

The mechanism of ipsilateral ataxia in lacunar hemiparesis: SPECT perfusion imaging.

BACKGROUND AND PURPOSE: Although ataxic hemiparesis is a common lacunar syndrome, the precise mechanism underlying hemiataxia is not clear. We attempted to identify ataxia-related, cerebral blood flow changes in patients presenting with ataxic hemiparesis after acute capsular infarct. METHODS: We used 99mTc-ECD brain perfusion single-photon emission computed tomography to evaluate regional cerebral blood flow in 12 patients with ataxic hemiparesis caused by capsular infarct, and we compared the regional blood flow of these patients with that of 11 patients with pure motor hemiparesis caused by similar lesions. RESULTS: The ipsilateral red nucleus blood flow was significantly decreased in the ataxic hemiparesis patients, whereas the ipsilateral red nucleus blood flow was increased in the pure motor hemiparesis patients. Crossed cerebellar diaschisis (decreased contralateral cerebellar blood flow) was seen in ataxic hemiparesis patients; similarly, it was seen in pure motor hemiparesis patients. CONCLUSIONS: Our findings suggest that ataxia in hemiparetic patients with capsular infarct can be caused by ipsilateral red nucleus dysfunction secondary to cortico-rubral pathway disruption at the internal capsule.

Hemichorea in a thymoma patient without anti-CRMP-5 antibody.

We reported a 72-year-old man with thymoma who presented with hemichorea. Although his brain CT and MRI revealed no abnormality, regional cerebral blood flow changes, identified by single photon emission computed tomography, suggested that the mechanism underlying the chorea seemed to be a dysfunction of the subthalamic nucleus and pallidum. His hemichorea was completely resolved after thymectomy. Absence of serum anti-neural autoantibodies, including small-cell lung carcinoma-related chorea anti-CRMP-5 antibody, suggests that mechanisms different from cross-talk neural-targeted tumor immune response can be responsible for the thymoma-associated paraneoplastic chorea.

Coaxial Method of PTA Balloon and Aspiration catheter using the delivery wire of a stent retriever for tandem occlusion: CoMBAt tandem occlusion.

PURPOSE: Tandem occlusion, in which the intracranial artery is obstructed along with proximal carotid occlusive or stenotic lesions, occurs in 10-15% of patients with large vessel occlusion. Our study introduces a novel technique for tandem occlusion treatment that involves the simultaneous coaxial deployment of a percutaneous transluminal angioplasty balloon and aspiration catheters with the delivery wire of a stent retriever. After percutaneous transluminal angioplasty of the carotid lesion with a thin balloon catheter, the aspiration catheter was advanced over the balloon to eliminate the ledge between the catheter tip and delivery wire. After balloon removal, intracranial thrombectomy was performed using an aspiration catheter and stent retriever. This study aimed to evaluate the safety and efficacy of this approach. MATERIALS AND METHODS: Medical records of patients with acute stroke due to tandem occlusion treated using our technique were analyzed for its effectiveness and safety. The puncture-to-recanalization time, modified thrombolysis in cerebral infarction (mTICI) grade, functional prognosis and incidence of hyperperfusion were assessed. RESULTS: Seven patients were included in this study. In all patients, mTICI 2b-3 recanalization was achieved after smooth delivery of the aspiration catheter from the carotid lesion to the intracranial thrombus. The median puncture-to-recanalization time was 52 min. Ninety days post-stroke onset, six of seven patients had a modified Rankin Scale score of 0-2, and none of the patients had perioperative hyperperfusion syndrome. CONCLUSION: Our technique allows simultaneous treatment of carotid and intracranial lesions, leading to faster recanalization. Furthermore, percutaneous transluminal angioplasty with a thin balloon may reduce the risk of hyperperfusion.

Pseudo-subarachnoid hemorrhage in cryptococcal meningitis: MRI findings and pathological study.

A pseudo-subarachnoid hemorrhage (pseudo-SAH) is a brain computed tomography (CT) finding that is seen as high-density areas along the basal cisterns, the sylvian vallecula/fissure, the tentorium cerebella, or the cortical sulci, although no SAH is found upon lumbar puncture or at autopsy. There is one report of cryptococcal meningitis presenting as pseudo-SAH, but the explanatory pathology is unknown. A 68-year-old woman with headache, fever, decreased hearing, and decreased vision was admitted to our hospital. Cerebrospinal fluid India ink staining was positive, and culture yielded Cryptococcus neoformans. Cryptococcus meningitis was diagnosed. Head CT and magnetic resonance imaging (MRI) showed no abnormality upon admission, but 1 month later, head CT showed iso- to high-density areas within the sulci, and fluid-attenuated inversion recovery MRI showed high signal intensity within the convexity sulci resembling an SAH. These areas were enhanced by gadolinium on T1-weighted images. Lumber puncture produced no evidence of bleeding. Biopsy of the left frontal lobe sulci was performed, and histopathological study revealed inflammation and granulation with capsules of C. neoformans. The inflammation and granulation at the convexity sulci induced by the C. neoformans infection explained the pseudo-SAH in this case. Physicians should be aware that cryptococcal meningitis-induced inflammation and granulation at the sulci can present as pseudo-SAH on CT and MRI.

Visual suppression of vestibulo-ocular reflex in patients treated with carotid artery revascularization: A potential biomarker for cerebral perfusion.

BACKGROUND: Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are common treatments for ischemic stroke prevention in patients with carotid artery stenosis. However, the beneficial effects of CEA/CAS for cerebral hypoperfusion due to carotid artery stenosis have yet to be fully established. As dizziness is a common symptom in patients with carotid artery stenosis, we aimed to evaluate the effects of CEA/CAS on cerebral function in patients with carotid artery stenosis, using equilibrium function tests. METHODS: This prospective observational cohort study included 50 patients who had carotid artery stenosis and were scheduled to undergo CEA or CAS. Before CEA/CAS, we quantitatively evaluated the vestibulo-ocular reflex (VOR) and vestibular evoked myogenic potential (VEMP), as indicators of brainstem/inner ear functions related to balance, and visual suppression of VOR, as an indicator of cerebral control over the brainstem reflex related to balance. These were then compared with supratentorial cerebral blood flow (CBF). Changes in VOR, VEMP, visual suppression of VOR, CBF, and dizziness after CEA/CAS were also evaluated. RESULTS: The visual suppression rates of VOR correlated with supratentorial CBFs before CEA/CAS (correlation coefficient = 0.47, p = 0.003). The visual suppression rates of VOR (p < 0.001) and supratentorial CBFs (p = 0.003) were improved by CEA/CAS, while VOR and VEMP did not change. Symptoms of dizziness improved after CEA/CAS. CONCLUSIONS: Our results suggest that visual suppression of the VOR may be a novel and practical marker for the beneficial effects of CEA/CAS on supratentorial cerebral function.

Reduced likelihood of the Poggendorff illusion in cerebellar strokes: a clinical and neuroimaging study.

This study aimed to test our hypothesis that the cerebellum plays an important role in the generation of the optical-geometric illusion known as the Poggendorff illusion, the mechanism of which has been explained by accumulated experience with natural scene geometry. A total of 79 participants, comprising 28 patients with isolated cerebellar stroke, 27 patients with isolated cerebral stroke and 24 healthy controls, performed Poggendorff illusion tasks and 2 different control tasks. We also investigated core brain regions underpinning changes in the experience of the illusion effect using multivariate lesion-symptom mapping. Our results indicate that patients with isolated cerebellar stroke were significantly less likely to experience the Poggendorff illusion effect than patients with isolated cerebral stroke or healthy controls (74.6, 90.5 and 89.8%, respectively; F(2,76) = 6.675, P = 0.002). However, there were no inter-group differences in the control tasks. Lesion-symptom mapping analysis revealed that the brain lesions associated with the reduced frequency of the Poggendorff illusion effect were mainly centred on the right posteromedial cerebellar region, including the right lobules VI, VII, VIII, IX and Crus II. Our findings demonstrated, for the first time, that patients with cerebellar damage were significantly less likely to experience the Poggendorff illusion effect and that right posteromedial cerebellar lesions played an important role in this effect. These results provide new insight into alterations of a geometric illusion effect in patients with cerebellar disorders and pave the way for future clinical use of the illusion task to detect cerebellar abnormalities.

[Vertigo and dizziness].

Pathophysiology of vertigo/dizziness can be understood by eye deviation (nystagmus). In benign paroxysmal positional vertigo, eye deviation of causative semicircular canal stimulation is directly observed. In other peripheral vestibular disorders, eye deviation results from the sum of unilateral all semicircular canal disorders. The central vestibular pathway is controlled by the cerebellum. Thus, in vertigo/dizziness of central origin, not only eye deviation due to impairment of the central vestibular pathway but also deviation due to disinhibition of the pathway from the cerebellum is observed. The cerebellar control on the central vestibular pathway also plays an important role in vestibular compensation. When treating vertigo/dizziness, it is necessary to understand the pathophysiology of the vertigo/dizziness, to set the treatment target based on the pathophysiology, and to intervene for the target.

Antiplatelet Loading Effects Prior to Endovascular Treatment: Carotid Artery Stenosis versus Unruptured Cerebral Aneurysms.

Objective: Carotid artery stenosis and cerebral aneurism may have different platelet functions and antiplatelet responses because these diseases have different etiologies. In this study, we compared the antiplatelet loading effects prior to endovascular treatment between carotid artery stenosis and unruptured cerebral aneurysm (UCA) patients. Methods: Nine patients with asymptomatic carotid artery stenosis (ACS), 14 with symptomatic carotid artery stenosis (SCS), and 20 with unruptured cerebral aneurysms were enrolled in this study. Antiplatelet (aspirin + clopidogrel) loading effects prior to endovascular treatment were evaluated using light transmission aggregometry and platelet aggregate detection methods. Results: Although there are differences in the prevalence of atherosclerosis risk factors, maximum aggregation rates in light transmission aggregometry and platelet aggregation-prone properties were not different in the three disease groups. Conclusion: Preoperative dual antiplatelet therapy with aspirin and clopidogrel may be appropriate for both carotid artery stenosis and cerebral aneurism patients even though their conditions and background factors differ.

Bedside video-oculographic evaluation of eye movements in acute supratentorial stroke patients: A potential biomarker for hemispatial neglect.

BACKGROUND AND PURPOSE: The presence of hemispatial neglect adversely affects functional outcomes in stroke patients; consequently, it warrants early targeted rehabilitative intervention. Nevertheless, hemispatial neglect in the acute phase of stroke has often been underdiagnosed. In this study, we aimed to detect hemispatial neglect at the bedside in acute stroke patients by measuring eye movements using video-oculography (VOG). METHODS: Forty-seven patients with acute unilateral supratentorial stroke were enrolled. We quantitatively measured horizontal saccade (latency, velocity, and amplitude) and smooth pursuit (gain) at the bedside using VOG and compared these variables with scores on the Behavioral Inattention Test (BIT), a screening battery to assess hemispatial neglect. RESULTS: Contralesional saccade latency, velocity, and amplitude, and ipsilesional smooth pursuit gain were suppressed compared with those in the opposite directions (p = 0.08, 0.02, 0.04, and 0.02, respectively). These directional ocular hypokinesia values correlated with the total BIT score (correlation coefficients -0.53, 0.48, 0.51, and 0.39, respectively). The association was significant even after adjusting for age and stroke severity. CONCLUSIONS: Eye movement measurements performed using VOG significantly correlated with the tendency for hemispatial neglect in acute supratentorial stroke patients. Bedside VOG measurement may be a simple biomarker for detecting hemispatial neglect even in patients in the supine position during the acute phase of stroke.

Cerebral perfusion changes in chronic dizziness: A single-photon emission computed tomography study.

BACKGROUND AND PURPOSE: Dizziness may persist even after the causative vestibular imbalance subsides. Although the precise mechanism of chronic dizziness is unknown, various cerebral activity changes associated with it have been reported. To understand its mechanism in the absence of the causative vestibular imbalance, we compared cerebral changes in chronic dizziness with and without persistent vestibular imbalance. METHODS: Between September 2014 and March 2020, we examined regional cerebral blood flow (rCBF) in 12 patients having chronic post-lateral medullary infarction dizziness with persistent brainstem vestibular imbalance and 23 patients having chronic dizziness without currently active vestibular imbalance using single-photon emission computed tomography (SPECT) with 99m Technetium-ethyl cysteinate dimer. Further, we analyzed the SPECT images using a voxel-based group comparison. RESULTS: We observed a decreased rCBF in the occipital lobe and increased rCBF in the medial and inferior parts of the temporal lobe in patients having chronic dizziness with and without active vestibular imbalance compared to healthy controls. However, only patients having chronic dizziness without active vestibular imbalance exhibited increased rCBF in the frontal lobe, including the orbitofrontal cortex. CONCLUSION: This is the first study to highlight the difference in rCBF changes between patients having chronic dizziness with and without active vestibular imbalance. Decreased occipital lobe activity and increased medial and inferior temporal lobe activity may be related to keeping dizziness perception triggered regardless of the presence or absence of active vestibular imbalance, whereas increased frontal lobe activity may explain the dizziness background to persist after the disappearance of vestibular imbalance.