[Implementation of Penumbra-assisted Half-Stent Thrombectomy for Patients with Acute M2 Occlusion:Results of Initial Experiences].

The benefits of mechanical thrombectomy(MT)for acute M2 occlusion have remained unclear because of unavoidable device-related complications due to vascular morphological characteristics. We developed a Penumbra-assisted half-stent thrombectomy for achieving secure retrieval of thrombus with minimal damage to the small-caliber vessel. In total, 6 patients were treated with MT for acute M2 occlusion using this technique between November 2016 and May 2017, including 3 men and 3 women, mean age 74.8(51-98)years. The mean baseline National Institutes of Health Stroke Scale score was 17.5(6-32), and Alberta Stroke Program Early Computed Tomography Score-Diffusion-Weighted Imaging was 7.5(6-9). After navigation of the microcatheter through the thrombus in M2 supported by a Penumbra 4MAX as a distal access catheter, the stent retriever(SR)was partially deployed to cover the entire thrombus. The 4MAX was then advanced towards the caudal end of the thrombus, and the SR was pulled back into the 4MAX with simultaneous aspiration of the 4MAX. We used the Trevo XP3 in 5 patients and Revive SE in 1 patient. The mean procedure time from groin puncture to recanalization was 60(54-66)min. Successful recanalization(Thrombolysis in Cerebral Infarction score 2b or 3)was achieved in 5(83%)patients. There were no cases of symptomatic intracranial hemorrhage. Good outcome(modified Rankin Scale score 0 to 2)at 3 months was achieved in 3(50%)patients. Penumbra-assisted half-stent thrombectomy appears to be an effective alternative strategy in MT for acute M2 occlusion.

Duplex-assisted carotid artery stenting without administration of contrast medium for patients with chronic kidney disease or allergic reaction.

INTRODUCTION: We aimed to investigate the safety and feasibility of duplex-assisted carotid artery stenting (CAS) without administration of contrast medium for the prevention of adverse reactions. METHODS: Fifteen patients (9 % of all CASs) with severe carotid stenosis (≥70 %) associated with chronic kidney disease (CKD) (stage ≥3) or allergy to contrast medium underwent duplex-assisted CAS without administration of contrast medium over 4 years. The procedural success rate and perioperative complication rates were compared between the duplex-assisted CAS (n = 15) and conventional CAS (n = 153) groups. RESULTS: The technical success rate was 100 % in both groups. Combined stroke or death rates during the post-procedural period did not differ significantly between the duplex-assisted CAS group (0/15, 0 %) and conventional CAS group (4/153, 2.6 %). None of the 14 patients with CKD in the duplex-assisted CAS group experienced further deterioration of renal function. The mean surface radiation dose of participants in the duplex-assisted CAS group (n = 13, 312 ± 131 mGy) was significantly lower than that of the conventional CAS group (n = 31, 1036 ± 571 mGy) (p < 0.001). The mean duration of CAS procedure was not significantly different between the duplex-assisted CAS group (156 ± 39.7 min) and the conventional CAS group (156 ± 37.4 min). CONCLUSION: Duplex-assisted CAS without administration of contrast medium could be an alternative option in selected patients deemed to be at high risk for renal failure from nephrotoxic contrast medium or who have an allergy to contrast medium.

Usefulness of "AcT ratio" in diagnosis of internal carotid artery stenosis: a multicenter, retrospective, observational study.

PURPOSE: The ratio of the internal carotid artery (ICA) to the common carotid artery (CCA), especially the "AcT ratio," which is a modified measurement method of acceleration time, is useful for diagnosing ICA-origin stenosis. However, previous studies were single-center studies. Therefore, this multicenter, retrospective, cross-sectional study aimed to determine whether a method using the AcT ratio is useful for estimating stenosis rates. METHODS: This study included 461 vessels subjected to carotid artery ultrasonography and evaluation for ICA-origin stenosis via NASCET at four hospitals. The duration from the steep rise point to the inflection point or the first peak was defined as AcT on pulsed wave Doppler. The AcT ratio was calculated as AcT of ICA/AcT of ipsilateral CCA. The AcT ratio and rate of ICA-origin stenosis were analyzed using Pearson's correlation coefficient, simple regression analysis, and ROC curve. RESULTS: A significant positive correlation was observed between the AcT ratio and NASCET stenosis. NASCET stenosis of ≥ 50% had a sensitivity, specificity, and negative predictive value (NPV) of 70.2%, 71.6%, and 91.5%, respectively, when the cut-off value of the AcT ratio was 1.17. NASCET stenosis of ≥ 70% had a sensitivity, specificity, and NPV of 70.5%, 72.1%, and 95.9%, respectively, when the cut-off value of the AcT ratio was 1.22. CONCLUSIONS: The findings of this multicenter, retrospective, cross-sectional study suggest that the AcT ratio is useful for diagnosing ICA-origin stenosis, especially for diagnosis by exclusion. NASCET stenosis of ≥ 50% was considered unlikely if the Act ratio was ≤ 1.17, whereas NASCET stenosis of ≥ 70% was considered unlikely if it was ≤ 1.22.

SPTLC2 variants are associated with early-onset ALS and FTD due to aberrant sphingolipid synthesis.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a devastating, incurable neurodegenerative disease. A subset of ALS patients manifests with early-onset and complex clinical phenotypes. We aimed to elucidate the genetic basis of these cases to enhance our understanding of disease etiology and facilitate the development of targeted therapies. METHODS: Our research commenced with an in-depth genetic and biochemical investigation of two specific families, each with a member diagnosed with early-onset ALS (onset age of <40 years). This involved whole-exome sequencing, trio analysis, protein structure analysis, and sphingolipid measurements. Subsequently, we expanded our analysis to 62 probands with early-onset ALS and further included 440 patients with adult-onset ALS and 1163 healthy controls to assess the prevalence of identified genetic variants. RESULTS: We identified heterozygous variants in the serine palmitoyltransferase long chain base subunit 2 (SPTLC2) gene in patients with early-onset ALS. These variants, located in a region closely adjacent to ORMDL3, bear similarities to SPTLC1 variants previously implicated in early-onset ALS. Patients with ALS carrying these SPTLC2 variants displayed elevated plasma ceramide levels, indicative of increased serine palmitoyltransferase (SPT) activity leading to sphingolipid overproduction. INTERPRETATION: Our study revealed novel SPTLC2 variants in patients with early-onset ALS exhibiting frontotemporal dementia. The combination of genetic evidence and the observed elevation in plasma ceramide levels establishes a crucial link between dysregulated sphingolipid metabolism and ALS pathogenesis. These findings expand our understanding of ALS's genetic diversity and highlight the distinct roles of gene defects within SPT subunits in its development.

Molecular pathology of Sandhoff disease with p.Arg505Gln in HEXB: application of simulation analysis.

Sandhoff disease is a GM2 gangliosidosis caused by mutations in HEXB encoding the ß-subunit of ß-hexosaminidase A. ß-Hexosaminidase A exists as a heterodimer consisting of α- and ß-subunits, and requires a GM2 activator protein to hydrolyze GM2. To investigate the molecular pathology in an adult Sandhoff disease patient with an early disease onset, we performed mutation detection, western blot analysis and molecular simulation analysis. The patient had compound heterozygous mutations p.Arg505Gln and p.Ser341ValfsX30. Western blot analysis showed that the amount of mature form of the α- and ß-subunits was markedly decreased in the patient. We then performed docking simulation analysis of the α- and ß-subunits with p.Arg505Gln, the GM2AP/GM2 complex and ß-hexosaminidase A, and GM2 and ß-hexosaminidase A. Simulation analysis showed that p.Arg505Gln impaired each step of molecular conformation of the α- and ß-subunits heterodimer, the activator protein and GM2. The results indicated that p.Ser341ValfsX30 reduced the amount of ß-subunit, and that p.Arg505Gln hampered the maturation of α- and ß-subunits, and hindered the catalytic ability of ß-hexosaminidase A. In conclusion, various methods including simulation analysis were useful to understand the molecular pathology in Sandhoff disease.

Clinical features of late-onset poststroke seizures.

BACKGROUND: Compared to the patients with early-onset seizures (ES), those with late-onset seizures (LS) have a high risk of epilepsy that is a feared complication after stroke. However, few studies have described detailed clinical features of LS in Japanese patients. METHODS: To elucidate the clinical features of LS, a series of 448 stroke patients (cerebral infarction n = 286; cerebral hemorrhage n = 162) in our hospital were retrospectively examined in this study. Stroke location was determined by computed tomographic and/or magnetic resonance imaging scans. Lesion size was evaluated using the Alberta Stroke Program Early Computed Tomographic Score. We examined occurrence rate, onset time, and recurrence rate of LS. In addition, clinical features of the infarction of LS and non-LS group were compared on age, gender, laterality, location, and extent, respectively. RESULTS: LS occurred in 18 patients (4.0%). Of these, 17 experienced LS within 1.5 years after stroke. While epilepsy developed in none of the patients with ES, it developed in 33% of those with LS. Patients with cortical and a larger infarction involving the middle cerebral artery had at significantly greater risk of LS (P < .05). CONCLUSIONS: Patients with cortical and a larger infarction involving the middle cerebral artery should be carefully observed because of a high risk of LS.

Point-of-care ultrasound for stroke patients in the emergency room.

Stroke requires rapid determination of the cause to provide timely and appropriate initial management. Various ultrasonographic techniques have been evaluated as ways to determine the cause of stroke; among them, carotid artery ultrasonography is particularly useful since it provides considerable information within a short time period when used to evaluate a specific site. In the emergency room, carotid artery ultrasonography can be used to diagnose internal carotid artery stenosis, predict an occluded vessel, and infer the cause of ischemic stroke. Additionally, carotid artery ultrasonography can diagnose different conditions including subclavian artery steal syndrome, bow hunter's stroke, Takayasu's arteritis, moyamoya disease, and dural arteriovenous fistula. Furthermore, patients with ischemic stroke with a pulse deficit or hypotension must be differentiated from acute type A aortic dissection, which requires emergency surgery; carotid artery ultrasonography can immediately differentiate between the two conditions by identifying the intimal flap of the common carotid artery. The following article provides an overview of carotid artery ultrasonography performed as point-of-care ultrasound in the emergency room in patients with suspected stroke.

Ultrasound diagnosis of carotid artery stenosis and occlusion.

Carotid artery ultrasonography is capable of diagnosing or inferring the presence or absence of stenosis or occlusion of the internal carotid artery (ICA) and vertebral artery (VA), as well as the not directly observable distal ICA, middle cerebral artery (MCA), and basilar artery (BA). Stenosis at the origin of the ICA is mainly evaluated using the parameter peak systolic velocity (PSV), with values of ≥ 200-230 cm/s indicating severe stenosis. Recently, the acceleration time ratio has been reported for diagnosis of ICA origin stenosis. An indicator called the end-diastolic (ED) ratio can be used for diagnosing occlusion of the distal ICA or the M1 segment of the MCA. The PSV of stenosis can be used to diagnose stenosis at the beginning of the VA or V1, and mean flow velocity, mean ratio, and diameter ratio can be used to diagnose distal VA occlusion. Furthermore, the usefulness of the VA pulsatility index and resistance index has been suggested for diagnosing stenosis or occlusion of the BA. This review outlines diagnostic sonography criteria for stenosis and occlusion of extracranial and intracranial arteries.

Correction to: Intervendor variability of carotid intima-media thickness measurement: validation study using newly developed ultrasound phantom.

In the Original publication of the article Table 3 was published incorrectly.

Intervendor variability of carotid intima-media thickness measurement: validation study using newly developed ultrasound phantom.

PURPOSE: Ultrasonography-derived carotid artery intima-media thickness (IMT) has been established as an early atherosclerotic imaging biomarker. The IMT reference value of a healthy person is approximately 0.1 × (every 10 years of age) + 0.2 (mm); accordingly, it requires an accuracy of at least 0.1 mm. However, one concern of IMT measurement is intervendor variability. In this study, we aimed to verify the intervendor variability using an IMT phantom. METHODS: An improved IMT phantom was developed, and it was possible to analyze the IMT by software for all vendors. RESULTS: With the vendor-specific software, the maximum difference between the devices was 0.08 mm, and the difference in quartile range was 0.06 mm. On the other hand, with the vendor-independent offline software, the maximum difference between the devices was 0.16 mm, and the quartile range of variation was 0.06 mm. CONCLUSION: The intervendor variability assessed using our IMT phantom was less than 0.10 mm, and the on-board vendor-specific software was shown to reduce the difference between the devices significantly compared with the vendor-independent offline software. To further improve the vender difference, adjustment by means of vendor-specific software based on a standardized IMT phantom is warranted.

Elevation of cerebrospinal fluid protein in patients with diabetes mellitus is associated with duration of diabetes.

We investigated the relationships between total cerebrospinal fluid (CSF) protein in diabetic patients and the clinical characteristics of diabetes mellitus. The subjects comprised 16 diabetic patients (median age = 60.5 years, range = 47-71) who were studied retrospectively. Patients with diseases known to be associated with increases in total CSF protein were excluded as far as possible. The median total CSF protein and albumin quotient in the diabetic group were 52.5 mg/dl (range = 41-84) and 6.13 x 10(-3) (range = 4.0 x 10(-3) to 13.1 x 10(-3)), respectively. These results were significantly higher than those in 28 age-matched nondiabetic patients (median = 59.0 years, range = 50-71) (p < 0.01). Duration of diabetes was associated with total CSF protein (r = 0.642, p < 0.01). If the CSF shows increased total protein in a diabetic patient who has not suffered from long-term diabetes (> or =5 years), causes other than diabetes should be considered to explain increases in total CSF protein. We need to confirm the present results by studying a larger population of diabetic patients.

[Clinical and pathological significance of carotid siphon calcification observed on bone condition of brain CT].

PURPOSE: On plain brain computed tomography (CT), it is difficult to evaluate stenosis of internal carotid artery (ICA) because ICA is surrounded by structures, even though we can observe calcification of carotid siphon in some patients by using bone condition. However the pathologic significance has not been well known. We studied the pathologic significance of carotid siphon calcification observed on bone condition of brain CT. METHODS: A total of 112 patients who were diagnosed or suspected as cerebrovascular diseases were registered. We classified the calcification into four levels (none, mild, moderate, severe) based on the degree of calcification. Then we compared it with the degree of stenosis of carotid siphon seen on brain magnetic resonance angiography (MRA) and with max intima-medial thickness (IMT) from common carotid artery (CCA) to ICA on carotid ultrasonography. RESULT: The mean +/- standard deviation of max IMT to none, mild, moderate and severe in the degree of calcification were 1.03 +/- 0.64 (0.4-2.8), 1.65 +/- 0.83 (0.5-4.1), 2.03 +/- 0.83 (0.8-4.1) and 2.81 +/- 1.15 (0.7-6.5) mm, respectively. The calcification on brain CT significantly correlated with the degree of stenosis on brain MRA and with max IMT on carotid ultrasonography. CONCLUSION: The calcification of carotid siphon on bone condition of brain CT correlated with stenosis of the same portion and atherosclerosis of CCA bifurcation. Recently, on DICOM viewer, clinicians can convert plain condition into bone condition on brain CT due to popularization of PACS. We should pay attention to calcification of carotid siphon in patients with ischemic cerebrovascular diseases because we can estimate the atherosclerosis of both carotid siphon and CCA bifurcation easily and immediately.

Validation of the R2CHADS2 and CHADS2 Scores for Predicting Post-stroke Cognitive Impairment.

Objective Post-stroke cognitive impairment often afflicts stroke survivors and is a major obstacle both for cognitive and physical rehabilitation. Stroke risk scores ["Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, Stroke" (CHADS2) and "CHADS2 + creatinine clearance <60 mL/min" (R2CHADS2)] are used to assess the future risk of cardioembolic stroke in patients with atrial fibrillation (AF). However, congestive heart failure, hypertension, aging, diabetes mellitus, stroke, and renal dysfunction are also risk factors for cognitive impairment. Methods Sixty-two patients with nonvalvular AF-induced cardioembolic stroke underwent cognitive testing, including the Japanese version of the Montreal Cognitive Assessment (MoCA-J), Mini-Mental State Examination (MMSE), and Apathy Scale. The correlations between the MoCA-J/MMSE/Apathy Scale scores and stroke risk scores were examined. Results The average CHADS2 and R2CHADS2 scores were 4.1±1.0 and 5.6±1.6, respectively. The average MoCA-J, MMSE, and Apathy Scale scores were 17.4±6.2, 22.0±5.3, and 20.0±8.9, respectively. The CHADS2 and R2CHADS2 scores were negatively correlated with the MoCA-J/MMSE and positively correlated with the Apathy Scale. The R2CHADS2 score was more sensitive to poststroke cognitive impairment than the CHADS2 score. This correlation was stronger for MoCA-J than for MMSE, as the MMSE scores were skewed toward the higher end of the range. The results for individual MoCA-J and MMSE subtests indicated that the visuoexecutive, calculation, abstraction, and remote recall functions were significantly decreased after cardioembolic stroke. Conclusion These results suggest that the R2CHADS2 and CHADS2 scores are useful for predicting post-stroke cognitive impairment.

Ultrasonographic findings of proximal median neuropathy: A case series of suspected distal neuralgic amyotrophy.

Spontaneous anterior interosseous nerve (AIN) palsy develops following the resolution of nerve pain, which may be considered as distal neuralgic amyotrophy. NA is assumed to have a complex etiology, but an autoimmune mechanism is likely involved. However, precise assessment of the lesion is challenging. We examined five consecutive patients with suspected spontaneous AIN palsy using ultrasonography. On electromyography, all patients exhibited denervation potentials in the muscles, not only in the AIN territory, but also in the proximal median nerve territory (e.g., the flexor carpi radialis or pronator teres). Ultrasonography of the median nerve demonstrated neural swelling at the proximal side of the medial epicondyle in four patients and an hourglass-like constriction of the nerve fascicle in three patients. Four patients were diagnosed with distal neuralgic amyotrophy; of these, three received intravenous immunoglobulin administration, but only limited beneficial effect was achieved in one patient with early stage disease. One patient showed significant median nerve hypertrophy on ultrasonography and was diagnosed with neurolymphomatosis following the detection of malignant lymphoma during a systemic survey. Our experience demonstrates that ultrasonography for proximal median neuropathy presenting as AIN palsy may be useful for the accurate lesion assessment.

[Intermittent intravenous immunoglobulin infusion prevented relapses in patients with remission-exacerbation type chronic inflammatory demyelinating polyradiculoneuropathy].

The intravenous immunoglobulin infusion therapy (IVIg) has recently acquired an important role in the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Some patients, however, require repetitive infusions to maintain the improvement. We planned a one-day therapy with 0.4 g/kg of IVIg in every 7 or 10 days for two CIDP patients who had required a 5-day course of IVIg in every month because of frequent exacerbations. Serum levels of IgG in both patients were kept as high as 2,000 mg/dl resulting in maintaining the improvement without any side effects.

[Medial longitudinal fasciculus (MLF) syndrome in a patient with giant cell arteritis].

A 76-year-old female was referred to our department because of diplopia for two months and intermittent claudication for five months. She showed medial longitudinal fasciculus (MLF) syndrome. Brain MRI (T2WI) showed multiple infarctions in the right pontine tegmentum and left paramedian midbrain. A biopsy of superficial temporal artery showed the characteristic findings of glanulomatous inflammation indicative of giant cell arteritis. We thought the mechanism of this cerebral infarction as artery to artery embolization or intracranial arteritis. Treatment with oral prednisolone (1 mg/kg/day) improved her limb claudication and normalized serum C-reactive protein level.

HLA typing in focal myositis.

It is still controversial if idiopathic focal myositis is a part of systemic polymyositis. We present here four patients, including identical twins, with focal myositis accompanied by the same HLA typings. Gradually developing unilateral calf muscle pain was an initial symptom in all patients. Neither muscular weakness nor creatine kinase (CK) elevation was observed, while minimal inflammatory findings such as erythrocyte sedimentation rate (ESR) increase appeared in serum. Magnetic resonance imaging (MRI) revealed localized abnormalities of calf muscles. Biopsy specimen was characterized by perimysial and endomysial inflammatory infiltration consisted of T cells and macrophages and rare necrotic fibers. Corticosteroid administrations ameliorated their symptoms and signs, though recurrence occurred along with decreasing doses. HLA typings common to all patients were A2, B62, Cw3, and DQ3, whereas HLA-D DNA typings were DQB1 *0303 for two patients, and DQB1*0302 for three patients. These findings suggest that at least some focal myositis may be a new disease unit, with a common genetic background but not a part of systemic polymyositis.