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.

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.

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.

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.

[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.

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.

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.

[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.

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.

[Reversible cerebral vasoconstriction syndrome in a stroke patient with systemic lupus erythematosus and antiphospholipid antibody].

A 36-year-old female with systemic lupus erythematosus and antiphospholipid syndrome was referred to our department because of mild weakness of left arm and an episode of right amaurosis fugax for twenty days. Brain MRI showed right ACA/MCA/PCA border zone infarction on DWI/T2WI/FLAIR and MR angiography (MRA) showed multiple segmental stenosis in right internal carotid artery, right and left middle cerebral artery, and bilateral posterior cerebral arteries. Treatment with oral aspirin (100 mg/day) and continuous infusion of heparin kept her neurological symptoms and signs stable. MRA on 28 days revealed complete recovery of multiple stenotic lesions, thus, diagnosis of reversible cerebral vasoconstriction (RCVS) was made. RCVS should be considered as a cause of neurological deficit in patients with SLE regardless of thunderclap headache.

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.

The effect of pramipexole on depressive symptoms in Parkinson's disease.

Depression is a common occurrence in patients with Parkinson's disease (PD). Pramipexole is a dopamine agonist that has been used to treat both motor and non-motor symptoms associated with PD. We conducted a study to elucidate the effect of pramipexole on each of the depressive symptoms as assessed by the Zung Self-Rating Depression Scale (SDS). Twenty patients with PD were treated with pramipexole 1.5-3.0 mg daily for 2-3 months. The SDS and the Unified Parkinson Disease Rating Score (UPDRS) were measured in each subject before and after the treatment. Both the SDS and the UPDRS decreased significantly after treatment with pramipexole. Individual assessment of each item in the SDS indicated that "crying spell", "confusion", "psychomotor retardation", "emptiness", and "dissatisfaction" symptoms improved significantly following treatment, while "depressed affect", "decreased libido", "constipation", and "indecisiveness" symptoms were worse after the treatment. As the symptom of "indecisiveness" did not respond to treatment, it might be an essential symptom in patients with PD.