Bathing-Related Ischemic Stroke: Association between Stroke Subtype and Cerebral Small Vessel Disease.

AIMS: Bathing-related ischemic stroke (BIS) is sometimes fatal. However, its mechanisms and risk factors remain unclear. We aimed to identify the incidence of stroke subtypes in BIS, and clarify the impact of cerebral small vessel disease (CSVD) on BIS. METHODS: Consecutive patients with ischemic stroke between October 2012 and February 2022 were retrospectively screened. The inclusion criteria were: 1) onset-to-door time within 7 days; and 2) availability of the results of MRI evaluation of CSVD markers during hospitalization. BIS was defined as an ischemic stroke that occurred while or shortly after bathing. We investigated the incidence of the stroke subtype and the correlation between CSVD markers and BIS. RESULTS: 1,753 ischemic stroke patients (1,241 [71%] male, median age 69 years) were included. 57 patients (3%) were included in the BIS group. A higher frequency of large artery atherosclerosis (LAA) (prevalence ratio [PR] 2.069, 95% confidence interval [CI] 1.089 to 3.931, p=0.026) and lower frequency of cardio-embolism (CES) (PR 0.362, 95% CI 0.132 to 0.991, p=0.048) in BIS cases were identified. Moreover, lower periventricular hyperintensity (PVH) Fazekas grade (PR 0.671, 95% CI 0.472 to 0.956, p=0.027) and fewer cerebral microbleeds (CMBs) in deep brain region (PR 0.810, 95%CI 0.657 to 0.999, p=0.049) were associated with BIS cases. CONCLUSIONS: The BIS group was more likely to develop LAA and less likely to develop CES. Lower PVH grade and fewer CMBs in deep brain region were associated with the development of BIS.

Relationship between ω3 and ω6 polyunsaturated fatty acids and atrial fibrillation in acute ischemic stroke.

BACKGROUND & AIMS: Some ω3 polyunsaturated fatty acids (PUFAs) are said to demonstrate a dose-related risk of atrial fibrillation (AF), conversely, some ω6 PUFAs might have AF protective potential. However, few investigated the relation among ischemic strokes. Primarily, we aimed to examine a relation between ω3 and ω6 PUFAs and the presence of AF in ischemic strokes. Further, since, some PUFAs are said to affect the cardiac load, we secondarily aimed to investigate the association between ω3 and ω6 PUFAs and brain natriuretic peptide (BNP) and the occurrence of cerebral large vessel occlusion (LVO) in ischemic strokes with AF. METHODS: Consecutive patients with ischemic stroke admitted between 2012 and 2022 were retrospectively screened. Plasma levels of PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid, dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA), were assayed. Data were analyzed using a Poisson regression analysis with a robust variance estimator and a multiple linear regression analysis. RESULTS: We screened 2112 consecutive ischemic strokes, including 1574 (1119 [71%] males, median age 69 years). Lower DGLA (prevalence ratio (PR) 0.885, 95% CI 0.811-0.966, p = 0.006), lower AA (PR 0.797, 95% CI 0.649-0.978, p = 0.030), and higher EPA/AA ratio (PR 1.353, 95% CI 1.036-1.767, p = 0.026) were associated with AF. Checking the linearity between AF and PUFAs, negative linear trends were observed between DGLA quartiles (Q1: PR 1.901, Q2: PR 1.550, Q3: PR 1.423, Q4: 1.000, p < 0.001 for trend) and AA quartiles (Q1: PR 1.499, Q2: PR 1.204, Q3: PR 1.125, Q4: 1.000, p = 0.004 for trend), with positive linear trends between EPA/AA ratio quartiles (Q1: 1.000, Q2: PR 1.555, Q3: PR 1.612, Q4: PR 1.797, p = 0.001 for trend). Among patients with AF, a negative association between AA and BNP (unstandardized coefficient -1.316, 95% CI -2.290∼-0.342, p = 0.008) was observed, and lower AA was associated with LVO (PR 0.707, 95% CI 0.527-0.950, p = 0.021). CONCLUSION: Lower DGLA and AA and a higher EPA/AA ratio might be related to the development of AF in ischemic strokes. Further, AA might have a cardio-cerebrovascular protective role in ischemic strokes with AF.

Peripheral immune profile in drug-naïve dementia with Lewy bodies.

BACKGROUND: Accumulating evidence suggests that peripheral inflammation is associated with the pathogenesis of Parkinson's disease (PD). We examined peripheral immune profiles and their association with clinical characteristics in patients with DLB and compared these with values in patients with PD. METHODS: We analyzed peripheral blood from 93 participants (drug-naïve DLB, 31; drug-naïve PD, 31; controls, 31). Absolute leukocyte counts, absolute counts of leukocyte subpopulations, and peripheral blood inflammatory indices such as neutrophil-to-lymphocyte ratio were examined. Associations with clinical characteristics, cardiac sympathetic denervation, and striatal 123I-2-carbomethoxy-3-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) binding were also examined. RESULTS: Patients with DLB had lower absolute lymphocyte and basophil counts than did age-matched controls (both; p < 0.005). Higher basophil counts were marginally associated with higher global cognition (p = 0.054) and were significantly associated with milder motor severity (p = 0.020) and higher striatal 123I-FP-CIT binding (p = 0.038). By contrast, higher basophil counts were associated with more advanced PD characterized by decreased global cognition and severe cardiac sympathetic denervation. Although lower lymphocyte counts had relevance to more advanced PD, they had little relevance to clinical characteristics in patients with DLB. Higher peripheral blood inflammatory indices were associated with lower body mass index in both DLB and PD. CONCLUSIONS: As in patients with PD, the peripheral immune profile is altered in patients with DLB. Some peripheral immune cell counts and inflammatory indices reflect the degree of disease progression. These findings may deepen our knowledge on the role of peripheral inflammation in the pathogenesis of DLB.

Small ischemic lesions accompanying intracerebral hemorrhage: The underlying influence of old lacunes and polyunsaturated fatty acids.

BACKGROUND AND AIMS: Small ischemic lesions (SILs) accompanying intracerebral hemorrhage (ICH) might be induced by small-vessel vulnerability and hypercoagulation. Some polyunsaturated fatty acids (PUFAs) have been associated with hypercoagulation in cardiovascular diseases. Our aim here is to determine how pre-existing small-vessel disease (SVD) and PUFAs may affect SILs. METHODS AND RESULTS: We screened consecutive ICH patients (October 2012-December 2021) meeting two inclusion criteria: (1) the patients were hospitalized for acute ICH and were undergoing magnetic resonance imaging and (2) the patients' PUFA measurements were available. After excluding patients with isolated intraventricular hemorrhage, we evaluated whether three SVD markers (white matter hyperintensities, old lacunes, cerebral microbleeds) and PUFAs might be associated with the development of SILs. We selected 319 participants from 377 screened consecutive ICH patients (median age = 64, males = 207 [65 %]). Of the 319 patients, 45 patients (14 %) developed SILs. In a multivariable logistic regression analysis, the factors associated with SILs were old lacunes (OR 3.255, 95 % CI 1.101-9.622, p = 0.033) and DHA/AA ratio (OR 0.180, 95 % CI 0.046-0.704, p = 0.013). Furthermore, in our multivariable analysis using DHA/AA ratio tertiles with and without SILs, we observed a linear trend between SILs and the Higher Tertile of the DHA/AA ratio (DHA/AA ratio Mid-Tertile: OR 1.330, 95%CI 0.557-3.177, p = 0.521, and DHA/AA ratio Lower Tertile: OR 2.632, 95%CI 1.124-6.162, p = 0.026). CONCLUSION: The presence of old lacunes and lower DHA/AA ratios might be associated with SILs accompanying ICH.

Deep and infratentorial cerebral microbleeds are related to wake-up stroke by large-artery atherosclerosis and cardioembolism.

BACKGROUND AND AIMS: Circadian variability of blood pressure (BP) and hypercoagulation in the morning have been proposed as underlying mechanisms of wake-up stroke (WUS). The aim was to determine the impact of cerebral microbleeds (CMBs), showing BP fluctuation and background hypercoagulability, on WUS. METHODS: Consecutive patients with acute ischemic stroke onset-to-door time within one week were screened. WUS was defined as an ischemic stroke that occurred during sleep at night. CMBs were categorized into three: "strictly Lobar", "strictly Deep (D) and/or Infratentorial (I)", and "Mixed". Moderate to severe CMBs were defined as having more than three in total. First, whether CMBs are associated with WUS was examined. Second, the same analysis was performed according to the stroke subtype classified as large-artery atherosclerosis (LAA), cardioembolism (CE), and small-vessel occlusion (SVO). RESULTS: A total of 1477 patients (1059 [72%] male, median age 69 years) were included, and WUS was observed in 363 (25%) patients. On Poisson regression analysis with a robust variance estimator in the total cohort, moderate to severe strictly D and/or I CMBs (PR 1.505, 95% CI 1.154-1.962, p = 0.003) were associated with WUS. From the perspective of stroke subtype, the same result was confirmed in LAA (PR 2.223, 95% CI 1.036-4.768, p = 0.040) and CE (PR 1.668, 95% CI 1.027-2.709, p = 0.039), not SVO. CONCLUSIONS: The presence of moderate to severe strictly D and/or I CMBs might be associated with the development of WUS. By stroke subtype, the same result was confirmed in LAA and CE.

Arachidonic acid level is related to early motor recovery following intracerebral hemorrhage with severe motor paralysis.

BACKGROUND: Low arachidonic acid (AA) levels are reportedly associated with unfavorable outcomes in intracerebral hemorrhage (ICH). OBJECTIVE: We aimed to clarify whether serum AA levels might be associated with a good recovery from severe motor paralysis in the early stage of hospitalization. METHODS: From among consecutive ICH patients between October 2012 and December 2021, patients with a sum of upper and lower extremity National Institutes of Health stroke scale (NIHSS) scores of 4-8 at admission (severe motor paralysis) were included. We defined good early recovery from severe motor paralysis as a sum of upper and lower extremity NIHSS scores of 0-3 on day 7 after admission, and that of individual upper and lower extremities as NIHSS scores of 0-1 on day 7 after admission. We aimed to assess whether serum AA levels might be associated with good early recovery from severe motor paralysis. RESULTS: We screened 377 consecutive ICH patients, including 140 with severe motor paralysis (88 (63%) males, median age 64 years). Recovery from severe motor paralysis was seen in 48 (34%). Higher AA levels (PR 1.243, 95% CI 1.042 to 1.483, p = 0.016) were independently associated with good overall recovery, and good recovery of upper and lower extremities separately (upper extremity: PR 1.319, 95% CI 1.101 to 1.580, p = 0.003; lower extremity: PR 1.293, 95% CI 1.115 to 1.499, p = 0.001). CONCLUSIONS: Higher AA levels may contribute to a good early motor recovery in patients with severe motor paralysis due to ICH.

Interactive effect of orthostatic hypotension on gray matter atrophy associated with hyposmia and RBD in de novo Parkinson's disease.

BACKGROUND: Orthostatic hypotension (OH) is a potential modifiable risk factor for cognitive impairment in patients with Parkinson's disease (PD). Although other risk factors for dementia, hyposmia and REM sleep behavior disorder (RBD), are closely associated with autonomic dysfunction in PD, little is known about how these risk factors influence cognitive function and cerebral pathology. OBJECTIVE: We investigated how these three factors contribute to gray matter atrophy by considering the interaction of OH with hyposmia and RBD. METHODS: We analyzed cortical thickness, subcortical gray matter volume, and cognitive measures from 78 patients with de novo PD who underwent the head-up tilt test for the diagnosis of OH. RESULTS: Whole-brain analyses with Monte Carlo corrections revealed that hyposmia was associated with decreased cortical thickness in a marginal branch of the cingulate sulcus among patients with OH, and cortical thickness in this area correlated with cognitive functioning only in patients with OH. Subcortical gray matter volume analysis indicated that severe RBD was associated with decreased volume in the left hippocampus and bilateral amygdala among patients with OH. CONCLUSION: Even in early PD, OH exerts effects on gray matter atrophy and cognitive dysfunction by interacting with RBD and hyposmia. OH might exacerbate cerebral pathology induced by hyposmia or RBD.

Neuromyelitis optica spectrum disorder with deafness and an extensive brainstem lesion.

A 49-year-old woman developed vomiting, hiccups, double vision, and bilateral ptosis, after which tinnitus and deafness appeared. Head magnetic resonance imaging (MRI) showed a brainstem lesion focused on the midbrain and pons. Anti-aquaporin 4 (AQP4) antibody was positive, and there was no evidence of optic neuritis or myelitis, leading to the diagnosis of neuromyelitis optica spectrum disorder (NMOSD). The auditory brainstem response (ABR) showed no derivation of wave V on left stimulation and extended latency between waves III and V on right stimulation, so impairment between the midbrain and pons was suspected. It was useful to evaluate head MRI and the ABR for identification of the location of auditory pathway dysfunction.

[Intravenous immunoglobulin-induced thrombocytopenia in patient with chronic inflammatory demyelinating polyneuropathy].

A 69-year-old man was admitted to our hospital because of dysesthesia in right palm and left upper limb, gait disturbance, and muscle weakness in both lower limbs. At the same time of neurological impairment appeared, he developed pemphigoid. Lumber MRI showed swelling of cauda equina nerve root. We diagnosed as chronic inflammatory demyelinating polyneuropathy based on an electrophysiological examination, and 2 courses of intravenous immunoglobulin therapy (IVIG) were initiated. After the treatments, symptoms improved immediately. However, thrombocytopenia was seen after each treatment which began on the second day of treatment start, reaching the lowest point from about 10 to 14 days, and improved naturally from 10 to 15 days after the end of IVIG. Difficulty in hemostasis was seen during dialysis due to thrombocytopenia. As a cause of thrombocytopenia, formation of IgG-platelet complexes could be considered, and the presence of multiple inflammatory diseases which activated Fcγ receptors play key roles could be a risk for IVIG related thrombocytopenia.

Inflammatory myopathy associated with PD-1 inhibitors.

OBJECTIVE: To characterize the inflammatory myopathy associated with programmed cell death 1 inhibitors (PD-1 myopathy). METHODS: We studied 19 Japanese patients with PD-1 myopathy (13 men and 6 women, mean age 70 years), who were referred to Keio University. As control groups, we used 68 patients with anti-signal recognition particle antibodies, 51 patients with anti-aminoacyl transfer RNA synthetase antibodies and 460 healthy subjects. RESULTS: In regard to muscle-disease severity, 10 patients showed a mild form of disease and 9 patients showed a severe form. Non-small cell lung cancer was the most common underlying cancer. PD-1 inhibitor consisted of 11 nivolumab and 8 pembrolizumab. PD-1 myopathy occurred 29 days on average after the first administration of PD-1 inhibitor. The initial manifestation of muscle weakness was ptosis in 10 patients, 15 patients had ptosis, 13 diplopia, 8 facial muscle weakness, 10 bulbar symptoms, 13 limb weakness, 14 neck weakness, 4 cardiac involvement, 6 respiratory involvement and 16 myalgia. Ocular, facial, cardiac and respiratory involvement and myalgia were more frequently observed than controls. Serum creatine kinase was increased to 5247 IU/L on average. Autoantibodies related to inflammatory myopathy were negative, while anti-striational antibodies were found in 13 (68%) patients. HLA-C*12:02 alleles were more frequently detected than healthy controls. Muscle pathology was characterized by multifocal necrotic myofibers with endomysial inflammation and expression of MHC class I. Immunosuppressive therapy with corticosteroids was generally effective for muscle weakness. CONCLUSIONS: Based on our clinical, histological and immunological findings, PD-1 myopathy is a discrete subset of inflammatory myopathy.

Pembrolizumab-induced Ocular Myasthenia Gravis with Anti-titin Antibody and Necrotizing Myopathy.

A 73-year-old man developed diplopia after the administration of pembrolizumab for lung adenocarcinoma. He had ptosis and external ophthalmoplegia without general muscle weakness. Serum CK levels were elevated. Although autoantibodies to acetylcholine receptor and muscle-specific kinase, the edrophonium test, and the repetitive nerve stimulation test were all negative, anti-titin autoantibody was positive, leading to the diagnosis of myasthenia gravis (MG). Muscle pathology showed necrotizing myopathy with tubular aggregates. Unlike previously reported cases of pembrolizumab-associated MG, the present case showed ocular MG. This is the first case of pembrolizumab-associated MG with anti-titin antibody, as well as the first case with tubular aggregates.

[A case of histoplasmosis with chronic basilar meningitis diagnosed relatively early].

A 41-year-old man left for Mexico in May 2015. Right pulmonary nodule was detected at a health examination in May 2016, and he subsequently showed headache and slight fever. Contrast-enhanced magnetic resonance imaging of the brain revealed basilar meningitis, so he was admitted to our hospital. We considered imported mycosis due to his travel history to Mexico. We diagnosed histoplasmosis based on the presence of antibodies against Histoplasma in both serum and cerebrospinal fluid. Symptoms almost completely recovered with a liposomal formulation of amphotericin B. Central nervous system histoplasmosis is very rare in Japan. Immunocompetent hosts can develop histoplasmosis, and this pathology is important to consider in patients presenting with basilar meningitis and a positive travel history.