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.

Urinary Immunoglobulin G Is Associated with Deep and Infratentorial Cerebral Microbleeds in Stroke Patients.

BACKGROUND: Cerebral microbleeds (CMBs) detected on susceptibility-weighted imaging (SWI) are associated with cerebral small vessel disease. Chronic kidney disease and microalbuminuria have been associated with the presence of CMBs in stroke patients. Urinary immunoglobulin G (IgG) is measured to document glomerular injury; however, the relationship between urinary IgG and CMBs is unknown. METHODS: We retrospectively enrolled consecutive patients who had been admitted with transient ischemic attack (TIA) or ischemic stroke and identified those who had undergone SWI and a spot urine test. The location of CMBs was classified on magnetic resonance imaging as strictly lobar, deep/infratentorial (D/I), or mixed areas. We analyzed the association between urinary IgG and the presence and location of CMBs. RESULTS: We included 298 patients (86 female, median age 70 years, median eGFR 65.8 mL/min/1.73 m2). Positive urinary IgG and CMB results were found in 58 (19%) and 160 patients (54%), respectively. Urinary IgG positivity was significantly associated with CMBs compared with non-CMBs (28% vs. 9%, p < 0.001), and with D/I or mixed CMBs compared with non-D/I or mixed CMBs (34% vs. 10%, p < 0.001). Multivariate analysis revealed that urinary IgG and hypertension positivity were strongly associated with D/I or mixed CMBs (OR 3.479, 95% CI: 1.776-6.818, p < 0.001; OR 3.415, 95% CI: 1.863-6.258, p < 0.001). CONCLUSIONS: Urinary IgG was associated with the prevalence of D/I or mixed location CMBs in TIA or ischemic stroke patients. Our findings provide new insights into the association between urinary IgG and the distribution of CMBs.

Magnetic Resonance Imaging/cerebrospinal Fluid-negative Myelitis Following COVID-19 with a Dramatic Response to Early Aggressive Immunosuppressive Therapy.

A 57-year-old man presented with subacute-onset paraparesis, bilateral dysesthesia in his lower extremities, and bladder/bowel disturbance six weeks after being infected with SARS-CoV-2 infection (COVID-19). A neurological examination suggested transverse myelitis at the level of the lower thoracic spinal cord. However, repeated spinal magnetic resonance imaging (MRI) showed no abnormalities in the spinal cord. Laboratory and cerebrospinal fluid (CSF) tests ruled out other etiologies of myelitis, eventually suggesting COVID-19-associated myelitis. Aggressive immunosuppressive therapy, started soon after hospitalization, dramatically improved his symptoms. Early aggressive immunosuppressive therapy should therefore be considered in cases of MRI/CSF-negative myelitis associated with COVID-19.

Retropharyngeal abscess due to Fusobacterium necrophorum complicated by progressive internal carotid artery stenosis and multiple cranial nerve palsies.

BACKGROUND: A case of retropharyngeal abscess complicated by both artery and nerve injury has rarely been reported. METHODS: A 36-year-old woman suddenly presented with right eye visual loss, dilated pupil, reduced direct light reflex, ptosis and ocular motility disorder on the side of inflammation progression, and was diagnosed with retropharyngeal abscess due to Fusobacterium necrophorum. The patient was treated only with antibiotics and, no further surgery was necessary but tracheotomy. Four months later, MRA showed right ICA occlusion and left ICA stenosis. MRI revealed continuous spread of inflammation due to the abscess from the retropharyngeal to the intracranial space. RESULTS: These severe complications would be attributed to an endothelial damage to the arterial wall and an ischemic neuropathy caused by inflammation and thrombogenesis due to Fusobacterium necrophorum. CONCLUSIONS: This case should provide a better understanding of the mechanism of vascular and cranial nerve injury due to retropharyngeal infections, and highlights the need for early antibiotic therapy and repeated vascular evaluation.

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.

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.

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.

Urinary Immunoglobulin G Is a Novel Biomarker for Atherosclerotic Burden in Mild Acute Ischemic Stroke Patients.

AIMS: Urinary immunoglobulin G (IgG) may be a stronger marker of atherosclerosis than microalbuminuria are because urinary IgG reflects proteinuria level and size-selectivity loss. Microalbuminuria-not urinary IgG-is associated with mild acute ischemic stroke (MAIS). METHODS: Using the Jikei University School of Medicine Stroke Registry, we selected and screened patients with symptomatic acute ischemic stroke (onset-to-door time ≤ 24 h). The exclusion criteria were (1) on-admission NIHSS scores ＞10, (2) a modified Rankin Scale (mRS) score ≥ 2 prior to stroke onset, (3) incomplete data (no urinalysis ≤ 3 days after admission or no mRS score at 90 days from stroke onset), and (4) an active malignancy. Patients at 90 days post-discharge were divided into those with favorable mRS scores of 0-1 and those with unfavorable mRS scores of 2-6. Clinical backgrounds were compared for (1) patients with positive and negative urinary IgG results, and (2) patients with favorable and unfavorable outcomes. RESULTS: Of our study's 210 patients (164=male, median age=68, median eGFR=53.2 ml/min/1.73 m2), 30 (14%) presented with positive urinary IgG, which was associated with cardiovascular risk factors. Higher BNP, higher D-dimer, lower eGFR, and higher CAVI were associated with higher positive urinary IgG. The favorable group, comprising 155 (74%) patients, had higher negative urinary IgG than the unfavorable group (89% vs 76%, P=0.026). No statistical difference emerged regarding microalbuminuria (29% vs 29%, P=1.000). CONCLUSION: In MAIS, urinary IgG was associated with both the presence of atherosclerosis and an unfavorable outcome at 90 days after stroke onset.

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.