Asymptomatic acute ischemic lesions in intracerebral hemorrhage: Its frequency, MRI features, and risk factors.

BACKGROUND: Asymptomatic acute ischemic lesions (AIL) may be coincidentally found on brain magnetic resonance imaging (MRI) obtained during the acute phase of intracerebral hemorrhage, but its clinical significance has yet to be determined. The objective of this study is to determine the frequency of asymptomatic AIL, its characteristic features of brain MRI and risk factors in patients with acute intracerebral hemorrhage. METHODS: We retrospectively reviewed the clinical information of 108 patients with intracerebral hemorrhage who underwent brain MRIs within 30 days of hospitalization between April 2013 and January 2018. We determined the frequency of asymptomatic AIL, its brain MRI features, and risk factors. RESULTS: AIL was found in 26 of 108 patients; symptomatic in 2 and asymptomatic in 24 (22.2%). Asymptomatic AIL were small, multiple, mainly distributed to the white matter in the anterior circulation (22/24, 91.7%), and occasionally seen in deep watershed areas (15/24, 62.5%). Only 2 patients had severe major vessel stenosis. Asymptomatic AIL was associated with high mean blood pressure (BP) on admission (> 145 mmHg), excessive drug-induced reduction in mean BP (≥ 55 mmHg), and large hemorrhage (> 31 mL in volume). CONCLUSIONS: Asymptomatic AIL were found in 22.2% of patients with intracerebral hemorrhage within 30 days of hospitalization. Asymptomatic AIL were often small, multiple and occasionally developed in deep watershed areas despite the absence of major vessel stenosis. High mean BP on admission, excessive drug-induced BP reduction, and larger hemorrhage may be a risk factor for development of asymptomatic AIL.

Cholesterol crystal embolism-related cerebral infarction: Magnetic resonance imaging and clinical characteristics.

BACKGROUND AND AIMS: Cholesterol crystal embolism-related cerebral infarction (CCE-CI) is frequently misdiagnosed due to the lack of specific symptoms. To aid in differential diagnosis, this study comprehensively characterized the magnetic resonance imaging (MRI) and clinical manifestations of CCE-CI and compared these features to those of atherothrombotic cerebral infarction (ACI). METHODS: This single-center, retrospective, observational study was conducted at Kitasato University Hospital, Kanagawa, Japan. We identified 37 clinically or histopathologically confirmed CCE-CI cases and 110 ACI cases treated from January 2006 to May 2020. Groups were compared for mean age, sex ratio, clinical presentations, imaging manifestations, precipitating factors, comorbid conditions, medications, and smoking history. RESULTS: Of 37 eligible patients with CCE-CI, 10 (27.0%) received brain MRI, of which 8 (21.6%) exhibited high-intensity signals indicative of brain lesions on diffusion-weighted imaging (DWI). However, two patients with DWI lesions exhibited no detectable neurological abnormalities. Patients with CCE-CI frequently demonstrated bilateral DWI lesions involving the bilateral anterior and posterior circulation, a pattern absent in ACI (50% vs. 0%, p < 0.001). Compared to patients with ACI, CCE-CI patients also demonstrated significantly lower estimated glomerular filtration rate (p < 0.001) as well as more frequent eosinophilia (p = 0.006), atherosclerotic plaques ≥4-mm thick in the ascending aorta or proximal arch (p = 0.001), and aortic aneurysm (p < 0.001). CONCLUSIONS: Patients with CCE-CI develop multiple DWI lesions across several vascular territories, even in the absence of neurological symptoms. Comorbid aortic aneurysm may increase CCE-CI risk. These findings could help in the differential diagnosis of CCE-CI.

A Case of Subcortical Hemorrhage in the Left Temporal Lobe Caused by Multiple Dural Arteriovenous Fistulas.

Transverse sinus-sigmoid sinus (TS-SS) dural arteriovenous fistula (dAVF) is common type of dAVF, on the other hand, anterior condylar confluence (ACC) dAVF is relatively rare. There has been no report presenting patients with TS-SS dAVF and ACC dAVF identified simultaneously yet. We present a case of TS-SS dAVF and ACC dAVF that developed subcortical hemorrhage of left temporal lobe. A 66-year-old woman with no past history was transferred to our hospital for sudden-onset consciousness disturbance, and was urgently admitted after the detection of a subcortical hemorrhage in the left temporal lobe. We suspected a dAVF based on magnetic resonance angiography and performed digital subtraction angiography (DSA). DSA revealed that the left occipital artery, left ascending pharyngeal artery, left middle meningeal artery, left tentorial artery, and posterior meningeal artery flowed into the TS-SS and ACC. DSA also showed outflow from the TS-SS to the brain surface through the vein of Labbé and the vein of Trolard. We performed transvenous embolization to prevent re-bleeding, she was then discharged from our hospital and her remaining sensory aphasia gradually improved. In the present study, the active investigation to determine the cause of subcortical hemorrhage led to a definitive diagnosis. The combination of ACC dAVF and TS-SS dAVF has not been reported thus far and this is considered a valuable case.

Correction to: A cluster of disseminated small cortical lesions in MELAS: its distinctive clinical and neuroimaging features.

The author would like to correct the errors in the publication of the original article. The corrected details are given below for your reading.

A cluster of disseminated small cortical lesions in MELAS: its distinctive clinical and neuroimaging features.

OBJECTIVES: To investigate a diversity of stroke-like episodes (SLEs) in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), and report a disseminated form of SLEs (D-SLEs) attributed to a cluster of disseminated small cortical lesions. METHODS: We retrospectively reviewed the clinical information of 27 MELAS patients seen at Kitasato University Hospital between January 1990 and April 2018. Among those, we selected 13 patients with m.3243A>G mutation [median age at onset, 35 years (11-68 years), two pediatric onset < 17 years] who had at least one SLE. SLEs were classified into classic or non-classic based on characteristic features of stroke-like lesions. RESULTS: 44 SLEs were identified during a median observational period of 119 months (3-240 months). Among those, 29 (65.9%) were classic SLEs (C-SLEs) mainly attributed to a single continuous lobular lesion incongruent to vascular territory and occasionally accompanied by a gradual spread associated with hyperperfusion and persistent seizure activity. The remaining 15 were non-classic attributed to sparsely distributed (n = 10), disseminated (n = 4) or cerebellar lesions (n = 1). C-SLEs developed in all patients but non-classic SLEs in 5; D-SLEs developed in 4 patients accounting for 4 of 44 SLEs (9.1%). Non-classic SLEs developed more frequently in pediatric-onset than in adult-onset patients (12/15 vs. 3/29, p < 0.0001). SLEs began with acute onset of symptoms in 42 SLEs (95.5%), but D-SLEs of 2 adult-onset patients began with ill-defined subacute-onset fluctuating encephalopathy. CONCLUSIONS: This study showed a diversity of SLEs in patients with m.3243A>G mutation. Further studies are required to elucidate the pathophysiological mechanisms of non-classic SLEs including D-SLEs.

Autoimmune Encephalitis as an Extra-articular Manifestation of Rheumatoid Arthritis.

Autoimmune encephalitis (AE) is an immune-mediated encephalitis characterized by the subacute onset of memory deficits, altered mental status, or psychiatric symptoms. Limbic encephalitis associated with rheumatoid arthritis (RA) has not been reported yet. A 57-year-old man presented with the subacute onset of headache, depression, and anorexia 7 months before the onset of RA. Brain magnetic resonance imaging showed symmetric parenchymal lesions involving the medial temporal lobes. He was diagnosed with RA and AE, but no autoantibodies to neuronal intracellular or cell-surface antigens were identified in either the serum or cerebrospinal fluid. His symptoms improved with immunotherapy. AE can develop as an extra-articular manifestation of RA.

Practical issues in measuring autoantibodies to neuronal cell-surface antigens in autoimmune neurological disorders: 190 cases.

OBJECTIVES: To address practical issues in measuring autoantibodies to neuronal cell-surface antigens (NSAs) in various autoimmune neurological disorders (ANDs). METHODS: We retrospectively reviewed the clinical information of 221 patients with clinically suspected ANDs who underwent antibody testing for NSAs between January 2007 and September 2017. 31 were excluded. In 190 patients, antibody-detection rate (ADR) and antibody-phenotype association were assessed. RESULTS: Fifty-four patients had NSA-antibodies: NMDA receptor (NMDAR) (n = 39), AMPA receptor (n = 3), leucine-rich glioma inactivated 1 (LGI1) (n = 3), glycine receptor (GlyR) (n = 3), GABA(A) receptor (n = 2), GABA(B) receptor (n = 1), metabotrophic glutamate receptor 5 (n = 1), or unknown (n = 6); 3 had multiple NSA-antibodies. ADR in patients with diagnostic criteria for "possible autoimmune encephalitis (AE)", "probable anti-NMDAR encephalitis", "definite autoimmune limbic encephalitis (ALE)", and "stiff-person spectrum disorder (SPSD)", was 34% (46/134), 85% (34/40), 46% (11/24), and 22% (4/18), respectively, but NSA-antibodies were not identified in 11 patients with systemic autoimmune disorders (SADs). Among 134 patients with "possible AE" criteria, NMDAR-antibodies were more frequently identified in patients with typical anti-NMDAR encephalitis than those without (34/40 [85%] vs. 4/94 [4%], p < 0.0001). LGI1-antibodies were identified in patients with ALE but not in the others (3/24 [13%] vs. 0/110 [0%], p = 0.005). GlyR-antibodies were identified in those with stiff-person syndrome plus (2/8, 25%) or stiff-limb syndrome (1/6, 17%). CONCLUSIONS: NSA-antibodies were most frequently identified in "probable anti-NMDAR encephalitis", followed by "definite ALE", "possible AE", and "SPSD", but not identified in SADs. NMDAR, LGI1 and GlyR were associated with clinical phenotype. Cell-surface antigens should be determined based on individual phenotype.

Biphasic neurovascular changes in prolonged migraine aura in familial hemiplegic migraine type 2.

OBJECTIVE: To report biphasic changes in cerebral blood flow (CBF) in the acute phase of hemiplegic migraine with prolonged aura (HMPA), in which aura symptoms lasted longer than 24 h, in three patients with familial hemiplegic migraine (FHM) carrying a p.H916L mutation in ATP1A2 gene. METHODS: We assessed neurovascular changes with time in the affected cerebral hemisphere corresponding to aura symptoms during the acute phase of HMPA. Arterial spin labelling MRI, SPECT for CBF measurement and EEG in three attacks, in one attack FDG-PET measurement for cerebral metabolism was performed. We evaluated CBF at different phases of aura symptoms in 11 attacks of HMPA. RESULTS: In two attacks, we found biphasic CBF changes beginning with hypoperfusion followed by persistent hyperperfusion. FDG-PET revealed increased cerebral glucose metabolism in the regions corresponding to hyperperfusion on day 4 when aura symptoms still persisted. In four attacks, Z-score-based CBF mapping revealed multifocal hypoperfusion in the early phase. Hypoperfusion in our study was seen within 19 h of the onset of the symptoms in five of seven attacks, while hyperperfusion was seen 18 h or later in eight of nine attacks. EEG showed attenuated alpha activity without paroxysmal discharge. CONCLUSIONS: This is the first report showing biphasic CBF changes during the prolonged aura of FHM2. This study suggested that the results of cross-sectional CBF studies should be interpreted carefully. Initial multifocal hypoperfusion is likely due to functional depression of multifocal origin in the affected hemisphere, but the mechanism of persistent hyperperfusion requires further investigation.

Factors decreasing caregiver burden to allow patients with cerebrovascular disease to continue in long-term home care.

BACKGROUND: This study attempted to assess continued long-term home care by examining patients' independent activities of daily living (ADLs) and caregivers' free time. METHODS: We surveyed the main caregivers of 52 patients with cerebrovascular disease with continuous home care from 1999 to 2010. Survey items were patients' ADLs, the frequency of use of care services, care requirements, and caregiver sense of burden. We compared the survey results between years. RESULTS: ADLs of excretory control, verbal expression, verbal comprehension, and range of activities showed significant deterioration from 1999 to 2010. Patient need for care increased significantly but use of care services did not. Main caregivers were typically spouses who aged together with the patients. Main caregivers rarely changed; occasionally, a son or daughter-in-law became the main caregiver. Patients typically required less than 3 hours of care daily, which did not change over time. Caregivers had significantly more difficulty maintaining their own health in 2010 than 1999. However, they did not identify increases in difficulties with housework or coping with work. They felt that caregiving was a burden but did not indicate that the family relationship had deteriorated. CONCLUSIONS: Regardless of degree of independence of patients' ADLs, caregiver burden was severe. To decrease caregiver burden, it is necessary to use care services, reduce care time, and allow caregivers free time. In addition, it is possible to continue long-term home care by maintaining their relationships.

RGMa modulates T cell responses and is involved in autoimmune encephalomyelitis.

In multiple sclerosis, activated CD4(+) T cells initiate an immune response in the brain and spinal cord, resulting in demyelination, degeneration and progressive paralysis. Repulsive guidance molecule-a (RGMa) is an axon guidance molecule that has a role in the visual system and in neural tube closure. Our study shows that RGMa is expressed in bone marrow-derived dendritic cells (BMDCs) and that CD4(+) T cells express neogenin, a receptor for RGMa. Binding of RGMa to CD4(+) T cells led to activation of the small GTPase Rap1 and increased adhesion of T cells to intracellular adhesion molecule-1 (ICAM-1). Neutralizing antibodies to RGMa attenuated clinical symptoms of mouse myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) and reduced invasion of inflammatory cells into the CNS. Silencing of RGMa in MOG-pulsed BMDCs reduced their capacity to induce EAE following adoptive transfer to naive C57BL/6 mice. CD4(+) T cells isolated from mice treated with an RGMa-specific antibody showed diminished proliferative responses and reduced interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-4 and IL-17 secretion. Incubation of PBMCs from patients with multiple sclerosis with an RGMa-specific antibody reduced proliferative responses and pro-inflammatory cytokine expression. These results demonstrate that an RGMa-specific antibody suppresses T cell responses, and suggest that RGMa could be a promising molecular target for the treatment of multiple sclerosis.

[A case of pure motor isolated finger palsy due to cerebral infarction].

A 73-year-old man, a right-handed, has been pointed out his atrial fibrillation and seen a doctor regularly for varicose veins of left leg and hypertension. He had complaint of a sudden paralysis of his left thumb and index finger while drinking beer. The next day, there was no improvement and he was admitted to our hospital. Neurological examination revealed mild weakness of the most muscles of both thumb and index finger which were innervated by radial nerve, ulner nerve, and median nerve. But he had no any other neurological deficits including sensory system. A brain MRI revealed the acute-stage cerebral infarction in the right precentral knob. With other examinations, we diagnosed the cerebral infarction as cardiogenic embolism. Pure motor isolated finger palsy (PMIFP) in association with cerebrocortical small lesion is rare. It is probable that some cases with diagnosed of peripheral neuropathy was actually PMIFP from central nervous system disturbance.

Gender differences in long-term functional outcome after first-ever ischemic stroke.

OBJECTIVE: Recent studies have demonstrated gender differences in functional outcome after stroke. However, the underlying reasons for differences have been inconsistent. The present study examined whether gender differences in long-term functional outcomes exist among surviving patients with first-ever ischemic stroke and with individual subtypes of stroke. METHODS: A total of 997 patients (654 men, 343 women) were followed for 5 years after discharge. Patients were assigned to 4 subtypes of ischemic stroke (atherothrombotic, lacunar, cardioembolic and unclassified infarction). Functional outcomes were expressed as locomotor activity, assessed using a questionnaire delivered by mail 1 and 5 years after stroke. Locomotor function was classified into 5 categories according to the grade of disability. RESULTS: Women showed significantly worse locomotor function than men at both 1 and 5 years (p < 0.001 and p < 0.01, respectively). Furthermore, significant gender differences in functional outcome were observed in all subtypes of ischemic stroke at 1 and 5 years after stroke. Logistic regression analysis revealed that gender was a significant determinant for functional outcome at 1 and 5 years after stroke (p < 0.01 and p < 0.001, respectively). No significant gender difference was seen in the rate of stroke recurrence. Women also showed a worse survival ratio after stroke than men (p < 0.01). CONCLUSION: The present study demonstrated significantly worse functional outcomes for women than for men at 1 and 5 years after stroke. Gender differences in long-term functional outcomes by subtypes of ischemic stroke were also significant.