Absence of the Susceptibility Vessel Sign with Cancer-Associated Hypercoagulability-Related Stroke.

BACKGROUND AND PURPOSE: The susceptibility vessel sign, a hypointense signal on MR T2-weighted gradient-recalled echo images, is associated with erythrocyte-predominant thrombi, which are often present in cardioembolism. In contrast, cancer-associated hypercoagulability (CAH)-related stroke, which is presumably caused by fibrin-predominant thrombi, is associated with the absence of the susceptibility vessel sign. We hypothesized that the prevalence of the susceptibility vessel sign may be helpful in distinguishing CAH-related stroke from cardioembolism. This study attempted to validate this hypothesis and investigated the usefulness of the susceptibility vessel sign in differentiating CAH-related stroke from cardioembolism. MATERIALS AND METHODS: We retrospectively studied patients with both CAH-related stroke (CAH group) and cardioembolism (cardioembolism group) who had major cerebral artery occlusion on MRA that was performed within 6 hours of stroke onset. All patients visited our department from 2015 to 2021. CAH-related stroke was defined as the following: 1) complication of active cancer, 2) pretreatment D-dimer value of >3 µg/mL, 3) multiple vascular territory infarctions, and 4) lack of any other specifically identified causes of stroke. We compared susceptibility vessel sign positivity rates within each group. Multivariable logistic regression analysis was used to assess the association between the absence of the susceptibility vessel sign and CAH-related stroke. RESULTS: Of 691 patients with CAH-related stroke or cardioembolism, major cerebral artery occlusion was observed in 10 patients in the CAH group and 198 patients in the cardioembolism group. The absence of the susceptibility vessel sign was identified in 55 of 208 patients and was significantly more frequent in the CAH group versus the cardioembolism group (90% versus 24%, P < .05). For predicting CAH-related stroke, the absence of the susceptibility vessel sign demonstrated a sensitivity of 90% (95% CI, 59%-99%), specificity of 78% (95% CI, 71%-83%), a positive predictive value of 18% (95% CI, 10-31), a negative predictive value of 99% (95% CI, 96%-99%), and a likelihood ratio of 4.06. Multivariable logistic regression analysis revealed that the absence of the susceptibility vessel sign was independently associated with CAH-related stroke (OR, 43; 95% CI, 6.8-863; P < .01). CONCLUSIONS: The absence of the susceptibility vessel sign was more frequent in CAH-related stroke than in cardioembolism. These findings could potentially be helpful for clinical management and differentiating cardioembolism and CAH-related stroke.

Effects of preceding antiplatelet agents on severity of ischemic stroke in patients with a history of stroke.

INTRODUCTION: Antiplatelet agents are effective for secondary prevention of ischemic stroke and can reduce the severity of first-ever ischemic stroke. However, it is uncertain if prophylactic antiplatelet therapy reduces the severity of recurrent ischemic stroke. The aim of this study was to determine the effect of preceding antiplatelet treatment on the severity of thrombotic stroke (TS) in patients with a prior history of stroke. METHODS: From a prospective hospital registry of 1338 consecutive patients with acute ischemic stroke, we identified patients with a prior history of stroke who were admitted for cardioembolic stroke (CE); TS including large-artery atherosclerosis, small vessel occlusion, and branch atheromatous disease; or other cause or cryptogenic stroke (OCS). Cases in each subtype were categorized based on preceding medication: antiplatelet agents (AP) and none (N). Severity of stroke (National Institutes of Health Stroke Scale: NIHSS) on admission was compared between AP and N cases. RESULTS: The total cohort of 252 patients included 83 with CE, 102 with TS, and 67 with OCS. After excluding those with prior anticoagulants, the median NIHSS on admission was lower in AP cases than in N cases (3 vs. 5, p = 0.002). In multivariate analysis, preceding AP treatment was independently associated with minor stroke (NIHSS ≤4) on admission in CE group (OR 8.48, 95% CI 1.71-62.9, p = 0.008) and TS group (OR 4.24, 95% CI 1.44-13.4, p = 0.009). CONCLUSION: Preceding antiplatelet treatment in patients with a prior history of stroke may reduce the severity of subsequent thrombotic and cardiogenic stroke.

Early Recurrence in Patients with Symptomatic, Non-Cardioembolic, Internal Carotid Artery Occlusion.

INTRODUCTION: There are limited data on the clinical course of patients with non-cardioembolic, mostly atherosclerotic, internal carotid artery occlusion (ICAO). The purpose of this study was to elucidate the frequency and underlying pathogenesis of early recurrent ischemic stroke in symptomatic non-cardioembolic ICAO. MATERIALS AND METHODS: Consecutive patients with symptomatic non-cardioembolic ICAO were retrospectively reviewed. Those who had a tandem occlusion of the proximal middle cerebral artery (MCA) or underwent endovascular thrombectomy were excluded. Early recurrent stroke was defined as deterioration of the NIHSS score by ≥1 point with new lesions on magnetic resonance (MR) diffusion-weighted imaging (DWI) in the ipsilateral territory of the ICAO within 30 days of the index stroke onset. Patients were classified into two groups on carotid ultrasonography: cervical occlusion and intracranial occlusion. The presumed pathogenesis of recurrent stroke was categorized as embolic or hemodynamic according to the topographical features of subsequent lesions on DWI. RESULTS: Of 36 consecutive medically treated patients with symptomatic non-cardioembolic ICAO without tandem MCA occlusion, 23 patients had cervical occlusion, and 13 had intracranial occlusion. Early recurrent stroke occurred in 16 patients (44.4%), which happened much more with intracranial occlusion than with cervical occlusion (69.2% vs 30.4%, p<0.02). Focusing on the presumed pathogenesis, hemodynamic was more common than embolic (68.8% vs 31.2%), especially with intracranial occlusion (77.8%). CONCLUSIONS: Early recurrent stroke occurs at a high frequency in symptomatic non-cardioembolic ICAO, and intracranial occlusion may be a risk factor for early recurrent stroke. The pathogenesis of recurrence is more often hemodynamic than embolic.

Long-term effectiveness of anticoagulants in oldest-old stroke survivors with atrial fibrillation.

BACKGROUND: Long-term anticoagulant therapy in oldest-old persons poses the risk of bleeding complications. The aim of this study was to evaluate the long-term benefits of anticoagulant therapy for oldest-old stroke survivors with AF. METHODS: Patients with atrial fibrillation (AF) who were 90 years of age or older and were prescribed an anticoagulant on discharge were identified from a set of data from a prospective follow-up registry of 1,484 consecutive patients admitted for ischemic stroke or transient ischemic attack over a 4-year period beginning in 2014. The outcome measures were stroke and death following discharge. RESULTS: Of the 77 identified patients with AF who were 90 years of age or older, 71 were prescribed an anticoagulant (median age 93 years, 73% women). Thirty-nine patients were given a direct oral anticoagulant (DOAC) (median age 92 years, 69% women), and 32 were given warfarin (median age 93 years, 78% women). During the follow-up period (median 466 days), 9 patients (13%) had stroke recurrence (recurrence rate: 14%/year), and 25 patients (35%) died (mortality rate: 33%/year). The type of all recurrent strokes was ischemic, and no fatal bleeding occurred. There was no difference in the incidence of recurrent strokes according to anticoagulant type (DOAC 15%/year, warfarin 13%/year, P = 0.743), but a higher proportion of patients on warfarin died (21% vs. 47%, P = 0.002). CONCLUSIONS: Given that a higher proportion of oldest-old stroke survivors with AF on anticoagulant therapy have recurrent ischemic stroke rather than hemorrhagic stroke, long-term anticoagulant therapy may be justified for secondary stroke prevention.

Progressive Encephalomyelitis with Rigidity and Myoclonus (PERM)-like Symptoms Associated with Anti-ganglionic Acetylcholine Receptor Antibodies.

This report describes a 59-year-old woman who presented with progressive encephalomyelitis with rigidity and myoclonus (PERM)-like symptoms and severe dysautonomia, including orthostatic hypotension, sinus bradycardia, dysuria, and prolonged constipation. Her neurological symptoms improved after immunotherapy, but the dysautonomia persisted. Anti-ganglionic acetylcholine receptor (gAChR) α3 subunit antibodies, which are frequently identified in patients with autoimmune autonomic ganglionopathy, were detected in the pre-treatment serum. The central distribution of the nicotinic acetylcholine receptors, a target of anti-gAChR antibodies, and immunotherapeutic efficacy observed in this case indicate that anti-gAChR α3 subunit antibodies are associated with the PERM-like features accompanied by autonomic manifestations.

Autoimmune Encephalitis Associated with Anti-gamma-aminobutyric Acid B Receptor Antibodies Mimicking Syncope.

Autoimmune encephalitis associated with autoantibodies to the gamma-aminobutyric acid B receptor (GABABR-AE) typically involves limbic symptoms with limbic abnormalities visible in brain magnetic resonance imaging (MRI). We herein report a case of a 48-year-old man with GABABR-AE whose initial presentation was limited to syncope without limbic symptoms or MRI abnormalities. Interestingly, serial MRI also revealed no abnormalities even after the appearance of limbic symptoms. Our findings suggest that GABABR-AE can initially mimic common syncope and that MRI findings may remain normal throughout the clinical course. Even if patients have normal MRI findings, GABABR-AE should be considered if limbic symptoms worsen.

Serial brain MRI changes related to autoimmune pathophysiology in Hashimoto encephalopathy with anti-NAE antibodies: A case-series study.

PURPOSE: Hashimoto encephalopathy (HE) is an autoimmune-mediated encephalopathy associated with anti-thyroid antibodies. We previously discovered serum autoantibodies against the NH2-terminal of α-enolase (NAE), which serve as a specific diagnostic biomarker for HE and may be involved in the autoimmune pathophysiology of HE, including vasculitis. Although the common findings of brain magnetic resonance imaging (MRI) in HE have been recognized as normal or non-specific white matter lesions, serial MRI changes have been less well studied. The aim of this study was to clarify detailed and longitudinal MRI changes in HE associated with anti-NAE antibodies. METHODS: We investigated serial brain MR images in 12 Japanese patients with HE who had serum anti-NAE antibodies. RESULTS: Brain MRI showed diffuse white matter abnormalities and/or multiple small subcortical lesions in 10 patients. These lesions were apparently non-specific; however, in 7 of these patients we observed expanding and diminishing white matter lesions, emerging subcortical high-intensity spots on diffusion-weighted images, or reversible limbic lesions, which worsened at relapse and improved after recovery following immunotherapies. CONCLUSION: MRI lesions that fluctuate according to the disease condition were frequently observed in HE patients with anti-NAE antibodies, which suggests that these fluctuation may be associated with the autoimmune pathophysiology of HE.

Limbic encephalitis associated with anti-NH2-terminal of α-enolase antibodies: A clinical subtype of Hashimoto encephalopathy.

Several types of autoantibodies have been reported in autoimmune limbic encephalitis (LE), such as antibodies against the voltage-gated potassium channel (VGKC) complex including leucine-rich glioma inactivated 1 (LGI1). We recently reported a patient with autoimmune LE and serum anti-NH2-terminal of α-enolase (NAE) antibodies, a specific diagnostic marker for Hashimoto encephalopathy (HE), who was diagnosed with HE based on the presence of antithyroid antibodies and responsiveness to immunotherapy. This case suggests that LE patients with antibodies to both the thyroid and NAE could be diagnosed with HE and respond to immunotherapy. The aim of this study was to clarify the clinicoimmunological features and efficacy of immunotherapy in LE associated with anti-NAE antibodies to determine whether the LE is a clinical subtype of HE.We examined serum anti-NAE antibodies in 78 LE patients with limbic abnormality on magnetic resonance imaging and suspected HE based on positivity for antithyroid antibodies. Nineteen of the 78 patients had anti-NAE antibodies; however, 5 were excluded because they were double positive for antibodies to the VGKC complex including LGI1. No antibodies against the N-methyl-D-aspartate receptor (NMDAR), contactin-associated protein 2 (Caspr2), γ-aminobutyric acid-B receptor (GABABR), or α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) were detected in the 19 patients. Among the remaining 14 who were positive only for anti-NAE antibodies, the median age was 62.5 (20-83) years, 9 (64%) were women, and 8 (57%) showed acute onset, with less than 2 weeks between onset and admission. Consciousness disturbance (71%) and memory disturbance (64%) were frequently observed, followed by psychiatric symptoms (50%) and seizures (43%). The frequency of these symptoms significantly differed between the acute- and subacute-onset groups. Abnormalities in cerebrospinal fluid and electroencephalogram were commonly observed (92% for both). Tumors were not identified in any cases. All patients responded to immunotherapy or spontaneously remitted, thereby fulfilling the criteria of HE.This study demonstrated that LE associated with anti-NAE antibodies is a nonparaneoplastic LE and various limbic symptoms that depend on the onset type. Favorable therapeutic efficacy suggests that this LE can be considered a clinical subtype of HE and that anti-NAE antibodies may be a promising indicator of the need for immunotherapy.

[A long-term follow up of right ophthalmoplegia and severe right middle cerebral artery stenosis with right herpes zoster ophthalmics: a case report].

Here we report a case of a 68-year-old man with severe stenosis of the right middle cerebral artery (MCA) following herpes zoster ophthalmicus. He presented with right-sided ptosis and ophthalmoplegia 2 months after herpes zoster ophthalmicus. Cerebrospinal fluid (CSF) analysis revealed monocytosis, increased protein levels, and positivity for herpes zoster virus immunoglobulin M (IgM). Brain magnetic resonance imaging (MRI) revealed a small asymptomatic infarct in the right basal ganglia and severe stenosis of the right MCA (M1 segment). One month later, he presented with muscle weakness of the fingers of the left hand. Repeat CSF analysis revealed similar abnormalities to the previous analysis, and MRI showed a new small infarct in the right-sided motor area corresponding to the left fingers. He was treated with acyclovir (750 mg/day), prednisolone (1 mg/kg/day), and aspirin (100 mg/day). O2-gas positron emission tomography (PET) revealed decreased cerebral blood flow (CBF) after acetazolamide injection and normal cerebral vascular reactivity (CVR). He was on continuous treatment with prednisolone and aspirin for 1 year. The muscle weakness of the fingers of the left hand and right-sided ophthalmoplegia improved, and magnetic resonance angiography revealed considerable decrease in the stenosis of the right middle cerebral artery. CBF before and after acetazolamide injection and CVR on O2-gas PET also normalized. These results suggested that long-term treatment may prevent subsequent infarcts following herpes zoster ophthalmics.

[The biomarker and treatment in Hashimoto's encephalopahty].

Hashimoto's encephalopathy (HE) is a treatable disease based on autoimmune mechanisms associated with Hashimoto's thyroiditis. We recently discovered the serum autoantibodies (Abs) against the NH2-terminal of alpha-enolase (NAE) as a diagnostic biomarker for HE. The serum anti-NAE Abs are not detected in normal individuals and other disorders such as infections, collagen diseases, multiple sclerosis and other autoimmune conditions. The specificity of the serum anti-NAE Abs is 91% for HE whereas the sensitivity is 50%. In our clinical study of 80 cases of HE with anti-NAE Abs, the acute encephalopathic form was the most common clinical feature, and followed by chronic psychiatric form and progressive ataxia form. The common neuropsychiatric features were consciousness disturbance, psychosis (especially delirium and hallucination), seizures and dementia. Abnormalities on EEG and decreased blood flow on SPECT were common while abnormalities on brain MRI were rare. The early diagnosis and treatment for HE could lead to good recovery from the disease. Taken together, the serum anti-NAE Abs are a useful diagnostic biomarker for HE.