Longitudinal Changes in Iron and Myelination Within Ischemic Lesions Associate With Neurological Outcomes: A Pilot Study.

BACKGROUND: Combined quantitative susceptibility mapping and R2* relaxometry can distinguish iron and myelin components in ischemic lesions. We aimed to investigate whether longitudinal changes in magnetic susceptibility and R2* values within ischemic lesions were associated with neurological outcomes. METHODS: In this single-center prospective study, we included patients, 20 to 90 years of age, who were consecutively admitted to the stroke care unit between August 2020 and March 2022 due to acute ischemic stroke. The participants underwent 2 instances of quantitative susceptibility mapping and R2* relaxometry scanning before and after stroke rehabilitation. We compared the changes in these quantitative measures across different subtypes of acute ischemic stroke. Multiple linear regression models were used to investigate the associations between the National Institutes of Health Stroke Scale scores and the mean magnetic susceptibility and R2* values in ischemic lesions. RESULTS: Among a total of 112 patients with acute ischemic stroke, 32 participants (aged 73.3±9.4 years; 20 men and 12 women) were evaluated. The median time from stroke onset to the first imaging was 5 days and that to the second imaging was 102 days. The changes in magnetic susceptibility values of branch atheromatous disease were higher than those of cardioembolism (mean difference, 0.018 [95% CI, 0.009-0.027] ppm; P<0.001) and lacunar (mean difference, 0.013 [95% CI, 0.005-0.020] ppm; P=0.004). Across all patients, the changes in National Institutes of Health Stroke Scale scores were associated with those of magnetic susceptibility values (coefficient, 0.311 [95% CI, 0.098-0.520]; P=0.017) but not with R2* values (coefficient, 0.114 [95% CI, -0.127 to 0.345]; P=0.291). CONCLUSIONS: The longitudinal changes in the magnetic susceptibility values within ischemic lesions were associated with neurological outcomes during the restorative stages poststroke in patients experiencing acute ischemic stroke. REGISTRATION: URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000050719.

A Case of Posterior Circulation Embolism Due to a Subtype of Bow Hunter's Syndrome Diagnosed by Non-Invasive Examination.

Bow hunter's syndrome is the mechanical compression of the vertebral artery due to cervical rotation, resulting in ischemic symptoms in the vertebrobasilar artery territory. However, some cases present without typical symptoms and exhibit compression of the non-dominant side of the vertebral artery. We encountered a case of posterior circulation embolism due to a subtype of bow hunter's syndrome in a 74-year-old man. Although the right vertebral artery was not visualized on time-of-flight magnetic resonance angiography in the neutral position, duplex ultrasonography and time-of-flight magnetic resonance angiography in the left cervical rotation position showed blood flow in the right vertebral artery. In this case, blood flow in the contralateral vertebral artery was normal, and typical bow hunter's syndrome symptoms did not occur. In a case of posterior circulation embolism with undetermined etiology, wherein the routine duplex ultrasonography and time-of-flight magnetic resonance angiography results were inconclusive, additional testing with head positioning led to the diagnosis of a subtype of bow hunter's syndrome.

Quantitative arterial spin labeling magnetic resonance imaging analysis of reversible cerebral vasoconstriction syndrome: A case series.

OBJECTIVE: This study aimed to quantify chronological cerebral blood flow (CBF) changes using arterial spin labeling (ASL) magnetic resonance imaging in patients with reversible cerebral vasoconstriction syndrome (RCVS). BACKGROUND: Quantitative ASL analyses in RCVS have not been well described in the literature. METHODS: Quantification of ASL using an automated region-of-interest placement software and a 5-point visual scale of vasoconstriction severity was performed in five RCVS patients. The association between CBF changes and RCVS-related complications was evaluated. RESULTS: Quantitative ASL revealed variable patterns of decreasing CBF in the first week, followed by subsequent increases. Notably, arterial vasoconstriction paradoxically progressed despite an increase in CBF from the first to the second week; this increase was relatively higher in patients with both cortical subarachnoid hemorrhage and posterior reversible encephalopathy syndrome. CONCLUSIONS: Quantitative ASL revealed that CBF initially decreased and subsequently increased, especially in the second week. These changes may serve as surrogate imaging markers for RCVS-related complications, and could further contribute to understanding the pathology of RCVS.

First case report of fungal meningitis due to a polypore mushroom Irpex lacteus.

A 73-year-old Japanese man with a medical history of sarcoidosis was diagnosed with meningitis caused by an undetermined fungus. For further identification, the cerebrospinal fluid sample was analyzed for the rDNA internally transcribed spacer regions, and the fungus was identified as Irpex lacteus. I. lacteus is classified under phylum Basidiomycota and is a wood-rotting bracket mushroom. Although there is no standard treatment regimen for I. lacteus infections, amphotericin B was effective in this patient. Herein, we present, to our knowledge, the first reported case of fungal meningitis caused by I. lacteus, its treatment course, and review relevant published literature.

Reproducible Presyncope Due to Osteophyte Compression Into Transverse Foramen of the C5 Vertebra.

Beauty parlor stroke syndrome is characterized by the development of various neurological symptoms during cervical hyperextension, followed by inadequate blood flow through the posterior circulation of the brain. However, there are few reports of beauty parlor stroke syndrome wherein the cause of the posterior circulatory inadequacy has been directly identified. Here we report a case where we could directly detect the origin of the posterior circulatory inadequacy. A 76-year-old Japanese man with hypertension presented with presyncope following cervical retroflexion. Head magnetic resonance angiography revealed that the vertebrobasilar circulation was exclusively supplied by the right vertebral artery. Cervical spine computed tomography showed compression of the osteophytes on the right superior articular process of C6 into the right transverse foramen of C5. Moreover, computed tomography angiography and carotid duplex ultrasonography showed decreased blood flow in the right vertebral artery on gradual retroflexion of the neck. Based on the above findings, we speculate that the right vertebral artery was compressed by the osteophytes, with the decreased blood flow being the cause of presyncope following cervical retroflexion.

Importance of Chronological Changes on High-Resolution Vessel Wall Imaging for Diagnosis of Isolated Anterior Cerebral Artery Dissection.

INTRODUCTION: The accurate diagnosis of isolated anterior cerebral artery dissection (iACA-D) is made difficult by the spatial resolution on conventional magnetic resonance imaging (MRI) techniques including time-of-flight magnetic resonance angiography that is too limited to detect minute arterial wall abnormalities. Recent advances in high-resolution vessel wall imaging (HRVWI), which can detect intramural hematomas (IMH), have improved the noninvasive diagnostic accuracy of iACA-D. However, despite the risk of overlooking minute IMH and aneurysmal dilations especially at the early disease stage, the utility of T1-weighted and T2-weighted HRVWI at each disease stage (i.e., acute, early subacute, late subacute and chronic) has not been evaluated thoroughly enough. This prompted us to undertake the present study to determine the diagnostic value of chronological changes of IMHs on T1-weighted HRVWI and arterial dilations on T2-weighted HRVWI to achieve the earliest possible and most accurate diagnosis of iACA-D. METHODS: In addition to six patients with iACA-D, five previously reported iACA-D patients from three institutions for whom reliable information on HRVWI and its examination date was available were enrolled in this study. IMHs on T1-weighted HRVWI and aneurysmal dilations on T2-weighted HRVWI and their chronological changes were visually evaluated. RESULTS: Either or both of IMHs on T1-weighted HRVWI and aneurysmal dilations on T2-weighted HRVWI were detected in all our six patients and the five previously reported ones. The disease stage showed a notable influence on the degree of their visualization. In contrast to IMHs which are regarded as the gold standard for the diagnosis of intracranial dissections, aneurysmal dilations were identified in 80% of cases even at the acute stage, reaching 100% at the early subacute stage. Despite the excellent detection rate of IMHs at the late subacute stage (100%), their detectability is poor at the acute and early subacute stages (0 and 40%, respectively). CONCLUSION: The results of this study highlighted the importance of aneurysmal dilations on T2-weighted HRVWI as a diagnostic marker to raise suspicion of iACA-D at the acute and early subacute stages, and similarly IMHs on T1-weighted HRVWI to confirm the diagnosis of iACA-D at the late subacute stage. These stage-dependent detectability changes in IMHs and aneurysmal dilations make an understanding of the chronological changes of these abnormal imaging findings mandatory to achieve an early and accurate diagnosis of iACA-D.

Optical coherence tomography findings in acute myocardial infarction patients with familial moyamoya disease.

It has been reported that patients with moyamoya disease have a high prevalence of coronary artery disease. On the other hand, the pathology of coronary artery disease is not fully understood. We were able to evaluate vascular properties using optical coherence tomography in a case of acute myocardial infarction that occurred in a relatively young woman with moyamoya disease. Previous reports using intravascular ultrasound have shown that coronary artery lesions in patients with moyamoya disease are caused by fibrous cell proliferation. Optical coherence tomography of our case showed a fibrous plaque rich in macrophages and a lipidic plaque. We believe that our case may lead to elucidation of the etiology of coronary artery disease in patients with moyamoya disease. Learning objective: It is known that patients with moyamoya disease develop coronary artery disease at a young age, but the etiology has not been clarified. We used optical coherence tomography to evaluate the intravascular conditions of coronary artery disease patients with moyamoya disease. The lesions of coronary artery disease associated with moyamoya disease were mainly arteriosclerotic lesions rich in inflammation.

Assessing white matter microstructural changes in idiopathic normal pressure hydrocephalus using voxel-based R2* relaxometry analysis.

Background: R2* relaxometry and quantitative susceptibility mapping can be combined to distinguish between microstructural changes and iron deposition in white matter. Here, we aimed to explore microstructural changes in the white matter associated with clinical presentations such as cognitive impairment in patients with idiopathic normal-pressure hydrocephalus (iNPH) using R2* relaxometry analysis in combination with quantitative susceptibility mapping. Methods: We evaluated 16 patients clinically diagnosed with possible or probable iNPH and 18 matched healthy controls (HC) who were chosen based on similarity in age and sex. R2* and quantitative susceptibility mapping were compared using voxel-wise and atlas-based one-way analysis of covariance (ANCOVA). Finally, partial correlation analyses were performed to assess the relationship between R2* and clinical presentations. Results: R2* was lower in some white matter regions, including the bilateral superior longitudinal fascicle and sagittal stratum, in the iNPH group compared to the HC group. The voxel-based quantitative susceptibility mapping results did not differ between the groups. The atlas-based group comparisons yielded negative mean susceptibility values in almost all brain regions, indicating no clear paramagnetic iron deposition in the white matter of any subject. R2* and cognitive performance scores between the left superior longitudinal fasciculus (SLF) and right sagittal stratum (SS) were positively correlated. In addition to that, R2* and gait disturbance scores between left SS were negatively correlated. Conclusion: Our analysis highlights the microstructural changes without iron deposition in the SLF and SS, and their association with cognitive impairment and gait disturbance in patients with iNPH.

Penumbra Detection With Oxygen Extraction Fraction Using Magnetic Susceptibility in Patients With Acute Ischemic Stroke.

BACKGROUND: The oxygen extraction fraction (OEF) has been applied to identify ischemic penumbral tissue, but is difficult to use in an urgent care setting. This study aimed to investigate whether an OEF map generated via magnetic resonance quantitative susceptibility mapping (QSM) could help identify the ischemic penumbra in patients with acute ischemic stroke. MATERIALS AND METHODS: This prospective imaging study included 21 patients with large anterior circulation vessel occlusion who were admitted <24 h after stroke onset and 21 age-matched healthy controls. We identified the ischemic penumbra as the region with a Tmax of >6 s during dynamic susceptibility contrast-magnetic resonance imaging (DSC-MRI) and calculated the perfusion-core mismatch ratio between the ischemic penumbra and infarct core volumes. The OEF values were measured based on magnetic susceptibility differences between the venous structures and brain tissues using rapid QSM acquisition. Volumes with increased OEF values were compared to the ischemic penumbra volumes using an anatomical template. RESULTS: Eleven patients had a perfusion-core mismatch ratio of ≥1.8, and reperfusion therapy was recommended. In these patients, the volumes with increased OEF values of >51.5%, which was defined using the anterior circulation territory OEF values from the 21 healthy controls, were positively correlated with the ischemic penumbra volumes (r = 0.636, 95% CI: 0.059 to 0.895, P = 0.035) and inversely correlated with the 30-day change in the National Institutes of Health Stroke Scale scores (r = -0.624, 95% CI: -0.891 to -0.039, P = 0.041). CONCLUSION: Tissue volumes with increased OEF values could predict ischemic penumbra volumes based on DSC-MRI, highlighting the potential of the QSM-derived OEF map as a penumbra biomarker to guide treatment selection in patients with acute ischemic stroke.

[Varicella-zoster meningoencephalitis and vasculitis after treatment with amenamevir to herpes zoster in the trigeminal nerve area].

A 78-year-old woman was diagnosed with herpes zoster in the first branch of the trigeminal nerve and was treated with amenamevir. Subsequently, she was hospitalized for postherpetic neuralgia. Fever and unconsciousness were observed, and a diagnosis of varicella-zoster virus meningoencephalitis and vasculitis was made. In addition to the antithrombotic therapy, she was treated with intravenous acyclovir and steroid pulse therapy; however, her unconsciousness persisted. Amenamevir was not transferrable to the spinal fluid and resulted in an incomplete treatment of herpes zoster in the cerebral nerve region, suggesting that this case may be related to the severe course of the disease.

Severe Measles Encephalitis and Acute Disseminated Encephalomyelitis in an Immunocompetent Japanese Young Male.

Measles encephalitis rarely affects young adults and has no established treatment strategy. This brief report described the rare case of an immunocompetent 30-year-old man with severe measles pneumonia and encephalitis, following the autoimmune disease acute disseminated encephalomyelitis, during a large measles outbreak in 2018 in Japan. With multidisciplinary treatments, including corticosteroids, intravenous immunoglobulins, vitamin A, and therapeutic plasma exchange, the patient was successfully treated. This case provides a new strategy for treating measles encephalitis and its complications during measles outbreak.

Heterozygous Cysteine-sparing NOTCH3 Variant p.Val237Met in a Japanese Patient with Suspected Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy.

A 64-year-old Japanese man with recurrent cerebral ischemic events and cognitive impairment was suspected of having cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) because of a family history and brain magnetic resonance imaging findings of cerebral white matter hyperintensities. The cysteine-sparing variation p.Val237Met was identified in NOTCH3. An intensive skin biopsy showed negative results (no granular osmiophilic material or positive NOTCH3 immunostaining), suggesting that the patient's definite diagnosis and pathogenicity of p.Val237Met were uncertain. We additionally reviewed previous reports of two Japanese families with p.Val237Met.

[Confusional migraine in a young adult female: Is it a subtype of migraine with aura?]

A 22-year-old female was admitted to our hospital due to acute onset of severe headache, confusion, and deterioration of consciousness. Results of initial examinations did not suggest cerebrovascular diseases, encephalitis, or nonconvulsive status epilepticus. Over the next several weeks, her level of consciousness fluctuated in parallel with the severity of headache. The electroencephalogram, recorded during a symptomatic episode, showed lack of posterior dominant rhythm, and the single-photon emission CT (SPECT) also revealed a decrease in cerebral blood flow predominantly in the occipital lobes. Administration of sodium valproate and topiramate, recommended as treatment for migraine, dramatically ameliorated her headache and consciousness. Although this was an adult-onset case, her symptoms and clinical course were similar with the diagnosis of ICHD-3-unlisted confusional migraine rather than other listed subtypes of migraine with aura. Further accumulation of similar adult-onset cases is necessary to clarify the nature of this illness.

Utility of T2-weighted high-resolution vessel wall imaging for the diagnosis of isolated posterior inferior cerebellar artery dissection at acute and early subacute stages.

Recent advances in magnetic resonance high-resolution vessel wall imaging (HRVWI), which can detect intramural hematomas (IMH), improve the noninvasive diagnostic accuracy of isolated posterior inferior cerebellar artery dissection (iPICA-D). However, despite the risk of overlooking minute IMH, the utility of T2-weighted HRVWI has not been thoroughly evaluated. This study aimed to compare the utility of T2-weighted HRVWI with that of T1-weighted HRVWI, basiparallel anatomical scanning (BPAS), and magnetic resonance angiography (MRA) for the diagnosis of iPICA-D mainly in the acute and early subacute stages in 6 iPICA-D patients (three acute, two early subacute and one late subacute stages on initial examinations). Dissection-related abnormalities included IMH on T1-weighted HRVWI, aneurysmal dilations on T2-weighted HRVWI and discrepancy between BPAS and MRA. On initial examinations, T2-weighted HRVWI revealed iPICA-D-related abnormalities more conspicuously than did T1-weighted HRVWI and combination of BPAS and MRA. Except in a single case with a discrepancy between the outer contour on BPAS and inner contour on MRA, no specific abnormalities were detected besides T2-weighted HRVWI at acute or early subacute stages. In addition to T1-weighted HRVWI, BPAS and MRA, T2-weighted HRVWI should be performed to diagnose acute and early subacute iPICA-D.

[Multiple mononeuropathy associated with systemic sclerosis with vasculitis confirmed by nerve biopsy: a case report].

A 68-year-old woman with a medical history of interstitial pneumonia associated with systemic sclerosis (SSc) presented with numbness of the lower limbs and left drop foot. She was diagnosed with multiple mononeuropathy based on the laterality of her symptoms, muscle weakness, thermal hypoalgesia, and nerve conduction study findings. Left sural nerve biopsy showed vasculitis, and steroid therapy was effective. This case highlights the importance of histopathological assessment to select an appropriate treatment strategy.

Endovascular Intervention in Basilar Artery Entrapment within the Longitudinal Clivus Fracture: A Case Report.

Although vascular complications after head trauma is well recognized, basilar artery entrapment within the longitudinal clivus fracture is rare. A 69-year-old man presented with progressive disturbance of consciousness and right hemiplegia after trauma. Computed tomography scan showed a right-sided acute subdural hematoma and multiple skull fractures, including a longitudinal clivus fracture. Magnetic resonance imaging revealed basilar artery occlusion and a small infarction at the ventral part of the pons. On the assumption of acute arterial occlusion caused by thrombus, endovascular thrombectomy was attempted, but resulted in perforation. After the procedure, basilar artery entrapment within the longitudinal clivus fracture turned out to be the cause of the occlusion. The present case suggests that basilar artery entrapment within the longitudinal clivus fracture is a possible cause of neurological deficits after trauma. In this subset, endovascular intervention without a correct diagnosis of this phenomenon is high risk.

[Idiopathic CD4-positive lymphocytopenia-associated progressive multifocal leukoencephalopathy confirmed by brain biopsy following negative results of repeated CSF-JC-virus tests: a case report].

A 75-year-old man presented with dysarthria and left facial paralysis. Brain diffusion-weighted MRI revealed a high-signal intensity in the right precentral gyrus, and he was hospitalized under the diagnosis of cerebral infarction. His symptoms worsened and brain MRI findings were consistent with progressive multifocal leukoencephalopathy (PML). Cerebrospinal fluid (CSF) JC virus (JCV) was undetectable in the DNA polymerase chain reaction (PCR) test four times, but brain biopsy revealed typical PML histopathology. He had no human immunodeficiency virus infection and history of immunosuppressive treatment, but he was found to have CD4+ lymphocytopenia. He was treated with mefloquine and mirtazapine, and died 29 months after symptoms onset. In cases whose repeated DNA PCR results are negative for CSF JCV, brain biopsy may be useful for the diagnosis of PML.

Effects of Paraoxonase 1 gene polymorphisms on organophosphate insecticide metabolism in Japanese pest control workers.

OBJECTIVES: Paraoxonase 1 (PON1) in serum detoxifies organophosphate (OP) insecticides by hydrolysis. The present cross-sectional study aimed to clarify the relationship between PON1 single nucleotide polymorphisms (SNPs) and enzyme activities or OP metabolite concentrations in urine of workers occupationally exposed to low-level OPs. METHODS: Among 283 workers in 10 pest control companies located in central Japan who underwent checkups, 230 subjects (male 199, female 31, average age 38.9 ± 11.1 years old) participated in the study. Q192R and L55M polymorphisms were determined by TaqMan assay. PON1 activity was measured using fenitrothion (FNT) oxon, chlorpyrifos-methyl (CPM) oxon, chlorpyrifos (CP) oxon, and phenyl acetate as substrates. Urinary OP metabolite concentrations were measured with gas chromatography-mass spectrometry. RESULTS: The maximum differences in enzyme activities between individuals were 64.6-, 6.3-, 7.7-, and 2.0-fold for FNT oxonase, CPM oxonase, CP oxonase, and arylesterase (ARE), respectively. The activities of CPM oxonase and ARE in workers having the RR genotype were 53.5% and 18.2% lower than in those with the QQ genotype, respectively. CP oxonase activity was 15.0% lower in those having the M allele (LM + MM compared with LL). Urinary metabolite concentrations were not associated with PON1 polymorphisms, but negative associations were observed between the concentrations and activities of FNT oxonase and ARE. CONCLUSIONS: While PON1 SNPs can explain differences in catalytic activities toward some OPs, differences in urinary concentrations of OP metabolites are not attributable to PON1 SNPs but instead are attributable to its serum activities. Its serum activities might be more sensitive biomarkers for estimation of individual susceptibility to OP toxicities.