Brain perfusion SPECT in dementia: what radiologists should know.

The findings of brain perfusion single-photon emission computed tomography (SPECT), which detects abnormalities often before changes manifest in morphological imaging, mainly reflect neurodegeneration and contribute to dementia evaluation. A major shift is about to occur in dementia practice to the approach of diagnosing based on biomarkers and treating with disease-modifying drugs. Accordingly, brain perfusion SPECT will be required to serve as a biomarker of neurodegeneration. Hypoperfusion in Alzheimer's disease (AD) is typically seen in the posterior cingulate cortex and precuneus early in the disease, followed by the temporoparietal cortices. On the other hand, atypical presentations of AD such as the posterior variant, logopenic variant, frontal variant, and corticobasal syndrome exhibit hypoperfusion in areas related to symptoms. Additionally, hypoperfusion especially in the precuneus and parietal association cortex can serve as a predictor of progression from mild cognitive impairment to AD. In dementia with Lewy bodies (DLB), the differentiating feature is the presence of hypoperfusion in the occipital lobes in addition to that observed in AD. Hypoperfusion of the occipital lobe is not a remarkable finding, as it is assumed to reflect functional loss due to impairment of the cholinergic and dopaminergic systems rather than degeneration per se. Moreover, the cingulate island sign reflects the degree of AD pathology comorbid in DLB. Frontotemporal dementia is characterized by regional hypoperfusion according to the three clinical types, and the background pathology is diverse. Idiopathic normal pressure hydrocephalus shows apparent hypoperfusion around the Sylvian fissure and corpus callosum and apparent hyperperfusion in high-convexity areas. The cortex or striatum with diffusion restriction on magnetic resonance imaging in prion diseases reflects spongiform degeneration and brain perfusion SPECT reveals hypoperfusion in the same areas. Brain perfusion SPECT findings in dementia should be carefully interpreted considering background pathology.

Substitution of Glu to Lys at Codon 332 on the GFAP Gene Alone Is Causative for Adult-onset Alexander Disease.

A 57-year-old man whose mother had been pathologically diagnosed with Alexander disease (ALXDRD), presented with cerebellar ataxia, pyramidal signs, and mild dysarthria. Brain magnetic resonance imaging revealed typical ALXDRD alterations, such as atrophy of the medulla oblongata (MO) and cervical spinal cord, a reduced sagittal diameter of the MO, and garland-like hyperintensity signals along the lateral ventricular walls. A genetic analysis of GFAP by Sanger sequencing revealed a single heterozygous mutation of Glu to Lys at codon 332 (c.994G>A) in the GFAP gene. Our results newly confirmed that p.E332K alone is the pathogenic causative mutation for adult-onset ALXDRD.

Serial changes in regional cerebral blood flow in Gerstmann-Sträussler-Scheinker disease caused by a Pro-to-Leu mutation at codon 105 in the prion protein gene.

Gerstmann-Sträussler-Scheinker disease with a Pro-to-Leu substitution at codon 105 in the prion protein gene (GSS-P105L) is a rare variant of human genetic prion disease. Herein, we report the case of a patient with GSS-P105L, who showed serial changes in regional cerebral blood flow (rCBF) on single-photon emission computed tomography (SPECT). A 42-year-old woman, with an affected father presenting with similar symptoms, had a 1-year history of progressive gait disturbance, lower-limb spasticity, and psychiatric symptoms. Genetic analysis confirmed the diagnosis of GSS-P105L. Eleven months after disease onset, brain magnetic resonance imaging (MRI) showed bilateral frontal lobe-dominant cerebral atrophy without hyperintensity on diffusion-weighted imaging (DWI) sequences; meanwhile, SPECT revealed non-specific mild hypoperfusion. Follow-up MRI at 52 months after onset demonstrated progressive frontal lobe-dominant cerebral atrophy without hyperintensity on DWI, while SPECT revealed a marked decrease in rCBF in the bilateral right-dominant frontal lobe. Patients with GSS with a Pro-to-Leu substitution at codon 102 (GSS-P102L) have been reported to exhibit hyperintensity on DWI-MRI and a diffuse decrease in CBF with a mosaic-like pattern on SPECT, which is absent in patients with GSS-P105L, thereby possibly reflecting the differences in pathophysiology between GSS-P102L and GSS-P105L.

Nationwide Laboratory Surveillance of Progressive Multifocal Leukoencephalopathy in Japan: Fiscal Years 2011-2020.

Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating disease caused by JC virus (JCV), predominantly affecting patients with impaired cellular immunity. PML is a non-reportable disease with a few exceptions, making national surveillance difficult. In Japan, polymerase chain reaction (PCR) testing for JCV in the cerebrospinal fluid (CSF) is performed at the National Institute of Infectious Diseases to support PML diagnosis. To clarify the overall profile of PML in Japan, patient data provided at the time of CSF-JCV testing over 10 years (FY2011-2020) were analyzed. PCR testing for 1537 new suspected PML cases was conducted, and 288 (18.7%) patients tested positive for CSF-JCV. An analysis of the clinical information on all individuals tested revealed characteristics of PML cases, including the geographic distribution, age and sex patterns, and CSF-JCV-positivity rates among the study subjects for each type of underlying condition. During the last five years of the study period, a surveillance system utilizing ultrasensitive PCR testing and widespread clinical attention to PML led to the detection of CSF-JCV in the earlier stages of the disease. The results of this study will provide valuable information not only for PML diagnosis, but also for the treatment of PML-predisposing conditions.

Peripheral administration of nanomicelle-encapsulated anti-Aß oligomer fragment antibody reduces various toxic Aß species in the brain.

BACKGROUND: Although a large amount of evidence has revealed that amyloid ß (Aß), especially Aß oligomers, protofibrils, and pyroglutamated Aßs, participate primarily in the pathophysiological processes of Alzheimer's disease, most clinical trials of anti-Aß antibody therapy have never acquired successful efficacy in human clinical trials, partly because peripheral administration of antibody medications was unable to deliver sufficient amounts of the molecules to the brain. Recently, we developed polymeric nanomicelles capable of passing through the blood-brain barrier that function as chaperones to deliver larger amounts of heavy molecules to the brain. Herein, we aimed to evaluate the efficacy of newly developed antibody 6H4 fragments specific to Aß oligomers encapsulated in polymeric nanomicelles on the development of Alzheimer's disease pathology in Alzheimer's disease model mice at the age of emergence of early Alzheimer's disease pathology. RESULTS: During the 10-week administration of 6H4 antibody fragments in polymeric nanomicelles, a significant reduction in the amounts of various toxic Aß species, such as Aß oligomers, toxic Aß conformers, and pyroglutamated Aßs in the brain was observed. In addition, immunohistochemistry indicated inhibition of diameters of Aß plaques, Aß-antibody immunoreactive areas, and also plaque core formation. Behavioral analysis of the mice model revealed that the 6H4 fragments-polymeric nanomicelle group was significantly better at maintaining long-term spatial reference memory in the probe and platform tests of the water maze, thereby indicating inhibition of the pathophysiological process of Alzheimer's disease. CONCLUSIONS: The results indicated that the strategy of reducing toxic Aß species in early dementia owing to Alzheimer's disease by providing sufficient antibodies in the brain may modify Alzheimer's disease progression.

Health-related quality of life in Japanese patients with multiple sclerosis.

OBJECTIVES: Neurological disabilities, especially physical issues, can adversely affect the daily lives of people with multiple sclerosis (MS) and negatively impact their health-related quality of life (HRQOL). On the other hand, physical and psychiatric symptoms are variable in people with MS, and QOL can be influenced by cultural and educational background. This study aimed to evaluate the association of HRQOL with disabilities, fatigue, and depression in Japanese subjects with MS. METHODS: Evaluation of HRQOL, fatigue, and depression was performed in 184 Japanese individuals with MS, using the Functional Assessment of MS (FAMS), Fatigue Severity Scale (FSS), and Beck Depression Inventory-Second Edition (BDI-II), respectively. RESULTS: Multiple linear regression analysis demonstrated negative correlations of the Expanded Disability Status Scale (EDSS) with scores on the FAMS subscales of mobility, symptoms, thinking and fatigue, total FAMS, and additional concerns. The FSS score had negative correlations with mobility, symptoms, emotional well-being, thinking and fatigue, total FAMS, and additional concerns. There were negative correlations between BDI-II scores and all items of FAMS. CONCLUSIONS: HRQOL had relatively close correlations with disabilities and fatigue, and depression had an especially close relationship with HRQOL.

Systematic Review of Clinical and Pathophysiological Features of Genetic Creutzfeldt-Jakob Disease Caused by a Val-to-Ile Mutation at Codon 180 in the Prion Protein Gene.

Genetic Creutzfeldt-Jakob disease (gCJD) is a subtype of genetic prion diseases (gPrDs) caused by the accumulation of mutated pathological prion proteins (PrPSc). gCJD has a phenotypic similarity with sporadic CJD (sCJD). In Japan, gCJD with a Val to Ile substitution at codon 180 (V180I-gCJD) is the most frequent gPrD, while the mutation is extremely rare in countries other than Japan and Korea. In this article, we aim to review previously elucidated clinical and biochemical features of V180I-gCJD, expecting to advance the understanding of this unique subtype in gCJD. Compared to classical sCJD, specific clinical features of V180I-gCJD include older age at onset, a relatively slow progression of dementia, and a lower positivity for developing myoclonus, cerebellar, pyramidal signs, and visual disturbance. Diffuse edematous ribboning hyperintensity of the cerebral cortex, without occipital lobes in diffusion-weighted magnetic resonance imaging, is also specific. Laboratory data reveal the low positivity of PrPSc in the cerebrospinal fluid and periodic sharp wave complexes on an electroencephalogram. Most patients with V180I-gCJD have been reported to have no family history, probably due to the older age at onset, and clinical and biochemical features indicate the specific phenotype associated with the prion protein gene mutation.

Clinical impact of amyloid PET using 18F-florbetapir in patients with cognitive impairment and suspected Alzheimer's disease: a multicenter study.

OBJECTIVE: Amyloid positron emission tomography (PET) can reliably detect senile plaques and fluorinated ligands are approved for clinical use. However, the clinical impact of amyloid PET imaging is still under investigation. The aim of this study was to evaluate the diagnostic impact and clinical utility in patient management of amyloid PET using 18F-florbetapir in patients with cognitive impairment and suspected Alzheimer's disease (AD). We also aimed to determine the cutoffs for amyloid positivity for quantitative measures by investigating the agreement between quantitative and visual assessments. METHODS: Ninety-nine patients suspected of having AD underwent 18F-florbetapir PET at five institutions. Site-specialized physicians provided a diagnosis of AD or non-AD with a percentage estimate of their confidence and their plan for patient management in terms of medication, prescription dosage, additional diagnostic tests, and care planning both before and after receiving the amyloid imaging results. A PET image for each patient was visually assessed and dichotomously rated as either amyloid-positive or amyloid-negative by four board-certified nuclear medicine physicians. The PET images were also quantitatively analyzed using the standardized uptake value ratio (SUVR) and Centiloid (CL) scale. RESULTS: Visual interpretation obtained 48 positive and 51 negative PET scans. The amyloid PET results changed the AD and non-AD diagnosis in 39 of 99 patients (39.3%). The change rates of 26 of the 54 patients (48.1%) with a pre-scan AD diagnosis were significantly higher than those of 13 of the 45 patients with a pre-scan non-AD diagnosis (χ2 = 5.334, p = 0.0209). Amyloid PET results also resulted in at least one change to the patient management plan in 42 patients (42%), mainly medication (20 patients, 20%) and care planning (25 patients, 25%). Receiver-operating characteristic analysis determined the best agreement of the quantitative assessments and visual interpretation of PET scans to have an area under the curve of 0.993 at an SUVR of 1.19 and CL of 25.9. CONCLUSION: Amyloid PET using 18F-florbetapir PET had a substantial clinical impact on AD and non-AD diagnosis and on patient management by enhancing diagnostic confidence. In addition, the quantitative measures may improve the visual interpretation of amyloid positivity.

Spinocerebellar Ataxia Type 31 Exacerbated by Anti-amino Terminal of Alpha-enolase Autoantibodies.

We herein report a 61-year-old woman who was genetically diagnosed with spinocerebellar ataxia type 31 whose symptoms were modified by anti-amino terminal of alpha-enolase (NAE) antibodies, known as a biomarker of Hashimoto's encephalopathy (HE), and ultimately responded to immunotherapy. The relative titers of anti-NAE antibodies increased when her cerebellar ataxia showed acute deterioration and decreased after immunotherapy. This is the first report of cerebellar ataxia associated with genetic spinocerebellar ataxia with concomitant cerebellar type HE. Physicians should be mindful of measuring anti-NAE antibodies to prevent overlooking patients with genetic spinocerebellar ataxia with treatable simultaneous ataxic diseases.

Case Report: Dural Dissection With Ventral Spinal Fluid-Filled Collection in Superficial Siderosis: Insights Into the Pathology From Anterior-Approached Surgical Cases.

Superficial siderosis (SS) of the central nervous system is a rare disease caused by chronic and repeated hemorrhages in the subarachnoid space. Recently, attention has been paid on the association of SS and dural defect with ventral fluid-filled collection in the spinal canal (VFCC). The pathophysiology of hemosiderin deposition in patients with SS and dural defects is still unclear. However, previous studies have suggested the possible mechanism: cerebrospinal fluid (CSF) leaks into the epidural space through the ventral dural defect, and repetitive bleeding occurs from the epidural vessels that circulate back to the subarachnoid space through the dural defect, leading to hemosiderin deposition on the surface of the brain, the central nerves, and the spinal cord. Previously, the surgical closure of dural defect via the posterior approach has been reported to be effective in arresting the continued subarachnoid bleeding and disease progression. Herein, we describe SS cases whose dural defects were repaired via the anterior approach. From the direct anterior approach to the ventral dural defect findings, we confirmed that the outer fibrous dura layer is intact, and the defect is localized in the inner thin layer. From the findings of this study, our proposed theory is that dural tear at the inner dural layer causes "dural dissection," which is likely to occur between the outer fibrous layer and inner dural border cellular layer. Bleeding from the vessels between the inner and outer Line 39-40 dural layers seems to be the pathology of SS with dural defect.

High-efficacy therapy reduces subcortical grey matter volume loss in Japanese patients with relapse-onset multiple sclerosis: A 2-year cohort study.

BACKGROUND: Different treatment strategies can have varying effects on disability and whole brain volume in patients with multiple sclerosis (MS). However, the association between regional brain volume and treatment efficacy is currently unclear. Our objective was to determine whether whole brain volume, as well as the regional volume of cortical and subcortical grey matter, differ with the administration of high-efficacy therapy (HET) versus low-efficacy therapy (LET). METHODS: We evaluated clinical data and change in regional brain volume in 44 patients with relapse-onset MS, who underwent HET (n = 19) or LET (n = 25). Regional brain volume was determined with three-dimensional T1-weighted magnetic resonance imaging using FreeSurfer. The association between volume change and treatment type was assessed via generalised linear mixed models (GLMMs). RESULTS: During the observation period (2.0 ± 0.16 years), the proportion of patients with a "no evidence of disease activity-3″ status was significantly greater in those who underwent HET versus LET (p = 0.012). HET was positively associated with volume changes in the cortex (ß = 0.64, p = 0.0499), left (ß = 0.98, p = 0.0033) and right (ß = 0.77, p = 0.019) caudate and right putamen (ß = 0.87, p = 0.0077), after adjusting for age, sex, and MS severity scores in the GLMMs. Further correction for multiple comparisons by false discovery rate revealed that HET was consistently associated with the volume changes of the left caudate (p = 0.049) and right putamen (p = 0.049). CONCLUSION: HET can improve the mid-term prognosis of Japanese patients with relapse-onset MS by reducing disease activity and regional brain volume loss.

[Neurological Manifestations of COVID-19: Meningoencephalitis and Encephalopathy].

Coronavirus disease (COVID-19) causes neurological symptoms in a high percentage of patients and is associated with various types of encephalitides and encephalopathies, which are etiologically classified into (a)direct infection of the central nervous system with severe acute respiratory syndrome coronavirus 2 and resultant meningoencephalitis (this is a rare presentation), (b)COVID-19-induced cytokine storms, which trigger endothelial cell injury, blood-brain barrier disruption, and microangiopathy and consequent encephalopathy and, (c)autoimmune encephalitis secondary to para- or post-infectious mechanisms that play a key role during the acute or post-COVID-19 phase. Notably, some patients present with neurological symptoms as the first manifestation. Radiologically characteristic encephalitides and encephalopathies, such as acute necrotizing encephalopathy, acute disseminated encephalomyelitis, posterior reversible encephalopathy syndrome, and clinically mild encephalitis/encephalopathy with a reversible splenial lesion are also complicated by COVID-19. Further investigations and appropriate treatments are warranted in patients with COVID-19, who develop new neurological symptoms.

Specific electroencephalogram features in the very early phases of sporadic Creutzfeldt-Jakob disease.

Studies on the very early electroencephalography (EEG) features prior to the emergence of generalized periodic discharges (GPDs, generally known as periodic sharp-wave complexes) in Creutzfeldt-Jakob disease (CJD) are rare. Fourteen patients with sporadic CJD (sCJD) (eight with MM1/classic and six with MM2c) were included in this study. The predominant findings of the first EEG were categorized as 1) lateralized periodic discharges (LPDs), 2) central sagittal sporadic epileptiform discharges (CSSEDs) showing midline predominant generalized spike-and-wave complexes and/or sharp waves in the central sagittal regions, or 3) focal epileptiform discharges. Clinical records, magnetic resonance imaging (MRI), and changes in EEG were compared between three groups (LPD in MM1/classic, CSSED in MM1/classic, and focal epileptiform discharge in MM2c). Three (37.5%) and five (62.5%) patients with MM1/classic sCJD were classified into the LPD and CSSED groups, respectively. Patients in the LPD group were accompanied by cortical hyperintensities at the corresponding areas on MRI, while those in the CSSED group showed hyperintensities on MRI at unassociated cortical areas. Follow-up EEG of three (100%) patients in the LPD group and four (80%) in the CSSED group showed transitions to GPDs. All patients with MM1/classic sCJD showed myoclonus on initial EEG, and the symptomatic side was opposite to the hemisphere showing LPDs or higher-amplitude central sagittal epileptiform activity. The periodicity after these EEGs likely contributes to the diagnostic confidence of physicians when patients are in the very early stages of MM1/classic sCJD.

Methionine homozygosity for PRNP polymorphism and susceptibility to human prion diseases.

BACKGROUND: No studies have assessed the independent association of methionine homozygosity at codon 129 with the susceptibility to prion diseases, controlling for the effects of the codon 219 polymorphisms and other potential confounders, using a large-scale population-based dataset. METHODS: We conducted a case-control study using a Japanese nationwide surveillance database for prion diseases. The main exposure was methionine homozygosity at codon 129, and the outcome was development of prion diseases. Multivariable logistic regression models were employed for specific disease subtypes (sporadic Creutzfeldt-Jakob disease (CJD), genetic CJD and Gerstmann-Sträussler-Scheinker disease (GSS)). RESULTS: Of 5461 patients registered in the database, 2440 cases and 796 controls remained for the analysis. The cases comprised 1676 patients with sporadic CJD (69%), 649 with genetic CJD (27%) and 115 with GSS (5%). For patients with methionine homozygosity, potential risk for occurring prion diseases: adjusted OR (95% CI) was 2.21 (1.46 to 3.34) in sporadic CJD, 0.47 (0.32 to 0.68) in genetic CJD and 0.3 (0.17 to 0.55) in GSS. Among patients with specific prion protein abnormalities, the potential risk was 0.27 (0.17 to 0.41) in genetic CJD with 180 Val/Ile, 1.66 (0.65 to 5.58) in genetic CJD with 200 Glu/Lys, 3.97 (1.2 to 24.62) in genetic CJD with 232 Met/Arg and 0.71 (0.34 to 1.67) in GSS with 102 Pro/Leu. CONCLUSIONS: Methionine homozygosity at codon 129 was predisposing to sporadic CJD, but protective against genetic CJD and GSS, after adjustment for codon 219 polymorphism effect. However, the impacts differed completely among patients with specific prion protein abnormalities.

Amyloid-ß oligomers interact with NMDA receptors containing GluN2B subunits and metabotropic glutamate receptor 1 in primary cortical neurons: Relevance to the synapse pathology of Alzheimer's disease.

Recent evidence suggests that soluble amyloid-ß oligomers (AßOs) act as a key factor in the pathogenetic mechanism of Alzheimer's disease (AD). AßOs induce neurotoxic and synaptotoxic effects probably through binding to certain receptors, however it remains unclarified which receptors are most critically involved. In addition, dysregulation in glutamatergic signaling is implicated in AD. In this study, we used a rat primary cortical neuron model to investigate AßO-induced aberrations of synaptic proteins and binding of extracellular AßOs to candidate receptors in the glutamatergic system. Immunocytochemical analyses showed that both presynaptic (SNAP-25, synapsin I) and postsynaptic (spinophilin, homer 1b/c) proteins appeared to aberrantly dislocate from synapses upon AßO treatment. Double immunofluorescence staining of AßO-treated neurons without permeabilization pretreatment revealed that extracellular AßOs exist over neuronal soma and neurites and clearly colocalized with GluN1 and GluN2B subunits of NMDA receptors and metabotropic glutamate receptor 1 (mGluR1), but not with NMDA GluN2A subunits and mGluR5. AßO treatment altered neither total protein levels nor intracellular localizations of these receptors. These results suggest that extracellular AßOs specifically bind to both NMDA receptors containing GluN2B subunits and mGluR1. It is likely that binding of AßOs to these receptors induces various pathological responses, consequently leading to synaptic disruptions. Our study thus highlights the important roles of GluN2B-containing NMDA receptors and mGluR1 receptors in the synapse pathology in AD.

Correlation of the symbol digit modalities test with the quality of life and depression in Japanese patients with multiple sclerosis.

BACKGROUND: This study aimed to evaluate the association between cognitive impairment and health-related quality of life (HRQOL), fatigue, and depression in Japanese patients with multiple sclerosis (MS). METHODS: The Brief International Cognitive Assessment for MS (BICAMS) was performed in 184 Japanese patients with MS. The Functional Assessment of MS (FAMS), Fatigue Severity Scale (FSS), and Beck Depression Inventory-Second Edition (BDI-II) were used to evaluate HRQOL, fatigue, and depression, respectively. RESULTS: Multiple linear regression analysis demonstrated positive correlations of the Symbol Digit Modalities Test (SDMT) with the scores on the FAMS subscales of mobility, symptoms, emotional well-being, and additional concerns and with the total FAMS score even after controlling for the Expanded Disability Status Scale score, age at examination, and duration of education. The SDMT score in the BICAMS battery had negative correlations with the BDI-II score, as revealed by multiple linear regression analysis. None of the three tests in the BICAMS had any correlation with the FSS score. CONCLUSION: The SDMT has a significant relationship with HRQOL and depression in Japanese patients with MS.

Quantitative clinical and radiological recovery in post-operative patients with superficial siderosis by an iron chelator.

BACKGROUND: Superficial siderosis is a rare neurodegenerative disease caused by hemosiderin deposition on the brain surface. Although the efficacy of the iron chelator-deferiprone-in superficial siderosis has recently been documented, a comparative study of patients who underwent surgical ablation of their bleeding source and subsequently received treatment with or without deferiprone has not yet been conducted. METHODS: Fifteen postoperative patients with superficial siderosis were recruited, and seven patients were administered deferiprone (combination therapy group). Quantitative changes in the hypointense signals on T2*-weighted magnetic resonance images were acquired; additionally, cerebellar ataxia was assessed (International Cooperative Ataxia Rating Scale score and Scale for the Assessment and Rating of Ataxia). Audiometry was performed and the results were compared with those of patients who did not receive deferiprone (surgical treatment group; controls). RESULTS: Significant improvements in signal contrast ratios were noted in the lateral orbitofrontal gyrus, superior temporal lobe, insular lobe, brainstem, lingual gyrus, and cerebellar lobe in the combination therapy group. The scores of patients in the combination therapy group on the cerebellar ataxia scales significantly improved. The degree of signal improvement in the cerebellar lobe correlated with the improvement of cerebellar ataxia scores. Early deferiprone administration after disease onset and long-term administration were correlated with greater signal improvements on magnetic resonance imaging. No adverse effects were observed in the clinical or laboratory parameters. CONCLUSIONS: Deferiprone administration significantly improved radiological and clinical outcomes in patients with postoperative superficial siderosis. Earlier and longer courses of deferiprone could result in better patient prognosis.

Sacral dural arteriovenous fistula mimicking multiple mononeuropathy.

A sacral dural arteriovenous fistula (dAVF) is extremely rare, and the pathophysiological and clinical features have not been established. A 70-year-old man developed gradually progressive right-dominant bilateral sensory disorder of the lower limbs. His clinical course and electrophysiological findings were similar to those of multiple mononeuropathy. However, angiography showed a sacral dAVF at the right intervertebral foramen between the fifth lumbar and first sacral vertebrae. Endovascular embolization of the dAVF improved his clinical symptoms and electrophysiological findings. A sacral dAVF can mimic multiple mononeuropathy in terms of its clinical features and electrophysiological findings. A sacral dAVF is a treatable disease and should be considered as a differential diagnosis of lower extremity disorders.

Serum amyloid A level correlates with T2 lesion volume and cortical volume in patients with multiple sclerosis.

It is unclear whether brain atrophy in multiple sclerosis (MS) is associated with not only neuroinflammation but also systemic inflammation. Here we found that systemic inflammatory marker serum amyloid A (SAA) was moderately correlated with cortical volume in the patients with clinically isolated syndrome (CIS) and MS (r = -0.41, p = 0.019). SAA was also significantly correlated with T2 lesion volume (T2LV) even after adjusting for age, disease duration, and disease modifying therapy (p = 0.0050). Thus, systemic inflammation may be associated with cortical atrophy, possibly via an increase in the T2LV in patients with CIS/MS.