島 さゆり

INTRODUCTION: Progressive supranuclear palsy (PSP) involves midbrain structures, including the red nucleus (RN), an iron-rich region that appears as a high-contrast area on quantitative susceptibility mapping (QSM). RN may serve as a promising biomarker for differentiating parkinsonism. However, RN deformation in PSP remains elusive. This study aimed to evaluate RN deformation in PSP using coronal QSM images and compare them with those of Parkinson's disease (PD) and healthy controls (HC). METHODS: We evaluated the QSM images of 22 patients with PSP, 37 patients with PD, and 43 HC. We developed a grading system to assess RN deformation on coronal QSM images and classified them into three grades. The midbrain and RN volumes were extracted using distinct approaches, and their relationship with grading was investigated. For validation, coronal QSM images of 16 PSP patients from a different institution were assessed. RESULTS: In PSP, 59 % of the patients displayed a flattened RN of grade 3, which we termed a Rice-Grain Appearance. The volume reductions in midbrain and RN were associated with deformation. Differentiation based on the presence of this appearance yielded a specificity of 1.000 (CI: 1.000-1.000) and sensitivity of 0.591 (0.385-0.796) for distinguishing PSP from others. Secondary dataset also showed that 56 % of patients with PSP were classified as grade 3. CONCLUSION: In coronal QSM images, the flattened RN shape appears to be specific to PSP compared to PD and HC and may serve as a marker to help differentiate PSP in future clinical settings.

BACKGROUND: Recent evidence suggests a link between glycoprotein non-metastatic melanoma protein B (GPNMB) and Parkinson's disease (PD) pathogenesis. Although elevated plasma GPNMB levels associated with disease severity have been reported in PD, cerebrospinal fluid (CSF) alterations remain elusive. OBJECTIVE: To explore CSF GPNMB alterations and its clinical significance in PD. METHODS: This study enrolled 118 sporadic PD patients and 40 controls. We examined the potential associations between CSF GPNMB levels and the clinical characteristics or biomarkers of neurodegenerative pathogenesis. RESULTS: PD patients had higher CSF GPNMB levels than controls (p = 0.0159). In the PD group, CSF GPNMB levels correlated with age (age at examination: rs = 0.2511, p = 0.0061; age at onset: rs = 0.2800, p = 0.0021) and the severity of motor and cognitive dysfunction (MDS-UPDRS III score: rs = 0.1998, p = 0.0347; Mini-Mental State Examination score: rs = -0.1922, p = 0.0370). After correcting for multiple comparisons, the correlation with age at onset remained significant. CSF GPNMB levels were also positively correlated with CSF soluble triggering receptor expressed on myeloid cells 2 (sTREM2) levels in both the PD (rs = 0.3582, p < 0.0001) and control (rs = 0.4743, p = 0.0023) groups. Furthermore, multiple regression analysis revealed CSF sTREM2 level as the strongest determinant of CSF GPNMB levels in the PD group (t-value = 3.49, p = 0.0007). CONCLUSIONS: Elevated CSF GPNMB levels, linked with age and microglial activation, may be a valuable marker for understanding the interplay between aging, neuroinflammation, and PD pathology.

The relationship between reduced serum uric acid (UA) levels and Parkinson's disease (PD), particularly purine metabolic pathways, is not fully understood. Our study compared serum and cerebrospinal fluid (CSF) levels of inosine, hypoxanthine, xanthine, and UA in PD patients and healthy controls. We analyzed 132 samples (serum, 45 PD, and 29 age- and sex-matched healthy controls; CSF, 39 PD, and 19 age- and sex-matched healthy controls) using liquid chromatography-tandem mass spectrometry. Results showed significantly lower serum and CSF UA levels in PD patients than in controls (p < 0.0001; effect size r = 0.5007 in serum, p = 0.0046; r = 0.3720 in CSF). Decreased serum hypoxanthine levels were observed (p = 0.0002; r = 0.4338) in PD patients compared to controls with decreased CSF inosine and hypoxanthine levels (p < 0.0001, r = 0.5396: p = 0.0276, r = 0.2893). A general linear model analysis indicated that the reduced UA levels were mainly due to external factors such as sex and weight in serum and age and weight in CSF unrelated to the purine metabolic pathway. Our findings highlight that decreased UA levels in PD are influenced by factors beyond purine metabolism, including external factors such as sex, weight, and age, emphasizing the need for further research into the underlying mechanisms and potential therapeutic approaches.

Herpes simplex encephalitis (HSE) is an acute form of encephalitis that can lead to poor neurological outcomes. Although the exact pathogenesis of HSE remains elusive, recent reports suggest a significant role for postinfectious immune-inflammatory processes in the central nervous system (CNS). This study aimed to clarify the association between CNS autoimmune responses and clinical presentation in patients with HSE, focusing on cerebrospinal fluid (CSF) characteristics, particularly the IgG index. We retrospectively analyzed 176 consecutive patients suspected of having aseptic meningitis /encephalitis for chronological changes in CSF findings and clinical presentations. These patients underwent PCR screening for herpesviruses (HV) in their CSF. We identified seven patients positive for herpes simplex virus type 1 (HSV-1), 20 patients positive for varicella-zoster virus, and 17 patients who met the criteria for aseptic meningitis but were PCR-negative for HV. Patients in the HSV-1-positive group exhibited a significant increase in the IgG index at the time of PCR-negative conversion compared with on admission (p = 0.0156), while such a change was not observed in the other two groups. Additionally, all patients in the HSV-1-positive group tested negative for anti-neural autoantibodies in CSF and serum samples collected approximately 3 weeks after onset. This study, therefore, highlights that CSF IgG index elevation occurs even after PCR-confirmed HSV-1 clearance, which might indicate immunopathogenesis that is independent of antibody-mediated mechanisms.