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Periventricular and Perivascular-Space Diffusion MRI Measures, Amyloid Abnormality, and Executive Decline in the Alzheimer's Disease Continuum: A Longitudinal Study.

Chen Cheng C, Gu Jialong J, Hu Qili Q, Alzheimer's Disease Neuroimaging Initiative et al.

Amyloid abnormality is a defining component of Alzheimer disease (AD) biology but does not fully account for variation in executive-function decline, which may also reflect white matter and periventricular injury. To compare periventricular diffusivity (PVeD), diffusion tensor image analysis along the perivascular space (ALPS), and G-Along Perivascular Space (G-ALPS), an algebraic variation of ALPS, as diffusion MRI measures in relation to amyloid abnormality and longitudinal executive-function decline. Retrospective. The imaging-baseline cohort included 1190 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) (70.6 ± 7.5 years; 666 female, 524 male). The primary analytic sample included 302 participants (70.6 ± 6.1 years; 168 female, 134 male). 3 T/diffusion-weighted spin-echo echo-planar imaging and 3D T1-weighted inversion-prepared gradient-echo imaging. PVeD, ALPS, and G-ALPS were evaluated in relation to cerebrospinal fluid Aβ42, amyloid positron emission tomography (PET) Centiloid, structural MRI measures, white matter hyperintensity (WMH), and longitudinal Alzheimer's Disease Neuroimaging Initiative Executive Function composite (ADNI-EF). Group comparisons, regression, longitudinal models, and bootstrap indirect-effect analyses with Benjamini-Hochberg correction were performed. All three diffusion MRI measures differed across diagnostic groups, with mean values of PVeD, ALPS, and G-ALPS showing lower levels in dementia than cognitively normal participants (PVeD: 0.456 ± 0.048 vs. 0.430 ± 0.047; ALPS: 1.291 ± 0.188 vs. 1.163 ± 0.186; G-ALPS: 1.757 ± 0.512 vs. 1.393 ± 0.467). G-ALPS showed the most consistent association with ADNI-EF trajectory (β = 0.031, 95% CI: 0.003-0.059). Exploratory models identified statistical indirect effects involving inverted CSF Aβ42, ADNI-EF decline, and PVeD (-0.0518), ALPS (-0.0407), or G-ALPS (-0.0460); all survived Benjamini-Hochberg correction, with a corresponding G-ALPS effect for amyloid PET Centiloid (-0.0169). Periventricular and perivascular-space diffusion MRI measures were associated with amyloid abnormality and executive-function decline, mainly in cognitively normal and mild cognitive impairment participants. 3. Stage 2.

Antimicrobial Decision-Making in Culture-Negative Bacterial Meningitis with mNGS-Detected Prevotella-Dominant Anaerobic Signals: Two Case Reports and a Literature Review.

Li Yan Y, Hu Yuyuan Y, Yang Yuhang Y, Li Wen Yuan WY et al.

Anaerobic meningitis is uncommon and may be underrecognized when cerebrospinal fluid (CSF) culture is non-diagnostic, particularly after antimicrobial exposure or when anaerobic collection, transport, and incubation conditions are suboptimal. Metagenomic next-generation sequencing (mNGS) can provide complementary microbiological evidence in selected culture-negative central nervous system (CNS) infections, but low-biomass CSF results require explicit quality-control reporting and careful assessment of contamination and clinical plausibility. We report two culture-negative bacterial meningitis cases in which CSF mNGS showed a Prevotella-dominant anaerobic signal. Prevotella oris was the predominant species-level detection in both cases, accompanied by lower-abundance anaerobic co-detections. Because P. oris was not recovered by culture or independently confirmed by species-specific PCR, the results were classified as mNGS-supported Prevotella-dominant signals rather than confirmed monomicrobial P. oris meningitis. Both patients received case-specific antimicrobial therapy adjusted according to clinical status, serial CSF findings, neuroimaging evolution, and adverse-event monitoring. Case 1 required meropenem re-escalation after radiological progression and recurrent intracranial hypertension, whereas Case 2 improved after escalation to meropenem followed by the documented de-escalation to metronidazole. Both patients achieved favorable functional outcomes. These cases illustrate how CSF mNGS may be used as an adjunct when conventional microbiology is non-diagnostic, while emphasizing that sequencing signals, serial CSF changes, imaging, and treatment response must be interpreted together. The two observations do not establish P. oris causality or a standardized escalation/de-escalation regimen.

Diagnostic challenge of GAD65-associated autoimmune encephalitis mimicking post-traumatic complications in an older adult: a case report.

Huang Xiuqing X, Zhang Qile Q, Huang Li L, Xu Jian J

Glutamic acid decarboxylase 65 (GAD65) antibody-associated autoimmune encephalitis is an uncommon immune-mediated neurological disorder with heterogeneous neuropsychiatric manifestations. Diagnosis is particularly challenging in older adults when symptoms of recent traumatic brain injury (TBI) overlap with structural or metabolic conditions. We report a 79-year-old man who developed recurrent headache, progressive confusion, abnormal behavior, poor oral intake, intermittent myoclonic jerks, and low-grade fever after TBI complicated by chronic subdural hematoma. Initial laboratory testing revealed hyponatremia, and the working diagnosis was post-traumatic brain syndrome with syndrome of inappropriate antidiuretic hormone secretion (SIADH). Although serum sodium was corrected and nocturnal agitation partially improved, persistent daytime confusion, cognitive impairment, behavioral abnormalities, and low-grade fever prompted further investigation. Cerebrospinal fluid (CSF) analysis showed mild inflammatory changes with pleocytosis and elevated protein. CSF metagenomic next-generation sequencing (mNGS) and paraneoplastic antibody testing were negative, whereas the autoimmune encephalitis panel was positive for GAD65 antibody at a titer of 1:32. Whole-body positron emission tomography-computed tomography (PET-CT) did not reveal malignancy. The diagnosis was therefore revised to GAD65 antibody-associated autoimmune encephalitis. Because high-dose corticosteroids were considered unsuitable owing to his history of gastric ulcer and previous gastrointestinal bleeding, he was treated with intravenous immunoglobulin (IVIG) at a total dose of 2 g/kg divided over 3 consecutive days followed by oral azathioprine 50 mg daily. His fever resolved within 1 week, and his mental status and responsiveness gradually improved. At 6-month follow-up, he had achieved near-baseline mental status, was able to walk with a cane, and was almost fully independent in daily activities, without relapse or serious treatment-related adverse events. This case highlights the diagnostic difficulty of recognizing autoimmune encephalitis after TBI. The clinical overlap between post- traumatic syndrome and immune-mediated brain injury often delays diagnosis, emphasizing the value of targeted CSF autoantibody testing in atypical cases. Traumatic brain injury may obscure the onset of GAD65-associated autoimmune encephalitis. Early recognition and a corticosteroid-sparing immunotherapy strategy (IVIG and azathioprine) can yield favorable outcomes in elderly patients with medical comorbidities.

Adopting a Hyperlordotic Posture can Prevent the Leakage of Cerebrospinal Fluid (CSF) After Lumbar Puncture and Thus Prevent Post-Dural Puncture Headache.

Finsterer Josef J