Journal of Neurology最新文献

Background: Orthostatic hypotension (OH) is a common symptom of multiple system atrophy (MSA), however, its role in cognitive impairment and the mechanism in these patients remains unclear. This study aims to assess the role of OH on cognitive impairment in MSA patients, as well as to explore the potential association of cerebral autoregulation (CA) and white matter hyperintensities (WMHs) on cognitive impairment.

Methods: This observational study was conducted in three general hospitals in China from January 2018 to October 2023, with patients at one center followed up for 6 months after enrollment. The primary outcomes included cognitive function assessed using the Mini-Mental State Examination (MMSE) and Montreal cognitive assessment (MoCA). Secondary outcomes included the results of the Head-up tilt test, scores for CA and the extent of WMHs.

Results: The 132 MSA patients included 72 men (54.54%) with a mean age of 61.16 (7.80) years. Among them, 80 patients (60.61%) had orthostatic hypotension, and 48 patients (36.36%) had cognitive impairment. OH plays an important role in cognitive impairment in MSA patients (OR = 0.328,95% CI 0.135-0.797, P = 0.014). Cognitive impairment was associated with impaired CA (OR = 0.088,95% CI 0.012-0.657, P = 0.018) and severe WMHs (OR = 0.030,95% CI 0.002-0.423, P = 0.009), particularly in the presence of OH.

Conclusion: OH is associated with cognitive impairment in MSA patients, and cognitive decline is linked to impaired CA and increased WMHs. Future studies are needed to explore the mechanisms underlying cognitive impairment in MSA patients.

Background: Cognitive dysfunction is increasingly recognized in multiple system atrophy (MSA). Locus coeruleus (LC) integrity is associated with cognitive performance both in healthy controls (HC) and neurodegenerative conditions such as Parkinson's disease (PD). Furthermore, cortical glucose hypometabolism is associated with impaired cognitive performance in MSA. However, knowledge about LC sub-regional degeneration and its association with cognitive dysfunction and cortical glucose metabolism is lacking.

Objective: To investigate LC sub-regional involvement and its association with cognitive impairment and brain metabolism in MSA.

Methods: Eleven MSA, eighteen PD, and eighteen HC participants were included in the study. Neuromelanin-sensitive MRI was used to determine rostral, middle and caudal LC neuromelanin signals. Brain glucose metabolism was investigated with [¹⁸F]Fluorodeoxyglucose PET (FDG-PET). The Montreal Cognitive Assessment (MoCA) was used as a measure of global cognition.

Results: Middle LC neuromelanin signal was significantly reduced in MSA [t(43) = 3.70, corrected-p = 0.004] and PD [t(43) = 2.63, corrected-p = 0.041] compared to HC, while caudal LC was only reduced in MSA [t(43) = 2.82, corrected-p = 0.030]. In MSA, decreased rostral LC neuromelanin was associated with lower MoCA scores (ρ = 0.760, p = 0.006) which, in turn, were associated with lower frontal cortex glucose metabolism. An association between rostral LC neuromelanin signal and frontal cortex glucose metabolism was found in exploratory analyses.

Conclusion: Loss of LC neuromelanin signal was found in MSA, the middle and caudal parts being targeted. Rostral LC neuromelanin signal loss was associated with both frontal cortex hypometabolism and lower MoCA scores. This pathophysiological link should be further investigated as the noradrenergic system transmission is amenable to pharmacological manipulation.

Background: Inherited peripheral neuropathies (IPNs) encompass a wide range of disorders affecting the peripheral nervous system, often with complex genetic causes and frequent underdiagnosis. The variants in the superoxide dismutase 1 (SOD1) gene, primarily linked to amyotrophic lateral sclerosis (ALS), have also been associated with peripheral neuropathy. The recent approval of Tofersen, targeting SOD1-related ALS, highlights the importance of precise genetic diagnosis. This study explores the clinical and genetic profiles of SOD1-related IPNs (SOD1-IPN) in a nationwide Japanese IPN cohort.

Methods: Clinical and genetic data were assessed from 1483 Japanese patients with IPN, with a focus on those harboring SOD1 pathogenic variants. The clinical evaluations included age of onset, gender, muscle weakness patterns, sensory disturbances, reflex responses, and electrophysiological findings.

Results: Seventeen patients with SOD1 pathogenic variants were identified, reinforcing SOD1's role in IPN. The average onset age was 47, with a slight male predominance. Distal muscle weakness was noted in 9 of 13 patients, and asymmetric muscle weakness and atrophy in 10 of 14 cases. Mild sensory disturbances were observed in eight patients, with some showing hyperreflexia and abnormal reflexes. Electrophysiology predominantly indicated a length-dependent, motor-dominant axonal neuropathy.

Conclusion: This study reveals the clinical variability and likely underdiagnosis of SOD1-IPN, supporting the integration of SOD1 screening in IPN genetic testing, especially for patients with asymmetric, length-dependent axonal neuropathy evident in clinical and electrophysiological assessments.

Accelerometry enables passive, continuous, high-frequency monitoring under free-living conditions. For individuals with isolated REM sleep behavior disorder (iRBD), a potential prodromal phase of Parkinson's disease (PD) and dementia with Lewy bodies, accelerometry has been primarily applied to aid diagnosis and to assess phenoconversion risk. To extend this knowledge, we cross-sectionally combined clinical assessments focusing on non-motor symptoms with accelerometry-derived features of physical activity (PA), sleep, and circadian rhythm of N = 68 individuals with iRBD (age: 69.48 ± 6.01 years, self-reported RBD symptom duration: 9.46 ± 6.21 years, 85 % male). Accelerometry-assessed PA was associated with more stable circadian rhythms. Additionally, higher PA and more stable circadian rhythms were linked to a lower burden of overall non-motor symptoms, depressive symptoms, and fatigue with small to moderate effect sizes. Furthermore, including accelerometry-derived features improved the prediction of individual clinical scores, particularly for cognitive performance. Our findings contribute to the growing body of evidence highlighting the complex interplay between PA, sleep, circadian rhythm, and non-motor symptoms in α-synucleinopathies. Future research should focus on longitudinal studies to monitor changes in clinical outcomes and digital biomarkers over time to enhance our understanding of symptom progression and corresponding lifestyle changes in prodromal and manifest α-synucleinopathies.

Background: This study aims to elucidate and predict the global disease burden and trends associated with central nervous system (CNS) tumors and cancers among older patients.

Methods: Data from the Global Burden of Disease 2021 database were used to calculate the age-standardized incidence rate (ASIR), prevalence rate (ASPR), death rate (ASDR), disability-adjusted life-years (DALYs), and the average annual percentage change (AAPC) to assess burden and trends from 1990 to 2021. A Bayesian age-period-cohort model was applied to project the global burden of CNS tumors and cancers in older patients over the next 30 years.

Results: The ASIR among older adults worldwide increased by 3.59 cases per 100,000 population from 1990 to 2021, with an AAPC of 0.86%. The ASPR rose by 9.83 cases per 100,000 people, with an AAPC of 1.57%. The ASDR increased from 10.99 per 100,000 people to 13.01 per 100,000 people. DALYs also rose continuously from 234.21 per 10,000 population to 265.1, with an AAPC of 0.4%. It is anticipated that from 2021 to 2051, the ASIR, ASDR, and age-standardized DALYs will exhibit a declining pattern; however, the ASPR will initially experience a slight decrease before gradually rising again.

Conclusions: The global burden has significantly increased from 1990 to 2021. Projections indicate that over the next 30 years, the total number of patients will rise, while the age-standardized rates will show a slow downward trend.

Background and objective: The brain glymphatic system is involved in the clearance of misfolded α-synuclein, and the impaired glymphatic system may contribute to the progression of Parkinson's disease (PD). This study aimed to investigate the association between glymphatic function, as assessed by the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, and disease progression in PD.

Methods: One hundred thirty nine PD patients and 62 healthy controls (HCs) were enrolled in this prospective cohort study and followed up for 4 years. At baseline and 1-, 2-, and 4-year follow-ups, the enrolled population was examined with DTI scans, and the ALPS index was calculated. Unified Parkinson's Disease Rating Scale (UPDRS)-III and Montreal Cognitive Assessment (MoCA) were used to assess the motor and cognitive functions of the patients, respectively.

Result: The ALPS index was significantly lower in PD patients compared with HCs. Receiver operating characteristic curve analysis demonstrated that the ALPS index had a great diagnostic ability on PD, both at baseline and subsequent follow-ups (AUC_baseline: 0.729; AUC_1-year: 0.653; AUC_2-year: 0.714; AUC_4-year: 0.728). The adjusted linear mixed-effects models showed that the ALPS index was significantly associated with UPDRS-III scores (β: - 5.173, 95%CI: - 8.850 to - 1.497, p = 0.006), but this association was lost for MoCA. A lower baseline ALPS index was associated with a faster increase in UPDRS-III, but not for MoCA.

Conclusion: The ALPS index could be used as an early potential imaging marker not only to differentiate PD patients from HCs but also to predict longitudinal motor function progression in PD.

Background: In this qualitative study, we aimed to obtain and synthesise the views of patients with functional neurological disorder (FND), their caregivers, and relevant healthcare professionals (HCPs) on outcome measurement in FND.

Methods: Semi-structured interviews were conducted with 22 FND patients, 18 caregivers and 21 HCPs, sampled purposively in the United Kingdom. Transcripts were analysed through inductive thematic analysis.

Results: Whilst reduction or resolution of FND symptoms were frequently mentioned as important treatment goals in all groups, this was reported by a larger proportion of caregivers and HCPs than patients. Patients most frequently hoped for improvements in mental health/well-being. Other important treatment goals were resuming work, and an increase in independence, self-management or self-efficacy. Of the 20 domains deemed relevant for outcome assessment, improvements in FND symptoms, emotional well-being, activities of daily living and quality-of-life, were mentioned most frequently. None of the participants thought that outcome assessment should be purely clinician-rated or objective; all believed that the patient's subjective experience should be central. Nevertheless, participants in all groups acknowledged that clinician-rated or objective OMIs have added value in clinical outcome assessment. The benefits of digital outcome assessment were also mentioned by several participants.

Conclusions: This is the first study to capture the views of key stakeholders on outcome assessment in FND. The findings indicate that outcome measures for FND should be patient-centred, whilst also including HCP opinion. Critical domains for assessment are FND symptoms, mental health, quality-of-life and the ability to perform activities of daily living.

Background and objective: Progressive multifocal leukoencephalopathy (PML) is a severe, disabling infection caused by JC virus reactivation. PML-related disability complicates the MRI monitoring needed to assess treatment interventions in clinical trial or compassionate use settings. Portable ultra-low-field MRI (pULF-MRI) offers a convenient approach when such frequent imaging is needed. We evaluated the potential utility of pULF-MRI as an adjunctive tool for decreasing the burden of clinical study participation and clinical management in PML.

Methods: We examined paired high-field (HF) and pULF-MRI scans from 11 patients, aged 49 ± 15 years. pULF-MRI images with corresponding HF-MRI were coupled to depict key imaging findings of PML, including three patients with longitudinal evaluations, one with bedside pULF-MRI. The images were then independently assessed by two blinded raters, not involved in image acquisition or initial evaluations, who sequentially rated diagnostic accuracy of pULF-MRI scans compared to the HF-MRI. Longitudinal evaluations were performed for three patients, one with bedside pULF-MRI.

Results: T2-FLAIR lesions were detected with pULF-ULF in all cases when present on HF-MRI. Median sensitivity and specificity were 62% and 100%, respectively. T1WI hypointense areas showed similar performance. Focal volume loss was present in 8/11 HF-MRI scans, with sensitivity and specificity of detection by pULF-MRI of 100% and 94%, respectively. Contrast enhancement was seen in a single case on both pULF- and HF-MRI. Follow-up pULF-MRI showed lesion changes in two cases, and stable findings in one case, consistent with HF-MRI.

Discussion: pULF-MRI shows promise in evaluation and monitoring of PML, showing moderate-to-high accuracy even when evaluations were unaided by HF-MRI. Our results highlight a potential application of pULF-MRI for facilitating participation in PML clinical research and more generally as a way to reduce burden of clinical management for this disabled patient population.

MRI has traditionally been employed to rule out alternative diagnoses in unilateral acute vestibular syndrome (UAVS), but delayed 3D-FLAIR sequences offer the potential for imaging to contribute to both diagnosis and management. This study aimed to assess abnormalities on delayed 3D-FLAIR MRI in UAVS patients and correlate these findings with clinical outcomes. A retrospective multicenter study was conducted between January 2018 and May 2024 at a university hospital and a private vestibular clinic, representing a diverse clinical setting. It included 92 patients with UAVS (47 women, 45 men; mean age 50.6 years) diagnosed according to Bárány Society guidelines, with acute vertigo lasting at least 24 h, spontaneous horizontal-rotatory nystagmus, and a reduced vestibulo-ocular reflex (VOR) on the affected side, without auditory or neurological symptoms. The MRI findings were blindly assessed to identify potential blood-labyrinth barrier (BLB) impairment, nerve enhancement, or canal fibrosis. These imaging abnormalities were then correlated with initial and follow-up video head impulse test (vHIT) results. BLB impairment was found in 63% of patients and canal fibrosis in 14.1%, with no nerve enhancement detected. BLB impairment significantly correlated with initial VOR deficits and was linked to poorer vHIT recovery, suggesting its role in predicting persistent vestibular dysfunction. These findings suggest that delayed 3D-FLAIR MRI can identify biomarkers, particularly BLB impairment, that are predictive of vestibular recovery, highlighting MRI's role in guiding UAVS treatment.

The key symptoms of vestibular paroxysmia (VP) due to neurovascular cross-compression (classical VP) or compression of the eighth nerve by space-occupying cerebellar-pontine angle processes (secondary VP) are frequent short attacks of vertigo and dizziness with unsteadiness which last seconds to minutes. They can be accompanied by unilateral auditory symptoms such as tinnitus or hyperacusis. Head movements and hyperventilation can induce nystagmus and VP attacks that most often occur spontaneously. VP is diagnosed in 3% of patients in a tertiary vertigo care center and very rarely affects children. The mean age of first appearance is 47 to 51 years with equal sex distribution. A combination of high-resolution MRI sequences (with constructive interference in steady-state/fast imaging employing steady-state, 3D-CISS/ FIESTA) of the cerebello-pontine may support the diagnosis although the beneficial treatment with sodium channel blockers is the most reliable clinical sign for classical VP, secondary VP and idiopathic VP (without verification of a causative pathology). Because of the frequency, shortness, and audiovestibular symptomatology of the attacks, the differential diagnosis to other conditions such as paroxysmal brainstem attacks, vestibular epilepsy, rotational vertebral artery compression syndrome or "near"-narrowed internal auditory canal syndrome is only relevant in exceptional cases. However, imaging of the posterior fossa including the inner ear is mandatory to distinguish between classical, secondary and idiopathic VP forms. Randomized controlled trials for medical treatment are still needed. Practical therapy of choice is medical treatment with sodium channel blockers (carbamazepine, oxcarbazepine, lacosamide). A microsurgical decompression is effective in secondary VP but is the ultimate therapy in cases with classical or idiopathic VP when medication is not tolerated.