Journal of Neurology最新文献

Background: BDNF has increasingly gained attention as a key molecule controlling remyelination with a prominent role in neuroplasticity and neuroprotection. Still, it remains unclear how BDNF relates to clinicoradiological characteristics particularly at the early stage of the disease where precise prognosis for the further MS course is crucial.

Methods: BDNF, NfL and GFAP concentrations in serum and CSF were assessed in 106 treatment naïve patients with MS (pwMS) as well as 73 patients with other inflammatory/non-inflammatory neurological or somatoform disorders using a single molecule array HD-1 analyser. PwMS were evaluated for highly active profiles by applying the aggressive disease course criteria proposed by ECTRIMS. Serum/CSF values were logarithmically transformed and compared across groups using one-way ANOVA, while correlations were calculated using Pearson's correlations. ROC analysis and AUC comparisons for diagnostic performance of the three biomarkers were computed in an explorative analysis.

Results: Serum BDNF (sBDNF) concentrations were higher in treatment naïve pwMS with disease onset after the age of 40 years (p = 0.029), in pwMS with ≥2 gadolinium-enhancing lesions (p = 0.009) and with motor, cerebellar, cognitive or sphincter symptoms at onset (p = 0.036). BDNF correlated positively with NfL (r = 0.198, p = 0.014) and GFAP (r = 0.253, p = 0.002) in serum, but not in CSF. Neurological patients with an acute inflammatory relapse showed significantly higher sBDNF levels (p = 0.03) compared to somatoform controls, while patients without acute relapse did not differ from somatoform controls (p = 0.4). Better diagnostic performance was found for sBDNF than sNfL and sGFAP in differentiating between patients with vs. without 2 or more gadolinium-enhancing lesions (p < 0.05) and for sBDNF as compared to sNfL for separating patients with disease onset after vs. before age of 40 years.

Conclusion: In pwMS, BDNF serum levels differ depending on disease-related characteristics, suggesting that not only inflammatory activity but also remyelination capacities may vary with disease severity. BDNF is increased when other biomarkers of neuroaxonal damage and neurodegeneration, such as NfL and GFAP, are elevated, possibly as a compensatory mechanism, and reflect possibly further pathophysiological aspects in MS beyond NfL and GFAP, probably including an apoptotic role for BDNF in neuroinflammation.

Background: Drooling, defined as the unintentional loss of saliva from the anterior oral cavity, remains poorly understood in terms of the underlying clinical factors in people with Parkinson's disease (PwP). This study aims to clarify these factors by analyzing predictors and secondarily the correlates with the severity of drooling in PwP.

Methods: We conducted a cross-sectional study involving 42 PwP with drooling and 59 without drooling. Clinical assessments were performed, and the primary outcome was the item 2.2 Saliva and drooling of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale. The Mann-Whitney test was used to compare the distribution differences in clinical variables between PwP with and without drooling. The Spearman test was used to examine correlations with drooling, and ordinal logistic regression was used to examine predictors of drooling.

Results: PwP with drooling showed significantly greater impairments in axial signs, posture, facial expression, speech, swallowing, oromotor, motor and non-motor domains than PwP without drooling. Longer disease duration, higher disease severity, levodopa equivalent daily dose, axial signs, unstimulated salivary flow rate, and impairments in speech, posture, facial expression, swallowing, oromotor, motor and non-motor domains were significantly correlated with a higher score on the item 2.2. Male sex, poorer swallowing, oromotor and speech functions were strong predictors of higher scores on the item 2.2 Saliva and drooling.

Conclusions: Male PwP with swallowing disorders, oromotor and speech impairments are significantly more likely to have severe drooling. Targeted interventions aimed at these swallowing, oromotor, and speech impairments may offer promising approaches to reducing drooling severity in PwP.

Objective: This study aims to evaluate our experience in the diagnosis of hereditary ataxias (HAs), to analyze data from a real-world scenario.

Study design: This is a retrospective, cross-sectional, descriptive study conducted at a single Italian adult neurogenetic outpatient clinic, in 147 patients affected by ataxia with a suspicion of hereditary forms, recruited from November 1999 to February 2024. A stepwise approach for molecular diagnostics was applied: targeted gene panel (TP) next-generation sequencing (NGS) and/or clinical exome sequencing (CES) were performed in the case of inconclusive first-line genetic testing, such as short tandem repeat expansions (TREs) testing for most common spinocerebellar ataxias (SCA1-3, 6-8,12,17, DRPLA), other forms [Fragile X-associated tremor/ataxia syndrome (FXTAS), Friedreich ataxia (FRDA) and mitochondrial DNA-related ataxia, RFC1-related ataxia/CANVAS] or inconclusive phenotype-guided specific single gene sequencing.

Result: A definitive diagnosis was reached in 36.7% of the cases. TREs testing was diagnostic in 30.4% of patients. The three most common TREs ataxias were FRDA (36.1%), SCA2 (27.8%), and RFC1-related ataxia/CANVAS (11.1%). In five patients, the molecular diagnosis was achieved by single gene sequencing and causative mutations were identified in POLG (2), SACS (1), DARS2 (1), MT-ATP6 (1). Of 94 patients with a suspicion of HAs of indeterminate genetic origin, 68 underwent new molecular evaluation using the NGS approach. In 28 of these cases, CES was performed after the TP sequencing resulted negative. In 13 patients, the diagnosis was achieved by NGS approach. In 7 of these 13 patients, the diagnosis was made by CES. Genes mutations identified as causative of HAs were found in SPG7 (4), SACS (1), CACNA1A (1), CACNA1G (1), EEF2 (1), PRKCG (1), KCNC3 (1), ADCK3 (1), SYNE1 (1), ITPR1 (1). A positive family history of ataxia and early onset of symptoms were associated with a higher likelihood of obtaining a definite diagnosis.

Conclusion: The molecular diagnosis of HAs remains a significant challenge for neurologists. Our data indicate that, in most cases, a diagnosis of HA can be established through first line genetic testing, particularly TREs testing. However, for patients with a clinical diagnosis of HA who do not achieve a molecular diagnosis through initial genetic tests, the use of NGS proves to be a valuable tool, providing a definitive diagnosis in approximately 20% of cases. Therefore, when feasible in clinical practice, integrating NGS testing, especially exome sequencing, into the diagnostic decision-making process for unsolved cases is crucial.

Background: Patients with Parkinson's disease (PD) and atypical parkinsonian syndromes are at increased risk of falls and should be actively screened and treated for osteoporosis. In 2024, the Royal Australian College of General Practitioners (RACGP) revised their practice guidelines for diagnosing and managing osteoporosis in postmenopausal women and men aged over 50 years.

Objective: We conducted the first Australian study to audit these guidelines in patients with PD and atypical parkinsonian syndromes.

Method: We audited all PD, Dementia with Lewy Bodies, Progressive Supranuclear Palsy and Multiple System Atrophy cases attending our neurology service between January and March 2024 against the RACGP osteoporosis guidelines. We identified patients at risk of osteoporosis or minimal trauma fractures and assessed if they had been referred to their general practitioner (GP) for appropriate management or were already receiving appropriate osteoporosis treatment.

Results: This audit evaluated 230 patients, 199 of which had PD. We identified 78 patients over the age of 50 years with risk factors that should trigger a GP bone health assessment as per the guidelines. Twenty-six of these patients were already being managed appropriately. However, only 12 of the remaining 52 'at risk' patients (23%) were directed to seek screening for osteoporosis by their GP, leaving 77% (40/52) without appropriate guidance.

Conclusion: Our major recommendations include following the guidelines and referring patients for a bone health screen with their GP if they have risk factors for osteoporosis. This audit highlighted that assessment of osteoporosis and fracture risk by Specialists needs to be improved.

Background: Although optic neuritis (ON) is common in multiple sclerosis (MS), lesions of the optic nerve are not included as an anatomical substrate for dissemination in space and time (DIS and DIT).

Objective: To assess the increase in sensitivity of including MRI lesions of the optic nerve for the diagnosis of MS in patients with ON.

Methods: We included patients consecutively referred with first time, monosymptomatic ON, with no known cause of the ON, who underwent orbital MRI including fat suppressed T2 and T1-sequences with and without gadolinium contrast.

Results: One hundred and twenty patients were included. Optic nerve T2 lesions and/or T1-contrast enhancement was shown in 104 patients. Sixty-three patients were diagnosed with MS at baseline. Nine patients developed MS during follow-up. The inclusion of optic nerve MRI lesions led to the diagnosis of 8 additional patients and increased sensitivity to 0.99 (95% CI 0.96-1.00) compared to 0.88 (95% CI 0.79-0.95) for 2017 criteria, while decreasing the specificity to 0.81 (95% CI 0.70-0.92) compared to 1.00.

Conclusion: Amending the diagnostic criteria for MS to include MRI lesions of the optic nerve as a substrate for DIS and DIT may increase sensitivity and lead to more rapid diagnosis of MS.

Background: Neurological disorders pose a substantial burden worldwide in healthcare and health research. eHealth has emerged as a promising field given its potential to aid research, with lower resources. With a changing eHealth landscape, identifying available tools is instrumental for informing future research. A systematic review aimed to map existing software and hardware eHealth assessing neurological signs and/or symptoms for research was conducted. In this second part, the results on hardware are presented.

Methods: We searched for relevant literature using four search engines (PubMed, Web of Science, Scopus, & EBSCOHost). eHealth software tools have been described elsewhere, and this paper reports hardware tools only. Data extraction focused on collecting the main characteristics of each tool, including the device type and size, the tool setup, and the neurological components assessed. The data were then summarised in tables.

Findings: This review captured and described 45 relevant hardware tools. They assessed signs and/or symptoms of five neurological domains: cognitive function, cranial nerves, motor function, posture, gait & coordination, and sensation. Heterogeneity among tool types and setups was high, with most tools assessing posture, gait, & coordination. Over time, there has been an increase in the simplification and versatility of tools, with a preference for commercially available and easily accessible hardware.

Interpretation: There is already a considerable number of hardware eHealth assessing neurological function that can be used for research purposes. Furthermore, commercially available tools, such as sensors, appear to be preferred due to their reduced costs, easy setup, and high portability. This opens new opportunities to extend neuroepidemiological research cost-effectively, efficiently, and adaptively.

Background: Married or long-term partnered patients with chronic diseases generally have better outcomes than unmarried patients, likely due to the potential for multifaceted support. However, the impact of marital status on multiple sclerosis (MS) radiographic disease burden is currently unknown.

Objective: To compare total white matter hyperintensity lesion volumes, periventricular lesion volumes, and whole brain and grey matter volumes in married and unmarried people with MS (PwMS).

Methods: We utilized multivariable linear regression to assess for differences in brain atrophy and lesion volumes between these two groups controlling for sex, MS disease duration in years, hypertension, history of smoking, alcohol consumption, history of depression and/or anxiety, and medication possession ratio (MPR).

Results: Married PwMS had significantly lower total lesion volumes (β =  - 6.3, 95% CI - 12.1 to - 0.5, p = 0.033), lower PV lesion volumes (β =  - 6.1, 95% CI - 11.7 to - 0.6, p = 0.030), higher normalized whole brain volumes (β = 38.3, 95% CI 6.0 to 70.7, p = 0.021), and higher normalized grey matter volumes (β = 20.9, 95% CI - 0.7 to 42.6, p = 0.058) than unmarried PwMS.

Conclusion: Being married may be associated with improved MS outcomes as evidenced by decreased radiographic MS disease burden.

Background and objectives: The total functioning capacity (TFC) assessment has been integral to Huntington's disease (HD) research and clinical trials, measuring disease stage and progression. This study investigates the natural progression of function in HD, focusing on changes in TFC scores related to age and CAG-repeat length, and evaluates TFC's strengths and weaknesses in longitudinal studies.

Methods: Using Enroll-HD platform's clinical dataset version 5, including Registry-3, we analysed data from 21,079 participants, with 16,083 having an expanded CAG repeat. Our final analysis encompassed 15,527 patients and 52,457 visits, with TFC scores ranging from 0 to 13.

Results: Alluvial charts show that most individuals maintain maximum functional capacity over time. 3505 individuals experienced change in TFC scores, over the subsequent 4 years, 2224 (64.1%) experienced declining TFC scores, while 661 (18.6%) showed improvement within a year. The remaining 17.3% exhibited stable TFC scores. Age-related changes followed a specific sequence: occupation, household chores/finances, daily living, and care. Longer CAG-repeat lengths were linked to earlier functional decline, with some geographic regions showing earlier losses in specific domains. Reduced penetrance CAG-repeat groups exhibited different trajectories from full penetrance HD participants.

Discussion: When we focus on those who experienced a change in TFC score, the number of HD patients with regained functional capacity is substantial, even considering interrater variability, which may influence outcome assessments in clinical trials. The TFC effectively reflects changes in functional domains as intended. Analysis of the reduced penetrance group suggests potential selection biases in seeking medical attention earlier and for reasons unrelated to HD.

Background: Impaired impulse control is often seen in Parkinson's disease (PD) patients using dopamine agonists.

Methods: We performed a therapeutic drug monitoring study of 100 PD patients using ropinirole or pramipexole extended release. Three blood samples were collected on the same day. Serum concentrations were measured, and 24 h area under the curve (AUC) calculated. The validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) was used for assessing impulse control.

Results: Total ropinirole drug exposure showed weak, but significant correlation to the QUIP-RS score. No correlation between pramipexole serum concentrations and QUIP-RS was found. In ropinirole patients, both agonist dose and total dopaminergic treatment were correlated with QUIP-RS. Duration of ropinirole treatment correlated with impaired impulse control, and duration of dopaminergic treatment of any type correlated with QUIP-RS scores in both ropinirole and pramipexole patients.

Conclusions: Our main finding is that impaired impulse control is correlated to both total drug exposure (AUC) and dopamine agonist dose for ropinirole, but not for pramipexole. These observations indicate that different strategies may be useful for treating PD patients with impaired impulse control: ropinirole dose reduction could be beneficial, whereas pramipexole treatment may have to be stopped.