Journal of Neurology最新文献

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.

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 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: Vestibular dysfunction causing imbalance affects c. 80% of acute hospitalized traumatic brain injury (TBI) cases. Poor balance recovery is linked to worse return-to-work rates and reduced longevity. We previously showed that white matter network disruption, particularly of right inferior longitudinal fasciculus, mediates the overlap between imbalance and impaired vestibular perception of self-motion (i.e., vestibular agnosia) in acute hospitalized TBI. However, there are no prior reports tracking the acute-longitudinal trajectory of objectively measured vestibular function for hospitalized TBI patients. We hypothesized that recovery of vestibular agnosia and imbalance is linked and mediated by overlapping brain networks.

Methods: We screened 918 acute major trauma in-patients, assessed 146, recruited 39 acutely, and retested 34 at 6 months. Inclusion criteria were 18-65-year-old adults hospitalized for TBI with laboratory-confirmed preserved peripheral vestibular function. Benign paroxysmal positional vertigo and migraine were treated prior to testing. Vestibular agnosia was quantified by participants' ability to perceive whole-body yaw plane rotations via an automated rotating-chair algorithm. Subjective symptoms of imbalance (via questionnaires) and objective imbalance (via posturography) were also assessed.

Results: Acute vestibular agnosia predicted poor balance recovery at 6 months. Recovery of vestibular agnosia and linked imbalance was mediated by bihemispheric fronto-posterior cortical circuits. Recovery of subjective symptoms of imbalance and objective imbalance were not correlated.

Conclusion: Vestibular agnosia mediates balance recovery post-TBI. The link between subjective dizziness and brain injury recovery, although important, is unclear. Therapeutic trials of vestibular recovery post-TBI should target enhancing bi-hemispheric connectivity and linked objective clinical measures (e.g., posturography).

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.

Ataxia-Telangiectasia (A-T) is a very rare multisystem disease of DNA repair, associated with progressive disabling neurological symptoms, respiratory failure, immunodeficiency and cancer predisposition, leading to premature death. There are no curative treatments available for A-T but clinical trials have begun. A major limiting factor in effectively evaluating therapies for A-T is the lack of suitable outcome measures and biomarkers. We have performed a systematic review to collect the information currently available on biomarkers for A-T both in patients and preclinical studies. We have identified 56 reports discussing potential A-T biomarkers in both pre-clinical models and patients. These studies report on diagnostic biomarkers but prognostic biomarkers and responsive markers of clinical status are currently lacking. Some biomarkers of neurodegeneration in A-T show promise, including non-invasive neuroimaging biomarkers. Some biomarkers of oxidative stress and responsive markers to radiotherapy and steroid treatment have potential value in clinical trials. The formation of the A-T biomarker working group with international experts is an important step forward to facilitate the sharing of materials, data and expertise with the common goal of finding effective biomarkers for A-T.

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.

Background: Temporal lobe epilepsy with isolated amygdala enlargement (TLE-AE) still lacks a definite characterization and controversies exist.

Methods: We conducted a retrospective study identifying brain MRI scans with isolated AE between 2015 and 2021. We collected clinical and paraclinical data of patients with TLE-AE and evaluated the outcome.

Results: Forty-one subjects were included (20 males; AE: right 13; left 24; bilateral 4). A strong correlation was found between AE and MRI T2-hyperintensity (right: p < 0.005; left: p < 0.003). There was no history of febrile seizures; 85,4% had focal seizures with impaired awareness, 78,1% reported auras (epigastric sensation, déjà-vu, anxiety), 37% had psychiatric disturbances, 48,6% presented with cognitive impairment. We report that AE correlates with FDG-PET temporomesial hypometabolism (right: p = 0.022; left: p = 0.053), temporal interictal activity on EEG (n = 41), and temporal ictal findings during long-term video-EEG monitoring (n = 23). Epilepsy surgery (n = 17) revealed gliosis (n = 4), inflammatory infiltrates (n = 4), or low-grade epilepsy-associated neuroepithelial tumors (n = 5) in the amygdala. Other treatments were immunotherapy (n = 6) and only antiseizure medications (n = 17), with good prognosis (58,1% seizure-free and 17,1% only with auras at last follow-up). There was no correlation between longitudinal changes in seizure frequency and amygdala size (p = 0.848) and T2-hyperintensity (p = 0.909).

Conclusions: AE should be searched in TLE patients with typical aura, psychiatric and/or neurocognitive disturbances. The strong correlations found between AE lateralization and neurophysiological, FDG-PET, and MRI data support involvement of AE in the epileptogenic network. Drug resistance should prompt presurgical study. Inflammation in amygdala specimens and response after immunotherapy suggest an immune-mediated etiology in some TLE-AE cases.