Neuromelanin-MRI using 2D GRE and deep learning: considerations for improving the visualization of substantia nigra and locus coeruleus

An optimized clinically feasible neuromelanin-MRI imaging protocol for visualising the SN and LC simultaneously using deep learning reconstruction is presented. We optimize flip-angle for optimal combined SN and LC depiction. We also experimented with combinations of anisotropic and isotropic in-plane resolution, partial vs full echoes and the number of averages. Phantom and in-vivo experiments on three healthy volunteers illustrate that high-resolution imaging combined with deep-learning denoising shows good depiction of the SN and LC with a clinically feasible sequence of around 7 minutes.Comment: An article based on ECR and ISMRM abstracts, with more text & figure

Neurologic syndromes related to anti-GAD65: Clinical and serologic response to treatment

OBJECTIVE: Antibodies against glutamic acid decarboxylase 65 (anti-GAD65) are associated with a number of neurologic syndromes. However, their pathogenic role is controversial. Our objective was to describe clinical and paraclinical characteristics of anti-GAD65 patients and analyze their response to immunotherapy. METHODS: Retrospectively, we studied patients (n = 56) with positive anti-GAD65 and any neurologic symptom. We tested serum and CSF with ELISA, immunohistochemistry, and cell-based assay. Accordingly, we set a cutoff value of 10,000 IU/mL in serum by ELISA to group patients into high-concentration (n = 36) and low-concentration (n = 20) groups. We compared clinical and immunologic features and analyzed response to immunotherapy. RESULTS: Classical anti-GAD65-associated syndromes were seen in 34/36 patients with high concentration (94%): stiff-person syndrome (7), cerebellar ataxia (3), chronic epilepsy (9), limbic encephalitis (9), or an overlap of 2 or more of the former (6). Patients with low concentrations had a broad, heterogeneous symptom spectrum. Immunotherapy was effective in 19/27 treated patients (70%), although none of them completely recovered. Antibody concentration reduction occurred in 15/17 patients with available pre- and post-treatment samples (median reduction 69%; range 27%-99%), of which 14 improved clinically. The 2 patients with unchanged concentrations showed no clinical improvement. No differences in treatment responses were observed between specific syndromes. CONCLUSION: Most patients with high anti-GAD65 concentrations (>10,000 IU/mL) showed some improvement after immunotherapy, unfortunately without complete recovery. Serum antibody concen

Breakpoint mapping of 13 large parkin deletions/duplications reveals an exon 4 deletion and an exon 7 duplication as founder mutations

Early-onset Parkinson’s disease (EOPD) has been associated with recessive mutations in parkin (PARK2). About half of the mutations found in parkin are genomic rearrangements, i.e., large deletions or duplications. Although many different rearrangements have been found in parkin before, the exact breakpoints involving these rearrangements are rarely mapped. In the present study, the exact breakpoints of 13 different parkin deletions/duplications, detected in 13 patients out of a total screened sample of 116 EOPD patients using Multiple Ligation Probe Amplification (MLPA) analysis, were mapped using real time quantitative polymerase chain reaction (PCR), long-range PCR and sequence analysis. Deletion/duplication-specific PCR tests were developed as a rapid and low cost tool to confirm MLPA results and to test family members or patients with similar parkin deletions/duplications. Besides several different deletions, an exon 3 deletion, an exon 4 deletion and an exon 7 duplication were found in multiple families. Haplotype analysis in four families showed that a common haplotype of 1.2 Mb could be distinguished for the exon 7 duplication and a common haplotype of 6.3 Mb for the deletion of exon 4. These findings suggest common founder effects for distinct large rearrangements in parkin

The Dutch Normal-Pressure Hydrocephalus Study. How to select patients for shunting? An analysis of four diagnostic criteria

BACKGROUND. Comparison of the predictive value of four 'diagnostic tests' for the outcome of shunting in patients with normal-pressure hydrocephalus (NPH). METHODS. Ninety-five NPH patients who received shunts were followed for 1 year. Gait disturbance and dementia were quantified by an NPH scale and handicap by a modified Rankin scale. Primary outcome measures were differences between the preoperative and last scores on both the NPH scale and the modified Rankin scale. Clinical and computed tomographic (CT) findings typical of NPH, absence of cerebrovascular disease, and a resistance to outflow of cerebrospinal fluid (CSF) ≥ 18 mmHg/ml/minute were designated as a positive test outcome; clinical and CT findings compatible with NPH, presence of cerebrovascular disease, and an outflow resistance < 18 mmHg/ml/minute as a negative test outcome. RESULTS. For each of the four tests the percentage of patients classified as improved was significantly greater for those with positive than with negative test results. Measurement of CSF outflow resistance was the only significant prognostic factor for the improvement ratio in NPH scale and CT in the modified Rankin scale according to multivariate logistic regression analysis. The accurate predictive value of the combination of typical clinical and CT findings was 0.65, that of the positive test results of outflow resistance, clinical and CT findings was 0.74. CONCLUSION. The best strategy is to shunt NPH patients if their outflow resistance is ≥ 18 mmHg/ml/minute or, when the outflow resistance is lower, if their clinical as well as their CT findings are typical of NPH. Copyright (C) 2000 Elsevier Science Inc

Dutch normal-pressure hydrocephalus study: The role of cerebrovascular disease

Object. This study was conducted to determine the prevalence of cerebrovascular disease and its risk factors among patients with normal- pressure hydrocephalus (NPH) and to assess the influence of these factors on the outcome of shunt placement. Methods. A cohort of 101 patients with NPH underwent shunt placement and was followed for 1 year. Gait disturbance and dementia were quantified using an NPH scale and handicap was determined using a modified Rankin scale (mRS). Primary outcome measures consisted of the differences between preoperative and last NPH scale and mRS scores. The presence of risk factors such as hypertension, diabetes mellitus, Cardiac disease, peripheral vascular disease, male gender, and advancing age was recorded. Cerebrovascular disease was defined as a history of stroke or a computerized tomography (CT) scan revealing infarcts or moderate-to-severe White matter hypodense lesions. The prevalence of risk factors for cerebrovascular disease was higher in the 45 patients with cerebrovascular disease than the 56 without it. Risk factors did not influence outcome after shunt placement. Intent-to-treat analysis revealed that the mean improvement in the various scales was significantly less for patients with a history of stroke (14 patients), CT Scans revealing infarctions (13) or white matter hypodense lesions (32 patients) than for those without cerebrovascular disease. The proportion of patients who responded to shunt placement was also significantly lower among patients with than those without cerebrovascular disease (p = 0.02). Conclusions. The authors identified a subgroup of patients with NPH and cerebrovascular disease who showed disappointing results after shunt placement. Cerebrovascular disease was an important predictor of poor outcome

Serum neurofilament light chain in progressive supranuclear palsy

Introduction: Neurofilament light chain (NfL) is a promising biomarker in neurodegenerative diseases. Elevated NfL levels in CSF and blood have been observed in a growing number of neurodegenerative disorders, including frontotemporal dementia and Alzheimer's disease. We studied serum NfL levels in patients with progressive supranuclear palsy (PSP) in relation to disease severity and survival. Methods: Serum NfL levels were determined cross-sectionally in a retrospective cohort of 131 patients with PSP and 95 healthy controls. Detailed clinical examination was performed and disease severity was assessed by several rating scales. Results: We found that serum NfL levels in PSP were twice as high as those in controls, and that NfL levels correlated with worse functional, motor and cognitive functioning. During follow-up, 119 PSP patients had died, and higher NfL levels were associated with a shorter survival. Conclusion: This study provides evidence that serum NfL is a relevant and promising biomarker in PSP for disease severity, and may be used as a prognostic tool to predict survival in clinical practice