HLA-DRB1*15 influences the development of brain tissue damage in early PPMS

OBJECTIVES To investigate whether (1) there were differences between HLA-DRB1*15-positive and -negative patients at baseline, and (2) HLA-DRB1*15-positive patients showed a greater development of brain and spinal cord damage, as assessed by MRI, and greater progression of disability, during a 5-year follow-up, compared with HLA-DRB1*15-negative patients. METHODS HLA-DRB1*15 typing was performed in 41 patients with primary progressive multiple sclerosis (PPMS) who were recruited within 5 years of symptom onset. All patients and 18 healthy controls were studied clinically and with MRI at baseline, and every 6 months for 3 years, and then at 5 years. Magnetization transfer ratio parameters and volumes for brain gray matter and normal-appearing white matter, brain T2 lesion load, and spinal cord cross-sectional area were obtained. Patient disability was assessed at each visit using the Expanded Disability Status Scale and Multiple Sclerosis Functional Composite subscores. RESULTS There were no significant differences between HLA-DRB1*15-positive and -negative patients at baseline. HLA-DRB1*15-positive patients showed a greater decline in brain magnetization transfer ratio for gray matter and normal-appearing white matter (both p = 0.005) than HLA-DRB1*15-negative patients over 5 years, while the same parameters did not change over time in healthy controls. HLA-DRB1*15-positive patients also showed a trend toward a faster increase in brain T2 lesion load than HLA-DRB1*15-negative patients (0.29 [95% confidence interval 0.20-0.38] vs 0.21 [0.13-0.30] mL/mo, p = 0.085) and higher T2 lesion volumes at all time points (average difference [95% confidence interval]: 10.58 mL [7.09-14.07], p < 0.001) during the follow-up, after adjusting for disease duration. CONCLUSIONS These findings suggest that HLA-DRB1*15 influences the progression of brain pathology in PPMS

Clinical relevance of cortical network dynamics in early primary progressive MS.

BACKGROUND: Structural cortical networks (SCNs) reflect the covariance between the cortical thickness of different brain regions, which may share common functions and a common developmental evolution. SCNs appear abnormal in neurodegenerative conditions such as Alzheimer's and Parkinson's diseases, but have never been assessed in primary progressive multiple sclerosis (PPMS). OBJECTIVE: The aim of this study was to test whether SCNs are abnormal in early PPMS and change over 5 years, and correlate with disability worsening. METHODS: A total of 29 PPMS patients and 13 healthy controls underwent clinical and brain magnetic resonance imaging (MRI) assessments for 5 years. Baseline and 5-year follow-up cortical thickness values were obtained and used to build correlation matrices, considered as weighted graphs to obtain network metrics. Bootstrap-based statistics assessed SCN differences between patients and controls and between patients with fast and slow progression. RESULTS: At baseline, patients showed features of lower connectivity (p = 0.02) and efficiency (p < 0.001) than controls. Over 5 years, patients, especially those with fastest clinical progression, showed significant changes suggesting an increase in network connectivity (p < 0.001) and efficiency (p < 0.02), not observed in controls. CONCLUSION: SCNs are abnormal in early PPMS. Longitudinal SCN changes demonstrated a switch from low- to high-efficiency networks especially among fast progressors, indicating their clinical relevance

Validation of the 2023 International Diagnostic Criteria for MOGAD in a Selected Cohort of Adults and Children

BACKGROUND AND OBJECTIVES: To test the performance of the 2023 myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) criteria in adults and children with inflammatory demyelinating conditions who were tested for MOG antibodies (Abs). // METHODS: This was a retrospective study of patients tested for MOG-Abs from 2018 to 2022 in 2 specialist hospitals. The inclusion criteria comprised ≥1 attendance in an adult or pediatric demyelinating disease clinic and complete clinical and MRI records. The final clinical diagnosis of MOGAD, made by the treating neurologist, was taken as the benchmark against which the new criteria were tested. The international MOGAD diagnostic criteria were applied retrospectively; they stipulate at least 1 clinical or MRI supporting feature for MOGAD diagnosis in positive fixed MOG cell-based assay without a titer. The performance MOG-Ab testing alone for MOGAD diagnosis was also assessed and compared with that of MOGAD criteria using the McNemar test. // RESULTS: Of the 1,879 patients tested for MOG-Abs, 539 (135 pediatric and 404 adults) met the inclusion criteria. A clinical diagnosis of MOGAD was made in 86/539 (16%) patients (37 adults, 49 children), with a median follow-up of 3.6 years. The MOGAD diagnostic criteria had sensitivity of 96.5% (adults 91.9%, children 100%), specificity of 98.9% (adults 98.8%, children 98.9%), positive predictive value of 94.3% (adults 89.4%, children 98%), negative predictive value of 99.3% (adults 99.2%, children 100%), and accuracy of 98.5% (adults 98.3%, children 99.2%). When compared with MOG-Ab testing alone, a difference was seen only in adults: a significantly higher specificity (98.9% vs 95.6%, p = 0.0005) and nonstatistically significant lower sensitivity (91.9% vs 100%, p = 0.08). // DISCUSSION: The international MOGAD diagnostic criteria exhibit high performance in selected patients with inflammatory demyelinating diseases (who had a high pretest probability of having MOGAD) compared with best clinical judgment; their performance was better in children than in adults. In adults, the MOGAD criteria led to an improvement in specificity and positive predictive value when compared with MOG-Ab testing alone, suggesting that the requirement of at least 1 clinical or MRI supporting feature is important. Future work should address the generalizability of the diagnostic criteria to cohorts of greater clinical diversity seen within neurologic settings

Normal-Appearing Brain T1 Relaxation Time Predicts Disability in Early Primary Progressive Multiple Sclerosis

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Magnetization transfer ratio in gray matter: a potential surrogate marker for progression in early primary progressive multiple sclerosis

BACKGROUND Magnetization transfer imaging has the potential to provide a surrogate marker for progression in primary progressive multiple sclerosis (PPMS). OBJECTIVES To investigate whether brain magnetization transfer imaging, T2 lesion load, and atrophy changes over 3 years reflect concurrent clinical changes, and which baseline imaging measure best predicts progression over 3 years in early PPMS. DESIGN Prospective study. SETTING National Hospital for Neurology and Neurosurgery and the Institute of Neurology, London, England. PATIENTS Forty-seven patients with PPMS (of whom 43 completed the study) and 18 control subjects. INTERVENTIONS Brain magnetization transfer imaging (including T2-weighted images) and volume sequences every 6 months for 3 years. MAIN OUTCOME MEASURES Changes in Expanded Disability Status Scale (EDSS) score and associations with rate of change in imaging variables. RESULTS More rapid decline in gray matter mean and peak location magnetization transfer ratio and T2 lesion load increase were associated with greater rates of progression on the EDSS. Baseline gray matter peak height magnetization transfer ratio best predicted progression over 3 years. CONCLUSION Gray matter magnetization transfer ratio meets many of the criteria for a surrogate marker of progression in early PPMS

Magnetization transfer ratio in gray matter: a potential surrogate marker for progression in early primary progressive multiple sclerosis.

BackgroundMagnetization transfer imaging has the potential to provide a surrogate marker for progression in primary progressive multiple sclerosis (PPMS).ObjectivesTo investigate whether brain magnetization transfer imaging, T2 lesion load, and atrophy changes over 3 years reflect concurrent clinical changes, and which baseline imaging measure best predicts progression over 3 years in early PPMS.DesignProspective study.SettingNational Hospital for Neurology and Neurosurgery and the Institute of Neurology, London, England.PatientsForty-seven patients with PPMS (of whom 43 completed the study) and 18 control subjects.InterventionsBrain magnetization transfer imaging (including T2-weighted images) and volume sequences every 6 months for 3 years.Main outcome measuresChanges in Expanded Disability Status Scale (EDSS) score and associations with rate of change in imaging variables.ResultsMore rapid decline in gray matter mean and peak location magnetization transfer ratio and T2 lesion load increase were associated with greater rates of progression on the EDSS. Baseline gray matter peak height magnetization transfer ratio best predicted progression over 3 years.ConclusionGray matter magnetization transfer ratio meets many of the criteria for a surrogate marker of progression in early PPMS

Why neurology? The career choices of current UK neurology trainees [Conference Abstract]

Introduction It is important that we attract high-calibre medics to neurology. There are few studies of what motivated neurologists to choose their speciality, when they chose, or what else they might have become. Methods All UK neurology trainees were invited to complete an online survey. Results 160 trainees responded (53% female; 17% less-than-fulltime). 54% decided on neurology before graduating (6% before medical school), whilst 29% decided after foundation training. Common reasons to choose neurology included: academically interesting (72%); clinical exposure as a student or junior (67%); personality fit (53%); influential role-model (37%). Less common motivations included lifestyle, family friendliness, prestige, and family members with neurological conditions. Two trainees chose neurology because they personally have a neurological condition. When asked what their second choice of medical career would have been the answers were diverse and 31 different specialties were named, but only one might have been a neurosurgeon. Conclusions Careers advice should begin early in medical school and continue through medical training with direct exposure to clinical neurology. Traditional neurology values such as the intellectual challenge should be emphasised. Neurologists have a broad interest in medical and psychiatric specialties underlining the importance of core medical training to developing neurologists of the future

T2 lesion location really matters: a 10-year follow-up study in primary-progressive MS

International audienceObjectives: Prediction of long-term clinical outcome in patients with primary-progressive multiple sclerosis (PPMS) using imaging has important clinical implications, but remains challenging. We aimed to determine whether spatial location of T2 and T1 brain lesions predicts clinical progression during a 10-year follow-up in PPMS. Methods: Lesion probability maps of the T2 and T1 brain lesions were generated using the baseline scans of 80 patients with PPMS, who were clinically assessed at baseline and then after one, two, five and ten years. For each patient, the time (in years) taken before bilateral support was required to walk (time-to-event, TTE), was used as a measure of progression rate. The probability of each voxel being “lesional” was correlated with TTE, adjusting for age, gender, disease duration, centre, and spinal cord cross-sectional area, using a multiple linear regression model. To identify the best, independent predictor of progression, a Cox regression model was used. Results: A significant correlation between a shorter TTE and a higher probability of a voxel being lesional on T2 scans was found in the bilateral cortico-spinal tract and superior longitudinal fasciculus, and in the right inferior fronto-occipital fasciculus (p<0.05). The best predictor of progression rate was the T2 lesion load measured along the right inferior fronto-occipital fasciculus (p=0.016, Hazard Ratio 1.00652, 95% Confidence Interval 1.00121, 1.01186). Conclusion: Our results suggest that the location of T2 brain lesions in the motor and associative tracts is an important contributor to the progression of disability in PPMS, and is independent of spinal cord involvement