Disruptions to in-person medical visits across the United States during the COVID-19 pandemic: evolving disparities by medical specialty and socio-economic status.

OBJECTIVES: This study aimed to investigate how people's health-seeking behaviors evolve in the COVID-19 pandemic by community and medical service category. STUDY DESIGN: This is a longitudinal study using mobility data from 19 million mobile devices of visits to all types of health facility locations for all US states. METHODS: We examine the variations in weekly in-person medical visits across county, neighborhood, and specialty levels. Different regression models are used for each level to investigate factors that influence the disparities in medical visits. County-level analysis explores associations between county medical visit patterns, political orientation, and COVID-19 infection rate. Neighborhood-level analysis focuses on neighborhood socio-economic compositions as potential determinants of medical visit levels. Specialty-level analysis compares the evolution of visit disruptions in different specialties. RESULTS: A more left-leaning political orientation and a higher local infection rate were associated with larger decreases in in-person medical visits, and these associations became stronger, moving from the initial period of stay-at-home orders into the post-lockdown period. Initial reactions were strongest for seniors and those of high socio-economic status, but this reversed in post-lockdown period where socio-economically disadvantaged communities stabilized at a lower level of medical visits. Neighborhoods with more female and young people exhibited larger decreases in in-person medical visits throughout the initial and post-lockdown periods. The evolution of disruptions diverges across medical specialties, from only short-term disruption in specialties such as dentistry to increasing disruption, as in cardiology. CONCLUSIONS: Given distinct patterns in visit between communities, medical service categories, and between different periods in the pandemic, policy makers, and providers should concentrate on monitoring patients in disrupted specialties who overlap with the at-risk contexts and socio-economic factors in future health emergencies.

Brain lesion location and clinical status 20 years after a diagnosis of clinically isolated syndrome suggestive of multiple sclerosis.

BACKGROUND/OBJECTIVES: The objective of this study was to investigate associations between the spatial distribution of brain lesions and clinical outcomes in a cohort of people followed up 20 years after presentation with a clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). METHODS: Brain lesion probability maps (LPMs) of T1 and T2 lesions were generated from 74 people who underwent magnetic resonance imaging (MRI) and clinical assessment a mean of 19.9 years following a CIS. One-tailed t-test statistics were used to compare LPMs between the following groups: clinically definite (CD) MS and those who remained with CIS, with an abnormal MRI; people with MS and an Expanded Disability Status Scale (EDSS) ≤3 and >3; people with relapsing-remitting (RR) and secondary progressive (SP) MS. The probability of each voxel being lesional was analysed adjusting for age and gender using a multiple linear regression model. RESULTS: People with CDMS were significantly more likely than those with CIS and abnormal scan 20 years after onset to have T1 and T2 lesions in the corona radiata, optic radiation, and splenium of the corpus callosum (periventricularly) and T2 lesions in the right fronto-occipital fasciculus. People with MS EDSS >3, compared with those with EDSS ≤3, were more likely to have optic radiation and left internal capsule T2 lesions. No significant difference in lesion distribution was noted between RRMS and SPMS. CONCLUSION: This work demonstrates that lesion location characteristics are associated with CDMS and disability after long-term follow-up following a CIS. The lack of lesion spatial distribution differences between RRMS and SPMS suggests focal pathology affects similar regions in both subgroups.

MRI only conversion to multiple sclerosis following a clinically isolated syndrome.

OBJECTIVES: Using current diagnostic criteria, patients who present with a clinically isolated syndrome (CIS) may develop multiple sclerosis (MS) by subsequently exhibiting dissemination in space and time on clinical (clinically definite (CD) MS) or radiological (MRI) grounds. This study investigated the frequency of radiological without clinical conversion to MS after long term follow-up as this has not previously been defined. METHODS: Two cohorts who underwent serial clinical and MRI studies from presentation with a CIS and who were followed-up over a mean of 6 and 20 years were investigated. The distribution and formation of lesions visible on brain MRI were assessed using the revised McDonald criteria (2005). Radiologically defined (RD) MS was determined by fulfilment of the MRI but not the CDMS criteria. RESULTS: 105 people were followed-up for 6 years after a CIS, of whom 51% developed CDMS, 15% RDMS and the remainder were classified as still having had a CIS. 70 people were followed-up at 20 years, of whom 61% and 11% had developed CDMS and RDMS, respectively. CONCLUSION: About 10-15% of CIS patients may develop MS on MRI criteria only, without further clinical events for up to two decades.

Early MRI in optic neuritis: the risk for clinically definite multiple sclerosis.

MRI brain lesions at presentation with optic neuritis (ON) increase the risk for developing clinically definite (CD) multiple sclerosis (MS). More detailed early MRI findings may improve prediction of conversion. The objectives of this study were to investigate the influence of number, location and activity of lesions at presentation, new lesions at early follow-up and non-lesion MRI measures on conversion from optic neuritis (ON) to CDMS. 142/143 ON patients, prospectively recruited into a serial MRI and clinical follow-up study, were followed-up at least once. Cox regression analysis determined independent early MRI predictors of time to CDMS from: (i) baseline lesion number, location and activity measures, (ii) three-month lesion activity measures and (iii) brain atrophy, magnetization transfer ratio and spectroscopy measures. 114/142 (80%) had abnormal baseline brain or cord MRI. 57 (40%) developed CDMS (median of 16 months from clinically isolated syndrome onset). Median follow-up of the non-converters was 62 months. Multivariate analysis of baseline parameters revealed gender, periventricular and gadolinium-enhancing lesions as independent predictors of CDMS. Considering both scans together, gender, baseline periventricular and new T2 lesions at follow-up remained significant (hazard ratios 2.1, 2.4 and 4.9, respectively). No non-conventional measure predicted CDMS. It was concluded that new T2 lesions on an early follow-up scan were the strongest independent predictor of CDMS.

Early MRI in optic neuritis: the risk for disability.

BACKGROUND: MRI findings influence the risk of patients with optic neuritis (ON) developing clinically definite (CD) multiple sclerosis (MS) but their influence on future disability is less clear. OBJECTIVE: To investigate in patients with ON the influence of lesion number, location and activity, and non-lesion MRI measures obtained on early scans on disability. METHODS: A total of 106 of 143 prospectively recruited patients with ON had reached a scheduled 5-year follow-up, of whom 100 were evaluated clinically. Lesion number, location, and activity measures were analyzed at baseline (within 3 months of onset) and lesion activity measures were studied at 3-month follow-up. Brain atrophy, magnetization transfer ratio, and spectroscopy measures were also analyzed. Ordinal logistic regression assessed the association between early MRI findings and subsequent disability. RESULTS: At median 6 years follow-up, 48% had converted to CDMS and 52% remained with clinically isolated syndrome (median Expanded Disability Status Scale 2 and 1). In the final models, both the presence and the number of spinal cord lesions at baseline (odds ratios [OR] 3.30, 1.94) and new T2 lesions at follow-up (OR 7.12, 2.06) were significant independent predictors of higher disability. Disability was also predicted by the presence at baseline of gadolinium-enhancing lesions (OR 2.78) and number of infratentorial lesions (OR 1.82). Only spinal cord lesions predicted disability in patients converting to CDMS. CONCLUSION: Spinal cord, infratentorial, and gadolinium lesions within 3 months of optic neuritis onset and new T2 lesions after 3 months predicted disability after 6 years; only spinal cord lesions were predictive of disability in those developing clinically definite multiple sclerosis.

Is the frequency of abnormalities on magnetic resonance imaging in isolated optic neuritis related to the prevalence of multiple sclerosis? A global comparison.

The link between optic neuritis and multiple sclerosis is well established, as is the increased risk of conversion to multiple sclerosis, with lesions seen at presentation on the magnetic resonance imaging (MRI) scan of the brain. One or more asymptomatic lesions were present in 77% of the optic neuritis cohort from London, UK, a higher proportion than that reported in other large cohorts studied elsewhere, where generally lower prevalence rates for multiple sclerosis are also reported. These observations may support the hypothesis that optic neuritis is more likely to be associated with abnormalities on MRI and to be due to multiple sclerosis in geographical regions where multiple sclerosis is more common.

Ventricular enlargement in MS: one-year change at various stages of disease.

OBJECTIVES: To investigate ventricular enlargement (VE) over 1 year at three different stages of multiple sclerosis (MS). METHODS: A semi-automated technique for measuring VE was applied to MRI scans in 26 patients with clinically isolated syndromes (CIS) suggestive of MS, 30 with early relapse-onset MS of 1 year duration, 41 with established relapsing remitting (RR) MS, and 23 with secondary progressive (SP) MS. RESULTS: VE at 1 year was seen in early MS (median increase 0.3 mL [p = 0.003]), RRMS (median increase 0.5 mL [p = 0.001]), and SPMS (median increase 1.1 mL [p = 0.001]). Allowing for age there was more VE in the SPMS group (p = 0.005). No VE was observed in the CIS only group (median decrease -0.001 mL [p = 0.829]). Significant increases in T2 and T1 hypointense lesion load volume were seen in all MS subgroups: there were no differences between the groups in T2 volume increase but there was a larger increase in T1 hypointense lesion volume in the SPMS group compared with early RRMS. CONCLUSIONS: Ventricular enlargement is a sensitive measure of progressive cerebral atrophy that is seen at all stages of multiple sclerosis (MS) and is more marked in secondary progressive than relapsing remitting MS.

Modification of MRI criteria for multiple sclerosis in patients with clinically isolated syndromes.

BACKGROUND: The McDonald criteria include MRI evidence for dissemination in space and dissemination in time for the diagnosis of multiple sclerosis in young adult patients who present with clinically isolated syndromes (CIS) typical of the disease. Although a major advance, the criteria have limited sensitivity for making an early diagnosis. OBJECTIVE: To compare the performance of McDonald criteria and modified McDonald criteria for dissemination in space and time for assessing the development of clinically definite multiple sclerosis. METHODS: McDonald criteria were modified using the combination of a less stringent definition for dissemination in space and allowing a new T2 lesion per se after three months as evidence for dissemination in time. Modified and McDonald criteria were applied in 90 CIS patients at baseline and at three month follow up scans. RESULTS: Both criteria were highly specific (>90%) but the modified criteria were more sensitive (77% v 46%) and more accurate (86% v 73%). CONCLUSIONS: These modified criteria should be evaluated in other CIS cohorts.

Magnetization transfer histograms in clinically isolated syndromes suggestive of multiple sclerosis.

In established multiple sclerosis, magnetization transfer ratio (MTR) histograms reveal abnormalities of normal-appearing white matter (NAWM) and grey matter (NAGM). The aim of this study was to investigate for such abnormalities in a large cohort of patients presenting with clinically isolated syndromes suggestive of multiple sclerosis. Magnetization transfer imaging was performed on 100 patients (67 women, 33 men, median age 32 years) a mean of 19 weeks (SD 3.8, range 12-33 weeks) after symptom onset with a clinically isolated syndrome and in 50 healthy controls (34 women, 16 men, median age 32.5 years). SPM99 software was used to generate segmented NAWM and NAGM MTR maps. The volumes of T2 lesions, white matter and grey matter were calculated. Eighty-one patients were followed up clinically and with conventional MRI after 3 years (n = 61) or until they developed multiple sclerosis if this occurred sooner (n = 20). Multiple regression analysis was used to investigate differences between patients and controls with age, gender and volume measures as covariates to control for potential confounding effects. The MTR histograms for both NAWM and NAGM showed a reduction in the mean (NAWM, 38.14 versus 38.33, P = 0.001; NAGM 32.29 versus 32.50, P = 0.009; units in pu) and peak location, with a left shift in the histogram. Mean NAWM and NAGM MTR were also reduced in the patients who developed clinically definite multiple sclerosis and multiple sclerosis according to the McDonald criteria but not in the 24 patients with normal T2-weighted brain magnetic resonance imaging (MRI). MTR abnormalities occur in the NAWM and NAGM at the earliest clinical stages of multiple sclerosis.

Anti-myelin antibodies do not allow earlier diagnosis of multiple sclerosis.

This study investigates whether the presence of serum and plasma anti-myelin oligodendrocyte glycoprotein (MOG) and anti-myelin basic protein (MBP) in patients presenting with a clinically isolated syndrome compatible with demyelination (CIS) predicts early conversion to multiple sclerosis (MS). Forty-seven patients with CIS (46 with optic neuritis) had anti-MOG and anti-MBP antibodies analysed at baseline, and clinical and magnetic resonance imaging assessments. There was no evidence that the MS status based on either the McDonald or Poser criteria relates to the antibody status.

Estimation of the macromolecular proton fraction and bound pool T2 in multiple sclerosis.

This study used a model for magnetization transfer (MT) to estimate two underlying parameters: the macromolecular proton fraction (f) and the bound pool T2 (T2b) in patients with multiple sclerosis (MS). Sixty patients with clinically definite MS and 27 healthy controls were imaged using: (1) a dual echo fast spin echo sequence, (2) a MT sequence (with ten MT power and offset frequency combinations) and (3) proton density and T1 weighted sequences (for T1 relaxation time estimation). Fourteen normal-appearing white matter (NAWM) regions of interest (ROI) and six normal-appearing gray matter (NAGM) ROIs were outlined in all subjects. Lesions were also contoured in subjects affected by MS. The model was fitted to the data leading to estimates of T2b and f. Results showed that T2b was increased in lesions whereas f was reduced. In NAWM, f was decreased while T2b was only increased in secondary progressive MS. NAWM f correlated modestly with disability. Further studies are needed to investigate the pathological basis of the abnormalities observed.

Elevated white matter myo-inositol in clinically isolated syndromes suggestive of multiple sclerosis.

Normal-appearing white matter (NAWM) in established multiple sclerosis has been shown to be abnormal using a variety of magnetic resonance (MR) techniques, including proton MR spectroscopy ((1)H-MRS), although the stage at which these changes first appear is less clear. Using a 1.5 T scanner and single-voxel (1)H-MRS [TR 3000 ms, TE 30 ms, point-resolved spectroscopy (PRESS) localization], we determined NAWM metabolite concentrations in 96 patients a mean of 19 weeks (range 12-28 weeks) after onset of a clinically isolated syndrome (CIS) suggestive of multiple sclerosis and in 44 healthy control subjects. Absolute concentrations of N-acetyl-aspartate, total creatine and phosphocreatine (Cr), choline-containing compounds, glutamate plus glutamine, and myo-inositol (Ins) were estimated automatically using the LCModel. Compared with control subjects, the concentration of Ins was elevated in CIS NAWM (mean 3.31 mM, SD 0.86 versus mean 3.82 mM, SD 1.06; P = 0.001). The increase in Ins was also seen in the patient subgroup with abnormal T2-weighted MRI (mean 3.88 mM, SD 1.10; P = 0.001) and in those who satisfied the McDonald criteria for multiple sclerosis (mean 4.04 mM, SD 1.31; P = 0.001). An increase in Cr was also observed in CIS NAWM (P = 0.023), but other metabolites did not significantly differ between the whole CIS group and control subjects. There was no significant correlation between NAWM Ins and T2 lesion load. The early increase in Ins may reflect a process of pathogenic importance in multiple sclerosis NAWM. Follow-up studies will investigate whether the increase in NAWM Ins is of prognostic importance for future relapses and disability.

Spinal cord MRI in clinically isolated optic neuritis.

BACKGROUND/METHODS: One hundred and fifteen patients with clinically isolated optic neuritis underwent magnetic resonance imaging (MRI) of the brain and spinal cord within 3 months of the onset of symptoms. RESULTS: Eighty one (70%) patients had brain lesions and 31 (27%) had cord lesions. Cord lesions were seen in 12% with a normal brain MRI, 21% with between one and eight brain lesions, and 45% with nine or more brain lesions. When the new diagnostic criteria for MS were applied, MRI cord imaging used for evidence of dissemination in time and space allowed a diagnosis of MS in only one additional asymptomatic patient at 1 year, two additional asymptomatic patients at 3 years. CONCLUSIONS: Using existing criteria, spinal cord imaging rarely contributes to the diagnosis in patients with clinically isolated optic neuritis.

Preliminary magnetic resonance study of the macromolecular proton fraction in white matter: a potential marker of myelin?

We report on a new quantitative magnetization transfer (MT) technique that allows for the in vivo estimation of the macromolecular proton fraction (f) and the bound pool T2 relaxation time (T2b), whilst permitting whole brain coverage. In this pilot study, five subjects with multiple sclerosis (MS) and five healthy controls were studied. Both f and T2b were significantly different between MS lesions and normal control white matter (WM). Relationships between f and T1 relaxation time [Spearmans rank correlation coefficient (r(s)) = -0.97, P < 0.001] and f and the magnetization transfer ratio (MTR; r(s) = 0.80, P < 0.001) were observed. Compared with MTR, f and T2b have the potential advantage of relative independence from MT acquisition protocol while offering more pathologically specific information. In particular, f may provide a more direct indication of myelin content in WM.

Management of acute optic neuritis.

Optic neuritis is a common condition that causes reversible loss of vision. It can be clinically isolated or can arise as one of the manifestations of multiple sclerosis. Occasional cases are due to other causes, and in these instances management can differ radically. The treatment of optic neuritis has been investigated in several trials, the results of which have shown that corticosteroids speed up the recovery of vision without affecting the final visual outcome. Other aspects of management, however, are controversial, and there is uncertainty about when to investigate and when to treat the condition. Here we review the diagnostic features of optic neuritis, its differential diagnosis, and give practical guidance about management of patients. The condition's association with multiple sclerosis will be considered in the light of studies that define the risk for development of multiple sclerosis and with respect to results of trials of disease-modifying drugs in these individuals.

Normal-appearing brain tissue MTR histograms in clinically isolated syndromes suggestive of MS.

Segmented normal-appearing brain tissue (NABT) was investigated in 40 patients with a recent onset and 13 patients with a remote onset of a clinically isolated syndrome (CIS) using magnetization transfer ratio (MTR) histograms. Abnormalities were present in patients with a high risk for MS (recent onset and T2-weighted lesions present) and in those with a low risk for relapse (recent onset without T2-weighted lesions). Similar mild NABT abnormality was present with CIS and no further disease activity 14 years later. NABT MTR abnormality in CIS may indicate susceptibility to demyelination but not to disease progression.

Progressive ventricular enlargement in patients with clinically isolated syndromes is associated with the early development of multiple sclerosis.

BACKGROUND: In patients with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS), the extent of brain magnetic resonance imaging (MRI) lesion load influences the probability and time to development of clinically definite MS. Cerebral atrophy is recognised in established MS, but its time of onset and whether, in early disease, it is related to MRI lesion load or clinical outcome is less certain. OBJECTIVES: This study investigated ventricular enlargement over one year in CIS patients and explored its relation with lesion load and clinical outcome. METHODS: A semi-automated thresholding technique for measuring ventricular volume (MIDAS) was applied to MRI scans in a cohort of 55 patients with CIS, recruited consecutively and imaged within three months of the onset of symptoms and again after one year. RESULTS: Clinical MS had developed after one year in 16 of 40 patients with an abnormal baseline T2 scan and 2 of 15 with a normal scan. Significant ventricular enlargement was seen in 27 of 55 patients who fulfilled the new McDonald MRI criteria for MS using all available MRI at clinical follow up (median increase 0.3 cm(3), p=0.005) Significant increase in ventricular volume was also seen in the 18 of 55 patients who developed clinical MS over the follow up period (median increase 0.5 cm(3), p=0.006). There were significant but modest correlations between baseline lesion measures and subsequent ventricular enlargement. CONCLUSIONS: (1) Lesions and atrophy are both associated with early relapse leading to a diagnosis of clinical MS; (2) while lesions contribute to the development of atrophy, atrophy may also develop by other mechanisms. This suggests that MR measures have a complementary role in monitoring the course of MS, even from the earliest clinical stage.