To estimate the relative contributions of baseline thalamic atrophy and abnormalities shown at magnetization transfer (MT) magnetic resonance (MR) imaging, as well as their 12-month changes, in ...predicting accumulation of disability in a relatively large sample of patients with relapse-onset multiple sclerosis (MS) during an 8-year period.
The study was conducted with approval of the institutional review board. Written informed consent was obtained from each participant. Conventional and MT MR imaging of the brain was performed at baseline and at 12-month follow-up in 13 healthy control subjects and 73 patients with relapse-onset MS; participants were monitored with clinical visits for 8 years. The following parameters were evaluated at baseline and at 12-month follow-up: volume of lesions with high signal intensity at T2-weighted imaging, volume of lesions with low signal intensity at T1-weighted imaging, mean lesion MT ratio, thalamic fraction, and thalamic MT ratio. A multivariate analysis was used to evaluate the predictors of long-term neurologic deterioration.
At 8-year follow-up, 44 patients showed worsening disability. During follow-up, reduction in thalamic fraction was more pronounced in patients with relapsing-remitting MS than in those with secondary progressive MS (P = .001); thalamic MT ratio decreased only in patients with secondary progressive MS (P = .007). In the multivariable model, baseline thalamic fraction (odds ratio = 0.62, P = .01) and mean percentage change in lesion MT ratio after 12 months (odds ratio = 0.90, P = .04) were independent predictors of worsening disability at 8 years. At baseline, thalamic fraction was correlated with lesion volumes at T2-weighted imaging (r = -0.75, P < .001) and T1-weighted imaging (r = -0.60, P < .001).
Thalamic atrophy is correlated with long-term accumulation of disability in patients with MS. White matter lesions are likely to contribute to the loss of tissue seen in the thalamus of patients with MS.
Objectives
To validate imaging features able to discriminate neuromyelitis optica spectrum disorders from multiple sclerosis with conventional magnetic resonance imaging (MRI).
Methods
In this ...cross‐sectional study, brain and spinal cord scans were evaluated from 116 neuromyelitis optica spectrum disorder patients (98 seropositive and 18 seronegative) in chronic disease phase and 65 age‐, sex‐, and disease duration–matched multiple sclerosis patients. To identify independent predictors of neuromyelitis optica diagnosis, after assessing the prevalence of typical/atypical findings, the original cohort was 2:1 randomized in a training sample (where a multivariate logistic regression analysis was run) and a validation sample (where the performance of the selected variables was tested and validated).
Results
Typical brain lesions occurred in 50.9% of neuromyelitis optica patients (18.1% brainstem periventricular/periaqueductal, 32.7% periependymal along lateral ventricles, 3.4% large hemispheric, 6.0% diencephalic, 4.3% corticospinal tract), 72.2% had spinal cord lesions (46.3% long transverse myelitis, 36.1% short transverse myelitis), 37.1% satisfied 2010 McDonald criteria, and none had cortical lesions. Fulfillment of at least 2 of 5 of absence of juxtacortical/cortical lesions, absence of periventricular lesions, absence of Dawson fingers, presence of long transverse myelitis, and presence of periependymal lesions along lateral ventricles discriminated neuromyelitis optica patients in both training (sensitivity = 0.92, 95% confidence interval CI = 0.84–0.97; specificity = 0.91, 95% CI = 0.78–0.97) and validation samples (sensitivity = 0.82, 95% CI = 0.66–0.92; specificity = 0.91, 95% CI = 0.71–0.99). MRI findings and criteria performance were similar irrespective of serostatus.
Interpretation
Although up to 50% of neuromyelitis optica patients have no typical lesions and a relatively high percentage of them satisfy multiple sclerosis criteria, several easily applicable imaging features can help to distinguish neuromyelitis optica from multiple sclerosis. ANN NEUROL 2019;85:371–384.
Although the importance of bilateral cortical innervation in the control of swallowing is well known, neurogenic dysphagia caused by unilateral hemispheric ischemic lesion has been also reported. Our ...patient is a 41-year-old male who developed difficulty swallowing liquids, oral apraxia, and motor dysphasia, followed by right-hand ataxia. Brain magnetic resonance imaging (MRI) showed subcortical tumefactive conglomerate of cystic lesions in the left frontal, precentral region, which were sharp edged, with perilesional edema, concordant with lesions in Marburg's variant of multiple sclerosis. Steroid treatment and plasma exchange therapy led to disappearance of neurological symptoms. Treatment with interferon β-1a 40 mcg sc was initiated. During a 3-year follow-up, clinical/brain MRI scan showed no new neurological manifestations, a significant regression of lesion size, and no new brain lesions. To the best of our knowledge, this is a first case of dysphagia caused by unilateral hemispheric lesion in a multiple sclerosis patient.
Background:
The features of functional network connectivity reorganization at the earliest stages of MS have not been investigated yet.
Objective:
To combine static and dynamic analysis of resting ...state (RS) functional connectivity (FC) to identify mechanisms of clinical dysfunction and recovery occurring in clinically isolated syndrome (CIS) patients.
Methods:
RS functional magnetic resonance imaging (fMRI) and clinical data were prospectively acquired from 50 CIS patients and 13 healthy controls (HC) at baseline, month 12 and month 24. Between-group differences and longitudinal evolution of network FC were analysed across 41 functionally relevant networks.
Results:
At follow-up, 47 patients developed MS. Disability remained stable (and relatively low). CIS and HC exhibited two recurring RS FC states (states 1 and 2, showing low and high internetwork connectivity, respectively). At baseline, patients showed reduced state 2 connectivity strength in the default-mode and cerebellar networks, and no differences in global dynamism versus HC. A selective FC reduction in networks affected by the clinical attack was also detected. At follow-up, increased state 2 connectivity strength and global connectivity dynamism was observed in patients versus HC.
Conclusion:
Longitudinal FC modifications occurring relatively early in the course of multiple sclerosis may represent a protective mechanism contributing to preserve clinical function over time.
Background:
Functional magnetic resonance imaging (fMRI) correlates of cognitive deficits have not been thoroughly studied in patients with neuromyelitis optica spectrum disorders (NMOSDs).
...Objective:
To investigate resting state (RS) functional connectivity (FC) abnormalities within the main cognitive networks in NMOSD patients and their correlation with cognitive performance.
Methods:
We acquired RS fMRI from 25 NMOSD patients and 30 healthy controls (HC). Patients underwent an extensive neuropsychological evaluation. Between-group RS FC comparisons and correlations with cognitive performance were assessed on the main cognitive RS networks identified by independent component analysis.
Results:
NMOSD patients showed higher RS FC versus HC in the precuneus of the default mode network (DMN) and right working memory network (WMN), as well as in several frontoparietal regions of the salience network (SN) and bilateral WMNs. Reduced frontal RS FC in NMOSD versus HC was detected in the left WMN. Increased RS FC in the DMN and right WMN was correlated with better cognitive performance, while decreased RS FC in the left WMN was associated with worse cognitive performance.
Conclusion:
Cognitive-network reorganization occurs in NMOSD. Clinico-imaging correlations suggest an adaptive role of increased RS FC. Conversely, reduced RS FC seems to be a maladaptive mechanism associated with a worse cognitive performance.
Objectives
To apply a deep-learning algorithm to brain MRIs of seronegative patients with neuromyelitis optica spectrum disorders (NMOSD) and NMOSD-like manifestations and assess whether their ...structural features are similar to aquaporin-4-seropositive NMOSD or multiple sclerosis (MS) patients.
Patients and methods
We analyzed 228 T2- and T1-weighted brain MRIs acquired from aquaporin-4-seropositive NMOSD (
n
= 85), MS (
n
= 95), aquaporin-4-seronegative NMOSD
n
= 11, three with anti-myelin oligodendrocyte glycoprotein antibodies (MOG), and aquaporin-4-seronegative patients with NMOSD-like manifestations (idiopathic recurrent optic neuritis and myelitis,
n
= 37), who were recruited from February 2010 to December 2019. Seventy-three percent of aquaporin-4-seronegative patients with NMOSD-like manifestations also had a clinical follow-up (median duration of 4 years). The deep-learning neural network architecture was based on four 3D convolutional layers. It was trained and validated on MRI scans of aquaporin-4-seropositive NMOSD and MS patients and was then applied to aquaporin-4-seronegative NMOSD and NMOSD-like manifestations. Assignment of unclassified aquaporin-4-seronegative patients was compared with their clinical follow-up.
Results
The final algorithm differentiated aquaporin-4-seropositive NMOSD and MS patients with an accuracy of 0.95. All aquaporin-4-seronegative NMOSD and 36/37 aquaporin-4-seronegative patients with NMOSD-like manifestations were classified as NMOSD. Anti-MOG patients had a similar probability of being NMOSD or MS. At clinical follow-up, one unclassified aquaporin-4-seronegative patient evolved to MS, three developed NMOSD, and the others did not change phenotype.
Conclusions
Our findings support the inclusion of aquaporin4-seronegative patients into NMOSD and suggest a possible expansion to aquaporin-4-seronegative unclassified patients with NMOSD-like manifestations. Anti-MOG patients are likely to have intermediate brain features between NMOSD and MS.
Abstract Purpose Sexual dysfunction (SD) is a common but often overlooked and undertreated symptom in multiple sclerosis (MS). The purpose of our longitudinal study was to explore the changes in the ...level of sexual functioning in MS cohort after a period of 3 and 6 years of follow-up, as well as to investigate the predictors of changes in SD during the period of observation. Methods The study population comprise a cohort of 93 patients with MS (McDonald's criteria, 2001) who were assessed at three time points during the study (baseline, and at the 3- and 6-year follow-up). The presence and severity of SD was quantified by Szasz sexual functioning scale. Independent predictors of the ordinal-scaled measure of sexual problems were identified using a generalized linear mixed regression models. Results The number of reported SD symptoms increased markedly for both genders during the whole period of observation. Duration of follow-up, age, level of physical disability, depression and fatigue were identified as independent prognostic factors for deterioration of sexual functioning in patients with MS during the 6-year follow-up. Conclusion Our study provides insight into dynamics of change in sexual function among patients with MS and predictors of change, over the period of 6 years.
Background:
Optic radiation (OR) damage occurs in multiple sclerosis (MS).
Objectives:
The purpose of this study was to explore the contribution of local and distant mechanisms associated with OR ...damage in MS.
Methods:
Diffusion tensor (DT) magnetic resonance imaging (MRI) tractography probability maps of the ORs were derived from 102 MS patients and 11 controls. Between-group differences of OR normal-appearing white matter (NAWM) damage and topographical distribution of OR damage were assessed using quantitative and voxel-wise analyses, considering the influence of previous optic neuritis (ON+) and T2 OR lesions (T2 OR+).
Results:
OR NAWM diffusivity abnormalities were more severe in ON+ patients vs patients without previous optic neuritis (ON–) and T2 OR+ vs T2 OR– patients. Damage to the anterior portions of the ORs was more severe in ON+ vs ON– patients. Compared to controls and T2 OR– patients, T2 OR+ patients experienced a more distributed pattern of DT MRI abnormalities along the ORs, with an increased axial diffusivity limited to the anterior portions of the ORs. In T2 OR+ group, ON+ vs ON– patients showed DT MRI abnormalities in the middle portion of the ORs, in correspondence with focal lesions. OR damage correlated with OR T2 lesion volume, visual dysfunction and optic nerve atrophy.
Conclusions:
Both trans-synaptic degeneration secondary to optic nerve damage and Wallerian degeneration due to local T2 lesions contribute to OR damage in MS.
Background
Comorbidities occur frequently in persons with multiple sclerosis (MS). The aim of the present study was to determine the prevalence of the most common comorbidities in the population of ...MS patients in Belgrade, Serbia.
Material and methods
Data on diagnosed and fully documented comorbidities were taken from the Belgrade MS population registry. The list of explored comorbidities included cardiovascular, malignant, and autoimmune diseases; psychiatric disorders; epilepsy; and type 2 diabetes. In the data analysis, crude, age- and gender-specific, and age-adjusted prevalence was calculated. Additionally, comorbidities were analyzed in patients with various MS phenotypes.
Results
The most prevalent group of comorbidities were psychiatric (prevalence (Prev) = 20.59%, 95% CI 19.10–22.17) and cardiovascular comorbidities (Prev = 15.23%, 95% CI 13.93–16.63). The most prevalent single comorbidities were depression (Prev = 11.82%, 95% CI 10.64–13.11) and hypertension (Prev = 11.41%, 95% CI 10.25–12.68). Type 2 diabetes was significantly more prevalent in patients with primary progressive MS compared with the patients with relapsing-remitting and secondary progressive MS (
p
< 0.001). We found statistically significant positive correlation between number of comorbidities and progression index (
p
< 0.001). Patients treated with disease-modifying therapies (DMTs) had significantly higher risk of developing comorbidity, after treatment initiation, compared with those who were untreated (
p
= 0.001).
Conclusions
Our study demonstrated high prevalence of comorbidities in persons with MS, with psychiatric and cardiovascular diseases being the most common. Furthermore, our findings confirmed the association of comorbidities with progression of disability and emphasized their role in treatment decision-making in MS.