Months Of Clinical Onset Research Articles

Timing of MOG-IgG Testing Is Key to 2023 MOGAD Diagnostic Criteria.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a recently identified autoimmune demyelinating disorder of the CNS affecting both adults and children. Diagnostic criteria for MOGAD have recently been published. We aimed to validate the 2023 MOGAD diagnostic criteria in a real-world cohort of patients with atypical CNS inflammation. All patients referred to the National neuromyelitis optica spectrum disorder (NMOSD) specialized service at The Walton Center NHS Foundation Trust between 2012 and 2023 with an atypical demyelinating syndrome were evaluated. We systematically applied the 2023 MOGAD diagnostic criteria and previous 2018 International Diagnostic Recommendations for MOG encephalomyelitis to our retrospective cohort. 474 patients were screened and 66 were excluded for lack of clinical information. Preexisting diagnoses within our cohort included the following: MOGAD, n = 127; AQP4-IgG NMOSD, n = 125; seronegative NMOSD, n = 33; multiple sclerosis (MS), n = 10; and other diagnoses, n = 113. Of patients with preexisting MOGAD, 97% (123/127) fulfilled the 2023 MOGAD diagnostic criteria. Three patients with a low-positive MOG-IgG did not meet supportive features though 2/3 had insufficient investigations. Alternative diagnoses could not be excluded in 1 patient with MS-MOGAD overlap. No patients with a non-MOGAD diagnosis were found to fulfill the 2023 diagnostic criteria. The sensitivity and specificity of the 2023 MOGAD diagnostic criteria were 97% and 100% with no false positives, improving on 2018 International Diagnostic Recommendations for MOG encephalomyelitis. Low-positive MOG-IgG results were more often associated with a longer time from disease onset to sampling (p < 0.001). In addition, in patients with a MOG-IgG1 test within 6 months of clinical onset, approximately 25% can become low positive by 6 months. Of patients with preexisting MOGAD, 9% (12/127) had insufficient investigations and examinations to fully evaluate additional supportive features. However, in those who were completely evaluated, supportive features were fulfilled in 97% (111/115). The 2023 MOGAD diagnostic criteria were highly sensitive and specific and closely align with historically established cases of MOGAD. However, because additional supportive features are stipulated for patients with a low-positive MOG-IgG result, missed diagnoses may occur due to delayed testing or insufficient investigations.

Fatigue and depression predict quality of life in patients with early multiple sclerosis: a longitudinal study.

The clinical predictors of health-related quality of life (HRQoL) in multiple sclerosis (MS) have mainly been studied in patients with long-standing disease. The objective of this study was to investigate the longitudinal association among HRQoL and clinical characteristics in early MS. Relapsing MS patients within 12 months of clinical onset were enrolled in a neuroprotection trial of riluzole versus placebo as an add-on to weekly interferon with up to 36 months of follow-up. Serial clinical measures included Short Form-36 (SF-36) as the measure of HRQoL, MS Functional Composite (as a measure of disability), Modified Fatigue Impact Scale, Patient Health Questionnaire-9 (as a measure of depression) and a cognitive battery. Multivariable linear regression analyses assessed cross-sectional associations. Mixed model regressions with mutual adjustments were used to assess the longitudinal association of HRQoL components and clinical, cognitive and demographic variables. Forty-three patients were enrolled within 7.5 ± 4.9 months of clinical onset (72% female, mean age 36 years). The baseline severity of fatigue and depression predicted subsequent changes in SF-36 Physical Component Summary (PCS) (P values of 0.001 and 0.021, respectively). In longitudinal analyses, changes in disability and depression were associated with changes in SF-36 PCS (P values of 0.002 and 0.009, respectively), whereas changes in cognitive function and fatigue were associated with changes in SF-36 Mental Component Summary (P values of 0.037 and 0.001, respectively). A 1-unit increase in MS Functional Composite was associated with a 7.1-point increase in SF-36 PCS (95% CI, 2.6-11.6). Fatigue, depression, cognition and disability are independently associated with HRQoL in early MS.

Subcortical grey matter volumes predict subsequent walking function in early multiple sclerosis

BackgroundAtrophy of subcortical grey matter structures has been reported to be associated with clinical measures of disability in multiple sclerosis (MS) patients. It is not clear if the degree of tissue loss in patients with very early MS is associated with changes in disability measures. ObjectiveTo study the association between subcortical grey matter structure volumes and clinical disability outcomes. MethodsRelapsing MS patients within 12months of clinical onset were enrolled in a neuroprotection trial of riluzole versus placebo with up to 36months of follow-up and serial brain MRI and clinical assessments. MRI metrics, including thalamic, putamen, caudate, pallidum and cerebellar cortical volume, were measured by an automated, custom-made FreeSurfer pipeline. Volumes were normalized for head size. Clinical measures included EDSS, MSFC scores and its components. Mixed model regression measured time trends and associations between imaging and clinical outcomes. Results42 patients with a mean follow-up of 30.6months were analyzed in this study. There was a statistically significant decrease in thalamus, caudate and putamen volumes, but not cerebellar cortical and pallidum volumes during the follow-up period. Baseline thalamus, caudate and putamen volumes predicted subsequent changes in the timed 25-ft walk test (p=0.036) and MSFC (p=0.024). There was a trend for an association between baseline caudate volume and subsequent change in the timed 25-ft walk test (p=0.084). No association between baseline imaging and subsequent EDSS changes were seen. ConclusionSubcortical grey matter volumes at early stages of MS are associated with subsequent changes in disability measures.

Longitudinal associations between brain structural changes and fatigue in early MS

BackgroundFatigue is a common and disabling symptom of multiple sclerosis (MS) patients. Structural changes in several brain areas have been reported to correlate with fatigue in MS patients but none consistently. ObjectiveTo study the association between global and regional measures of brain atrophy and fatigue in patients with early relapsing MS. MethodsClinically isolated syndrome and relapsing MS patients within 12 months of clinical onset were enrolled in a neuroprotection trial of riluzole versus placebo with up to 36 months of follow-up. MRI metrics included brain volumes measured by SIENAX normalized measurements [normalized brain parenchymal volume (nBPV), normalized normal-appearing white and gray matter volume (nNAWMV and nGMV)] and T2 lesion volume (T2LV). Cortical thickness, thalamic volume and cerebellar cortical volume were measured using Freesurfer's longitudinal pipeline (v5.3) and a lesion inpainting approach. Fatigue was evaluated using the Modified Fatigue Impact Scale (MFIS). Mixed model regression measured time trends and associations between imaging and fatigue severity, adjusting for age and sex. ResultsForty-three patients (mean age 36 years; 31 females) were enrolled within 7.5±4.9 months of symptom onset. Baseline and change over baseline in lesion volumes, grey matter, white matter, basal ganglia and total parenchymal volumes were not associated with change in MFIS score over time. Lower thalamic volume at baseline predicted increasing physical subscale of MFIS score during the study (p=0.017). There was a trend toward baseline thalamic volume and cerebellar cortical volume predicting subsequent change in total MFIS score (p=0.055 and 0.082 respectively). On-study change in thalamic or cerebellar cortical volume was not associated with on-study change in MFIS score. ConclusionGlobal measures of tissue loss are not strongly associated with fatigue in patients with early MS. However, thalamic and cerebellar cortical atrophy may be predictive of subsequent changes in fatigue in these patients.

Clinically Isolated Syndrome Suggestive of Multiple Sclerosis: Dynamic Patterns of Gray and White Matter Changes-A 2-year MR Imaging Study.

To investigate the patterns of regional gray matter (GM) and white matter (WM) atrophy, WM microstructural tissue damage, and changes in patients with a clinically isolated syndrome (CIS) suggestive of multiple sclerosis at 2 years from clinical onset. Institutional review board approval and written informed consent from all patients were obtained. Neurologic assessment and conventional, diffusion-tensor, and volumetric brain MR imaging sequences were performed in 37 patients with CIS within 2 months of clinical onset, and after 3, 12, and 24 months. Fourteen healthy control subjects also were studied. Longitudinal GM and WM volume changes and WM microstructural abnormalities were assessed by using voxel-based morphometry (P < .001, uncorrected) and tract-based spatial statistics (P < .05, corrected). At 24 months, 33 of 37 (89%) patients had developed multiple sclerosis. At month 3, patients with CIS showed a transient volume increase in frontal, parietal, temporal, and cerebellar GM regions. At 12 months, patients with CIS developed atrophy of the thalami, caudate nuclei, cerebellum, and frontal, parietal, and temporal lobes. At 24 months GM volume of the frontal, temporal, and parietal cortical areas further decreased from that at 12 months. WM atrophy involved only a few WM regions at 2 months from clinical onset, with progressive involvement of additional WM tracts with time. A diffuse pattern of WM microstructural abnormalities was detected within 2 months of onset and had worsened at 24 months. After an acute inflammatory event, dynamic modifications of regional GM and WM damage occur in patients with CIS, with a progressive evolution of WM damage from disease onset and a transient, early increase in GM volume, followed by GM atrophy. Neurodegenerative processes start early in patients with multiple sclerosis.

Acute hepatitis C: prevention and treatment

HCV can cause acute or chronic hepatitis and is a health problem all over the world. It is one of the leading causes of cirrhosis and hepatocellular carcinoma, and is a common indication for liver transplantation. Unrecognized patients with HCV infection may transmit the virus to uninfected people. The acute form of the disease leads to chronic hepatitis in the majority of cases. Since the success rate of treatment given in the chronic phase is much lower than that given in the acute phase, recognizing acute hepatitis is critical. Although HCV is less prevalent since 1990s in the Western world after improved blood-donor screening programs, needle-exchange facilities and education among intravenous drug users, it is still endemic in some regions, including African countries, Egypt, Taiwan, China and Japan. Acute HCV infection may be a challenge for the clinician; since it is often asymptomatic, detection and diagnosis are usually difficult. After an incubation period of 7 weeks (2–12 weeks), only a minority of patients (10–15%) report symptoms. The spontaneous clearance of the virus is more frequent primarily during the first 3 months of clinical onset of the disease, but may occur anytime during the 6 months of acute infection. This spontaneous resolution seems to be more frequent in symptomatic cases. Viremia persisting more than 6 months is accepted as chronic infection. The virus is transmitted more frequently through infected blood or body fluids. Detection of antibodies against HCV is not a reliable method of diagnosing acute HCV infection since the appearance of antibodies against HCV can be delayed in up to 30% of patients at the onset of symptoms. Thus, the diagnosis of acute hepatitis C relies on the qualitative detection of HCV RNA, which may appear as early as 1–2 weeks after exposure quickly followed by highly elevated alanine aminotransferase. After a follow-up period of 8–12 weeks for allowing spontaneous resolution, treatment should be initiated. Pegylated interferon monotherapy for 24 weeks seems effective, and the therapy can be individualized according to the characteristics of the patient.

First hundred cases of variant Creutzfeldt-Jakob disease: retrospective case note review of early psychiatric and neurological features

Objective: To describe the early psychiatric and neurological features of variant Creutzfeldt-Jakob disease.Design: Cohort study.Setting: National surveillance system for Creutzfeldt-Jakob disease in the United Kingdom.Participants: The first 100 cases of...