A case report of ChAdOx1 nCoV-19 vaccine-associated encephalitis.

BACKGROUND: Vaccination against COVID-19 continues apace, but side-effects, both common and severe, continue to be reported. We report here the first published case of COVID-19 vaccine-related encephalitis. CASE PRESENTATION: A young woman presented with acute neuropsychiatric symptoms following recent ChAdOx1 nCoV-19 vaccination. Extensive investigation did not identify alternative causes. CONCLUSIONS: This difficult case is here described, including presentation, investigation, and management. Further study on neuropsychiatric side-effects of COVID-19 vaccination, including investigation as to whether there may be a causal link, is required.

Should the symptomatic region be included in dissemination in space in MRI criteria for MS?

OBJECTIVES: To investigate whether inclusion of lesions in the symptomatic region influences the performance of dissemination in space (DIS) criteria for a diagnosis of clinically definite multiple sclerosis (CDMS) in patients with a clinically isolated syndrome (CIS). METHODS: We studied 30 patients with CIS with brainstem/cerebellar and spinal cord syndromes who had MRI scans at the time of CIS and were followed up for the development of CDMS. We retrospectively applied the McDonald 2010 DIS criteria (excluding all lesions in the symptomatic region) to baseline MRI scans and 2 modified DIS criteria: (1) the inclusion of asymptomatic lesions in the symptomatic region in DIS, and (2) the inclusion of any lesion in the symptomatic region in DIS. The performance of the McDonald 2010 DIS criteria and the 2 modified criteria for the development of CDMS was compared. RESULTS: The sensitivity, specificity, and accuracy of the DIS criteria was, respectively, 73%, 73%, and 73% for the McDonald 2010 criteria, 80%, 73%, and 77% when asymptomatic lesions in the symptomatic region were included, and 87%, 73%, and 80% when any lesion in the symptomatic region was included in DIS. CONCLUSIONS: Including lesions in the symptomatic region in DIS increases the sensitivity of MRI criteria for diagnosing multiple sclerosis without compromising specificity. These findings may help inform future revisions of the diagnostic criteria for multiple sclerosis. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with CIS, including lesions in the symptomatic region as part of the criteria for DIS does not significantly increase the accuracy for predicting the development of CDMS. The study lacks the precision to detect an important change in accuracy.

Early prognosis of multiple sclerosis.

Establishing the prognosis for multiple sclerosis (MS) early in the disease course is critically important for patients who develop this disease. Potentially, this information could be used to guide the selection of which disease modifying therapy (if any) should be started in which individual and to determine, over course of the illness, when the therapeutic approach needs to be modified. Regardless, of its importance, however, we only have a limited ability to predict how an individual's illness will evolve. For several decades, we have known about certain clinical features of MS that seem to associated with a more benign course (e.g., female gender, clinical onset before the age of 40 years, few early relapses, slow early accumulation of fixed deficits, and the initial involvement of only sensory systems). Nevertheless, the prognostic value of these clinical features offer only limited help to individual patients in making their different (and difficult) life-choices. For this reason, there have been numerous attempts to develop paraclinical tests, which can augment (and improve upon) this clinical prognostic information. These approaches have included the use of magnetic resonance imaging (MRI) measures such as gadolinium enhancement, new T2 lesions, the volume of T2 lesion burden, brain atrophy (either whole brain or separately for grey and white matter), spinal cord atrophy, cortical connectivity, and determining the characteristics and chemical composition of the normal appearing white matter. They have also included investigations of the use of immunological markers for establishing prognosis. Nevertheless, this field is still only in its infancy and our ability to predict accurately the outlook for an individual remains limited at best. This chapter reviews the current evidence, taken from both clinical and paraclinical sources, as it relates to establishing this prognosis and provides insight to where, in the future, we need to look.

Changing associations between cognitive impairment and imaging in multiple sclerosis as the disease progresses.

The authors explored cross-sectional associations between MRI parameters (lesion metrics, brain volumes, magnetization transfer ratio histograms, and metabolite concentrations) and cognition in 61 patients who experienced clinically-isolated syndromes (CIS) 7 years earlier. IQ decline and poorer overall cognition were associated with T2 white-matter lesions, and slow information-processing with both T2 lesions and gray-matter atrophy. In a previous study of the same cohort, gray-matter atrophy measured shortly after CIS failed to predict development of cognitive impairment years later. Our findings suggest that gray-matter pathology, reflected by atrophy measurements, becomes increasingly important in determining cognition as MS progresses.

A single, early magnetic resonance imaging study in the diagnosis of multiple sclerosis.

BACKGROUND: A diagnosis of multiple sclerosis in patients who present for the first time with a clinically isolated syndrome (CIS) can be established with brain magnetic resonance imaging (MRI) if the MRI demonstrates demyelinating lesions with dissemination in space (DIS) and dissemination in time (DIT). OBJECTIVE: To investigate the diagnostic performance of a single MRI study obtained within the first 3 months after symptom onset in a cohort of patients with a CIS suggestive of multiple sclerosis at presentation. DESIGN: Multicenter inception cohort with a follow-up of at least 24 months. SETTING: Referral hospitals. Patients Patients with CIS onset between April 1, 1995, and September 30, 2004, who fulfilled the following criteria were included: (1) age of 14 to 50 years and (2) clinical follow-up for at least 24 months after CIS onset or until development of clinically definite multiple sclerosis (CDMS), if this occurred within 2 years. Main Outcome Measure All patients underwent 2 comparable brain MRI examinations, the first within 3 months (early) and the second between 3 and 12 months (delayed) after CIS onset. We defined DIS using several existing MRI criteria, and DIT was inferred when there were simultaneous gadolinium-enhancing and nonenhancing lesions on a single MRI. RESULTS: Two hundred fifty patients were included in the study. The comparison of the diagnostic performance of various MRI criteria for identifying early converters to CDMS showed similar sensitivity and specificity between early and delayed MRIs. In addition, the use of less stringent criteria for DIS yielded better sensitivity and similar specificity, particularly when assessed in the first weeks after CIS onset. CONCLUSION: A single brain MRI study that demonstrates DIS and shows both gadolinium-enhancing and nonenhancing lesions that suggest DIT is highly specific for predicting the early development of CDMS, even when the MRI is performed within the first 3 months after the onset of a CIS.

MRI criteria for multiple sclerosis in patients presenting with clinically isolated syndromes: a multicentre retrospective study.

BACKGROUND: The 2001 and 2005 McDonald criteria allow MRI evidence for dissemination in space (DIS) and dissemination in time (DIT) to be used to diagnose multiple sclerosis in patients who present with clinically isolated syndromes (CIS). In 2006, new criteria were proposed in which DIS requires at least one T2 lesion in at least two of four locations (juxtacortical, periventricular, infratentorial, and spinal-cord) and DIT requires a new T2 lesion on a follow-up scan. We applied all three criteria in a large cohort of CIS patients to assess their performance by use of conversion to clinically definite multiple sclerosis (CDMS) as the outcome. METHODS: Patients who had two MRI scans within 12 months of CIS onset were identified in four centres in the Magnims European research network. The specificity and sensitivity of MRI criteria for CDMS after 3 years was assessed in 208 patients. A Cox proportional hazards model was applied in a larger cohort of 282 patients that included all patients irrespective of length of follow-up. FINDINGS: The specificity of all criteria for CDMS was high (2001 McDonald, 91%; 2005 McDonald, 88%; new, 87%). Sensitivity of the new (72%) and 2005 McDonald (60%) criteria were higher than the 2001 McDonald criteria (47%). The Cox proportional hazards model showed a higher conversion risk for all three criteria in those with both DIS and DIT than those with either DIS or DIT alone. When all three criteria were included in the model, only the new criteria had an independent significant effect on conversion risk. INTERPRETATION: The new criteria are simpler than the McDonald criteria without compromising specificity and accuracy. The presence of both DIS and DIT from two MRI scans has a higher specificity and risk for CDMS than either DIS or DIT alone.

Bone mineral density in institutionalised patients with refractory epilepsy.

Bone mineral density (BMD) and content (BMC) were measured in 208 institutionalised patients with refractory epilepsy. BMD was in the osteoporotic range in 43% of males and 21% of females. BMC was reduced only in male patients. Apart from age and gender, no other factor or specific AED was particularly associated with reduced BMD or BMC. This study indicates the magnitude of the problem of bone disease in refractory epilepsy, in particular affecting young and male patients with chronic epilepsy.

Selective magnetization transfer ratio decrease in the visual cortex following optic neuritis.

Patients with clinically isolated syndromes suggestive of multiple sclerosis have evidence for abnormality in normal appearing grey matter detected using the magnetization transfer ratio (MTR), a quantitative MRI measure. One potential mechanism for the decreased grey matter MTR (GM MTR) observed is trans-synaptic morphological abnormality secondary to demyelinating lesions that are in an anatomically linked pathway but remote location. We investigated this potential association by studying the location of abnormalities using voxel-based analysis of GM MTR maps in a group of 80 patients studied within 6 months of presenting with isolated optic neuritis and compared the findings with those seen in 50 age- and sex-matched healthy controls. Occipital cortex and whole brain analysis comparing all optic neuritis patients and controls revealed a selective decrease of MTR bilaterally in the visual cortex in patients [Brodmann area (BA) 17]. Whole brain analysis of patients fulfilling the McDonald criteria for multiple sclerosis (n = 20) showed a lower MTR compared to controls bilaterally in the visual cortex (BA 17/18), left hippocampus, bilateral superior temporal gyrus, bilateral lenticular nuclei and the right cerebellum. There was no significant difference in the percentage of grey matter between patients and controls in the regions of abnormal MTR detected in the visual cortex. The intrinsic MTR decrease seen in patients suggests that there are structural changes in the visual cortex following an attack of optic neuritis. Potential mechanisms for this include trans-synaptic neuronal degeneration and cortical synaptic morphological changes; such abnormalities may also contribute to MTR abnormalities observed in the normal appearing grey matter in multiple sclerosis.

Mixed connective tissue disease: still crazy after all these years.

Mixed connective tissue disease (MCTD) remains a controversial diagnosis. The classification criteria have changed significantly from the original description by Sharp and colleagues in 1972 after follow-up of the original and other MCTD patients. In this article we review the clinical, serologic, and genetic studies of MCTD published in the last 10 years and ask if this term is appropriate.