Diagnosis Of Clinically Isolated Syndrome Research Articles

Clinical and paraclinical characteristics of optic neuritis in the context of the McDonald criteria 2017

Optic neuritis is often an initial symptom in multiple sclerosis (MS) or clinically isolated syndrome (CIS), yet comprehensive studies using the 2017 McDonald criteria for MS are scarce. Patient records from our academic centre (2010–2018) were reviewed. Using the 2017 McDonald criteria, three groups were formed: MS optic neuritis (optic neuritis with confirmed MS), CIS optic neuritis (optic neuritis without confirmed MS) and suspected optic neuritis (sON). We compared clinical and paraclinical findings among the groups to identify predictors for CIS- or MS-optic neuritis. The study included 129 MS, 108 CIS, and 44 sON cases. The combination of visual impairment, dyschromatopsia, and retrobulbar pain was observed in 47% of MS patients, 42% of CIS patients, and 30% of sON patients. Dyschromatopsia was the strongest indicator of MS or CIS diagnosis in the backward regression model. 56% of MS patients had relative afferent pupillary defect, 61% optic nerve anomalies within magnetic resonance imaging, and 81% abnormal visual evoked potentials. Our results emphasize the challenges in diagnosing optic neuritis, as not all patients with objectively diagnosed MS exhibit the triad of typical symptoms. To address potentially missing clinical features, incorporating additional paraclinical findings is proposed.

Adverse effects of immunotherapies for multiple sclerosis: a network meta-analysis.

Adverse effects of immunotherapies for multiple sclerosis: a network meta-analysis.

Factors Related to the Progression of Clinically Isolated Syndrome to Multiple Sclerosis: A Retrospective Study in Lithuania.

Background and Objectives: Multiple sclerosis (MS) is a demyelinating disease which usually manifests as clinically isolated syndrome (CIS). Approximately 70% of patients with CIS progress to MS. Therefore, there is a pressing need to identify the most accurate predictive factors of CIS developing into MS, some of which could be a clear clinical phenotype of early MS as well as lesions in magnetic resonance imaging (MRI), pathological findings in cerebrospinal fluid (CSF) and evoked potentials (EP) tests. The problem is of outstanding importance since early MS diagnosis and treatment prevents long-term disability. The aim of our study is to analyze the factors that could influence the progression of CIS to MS. Materials and Methods: This study is a retrospective data analysis which included patients with their primary CIS diagnosis between 1st January 2015 and 1st January 2020. The prevalence and predictive value of clinical symptoms, MRI lesions, pathological CSF and EP findings were evaluated in accordance with the final diagnosis and compared between the sexes and age groups. Results: Out of 138 CIS patients, 49 (35.5%) patients progressed to MS. MS patients were more likely to have a diminished sense of vibration and proprioception (χ2 = 9.033, p = 0.003) as well as spinal cord MRI lesions (χ2 = 7.209, p = 0.007) in comparison with the non-MS group. Positive oligoclonal bands (OCBs) in CSF (χ2 = 34.859, p ≤ 0.001) and pathological brainstem auditory evoked potential (BAEP) test findings (χ2 = 10.924, p ≤ 0.001) were more prevalent in the MS group. Diminished sense of vibration and proprioception increased the risk for developing MS by 13 times (p = 0.028), whereas positive OCBs in CSF increased the risk by 100 times (p < 0.001). MS patients that were older than 50 years were more likely to exhibit positive Babinski’s reflex (χ2 = 6.993, p = 0.03), decreased muscle strength (χ2 = 13.481, p = 0.001), ataxia (χ2 = 8.135, p = 0.017), and diminished sense of vibration and proprioception (χ2 = 7.918, p = 0.019) in comparison with both younger age groups. Conclusions: Diminished sense of vibration and proprioception, spinal cord MRI lesions, positive OCBs and pathological BAEP test findings were more common among patients that developed MS. Diminished sense of vibration and proprioception along with positive CSF OCBs are predictors of CIS progressing to MS. Older patients that develop MS have more symptoms in general, such as positive Babinski’s reflex, decreased muscle strength, ataxia, and diminished sense of vibration and proprioception.

Does MRZ Reaction Have a Real Significance in the Diagnosis of Multiple Sclerosis?

Despite the diagnostic criteria for multiple sclerosis have been well established, there still remain a significant group of patients presenting with various clinical symptoms suspicious of demyelinating disease but not fulfilling these diagnostic criteria. MRZ reaction evaluates intrathecal synthesis of specific IgG antibodies against neurotrophic viruses of morbilli (M), rubella (R) and zoster (Z). MRZ reaction (positive was evaluated 2/3 or 3/3 for clinically isolated syndrome (CIS) or multiple sclerosis (MS) and negative 0/3 or 1/3), brain magnetic resonance imaging (MRI) (positive vs. negative regarding fulfilling diagnostic criteria for MS) and oligoclonal bands (OCB) in the cerebrospinal fluid (CSF) were examined in 57 subjects with CIS and 55 with MS. At the time of lumbar puncture the diagnosis was not yet known. In the subgroup of CIS the sensitivity of brain MRI was 63.16%, of OCB 87.72% and MRZ 35.09%, and the specificity of brain MRI was 83.44%, of OCB 65.23 and of MRZ 91.72%. In the subgroup of MS the sensitivity of brain MRI was 81.82%, of OCB 87.27% and MRZ 38.18%, and the specificity of brain MRI was 86.51%, of OCB 64.80 and of MRZ 92.11%. In the subgroup analysis we found 4 out of 55 subjects with final diagnosis of MS (7.27%) and 7 out of 57 in the final CIS group (12.28%) with positive MRZ reaction (2/3 or 3/3) and brain MRI not fulfilling the diagnostic criteria for MS. Of course in vast majority (but not all) of cases the diagnosis of CIS or MS is easily made by fulfilling revised McDonald criteria – with contribution of brain and spinal cord MRI. Despite low sensitivity of MRZ reaction found in our cohort this diagnostic tool can be of special significance in the cases with clinical symptoms consistent with demyelinating disease of the CNS, but with initial brain MRI not fulfilling the diagnostic criteria. In these cases very high specificity of MRZ reaction can shift the diagnosis to either CIS or MS and thus contribute to earlier diagnosis and treatment.

How much do periventricular lesions assist in distinguishing migraine with aura from CIS?

To evaluate in clinically isolated syndrome (CIS) and migraine with aura (MA) how the number of periventricular lesions (PVLs) detected at MRI influences diagnostic performance when the Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) or the 2017 revised criteria are applied. In this retrospective study, white matter hyperintensities (WMH) of 84 patients with MA and 79 patients with CIS were assessed using manual segmentation technique. Lesion probability maps (LPMs) and voxel-wise analysis of lesion distribution by diagnosis were obtained. Furthermore, we performed a logistic regression analysis based on lesion locations and volumes. Compared to patients with MA, patients with CIS showed a significant overall higher T2 WMH mean number and volume (17.9 ± 16.9 vs 6.2 ± 11.9 and 3.1 ± 4.2 vs 0.3 ± 0.6 mL; p < 0.0001) and a significantly higher T2 WMH mean number in infratentorial, periventricular, and juxtacortical areas (p < 0.0001). LPMs identified the periventricular regions as the sites with the highest probability of detecting T2 WMH in patients with CIS. Voxel-wise analysis of lesion distribution by diagnosis revealed a statistically significant association exclusively between the diagnosis of CIS and the PVLs. MAGNIMS criteria demonstrated the highest specificity in differentiating patients with CIS from patients with MA (100% vs 87%) against a predictable lower sensitivity (63% vs 72%). PVLs play a key role in the differential diagnosis between MA and CIS, particularly when there are more than 3. Future studies on multiple sclerosis criteria might reconsider the 3 PVLs to minimize the risk of misdiagnosis. This study provides Class IV evidence that the presence at least 3 PVLs increases the specificity in distinguishing MA from CIS.

Classification of radiologically isolated syndrome and clinically isolated syndrome with machine-learning techniques.

The unanticipated detection by magnetic resonance imaging (MRI) in the brain of asymptomatic subjects of white matter lesions suggestive of multiple sclerosis (MS) has been named radiologically isolated syndrome (RIS). As the difference between early MS [i.e. clinically isolated syndrome (CIS)] and RIS is the occurrence of a clinical event, it is logical to improve detection of the subclinical form without interfering with MRI as there are radiological diagnostic criteria for that. Our objective was to use machine-learning classification methods to identify morphometric measures that help to discriminate patients with RIS from those with CIS. We used a multimodal 3-T MRI approach by combining MRI biomarkers (cortical thickness, cortical and subcortical grey matter volume, and white matter integrity) of a cohort of 17 patients with RIS and 17 patients with CIS for single-subject level classification. The best proposed models to predict the diagnosis of CIS and RIS were based on the Naive Bayes, Bagging and Multilayer Perceptron classifiers using only three features: the left rostral middle frontal gyrus volume and the fractional anisotropy values in the right amygdala and right lingual gyrus. The Naive Bayes obtained the highest accuracy [overall classification, 0.765; area under the receiver operating characteristic (AUROC), 0.782]. A machine-learning approach applied to multimodal MRI data may differentiate between the earliest clinical expressions of MS (CIS and RIS) with an accuracy of 78%.

Diagnostic value of the 2017 McDonald criteria in patients with a first demyelinating event suggestive of relapsing-remitting multiple sclerosis.

For the diagnosis of relapsing-remitting multiple sclerosis (RRMS), the revised 2017 McDonald criteria include cerebrospinal fluid specific oligoclonal bands as a new criterion for dissemination in time. Amongst other things, one expectation of the new criteria is to marginalize the diagnosis of clinically isolated syndrome (CIS), thus allowing for a faster and at the same time still reliable diagnosis of RRMS. In this study, data from an unselected patient cohort with a typical CIS and dissemination in space at a large German Multiple Sclerosis Center from 2013 to 2016 were re-analysed to compare differences in diagnosing RRMS with the 2017 versus 2010 McDonald criteria in everyday practice. Out of a cohort of 290 patients presenting with a typical first demyelinating event, 52% (152 patients) with the diagnosis of RRMS and 48% (138 patients) with the diagnosis of CIS according to the 2010 McDonald criteria were identified. The application of the 2017 McDonald criteria in the same patients increased the number of definite RRMS to 94% (273), thus leaving only 6% of patients with the diagnosis of CIS. The reason for this shift was the presence of cerebrospinal fluid specific oligoclonal bands which was found in 92.7% of the total population and in all patients with 2017 McDonald RRMS. Over a mean follow-up of 1.5years, 50% of patients formerly diagnosed with CIS who are now RRMS also fulfilled the 2010 McDonald criteria. Our data support the use of the 2017 McDonald criteria for a more sensitive, but not that specific, diagnosis of RRMS in everyday practice.

Validation of CSF free light chain in diagnosis and prognosis of multiple sclerosis and clinically isolated syndrome: prospective cohort study in Buenos Aires.

The objective was to evaluate the precision of kappa and lambda free light chains (KFLC and LFLC) in CSF for the diagnosis of multiple sclerosis (MS) and prognosis of clinically isolated syndrome (CIS). CSF and serum samples from CIS, MS and other neurological non-MS disease were collected between 2015 and 2017. FLC concentrations were measured using immunoassay Freelite™. Results were correlated with the patients' diagnoses and ROC curve analysis was used to determine accuracy. In CIS patients, analysis of FLC were compared in CIS converters vs. non-converter during follow-up. In the MS group (n = 41), the optimal cut-off for KFLC determined was 7mg/L, with a diagnostic sensitivity and specificity of 95% and 97%, respectively. The optimal cut-off for LFLC was 0.7mg/L, with a diagnostic sensitivity and specificity of 71% and 81%, respectively. 36 CIS patients were included; mean follow-up time was 28 ± 9months, and 22 (61.1%) patients converted to MS. The median concentration of CSF K and LFLCs at CIS diagnosis was slightly higher in CIS-converters compared to non-converters, but this did not reach statistical significance (KFLC: median 7 ± 5.3mg/L vs. 5 ± 2.3mg/L, p = 0.11; LFLC 0.7 ± 0.33mg/L vs. 0.5 ± 0.23mg/L p = 0.16). A strong correlation was observed between the concentration of K and L FLCs at diagnosis and the change in PBVC during follow-up (r = 0.72 and r = 0.65, respectively). KFLCs have a high sensitivity and specificity for the diagnosis of MS. FLC concentrations at CIS diagnosis were not significantly higher in CIS-converters.

Higher Serum Immunoglobulin G3 Levels May Predict the Development of Multiple Sclerosis in Individuals With Clinically Isolated Syndrome.

Clinically isolated syndrome (CIS) is a first episode of neurological symptoms that may precede a diagnosis of multiple sclerosis (MS). Therefore, studying individuals with CIS may lead to breakthroughs in understanding the development and pathogenesis of MS. In this study, serum levels of immunoglobulin (Ig)G, IgA, IgM, and IgG1–4 were measured in 20 people with CIS and compared with those in 10 healthy controls (HC) and 8 people with MS. Serum Ig levels in individuals with CIS were compared with (a) the time to their conversion from CIS to MS, (b) serum levels of antibodies to Epstein–Barr virus, (c) frequencies of T regulatory (Treg), T follicular regulatory (Tfr), and B cell subsets, and (d) Treg/Tfr expression of Helios. Serum IgG, IgM, and IgG2 levels were significantly lower in people with CIS than HC, and IgG, IgM, and IgG1 levels were significantly lower in people with CIS than MS. After adjusting for age, sex, and serum 25(OH) vitamin D3 [25(OH)D] levels, CIS was associated with lower serum levels of IgG and IgG2 compared with HC (p = 0.001 and p < 0.001, respectively). People with MS had lower IgG2 levels (p < 0.001) and IgG2 proportions (%IgG; p = 0.007) compared with HC. After adjusting for age, sex, and 25(OH)D, these outcomes remained, in addition to lower serum IgA levels (p = 0.01) and increased IgG3 levels (p = 0.053) in people with MS compared with HC. Furthermore, serum from people with MS had increased proportions of IgG1 and IgG3 (p = 0.03 and p = 0.02, respectively), decreased proportions of IgG2 (p = 0.007), and greater ratios of “upstream” to “downstream” IgG subclasses (p = 0.001) compared with HC. Serum IgG3 proportions (%IgG) from people with CIS correlated with the frequency of plasmablasts in peripheral blood (p = 0.02). Expression of Helios by Treg and Tfr cell subsets from individuals with CIS correlated with levels of serum IgG2 and IgG4. IgG3 levels and proportions of IgG3 (%IgG) in serum at CIS diagnosis were inversely correlated with the time until conversion to MS (p = 0.018 and p < 0.001, respectively), suggesting they may be useful prognostic markers of individuals with CIS who rapidly convert to MS.

Treatment choices and neuropsychological symptoms of a large cohort of early MS.

ObjectiveTo assess clinical characteristics, distribution of disease-modifying treatments (DMTs), and neuropsychological symptoms in a large cohort of patients with early-stage MS.MethodsThe German National MS Cohort is a multicenter prospective longitudinal cohort study that has recruited DMT-naive patients with clinically isolated syndrome (CIS) and relapsing-remitting MS (RRMS) since 2010. We evaluated their baseline characteristics and the prevalence of neuropsychological symptoms.ResultsOf 1,124 patients, with a 2.2:1 female-to-male ratio and median age at onset of 31.71 years (interquartile range [IQR]: 26.06–40.33), 44.6% and 55.3% had CIS and RRMS, respectively. The median Expanded Disability Status Scale (EDSS) score at baseline was 1.5 (IQR: 1.0–2.0). A proportion of 67.8% of patients started DMT after a median time of 167.0 days (IQR 90.0–377.5) since the first manifestation. A total of 64.7% and 70.4% of the 762 patients receiving early DMT were classified as CIS and RRMS, respectively. Fatigue, depressive symptoms, and cognitive dysfunction were detected in 36.5%, 33.5%, and 14.7% of patients, respectively.ConclusionBaseline characteristics of this large cohort of patients with early, untreated MS corroborated with other cohorts. Most patients received early DMT within the first year after disease onset, irrespective of a CIS or RRMS diagnosis. Despite the low EDSS score, neuropsychological symptoms affected a relevant proportion of patients.

Anatomical Wiring and Functional Networking Changes in the Visual System Following Optic Neuritis

Clinical outcome in multiple sclerosis was suggested to be driven by not only remyelination but also adaptive reorganization. This mechanism needs to be further understood. To explore anatomical and functional visual networks in patients with optic neuritis (ON) to assess the relative weight of each connectivity modality to expedite visual recovery. Between March 11, 2011, and May 26, 2014, 39 patients with either clinically isolated syndrome (CIS) ON (n = 18) or other CIS (non-ON) (n = 21) were recruited 1 to 28 months following an initial clinical event. These patients enrolled in an ongoing prospective cohort study (107 participants at the time of this present study) about the disease course of CIS and multiple sclerosis. Inclusion criteria were an age of 18 to 65 years, the suggestive clinical and paraclinical diagnosis of CIS or multiple sclerosis after relevant differential diagnoses have been ruled out, the existence of complete imaging data, and no ocular comorbidities. Anatomical connectivity was evaluated by diffusion tensor imaging, and functional connectivity was evaluated by resting-state functional magnetic resonance imaging. The visual pathways, including optic tracts, optic radiations, and splenial fibers, were delineated, and the resting-state visual networks were detected. Data analysis took place from September 1, 2015, to December 1, 2015. Connectivity changes were quantified and compared to determine the association of ON with the visual network. This study included 18 patients with CIS ON, 11 (61%) of whom were women with a mean (SD) age of 32.83 (8.53) years, and 21 patients with CIS non-ON (11 [52%] of whom were women with a mean [SD] age of 30.86 [7.54] years). With the use of diffusion tensor imaging, reduced diffusivity (mean [SD] fractional anisotropy, 0.35 [0.03] vs 0.38 [0.03]; P < .01) was evident along the optic tracts of patients with ON, suggesting the extension of axonal injury from the damaged optic nerve. Neither the optic radiations nor the splenial fibers showed evidence of loss of integrity. Yet, in the presence of an intact postgeniculate anatomical network, the functional connectivity within the visual network was higher in the ON cohort. Functional connectivity observed in cortical motion-related areas was inversely correlated with the visual evoked potential-measured conduction velocity (r = -0.59; P < .05). In this cohort, local optic nerve demyelinating damage does not affect distant wiring, but even in the presence of an intact anatomical network, functional modification may occur. These functional network changes may be part of the recovery process, but further research is needed to elucidate this process.

Clinically Isolated Syndromes: Clinical Characteristics, Differential Diagnosis, and Management.

Clinically isolated syndrome (CIS) is a term that describes the first clinical onset of potential multiple sclerosis (MS). The term CIS is typically applied to young adults with episodes of acute or subacute onset, which reaches a peak quite rapidly within 2-3 weeks. In 85% of young adults who develop MS, onset occurs with an acute, CIS of the optic nerves, brainstem, or spinal cord. When clinically silent brain lesions are seen on MRI, the likelihood of developing MS is high. Because no single clinical feature or diagnostic test is sufficient for the diagnosis of CIS, diagnostic criteria have included a combination of both clinical and paraclinical studies. Diagnostic criteria from the International Panel of McDonald and colleagues incorporate MRI evidence of dissemination in time and space to allow a diagnosis of definite MS in patients with CIS. As CIS is typically the earliest clinical expression of MS, research on patients with CIS may provide new insights into early pathological changes and pathogenetic mechanisms that might affect the course of the disorder. With recent improvements in diagnosis and the advent of disease-modifying treatments for MS, there has been growing interest and research in patients with CIS.

Clinically isolated syndrome — Rethinking the diagnosis

A diagnostic lacuna in clinically isolated syndrome (CIS) is the prognostic uncertainty of approximately 20% of patients who do not meet the radiological criteria based on magnetic resonance imaging (MRI) of the brain. A study by Tintore et al. noted that 23% of patients who had normal MRI findings but had oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) developed clinically definite multiple sclerosis (CDMS), compared with 4% who had normal MRI findings but no OCBs in CSF (Tintore et al. 2008). Since a diagnosis of CIS cannot be made if MRI data are equivocal, the opportunity for early treatment is lost if non-radiological data are not taken into diagnostic consideration. In this article, a case for inclusion of cerebrospinal fluid data in the diagnosis of CIS is made, and a distinction is drawn in certain patient cohorts based on ethnicity, that demands urgent research. Certain ethnic cohorts such as African Americans (AAs) may have a higher risk of delayed diagnosis if CSF data are ignored. At the current time, the diagnosis of CIS continues to favor clinical and radiological evidence and this article aims to change that perspective.

Multiple sclerosis: improved identification of disease-relevant changes in gray and white matter by using susceptibility-based MR imaging.

To evaluate the potential of quantitative susceptibility (QS) and R2* mapping as surrogate biomarkers of clinically relevant, age-adjusted demyelination and iron deposition in multiple sclerosis (MS). All study participants gave written informed consent, and the study was approved by the institutional review board. Quantitative maps of the magnetic resonance imaging susceptibility parameters (R2* and QS) were computed for 25 patients with either clinically isolated syndrome (CIS) or relapsing-remitting MS, as well as for 15 age- and sex-matched control subjects imaged at 7 T. The candidate MR imaging biomarkers were correlated with Extended Disability Status Scale (EDSS), time since CIS diagnosis, time since MS diagnosis, and age. QS maps aided identification of significant, voxel-level increases in iron deposition in subcortical gray matter (GM) of patients with MS compared with control subjects. These voxel-level increases were not observed on R2* maps. Region-of-interest analysis of mean R2* and QS in subcortical GM demonstrated that R2* (R ≥ 0.39, P < .01) and QS (R ≥ 0.44, P < .01) were strongly correlated with EDSS. In white matter (WM), the volume of total WM damage (defined by a z score of less than -2.0 criterion, indicating demyelination) on QS maps correlated significantly with EDSS (R = 0.46, P = .02). Voxelwise QS also supported a significant contribution of age to demyelination in patients with MS, suggesting that age-adjusted clinical scores may provide more robust measures of MS disease severity compared with non-age-adjusted scores. Using QS and R2* mapping, evidence of both significant increases in iron deposition in subcortical GM and myelin degeneration along the WM skeleton of patients with MS was identified. Both effects correlated strongly with EDSS.

Relationship between working hours and power of attention, memory, fatigue, depression and self-efficacy one year after diagnosis of clinically isolated syndrome and relapsing remitting multiple sclerosis.

The role of cognitive domain dysfunction with respect to vocational changes in persons with Clinically Isolated Syndrome (CIS) and early Relapsing Remitting Multiple Sclerosis (eRRMS) is insufficiently known. We investigated thirty-three patients - 14 CIS, 19 eRRMS -, mean (standard deviation [SD]) time since diagnosis 13.5 (4.8) months and mean (SD) Expanded Disability Status Scale (EDSS) score 1.3 (1.1). Patients were assessed on the CDR System, a set of automated tests of cognitive function, which yielded scores for Power of Attention (ms), Continuity of Attention (#), Working Memory (SI), Episodic Memory (#) and Speed of Memory (ms). Work-related items and the confounding variables fatigue, depression, disease impact and self-efficacy, were assessed by self-report questionnaires. Patients had poorer Power of Attention compared to normative data (1187 [161.5] vs. 1070 [98.6]; P<0.0001) and slower Speed of Memory (4043 [830.6]) vs. 2937 [586.1]; P<0.0001). Power of Attention (Pearson r = −0.42; P<0.04), Working Memory (r = 0.42; P<0.04) and depression r = −0.41; P<0.05) correlated with number of days worked per week. Fatigue (r = −0.56; P<0.005), self-efficacy (r = 0.56; P<0.005) and disease impact (r = −0.46; P<0.05) correlated with number of hours worked per week. Persons who wished to work less had poorer Power of Attention (1247 vs. 1116 ms; P<0.02), those who wished to change job had poorer Episodic Memory (1.35 vs. 1.57; p<0.03). People who reduced working hours within 12 months after diagnosis had higher fatigue and disease impact, and lower self-efficacy. The findings of this pilot study indicate that one year after the diagnosis of CIS and RRMS Power of Attention and Speed of Memory are reduced, that Power of Attention and Memory are associated with a capability of working less hours, and that fatigue, depression and disease impact may negatively, and self-efficacy positively affect working hours.

Effect of the disclosure of MS diagnosis on anxiety, mood and quality of life of patients: a prospective study

In the light of the new diagnostic criteria for multiple sclerosis (MS) and currently available early treatment, this study aimed to explore whether, and to what extent, disclosure of the diagnosis of MS or clinically isolated syndrome (CIS) affects patients' anxiety, mood and quality of life (QoL). Eligible participants were all patients referred for the first time to the Neurological Unit who had manifested symptoms suggestive of MS for no more than 6 months. All patients were evaluated for (i) QoL (SEIQoL and MS-QoL54), (ii) Anxiety (STAI) and Depression (CMDI) on study inclusion (T0), 30 days after diagnosis disclosure (T30), and after 1 (T1y) and 2 (T2y) years' follow-up. Two hundred and twenty-nine patients were enrolled; 93 of these were unaware of their diagnosis. Patients who already knew their diagnosis (100 with CIS and 22 with MS) were excluded from the main analyses and used to perform control analyses. At the end of the screening, an MS diagnosis was disclosed to 18 of the 93 patients, whereas a CIS diagnosis was disclosed to 62 patients (12 patients received a diagnosis other than MS or CIS). Thirty days after diagnosis disclosure, irrespective of the diagnosis disclosed, both QoL and Anxiety and Depression were significantly rated as better compared to the start of screening, (p(s) < 0.03), and this improvement remained stable over the two annual follow-ups. However, as suggested by a significant 'Time' × 'Diagnosis' interaction with regard to both QoL and Anxiety and Depression (p(s) < 0.02), the effect of the disclosure in the short term differed depending on CIS or MS diagnosis. Specifically, on MSQoL, which is a health-related QoL scale, we found a statically significant improvement, immediately after the diagnosis disclosure, in both the MS and CIS groups (p(s) < 0.01). Differently, on SEIQoL, which is a non health-related QoL measure, and on the anxiety scale, we observed a statistically significant improvement only in the group which received a MS diagnosis (p(s) < 0.03). This first prospective study provides objective data showing that early disclosure of MS diagnosis improves both the patient's QoL and psychological well-being. In addition, the results seem to suggest that CIS disclosure does not lead to the same favourable effects.

The "New" Clinically Isolated Syndrome: To Treat or Not to Treat?

Clinically isolated syndrome (CIS) refers to the first neurologic episode in which a person experiences multiple sclerosis (MS)-related symptoms. The diagnosis of CIS is reserved for patients who do not meet the criterion of dissemination in space and/or dissemination in time clinically and in the first magnetic resonance image. This article debates whether or not patients with CIS should be treated.

Demyelinating optic neuritis presenting as a clinically isolated syndrome

Background Clinically isolated syndrome (CIS) describes a single, first-occurrence attack caused by inflammation/demyelination in 1 or more locations in the central nervous system. The optic nerve is a frequent site affected by this neurologic event. As the name implies, CIS is an isolated condition but is often considered a precursor to multiple sclerosis (MS). When distinctive brain lesions detected by magnetic resonance imaging (MRI) accompany CIS, the person is considered at a high risk for MS. Treatment is aimed at delaying the onset of a second neurologic episode, reducing the accumulation of MRI-detected brain lesions and delaying the development of definite MS. Case Report This article describes a 40-year-old woman who experienced a sudden loss of vision in the right eye. Testing ultimately found a normal MRI, demyelination of the optic nerve, and progressive thinning of the retinal nerve fiber layer, leading to a diagnosis of CIS.

New symptoms in a patient with diagnosed porphyria – untypical clinical course or another disease? Extended differential diagnosis of multiple sclerosis

Acute liver porphyrias are caused by mutations of genes encoding the heme biosynthesis enzymes. A lack of any of these enzymes leads to a decrease in the heme level, which in each case is manifested by identical clinical symptoms. Nervous tissue is particularly susceptible to a depletion of heme levels. Three classical symptoms of a porphyria attack include: abdominal pain (as a manifestation of autonomic neuropathy), peripheral neuropathy, and psychic disturbances. Apart from the main symptoms, porphyria attacks may be manifested as various neurological disturbances, such as: bulbar palsy, epileptic seizures, psychic disturbances and focal symptoms of CNS damage. The intensity of individual symptoms can vary. Although neurological symptoms usually disappear after the attack, they may cause permanent deficits. Through involving CNS, porphyria can mimic other neurological disorders. Damage to the nervous system can be confirmed by additional examinations. Thus far, disseminated focal changes during the attack, which disappear after the regression of clinical symptoms, have been described in magnetic resonance imaging (MRI) scans of the brain. Spinal cord abnormalities in MRI scans have not been described yet, despite the fact that damage to the anterior horn associated with porphyria has been confirmed in literature. While examining cerebrospinal fluid during the attack, an elevated protein level has been noticed, so far without the presence of oligoclonal bands. This paper aimed to demonstrate that porphyria should be considered in differential diagnosis of clinically isolated syndrome (CIS) and multiple sclerosis (MS). This paper is based on the case of a symptomatic patient who carried a mutation in one of the genes for porphyria, and who developed a clinical manifestation of focal damage to CNS. A differential diagnosis of porphyria and CIS, with a subsequent conversion to a clinically defined MS, was carried out. The results of additional examinations performed routinely in both disorders, the clinical picture and data from medical literature have been used in the analysis of this case. The authors present the case of a patient with confirmed genetic porphyria, who was hospitalized for purposes of establishing a diagnosis due to weakened lower extremities. The patient manifested spastic lower extremity paresis, sensation disorders and urinary incontinence, which indicated spinal cord damages. An MRI scan of the thoracic spine revealed disseminated foci with contrast enhancement. A high level of proteins and oligoclonal bands were detected in the cerebrospinal fluid. On the basis of a new clinical picture (differing from the previous attack symptoms), prolonged symptoms, spinal cord lesions in MRI, and the presence of oligoclonal bands, CIS was diagnosed. Quick and complete recovery was obtained due to the administering of a steroid therapy. After several months, the patient reported a similar, passing episode, which, according to the authors, confirmed the diagnosis and an expected conversion to a clinically defined MS. Taking into consideration the clinical manifestation of spinal cord involvement untypical of porphyria, the detection of spinal lesions in an MRI scan, the presence of oligoclonal bands in the cerebrospinal fluid and the positive effect of steroid therapy, the authors believe that this described patient, who was a symptomatic carrier of a mutation in a gene for porphyria, developed CIS. This reported case, supported by data from medical literature, shows that porphyria should be taken into consideration in any differential diagnosis of CIS and MS.

Optimizing Outcomes in Multiple Sclerosis – A Consensus Initiative

Background Initiation of immunomodulators in patients experiencing a clinically isolated syndrome (CIS) may delay progression to clinically definite MS. However, lack of consensus remains on many issues affecting optimal management of MS. Method A panel of 21 MS experts met during 9 meetings to explore key issues in MS and CIS. Meetings addressed 3 phases: 1. CIS definition and diagnosis; 2. initial therapy; and 3. monitoring disease progression and treatment efficacy. Newsletters covering each phase were sent to 5000 U.S.-based neurologists who were invited to participate in an online survey on key issues. Results Most panel members agreed that early treatment may minimize neurodegeneration and most would recommend it for patients; that a dose-response relationship exists for beta-interferon therapy; that more aggressive therapy was most effective early in the disease course; and, that MRI has a role in monitoring disease progression. In face of suboptimal response, most would switch patients to a different therapy; while combination therapy would be reserved for those failing monotherapy regimes. Most online survey respondents agreed with these positions. Conclusions There was uniform consensus from this panel of MS experts that early initiation of immunomodulator therapy was beneficial for CIS patients.