Differential Diagnosis Of Multiple Sclerosis Research Articles

Clinical significance and prognostic value of serum autoantibody tests in multiple sclerosis.

It is known that multiple sclerosis (MS) often coexists with other autoimmune diseases. Hence, autoantibody (auto-Ab) tests may prove useful in the differential diagnosis of MS. The objectives of this study were to: (a) investigate the prevalence of auto-Ab positivity at the beginning of the MS diagnostic process; (b) assess whether Auto-Ab+ and Auto-Ab- patients differ in baseline clinical, laboratory, and radiological parameters; and (c) investigate the prognostic value during a two-year follow-up period. This retrospective study consisted of 450 patients aged between 18 and 55 years. All patients underwent a wide range of auto-Ab tests, anti-nuclear antibody (ANA) tests in particular. The expanded disability status scale (EDSS) scores of the patients were recorded at the time of diagnosis and at the end of a two-year follow-up period. The mean age of the 212 patients, 148 (69.8%) female and 64 (30.2%) male, included in the study sample was 37 ± 10.83 years. The rate of relapsing cases was 84% (178). Oligoclonal band (OCB) was positive in 142 (86.6%) of the 164 tested cases. At least one of the auto-Ab tests was positive in 51 (24.1%) of the cases. ANA test was positive in 21 (9.9%) cases. There was no significant difference between patients with at least one positive auto-Ab test and without any positive auto-Ab test and between ANA-positive and ANA-negative patients in terms of age, gender, clinical features of MS, presence of brain stem lesion, presence of spinal lesion, OCB positivity, level of clinical improvement after the first pulse steroid treatment, family history, presence of comorbidity, presence of autoimmune disease, or EDSS scores recorded at the end of the two-year follow-up period (p > 0.05). Our study findings revealed that Auto-Ab positivity was more common in MS patients than in the general population. However, given their limited contribution to the diagnosis and differential diagnosis of MS with no effect on the prognostic process, auto-Ab tests should be requested only in the event of accompanying autoimmune disease symptoms, and in cases where the diagnosis of MS may be suspected.

Joint radiomics and spatial distribution model for MRI-based discrimination of multiple sclerosis, neuromyelitis optica spectrum disorder, and myelin-oligodendrocyte-glycoprotein-IgG-associated disorder.

To develop a discrimination pipeline concerning both radiomics and spatial distribution features of brain lesions for discrimination of multiple sclerosis (MS), aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorder (NMOSD), and myelin-oligodendrocyte-glycoprotein-IgG-associated disorder (MOGAD). Hyperintensity T2 lesions were delineated in 212 brain MRI scans of MS (n = 63), NMOSD (n = 87), and MOGAD (n = 45) patients. To avoid the effect of fixed training/test dataset sampling when developing machine learning models, patients were allocated into 4 sub-groups for cross-validation. For each scan, 351 radiomics and 27 spatial distribution features were extracted. Three models, i.e., multi-lesion radiomics, spatial distribution, and joint models, were constructed using random forest and logistic regression algorithms for differentiating: MS from the others (MS models) and MOGAD from NMOSD (MOG-NMO models), respectively. Then, the joint models were combined with demographic characteristics (i.e., age and sex) to create MS and MOG-NMO discriminators, respectively, based on which a three-disease discrimination pipeline was generated and compared with radiologists. For classification of both MS-others and MOG-NMO, the joint models performed better than radiomics or spatial distribution model solely. The MS discriminator achieved AUC = 0.909 ± 0.027 and bias-corrected C-index = 0.909 ± 0.027, and the MOG-NMO discriminator achieved AUC = 0.880 ± 0.064 and bias-corrected C-index = 0.883 ± 0.068. The three-disease discrimination pipeline differentiated MS, NMOSD, and MOGAD patients with 75.0% accuracy, prominently outperforming the three radiologists (47.6%, 56.6%, and 66.0%). The proposed pipeline integrating multi-lesion radiomics and spatial distribution features could effectively differentiate MS, NMOSD, and MOGAD. The discrimination pipeline merging both radiomics and spatial distribution features of brain lesions may facilitate the differential diagnoses of multiple sclerosis, neuromyelitis optica spectrum disorder, and myelin-oligodendrocyte-glycoprotein-IgG-associated disorder. • Our study introduces an approach by combining radiomics and spatial distribution models. • The joint model exhibited superior performance in distinguishing multiple sclerosis from aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorder and myelin-oligodendrocyte-glycoprotein-IgG-associated disorder as well as discriminating the latter two diseases. • The three-disease discrimination pipeline showcased remarkable accuracy, surpassing the performance of experienced radiologists, highlighting its potential as a valuable diagnostic tool.

Differentiation between multiple sclerosis and neuromyelitis optica spectrum disorder using a deep learning model

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are autoimmune inflammatory disorders of the central nervous system (CNS) with similar characteristics. The differential diagnosis between MS and NMOSD is critical for initiating early effective therapy. In this study, we developed a deep learning model to differentiate between multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) using brain magnetic resonance imaging (MRI) data. The model was based on a modified ResNet18 convolution neural network trained with 5-channel images created by selecting five 2D slices of 3D FLAIR images. The accuracy of the model was 76.1%, with a sensitivity of 77.3% and a specificity of 74.8%. Positive and negative predictive values were 76.9% and 78.6%, respectively, with an area under the curve of 0.85. Application of Grad-CAM to the model revealed that white matter lesions were the major classifier. This compact model may aid in the differential diagnosis of MS and NMOSD in clinical practice.

Differentiating neurosarcoidosis from multiple sclerosis using combined analysis of basic CSF parameters and MRZ reaction.

Neurosarcodosis is one of the most frequent differential diagnoses of multiple sclerosis (MS) and requires central nervous system (CNS) biopsy to establish definite diagnosis according to the latest consensus diagnostic criteria. We here analyzed diagnostic values of basic cerebrospinal fluid (CSF) parameters to distinguish neurosarcoidosis from MS without CNS biopsy. We retrospectively assessed clinical, radiological and laboratory data of 27 patients with neurosarcoidosis treated at our center and compared following CSF parameters with those of 138 patients with relapsing-remitting MS: CSF white cell count (WCC), CSF/serum albumin quotient (Qalb), intrathecal production of immunoglobulins including oligoclonal bands (OCB), MRZ reaction, defined as a polyspecific intrathecal production of IgG reactive against ≥2 of 3 the viruses measles (M), rubella (R), and zoster (Z) virus, and CSF lactate levels. Additional inflammatory biomarkers in serum and/or CSF such as neopterin, soluble interleukin-2 receptor (sIL-2R) and C-reactive protein (CRP) were assessed. There was no significant difference in the frequency of CSF pleocytosis, but a CSF WCC > 30/μl was more frequent in patients with neurosarcoidosis. Compared to MS, patients with neurosarcoidosis showed more frequently an increased Qalb and CSF lactate levels as well as increased serum and CSF levels of sIL-2R, but a lower frequency of intrathecal IgG synthesis and positive MRZ reaction. Positive likelihood ratio (PLR) of single CSF parameters indicating neurosarcoidosis was highest, if (a) CSF WCC was >30/μl (PLR 7.2), (b) Qalb was >10 × 10-3 (PLR 66.4), (c) CSF-specific OCB were absent (PLR 11.5), (d) CSF lactate was elevated (PLR 23.0) or (e) sIL-2R was elevated (PLR>8.0). The combination of (a) one of three following basic CSF parameters, i.e., (a.1.) CSF WCC >30/ul, or (a.2.) QAlb >10 × 10-3, or (a.3.) absence of CSF-specific OCB, and (b) absence of positive MRZ reaction showed the best diagnostic accuracy (sensitivity and specificity each >92%; PLR 12.8 and NLR 0.08). Combined evaluation of basic CSF parameters and MRZ reaction is powerful in differentiating neurosarcoidosis from MS, with moderate to severe pleocytosis and QAlb elevation and absence of intrathecal IgG synthesis as useful rule-in parameters and positive MRZ reaction as a rule-out parameter for neurosarcoidosis.

Cerebrospinal Fluid Biomarkers in Differential Diagnosis of Multiple Sclerosis and Systemic Inflammatory Diseases with Central Nervous System Involvement

Diagnosis of multiple sclerosis (MS) is established on criteria according to clinical and radiological manifestation. Cerebrospinal fluid (CSF) analysis is an important part of differential diagnosis of MS and other inflammatory processes in the central nervous system (CNS). In total, 242 CSF samples were collected from patients undergoing differential MS diagnosis because of the presence of T2-hyperintensive lesions on brain MRI. The non-MS patients were subdivided into systemic inflammatory diseases with CNS involvement (SID) or cerebrovascular diseases (CVD) or other non-inflammatory diseases (NID). All samples were analyzed for the presence of oligoclonal bands and ELISA was performed for detection of: INF gamma, IL-6, neurofilaments light chain (NF-L), GFAP, CHI3L1, CXCL13, and osteopontin. The level of IL-6 (p = 0.024), osteopontin (p = 0.0002), and NF-L (p = 0.002) was significantly different among groups. IL-6 (p = 0.0350) and NF-L (p = 0.0015) level was significantly higher in SID compared to NID patients. A significantly higher level of osteopontin (p = 0.00026) and NF-L (p = 0.002) in MS compared to NID population was noted. ROC analysis found weak diagnostic power for osteopontin and NFL-L. The classical and non-standard markers of inflammatory process and neurodegeneration do not allow for sufficient differentiation between MS and non-MS inflammatory CNS disorders. Weak diagnostic power observed for the osteopontin and NF-L needs to be further investigated.

How relevant are cerebral white matter lesions in the D313Y variant of the α-galactosidase A gene? Neurological, cardiological, laboratory, and MRI data of 21 patients within a follow-up of 3years.

Fabry disease is an inherited metabolic disorder with various symptoms. Neurological manifestations are small fiber neuropathy, cerebral white matter lesions (WML), megadolicho basilar artery, and stroke. The relevance of the D313Y variant in the galactosidase alpha gene is controversially discussed. We aimed at elucidating the implications of this differential diagnosis of multiple sclerosis (MS), focussing on the analysis of WML over time and correlations with other markers. We reviewed retrospectively the clinical, laboratory, and magnetic resonance imaging data of 21 carriers of the D313Y variant at a single German outpatient clinic for MS between 2004 and 2021. In our cohort (15 females, 6 males), mean age at diagnosis was 44.1 ± 16.3years, and mean follow-up duration was 3.1 ± 3.9years. WML were rated on both, the Fazekas scale and the age-related white matter changes rating scale, and were of variable interindividual extent. Follow-up imaging showed virtually no progress. WML did not correlate with the severity of clinical findings or lysoGb3 levels. Symptomatic carriers of the variant are characterized by an almost complete lack of internal organ manifestations and laboratory findings, usually associated with Fabry disease. WML in carriers of the D313Y variant do not seem to be suitable for assessing or predicting the (para-) clinical status. Concerning MS patients, the variant and its clinical signs can be a differential diagnosis, but also a co-factor. Imaging and cerebrospinal fluid findings facilitate the distinction between both entities.

Primary angiitis of the central nervous system as a mimic of multiple sclerosis: A case report

BackgroundPrimary angiitis of the central nervous system is a rare inflammatory vasculopathy and it is a difficult diagnosis to make because of its kaleidoscopic presentation and its multiple mimics, including multiple sclerosis. Case presentationA 21-year-old men presented a four-year history of progressive gait deterioration. Magnetic resonance imaging of the brain and spine showed hyperintense round-shaped lesions on T2 images, many with contrast enhancement, in supra/infratentorial and spinal segments. He received treatment for multiple sclerosis but presented clinical worsening, and follow-up neuroimaging showed persistent contrast enhancement lesions and a cerebellar hematoma. Brain biopsy was performed and demonstrated inflammatory infiltrations in blood vessels. The patient received 6 monthly schedules of 5 g methylprednisolone and 1 g cyclophosphamide with clinical stabilization. DiscussionOur patient presented a primary angiitis central nervous system according to the Birnbaum and Hellmann proposed criteria. This case reinforces the importance of advancing the differential diagnosis of patients that present red flags in brain neuroimaging. ConclusionThe presence of the micro/macrobleeds and persistent contrast enhancing lesions should raise the suspicion of vasculitis in the differential diagnosis of multiple sclerosis.

Evaluation of cerebrospinal fluid neurofilament light chain levels in multiple sclerosis and non-demyelinating diseases of the central nervous system: clinical and biochemical perspective.

The neurofilament light chain (NfL) is a promising biomarker in the diagnosis, prognosis, and treatment response evaluation of neurological diseases. The aims of this study were to compare the cerebrospinal fluid (CSF) NfL levels in multiple sclerosis (MS) and certain non-demyelinating diseases of the central nervous system (NDCNS); to determine the relationship between clinical and radiological features and CSF NfL levels in patients with MS; and to compare the enzyme-linked immunosorbent assay (ELISA) and single molecule array (SIMOA) methods for NfL measurement using paired CSF and serum samples. We retrospectively analyzed the clinical data and performed NfL measurements in CSF and serum samples of newly diagnosed and treatment-naive patients with CNS diseases evaluated between 1 January 2019 and 1 January 2020. Eligible patients were divided into three groups: MS (n = 23), differential diagnosis of MS (n = 19), and NDCNS (n = 42). First, we compared the CSF NfL levels among the three groups using the previously validated CSF ELISA assay. Next, we evaluated the relationship between CSF NfL levels and the clinical and radiological findings in MS group. Finally, we compared CSF and serum samples from patients of the MS groups (paired serum and CSF samples, n = 19) using two different methods (ELISA and SIMOA). The CSF NfL level was the highest in the NDCNS group (1169.64 [535.92−5120.11] pg/mL, p = 0.025). There was a strong positive correlation between the number of T2 lesions and CSF NfL level (r = 0.786, p < 0.001) in the MS group. There was excellent consistency between ELISA and SIMOA for CSF samples, but not for serum samples. Our results indicated that CSF NfL levels may also be used in the management of NDCNS and that SIMOA is the most reliable method for serum NfL determination.

Analysis of CSF D-Dimer to Identify Intrathecal Fibrin-Driven Autoimmunity in Patients With Multiple Sclerosis.

Background and ObjectivesProteins of the coagulation system contribute to autoimmune inflammation in patients with multiple sclerosis (MS). On blood-brain barrier (BBB) disruption, fibrinogen enters the CNS and is rapidly converted to fibrin, unfolding pleiotropic autoimmune mechanisms. Fibrin accumulation leads to subsequent proteolytic degradation that results in D-dimer generation. The primary objective of this study was to determine intrathecal levels of D-dimer in CSF as a measure of intrathecal coagulation cascade activation and to evaluate its diagnostic utility in patients with MS in contrast to healthy subjects. Key secondary objectives included analysis of CSF D-dimer in differential diagnoses of MS and its relation to routine clinical markers of disease activity.MethodsPatients admitted for the assessment of suspected MS were prospectively recruited from October 2017 to December 2020. Blood plasma and citrated CSF samples were analyzed using a highly sensitive luminescent oxygen channeling immunoassay. Intrathecal generation of D-dimer was analyzed by adjusting for CSF/serum albumin (Qalb) and CSF/plasma D-dimer quotients (QD-dimer), and corresponding CSF fibrinogen levels were determined. Final diagnoses after full evaluation and clinical data were recorded.ResultsOf 187 patients, 113 patients received a diagnosis of MS or clinically/radiologically isolated syndrome. We found increased intrathecal CSF D-dimer generation levels (QD-dimer/Qalb-index) for patients with relapsing-remitting MS (RRMS; n = 71, median 4.7, interquartile range [IQR] 2.5–8.0) when compared with those for disease controls (n = 22, median 2.6, IQR 2.1–4.8, p = 0.031). Absolute CSF D-dimer values correlated with CSF fibrinogen levels (r = 0.463; p < 0 .001) and CSF leukocytes (r = 0.273; p = 0.003) and were elevated in MS patients with contrast enhancement (CE) compared with MS patients without CE on MRI (n = 48, median 6 ng/mL, and IQR 3–15.25 vs n = 41, median 4 ng/mL, and IQR 2–7; p = 0.026). Exploratory subgroup analyses indicated a correlation of intrathecal inflammatory activity and CSF D-dimer levels.DiscussionD-dimer in CSF can be reliably determined and correlates with markers of CNS inflammation and CSF fibrinogen levels. Adjusted for BBB dysfunction, CSF D-dimer may allow the identification of intrathecal coagulation cascade activation in patients with MS.Classification of EvidenceThis study provides Class I evidence that CSF D-dimer levels are elevated in patients with RRMS.

Differential diagnosis of multiple sclerosis in children

At the onset, multiple sclerosis (MS) in children is characterized by a phase of active inflammation with extensive demyelination of the white matter of the CNS, which often mimics this nosology with a whole spectrum of inflammatory demyelinating diseases such as ADEM, anti-MOG encephalitis, ONMSD. In order to formalize the diagnostic process, the International Pediatric Multiple Sclerosis Study Group (IPMSSG) proposed diagnostic criteria for the main immune-mediated demyelinating diseases of the CNS in children, which, in theory, should simplify the diagnostic search. However, in practice, the range of nosologies in the course of differential diagnosis is much wider and often it is not possible to establish an unambiguous diagnosis in the early stages. The authors analyze their own clinical observations based on a sample of 100 pediatric patients with a referral diagnosis of «MS?» and describe a clinical case of the onset of highly active MS with an assessment of the dynamics of the clinical and paraclinical course of the disease.

Optical Coherence Tomography in the Differential Diagnosis of Patients with Multiple Sclerosis and Patients with MRI Nonspecific White Matter Lesions.

In the differential diagnosis of nonspecific white matter lesions (NSWMLs) detected on magnetic resonance imaging (MRI), multiple sclerosis (MS) should be taken into consideration. Optical coherence tomography (OCT) is a promising tool applied in the differential diagnostic process of MS. We tested whether OCT may be useful in distinguishing between MS and NSWMLs patients. In patients with MS (n = 41) and NSWMLs (n = 19), the following OCT parameters were measured: thickness of the peripapillary Retinal Nerve Fibre Layer (pRNFL) in superior, inferior, nasal, and temporal segments; thickness of the ganglion cell-inner plexiform layer (GCIPL); thickness of macular RNFL (mRNFL); and macular volume (MV). In MS patients, GCIPL was significantly lower than in NSWMLs patients (p = 0.024). Additionally, in MS patients, mRNFL was significantly lower than in NSWMLs patients (p = 0.030). The average segmental pRNFL and MV did not differ between MS and NSWMLs patients (p > 0.05). GCIPL and macular RNFL thinning significantly influenced the risk of MS (18.6% [95% CI 2.7%, 25.3%]; 27.4% [95% CI 4.5%, 62.3%]), and reduced GCIPL thickness appeared to be the best predictor of MS. We conclude that OCT may be helpful in the differential diagnosis of MS and NSWMLs patients in real-world settings.

Differential diagnosis of multiple sclerosis

Background and objectivesDespite immense progress of imaging and updates in the MacDonald criteria, the diagnosis of multiple sclerosis remains difficult as it must integrate history, clinical presentation, biological markers, and imaging. There is a multitude of syndromes resembling multiple sclerosis both clinically or on imaging. The goal of this review is to help clinicians orient themselves in these various diagnoses. We organized our review in two categories: inflammatory and autoimmune diseases that are close or can be confused with multiple sclerosis, and non-inflammatory syndromes that can present with symptoms or imaging mimicking those of multiple sclerosis. MethodReview of literature ConclusionProgress of imaging and biological sciences have drastically changed the approach and management of multiple sclerosis. But these developments have also shined a light on a variety of diseases previously unknown or poorly known, therefore greatly expanding the differential diagnosis of multiple sclerosis. While autoimmune, many of these diseases have underlying biological mechanisms that are very different from those of multiple sclerosis, rendering MS therapies usually inefficient. It is crucial to approach these diseases with utmost thoroughness, integrating history, clinical exam, and evolving ancillary tests.

Difficulties in the differential diagnosis of multiple sclerosis and Susak syndrome

Retino-cochleo-cerebral angiopathy or Susac syndrome is a rare autoimmune disease that selectively affects the vessels of the retina, the inner ear and the central nervous system. Differentiation of Susac syndrome and multiple sclerosis presents difficulties due to the similarity of MRI semiotics of these two diseases. This article presents two clinical cases of patients with Susac syndrome who were diagnosed with multiple sclerosis at the onset of the disease. Based on the analysis of our own clinical observations and literature data, the issues of differential diagnosis of Susac syndrome and multiple sclerosis are highlighted. For the first time a variant of the MRI picture transformation in Susac syndrome is presented.

Magnetic resonance imaging in the diagnosis of non-tumorous multifocal brain lesions mimicking multiple sclerosis

The diagnosis of multiple sclerosis (MS) is quite challenging due to its variable clinical manifestations and lack of a definitive test. Magnetic resonance imaging (MRI) is one of the tools to confirm the diagnosis and also helps in differential diagnosis with other disorders and in exclusion of MS-mimicking diseases. In this article, based on the analysis of clinical cases, we discuss the differential diagnosis of MS with the following non-tumorous multifocal brain lesions: vascular abnormalities caused by hypoxia and ischemia, cerebral autosomal dominant angiopathy with subcortical infarctions and leukoencephalopathy, Susac syndrome, primary angiitis of the central nervous system, and neurosarcoidosis. We present both MRI criteria for MS and disorders that have similar MRI signs, and additional clinical and laboratory data that is essential for correct diagnosis.

Pediatric multiple sclerosis - current status of epidemiology, diagnosis and treatment.

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system that mostly affects younger adults. However, the first symptoms of MS can appear in children and adolescents before the age of 18, and we call this paediatric MS (PMS). It is estimated that paediatric MS accounts for 3-5% of the general population of patients with MS. Despite the fundamental si-milarities to adult MS, PMS has many distinctive features. Paediatric MS has a milder course compared to adults, but leads to sig-nificant disability at an early age. PMS is relapsing-remitting in 95-98% of cases; the primary progressive manifestation is much less common than in adults. The differential diagnosis of MS in children should include other childhood demyelinating diseases, mitochondrial and metabolic diseases, connective tissue diseases, and neuroborreliosis. Differentiating acute disseminated en-cephalomyelitis (ADEM) from the first onset of MS remains the biggest challenge. Over the past 10 years, understanding of the epidemiology, pathophysiology, diagnosis, and treatment of MS in children has significantly expanded. The diagnostic criteria leading to earlier diagnosis and initiation of disease-modifying therapy (DMT) have changed, and the number of drugs used in children has increased. However, many important issues require further research. This review discusses the current state of knowledge regarding the epidemiology, diagnosis, and treatment of multiple sclerosis in children.

Diagnosis of multiple sclerosis in times of MOG and AQP4 autoantibody testing – A monocentric study

BackgroundMyelin oligodendrocyte glycoprotein-IgG-associated encephalomyelitis (MOG-EM) and neuromyelitis optica spectrum disorders are challenging differential diagnoses of multiple sclerosis (MS). Hence, there is uncertainty, whether to test all MS patients for corresponding antibodies. Our objective was to provide a systematic study on the frequency of MOG and Aquaporin-4 (AQP4) autoantibodies in MS patients to evaluate a possible risk of misclassification. MethodsRetrospective study in MS patients (including an unselected cohort of patients diagnosed with MS, a cohort of patients with PPMS and a healthy control group) for seroprevalence of MOG and AQP4 autoantibodies by cell-based assay. ResultsNone of 241 patients with relapsing-remitting, 19 with secondary progressive and 82 with primary progressive MS revealed MOG or AQP4 autoantibodies. ConclusionGeneral testing of MOG and AQP4 autoantibodies in MS patients seems not necessary, but should be limited to selected cases only.

The central vein sign in the differential diagnosis of multiple sclerosis

The current diagnosis of multiple sclerosis (MS) is based on confirmation of the disseminated pathological process in space and time in accordance with the McDonald criteria. Despite this, the search continues for specific markers of the disease, including those detected using neuroimaging techniques that have high sensitivity and specificity in the diagnosis of MS.The paper considers the central vein sign, a new promising diagnostic one of MS. This sign refers to a parenchymal vein visualized in the focus of demyelination, by using special magnetic resonance imaging (MRI) modes. Studies show that the central vein sign has high sensitivity and specificity in the diagnosis of MS, allowing it to be differentiated from other demyelinating, vascular, and systemic diseases that have an MRI pattern similar to that of MS. According to various authors, a threshold of 40–50% perivenular lesions allows MS and MS-like diseases to be differentiated with high accuracy.

The Role of Optical Coherence Tomography in Differential Diagnosis of Multiple Sclerosis and Autoimmune Connective Tissue Diseases with CNS Involvement.

The purpose of this study was to examine whether application of optical coherence tomography (OCT) measurements can provide a useful biomarker for distinguishing central nervous system (CNS) involvement in autoimmune connective tissue diseases (CTD) from multiple sclerosis (MS). An observational study included non-optic neuritis eyes of 121 individuals: 59 patients with MS, 30 patients with CNS involvement in CTD, and 32 healthy controls. OCT examination was performed in all subjects to measure retinal nerve fiber layer (RNFL) thickness, ganglion cell complex (GCC) thickness, ganglion cell layer-inner plexiform layer (GCIPL) thickness, and volume of the macula. There was a significant group effect with regard to superior optic disc RNFL, macular RNFL, GCC, and GCIPL thickness, and macular volume. Post-hoc analysis revealed that MS patients have significantly smaller macular volume and thinner superior optic disc RNFL, macular RNFL, GCC, and GCIPL compared to healthy controls. CTD patients have significantly smaller superior optic disc RNFL, GCIPL, and GCC thickness compared to healthy controls. However, no significant group differences were observed between the patient groups (MS vs. CTD) on any outcome. Although a prominent retinal thinning may be a useful biomarker in MS patients, in a general population of individuals with a confirmed CNS involvement the use of OCT is not specific enough to discriminate between MS and autoimmune CTD.

Prevalence of GLA gene mutations and polymorphisms in patients with multiple sclerosis: A cross-sectional study

PurposeFabry Disease (FD) has been frequently proposed as possible underestimated differential diagnosis of Multiple Sclerosis (MS), but no study has been performed to test prevalence of GLA gene mutations in a population fulfilling diagnostic criteria of MS. Aim of this study is to determine the prevalence of GLA gene mutations in a large and representative population diagnosed with MS, simultaneously providing a critical revision of current literature reports of coexistence or misdiagnosis between these two conditions. MethodsIn this mono-centric cross-sectional study, 927 patients fulfilling McDonald diagnostic criteria and encompassing all MS phenotypes were enrolled. Patients underwent evaluation of α-GalA activity and genotyping. Both genetic variants annotated as pathogenic and GVUS were considered. Estimated alleles frequencies were then compared to the ones reported in the gnomAD database. ResultsGLA gene variants were found in seven individuals. Five patients carried variants previously described having controversial impact on FD phenotype, and the analysis of exome database revealed that they are not rare among healthy individuals. One patient showed a new variant never described before, and another one carried a late-onset FD cardiac variant. ConclusionsThe overall prevalence of GLA gene variants in MS patients is comparable to the one estimated in healthy population. This result is further supported by critical revision of current literature evidences of misdiagnosis between MS and FD, arguing in favour of independence between these disorders.

Migraine related white matter lesions in the differential diagnosis of multiple sclerosis: Magnetic resonance imaging features

Aim: This study aims to describe the lesion characteristics of conventional magnetic resonance imaging (MRI) of patients who are directed to a university hospital with a pre-diagnosis of demyelinating disease who are finally diagnosed as MrWMLs.Material and Methods: Individuals who were referred to an MS outpatient clinic of a university hospital with a pre-diagnosis of demyelinating disease and finally diagnosed with migraine according to the International Classification of Headache Disorders (ICHD) -3 (β) criteria who also have MrWMLs and 45 age and gender-matched individuals who are diagnosed with MS according to the 2017 McDonald diagnostic criteria, without migraine-type headache were retrospectively analyzed. Results: Forty-five individuals with migraine and 45 age and gender-matched individuals who are diagnosed with MS were included. The median time since diagnosis was 10 (0.5-32) years for the migraine group and 5 (0.3-20) years in the group with MS (p=0.031). The median age of the group with migraine was 35 (23-54) years, while the median age of the group with MS was 34 (20-55) years. There was no significant difference between the groups in terms of average age and gender distribution (p=0.342 and p=0.389). The total number of T1 and T2 lesions were significantly higher in the MS group. Similarly, the number of infratentorial and periventricular lesions was higher in the MS group (p0.001). The number of deep white matter lesions was higher in the migraine group (p0.05).Conclusion: In this study, conventional MRI tips were defined for differentiating MS lesions from MrWMLs which has an important place in the differential diagnosis of MS. MrWMLs were deep white matter lesions that are predominantly located at the frontal and parietal lobes. Studies involving more individuals and using automated segmentation software may provide more information to differentiate MrWMLs from MS lesions.