Diagnosis of multiple sclerosis: progress and challenges

It may state two separate claims as one.

Advances in MRI, serological and genetic tests have greatly helped in distinguishing MS from conditions that mimic it, but misdiagnosis can occur.

“Advances in MRI, serological and genetic tests have greatly helped in distinguishing MS from these conditions, but misdiagnosis can occur.”

• cites [63] Solomon, 2013, Misdiagnosis of multiple sclerosis: frequency, causes, effects, and prevention, Curr Neurol Neurosci Rep sourceNot checked — no full text of the source
• cites [64] Solomon, 2012, “Undiagnosing” multiple sclerosis: the challenge of misdiagnosis in MS, Neurology sourcePartly supported

  The Discussion (page not provided) reports that MS specialists commonly encounter patients they believe were misdiagnosed and that improper interpretation of MRI findings may contribute. It does not establish that advances in MRI, serological, and genetic tests have greatly helped distinguish MS from mimicking conditions. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Probably not a substantial claim. The paper’s conclusions may not depend on it.

PPMS (10-15% of patients) is characterised by an insidious, slowly progressive increase in neurological disability over time, usually without relapses.

“PPMS (10-15% of patients) is characterised by an insidious, slowly progressive increase in neurological disability over time, usually without relapses.2”

• cites [2] Lublin, 2014, Defining the clinical course of multiple sclerosis: the 2013 revisions, Neurology sourcePartly supported

  The KEY CONSENSUS POINTS section on PPMS describes it as a progressive course distinguished by the absence of exacerbations before clinical progression. The sections on disease activity and progression acknowledge that PPMS patients can have relapses and that progression need not be uniform. Our copy does not substantiate the claim that PPMS accounts for 10–15% of patients; searches for that figure found no supporting passage. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

It may state two separate claims as one.

MS must be differentiated from other diseases in which demyelination is a feature, such as NMOSD and ADEM, and from non-demyelinating conditions such as chronic small vessel disease and other inflammatory, granulomatous, infective, metabolic and genetic causes that can mimic MS.

“It is important to differentiate MS not only from other diseases in which demyelination is a feature e.g.neuromyelitis spectrum disorder (NMOSD) and acute disseminated encephalomyelitis (ADEM), but also non-demyelinating conditions such as chronic small vessel disease and other inflammatory, granulomatous, infective, metabolic and genetic causes that can mimic MS.”

• cites [42] Miller, 2008, Differential diagnosis of suspected multiple sclerosis: a consensus approach, Mult Scler sourceSupported

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

Spinal cord MRI is recommended in patients with myelopathy or when MRI brain findings are not diagnostic of MS.

“Spinal cord MRI is recommended in patients with myelopathy or when MRI brain findings are not diagnostic of MS. 12”

• cites [12] Rovira, 2015, Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis-clinical implementation in the diagnostic process, Nat Rev Neurol sourceSupported

Probably not a substantial claim. The paper’s conclusions may not depend on it.

A post-contrast T1-weighted scan is recommended in patients with brain MRI lesions, to assist in diagnosis and differential diagnosis.

“A post-contrast T1-weighted scan is recommended in patients with brain MRI lesions, to assist in diagnosis and differential diagnosis.12”

• cites [12] Rovira, 2015, Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis-clinical implementation in the diagnostic process, Nat Rev Neurol sourceSupported

Probably not a substantial claim. The paper’s conclusions may not depend on it.

In addition to obtaining brain images with an axial orientation, a sagittal T2 FLAIR sequence is recommended for detecting juxtacortical and corpus callosum lesions, which can be helpful in differentiating MS from other disorders.

“In addition to obtaining brain images with an axial orientation, a sagittal T2 fluid-attenuated inversion recovery (FLAIR) sequence is recommended for detecting juxtacortical and corpus callosum lesions, which can be helpful in differentiating MS from other disorders.12,13”

• cites [12] Rovira, 2015, Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis-clinical implementation in the diagnostic process, Nat Rev Neurol sourceSupported
• cites [13] Garg, 2015, The corpus callosum in the diagnosis of multiple sclerosis and other CNS demyelinating and inflammatory diseases, J Neurol Neurosurg Psychiatry sourceNot checked — no full text of the source

It may state two separate claims as one.

The McDonald 2010 criteria are easily applied in a clinical setting and allow for an earlier diagnosis of MS.

“The McDonald 2010 criteria are easily applied in a clinical setting and allow for an earlier diagnosis of MS. 19”

• cites [19] Brownlee, 2015, Earlier and more frequent diagnosis of multiple sclerosis using the McDonald criteria, J Neurol Neurosurg Psychiatry sourcePartly supported

  The paper’s conclusion (page not specified in our copy) says the McDonald criteria allow earlier MS diagnosis in patients with a clinically isolated syndrome, and its results report a shorter mean time to diagnosis with the 2010 criteria. It does not say the criteria are easily applied in a clinical setting; the claim also omits the study’s CIS population qualifier. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

It may state two separate claims as one.

Using the McDonald 2010 criteria a diagnosis of MS can still be made on clinical grounds alone; however, MRI is used to provide evidence for dissemination in time and space, including in patients with CIS.

“Using the McDonald 2010 criteria a diagnosis of MS can still be made on clinical grounds alone; however, MRI is used to provide evidence for dissemination in time and space, including in patients with CIS. 1”

• cites [1] Polman, 2011, Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria, Ann Neurol sourceSupported

Probably not a substantial claim. The paper’s conclusions may not depend on it.

A standardised MRI protocol was recently proposed by the MAGNIMS network to assist in the diagnosis of MS.

“A standardised MRI protocol was recently proposed by the MAGNIMS network to assist in the diagnosis of MS. 12”

• cites [12] Rovira, 2015, Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis-clinical implementation in the diagnostic process, Nat Rev Neurol sourceSupported

It may state two separate claims as one.

A major discovery was the association between NMOSD and serum aquaporin-4 IgG (AQP4-IgG), confirming that NMOSD is a different disease from MS requiring distinct treatments.

“A major discovery was the association between neuromyelitis optica spectrum disorder (NMOSD) and serum aquaporin-4 IgG (AQP4-IgG), confirming that NMOSD is a different disease from MS requiring distinct treatments.4”

• cites [4] Wingerchuk, 2015, International consensus diagnostic criteria for neuromyelitis optica spectrum disorders, Neurology sourceSupported

It may state two separate claims as one.

Dissemination in time requires either asymptomatic gadolinium-enhancing and non-enhancing lesions on the same MRI scan or a new lesion on a follow up scan.

“Dissemination in time requires either asymptomatic gadolinium-enhancing and non-enhancing lesions on the same MRI scan or a new lesion on a follow up scan. 1”

• cites [1] Polman, 2011, Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria, Ann Neurol sourceSupported

It may state two separate claims as one.

MRI criteria were tested and validated in European populations with a high incidence of MS, although recent studies investigating the McDonald 2010 criteria in CIS cohorts in Latin America and Asia have reported a similarly good performance.

“Secondly, MRI criteria were tested and validated in European populations with a high incidence of MS 25 , although recent studies investigating the McDonald 2010 criteria in CIS cohorts in Latin America 26 and Asia 27 have reported a similarly good performance.”

• cites [25] Montalban, 2010, MRI criteria for MS in patients with clinically isolated syndromes, Neurology sourceNot checked — no full text of the source
• cites [26] Patrucco, 2013, Application of the McDonald 2010 criteria for the diagnosis of multiple sclerosis in an Argentinean cohort of patients with clinically isolated syndromes, Mult Scler sourceSupported
• cites [27] Huh, 2014, Evaluation of McDonald MRI criteria for dissemination in space in Korean patients with clinically isolated syndromes, Mult Scler sourceNot checked — no full text of the source

Probably not a substantial claim.

For RRMS, MRI evidence of dissemination in space requires ≥1 T2 lesion in at least two of four sites-periventricular, juxtacortical, and infratentorial regions and the spinal cord-with symptomatic lesions in the brainstem and spinal cord excluded.

“For RRMS, MRI evidence of dissemination in space requires ≥1 T2 lesion in at least two of four sitesperiventricular, juxtacortical, and infratentorial regions and the spinal cord (Figure 1), with symptomatic lesions in the brainstem and spinal cord excluded.1”

• cites [1] Polman, 2011, Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria, Ann Neurol sourceSupported

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

NMOSD shows a strong gender bias (female:male ratio up to 9:1) and a mean age at onset of 39 years, although all age groups can be affected including children and the elderly.

“NMOSD shows a strong gender bias (female:male ratio up to 9:1) and a mean age at onset of 39 years 46 , although all age groups can be affected including children and the elderly.”

• cites [46] Pandit, 2015, Demographic and clinical features of neuromyelitis optica: a review, Mult Scler sourcePartly supported

  The Gender ratio section reports strong female predominance, and the Effect of age section documents both pediatric and late onset. However, “up to 9:1” understates the highest ratios reported, while the mean onset age of 39 years appears in Table 2 for a German cohort, not as an overall NMOSD mean; the review gives a range of means across case series. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

It may state two separate claims as one.

Most patients with NMOSD have a relapsing course with accumulation of disability over time related to poor recovery from individual attacks and a secondary progressive course is rare.

“Most patients with NMOSD have a relapsing course with accumulation of disability over time related to poor recovery from individual attacks and a secondary progressive course is rare.45,47”

• cites [45] Zekeridou, 2015, Aquaporin-4 autoimmunity, Neurol Neuroimmunol Neuroinflamm sourceSupported
• cites [47] Kitley, 2012, Prognostic factors and disease course in aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder from the United Kingdom and Japan, Brain sourceSupported

It may state two separate claims as one.

Younger age, male gender and gadolinium-enhancing, cortical or spinal cord lesions may be associated with an increased risk of developing MS in RIS patients.

“Younger age, male gender and gadolinium-enhancing, cortical or spinal cord lesions may be associated with an increased risk of developing MS.29- 31”

• cites [29] Okuda, 2014, Radiologically isolated syndrome: 5-year risk for an initial clinical event, PLoS One sourcePartly supported

  The Results identify younger age, male sex, and cervical or thoracic spinal cord lesions as predictors of a first clinical event in RIS. However, Table 4 shows no association for juxtacortical lesions, and the Discussion explicitly says baseline contrast enhancement was not predictive. The paper therefore does not support the cortical-lesion and gadolinium-enhancement parts of the claim. (LLM, conf=0.91)

  Experimental — accuracy not yet measured
• cites [30] Lebrun, 2009, Association between clinical conversion to multiple sclerosis in radiologically isolated syndrome and magnetic resonance imaging, cerebrospinal fluid, and visual evoked potential: follow-up of 70 patients, Arch Neurol sourceNot checked — no full text of the source
• cites [31] Giorgio, 2011, Cortical lesions in radiologically isolated syndrome, Neurology sourceNot checked — no full text of the source

It may state two separate claims as one.

MRI findings in ADEM include large (>1-2cm), bilateral white matter lesions and deep grey matter lesions and contrast enhancement.

“MRI findings include large (>1-2cm), bilateral white matter lesions and deep grey matter lesions and contrast enhancement.42”

• cites [42] Miller, 2008, Differential diagnosis of suspected multiple sclerosis: a consensus approach, Mult Scler sourceSupported

Probably not a substantial claim.

At this time it is considered essential that a diagnosis of MS only be made in a patient who has symptoms suggestive of demyelination.

“At this time it is considered essential that a diagnosis of MS only be made in a patient who has symptoms suggestive of demyelination. 2”

• cites [2] Lublin, 2014, Defining the clinical course of multiple sclerosis: the 2013 revisions, Neurology sourceSupported

It may state two separate claims as one.

While some patients presenting with atypical demyelinating lesions have a monophasic course, 30-60% develop MS.

“While some patients presenting with atypical demyelinating lesions have a monophasic course, 30-60% develop MS. 38,40”

• cites [38] Wallner-Blazek, 2013, Atypical idiopathic inflammatory demyelinating lesions: prognostic implications and relation to multiple sclerosis, J Neurol sourcePartly supported

  The Results report that two-thirds or more of most lesion subgroups had no further attack during follow-up, supporting the possibility of a single-attack course. They also report new MS-typical MRI lesions in 29 of 69 patients (42%), but do not say that 30–60% developed a diagnosis of MS. The distinction between new lesions and an MS diagnosis limits support for that part of the claim. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites [40] Lucchinetti, 2008, Clinical and radiographic spectrum of pathologically confirmed tumefactive multiple sclerosis, Brain sourcePartly supported

  The Results (Clinical characteristics of the cohort; page not provided) report that 24% had a monophasic course, supporting the first part of the claim. They report that 70% developed definite multiple sclerosis, not 30–60%; they also note that a monophasic course did not preclude an MS diagnosis. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

NMOSD is approximately 100 times less common than MS in European and North American populations but is relatively more common in Asia and Africa where MS is less common.

“NMOSD is approximately 100 times less common than MS in European and North American populations but is relatively more common in Asia and Africa where MS is less common.46”

• cites [46] Pandit, 2015, Demographic and clinical features of neuromyelitis optica: a review, Mult Scler sourcePartly supported

  The Prevalence section (page unavailable) reports that NMO prevalence varies across geographic and ethnic cohorts, and the Atlas of MS Database section gives figures for European countries, Japan, South Africa, and Southeast Asia. Neither section establishes that NMOSD is approximately 100 times less common than MS in Europe and North America, or that its frequency relative to MS is higher across Asia and Africa. (LLM, conf=0.77)

  Experimental — accuracy not yet measured

It may state two separate claims as one.

MRI might help predict outcome; the presence of typical MS lesions and a closed-ring enhancement pattern have been associated with a higher risk of MS.

“MRI might help predict outcome; the presence of typical MS lesions and a closed-ring enhancement pattern have been associated with a higher risk of MS. 38”

• cites [38] Wallner-Blazek, 2013, Atypical idiopathic inflammatory demyelinating lesions: prognostic implications and relation to multiple sclerosis, J Neurol sourcePartly supported

  The Discussion (page unavailable) links additional MS-typical MRI lesions to a higher likelihood of having or developing MS. The Results and Discussion also report more subsequent attacks among patients with ring-like lesions, but the copy does not establish that a specifically closed-ring enhancement pattern predicts a higher risk of MS. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

It may state two separate claims as one.

An accurate diagnosis of NMOSD is essential since prompt treatment of acute attacks and long-term immunosuppression appear to reduce disability, while conventional MS treatments may aggravate NMOSD.

“An accurate diagnosis of NMOSD is essential since prompt treatment of acute attacks and long-term immunosuppression appear to reduce disability, while conventional MS treatments may aggravate NMOSD.44,48”

• cites [44] Trebst, 2014, Update on the diagnosis and treatment of neuromyelitis optica: recommendations of the Neuromyelitis Optica Study Group (NEMOS), J Neurol sourceSupported
• cites [48] Kimbrough, 2012, Treatment of Neuromyelitis Optica: Review and Recommendations, Mult Scler Relat Disord sourceSupported

It may state two separate claims as one.

The identification of a pathogenic IgG antibody directed against the aquaporin-4 (AQP4-IgG) water channel has established NMOSD as a specific disease entity that needs to be differentiated from MS because of important differences in prognosis and treatment.

“The identification of a pathogenic IgG antibody directed against the aquaporin-4 (AQP4-IgG) water channel has established NMOSD as a specific disease entity that needs to be differentiated from MS because of important differences in prognosis and treatment.44,45”

• cites [44] Trebst, 2014, Update on the diagnosis and treatment of neuromyelitis optica: recommendations of the Neuromyelitis Optica Study Group (NEMOS), J Neurol sourceSupported
• cites [45] Zekeridou, 2015, Aquaporin-4 autoimmunity, Neurol Neuroimmunol Neuroinflamm sourceSupported

It may state two separate claims as one.

The differential diagnosis of MS is broad and many neurologists use the approach of identifying 'red flag' clinical, imaging or other laboratory features that suggest an alternative diagnosis.

“The differential diagnosis of MS is broad and many neurologists use the approach of identifying”

• cites [42] Miller, 2008, Differential diagnosis of suspected multiple sclerosis: a consensus approach, Mult Scler sourcePartly supported

  The Discussion/conclusions says the range of diseases to exclude in MS diagnosis is wide, and Methods > Exclusion of diagnostic alternatives describes clinical, imaging, and laboratory red flags that point away from MS. The paper presents this as a consensus approach, but does not establish that many neurologists use it in practice; no page numbers are available in our copy. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

Probably not a substantial claim. The paper’s conclusions may not depend on it.

A history of autoimmunity including thyroid disease and connective tissue disorders is not uncommon in NMOSD.

“A history of autoimmunity including thyroid disease and connective tissue disorders (e.g.systemic lupus erythematosus, Sjogren's syndrome) is not uncommon.45”

• cites [45] Zekeridou, 2015, Aquaporin-4 autoimmunity, Neurol Neuroimmunol Neuroinflamm sourceSupported

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Diagnostic criteria for NMOSD have recently been updated.

“Diagnostic criteria for NMOSD have recently been updated (Supplementary Panel 2 ).47”

• cites [47] Kitley, 2012, Prognostic factors and disease course in aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder from the United Kingdom and Japan, Brain sourcePartly supported

  The References list revised diagnostic criteria for neuromyelitis optica (NMO) from 2006. But the Discussion says incorporating broader NMO spectrum disorder phenotypes into those criteria still needs debate; it does not report an update to NMOSD diagnostic criteria. Page numbers are unavailable in our copy. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

It may state two separate claims as one.

In a survey of MS specialist neurologists in the United States, 95% of respondents had seen one or more patients in the previous year who had been misdiagnosed with MS, many of whom were being treated inappropriately with disease-modifying therapies.

“In a survey of MS specialist neurologists in the United States, 95% of respondents had seen one or more patients in the previous year who had been misdiagnosed with MS, many of whom were being treated inappropriately with disease-modifying therapies.”

• cites [64] Solomon, 2012, “Undiagnosing” multiple sclerosis: the challenge of misdiagnosis in MS, Neurology sourceSupported

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

Current guidelines recommend spinal cord MRI in patients with symptoms of myelopathy or when brain MRI findings are not diagnostic of MS.

“Current guidelines recommend spinal cord MRI in patients with symptoms of myelopathy or when brain MRI findings are not diagnostic of MS. 12”

• cites [12] Rovira, 2015, Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis-clinical implementation in the diagnostic process, Nat Rev Neurol sourceSupported

It may state two separate claims as one.

MOG-IgG is also found in some patients with ADEM (particularly in children), and in ADEM followed by optic neuritis, and isolated or recurrent optic neuritis.

“MOG-IgG is also found in some patients with ADEM (particularly in children), and in ADEM followed by optic neuritis, and isolated or recurrent optic neuritis.58,59”

• cites [58] Kim, 2015, Antibodies to MOG in adults with inflammatory demyelinating disease of the CNS, Neurol Neuroimmunol Neuroinflamm sourcePartly supported

  The Discussion reports MOG antibodies in pediatric ADEM cohorts and in 1 of 8 adults with clinical features of ADEM. The Results describe both isolated and recurrent optic neuritis in MOG-antibody-positive patients. Neither section establishes the specific sequence of ADEM followed by optic neuritis. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [59] Hacohen, 2015, Myelin oligodendrocyte glycoprotein antibodies are associated with a non-MS course in children, Neurol Neuroimmunol Neuroinflamm sourcePartly supported

  The Results (page unavailable) report MOG antibodies in 4/12 children presenting with ADEM and 12/24 presenting with optic neuritis. The Discussion mentions recurrent optic neuritis as a possible MOG-positive phenotype, but our copy does not document ADEM followed by optic neuritis or establish recurrent optic neuritis among this cohort’s antibody-positive cases. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

Probably not a substantial claim. It may state two separate claims as one.

Although the first attack of NMOSD can mimic CIS, routine testing for AQP4-IgG in CIS populations with a high incidence of MS and low incidence of NMOSD has a very low yield and is not recommended.

“Although the first attack of NMOSD can mimic CIS (e.g.acute unilateral optic neuritis or short-segment partial myelitis 61 ), routine testing for AQP4-IgG in CIS populations with a high incidence of MS and low incidence of NMOSD has a very low yield and is not recommended.62”

• cites [61] Flanagan, 2015, Short myelitis lesions in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorders, JAMA Neurol sourceSupported
• cites [62] Costa, 2012, Value of NMO-IgG determination at the time of presentation as CIS, Neurology sourceNot checked — no full text of the source

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Routine imaging of the whole spinal cord in all patients with suspected MS has recently been proposed.

“Therefore routine imaging of the whole spinal cord in all patients with suspected MS has recently been proposed.68”

• cites [68] Filippi, 2016, MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines, Lancet Neurol sourcePartly supported

  The Methods section (‘Spinal cord imaging’; page unavailable) recommends imaging the entire cord when spinal cord MRI is used to assess dissemination in space. It recommends spinal cord imaging at symptom onset for specified patient groups, however, not routinely for all patients with suspected MS. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

It may state two separate claims as one.

Using the McDonald criteria, MS is being diagnosed significantly earlier than with the use of clinical criteria alone facilitating earlier treatment.

“Using the McDonald criteria, MS is being diagnosed significantly earlier than with the use of clinical criteria alone facilitating earlier treatment.19”

• cites [19] Brownlee, 2015, Earlier and more frequent diagnosis of multiple sclerosis using the McDonald criteria, J Neurol Neurosurg Psychiatry sourcePartly supported

  The results (page unavailable) report significantly earlier MS diagnosis with McDonald criteria than with clinical criteria in patients with clinically isolated syndrome. The discussion says earlier diagnosis allows timely conversations about disease-modifying treatment, but does not establish that treatment began earlier. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

It may state two separate claims as one.

Gadolinium-enhancing lesions provide evidence for dissemination in time and can also assist in differential diagnosis.

“Gadolinium-enhancing lesions provide evidence for dissemination in time and can also assist in differential diagnosis.1,12”

• cites [1] Polman, 2011, Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria, Ann Neurol sourcePartly supported

  In Recommended Modifications to the McDonald Criteria, the paper says that gadolinium-enhancing lesions together with nonenhancing lesions can establish dissemination in time on a single scan, provided the enhancement is not due to non-MS pathology. It discusses differential diagnosis elsewhere, but does not say that gadolinium-enhancing lesions themselves assist in distinguishing MS from other conditions. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [12] Rovira, 2015, Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis-clinical implementation in the diagnostic process, Nat Rev Neurol sourceSupported

It may state two separate claims as one.

The McDonald 2010 criteria do not mandate a CSF examination and there is much variation between neurologists as to how often a lumbar puncture is done in the diagnosis of MS.

“The McDonald 2010 criteria do not mandate a CSF examination and there is much variation between neurologists as to how often a lumbar puncture is done in in the diagnosis of MS. 66”

• cites [66] Hutchinson, 2013, CSF oligoclonal bands are important in the diagnosis of multiple sclerosis, unreasonably downplayed by the McDonald criteria 2010: Commentary, Mult Scler sourceSupported

It may state two separate claims as one.

Attacks of myelitis in NMOSD are associated with longitudinally-extensive spinal cord lesions on MRI (≥3 vertebral bodies) with prominent involvement of the central cord, in contrast to MS where lesions are usually short (<1-2 vertebral bodies) and located peripherally.

“Attacks of myelitis are associated with longitudinally-extensive spinal cord lesions on MRI (≥3 vertebral bodies) with prominent involvement of the central cord 49 (Supplementary Figure 4), in contrast to MS where lesions are usually short (<1-2 vertebral bodies) and located peripherally.”

• cites [49] Kim, 2015, MRI characteristics of neuromyelitis optica spectrum disorder: an international update, Neurology sourcePartly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

It may state two separate claims as one.

Approximately 70% of patients with relapsing NMOSD are AQP4-IgG positive, with the sensitivity increased with the use of cell-based rather than ELISA assays.

“Approximately 70% of patients with relapsing NMOSD are AQP4-IgG positive, with the sensitivity increased with the use of cell-based rather than ELISA assays.53,54”

• cites [53] Waters, 2012, Serologic diagnosis of NMO: a multicenter comparison of aquaporin-4-IgG assays, Neurology sourcePartly supported

  The Abstract reports AQP4-IgG detection in roughly 70% of the combined NMO/NMOSD cohort and higher sensitivity for cell-based assays than for ELISA. The Methods describe some patients with recurrent disease, but the reported percentages are for the combined cohort, not specifically patients with relapsing NMOSD. (LLM, conf=0.87)

  Experimental — accuracy not yet measured
• cites [54] Pittock, 2014, Seroprevalence of aquaporin-4-IgG in a northern California population representative cohort of multiple sclerosis, JAMA Neurol sourceNot checked — no full text of the source

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Current guidelines recommend a post-contrast T1-weighted scan as part of the diagnostic evaluation of patients with suspected MS.

“Current guidelines recommend a post-contrast T1weighted scan as part of the diagnostic evaluation of patients with suspected MS. 12”

• cites [12] Rovira, 2015, Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis-clinical implementation in the diagnostic process, Nat Rev Neurol sourceSupported

It may state two separate claims as one.

Despite the current usefulness of the McDonald criteria, the MAGNIMS network have recently proposed a number of modifications, such as inclusion of optic nerve, cortical and symptomatic lesions in dissemination in space and standardisation of dissemination in space criteria for RRMS, PPMS and RIS.

“Despite the current usefulness of the McDonald criteria, the MAGNIMS network have recently proposed a number of modifications, such as inclusion of optic nerve, cortical and symptomatic lesions in dissemination in space and standardisation of dissemination in space criteria for RRMS, PPMS and RIS.68”

• cites [68] Filippi, 2016, MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines, Lancet Neurol sourceSupported

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

Some of these recommendations are evidence-based and others are based on expert consensus.

“Some of these recommendations are evidence-based 73,74 and others are based on expert consensus.”

• cites [73] Filippi, 2010, Intracortical lesions: relevance for new MRI diagnostic criteria for multiple sclerosis, Neurology sourceNot checked — no full text of the source
• cites [74] Brownlee, 2016, Should the symptomatic region be included in dissemination in space in MRI criteria for MS?, Neurology sourceSupported

It may state two separate claims as one.

Clinical features that suggest demyelination as the cause of a first episode include age <40 years, an acute/subacute onset over hours to days, maximal deficit within 4 weeks of onset and spontaneous remission.

“Clinical features that suggest demyelination as the cause of such an episode include age <40 years, an acute/subacute onset over hours to days, maximal deficit within 4 weeks of onset and spontaneous remission.”

It may state two separate claims as one.

Non-specific antibodies are frequently detected that may not be clinically relevant with low-titre antinuclear antibodies (ANA) particularly prevalent in patients with MS.

“Non-specific antibodies are frequently detected that may not be clinically relevant with low-titre antinuclear antibodies (ANA) particularly prevalent in patients with MS. 17”

• cites [17] Negrotto, 2015, Should we systematically test patients with clinically isolated syndrome for auto-antibodies?, Mult Scler sourceNot checked — no full text of the source

It may state two separate claims as one.

The onset of PPMS is characterised by slowly progressive symptoms, most often an asymmetric paraparesis that evolves over months or years or, less commonly, a progressive hemiparesis or cerebellar ataxia or very rarely, visual failure or dementia.

“The onset of PPMS in contrast is characterised by slowly progressive symptoms, most often an asymmetric paraparesis that evolves over months or years 6 or, less commonly, a progressive hemiparesis or cerebellar ataxia or very rarely, visual failure or dementia.6”

• cites [6] Miller, 2007, Primary-progressive multiple sclerosis, Lancet Neurol sourceNot checked — no full text of the source

It may state two separate claims as one.

Common CIS presentations include acute unilateral optic neuritis, a partial myelitis or a brainstem syndrome.

“Common CIS presentations include acute unilateral optic neuritis, a partial myelitis or a brainstem syndrome.5”

• cites [5] Brownlee, 2014, Clinically isolated syndromes and the relationship to multiple sclerosis, J Clin Neurosci sourceNot checked — no full text of the source

Probably not a substantial claim. The paper may give no reason why it holds.

Progressive worsening over a period of at least 12 months provides evidence of dissemination in time.

“Progressive worsening over a period of at least 12 months provides evidence of dissemination in time.”

It may state two separate claims as one.

The McDonald MRI criteria were developed and tested in CIS patients with symptoms typical of MS and they should not be applied to patients with non-specific neurological symptoms such as paraesthesia, dizziness or headache, in which the diagnosis is much less likely.

“The McDonald MRI criteria were developed and tested in CIS patients with symptoms typical of MS (e.g.unilateral optic neuritis) and they should not be applied to patients with non-specific neurological symptoms such as paraesthesia, dizziness or headache, in which the diagnosis is much less likely.23”

• cites [23] Selchen, 2012, MS, MRI, and the 2010 McDonald criteria: a Canadian expert commentary, Neurology sourceNot checked — no full text of the source

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.

PPMS typically presents at an older age than RRMS (mean age at onset 40 years) and there is no gender bias.

“PPMS typically presents at an older age than RRMS (mean age at onset 40 years) and there is no gender bias.”

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

The widespread use of MRI means incidental findings suggestive of MS are sometimes identified in some people who have no clinical symptoms; this is referred to as a radiologically isolated syndrome (RIS).

“The widespread use of MRI means incidental findings suggestive of MS are sometimes identified in some people who have no clinical symptoms.This is referred to as a radiologically isolated syndrome (RIS).28”

• cites [28] Okuda, 2009, Incidental MRI anomalies suggestive of multiple sclerosis: the radiologically isolated syndrome, Neurology sourceNot checked — no full text of the source

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

Advances in MRI, immunological and genetic tests have improved the diagnosis of other conditions that can be mistaken for MS.

“Advances in MRI, immunological and genetic tests have improved the diagnosis of other conditions that can be mistaken for MS.”

It may state two separate claims as one.

OCBs are found in up to 90% of people with MS (less often in CIS patients) and sometimes in other neuroinflammatory disorders and their presence needs to be interpreted carefully.

“OCBs are found in up to 90% of people with MS (less often in CIS patients) 15 and sometimes in other neuroinflammatory disorders and their presence needs to be interpreted carefully.”

• cites [15] Dobson, 2013, Cerebrospinal fluid oligoclonal bands in multiple sclerosis and clinically isolated syndromes: a meta-analysis of prevalence, prognosis and effect of latitude, J Neurol Neurosurg Psychiatry sourceNot checked — no full text of the source

It may state two separate claims as one.

When a patient presents with symptoms or signs that could indicate MS, an MRI is essential as an abnormal brain MRI is seen in virtually all patients with established MS and over 80% of CIS patients who develop MS.

“When a patient presents with symptoms or signs that could indicate MS, an MRI is essential as an abnormal brain MRI is seen in virtually all patients with established MS 7 and over 80% of CIS patients who develop MS. 8”

• cites [7] Offenbacher, 1993, Assessment of MRI criteria for a diagnosis of MS, Neurology sourceNot checked — no full text of the source
• cites [8] Fisniku, 2008, Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis, Brain sourceNot checked — no full text of the source

It may state two separate claims as one.

Brain T2 lesion load tends to be lower in PPMS and the combination of MRI and CSF findings provides a higher sensitivity than MRI alone.

“Brain T2 lesion load tends to be lower in PPMS 6 and the combination of MRI and CSF findings provides a higher sensitivity than MRI alone.20”

• cites [6] Miller, 2007, Primary-progressive multiple sclerosis, Lancet Neurol sourceNot checked — no full text of the source
• cites [20] Montalban, 2009, Primary progressive multiple sclerosis diagnostic criteria: a reappraisal, Mult Scler sourceNot checked — no full text of the source

It may state two separate claims as one.

Spinal cord lesions occur in 80-90% of patients with established MS and up to half of patients with CIS, most often in the cervical cord.

“Spinal cord lesions occur in 80-90% of patients with established MS and up to half of patients with CIS, most often in the cervical cord.10,11”

• cites [10] Sombekke, 2013, Spinal cord lesions in patients with clinically isolated syndrome: a powerful tool in diagnosis and prognosis, Neurology sourceNot checked — no full text of the source
• cites [11] Bot, 2002, Differentiation of multiple sclerosis from other inflammatory disorders and cerebrovascular disease: value of spinal MR imaging, Radiology sourceNot checked — no full text of the source

It may state two separate claims as one.

MRI is helpful in excluding other pathologies, for example, a compressive lesion in a patient with a progressive myelopathy, or identifying abnormalities that suggest an alternative diagnosis.

“MRI is also helpful in excluding other pathologies, for example, a compressive lesion in a patient with a progressive myelopathy, or identifying abnormalities that suggest an alternative diagnosis (e.g.leptomeningeal enhancement, longitudinally-extensive spinal cord lesion).”

It may state two separate claims as one.

CSF findings in MS include a normal or mildly raised white cell count (<25 cells/cm3, predominantly lymphocytes) and protein (usually <1g/L), a raised IgG index and IgG oligoclonal bands (OCBs) not present in serum.

“CSF findings in MS include a normal or mildly raised white cell count (<25 cells/cm 3 , predominantly lymphocytes) and protein (usually <1g/L), a raised IgG index and IgG oligoclonal bands (OCBs) not present in serum.14”

• cites [14] Freedman, 2005, Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple sclerosis: a consensus statement, Arch Neurol sourceNot checked — no full text of the source

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

The initial presentation of MS is varied and depends both on the location of lesions within the CNS and their onset (relapsing or progressive).

“The initial presentation of MS is varied and depends both on the location of lesions within the CNS and their onset (relapsing or progressive).”

It may state two separate claims as one.

A prolonged latency and well-preserved waveform on evoked potential testing is suggestive of demyelination but is not specific.

“A prolonged latency and well-preserved waveform on evoked potential testing is suggestive of demyelination but is not specific.16”

• cites [16] Leocani, 2014, Clinical neurophysiology of multiple sclerosis, Handb Clin Neurol sourceNot checked — no full text of the source

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

In most patients with a typical clinical picture and MRI findings, CSF examination is usually not necessary, but can provide supportive evidence of MS.

“In most patients with a typical clinical picture and MRI findings a Cerebrospinal fluid (CSF) examination is usually not necessary, but can provide supportive evidence of MS.”

Probably not a substantial claim. It may state two separate claims as one.

Patients with RIS are at significant risk for developing MS and should be counselled and offered follow up as appropriate.

“However, patients with RIS are at significant risk for developing MS and should be counselled and offered follow up as appropriate.”

It may state two separate claims as one.

Brain lesions in MS are typically small (<1cm diameter) and ovoid with a homogenous signal on T2-weighted sequences.

“Brain lesions in MS are typically small (<1cm diameter) and ovoid with a homogenous signal on T2-weighted sequences.9”

• cites [9] Fazekas, 1999, The contribution of magnetic resonance imaging to the diagnosis of multiple sclerosis, Neurology sourceNot checked — no full text of the source

It may state two separate claims as one.

In younger children (<12 years) MS may present differently from adolescents and adults; encephalopathy, multifocal neurological deficits (often with prominent brainstem/cerebellar involvement) and seizures are more common.

“In younger children (<12 years) MS may present differently from adolescents and adults; encephalopathy, multifocal neurological deficits (often with prominent brainstem/cerebellar involvement) and seizures are more common.32”

• cites [32] Krupp, 2013, International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions, Mult Scler sourceNot checked — no full text of the source

It may state two separate claims as one.

ADEM is almost always monophasic; however, an encephalopathic ADEM-like illness can sometimes be the first presentation of MS in both children and adults and diagnostic criteria for ADEM remain imperfect.

“ADEM is almost always monophasic; however, an encephalopathic ADEM-like illness can sometimes be the first presentation of MS in both children 32,34 and adults 43 and diagnostic criteria for ADEM remain imperfect.”

• cites [32] Krupp, 2013, International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions, Mult Scler sourceNot checked — no full text of the source
• cites [34] Peche, 2013, A long-term follow-up study using IPMSSG criteria in children with CNS demyelination, Pediatr Neurol sourceNot checked — no full text of the source
• cites [43] Schwarz, 2001, Acute disseminated encephalomyelitis: a follow-up study of 40 adult patients, Neurology sourceNot checked — no full text of the source

It may state two separate claims as one.

In older adults with MS, males are over-represented and a progressive onset is more common.

“In this age group males are over-represented and a progressive onset is more common.”

It may state two separate claims as one.

In older adults, a stringent interpretation of brain MRI criteria for MS is mandatory and spinal cord MRI is helpful since spinal cord lesions do not occur with healthy aging.

“In this situation a stringent interpretation of brain MRI criteria for MS is mandatory and spinal cord MRI is helpful since spinal cord lesions do not occur with healthy aging.11”

• cites [11] Bot, 2002, Differentiation of multiple sclerosis from other inflammatory disorders and cerebrovascular disease: value of spinal MR imaging, Radiology sourceNot checked — no full text of the source

It may state two separate claims as one.

There are no accepted diagnostic criteria for RIS, but the Okuda 2009 criteria exist.

“There are no accepted diagnostic criteria for RIS, but the Okuda 2009 criteria 28”

• cites [28] Okuda, 2009, Incidental MRI anomalies suggestive of multiple sclerosis: the radiologically isolated syndrome, Neurology sourceNot checked — no full text of the source

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.

A CSF examination looking for OCBs can also be particularly helpful in older adults, as may visual evoked potentials.

“A CSF examination looking for OCBs can also be particularly helpful in older adults, as may visual evoked potentials.”

It may state two separate claims as one.

Up to 5% of people with MS develop their first symptoms in childhood, almost always RRMS.

“Up to 5% of people with MS develop their first symptoms in childhood, almost always RRMS. 32”

• cites [32] Krupp, 2013, International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions, Mult Scler sourceNot checked — no full text of the source

It may state two separate claims as one.

The performance of the McDonald 2010 criteria has been tested in children with CIS and the criteria have a similar sensitivity/specificity for the development of MS as in adult populations but should not be applied in the setting of encephalopathy (i.e. ADEM).

“The performance of the McDonald 2010 criteria has been tested in children with CIS and the criteria have a similar sensitivity/specificity for the development of MS as in adult populations 35 but should not be applied in the setting of encephalopathy (i.e.ADEM).32”

• cites [35] Sadaka, 2012, 2010 McDonald criteria for diagnosing pediatric multiple sclerosis, Ann Neurol sourceNot checked — no full text of the source
• cites [32] Krupp, 2013, International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions, Mult Scler sourceNot checked — no full text of the source

Probably not a substantial claim. It may state two separate claims as one.

Studies investigating MRI criteria for a diagnosis of MS have typically excluded patients older than 50 years and the McDonald criteria have not been investigated in this group.

“Studies investigating MRI criteria for a diagnosis of MS have typically excluded patients older than 50 years and the McDonald criteria have not been investigated in this group.”

It may state two separate claims as one.

The clinical, imaging and laboratory features of ADEM and MS overlap and diagnostic criteria emphasise the requirement of encephalopathy in making the diagnosis of ADEM.

“The clinical, imaging and laboratory features of ADEM and MS overlap and diagnostic criteria emphasise the requirement of encephalopathy (altered level of consciousness, behavioural or cognitive change) in making the diagnosis of ADEM (Supplementary Panel 1).32”

• cites [32] Krupp, 2013, International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions, Mult Scler sourceNot checked — no full text of the source

It may state two separate claims as one.

ADEM is an inflammatory demyelinating disorder of the CNS distinct from MS that occurs mainly in childhood and is rare in adults.

“ADEM is an inflammatory demyelinating disorder of the CNS distinct from MS that occurs mainly in childhood and is rare in adults.”

It may state two separate claims as one.

CSF findings in ADEM include a lymphocytic pleocytosis and raised protein.

“CSF findings include a lymphocytic pleocytosis and raised protein.”

It may state two separate claims as one.

Atypical demyelinating lesions may have the appearance of a neoplasm or infection, sometimes necessitating brain biopsy.

“These lesions may have the appearance of a neoplasm (glioma, primary CNS lymphoma) or infection (brain abscess, progressive multifocal leukoencephalopathy), sometimes necessitating brain biopsy.”

It may state two separate claims as one.

Conventional brain MRI findings around the time of diagnosis are only modestly predictive of long-term disability and there is uncertainty as to the extent to which criteria for diagnosis and treatment should be linked.

“Conventional brain MRI findings around the time of diagnosis are only modestly predictive of long-term disability 8 and there is uncertainty as to the extent to which criteria for diagnosis and treatment should be linked.”

• cites [8] Fisniku, 2008, Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis, Brain sourceNot checked — no full text of the source

It may state two separate claims as one.

Compared with MS, optic neuritis in NMOSD is more likely to be bilateral (either simultaneous or rapidly sequential) and associated with poor visual recovery.

“Compared with MS, optic neuritis in NMOSD is more likely to be bilateral (either simultaneous or rapidly sequential) and associated with poor visual recovery.”

It may state two separate claims as one.

OCBs may provide additional prognostic information and may increase diagnostic confidence, especially when considering long-term disease-modifying treatment.

“However, OCBs may provide additional prognostic information 15 and may increase diagnostic confidence, especially when considering long-term disease-modifying treatment.”

• cites [15] Dobson, 2013, Cerebrospinal fluid oligoclonal bands in multiple sclerosis and clinically isolated syndromes: a meta-analysis of prevalence, prognosis and effect of latitude, J Neurol Neurosurg Psychiatry sourceNot checked — no full text of the source

Probably not a substantial claim.

MRI criteria for MS require a balance between sensitivity (diagnosing MS at an early stage) and specificity (making an accurate diagnosis).

“MRI criteria for MS require a balance between sensitivity (diagnosing MS at an early stage) and specificity (making an accurate diagnosis).”

It may state two separate claims as one.

CSF in NMOSD occasionally shows features distinct from MS (white cell count >50 cells/cm3, neutrophils or eosinophils >5 cells/cm3); however, a mild CSF pleocytosis is more common (white cell count <25 cells/cm3).

“CSF occasionally shows features distinct from MS (white cell count >50 cells/cm 3 , neutrophils or eosinophils >5 cells/cm 3 ); however, a mild CSF pleocytosis is more common (white cell count <25 cells/cm 3 ).52”

• cites [52] Jarius, 2011, Cerebrospinal fluid findings in aquaporin-4 antibody positive neuromyelitis optica: results from 211 lumbar punctures, J Neurol Sci sourceNot checked — no full text of the source

It may state two separate claims as one.

The sensitivity of OCBs is <100% and may be significantly lower in people with a first demyelinating event, the time when a lumbar puncture is most likely to be performed.

“As noted previously the sensitivity of OCBs is <100% and may be significantly lower in people with a first demyelinating event 15 , the time when a lumbar puncture is most likely to be performed.”

• cites [15] Dobson, 2013, Cerebrospinal fluid oligoclonal bands in multiple sclerosis and clinically isolated syndromes: a meta-analysis of prevalence, prognosis and effect of latitude, J Neurol Neurosurg Psychiatry sourceNot checked — no full text of the source

It may state two separate claims as one.

Spinal cord lesions can be very helpful in making a diagnosis of MS (cord lesions do not occur with healthy aging or cerebrovascular disease and provide additional evidence of dissemination in space) and may provide important prognostic information.

“However, spinal cord lesions can be very helpful in making a diagnosis of MS (cord lesions do not occur with healthy aging or cerebrovascular disease 11 and provide additional evidence of dissemination in space 10 ) and may provide important prognostic information.67”

• cites [11] Bot, 2002, Differentiation of multiple sclerosis from other inflammatory disorders and cerebrovascular disease: value of spinal MR imaging, Radiology sourceNot checked — no full text of the source
• cites [10] Sombekke, 2013, Spinal cord lesions in patients with clinically isolated syndrome: a powerful tool in diagnosis and prognosis, Neurology sourceNot checked — no full text of the source
• cites [67] Swanton, 2009, Early MRI in optic neuritis: The risk for disability, Neurology sourceNot checked — no full text of the source

Probably not a substantial claim. The paper’s conclusions may not depend on it.

The criteria are intended to provide diagnostic rather than prognostic information.

“However, the criteria are intended to provide diagnostic rather than prognostic information.”

It may state two separate claims as one.

A recently identified subgroup of AQP4-IgG seronegative NMOSD patients have antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) and may have a more favourable course.

“A recently identified subgroup of AQP4-IgG seronegative NMOSD patients have antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) 56 and may have a more favourable course.50,57”

• cites [56] Kitley, 2012, Myelin-oligodendrocyte glycoprotein antibodies in adults with a neuromyelitis optica phenotype, Neurology sourceNot checked — no full text of the source
• cites [50] Ramanathan, 2016, Radiological differentiation of optic neuritis with myelin oligodendrocyte glycoprotein antibodies, aquaporin-4 antibodies, and multiple sclerosis, Mult Scler sourceNot checked — no full text of the source
• cites [57] Kitley, 2014, Neuromyelitis optica spectrum disorders with aquaporin-4 and myelin-oligodendrocyte glycoprotein antibodies: a comparative study, JAMA Neurol sourceNot checked — no full text of the source

Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

The optimal balance of sensitivity and specificity using MRI criteria is uncertain.

“The optimal balance of sensitivity and specificity using MRI criteria is uncertain.”

It may state two separate claims as one.

These disorders usually present quite differently to MS and reasons for misdiagnosis included misinterpretation of clinical findings (symptoms not typical of demyelination, absence of objective neurological signs) and inappropriate application of MRI criteria.

“These disorders usually present quite differently to MS and reasons for misdiagnosis included misinterpretation of clinical findings (symptoms not typical of demyelination, absence of objective neurological signs) and inappropriate application of MRI criteria.63”

• cites [63] Solomon, 2013, Misdiagnosis of multiple sclerosis: frequency, causes, effects, and prevention, Curr Neurol Neurosci Rep sourceNot checked — no full text of the source

It may state two separate claims as one.

AQP4-IgG is highly specific for NMOSD, although false positives occur in up to 0.5% of MS patients using ELISA assays, potentially resulting in misdiagnosis.

“AQP4-IgG is highly specific for NMOSD, although false positives occur in up to 0.5% of MS patients using ELISA assays, potentially resulting in misdiagnosis.54,55”

• cites [54] Pittock, 2014, Seroprevalence of aquaporin-4-IgG in a northern California population representative cohort of multiple sclerosis, JAMA Neurol sourceNot checked — no full text of the source
• cites [55] Kister, 2015, Pushing the boundaries of neuromyelitis optica: does antibody make the disease?, Neurology sourceNot checked — no full text of the source

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Additional articles were sought from the reference lists of relevant articles.

“Additional articles were also sought from the reference lists of relevant articles.”

Probably not a substantial claim. The paper may give no reason why it holds.

Further supportive information from CSF and/or evoked potentials can be obtained if diagnostic uncertainty remains.

“Further supportive information from CSF and/or evoked potentials can be obtained if diagnostic uncertainty remains.”

It may state two separate claims as one.

Current diagnostic criteria for MS integrate clinical and MRI findings and enable an earlier and more reliable diagnosis of MS than with clinical findings alone, potentially facilitating earlier treatment.

“Current diagnostic criteria for MS integrate clinical and MRI findings and enable an earlier and more reliable diagnosis of MS than with clinical findings alone, potentially facilitating earlier treatment.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Where appropriate, review articles were referenced to provide more detailed information on individual topics.

“Where appropriate review articles have been referenced to provide more detailed information on individual topics.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

The review searched MEDLINE (01 January 1995 -15 May 2016) using the search terms "multiple sclerosis", "neuromyelitis optica", "acute disseminated encephalomyelitis", "diagnosis", "diagnostic criteria" and "differential diagnosis" for articles published in the English language.

“We searched MEDLINE (01 January 1995 -15 May 2016) using the search terms “multiple sclerosis”, “neuromyelitis optica”, “acute disseminated encephalomyelitis, “diagnosis”, “diagnostic criteria” and “differential diagnosis” for articles published in the English language.”

Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds. It may state two separate claims as one.

The criteria are best applied in an individual patient when there are typical symptoms and signs of MS and when relevant differential diagnoses have been excluded.

“The criteria are best applied in an individual patient when there are typical symptoms and signs of MS and when relevant differential diagnoses have been excluded.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Priority was given to new studies published in the last 5 years.

“Priority was given to new studies published in the last 5 years.”