A Tingling Sensation – Multiple Sclerosis Summary, Morning Report May 3, 2022

In Morning Report on Tuesday May 3, 2022, we discussed a case of a new presentation of multiple sclerosis, possible syndromes and patterns of disease, as well as how to differentiate this from other syndromes such as neuromyelitis optica spectrum disorder (NMOSD) and anti-myelin oligodendrocyte glycoprotein (MOG) antibody syndrome.

1. Introduction and MS Syndromes

Multiple sclerosis (MS) is the most common immune-mediated inflammatory demyelinating disease of the central nervous system. Some possible syndromes that can occur with multiple sclerosis are:

  • Optic neuritis (relative afferent pupillary defect on examination)
  • Brainstem syndromes such as internuclear ophthalmoplegia and trigeminal neuralgia
    • Internuclear ophthalmoplegia (INO) leads to an inability to perform lateral gaze as there is a lesion in the medial longitudinal fasciculus
      • Impaired adduction to the ipsilateral side of the lesion, abduction nystagmus contralateral to the side of the lesion
  • Cerebellar syndromes
  • Transverse myelitis

Other features of MS:

  • Lhermitte sign (electric shock sensation down spine)
  • Onset between age 15 and 50 years
  • Uhthoff phenomenon (heat sensitivity)
  • Fatigue

Four disease courses have been identifed:

  • If patient does not meet criteria for MS but has a single attack typical for MS demyelination, then this term is called clinically isolated syndrome. This may represent a first attack but does not meet full McDonald criteria for a diagnosis of MS.
  • Relapsing-remitting –> Unpredictable attacks which can leave patients with disabilities after attack, followed by episodes of remission
  • Primary progressive –> steady increase in disability without attacks
  • Secondary progressive MS –> Initial relapsing-remitting then gradual worsening

2. McDonald Criteria – 2017

Number of clinical attacks (dissemination in time)Number of lesions with objective clinical evidence (space)Additional data needed for diagnosis
>= 2>= 2None
>= 21 (as well previous attack involving a lesion in a specific anatomic lesion based on a clear history)None
>= 21Dissemination in space shown by an additional clinical attack involving a different CNS system or MRI
1>= 2Dissemination in time shown by an additional clinical attack or by MRI or demonstration of CSF-specific oligoclonal bands
11Dissemination in space shown by an additional clinical attack implicating a different CNS site or by MRI   and   Dissemination in time shown by an additional clinical attack or by MRI or demonstration of CSF-specific oligoclonal bands
Adapted from olomon A. J. (2019). Diagnosis, Differential Diagnosis, and Misdiagnosis of Multiple Sclerosis. Continuum (Minneapolis, Minn.)25(3), 611–635. https://doi.org/10.1212/CON.0000000000000728

Part of the diagnosis requires that there isn’t another inflammatory condition or myelopathy to explain the presentation or syndrome.

Dissemination in Space

  • When it comes to assessing dissemination in space with imaging features, there are four areas in the brain where you can see T2-hyperintense MRI lesions. The presence of one MRI T2-hyperintense lesion in two of these regions is required:
    • (1) Periventricular
    • (2) Cortical or juxtacortical
    • (3) Infratentorial brain regions
    • (4) Spinal cord

Dissemination in Time

Other than the history, some features that point to dissemination in time are:

  • Single MRI with enhancing and non-enhancing (by gadolinium) on MRI OR
  • The appearance of a new T2-hyperintense or gadolinium-enhancing lesion on follow-up MRI compared to an initial baseline MRI scan
  • Two or more oligoclonal bands can be used instead of clinical or MRI dissemination in time. (Oligoclonal bands: proteins made of immunoglobulin G antibodies – two ways to check which are protein electrophoresis or isoelectric focusing/silver staining)

3. Features Atypical for Multiple Sclerosis

The differential diagnosis for MS may include neuromyelitis optica spectrum disorder (NMOSD), syndromes associated with myelin oligodendrocyte glycoprotein (MOG) antibody, neurosarcoidosis, and CNS manifestations of rheumatologic diseases and oncologic disease.

There are some features that may point towards another disease entity other than multiple sclerosis. The feature are listed below:

  • Severe or bilateral optic neuritis –> points more towards NMOSD
  • Longitudinally extensive transverse myelitis –> NMOSD, neurosarcoidosis, anti-MOG–associated myelitis, systemic rheumatologic disease, or a paraneoplastic disorder
  • Complete spinal cord lesions or intractable vomiting – NMOSD (whereas partial Brown Sequard, which means hemicord, is more typical for MS)
  • Transverse myelitis with prodromal symptoms or MRI T2 signal abnormality confined to spinal cord gray matter may suggest anti-MOG–associated myelitis
  • Multiple cranial nerves involved –> think about neurosarcoid
  • Transverse myelitis or optic neuritis with high CSF pleocytosis –> consider of infectious or inflammatory disorders other than MS.
  • Systemic symptoms such as joint pain, skin changes, and weight loss might suggest either rheumatologic or paraneoplastic disease

4. Multiple Sclerosis and Associated Disorders

There are certain CNS inflammatory disease syndromes such as neuromyelitis optica spectrum disorder (NMOSD) and anti-myelin oligodendrocyte glycoprotein (MOG) antibody syndrome that can present similarly to MS. Some differences are outlined below:

AttributeMultiple SclerosisAQP4-IgGMOG-IgG
AgeAny (median age at onset in third decade)Any (median age onset in fourth decade)Any (children and young adults)
Female:male sex predominance2:19:11.5:1
EpidemiologyCommon in terms of prevalence. Ethnicity: Caucasians more commonly affectedPrevalence is rare, ethnicity: African-Americans and Afro-Caribbeans more predisposedUnknown prevalence and unknown re: ethnicity predominance
Common manifestationsManifestations can include myelitis, optic neuritis, brainstem, cerebral episodes, myelopathy for progressive multiple sclerosisNMOSD (single/recurrent myelitis, optic neuritis, area postrema syndrome hiccups, nausea, uncontrollable vomiting)Initial episode: optic neuritis, acute disseminated encephalomyelitis (ADEM), NMOSD, myelitis.
Relapse: optic neuritis
Blood biomarker/antibodyNoneAQP4-IgGMOG-IgG
CSFWBC < 50/mm^3 (lymphocytic), can be normal, oligoclonal bands in 85%WBC variable (usually lymphocytic but can be neutrophilic or eosinophilic), oligoclonal bands in 30%WBC variable (lymphocytic), oligoclonal bands < 15%
Brain MRILesions are ovoid, periventricular (Dawson fingers which are e a radiographic feature of demyelination characterized by periventricular demyelinating plaques along medullary veins), juxtacortical/cortical, infratentorial.
Can also be ring/open-ring enhancing
Can be normal or non-specific. If there are lesions: area postrema can be involved (structure in the medulla oblongota and involved in controlling thirst, vomiting, hunger).
Also lesions around the third and fourth ventricles, splenium, corpus callosum, pencil thin ependymal or cloud enhancement.
ADEM-like fluffy white matter, deep gray matter, diffuse/confluent brainstem lesions and involving the peduncles of the cerebellum.
Optic nerveUnilateralBilateralBilateral
Spine MRIMultiple short lesions, periphery of cordSingle spinal cord lesions, 85% longitudinally extensive transverse myelitis Multiple lesions, 75% are longitudinally extensive; conus involved
Acute treatmentIV steroids
(Rarely PLEX)
IV steroids
Often PLEX
IV steroids
Often PLEX
IVIG in kids
MaintenanceVariety of immunomodulatory drugsNone approved Steroid sparing recommended examples include azathioprine, rituximab among othersNone approved None needed if monophasic Steroid sparing-agents if relapsing disease
PrognosisMost can ambulate after 20 years, disability occurs in secondary progressive phaseAccumulation of disability based on attacks Most disability with first attack Persistent seropositivity and higher titer are predictors of relapse
Adapted from Flanagan E. P. (2019). Neuromyelitis Optica Spectrum Disorder and Other Non-Multiple Sclerosis Central Nervous System Inflammatory Diseases. Continuum (Minneapolis, Minn.)25(3), 815–844. https://doi.org/10.1212/CON.0000000000000742

5. References

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