Multiple Sclerosis (MS)

Authors:

Tuba Khan,

Junaid Kalia MD

Introduction

• Multiple Sclerosis (MS) is an immune-mediated demyelinating inflammatory disease of the central nervous system that can cause loss of function and debilitating effects in different neurological systems.

• Other variants include Balo Concentric Sclerosis, Schilder’s disease, and Neuromyelitis Optica.

• Relapsing-remitting course.

• Relapsing-Remitting MS (RRMS)

• Secondary-Progressive MS (SPMS)

• Primary-Progressive MS (PPMS)

Epidemiology

• Less than 5% of patients with MS have this disease.

Predisposing Factors

• Cause is unknown

• Genetic factors may play a role

• Affecting mostly children and adults

Clinical Presentation

History

• Relapses and remissions of symptoms (stated below)

• Symptoms may be preceded by fevers

• Patients may present with severe respiratory/cardiac compromise

• Patients may complain of the following symptoms:
• Numbness or Tingling
• MS Hug (Squeezing sensation around torso)
• Vertigo
• Dizziness
• Stiffness
• Weakness
• Bladder and bowel problems (e.g. Constipation)
• Weakness
• Visual difficulties (blurry vision, eye pain on movement)
• Focus and attention difficulties
• Mood swings including depression
• Walking difficulties
• Fatigue

• The quick onset of symptoms in Marburg’s Variant;
• Seizures
• Inability to talk
• Inability to move
• Severe confusion

Neurological Examination

• Optic neuritis
• Vision loss
• Eye Pain
• Afferent pupillary defect
• Visual field defect

• Lhermitte sign
• Electric shock-like sensation when the neck is flexed/moved

• Internuclear ophthalmoplegia
• Ocular movement disorder is characterized by impaired adduction of the ipsilateral eye along with nystagmus of the abducting eye.

• Heat sensitivity (Uhthoff phenomenon)

• Spasticity

• Cognitive deficits

Diagnosis

• MRI shows demyelination, mass effect, and incomplete/irregular multiple ring enhancements. Rarely small numerous lesions are seen throughout.

• MRI (brain and spine) and blood tests can help rule out other diseases since fulminating MS has similar symptoms to remitting relapsing MS.

• Spinal Tap to examine CSF. It may show an increase in WBC and antibody formation along with oligoclonal bands.

• Biopsy to determine the level of demyelination is done. Axon and myelin destruction with tissue necrosis and presence of macrophages.

• Nerve function test

Figure 1: MRI of a patient with fulminant MS

Figure 2: MRI showing MS lesions

Differential Diagnosis

• Balo’s Concentric Sclerosis

• Acute Disseminated Encephalomyelitis (ADEM)

• Tumefactive MS

Treatment

• There is no treatment for fulminant MS

• Corticosteroids can shorten and reduce the symptoms of remission

• Beta-Interferons can reduce relapsing-remitting episodes of MS.
• Available in the form of powder in vials for mixing, prefilled injections, or pen.
• Interferon-beta 1a is injected once weekly 30 mcg intramuscular.
• Interferon-beta 1b is injected 0.25 mg subcutaneous every other day.

• Plasma exchange in conjunction with high dose glucocorticoids (Approximately IV-MP 1000 mg/day)

• Immunosuppression (monthly mitoxantrone or cyclophosphamide).
• High-dose cyclophosphamide treatment consists of four consecutive days with 50 mg/kg/day, a cumulative absolute dose of 14 g, and ocrelizumab as maintenance therapy.

• Chemotherapy

• Immunoglobulin

Prognosis

• Brain stem involvement or herniation usually lead to death within 1-2 years

• Many of the patients die within weeks or even months

• Rarely remyelination occurs

• Severe disability in those who survive

Further Reading

• Gobbin, F., Marangi, A., Orlandi, R., Richelli, S., Turatti, M., Calabrese, M., ... & Gajofatto, A. (2017). A case of acute fulminant multiple sclerosis treated with alemtuzumab. Multiple sclerosis and related disorders, 17, 9-11.

• Johnson, M. D., Lavin, P., & Whetsell, W. O., Jr (1990). Fulminant monophasic multiple sclerosis, Marburg's type. Journal of neurology, neurosurgery, and psychiatry, 53(10), 918–921. https://doi.org/10.1136/jnnp.53.10.918

Bibliography

• Kimiskidis, V., Sakellari, I., Tsimourtou, V., Kapina, V., Papagiannopoulos, S., Kazis, D., Vlaikidis, N., Anagnostopoulos, A., & Fassas, A. & Fassas, A. (2008). Autologous stem-cell transplantation in malignant multiple sclerosis: a case with a favorable long-term outcome. Multiple Sclerosis (Houndmills, Basingstoke, England), 14(2), 278–283. https://doi.org/10.1177/1352458507082604

• "SSA - POMS: DI 23022.620 - Malignant Multiple Sclerosis - 09/16/2020". secure.ssa.gov. Retrieved 2021-10-26.

• Siddiqui, N., Bell, D. Marburg variant of multiple sclerosis. Reference article, Radiopaedia.org. (accessed on 20 Jan 2022) https://doi.org/10.53347/rID-12276

• Rahmlow, M. R., & Kantarci, O. (2013). Fulminant demyelinating diseases. The Neurohospitalist, 3(2), 81–91. https://doi.org/10.1177/1941874412466873

• Koska V, Förster M, Brouzou K, Hatami M, Arat E, Aytulun A, Albrecht P, Aktas O, Küry P, Meuth SG, and Kremer D (2021) Case Report: Successful Stabilization of Marburg Variant Multiple Sclerosis With Ocrelizumab Following High-Dose Cyclophosphamide Rescue. Front. Neurol. 12:696807. DOI: 10.3389/fneur.2021.696807

• Fontaine, B. (2001). "Les formes frontières de sclérose en plaques" [Borderline forms of multiple sclerosis]. Revue Neurologique (in French). 157 (8–9 Pt 2): 929–34. PMID 11787357.

• Case Report: Successful Stabilization of Marburg Variant Multiple Sclerosis With Ocrelizumab Following High-Dose Cyclophosphamide Rescue. (2021). Frontiers in Neurology. https://doi.org/10.3389/fneur.2021.696807