Multiple Sclerosis (MS)

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.

Primary Category
Multiple Sclerosis
Secondary Category


  • 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.
Acute Fulminating MS is a malignant/aggressive type of MS that is also known as Marburg Multiple Sclerosis
  • It has a rapidly progressive course over a short period of time.
  • Other variants include Balo Concentric Sclerosis, Schilder’s disease, and Neuromyelitis Optica.
  • Relapsing-remitting course.
Other Types of Multiple Sclerosis:
  • Relapsing-Remitting MS (RRMS)
  • Secondary-Progressive MS (SPMS)
  • Primary-Progressive MS (PPMS)


  • 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


Onset between the ages 15 and 50 years
  • 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


  • 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

notion image
Case courtesy of Dr. Mohammad A. ElBeialy, From the case

Figure 2: MRI showing MS lesions

notion image
Courtesy of Intermountain Medical Imaging, Boise, Idaho.

Differential Diagnosis

  • Balo’s Concentric Sclerosis
  • Acute Disseminated Encephalomyelitis (ADEM)
  • Tumefactive MS


  • 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


  • 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.


  • 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.
  • 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.
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Written by

Tuba Khan

    Junaid Kalia MD

    Written by

    Junaid Kalia MD

    Founder NeuroCare.AI, Practicing Neurologist, sub-specialized in the field of Neurocritical Care, Stroke & Epilepsy

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