SARS-CoV-2-Induced Transformation of Multiple Sclerosis into Tumefactive Demyelinating Lesions


Multiple Sclerosis (MS) is an autoimmune disease characterized by demyelination in the central nervous system, leading to various clinical phenotypes and disease progressions. The global incidence of MS stands at a median of 35.9 cases per 100,000 people, with even lower rates in China, where it is considered a rare disease (Walton et al., 2020; Tian et al., 2020).

MS can manifest as relapsing–remitting MS (RRMS), secondary progressive MS (SPMS), primary progressive MS (PPMS), or progressive-relapsing MS (PRMS) (Lublin et al., 2014). Additionally, patients with MS may develop tumefactive demyelinating lesions (TDLs), a rare form of central nervous system demyelination, with an incidence rate of approximately (1 ~ 3)/1,000 in MS (Algahtani et al., 2017).

TDLs, also known as tumefactive inflammatory demyelinating disorder (TID), are associated with autoimmunity and represent a unique challenge in diagnosis and management (Altintas et al., 2012). Recently, there have been reports suggesting a potential link between SARS-CoV-2 infection and the triggering or exacerbation of central nervous system demyelinating diseases, including MS (Fajgenbaum and June, 2020; Bellucci et al., 2021). However, to date, no cases have been documented where MS transforms into TDLs following infection with the SARS-CoV-2 virus.

Case Presentation

In this context, we present a novel case of a female patient with RRMS who experienced the transformation of her condition into TDLs after contracting SARS-CoV-2. The patient’s clinical history and diagnostic journey underscore the intricacies and challenges faced by healthcare professionals in diagnosing and managing TDLs in MS patients during a concurrent SARS-CoV-2 infection.

The patient, previously diagnosed with RRMS, had been managed according to established treatment protocols. However, following a confirmed SARS-CoV-2 infection, she exhibited neurological symptoms that prompted further investigation. Imaging studies revealed the presence of tumefactive demyelinating lesions in the central nervous system, a phenomenon not previously reported in MS patients post-SARS-CoV-2 infection.


This case report sheds light on the intricate relationship between SARS-CoV-2 infection and the exacerbation of multiple sclerosis (MS), leading to the development of tumefactive demyelinating lesions (TDLs). The patient’s journey presents a complex interplay of factors that may contribute to the worsening of MS symptoms, and understanding these mechanisms is crucial for future research and clinical management.

SARS-CoV-2 as an Environmental Trigger:

The patient’s pre-existing MS condition and the subsequent SARS-CoV-2 infection raise intriguing questions about the virus’s role as an environmental trigger for MS exacerbation. The literature supports the idea that the virus can induce a robust immune response, including cytokine storms that may contribute to demyelination.

The observed increase in B cell activity in the patient’s peripheral blood further suggests a potential link between SARS-CoV-2 infection and the autoimmune response in MS. This aligns with existing studies indicating that viruses can indirectly disrupt the blood–brain barrier, allowing inflammatory cells and molecules to enter the central nervous system.

The discussion emphasizes the need for a deeper understanding of the cytokine storm produced after SARS-CoV-2 infection to tailor personalized treatments for demyelinating diseases.

Direct Neuroinvasion by SARS-CoV-2:

The narrative explores the possibility of direct neuroinvasion by SARS-CoV-2 through the olfactory pathway, raising concerns about the virus’s ability to infect neurons and glial cells, including astrocytes and oligodendrocytes. This direct invasion may lead to demyelination and induce neuroinflammation, exacerbating MS symptoms. The discussion underscores the importance of considering both direct viral damage to the myelin sheath and axons and the potential activation of T cells and autoantibodies against neural tissue.

Complex Interaction Between SARS-CoV-2 and MS:

The case report proposes a complex interaction between SARS-CoV-2 infection and MS, where the inflammatory response and factors induced by the virus enhance the demyelination response in the central nervous system. The patient’s clinical progression, with a rapid onset of CNS symptoms following SARS-CoV-2 infection, supports the notion that the virus or its proteins can trigger abnormal immune responses, leading to attacks on the CNS.

The authors suggest that this case provides clinical evidence for further basic research, emphasizing the importance of understanding the intricate relationship between viral infections and autoimmune diseases.

Teriflunomide Treatment Efficacy:

The patient’s treatment with teriflunomide is thoroughly discussed, providing reasons for its selection and the subsequent realization that it failed to control the transformation of TDLs. The discussion refers to a literature review supporting the use of teriflunomide in MS patients infected with SARS-CoV-2 but highlights the limitations observed in this specific case.

The inefficacy of teriflunomide as a disease-modifying treatment for tumefactive multiple sclerosis (TMS) patients prompts a call for vigilant monitoring and consideration of alternative, more targeted medications.

Recommendations for Future Research and Clinical Management:

The authors acknowledge the limitations of the case report, including its rarity and the short follow-up period. The discussion concludes with recommendations for future research, emphasizing the need for more cases and mechanistic studies to comprehensively understand MS patients transitioning to TDLs due to SARS-CoV-2 infection. The case, despite its limitations, serves as a valuable clinical reference, offering suggestions for refining treatment strategies and guiding future investigations into this unique intersection of viral infection and demyelinating diseases.

TABLE 1 – Tumefactive multiple sclerosis (TMS)

Tumefactive multiple sclerosis (TMS) is a rare variant of multiple sclerosis (MS) characterized by a single or multiple large lesions in the central nervous system (CNS) that are larger than 2 cm in diameter. These lesions are typically located in the brain or spinal cord and are associated with surrounding edema, or swelling. The presentation of TMS can be similar to that of a brain tumor, making it a diagnostic challenge.

The exact cause of TMS is unknown, but it is thought to be related to the same autoimmune process that causes MS. In MS, the immune system mistakenly attacks the myelin sheath, a fatty layer that insulates nerve fibers in the CNS. This damage to the myelin sheath can disrupt the transmission of nerve signals, leading to a variety of symptoms. In TMS, the immune attack is more severe and localized, resulting in the development of large, inflamed lesions.

The symptoms of TMS can vary depending on the location of the lesions. Common symptoms include:

  • Vision problems: These may include blurred vision, double vision, or vision loss.
  • Weakness or numbness: This may affect the arms, legs, face, or other parts of the body.
  • Sensory changes: These may include tingling, numbness, or burning sensations.
  • Dizziness or vertigo: These may be due to lesions in the inner ear or brainstem.
  • Headache: This may be caused by increased pressure within the skull due to the lesion.

Diagnosing TMS can be challenging because it can resemble other conditions, such as a brain tumor. Diagnosis typically involves a thorough medical history and physical examination, along with diagnostic imaging studies such as magnetic resonance imaging (MRI). MRI can show the characteristic large, ring-enhancing lesions that are a hallmark of TMS. Cerebrospinal fluid (CSF) analysis may also be helpful to rule out other conditions.

Once TMS is diagnosed, treatment is aimed at controlling the inflammation and preventing further damage to the CNS. Corticosteroids are often used initially to reduce the inflammation. In some cases, other immunosuppressive medications may be prescribed.

The prognosis for TMS is generally good, with most patients experiencing a full recovery. However, some patients may have residual symptoms, such as numbness or weakness. Relapses are also more common in patients with TMS than in those with other forms of MS.

Here are some additional things to keep in mind about TMS:

  • TMS is typically seen in younger adults, with a peak incidence in the 20s and 30s.
  • There is no one-size-fits-all treatment for TMS, and the specific treatment plan will vary depending on the individual patient’s symptoms and overall health.
  • It is important to follow up with your doctor regularly to monitor your progress and make any necessary adjustments to your treatment plan.

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