Toxicities of immunosuppressive treatment of autoimmune neurologic diseases

Abstract

In parallel to our better understanding of the role of the immune system in neurologic diseases, there has been an increased availability in therapeutic options for autoimmune neurologic diseases such as multiple sclerosis, myasthenia gravis, polyneuropathies, central nervous system vasculitides and neurosarcoidosis. In many cases, the purported benefits of this class of therapy are anecdotal and not the result of good controlled clinical trials. Nonetheless, their potential efficacy is better known than their adverse event profile. A rationale therapeutic decision by the clinician will depend on a comprehensive understanding of the ratio between efficacy and toxicity. In this review, we outline the most commonly used immune suppressive medications in neurologic disease: cytotoxic chemotherapy, nucleoside analogues, calcineurin inhibitors, monoclonal antibodies and miscellaneous immune suppressants. A discussion of their mechanisms of action and related toxicity is highlighted, with the goal that the reader will be able to recognize the most commonly associated toxicities and identify strategies to prevent and manage problems that are expected to arise with their use.

Keywords: Immunosuppressive therapy; auto-immune neurologic disease.; toxicity.

Fig. (1)

A 54 year old woman with auto-immune hepatitis on treatment with azathioprine for five years who presented with sub-acute neurologic symptoms of right facial drooping and loss of vision in the right eye. MRI revealed a ring-enhancing pontine lesion. Pathological examination proved this to be large B-cell primary central nervous system lymphoma (PCNSL). The imaging characteristics of the tumor were that of a ring-enhancing mass typical of PCNSL found in HIV patients.

Fig. (2)

A 25 year old man with a diagnosis of MS had sudden change in neurologic status after discontinuation of natalizumab. He had been on therapy for two years with good response but natalizumab was discontinued due to concerns of increased risk for PML. He switched to glatiramer acetate but after three months from discontinuation of natalizumab, he had acute symptoms of ataxia and fatigue. MRI revealed multiple new T2/FLAIR hyperintensities and T1 enhancing lesions. He was treated with a 5 day course of methylprednisolone and his symptoms promptly resolved (case report and MRI courtesy of Ann Cabot, D.O.).