Movement Disorders in Oncology: From Clinical Features to Biomarkers

Abstract

Background: the study of movement disorders associated with oncological diseases and anticancer treatments highlights the wide range of differential diagnoses that need to be considered. In this context, the role of immune-mediated conditions is increasingly recognized and relevant, as they represent treatable disorders.

Methods: we reappraise the phenomenology, pathophysiology, diagnostic testing, and treatment of movement disorders observed in the context of brain tumors, paraneoplastic conditions, and cancer immunotherapy, such as immune-checkpoint inhibitors (ICIs).

Results: movement disorders secondary to brain tumors are rare and may manifest with both hyper-/hypokinetic conditions. Paraneoplastic movement disorders are caused by antineuronal antibodies targeting intracellular or neuronal surface antigens, with variable prognosis and response to treatment. ICIs promote antitumor response by the inhibition of the immune checkpoints. They are effective treatments for several malignancies, but they may cause movement disorders through an unchecked immune response.

Conclusions: movement disorders due to focal neoplastic brain lesions are rare but should not be missed. Paraneoplastic movement disorders are even rarer, and their clinical-laboratory findings require focused expertise. In addition to their desired effects in cancer treatment, ICIs can induce specific neurological adverse events, sometimes manifesting with movement disorders, which often require a case-by-case, multidisciplinary, approach.

Keywords: autoimmune; immune-checkpoint inhibitors; movement disorders; oncology; paraneoplastic.

Figure 1

Immune-related adverse events of central nervous system associated with immune checkpoint-inhibitors. Figure is derived from observations of Marini et al. [43]. Ir-encephalitis represent 55% of cases, and movement disorders are associated in 1 out of 5 cases. Ataxia is present in 1 out of 4 cases of “Other ir-CNS syndromes”. Movement disorders are rare in other ir-related conditions. MRI, magnetic resonance imaging; CSF, cerebrospinal fluid; Anti-PDE10A Abs, antibodies anti phosphodiesterase 10A; OCBs, oligoclonal bands.

Figure 2

Main antibodies found in association with different paraneoplastic movement disorders, stratified per probability of having an underlying neoplastic condition. High-risk antibodies are associated with 70% probability or more of an underlying cancer. Intermediate risk antibodies with 30–70%, and low-risk antibodies with less than 30% probability of developing cancer, respectively. Each movement disorder is represented within one of three categories, together with most relevant associated antibodies. A huge overlap exists between some of these conditions, and same antibody may be found in association with different movement disorders. OMS, opsoclonus-myoclonus; OMS, opsoclonus-myoclonus ataxia syndrome; PERM, progressive encephalomyelitis with rigidity and myoclonus.