Paraneoplastic Neurological Syndromes: General Treatment Overview

ArticleinCurrent Treatment Options in Neurology 15(2) · February 2013with27 Reads
DOI: 10.1007/s11940-013-0220-2 · Source: PubMed
Opinion statement: Major recent discoveries have bringing out a revised definition of paraneoplastic neurological syndromes (PNS), bringing out the concept of antibody-mediated neurological disorders, triggered or not by cancer. Classification of these diseases is not based anymore on the clinical pattern or an underlying tumor, but on the location of the targeted antigens. Indeed, evolution, response to treatment, and pathophysiology are radically different according to the associated antibodies. In some patients with newly described antibodies targeting cell-surface antigens, humoral immunity seems to play a direct role and a dramatic improvement is observed with immunomodulator treatments. In these patients, an associated tumor is less frequent. Conversely, patients with antibodies directed against intracellular targets are, in most cases, characterized by a high degree of irreversible neuronal death mediated by cytotoxic T-cells and do not improve after immunomodulator treatments. In these patients, an associated tumor is highly frequent and must be cured as soon as possible. A third group of patients can be identified with anti-GAD65 and anti-Amphiphysin antibodies. In patients with these antibodies, the efficiency of immunomodulator treatments is less clear as well as the type of immune response that could be a mix between humoral and cellular. In this last group, the antigen is intracellular, but patients may improve with immunomodulator treatments and associated tumors are rare. Thus, identification of associated antibodies should be prompt and the treatment guided according the identified antibody. Mainstream of treatment include the quest of a tumor and its cure. Immunotherapy must be promptly initiated, targeting humoral, or cellular immune response, or both, according to the associated antibodies. Furthermore, in some situations such as Lambert-Eaton Myasthenic Syndromes and Stiff-Person Syndromes, symptomatic drugs can be useful to control the symptoms.
    • "Thus, confirming paraneoplastic etiology of neurological syndrome may be helpful in planning the most effective therapeutic strategy. In a significant number of PNS patients, particularly in those with autoimmune response directed against intracellular proteins, the most effective is a therapy of the associated tumor, leading to elimination of the triggering antigen of the immune response and stabilization or even regression of neurological symptoms (de Beukelaar and Sillevis Smitt, 2006; Vedeler et al., 2006; Belousov et al., 2007; Antoine and Camdessanché, 2013; Viaccoz and Honnorat, 2013). Some PNS may need some kind of immunotherapy, that is usually successful in the group of diseases mediated by antibodies towards neuronal surface or ion channel antigens (Graus et al., 2010; Greenlee, 2010; Grisold et al., 2011; Vincent et al., 2011; Graus and Dalmau, 2012). "
    [Show abstract] [Hide abstract] ABSTRACT: This study determined the prevalence of classical onconeural Ab in a series of 2063 consecutive patients that were investigated because of suspicion of PNS as well as evaluated individual onconeural Ab in relationship to the clinical spectrum of associated neurological syndromes and tumor types detected in 70 patients finally diagnosed with PNS. We conclude that detectability of onconeural Ab is low among patients suspected with PNS. Specification of Ab is helpful in defining a neurological syndrome as paraneoplastic as well as in searching of underlying tumor. The success in tumor screening depends on the type of onconeural Ab.
    Full-text · Article · Apr 2013
  • [Show abstract] [Hide abstract] ABSTRACT: Paraneoplastic neurological syndromes (PNS) are a large group of rare, immune-related disorders that result as a complication of cancer without direct invasion of the nervous system by neoplastic cells. The numerous different clinical presentations depend on which component of the nervous system is affected. Antibodies initially directed against cancer cell antigens can inadvertently cross-react with normal neuronal antigens, which can either be intracellular or extracellular. Identification of these autoantibodies has permitted a refinement of the classification of PNS. Once other neurological disorders and metastases have been ruled out, confirmation of the presence of autoantibodies in the cerebrospinal fluid or serum in association with a classical clinical syndrome helps ascertain the diagnosis. Key PNS include: encephalomyelitis, limbic encephalitis, the recently described anti-NMDA receptor encephalitis, subacute cerebellar degeneration, opsoclonus-myoclonus, subacute sensory neuropathy, chronic intestinal pseudo-obstruction, Lambert-Eaton myasthenic syndrome and dermatomyositis, each with a distinct set of clinical manifestations. Diagnosing a PNS can be challenging. Neurologists are usually the first specialists to see these patients because the syndrome often precedes the identification of cancer. Nevertheless, oncologists may encounter patients who develop a PNS while in their care, and not infrequently will consider it in their differential diagnoses of a new or recurrent neurological disorder. Some neurological symptoms may be permanent. While therapy directed to the underlying tumour is considered a central part of management, other treatment modalities exist; however, there are no evidence-based studies to guide treatment decisions. Treatment modalities include immune modulation and immunosuppression, removal of the autoantibodies, and supportive care. This article will present an overview of PNS with a focus on management options.
    Article · Jul 2014
  • [Show abstract] [Hide abstract] ABSTRACT: Amphiphysin antibody causes paraneoplastic stiff-person syndrome but can also result in a variety of neurological manifestations. Here, we investigated the clinical spectrum of 20 patients with non-stiff anti-amphiphysin syndrome and their responses to immunotherapy. The most common neurological manifestation was limbic encephalitis (n = 10), followed by dysautonomia (n = 9), and cerebellar dysfunction (n = 6). Cancer was detected in only seven patients. Intravenous immunoglobulin or steroid treatment was effective in most patients, but three improved only after rituximab treatment. Our study suggests that anti-amphiphysin syndrome can manifest as non-stiff encephalomyelitis and is only partially associated with cancer. Active immunotherapy, including rituximab, would be beneficial.
    Article · Sep 2014