Paraneoplastic Autonomic Neuropathy Research Articles

Orthostatic Hypotension and Concomitant Paraneoplastic Syndromes: A Case Report

This case study discusses the incidence of a paraneoplastic autonomic neuropathy in an elderly male who had an otherwise negative work-up for their aetiology of orthostatic hypotension. This case illustrates the importance of trying to correctly identify the aetiology of orthostatic hypotension, which is often overlooked, and frequently diagnosed as idiopathic. Orthostatic hypotension is most prevalent in elderly populations and can be debilitating, leading to a higher incidence of falls and trauma. Thus, it is important to obtain further work-up when traditional treatments are ineffective. In patients with new and insidious onset of orthostatic hypotension, previous history of malignancy, and possible symptoms consistent with ongoing malignancy, it is imperative to consider paraneoplastic autonomic neuropathy as a potential cause of orthostatic hypotension.

Hypotension as a symptom of autonomic neuropathy in patients with advanced malignancies.

Hypotension can be a symptom of paraneoplastic autonomic neuropathy (PAN). Onconeural antibodies (OA) provide strong evidence for the paraneoplastic origin of neurological syndromes. Our goal was to assess the frequency of PAN among patients with advanced malignancies and hypotension using OA. Patients with advanced malignancies and hypotension were screened and enrolled as per protocol. Plasma levels of six classical OAs were assessed in these patients. We prospectively evaluated other symptoms of PAN in these patients. 31 patients out of 740 screened met the criteria of this cross-sectional study. OAs were present in 4 patients (12.9%). Anti-amphiphysin was found in 1 patient (3.23%), anti- CV2 (anti-CRPM5, anti- collapsin- response mediator protein) was present in 1 patient (3.23%), 1 patient (3.23%) was positive for anti-Hu and anti-Ma2 was present in 1 patient (3.23%). No patient was positive for 2 or more OAs. Normalization of blood pressure in concordance with partial remission occurred in 5 patients. The most used criteria for PAN were fulfilled in 9 patients. The frequency of PAN may be underestimated in a busy oncology clinic. Assessing OAs may aid in the differential diagnosis of hypotension of unknown origin.

Chapter 22 - Autoimmune autonomic disorders

Autoimmune autonomic disorders occur because of an immune response directed against sympathetic, parasympathetic, and enteric ganglia, autonomic nerves, or central autonomic pathways. In general, peripheral autoimmune disorders manifest with either generalized or restricted autonomic failure, whereas central autoimmune disorders manifest primarily with autonomic hyperactivity. Some autonomic disorders are generalized, and others are limited in their anatomic extent, e.g., isolated gastrointestinal dysmotility. Historically, these disorders were poorly recognized, and thought to be neurodegenerative. Over the last 20 years a number of autoantibody biomarkers have been discovered that have enabled the identification of certain patients as having an autoimmune basis for either autonomic failure or hyperactivity. Peripheral autoimmune autonomic disorders include autoimmune autonomic ganglionopathy (AAG), paraneoplastic autonomic neuropathy, and acute autonomic and sensory neuropathy. AAG manifests with acute or subacute onset of generalized or selective autonomic failure. Antibody targeting the α3 subunit of the ganglionic-type nicotinic acetylcholine receptor (α3gAChR) is detected in approximately 50% of cases of AAG. Some other disorders are characterized immunologically by paraneoplastic antibodies with a high positive predictive value for cancer, such as antineuronal nuclear antibody, type 1 (ANNA-1: anti-Hu); others still are seronegative. Recognition of an autoimmune basis for autonomic disorders is important, as their manifestations are disabling, may reflect an underlying neoplasm, and have the potential to improve with a combination of symptomatic and immune therapies.

Suspected Paraneoplastic Autonomic Neuropathy in a Patient with Newly Diagnosed Glioblastoma Multiforme (P3.322)

Suspected Paraneoplastic Autonomic Neuropathy in a Patient with Newly Diagnosed Glioblastoma Multiforme (P3.322)

Orthostatic hypotension secondary to CRMP-5 paraneoplastic autonomic neuropathy

The collapsin response mediator protein 5 (CRMP-5) autoantibody is one of only several paraneoplastic antibodies associated with autonomic neuropathy. Such paraneoplastic neuropathies manifest with a constellation of autonomic abnormalities. We present a unique case of orthostatic hypotension as the sole feature of a CRMP-5 paraneoplastic autonomic neuropathy in a patient with small cell lung cancer. Given the poor prognosis of paraneoplastic autonomic dysfunction, it is important to accurately diagnose the cause of orthostatic hypotension occurring on a background of malignancy.

Paraneoplastic neurological disorders

The article provides an overview on the diagnosis and pathogenesis of paraneoplastic neurological disorders (PNDs), and subsequently the current therapeutic strategies in these patients. PNDs are nervous system dysfunctions in cancer patients, which are not due to a local effect of the tumor or its metastases. Most of these clinically defined syndromes in adults are associated with lung cancer, especially small-cell lung cancer, lymphoma and gynecological tumors. In a part of the PND, an overlapping of different clinical syndromes can be observed. Highly specific autoantibodies directed against onconeuronal antigens led to the current hypothesis of an autoimmune pathophysiology. Whereas the most central nervous PNDs are more T-cell-mediated, limbic encephalitis can be caused by pathogenic receptor autoantibodies. The PND of the neuromuscular junction and paraneoplastic autonomic neuropathy are mainly associated with receptor or ion channel autoantibodies. The childhood opsoclonus–myoclonus syndrome and the PNDs associated with receptor/ion channel autoantibodies often respond to immunosuppressive therapies, plasmapheresis and intravenous immunoglobulins. By contrast, most CNS PNDs associated with defined antineuronal antibodies directed against intracellular antigens only stabilize after tumor treatment.

Autonomic Disorders and the Eye

Autonomic Disorders and the Eye

Autoantibodies to ganglionic acetylcholine receptors in autoimmune autonomic neuropathies.

Idiopathic autonomic neuropathy is a severe, subacute disorder with a presumed autoimmune basis. It is indistinguishable from the subacute autonomic neuropathy that may accompany lung cancer or other tumors. Autoantibodies specific for nicotinic acetylcholine receptors in the autonomic ganglia are potentially pathogenic and may serve as serologic markers of various forms of autoimmune autonomic neuropathy. We tested serum from 157 patients with a variety of types of dysautonomia. Immunoprecipitation assays with iodine-125-labeled epibatidine and solubilized human neuroblastoma acetylcholine receptors were used to detect autoantibodies that bound to or blocked ganglionic receptors. Ganglionic-receptor-binding antibodies were found in 19 of 46 patients with idiopathic or paraneoplastic autonomic neuropathy (41 percent), in 6 of 67 patients with postural tachycardia syndrome, idiopathic gastrointestinal dysmotility, or diabetic autonomic neuropathy (9 percent), and in none of 44 patients with other autonomic disorders. High levels of the binding antibodies correlated with more severe autonomic dysfunction (including the presence of tonic pupils). Levels of these antibodies decreased in patients who had clinical improvement. All seven patients with ganglionic-receptor-blocking antibodies had ganglionic-receptor-binding antibodies and had idiopathic or paraneoplastic autonomic neuropathy. Seropositivity for antibodies that bind to or block ganglionic acetylcholine receptors identifies patients with various forms of autoimmune autonomic neuropathy and distinguishes these disorders from other types of dysautonomia. The positive correlation between high levels of ganglionic-receptor antibodies and the severity of autonomic dysfunction suggests that the antibodies have a pathogenic role in these types of neuropathy.