Paraneoplastic neurological syndromes

Abstract

Paraneoplastic neurological syndromes (PNS) can be defined as remote effects of cancer that are not caused by the tumor and its metastasis, or by infection, ischemia or metabolic disruptions. PNS are rare, affecting less than 1/10,000 patients with cancer. Only the Lambert-Eaton myasthenic syndrome is relatively frequent, occurring in about 1% of patients with small cell lung cancer. PNS can affect any part of the central and peripheral nervous system, the neuromuscular junction, and muscle. They can be isolated or occur in association. In most patients, the neurological disorder develops before the cancer becomes clinically overt and the patient is referred to the neurologist who has the charge of identifying a neurological disorder as paraneoplastic. PNS are usually severely disabling. The most common PNS are Lambert-Eaton myasthenic syndrome (LEMS), subacute cerebellar ataxia, limbic encephalitis (LE), opsoclonus-myoclonus (OM), retinopathies (cancerassociated retinopathy (CAR) and melanoma-associated retinopathy (MAR), Stiff-Person syndrome (SPS), chronic gastrointestinal pseudoobstruction (CGP), sensory neuronopathy (SSN), encephalomyelitis (EM) and dermatomyositis. PNS are caused by autoimmune processes triggered by the cancer and directed against antigens common to both the cancer and the nervous system, designated as onconeural antigens. Due to their high specificity (> 90%), the best way to diagnose a neurological disorder as paraneoplastic is to identify one of the well-characterized antionconeural protein antibodies in the patient's serum. In addition, as these antibodies are associated with a restricted range of cancers, they can guide the search for the underlying tumor at a stage when it is frequently not clinically overt. This is a critical point as, to date, the best way to stabilize PNS is to treat the cancer as soon as possible. Unfortunately, about one-third of patients do not have detectable antibodies and 5% to 10% have an atypical antibody that is not well-characterized. As PNS are believed to be immune-mediated, suppression of the immune response represents another treatment approach. Disease name Paraneoplastic neurological syndromes (PNS) Definition and diagnostic criteriaParaneoplastic neurological syndromes (PNS) can be defined as remote effects of cancer that are not caused by the tumor and its metastasis, or by infection, ischemia or metabolic disruptions [1,2]. In most patients, the neurological disorder develops before the cancer becomes clinically overt and the patient is referred to neurologist who has the charge of identifying a neurological disorder as paraneoplastic.

CRMP5 (Collapsin Response Mediator Protein 5) Regulates Dendritic Development and Synaptic Plasticity in the Cerebellar Purkinje Cells

“…Like other types of CRMP family proteins, CRMP5 is expressed throughout the nervous system (Wang and Strittmatter, 1996;Fukada et al, 2000). Interestingly, anti-CRMP5 antibody is often detected in serum of patients with subacute cerebellar ataxia, and has been recognized as one of the main antibodies associated with paraneoplastic syndromes (Yu et al, 2001;Cross et al, 2003;Pittock et al, 2004;Honnorat and Antoine, 2007). However, the in vivo roles of CRMP5 remain unknown.…”

Anti-Collapsing Response-Mediating Protein-5 Antibody–Positive Paraneoplastic Perioptic Neuritis without Typical Neurological Symptoms

“…6,13,14 CRMP-5 is expressed in the optic nerve, neurons of the central and peripheral nervous systems, oligodendrocytes, and the cytoplasm of SCLC cells. 5,6,10,11,[13][14][15] It has been suggested that autoantibodies generated against the neoplastic CRMP-5 react as a host immune response to normal tissues, resulting in various neuronal disorders.- 6,10,16 In our case, bilateral meningeal enhancement of the optic nerve was evident on MRI, indicating that the main pathogenesis of the optic neuropathy was bilateral perioptic neuritis due to the involvement of oligodendrocytes around the optic nerve. This cause is consistent with preserved central visual acuity, prominent disc swelling, and prompt disappearance of disc swelling in response to the cancer treatment.…”

“…1,2 Most PON patients exhibit many neurological symptoms, including ophthalmoplegia, cerebellar ataxia, seizures, dementia, and various sensory and/ or motor abnormalities. 1,[3][4][5] The various neurological symptoms are believed to be caused by an antitumour immune response 3,6 associated with an increased level of autoantibodies against collapsing response-mediating protein-5 (CRMP-5), 4,5,[7][8][9] which is expressed in the optic nerve, neurons of the central and peripheral nervous systems, oligodendrocytes, the cytoplasm of small cell lung carcinoma (SCLC) cells, or thymomas.- 5,6,[9][10][11] Only a few studies have reported anti-CRMP-5 antibody-positive PON cases that presented with optic neuropathy as the only clinical symptom. Magnetic resonance imaging (MRI) of these cases has been reported as normal, 8,12 or involving unilateral optic nerve involvement.…”

Clinical Profile and Differential Diagnosis of Classical Paraneoplastic Neurologic Syndromes in Lymphomas

“…Все ПНС разделены на классические и неклассические. Классические ПНС (паранеопластическая моз-жечковая дегенерация, лимбический энцефа-лит, дерматомиозит, полинейропатии, синдром опсоклонус-миоклонус, миастенический синдром Ламберта-Итона, хроническая гастроинтести-нальная псевдообструкция), как правило, ассо-циированы со злокачественными новообразова-ниями, тогда как крайне редкие неклассические (паранеопластическая хорея, синдром «ригидного человека») выявляются и при других заболеваниях [2][3][4].…”