Paraneoplastic Myeloneuropathies: Clinical, Oncologic, and Serologic Accompaniments.

OBJECTIVE: To test the hypothesis that myeloneuropathy is a presenting phenotype of paraneoplastic neurologic syndromes we retrospectively reviewed clinical, radiologic, and serologic features of 32 patients with concomitant paraneoplastic spinal cord and peripheral nervous system involvement. METHODS: Observational study investigating patients with myeloneuropathy and underlying cancer or onconeural antibody seropositivity. RESULTS: Among 32 patients with paraneoplastic myeloneuropathy, 20 (63%) were women with median age 61 years (range 27-84 years). Twenty-six patients (81%) had classified onconeural antibodies (amphiphysin, n = 8; antineuronal nuclear antibody [ANNA] type 1 [anti-Hu], n = 5; collapsin response mediator protein 5 [CRMP5] [anti-CV2], n = 6; Purkinje cell cytoplasmic antibody type 1 [PCA1] [anti-Yo], n = 1; Purkinje cell cytoplasmic antibody type 2 [PCA2], n = 2; kelch-like protein 11 [KLHL11], n = 1; and combinations thereof: ANNA1/CRMP5, n = 1; ANNA1/amphiphysin, n = 1; ANNA3/CRMP5, n = 1). Cancer was confirmed in 25 cases (onconeural antibodies, n = 19; unclassified antibodies, n = 3; no antibodies, n = 3). Paraneoplastic myeloneuropathies had asymmetric paresthesias (84%), neuropathic pain (78%), subacute onset (72%), sensory ataxia (69%), bladder dysfunction (69%), and unintentional weight loss >15 pounds (63%). Neurologic examination demonstrated concomitant distal or asymmetric hyporeflexia and hyperreflexia (81%), impaired vibration and proprioception (69%), Babinski response (68%), and asymmetric weakness (66%). MRI showed longitudinally extensive (45%), tract-specific spinal cord T2 hyperintensities (39%) and lumbar nerve root enhancement (38%). Ten of 28 (36%) were unable to ambulate independently at last follow-up (median 24 months, range 5-133 months). Combined oncologic and immunologic therapy had more favorable modified Rankin Scale scores at post-treatment follow-up compared to those receiving either oncologic or immunologic therapy alone (2 [range 1-4] vs 4 [range 2-6], p < 0.001). CONCLUSIONS: Paraneoplastic etiologies should be considered in the evaluation of subacute myeloneuropathies. Recognition of key characteristics of paraneoplastic myeloneuropathy may facilitate early tumor diagnosis and initiation of immunosuppressive treatment.

Paraneoplastic subacute sensory neuropathy with triple positive antineuronal antibodies associated with small-cell lung cancer.

A 67-year-old woman with a history of smoking and cardiovascular risk factors was admitted to the emergency room for uncontrolled diabetes, loss of appetite, nausea, significant weight loss and asthenia. The initial investigation, including cerebral and gastrointestinal explorations, were normal. One month later, she started presenting severe asymmetric proprioceptive ataxia of the lower extremities. She also reported paresthesia and neuropathic pain in both feet and ankles. A positron emission tomography (PET)-scanner showed a hypermetabolic nodule in the right lung. The neurological symptoms were attributed to paraneoplastic sensory and dysautonomic neuropathy, even though the bronchoscopic biopsies came back negative at first. Anti-Hu, anti-CV2/CRMP5 and anti-SOX1 antibodies were documented. Due to the severity and rapid progression of symptoms (from the lower to the upper limbs), corticosteroids, intravenous immunoglobulins and immunosuppressants were introduced prior to biopsies revealing a small-cell lung cancer. Despite these treatments and antineoplastic chemotherapy, her status deteriorated rapidly.

A Pilot Randomized Sham-Controlled Trial of MC5-A Scrambler Therapy in the Treatment of Chronic Chemotherapy-Induced Peripheral Neuropathy (CIPN).

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) affects 30% to 40% of patients with cancer with long-lasting disability. Scrambler therapy (ST) appeared to benefit patients in uncontrolled trials, so we performed a randomized sham-controlled Phase II trial of ST. METHODS: The primary end point was "average pain" after 28 days on the Numeric Rating Scale. Each received ten 30-minute sessions of ST on the dermatomes above the painful areas, or sham treatment on the back, typically at L3-5 where the nerve roots would enter the spinal cord. Outcomes included the Brief Pain Inventory (BPI)-CIPN and the EORTC CIPN-20 scale. Patients were evaluated before treatment (day 0), day 10, and days 28, 60, and 90. RESULTS: Data regarding pain as a primary outcome were collected for 33 of the 35 patients. There were no significant differences between the sham and the "real" ST group at day 10, 28, 60, or 90, for average pain, the BPI, or EORTC CIPN-20. Individual responses were noted during the ST treatment on the real arm, but most dissipated by day 30. There was improvement in the sensory subscale of the CIPN-20 at 2 months in the "real" group (P = .14). All "real" patients wanted to continue treatment if available. DISCUSSION: We observed no difference between sham and real ST CIPN treatment. Potential reasons include at least the following: ST does not work; the sham treatment had some effect; small sample size with heterogeneous patients; misplaced electrodes on an area of nonpainful but damaged nerves; or a combination of these factors.

Paraneoplastic sensorimotor polyneuropathy in prostatic adenocarcinoma: A case report.

RATIONALE: Paraneoplastic syndrome is a very rare syndrome among prostate cancer patients. In particular, paraneoplastic sensorimotor neuropathy has never been reported as a complication of prostatic adenocarcinoma. PATIENT CONCERNS: A 75-year-old man who was diagnosed with prostatic adenocarcinoma with multiple metastases received cancer treatment. But, numbness and tingling sensations in both sides of the upper and lower limbs got progressively worse. DIAGNOSESE: He was diagnosed with positive anti-Hu antibodies paraneoplastic sensorimotor polyneuropathy caused by prostatic adenocarcinoma. INTERVENTIONS: The patient received physical therapy, occupational therapy, and opioid medication during 3 weeks at cancer rehabilitation department during 3 weeks. OUTCOMES: There was no improvement in functional outcome in this patient. But, the patient's neuropathic pain was improved by the use of opioid agents. LESSONS: This case report is the first to report anti-Hu antibody-positive paraneoplastic sensorimotor neuropathy in a patient with adenocarcinoma of the prostate.

Paraneoplastic neuromyelitis optica spectrum disorder: A case report and review of the literature.

Neuromyelitis optica spectrum disorders (NMOSD) are demyelinating, autoimmune diseases affecting the central nervous system. Typically, recurrent optic neuritis and longitudinal extensive transverse myelitis dominates the clinical picture. In most cases NMOSD are associated with autoantibodies targeting the water channel aquaporin-4 (AQP-4). NMOSD usually present in young adults. Clinical findings suggestive of NMOSD in elderly patients should raise the suspicion of a paraneoplastic etiology. To our knowledge, we report the first case of a 66 year-old female patient with paraneoplastic NMOSD that is associated with squamous cell lung carcinoma. Anti-AQP-4 was present in both the serum and cerebrospinal fluid of the patient. However, immunhistological staining of the malignant tissue did not show presence of AQP-4 on the surface of tumour cells.

Paraneoplastic neuropathies.

PURPOSE OF REVIEW: To review recent advances in paraneoplastic neuropathies with emphasis on their definition, different forms and therapeutic development. RECENT FINDINGS: A strict definition of definite paraneoplastic neuropathies is necessary to avoid confusion. With carcinoma, seronegative sensory neuronopathies and neuronopathies and anti-Hu and anti-CV2/Contactin Response Mediator Protein 5 antibodies are the most frequent. With lymphomas, most neuropathies occur with monoclonal gammopathy including AL amyloidosis, Polyneuropathy-Organomegaly-Endocrinopathy-M component-Skin changes (POEMS) syndrome, type I cryoglobulinemia and antimyelin-associated glycoprotein (MAG) neuropathies and Waldenström's disease. Neuropathies improving with tumor treatment are occasional, occur with a variety of cancer and include motor neuron disease, chronic inflammatory demyelinating neuropathy and nerve vasculitis. If antibodies toward intracellular antigens are well characterized, it is not the case for antibodies toward cell membrane proteins. Contactin-associated protein-2 antibodies occur with neuromyotonia and thymoma with the Morvan's syndrome in addition to Netrin 1 receptor antibodies but may not be responsible for peripheral nerve hyperexcitability. The treatment of AL amyloidosis, POEMS syndrome, anti-MAG neuropathy and cryoglobulinemia is now relatively well established. It is not the case with onconeural antibodies for which the rarity of the disorders and a short therapeutic window are limiting factors for the development of clinical trials. SUMMARY: A strict definition of paraneoplastic neuropathies helps their identification and is necessary to allow an early diagnosis of the underlying tumor.

Neuronopatía sensitiva paraneoplásica asociada a carcinoma escamoso de laringe / Paraneoplastic sensory neuropathy associated with squamous cell carcinoma of the larynx

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Paraneoplastic Demyelinating Neuropathy, a Multifactorial Disease and Approach to Management.

We report a 53-year-old male with demyelinating polyneuropathy due to a paraneo- plastic syndrome from lymphoplasmacytic lymphoma. This syndrome is an immune-mediated event via plasma cell dyscrasia. The patient suffered near quadriplegia requiring prolonged ventilation. He was treatedwith systemic therapyforhis malignancy, as well as immunemodulating therapy with a recovery near his baseline. We propose it is important to not only control malignant plasma cell dyscrasia, but also target peripheral antibodies carrying out the attack in order to prevent further damage to the nervous system.

Paraneoplastic neuropathies.

PURPOSE OF REVIEW: This article provides an approach to the recognition and management of paraneoplastic neuropathies. RECENT FINDINGS: Paraneoplastic neuropathies may have unique phenotypic presentations, such as sensory neuronopathy, autonomic enteric neuropathy, demyelinating neuropathy, and, rarely, motor neuropathy. Paraneoplastic sensorimotor neuropathy, on the other hand, may be indistinguishable from other common types of axonal polyneuropathy. Certain patterns of neuropathies are commonly seen with different types of cancers, but this relationship is not exclusive and not all patients whose pattern of neuropathy suggests a paraneoplastic disorder have an underlying cancer. In addition to definitive therapy for malignancy, immunomodulatory therapy, such as corticosteroids, IV immunoglobulin (IVIg), or immunosuppressants, may benefit some patients, but there are very few published treatment data for paraneoplastic neuropathies. SUMMARY: Prompt recognition of paraneoplastic neuropathies may lead to identification and treatment of an occult cancer. Treatment can potentially arrest the progression of neuropathy.

Paraneoplastic neuropathy.

Recent progress in serological screening of paraneoplastic antibodies and in diagnostic imaging techniques to detect malignancies has enabled a broadening of the concept of paraneoplastic neurological syndromes by integrating nonclassic clinical features. The peripheral nervous system is frequently involved in patients with paraneoplastic syndrome and may be seen alone or in combination with involvement of other areas of the nervous system. Destruction of dorsal root ganglion cells due to lymphocytic infiltration, especially with CD8-positive cytotoxic T cells, has been postulated to mediate the classic syndrome of subacute sensory neuronopathy. However, the motor and autonomic nervous systems are frequently affected. Indeed, patients can develop clinical features compatible with Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, or brachial plexopathy. Other forms of paraneoplastic neuropathy are vasculitic neuropathy, autoimmune autonomic ganglionopathy, and chronic intestinal pseudo-obstruction. Various onconeural antibodies, including anti-Hu, anti-CV2/CRMP-5, and anti-ganglionic acetylcholine receptor antibodies, are associated with neuropathy. Somatic neuropathy is the most common manifestation in patients with anti-Hu and anti-CV2/CRMP-5 antibodies, while anti-ganglionic acetylcholine receptor antibody is associated with autonomic neuropathies. A whole-body fluorodeoxyglucose positron emission tomography scan may be useful to detect malignancy in patients with unremarkable conventional radiological findings. Recognition and diagnosis of paraneoplastic neuropathy is important, as neuropathic symptoms usually precede the identification of the primary tumor, and treatment at an earlier stage provides better chances of good outcomes.

Therapeutic plasma exchange in neurology: 2012.

In treating neuroimmunological diseases, neurologists have a number of different drugs to choose from ranging from corticosteroids to IVIg to more specific cell based therapies, the latter most frequently from the world of oncology. In some diseases, therapeutic plasma exchange, a procedure rather than a drug, is used. The most obvious advantage of therapeutic plasma exchange is the usually rapid onset of action presumably due to removal of pathogenic auto-antibodies. In some diseases, a single course of therapeutic plasma exchange is used while in others prolonged treatment with therapeutic plasma exchange is used. This article will review the use of therapeutic plasma exchange in neurology and will draw heavily upon recent consensus statements from the American Society for Apheresis and the American Academy of Neurology and by Cochrane reviews.

Treatment for paraneoplastic neuropathies.

BACKGROUND: It is not unusual to observe peripheral nervous system involvement in people with tumours outside the nervous system. Any part of the peripheral nervous system can be involved, from sensory and motor neurons to nerve roots and plexuses, from distal trunks to neuromuscular junctions. Pathogenesis also varies from direct infiltration by cancer cells, to treatment toxicity, to metabolic derangement, cachexia, infections and paraneoplastic syndromes.Paraneoplastic neurological syndromes are symptoms or signs resulting from damage to organs or tissues that are remote from the site of the malignancy or its metastases. The pathogenesis is thought to be immune-mediated as a result of a cross-reaction against antigens shared by the tumour and nervous system cells.Paraneoplastic neuropathies are the most frequently reported paraneoplastic syndromes. They are, however, heterogeneous and require several therapeutic approaches. This review was undertaken to systematically assess any data available from randomised controlled trials (RCTs) on the treatment of paraneoplastic syndromes of the peripheral nervous system and not the whole range of paraneoplastic neurological syndromes. OBJECTIVES: To assess the benefits and harms of treatments for paraneoplastic neuropathies. SEARCH METHODS: We searched the Cochrane Neuromuscular Disease Group Specialized Register (14 February 2012), CENTRAL (2012, Issue 1), MEDLINE (January 1966 to February 2012), EMBASE (January 1980 to February 2012) and LILACS (January 1982 to February 2012) for RCTs, quasi-RCTs, historically controlled studies and trials with concurrent controls.We adapted this strategy to search MEDLINE from 1966 and EMBASE from 1980 for comparative cohort studies, case-control studies and case series. SELECTION CRITERIA: We planned to include all RCTs and quasi-RCTs (in which allocation is not random but is intended to be unbiased, for example alternate allocation) of any treatment for paraneoplastic neuropathies. Since we expected there to be few or no included studies, we also planned to assess and summarise observational studies, prospective and retrospective comparative cohort studies, case-control studies and case series that met minimum criteria in the discussion. DATA COLLECTION AND ANALYSIS: Three review authors selected the trials for inclusion. When there was any disagreement we reached an agreement by discussion. Two review authors extracted data independently onto a specially designed data extraction form. We would have collected adverse event data from included studies. MAIN RESULTS: Despite many reports on paraneoplastic neuropathy, we identified no RCT or quasi-RCTs for inclusion in this review. We found only six studies, involving 54 participants, from among the non-randomised evidence that were judged by predefined criteria to be of suitable quality for inclusion in the discussion. These studies were not readily comparable. The treatments focused on tumour treatment and immunomodulation, mainly intravenous immunoglobulin. AUTHORS' CONCLUSIONS: At present there are no RCTs or quasi-RCTs of treatment for paraneoplastic neuropathies on which to base practice. There is only evidence from case series, case reports or expert opinion (class IV evidence) for the effect of immunomodulation (intravenous immunoglobulin, plasma exchange, steroid treatment or chemotherapy) on paraneoplastic neuropathy.  

Paraneoplastic neuropathy: wide-ranging clinicopathological manifestations.

PURPOSE OF REVIEW: Recent progress in serological screening for paraneoplastic autoantibodies and diagnostic imaging techniques to detect malignancies has resulted in a broadening of the concept of paraneoplastic neurologic syndromes through the characterization of nonclassical clinical features. The goal of this article was to review the recent literature describing the wide-ranging clinicopathological manifestations of paraneoplastic neuropathy. RECENT FINDINGS: The classical feature of paraneoplastic neuropathy is subacute sensory neuronopathy; in addition, sensorimotor neuropathies, such as Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, brachial plexopathy, and vasculitic neuropathy, are sometimes observed. Some studies also describe the occurrence of autonomic neuropathies, including autoimmune autonomic ganglionopathy and chronic gastrointestinal pseudo-obstruction. Whole-body fluorodeoxyglucose positron emission tomography (FDG-PET) or FDG-PET/computed tomography may be helpful to detect malignancies that cannot be detected by conventional screening tests. The presence of paraneoplastic neuropathy should be considered in all patients with malignancy and can occur at any point in the disease, even during or after chemotherapy, radiation, or stem cell transplantation. The presence of paraneoplastic autoantibodies, especially anti-Hu and anti-CV2/CRMP-5 antibodies, may support the diagnosis of paraneoplastic neuropathy. Immunomodulatory treatment before, during, or after antineoplastic therapy may be of benefit for patients with paraneoplastic neuropathy and has been used even when the underlying malignancy cannot be identified. SUMMARY: Recognition of the variable manifestations of paraneoplastic neuropathy is important, as diagnosis at an earlier stage facilitates prompt treatment and provides better chances of good outcomes.

Paraneoplastic syndromes: an approach to diagnosis and treatment.

Recent medical advances have improved the understanding, diagnosis, and treatment of paraneoplastic syndromes. These disorders arise from tumor secretion of hormones, peptides, or cytokines or from immune cross-reactivity between malignant and normal tissues. Paraneoplastic syndromes may affect diverse organ systems, most notably the endocrine, neurologic, dermatologic, rheumatologic, and hematologic systems. The most commonly associated malignancies include small cell lung cancer, breast cancer, gynecologic tumors, and hematologic malignancies. In some instances, the timely diagnosis of these conditions may lead to detection of an otherwise clinically occult tumor at an early and highly treatable stage. Because paraneoplastic syndromes often cause considerable morbidity, effective treatment can improve patient quality of life, enhance the delivery of cancer therapy, and prolong survival. Treatments include addressing the underlying malignancy, immunosuppression (for neurologic, dermatologic, and rheumatologic paraneoplastic syndromes), and correction of electrolyte and hormonal derangements (for endocrine paraneoplastic syndromes). This review focuses on the diagnosis and treatment of paraneoplastic syndromes, with emphasis on those most frequently encountered clinically. Initial literature searches for this review were conducted using PubMed and the keyword paraneoplastic in conjunction with keywords such as malignancy, SIADH, and limbic encephalitis, depending on the particular topic. Date limitations typically were not used, but preference was given to recent articles when possible.

[Subacute sensory neuronopathy associated with squamous cell carcinoma of the lung: a case report].

We report a 59-year-old man who developed dysesthesia in all extremities with severe loss of deep sensation over three months. A radiating radicular pain was also noted in the extremities. The nerve conduction study barely elicited sensory nerve action potentials both in the median and in the sural nerve. An extensive search for anti-neuronal antibodies including anti-Hu and anti-CV2 antibody was negetive. The biopsy specimen of an enlarged tracheobronchial lymph node revealed squamous cell carcinoma. The subsequent chemotherapy and radiation therapy for the neoplasm improved the radicular pain and the deep sensation to a moderate extent, leading to the diagnosis of paraneoplastic subacute sensory neuropathy (SSN). In general, cases with paraneoplastic SSN are associated mostly with small cell lung cancer, and quite rarely with squamous cell lung cancer. The early detection and the treatment of the primary tumor are crucial in a patient with subacute progression of sensory-dominant neuropathy.

Thymoma associated with myasthenia and autonomic anti-Hu paraneoplastic neuropathy.

Along with myasthenia, other paraneoplastic neurological syndromes (PNS) may occur in thymoma. Anti-Hu antibodies and a clinical "anti-Hu syndrome" characterized by encephalitis and/or painful neuropathies have been reported in only three patients at the time of the diagnosis of thymoma. We describe a severe anti-Hu-related autonomic neuropathy with gastrointestinal paresis and intestinal pseudo-obstruction with malabsorption that occurred concomitantly with the worsening of myasthenic symptoms long after the initial diagnosis of thymoma in a young patient. The clinical anti-Hu syndrome preceded the radiological diagnosis of thymoma recurrence. Treatment with plasma exchange led to a transient improvement of neurological symptoms.