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.

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.

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.

Ataxic vs painful form of paraneoplastic neuropathy.

OBJECTIVE: To characterize the clinicopathologic features of ataxic and painful forms of paraneoplastic neuropathy. METHODS: Clinical, electrophysiologic, and histopathologic findings were assessed in 17 patients with paraneoplastic neuropathy. RESULTS: Clinical features can be categorized into two groups: one group (13 patients) with predominantly deep sensory disturbance and a second group (4 patients) with predominantly superficial sensory disturbance. The former group showed severe sensory ataxia and predominantly large myelinated fiber loss in the sural nerve. The latter group showed marked pain, in particular, severe mechanical hyperalgesia, and predominantly small myelinated and unmyelinated fiber loss. Nerve conduction assessment indicated an axonal neuropathy pattern in both groups, while sensory action potentials were more markedly diminished in the sensory ataxic form. Anti-Hu antibodies were detected in half of the patients in both groups. Treatment for cancer was effective to improve or stabilize neuropathic symptoms in some cases from both groups. Immunotherapy was effective only for a short time. CONCLUSIONS: Paraneoplastic neuropathy can be characterized into two groups by the presence of sensory ataxia or severe spontaneous pain and severe mechanical hyperalgesia. Preferential small myelinated and unmyelinated fiber loss correlated to the cases of severe pain.

Antinuclear antibodies define a subgroup of paraneoplastic neuropathies: clinical and immunological data.

OBJECTIVE: Paraneoplastic neuropathy is a clinical and immunological heterogeneous disorder and attempts have been made to classify subgroups of this disease. Only 30-50% of the clinical defined cases have antineuronal antibodies. METHODS: The clinical and immunological features of 36 patients with paraneoplastic neuropathy from the authors' database were analysed including the type and course of the neuropathy, associated tumours, and the presence of antineuronal and other autoantibodies. RESULTS: Antineuronal antibodies were detected in 17/36 patients (47%) and anti-Hu was the most frequent antineuronal antibody. Nine patients had high titre antinuclear antibodies (ANA, median titre 1/1000) without antineuronal antibodies. ANA reactivities were different in most patients. Comparison of the ANA positive and ANA negative patients revealed that ANA positive paraneoplastic neuropathy is more frequently associated with breast cancer but is not associated with lung cancer (p<0.05). The main clinical type in these patients was sensorimotor neuropathy. No ANA positive patient had central nervous system involvement. Although the Rankin score at the time of diagnosis was not different, the functional outcome in ANA positive patients was better than in ANA negative patients (p<0.05). CONCLUSIONS: Paraneoplastic neuropathy is a heterogeneous disorder. ANA may define a subgroup of paraneoplastic neuropathy with different clinical and immunological features and may be related to better prognosis of the neuropathic symptoms.

Diagnosis and treatment of paraneoplastic neurological disorders.

In about two thirds of cases, patients with paraneoplastic neurological disorders present to the neurologist without a known tumor. Due to the ongoing immune response, this tumor tends to stay biologically relatively benign, and therefore difficult to diagnose. In patients with a known tumor, the neurological symptoms often precede a tumor recurrence. In both scenarios, anti-neuronal antibodies are an invaluable diagnostic help to the clinician, and may be supplemented by other diagnostic tests such as MRI, CSF, and electrophysiology. Tumor therapy remains the mainstay of therapeutic options, although early immune therapy must be started in parallel. It is hoped that the recent fundamental advances in understanding the autoimmune pathology of these disorders, especially the role of cytotoxic T cells, will eventually lead to more effective treatment options.

[Paraneoplastic peripheral neuropathies]. / Les neuropathies périphériques paranéoplasiques.

Paraneoplastic peripheral neuropathies constitute a heterogeneous group of conditions. A link between the tumor and the neuropathy has been demonstrated in a subgroup only. Definite paraneoplastic neuropathies correspond to neuropathies associated with antibodies reacting with antigens common to the peripheral nervous system and the cancer. Neuropathies associated with anti-Hu antibodies are the most frequent and consist mainly in subacute sensory neuronopathy. Sensory or sensory-motor neuropathies with anti-CV2 antibodies are less frequent. The link between the cancer and the neuropathy is less clear in the other forms. The frequency of cancer in this group varies from 1 to 18 p.cent.These neuropathies include inflammatory demyelinating neuropathies, neuropathy and vasculitis, lower motor neurone diseases, and autonomic neuropathies. Occasionally, the neuropathy improves with treatment of the tumor. Recent data suggest that gangliosides may be the target of the immune process in neuropathies associated with melanoma.