Paraneoplastic Peripheral Neuropathy Research Articles

Paraneoplastic peripheral neuropathy and lymphoma complicated by a macrophage activation syndrome

Paraneoplastic peripheral neuropathy and lymphoma complicated by a macrophage activation syndrome

A case of IVIg responsive paraneoplastic SOX1 peripheral neuropathy in a male with breast carcinoma

Background and aimsSOX1 antibodies are generally associated with small cell lung cancer and anti-Hu antibody overlap is common. This case demonstrates isolated anti-SOX1 antibodies with an uncommon tumor type, and relapse of a paraneoplastic syndrome with recurrence of tumor. MethodsWe describe a case of a 65-year-old male with a paraneoplastic peripheral neuropathy and anti-SOX1 antibody positivity in the context of a prior male breast Grade 2 ductal carcinoma, in remission at the time of the initial neurological presentation. ResultsTreatment response to intravenous immunoglobulin (IVIg) was demonstrated. After period of clinical stability on IVIg in the context of remission of breast carcinoma, the patient experienced a relapse of his neuropathy. This was associated with tumor recurrence and again responded to tumor excision, radiotherapy and IVIg. InterpretationMale breast carcinoma has not previously been associated with anti-SOX1 antibody positive paraneoplastic neuropathy.

Focal Peripheral Neuropathy Associated with Lymphoma in Dogs

Background: Peripheral neuropathies result in sensory, motor or autonomic dysfunctions due to impairment of peripheral spinal or cranial nerves. Neoplasms such as lymphoma are cited as one of the many aetiological causes and it may affect the nerve directly, by compression, or indirectly, or paraneoplastic, by remote action of the neoplasm located in an extra-neural site. This study aimed to report two cases of cranial nerve neuropathy (trigeminal and facial) associated with canine lymphoma, contributing to a better understanding of its paraneoplastic effects on the nervous system, as well as the diagnosis and treatment of these conditions.Cases: Two cases of canine lymphoma associated with possible signs of paraneoplastic peripheral neuropathy were attended at the Veterinary Hospital from the Universidade Federal de Minas Gerais (HV UFMG). Case 1. A spayed mixed breed bitch, with lethargy and unilateral exophthalmos. Brain computed tomography revealed a retrobulbar mass and cytology was diagnostic for extranodal lymphoma. Subsequent to computed tomography, the dog was presented with hypotrophy of the facial musculature and difficulty in grasping food, consistent with trigeminal nerve palsy, which resolved after institution of the 19-week chemotherapy protocol from the University of Wisconsin. Nevertheless, disease reccurred and a rescue protocol was initiated. Case 2. A female Dalmatian, spayed, was diagnosed with multicentric lymphoma, after cytology of the left mandibular lymph node. Chemotherapy was initiated with the same protocol of the previous case. However, the disease progressed and it was observed facial asymmetry with ptosis of the left eyelid, pina and lips, in addition to difficulty in grasping food, suggesting facial and trigeminal cranial nerve palsy. Clinical signs resolved after institution of a rescue chemotherapy protocol. However, in both cases, disease progression and poor clinical condition resulted in decision of euthanasia and necropsy was not authorized.Discussion: Canine lymphoma is often associated with paraneoplastic syndromes, with neuropathy being one of its possible clinical manifestations. In spite of that its pathogenesis remains unclear, with little information in the veterinary literature. Diagnosis is challenging and must be initially based on recognition of neurological clinical signs and lesion localization, as in the reported cases with lesions located on the fifth and seventh cranial nerves. In the patient from the first case, the absence of clinical signs and laboratory abnormalities suggestive of endocrinopathies, associated with neurological signs restricted to the trigeminal nerve, bilaterally, before starting chemotherapy and without the identification of brain lesions in computed tomography, suggested paraneoplastic involvement as the cause of neuropathy. In the second case described, the absence of clinical signs and laboratory abnormalitiess suggestive of endocrinopathies or nutritional deficiencies, associated with neurological signs restricted to the facial and trigeminal cranial nerves, suggested direct or indirect tumour involvement. Both cases showed improvement of neurological clinical signs after chemotherapy which favored the therapeutic diagnosis. Nevertheless, failure to authorize necropsy of patients made it impossible to confirm that peripheral neuropathy is secondary to the remote effect of lymphoma.

A case of paraneoplastic peripheral neuropathy in metastatic neuroendocrine tumour in pregnancy

A case of paraneoplastic peripheral neuropathy in metastatic neuroendocrine tumour in pregnancy

Pain as a First Manifestation of Paraneoplastic Neuropathies: A Systematic Review and Meta-Analysis.

IntroductionParaneoplastic neurological syndromes (PNS) consist of a heterogeneous group of neurological disorders triggered by cancer. The aim of this systematic review is to estimate the reported prevalence of pain in patients with paraneoplastic peripheral neuropathy (PPN).MethodsA systematic computer-based literature search was conducted on PubMed database.ResultsOur search strategy resulted in the identification of 126 articles. After the eligibility assessment, 45 papers met the inclusion criteria. Full clinical and neurophysiological data were further extracted and involved 92 patients with PPN (54.5% males, mean age 60.0 ± 12.2 years). The commonest first manifestation of PPN is sensory loss (67.4%), followed by pain (41.3%), weakness (22.8%), and sensory ataxia (20.7%). In 13.0% of the cases, pain was the sole first manifestation of the PPN. During the course of the PPN, 57.6% of the patients may experience pain secondary to the neuropathy.ConclusionsPain is very prevalent within PPN. Pain specialists should be aware of this. Detailed history-taking, full clinical examination, and requesting nerve conduction studies might lead to an earlier diagnosis of an underlying malignancy.

Intrathecal synthesis of anti-Hu antibodies distinguishes patients with paraneoplastic peripheral neuropathy and encephalitis.

BackgroundParaneoplastic syndromes are serious immune caused diseases of the peripheral and/or central nervous system associated with malignant neoplasm. Symptoms develop when antibodies against antigens expressed by tumor cells cross-react with neuronal proteins. Antineuronal antibodies are usually examined in patient’s sera while examination of the cerebrospinal fluid (CSF) often fails. Furthermore, the few previous reports describing CSF data summarized different antineuronal antibodies and/or regarded patients with different neurological symptoms as one group.MethodsWe retrospectively evaluated data of 18 patients with paraneoplastic syndromes due to anti-Hu antibodies. The study aimed to differentiate patients with peripheral neuropathy and encephalitis by cerebrospinal fluid (CSF) parameters including anti-Hu antibody titers.ResultsOur results confirm previous observations that serum titers of anti-Hu antibodies and standard CSF values do not differ between patients with neuropathy and encephalitis. However, analysis of CSF anti-Hu titers and calculating the intrathecal synthesis helped to discriminate between both groups.ConclusionIn conclusion, our results indicate that patients even with one defined antineuronal antibody need to be regarded separately depending on the involved location of the nervous system. We recommend incorporation of anti-Hu analyses in the CSF and calculating the intrathecal synthesis in patients with anti-Hu syndrome.

Sry‐like high‐mobility group box antibody‐related paraneoplastic cerebellar degeneration in the background of underlying non‐small cell lung cancer

AbstractBackgroundParaneoplastic neurological syndromes (PNS) are defined as all non‐metastatic neurological complications of cancer in which no other etiologies, such as vascular, infectious or metabolic, were determined. Recently, Sry‐like high‐mobility group box (SOX1) antibody associated with PNS has been described, and is associated with Lambert–Eaton myasthenic syndrome, paraneoplastic cerebellar degeneration and paraneoplastic peripheral neuropathy invariably in the background of underlying small‐cell lung cancer.Case presentationA 75‐year‐old man was admitted to our neurology clinic at Hacettepe University Hospital, Sihhiye, Ankara, Turkey with complaints of imbalance and memory impairment that had started 2 months earlier and progressively increased. Neurological examination showed a state of delirium in the background of rapid progressive dementia and severely truncal ataxia. Cranial magnetic resonance imaging was unremarkable; however, in further investigations, thoracic tomography yielded bilateral hilar lymphadenopathy, and paraneoplastic antibody investigations resulted in positive SOX1 antibody. The following thoracic excisional lymph node biopsy investigations supported the diagnosis of non‐small‐cell lung cancer and paraneoplastic cerebellar degeneration associated with SOX1 antibody in the background of non‐small‐cell lung cancer. Adjuvant chemotherapy was started, but the patient deteriorated, which prevented proper plasmapheresis therapy. He died in the second month of admission as a result of severe sepsis leading to septic shock.ConclusionsHere, we show the second case diagnosed with PNS in association with non‐small‐cell lung cancer. We note the importance of SOX1 antibody as a marker for PNS, and suggest that investigations of this antibody be carried out in larger case studies.

Peripheral neuropathies associated with antibodies directed to intracellular neural antigens

Antibodies directed to intracellular neural antigens have been mainly described in paraneoplastic peripheral neuropathies and mostly includes anti-Hu and anti-CV2/CRMP5 antibodies. These antibodies occur with different patterns of neuropathy. With anti-Hu antibody, the most frequent manifestation is sensory neuronopathy with frequent autonomic involvement. With anti-CV2/CRMP5 the neuropathy is more frequently sensory and motor with an axonal or mixed demyelinating and axonal electrophysiological pattern. The clinical pattern of these neuropathies is in keeping with the cellular distribution of HuD and CRMP5 in the peripheral nervous system. Although present in high titer, these antibodies are probably not directly responsible for the neuropathy. Pathological and experimental studies indicate that cytotoxic T-cells are probably the main effectors of the immune response. These disorders contrast with those in which antibodies recognize a cell surface antigen and are probably responsible for the disease. The neuronal cell death and axonal degeneration which result from T-cell mediated immunity explains why treating these disorders remains challenging.

The Collapsin Response Mediator Protein 5 Onconeural Protein Is Expressed in Schwann Cells Under Axonal Signals and Regulates Axon—Schwann Cell Interactions

Collapsin response mediator protein 5 (CRMP5) is one of the rare peripheral nerve antigens that is a target of autoantibodies in a paraneoplastic peripheral neuropathy. The pattern of axonal and myelin alterations suggests that CRMP5 is involved in axon-Schwann cell interaction. We examined CRMP5 expression and function in primary cultures of Schwann cells and neurons and at various developmental and regenerating stages of rat sciatic nerve and in CRMP5-deficient mice in vivo. Collapsin response mediator protein 5 was strongly expressed during postnatal development and regeneration and decreased with myelination. It was mainly expressed by immature Schwann cells and persisted in Remak cells in the adult; however, a subpopulation of Schwann cells that were induced to myelinate also expressed CRMP5. We identified 2 axonal molecular cues regulating CRMP5 expression: human neuregulin type 1, which induces CRMP5 expression in immature and premyelinating Schwann cells, and cyclic adenosine monophosphate, which inhibits CRMP5 expression when Schwann cells begin myelination. Collapsin response mediator protein 5-deficient mice showed abnormal Schwann process extension resulting in abnormal cell-axon segregation, indicating that CRMP5 is involved in the morphologic adaptation of Schwann cells to surround axons. These results demonstrate the importance of CRMP5 in axon-Schwann cell cooperation during development and regeneration.

Les neuropathies périphériques paranéoplasiques

The PNS Euronet group criteria have classified paraneoplastic peripheral neuropathies as definite or possible according as to whether the neuropathy is a classical paraneoplastic disorder, the presence of onconeural antibodies, the delay between tumor and neuropathy, and improvement of the neuropathy with tumor treatment. Denny Brown’s subacute sensory neuronopathy and neuropathies with anti-Hu or anti-CV2 antibodies are definite paraneoplastic disorders. Possible paraneoplastic neuropathies are heterogeneous. This classification is useful for the diagnostic of these disorders and the selection of patients in whom a search for cancer is warranted.

Impairment of Trk-Neurotrophin Receptor by the Serum of a Patient With Subacute Sensory Neuropathy

Paraneoplastic peripheral neuropathy is sometimes associated with unidentified neuronal autoantibodies. To examine the effects of serum from a patient with subacute sensory axonopathy on the function of the Trk high-affinity nerve growth factor receptor. An 86-year-old man with sensory neuropathy exhibiting an autoantibody to Trk. Immunoblot analyses of the brain homogenates and immunoprecipitation were performed with human sera. We further examined the effect of sera on nerve growth factor-induced neurite outgrowth and Trk autophosphorylation. The patient showed sensory nerve axonopathy without well-known paraneoplastic autoantibodies. His serum inhibited nerve growth factor-induced neurite outgrowth and Trk autophosphorylation in PCtrk cells. Moreover, the patient's serum, but not control serum, immunoprecipitated Trk and recognized Trk in brain homogenates as well as in Trk immunoprecipitates. These data strongly suggest that an anti-Trk autoantibody might cause subacute sensory neuropathy.

Intravenous Immunoglobulin in Therapy of Peripheral Neuropathy

Peripheral neuropathy (PN) can be a manifestation of various neurological, infectious, metabolic, autoimmune, rheumatic, and malignant diseases. During the past decade, intravenous immunoglobulin (IVIg) has been increasingly used in the therapy of PN. Compared with other immunomodulatory therapies, IVIg has an excellent safety profile. IVIg is used today as a first-line therapy in the treatment of Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and multifocal motor neuropathy. Some small studies and reports of clinical cases presented in this article found benefit from IVIg in treating PN associated with diabetes, paraproteinemia, HIV, multisystem rheumatic diseases, and paraneoplastic PN. No clear recommendations can be made relating the use of IVIg in these conditions. Prospective, randomized trials are required to clarify this issue.

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.

Neuropathic pain due to malignancy: Mechanisms, clinical manifestations and therapy

Neuropathic pain in cancer patients requires a focused clinical evaluation based on knowledge of common neuropathic pain syndromes. Neuropathic pain is a non-nociceptive pain or "deafferentation" pain, which suggests abnormal production of impulses by neural tissue that is separated from afferent input. Impulses arise from the peripheral nervous system or central nervous system. CAUSES OF NEUROPATHIC PAIN DUE TO MALIGNANCY: Neuropathic pain is caused directly by cancer-related pathology (compression/infiltration of nerve tissue, combination of compression/infiltration) or by diagnostic and therapeutic procedures (surgical procedures, chemotherapy, radiotherapy). Pathophysiological mechanisms are very complex and still not clear enough. Neuropathic pain is generated by electrical hyperactivity of neurons along the pain pathways. Peripheral mechanisms (primary sensitization of nerve endings, ectopically generated action potentials within damaged nerves, abnormal electrogenesis within sensory ganglia) and central mechanisms (loss of input from peripheral nociceptors into dorsal horn, aberrant sprouting within dorsal horn, central sensitization, loss of inhibitory interneurons, mechanisms at higher centers) are involved. The quality of pain presents as spontaneous pain (continuous and paroxysmal), abnormal pain (allodynia, hyperalgesia, hyperpathia), paroxysmal pain. Clinically, neuropathic pain is described as the pain in the peripheral nerve (cranial nerves, other mononeuropathies, radiculopathy, plexopathy, paraneoplastic peripheral neuropathy) and relatively infrequent, central pain syndrome. Treatment of neuropathic pain remains a challenge for clinicians, because there is no accepted algorithm for analgesic treatment of neuropathic pain. Pharmacotherapy is considered to be the first line therapy. Opioids combined with non-steroidal antiinflammatory drugs are warranted. If patient is relatively unresponsive to an opioid, a trial with adjuvant analgesics might be considered. Tricyclic antidepressants might be selected for patients with continuous dysesthesia, and anticonvulsants might be used if the pain is predominanty lancinating or paroxysmal. The complexity of neuropathic syndromes and underlying etiologic mechanisms warrant clinical trials to determine appropriate treatment.

Pramipexole in restless legs syndrome

Sirs: The Restless Legs Syndrome (RLS) is characterized by a disagreeable sensation in the limbs and motor restlessness occurring at rest, especially in the evening and at night, which improves temporarily with activity [1]. More than 80 % of RLS patients have periodic legs movements (PLM) during sleep (PLMS) and wakefulness (PLMW) [2, 3]. D3-receptors nonergoline dopaminergic agents, such as pramipexole and ropirinole, are commonly used in RLS therapy, although detailed data on their effect on PLM are lacking. The aim of our study was to determine pramipexole efficacy on RLS symptoms and motor component by means of the Suggested Immobilization Test (SIT). Twenty-four never treated patients (mean age 62.4 ± 7.1 years; 13 females, 11 males) were selected according to the standard diagnostic criteria defined by the International RLS Study Group (IRLSSG) [2]. On the basis of the medical history, neurological examination, laboratory tests, electroneurography and F-wave, 20 patients were classified as having primary RLS, and 4 as secondary RLS (2 renal failure, 1 peripheral neuropathy, 1 paraneoplastic peripheral neuropathy). The initial dose of pramipexole was of 0.125 mg/d at 7 p. m., and it was increased every 3 days by 0.125 mg/d until a satisfactory control of symptoms was achieved or until side effects began to appear. At evaluation time therapy ranged from 0.25 to 0.50 mg/d. The subjective assessment of the global RLS severity was performed between 30 and 60 days (mean 39) after reaching the final dosage of pramipexole by using the IRLSSG Rating Scale [4]. This is a recently validated scale consisting in a clinician-administered questionnaire ranging from 0 to 40 points (1 to 10 points = mild, 11 to 20 points = moderate, 21 to 30 points = severe and 31 to 40 points = very severe). SIT was validated in 1998 as a polygraphic test able to identify and score PLMW [5]. During the test the patients were asked to sit at a 45-degree angle in bed with their legs outstretched, and were instructed not to move. Sleep was scored by a standard method; if any patient fell asleep he was awakened after 20 seconds of any stage of sleep [6]. Coleman’s criteria were used to score PLMW, whereas duration criterion was considered for any single movement that ranged from 0.5 to 10 seconds, because during wakefulness movements may often exceed 5 seconds [5, 7]. The following measures were made: Movement Index (MI = number of leg movements per hour of SIT), number of leg movements during the first 30 minutes of recording (MIF30), number of leg movements during the last 30 minutes of recording (MIL30), Lateralization Index (LI = left + right movements/MI), Mean Interval between Movements in seconds (MIM), Mean Duration of single movements in seconds (MD), the minute of appearance of first movement (Mst). According to Montplaisir et al. MI > 40 was considered abnormal [5]. Ten patients (mean age 61.2 ± 8.6 years; 5 females, 5 males) affected by primary RLS underwent SIT at baseline (without medication) and between 30 and 60 days (mean 46 days) after reaching the final dosage of pramipexole. Comparison between IRLSSG Rating Scale and SIT data, recorded before and after treatment, was made by using the paired-sample t-test. All 24 patients completed the study. The mean IRLSSG Rating Scale score was 22.6 (SD±6.3) at baseline, and significantly decreased to 11.3 (SD±6.5) between 30–60 days after therapy (Fig. 1). Moreover the mean MI also significantly decreased from 118.8 (SD±74.5) to 54.9 (SD±53.2). PLMW were most prevalent in the second half hour of SIT. Reduction in PLMW occurred mainly in the first 30 minutes (–55 %) as compared with the last 30 minutes (–47 %). Pramipexole significantly increased both the mean Mst and MIM, while MD and LI did not change with therapy (Tab. 1). Low doses of pramipexole have significantly improved the subjective symptoms of RLS. Patients reported that the improvement was achieved a few days after treatment, with a good compliance. Pramipexole also produced a significant reduction in PLMW, but LETTER TO THE EDITORS

Paraneoplastic Peripheral Neuropathy Associated With Anti‐hu Antibodies. A Clinical And Electrophysiological Study Of 20 Patients

Although paraneoplastic subacute sensory neuronopathy is the most frequent presentation of peripheral neuropathy in patients with anti‐Hu antibodies, other neuropathies have been reported. In order to investigate the clinical and electrophysiological manifestations of neuropathies associated with anti‐Hu antibodies, we conducted a retrospective study of 20 patients. For the electrophysiological study, each nerve was classified as normal, demyelinating, axonal/neuronal or axonal/ demyelinating. Peripheral neuropathy was the presenting symptom in 95% of patients. CNS and autonomic neuropathy were present in 40% and 30% of patients, respectively. The course of the neuropathy was acute, mimicking Guillain‐Barré syndrome in one patient (5%), and subacute (55%) or progressive (40%) in the others. Clinically, the neuropathy was sensory (70%), sensorimotor (25%) or motor (5%). At onset, symptoms were symmetrical (65%), asymmetrical (25%) or multifocal (10%). Pain was a predominant manifestation (80%). Amyotrophia and fasciculations were rare. The median Rankin's score was 2, three patients having an indolent form. Electrophysiology showed the axonal/neuronal pattern to be the most frequent (46.9% of studied nerves); an axonal/demyelinating or demyelinating pattern being seen in 18.3% and 4.9% of nerves, respectively. The axonal/neuronal pattern was more frequent in sensory nerves and the mixed axonal/demyelinating pattern more frequent in motor nerves (P < 0.01). A higher proportion of abnormal nerves correlated with a progressive course (P < 0.05) or a Rankin's score between 3 and 5 (P < 0.01). In patients with sensory neuropathy, 88.5% of sensory nerves were abnormal, mostly with an axonal/neuronal pattern. In addition, 47% of motor nerves were abnormal so that only four out of 14 patients with a clinically pure sensory neuropathy (28.6%) had an electrophysiological pattern typical of sensory neuronopathy. In patients with a sensorimotor neuro‐ pathy, 96.6% of sensory and 71% of motor nerves were abnormal. The only statistical difference between sensory and sensorimotor neuropathies was that patients with sensorimotor neuropathy had more frequent motor nerve involvement (P < 0.05) without differences concerning the distribution of the abnormal patterns. Needle neuromyography showed only limited evidence of motor neurone degeneration in both sensory and sensorimotor neuropathy. The present work shows that the typical clinical and electrophysiological pattern of subacute sensory neuronopathy is rarely encountered in patients with anti‐Hu antibody and that motor nerve involvement is frequently seen, even in the absence of a motor deficit. In addition to their potential pathophysiological involvement in the mechanism of the paraneoplastic neuropathy, these findings have practical consequences for the diagnosis of the disorder.

Paraneoplastic peripheral neuropathy associated with anti-Hu antibodies. A clinical and electrophysiological study of 20 patients.

Although paraneoplastic subacute sensory neuronopathy is the most frequent presentation of peripheral neuropathy in patients with anti-Hu antibodies, other neuropathies have been reported. In order to investigate the clinical and electrophysiological manifestations of neuropathies associated with anti-Hu antibodies, we conducted a retrospective study of 20 patients. For the electrophysiological study, each nerve was classified as normal, demyelinating, axonal/neuronal or axonal/demyelinating. Peripheral neuropathy was the presenting symptom in 95% of patients. CNS and autonomic neuropathy were present in 40% and 30% of patients, respectively. The course of the neuropathy was acute, mimicking Guillain-Barré syndrome in one patient (5%), and subacute (55%) or progressive (40%) in the others. Clinically, the neuropathy was sensory (70%), sensorimotor (25%) or motor (5%). At onset, symptoms were symmetrical (65%), asymmetrical (25%) or multifocal (10%). Pain was a predominant manifestation (80%). Amyotrophia and fasciculations were rare. The median Rankin's score was 2, three patients having an indolent form. Electrophysiology showed the axonal/neuronal pattern to be the most frequent (46.9% of studied nerves); an axonal/demyelinating or demyelinating pattern being seen in 18.3% and 4.9% of nerves, respectively. The axonal/neuronal pattern was more frequent in sensory nerves and the mixed axonal/demyelinating pattern more frequent in motor nerves (P < 0.01). A higher proportion of abnormal nerves correlated with a progressive course (P < 0.05) or a Rankin's score between 3 and 5 (P < 0.01). In patients with sensory neuropathy, 88.5% of sensory nerves were abnormal, mostly with an axonal/neuronal pattern. In addition, 47% of motor nerves were abnormal so that only four out of 14 patients with a clinically pure sensory neuropathy (28.6%) had an electrophysiological pattern typical of sensory neuronopathy. In patients with a sensorimotor neuropathy, 96.6% of sensory and 71% of motor nerves were abnormal. The only statistical difference between sensory and sensorimotor neuropathies was that patients with sensorimotor neuropathy had more frequent motor nerve involvement (P < 0.05) without differences concerning the distribution of the abnormal patterns. Needle neuromyography showed only limited evidence of motor neurone degeneration in both sensory and sensorimotor neuropathy. The present work shows that the typical clinical and electrophysiological pattern of subacute sensory neuronopathy is rarely encountered in patients with anti-Hu antibody and that motor nerve involvement is frequently seen, even in the absence of a motor deficit. In addition to their potential pathophysiological involvement in the mechanism of the paraneoplastic neuropathy, these findings have practical consequences for the diagnosis of the disorder.

Paraneoplastic anti-CV2 antibodies react with peripheral nerve and are associated with a mixed axonal and demyelinating peripheral neuropathy.

Subacute sensory neuronopathy with anti-Hu antibodies is the best-characterized paraneoplastic peripheral neuropathy associated with carcinoma. Anti-CV2 antibodies, another group of paraneoplastic antibodies, react with a 66-kd brain protein belonging to the family of Ulip/CRMP proteins. The manifestations associated with anti-CV2 antibodies include cerebellar degeneration, uveitis, and peripheral neuropathy. Some of these patients also have anti-Hu antibodies. We have compared the clinical, electrophysiological, and pathological characteristics of the peripheral neuropathy in 9 patients with anti-CV2 antibodies (3 of whom also had anti-Hu antibodies) and 12 patients with only anti-Hu antibodies. Data for patients with anti-Hu antibodies alone indicated subacute sensory neuronopathy. Patients with anti-CV2 antibodies had a mixed axonal and demyelinating sensory motor neuropathy that was sometimes superimposed on subacute sensory neuronopathy when both anti-CV2 and anti-Hu antibodies were present. Unlike anti-Hu antibodies, anti-CV2 antibodies reacted with peripheral nerve antigens, as shown by their ability to bind to a 66-kd protein in human and rat nerve on Western blot analysis and to immunolabel peripheral nerve axons and sensory neurons on immunohistochemical study.

Immunological mechanisms in paraneoplastic peripheral neuropathy.

PPN are not rare disorders and correspond to a wide range of diseases of the PNS, involving either the neuron cell body, the axon, or the myline sheath. Great progress has been achieved in the understanding of their pathophysiology. Today, the only demonstrated links between a tumor and a paraneoplastic neuropathy involve immunological mechanisms. Beside improving our knowledge of the machanisms of autoimmunity in relation to cancer, these immunological perturbations have proved to be very sensitive and specific diagnostic tools. The detection in the serum of a patient referred for neuropathy of one of the autoantibodies described earlier is the best way to diagnose the paraneoplastic origin of the neuropathy.

Carcinoma associated paraneoplastic peripheral neuropathies in patients with and without anti-onconeural antibodies

OBJECTIVEWhen to suspect a paraneoplastic disorder is a puzzling problem that has not recently been studied in a large series of patients referred for peripheral neuropathy.METHODSFrom 422 consecutive patients with...