P/Q‐type voltage‐gated calcium channel antibodies in paraneoplastic disorders of the central nervous system

Whether P/Q‐type voltage‐gated calcium channel (VGCC) antibodies are present in the serum of patients with paraneoplastic syndromes other than the Lambert–Eaton myasthenic syndrome (LEMS) and tumors other than small‐cell lung cancer (SCLC) is controversial. Using a commercially available radioimmunoprecipitation assay kit, we examined the sera of 93 patients with paraneoplastic syndromes of the central nervous system (CNS), including 27 patients with paraneoplastic cerebellar degeneration (PCD) associated with tumors other than SCLC and 66 SCLC patients with paraneoplastic encephalomyelitis and sensory neuronopathy (PEM/SN). All PCD sera from patients with tumors other than SCLC were negative for P/Q‐type VGCC antibodies. Eight of 66 (12%) SCLC patients with PEM/SN had P/Q‐type VGCC antibodies; 4 had LEMS and the other 4 had no symptoms of LEMS or they were overlooked and, therefore, not examined electrophysiologically. In patients with paraneoplastic syndromes of the CNS, the detection of P/Q‐type VGCC antibodies supports the diagnosis of LEMS; in our series, only 6% of patients with SCLC and PEM/SN may have had a false positive antibody result, or undiagnosed LEMS. © 1999 John Wiley & Sons, Inc. Muscle Nerve 22: 119–122, 1999     

Complicated paraneoplastic neurological syndromes: a report of two patients with small cell or non-small cell lung cancer

Paraneoplastic neurological syndromes are frequently associated in patients with small cell lung cancer (SCLC) and antineuronal antibodies are involved in the autoimmune mechanism. Multiple syndromes are sometimes complicated in a single patient with SCLC. However, little is known about non-SCLC-associated neurological manifestations. We report two patients with complicated paraneoplastic neurological syndromes. Patient 1 showed paraneoplastic limbic encephalitis (PLE), paraneoplastic sensory neuropathy (PSN) and Lambert-Eaton myasthenic syndrome (LEMS) associated with SCLC. Patient 2 developed opsoclonus-ataxia and probable PLE associated with non-SCLC. Analysis of various antineuronal antibodies revealed that anti-Hu and P/Q-type voltage-gated calcium channel (VGCC) antibodies were positive in Patient 1 but any antibodies were not in Patient 2. Brain MRI demonstrated high intensity signals in temporal lobes particularly on fluid-attenuated inversion recovery (FLAIR) or diffusion-weighted images. These findings suggest that complicated paraneoplastic neurological syndromes occur in non-SCLC as well as SCLC and that unidentified antineuronal autoantibodies may underlie the pathophysiology.     

Anti-glial nuclear antibody: marker of lung cancer-related paraneoplastic neurological syndromes

We describe a new antibody, called anti-glial nuclear antibody (AGNA), in patients with paraneoplastic neurological syndromes (PNS) and small-cell lung carcinoma (SCLC). AGNA was initially identified in 24 sera of our archives by immunohistochemistry on rat cerebellum. AGNA positive sera showed a characteristic nuclear staining of the Bergmann glia in the Purkinje cell layer. Immunoblots and probing a cerebellar expression library with AGNA sera did not identify the antigen. Twenty of the 24 patients with AGNA had PNS and all but two had lung cancer. AGNA was identified in 13/113 (11.5%) patients with SCLC compared with 0/122 with other types of cancer (p<0.0001). The frequency of AGNA was not higher than expected for the presence of SCLC in the different PNS subtypes except in LEMS (p=0.0002). AGNA was present in 13/30 (43%) of LEMS patients with SCLC, compared with 0/19 of LEMS patients without cancer (p=0.0006). We conclude that the recognition of AGNA is helpful since this antibody is found in PNS associated with SCLC, particularly LEMS, in which other onconeural antibodies are absent.     

Lambert-Eaton syndrome antibodies: reaction with membranes from a small cell lung cancer xenograft

Lambert-Eaton myasthenic syndrome (LEMS) is a paraneoplastic autoimmune disorder caused by an IgG-mediated reduction in number of presynaptic voltage-gated calcium channels (VGCC) at the neuromuscular junction. In at least 50% of cases, the stimulus for antibody production may be VGCC on small cell lung cancer (SCLC). In this study membranes isolated from a human small cell lung cancer xenograft (Mar), that bound [3H]PN200-110, a VGCC antagonist, were subjected to Western blotting using plasma from 12 LEMS patients and eight controls. Although one band recognised by 3/12 LEMS IgGs might be associated with the VGCC, a number of other proteins were recognised both by LEMS plasma, and by plasma from patients with other disorders. The results illustrate the difficulties found using Western blotting with autoimmune plasma to identify specific polypeptides in a crude antigen preparation.     

Lambert-Eaton myasthenic syndrome

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease of the neuromuscular junction, and approximately 60% of patients with LEMS have a tumor, mostly small cell lung cancer (SCLC), as a paraneoplastic neurological syndrome. The clinical data of Japanese patients in the present study are as follows: the ratio of men to women is 3: 1 (mean age, 62 years; age range, 17-80 years). Of the patients with LEMS, 61% have SCLC, whereas the others do not have cancer. Clinical symptoms are usually characterized by proximal muscle weakness and dysautonomia. In less than 10% of the patients, there are signs of cerebellar dysfunctions (paraneoplastic cerebellar degeneration with LEMS; PCD-LEMS), and these are usually associated with SCLC. The diagnosis can be confirmed by detecting a specific antibody in a radioimmunoprecipitation assay and finding reduced amplitude of compound muscle action potential that increases by over 100% after maximum voluntary activation or 50Hz of nerve stimulation. The pathomechanism of LEMS is characterized by impaired transmission across the neuromuscular junction because of autoantibodies directed against the presynaptic P/Q-type voltage-gated calcium channels (P/Q-VGCCs). Histopathologic evaluation of the cerebellum in patients with PCD-LEMS showed a reduced number of P/Q-type VGCCs in the molecular layer. Therefore, it was hypothesized that P/Q-VGCC antibodies may induce cerebellar dysfunction after entering the CNS in patients with PCD-LEMS. Specific tumor therapy in patients with LEMS as well as cancer often improves the neurologic deficit. Tumor removal is the primary treatment for LEMS. If the result of the primary screening is negative, screening should be repeated after 3-6 months and thereafter every 6 months for up to 2 years. Most patients benefit from 3, 4-diaminopyridine administered with pyridostigmine. In those with severe weakness, intravenous gamma globulin (IVIg) or plasmapheresis confers short-term benefits. Prednisone when administered alone or in combination with immunosuppressive drugs can achieve long-term control of the disorder.     

Paraneoplastic cerebellar degeneration. III. Cerebellar degeneration, cancer, and the Lambert-Eaton myasthenic syndrome.

We studied nine patients with a subacute onset of a pancerebellar syndrome. Six had known cancer (three small-cell carcinoma of the lung [SCLC], one metastatic small-cell carcinoma, one small-cell carcinoma of the prostate, and one non-Hodgkin's lymphoma). Six of eight who had neurophysiologic testing, including the three patients without detectable cancer, had coexistent Lambert-Eaton myasthenic syndrome (LEMS). In two of the patients, LEMS was discovered only by neurophysiologic testing. We looked for anti-Purkinje cell autoantibodies in all patient's sera and in four patients' CSF. We also looked for autoantibodies to voltage-gated calcium channels (VGCCs) in seven patients' sera and two patients' CSF, using the 125I-omega-conotoxin radioimmunoassay. We were unable to detect anti-Purkinje cell autoantibodies in any patients' serum or CSF. However, there were raised titers of anti-VGCC autoantibodies in five of seven patients' serum, including one patient with SCLC who did not have LEMS, and in the CSF of one of two patients. We conclude that the frequency of presentation of a pancerebellar syndrome with LEMS is higher than expected by chance and is usually associated with cancer. In some of these patients, LEMS may be clinically occult. The presence of LEMS and raised titers of anti-VGCC autoantibodies in some patients with subacute cerebellar degeneration is suggestive of an autoimmune etiology even though anti-Purkinje cell antibodies could not be detected. Anti-VGCC autoantibodies are not confined to LEMS. They may be found at high titer in CSF as well as serum.     

Autoantibodies in paraneoplastic syndromes associated with small-cell lung cancer

An antineuronal autoantibody has been identified in serum from 14 patients, 8 women and 6 men, with small-cell lung carcinoma (SCLC) and a neurologic disorder. Neurologic symptoms began prior to diagnosis of the SCLC in 12 patients. The dominant neurologic disorder was a subacute sensory neuronopathy (SSN) in eight patients, SSN plus lower motor neuron weakness (2 patients), SSN plus autonomic neuropathy (1 patient), cerebellar ataxia (1 patient), myelopathy (1 patient), and multifocal nervous system disease (encephalomyelitis) in one patient. The presence of the same autoantibody in patients with SSN, encephalomyelitis, and autonomic neuropathy suggests that these diseases are different manifestations of the same nosologic process. With one exception, treatment of the tumor, immunosuppressive drugs, and plasmapheresis did not influence the course of the neurologic illness. The autoantibody was not identified in sera from more than 400 controls subjects, including patients with SSN associated with other tumors, SSN without malignancy, other paraneoplastic syndromes, and SCLC without neurologic symptoms. The autoantibody is a highly specific marker of the paraneoplastic syndromes associated with SCLC and its detection in a patient not known to have cancer should prompt a careful search for SCLC.     

P/Q-type calcium channel antibodies, Lambert-Eaton myasthenic syndrome and survival in small cell lung cancer

To assess the survival impact of the presence of P/Q-type calcium channel antibodies in patients with small cell lung carcinoma (SCLC), we examined the frequency of the antibodies and Lambert-Eaton myasthenic syndrome (LEMS) in 148 consecutive patients with SCLC, and in 30 patients with paraneoplastic cerebellar degeneration and SCLC, and studied their relation with survival. In both series, only patients with LEMS had a remarkably long survival, whereas presence of the antibodies without LEMS did not result in a better prognosis.     

Sensory neuronopathy and small cell lung cancer: antineuronal antibody reacting with neuroblastoma cells

The anti-Hu antibody is associated with a paraneoplastic subacute sensory neuronopathy (SSN) described in cases of small cell lung cancer (SCLC). The Hu antigen is a pan-neuronal nuclear antigen with a molecular weight of 35–40 kDa. In this study we demonstrated the presence of the paraneoplastic Hu antigen in different neuroblastoma cell lines. We showed that by indirect immunocytochemistry the serum of patients with SSN and SCLC reacts with the nuclei of neuroblastoma cell lines SKN-SH and LAN-1. Western blot analysis of nuclear extracts from neuroblastoma cell lines SKN-SH, IMR-32 and LAN-1 confirmed the presence of the Hu antigen in these neuroblastoma cell lines. By comparing the immunocytochemical method and the Western blot analysis we were able to determine that the Western blot analysis was a more sensitive test. Screening of the sera of a large population (a total of 122 patients with SCLC, 17 with paraneoplastic disorders as well as 121 controls with other neurological disorders) was performed and showed all 5 of the patients with SSN and SCLC to be positive for the anti-Hu antibody, whereas only 11 of the 122 SCLC patients and none of the controls were positive, thereby suggesting that this test has a very high degree of sensitivity.     

Lambert-Eaton syndrome: clinical and electrophysiological study of 18 cases associated with lung cancer]

The clinical and electrophysiological data of 18 consecutive adult patients with paraneoplastic Lambert-Eaton myasthenic syndrome (LMES) have been reviewed. The cancer associated with LEMS was small-cell lung carcinoma (SCLC) in 15 cases and epidermoid lung carcinoma in 3 cases. The main clinical neurological features were proximal lower limb weakness (100%), depressed tendon reflexes (94%) and dryness of the mouth (66%). The results of repetitive nerve stimulation (RNS) were not statistically different in the paraneoplastic LEMS group and in a group of 6 LMS patients in whom no carcinoma had been detected. Low-amplitude compound muscle action potential (CMAP) was present in all cases; decremental response at low stimulation rates was present in 13/15 cases. An abnormal incremental response at high stimulation rates was observed in all cases. A close correlation between CMAP amplitude and clinical condition was found in 4 cases during the long-term follow-up. In one patient the RNS electrical pattern could be misinterpreted as myasthenia gravis in only one muscle tested. We underline the usefulness of a 50 Hz stimulation during 4 seconds to establish the diagnosis unequivocally, and that of post-exercise facilitation in routine detection among an SCLC population. Our results suggest that CAMP amplitude and RNS test could be used to evaluate the short-term improvement of LMS under treatment and, in some cases, for the long-term follow-up. The infraclinical axonal neuropathy detected in 8 patients probably was another associated autoimmune paraneoplastic complication.     

Lambert-Eaton myasthenic syndrome has a more progressive course in patients with lung cancer

We studied whether a difference exists in the development of symptoms of the Lambert-Eaton myasthenic syndrome (LEMS) between patients with or without small cell lung cancer (SCLC). We assessed symptoms in 38 LEMS patients, 13 with SCLC, by interviewing them using a structured checklist, backed up by a review of their clinical records, and compared the frequency and time scale of symptoms during the course of LEMS. Bulbar (87%) and autonomic (95%) symptoms for the whole group were more common than reported in the literature. Frequencies of symptoms did not differ significantly between patients with and without SCLC, but symptoms in patients with SCLC appeared within a shorter time-frame, indicating a more rapid clinical course. The presence of a particular symptom associated with LEMS did not predict the presence of SCLC, but in patients with rapidly progressive LEMS the possibility of underlying lung cancer should be of particular concern.     

The epidemiology of myasthenia gravis,Lambert-Eaton myasthenic syndrome and their associated tumours in the northern part of the province of South Holland

We studied the epidemiology of myasthenia gravis (MG) and the Lambert-Eaton myasthenic syndrome (LEMS), and their association with small cell lung carcinoma (SCLC) and thymoma, in a well defined region of the Netherlands. Available data on all the patients with MG, LEMS, thymoma or SCLC living between 1 January 1990 and 31 December 1999 in the northern region of South Holland, with a population of 1.7 million inhabitants, were evaluated. A total of 202 patients with MG (20 with thymoma) and ten patients with LEMS (seven with SCLC) were identified. LEMS was 46 times less prevalent (2.32 x 10(-6)) than MG (106.1 x 10(-6)), whereas the annual incidence rate of LEMS was 14 times lower (0.48 x 10(-6)) than of MG (6.48 x 10(-6)), reflecting the poor survival of LEMS patients with SCLC. SCLC was diagnosed in 1593 patients, seven (0.44 %) of whom developed LEMS. Mean age at diagnosis of SCLC was significantly lower in SCLC patients with LEMS (p = 0.006). A thymoma was diagnosed in 32 patients, of whom the ten patients with MG (31 %) had a younger age at diagnosis of thymoma than the patients without MG (p = 0.27). This study confirms the increasing prevalence of MG over the last few decades as reported by others, and underscores the relative rarity of LEMS. The frequency of LEMS in our patients with SCLC was lower than reported in previous studies. In patients with a SCLC or thymoma, the tumour was diagnosed at younger age in those who had the associated myasthenic syndrome.     

SOX1 antibodies in sera from patients with paraneoplastic neurological syndromes

Objectives – SOX1 antibodies have been described in patients with Lambert–Eaton myasthenic syndrome (LEMS) in association with voltage‐gated calcium channel antibodies as serological markers of small cell lung cancer (SCLC). This study was aimed to screen for additional SOX1 autoimmunity in onconeural antibody‐positive sera from patients with paraneoplastic neurological syndromes (PNS) other than LEMS and to identify the clinical–immunological profile and associated tumours of patients with coexisting SOX1 antibodies. Methods– We retrospectively analysed sera from 55 patients with different PNS positive for well‐characterized antineuronal antibodies for the presence of SOX1 antibodies by recombinant ELISA and immunoblot. Results– Eight (14.5%) patients showed additional SOX1 antibodies in the ELISA and the recombinant immunoblot. Five patients had coexisting Hu antibodies, while the other three showed coexisting CV2/CRMP5, amphiphysin, and coexisting CV2/CRMP5 and Hu antibodies, respectively. PNS included (partially overlapping) subacute sensory neuropathy, subacute sensorimotor neuropathy, cerebellar degeneration, brainstem encephalitis, encephalomyelitis and limbic encephalitis. No tumour was detected in two patients, while the others had lung cancer (four SCLC and two non‐SCLC). One patient showed SOX1‐specific intrathecal antibody synthesis. Conclusions– We describe SOX1 reactivity for the first time overlapping with CV2/CRMP5 and amphiphysin antibodies. SOX1 reactivity is predominantly associated with Hu antibodies and SCLC, but can occur also in other types of lung cancer. Neurological manifestations present in patients with coexisting SOX1 antibodies and well‐characterized antineuronal antibodies do not differ from those previously described in patients positive for antineuronal antibodies but no SOX1‐specific anti‐glial antibodies.     

Paraneoplastic antibodies against HuD detected by a sensitive radiobinding assay

Abstract. Patients with paraneoplastic encephalomyelitis(subacute sensory neuronopathy) (PEM/SSN), most commonly associated with small-cell lung cancer (SCLC), frequently harbor Hu antibodies, which are usually detected by indirect immunohistochemistry or immunoblot. We developed a new radioimmunobinding assay to detect Hu antibodies based on in vitro transcribed and translated (ITT) HuD. High levels of Hu antibodies were detected in all seven PEM/SSN patients tested, but not in any of 15 patients with other paraneoplastic syndromes, 20 patients with Sjögrens syndrome, 20 patients with miscellaneous tumors and 99 of 100 blood donors. One of the blood donors had low levels of Hu antibodies. The radiobinding assay detected Hu antibodies in 45 of 191 (24%) patients with SCLC, in comparison with immunofluorescence and immuno dot blot, where only 34 of 191 (18%) were detected. All patients with Hu antibodies detected by immunofluorescence and immuno dot-blot were also positive by the radioimmunobinding assay. The results demonstrate that this assay is very specific and sensitive for the detection of Hu antibodies.     

A Lambert-Faton myasthenic syndrome and subacute cerebellar degeneration with a favorable clinical course after resection of small-cell lung cancer]

A case of Lambert-Eaton myasthenic syndrome (LEMS) and subacute cerebellar degeneration (SCD) was associated with small-cell lung cancer (SCLC). The patient, a 52-year-old man, who had noticed impotence one year previously, began to have ataxic gait, scanning speech and thirst progressing for 3 months, followed by weakness of the lower limbs, bilateral blepharoptosis, and double vision. Electromyographic studies showed low amplitude of compound muscle action potential (CMAP) and waxing phenomenon in high frequency stimulation of the ulnar nerve. A chest x-ray showed a mass lesion in the left hilar region, and small cell lung cancer was diagnosed on the basis of biopsy specimens. Anti-voltage-gated calcium channel (VGCC) antibody was positive. Anti-Yo and anti-Hu antibodies were negative. The patient was treated by lobectomy and chemotherapy, which resulted in improvement in the LEMS and SCD. Anti-VGCC antibody, the CMAP amplitude, and waxing phenomenon were improved. Operable cases of SCLC are rare. But we propose that anti-neoplastic treatment including resection of the tumor is the first choice for the treatment of paraneoplastic syndrome associated with SCLC.     

Phenotypic and neuropathologic heterogeneity of anti-Hu antibody-related paraneoplastic syndrome presenting with progressive dysautonomia: report of two cases

The anti-Hu antibody (HuAb) is directed against RNA-associated neuronal proteins and is known to cause paraneoplastic encephalomyelitis/sensory neuronopathy syndrome mostly when associated with small cell lung cancer (SCLC). Paraneoplastic encephalomyelitis/sensory neuronopathy syndrome with concurrent autonomic neuropathy has been reported to occur in paraneoplastic syndromes, although its occurrence concomitant with acute pandysautonomia is less frequent. The authors describe the clinical, neuropathologic, and serologic features of two cases with an anti-Hu-related paraneoplastic syndrome presenting with progressive autonomic neuropathy. Both patients showed features of dysautonomia, including postural dizziness, abdominal pain, and diarrhea, and symptoms of sensory neuropathy. Investigations disclosed severe sensory and autonomic neuropathy and positive HuAb titers. The disease of patient 1 had a very rapid progression, and the patient died of cardiac arrest within 2 months of the onset of symptoms. The autopsy revealed SCLC. In contrast, the disease of patient 2 had a less aggressive course. An extensive tumor search disclosed SCLC only 28 months after onset of symptoms, and the patient died 1 month later of cardiorespiratory arrest. Autopsies in both cases showed inflammation involving the intermediolateral columns and the dorsal root ganglia. These two cases illustrate the association of early dysautonomia with HuAb-related paraneoplastic syndrome and the variations of clinical, neuropathologic, and serologic findings in these types of cases.     

HLA and smoking in prediction and prognosis of small cell lung cancer in autoimmune Lambert-Eaton myasthenic syndrome

Patients with small cell lung cancer (SCLC) survive longer if they have the antibody-mediated Lambert-Eaton myasthenic syndrome (LEMS), making this autoimmune disorder a prototype disease for studying cancer immunosurveillance. Patients with nontumor LEMS (NT-LEMS) never develop SCLC but are otherwise indistinguishable clinically. Therefore, we have compared immunogenetic factors in SCLC-LEMS and NT-LEMS and studied their role in the pathogenesis of LEMS and survival from SCLC. In 48 British and 29 Dutch Caucasian LEMS patients, we studied clinical symptoms, antibody titers, HLA types and alleles at six nearby located microsatellite loci. Highly significant associations were found in NT-LEMS, which appeared strongest with HLA-B8, but also involved HLA-DQ2, -DR3 and six flanking microsatellite alleles. SCLC-LEMS patients were not different from controls. Smoking was a strong predictor of SCLC. In contrast, HLA-B8 positivity correlated with a decreased risk of SCLC even among the smokers. Moreover, in SCLC-LEMS patients, HLA-B8 positivity correlated with prolonged survival after LEMS onset. We propose that two distinct immunopathogenetic routes can lead to one clinically and serologically indistinguishable autoimmune myasthenic syndrome. HLA-DR3-B8 is strongly associated with LEMS in nontumor patients only. In other LEMS patients, SCLC apparently provides a powerful autoimmunogenic stimulus that overrides HLA restrictions in breaking tolerance to calcium channels. Moreover, negativity for HLA-B8 combined with smoking behavior points more strongly to an underlying SCLC and predicts a worse prognosis in SCLC-LEMS patients.     

Lambert-Eaton肌无力综合征与癌

目的　 Lambert-Eaton肌无力综合征 (LEMS)临床少见。此报告旨在增进人们对这一综合征的认识。方法　对 2 3例 LEMS患者的临床资料做回顾性分析。结果　全组 2 3例 ,伴癌者 1 9例 (83 % ) ,其中小细胞肺癌(SCLC) 1 5例。首发症状以双下肢无力最常见 (5 2 % )。随访期间有颅神经受累 (61 % )、上肢无力 (70 % )、下肢无力 (1 0 0 % )、自主神经症状 (3 0 % )、腱反射减低 (87% )。高频 (2 0～ 5 0 Hz)重复神经电刺激波幅递增 1 0 0 %～71 8% ,平均增 2 82 %。有 1 5例 (79% )肌无力症状早于肺部症状平均 4.5个月。抗肿瘤治疗 1 2例 ,有 8例 LEMS症状显著改善或消失。结论　 LEMS与癌有显著相关倾向 ,尤其与 SCLC更明显。对 40岁以上男性 LEMS患者应积极寻找潜在的恶性肿瘤     

Associated autoimmune diseases in patients with the Lambert-Eaton myasthenic syndrome and their families

Abstract. In view of the clustering of autoimmune diseases (AIDs), we studied the frequency and nature of additional AIDs in patients with the Lambert-Eaton myasthenic syndrome (LEMS) and their family members, in both small cell lung carcinoma (SCLC) related and non-tumour (NT) related cases. Additional AIDs in patients with LEMS were assessed by interviewing the patient and studying the medical record. Family histories up to second-degree family members were established by interviewing patients, controls and family members. Forty-four patients with LEMS were assessed, of whom eighteen (41%) had SCLC. In the NT group seven patients (27%) had an additional AID, in the SCLC group two (11 %) (p=0.20). Thyroid disorder (five patients) and insulin dependent diabetes mellitus (two patients) were the most common AIDs. AIDs were significantly more frequent in families of patients with NT-LEMS (64%) than in control families (27%) (p=0.002), which was not found in SCLC-LEMS (36%, p=0.53). Affected family members were linked to the NT-LEMS patient through the maternal line in all cases. In conclusion, AIDs were more frequently found in LEMS patients without a tumour and their families, which could not be shown for SCLC-LEMS. This suggests that NT-LEMS shares immunogenetic factors with other AIDs. In families of NT-LEMS, a remarkable preponderance of maternal inheritance was seen, as has been reported previously in myasthenia gravis.     

Intravenous immunoglobulin treatment in paraneoplastic neurological syndromes with antineuronal autoantibodies.

OBJECTIVE: To evaluate the effect of intravenous high dose human immunoglobulin (IVIg) therapy on the clinical course and autoantibody titres of patients with neurological paraneoplastic syndromes. METHODS: Twenty two patients with paraneoplastic encephalomyelitis and sensory neuronopathy syndrome associated with anti-Hu antibodies (18) or paraneoplastic cerebellar degeneration (PCD) with anti-Yo antibodies (four), were treated with 1-26 (mean 5.8) cycles of IVIg. The Rankin scale was used to evaluate the response. RESULTS: The only serious toxicity was one case of haemolytic anaemia. Twenty one patients were evaluable for therapeutic response. One patient, with subacute sensory neuronopathy (SSN), improved for at least 15 months, 10 remained stable (eight with anti-Hu and two with anti-Yo antibodies), and 10 deteriorated (eight with anti-Hu and two with anti-Yo antibodies). In seven of the 10 patients who stabilised, the syndrome had already made a plateau when the treatment was started but three patients (one with anti-Hu and two with anti-Yo antibodies) who had still been progressing stabilised for six, eight, and more than 48 months, including one patient with SSN who achieved stabilisation when the neurological dysfunction was only moderate (Rankin scale = 3). Another patient with SSN and initial stable response worsened when IVIg was reduced and improved when it was increased. No significant predictive factors of outcome could be identified but improvement or stabilisation was more frequent in patients with isolated involvement of the peripheral nervous system (62%) than in patients with evidence of CNS damage (37%) at the onset of treatment. Stabilisation in patients with CNS involvement was only achieved when the neurological dysfunction was already severe (Rankin scale > 3). The titres of autoantibodies did not change significantly. CONCLUSION: Treatment with IVIg at the doses given in the present protocol was not effective in paraneoplastic CNS syndromes associated with antineuronal antibodies. The role of this regime in the treatment of SSN should be further evaluated.