A Retrospective Study Of 28 Cases With Paraneoplastic Neurological Syndromes

Backgrounds Paraneoplastic neurological syndromes(PNS)are a diverse group of nervous system disorders,the cause of which is generally considered to be autoimmune response associated with malignant tumors.Previous studies have found that the onset of PNS is determined by personal immunity function,population characteristics,genetic factors and so on.So far,there have been only a few studies focusing on the clinical characteristics of Chinese Han population.This retrospective study was performed at General Hospital of Jinan Military Command,a single center from Shandong,aiming at analyzing the clinical features of PNS patients and providing a foundation for further study.Methods Medical records and follow-up data were intensively reviewed for 28 PNS patients between February 2011 and December 2014,including patient characteristics,clinical manifestations,laboratory tests,ancillary examinations,results of tumor screening and therapeutic methods.Well-characterized onconeural antibodies were evaluated by immunoblot and anti-N-methyl-D-aspartate receptor(anti-NMDAR)antibodies were examined by indirect immunofluorescence test.Results This study included a total of 28 patients who had been diagnosed with PNS.The median age of onset was 56 years(range,47-64 years),and the ratio of male to female was 2.5(71.4% for male and 28.6% for female).The onset was acute in 4 patients(14.3%)and subacute or chronic in the other 24 patients(85.7%).The most common clinical symptom was mild myasthenia.There were 21 cases with classical syndromes and 7 cases with non-classical syndromes.Sensory or motor peripheral neuropathy(7 cases,25.0%),Lambert-Eaton myasthenic syndrome(LEMS,6 cases,21.4%)and limbic encephalitis(5 cases,17.9%)were the three most common clinical syndromes.Among the 7 patients with sensory or motor neuropathy,there were 6 patients with sensorimotor neuropathy and 1 patient with sensory neuropathy.Electromyography(EMG)and repetitive nerve stimulation(RNS)were examined in the 6 patients with LEMS.All of them showed an decrease in compound muscle action potential(CMAP)amplitude at low-frequency(1-5Hz)RNS,while an increase in CMAP amplitude higher than 100% at high-frequency(50Hz)RNS.In all of the 5 patients with limbic encephalitis,electroencephalography(EEG)showed generalized slow-wave activities and inflammatory changes were found in cerebrospinal fluid(CSF).However,abnormal MRI signal was found in only two patients,while anti-NMDAR antibodies were positive in both serum and CSF of 3 patients.Evaluated tumor markers in serum were found in 44% of the patients,while both CEA and NSE had the highest positive rate.Abnormal onconeural antibodies were found in 40.7% of patients,and anti-Hu antibodies showed the highest positive rate.The positive rate of neither tumor markers nor onconeural antibodies had significant difference to the occurrence rate of primary tumors.Twenty-five(25/28,89.3%)patients exhibited nervous system lesions prior to occult tumors,while the other 3(3/28,10.7%)patients were diagnosed with cancer before neurological symptoms appeared.Tumours were found in a total of 21 patients,and the most common primary tumor was lung carcinoma(10 cases,47.6%),followed by gastrointestinal carcinoma(3 cases,14.3%).Six of the 10 patients with lung carcinoma were confirmed by pathological findings,and 4 of them were diagnosed with small cell lung cancer(SCLC).Although the occurrence rate of primary tumors was 81.3%(13/16)in classical syndromes and 75.0%(6/8)in non-classical syndromes,there was no significant difference between these two groups.Seventeen patients received anti-tumor and/or immunological therapy,the short-term quality of life was improved in 76.5% of the patients according to modified Rankin Scale(m RS)before treatment and at 1 month after treatment.The effective rate showed no significant difference between positive and negative groups of onconeural antibodies.Conclusions In the majority of PNS patients,the onset is subacute or chronic.Nervous system lesions are usually prior to occult tumours with complicated and various clinical manifestations.Whole-body screening should be performed in patients with clinical syndromes or positive onconeural antibodies.Those patients whose initial screening were negative should be long-term followed up.Short-term quality of life of the patients were improved after anti-tumor or immunological therapy,and there was no significant difference between the positve and negative groups of onconeural antibodies.