Paraneoplastic Syndromes of the CNS

PEM is one of the most frequent cancer-associated syndromes. This complex disorder usually affects several areas of the CNS. Cerebellar and brain stem disorders, as well as limbic encephalitis, are the most common clinical presentations of PEM [31, 32], Focal involvement of the sensorimotor cortex has been described in a few cases [33], and PEM may manifest as epileptic seizures or epilepsia partialis continua [33, 34], or as extrapyramidal symptoms [35], Two-thirds of the patients are affected in both the CNS and the peripheral nervous system. The predominant feature in more than half of these is SN [32, 36], hence the commonly used term is PEM/SN. Autonomic dysfunction is common in PEM/SN patients [36], often presenting as gastrointestinal dysmotility [37]. 

The most common malignancy associated with PEM is SCLC [32], but several other tumors have also been associated with PEM [32,38,39]. The Hu antibody is the most common associated antibody, but several other antibodies are found in isolated PEM (Table 1). In the majority of cases, PEM precedes the tumor diagnosis, but when the cancer is already acknowledged, PEM often predicts tumor progression or relapse [32]. 

The main pathological features of PEM/SN are inflammation, nonapop-totic neuronal loss, gliosis and cellular infiltrates [40, 41]. The distribution of 

The main features of LE are epileptic seizures and mental symptoms such as depression, personality changes, and cognitive dysfunction. The onset is usually subacute and progressive [43]. LE is the predominant feature in about 9% of PEM cases, and LE patients often exhibit additional symptoms from other CNS locations [44]. Not surprisingly, SCLC is found in about half of the LE patients, and in this group, most are Hu antibody positive [43]. 

The second most common tumor in LE is testicular germ cell cancer [43], and these patients usually harbor antibodies to the Ma2 protein. Antibodies to Ma2 antigen alone are usually associated with testicular cancer. Similar to many other onconeural antibodies, Ma2 is associated with clinical multi-focality. Many patients have symptoms of brain stem and hypothalamic dysfunction, and only one-fourth of Ma2 positive patients exhibit classical LE [45]. Patients with antibodies to the major antigen Ma2 and antibodies to Mai or Ma3 have different tumors [43, 46], and are more likely to have additional neurological signs [45], 

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