In most of these cases, MRI shows abnormal T2 hyperintensity and edema in affected regions, though occasionally the brain appears normal. In severe cases, zones of focal necrosis may be seen. Odd seizures, including epilepsia partialis continua, have been observed with this disorder, but they must be uncommon. Sensory symptoms may be related to neuronal loss in the posterior horns of the spinal cord or the dorsal root ganglia as mentioned earlier and discussed further on.
Many patients with small cell lung cancer and any of the types of paraneoplastic encephalomyelitis have been found to harbor circulating polyclonal IgG antibodies (anti-Hu, or antineuronal nuclear antibody type 1 (ANNA 1)) that bind to the nuclei of neurons in many regions of the brain and spinal cord, dorsal root ganglion cells, and peripheral autonomic neurons. The antibodies are reactive with certain nuclear RNA-binding proteins. Cancers of the prostate and breast and neuroblastoma may rarely produce a similar antibody. The antibody titer is higher in the CSF than in the serum (as it is for the anti-Purkinje cell antibody, anti-Yo, in paraneoplastic cerebellar degeneration discussed further on), indicating production of antibody within the nervous system. Low titers of anti-Hu are found in approximately 15 percent of patients with small cell cancer who are neurologically normal, probably because these tumors have expressed only low levels of antigens that are recognized by anti-Hu. Antibodies to the voltage-gated potassium channel (VGKC) and its associated proteins leucine-rich glioma inactivated 1 (LGI 1) and contactin-associated protein 2 (CASPR 2) have been identified in patients with limbic encephalitis without, or less often with, cancer (Vincent et al and van Sonderen et al).
Treatment Beyond identification and treatment of an underlying malignancy in cases of paraneoplastic encephalitis, plasma exchange or intravenous gamma globulin is used, with variable clinical outcomes that most likely reflect the extent of irreversible neuronal loss.
Several unusual patterns have been observed from the effects of the anti-VGKC antibodies as well as antibodies to the associated proteins LGI 1 and CASPR 2. About half of patients with LGI 1 antibodies have faciobrachial dystonic seizures in addition to limbic encephalitis. VGKC and CASPR 2 antibodies are associated with peripheral motor hyperexcitability in addition to limbic encephalitis (discussed further in Chap. 46).
A form of paraneoplastic encephalitis that presents itself as an acute or subacute psychiatric syndrome consisting of some combination of hallucinations, panic, delusions, and incoherence, coupled with seizures, memory disturbance and hypoventilation was described by Vitaliani and colleagues in four women with ovarian teratoma. Many patients have a nondescript prodrome of malaise, fatigue, headache excessive sleepiness, or low fever. Dalmau and coworkers (2007) demonstrated that this syndrome is associated with antibodies against a component of the NMDA receptor. The teratoma in one of their patients was located in the mediastinum instead of the ovary and rare cases have occurred with small cell lung cancer, including in men. Dalmau’s series of 100 patients (2008) is instructive in that they were very predominantly women in their twenties with presentations or psychiatric or memory deterioration but a large number had dyskinesias, seizures, or hypoventilation. Almost all had several or dozens of white blood cells in the CSF, a majority had oligoclonal bands and MRI showed abnormal T2 hyperintensity in the medial temporal lobes, similar to the anti-Hu type of limbic encephalitis.