Autonomic overactivity in patients with this syndrome is well described. Episodes of hypertension, tachycardia, and diaphoresis can be pronounced, as is excessive salivation, pupillary dilation, and other signs of sympathetic dysfunction, individually or concurrently.
Dalmau and colleagues have identified the target of the antibody as the subunit of the NMDA receptor, NR1. There is a reasonable degree of certainty that the antibody is pathogenic.
Treatment A premium is attached to early identification of this disorder and rapid removal of the ovary containing the teratoma or resection of another inciting tumor. Vaginal ultrasound may be necessary for the demonstration of the ovarian lesion but a more extensive examination such as CT or PET is needed for the detection of other tumors. Improvement after tumor removal is associated with subsidence of the antibody titer over many weeks and a good outcome occurs in a majority of cases. Decisions regarding oophorectomy are difficult in view of reducing fertility in young women.
It has become apparent that a fair proportion of cases with circulating anti-NMDA antibody do not have a tumor that is detectable and immune treatments such as intravenous gamma globulin may then be used. It is reasonable to start these same immune treatments while awaiting tumor surgery in cases that are highly symptomatic.
Paraneoplastic Sensory Neuronopathy (Ganglionopathy) (See Also Chap. 43)
This is a distinctive syndrome that is associated in most cases with the anti-Hu antibody. It should be emphasized that a nondescript, mainly sensory neuropathy is a more common accompaniment of systemic cancer, and it may or may not be associated with the anti-Hu antibody. As discussed further in Chap. 43, a sensory polyneuropathy from chemotherapeutic agents, notably the platinum-based ones and vincristine, also needs to be distinguished from the anti-Hu neuropathy syndrome.
The sensory neuronopathy and neuropathy were first described by Denny-Brown in 1948 and are notable because they served to introduce the modern-day concept of paraneoplastic neurologic disease. The initial symptoms in both processes are numbness or paresthesias, sometimes painful, in a limb or in both feet. There may be lancinating pains at the onset. Over a period of days in some cases, but more typically over weeks, the initially focal symptoms become bilateral and may spread to all limbs and their proximal portions and then to the trunk. It is this widespread and proximal distribution and the involvement of the face, scalp, and often the oral and genital mucosa that mark the process as a sensory ganglionitis and radiculitis and when subacute are highly suggestive of a paraneoplastic process.
As the illness progresses, all forms of sensation are greatly reduced, resulting in disabling ataxia and pseudoathetoid movements of the outstretched hands. The reflexes are lost, but not always at the outset, and strength is relatively preserved. Autonomic dysfunction—including constipation or ileus, sicca syndrome, pupillary areflexia, and orthostatic hypotension—is sometimes associated. Also, a virtually pure form of peripheral autonomic failure has been recorded as a paraneoplastic phenomenon (paraneoplastic dysautonomia). One of our patients with sensory neuronopathy had gastric atony with fatal aspiration after vomiting and another died of unexpected cardiac arrhythmia. Very early in the illness, the electrophysiologic studies may be normal, but this soon gives way to a loss of all sensory potentials, sometimes with indications of a mild motor neuropathy.