Anti‐myelin‐associated glycoprotein–negative distal acquired demyelinating symmetric neuropathy in association with a neuroendocrine tumor

We followed with interest the fascinating cases of antimyelin-associated glycoprotein (anti-MAG)–positive distal acquired demyelinating symmetric (DADS) neuropathy in studies by Ayyappan et al. and Galassi and Luppi. We would like to add to this stimulating debate on the relationship between neoplasia and DADS neuropathy. A 75-year-old woman was referred to our neurology service with a 4-month history of paresthesia affecting the hands and feet. She had a 2-year history of metastatic neuroendocrine tumor after an abdominal lymph node biopsy was strongly positive for CD56 and chromogranin. Cauda equina syndrome occurred shortly after diagnosis due to a metastatic deposit at S2. Neurological examination at this time revealed saddle anesthesia, lower limb weakness, and absent lower limb reflexes. A course of radiotherapy, steroids, and somatostatin analog treatment improved leg strength sufficiently for mobilization with a walking stick. Examination revealed no upper limb ataxia but mild lower limb heel–shin ataxia. Tandem walking was difficult. Speech was normal. There was a loss of vibration sensation up to the knees bilaterally, but joint position sense was preserved. Tendon stretch reflexes were absent throughout; power was normal in the arms and reduced proximally in the legs. Nerve conduction studies demonstrated unrecordable sensory nerve action potentials in the upper and lower limbs, with markedly prolonged distal motor latencies and reduced terminal latency indices, particularly in the upper limbs (Table 1). Blood tests, including anti-MAG/immunoglobulin M, anti–glutamic acid decarboxylase, anti-neuronal nuclei, anti-Hu, antiYo, anti–Purkinje cell, anti-CV2/CRMP-5, anti-PNMA2 (Ma/Ta), anti-Tr, voltage-gated calcium channel, and anti-ganglioside antibodies were all negative. Celiac serology was also negative. Magnetic resonance spectroscopy showed significant reduction of the N-acetylaspartate/ creatine (NAA/Cr) ratio from the vermis and right hemisphere but without cerebellar atrophy. Treatment with intravenous immunoglobulin produced no improvement, and her symptoms progressed. Treatment with 10 mg prednisolone led to symptomatic stabilization. Unfortunately, she died approximately 2 years after her neuropathy diagnosis due to metastatic disease, with no significant change in her neurological condition. Our conclusion at the time of diagnosis was that the anti-MAG–negative DADS neuropathy was paraneoplastic in nature. A third of DADS cases may be negative for anti-MAG antibodies, suggesting the antibody is a marker for disease, rather than being pathognomonic. Larue et al. reported 10 patients with anti-MAG–negative DADS neuropathy, 9 of whom had an associated hematological condition. Although the lack of paraneoplastic antibodies makes our association less firm, this may help explain the plateau in symptoms. It is also worth noting that antibodies are only present in around 50% of patients with paraneoplastic syndromes. Unfortunately, the palliative nature of the patient we described also precludes association by improvement after cancer treatment; by the criteria of Graus et al., our case would be considered “possible paraneoplastic.” Stabilization of the patient’s condition despite continuing malignant disease raises the possibility that the pathological process leading to the neuropathy was transient in nature. Overall, our experience leads to us to agree with Ayyappan et al., in their conclusion that DADS was associated with malignancy, and also with Galassi and Luppi, in their assertion that clinicians should maintain vigilance in neuropathies with a possible paraneoplastic association, including the DADS variant.