Bilateral Tonic Pupils with Evidence of Anti-Hu Antibodies as a Paraneoplastic Manifestation of Small Cell Lung Cancer

Abstract

Introduction: Ophthalmological manifestations of systemic malignancies can be either direct, metastatic or paraneoplastic. The latter are remote effects of carcinoma, often caused by autoantibodies. Ophthalmological manifestations include cancer-associated retinopathy, melanoma-associated retinopathy, opsoclonus-myoclonus syndrome or motility disorders due to effects on the neurological system. A unilateral tonic pupil is usually a benign finding but has also been described in the context of paraneoplastic syndromes, in some cases associated with anti-Hu antibodies. Case Reports: The authors describe 2 patients with bilateral symptomatic tonic pupils due to a paraneoplastic syndrome. Both patients had been treated for small cell lung cancer and had evidence of anti-Hu antibodies (autoantibodies against nuclei of neural cells) in serum and cerebrospinal fluid. Both had typical pupillary findings and hypersensitivity to diluted pilocarpine. The first patient also had sensory neuronopathy, the second affection of several cranial nerves. Discussion: To the best of our knowledge, to date no case of bilateral tonic pupils has been published due to a paraneoplastic disorder with evidence of autoantibodies. This is surprising, as it is probable that autoantibodies in paraneoplastic disorders affect both ciliary ganglions in a similar way.

Paraneoplastic neurological syndromes

“…SSN, LE and cerebellar ataxia are the most common clinical syndromes. The autonomic nervous system is affected in 30% of the patients (orthostatic hypotension, urinary retention, pupillary abnormalities [51], impotence and dry mouth). Most of the patients present Hu-Ab, CV2-Ab or amphiphysin-Ab [12,21,31,52].…”

Reversible Paraneoplastic Tonic Pupil with PCA-Tr IgG and Hodgkin Lymphoma

“…3 Our patient had normal reflexes and thermoregulatory sweating, consistent with lack of widespread cholinergic involvement. 6 In our case, ageusia was not associated with olfactory impairment; improvements after chemotherapy suggest that it also represented a paraneoplastic manifestation. However, unilateral or bilateral tonic pupils have been described with underlying neoplasms, in the context of sensory ganglionopathy, 4 and as a limited dysautonomic accompaniment to Lambert-Eaton myasthenic syndrome.…”

“…3 Tonic pupils show supersensitivity to topical application of pilocarpine or other muscarinic agonists (not performed in our patient). 5 Adie tonic pupil most often occurs in the context of small-cell lung carcinoma associated with ANNA-1 (anti-Hu) 6 ; rarer associations include testicular seminoma, colon adenocarcinoma, and neuroblastoma. 3 Our patient had normal reflexes and thermoregulatory sweating, consistent with lack of widespread cholinergic involvement.…”

Paraneoplastic neurological complications of breast cancer

“…It can lead to limbic encephalitis (LE), brain stem syndromes, autonomic dysfunction, myelitis, chronic gastrointestinal pseudo-obstruction (CGP), cerebellar ataxia and sensory polyneuropathy (SSN). Limbic encephalitis, SSN and cerebellar ataxia are the most common clinical presentations and autonomic neuropathy is present in around 30 % of the patients [38, 107]. …”