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Opsoclonus as a paraneoplastic manifestation of pancreatic carcinoma
  1. ARUN AGGARWAL,
  2. DAVID WILLIAMS
  1. Clinical Neurophysiology Unit, John Hunter Hospital, Locked Bag No1 Hunter, Region Mail Centre, Newcastle, NSW 2310, Australia
  1. Dr Arun Aggarwal, 3 D’aram Street, Hunters Hill, NSW 2110, Australia.

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Opsoclonus refers to involuntary, repetitive, and disorganised rapid congugate eye movements in all directions of gaze.1The diagnosis is usually a clinical one as, strictly speaking, it requires the demonstration of no intersaccadic interval on oculography.2 It may be associated with myoclonus of the trunk and limbs and cerebellar dysfunction.3 Opsoclonus can occur at any age, and has been associated with numerous neoplastic conditions, including neuroblastoma in children and breast, lung, uterine, ovarian, and thyroid carcinoma, and Hodgkin’s disease in adults.4-6 It has not previously been reported as a paraneoplastic phenomenon associated with carcinoma of the pancreas.

A 70 year old man, with a past medical history of hypertension and osteoarthritis, presented with a 10 day history of intermittent vomiting and increasing gait unsteadiness. He complained of vertigo, which was worse on standing, and ataxia, falling to the right. There was no history of headache, neck stiffness, photophobia, blurred vision, deafness or tinnitus. Prior to his presentation to hospital, he had been commenced on promethazine by his local doctor, with no effect on his symptoms. Other medications at this stage included perindopril and indapamide for hypertension, and aspirin. He drank only 20 g (two standard drinks) of alcohol a day and ceased smoking one year previously, after a 25 pack-year history. The only neurological signs on examination were nystagmus to the right on horizontal gaze and an unsteady gait. Brain CT showed age related cerebral atrophy, with no infarction. A provisional diagnosis of vestibular neuronitis was made, and he was started on 500 μg clonezapam twice a day.

Over the next four days, he remained nauseated and vertiginous. He then developed a left upper motor neuron facial weakness, left upper limb clumsiness, left ptosis, bidirectional nystagmus, and dysarthria. A provisional diagnosis of a brainstem infarct was made, intravenous heparin started, and a cerebral MRI organised. The next day, his pupils were small but equal and reactive, and there was a partial left lateral rectus palsy. His visual axes were disturbed with left over right hypertropia. Opsoclonus was present with involuntary, repetitive, and disorganised rapid congugate eye movements in all directions of gaze. Speech and swallowing were unimpaired, and there were no long tract signs. The cerebral MRI showed atrophic changes in the deep white matter of both hemispheres, but no other abnormalities.

One week later he was still nauseated, and had developed past pointing on the right more than the left, with an action tremor of his hand. He now had a complete left lateral rectus palsy and the left upper motor neuron facial weakness had recurred. Opsoclonus was still evident. Power and deep tendon relexes of his upper limb were normal.

A lumbar puncture showed a CSF protein of 0.66 g/l, with 30 × 106 mononuclear cells and no polymorphonuclear cells. Paraneoplastic antibodies were not detected in the serum or in the CSF.

The patient’s overall condition deteriorated over the next few days and he required nasogastric feeding. Episodes of respiratory distress, possibly as a result of aspiration, became more frequent and he died two days later.

A postmortem disclosed an occult 3 cm multiloculated cyst in the tail of the pancreas. The morphological diagnosis was primary large duct adenocarcinoma of the pancreas. There was also a 6 cm subcapsular hepatic nodule consistent with a metastasis from a pancreatic primary. There was no macroscopic evidence of cerebral haemorrhage, infection, or infarction. Microscopically, there was perivascular lymphocyte cuffing in the upper medulla, pons, midbrain, thalamus, and hippocampus, with some microglial proliferation and gliosis. This finding was thought to be consistent with a paraneoplastic meningoencephalitis.

We think that this is the first case to be reported in the literature of a paraneoplastic opsoclonus syndrome secondary to carcinoma of the pancreas. The syndrome has, however, been reported in association with other malignancies. Opsoclonus is considered to be due to an abnormality of omnipause neurons in the pontine paramedian reticular formation (PPRF), which are involved in the tonic inhibitory control of horizontal and vertical saccadic eye movements.7 The actual site may be within the PPRF or in descending pathways to the PPRF through the midbrain.

The patient had a macroscopically normal pons, midbrain, and cerebellum at postmortem. Microscopically however, there was perivascular lymphocyte cuffing in the upper medulla, pons, midbrain, thalamus, and hippocampus, with some microglial proliferation and gliosis. The perivascular lymphocyte cuffing, microglial proliferation, and gliosis in the pons could explain the dysfunction of the omnipause neurons in the PPRF. This abnormality may therefore provide a theoretical explanation for opsoclonus in this case.

An autoimmune basis to the syndrome has been suggested, but there seems to be insufficient evidence to support this.8-10Paraneoplastic autoantibodies, anti-Purkinje cell antibodies (anti-Yo), and the antineuronal nuclear antibodies type 1 (anti-Hu) and type 2 (anti-Ri or anti-Nova) were not detected.

Paraneoplastic neurological syndromes may present in many ways. Careful evaluation for the presence of an occult malignancy is important when there are more distinctive syndromes, such as Eaton-Lambert syndrome and subacute cerebellar degeneration. The index of suspicion of an occult malignancy should also be high in patients who present with opsoclonus.

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