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Case Reports / Journal of Clinical Neuroscience 16 (2009) 838839

A predominantly left upper limb sensory neuronopathy as a manifestation of a metastatic neuroendocrine malignancy
A. Lim a, A. Scriven a, W. Knezevic a,*, M. Texler b
a b

Department of Neurology, Fremantle Hospital, Alma Street, Fremantle, Western Australia 6160, Australia Department of Pathology, Fremantle Hospital, Fremantle, Western Australia, Australia

a r t i c l e

i n f o

a b s t r a c t
An 83-year-old woman presented with a predominantly left upper limb sensory ganglionopathy. She was found to have metastatic, poorly differentiated, neuroendocrine malignancy. Anti-neuronal antibodies were not detected. Crown Copyright 2008 Published by Elsevier Ltd. All rights reserved.

Article history: Received 25 February 2008 Accepted 21 August 2008

Keywords: Sensory neuronopathy Sensory ganglionopathy Paraneoplastic peripheral neuropathy Paraneoplastic neuroendocrine malignancy Anti-neuronal antibodies

1. Introduction Paraneoplastic syndromes often present a diagnostic challenge. Neurological manifestations are uncommon about 1% for solid tumours other than small cell lung cancer.1 Paraneoplastic syndromes manifesting as dorsal root ganglionopathies have been infrequently documented.2,3 We present a patient with a predominantly left upper limb sensory ganglionopathy who was discovered to have a neuroendocrine malignancy. 2. Case report An 83-year-old woman presented with a 6 week history of progressively ascending numbness, pain and clumsiness of her left hand and arm. She then noticed a burning sensation in her feet bilaterally. She had a history of controlled hypertension, atrial brillation and a 30 pack per year history of cigarette smoking. Neurologic examination showed drift of both upper limbs, more marked on the left. She had distal pseudoathetoid movements of the left hand. There was loss of joint position sense and proprioception at the left elbow with partial impairment of proprioception at the shoulder. Vibration sense was absent to the same level and there was impaired light touch, pinprick and temperature sensation of the left arm. There was bilateral sensory ataxia and astereoagnosia, most prominent of the left upper limb. Deep tendon reexes were absent throughout. She was unable to tandem walk and Rombergs test was positive. There was no sensory loss on examination of the trunk or lower limbs. Cranial nerve examination was normal. Power was normal throughout. Blood tests including antinuclear antibody and anti-Ro antibody were normal. Nerve conduction studies showed reduced supercial radial sensory responses, and unrecordable median, ulnar and sural sensory responses. Median, ulnar, peroneal and tibial motor amplitudes, conduction velocities and F-wave latencies were normal and there was no denervation on needle examination. These ndings were consistent with a diffuse sensory neuropathy or neuronopathy. A CT scan of her chest and abdomen was considered initially to be normal. MRI of the brain showed subcortical white matter change consistent with chronic small vessel ischaemia. MRI of
* Corresponding author. Tel.: +61 8 9431 3333; fax: +61 8 9431 2352. E-mail address: knezevic@cyllene.uwa.edu.au (W. Knezevic).

the spinal cord was normal. Cerebrospinal uid (CSF) analysis demonstrated a raised protein level of 1.1 g/L with other parameters being normal. There were no oligoclonal bands in the CSF and CSF cytology revealed no abnormalities. Screening for neoplasia included a normal serum quantitative electrophoresis, calcium, alpha-feto protein, and negative antineuronal antibodies (anti-Hu, anti-Yo and anti-Ri antibodies). A uorodeoxyglucose (FDG)-positron emission tomography (PET) scan showed increased uptake in the hilum of the right lung and the left iliac crest (Fig. 1). A biopsy of the iliac crest lesion revealed a poorly differentiated neuroendocrine tumour. Cells were positive for synaptophysin antigen but negative for chromogranin-A antigen. There was patchy positivity with CD56 (neural cellular adhesion molecule, NCAM) in keeping with neuroendocrine differentiation. The lesion was negative for thyroid transcription factor 1 (TTF-1) antigen. A trial of intravenous immunoglobulins (IVIG) at 0.4 g/kg daily for 5 days was given without benet. The patient was referred to the respiratory physicians and oncology; however, she declined any further interventions and was discharged home. 3. Discussion In this patient, a progressive sensory ganglionopathy that affected predominantly the left upper limb preceded the diagnosis of a neoplasm. In most reported cases the rst sensory modalities to be lost are vibration and joint position sense. Deafferentation due to loss of large diameter sensory neurons leads to sensory ataxia and pseudoathetoid movements.2,4 The neurological presentation and initially negative neoplasia screen raised the possibility of Sjogrens syndrome, a major differential diagnosis for a sensory ganglionopathy presenting in this manner.5 The negative antinuclear antibodies, antineuronal antibodies, lack of signicant CSF ndings and a CT scan that was thought not to rule out an occult neoplasm, were followed by a FDG-PET scan that revealed the hilar and iliac crest lesions (a review of the CT scan showed a 25 mm 15 mm lesion in the right hilum). FDG-PET is increasingly recognized as being a valuable imaging tool in the diagnosis of neoplastic lesions. Whether there is value in performing this test in patients who are antineuronal antibody negative is debatable, given that other tests may also reveal the tumour and there are false negatives and positives with PET.6,7 The PET scan was critical in drawing attention to the lesion in the right hilum in our patient and in demonstrating the lesion in the iliac

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nomas, 94% of small cell lung carcinoma, and > 95% of thyroid neoplasms. The absence of TTF-1 antigens could be considered the result of poor tumour differentiation rather than an alternative primary location. However, an extrapulmonary primary source needs consideration in the absence of TTF-1 immunostaining. TTF-1 can be used on formalin xed and parafn embedded material. The decalcication procedure required for the bone core should not affect antigen retrieval.9,10 Treatment for paraneoplastic sensory neuropathies includes treatment of the underlying tumour, steroids, and other immunosuppression.11 The usefulness of IVIG remains inconclusive due to few patient numbers.12,13 Paraneoplastic subacute sensory neuronopathies can occur without the presence of anti-neuronal (in particular, anti-Hu) antibodies.1,2,14 After the tissue diagnosis was made, treatment options were discussed with the patient and her family. Further therapy was declined and palliative therapy was given. The upper limb neuropathy continued to deteriorate rapidly, although the patient remained able to walk with assistance until a few weeks before her death, 4 months after diagnosis. Our report emphasises clinical features leading to a consideration of paraneoplastic phenomenon and the value of the use of FDG-PET in a patient with suspected paraneoplastic neurological syndrome. The atypical and clinically confounding features in this case include upper limb predominance and lateralisation.

References
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Fig. 1. A uorodeoxyglucose positron emission tomography scan showing (A) increased uptake in the hilum of the right lung and (B) the left iliac crest.

crest, from which a tissue diagnosis was easily obtained. A recent report supports the use of both PET and CT scans in increasing the sensitivity of diagnosis of an associated tumour.8 The primary tumour location was probably pulmonary. The presence of synaptophysin and CD56 positivity support neuroendocrine differentiation. TTF-1 is positive in 73% of lung adenocarci-

doi:10.1016/j.jocn.2008.08.036