Neurology India Medknow Publications on behalf of the Neurological Society of India ISSN: 0028-3886 EISSN: 1998-4022 Vol. 51, Num. 2, 2003, pp. 244-245

Neurology India, Vol. 51, No. 2, April-June, 2003, pp. 244-245

Case Report

Acute onset paraneoplastic cerebellar degeneration in a patient with small cell lung cancer

R. Bhatia, S. Prabhakar, V. Lal, D. Khurana, C. P. Das

Deparment of Neurology, Postgraduate Institute of Medical Education and Research, Sector-12, Chandigarh-160012.

Rohit Bhatia
Assistant Professor, Department of Neurology, Neurosciences Centre, All India Institute of Medical Sciences, New Delhi-110029.
E-mail: rohitbhatia71@yahoo.com.

Accepted on 06.11.2002.

Code Number: ni03074

ABSTRACT

A patient with small cell lung cancer presented with a rare presentation of an acute onset pancerebellar dysfunction. His clinical condition markedly improved following the surgical removal of the tumor and chemo- and radiotherapy.

Key Words: Paraneoplastic neurological syndromes, Cerebellar degeneration.

The term paraneoplastic syndrome refers to a group of disorders that are caused by or associated with cancer, but are not a direct effect of the primary tumor mass or of a metastasis to the involved organ.¹ Patients may present with these syndromes months or years before the diagnosis of underlying malignancy is established.² The pathophysiological mechanism of these syndromes is uncertain. Most of these disorders are thought to be immune-mediated. In certain types of malignancies specific types of autoantibodies have been detected.³ Studies indicate that the antibodies found in the brain and the tumor are the same antibodies that react with onconeural antigens.⁴ We report a rare patient with small cell lung cancer and acute onset pancerebellar dysfunction.

CASE REPORT

A 47-year-old male was admitted with sudden onset instability of gait for the preceding 15 days. Over the next two weeks he developed clumsiness of hands, alteration in speech, and marked imbalance. He was a chronic smoker and a known diabetic and hypertensive. General physical examination was unremarkable. Respiratory system examination showed features of emphysema. Apart from the cerebellar signs, the rest of the neurological examination was unremarkable. His speech was slurred and had a scanning character. Ocular examination revealed bilateral gaze-evoked nystagmus, ocular flutter and ocular dysmetria. He had limb in-coordination and severe stance and gait ataxia. Both brain CT scan and cranial MRI were unremarkable. Cerebrospinal fluid (CSF) analysis showed normal biochemistry and cell count. Cytology for malignant cells was negative. Oligoclonal bands were present in the CSF. Chest X-ray revealed features of emphysema with a relative prominence of right hilum. CECT scan of the chest revealed a soft tissue mass in the right hilum just superior to the pulmonary artery (Figure 1). Open thoracotomy was performed and the growth was excised. Histopathology of the excised tissue confirmed small cell carcinoma of the lung. The patient received radiotherapy and also chemotherapy as per protocol. His neurological condition showed considerable improvement over the next two months and his condition was stable at the last follow-up.

DISCUSSION

Paraneoplastic cerebellar degeneration is a rare but best-characterized paraneoplastic syndrome.⁵ The reported incidence is less than 1% in patients with all cancers.⁶ It may complicate any malignant tumor but is more common with small cell lung cancer, ovarian and breast cancers, and Hodgkin's disease.⁷ Males and females are equally affected, and the age incidence reflects the age distribution of cancer.⁸ Neurological manifestation may precede cancer symptoms in more than half the patients.^1,9 Typically, this disorder begins subacutely with incoordination in walking evolving over weeks to a few months, to limb ataxia and other symptoms.^3,9 Abrupt onset, like in our patient, is rare.^1,3,8 The disorder is considered to be immune-mediated and the evidence to suggest immune basis includes perivascular inflammatory infiltrates in the cerebellum, ⁹ presence of oligoclonal bands in the CSF,^10,11 and improvement with immunomodulatory therapy.¹² The strongest evidence is the presence of circulating antineuronal antibodies.^11,13,14 The patients can be characterized into subsets according to the type of autoantibody and histological confirmation. A recent study has shown that CSF from such patients may have activated CD12 specific cytotoxic T lymphocytes in CNS causing Purkinje cell death, and the drug tacrolimus may benefit such patients.¹⁵ Characteristic pathology consists of loss of Purkinje cells in the cerebellum.¹⁶ Improvement in the clinical condition may be seen with the treatment of the underlying malignancy and is probably related to early removal of antigen producing mass.³ It is plausible that the shorter course of the disease may be associated with reversible damage of Purkinje cells.

REFERENCES

1. Posner JB. Paraneoplastic syndrome involving the nervous system. In: Aminoff MJ, editor. Neurology and General Medicine. New York: Churchill Livingstone; pp. 401-20.
2. Cher LM, Henson JW, Das A, Hochberg FH. Paraneoplastic syndromes. In: Aminoff MJ, Goetz CG, editors. Handbook of Clinical Neurology. Systemic Diseases, Part III, Elsevier Science. B.V; 1998. Vol 27. pp. 673-704.
3. Dalmau JO, Posner JB. Paraneoplastic syndromes. Arch Neurol 1999;56:405-8.
4. Dalmau JO, Furnoux HM, Rosenblum MK, Graus F, Posner JB. Detection of the anti-Hu antibody in specific regions of nervous system and tumor from the patients with paraneoplastic encephalomyelitis/sensory neuronopathy. Neurology 1991;41:1757-64.
5. Hammack JE, Posner JB. Paraneoplastic cerebellar degeneration. In: Platakis A, editor. Cerebellar Degeneration. Clinical Neurobiology. Kluwer: Boston; 1992;475-9.
6. Croft PB, Wilkinson M. The incidence of carcinomatous neuromyopathy in patients with various types of carcinoma. Brain 1965;88:427-34.
7. Graus F, Dalmau J, Vallderoriola F, et al. Immunological characterization of a neuronal antibody (anti-Tv) associated with paraneoplastic cerebellar degeneration and Hodgkin's disease. J Neuroimmunol 1997;74:55-61.
8. Posner JB. Paraneoplastic syndromes. In: Bradley WG, Daroff RB, Fenichel GM, Marsden CD, editors. Neurology in Clinical Practice. Boston: Butterworth Heinemann; pp. 1299-308.
9. Henson RA, Urich H. Cortical cerebellar degeneration. In: Cancer and Nervous System. Oxford: Blackwell Scientific; 1982. pp. 346-67.
10. Hammack JE, Kimmel DW, O'Neill BP, Lennon VA. Paraneoplastic cerebellar degeneration : A clinical comparison of patients with and without Purkinje cell cytoplasmic antibodies. Mayo Clin Proc 1998;65:1423-31.
11. Peterson K, Rosenblum MK, Kotanidws H, Posner JB. Paraneoplastic cerebellar degeneration : A clinical analysis of 55 anti-Yo antibody positive patients. Neurology 1992;42:1931-7.
12. Dvopcho EJ. Autoimmune CNS paraneoplastic disorders: Mechanisms, diagnosis and therapeutic options. Ann Neur 1995;37(Suppl):S102-13.
13. Anderson NE, Rosenblum MK, Posner JB. Paraneoplastic cerebellar degeneration: Clinical Immunological correlations. Ann Neurol 1988;24:559-67.
14. Moll JW, Antoine JC, Bzashear HR, et al. Guidelines on the detection of paraneoplastic antineuronal specific antibodies. Neurology 1995;45:1937-41.
15. Albert ML, Austin LM, Darnell RB. Detection and treatment of activated T cells in the cerebrospinal fluid of patients with paraneoplastic cerebellar degeneration. Ann Neurol 2000;47:9-17.
16. Verschuuven J, Chuang L, Rosenblum MK, et al. Inflammatory infiltrates and complete absence of Purkinje cells in anti-Yo associated paraneoplastic cerebellar degeneration. Acta Neuropathol 1996;91:519-25.

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