Antiamphiphysin positive Stiff-person syndrome associated with small cell lung cancer

Stiff-person syndrome (SPS) is a rare neurologic disorder characterized by progressive muscle rigidity mostly of autoimmunological aetiology, typically associated with autoantibodies to glutamic acid decarboxylase (GADs). However, approximately 5–10% of cases are of paraneoplastic aetiology usually having breast adenocarcinoma and are positive for autoantibodies against amphiphysin. Here, we describe the first case of a patient whose antiamphiphysin(+) SPS due to a small cell cancer of the lung.

A 56-year old women presented with a six month history of increasing muscle cramps, stiffness of the right lower limb, unability to walk independently and 10kg weight loss. EMG revealed involuntary continuous motor unit activity (CMUA) in all affected muscles typical for SPS. Laboratory results were negative for GAD-antibodies but anti-amphiphysin antibodies were highly increased (1:409600) suggesting a paraneoplastic SPS. Given a normal mammogram and whole-body CAT scan, a whole-body 18F-fluorodesoxyglucose (FDG)-PET was performed showing areas of increased FDG-uptake surrounded by a decreased uptake in central regions of the right frontal lobe suggesting metastasis. Two extracranial areas of increased FDG-uptake were seen retrosternal and adjacent to the right pulmonary hilus. A biopsy from the area in the right frontal lobe was taken showing metastasis of a small cell lung carcinoma on histology.

Symptomatic therapy was initiated with benzodiazepines and corticosteroids followed by causal cancer therapy with cisplatin/etoposid and radiotherapy which led to a remarkable improvement of mobility during the following months.

The present case had a typical history and clinical picture of SPS, confirmed by EMG. The rapid progression combined with positive anti-amphiphysin antibodies was suggestive of a paraneoplastic disorder, which in SPS is usually associated with breast cancer. Our case shows that small cell lung cancer should be ruled out in patients with an antiamphiphysin(+) SPS if there is no evidence for breast cancer. As in our case, GAD antibodies are typically negative in antiamphiphysin(+) paraneoplastic SPS. Antiamphiphysin antibodies are a useful screening tool for a presumed paraneoplastic neurological syndrome since they are rarely found in patients with cancer without a neurological deficit. However, they are not specific and may be associated with a variety of different neurological syndromes and tumors (see Table).

Reference	Neurologic syndrome	Tumor
Petzold GC et al., 2004 Ann Neurol	SPS + rhabdolmyolysis	Breast
De Camilli P et al. 1993J Exp Med	SPS	Breast
Floyd S et al. 1998 Mol Med	SPS	Breast
Folli F et al. 1993 NEJM	SPS	Breast
Kocak E et al. 2004 The Breast J	SPS	Breast
Antoine et al., 1999, Arch Neurol	SN + Encephalomyelitis	Breast
	Limbic encephalitis	SCLC
	Encephalomyelitits	Ovary
	Lambert-Eaton + cerebellar degeneration	SCLC
	Lambert-Eaton Syndrome	SCLC
Dropcho E 1996, Ann Neurol.	Encephalomyelitis	SCLC