An unusual cause of dysphagia
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神经科学杂志 2005年第1期
St Thomas’ Hospital, London
Keywords: Lambert-Eaton Myasthenic Syndrome (LEMS); dysphagia; paraneoplastic syndromes
We report a case of a patient with Lambert Eaton Myasthenic Syndrome (LEMS) associated with small cell lung cancer (SCLC) presenting with a 2 year history of dysphagia. This presentation has not been described in previous literature.
Case
A 71 year old right handed deck worker initially presented with a 6 month history of dysphagia, weight loss, nausea, and fatigue. He was cachetic with no other clinical signs to be found on examination. Baseline blood tests were unremarkable. Upper gastrointestinal (GI) endoscopy revealed a small hiatus hernia only. Subsequent investigations included a barium swallow, computer tomography (CT) scans of the chest and abdomen, oesophageal manometry, small bowel follow through, and laparoscopy, which were all normal. He was empirically started on cisapride and managed on an appropriate pureed diet.
Eighteen months after his initial presentation the patient complained of a gradual deterioration in his speech and problems with proximal muscle weakness. Clinical examination demonstrated an obvious dysarthria and broad based gait. There was no limb weakness or sensory neuropathy and reflexes were preserved with no post-tetanic potentiation. There was no disturbance of extraocular eye movements or ptosis. The patient did not display any cognitive impairment. He subsequently developed involuntary choreo-athetoid movements.
Baseline blood tests and chest x ray (CXR) were again normal. Magnetic resonance imaging of the brain demonstrated evidence of small vessel disease. Electromyography and nerve conduction studies were performed. Sensory conduction velocities were within normal limits. Motor conduction velocities demonstrated a clear and reproducible decremental response to repetitive stimulation in the right ulnar nerve (32%) and in the right median nerve (25%), maximal at 3 Hz stimulation. Compound action potentials in the muscles tested increased by more than 50% following a period of exercise (right ulnar nerve 0.9 to 2.8 mV, right median nerve 1.7 to 2.8 mV). Electromyogram (EMG) of the right biceps and 1st dorsal interosseous muscles were normal. Overall the results were felt to be consistent with a diagnosis of Lambert-Eaton Myasthenic Syndrome (LEMS). The presence of anti-voltage gated calcium channel antibodies confirmed the diagnosis.
Repeat CT scanning in combination with positron emission tomography (PET) scanning revealed enlarged subcarinal lymph nodes only. A transbronchial lymph node aspiration confirmed the diagnosis of small cell lung cancer. Anti-Hu antibodies were found to be positive.
The patient initially received a course of intravenous immunoglobulins (IVIg)(1 g/kg for 5 days), which resulted in an improvement in speech, swallowing, and gait. He then proceeded to start treatment with cisplatin/etoposide chemotherapy and concomitant radiotherapy. His movement disorder improved slightly during this time but his dysphagia resolved completely. Repeat CT staging after completion of his treatment demonstrated a complete response.
Discussion
Dysphagia occurs in 24–34% of patients with LEMS.1 This usually develops late in the course of the disease, but may be present at the onset.2 Dysphagia as the sole presenting symptom of LEMS is extremely rare however.
Proximal lower limb girdle weakness is the most frequent presentation. In a case series of 50 consecutive patients, leg weakness was the presenting complaint in 62% of patients.1 Less frequent presentations are generalised weakness, aching and stiffness, autonomic symptoms (impotence, dry mouth, constipation), arm weakness, diplopia, and dysarthria.
Guruprakash et al reported a case of a 59 year old man presenting with dysphagia who was subsequently found to have LEMS.3 Further investigation revealed adenocarcinoma of the prostate with bony metastases. The dysphagia resolved completely with a combination of preoperative guanidine hydrochloride, followed by bilateral orchidectomy and diethylstilbestrol diphosphate.
Recognising LEMS swiftly is important, as it may be an early warning sign of an underlying malignancy. Approximately 60% of LEMS patients have cancer, usually SCLC.4 Other less commonly associated malignancies include lymphoproliferative disorders, carcinoma of the breast, colon, stomach, gall bladder, kidney and bladder, adenocarcinoma of the lung, pancreas and prostate, and intrathoracic carcinoid. The diagnosis of LEMS usually precedes the cancer diagnosis by a median of 6 months.4 Carcinoma associated LEMS patients tend to present at an older age than LEMS without carcinoma. A male predominance has been noted in the past, but more recent epidemiology does not support this, likely reflecting the changes in smoking patterns.
Our patient also developed chorea. Multiple paraneoplastic syndromes are very rare but have been previously described. Vernino et al reported a series of 16 patients with paraneoplastic chorea, of which one patient in the series also had a diagnosis of LEMS.5
Currently an autoimmune aetiology is favoured for the development of paraneoplastic syndromes. Antibodies have been demonstrated against calcium channel antigens shared between SCLC and presynaptic cholinergic synapses in LEMS. Anti-HuD antibodies have also been detected in patients with SCLC presenting with other paraneoplastic syndromes. This antigen is common to SCLC cells and the nuclei of neurones in the central and peripheral nervous systems.
Management of LEMS includes the use of 3,4 Diaminopyridine, which provides symptomatic improvement in patients with or without a neoplasm. Steroids and immunosuppression with azathioprine or cyclosporin are of particular value in patients with non-cancer associated LEMS.
Our patient was successfully treated with IVIg and chemoradiotherapy. This resulted in resolution of the dysphagia and some improvement in the chorea. The role of IVIg in treating LEMS is established. It is also recognised that treatment of the underlying tumour can result in improvement or remission of symptoms relating to the paraneoplastic syndromes.
This case illustrates that LEMS is an unusual but important cause of swallowing difficulties. In the present patient, establishing the cause of dysphagia led to the diagnosis and treatment of the underlying SCLC.
ACKNOWLEDGEMENTS
Thank you to Mr R Mason (Consultant General Surgeon, St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH) and Mr J Prendeville (Consultant Medical Oncologist, Guys Hospital, St Thomas Street, London SE1 9RT) for their review of this case.
References
O’Neill JH, Murray NM, Newsom-Davis J. The Lambert-Eaton myasthenic syndrome. A review of fifty cases. Brain 1988;111:577–96.
Heath JP, Ewing DJ, Cull RE. Abnormalities of autonomic function in the Lambert-Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry 1988;51:436–9.
Guruprakash GH, Ahmed I, Shadchehr A. Report of a case presenting with dyshagia due to Eaton-Lambert Syndrome. J Kans Med Soc 1982;83:617–9.
Wirtz PW, Smallegange TM, Wintzen AR, et al. Differences in clinical features between the Lambert-Eaton myasthenic syndrome with and without cancer: an analysis of 227 published cases. Clin Neurol Neurosurg 2002;104:359–63.
Vernino S, Tuite P, Adler CH, et al. Paraneoplastic chorea associated with CRMP- 5 neuronal antibody and lung carcinoma. Annal Neurol 2002;51:625–30.(S Payne, D Wilkins and R )
Keywords: Lambert-Eaton Myasthenic Syndrome (LEMS); dysphagia; paraneoplastic syndromes
We report a case of a patient with Lambert Eaton Myasthenic Syndrome (LEMS) associated with small cell lung cancer (SCLC) presenting with a 2 year history of dysphagia. This presentation has not been described in previous literature.
Case
A 71 year old right handed deck worker initially presented with a 6 month history of dysphagia, weight loss, nausea, and fatigue. He was cachetic with no other clinical signs to be found on examination. Baseline blood tests were unremarkable. Upper gastrointestinal (GI) endoscopy revealed a small hiatus hernia only. Subsequent investigations included a barium swallow, computer tomography (CT) scans of the chest and abdomen, oesophageal manometry, small bowel follow through, and laparoscopy, which were all normal. He was empirically started on cisapride and managed on an appropriate pureed diet.
Eighteen months after his initial presentation the patient complained of a gradual deterioration in his speech and problems with proximal muscle weakness. Clinical examination demonstrated an obvious dysarthria and broad based gait. There was no limb weakness or sensory neuropathy and reflexes were preserved with no post-tetanic potentiation. There was no disturbance of extraocular eye movements or ptosis. The patient did not display any cognitive impairment. He subsequently developed involuntary choreo-athetoid movements.
Baseline blood tests and chest x ray (CXR) were again normal. Magnetic resonance imaging of the brain demonstrated evidence of small vessel disease. Electromyography and nerve conduction studies were performed. Sensory conduction velocities were within normal limits. Motor conduction velocities demonstrated a clear and reproducible decremental response to repetitive stimulation in the right ulnar nerve (32%) and in the right median nerve (25%), maximal at 3 Hz stimulation. Compound action potentials in the muscles tested increased by more than 50% following a period of exercise (right ulnar nerve 0.9 to 2.8 mV, right median nerve 1.7 to 2.8 mV). Electromyogram (EMG) of the right biceps and 1st dorsal interosseous muscles were normal. Overall the results were felt to be consistent with a diagnosis of Lambert-Eaton Myasthenic Syndrome (LEMS). The presence of anti-voltage gated calcium channel antibodies confirmed the diagnosis.
Repeat CT scanning in combination with positron emission tomography (PET) scanning revealed enlarged subcarinal lymph nodes only. A transbronchial lymph node aspiration confirmed the diagnosis of small cell lung cancer. Anti-Hu antibodies were found to be positive.
The patient initially received a course of intravenous immunoglobulins (IVIg)(1 g/kg for 5 days), which resulted in an improvement in speech, swallowing, and gait. He then proceeded to start treatment with cisplatin/etoposide chemotherapy and concomitant radiotherapy. His movement disorder improved slightly during this time but his dysphagia resolved completely. Repeat CT staging after completion of his treatment demonstrated a complete response.
Discussion
Dysphagia occurs in 24–34% of patients with LEMS.1 This usually develops late in the course of the disease, but may be present at the onset.2 Dysphagia as the sole presenting symptom of LEMS is extremely rare however.
Proximal lower limb girdle weakness is the most frequent presentation. In a case series of 50 consecutive patients, leg weakness was the presenting complaint in 62% of patients.1 Less frequent presentations are generalised weakness, aching and stiffness, autonomic symptoms (impotence, dry mouth, constipation), arm weakness, diplopia, and dysarthria.
Guruprakash et al reported a case of a 59 year old man presenting with dysphagia who was subsequently found to have LEMS.3 Further investigation revealed adenocarcinoma of the prostate with bony metastases. The dysphagia resolved completely with a combination of preoperative guanidine hydrochloride, followed by bilateral orchidectomy and diethylstilbestrol diphosphate.
Recognising LEMS swiftly is important, as it may be an early warning sign of an underlying malignancy. Approximately 60% of LEMS patients have cancer, usually SCLC.4 Other less commonly associated malignancies include lymphoproliferative disorders, carcinoma of the breast, colon, stomach, gall bladder, kidney and bladder, adenocarcinoma of the lung, pancreas and prostate, and intrathoracic carcinoid. The diagnosis of LEMS usually precedes the cancer diagnosis by a median of 6 months.4 Carcinoma associated LEMS patients tend to present at an older age than LEMS without carcinoma. A male predominance has been noted in the past, but more recent epidemiology does not support this, likely reflecting the changes in smoking patterns.
Our patient also developed chorea. Multiple paraneoplastic syndromes are very rare but have been previously described. Vernino et al reported a series of 16 patients with paraneoplastic chorea, of which one patient in the series also had a diagnosis of LEMS.5
Currently an autoimmune aetiology is favoured for the development of paraneoplastic syndromes. Antibodies have been demonstrated against calcium channel antigens shared between SCLC and presynaptic cholinergic synapses in LEMS. Anti-HuD antibodies have also been detected in patients with SCLC presenting with other paraneoplastic syndromes. This antigen is common to SCLC cells and the nuclei of neurones in the central and peripheral nervous systems.
Management of LEMS includes the use of 3,4 Diaminopyridine, which provides symptomatic improvement in patients with or without a neoplasm. Steroids and immunosuppression with azathioprine or cyclosporin are of particular value in patients with non-cancer associated LEMS.
Our patient was successfully treated with IVIg and chemoradiotherapy. This resulted in resolution of the dysphagia and some improvement in the chorea. The role of IVIg in treating LEMS is established. It is also recognised that treatment of the underlying tumour can result in improvement or remission of symptoms relating to the paraneoplastic syndromes.
This case illustrates that LEMS is an unusual but important cause of swallowing difficulties. In the present patient, establishing the cause of dysphagia led to the diagnosis and treatment of the underlying SCLC.
ACKNOWLEDGEMENTS
Thank you to Mr R Mason (Consultant General Surgeon, St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH) and Mr J Prendeville (Consultant Medical Oncologist, Guys Hospital, St Thomas Street, London SE1 9RT) for their review of this case.
References
O’Neill JH, Murray NM, Newsom-Davis J. The Lambert-Eaton myasthenic syndrome. A review of fifty cases. Brain 1988;111:577–96.
Heath JP, Ewing DJ, Cull RE. Abnormalities of autonomic function in the Lambert-Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry 1988;51:436–9.
Guruprakash GH, Ahmed I, Shadchehr A. Report of a case presenting with dyshagia due to Eaton-Lambert Syndrome. J Kans Med Soc 1982;83:617–9.
Wirtz PW, Smallegange TM, Wintzen AR, et al. Differences in clinical features between the Lambert-Eaton myasthenic syndrome with and without cancer: an analysis of 227 published cases. Clin Neurol Neurosurg 2002;104:359–63.
Vernino S, Tuite P, Adler CH, et al. Paraneoplastic chorea associated with CRMP- 5 neuronal antibody and lung carcinoma. Annal Neurol 2002;51:625–30.(S Payne, D Wilkins and R )