A Man with a Gait Disorder
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《新英格兰医药杂志》
To the Editor: In the Case Record describing a 77-year-old man with a rapidly progressive gait disorder (July 20 issue),1 paraneoplastic syndrome might have been discussed in more depth. The fluctuating clinical course of encephalopathy and motor neuron disease is consistent with amyotrophic lateral sclerosis (ALS), but it is not pathognomonic. These neurophysiological findings are also described in patients with paraneoplastic motor neuron disease.2 Tests for the Eaton–Lambert syndrome or a myasthenic syndrome were apparently not done. Stress incontinence, sensory disturbance, a dry cough (in the absence of bulbar signs), and the reported manifest weakening during continued activity — a hallmark of a neuromuscular junction disorder — provide support for the hypothesis of an occult malignant condition. A pulmonary small-cell carcinoma and an associated paraneoplastic syndrome are not ruled out by the negative finding on tests for anti-Hu antibodies. Even patients with prion disease may present with encephalopathy and motor neuron disease.3 We agree that ALS can have a rapid course, but we think that the pace of events in this case deserves a wider scope in the discussion of its diagnosis.
Henning Mast, M.D.
Neurological Institute
New York, NY 10032
hmast@neuro.columbia.edu
Julia Kejda
Bergmannstrost
06112 Halle, Germany
Jay P. Mohr, M.D.
Neurological Institute
New York, NY 10032
References
Case Records of the Massachusetts General Hospital (Case 22-2006). N Engl J Med 2006;355:296-304.
Verma A, Berger JR, Snodgrass S, Petito C. Motor neuron disease: a paraneoplastic process associated with anti-Hu antibody and small-cell lung carcinoma. Ann Neurol 1996;40:112-116.
Worrall BB, Rowland LP, Chin SS, Mastrianni JA. Amyotrophy in prion diseases. Arch Neurol 2000;57:33-38.
The discussant replies: Paraneoplastic and prion diseases are considerations in patients with rapidly progressing motor weakness, but I would note several points. First, the patient's incontinence was temporally related to his prostatectomy 8 years earlier; a recent onset of dysautonomia was not described. Second, the findings from the electrophysiological study in this patient were compatible with the presence of a lower motor neuronopathy, but in the context of his hyperreflexia and bilateral Babinski responses, a neuronopathy was less likely. Hyperreflexia would be atypical for myasthenic syndromes, which are associated with depressed reflexes.1 Third, although a dry cough could suggest a bronchial neoplasm, the cough occurred with bulbar dysfunction characterized by dysarthria and tongue weakness. Moreover, chest radiography and computed tomography of the abdomen and pelvis did not show a tumor. Furthermore, despite earlier anecdotal reports, comprehensive studies have shown no clear association between ALS and cancer.2 Finally, amyotrophy may occur with prion diseases, but in this patient, mild confusion occurred only once and normal cognition was documented at later examinations, which would be unusual in a patient with a prion-associated spongiform encephalopathy.3 For these reasons and because of space constraints, a more detailed discussion of prion disease was not included.
Gilmore N. O'Neill, M.B., M.Med.Sci.
Massachusetts General Hospital
Boston, MA 02114
gilmore.oneill@biogenidec.com
References
Newsom-Davis J. Lambert-Eaton myasthenic syndrome. Rev Neurol (Paris) 2004;160:177-180.
Forsyth PA, Dalmau J, Graus F, Cwik V, Rosenblum MK, Posner JB. Motor neuron syndromes in cancer patients. Ann Neurol 1997;41:722-730.
Worrall BB, Rowland LP, Chin SS, Mastrianni JA. Amyotrophy in prion diseases. Arch Neurol 2000;57:33-38.
Henning Mast, M.D.
Neurological Institute
New York, NY 10032
hmast@neuro.columbia.edu
Julia Kejda
Bergmannstrost
06112 Halle, Germany
Jay P. Mohr, M.D.
Neurological Institute
New York, NY 10032
References
Case Records of the Massachusetts General Hospital (Case 22-2006). N Engl J Med 2006;355:296-304.
Verma A, Berger JR, Snodgrass S, Petito C. Motor neuron disease: a paraneoplastic process associated with anti-Hu antibody and small-cell lung carcinoma. Ann Neurol 1996;40:112-116.
Worrall BB, Rowland LP, Chin SS, Mastrianni JA. Amyotrophy in prion diseases. Arch Neurol 2000;57:33-38.
The discussant replies: Paraneoplastic and prion diseases are considerations in patients with rapidly progressing motor weakness, but I would note several points. First, the patient's incontinence was temporally related to his prostatectomy 8 years earlier; a recent onset of dysautonomia was not described. Second, the findings from the electrophysiological study in this patient were compatible with the presence of a lower motor neuronopathy, but in the context of his hyperreflexia and bilateral Babinski responses, a neuronopathy was less likely. Hyperreflexia would be atypical for myasthenic syndromes, which are associated with depressed reflexes.1 Third, although a dry cough could suggest a bronchial neoplasm, the cough occurred with bulbar dysfunction characterized by dysarthria and tongue weakness. Moreover, chest radiography and computed tomography of the abdomen and pelvis did not show a tumor. Furthermore, despite earlier anecdotal reports, comprehensive studies have shown no clear association between ALS and cancer.2 Finally, amyotrophy may occur with prion diseases, but in this patient, mild confusion occurred only once and normal cognition was documented at later examinations, which would be unusual in a patient with a prion-associated spongiform encephalopathy.3 For these reasons and because of space constraints, a more detailed discussion of prion disease was not included.
Gilmore N. O'Neill, M.B., M.Med.Sci.
Massachusetts General Hospital
Boston, MA 02114
gilmore.oneill@biogenidec.com
References
Newsom-Davis J. Lambert-Eaton myasthenic syndrome. Rev Neurol (Paris) 2004;160:177-180.
Forsyth PA, Dalmau J, Graus F, Cwik V, Rosenblum MK, Posner JB. Motor neuron syndromes in cancer patients. Ann Neurol 1997;41:722-730.
Worrall BB, Rowland LP, Chin SS, Mastrianni JA. Amyotrophy in prion diseases. Arch Neurol 2000;57:33-38.