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A 62 year old male patient presented with a longstanding history of slowly progressive limb weakness, speech, and swallowing difficulties. In 1983 a diagnosis of amyotrophic lateral sclerosis had been made. At that time his physical examination showed tongue atrophy with fibrillations, proximal limb weakness, and brisk lower limb tendon reflexes. Electromyography showed abnormal “spontaneus activity” with fibrillations and positive sharp waves in muscles of all limbs. His further medical and family history was unremarkable.
In January 2000 neurological examination showed mild facial weakness, marked atrophy and fibrillations of the tongue, severe dysarthria and dysphagia, atrophy, and weakness of the shoulder girdle and arm muscles, and an unsteady and broad based gait. Apart from brisk knee jerks, deep tendon reflexes were absent and plantar responses were negative. Sensory testing was normal. General physical examination showed slight gynaecomastia. Laboratory testing showed raised creatine kinase (305 U/l) and lactate dehydrogenase (195 U/l) concentrations. Needle EMG demonstrated positive sharp waves and fibrillation potentials and long duration polyphasic motor unit potentials with increased amplitudes in muscles of all limbs. By contrast, motor and sensory nerve conduction studies gave normal results.
As cervical myelopathy is an important differential diagnosis in patients with suspected motor neuron disease, cervical MRI was performed. As shown in figure 1, MRI disclosed marked cervical spondylosis with appreciable narrowing of the spinal canal between C3 and C6. In addition, T2 weighted images showed intramedullar changes with foci of high signal intensity at the level of C5 indicating myelopathy. Although these changes may readily explain the weakness in his upper limbs, the cause of bulbar symptoms and denervation in his lower limbs remained unclear.
The presence of slight bilateral gynaecomastia prompted us to look for androgen receptor gene mutations, which cause X linked spinal bulbar muscular atrophy.1 This disorder, also known as Kennedy syndrome, is caused by an unstable expansion of a CAG repeat in exon 1 of the androgen receptor gene (Xq11–12). The androgen receptor is highly expressed in motor neurons of the brain stem and spinal cord. The CAG repeat expansion is thought to confer a toxic gain of function to the androgen receptor protein resulting in irreversible damage of brain stem and spinal cord motor neurons. In addition, the impaired ability to transactivate androgen sensitive genes of the mutated receptor may account for endocrine features such as gynaecomastia or testicular atrophy in spinal bulbar muscular atrophy.2-4
Genetic analysis in our patient showed one allele carrying an abnormally expanded CAG repeat (44; normal range 16–33) thus confirming the diagnosis of Kennedy syndrome.
The present patient with coexisting cervical spondylotic myelopathy and Kennedy syndrome highlights the diagnostic value of an intensified investigation including cervical MRI and androgen receptor gene analysis in patients with an unusual clinical presentation of motor neuron disease.
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