A 58-year-old woman was evaluated for progressive four limb paresthesias and difficulty with gait and balance. Six months before the evaluation, she noticed numbness, tingling, and burning sensations in both legs and more recently developed numbness and tingling in both hands. She also had gait difficulty and loss of balance, which worsened in the last month to the point that she was unable to walk without support. She also had mild weakness in her legs.
Her medical history included hypertension, diabetes, chronic obstructive pulmonary disease, anemia, obstructive sleep apnea, depression, restless leg syndrome, coronary artery disease, cardiomyopathy, internal cardiac defibrillator placement for polymorphic ventricular tachycardia, and gastric bypass surgery for obesity.
Her medications included bronchodilators, carvedilol, alprazolam, citalopram, ropinirole, and zinc sulfate.
The family history was noncontributory.
She was a remote smoker and did not drink alcohol or use any illicit drugs.
Examination revealed a normal mental status and speech. Cranial nerve examination was essentially unremarkable. Motor exam showed normal strength in the upper extremities; hip flexion was 4/5 bilaterally, whereas the remaining lower extremity muscle groups had normal strength. Muscle stretch reflexes were normal and symmetric, except for decreased ankle reflexes bilaterally. She had a positive Babinski sign on the right. There was decreased light touch and pain sensation to the level of the knee, markedly decreased vibration and proprioception sensation in the toes, and decreased vibration sensation in the ankles and knees bilaterally. Coordination was intact on the finger-to-nose and heel-to-shin maneuvers with eyes open but was impaired with eyes closed. Gait was wide base and she had a positive Romberg sign.
What is the Differential Diagnosis?
This patient had an apparent myelopathy and neuropathy. She also had bariatric surgery and can have many complications that should be considered ( Table 48-1 ). This patient could have combined degeneration of the spinal cord, from B 12 deficiency, a condition that affects the posterior columns and corticospinal tracts, and the patient may also have a neuropathy. Folate deficiency may also present with combined degeneration of the spinal cord. Syphilis is unlikely as patients with tabes dorsalis do not have evidence of corticospinal tract involvement; they usually have pupillary irregularities. HIV infections produce a vacuolar myelopathy which occurs in late stages of AIDS. In typical cases, a slowly progressive spastic paraparesis can be seen. The upper extremities are usually normal. Multiple sclerosis is another possibility; although she is somewhat old for this condition, it may present in this manner. Devic disease should be a consideration in a patient presenting with a myelopathy, either with or without optic nerve involvement.
| Encephalopathy |
| Behavioral abnormalities |
| Seizures |
| Cranial nerve palsies |
| Ataxia |
| Myelopathy |
| Plexopathies |
| Peripheral neuropathy |
| Mononeuropathies |
| Carpal tunnel syndrome |
| Meralgia paresthetica |
| Compartment syndromes |
| Myopathy |
| Myotonia |
Other possibilities include Sjögren syndrome, lupus, and a paraneoplastic syndrome. HTLV-1 is more common in other countries, but not in the United States, and this is slowly progressive in myelopathy, and patients may also have a mild neuropathy. Neurosarcoidosis can present with spinal cord dysfunction.
Another possibility is copper deficiency myelopathy, which can also have this presentation.
What tests should be done?
An MRI was not done in this case. B 12 , methylmalonic acid levels, and folic acid levels were normal. HSTLV-1 was normal. Serum vitamin B 1 level was 4.8 µg/dL. The alpha-tocopherol level was 18.7 (normal 5.5–18). The serum zinc level was 881 which was normal. The copper level was undetectable. RPR was negative as well as HTLV-1 and HIV.
EMG showed a mild neuropathy.
Discussion
It was concluded that this patient has copper deficiency myeloneuropathy, and she was treated with copper supplementation.
Copper is an essential trace metal and is a component of many key metalloenzymes, and many proteins are involved in the structure and function of the CNS.
Copper absorption in humans most likely occurs in the stomach and proximal duodenum. Its deficiency can be divided into two categories, inherited and acquired. Menkes disease is an X-linked inherited copper deficiency, which is associated with mutations in the ATP7A gene. This encodes a P-type adenosine triphosphatase (MNK) that has multiple copper-binding motifs near its amino terminus. Loss of function of this protein causes failure of copper transfer across the gastrointestinal tract and blood–brain barrier with resultant copper deficiency and its neurologic disturbances. Because of copper’s ubiquitous distribution and low daily requirement, acquired copper deficiency is rare. In humans, populations at the highest risk are elderly people who have a history of gastrointestinal surgery (including gastroplasty, gastrectomy, and small bowel resection), excessive zinc ingestion, malabsorption states, renal and liver disease, and prolonged total parenteral nutrition ; however, often the cause is unknown. An elevated serum zinc level in either excessive zinc ingestion or absence of exogenous ingestion is commonly seen.
Zinc is known to cause upregulation of metallothionein production in the enterocyte, which effectively decreases intestinal absorption of copper.
An ataxic myelopathy resulting from copper deficiency has been documented in ruminant animals, known as swayback. The neurologic manifestations of acquired copper deficiency in humans have been increasingly recognized in the last decade. The most common manifestation is myelopathy as well as an associated peripheral neuropathy. Its symptoms include sensory ataxia, spastic gait, and acral paresthesias. An isolated peripheral neuropathy, CNS demyelination, and optic neuritis have also been reported to be associated with copper deficiency. Other associated abnormalities include anemia and leukopenia. The anemia may be microcytic, macrocytic, or normocytic. Thrombocytopenia and resulting pancytopenia are relatively rare ( Table 48-2 ).
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