Case Reports

Phenelzine associated peripheral neuropathy electrophysiologic findings

- clinical and

R. S. Goodheart Senior Neurology Registrar, Department of Neurology, Royal Perth Hospital, WA.

J. W. Dunne Consultant Neurologist, Department of Neurology, Royal Perth Hospital, WA.

R. H. Edis Consultant Neurologist, Department of Neurology, Royal Perth Hospital, WA

Abstract: Phenelzine associated sensorimotor peripheral neuropathy is reported in two patients. Symptoms were predominantly sensory, and improvement occurred after withdrawal of phenelzine. Electrophysiologic findings were consistent with an axonal process. (Aust NZ J Med 1991; 21: 339-340.) Key words: Phenelzine, peripheral neuropathy.

Phenelzine sulphate, a monoamine oxidase inhibitor, has rarely been associated with peripheral n e u r ~ p a t h y . ' -We ~ report two patients with generalised sensorimotor neuropathy having a clear relationship to phenelzine therapy. In both, improvement in symptoms and clinical findings occurred after discontinuing phenelzine.

CASE REPORT Case 1

A 43-year-old man presented with a six month history of increasing numbness and dysaesthesia in the feet, with the more recent emergence of paraesthesia of the fingertips. Mild weakness of the feet was noted. He had suffered from depression for eight years, having been treated with phenelzine sulphate for two years (dosage of 30 mg b.d. at presentation). No personal or family history of diabetes mellirus or other conditions predisposing to peripheral neuropdthy was present. Examination showed reduced pinprick and light touch sensation to the level of the elbows and knees. Two point discrimination was impaired to 8 mm at the fingertips. Vibration sense was moderately impaired at hoth ankles. Knee reflexes were reduced and ankle jerks absent. Mild weakness of ankle dorsiflexion, eversion and plantar flexion was evident. He had difficulty walking on his heels. Nerve conduction studies showed absent sensory responses (surd, median and ulnar), and low amplitude (tibial/abductor hallucis) or absent (peronealiextensor digitorum brevis) lower limb compound muscle action potentials. Upper limb motor conduction studies showed a mild, non-localised reduction in ulnar conduction velocity to 48 m/sec (normal > 5 1 mlsec), but were otherwise normal, including F-wave latencies. Needle examination revealed fibrillation

potentials and large, sometimes polyphasic motor unit potentials in distal lower limb muscles, with minor motor unit potential changes alone in the right first dorsal interosseous. Paraspinal muscles were normal. These findings were consistent with a moderate generalised sensorimotor peripheral neuropathy, axonal in type. A search for other causes of peripheral neuropathy including serum vitamin assays (RI, R6, B12 and folate); blood sugar level; liver, renal and thyroid function tests; autoantibody screen; plasma protein quantitative electrophoresis (QEP), full blood picture, ESR; chest X-ray; syphilis and hepatitis B serology; urinary porphyrins and heavy metal levels were normal or negative. T h e serum pyridoxine level was 35 mmol/L (normal range = 23-59). Phenelzine sulphate therapy was ceased and clinical and electrophysiologic improvement followed. Repeat electromyography (EMG) and nerve conduction studies after a period of six months showed a return of median and ulnar sensory nerve action potentials, and less severe EMG findings on needle examination, with reduction in previously prominent fibrillation potentials. After 14 months muscle power was normal in the legs and sensation only minimally impaired. The knee reflexes were easily elicitable although the ankle jerks remained absent. Vibration sense was still modeiately impaired to the ankles and two point discriminatiun was 5 mm at the fingertips. Symptoms, signs and electrophysiologic findings have remained unaltered over four years of follow-up. Case 2

A 46-year-old man had suffered from major depression and endogenous anxiety for three years. Phenelzine sulphate had been prescribed for two years. A past history of excessive alcohol consumption was present but abstinence for ten years was documented. Phenelzine sulphate dosage was initially 50 mg b.d. but after one ~

Reprint requesls 10: Dr J. W. Dunne, Department of Neurology, Royal Perth Hospital, 1'0 Box X2211 GPO, Perth 6001, Australia. PHENELZINE ASSOCIATED PERIPHERAL NEUKOPATIIY

Aust N Z J Med 1991; 21

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year it was increased to 60 mg b.d. At that time he complained of an abnormal sensation in the medial aspect of the right lower leg, and an inconsistent decrease of pinprick sensation was found on examination. The sensory symptoms in the legs progressed with paraesthesia in the toes and soles of the feet, occasional cramps in the calves and a tendency to stumble when walking. After three months, mild weakness of ankle dorsiflexion and toe extension had emerged, and the ankle reflexes were absent. Diminution of light touch and pinprick sensation was found in a glove and stocking distribution below the knees and wrists. A tendency to drag the feet while walking and difficulty with walking on the heels were present. Nerve conduction studies showed absent sural sensory responses, low amplitude median and ulnar antidromic sensory nerve action potentials of normal latencies, and low amplitude tibia1 and peroneal compound muscle action potentials. Upper limb median and ulnar motor conduction studies were normal, including conduction velocities and F-wave latencies. Needle examination revealed fibrillation potentials and large motor unit potentials in foot muscles. These findings were consistent with a mild generalised sensorimotor peripheral neuropathy, axonal in type. Serum vitamin assays (Bl, B6, B12 and folate); blood sugar level: liver, renal and thyroid function tests; auto antibody screen; QEP, full blood picture, ESR chest X-ray; syphilis and hepatitis B serology; urinary porphyrins and heavy metal levels were normal or negative. Serum pyridoxine level was 24 mmollL (normal range = 23-59). The patient ceased phenelzine sulphate on his own initiative since he felt that it may be contributing to his symptoms. Over the next six weeks sensory symptoms improved and limb power almost completely recovered. Due to continued depression the phenelzine sulphate was recommenced, and over the ensuing months increasing numbness in the hands and feet, sore calves and trouble waking on uneven surfaces re-emerged. He remained on phenelzine sulphate for a further six months. Examination showed diminished perception of light touch and pinprick sensation in the hands, and distal weakness ofthe hands and feet. While symptoms partially resolved after again withdrawing phenelzine sulphate, clinical signs and electrophysiologic findings did not significantly alter. Repeat pyridoxine was 30 mmol/L.

DISCUSSION Phenelzine sulphate is commonly used in the treatment of depression, and side effects are frequent. Adverse effects include orthostatic hypotension, drowsiness, weakness and fatigue.' Peripheral paraesthesia may be seen as a part of dose related and reversible autonomic effects. Recently six cases of numbness, paraesthesia and puffy hands have been

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reported in relation to phenelzine therapy.2 However an association with a sensorimotor peripheral neuropathy has rarely been r e c o g n i ~ e d . ~ . ~ We have described two patients in whom symptoms and signs of a generalised peripheral neuropathy were clearly related to phenelzine sulphate therapy. Electrophysiologic findings were consistent with an axonal process. In both patients improvement of clinical symptoms and signs followed withdrawal of phenelzine sulphate. In the first patient improvement of electrophysiologic abnormalities was documented, and in the second a relationship between symptoms and administration of phenelzine sulphate was demonstrated on two occasions. It has been postulated that the phenelzine sulphate may cause peripheral neuropathy by inducing a pyridoxine defi~ i e n c y .Similar ~ mechanisms have been proposed for the neuropathy associated with isoniazid and hyd~alazine.~ Pyridoxine levels were shown to be normal in both of our patients, although in the second, levels were initially at the lower limit of the normal range. A single previously reported case of phenelzine induced neuropathy was associated with pyridoxine deficiency, although pyridoxine therapy was ineffe~tive.~ While phenelzine has an impact on pyridoxine metabolism, the lack of a consistent association with pyridoxine deficiency, or of a response to pyridoxine therapy, suggests that direct drug toxicity may contribute to or cause the sensorimotor peripheral neuropathy. w Accepted for publication: 29 August 1990

References 1. Reynolds JEF (Ed.). Martindale - the extra pharmacopoeia. 29th edn. London: The Pharmaceutical Press, 1989: 377-80. 2. Stewart JW, Harrison W, Quitkin F, Liebowitz MR. Phenelzine induced pyridoxine deficiency. J Clin Psychopharmacol 1984; 4: 225-6. 3. Heller CA, Friedman PA. Pyridoxine deficiency and peripheral neuropathy associated with long-term phenelzine therapy. Am J Med 1983; 75: 887-8. 4. Barberini E. Experienze terapeutiche con vitamina B6 negli effetti collaterali da farmaci inhibitori delle monoaminoossidassi. Clin Ter 1966; 36: 46-55. 5. Raskin NH, Fishman RA. Pyridoxine deficiency neuropathy due to hydralazine. N Engl J Med 1965; 273: 1182-5.

Aust NZ J Med 1991; 21

GOODHEART ET AL.

Phenelzine associated peripheral neuropathy--clinical and electrophysiologic findings.

Phenelzine associated sensorimotor peripheral neuropathy is reported in two patients. Symptoms were predominantly sensory, and improvement occurred af...
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