Acute, Progressive Akinetic-Rigid Syndrome Induced by Neuroleptics in a Case of Wilson's Disease

A 25-year-old male presented with a severe extrapyramidal syndrome of acute onset. A diagnosis of Wilson's disease was made when the patient, at age 8 years, developed hepatic disease accompanied by low concentration of serum ceruloplasmin and increased amounts of urine copper. He was successfully treated with d-penicillamine, 250 mg four times daily, which unfortunately was discontinued 9 years later. He remained well, working as an excavator operator, until the age of 25, when he gradually developed paranoid ideation, social withdrawal, and depressed mood. An attempt to treat the patient with risperidone 4 mg daily was followed the next day by the appearance of a rapidly deteriorating akinetic-rigid syndrome, not responding to anticholinergic medication (biperiden, 2 mg two times daily). Olanzapine (10 mg daily) was substituted for risperidone, and a few weeks later, because of the severity of neurological symptoms, he was referred to hospital.

The neurological examination showed marked bradykinesia, masklike face, excessive drooling, monotonous and hypophonic speech, slow and restricted tongue movements, tremor at rest in the upper limbs, bilateral cogwheel rigidity, and typical parkinsonian posture and gait. Assessment using the Unified Parkinson's Disease Rating Scale (UPDRS),³ except for the section on complications of therapy, yielded a total score of 85 (maximum disability score 124). There were no pyramidal, sensory, or cerebellar signs, and the tendon reflexes were normal.

Psychiatric assessment revealed some evidence of psychosis, marked symptoms of anxiety, and moderate symptoms of depression. Psychometric assessment (Mini-Mental State Examination) showed no evidence of cognitive impairment.

Routine blood analysis, including renal and liver function tests, showed normal findings. Serum ceruloplasmin was 18.9 (normal range 18–45 mg/dl). Brain MRI disclosed extensive basal ganglia abnormalities and the slit-lamp eye examination revealed bilateral Kayser-Fleischer rings.

Reinitiation of d-penicillamine treatment (250 mg four times daily) appeared to stabilize the condition initially. However, on follow-up 3 years later, the neurological syndrome had dramatically progressed so that the patient was unable to walk, dress, or feed himself unaided (total UPDRS score 110). Attempts to control the extrapyramidal symptoms with l-dopa (Madopar tablets, 250 mg three times daily), dopa agonist (ropinirole 1 mg four times daily) and biperiden (2 mg three times daily), administered either alone or in combination, failed.

The inadvisability of using neuroleptic medication to treat the psychosis in Wilson's disease has been emphasized by Tu.² Furthermore, improvement of psychotic symptoms in Wilson's disease by administration of d-penicillamine, with no neuroleptic medication required, has been reported.⁴ In the present case, a brief exposure to neuroleptics triggered a severe akinetic-rigid syndrome, which eventually progressed rather rapidly despite therapy with d-penicillamine. One can postulate that the already impaired but still functioning striatum was further damaged by the neuroleptics, resulting in the overt manifestation of the neurological syndrome. Likewise, severe depletion or sudden change of the sensitivity of dopamine receptors in this patient could also account for the unresponsiveness to l-dopa, a drug that has been equivocally effective in other Wilson's cases.^5,6