Severe neuropsychiatric presentation of Wilson's disease.

Wilson's disease (WD) is a relatively rare disease of copper metabolism. The diagnosis is often missed initially. The presentation is usually neurologic or hepatic, seen in 40% of patients. Psychiatric presentation of WD is reported in only 15% of patients. We present a 32-year-old patient with severe psychiatric manifestations. On examination, he had mild rest and postural tremors and a KF ring was seen. Serum ceruloplasmin was low and 24-hour urinary copper was elevated. The patient responded to penicillamine, lorazepam and quetiapine, and is being followed up.

INTRODUCTION

Wilson's disease (WD) is a relatively rare disease of copper metabolism. The initial manifestations are neurologic in 40% of patients, hepatic in 40% and psychiatric in 15% of patients. WD is an autosomal recessive condition characterized by inability of the liver to transport and store normally absorbed dietary copper, resulting in abnormal deposition of copper in the basal ganglia, eyes, liver and other tissues. In 1912, Dr. Kinnier Wilson published a description of 12 patients who presented with extrapyramidal motor disease and, on autopsy, demonstrated softening of the lenticular nucleus and cirrhosis of the liver.[1] He further noted that these patients exhibited “emotionalism”, and 2 of his 12 patients presented with schizophrenic-like psychoses. Scheinberg and Sternlieb[2] wrote that 10–25% of patients with WD initially present with psychiatric symptoms. Psychiatric symptoms in WD may range from major depression, mania, and anti-social behavior to psychosis.[3]

CASE REPORT

Mr. G. D., a 32-year-old unmarried gentleman born of non-consanguineous parents, presented with personality change and behavioral disturbances since the last 6 months. The behavioral disturbances were in the form of emotional liability, aggressiveness and disinhibition and delusions. He had past history of jaundice at 18 years of age which resolved in 3 months.

Physical examination at the time of the admission revealed a KF ring obvious on naked eye examination and risus sardonicus. Vitals were normal, and there was no icterus.

Higher mental function examination revealed impaired attention span – 7 days of week forward and 2 days of a week backward, and he was able to comprehend two-stage axial commands. Mini-Mental State Examiantion scoring was limited due to poor attention. The MMSE score was 18/30. He lost three points in orientation to time, two points in orientation to place, five points for calculation, one point in construction and one point in recall. Frontal Assesment Battery was significantly abnormal with a score of 6/18. He had impaired conceptualization, lexical fluency, sensitivity to interference and inhibitory control. He had impaired abstract thinking and could not explain the meaning of a given proverb. He did not have apraxia, agnosia.

Cranial nerve examination was normal apart from broken smooth pursuit. Motor system examination revealed symmetrical rigidity in the limbs. He had tremors of the upper and lower limbs. The tremors were present at rest and increased during action. A clinical diagnosis of WD was made. His routine lab investigations were as follows. Complete blood count (CBC) was normal; total bilirubin: 0.6 mg%; direct bilirubin: 0.15 mg/dl; total protein: 8.2 g/dl; albumin: 4.8 g/dl; globulin: 3.4 g/dl; serum glutamic oxaloacetic transaminase (SGOT): 35 IU; serum glutamic pyruvic transaminase (SGPT): 22 IU; alkaline phosphatase: 84 U/l, gamma glutamyl transferase: 23 U/l. Serum copper was 43.3 μg/dl (normal 70–150 μg/dl). The 24-hour urinary copper was significantly elevated, i.e. 635.52 μg/day (normal 32-64 μg/day). Serum ceruloplasmin levels were decreased, i.e. <0.08 g/l (normal 0.20–0.60 g/l). USG abdomen revealed liver parenchymal disease with minimal free fluid in the abdomen along with splenomegaly. Venous Doppler was normal with no evidence of portal hypertension. Magnetic resonance imaging (MRI) brain revealed classical “face of the giant panda”[4] appearance on T2-weighted images. There were hyperintensities in the caudate, putamen, thalami and pontine tegmentum.

For the severe agitation and restlessness, he was given injection haloperidol 5 mg IM in bid doses for 2 days. He still remained agitated and was subsequently given Tab lorazepam 2 mg tid. This was gradually tapered to 1 mg bid over 2 weeks. Haloperidol was replaced with quetiapine 25 mg tablet which was increased to bid over the next 2 weeks. After 2 weeks of inpatient treatment with antipsychotics and sedatives, his behavior was controlled. Trihexyphenidyl 2 mg tid was used to treat tremors and extrapyramidal effects of antipsychotics. Mild increase in rigidity and bradykinesia was noted.

The patient was started on penicillamine 250 mg daily which was gradually increased to 250 mg five times a day supplemented with pyridoxine 40 mg daily. The leukocyte counts were normal at follow-up after 3 months. There was no worsening of neurologic symptoms after the initiation of penicillamine.[5]

DISCUSSION

WD is an autosomal recessive disease characterized by inability of the liver to transport and store normally absorbed dietary copper, resulting in abnormal deposition of copper in the basal ganglia, eyes, liver and other tissues.[6] The psychiatric manifestations may precede the neurologic features in the early course of WD.

Our patient presented with a 6-month history of behavior disturbance. He had mild tremors for 5 years which he had not noticed. The tremors were mild and were present at rest and action. The patient was not troubled with this movement disorder for 5 years. He did not seek any medical advice for these symptoms. He subsequently developed disinhibition and aggression for which a consultation was made. There was an obvious KF ring[7] on examination. A clinical diagnosis of WD was made. Lab studies showed elevated urinary copper and low serum ceruloplasmin.

Psychiatric presentation of WD is rare and seen in only 15% of patients. Our patient had severe neuropsychiatric symptoms as presenting symptoms. He had emotional lability, disinhibition and was severely agitated, restless with delusional thoughts. He had initially mild tremors which did not bother him. Five years later in the course, he developed severe psychiatric symptoms. Presentation of WD with severe psychiatric symptoms is rare. Since the psychiatric symptoms in WD are generally mild, patients may not present with these symptoms. In one study, 67% patients submitted to psychiatric evaluation had mild psychiatric symptom. Of the 108 patients, only 9 (8.3%) manifested severe psychiatric symptoms that required admission. Among these patients, only one patient developed bipolar disorder that began some months before the onset of neurologic disorder. Majority of patients with WD present with motor disorder.[8] Our patient presented with severe neuropsychiatric symptoms and had tremors on examination which were present since 5 years. Tremors in a patient with any psychiatric disorder should alert one for suspecting WD. Severe neuropsychiatric symptoms can be a presentation of WD. A high degree of suspicion and early detection of WD is critical because early initiation of chelation therapy can prevent a catastrophic outcome.