Wilson's Disease: An Update

Shyamal K Das; Kunal Ray

Disclosures

Nat Clin Pract Neurol. 2006;2(9):482-493. 

In This Article

Clinical Presentation

The majority of patients with WD present with either predominantly hepatic or neuropsychiatric symptoms, and with either clinically asymptomatic or symptomatic liver involvement. The remaining 20% of patients, however, may present with symptoms attributable to the involvement of other organs, as described in Box 1 .

Patients with hepatic WD usually present in late childhood or adolescence, and exhibit features of acute hepatitis, fulminant hepatic failure, or progressive chronic liver disease in the form of either chronic active hepatitis or cirrhosis of the macronodular type.[21,22] The degree of liver involvement is variable, ranging from asymptomatic hepatosplenomegaly with mild elevations of certain liver enzymes, to complete liver failure. Associated symptoms include nonspecific general symptoms, ascites and jaundice, and symptoms such as hematemesis and melena that are caused by portal hypertension. In general, the younger the age of the patient at symptom onset, the greater the degree of liver involvement.[22]

The mean age of onset of 'neurological WD' is in the second to third decade, although it has been reported as late as 72 years of age.[25] The majority of patients become symptomatic before the age of 50.[26] In the Indian subcontinent, the disorder tends to manifest one decade earlier, which is possibly related to the traditional practice of cooking and eating food using copper utensils.[27]

Patients commonly present with extrapyramidal, cerebellar and cerebral-related symptoms,[26,28] in either a subacute or a chronic fashion. An acute presentation is seen in rare cases. The most common initial presentation is bulbar symptoms characterized by difficulties with speech and swallowing, and drooling.[28] These symptoms are related to dystonia of the bulbar muscles, or pseudobulbar palsy. Abnormal posturing caused by limb dystonia interferes with writing and walking, and features of parkinsonism commonly occur in combination. A few patients present with cerebellar features such as unsteadiness of gait, and incoordination of speech and limbs.[29] Writer's cramp and acute generalized severe dystonia known as status dystonicus are rarer presentations. Acute onset of tremor of the head, neck and limbs can also be a rare dramatic presentation.

About one-third of patients experience psychiatric disturbances.[30] These disturbances can manifest as changes in school-related or work-related performance, attention deficit hyperactivity disorder, impulsivity, paranoid psychosis, obsessive behavior, depression, suicidal tendencies or bizarre behavior, and can occur early or late in the disease course.

Rarely, patients exhibit chorea of generalized or localized distribution over one half of the body.[31] Myoclonic or tonic-clonic seizure disorders—of either the generalized or the partial variety—are seen infrequently. Isolated gait difficulty and cognitive disturbance is possible although extremely uncommon, and patients can occasionally show painful proximal weakness suggestive of myopathy.

The most important sign in WD is the KF ring (Figure 2), which is best visualized with the use of a slit lamp. The presence of the KF ring reflects copper deposition in the brain. A common differential diagnosis of the KF ring is arcus juvenilis, and cholestatic jaundice can also induce a faint KF ring.

Abnormalities in ocular movements, such as slow horizontal saccades, upward gaze restriction and impaired convergence, are also common in WD. Recently, one of the authors had a case of WD presenting with bilateral eyelid apraxia that responded to botulinum toxin (SK Das, unpublished observation). Dysarthria is frequent, and can be of various types depending on the underlying pathology; examples include ataxic, hypophonic, scanning, spastic and slurred dysarthria. Rarely, patients can become virtually anarthric and mute.

Dystonic posturing is frequently evident in the face, jaw, neck, trunk and limbs, and can become permanent and fixed in the limbs if appropriate treatment is delayed or unavailable. Dystonia of the facial and jaw muscles can produce a stiff face with a gaping mouth known as a 'vacuous smile' (Figure 3). In the parkinsonian variety of WD, rigidity, bradykinesia, hypophonic speech and micrographia are all common, and tremor can be postural, action-induced, intentional or of the resting type. A swinging movement of the proximal upper limb known as 'wing-beating' tremor can also be observed,[32] which is usually caused by a lesion close to the red nucleus that interrupts the striatonigral and dentatorubral pathways. Cerebellar involvement is associated with ocular movement abnormalities, limb incoordination, impaired tandem gait, and a wide-based gait. Autonomic disturbances including postural hypotension, abnormal sweating, and sphincter and sexual dysfunction are frequently present.[33]

The 'vacuous smile' typified by mask facies with an open mouth caused by dystonia of the facial and mandibular muscles.

Very rarely, teenage patients exhibit myoclonic jerking similar to that seen in progressive myoclonic syndrome. Pyramidal tract involvement is infrequent, being observed in around 10% of cases. Interestingly, the sensory system remains intact.

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