Prognostic factors in patients presenting with severe neurological forms of Wilson's disease

BACKGROUND: Wilson's disease (WD), a metabolic disorder, is believed to be potentially reversible, even in its severe form. However, some patients do not respond to treatment. AIM: To analyse prognostic factors in severe WD. DESIGN: Retrospective audit. METHODS: A total of 140 patients were regularly followed from February 2002 to May 2004. Twenty-nine (18 males, 11 females) had severe disease, as defined by Modified Schwab and England Activities of Daily Living score (MSEADL) of < or=50% or Chu stage of 3. We analysed their clinical, laboratory and MRI features with respect to prognosis. RESULTS: For the severe form, mean age at symptom onset was 11.5 +/- 6.4 years, and at diagnosis, 13.3 +/- 7.0 years. Mean Neurological Symptom Score (NSS), Chu stage, and MSEADL were 26.5 +/- 8.2, 2.7 +/- 0.5 and 24.8 +/- 17.4, respectively. Twenty-one patients underwent MRI; 14 had repeat MRI. Following treatment, 14 (group A) had progressive worsening, including death in two, while 15 (group B) had sustained clinical improvement. Baseline demographic, clinical and laboratory features and MRI scores did not significantly differ between the two groups. However, diffuse white-matter abnormalities were more extensive in group A. Full-dose initial penicillamine therapy could have contributed to worsening in four patients. Drug compliance was poor in both groups but resumption of treatment did not benefit patients in group A. Serial MRI showed regression of lesions only among patients with clinical improvement. DISCUSSION: Severe WD remains a therapeutic challenge, with early diagnosis and treatment are essential. Specific MRI observations, a 'start low-go slow' regimen for penicillamine, and compliance may have prognostic significance. In absence of clinical predictors, genetic attributes need to be explored.