A study of MRI changes in Wilson disease and its correlation with clinical features and outcome

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Highlights

  • MRI was abnormal in all patients.

  • Putamen was involved most commonly (85.3%).

  • Sensitivity of T2 and FLAIR was highest 97.1% each.

  • MRI load correlated with age, tremor, psychiatric disorder, choreoathetosis, and severity.

Abstract

Objective

To evaluate the sensitivity of different MRI sequences in Wilson disease (WD) with neurological manifestations and its correlation with clinical features and outcome.

Methods

34 WD patients with neurological manifestation with a median age of 14 years were included. Their Mini Mental State Examination (MMSE) score, movement disorders and laboratory findings were noted. Cranial MRI in T1, T2, FLAIR and DW sequences were done. Outcome at 6 months was categorized into improved (>1 grade improvement), static or worsening.

Results

MRI was abnormal in all and revealed involvement of putamen in 29 (85.3%), caudate in 23 (67.6%), brainstem and globus pallidus in 21 (61.8%) each, thalamus in 20 (58.8%), cerebral cortex in 9 (26.5%), subcortical white matter in 8 (23.5%), and cerebellum in 2 (5.9%) patients. The overall sensitivity of T2 and FLAIR was 97.1% each, DWI 38.2% and T1 31.4%. None had contrast enhancement and 4 had reduced ADC value. Choreoathetosis correlated with thalamic, pallidal and putaminal lesions; MMSE with subcortical white mater. MRI load correlated with age, tremor, psychiatric disorder, choreoathetosis, and severity of WD. At 6 months 9 (26.5%) patients improved, 18 (52.9%) remained static and 6 (17.6%) deteriorated.

Conclusion

In neurologic WD, putaminal involvement is the commonest; T2 and FLAIR sequences have similar sensitivity and number of MRI lesions correlated with disease severity but not with outcome.

Introduction

Wilson disease (WD) is an autosomal recessive disease due to mutation of ATP7B gene in chromosome 13q 14.3. This genetic defect results in impaired excretion of copper into the bile resulting in accumulation of copper in liver, kidney, cornea, brain and other body organs. Neurological manifestation in WD occurs in the second decade and manifests with cognitive decline, drooling, extrapyramidal and pyramidal features. Cranial MRI reveals characteristic signal changes which are reported to correlate with neurological symptoms and severity of illness [1]. In a large study on cranial MRI, putaminal involvement was the commonest (72%) followed by cerebral atrophy (70%), brainstem (66%), caudate (61%) and thalamic (58%) involvement. Cerebellum was least affected in this study. MRI changes correlated with disease severity but not with duration of illness [2]. The sensitivity of different MRI sequence may vary in revealing the pathological changes. MRI changes may also suggest the disease severity and predict the outcome. There is paucity of studies evaluating the sensitivity of various MRI sequences in WD. In a study, FLAIR sequence revealed abnormality in all symptomatic WD but DW1 was abnormal in 84.6% patients [3]. Abnormality in DW1 correlated with clinical disability [3]. The diagnostic and prognostic role of different MRI sequences therefore may be different. There is no study evaluating the role of MRI sequence in the prognosis of WD. In this study, we therefore evaluate the sensitivity of different MRI sequences in revealing abnormality in WD patients with neurological manifestations and their correlation with disease severity and outcome.

Section snippets

Inclusion

Consecutive patients with WD having neurological manifestations who attended to the neurology service of Sanjay Gandhi Post Graduate Institute of Medical Sciences during last 6 years were included. The patients enrolled during 2009–2013 were prospectively evaluated. Those patients who were enrolled prior to 2009 were retrospectively analyzed from a prospectively maintained WD registry. Their data were retrieved from the computerized hospital information service and their MRI scans were

Results

There were 34 patients with neurologic WD in whom all the four sequences of MRI were available for review. Their age ranged between 9 and 41 (median 14) years and 6 were females. Family history of WD was present in 12 patients. The median duration of neurological symptoms was 18 (range 2–156) months and median age of onset of neurological symptoms was 11 (range7–39) years. Fifteen patients had jaundice in the past. Five patients had seizure; focal with secondary generalized in 1 and generalized

Discussion

The present study on MRI changes in WD patients having neurological manifestations revealed higher sensitivity of FLAIR and T2 sequences (97.1%), followed by DW1 (41.2%) and T1 (32.4%) in revealing abnormality. The lesions were more apparent in FLAIR than T2 sequence. Putaminal involvement was the commonest (85.3%) which was nonenhancing and only 3 patients had reduced ADC values. The number of MRI lesions correlated with age at presentation, choreoathetosis, tremor, BFM score, psychiatric

Conflict of interest

There is no conflict of interest to declare.

Financial support

No.

Acknowledgement

We thank Mr. Rakesh Kumar Nigam and Mr. Deepak Kumar Anand for secretarial help.

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