White matter changes on magnetic resonance imaging in a patient with neurodegenerative disease.

A 14-year-old Sri Lankan male had progressive dysarthria, dysmetria, gait ataxia, tremor, bradykinesia for 6 years with cognitive decline ensuing 1 year prior to admission. His sister was suffering from a similar illness. His parents were non-consanguineous. On examination, the patient had a Glasgow coma score of 8. He had quadrihyperreflexia with extensor plantar response. Cerebellar assessment was difficult. Cogwheel rigidity was noted. There was no flapping tremor. Hepatosplenomegaly was elicited on abdominal examination. Kayser-Fleischer (KF) rings were confirmed by slit lamp examination.

Magnetic resonance imaging (MRI) showed increased signal intensity on T2-weighted image in basal ganglia and supratentorial with infratentorial gray and white matter [Figure 1].

Figure 1

Magnetic resonance imaging brain shows diffuse abnormal high signal intensities in cerebral white matter bilaterally (white arrows) with cerebral atrophy. These changes extend to involve the grey matter as well. Abnormal high T2 signal is seen in bilateral external capsules and slightly high T2 signal intensity is seen in both putamens (black arrows)

Biochemical analysis is as follows: Serum ceruloplasmin level - 1 mg/dl (18-45), urinary copper excretion - 4.5 μmol/24 h, Aspartate transaminase (AST) (SGOT) - 48 U/l (10-35), Alanine transaminase (ALT) (SGPT) - 57 U/l (10-40), alkaline phosphatase - 226 U/l (100-360), serum bilirubin - 9.2 μmol/l (5-21), serum protein - 70 g/l, albumin - 39 g/l, globulin - 31 g/l, prothrombin time - 12.8 s International normalized ratio (INR 1.3), APTT - 20 s, serum ammonia - 25 μmol/l (<35 μmol/l), Na+ - 140 mmol/l, K+ - 4.5 mmol/l, serum creatinine - 62 μmol/l. Cerebrospinal fluid analysis was normal.

Commentary

Extrapyramidal features including bradykinesia and cogwheel rigidity, hepato-splenomegaly, the presence of KF rings, very low serum ceruloplasmin levels and increased urinary copper excretion seen in the above patient confirmed Wilson disease (WD). In the majority of patients with symptomatic WD neuroimaging studies are abnormal. WD has a wide spectrum of neuroimaging abnormalities.[1] The most conspicuous observations are atrophy of the brain and signal abnormalities in the basal ganglia. However, nearly all areas of gray and white matter can have T2 high signal changes.[2] The above case highlights the striking white matter changes on MRI.

The white matter changes in the above patient are diffuse. When a child presents with progressive cognitive decline over a long period of time with such MRI changes a heritable leukoencephalopathy needs to be considered. When the changes are diffuse and the patient does not have megalencephaly the differentials to be considered are: Vanishing white matter disease, Pelizaeus-Merzbacher disease and mitochondrial disorders.[3] It is unusual for WD to present with diffuse white matter changes as the changes are generally found in the posterior part of the brain. However, clinical and laboratory findings in the above patient confirmed WD and diffuse changes have been reported previously.[1]

The high signal intensity of white matter on T2-weighted images in the above patient can be due to demyeliniation, softening, spongy formation and cavitary disintegration.[1] The MRI images in the above patient also demonstrate grey matter T2 high signal intensity changes, which are due to edema gliosis necrosis and cystic degeneration.[1]

Although white matter changes are known to occur with long-term disease or following penicillamine therapy there are cases of white matter changes in the early stages of the disease as well. The incidence of white matter changes have been reported by several studies. Van Wassenaer-van Hall et al. reported an incidence of 41% in 1995.[4] Two Indian studies revealed white matter changes in 10% and 25% of WD.[56] There is a paucity of data from Sri Lanka.

This case highlights the importance of recognizing white matter changes, which occur in WD especially when evaluating a neuropsychiatric disorder.