Treatment of symptomatic heterozygous aceruloplasminemia with oral zinc sulphate.

Aceruloplasminemia is an autosomal recessive and phenotypically primarily neurodegenerative disease caused by a homozygous mutation of the ceruloplasmin gene. The absence of ceruloplasmin and its ferroxidase activity leads to pathological iron overload in the brain and other organs. While heterozygous carriers of ceruloplasmin gene mutations have been believed to be asymptomatic, a number of cases with neurological deficits have recently been described. To date, an effective treatment has not been established for either aceruloplasminemia or symptomatic heterozygous aceruloplasminemia. The present report concerns the beneficial treatment of an 18-year-old girl with extrapyramidal and cerebellar-mediated movement disorder caused by a heterozygous mutation of the ceruloplasmin gene using oral zinc sulphate.

Transient myelopathy of the cervical posterior columns in a young man with recently diagnosed diabetes mellitus.

We present the case of a young man with recently manifesting type I diabetes mellitus who progressively developed clinical and radiological signs and symptoms of cervical posterior column myelopathy with eventually spontaneous and complete recovery as concerns both clinical symptomatology and MRI abnormalities.

Neuropathological analysis of pathological forms of astroglia in Wilson's disease.

A neuropathological study of Alzheimer type I (Alz I) and Alzheimer type II (Alz II) as well as Opalski (Opl) cells was performed serially on brain tissue from nine autopsied Wilson's disease (WD) cases. Conventional staining methods (Kluver-Barrera, HE, PAS) and immunocytochemical techniques (anti-GFAP and anti-Metallothionein-MT) were used. On conventional staining, each of the studied abnormal cell types retained common morphological characteristics of astroglia, and concurrently demonstrated its own distinctive features, specific only for a given cell type. Anti-GFAP staining revealed positive immunoreactivity of Alz I and Opl cells, and its absence in Alz II cells. On anti-MT staining both the cytoplasm and nucleus of Alz I and Opl cells showed positivity whereas in Alz II cells the cytoplasm was positive in contrast to the negative nucleus. The results of our study confirm the hypothesis of the astroglial origin of all three types of cells. The lack of immunoreactivity for GFAP and similar immunocytochemical staining patterns for MT in Alz II cells and protoplasmic astrocytes may suggest that Alz II cells originate from the protoplasmic type of astroglia. The fact that Alz I and Opl cells resemble fibrous astrocytes in their immunoreactive positivity for GFAP may lead to a supposition that they originate from the fibrous type of astroglia. MT-positive expression by the three abnormal cell types suggests that they may be involved in the process of copper detoxification in WD.

[Clinical thinking and decision-making in practice. A nurse with low back pain radiating to both legs]. / Klinisch denken en beslissen in de praktijk. Een verpleegster met pijn onder in de rug uitstralend in beide benen.

A 50-year-old nurse with chronic back pain developed painful paraesthesia in the legs and saddle region during walking. Because pain in the legs could not be provoked by standing erect, the orthotic-lordotic cauda syndrome or neurogenic intermittent claudication (spinal canal stenosis) became unlikely and vascular intermittent claudication likely. The femoral pulses were absent. Angiography showed severe stenosis of the distal aorta which was successfully treated by percutaneous transluminal angioplasty.

Differentiation between portal-systemic encephalopathy and neurodegenerative disorders in patients with Wilson disease: H-1 MR spectroscopy.

PURPOSE: To investigate the extent to which neurodegeneration and metabolic changes caused by portosystemic shunting occur in Wilson disease. MATERIALS AND METHODS: Twenty-two adult patients with biochemically proved Wilson disease underwent magnetic resonance (MR) imaging, hydrogen-1 MR spectroscopy, neurologic and psychometric testing, and ultrasound evaluation of the liver. In addition, 13 age-matched adult control subjects underwent MR imaging and H-1 MR spectroscopy. For MR spectroscopy, the authors used a single-voxel technique with a repetition time of 2,000 msec and an echo time of 31 msec. The volume of interest included the right and left globi pallidus, which are the most common sites of lesions in Wilson disease. RESULTS: N-acetylaspartate-creatine and choline-creatine ratios were decreased in patients with Wilson disease versus control subjects (P < .001 for N-acetylaspartate-creatine ratio, P < .05 for choline-creatine ratio). Also, patients with Wilson disease and portosystemic shunting had lower myo-inositol-creatine ratios than did patients with Wilson disease and no portosystemic shunting (P < .05). CONCLUSION: Reductions in N-acetylaspartate indicate neuronal loss consistent with the neurodegenerative pattern associated with Wilson disease. In addition, H-1 MR spectroscopy shows metabolic abnormality in the brain, as decreased myoinositol, caused by portosystemic shunting.

Wilson disease: findings at MR imaging and CT of the brain with clinical correlation.

PURPOSE: To describe the spectrum of brain abnormalities in Wilson disease (hepatolenticular degeneration) as depicted at magnetic resonance (MR) imaging and computed tomography (CT) and to relate these findings to neurologic and hepatologic abnormalities. MATERIALS AND METHODS: Fifty patients with Wilson disease participated in the cross-sectional study: Patients underwent cerebral MR imaging (n = 49), CT (n = 44), abdominal duplex ultrasound (US) (n = 46), and neurologic examination (n = 50) within a week. Relative risk and the Fisher exact test were used for statistical analysis. RESULTS: Supratentorial and infratentorial abnormalities in the gray and white matter were found in the pyramidal and extrapyramidal system. In Wilson disease, an abnormal striatum depicted on MR images correlated with pseudoparkinsonian signs, an abnormal dentatothalamic tract correlated with cerebellar signs, and an abnormal pontocerebellar tract correlated with pseudoparkinsonian signs. The presence of portosystemic shunt was strongly associated with abnormality of the globus pallidus. CONCLUSION: MR imaging findings were of some use in the clinical treatment of patients with Wilson disease.

Cranial MR in Wilson disease: abnormal white matter in extrapyramidal and pyramidal tracts.

PURPOSE: To describe abnormal white matter in the brain on MR in Wilson disease and to compare with anatomic location of white matter tracts. METHODS: Forty-six patients with Wilson disease were examined. Axial T1-weighted inversion-recovery, axial T2-weighted spin-echo, and coronal T2*-weighted gradient-echo MR images were performed. Imaging studies were compared with clinical data. RESULTS: Seventeen patients showed abnormalities in the region coinciding with the following white matter tracts: corticospinal tract (24%, n = 11), dentatorubrothalamic tract (24%, n = 11), and pontocerebellar tract (17%, n = 8). CONCLUSION: Abnormal extrapyramidal and pyramidal white matter tracts are part of the neuroimaging spectrum of Wilson disease. No significant correlation was found with neurologic groups and individual white matter tracts affected.

H714Q mutation in Wilson disease is associated with late, neurological presentation.

Wilson disease is an autosomal recessive copper storage disease resulting from an inability of the liver to excrete copper. Patients can present at a young age, generally with symptoms of liver copper intoxication, or later on, generally with neurological symptoms. The gene for Wilson disease has recently been cloned. Five mutations have been described so far, but only one is found frequently, H714Q. We analysed 38 Dutch symptomatic Wilson disease patients for the H714Q mutation and correlated this finding with age and symptoms at presentation. Ten patients homozygous for the H714Q mutation presented at a mean age of 20.3 (SD 6.1) years, with either neurological symptoms or a Kayser-Fleischer ring. Six patients with a H714Q mutation in one chromosome and an unknown mutation in the other chromosome presented at a mean age of 17.8 (SD 5.8) years, with either neurological or hepatic symptoms. With the exception of one, all 22 patients with an uncharacterised mutation in both chromosomes presented with liver involvement, at a mean age of 9.9 (SD 2.4) years. The difference in age at presentation between the H714Q/H714Q group and the patients with an unknown mutation was highly significant (p < 0.0001). This suggests that the H714Q mutation represents a relatively mild mutation, possibly with some residual function in the copper transporting protein, resulting in a slower build up of copper.

[Wilson's disease; diagnosis with the aid of magnetic resonance tomography]. / Ziekte van Wilson; ontmaskering met behulp van kernspinresonantie-tomografie.

In a 21-year-old woman with a smaller and sloppy handwriting, drooling especially when stooping, sporadic choking, clumsiness, and frequent stumbling, Wilson's disease was diagnosed. The medical history disclosed a short period of haemolytic anaemia with transient hepatic failure, and irregular menstruation periods with infertility. On examination there were no signs of liver or spleen enlargement. She was slow, had an expressionless face and mild dysarthria, and slight impairment of the coordination of the limbs. Magnetic resonance imaging of the brain showed bilateral hyperintensive lesions of the basal ganglia on T2W images. Zinc therapy induced a good biochemical response and there was also some clinical improvement. Linkage analysis within the family identified one other asymptomatic homozygotically affected sister. A diagnostic delay occurs frequently due to relative unfamiliarity with this rare disease and due to its variable clinical expression.

31P magnetic resonance spectroscopy of the liver: correlation with standardized serum, clinical, and histological changes in diffuse liver disease.

The goal of this study was to analyze the possibilities of 31P MR spectroscopy to detect abnormal hepatic histological changes in patients with diffuse liver disease. 31P MR spectroscopy was performed, on a 1.5 T whole-body spectrometer using an image guided localization technique (ISIS), on 38 patients with various diffuse liver diseases, who all underwent histological and serum analysis, and 22 healthy volunteers. Phosphomonoester expressed as a fraction of total phosphorus (PME/P) showed a correlation with abnormal serum aspartate transaminase (AST), histological intralobular degeneration/focal necrosis, portal inflammation, and piecemeal necrosis. We found a lower correlation for PME/P with fibrosis. It was not possible to differentiate between fibrosis and cirrhosis. In summary, 31P MR spectroscopy is a technique to detect intralobular degeneration, inflammation and necrosis and to a less extent fibrosis. No diagnostic value was found with respect to steatosis and cholangitis. Furthermore, 31P MR spectroscopy is a poor method for classifying patients into diagnostic categories.