MRI of disseminated developmental dysmyelination in Fukuyama type of CMD

Whether the pathologic origin of white matter lesions in Fukuyama type of congenital muscular dystrophy (FCMD) is delayed myelination or dysmyelination is a controversial issue. This study investigated pathologic distribution in white matter with heavily T₂-weighted images using fluid-attenuated inversion recovery (FLAIR) pulse sequence. For detection of abnormal white matter lesions, FLAIR images were approximately twice as sensitive as T₂-weighted images and five times as sensitive as T₁-weighted images of spin echo sequence. The distribution of the white matter lesions was disseminated and not correlated with cortical disarrangement. The distribution was not consistent with delayed myelination. These findings support the evidence found using in vitro proton-NMR spectroscopy that the pathologic origin of white matter lesions is dysmyelination. When conventional magnetic resonance imaging is used, masked white matter lesions are easy to misidentify as delayed myelination instead of disseminated developmental dysmyelination. The lesions in the white matter of FCMD are masked because of brain development.     

Adult-type metachromatic leukodystrophy with a compound heterozygote mutation showing character change and dementia

A 26-year-old Japanese woman slowly developed a change of character such as hypospontaneity and blunted affect, followed by obvious mental deterioration. She was diagnosed as having a disorganized type of schizophrenia at the first examination. Brain magnetic resonance imaging demonstrated diffuse high intensity in the cerebral white matter, particularly in the frontal lobes. The single photon emission computed tomography images using 123I-IMP disclosed diffuse cerebral hypofusion, especially in the frontal lobes. Electroencephalogram showed a moderate amount of 5-6Hz theta waves on the background of alpha activity. Nerve conduction velocities in the extremities were delayed. The level of leucocyte arylsulphatase was low. In the arylsulphatase A gene analysis, a compound heterozygote having the 99Gly-->Asp and 409Thr-->Ile mutations was confirmed. The patient was diagnosed as having metachromatic leukodystrophy. She gradually showed obvious dementing symptoms such as memory disturbance and disorientation. The characteristics of the psychiatric symptoms in the leukodystrophy are discussed.     

Multifocal slowing of nerve conduction in metachromatic leukodystrophy

Polyneuropathy is invariably associated with the late-infantile form of metachromatic leukodystrophy (MLD), and occurs frequently in the early juvenile, juvenile, and adult variants. Uniform slowing of nerve conduction velocity is the neurophysiologic hallmark of metachromatic leukodystrophy and other inherited demyelinating polyneuropathies. To evaluate the consistency of this principle, we reviewed nerve conduction studies in 9 children with late-infantile or early-juvenile metachromatic leukodystrophy. Each child had significant slowing of motor nerve conduction velocity (NCV). The compound muscle action potentials showed abnormal temporal dispersion in 3 of the 9 children, which is usually regarded as the hallmark of acquired demyelinating polyneuropathies. There are reports of multifocal slowing in other hereditary processes including X-linked Charcot-Marie-Tooth disease, hereditary neuropathy with liability to pressure palsies, and adrenomyeloneuropathy. Although multifocal NCV slowing in a child with polyneuropathy is seen most commonly in acquired conditions, a hereditary process, including MLD, cannot always be excluded in this setting.     

Corticosteroid-responsive parkinsonism associated with primary Sjögren's syndrome

A 74-year-old woman with primary Sjögren's syndrome confirmed by salivary gland biopsy presented with parkinsonism. Magnetic resonance imaging (MRI) of the brain revealed multiple small high intensity lesions in the deep white matter, basal ganglia and pons on T₂-weighted images. Treatment with -dopa failed to improve the parkinsonian features. After the initiation of prednisolone 30 mg/day, the parkinsonian signs and symptoms significantly improved. Some lesions on MRI were decreased in size after corticosteroid therapy. These findings suggest that parkinsonism associated with primary Sjögren's syndrome is at least in part attributable to small vessel vasculopathy such as focal inflammation or edema.     

CT and MRI in late-onset metachromatic leukodystrophy

A 23-year-old patient suffering from mental deterioration was referred for CT study following her first epileptic fit. The study disclosed generalized atrophy and diffuse symmetric white matter hypodensities. Similar findings were found in her 13-year-old retarded sister. The diagnosis of metachromatic leukodystrophy (MLD) was confirmed by the finding of low arylsulfatase A (ASA) levels in cultured fibroblasts in both sisters. MRI study revealed widespread high intensity signals of T2 nature in the periventricular regions indicating changes in white matter composition.     

Glutaric aciduria type I diagnosed after poliovirus immunization: magnetic resonance findings

Glutaric aciduria type I is an uncommon inborn error of metabolism. It is a serious disease, often with a fatal outcome. Magnetic resonance imaging findings and the clinical course of monozygotic twin females with glutaric aciduria type I who were admitted with acute encephalopathic crisis symptoms 3 days after immunization for poliovirus are presented in this report. Magnetic resonance imaging findings revealed hyperintensity in the putamen, head of the left caudate nucleus, and globus pallidus, periventricular white matter (on T₂-weighted images), arachnoid cysts in bilateral temporal regions, and enlargement of the sylvian fissures. Glutaric aciduria type I should be included in the differential diagnosis of patients with acute encephalopathic crisis occurring shortly after poliovirus immunization. Typical magnetic resonance findings guide urinary organic acid analysis in these patients.     

Magnetic resonance imaging in leukodystrophies of childhood

Magnetic resonance imaging (MRI) is particularly valuable in the diagnosis of childhood brain disorders with abnormal myelination because MRI may identify lesions not always seen with x-ray CT scans. We report the clinical and magnetic resonance findings of six children with leukodystrophy. T2 weighted (spin-echo) images disclosed striking asymmetric involvement of cerebral white matter, particularly in periventricular white matter and visual radiations. Calculated T1 values were significantly elevated in the children with leukodystrophy.     

MRI in neurofibromatosis type I: Using fluid-attenuated inversion recovery pulse sequences

Cranial magnetic resonance imaging results of 14 patients with neurofibromatosis type I were examined with T₂-weighted fluid-attenuated inversion recovery pulse sequences, as well as conventional T₂-weighted spin-echo sequences. Definition was better in 62 of 79 lesions or groups of lesions on fluid-attenuated inversion recovery images than on T₂-weighted spin-echo images. The lesions were demonstrated not only in the brainstem, cerebellum, globus pallidus, and cerebral white matter, but also in the hippocampus, pulvinar thalami, and splenium of the corpus callosum. The latter 3 lesions have not been demonstrated or emphasized in previous studies. It is concluded that fluid-attenuated inversion recovery imaging is more effective in detecting multiple lesions in patients with neurofibromatosis type I than conventional T₂-weighted spin-echo imaging.     

Computed tomography in late-infantile metachromatic leukodystrophy

Computed tomography of 2 patients with late-infantile metachromatic leukodystrophy (MLD) demonstrated generalized white matter lucency and moderate ventricular enlargement. CAT scan findings in other white matter diseases likely to be confused clinically with MLD are sufficiently dissimilar to allow differentiation.     

MRI findings in children infected by Borrelia burgdorferi.

Cranial magnetic resonance imaging abnormalities were observed in 8 children (5 boys, 3 girls; ages 4–14 years) with neurologic problems following infection by Borrelia burgdorferi, the etiologic agent of Lyme disease. Neurologic features included headache (6), behavioral changes (5), facial palsy (2), papilledema (2), papilledema with diplopia (1), disturbance of sleep pattern (2), and carpal tunnel syndrome (1). Two MRI studies demonstrated multiple focal areas of increased signal intensity in white matter on long TR (both proton-density and T₂-weighted) images.     

Computed tomography and magnetic resonance imaging in adult-onset leukodystrophy

Five clinically affected and nine at-risk members of a kindred with an autosomal dominant adult-onset leukodystrophy simulating chronic progressive multiple sclerosis were studied with computed tomography (CT) and magnetic resonance imaging (MRI). Computed tomographic scans showed white matter lucencies occurring earliest and most prominently in the frontoparietal region. The lesions were nondiscrete, diffuse, and bilaterally symmetric. These changes were more clearly visualized as areas of increased signal intensity with T2-weighted MRI. Magnetic resonance imaging also showed increased signal intensity in the brain stem, cerebellar white matter, or both of four patients. Both MRI and CT differentiated this entity from multiple sclerosis, but MRI was superior to CT in detailing the extent of white matter involvement.     

Sturge-Weber syndrome without facial nevus

An 11-month-old patient with Sturge-Weber syndrome with the absence of facial angioma and normal mental development is presented. Noncontrast computed tomography revealed left parieto-occipital atrophy with heavy gyriform calcifications. Axial T₂-weighed magnetic resonance imaging confirmed the presence of low-signal areas corresponding to the gyral calcifications evident on computed tomography. Contrast-enhanced T₁-weighted axial and coronal images exhibited high signals in the left parieto-occipital cortical and subcortical areas, representing angiomatous malformations. The clinical appearance and pathologic features of the reported patient were compared with those of similar patients described in published reports.     

Early diagnosis of leukoencephalopathy of acute lymphocytic leukemia by MRI

Using repeated computed tomographic and magnetic resonance imaging scans, we examined 8 patients with acute lymphocytic leukemia during remission induction therapy between 1988 and 1989. In 3 patients, leukoencephalopathy was diagnosed by T₂-weighted magnetic resonance imaging. In 1 patient, leukoencephalopathy was progressive and irreversible brain damage and mental retardation persisted. In the other 2 patients, hyperintense lesions in the periventricular white matter were transient and no neurologic sequelae ensued. Magnetic resonance imaging was more useful than computed tomography in the early diagnosis and management of these acute lymphocytic leukemia patients with leukoencephalopathy.     

MRI and CT findings in Krabbe disease

The progression and characteristics of magnetic resonance imaging (MRI) and computed tomographic (CT) findings in 3 patients with infantile Krabbe disease (i.e., globoid cell leukodystrophy or galactocerebroside beta-galactosidase deficiency) are reported. We obtained initial CT and MRI studies when patients demonstrated hyperirritability and hypertonicity. The following results facilitated early diagnoses: increased density in the thalami, corona radiata, and cerebellar cortex on CT and plaque-like, high signal intensity in the periventricular region and cerebellar white matter on MRI T2-weighted images. After severe motor and mental deterioration and spasticity had developed, progressive brain atrophy, low density in the white matter, and calcification-like, symmetric, punctate high-density areas in the corona radiata were evident on CT and high signal intensity in T2-weighted images and low signal intensity in T1-weighted images in the white matter were present on MRI. In particular, linear patterns were observed in the centrum semiovale on MRI.     

A 40-year-old woman with progressive dementia and abnormal behavior]

We report a 40-year-old Japanese woman who died after 12 years history of progressive dementia and abnormal behaviors. She was well until 1985 at her age of 28 years old, when she had an onset of behavioral change in which she drank much, neglected house-keeping works, and her life style became sloppy. At age 30, she became unable to understand written sentences, and paced up- and down in and out of her house. She was admitted to other hospital where marked dementia with disorientation and memory loss were noted. Slight increase in CSF protein and decrease in the peripheral nerve conduction velocity were also noted at that time. In the next year, she started to have convulsions. These symptoms had progressively become worse and was admitted to Tokyo Metropolital Matsuzawa Hospital in June of 1991 when she was 34 years of age. Despite marked dementia, she was able to walk normally, no motor paralysis, cerebellar ataxia, nor dyskinesia were noted. Deep tendon reflexes were diminished. MRI revealed T-2 high signal intensity lesions involving the white matter of the cerebrum predominantly in the frontal region. In about one year, she started to show difficulty in gait, and she became bed-ridden in July of 1994. She was discharged to home for a while, but required admission again. She expired on February 5, 1998. Her younger brother had an essentially similar dementing disease and he expired at the age of 35 years. The parents were of first cousins. The patient was discussed in a neurological CPC, and the chief discussant arrived at the conclusion that the patient had adult form of metachromatic leukodystrophy, because of white matter change in the frontal lobe, decrease in nerve conduction velocity, convulsion, marked dementia, and consanguineous marriage with a similarly affected brother. Most of the audience agreed with this conclusion, but the differential diagnosis from globoid cell leukodystrophy was felt difficult from the clinical findings alone. Post-mortem examination revealed marked atrophy in the frontal lobe. Cerebellum appeared to be smaller than normal. In the coronal sections, marked atrophy of the white matter with brown discoloration was noted. The lateral ventricles were dilated. Klüver-Barrera staining revealed marked demyelination with relative preservation of the U-fibers. PAS-positive materials were deposited in some astrocytes as well as neurons. Metachromatic deposits were noted not only in the cerebrum but also cerebllum after staining with acid cresyl violet. Pathologic diagnosis was consistent with adult type of metachromatic leukodystrophy.     

Update on genetic disorders affecting white matter

The classification of diseases affecting white matter has changed dramatically with the use of magnetic resonance imaging. Classical leukodystrophies, such as metachromatic leukodystrophy and Krabbe's disease, account for only a small number of inherited diseases that affect white matter. Magnetic resonance imaging has clarified genetic disorders that result in white matter changes or leukoencephalopathies. The term leukoencephalopathy is used to reflect the broader number of diseases that may cause as either primary or secondary changes in myelin development. This review attempts to categorize white matter disorders into classes such as lipid, myelin protein, organic acids, and defects in energy metabolism, in addition to other causes.     

Use of computed tomography, magnetic resonance imaging, and localized 1H magnetic resonance spectroscopy in Canavan's disease: a case report

The neuroradiological evaluation of Canavan's disease in a 38-month-old girl is discussed. Computed tomography showed diffuse symmetrical low attenuation values of the subcortical and deep cerebral white matter. Magnetic resonance imaging demonstrated symmetrical diffuse low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. With the use of 1H magnetic resonance spectroscopy, we were able to show elevated levels of N-acetylaspartic acid in the occipital lobe of our patient. The in vivo measurement of N-acetylaspartic acid in the brain by 1H magnetic resonance spectroscopy offers an additional noninvasive diagnostic test for establishing the diagnosis of Canavan's disease. With the increasing availability of magnetic resonance spectroscopy, clinicians may be able to confirm the diagnosis of Canavan's disease immediately after magnetic resonance imaging reveals the typical abnormalities of the white matter.     

Neuroradiological findings in classical late infantile neuronal ceroid-lipofuscinosis

We describe a girl aged 5 years, 6 months who began to have seizures at the age of 3 years, 9 months. A cranial CT scan revealed mild, generalized cerebral atrophy. During the next year, she gradually developed ataxia, myoclonic jerks, and bilateral optic nerve atrophy and lost motor skills. A second CT scan performed 12 months after the onset of first symptoms revealed marked progression of cerebral atrophy, especially in the infratentorial area. MRI demonstrated bilateral, periventricular hyperintensities in the T₂-weighted images but no changes in the basal ganglia. Electron microscopic investigations of skin biopsies demonstrated curvilinear bodies, confirming the suspected diagnosis of late infantile neuronal ceroid-lipofuscinosis (LINCL). Predominance of cerebral atrophy in the infratentorial area is typical of LINCL. Periventricular white matter lesions may be evident on MRI scans of patients with classical and LINCL-variant disease. In contrast to neuroradiological findings in patients with LINCL-variant disease, findings in patients with classical LINCL revealed no changes in the basal ganglia.     

Dysmyelinating neuropathy in benign form of megalencephalic leukoencephalopathy with subcortical cysts: a novel observation from south India

A 37-year-old gentleman presented with macrocephaly since early childhood and progressive impairment of motor and cognitive functions. Magnetic resonance imaging revealed extensive white matter involvement and frontotemporal subcortical cysts. Absent ankle jerk and abnormal nerve conduction study raised a possibility of associated peripheral neuropathy. Sural nerve biopsy was suggestive of dysmyelinating neuropathy. This report serves to expand the clinical spectrum of this rare leukodystrophy.     

Thalamic hyperdensity on CT in infantile GM1-gangliosidosis

Thalamic hyperdensity on computer-associated tomography (CT) has been reported as a disease-specific finding for GM₂-gangliosidosis. However, a boy with the typical clinical symptoms and enzyme defect of infantile GM₁-gangliosidosis had hyperdense thalamic lesions at 12 months of age. At the age of 34 months, the thalamus showed atrophy and the hyperdensity was restricted to the medial part of the thalamus, which exhibited increased intensity on T₁-weighted and decreased intensity on T₂-weighted images. Thalamic hyperdensity may be specific not only to GM₂-gangliosidosis but also to GM₁-gangliosidosis.