Sanna-Leena Vanhanen

MRI of neuronal ceroid lipofuscinosis. II. Postmortem MRI and histopathological study of the brain in 16 cases of neuronal ceroid lipofuscinosis of juvenile or late infantile type

Abstract Postmortem MRI was carried out on the formalin-fixed brains of 14 patients with juvenile (JNCL) and two with late infantile neuronal ceroid lipofuscinosis, one of variant and the other of classical type. Two patients with JNCL had also undergone MRI during life. After MRI, specimens for histopathological analysis were taken from standard areas of the cerebral cortex, deep nuclei and white matter. The signal intensity of the periventricular white matter was usually higher than that of the peripheral white matter, a finding which correlated with the severe periventricular loss of myelin and gliosis observed histologically. The signal intensity was usually lower in the thalamus than in the putamen; in some patients the signal intensity of the thalamus was equal to or even lower than that of the white matter. However, myelin loss, gliosis, the storage process or neuronal loss in the thalamus did not correlate with the MRI findings. Since in one patient with JNCL the ante- and postmortem MRI did not differ basically, it appears probable that the periventricular changes detected in vivo on MRI are due to the severe loss of myelin and gliosis observed in this study. However, changes resulting from the fixation process must be considered, when postmortem and in vivo MRI are correlated.

MRI Evaluation of the Brain in Infantile Neuronal Ceroid-Lipofuscinosis: Part 2: MRI Findings in 21 Patients

The purpose of this study was to demonstrate the course of infantile neuronal ceroid-lipofuscinosis with brain magnetic resonance imaging (MRI) in children aged 3 months to 11 years. Twenty-one patients and 46 neurologically normal controls of the same age were examined. The images were evaluated visually; then signal intensities were measured and related to those of references. MRI abnormalities were detectable before clinical symptoms. The radiologic picture of the brain varied with the duration of the disease. Pathognomonic MRI findings in the early stage of the disease were generalized cerebral atrophy, strong thalamic hypointensity to the white matter and to the basal ganglia, and thin periventricular high-signal rims from 13 months onward on T2-weighted images. In patients over 4 years old, cerebral atrophy was extreme, and the signal intensity of the entire white matter was higher than that of the gray matter, which is the reverse of normal. This study showed that the abnormalities seen on MRI progress rapidly during the first 4 years of life, then stabilize, in conformity with the clinical and histopathologic pictures of infantile neuronal ceroid-lipofuscinosis. (J Child Neurol 1995; 10:444-450).

The normal brain stem from infancy to old age

Our purpose was to develop a method of measuring the size of the brain stem by routine MRI and to determine brain stem dimensions in a normal population. We examined 174 subjects, aged 4 months to 86 years, with no known brain disease. Sagittal midline diameters of the mesencephalon, pons and medulla oblongata were measured on sagittal T1-weighted images, coronal diameters from axial T2-weighted images. The adult midsagittal diameter of the mesencephalon was reached at the age of 6 years, and decreased slightly after 45–50 years. Pontine dimensions increased until the age of 20 years and did not subsequently decrease. The midsagittal and midcoronal diameters of the medulla oblongata stopped increasing at the ages of 6 and 8 years, respectively. Minimal reduction in the midsagittal diameter occurs after 50 years. Normal ranges for each dimension were recorded. Knowledge of the normal variation in size of the brain stem can be helpful in the investigation of neurodegenerative diseases. The method described is rapid and needs no additional hard-or osoftware. An additonal finding was an increase in large vermian sulci in subjects over 50 years of age.

Psychological symptoms and sleep disturbances in neuronal ceroid-lipofuscinoses (NCL).

Unrest, irritability and sleep disturbances are common symptoms in both infantile and juvenile NCL (INCL and JNCL) (Telakivi et al 1985; Santavuori 1988), and rarer in the late-infantile type (LINCL). In INCL irritability and sleep dysfunction may be the presenting symptoms of the disease. Irritability, often combined with unrest and a disturbed sleep cycle, with fluctuating intensity, were found in 90% of patients between 1 and 3 years of age (Santavuori 1988). They all reached a more peaceful period at the time they became bedridden. The symptoms recurred in about 60% of INCL children after the age of 6-8 years. Several patients had attacks of pain with opisthotonus lasting from some minutes to several hours, perhaps precipitated by frequent daily seizures. In the management of INCL, irritability, sleeping disorder, choreoathetotic behaviour and late pains have responded best to baclofen (15-25 mg/day, increasing to as much as 200mg/day) or tizanidine (1-9 mg/day, later 20-60mg/day), often in combination. Levomepromazine (5-20mg/day) or benzodiazepines have also been of help (and midazolam in older children showing severe sleep disorders). In the case of severe symptoms intrathecal baclophen should be used. Moreover, adjustments of everyday life such as a special kind of rocking chair, a car ride, a bubble bath or a water bed in a peaceful environment may relax the child. Only a few children with LINCL showed irritability and disturbance of the sleepwake cycle interfering with daily life. In order to find out how common psychological problems and sleep disorders are in JNCL patients in Finland, a survey was carried out in Spring 1992. The study included 42 patients living at home between September 1984 and March 1992 (series A), born between 1958 and 1984. Of these patients 37 were alive in Spring 1992. The corresponding figures for institutionalized patients (series B) were 13 patients, born 1940 and 1968, 3 alive. Psychological symptoms had been observed in 31/42 (series A) and 9/13 (series B) patients (Table 1). The symptoms were moderate in 20 and severe in 6 patients, respectively. The mean age at onset was 10.2 years (range 5-15 years) (series A). One

MRI of the normal brain from early childhood to middle age

The magnetic resonance images of 67 healthy subjects aged 4–50 years were studied for differences in general signal intensity between the different brain structures, the frequency of focal intensity changes in the brain, and variations in size of the cerebrospinal fluid (CSF) spaces. In adults over 25 years of age the thalamus gave lower signal than the putamen or caudate nucleus. Definite periventricular high signal was found in the white matter of one third of subjects of all ages. Small (<5 mm in diameter) high signal foci were found in the cerebral white matter on T2-weighted images in 27% of subjects (20% of healthy children and adolescents and 34% of adults). They gave high signal on both short and long echoes in 11% of children and adolescents and in 22% of adults; 51% of all foci gave high signal with both echoes. This does not support the hypothesis that they are caused mainly by enlarged Virchow-Robin spaces. Of the high signal foci on T2-weighted images, 86% were in watershead areas. Two foci were found in one subject in the periventricular watershed area (beside the tips of the frontal horns) and they were never seen in the other deep white matter regions. In healthy, relatively young subjects with no known risk factors, high signal foci other than Virchow-Robin spaces, were common; neither their prevalence nor their number correlated with age in this series. A few slightly large sulci were found in some adults.

MRI of the brain, EEG sleep spindles and SPECT in the early diagnosis of infantile neuronal ceroid lipofuscinosis.

Two patients with infantile neuronal ceroid lipofuscinosis are presented whose clinical diagnosis was based on the typical clinical picture, together with absent sleep spindles and MRI findings (hypointense thalami and hyperintense periventricular white matter) as early as 18 months in one girl. In addition to a flat cortical SEP, these abnormalities appeared earlier than the typical ERG and VEP findings used previously for clinical diagnosis of this condition. MRI of the other patient showed the same changes and EEG sleep spindles were absent by two years.

Magnetic resonance techniques in neuronal ceroid lipofuscinoses and some other lysosomal diseases affecting the brain

Magnetic resonance techniques in neuronal ceroid lipofuscinoses and some other lysosomal diseases affecting the brain

Aspartylglucosaminuria: radiologic course of the disease with histopathologic correlation

Twelve living patients (aged 19 months to 32 years) with aspartylglucosaminuria were examined by magnetic resonance imaging (MRI), and the magnetic resonance (MR) images of 16 healthy volunteers (aged 4 to 32 years) were used as controls. One patient was examined twice. Postmortem MRI and histopathologic analysis were done on the brains of four additional adult patients. Signal intensities determined quantitatively on T2-weighted images differed significantly between patients and controls, being higher from the white matter (P < .0002) and lower from the thalami (P < .03) in the patients. The generally increased signal intensity of the white matter was most obvious in the young patients, with many focal areas of very high signal intensity in the subcortical white matter. The subcortical white matter showed a somewhat increased signal intensity even at the age of 32 years. In two of the four postmortem MR images, the distinction between the gray and white matter was still poor. At histopathologic analysis, the basic cortical cytoarchitecture was generally preserved but most neurons contained vacuoles, which were also found in the neurons of the deep gray matter. In two of the four autopsy cases the white matter showed diffuse pallor of myelin staining and some gliosis. Thus aspartylglucosaminuria is primarily a gray-matter disease also affecting white matter by delaying myelination. (J Child Neurol 1997;12:369-375).

MRI Evaluation of the Brain in Infantile Neuronal Ceroid-Lipofuscinosis. Part 1: Postmortem MRI With Histopathologic Correlation

The purpose of this study was to correlate postmortem magnetic resonance imaging (MRI) with histopathologic findings in brains of a series of autopsied patients with infantile neuronal ceroid-lipofuscinosis, a recessively inherited progressive encephalopathy. Eight formalin-fixed brains (age range at death, 7 to 13 years) were examined with MRI. One patient had also undergone brain MRI 2 years before death. Histopathologic analyses were made from standard areas selected on the basis of the MRI scans. Postmortem MRI findings did not differ significantly from the findings in the patient who was also examined during life. Typical findings were extreme cerebral atrophy and hypointensity of the gray-matter structures in relation to the white matter on T2-weighted images, a pattern the reverse of normal. Characteristic histologic findings were almost complete loss of cortical neurons and secondary loss of axons and myelin sheaths in the white matter. The drastically altered relative intensities of the gray- and white-matter structures on the MRI scans reflected replacement of the neurons with hypertrophic astrocytes and/or macrophages filled with storage material. (J Child Neurol 1995;10:438-443).