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Biomedical subjects

T Autti

Publications and source records attributed to T Autti.

At least 37 records · Page 2Linked to original sources
PubMed1999

Extensive cerebral white matter abnormality without clinical symptoms: a new hereditary condition?

A 30-year-old father and his 2 sons with slight hyperkinesia and mildly dysmorphic features and their close relatives were examined clinically and with computed tomography (CT) and magnetic resonance imaging (MRI). Neurophysiological and biochemical examinations were normal; however, brain MRI of the father and sons revealed extensive cerebral white matter changes. No radiological progression could be detected at a 13-year follow-up examination of the father, and proton magnetic resonance spectroscopy (MRS) of the father at the age of 30 years was normal. MRI findings in the relatives were normal, suggesting an autosomal dominant syndrome due to a new mutation in the father.

Adult↗
PubMed1998

Atypical juvenile neuronal ceroid lipofuscinosis with granular osmiophilic deposit-like inclusions in the autonomic nerve cells of the gut wall.

In this 8-year-old boy, who had been exposed to alcohol and oxazepam during pregnancy, visual failure was the first symptom of a neuronal ceroid lipofuscinosis (NCL) disorder, noticed at the age of 5 years. Ophthalmological examinations revealed a cystic type of macular degeneration, which would be more likely to be found in variant late infantile NCL. However, vacuolated lymphocytes were found in peripheral blood films and a diagnosis of the juvenile form of NCL (JNCL) was made. Molecular genetic studies showed the patient to be homozygous for the major mutation of JNCL, a 1.02-kb deletion. In whole-night polysomnography, there was significantly more epileptiform activity than in other JNCL patients under 10 years of age. Using magnetic resonance imaging, the signal intensity of the white matter was increased, especially in the periventricular area. In addition, there were enlarged perivascular spaces in the watershead areas. The corpus callosum was thin. Finally, in the autonomic ganglion cells of the submucosal nerve plexus there were membrane-enclosed homogeneous and granular cytosomes resembling the granular osmiophilic deposits of infantile NCL. However, extraneural cells, including blood capillaries and smooth muscle, showed inclusions with fingerprint and curvilinear profiles. The features of the present case indicated a phenotypic variant of JNCL.

Child↗
PubMed1998

Muscle-eye-brain disease: clinical features, visual evoked potentials and brain imaging in 20 patients.

Clinical features, magnetic resonance imaging and visual evoked potentials were analysed and correlated in 20 Finnish patients with muscle-eye-brain disease. Significantly enhanced visual evoked potentials were found in 15 patients (giant in 14 of them). Magnetic resonance images were available in 17 cases. The images of 12 patients with giant visual evoked potentials showed typical brain malformation pachygyria with a nodular cortical surface i.e. cobblestone cortex, midline defect and hypoplastic pons but no significant abnormalities in the grey-white matter. One male had typical structural changes but flat visual evoked potentials. His extreme hydrocephalus with optic nerve compression may explain the findings. No structural changes on magnetic resonance images were found in the remaining four patients; however, in two of them marked alterations in the white matter were found. Three of these patients showed normal and one flat visual evoked potentials. Only one patient with giant visual evoked potentials and typical structural findings on magnetic resonance imaging had changes in a large area in the white matter (several attacks of status epilepticus might have caused the alterations in the white matter). Thus, the combination of giant visual evoked potentials and typical structural changes on magnetic resonance imaging with normal intensities of white matter and deep grey matter seems to be a good marker for patients with muscle-eye-brain disease.

Abnormalities, Multiple↗
PubMed1998

MRI of the brain in the Cohen syndrome: a relatively large corpus callosum in patients with mental retardation and microcephaly.

Our purpose was to perform the first systematic brain magnetic resonance imaging (MRI) study of a substantial number of Cohen syndrome (MIM n:o 216550) patients. 18 Cohen patients and 26 healthy volunteers were examined by MRI (1.0 T). All Cohen patients had essential features of this syndrome: typical facial and structural features, mental retardation, microcephaly, ophthalmologic symptoms, granulocytopenia and cheerful psychic disposition. All our patients belong to the recently published study of refined mapping of the Cohen syndrome gene by linkage disequilibrium. As visual analysis of MR images revealed an impression of a large corpus callosum (CC), quantitative analysis was performed. Sagittal diameter of the body of the CC was larger than that of controls (p = 0.02), whereas all sagittal diameters of the brain stem were markedly smaller (p < 0.0001), as was the midline internal skull surface (MISS) (p < 0.0001). The CC surface did not significantly differ from that of controls significantly. Our main finding, a relatively enlarged corpus callosum, has not previously been reported to associate with mental retardation. Though MRI alone can not confirm the diagnosis and no definite measurements can be recommended for clinical use, any clinical suspicion of this syndrome receives reinforcement through MRI: a relatively enlarged corpus callosum in a microcephalic head and normal signal intensities of the grey and white matters.

Abnormalities, Multiple↗
PubMed1998

Mice with an aspartylglucosaminuria mutation similar to humans replicate the pathophysiology in patients.

Aspartyglucosaminuria (AGU) is a lysosomal storage disease with autosomal recessive inheritance that is caused by deficient activity of aspartylglucosaminidase (AGA), a lysosomal enzyme belonging to the newly described enzyme family of N-terminal hydrolases. An AGU mouse model was generated by targeted disruption of the AGA gene designed to mimic closely one human disease mutation. These homozygous mutant mice have no detectable AGA activity and excrete aspartylglucosamine in their urine. Analogously to the human disease, the affected homozygous animals showed storage in lysosomes in all analyzed tissues, including the brain, liver, kidney and skin, and lysosomal storage was already detected in fetuses at 19 days gestation. Electron microscopic studies of brain tissue samples demonstrated lysosomal storage vacuoles in the neurons and glia of the neocortical and cortical regions. Magnetic resonance images (MRI) facilitating monitoring of the brains of living animals indicated cerebral atrophy and hypointensity of the deep gray matter structures of brain-findings similar to those observed in human patients. AGU mice are fertile, and up to 11 months of age their movement and behavior do not differ from their age-matched littermates. However, in the Morris water maze test, a slow worsening of performance could be seen with age. The phenotype mimics well AGU in humans, the patients characteristically showing only slowly progressive mental retardation and relatively mild skeletal abnormalities.

Acetylglucosamine↗
PubMed1998

Monitoring the CNS pathology in aspartylglucosaminuria mice.

Aspartylglucosaminuria (AGU) is a recessively inherited lysosomal storage disorder caused by the deficiency of the aspartylglucosaminidase (AGA) enzyme. The hallmark of AGU is slowly progressing mental retardation but the progression of brain pathology has remained uncharacterized in humans. Here we describe the long-term follow-up of mice carrying a targeted AGU-mutation in both alleles. Immunohistochemistry, histology, electron microscopy, quantitative magnetic resonance imaging (MRI) and behavioral studies were carried out to evaluate the CNS affection of the disease during development. The lysosomal storage vacuoles of the AGA -/- mice were most evident in central brain regions where MRI also revealed signs of brain atrophy similar to that seen in the older human patients. By immunohistochemistry and MRI examinations, a subtle delay of myelination was observed in AGA -/- mice. The life span of the AGA -/- mice was not shortened. Similar to the slow clinical course observed in human patients, the AGA -/- mice have behavioral symptoms that emerge at older age. Thus, the AGU knock-out mice represent an accurate model for AGU, both histopathologically and phenotypically.

Animals↗
PubMed1997

Clinical and magnetic resonance imaging findings in Batten disease: analysis of the major mutation (1.02-kb deletion).

A total of 36 patients with Batten disease (juvenile-onset neuronal ceroid lipofuscinosis), homozygous or heterozygous for the major mutation, a 1.02-kb deletion, in the CLN3 gene, were studied to relate their genotype to their clinical phenotype. The onset of visual failure and epilepsy was highly concordant in both groups. Great inter- and intrafamilial heterogeneity was demonstrated in the development of mental and physical handicap and in magnetic resonance imaging findings among both homozygous and heterozygous patients. The 1.02-kb deletion in homozygous form was always associated with mental and physical handicap, whereas the heterozygous phenotype could be extremely benign without affecting the intellectual level of the patient. Our data suggest that genetic background, modifying genes, and environmental factors all influence the final phenotype of Batten disease.

Adolescent↗
PubMed1997

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.

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.

Adolescent↗
PubMed1997

MRI of the brain in neurologically healthy middle-aged and elderly individuals.

Our purpose was to document the MRI appearances of the brain in healthy middle-aged to elderly subjects. T2- and proton density-weighted axial slices were obtained in 61 volunteers, 30-86 years of age. After visual inspection, signal intensities of brain structures were measured on T2-weighted images. Age-related changes became increasingly apparent after age 50. The main findings were that signal intensity of the white matter increased concomitantly with widening of the cerebrospinal fluid spaces; that basal ganglia remained stable; that high-signal foci in white matter increased in number and size after the age of 50 years; that periventricular high-signal foci were constant after the age of 65 years. Our visual impression of a decrease in signal intensity of the central grey matter with age seems to be mistaken. Pathological processes should be suspected if periventricular foci are found in middle-aged or young subjects.

Adult↗
PubMed1997

Somatosensory evoked magnetic fields from primary sensorimotor cortex in juvenile neuronal ceroid lipofuscinosis.

The present study evaluated neurophysiologic function of the primary sensorimotor cortex in juvenile neuronal ceroid lipofuscinosis. A 122-channel magnetometer, which allowed studies of the somatosensory system in millimeter and millisecond precision, was used to record somatosensory evoked magnetic fields to median nerve stimulation from 10 patients and their matched control subjects. In both patients and controls, the somatosensory evoked magnetic fields from primary sensorimotor area typically consisted of N20m, P35m, and P60m deflections. In the patients, N20m was significantly delayed, whereas P35m peaked earlier than in the control subjects. The source strengths for N20m and P35m were greater in the patients than in the controls. Both deflections showed a significant positive correlation with the disease duration: the sources were stronger in the older patients than in the younger ones. P60m deflections were normal or reduced in the patients. The results indicated increased thalamocortical excitability in the sensorimotor cortex in juvenile neuronal ceroid lipofuscinosis.

Adolescent↗
PubMed1997

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 health 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.

Acetylglucosamine↗
PubMed1996

MRI of neuronal ceroid lipofuscinosis. I. Cranial MRI of 30 patients with juvenile neuronal ceroid lipofuscinosis.

We studied 30 patients with juvenile neuronal ceroid lipofuscinosis (JNCL). The patients (aged 6-25 years) and 43 age-matched healthy volunteers underwent MRI. After visual assessment, the signal intensity was measured on T2-weighted images in numerous locations. The thickness of the cortex and corpus callosum and the dimensions of the brain stem were measured. Mild to moderate cerebral atrophy was found in 14 of 30 patients, most of them over 14 years of age; 5 older patients had mild to moderate cerebellar atrophy. There was reduction in the size of the corpus callosum and brain stem. The thalamus, caudate nucleus and putamen appeared to give low signal in patients from the ages of 7, 11 and 11 years, respectively. In contrast, the signal intensity measured from the thalamus in these patients showed only a slight (insignificant) decrease compared with controls. The most significant alteration, an increase in measured signal intensity, was found in the white matter (P < 0.0001), even in the youngest patients. The MRI findings correlated significantly with decreased intelligence, speech disturbances and motor problems. Although MRI findings in JNCL do not appear very specific and the visual changes develop relatively late, the absence of pathological MRI findings in the very early stage of the disease may play a part in differential diagnosis of the different types of NCL. Furthermore, the MRI findings may be used in assessing severity and prognosis, particularly in young patients.

Adolescent↗
PubMed1996

Brain MRI in children with migraine: a controlled morphometric study.

Sixteen children and adolescents, aged 5-17 years, with migraine and 24 migraine-free age-matched healthy volunteers underwent brain MRI (1.0 T). Signal intensities of the brain, midsagittal and coronal diameters of the brainstem were quantitatively measured. General signal intensities did not differ between the groups. Compared to controls (17%), more migraine patients (50%) had high-signal foci on T2-weighted images. The diameters of the pons were greater in the migraine group (p = 0.016), although within the normal range. The diameters of the mesencephalon and the medulla oblongata did not differ between the groups, perhaps because they reach the adult size in early childhood in contrast to the pons, which continues to grow. Childhood migraine may be associated with slightly more than average growth of the pons. As the pathophysiology of migraine is still unclear, it might be worth studying with new MR methods.

Adolescent↗
PubMed1996

Brain perfusion SPECT in infantile neuronal ceroid-lipofuscinosis (INCL). Comparison with clinical manifestations and MRI findings.

We studied brain perfusion in 19 patients with infantile neuronal ceroid-lipofuscinosis (INCL), aged 13 months to 11 years, using 99mTc-HMPAO single photon emission computed tomography (SPECT). SPECT findings were compared with clinical manifestations and MRI findings. The typical SPECT findings at an early stage of INCL were bilateral anterior frontal, posterior temporoparietal and occipital hypoperfusion. Initially cerebral hypoperfusion was localized and symmetrical, whereas atrophic findings were more generalized. Reduction in cerebellar perfusion appeared later, as did cerebellar atrophy. Progression from mild to severe cerebral and cerebellar hypoperfusion was rapid, corresponding to the clinical progression. However, the perfusion of deep grey matter structures (basal ganglia and thalami), although atrophic on MRI, was often well preserved up to the terminal stage. Severe perfusion defects in INCL, which appeared approximately at the age of four, were associated with grave clinical manifestations and neuropathologic findings. Particularly, the early SPECT perfusion abnormalities may assist in the differential diagnosis between INCL and other neurode-generative diseases.

Atrophy↗
PubMed1995

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.

Brain↗