Biomedical subjects

T Autti

Publications and source records attributed to T Autti.

At least 19 recordsLinked to original sources

PubMed2006

Chest CT screening of asbestos-exposed workers: lung lesions and incidental findings.

The objective of the present study is to determine the feasibility of chest computed tomography (CT) in screening for lung cancer among asbestos-exposed workers. In total, 633 workers were included in the present study and were examined with chest radiography and high-resolution CT (HRCT). A total of 180 current and ex-smokers (cessation within the previous 10 yrs) were also screened with spiral CT. Noncalcified lung nodules were considered positive findings. The incidental CT findings not related to asbestos exposure were registered and further examined when needed. Noncalcified lung nodules were detected in 86 workers. Five histologically confirmed lung cancers were found. Only one of the five cancers was also detected by plain chest radiography and three were from the group of patients with a pre-estimated lower cancer probability. Two lung cancers were stage Ia and were radically operated. In total, 277 individuals presented 343 incidental findings of which 46 required further examination. Four of these were regarded as clinically important. In conclusion, computed tomography and high-resolution computed tomography proved to be superior to plain radiography in detecting lung cancer in asbestos-exposed workers with many confounding chest findings. The numerous incidental findings are a major concern for future screenings, which should be considered for asbestos-exposed ex-smokers and current smokers.

Aged↗

PubMed2004

Five new cases of a recently described leukoencephalopathy with high brain lactate.

BACKGROUND: A new leukoencephalopathy with brainstem and spinal cord involvement and high brain lactate was recently defined. The authors describe five new patients with this entity. METHODS: Brain MRI was performed in all patients and spinal MRI and proton magnetic resonance spectroscopy (1H-MRS) in four patients. Laboratory examinations ruled out classic leukodystrophies. RESULTS: MRI showed signal abnormalities in the periventricular and deep white matter, in the pyramidal tracts, mesencephalic trigeminal tracts, in the cerebellar connections, and in dorsal columns of the spinal cord. MRS showed decreased N-acetylaspartate and increased lactate in the white matter of all patients. In one patient choline-containing compounds were elevated. A slowly progressive sensory ataxia and tremor manifested at the age of 3 to 16 years and distal spasticity in adolescence. One 13-year-old patient was asymptomatic. CONCLUSIONS: A slowly progressive sensory ataxia is a typical feature in this new leukodystrophy. MRS favors a primary axonal degeneration.

Adolescent↗

PubMed2004

Neuroradiological findings (MRS, MRI, SPECT) in infantile neuronal ceroid-lipofuscinosis (infantile CLN1) at different stages of the disease.

Infantile neuronal ceroid-lipofuscinosis (infantile CLN1) is a progressive and uniformly fatal lysosomal storage disease of the nervous system. The purpose of this study was to compare the findings of various radiological examinations of the brain in the course of infantile CLN1 in order to evaluate the relative usefulness of the methods and their potential for monitoring therapeutic interventions. We examined eight infantile CLN1 patients, 51 studies, in various stages of the disease--preclinical to late stage--with proton magnetic resonance spectroscopy (1H-MRS), MRI, and perfusion SPECT, and in addition three benzodiazepine (BZ) receptor ligand SPECT studies. Both 1H-MRS and MRI showed abnormal findings before clinical manifestations of the disease. Cortical hypoperfusion and loss of cortical BZ receptors revealed by SPECT appeared simultaneously with clinical signs. After the age of 4 years MRI and SPECT alterations progressed minimally, whereas 1H-MRS showed progressive deterioration of neurometabolism. Of the four methods used in this study, MRI proved to be the most practicable for diagnosing infantile CLN1; the final diagnosis of infantile CLN1 is confirmed by the characteristic clinical picture and DNA or PPT enzyme analysis. The combination of 1H- MRS and MRI could be most useful for monitoring therapeutic interventions.

Aspartic Acid↗

PubMed2003

A case of Salla disease with involvement of the cerebellar white matter.

Salla disease (SD) is a lysosomal disorder manifesting in infancy with hypotonia, nystagmus, ataxia and retarded motor development. MRI typically shows hypomyelination confined to the cerebral white matter. We describe a patient with two MRI studies in addition to repeated urine examinations. This case was problematic because the first urine examination did not show the elevation of free sialic acid typical of SD and MRI was also atypical, with abnormal signal intensity in cerebellar white matter. We recommend repeated urinary examinations and a search for SLC17A5 mutations in patients with cerebral signal intensity abnormalities typical of SD and emphasise that cerebellar white-matter involvement on MRI does not exclude the diagnosis.

Cerebellum↗

PubMed2002

Enlarged SI and SII somatosensory evoked responses in the CLN5 form of neuronal ceroid lipofuscinosis.

OBJECTIVES: To examine in detail the activation of the primary (SI) and secondary (SII) somatosensory cortex in CLN5, the Finnish variant of late infantile neuronal ceroid lipofuscinoses (NCL). METHODS: Somatory evoked magnetic fields were recorded with a 122-channel planar gradiometer in response to median nerve stimulation in 5 CLN5 patients (aged 8.8-16.7 years) and in 10 healthy age-matched controls. RESULTS: The first two responses from contralateral SI, N20m and P35m, were 6-20 times stronger in the patients than in the controls. The morphology of the subsequent deflections from SI was abnormal in the patients: a prominent N45m was detected, while the normally present P60m deflection was missing. In 4 patients the contra- and in two patients the ipsilateral SII responses were also enlarged. Furthermore, the SII activation was detected at shorter latency in patients than in controls. CONCLUSIONS: At SI, CLN5 is associated with a selective enhancement of the early cortical responses. We propose that the enlargement of N20m most likely reflects increased synchronous input from thalamus, whereas the altered morphology of the following responses may reflect defective interneuronal inhibition at the cortex. The enlargement of SII responses shows that the imbalance between excitation and inhibition in CLN5 extends outside the primary somatosensory areas.

Adolescent↗

PubMed2002

A quantitative controlled MRI study of the brain in 28 persons with Asperger syndrome.

BACKGROUND: As structural brain abnormalities have been reported in infantile autism, the aim of this study was to determine whether such findings also exist in Asperger Syndrome (AS). METHODS: The diagnosis of Asperger Syndrome was based on the criteria in ICD-10 and DSM-IV. Brain magnetic resonance imaging (MRI) was performed with a 1.5 T imager. T2-weighted axial and coronal slices and T1-weighted three dimensional sagittal slices were obtained and visual and quantitative analysis were performed. SUBJECTS: There were 28 Asperger individuals, 17 children and adolescents (age 6-19 years, mean 12.4 years), 11 adults (age 20-60 years, mean 37. 9 years) and 28 healthy age and gender matched controls. RESULTS: Mild inconsistent alterations were detected in 13/28 of the individuals with Asperger Syndrome compared to 6/23 in the comparable controls. There were no differences between the right and left hemispheres, nor was there any abnormality in terms of myelination or migration. The anterior-posterior diameters of the mesencephalon were statistically significantly shorter in the Asperger syndrome individuals than in the controls. CONCLUSIONS: No consistent focal brain abnormalities for Asperger Syndrome were detected. The reduced diameters of the mesencephalon in the Asperger group support the hypothesis that the mesencephalon may be involved in the pathogenesis of Asperger Syndrome.

Adolescent↗

PubMed2001

Hematopoietic stem cell transplantation in infantile neuronal ceroid lipofuscinosis.

OBJECTIVE: To study the effect of allogeneic hematopoietic stem cell transplantation (SCT) on the clinical course of infantile neuronal ceroid lipofuscinosis (INCL), a lysosomal storage disease. BACKGROUND: INCL is a progressive encephalopathy with severe neuronal loss, especially in the cerebral and cerebellar cortex and retina. Autofluorescent lipopigments constitute the typical storage material in INCL. The disease is caused by recessive mutations in the palmitoyl protein thioesterase 1 (PPT1) gene. PPT1 is a depalmitoylating enzyme, which is transported to lysosomes through the mannose-6-phosphate receptor-mediated pathway, and participates in the lysosomal degradation of fatty acylated proteins. METHODS: Three patients with INCL received transplants and were followed up after SCT at the Hospital for Children and Adolescents at the University of Helsinki. The first patient rejected the first graft at the age of 7 months and had mild symptoms of INCL at the second transplantation at 11 months. The two other patients were asymptomatic when they received their transplants at the age of 4 months. RESULTS: PPT1 enzyme activity was normalized in peripheral leukocytes, but remained low in the CSF and resulted only in a mild and transient amelioration of the classic INCL. All patients who received transplants developed INCL by the age of 2 or 3 years. CONCLUSIONS: More experimental animal and cell culture studies are needed to determine the in vivo function of PPT1. SCT currently cannot be recommended as therapy for INCL.

Child, Preschool↗

PubMed2001

Two brothers with macrocephaly, progressive cerebral atrophy and abnormal white matter, severe mental retardation, and Lennox-Gastaut spectrum type epilepsy: an inherited encephalopathy of childhood?

Two brothers with severe mental retardation of unknown origin were found to share several physical anomalies, including large round head, small concave nose, downslanted palpebral fissures, and gingival hyperplasia. In addition to relative macrocephaly, magnetic resonance imaging (MRI) showed severe cerebral atrophy, especially fronto-temporally. The brothers also had a thin corpus callosum and atrophic caudate nuclei. The reduced white matter showed patchy periventricular signal intensity changes. The lateral and third ventricles were large, but the fourth ventricle was of normal size. The boys had large cisterna magna, communicating widely with the fourth ventricle, but no vermian hypoplasia. Both boys had Lennox-Gastaut spectrum type epilepsy. No chromosomal anomalies were found, despite the suggestive clinical picture. Some of the clinical findings resembled fetal alcohol effects/fetal alcohol syndrome (FAE/FAS), which was also suggested by history. Current diagnostic criteria for FAE/FAS, however, excluded full-blown FAS in these cases and failed to explain the entire clinical picture in the boys. We argue that these boys had an unidentified inherited syndrome, possibly modified by fetal alcohol exposure.

Abnormalities, Multiple↗

PubMed2001

CNS manifestations of Nasu-Hakola disease: a frontal dementia with bone cysts.

BACKGROUND: Nasu-Hakola disease or polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) is a genetically heterogeneous disease characterized by a combination of systemic bone cysts and dementia. OBJECTIVE: The authors present a neurologic, neuroradiologic, and neuropathologic analysis of a series of PLOSL patients in which the diagnosis has been confirmed by molecular genetic methods. METHODS: Clinical, neurophysiologic, and imaging follow-up data on eight patients as well as autopsy samples of three patients were analyzed in this study. All eight patients were homozygous for a loss-of-function mutation in the DAP12 gene. RESULTS: In most patients, the disease debuted with pain in ankles and wrists after strain during the third decade, followed by fractures caused by cystic lesions in the bones of the extremities. Frontal lobe syndrome and dementia began to develop by age 30, leading to death by age 40. Neuroimaging disclosed abnormally high and progressively increasing bicaudate ratios and calcifications in the basal ganglia as well as increased signal intensities of the white matter on T2-weighted MR images even before the appearance of clinical neurologic symptoms. Three patients who had undergone autopsies showed an advanced sclerosing leukoencephalopathy with frontal accentuation, widespread activation of microglia, and microvascular changes. CONCLUSIONS: Although PLOSL in most patients manifests by bone fractures, some patients do not show any osseous symptoms and signs before the onset of neurologic manifestations. Consequently, patients with frontal-type dementia of unknown origin should be investigated by x-ray of ankles and wrists. The current results suggest early basal ganglia involvement in PLOSL.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Neuropsychological test battery in the follow-up of patients with juvenile neuronal ceroid lipofuscinosis.

The aim of the present study was to develop a neuropsychological test battery for patients with juvenile neuronal ceroid lipofuscinosis (JNCL) and to study the development of cognitive functions during the first 5 years after diagnosis. Fourteen patients with JNCL entered the study. Nine patients were homozygous for the major mutation, whereas five were compound heterozygotes. All patients were studied annually with a special neuropsychological test battery (NEPSY) adapted from Luria's neuropsychological test, and modified for the visually handicapped; the Wechsler Intelligence Scale for Children - Revised (WISC-R) was also included. The neurological examinations were scored. Furthermore, 1.OT magnetic resonance imaging scan was performed at the beginning of follow-up and after a mean of 5 years. A decline in verbal IQ (WISC-R) during the follow-up period was found in all subjects except one compound heterozygous male. Short-term memory and digit memory span were already impaired at an early stage of the disease. Orientation to time was found to decline more than orientation to person and place. Motor speed usually became impaired after 10 years of age. Spatial orientation was impaired only in the patients homozygous for the major mutation. The test battery was found to be reliable and easy to use, and offered valuable information on the progress of the disease. It also provided important guidelines for rehabilitation.

Adolescent↗

PubMed2001

Clinical and neuroradiological diagnostic aspects of neuronal ceroid lipofuscinoses disorders.

Early diagnosis is mandatory for avoiding further cases in families with hereditary metabolic brain disorders. This review lists the most important clinical symptoms and neuroradiological findings at the early stage of the seven most common childhood neuronal ceroid lipofuscinoses (NCL) types. In the infantile type the typical magnetic resonance imaging (MRI) findings can be seen even before the clinical signs. In the classic late infantile type (CLN2), MRI is less informative but in this and in the variant late infantile type CLN6 the characteristic neurophysiological findings are present at an early stage, although not in the Finnish variant CLN5. In the latter, the clinical diagnosis depends on ophthalmological and MRI findings. The combination of ophthalmological deficits and vacuolated lymphocytes is highly characteristic of the juvenile type (CLN3). A new NCL type, Northern epilepsy (CLN8), is also briefly reviewed.

Child↗

PubMed2001

Northern epilepsy syndrome (NES, CLN8)--MRI and electrophysiological studies.

Northern epilepsy syndrome (NES, EPMR, progressive epilepsy with mental retardation, CLN8), an inherited childhood-onset epilepsy with mental retardation, has been recently characterized to belong to the family of neuronal ceroid lipofuscinoses (NCLs). In this study, four patients (ages 26-44 years) with NES and eight healthy controls underwent magnetic resonance imaging (MRI) and electrophysiological evaluation with somatosensory evoked magnetic field (SEF) studies. The findings in NES were compared with the known findings in juvenile NCL (JNCL, CLN3) and Finnish variant late infantile NCL (vLINCLFIN, CLN5) that manifest around the same age as NES. Also postmortem MRI was performed on one brain. On the MRIs, slight to moderate cerebellar atrophy was seen in all patients, whereas only two patients had slightly enlarged cerebral sulci. None of the MRIs demonstrated signal intensity abnormalities that are commonly seen in JNCL and vLINCLFIN and are considered to reflect the Wallerian degeneration after neuronal death. Generally SEFs in NES were within normal limits, indicating that the disease had not impaired the function of the neurons on the somatosensory pathway. In conclusion, MRI imaging and SEF findings suggest that the cerebral neuronal death and dysfunction in NES are minimal compared with JNCL and vLINCLFIN.

Adult↗

PubMed2000

Phenotype-genotype correlation in eight patients with Finnish variant late infantile NCL (CLN5).

The authors analyzed the clinical phenotype, including MRI, of eight patients with Finnish variant late infantile neuronal ceroid lipofuscinosis (vLINCLFin; CLN5; MIM256731). Although the four known mutations, including one novel mutation identified in this study, have very different consequences for the predicted polypeptide, none of them results in an atypical phenotype, as has been reported in other forms of NCL. Thus, it seems likely that each mutation severely disturbs the normal function of the CLN5 protein.

Adolescent↗

PubMed2000

Decreased striatal dopamine transporter density in JNCL patients with parkinsonian symptoms.

OBJECTIVE: To explore whether striatal dopamine transporters are involved in juvenile neuronal ceroid lipofuscinosis (JNCL) with extrapyramidal signs. METHODS: Seventeen patients with JNCL entered the study (mean age, 15 years; age range, 10 to 31 years). For clinical evaluation, the authors used the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS). For studying the density of dopamine transporters in the striatum, they employed iodine-123-labeled 2beta-carbomethoxy-3beta-(4-iodophenyl) tropane as a SPECT tracer. The SPECT images were evaluated visually, and tracer accumulation was semiquantified from transverse slices as striatum-to-cerebellum activity ratios. MRI (1.5-T) signal intensities of the striatum were measured and compared with those of the thalamus. RESULTS: The mean UPDRS score was 20 (range, 2 to 41). On SPECT, the mean striatum-to-cerebellum uptake ratio was lower in patients than in control subjects (3.1 +/- 0.6 versus 6.8 +/- 1.0; p < 0.001), with the decrease being more pronounced in the putamen than in the caudate nucleus. On MRI, the mean striatum-to-thalamus signal intensity ratio was higher in patients than in control subjects (1.14 +/- 0.02 versus 1.08 +/- 0.02; p < 0.001). There was a negative correlation between uptake ratios in SPECT and UPDRS scores, and a positive correlation between the MRI ratios and UPDRS. The SPECT and MRI ratios also correlated significantly, providing additional evidence for the contributions of nigrostriatal, striatal, and thalamic dysfunction to the parkinsonian symptoms. CONCLUSIONS: The observed decrease in the striatal dopamine transporter density in JNCL offers a rational basis for a trial of dopaminergic drugs in this disease.

Adolescent↗

PubMed2000

Neuronal ceroid lipofuscinoses in childhood.

NCL disorders are progressive brain diseases with an autosomal recessive inheritance in all eleven childhood types. These occur world-wide but may be enriched in some countries. In Finland altogether about 400 patients have been diagnosed during the last forty years. The most common types are the infantile and classic juvenile forms with an incidence of 1: 20,000 and 1: 21,000, respectively Personally followed-up are patients with infantile, classic and Finnish variant late infantile and classic juvenile types. Clinical, neurophysiological and neuroimaging findings in these four NCL forms are reviewed including also management and diagnostic aspects.

Child↗

PubMed1999

Delayed classic and protracted phenotypes of compound heterozygous juvenile neuronal ceroid lipofuscinosis.

OBJECTIVE: To correlate the phenotypes with the genotypes of 10 Finnish juvenile neuronal ceroid lipofuscinosis (JNCL; late-onset Batten disease) patients who all are compound heterozygotes for the major 1.02-kb deletion in the CLN3 gene. METHODS: The mutations on the non-1.02-kb deletion chromosomes were screened in 6 patients; in the other 4 patients the mutations were known (one affecting a splice site, two missense mutations, and one deletion of exons 10 through 13). Clinical features were examined, and MRI, MRS, somatosensory evoked magnetic field (SEF), and overnight polysomnography (PSG) studies were performed. RESULTS: A novel deletion of exons 10 through 13 was found in 6 patients belonging to three families. In the patients carrying the deletions of exons 10 through 13 the clinical course of the disease was fairly similar. Variation was greatest in the time course to blindness. In these patients the mental and motor decline was slower than in classic JNCL, but more severe than in the two patients with missense mutations in exons 11 and 13. MRI showed brain atrophy in 4 patients. One patient had hyperintense periventricular white matter, otherwise brain signal intensities were normal. SEFs were enhanced in patients older than 14 years, whereas in PSG all but the youngest 6-year-old patient showed epileptiform activity in slow-wave sleep. CONCLUSIONS: JNCL can manifest as at least three different phenotypes: classic, delayed classic, and protracted JNCL with predominantly ocular symptoms. Finnish compound heterozygotes have the delayed classic or the protracted form of JNCL.

Adolescent↗

PubMed1999

Bone marrow transplantation in aspartylglucosaminuria--histopathological and MRI study.

This study comprised two patients with aspartylglucosaminuria (AGU), who were followed up for 4 and 7 years. The patients underwent allogeneic bone marrow transplantation (BMT) at the ages of 2 and 2.6 years. Both patients had abnormal speech development and gross motor clumsiness. At the time of the BMT, they were mentally retarded. We report on follow-up data of these patients obtained by MRI, in addition to the histopathological, biochemical and clinical investigations. MR images of six non-transplanted patients and seven healthy children served as controls. In the non-transplanted patients, MRI revealed evident delay of myelination in contrast to the two transplanted patients showing fair or evident grey- vs. white matter differentiation on T2-weighted images. The aspartylglucosaminidase (AGA) activity in blood leukocytes reached a heterozygous level. Urinary excretion of aspartylglucosamine and glycoasparagines slowly decreased but remained about a third of the pre-BMT level 5 years after BMT. Storage lysosomes in electron microscopic investigations were not decreased 6 months after BMT, but after 1.5-2 years, rectal mucosa samples showed a decrease in the storage vacuoles of different cells. Three years after BMT, no cells with storage vacuoles were present. Allogeneic BMT slowly normalises the pathological, biochemical and MRI findings in patients with AGU.

Aspartylglucosaminuria↗

PubMed1999

Brain involvement in Salla disease.

BACKGROUND AND PURPOSE: Our purpose was to document the nature and progression of brain abnormalities in Salla disease, a lysosomal storage disorder, with MR imaging. METHODS: Fifteen patients aged 1 month to 43 years underwent 26 brain MR examinations. In 10 examinations, signal intensity was measured and compared with that of healthy volunteers of comparable ages. RESULTS: MR images of a 1-month-old asymptomatic child showed no pathology. In all other patients, abnormal signal intensity was found: on T2-weighted images, the cerebral white matter had a higher signal intensity than the gray matter, except in the internal capsules. In six patients, the white matter was homogeneous on all images. In four patients, the periventricular white matter showed a somewhat lower signal intensity; in five patients, a higher signal intensity. In the peripheral cerebral white matter, the measured signal intensity remained at a high level throughout life. No abnormalities were seen in the cerebellar white matter. Atrophic changes, if present, were relatively mild but were found even in the cerebellum and brain stem. The corpus callosum was always thin. CONCLUSION: In Salla disease, the cerebral myelination process is defective. In some patients, a centrifugally progressive destructive process is also seen in the cerebral white matter. Better myelination in seen in patients with milder clinical symptoms.

Adolescent↗