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Biomedical subjects

R Riikonen

Publications and source records attributed to R Riikonen.

At least 19 recordsLinked to original sources
PubMed2004

Cerebrospinal fluid insulin-like growth factor-1, insulin growth factor binding protein-2 or nitric oxide are not increased in MS or ALS.

OBJECTIVES: Many studies have shown that nitric oxide (NO) and growth factors including insulin growth factors (IGFs) may be involved in the pathogenesis of multiple sclerosis (MS) and neurodegenerative diseases. Our previous studies suggested a relationship between cerebrospinal fluid (CSF) NO metabolites (nitrates and nitrites, NN(x)) and IGF-1 in patients with progressive encephalopathy, hypsarrhythmia and optic atrophy syndrome. MATERIAL AND METHODS: We examined CSF concentrations of NN(x), IGF-1 and IGF binding protein-2 (IGFBP-2) in 25 controls, 14 patients with MS and 14 patients with amyotrophic lateralis sclerosis (ALS). RESULTS: There were no significant differences in CSF levels of NN(x), IGF-1 or IGFBP-2 between the groups. CSF IGFBP-2 concentrations correlated significantly with age in controls, which may reflect age-related changes in the blood-brain barrier function. CONCLUSION: Upregulation of the production of NO and IGF-1 in the brain or spinal cord does not influence CSF levels of these molecules in MS or ALS.

Adolescent↗
PubMed2001

MECP2 gene analysis in classical Rett syndrome and in patients with Rett-like features.

OBJECTIVE: To discuss the diagnostic criteria for Rett syndrome based on mutational screening of the methyl-CpG-binding protein 2 gene ( MECP2 ) in patients with classic Rett syndrome and patients with Rett-like features. METHODS: Thirty-nine patients with classical Rett syndrome, one with preserved speech variant (PSV), and 12 patients with developmental delay and some features of Rett syndrome were recruited for sequence analysis of the MECP2 gene coding region. The phenotype of the patients was correlated with the presence and type of the mutation as well as the X-chromosome inactivation (XCI) pattern. RESULTS: found in 100% of the patients with classical Rett syndrome originating from Finland. One novel mutation, P127L, was detected in a patient with PSV. No mutations were found in other cases. The XCI status was found to be random in 72% of the patients with classical Rett syndrome, including the patient with PSV and all patients with developmental delay informative for the analysis. CONCLUSIONS: An MECP2 mutation can be found in almost every patient with classical Rett syndrome. More patients need to be analyzed in order to clarify the mutation prevalence in patients with atypical Rett syndrome and in patients with mental retardation.

Adolescent↗
PubMed2001

Epidemiological data of West syndrome in Finland.

The present study examined whether changes in the incidence of West syndrome (WS) could be used to evaluate changes in the quality of prenatal care over time. The incidence of WS in Finland did not change (1960-1991) in spite of increased survival of low-birth-weight infants. Small-for-gestational age (SGA) infants were more apt to develop infantile spasms than preterm average-for-gestational age infants. The number of SGA infants with neonatal hypoglycemia and infantile spasms decreased significantly. The number of cases of brain malformation and tuberous sclerosis increased; this probably reflects the development of more refined neuroradiological screening methods. Early prenatal factors seem to play a major role in the genesis of infantile spasms. Little can be done to reduce the incidence of WS, but every effort should be made to reduce the number of SGA infants by good prenatal care and treating neonatal hypoglycemia carefully.

Finland↗
PubMed2001

The PEHO syndrome.

The progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO) syndrome is a pediatric disorder of unknown origin, characterized by a combination of postnatally progressive encephalopathy, hypsarrhythmia, and optic atrophy. The pathological findings are early progressive atrophy of the cerebellum, brainstem, and optic nerves. Nitric acid (NO) has recently been implicated in the mechanisms of seizure activity and neurodegeneration, which are both very active in the PEHO syndrome. However, recent studies have provided evidence that insulin-like growth factor 1 (IGF-1) may prevent the NO-mediated neuronal damage and is essential for the survival of the cerebellar granule cells. These cells will degenerate in the PEHO syndrome. In this study, we set out to test the hypothesis that NO production is activated in the PEHO syndrome and that NO production may be correlated with the reduced production of IGF-1 in the brain. Cerebrospinal fluid IGF-1 was determined with an RIA kit and NO metabolites by the Griess calorimetric method. In patients with the PEHO syndrome, as compared with controls, the levels of IGF-1 were reduced and the levels of nitrite/nitrate were markedly elevated. Defective production of IGF-1 probably reflects the underlying neurodegeneration and the increase in NO production probably reflects the seizure activity and/or neurodegeneration. These are the first biochemical abnormalities found in the PEHO syndrome and their study may lead to a better understanding of this devasting disease.

Brain Diseases↗
PubMed2001

ACTH therapy of West syndrome: Finnish views.

To provide up-to-date information on adrenocorticotropic hormone (ACTH) therapy in the treatment of West syndrome, a review of the Finnish studies was made in answer to the questions: what are (1) its efficacy: doses and comparison with vigabatrin (VGB), (2) its tolerability, (3) its mechanism of action? Why do some patients respond, but others do not? No other drugs have been shown to be more effective than ACTH. High doses were not more effective than low doses. Synthetic derivatives were associated with more frequent side effects. Individualized therapy was developed on the basis of etiology and response. With therapy consisting of ACTH 3-6IU/kg/day, all the cryptogenic and half of the symptomatic spasms could be controlled within over 2-3 weeks therapy and with minimal risk of side effects. In a Finnish study, 26% of the patients responded to VGB as the first-line drug. Some of the non-responders responded to ACTH. In tuberous sclerosis, the initial response rate to ACTH was high (73%) and did not differ from the response rate to VGB in other series. Both drugs have severe side effects. The visual field defects caused by VGB occur even in children (in 18/91 Finnish children). The patients with cryptogenic spasms, who responded well to ACTH, differed in their biochemical parameters from the patients with symptomatic spasms. The therapeutic action of ACTH may be mediated by potentiation of nerve growth promoting activity. Neurodegeneration may be due to imbalance between nerve growth factors and nitrate/nitrite in the brain. ACTH should be used as the first choice for treatment of West syndrome (at the minimal effective dose and for shortest effective time). The side effects of steroids, unlike VGB, are well known, treatable, and reversible.

Adrenocorticotropic Hormone↗
PubMed2001

Long-term outcome of patients with West syndrome.

The long-term outcome of Finnish children with West syndrome was evaluated. Two hundred and fourteen patients were followed up for 20-35 years or until death. A third of the patients died before the age of 3 years. The most common cause of death was infection. Autopsy revealed brain anomalies in 25 of 38 (66%) autopsied patients. Intellectual outcome was normal or slightly impaired in a quarter of the patients. All of them completed their education at a normal school or in a school for the educationally impaired children. Another fourth were taught in special training schools. Specific cognitive deficits were seen in some patients with normal intelligence. Nine attended secondary schools and seven of them had a professional occupation. Ten were married and five had children. One third of the patients were seizure-free, another third had seizures daily or monthly, and the remaining patients had seizures less frequently. Factors associated with a good prognosis were cryptogenic etiology, normal development before the onset of the spasms, a short treatment lag, and a good response to adrenocorticotropic hormone; this was seen in both the symptomatic and the cryptogenic group, and there were no relapses. In this study, the late appearance of focal abnormalities in electroencephalography was not associated with an unfavorable outcome. Focal abnormalities in temporal region were often seen in patients with autism. The location of an abnormality may be of importance for the prognosis. In this study, all the patients (100%) could be followed, which may be due to the special circumstances characteristic of Finland. The outcome in children with West syndrome seems to be better than is generally believed.

Adrenocorticotropic Hormone↗
PubMed2001

Nitric oxide metabolites, nitrates and nitrites in the cerebrospinal fluid in children with west syndrome.

Nitric oxide (NO) has been implicated in the mediation of the neuronal excitotoxic cascade. In order to estimate brain NO production, cerebrospinal fluid (CSF) levels of NO metabolites, nitrates and nitrites (NN(x)) were measured in 31 children with west syndrome (WS) and in 12 controls. There was no age-related change in the NN(x) levels during the first year of life. The mean of the NN(x) levels was significantly higher in patients with WS than in controls (8.43 vs. 5.27 microM; P=0.01). Analysis of the etiological subgroups showed that the patients with a symptomatic etiology of WS had significantly higher NN(x) levels than controls (P<0.005) or than the patients with a cryptogenic etiology. The cryptogenic cases, in turn, did not differ from the controls (P=0.48). Levels of NN(x) were also significantly higher in children with focal brain abnormalities (infarction, atrophy or previous infection) than in those with other abnormalities or with normal neuroradiological findings (P<0.005). No correlation was found between the NN(x) levels and the duration of the symptoms, while paired samples obtained from eight children with WS showed that the NN(x) levels rose significantly (P=0.02) within the first 40 days of symptoms. The levels of NN(x) did not correlate with the CSF levels of neuronal growth factor or with the later decline in mental performance. This study demonstrates that the production of NO can be measured in human epileptic conditions and supports the idea gained from experimental studies that NO is involved in the pathophysiology of epilepsy. However, normal levels of NN(x) in patients with cryptogenic infantile spasms suggest that an increase in NO production be due to the concomitant neuronal damage rather than seizure activity per se. The findings suggest that there are no age-related changes in the NN(x) levels during the first year of life, and that children with symptomatic WS have elevated levels of NN(x), which rise during the first 40 days of symptoms. Although the NN(x) levels cannot be used to estimate the duration of symptoms or to predict the prognosis of mental development, they may support the differentiation of symptomatic from cryptogenic etiologies of WS.

Analysis of Variance↗
PubMed2001

Low levels of insulin-like growth factor-I in cerebrospinal fluid in children with autism.

Autism is a behaviourally defined syndrome characterized by disturbances of social interaction and communication and restrictions of behaviour patterns and imagination. The pathogenesis of autism is unknown but it is suspected that a number of genetic factors may be involved. Neurotrophic factors such as insulin-like growth factor-I (IGF-I) play a role in early brain development. The aim of this study was to determine whether IGF-I levels might be associated with the development of autism. IGF-I levels were measured in the CSF of 11 children with autism (4 females, 7 males; mean age 3.8 years, SD 1.1) using a sensitive radioimmunoassay method and compared with levels in 11 control participants (6 females, 5 males; mean age 3.8 years). Levels of IGF-I in the CSF were statistically significantly lower in the children with autism than in the control children (p=0.03). IGF-I may play a role in pathogenetic mechanisms of autism and the role of neurotrophic factors in autism and other neurodevelopmental diseases should be studied further.

Autistic Disorder↗
PubMed2001

Reversed visual field constrictions in children after vigabatrin withdrawal--true retinal recovery or improved test performance only?

While vigabatrin-associated visual field constrictions have been generally considered irreversible, some case reports have raised the hope of partial improvement after drug withdrawal in occasional patients. Here we describe seven children with epilepsy, whose visual field constrictions, as demonstrated by the kinetic perimetry (Goldmann), attenuated or recovered after discontinuation of vigabatrin therapy. While this improvement may be largely due to better performance in later test sessions, we want to raise the possibility that some visual field recovery may be possible at least in young patients.

Adolescent↗
PubMed2000

CSF insulin-like growth factor-1 in infantile neuronal ceroid lipofuscinosis.

BACKGROUND: Infantile neuronal ceroid lipofuscinosis (INCL) is a progressive encephalopathy in which the patients are severely disabled by the age of 3 years. It is characterized by cerebral atrophy, selective loss of cortical neurons, and secondary loss of axons and myelin sheaths of the white matter. INCL has been shown to result from a palmitoyl protein thioesterase deficiency. The authors suggested that insulin-like growth hormones and apoptosis might play a role in the pathogenesis of INCL. METHODS: The authors measured insulin-like growth factor-1 (IGF-1) and IGF binding protein 3 (IGFBP-3) in the CSF of patients with INCL by radioimmunoassay at an early stage when myelin was starting to diminish. RESULTS: The authors found low CSF IGF-1 but normal IGFBP-3 in patients with INCL compared with control subjects. Also, they observed apoptotic cell death in biopsies of INCL patients. CONCLUSIONS: Because the IGF system seems to be important for early brain development, myelination, and neuroprotection, the authors suggest that the pathology in INCL may be associated with low CSF IGF-1.

Apoptosis↗
PubMed2000

Integrin alpha(2)I domain recognizes type I and type IV collagens by different mechanisms.

The collagens are recognized by the alphaI domains of the collagen receptor integrins. A common structural feature in the collagen-binding alphaI domains is the presence of an extra helix, named helix alphaC. However, its participation in collagen binding has not been shown. Here, we have deleted the helix alphaC in the alpha(2)I domain and tested the function of the resultant recombinant protein (DeltaalphaCalpha(2)I) by using a real-time biosensor. The DeltaalphaCalpha(2)I domain had reduced affinity for type I collagen (430 +/- 90 nM) when compared with wild-type alpha(2)I domain (90 +/- 30 nM), indicating both the importance of helix alphaC in type I collagen binding and that the collagen binding surface in alpha(2)I domain is located near the metal ion-dependent adhesion site. Previous studies have suggested that the charged amino acid residues, surrounding the metal ion-dependent adhesion site but not interacting with Mg(2+), may play an important role in the recognition of type I collagen. Direct evidence indicating the participation of these residues in collagen recognition has been missing. To test this idea, we produced a set of recombinant alpha(2)I domains with mutations, namely D219A, D219N, D219R, E256Q, D259N, D292N, and E299Q. Mutations in amino acids Asp(219), Asp(259), Asp(292), and Glu(299) resulted in weakened affinity for type I collagen. When alpha(2) D219N and D292N mutations were introduced separately into alpha(2)beta(1) integrin expressed on Chinese hamster ovary cells, no alterations in the cell spreading on type I collagen were detected. However, Chinese hamster ovary cells expressing double mutated alpha(2) D219N/D292N integrin showed remarkably slower spreading on type I collagen, while spreading on type IV collagen was not affected. The data indicate that alpha(2)I domain binds to type I collagen with a different mechanism than to type IV collagen.

Animals↗
PubMed2000

Markedly elevated nitrate/nitrite levels in the cerebrospinal fluid of children with progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO syndrome).

PURPOSE: To compare the levels of brain nitric oxide production in patients with PEHO or PEHO-like syndrome and in controls with other neurologic disease. METHODS: Nitric oxide metabolites, nitrates, and nitrites (NNx), were measured in the cerebrospinal fluid (CSF) of children with PEHO syndrome or PEHO-like syndrome, and in controls with other neurologic diseases. RESULTS: The NNx levels were markedly higher in both PEHO (mean, 48 microM; p < 0.001) and PEHO-like (22 microM; p < 0.003) patients as compared with the controls (6 microM), but did not correlate with age or with brain atrophy or CSF levels of insulin-like growth factor-1 (IGF-1). CONCLUSIONS: Our findings suggest that in PEHO syndrome, production of nitric oxide is markedly increased, suggesting that nitric oxide is involved in the pathologic phenomena (i.e., seizures and neurodegeneration) of the disease.

Adolescent↗
PubMed2000

Decreased cerebrospinal fluid levels of beta-phenylethylamine in patients with Rett syndrome.

To clarify the mechanism of brain impairment in Rett syndrome, we measured the cerebrospinal fluid levels of beta-phenylethylamine (PEA) in 17 patients with Rett syndrome. Findings were compared with those obtained in age-matched controls and diseased controls. The cerebrospinal fluid level of PEA was significantly lower in patients with Rett syndrome than in the controls (31% of control values). The alteration in the cerebrospinal fluid level of PEA may reflect dopamine system impairment in Rett syndrome.

Adult↗
PubMed1999

Levels of cerebrospinal fluid nerve-growth factor differ in infantile autism and Rett syndrome.

Autism and Rett syndrome (RS) are both developmental disorders of unknown origin. Autism is a behaviourally defined syndrome. RS, which affects girls only, is characterized by a profound learning disability following early normal development, with a consistent cluster of clinical features. Differentiation of RS from infantile autism in the very early stages of the disorders is not always easy. Both syndromes still lack discriminative laboratory markers for accurate diagnosis and differentiation. We decided to compare the CSF nerve-growth factor (NGF) levels of children with infantile autism and children with RS using enzyme-linked immunosorbent assay (ELISA). Our findings of mainly normal CSF NGF in autism and low to negligible values in RS are in agreement with the different morphological and neurochemical findings (brain growth, affected brain areas, neurotransmitter metabolism) in the two syndromes. CSF NGF could be used as a biochemical marker for differentiation of patients with autism from those with RS.

Atrophy↗
PubMed1999

Brain perfusion SPECT and MRI in foetal alcohol syndrome.

Six boys and five girls with a mean age of 8.6 (range 3 to 13) years with foetal alcohol syndrome (FAS) were studied by MRI and single photon emission computed tomography (SPECT) to find specific areas of vulnerability. Morphological anomalies shown in six of 11 patients by MRI were situated both cortically and subcortically: cortical atrophy (N = 2), dilated ventricle (N = 1), corpus callosum hypoplasia (N = 1), cerebellar atrophy (N = 2), one of the latter with Arnold-Chiari malformation (N = 1). Delayed myelination of the white matter was seen in two patients. Volumetric studies of the hippocampus showed morphological left-right asymmetry in five of eight patients. However, SPECT showed mild hypoperfusion of the left hemisphere in all 10 subjects. The negative left-right index was located especially in the left parietooccipital region, i.e. in the brain areas implicated in arithmetical and logical-grammatical functions, which are known to be affected in FAS. Normal left-right dominance was also lacking in the frontal area, i.e. the brain area affected in attention-deficit-hyperactivity disorder (ADHD). Detection of these abnormalities, although they are not unique to FAS, may be helpful in the diagnosis and any attempts at rehabilitation. Diverse morphological and functional abnormalities are more frequent than has usually been believed even in less impaired children with FAS.

Adolescent↗
PubMed1999

Low insulin-like growth factor (IGF-1) in the cerebrospinal fluid of children with progressive encephalopathy, hypsarrhythmia, and optic atrophy (PEHO) syndrome and cerebellar degeneration.

PURPOSE: In patients with progressive encephalopathy, hypsarrhythmia, and optic atrophy (PEHO) syndrome, the pathophysiology underlying early progressive cerebellar and brainstem degeneration and severe epilepsy is unknown. Because insulin-like growth factor (IGF)-1 has been shown significantly to promote survival of cerebellar neurons, we wanted to see if the IGF system played a role in the pathogenesis of cerebellar atrophy. METHODS: We used a sensitive enzyme immunoassay kit for measuring cerebrospinal fluid (CSF) IGF-1 and insulin-like growth-binding protein (IGFBP)-3 in four groups of patients: PEHO syndrome patients (eight), PEHO-like patients (seven), age-matched controls (31), and patients with other types of cerebellar atrophy (11). RESULTS: Patients with PEHO syndrome and those with other progressive, degenerative cerebellar diseases had lower levels of CSF IGF-1 than the controls with other neurologic diseases. The CSF IGF-1 also allowed us to differentiate the "true" PEHO patients from the "PEHO-like" patients (those with similar clinical symptoms but without the typical neuroophthalmologic or neuroradiologic findings). The concentrations of IGFBP-3 did not significantly differ in any of the patient or control groups studied. CONCLUSIONS: CSF IGF-1 levels might be used as a marker of the degeneration of neurons in specific areas.

Atrophy↗
PubMed1998

Brain derived neurotrophic factor is increased in cerebrospinal fluid of children suffering from asphyxia.

Brain derived neurotrophic factor (BDNF) is a neurotrophic factor that is relatively highly expressed in developing and adult brain. Whereas clinical determinations of nerve growth factor (NGF) in human serum and cerebrospinal fluid (CSF) in different conditions have been undertaken there are no reports on levels of BDNF in human CSF. Here we show that BDNF is increased in CSF of neonatal children suffering from asphyxia which is characterised by periods of brain hypoxic-ischemia. In contrast to BDNF, levels of CSF NGF were largely decreased in these children. The present results show that BDNF can be detected in human CSF and that the levels increase following hypoxic-ischemic brain injury. As suggested by animal studies the increased BDNF might counteract neuronal damage observed in these patients following asphyxia.

Apgar Score↗