Low episodic memory performance as a premorbid marker of depression: evidence from a 3-year follow-up.

OBJECTIVE: To examine low episodic memory scores as a potential risk factor for depression. METHOD: A population-based sample of non-depressed individuals (20-64 years) were re-examined 3 years after an initial screening (n = 708). At baseline, information on episodic memory scores, demographic and socioeconomic factors, alcohol use and anxiety diagnoses was collected. The data for depression diagnoses were collected at both baseline and follow-up. RESULTS: Logistic regressions, conducted on three separate study groups that were defined according to three assessments of episodic memory (i.e. free + cued recall, free recall, cued recall) among individuals who scored in the 25 lowest or highest percentiles in the memory tests, revealed that low episodic memory performance defined as the sum of free and cued recalls of organizable words constitutes a risk of depression diagnosis 3 years later. CONCLUSION: Low episodic memory performance predated depressive diagnosis and might be considered as a premorbid marker of depression.

Cognitive functions in depressive disorders: evidence from a population-based study.

BACKGROUND: Most of the available evidence on the effects of depression is based on in- and out-patient samples focusing on individuals suffering from major depression. The aims of this study were to examine cognitive functioning in population-based samples and to determine whether cognitive performance varies as a function of depression subgroup. METHOD: Population-based samples (aged 20-64 years) with major depression (N = 68), dysthymia (N = 28), mixed anxiety-depressive disorder (N = 25) and minor depression (N = 66) were examined on a variety of cognitive tasks (i.e. episodic memory, verbal fluency, perceptual-motor speed and mental flexibility). One hundred and seventy-five non-depressed individuals served as controls. RESULTS: The total group of depressed individuals showed impairments in tasks tapping episodic memory and mental flexibility. Of more interest, however, was the observation that the pattern of impairments varied as a function of depression subgroup: the major depression and mixed anxiety-depressive disorder groups exhibited significant memory dysfunction, whereas individuals with dysthymia showed pronounced difficulties in mental flexibility. Minor depression did not affect cognitive performance. Verbal fluency and perceptual-motor speed were not affected by depression. CONCLUSIONS: These results indicate that persons with depressive disorders in the population exhibit cognitive impairments in tasks tapping episodic memory and mental flexibility and that cognitive impairment varies as a function of depressive disorder.

A population-based study on epilepsy in mentally retarded children.

PURPOSE: This study presents data on cumulative risk of seizures, cause, comorbidity, and remission of epilepsy among mentally retarded (MR) children followed until the age of 22 years. METHODS: A total of 151 MR children were identified at the age of 8 or 9 years by screening four birth cohorts of 12,882 children born from 1969 to 1972 in the Finnish province of Kuopio. Information about epilepsy was gathered longitudinally when children were 9 to 10, 17, and 22 years old. The guidelines for epidemiological studies on epilepsy proposed by the International League Against Epilepsy were followed. RESULTS: By the age of 10 years, 29 of the 151 MR children (19%) had epilepsy. The cumulative risk for epilepsy at 22 years was 21%. The probability of developing epilepsy was increased fivefold in severely MR children compared with mildly MR children, i.e., in 27 of the 77 severely MR children (35%) versus 5 of the 74 mildly MR children (7%). Postnatal causes of mental retardation or association with cerebral palsy increased the risk for epilepsy, especially in the mildly MR children. When these risk factors were not present, the mildly MR children exhibited only a 3% risk for epilepsy, whereas the respective risk was about 10-fold in severe mental retardation. The cumulative probability of epilepsy being in remission for 5 years by the age of 22 was 32%. CONCLUSIONS: The cumulative risk of epilepsy varies according to the severity and the cause of the retardation as well as the presence of additional disabilities. The cumulative probability of epilepsy remission tended to increase with age.

Clinical spectrum and diagnostic difficulties of infantile ponto-cerebellar hypoplasia type 1.

We present the clinical and histopathological features and the diagnostic difficulties encountered in five children affected by a motor neuron disorder other than spinal muscular atrophy. Investigations performed suggested the diagnosis of ponto-cerebellar hypoplasia type 1 (PCH-1). Severe respiratory difficulty was present at birth in two of these children; hypotonia, arthrogryposis, microcephaly and nystagmus were present in all. Early and progressive bulbar involvement with swallowing difficulties and stridor was also a common feature in these infants. Severe cognitive delay was invariably present. Brain magnetic resonance imaging showed ponto-cerebellar hypoplasia in four children while striking atrophy of the cerebellar vermis and cerebellar hemispheres were present in the fifth child. Electrophysiological and pathological investigations of proximal muscles performed at presentation in all these children were not conclusive, while the post-mortem studies, or the study of distal muscles during life, showed a clear neurogenic picture. Genetic studies excluded involvement of the SMN gene, or of other genes located on chromosome 5q, confirming that ponto-cerebellar hypoplasia type 1 is a different entity from typical proximal spinal muscular atrophy.

Genetic refinement of the hereditary neuralgic amyotrophy (HNA) locus at chromosome 17q25.

Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant, recurrent focal neuropathy. HNA is characterised by episodes of painful brachial plexus neuropathy with muscle weakness and atrophy, as well as sensory disturbances. Single episodes are commonly preceded by non-specific infections, immunisations or parturition. Mild dysmorphic features and short stature are present in some HNA families, but absolute co-segregation with HNA has not been described. To refine the previously described HNA locus on chromosome 17q25, we performed a genetic linkage study in five HNA families with different geographic origins. Significant linkage was obtained with chromosome 17q24-q25 short tandem repeat (STR) markers in three HNA families and suggestive linkage was found in the other two HNA families. Analysis of the informative recombinations in affected individuals allowed us to reduce the HNA linkage interval to a candidate region of 3.5 cM.

Sex differences in episodic memory: the impact of verbal and visuospatial ability.

The impact of verbal and visuospatial ability on sex differences in episodic memory was investigated. One hundred men and 100 women, 2040 years old, participated in a series of verbal and visuospatial tasks. Episodic memory was assessed in tasks that, to a greater or lesser extent, were verbal or visuospatial in nature. Results showed that women excelled in verbal production tasks and that men performed at a superior level on a mental rotation task. In addition, women tended to perform at a higher level than men on most episodic memory tasks. Taken together, the results demonstrated that (a) women perform at a higher level than men on most verbal episodic memory tasks and on some episodic memory tasks with a visuospatial component, and (b) women's higher performance on episodic memory tasks cannot fully be explained by their superior performance on verbal production tasks.

Dual cerebral processing of elementary auditory input in children.

We compared event-related responses (ERPs) to non-attended frequent and intermittent auditory input in school-aged children and in young adults. In adults, both inputs elicited prominent auditory N100 responses at vertex. In children, intermittent stimulation evoked vertex responses with similar latency and refractoriness, whereas frequently delivered identical tones evoked responses on average at 240 ms. Sensitization of a separate neuronal population at 260-300 ms was obvious during intermittent stimulation in children. The dual behaviour, simultaneous 'habituation' of one neuronal population response and sensitization of another, may reflect the process of redirecting the attention and setting up a neuronal model. Furthermore, results suggest that a simplistic interpretation of developmental ERPs in which shortening of latencies represents maturation is insufficient.

West syndrome: individualized ACTH therapy.

Individualized ACTH treatment of the West syndrome (WS) was assessed in a prospective multicenter study, in which each patient's dosage was increased stepwise according to response. Our series included six patients with cryptogenic and 24 with symptomatic infantile spasms. During the treatment period the total ACTH dose ranged from 58 to 373 i.u./kg. In the cryptogenic group one patient responded to pre-ACTH pyridoxine and four to the lowest dosage of ACTH (3 i.u./kg daily) with cessation of spasms and good outcome; one patient needed the highest dosage (12 i.u./kg daily) for cessation of seizures and became developmentally retarded. In the symptomatic group, 21 of the 24 patients needed 6-12 i.u./kg daily; 12 became seizure-free or having infrequent non-IS fits. Complications such as arterial hypertension, cerebral ventricle dilatation, cardiac hypertrophy, and prolonged adrenocortical hyporesponsiveness were related to the dose. The individualization provides all the benefits of ACTH treatment with minimal side effects and cost.

Vasopressin in the cerebrospinal fluid of febrile children with or without seizures.

Immaturity in water and electrolyte balance in the brain has been considered to increase the susceptibility of young animals and children to febrile convulsions (FCs). Arginine-vasopressin (AVP) is involved in the regulation of several centrally mediated events such as modulation of fever and the ease with which water permeates into and out of the brain. To evaluate the possible role of AVP in the control of water balance and susceptibility to convulsions during fever we measured the AVP concentration in the cerebrospinal fluid (CSF) and plasma of febrile children with or without convulsions. The febrile population consisted of 47 children, of whom 29 experienced seizures during fever. Seven children with epileptic symptoms and 18 children without seizures were included as nonfebrile controls. The CSF AVP concentration in febrile children without seizures and in nonfebrile convulsive children was significantly lower (0.60 +/- 0.07 pmol/l, mean +/- SEM, P < 0.01 and 0.65 +/- 0.19 pmol/l, P < 0.05, respectively) than in nonfebrile children without convulsions (0.83 +/- 0.06 pmol/l). However, the levels of CSF AVP were not significantly different in children with FCs (0.71 +/- 0.06 pmol/l) compared with other groups. CSF AVP correlated with the CSF osmolality (r = 0.33, P = 0.02). No statistical differences in plasma AVP levels between the groups could be found. The present data provide support for the hypothesis of synchronous regulation of osmolality and AVP concentration in CSF. During fever the concentration of CSF AVP was lower in nonconvulsive children compared with nonfebrile nonconvulsive children. CSF AVP levels were not affected in febrile children by convulsions.

Osmolality and electrolytes in cerebrospinal fluid and serum of febrile children with and without seizures.

UNLABELLED: During acute febrile diseases mild disturbances of water and electrolyte balance occur frequently. It has been suggested that changes in electrolyte balance, in particular hyponatraemia, might predispose a child to convulsions during febrile illness; however, the changes of electrolytes in the CSF are not known. We have studied the effects of fever and convulsions on water and electrolyte balance in CSF and serum by measuring osmolality and electrolyte concentrations in children. The febrile population consisted of 60 children, 36 of whom had seizures during fever. Twenty-one children without convulsions and nine children with epileptic symptoms were nonfebrile controls. We noticed that CSF is subject to changes in osmolality and electrolyte concentration during fever, while convulsions do not exhibit such changes. CSF osmolality and sodium concentrations were lower in febrile children than in nonfebrile controls. The osmolality in febrile children with convulsions was 3.8% (P < 0.01) and without seizures 3.5% (P < 0.01) lower than in nonfebrile nonconvulsive children. The changes in CSF sodium concentration, and to a lesser extent potassium and chloride concentrations, paralleled those of CSF osmolality. A positive correlation was observed between the CSF and serum osmolatities (r = 0.73, P < 0.0001), and sodium concentrations (r = 0.63, P < 0.0001). A negative correlation between the body temperature and both CSF osmolality (r = -0.66, P < 0.0001) and sodium concentration (r = -0.59, P < 0.0001) exhibits also the important regulative role of increased body temperature. CONCLUSION: Fever is an important factor for disturbances in fluid and electrolyte balance. The alterations in CSF osmolality and sodium concentration do not, however, give an unambiguous explanation for the susceptibility to simple febrile seizures.

Low sodium levels in serum are associated with subsequent febrile seizures.

Fever plays an important role in causing disturbances in fluid and electrolyte balance. Hyponatraemia has been thought to enhance the susceptibility to seizures associated with febrile illnesses in childhood. We have studied serum electrolyte levels in children with simple and complicated febrile convulsions. Sodium levels were lower in those children with complicated convulsions in comparison with those having simple convulsions (136.07 +/- 3.06 mmoll-1, mean +/- SD, n = 42, and 137.62 +/- 2.63 mmoll-1, n = 71, respectively; p < 0.01, Student's t-test). The sodium concentrations were lowest in children with repeated seizures (134.20 +/- 2.30 mmoll-1, n = 15) compared with children having simple (p < 0.01, ANOVA, Duncan's test) or other complicated types of febrile convulsions: focal seizures (137.08 +/- 3.82 mmoll-1, n = 12, p < 0.01), seizures lasting longer than 15 minutes (138.00 +/- 2.45 mmoll-1, n = 5, p < 0.05) and children over 5 years (136.70 +/- 2.06 mmoll-1, n = 10, p < 0.05). Serum potassium levels showed no statistically significant differences between the patient groups. Our results show that hyponatraemia may increase the risk for multiple convulsions during the same febrile illness.

The role of fever on cerebrospinal fluid glucose concentration of children with and without convulsions.

In febrile convulsions glucose concentrations are known to increase both in the blood and cerebrospinal fluid (CSF). The reason behind this increase is, however, incompletely understood. We have studied the effects of convulsion and fever on the CSF and blood glucose concentrations in four different groups of children: febrile and non-febrile children, with and without convulsions. The concentration of glucose in the CSF was significantly higher in febrile children with (4.4 +/- 0.1 mmol/l, mean +/- SEM n = 35, p < 0.01. ANOVA, Duncan's test) and without convulsions (3.9 +/- 0.2 mmol/l, n = 22, p < 0.05) than in non-febrile, non-convulsive children (3.3 +/- 0.1 mmol/l, n = 21). In non-febrile convulsive children, the CSF glucose concentration was 3.7 +/- 0.2 mmol/l (n = 10). Both fever and seizures increased the CSF glucose levels (p < 0.0001) and p = 0.028, respectively, analysis of covariance). There was a linear correlation between the body temperature and concentration of glucose in the CSF (r = 0.454, p < 0.0001, n = 88, Pearson's correlation analysis). The changes in blood glucose concentrations between the groups paralleled those found in the CSF. Our results show that hyperglycaemia and an increase in the CSF glucose concentration in febrile convulsions is not explained just by a stress reaction, evoked by the seizure, as has been hypothesized earlier, but by the influence of increased body temperature as well.

A population-based study on the causes of mild and severe mental retardation.

The causes of mental retardation (MR) were studied as part of a multidisciplinary epidemiological case-control study in 151 mentally retarded patients identified by screening four age cohorts (12,882 children) at 8-9 years of age in the province of Kuopio, Finland. The causes of MR in 77 severely retarded (SD < or = -3 SD) and 74 mildly retarded (-2 > SD > -3) children were divided into pre-, peri-, postnatal and unknown groups according to the probable time of onset. The causes were pre-, peri-, postnatal and unknown in 60%, 9%, 8% and 23%, and 22%, 1%, 3% and 74%, in the two populations, respectively. Genetic causes were found in 28% of all 151 cases; the three most common subgroups were trisomy 21, fragile X syndrome and aspartylglycosaminuria (13%, 4% and 2% respectively). The study design used provided reliable information on the causes of MR and also demonstrated those forms of genetic metabolic diseases typical of Finnish inheritance.

Histamine in cerebrospinal fluid of children with febrile convulsions.

Febrile convulsions (FC) are frequent acute neurologic disturbances of childhood. The cellular and neurochemical mechanisms causing FC are unclear. Among other mechanisms, the CNS histamine (HA) has been suggested to participate in seizure control and thermoregulation. We evaluated the possible role of HA in regulation of FC by measuring HA and tele-methylhistamine (t-MH) concentrations in the cerebrospinal fluid (CSF) of children with FC. The study group consisted of 35 children treated for acute FC in the hospital. The control groups consisted of (a) feverish children without seizures (n = 23), (b) convulsive children without fever (n = 7), and (c) children with neither fever nor convulsions (n = 21). HA was assayed by high-performance liquid chromatography (HPLC) with fluorescence detection, and t-MH was measured by gas chromatography-mass spectrometry. CSF HA concentration in the group of febrile children without seizures was significantly higher (0.69 +/- 0.16 pmol/ml, mean +/- SE) than in children with FC (0.36 +/- 0.07 pmol/ml, p < 0.05, analysis of variance, ANOVA). HA concentration was 0.37 +/- 0.18 pmol/ml in the group of nonfebrile convulsive children and 0.36 +/- 0.08 pmol/ml in the nonfebrile nonconvulsive group. No statistical differences in t-MH were detected between groups. The increased susceptibility to seizures during fever may be connected to the lack of increase in CSF HA in the FC group. The data support the hypothesis that the central histaminergic neuron system may be involved in inhibition of seizures associated with febrile illnesses in childhood.

Diurnal and age-related changes in cerebrospinal fluid tele-methylhistamine levels during infancy and childhood.

Histamine is a neurotransmitter participating in many physiological functions and behavior, including control of arousal and modulation of the circadian rhythms. Diurnal variation in cerebrospinal fluid (CSF) levels of tele-methylhistamine (t-MH), the main histamine metabolite, has been detected in several animal studies. In humans, such changes have not been described. Little is known on the development of histaminergic neurons in human brain. In children, the levels of CSF t-MH are not known. Therefore, we have measured the concentrations of CSF t-MH in 81 children, age ranging from 3 months to 14.6 years. t-MH levels were higher in infants, and near adult values were measured in adolescents, the relation between CSF t-MH and age being; CSF t-MH = -0.217 years + 7.31 (n = 81, r = 0.26, p = 0.021). The mean t-MH concentration was higher during the daytime (7.07 +/- 0.46 pmol/ml, mean +/- SEM) than in the night (5.35 +/- 0.60 pmol/ml, p = 0.0019, ANOVA). The results show a development change in the concentration of t-MH during childhood and a difference in t-MH levels between the daytime and night indicating a more active metabolism of brain HA in the waking period.

The concentrations of GABA, 5-HIAA and HVA in the cerebrospinal fluid of children with infantile spasms and the effects of ACTH treatment.

Children with infantile spasms (IS) are generally treated with ACTH although little is known of the biochemical basis of the symptoms and the mechanism of this therapy. We have measured the concentrations of gamma-aminobutyric acid (GABA), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the CSF of IS children, followed the effect of ACTH treatment on these parameters and correlated CSF GABA values with the cause of IS, cranial CT findings and antiepileptic treatment. While significant differences in GABA concentrations were found between the children with IS and those with febrile seizures or nonconvulsive symptoms, these could be accounted for by age, not the disease present. The CSF GABA level was highest in the IS children with normal CT, cryptogenic cause and no antiepileptic treatment, and lowest in those with abnormal CT, symptomatic cause and antiepileptic treatment. The basal level of CSF 5-HIAA in the IS children was higher than that in the nonconvulsive children, but HVA levels did not differ. ACTH therapy did not change the CSF levels of GABA, 5-HIAA and HVA significantly.

High prevalence of aspartylglycosaminuria among school-age children in eastern Finland.

A high prevalence of the lysosomal storage disease aspartylglycosaminuria was found in a study of four birth cohorts of 12882 children in eastern Finland. Using school achievement tests and registers of mentally retarded individuals, 178 mentally retarded children were identified. Randomized urine samples from 151 of the 178 retarded children and from 101 healthy children were analyzed quantitatively for aspartylglucosamine by high-performance liquid chromatography. The results identified three affected individuals in the retarded group indicating an exceptionally high prevalence of aspartylglycosaminuria (1:3643) in the study population, consistent with a carrier frequency of 1:30. The 95% confidence limits for the prevalence are 1:4 352-1:16389. This is the highest prevalence described for any glycoproteinosis in any population and comparable to the incidence figures of the most common lysosomal storage diseases, Gaucher disease type I and Tay-Sachs disease among Ashkenazi Jews. In the study group, aspartylglycosaminuria was, after trisomy 21 (n = 19) and the fragile X syndrome (n = 6), the most common genetic cause for mental retardation.

Taurine in normal and diseased human skeletal muscle.

Taurine content of 199 clinical muscle biopsies was determined and correlated to histometric data of 121 cases. Taurine concentration in muscles was markedly dependent on fiber type distribution, taurine being more abundant in the slow, oxidative type 1 fibers than in the type 2 fibers. Taurine concentration rose slightly with age and tended to be higher in denervations, muscular dystrophies and myotonias, but the differences from the control values were non-significant.