Normal concentrations of heavy metals in autistic spectrum disorders.

AIM: Autism is a neurological-psychiatric disease. In the last 20 years we witnessed a strong increase of autism diagnoses. To explain this increase, some scientists put forward the hypothesis that heavy metal intoxication may be one of the causes of autism. The origin of such an intoxication was hypothesised to be vaccines containing thimerosal as antimicrobic preservative. This preservative is mainly made up of mercury. The aim of our research was to investigate the correlation between autism and high biological concentrations of heavy metals. METHODS: Seventeen autistic patients, between 6 and 16 years old (average: 11.52 DS: 3.20) (15 males and 2 females), were investigated, as well as 20 non autistic subjects from neuropsychiatric service between 6 and 16 years (average: 10.41 DS: 3.20) (15 males and 2 females). In both groups blood, urine and hair samples were analysed trough means of a semiquantitative analysis of heavy metal dosing. The metals analysed were Lead, mercury, cadmium and aluminium, since their build-up may give both neurological and psychiatric symptoms. RESULTS: The comparison of the mean values of the concentrations between the groups, performed with ANOVA test, has shown no statistically relevant differences. CONCLUSION: There wasn't correlation between autism and heavy metal concentration.

Neuropsychological assessment in prepubertal patients with congenital adrenal hyperplasia: preliminary study.

AIM: Individuals with congenital adrenal hyperplasia (CAH) provide a test population for the theory that elevated testosterone levels alter pre-/perinatal brain development. METHODS: Seven prepuberal girls with CAH and seven matched controls has been submitted to a neuropsychological evaluation. We measured abilities where gender differences repeatedly has been observed or that had earlier shown differences between CAH subjects and controls. The following cognitive functions were tested: general intelligence, attention, verbal and non-verbal abilities, cerebral dominance for verbal and non-verbal material, frontal functions, peripheral dominance and motor fluency. Since several animal studies shown hippocampal morphological changes induced by prolonged hydrocortisone exposure, we also investigated memory functions. RESULTS: No differences were recorded between two groups on those abilities that are not sexually dimorphic. The mean general intelligence level of the patients was significantly lower than the controls', in agreement with previous studies. The verbal and non-verbal tasks revealed an age-related male-like pattern (i.e., verbal disadvantage) and an inversion of the hemispheric dominances. The latter observation was supported by a right-to-left shift of the peripheral dominances. The patients memory performances were all inferior to the controls'. The results are discussed in the light of possible hormonal influences. CONCLUSION: Our main findings support the hypothesis that elevated pre-/perinatal androgen exposure can influence some cognitive pattern of specific sexual dimorphic abilities in prepubertal subjects.

Specific learning disorder in the primary epilepsies of childhood.

AIM: The aim of this study was to investigate the presence of learning disorders in children with idiopathic epilepsy. METHODS: The study enrolled 16 children with idiopathic epilepsy, 8 with absence and 8 with rolandic epilepsy. This was a standardized neuropsychological assessment with particular attention to learning performance (reading and writing skills/number processing). RESULTS: Fourteen out of 16 subjects resulted with a specific learning disability, although specific patterns have not been identified. CONCLUSION: The study confirms the higher incidence of learning disorder in children with epilepsy (in front of normal prevalence, 2-10%). The importance of complete neuropsychological evaluation in children with focal or generalized epilepsy was highlighted.

Altered calcium homeostasis in autism-spectrum disorders: evidence from biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier AGC1.

Autism is a severe developmental disorder, whose pathogenetic underpinnings are still largely unknown. Temporocortical gray matter from six matched patient-control pairs was used to perform post-mortem biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier (AGC), which participates in the aspartate/malate reduced nicotinamide adenine dinucleotide shuttle and is physiologically activated by calcium (Ca(2+)). AGC transport rates were significantly higher in tissue homogenates from all six patients, including those with no history of seizures and with normal electroencephalograms prior to death. This increase was consistently blunted by the Ca(2+) chelator ethylene glycol tetraacetic acid; neocortical Ca(2+) levels were significantly higher in all six patients; no difference in AGC transport rates was found in isolated mitochondria from patients and controls following removal of the Ca(2+)-containing postmitochondrial supernatant. Expression of AGC1, the predominant AGC isoform in brain, and cytochrome c oxidase activity were both increased in autistic patients, indicating an activation of mitochondrial metabolism. Furthermore, oxidized mitochondrial proteins were markedly increased in four of the six patients. Variants of the AGC1-encoding SLC25A12 gene were neither correlated with AGC activation nor associated with autism-spectrum disorders in 309 simplex and 17 multiplex families, whereas some unaffected siblings may carry a protective gene variant. Therefore, excessive Ca(2+) levels are responsible for boosting AGC activity, mitochondrial metabolism and, to a more variable degree, oxidative stress in autistic brains. AGC and altered Ca(2+) homeostasis play a key interactive role in the cascade of signaling events leading to autism: their modulation could provide new preventive and therapeutic strategies.

Proteinuria in focal segmental glomerulosclerosis: role of circulating factors and therapeutic approach.

The clinical course of primary Focal Segmental Glomerulosclerosis (FSGS) is frequently complicated by nephrotic range proteinuria and progression to renal failure. The high recurrence rate of the disease in transplanted kidney suggests the hypothesis that such patients have a circulating factor that alters glomerular capillary permeability. In recent years some authors found that serum from patients with FSGS increases glomerular permeability to albumin and partially identified the permeability factor (PF) as a protein of 30-50 Kd m.w. The removal of this protein by means of Plasma Exchange (PE) or plasma Immunoadsorption by Protein A (IA) decreased proteinuria. In this report we provide preliminary data about the prevalence of PF and the therapeutic effect of its removal by IA, in 3 pts with recurrence in the transplanted kidney, and 4 with FSGS of the native kidneys. They were resistant to corticosteroids (CS) and immunosuppressive (IS) therapy. 10 IA sessions were performed in 4 weeks: if a remission was achieved IA was gradually tapered. The level of PF in the serum was measured by an in vitro assay to determine the glomerular permeability to albumin. The FSGS was histologically proven in all cases and the degree of evolution was evaluated. PF levels, serum creatinine, daily proteinuria and serum albumin were monitored. The 3 patients with recurrent FSGS had a normalization of the PF levels; 2 had a clinical remission. In FSGS of native kidneys PF was elevated in 3/4 cases; 1 had a clinical remission; 2 with extensive sclerohyalinosis and 1 without PF levels did not improve. Our results confirm that most patients with FSGS have high PF serum levels and suggest that its removal can be beneficial.

Crying abnormalities in congenital hypothyroidism: preliminary spectrographic study.

The aim of this preliminary study was to evaluate the acoustic patterns of the cries of hypothyroid newborns at the time of diagnosis and after the beginning of therapy. Cries were recorded at the nursery of the San Raffaele Hospital, Milan, Italy from 12 full-term subjects (three boys and nine girls) affected by congenital hypothyroidism. Results show that untreated hypothyroid infants at first recording had fewer voiceless and partially voiced cries than normal controls. The percent distribution of this pattern did not change at the second recording after the onset of substitutive therapy. Also, untreated hypothyroid infants had many more cry units showing a vibrato contour than did controls, and this pattern did not change after the onset of treatment. Starting, maximum, minimum, and end frequencies measured on the fundamental were significantly lower in the hypothyroid sample. Four hypothyroid subjects recorded before therapy and within 4 weeks after therapy onset significantly augmented their fundamental frequency parameters; however, in 25% of the sample, sound parameters remained unaltered after 3 or more weeks of treatment. To our knowledge the present preliminary study is the first one performed on follow-up of hypothyroid newborns and indicates that both central and peripheral damage might influence the pattern of crying in untreated hypothyroid infants.

Recognition of emotional facial expressions in depressed children and adolescents.

Of the neurobiological models of children's and adolescents' depression, the neuropsychological one is considered here. Experimental and clinical evidence has allowed us to identify a lateralization of emotional functions from the very beginning of development, and a right hemisphere dominance for emotions is by now well-known. Many studies have also correlated depression with a right hemisphere dysfunction in patients of different ages. The aim of our study was to analyze recognition of different facial emotions by a group of depressed children and adolescents. Patients affected by Major Depressive Disorder recognized less fear in six fundamental emotions than a group of healthy controls, and Dysthymic subjects recognized less anger. The group of patients' failure to recognize negative-aroused facial expressions could indicate a subtle right hemisphere dysfunction in depressed children and adolescents.

Panic disorder or temporal lobe epilepsy: A diagnostic problem in an adolescent girl.

Similarities in the clinical presentation of panic disorder and temporal lobe epilepsy suggest that the two disorders are related and can lead to difficulties in a differential diagnosis. We describe the case of a young girl suffering from paroxysmal anxiety, derealization-depersonalization and autonomic symptoms, lasting from seconds to several minutes; these episodes were very frequent and disabling. The interictal EEGs and MRI were normal. After having diagnosed panic disorder based mainly on the duration of the attacks and the family history, a pharmacological treatment was started.

Color-Doppler in the imaging work-up of primary hyperparathyroidism.

Primary hyperparathyroidism (PHP) is a rare disease that must be suspected in all the cases of recurrent calcium nephrolithiasis, and that may be totally corrected by surgery. The imaging techniques permit to locate the hyperplastic gland or adenoma before intervention, but their usefulness in patients without a history of previous neck surgery is still debated. Several imaging techniques have been proposed with the aim of locating parathyroid hyperfunctioning glands, including high resolution sonography (US) with color-Doppler (CD), scintigraphy, computed tomography (CT) and magnetic resonance imaging (MRI). We report here a case of recurrent calcium oxalate nephrolithiasis sustained by PHP, which demonstrates how US coupled with CD and echocontrast enhancement is useful in the preoperative location of parathyroid glands. US is the first choice technique in the evaluation of PHP because it is less expensive and useful in detailing lesions of the neck when carried out by a skilled operator. CD should be regarded as a useful complement of US enhancing its sensitivity (80 vs 90%) especially in the cases of associated thyroid gland diseases. Tc-99m SESTAMIBI scintigraphy coupled with MRI is mandatory in high risk surgical patients, namely in those undergoing repeated neck surgery. In conclusion, considering that surgeon must explore all the four parathyroid glands (because of the possibility of multiple adenomas or hyperplasia) a well definite location of the adenomatous lesion may reduce the risks and the time of intervention, and allow the use of alternative procedures, such as videoscopic surgery. On this view and in terms of economy, only US and CD coupled with Tc-99 SESTAMIBI scintigraphy should be considered before surgery.

Myoclonic encephalopathy and diabetes mellitus in a boy.

We describe an 18-month-old boy with insulin-dependent diabetes mellitus who developed idiopathic myoclonic encephalopathy (dancing eye syndrome) at 26 months of age. The neurological symptomatology (multifocal myoclonus, opsoclonus, ataxia, behavioural disturbance) developed within 10 to 14 days after presentation. Biological, neuroradiological, and scintigraphic examination excluded CNS infectious diseases, intoxication, or tumours. At onset of diabetes mellitus, anti-glutamic-acid decarboxylase (GAD) antibodies were observed, and markedly increased in titre when myoclonic encephalopathy occurred. Corticosteroid treatment resulted in a decrease in anti-GAD autoantibody titres and the disappearance of neurological disturbances. As GAD is expressed both in pancreatic beta-cells and cerebellar Purkinje cells, it is possible that a common autoimmune disorder in this patient may account for both the diabetes and myoclonic encephalopathy.

Serum calcitriol and dietary protein intake in idiopathic calcium stone patients.

In kidney stone patients, high protein intake and calcitriol overproduction are factors leading to hypercalciuria, but there are conflicting reports on the effects of dietary protein on calcitriol production. To investigate the relationships between serum calcitriol, dietary protein intake, and urinary calcium excretion, 33 male idiopathic calcium stone formers (aged 20-60 years), with normal renal function and on unrestricted diet, have been studied. Dietary protein intake was estimated by the protein catabolic rate determination. Abnormally elevated calcitriol levels were found in 16 patients (48.5%) who had similar levels of serum intact parathyroid hormone and phosphate, creatinine clearance, and calcium and phosphate urinary excretion, but lower protein catabolic rate (82+/-16 vs. 97+/-20 g/day, P<0.05) than the patients with normal calcitriol levels. The calcitriol to intact parathyroid hormone ratio was higher in hypercalciuric than in normocalciuric patients (2.4+/-1.1 vs. 1.6+/-0.8, P<0.05). Calcitriol was positively correlated with plasma calcium (r=0.41, P<0.01) and inversely with protein catabolic rate (r=-0.42, P<0.01). Protein catabolic rate was positively correlated with creatinine clearance (r=0.69, P<0.001) and urinary phosphate excretion (r=0.72, P<0.001). No relationship was observed between calcitriol and creatinine clearance. These results confirm the calcitriol overproduction in calcium stone disease and that the high calcitriol to intact parathyroid hormone ratio is the main feature associated with hypercalciuria. Calcitriol serum levels appear to be unrelated to creatinine clearance, whereas there is an inverse relationship with protein catabolic rate. This suggests that low rather than high dietary protein intake may favor the increase of calcitriol synthesis in male calcium stone formers with normal renal function.

Decoding of emotional expressions in children and adolescents.

The aim of this study was to assess whether different kinds of emotions are decoded in different ways during ontogeny. 151 normal subjects (80 boys; 71 girls) aged 8 to 16 were recruited in primary, secondary (middle), and high schools and 46 slides (3 male; 3 female) from Picture of Facial Affect showing six basic emotions were stimuli. Analysis showed that boys and girls in all age groups did not differ in decoding facial expression; happiness and disgust had the highest percentage scores in all age groups, 99% and 94%, respectively, while sadness and fear had the lowest percentage scores, 69% and 55%, respectively. This was possibly due to the intrinsic unpleasantness of those emotions for children. Competence in discrimination of sadness, fear, and surprise changed across age groups, but this growing competence did not show a linear trend and was not similar for all emotions.

Dietary treatment of diabetic nephropathy with chronic renal failure.

Thirty-two patients with diabetes mellitus (22 IDDM and 10 NIDDM, 21 males and 11 females, age 44+/-11.8 years) were followed for 5.2+/-3.8 years after the onset of chronic renal failure, with the aim of evaluating the effect of low protein diets on the rate of decline of the residual renal function. During the 1.8+/-1.6 year follow-up period on free or uncontrolled low protein diet the mean rate of decline of creatinine clearance was 0.9+/-0.6 ml/min/month, significantly greater than that observed during 3.7+/-3.1 years on low or very low protein diets. The reduction of protein intake was followed by a significant decrease in daily urinary protein loss. A better glycaemic control was obtained on the low protein diet, and the daily insulin requirement decreased. The anthropometry, as well as the serum concentrations of rapid turnover proteins, did not change, in spite of the low or very low protein dietary supply for a long duration. The values of mean arterial pressure were quite similar during the follow-up period on free or uncontrolled low protein diet and during the study period on the low protein diet. A good compliance with reduced dietary intake (as demonstrated by the measurement of the daily urea excretion) was obtained in a large number of patients. In conclusion, our study confirms the protective effect on the residual renal function of low protein diets in IDDM and NIDDM patients with chronic renal failure due to diabetic nephropathy, in the absence of any sign of protein malnutrition.

Newborns crying in different contexts: discrete or graded signals?

The aim of this study was to investigate whether human infants' cries show individually and contextually discriminable acoustic parameters. 20 full-term normal human newborns (aged 1 to 4 days) had their cries recorded during routine blood withdrawal (pain context) 30 min. before a scheduled feeding (hunger context) and when subjected to kinetic stimuli during neurological examination (manipulation context). Type of cries, melodic contours, F0 parameters, but not the "macro" trend of the start of the fundamental frequency, indicated a difference in pain cries in the other two contexts. All the acoustic features considered showed an individual specificity. The peak frequencies of voiceless or partially voiced wails had the interesting property of being optimised as long distance signals. We hypothesised that this feature of infants' cries may have evolved in a time window when the infants were left in collective nurseries and not carried on the mothers' backs as maintained by the traditional view.

A number of schizencephaly patients including 2 brothers are heterozygous for germline mutations in the homeobox gene EMX2.

We report here that some patients affected by schizencephaly are heterozygous for mutations in EMX2, a homeobox gene implicated in the patterning of the developing forebrain. Schizencephaly is a very rare human congenital disorder characterized by a full-thickness cleft within the cerebral hemispheres. Large portions of these may be absent and replaced by cerebrospinal fluid. We previously reported the presence of EMX2 mutations in 7 out of 8 sporadic cases of schizencephaly. We now extend this analysis to 10 additional patients, including 2 brothers. Six patients were found to be heterozygous for de novo mutations in EMX2. In particular, the 2 brothers show the same mutation affecting the splicing of the first intron, while this mutation is absent in their parents and in the 2 unaffected siblings.

Discordant clinical and neuroradiological features of congenital bilateral perisylvian syndrome in monozygotic female twins.

We here report a case of monozygotic female twins, only one of whom had congenital bilateral perisylvian syndrome (CBPS). The affected girl had all of the essential and some additional diagnostic criteria according to Kuzniecky et al. [1993]; her twin sister was completely normal both clinically and neuroradiologically. This observation may contribute towards our understanding of the etiopathogenetic mechanisms of cortical dysplasia in CBPS: fetal brain ischemia or hypoxia in only one twin seems to be a reasonable explanation in this particular case.

Neuropsychological and neuroradiological study of a case of early-onset Huntington's chorea.

The authors report a case of Huntington's disease in an 11-year-old boy with onset at six years of age. The neurological signs and symptoms were midway between the hyperkinetic and rigid forms of chorea. Intellectual development was characterized by a medium-grade deficit. MRI revealed marked atrophy of the head of the caudate nucleus, with diffuse hyperintensity of the putamen. The most characteristic neuropsychological feature was ideomotor apraxia. Neuropsychological and neuroradiological data are discussed in relation to the role of the basal nuclei and frontal cortex in the organization of movement.