Perineuronal and perisynaptic extracellular matrix in the human spinal cord.

Extracellular matrix (ECM) forms an active interface around neurons of the central nervous system (CNS). Whilst the components, chemical heterogeneity and cellular recruitment of this intercellular assembly in various parts of the brain have been discussed in detail, the spinal cord received limited attention in this context. This is in sharp contrast to its clinical relevance since the overall role of ECM especially that of its chondroitin sulphate-based proteoglycan components (CSPGs) was repeatedly addressed in neuropathology, regeneration, CNS repair and therapy models. Based on two post-mortem human specimen, this study gives the first and detailed description of major ECM components of the human spinal cord. Immunohistochemical investigations were restricted to the systematic mapping of aggrecan, brevican, proteoglycan link-protein as well as tenascin-R and hyaluronan containing matrices in the whole cranio-caudal dimension of the human spinal cord. Other proteoglycans like versican, neurocan and NG2 were exemplarily investigated in restricted areas. We show the overall presence of tenascin-R and hyaluronan in both white and grey matters whereas aggrecan, proteoglycan link-protein and brevican were restricted to the grey matter. In the grey matter, the ECM formed aggrecan-based perineuronal nets in the ventral and lateral horns but established single perisynaptic assemblies, axonal coats (ACs), containing link-protein and brevican in all regions except of the Lissauer's zone. Intersegmental differences were reflected in the appearance of segment-specific nuclei but not in overall matrix distribution pattern or chemical heterogeneity. Perineuronal nets were typically associated with long-range projection neurons including cholinergic ventral horn motorneurons or dorsal spinocerebellar tract neurons of the Clarke-Stilling nuclei. Multiple immunolabelling revealed that nociceptive afferents were devoid of individual matrix assemblies unlike glycinergic or GABAergic synapses. The detailed description of ECM distribution in the human spinal cord shall support clinical approaches in injury and regenerative therapy.

Perisynaptic aggrecan-based extracellular matrix coats in the human lateral geniculate body devoid of perineuronal nets.

The extracellular matrix surrounds different neuronal compartments in the mature nervous system. In a variety of vertebrates, most brain regions are loaded with a distinct type of extracellular matrix around the somatodendritic part of neurons, termed perineuronal nets. The present study reports that chondrotin sulfate proteoglycan-based matrix is structured differently in the human lateral geniculate body. Using various chondrotin sulfate proteoglycan-based extracellular matrix antibodies, we show that perisomatic matrix labeling is rather weak or absent, whereas dendrites are contacted by axonal coats appearing as small, oval structures. Confocal laser scanning microscopy and electron microscopy demonstrated that these typical structures are associated with synaptic loci on dendrites. Using multiple labelings, we show that different chondrotin sulfate proteoglycan components of the extracellular matrix do not associate exclusively with neuronal structures but possibly associate with glial structures as well. Finally, we confirm and extend previous findings in primates that intensity differences of various extracellular matrix markers between magno- and parvocellular layers reflect functional segregation between these layers in the human lateral geniculate body.

Chondroitin sulphate proteoglycan-based perineuronal net establishment is largely activity-independent in chick visual system.

Extracellular matrix components consisting of large aggregating chondroitin sulphate proteoglycans accumulate around neuronal perikarya to establish perineuronal nets. These perineuronal nets surround subpopulations of neurons in many vertebrates including man. In chickens, perineuronal nets show very fast matrix maturation after hatching which is probably due to the rapid establishment of neuronal morphology and immediate functional and behavioural performance of the animals. In mammals, maturation of extracellular matrix including perineuronal nets largely depends upon specific afferent activation. The present study shows that extracellular matrix maturation in mesencephalic, diencephalic and telencephalic visual centers of chicks tectofugal system is not principally determined by light activation. Perineuronal nets show an equally developed phenotypic character on monocularly light deprived animals in all investigated brain regions. Results suggest that establishment of extracellular matrix and perineuronal nets are largely activity-independent in the investigated precocial bird.

Otoacoustic emissions: a new method for newborn hearing screening.

Pediatric deafness is a handicap affecting approximately 2/1000 newborns. Currently, its diagnosis is markedly delayed, since it occurs approximately at 24 to 36 months of age; at this age rehabilitation procedures (i.e., acoustic prosthesis, speech therapy, psychological interventions on the family, or cochlear implants in the most serious situations) are unable to ensure a complete development of both the voice and the speech, thus preventing the full participation of the deaf child in social living. The turning point has taken place when methods and techniques were developed; they are aimed at the very early diagnosis of infantile deafness and are based on the recordings of otoacoustic emissions, that is, acoustic signals of extremely weak intensity originating in the inner ear, which not only is a passive transducer, but is able to generate sounds also. Any lack of or any change in otoacoustic emissions is a accurate index of disabling deafness. The test under study allows to perform selectively a mass screening on newborns (it is carried out 2 or 3 days after birth) since it is definetely non-invasive, it is done very rapidly (a few seconds only), it is cost-effective and higly reliable. The newborn hearing screening is being accepted, at a faster growing pace, by an increasing number of health systems in the whole world.

Cyclic vomiting syndrome and food allergy/intolerance in seven children: a possible association.

UNLABELLED: Cyclic vomiting syndrome (CVS) is characterized by repeated unpredictable, explosive and unexplained bouts of vomiting. The episodes have a rapid onset, persist over a number of hours or days, and are separated by symptom-free intervals. Despite the recent interest in this disorder, its aetiology, pathogenesis and even its target organ remain unknown. The purpose of this study is to investigate the role played by food allergy in CVS. The report concerns eight children (five male, three female), mean age 8 years (3-13 years), suffering from CVS for 2 years at least. The diagnosis of CVS was based on characteristic history, normal physical examination and negative laboratory, radiographic, neurological and endoscopic studies. Despite the absence of clinical signs typical of food allergy, skin prick tests were positive in six of the eight patients (75%). Specific IgE were present in 4/8 (50%) of the patients. Skin tests and specific IgE were positive for cow's milk proteins, egg white and soya. IgE levels were higher than the mean + 2SD in 5/8 (63%) of the patients. A double blind placebo controlled food challenge (DBPCFC) was carried out on seven of the eight patients who displayed clinical improvement after an elimination diet for cow's milk (and other foodstuffs indicated by positive skin tests). The DBPCFC was positive in all seven children. Clinical follow-up revealed a state of well-being over the 6 months of observation. CONCLUSION: It appears reasonable to suggest that food allergy plays a role in cyclic vomiting syndrome.

Migraine with visual aura in developing age: visual disorders.

Visual disorders are an important symptom in the migraine of developing age. Different kinds of visual disturbances can precede, accompany or follow a migraine attack. These visual disturbances can be grouped into negative (hemianopsia, quadrantopsia, scotoma) and positive (phosphene, teicopsia, metamorphopsia, macropsia, micropsia, teleopsia, diplopia, dischromatopsia, hallucination disturbances) disorders. The pathogenetic mechanism of the visual phenomena of migraine has not yet been clarified. Various hypotheses have been proposed: vasospasm with consequent ischemia of some cerebral areas, the opening of arteriovenous shunts between the intra and extra cerebral circulation, the formation of microthrombi in arterioles and dopaminergic hypersensitivity of some nervous centers. We have studied 1787 children, affected by migraine with (13%) or without (87%) aura. Among the patients, 211 (12%) referred visual disorders, especially scotoma and phosphene. These data let us hypothesize that a relationship between migraine and visual disorders is present also in pediatric age. However this relationship is less important than in adults.

Sleep disorders.

Sleep disorders occupay an important position among the pathologies which may precede the appearance of headache. Some authors consider sleep disorders an expression of a functional, biochemical and/or neurotransmission alteration at central nervous system level. Sleep disorders may be distinguished, according to the Association Sleep Disorders classification in: alteration of the sleep-awake cycle, hypersomnia, parasomnia, insomnia. We observed 1876 normal children ranging from 3 to 14 years of age, 1073 (60.4%) of whom presented sleep disorders. Few studies have been carried out on the incidence of sleep disorders on casistics of healthy children. Date reported in literature state that sleep disorders do not exceed 25% of cases that is not more than one child out of four presents sleep disorders. This percentage is much lower than the 60.4% rate observed by us in children suffering from primary headache. Our results stress the importance of sleep disorders as a cephalalgic risk factor.

Evaluation of anxiety and depression in childhood migraine.

Childhood migraine can be the expression of an unconscious attempt of the small patient to show a discomfort which is denied through the defence of somatization. We considered a sample of 73 children, 39 males and 34 females suffering from migraine. We evaluated the presence of emotional disorders through diagnostic interviews consisting of one by one submission of the Anxiety Scale Questionnaire for Evolutive Age and the Children Depression Scale Test. Within our sample we are able to distinguish three groups: a first group negative for both anxiety and depressive disorders, thus defined as control group; a second group presenting anxiety depressive disorders and a third one presenting a mostly depressive symptomatology. We found a significantly higher incidence of migraine in male firstborn children belonging to the group with a condition associated to anxiety and depression.

Fever: a novelty among the symptoms accompanying migraine attacks in children.

Our casistic of 1787 children with headache, is made up of 943 males (53%) and 844 females (47%) aged 3-14 years. 1724 had primary headache. To make a precise diagnosis of primary headache, all the children have been subjected to a rigorous anamnesis, physical and diagnostic examination (blood, urine test, head x-rays-scans, sight test with cat's eyes). Symptoms that frequently accompany headache are: phono-photophobia, (47%), pallor (43%) nausea (41%) vomit (31%) intolerance to movement (40%) and fever (9%). We especially focused on fever which presented together with migraine in 156 (9%) of the 1724 subjects examined. Headache is an important syndrome and frequent in early childhood. Actually the hypothesis used to explain the etiopathogenetic mechanism is based on a disregulation of the neurotransmitters like serotonin, catecholamine and the prostaglandins.

Erythrocyte and plasma levels of glutamate and aspartate in children affected by migraine.

In this study we determined plasma and erythrocyte amino acids in children affected by migraine, in order to evaluate glutamate and aspartate metabolism in the pathogenesis of this disorder. Fifteen children with migraine with aura (mean age +/- SD = 10.3 +/- 1.56), 19 children with migraine without aura (mean age +/- SD = 10.4 +/- 1.48) and 16 healthy normal controls (mean age +/- SD 10.6 +/- 1.53) were investigated. In both migraine groups there were significantly lower plasma glutamate and aspartate levels and significantly higher erythrocyte/plasma concentration (E/P) ratios of these amino acids with respect to the controls. Erythrocyte aspartate concentrations were significantly elevated in migraine children compared to the controls, while erythrocyte glutamate concentrations showed no significant differences between groups. Similar results were observed in both migraine groups. These results seem to suggest the presence of a higher activity of the erythrocytes' glutamate/aspartate transport system that could reflect a similar alteration at the neuronal/glial cell level in the CNS. Our study suggests an imbalance of the excitatory amino acid turnover in the pathogenesis of migraine in children.

Familial hemiplegic migraine in developmental age: report of two cases.

The authors report two cases of a particular type of migraine with aura, known as familial hemiplegic migraine (FHM). According to the International Headache Society (IHS) diagnostic criteria, the FHM can be diagnosed with the exception of organic causes, in a patient with migraine with aura including emiparesis of anything severity and with an end occurring a member of the family with similarity in the attach pattern. The two clinical cases reported clearly show these features and they can be considered exemplary for this type of pathology. This rare type of migraine has an unknown etiology, it seems to depend on a decreases of cerebral blood flow originative on the occipital lobe, over the subsequentially spreading anteriory region temporal and parietal lobe. The hypoperfusion with the next following neural ischemia is related to the variation of blood flow and/or "the spreading depression" supported by Leao and Olesen recently. We wanted to show these two cases so that the psychiatrist, the pediatrician, and the neurologist can be able to refer parents to the right approach, considering possibility of a pathology rare but benign; this is the FHM.

[Hemicrania and food allergy in children]. / Emicrania e allergia alimentare nel bambino.

Ninety-two children affected by migraine were studied, of which 49 had positive skin tests to one or more foods. Forty of those who tested positive (87%) improved after following an elimination diet for 4-6 weeks and were positive for at least one challenge test for the same types of foods which resulted in positive skin tests. Thirty-one children were cured following the elimination diet and 9 improved. At two years, despite the reintroduction of the suspected food or foods 6 to 12 months after the start of the elimination diet, these results remained unchanged.

Familial congenital bowing with short thick bones and metaphyseal changes, a distinct entity. Report of the clinical and radiological findings in two siblings.

The authors describe two siblings, a male and a female, with disproportionate short stature, rhizomelic-mesomelic shortening of the limb bones, marked bowing of the femora, moderate bowing of the humeri, radii and ulnae, straight tibiae and fibulae, normal hands, flared cupped metaphyses of the tibiae, ulnae, radii and ribs, and narrow chest. There was some improvement of the bone changes with advancing age. These two patients are similar to five other cases from the literature and strongly support Hall and Spranger's view that this pseudocampomelic condition most likely represents a distinct familial bowing syndrome. The differential diagnosis and the hereditary aspects in the two patients, are also briefly discussed.

[A simplified micromethod for the measurement of leukocyte candidacidal activity (author's transl)]. / Micrometodo semplificato per la determinazione dell'attivita' candidacida dei leucociti

A technicall simple micromethod for the assessment of leukocyte candidacidal activity is described. It is based on the alterations in Giemsa staining characteristics which Candida albicans cells develop when ingested by glass-adhering phagocytes. This method, which requires small quantities of whole blood and produces reliable results, may be of promising clinical usefulness for detecting primary and secondary phagocyte candidacidal defects in patients with chronic or recurrent localized and systemic candidiasis.

[A simplified micromethod for the measurement of leukocyte chemotaxis (author's transl)]. / Micrometodo semplificato per la determinazione della chemiotassi leucocitaria

A new in vitro micromethod for the assessment of chemotaxis, based on the measurement of glass-adhering phagocyte migration through a cellulose membrane filter in a standard tissue culture chamber, is described. This technically simple method, which requires only small volumes of whole blood and produces reliable results, may be of promising clinical usefulness for the study of the several disease states related to abnormalities of chemotaxis.