[Inconsolable crying revealing primary erythermalgia in a 6-month-old infant]. / Crises de pleurs inconsolables révélatrices d'une érythermalgie primitive chez un nourrisson de 6 mois.

Erythermalgia is a peripheral vascular disease triggered by exposure to heat. The primary infantile form is rare. No cases have been described in infants. We report a case in a 6-month-old child revealed by crying bouts associated with erythema of the lower limbs. A 6-month-old child was brought in for consultation for daily crying bouts, occurring six times a day, associated with erythema of the lower limbs. Blood count, abdominal ultrasound and endoscopy were normal, excluding gastroesophageal reflux and intussusception. Attacks disappeared during winter but recurred at high temperatures. The diagnosis was primary infant erythemalgia. Treatment with analgesics and ice packs was established. Erythermalgia is a rare peripheral vascular disease characterized by paroxysmal pain triggered by heat and relieved by cold. The primary form occurs in childhood but has never been reported in infants. The pathophysiology is based on an alteration of sodium channels inducing neuropathy in small-caliber fibers. Genetic mutations have been found in the SNC9 gene on chromosome 2q, with autosomal dominant transmission. Support of this condition is difficult due to resistance to conventional analgesics. The prognosis is sometimes poor with a significant death rate in the pediatric population.

Glial scar and axonal regeneration in the CNS: lessons from GFAP and vimentin transgenic mice.

Astrocytes play an active role in the brain and spinal cord. For example, they have a function in formation and maintenance of the blood-brain barrier, ion homeostasis, neurotransmitter transport, production of extracellular matrix, and neuromodulation. Moreover, they play a role in preserving or even restoring the structural and physiological integrity after tissue injury. Currently, the function of astrocytes was studied with regard to the controversially discussed aspects of permissivity on the one-hand-side and inhibition of the other side exerted by reactive astrocytes for axonal regrowth in the adult CNS. Accordingly, knock-out mice deficient in vimentin (VIM) and/or glial fibrillary acidic protein (GFAP), the two major IF-proteins of astrocytes, were investigated. In addition, in vitro studies were carried out, on whether the absence of one or both proteins (VIM, GFAP) influences axonal regeneration. In experimental animals, a hemisection of the spinal cord was performed utilizing the above mentioned double-mutant mice. The knock-out mice were generated by gene targeting. Double-mutants were obtained by crossing single null mice. The in vitro results indicate that both VIM and GFAP were absent in astrocytic cultures obtained from double-mutant mice. On the other side, the proteins were detected in more than 85%, of cultured cells from wild types. Co-culture of mutant mice astrocytes with neurons revealed that the neuronal density was different from that obtained in culture with wild type astrocytes. On the other side, there was a marked increase in neuronal density in co-cultures utilizing both GFAP knock-out- or double-mutant mice astrocytes again as compared to co-cultures with wild type astrocytes. Moreover, the neurite length of neurons was significantly increased in experiments with neurons growing on astrocytes from GFAP-knock-out or double-mutant mice. The in vivo experiments demonstrate an increase of nestin (NES) immunoreactivity at three days in the sectioned side of the spinal cord, in the perikaryon and astroglial processes. In double-mutant mice only a slight increase in NES-immunoreactivity was found in the lesion side, albeit confined to the perikaryon of astrocytes. Below the lesion, serotonin immunostaining was dramatically reduced three days after the insult in both sides, particularly in the lesion side. The decrease was more pronounced in double-mutant than in wild type mice. On the other side, double-mutant mice had a much higher density of serotonergic fibers in the ventral horn in the lesioned side. In conclusion, the findings demonstrate that in the absence of important astrocytic proteins as VIM and GFAP, the astroglial response to injury is significantly modified underlying reduced scar formation. Attenuation of scar formation may enhance axonal sprouting of serotonergic axons below the lesion, which specifically reinnervate motoneuron pools.

Axonal plasticity and functional recovery after spinal cord injury in mice deficient in both glial fibrillary acidic protein and vimentin genes.

The lack of axonal regeneration in the injured adult mammalian spinal cord leads to permanent functional disabilities. The inability of neurons to regenerate their axon is appreciably due to an inhospitable environment made of an astrocytic scar. We generated mice knock-out for glial fibrillary acidic protein and vimentin, the major proteins of the astrocyte cytoskeleton, which are upregulated in reactive astrocytes. These animals, after a hemisection of the spinal cord, presented reduced astroglial reactivity associated with increased plastic sprouting of supraspinal axons, including the reconstruction of circuits leading to functional restoration. Therefore, improved anatomical and functional recovery in the absence of both proteins highlights the pivotal role of reactive astrocytes in axonal regenerative failure in adult CNS and could lead to new therapies of spinal cord lesions.

Inactivation of the glial fibrillary acidic protein gene, but not that of vimentin, improves neuronal survival and neurite growth by modifying adhesion molecule expression.

Intermediate filaments (IFs) are a major component of the cytoskeleton in astrocytes. Their role is far from being completely understood. Immature astrocytes play a major role in neuronal migration and neuritogenesis, and their IFs are mainly composed of vimentin. In mature differentiated astrocytes, vimentin is replaced by the IF protein glial fibrillary acidic protein (GFAP). In response to injury of the CNS in the adult, astrocytes become reactive, upregulate the expression of GFAP, and reexpress vimentin. These modifications contribute to the formation of a glial scar that is obstructive to axonal regeneration. Nevertheless, astrocytes in vitro are considered to be the ideal substratum for the growth of embryonic CNS axons. In the present study, we have examined the potential role of these two major IF proteins in both neuronal survival and neurite growth. For this purpose, we cocultured wild-type neurons on astrocytes from three types of knock-out (KO) mice for GFAP or/and vimentin in a neuron-astrocyte coculture model. We show that the double KO astrocytes present many features of immaturity and greatly improve survival and neurite growth of cocultured neurons by increasing cell-cell contact and secreting diffusible factors. Moreover, our data suggest that the absence of vimentin is not a key element in the permissivity of the mutant astrocytes. Finally, we show that only the absence of GFAP is associated with an increased expression of some extracellular matrix and adhesion molecules. To conclude, our results suggest that GFAP expression is able to modulate key biochemical properties of astrocytes that are implicated in their permissivity.

GFAP null astrocytes are a favorable substrate for neuronal survival and neurite growth.

During the development of the CNS, astrocytes play a key role as a substrate for neuronal migration and axonal growth. These neuron-astrocyte interactions could be regulated, in part, by the astrocytic cytoskeleton. Nestin, vimentin, and glial fibrillary acidic protein (GFAP) are the three identified proteins constitutive of intermediate filaments present in astrocytes. In the present study, we used mice deficient in GFAP to define the influence of the major protein of the astrocytic cytoskeleton on neuron survival and axonal growth in a model of neuron-astrocyte coculture. We observed that GFAP null astrocytes are a better substrate for neuronal survival and neurite outgrowth than wild-type astrocytes. This may be correlated with the relatively late occurrence of GFAP expression in astrocyte maturation when the early steps of neurogenesis are completed.

Comparative anatomy of the cerebellar cortex in mice lacking vimentin, GFAP, and both vimentin and GFAP.

In the cerebellum of adult mammals, glial fibrillary acidic protein (GFAP) and vimentin (VIM) are coexpressed in Golgi epithelial cells (GEC), also known as Bergmann glia. In this study we used three transgenic knockout mice (GFAP, VIM and double GFAP and VIM) to analyze the involvement of these proteins in the building of glial filaments and in neuron-glia interactions. The cerebella of VIM, GFAP, and GFAP/VIM mutant mice were processed by the rapid Golgi method and also for electron microscopy. In VIM mutant mice, Bergmann fibers are hypertrophic with thickened appendages. In the electron microscope they appear as large glial profiles devoid of glial filaments, with embedded dendritic thorns and parallel fiber boutons. In addition, signs of degeneration are observed in Purkinje cells. In GFAP mutant mice, GEC exhibit fine, delicate processes, as those seen in wild-type animals, however, a large accumulation of lamellae and granular appendages was observed along their surfaces, which came into contact with each other. The electron microscope exhibited fine and scarce astroglial profiles containing some glial filaments, a stunted glia limitans, and the presence of large extracellular spaces. In double mutant mice, the two phenotypes are expressed but appear attenuated, with a total absence of glial filaments and the general appearance of immaturity for GEC. In conclusion, it appears that the absence of each of the proteins yields a specific phenotype and that the defects are not necessarily additive.

[Efficacy and tolerability of morniflumate in acute otitis in infants: results of a randomized study versus placebos]. / Efficacité et tolérance du morniflumate dans les otites aiguës du nourrisson: résultats d'une étude randomisée contre placebo.

In a randomized double-blind placebo-controlled, parallel group study, 79 infants with acute otitis media received treatment with suppositories containing either Nifluril (400 mg daily, morniflumate) or placebo for five days. Both groups of patients also received amoxicilline (50 mg/kg daily) for eight days. The combination of Nifluril with antibiotic therapy gave significantly greater relief from abnormalities of the tympanic membrane (after two days treatment), inflammation of the throat and nasal congestion than did antibiotic therapy alone. Overall clinical assessment confirmed a significantly greater recover rate in the Nifluril group compared with the placebo group. Very few side effects were recorded, limited to diarrhoea, without any drug interruption. Nifluril may be recommended as an effective safe adjuvant to the antibiotic treatment of acute otitis media in infants.