Music in the first days of life

In adults, specific neural systems with right-hemispheric weighting are necessary to process pitch, melody and harmony, as well as structure and meaning emerging from musical sequences. To which extent does this neural specialization result from exposure to music or from neurobiological predispositions? We used fMRI to measure brain activity in 1 to 3 days old newborns while listening to Western tonal music, and to the same excerpts altered, so as to include tonal violations or dissonance. Music caused predominant right hemisphere activations in primary and higher-order auditory cortex. For altered music, activations were seen in the left inferior frontal cortex and limbic structures. Thus, the newborn's brain is able to plenty receive music and to figure out even small perceptual and structural differences in the music sequences. This neural architecture present at birth provides us the potential to process basic and complex aspects of music, a uniquely human capacity

High incidence of severe cyclosporine neurotoxicity in children affected by haemoglobinopaties undergoing myeloablative haematopoietic stem cell transplantation: early diagnosis and prompt intervention ameliorates neurological outcome

<p>Abstract</p> <p>Background</p> <p>Neurotoxicity is a recognized complication of cyclosporine A (CSA) treatment. The incidence of severe CSA-related neurological complications following hematopoietic stem cell transplantation (HSCT) is 4-11%.</p> <p>Methods</p> <p>We describe 6 cases of CSA related neurotoxicity out of 67 matched related HSCT performed in paediatric Middle East patients affected by haemoglobinopaties (5 beta thalassemia major, 1 sickle cell disease-SCD). Conditioning regimen consisted of iv busulphan, cyclophosphamide and graft-versus-host-disease (GvHD) prophylaxis with CSA, methylprednisolone, methotrexate and ATG.</p> <p>Results</p> <p>All 6 patients presented prodromes such as arterial hypertension, headache, visual disturbances and vomiting, one to two days before overt CSA neurotoxicity. CSA neurotoxicity consisted of generalized seizures, signs of endocranial hypertension and visual disturbances at a median day of onset of 11 days after HSCT (range +1 to +40). Brain magnetic resonance imaging (MRI) performed in all subjects showed reversible leukoencephalopathy predominantly in the posterior regions of the brain (PRES) in 5/6 patients. EEG performed in 5/6 patients was always abnormal. Neurotoxicity was not explainable by high CSA blood levels, as all patients had CSA in the therapeutic range with a median of 178 ng/ml (range 69-250). CSA was promptly stopped and switched to tacrolimus with disappearance of clinical and radiological findings. All patients are symptoms-free at a median follow up of 882 days (range 60-1065).</p> <p>Conclusions</p> <p>Our experience suggests that paediatric patients with haemoglobinopaties have a high incidence of CSA related neurological events with no correlation between serum CSA levels and neurotoxicity. Prognosis is good following CSA removal. Specific prodromes such as arterial hypertension, headache or visual disturbances occurring in the early post-transplant period should be carefully evaluated with electrophysiological and MRI-based imaging in order to intervene promptly and avoid irreversible sequels.</p

Lentiviral Hematopoietic Stem Cell Gene Therapy Benefits Metachromatic Leukodystrophy

n/

A case of melanotic desmoplastic ganglioglioma

We describe a case of desmoplastic infantile ganglioglioma (DIG) in a 9-month-old boy located in the temporal lobe. Grossly the tumor was brown and superficially located. Histologically the tumor contained pigment in numerous neoplastic cells, shown to be melanosomal melanin by ultrastructural examination. Pigmented neoplasms have been reported at various sites in the central and peripheral nervous system. Previous reports on pigmented neuroepithelial tumors include neoplasms containing melanin, while others have contained neuromelanin and or lipofuscin. This case represents the first description of pigmented neoplastic cells in DIG, enlarging the spectrum of pigmented primary CNS tumors

Expanding the Spectrum of NUBPL -Related Leukodystrophy

Mitochondrial leukodystrophies constitute a group of different conditions presenting with a wide range of clinical presentation but with some shared neuroradiological features. Genetic defects in NUBPL have been recognized as cause of a pediatric onset mitochondrial leukodystrophy characterized by onset at the end of the first year of life with motor delay or regression and cerebellar signs, followed by progressive spasticity. Early magnetic resonance imagings (MRIs) show white matter abnormalities with predominant involvement of frontoparietal regions and corpus callosum. A striking cerebellar involvement is usually observed. Later MRIs show spontaneous improvement of white matter abnormalities but worsening of the cerebellar involvement evolving to global atrophy and progressive involvement of brainstem. After the 7 cases initially described, 11 more subjects were reported. Some of them were similar to patients from the original series while few others broadened the phenotypic spectrum. We performed a literature review and report on a new patient who further expand the spectrum of NUBPL-related leukodystrophy. With our study we confirm that the association of cerebral white matter and cerebellar cortex abnormalities is a feature commonly observed in early stages of the disease but beside the original and so far prevalent presentation, there are also uncommon phenotypes: clinical onset can be earlier and more severe than previously thought and signs of extraneurological involvement can be observed. Brain white matter can be diffusely abnormal without anteroposterior gradient, can progressively worsen, and cystic degeneration can be present. Thalami can be involved. Basal ganglia can also become involved during disease evolution

Prenatal Management of Congenital Human Cytomegalovirus Infection in Seropositive Pregnant Patients Treated with Azathioprine

Human cytomegalovirus (HCMV) is the leading infectious agent causing congenital disabilities. The risk of HCMV transmission to the fetus in pregnant women receiving immunosuppressive agents is unknown. We describe two cases of pregnant women with evidence of pre-conception HCMV protective immunity receiving azathioprine for ulcerative colitis or systemic lupus erythematosus. Both women reactivated the HCMV and transmitted the infection to the fetuses. One newborn showed unilateral hearing deficits and brain abnormalities while the other was asymptomatic. The mother of the symptomatic newborn had low levels of total and HCMV-specific blood CD4+ T cells. Women receiving immunosuppressive agents deserve information about the risk of HCMV congenital infection and should be monitored for HCMV infection during pregnancy. Their newborns should be screened for HCMV congenital infection

Luminescent Conjugates between Dinuclear Rhenium Complexes and Peptide Nucleic Acids (PNA): Synthesis, Photophysical Characterization, and Cell Uptake

Different PNA decamers have been appended to a luminescent [Re₂(μ-Cl)₂(CO)₆(μ-1,2-diazine)] complex, to obtain conjugates suitable for cellular imaging. The new compounds can be dissolved in water in the presence of an amount of DMSO as small as 0.4–0.6 mol %. The conjugation with PNA did not perturb the photoluminescence behavior of the organometallic fragment: emission from ³MLCT excited states, centered at ca. 610 nm, was observed, with satisfactory photoluminescence quantum yields (Φ = ca. 0.01, in aerated water). Moreover, the emission could be stimulated also by two-photon excitation. Experiments of cell uptake, performed with different cell lines and under different experimental conditions, showed that the nature of the PNA oligomer strongly affects the biointeraction, while no major differences were observed among the cell lines investigated. The Re-PNA conjugates containing neutral PNA decamers (either homothymine or a standard sequence of the four nucleobases) showed a marked tendency to concentrate in the nuclear region, whereas nucleus penetration was more difficult for the free dirhenium complex. Staining of nucleus and cytoplasm with different colors was generally observed. No nucleus penetration was instead observed for a water-soluble Re-PNA homothymine decamer end-capped with four lysine residues, which localized in endosome-like compartments