Presente y futuro de la estimulación magnética transcraneal / Present and future of the transcranial magnetic stimulation

La estimulación magnética transcraneal ha llamado la atención de neurocientíficos y público en general por la posibilidad de estimular y “controlar” el sistema nervioso de forma no invasiva, realizar diagnósticos más exactos, y aplicar tratamientos y programas de rehabilitación más efectivos en múltiples enfermedades que afectan el sistema nervioso. Así mismo, esta novedosa herramienta ha ayudado a develar la complejidad del comportamiento neural, sus conexiones y su modulación plástica. La estimulación magnética aplicada de manera simple o pareada, se ha convertido en una alternativa útil en el diagnóstico de enfermedades como esclerosis múltiple, enfermedad de Parkinson, epilepsia, distonía, esclerosis lateral amiotrófica, enfermedad cerebro vascular, así como el sueño y sus trastornos, entre otras alteraciones. A nivel terapéutico, se ha sugerido el uso de la estimulación magnética repetitiva con diferentes niveles de evidencia en depresión refractaria a tratamiento farmacológico convencional, tinitus, afonía psicógena, enfermedad de Alzheimer, autismo, enfermedad de Parkinson, distonías, accidente cerebro vascular, epilepsia, trastornos de ansiedad generalizada, estrés post-traumático, alucinaciones auditivas, dolor crónico, afasias, trastorno obsesivo compulsivo, disquinesias inducidas por L-Dopa, manía y síndrome de Rasmussen, entre otros trastornos. Su beneficio en neurorehabilitación es una realidad inocultable, en cuyo caso se ha podido usar con efectividad y, prácticamente, sin efectos secundarios.

Magnetic stimulation has called the attention of neuroscientists and the public due to the possibility to stimulate and “control” the nervous system in a non-invasive way. It has helped to make more accurate diagnosis, and apply more effective treatments and rehabilitation protocols in several diseases that affect the nervous system. Likewise, this novel tool has increased our knowledge about complex neural behavior, its connections as well as its plastic modulation. Magnetic stimulation applied in simple or paired-pulse protocols is a useful alternative in the diagnosis of diseases such as multiple sclerosis, Parkinson disease, epilepsy, dystonia, amyotrophic lateral sclerosis, cerebrovascular disease, and sleep disorders. From the therapeutic perspective, magnetic stimulation applied repetitively has been found useful, with different degrees of efficacy, in treating resistant depression, tinnitus, psychogenic dysphonia, Alzheimer disease, autism, Parkinson disease, dystonia, stroke, epilepsy, generalized anxiety as well as post traumatic stress disorder, auditory hallucinations, chronic pain, aphasias, obsessive-compulsive disorders, L-dopa induced dyskynesia, mania and Rasmussen syndrome, among others. The potential of magnetic stimulation in neurorehabilitation is outstanding, with excellent range of safety and, in practical terms, without side effects.

Neurorestoration Induced by Mesenchymal Stem Cells: Potential Therapeutic Mechanisms for Clinical Trials

Stem cells are emerging as therapeutic candidates in a variety of diseases because of their multipotent capacities. Among these, mesenchymal stem cells (MSCs) derived from bone marrow, umbilical cord blood or adipose tissue, comprise a population of cells that exhibit extensive proliferative potential and retain the ability to differentiate into multiple tissue-specific lineage cells including osteoblasts, chondrocytes, and adipocytes. MSCs have also been shown to enhance neurological recovery, although the therapeutic effects seem to be derived from an indirect paracrine effect rather than direct cell replacement. MSCs secrete neurotrophic factors, promote endogenous neurogenesis and angiogenesis, encourage synaptic connection and remyelination of damaged axons, decrease apoptosis, and regulate inflammation primarily through paracrine actions. Accordingly, MSCs may prevail as a promising cell source for cell-based therapy in neurological diseases.

Síndrome de Cornélia de Lange e deficiência auditiva: estudo de caso / Cornelia de Lange syndrome and hearing loss: case study

A síndrome de Cornélia de Lange é uma entidade neurológica de etiologia desconhecida, mas se acredita que tenha origem gênica e padrão de herança heterogêneo. As anomalias mais freqüentes são baixa estatura, retardo mental, microbraquicefalia, sobrancelhas hirsutas, micrognatia, hirsutismo, nariz pequeno. Alterações menos freqüentes podem ocorrer como refluxo gastroesofágico, malformações cardíacas, surdez, miopia e problemas respiratórios, entre outros. Este trabalho teve como objetivo descrever os aspectos audiológicos de um indivíduo diagnosticado com síndrome de Cornélia de Lange, do sexo feminino, cursando com deficiência auditiva sensório-neural sugestiva de grau grave, bilateralmente, conforme PEATE.

Isoprenoid pathway and free radical generation and damage in neuropsychiatric disorders.

Two substances which are products of the isoprenoid pathway, can participate in lipid peroxidation. One is digoxin, which by inhibiting membrane Na(+)-K+ ATPase, causes increase in intracellular Ca2+ and depletion of intracellular Mg2+, both effects contributing to increase in lipid peroxidation. Ubiquinone, another products of the pathway is a powerful membrane antioxidant and its deficiency can also result in defective electron transport and generation of reactive oxygen species. In view of this and also in the light of some preliminary reports on alteration in lipid peroxidation in neuropsychiatric disorders, a study was undertaken on the following aspects in some of these disorders (primary generalised epilepsy, schizophrenia, multiple sclerosis, Parkinson's disease and CNS glioma)--1) concentration of digoxin, ubiquinone, activity of HMG CoA reductase and RBC membrane Na(+)-K+ ATPase 2) activity of enzymes involved in free radical scavenging 3) parameters of lipid peroxidation and 4) antioxidant status. The result obtained indicates an increase in the concentration of digoxin and activity of HMG CoA reductase, decrease in ubiquinone levels and in the activity of membrane Na(+)-K+ ATPase. There is increased lipid peroxidation as evidenced from the increase in the concentration of MDA, conjugated dienes, hydroperoxides and NO with decreased antioxidant protection as indicated by decrease in ubiquinone, vit E and reduced glutathione in schizophrenia, Parkinson's disease and CNS glioma. The activity of enzymes involved in free radical scavenging like SOD, catalase, glutathione peroxidase and glutathione reductase is decreased in the above diseases. However, there is no evidence of any increase in lipid peroxidation in epilepsy or MS. The role of increased operation of the isoprenoid pathway as evidenced by alteration in the concentration of digoxin and ubiquinone in the generation of free radicals and protection against them in these disorders is discussed.

Espectroscopia de prótons (1H) por ressonância magnética, neuroquímica cerebral e diagnóstico de doenças neurológicas / Proton (1H) magnetic resonance spectroscopy, brain neurochemistry, and diagnosis of neurological diseases

A técnica de espectroscopia de prótons (1H) por ressonância magnética do cérebro permite identificar, in vivo e de modo näo-invasivo, neurometabolitos pertencentes a diversas vias do metabolismo intermediário. A análise desses achados é o objetivo da presente revisäo. As bases do método e os principais metabolitos que constituem o espectro säo considerados, assim como as vias neuroquímicas relacionadas com importantes funçöes metabólicas e os neurometabolitos representativos das mesmas, possíveis de serem observados no espectro em condiçöes normais e patológicas. O conhecimento dessas relaçöes aponta para aspectos neuroquímicos da amostra de tecido nervoso examinada e permite hipóteses fisiológicas e fisiopatológicas relativas às variaçöes dos principais metabolitos. Säo descritas variaçöes regionais e em relaçäo ao envelhecimento normal, importantes na seleçäo e comparaçäo de amostras adequadamente pareadas, sobretudo em situaçäo de pesquisa. A aplicaçäo da técnica no diagnóstico em neurologia também é considerada, com ênfase em doenças degenerativas. Conclui-se ser uma técnica de grande utilidade clínica e que contribui de modo significativo no aprofundamento disgnóstico, assim como na monitorizaçäo terapêutica e no acompanhamento evolutivo de doenças neurológicas

Metabolic assessment and enteral tube feeding usage in children with acute neurological diseases

Objective: To report on acquired experience of metabolic support for children with acute neurological diseases, emphasizing enteral tube feeding usage and metabolic assessment, and also to recommend policies aimed towards improving its implementation. Design: Retrospective analysis. Setting: Pediatric Intensive Care Unit of Hospital do Servidor Publico Estadual de Sao Paulo. Subjects: 44 patients consecutively admitted to the Pediatric ICU over a period of 3 years who were given nutrition and metabolic support for at least 72 hours. Head trauma, CNS infections and craniotomy post-operative period following tumor exeresis were the main diagnoses. Measurements: Records of protein-energy intake, nutrient supply route, nitrogen balance and length of therapy. Results: From a total of 527 days of therapy, single parenteral nutrition was utilized for 34.3 per cent and single enteral tube feeding for 79.1 per cent of that period 61.4 per cent of the children were fed exclusively via enteral tube feeding, 9.1 per cent via parenteral and 39.5 per cent by both routes. The enteral tube feeding was introduced upon admission and transpyloric placement was successful in 90 per cent of the cases. Feeding was started 48 hours after ICU admission. The caloric goal was achieved on the 7th day after admission, and thereafter parenteral nutrition was interrupted. The maximum energy supply was 104.2 + 23.15 kcal/kg. The median length of therapy was 11 days (range 4-38). None of the patients on tube feeding developed GI tract bleeding, pneumonia or bronchoaspiration episodes and, of the 4 patients who were given exclusive TPN, 2 developed peptic ulcer. The initial urinary urea nitrogen was 7.11 g/m2 and at discharge 6.44 g/m2. The protein supply increased from 1.49 g/kg to 3.65 g/kg (p<0.01). The nitrogen balance increased from - 7.05 to 2.2 g (p<0.01). Conclusions: Children with acute neurological diseases are hypercatabolic and have high urinary nitrogen losses. The initial negative nitrogen balance can be increased by more aggressive feeding regimes than the usual ones. Early tube feeding was well tolerated, which permits the conclusion that it is a safe and effective method for nutrition support. Recommendations of basic rules for metabolic support are made.