Cannabinoids for major neurocognitive disorder: case report and literature review / Uso de cannabinoides en trastorno neurocognitivo mayor: reporte de un caso y revisión de la literatura

ABSTRACT Introduction: Major neurocognitive disorder (MNCD) affects millions of people worldwide. However, the pharmacological options for its management are limited, ineffective and frequently associated with severe adverse reactions. Case report: An 85-year-old man with history of multiple chronic brain injuries (alcohol-use disorder, haemorrhagic stroke, brain trauma, chronic use of benzodiazepines) developed an MNCD, reaching 7 points on the Reisberg Global Deterioration Scale. He had minimal response to antidepressants, antipsychotics and anticholinergic medications. After the use of mother tincture of Indian hemp (cannabis), a significant improvement was found in his cognitive function, ability to carry out activities of daily living and independence. Discussion: The endocannabinoid system seems to be implicated in age-related cognitive decline. In addition, the evidence derived from in-vitro and animal models suggest that this system could play an important role in the management of MNCD of different causes. Conclusions: Cannabinoid treatment for MNCD emerges as a promising therapeutic approach that may benefit a growing number of patients who do not have other treatment options. It is therefore necessary to encourage more research efforts that will help to remove political and scientific barriers to its clinical use.

RESUMEN Introducción: El trastorno neurocognitivo mayor (TNM) afecta a millones de personas a nivel mundial. Sin embargo, las opciones farmacológicas para su manejo son limitadas, poco efectivas y se asocian a importantes reacciones adversas. Caso clínico: Se presenta el caso clínico de un hombre de 85 años, con antecedente de múltiples lesiones cerebrales crónicas (abuso de alcohol, enfermedad cerebrovascular, traumatismo cerebral, uso crónico de benzodiacepinas), quien desarrolló un TNM clasificado con 7 puntos en la Reisberg Global Deterioration Scale. Tuvo poca respuesta al manejo con antidepresivos, antipsicóticos y anticolinérgicos. Tras el uso de tintura madre de cáüamo índico (cannabis), se evidenció una mejoría en la función cognitiva, la capacidad de cuidado para las actividades de la vida diaria y la independencia. Discusión: El sistema endocanabinoide parece estar relacionado con los procesos de deterioro cognitivo asociados con la edad. Además, la evidencia derivada de modelos in vitro y animales sugiere que podría tener un papel importante en el manejo del TNM de diferentes etiologías. Conclusiones: El uso de cannabinoides en el TNM se presenta como una pista terapéutica prometedora. Por lo tanto, es necesario promover procesos de investigación que contribuyan a eliminar las barreras políticas y científicas para su uso clínico, beneficiando a un número creciente de pacientes que no poseen opciones terapéuticas eficaces.

Quantitative Proteomic Analysis Reveals Impaired Axonal Guidance Signaling in Human Postmortem Brain Tissues of Chronic Traumatic Encephalopathy

Chronic traumatic encephalopathy (CTE) is a distinct neurodegenerative disease that associated with repetitive head trauma. CTE is neuropathologically defined by the perivascular accumulation of abnormally phosphorylated tau protein in the depths of the sulci in the cerebral cortices. In advanced CTE, hyperphosphorylated tau protein deposits are found in widespread regions of brain, however the mechanisms of the progressive neurodegeneration in CTE are not fully understood. In order to identify which proteomic signatures are associated with CTE, we prepared RIPA-soluble fractions and performed quantitative proteomic analysis of postmortem brain tissue from individuals neuropathologically diagnosed with CTE. We found that axonal guidance signaling pathwayrelated proteins were most significantly decreased in CTE. Immunohistochemistry and Western blot analysis showed that axonal signaling pathway-related proteins were down regulated in neurons and oligodendrocytes and neuron-specific cytoskeletal proteins such as TUBB3 and CFL1 were reduced in the neuropils and cell body in CTE. Moreover, oligodendrocyte-specific proteins such as MAG and TUBB4 were decreased in the neuropils in both gray matter and white matter in CTE, which correlated with the degree of axonal injury and degeneration. Our findings indicate that deregulation of axonal guidance proteins in neurons and oligodendrocytes is associated with the neuropathology in CTE. Together, altered axonal guidance proteins may be potential pathological markers for CTE.

Effects of cysteinyl leukotrienes receptor antagonists on chronic brain injury after global cerebral ischemia/reperfusion / 浙江大学学报·医学版

OBJECTIVE@#: To investigate the effects of cysteinyl leukotrienes receptor (CysLTR) antagonists on global cerebral ischemia/reperfusion (CI/R) injury in gerbils, and to explore its mechanism.@*METHODS@#: Totally 40 gerbils weighting 45-65 g were randomized into sham, saline, Pranlukast and HAMI 3379 groups with 10 animals in each. The CI/R model was established in gerbils by bilateral common carotid occlusion for 10 min followed by reperfusion. After ischemia, the CysLTR antagonists Pranlukast (0.1 mg/kg) and HAMI 3379 (0.1 mg/kg) were injected intraperitoneally for 5 consecutive days in the last two groups,while the former two groups were injected with saline only (10 mL/kg). After 24 h or 14 d reperfusion, neurological deficit score was evaluated and the behavioral dysfunction was assessed, respectively. And 14 d after reperfusion, the neuron morphology of cerebral cortex was observed in brain sections stained with Cresyl violet. In addition, the Iba-1 (microgila) and GFAP (astrocyte) positive cells in cerebral cortex were observed by using immunohistochemitry method.@*RESULTS@#: CI/R models were successfully established in 21 out of 30 gerbils with 7 in saline group, 6 in Pranlukast group, and 8 in HAMI 3379 group. Compared with saline group, Pranlukast and HAMI 3379 significantly attenuated neurological deficits, improved the behavioral function 24 h after reperfusion(all 0.05). In addition, Pranlukast and HAMI 3379 also inhibited the neuron loss and injury, suppressed microgila and astrocyte activation 14 d after reperfusion(all <0.01).@*CONCLUSIONS@#: CysLTR antagonists Pranlukast and HAMI 3379 have long-term neuroprotective effect on chronic brain injury induced by global cerebral ischemia/reperfusion in gerbils.

Development of tau PET Imaging Ligands and their Utility in Preclinical and Clinical Studies / 대한핵의학회잡지

The pathological features of Alzheimer's disease are senile plaques which are aggregates of β-amyloid peptides and neurofibrillary tangles in the brain. Neurofibrillary tangles are aggregates of hyperphosphorylated tau proteins, and these induce various other neurodegenerative diseases, such as progressive supranuclear palsy, corticobasal degeneration, frontotemporal lobar degeneration, frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), and chronic traumatic encephalopathy. In the case of Alzheimer's disease, the measurement of neurofibrillary tangles associated with cognitive decline is suitable for differential diagnosis, disease progression assessment, and to monitor the effects of therapeutic treatment. This review discusses considerations for the development of tau ligands for imaging and summarizes the results of the first-in-human and preclinical studies of the tau tracers that have been developed thus far. The development of tau ligands for imaging studies will be helpful for differential diagnosis and for the development of therapeutic treatments for tauopathies including Alzheimer's disease.

An Autopsy Proven Child Onset Chronic Traumatic Encephalopathy

Here we present an autopsy case of chronic traumatic encephalopathy (CTE) in a 36-year-old man. He had a history of febrile seizures at the age of four and was severely demented at age 10 when he was admitted to a mental hospital. He had suffered repetitive self-harm, such as frequent banging of the head on the wall in his hospital record, but he had no clear history between the ages of four and ten. Autopsy revealed global cerebral atrophy, including the basal ganglia, thalamus, hippocampus, amygdala, mammilary bodies and lateral geniculate bodies. This case showed typical pathological features of CTE. Phosphorylated tau (p-tau)-positive neurofibrillary tangles (NFTs) and neuropil threads (NT) we are widely distributed in the brain, especially in the depth of the cerebral sulci. NFT and NT were also found in the basal ganglia, thalamus, amygdala and brainstem. Scanty β-amyloid deposits were found in the motor and sensory cortices, but α-synuclein was completely negative in the brain. This example showed that CTE can occur in young ages and that even children can experience CTE dementia.

Transcriptome analyses of chronic traumatic encephalopathy show alterations in protein phosphatase expression associated with tauopathy

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder that is associated with repetitive head injury and has distinctive neuropathological features that differentiate this disease from other neurodegenerative diseases. Intraneuronal tau aggregates, although they occur in different patterns, are diagnostic neuropathological features of CTE, but the precise mechanism of tauopathy is not known in CTE. We performed whole RNA sequencing analysis of post-mortem brain tissue from patients with CTE and compared the results to normal controls to determine the transcriptome signature changes associated with CTE. The results showed that the genes related to the MAP kinase and calcium-signaling pathways were significantly downregulated in CTE. The altered expression of protein phosphatases (PPs) in these networks further suggested that the tauopathy observed in CTE involves common pathological mechanisms similar to Alzheimer's disease (AD). Using cell lines and animal models, we also showed that reduced PPP3CA/PP2B phosphatase activity is directly associated with increases in phosphorylated (p)-tau proteins. These findings provide important insights into PP-dependent neurodegeneration and may lead to novel therapeutic approaches to reduce the tauopathy associated with CTE.

A Review of Sport-Related Head Injuries / 대한신경손상학회지

We review current topics in sport-related head injuries including acute subdural hematoma (ASDH), traumatic cerebrovascular disease, cerebral concussion, and chronic traumatic encephalopathy (CTE). Sports-related ASDH is a leading cause of death and severe morbidity in popular contact sports like American football and Japanese judo. Rotational acceleration can cause either cerebral concussion or ASDH due to rupture of a parasagittal bridging vein. Although rare, approximately 80% of patients with cerebral infarction due to sport participation are diagnosed with ischemia or infarction due to arterial dissection. Computed tomography angiography, magnetic resonance angiography, and ultrasound are useful for diagnosing arterial dissection; ultrasound is particularly useful for detecting dissection of the common and internal carotid arteries. Repeated sports head injuries increase the risks of future concussion, cerebral swelling, ASDH, and CTE. To avoid fatal consequences of CTE, it is essential to understand the criteria for safe post-concussion sports participation. Once diagnosed with a concussion, an athlete should not be allowed to return to play on the same day and should not resume sports before the concussion symptoms have completely resolved. Information about the risks and management of head injuries in different sports should be widely disseminated in educational institutions and by sport organization public relations campaigns.

Limitação de esforço terapêutico na pessoa com lesão encefálica grave / La limitación del esfuerzo terapéutico en persona con lesión cerebral grave / Limitation of therapeutic effort in person with severe brain injury

As discussões a respeito das condutas de limitação de esforço terapêutico (LET) são frequentes nas unidades de terapia intensiva e na especialidade médica oncológica e são também importantes em contextos hospitalares de internação de longa permanência para vítimas de grandes traumas e agravos que necessitam de cuidados prolongados à saúde e de reinserção social. Na prática clínica, a tomada de decisão para LET é complexa e deve envolver o indivíduo, a família e a equipe multiprofissional. O objetivo deste artigo é discorrer a respeito da LET como um abrangente processo de "adequação de medidas" por agregação consensual de fatores centrado na pessoa, pautado por intensificação dos cuidados paliativos...

Las discusiones acerca de las conductas de limitación del esfuerzo terapéutico (LET) son comunes en las unidades de cuidados intensivos y oncología y también son importantes en hospitales de larga estancia para las personas víctimas de traumatismos graves y lesiones que requieren atención de salud a largo plazo y la reintegración social. En la práctica clínica, la toma de decisiones para la LET es compleja y debe abordar al individuo, la familia y el equipo multiprofesional. El propósito de este artículo es discutir sobre LET como un proceso integral de "adecuación de medidas" mediante la agregación consensual de factores centrados en la persona, marcado por la intensificación de los cuidados paliativos...

Discussions about the limitation of therapeutic effort are common in intensive care units and oncology and are also important in long stay hospitals for victims of major trauma and injuries that require long-term health care and social reintegration. In clinical practice, the decision making for limitation of therapeutic effort is complex and multifactorial and should involve the individual, the family and the multidisciplinary team. The purpose of this article is to discuss about limitation of therapeutic effort as a comprehensive process of "adjustment of measures" for consensual aggregation of person-centered factors, marked by intensification of palliative care...

Conmoción cerebral asociado a un traumatismo craneoencefálico en los deportistas / Concussion associated with head trauma in athletes

Recientemente se ha puesto más atención en todo el mundo a las conmociones cerebrales que ocurren durante la práctica del deporte, a nivel escolar, amateur o profesional. La conmoción cerebral se define como una alteración repentina y transitoria en la conciencia inducida por fuerzas biomecánicas traumáticas de transmisión directa o indirectamente al cerebro. Este tipo de lesiones ocurren más comúnmente en deportes de contacto, como el boxeo, el fútbol americano y el soccer, luchas, hockey, entre otros. Se debe sospechar conmoción cerebral en cualquier deportista que sufra un traumatismo craneoencefálico, haya perdido o no el estado de conciencia. Estos deportistas, no deben regresar a la práctica deportiva de manera inmediata, y se recomiendan unos días de descanso mental y físico, para su total recuperación. Se deben evitar los traumatismos en la cabeza de manera repetitiva, ya que existe evidencia que en algunos deportistas puede producir un estado de encefalopatía traumática crónica. En la presente revisión se abordan las diferentes definiciones de conmoción cerebral, su manejo y sus consecuencias a largo plazo. Asimismo, se anexa la versión en español de la herramienta de evaluación de conmoción, Sport Concussion Assessment Tool 2 (SCAT2).

Recently, there has been increased attention to concussions that occur during sports activities, both at school level or amateur and professional level. Concussion is defined as a sudden and transient alteration of consciousness induced by traumatic biomechanical forces transmitted directly or indirectly to the brain. Such injuries most commonly occur in contact sports such as boxing, football, soccer, wrestling, hockey, among others. Concussion should be suspected in any athlete who suffers a head injury, whether or not it is associated to loss of consciousness. These athletes should not return to their sports activities immediately, and a few days of mental and physical leave are recommended in order to ensure full recovery. Repeat head injuries should be avoided, since there is evidence that in some athletes they can lead to chronic traumatic encephalopathy. The present review focuses on the different definitions of concussion, management and long-term consequences. It also contains the Spanish version of the Sport Concussion Assessment Tool 2 (SCAT2).

Encefalopatias: etiologia, fisiopatologia e manuseio clínico de algumas das principais formas de apresentação da doença / Encephalopathies: etiology, pathophysiology, and clinical management of some major forms of disease presentation

JUSTIFICATIVA E OBJETIVOS: As encefalopatias compõem um grupo heterogêneo de etiologias, onde a pronta e correta atuação médica direcionada à causa da doença, pode modificar o prognóstico do paciente. O objetivo deste estudo foi rever os aspectos fisiopatológicos das diferentes encefalopatias bem como seus principais fatores desencadeantes e manuseio clínico.CONTEÚDO: Foram selecionadas as mais frequentes encefalopatias observadas na prática clínica e discutir sua fisiopatologia, bem como sua abordagem terapêutica, destacando: encefalopatia hipertensiva, hipóxico-isquêmica, metabólica, Wernicke-Korsakoff, traumática e tóxica.CONCLUSÃO: Trata-se de uma complexa condição clínica que exige rápida identificação e preciso manuseio clínico com o intuito de reduzir sua elevada taxa de morbimortalidade. O atraso no reconhecimento dessa condição clínica poderá ser extremamente prejudicial ao paciente que estará sofrendo lesão cerebral muitas vezes irreversível.

BACKGROUND AND OBJECTIVES: Encephalopathies comprise a heterogeneous group of clinical conditions, in which the prompt and adequate medical intervention can modify patient prognosis. This paper aims to discuss the pathophysiological aspects of different encephalopathies, their etiology, and clinical management.CONTENTS: We selected the main encephalopathies observed in clinical practice, such as hypertensive, hypoxic-ischemic, metabolic, Wernicke-Korsakoff, traumatic, and toxic encephalopathies, and to discuss their therapeutic approaches.CONCLUSION: This is a complex clinical condition that requires rapid identification and accurate clinical management with the aim of reducing its high morbidity and mortality rates. Delay in recognizing this condition can be extremely harmful to the patient who is suffering from often irreversible brain injury.

Dementia Pugilistica with Clinical Features of Frontotemporal Dementia and Parkinsonism: Case Report

Dementia pugilistica (DP) or chronic traumatic encephalopathy (CTE) is a neurodegenerative disease or dementia that may affect amateur or professional boxers as well as athletes in other sports who suffer concussions. The condition is thought to affect around 15% to 20% of professional boxers and caused by repeated concussive or subconcussive blows. CTE was in the past referred to as dementia pugilistica, which reflected the prevailing notion that this condition was restricted to boxers. Recent research, however, has demonstrated neuropathological evidence of CTE in retired American football players, a professional wrestler, a professional hockey player and a soccer player, as well as in nonathletes. It is probable that many individuals are susceptible to CTE, including those who experience falls, motor vehicle accidents, assaults, epileptic seizures, or military combat, and that repeated mild closed head trauma of diverse origin is capable of instigating the neurodegenerative cascade leading to CTE. We report a 62-year old man suspicious of dementia pugilistica with clinical features of frontotemporal dementia and parkinsonism.

Efeitos da estimulação cortical por sintetização auditiva conjugada, na marcha de uma criança com diplegia espástica / Effects of auditory stimulation coupled with a program targeting mental gait in children with spastic diplegia

O termo paralisia cerebral é usado para um grupo de condições caracterizadas essencialmente por disfunção motora. Com base nesta assertiva, o presente estudo teve por objetivo investigar os efeitos da estimulação auditiva conjugada a um programa de direcionamento mental na marcha de uma criança com diplegia espástica (DE). Este programa foi, em parte, baseado na abordagem dos neurônios-espelho e nele a criança sendo estudada tinha que observar, mentalizar e executar o ato de levantar e andar que era demonstrado por outra criança. A metodologia é de um estudo de caso (N = 1) de um indivíduo com cinco anos de idade, gênero masculino, diagnosticado com DE, com rigidez muscular de membros inferiores, não deambulando com independência. Procedimentos: Foram aplicadas 48 sessões de 30 minutos de estimulação cerebral de ondas alfa, precedidos de exercícios do programa de educação motora. As mensurações foram feitas através do Sistema de Classificação da Função Motora Grossa para Paralisia Cerebral, da Bateria Psicomotora e da Sequência de Desenvolvimento de Habilidades Locomotoras. O resultado do item tonicidade da bateria psicomotora em medidas pré e pós-intervenção revelou-se significativo, com qui quadrado = 8,428, gl 1 e 18, p < 0,05. Este resultado coincidiu tanto com melhoras inequívocas observadas nos testes do Sistema de Classificação da Função Motora Grossa para Paralisia Cerebral quanto para os da Sequência de Desenvolvimento de Habilidades Locomotoras. A intervenção proposta no estudo pode gerar efeitos muito positivos na marcha de uma criança com DE, como a sua total independência na marcha, além da independência nas suas AVDs.

The term cerebral palsy (CP) is used for a group of conditions primarily characterized by motor dysfunction. The aim of this study was to investigate the effects of auditory cortical stimulation coupled with a program partially based upon the mirror neurons approach and in which a child with spastic diplegia (SD) had to mentally learn and practice the gait pattern observed from another child. This was a case study (N = 1) and the individual was 5 years old, male, with stifness of limbs, not ambulating independently. The combined program included 48 sections of 30 minutes of alpha waves brain stimulation, preceding with exercises within the motor education program. Measurements were taken by the use of The Gross Motor Function Classification System for Cerebral Palsy (GMFCS), a psychomotor battery, and a validated instrument for evaluating the Sequence of Locomotor Skills Development of children (SLSD).The result related to muscles tone parameter, measured by the psychomotor battery, compared between the pre and post-intervention data was significant, being the index Chi2 = 8.428, df 1 and 18, p < 0.05.The beneficial results seen on muscles tone coincided with a clear improvement in most of the itens of the GMFCS for Cerebral Palsy, as well as for the SLSD itens. It was discussed the proposed intervention in this study can be indicated as capable for promoting very positive effects on gait, as a basis for total gait independence, and for independence in ADLs of children with SD, due to a CP accident.

Control de la agresividad con olanzapina en pacientes post tec / Aggressiveness control using olanzapine in post tbi patients

Estudio caso-control con uso de olanzapina en pacientes portadores de Daño Orgánico Cerebral (DOC) con síntomas psiquiátricos significativos. Se estudiaron 21 casos y 10 controles. Se realizó un estudio prospectivo doble ciego sobre uso de olanzapina versus placebo en pacientes portadores de DOC post TEC con trastornos conductuales, fundamentalmente, agresividad, agitación psicomotora y conducta suicida. Se demuestra que la olanzapina es un fármaco de utilidad para el control de la irritabilidad en pacientes portadores de un DOC post TEC. También fue útil en el control del insomnio, la tristeza, la labilidad emocional y la verborrea.

Case-Control study, using Olanzapine in patients having Organic Brain Damage (OBD) with significant psychiatric symptoms. Twenty one cases and 10 controls were studied. A prospective double-blind study was conducted on the use of olazapine versus placebo in patients suffering from post TBI OBD with behaviourial disorders, mainly aggressiveness, psychomotor agitation and suicidal behaviour. It is shown that olazapine is a useful drug for the control of irritability in patients suffering from post TBI OBD. It was also useful in the control of insomnia, sadness, emotional weakness and verbosity.

Encefalopatía neonatal. Algo mas que asfixia al nacer / Neonathal encefhalopathy something more that perinatal asphysia

La hiperglicinemia no cetósica (HGNC) es un error innato del metabolismo, de carácter recesivo, debido a un defecto en el sistema de clivaje, que ocasiona acumulación de glicina en la sangre y en el sistema nervioso central, donde activa dos receptores diferentes. El receptor localizado en la médula espinal, inhibitorio, provoca la apnea y el hipo de estos pacientes. El receptor cortical, excitatorio, produce la lesión cerebral y las convulsiones. Se presenta la historia de un recién nacido masculino, a término, que se torna encefalopático en los primeros días de vida. No presentó hipoglicemia, acidosis metabólica, cetosis ni hiperamonemia. La ecografía transfontanelar fue normal. A los seis días ameritó ventilación mecánica. La cromatografía en capa fina mostró banda de glicina en plasma y orina. El paciente recibió manejo con benzoato de sodio, diazepam y restricción proteica. A los 20 días de vida presentó mejoría neurológica y salió del hospital a los 42 días de vida con igual manejo. El estudio de acilcarnitinas en sangre por tandem-masas hecho en Santiago de Compostela fue normal. La cuantificación de aminoácidos hecha en el CEDEM mostró aumento de los niveles de glicina en plasma y LCR y la relación glicina LCR / plasma confirmó el diagnóstico de hiperglicinemia no cetósica típica. Se revisan las causas de encefalopatía neonatal y se plantea una secuencia para el diagnóstico.

Manifestaciones neuropsiquiátricas en accidentes cerebrovasculares / Neuropsychiatric manifestations in cerebrovascular diseases

Introducción: Los accidentes cerebrovasculares puede producir manifestaciones neuro-psiquiátricas, la presente revisión intenta mostrar los avances y conceptos agregados hasta la fecha que ayudan al diagnóstico, tratamiento y la investigación. Método: Se revisó la bibliografía publicada en cuatro bases electrónicas (Medline, EBSCO, ProQuest, Ovid) usando términos relacionados con manifestaciones neuropsiquiátricas en el accidente cerebrovascular. Discusión: Esta revisión muestra que los accidentes cerebrovasculares pueden producir una serie de manifestaciones neuropsiquiátricas como depresión, manía, apatía, ansiedad, psicosis, etc. Recientemente se ha propuesto el término de Desorden de Expresión Emocional Involuntaria que pretende homogenizar criterios para el llanto y risa patológica, labilidad emocional o afectiva, emocionalismo, incontinencia emocional, emociones o afectos patológicos, y descontrol emocional, términos usados para describir una misma patología. Asimismo, el termino Deterioro Cognitivo Vascular ha sido propuesto para englobar el amplio espectro de cambios cognitivos y conductuales asociados a accidentes cerebrovasculares sin demencia. Además, se brinda especial atención al estudio e instrumentalización de las funciones ejecutivas, teoría de la mente y empatia, conceptos que describen habilidades propiamente humanas, que también se ven deterioradas. Conclusión: Los síntomas neuropsi-quiátricos obstaculizan el proceso de rehabilitación, deterioran el nivel de vida del paciente, creando institucionalización y agregando mayor carga emocional y economía a los responsables del paciente.

Background: Neuropsychiatric manifestations could occur following a cerebrovascular disease, the present review shows the advantages and update concepts which helps to the diagnostic, treatment and research. Method: we searched four electronic database (Medline, EBSCO, ProQuest, Ovid) using the terms in relation with neuropsychiatric manifestations in cerebrovascular disease. Discussion: The present review shows the different neuropsychiatric manifestations which could be occur following Cerebrovascular Lesions, like depression, mania, apathy, anxiety, psychosis, etc. Recently the term of Involuntary Emotional Expression Disorder has been proposed to unifying terms like pathological laughing and crying, pathological weeping, emotional or affective lability, emotionalism, emotional incontinence, pathologic emotionality or affect, and emotional dyscontrol, terms which are used to describe the same pathology. Also, the term vascular cognitive impairment has been proposed to include the broad spectrum of cognitive and behavioural changes associated with cerebrovascular lesions without dementia. In addition, there are special attention to the study and instrumentalization of the executive functions, theory of mind and empathy, concepts that describe abilities properly human, which also are deteriorated. Conclusions: The neuropsychiatric symptoms cause significant problems in the rehabilitation process, deterioration in patient's quality of life, creating institutionalization and adding greater emotional and economy load to the people in charge of the patient's care.

Encefalopatía infantil asociada con la mutación A3243G MELAS / Infantile encephalopathy associated with the MELAS A3243G mutation: case report

Las Encefalopatías mitocondriales son un grupo de enfermedades que tienen base una alteración del ADN mt. (ADN mitocondrial). El fenotipo MELAS (Encefalopatía mitocondrial, con acidosis láctica y accidentes cerebro vasculares) se ha relacionado con la mutación A3243G en aproximadamente el 80 por ciento de los casos reportados. El fenotipo MERRF (epilepsia mioclónica con fibras rojas rasgadas) ha sido relacionado con las mutaciones A8344G y A8566G del tARN Lys. Se describe un lactante femenino de 7 meses de edad, con un cuadro de inicio temprano, que se acompañaba de una encefalopatía asociada a la mutación A3243G. En los exámenes de laboratorio destacaba una acidosis láctica y el estudio EEG mostraba signos compatibles con proceso encefalopático. Se administró ACTH durante un mes con mejoría clínica y encefalográfica. Actualmente recibe tratamiento a base de Vitaminas del complejo B, L-carnitina y alcalinizantes urinarios. Se concluye que en los lactantes que presentan convulsiones, retraso en su desarrollo psicomotor, acidosis láctica y el estudio encefalográfico compatible con una encefalopatía, debería realizarse análisis del ADN mt, para descartar una enfermedad mitocondrial.

Changes of cortex mitochondrial function in chronic traumatic brain injury rats / 生物医学工程学杂志

This experimental study was aimed to evaluate the injurious effects of chronic traumatic brain injury on cortex mitochondrial function in rats. The head of rat was impacted by a metal sphere in a weight-drop device twice per day for 30 days, cortex mitochondria were isolated. Then the mitochondria membrane fluidity, swelling, respiratory function, the activities of mitochondria respiratory enzymes and superoxide dismutase (SOD), the levels of phospholipid, malondial dehyde (MDA) and Ca2+ were determined to analyze the function of mitochondria. The data indicated that chronic closed traumatic brain injury caused severe neuronal mitochondrial injuries. The swelling of mitochondria was aggravated, the decomposability of mitochondrial membrane phospholipid was increased, the membrane fluidity of mitochondria was decreased; the chronic closed traumatic brain injury also significantly depressed the activities of respiratory enzymes and SOD of mitochondria, increased the level of MDA and Ca2+. The chronic closed traumatic brain injury induced damage to rat cortex mitochondria. The mechanisms may be derived from the secondary increase of free radicals induced by mitochondrial membrane injury and the obstacle of rat brain energy metabolism.

[Investigation of TNF-alpha converting enzyme and activity of nf-kb in tolerance to ischemia induced by intermittent normobaric hyperoxia in rat model]

Recent studies suggest that intermittent and prolonged normobaric hyperoxia [HO] results in ischemic tolerance to reduce brain injury. In this research attempts were made to see the changes in TNF-alpha converting enzyme [TACE] and NF-kB activity following intermittent HO and ischemia preconditioning. The rats were divided into two experimental groups, each consisted of 20 animals. The first group was exposed to 95% inspired HO for 4h/day for 6 consecutive days [intermittent HO; InHO]. The second group acting as the control was exposed to 21% oxygen in the same chamber [normobaric normoxia or room air; RA] continuously for six days [intermittent RA; InRA]. Each main group was subdivided to MCAO-operated [middle cerebral artery occlusion], sham-operated [without MCAO], and intact [without any surgery] subgroups. After 24hr, MCAO-operated subgroups were subjected to 60 min of right MCAO. After 24 h reperfusion, neurologic deficit score [NDS] and infarct volume were assessed in MCAO-operated subgroups. Immediately and 48 h after pretreatment, blood sampling for assessment of serum TNF-alpha levels were subjected. Then, the effect of intermittent HO and ischemia on NF-kB activity and TACE expression were measured. Preconditioning with intermittent HO and ischemia decreased NDS and infarct volume. Moreover InHO and MCAO-InHO upregulate TACE and increase NF-kB activity significantly. Although further studies are needed to clarify the mechanisms of ischemic tolerance, InHO and ischemia seem to partly exert their effects via increase upregulation of TACE and NF-kB activity

Efectos de la estimulación magnética transvertebral repetitiva sobre la espasticidad y la función motora gruesa en dos niños con parálisis cerebral tipo cuadriparesia espástica / Anti-spastic effect of Trans spinal cord excitatory magnetic stimulation

Introducción. La parálisis cerebral espástica es una entidad frecuente cuyo tratamiento implica un gran reto para el equipo de rehabilitación. Los diferentes enfoques terapéuticos actuales (quirúrgico, farmacológico y de rehabilitación, entre otros), en muchos casos no han llenado las expectativas de los profesionales y padres a cargo de estos pacientes.Objetivo. Describir los efectos antiespásticos y funcionales motrices de la estimulación magnética transvertebral repetitiva (EMTv-r) en dos niños con parálisis cerebral espástica. Materiales y métodos. La valoración de la espasticidad, y funcionalidad motriz gruesa, de ambos pacientes fue llevada a cabo, antes, durante y después, por una fisioterapeuta ajena al equipo de rehabilitación de estos niños (enmascaramiento simple). Previa autorización de los padres, se realizó una sesión semanal de EMTv-r cervical y dorsal por cuatro semanas. Resultados. Se pudo evidenciar una disminución de la espasticidad en ambos pacientes con la subsecuente mejoría de la funcionalidad. No se observaron efectos secundarios por la EMTv-r. Conclusiones. La EMTv-r es una alternativa terapéutica complementaria, no invasiva que disminuye la espasticidad y mejora la funcionalidad motriz gruesa, de manera temporal (durante el tiempo que se realizó el estudio)

Comparación del rendimiento en pruebas cognitivas entre pacientes Asperger y pacientes con daño cerebral / Comparison of cognitive tests performance betwen patients with Asperger, and patients with brain damage

Objetivo. Comparar el rendimiento obtenido en pruebas neuropsicológicas entre un grupo de pacientes diagnosticados con síndrome de Asperger y un grupo de pacientes con daño orgánico cerebral (DOC). De acuerdo a la literatura revisada, el Síndrome de Asperger se caracterizaría por presentar un perfil neuropsicológico en el que se observa déficit de las funciones que dependen del hemisferio derecho. Metodología. La muestra se compone de 14 pacientes que presentan Síndrome de Asperger a los que se les aplicó la Batería Neuropsicológica Luria Nebraska (BNLN). Sus rendimientos fueron comparados con los obtenidos en esta Batería por 69 pacientes con DOC. Resultados. Los pacientes con Síndrome de Asperger muestran un perfil neuropsicológico menos alterado que los pacientes con DOC. Cuantitativamente se observa un déficit similar entre ambos grupos de pacientes en funciones mediadas por el hemisferio derecho, como ritmo y percepción visual. Por el contrario, las funciones verbales se encuetran conservadas sólo en los pacientes Asperger. Conclusiones. Los resultados tienden a confirmar la existencia de disfunción cerebral en los pacientes con Síndrome de Asperger, especialmente en las funciones cognitivas que dependen del hemisferio derecho. Estas alteraciones funcionales serían más específicas que las observadas en los pacientes con DOC, en los que se observan alteraciones más generalizadas y más graves de funcionamiento cerebral.