Altered thalamic neurotransmitters metabolism and functional connectivity during the development of chronic constriction injury induced neuropathic pain

BACKGROUND: To investigate the thalamic neurotransmitters and functional connections in the development of chronic constriction injury (CCI)-induced neuropathic pain. METHODS: The paw withdrawal threshold was measured by mechanical stimulation the right hind paw with the von frey hair in the rats of CCI-induced neuropathic pain. The N-acetylaspartate (NAA) and Glutamate (Glu) in thalamus were detected by magnetic resonance spectrum (MRS) process. The thalamic functional connectivity with other brain regions was scanned by functional magnetic resonance image (fMRI). RESULTS: The paw withdrawal threshold of the ipsilateral side showed a noticeable decline during the pathological process. Increased concentrations of Glu and decreased levels of NAA in the thalamus were significantly correlated with mechanical allodynia in the neuropathic pain states. The thalamic regional homogeneity (ReHo) decreased during the process of neuropathic pain. The functional connectivity among the thalamus with the insula and somatosensory cortex were significantly increased at different time points (7, 14, 21 days) after CCI surgery. CONCLUSION: Our study suggests that dynamic changes in thalamic NAA and Glu levels contribute to the thalamic functional connection hyper-excitation during CCI-induced neuropathic pain. Enhanced thalamus-insula functional connection might have a significant effect on the occurrence of neuropathic pain.

Doenças neurológicas em cães atendidos no Hospital Veterinário da Universidade Federal de Santa Maria, RS: 1.184 casos (2006-2013) / Neurological diseases in dogs examined at the Veterinary Teaching Hospital of the Federal University of Santa Maria, RS: 1.184 cases (2006-2013)

Foi realizado um estudo retrospectivo de cães atendidos no Serviço de Neurologia (SN) do Hospital Veterinário Universitário (HVU) da Universidade Federal de Santa Maria (UFSM), de 2006 a 2013, com o objetivo de identificar e caracterizar a idade, a raça, o sexo e as doenças neurológicas e classificá-las de acordo com a região anatômica e o acrônimo DINAMIT-V. Foram avaliadas 1.277 fichas neurológicas de cães e obtidas as informações para inclusão no estudo em 1.184 delas, sendo o diagnóstico confirmado em 525 cães (44,4%) e presuntivo em 659 (55,6%). A raça mais frequente foi Dachshund (28,7%), seguida dos cães sem raça definida. Os locais mais afetados foram medula espinhal entre T3-L3 (40,9%) e tálamo-córtex (17,5%). A maioria dos cães foi diagnosticada com doença degenerativa (49%), sendo a doença do disco intervertebral a mais observada, seguida das doenças inflamatórias/infecciosas (16,6%). Pode se concluir que a maior prevalência das doenças neurológicas de cães envolve a medula espinhal e o tálamo-córtex, sendo as degenerativas as mais frequentes e os dados obtidos podem auxiliar em futuros estudos sobre a frequência e a distribuição das principais doenças neurológicas em cães.

A retrospective study including dogs with neurological disease was conducted at the Service of Neurology (SN) of the Veterinary Teaching Hospital, Universidade Federal de Santa Maria (UFSM) from 2006 to 2013, with the objective to identify and characterize age, breed, sex and to neurological diseases, and classify them accordingly to the anatomical region and DINAMIT-V acronym. There were evaluated 1,277 neurological records of dogs and obtained the information for inclusion in the study in 1,184 of them being the diagnosis confirmed in 525 (44.4%) and presumptive in 659 dogs (55.6%). The most common breed was Dachshund (28.7%), followed by mixed breed. The most affected sites were the spinal cord between T3-L3 (40.9%) and thalamus-cortex (17.5%). Most dogs were diagnosed with degenerative disorders (49%), being intervertebral disk disease the most observed, followed by inflammatory/infectious diseases (16.6%). It can be concluded that the higher prevalence of neurological disorders in dogs involve the spinal cord and thalamus-cortex, with the most frequent being degenerative and the data obtained may assist future studies associated with frequency and distribution of the main neurological diseases in dogs.

Thalamic metabolic abnormalities in patients with Huntington's disease measured by magnetic resonance spectroscopy

Huntington's disease (HD) is a neurologic disorder that is not completely understood; its fundamental physiological mechanisms and chemical effects remain somewhat unclear. Among these uncertainties, we can highlight information about the concentrations of brain metabolites, which have been widely discussed. Concentration differences in affected, compared to healthy, individuals could lead to the development of useful tools for evaluating the progression of disease, or to the advance of investigations of different/alternative treatments. The aim of this study was to compare the thalamic concentration of metabolites in HD patients and healthy individuals using magnetic resonance spectroscopy. We used a 2.0-Tesla magnetic field, repetition time of 1500 ms, and echo time of 135 ms. Spectra from 40 adult HD patients and 26 control subjects were compared. Quantitative analysis was performed using the LCModel method. There were statistically significant differences between HD patients and controls in the concentrations of N-acetylaspartate+N-acetylaspartylglutamate (NAA+NAAG; t-test, P<0.001), and glycerophosphocholine+phosphocholine (GPC+PCh; t-test, P=0.001) relative to creatine+phosphocreatine (Cr+PCr). The NAA+NAAG/Cr+PCr ratio was decreased by 9% and GPC+PCh/Cr+PCr increased by 17% in patients compared with controls. There were no correlations between the concentration ratios and clinical features. Although these results could be caused by T1 and T2 changes, rather than variations in metabolite concentrations given the short repetition time and long echo time values used, our findings point to thalamic dysfunction, corroborating prior evidence.

Psychiatric comorbidities in temporal lobe epilepsy: possible relationships between psychotic disorders and involvement of limbic circuits / Comorbidades psiquiátricas na epilepsia do lobo temporal: possíveis relações entre desordens psicóticas e comprometimento de circuitos límbicos

OBJECTIVE: Mounting evidence suggests that the limbic system is pathologically involved in cases of psychiatric comorbidities in temporal lobe epilepsy (TLE) patients. Our objective was to develop a conceptual framework describing how neuropathological and connectivity changes might contribute to the development of psychosis and to the potential neurobiological mechanisms that cause schizophrenia-like psychosis in TLE patients. METHODS: In this review, clinical and neuropathological findings, especially brain circuitry of the limbic system, were examined together to enhance our understanding of the association between TLE and psychosis. Finally, the importance of animal models in epilepsy and psychiatric disorders was discussed. CONCLUSIONS: TLE and psychiatric symptoms coexist more frequently than chance would predict. Damage and deregulation among critical anatomical regions, such as the hippocampus, amygdala, thalamus, and the temporal, frontal and cingulate cortices, might predispose TLE brains to psychosis. Studies of the effects of kindling and injection of neuroactive substances on behavior and electrophysiological patterns may offer a model of how limbic seizures in humans increase the vulnerability of TLE patients to psychiatric symptoms.

OBJETIVO: Existem cada vez mais evidências de que o sistema límbico está envolvido na patologia das comorbidades psiquiátricas em pacientes com epilepsia do lobo temporal (ELT). Nosso objetivo foi elaborar um desenho conceitual descrevendo como aspectos neuropatológicos e de conectividade podem contribuir para o desenvolvimento de psicose em pacientes com ELT. MÉTODOS: Nesta revisão, achados clínicos e neuropatológicos, e especialmente os aspectos da circuitaria límbica, foram examinados em conjunto para auxiliar nossa compreensão sobre a associação entre ELT e psicose. Achados em modelos animais de epilepsia e esquizofrenia também foram levados em consideração. CONCLUSÕES: ELT e comorbidades psiquiátricas coexistem com maior frequência que o predito pela associação ao acaso. Dano e desregulação entre estruturas anatômicas críticas, como hipocampo, amígdala, tálamo, e córtices temporal, frontal e cingulado podem predispor o cérebro com ELT à psicose. Estudos sobre efeitos comportamentais e eletrofisiológicos do abrasamento elétrico e injeções de substâncias neuroativas em modelos animais podem oferecer pistas sobre como crises límbicas em humanos aumentam a vulnerabilidade de pacientes com ELT a sintomas psiquiátricos.

Could sudden cardiac death in epilepsy be related to the occurrence of thalamic dysfunction or anatomic change? / A morte súbita cardíaca em epilepsia poderia estar relacionada com a ocorrência de alterações anatômicas ou funcionais do tálamo?

Sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death in people with chronic epilepsy. Its physiopathology is still unknown; however, the most commonly suggested potential mechanisms involve cardiac or respiratory abnormalities. As the anatomical substrate of epileptic activity in the central nervous system (CNS) shows a direct relationship with cardiovascular alterations, this may suggests that patients with epilepsy associated with focal CNS lesions may be at particular risk of SUDEP. Currently, experimental and clinical data support an important role for thalamic nuclei in the behavioural manifestations, initiation and propagation of seizures. In view of the above findings, we purpose that SUDEP, at least in some cases, could be related to the occurrence of thalamic dysfunction or anatomic change.

A morte súbita e inesperada nas epilepsias (SUDEP) é a mais importante causa de morte em pacientes com epilepsia. A fisiopatologia da SUDEP ainda é desconhecida, no entanto, os prováveis mecanismos estão relacionados com alterações cardiovasculares ou respiratórias. Como o substrato anatômico da atividade epiléptica no sistema nervoso central (SNC) apresenta direta relação com alterações cardiovasculares, esse fato sugere que pacientes com epilepsia e lesões focais no SNC podem apresentar maior risco para SUDEP. Atualmente, dados experimentais e clínicos demonstram um importante papel dos núcleos talâmicos nas manifestações comportamentais, bem como no início e propagação das crises epilépticas. Sendo assim, nós acreditamos que a SUDEP, pelo menos em alguns casos, poderia estar relacionada com a ocorrência de alterações anatômicas ou disfunções talâmicas.

Modelagem neurocomputacional do circuito tálamo-cortical: implicações para compreensão do transtorno de défi cit de atenção e hiperatividade / A neurocomputational model for the thalamocortical loop: towards a better understanding of attention deficit hyperactivity disorder

CONTEXTO: A desatenção no transtorno de déficit de atenção e hiperatividade (TDAH) é principalmente associada à hipoatividade dopaminérgica mesocortical. Contudo, variações dopaminérgicas mesotalâmicas também afetam o controle da atenção e, possivelmente, originam alterações atencionais no TDAH. OBJETIVO: Elaboração de um modelo neurocomputacional a partir do conhecimento do funcionamento bioquímico dos sistemas dopaminérgicos mesocortical e mesotalâmico, a fim de investigar a influência dos níveis de dopamina na via mesotalâmica sobre o circuito tálamo-cortical e suas implicações nos sintomas de desatenção do TDAH. MÉTODO: Através de um conjunto de equações modelamos propriedades fisiológicas de neurônios talâmicos. A seguir, simulamos computacionalmente o comportamento do circuito tálamo-cortical variando os níveis de dopamina nas vias mesotalâmica e mesocortical. RESULTADOS: Em relação à via mesotalâmica, a hipoatividade dopaminérgica dificulta o deslocamento do foco de atenção, e a hiperatividade dopaminérgica acarreta desfocalização atencional. Quando tais situações são acompanhadas de hipoatividade dopaminérgica mesocortical, surge uma incapacidade em perceber estímulos, devido à competição sem vencedores entre regiões talâmicas pouco ativadas. A desatenção no TDAH também se origina em desequilíbrios dopaminérgicos na via mesotalâmica, que levam à focalização excessiva ou à desfocalização da atenção. CONCLUSÃO: O nosso experimento in silico sugere que no TDAH a desatenção relaciona-se com alterações dopaminérgicas, que não se restringem à via mesocortical.

BAKGROUND: Inattention symptoms observed in patients with attention deficit hyperactivity disorder (ADHD) are mostly related to a hipoactivity in the mesocortical dopaminergic pathway. However, mesothalamic dopaminergic variations also affect the attentional control, and possibly lead to attention alterations in ADHD. PURPOSE: Elaborating a neurocomputational model from biochemical knowledge of mesocortical and mesotalamic dopamine systems, to investigate how different levels of mesothalamic dopamine influence the thalamocortical loop, leading to some attention deficits observed in ADHD. METHOD: First, we model physiological properties of thalamic neurons with a set of mathematical equations. Next, we simulate computationally the modeled thalamocortical loop under different levels of mesothalamic dopamine, and also the mesocortical dopaminergic decrease. RESULTS: Low levels of mesothalamic dopamine hinders the attentional shift and, high levels of such neuromodulator lead to distraction. When such alterations occur together with a decrease in the mesocortical dopamine level, the attention deficit turns into incapacity of perceiving environmental stimuli, due to a no winner competition between low activated thalamic areas. Inattention in ADHD also has its origins in dopaminergic disturbs throughout the mesothalamic pathway, which enhance a high focusing or do not allow the attention focus consolidation. CONCLUSION: In ADHD, the inattention is related to dopaminergic alterations that are not restricted to the mesocortical system.

Amnesic Syndrome in a Mammillothalamic Tract Infarction

It is controversial whether isolated lesions of mammillothalamic tract (MTT) produce significant amnesia. Since the MTT is small and adjacent to several important structures for memory, amnesia associated with isolated MTT infarction has been rarely reported. We report a patient who developed amnesia following an infarction of the left MTT that spared adjacent memory-related structures including the anterior thalamic nucleus. The patient s memory deficit was characterized by a severe anterograde encoding deficit and retrograde amnesia with a temporal gradient. In contrast, he did not show either frontal executive dysfunction or personality change that is frequently recognized in the anterior or medial thalamic lesion. We postulate that an amnesic syndrome can develop following discrete lesions of the MTT.

Auditory evoked potential responses in chronic malnourished children.

Auditory evoked potential responses were recorded in 20 chronic malnourished children in age group 3-6 years and in 20 healthy age and sex matched controls using an 5200 Neuropack plus ( Nihon Koden, Japan) evoked potential recorder. The absolute peak latencies, inter peak latencies and amplitude of waves I-V of brainstem auditory evoked potentials (BAEPs) were analyzed. The mid latency responses (MLRs) were also studied in these children. Malnutrition was characterized by stunting, which indicated chronicity of nutritional deprivation. The children with chronic Protein energy malnutrition (PEM) had prolonged peak latencies of waves I, II, III and IV. The interpeak latencies I-III and III-V were also prolonged. The amplitude of wave I and V did not show any significant difference as compared to controls. The middle latency responses were not significantly different from the controls. Thus malnutrition affects the peripheral developmental process of auditory pathways only in the brainstem and the central thalamocortical projections of these pathways are spared.

Evaluation of Gilles de la Tourette syndrome with [99mTc] HMPAO Brain SPECT

Gilles de la Tourette syndrome (GLTS) is a disorder characterized by tics and several behavioral disturbances. Although GLTS is a relatively common disorder, little is known about its pathophysiology. Previous studies with SPECT and PET were performed in a small number of patients and have shown some discordant data. The aim of this study is to evaluate brain perfusion abnormalities in patients with GLTS and to correlate them with the clinical manifestations of the syndrome. Twenty-eight patients were submitted to brain [99mTc]-HMPAO SPECT. 82 percent of the patients had abnormal studies. The most frequent finding was perfusion abnormalities in the thalami in 16 patients (57 percent) and 85 percent of patients with hyperperfusion of one or both thalami had complex motor tics. This investigation has demonstrated that brain perfusion SPECT is able to identify cortical perfusion abnormalities, associated with clinical symptoms in patients with GLTS. These abnormalities involve the pre-frontal-striatal-thalamic-cortical pathways

Electroencephalographic study of iron-induced chronic focal cortical epilepsy in rat: propagation of cortical epileptic activity to substantia nigra and thalamus.

Cortical epileptic focus was produced by an intracortical injection of FeCl3 in rat cerebral cortex using standard techniques. How after its onset in the cortical focus, the epileptiform activity evolved with time in the thalamus and substantia nigra has been determined. To study the propagation of the epileptiform activity, the local EEG and multiple unit action potentials were recorded from these structures simultaneously with the cortical epileptiform EEG. The results showed that in thalamus and substantia nigra epileptiform activity appeared simultaneously with that in the cortical focus. Intensity of epileptic activity in thalamus and substantia nigra on the whole increased in parallel with that in the cortical focus. The results suggest that the thalamic and nigral epileptiform activity may reinforce the cortical epileptiform activity.

Encefalopatía hipóxico isquémica con lesiones ganglio-talámicas selectivas: presentación de un caso / The hypoxic-ischemic encephalopathy in neonate: a case report

El propósito de este informe es hacer notar la naturaleza selectiva de las lesiones encontradas en un neonato con encefalopatía hipóxico isquémica. Se hace mención de la utilidad del ultrasonido transfontanelar para identificarlas y, cómo se correlacionan los hallazgos con lo referido en la literatura médica. Caso clínico. Se presenta un recién nacido a término, que cursó con encefalopatía poshipóxica causada por la ruptura uterina. El paciente cursó con grave afectación neurológica y datos incompletos de muerte cerebral. Las imágenes del ultrasonido y la tomografía computarizada mostraron zonas hemorrágicas cuya extensión comprendió casi completamente los tálamos y los ganglios basales. Discusión. Los hallazgos ultrasonográficos y tomográficos encontrados en este caso suelen estar relacionados con una elevada letalidad y secuelas graves. Por lo tanto, son indicadores de valor pronóstico. Las lesiones encontradas son semejantes a las provocadas experimentalmente en primates mediante asfixia total.

A propósito de lo biológico en esquizofrenia / Biological alterations in Schizophrenia

Se exponen algunos hallazgos biologicos correspondientes a la alteracion de las estructuras cerebrales encontradas en esquizofrenicos. En los estudios post-mortem y enlos de imagenologia in vivo: se ha verificado disminucion del volumen cerebral, aumento de las cavidades ventriculares y de los surcos de la corteza, alteraciones neuronales y funcionales de los lobulos prefrontales y temporales medios, a predominio izquierdo y de sus conexiones, disminucion de la sustancia gris central, del numero de neuronas del nucleo dorsal del talamo y del nucleo accumbens. Es indudable la influencia del factor genetico, aunque los modelos del gen simple no son compatibles con los datos de los gemelos y familias. Es plausible la existencia de un desorden neurointegrativo asociado a un factor genetico y a circunstancias ambientales para la produccion de esquizofrenia. Acerca de la hipotesis dopaminergica, se ha aceptado mas para los sindromes positivos que muchos no los consideran propiamente esquizofrenicos, salvo los que se repiten y terminan en la cronicidad. Para los sindromes negativos "verdadera esquizofrenia", se propone la hipodopaminergia

Los síndromes de lesión talámica

En la unidad de Neurología del Centro Hospitalario San Juan de Dios de Bogotá, durante cuatro años (1986 a 1989), se estudiaron en forma consecutiva 25 pacientes con lesiones talámaticas no fatales. Se registraron los hallazgos neurológicos, neurosicológicos y neurooftalmológicos y los diagnósticos se confirmaron por tomografía computarizada (TC). Fueron 14 mujeres y 11 varones con una edad promedio de 52.5 y un rango de 25 a 84 años. La lesión talámica fue de origen vascular en 24 casos, ocho por infarto isquémico, cuatro por infarto hemorrágico y 12 con hematomas parenquimatosos. Diecisiete pacientes tenían hipertensión arterial sistémica y el único factor de riesgo en otros dos era el consumo de cocaína base (basuco). Ocho infartos se presentaron en el tálamo derecho, 12 en el izquierdo y cinco pacientes tuvieron lesiones bilaterales, uno de ellos con un glioma complobado por biopsia. En 5 pacientes con lesiónes bilateral se observó el síndrome del "Tope" de la arteria basilar, por compromiso del pedículo retromamilar; en todos ellos encontramos alteraciones sensitivomotoras, cerebelosas, oculomotoras bilaterales y demencia. Solamente un paciente presentó el clasicó síndrome de hiperpatía (Dejerine-Roussy). En los restantes se observaron asociaciones de síndromes sensitivomotores, cerebelosos, neurooftalmológicos, neuropsicológicos, y del comportamiento motor que remedan con frecuencia los hallazgos clínicos de la alteración cortical frontal, temporal o parietal.

Hemorragias talámicas: correlación clínico-tomográfica / Thalamic hemorrhage: clinic-tomography correlation

Se presenta y discuten tres casos de pacientes con hemorragias talámicas primarias diagnosticadas clínicas y tomográficamente. Se remarca la relevancia que tiene en la explicación de los síntomas la extensión vertical del hematoma por oposición a la extensión transversal usada principalmente en trabajos precedentes