Psychosis in Machado-Joseph Disease: Clinical Correlates, Pathophysiological Discussion, and Functional Brain Imaging. Expanding the Cerebellar Cognitive Affective Syndrome.

Machado-Joseph disease (MJD) is the most common spinocerebellar ataxia worldwide with a broad range of clinical manifestations, but psychotic symptoms were not previously characterized. We investigated the psychiatric manifestations of a large cohort of Brazilian patients with MJD in an attempt to characterize the presence of psychotic symptoms. We evaluated 112 patients with clinical and molecular diagnosis of MJD from February 2008 to November 2013. Patients with psychotic symptoms were referred to psychiatric evaluation and brain perfusion single-photon emission computed tomography (SPECT) analysis. A specific scale-Positive and Negative Syndrome Scale (PANSS)-was used to characterize psychotic symptoms in MJD patients. We also performed an autopsy from one of the patients with MJD and psychotic symptoms. Five patients presented psychotic symptoms. Patients with psychotic symptoms were older and had a late onset of the disease (p < 0.05). SPECT results showed that MJD patients had significant regional cerebral blood flow (rCBF) decrease in the cerebellum bilaterally and vermis compared with healthy subjects. No significant rCBF differences were found in patients without psychotic symptoms compared to patients with psychotic symptoms. The pathological description of a patient with MJD and psychotic symptoms revealed severe loss of neuron bodies in the dentate nucleus and substantia nigra. MJD patients with a late onset of the disease and older ones are at risk to develop psychotic symptoms during the disease progression. These clinical findings may be markers for an underlying cortical-cerebellar disconnection or degeneration of specific cortical and subcortical regions that may characterize the cerebellar cognitive affective syndrome.

The effectiveness of acupuncture as a treatment for tinnitus: a randomized controlled trial using (99m)Tc-ECD SPECT.

OBJECTIVE: Investigate the effect of acupuncture on brain perfusion using ethyl cysteinate dimer single-photon emission computed tomography ((99m)Tc-ECD SPECT) in patients with tinnitus. METHODS: This randomized, single-blind, sham-control study examined patients (18-60 years old) with normal hearing and chronic, idiopathic, continuous tinnitus. Fifty-seven subjects were randomly assigned to true (n = 30) or sham (n = 27) acupuncture (ACP); (99m)Tc-ECD SPECT examinations were performed before and after 12 twice-weekly ACP sessions. Secondary outcomes included changes in the Tinnitus Handicap Inventory (THI), Visual Analog Scale (VAS), Hamilton Anxiety Scale (HAS) and Beck Depression Inventory (BDI). Imaging data were analysed using Statistical Parametric Mapping (SPM8) software. Regression models were used to examine secondary outcomes via two paradigms: intention-to-treat (ITT; where multiple imputations were conducted because of study attrition) and complete cases. RESULTS: No between-group brain perfusion differences were observed. However, a significant improvement in THI scores was observed at the end of true ACP treatment for all domains (all p values < 0.01) except the catastrophic scale. CONCLUSIONS: ACP might reduce the effects of tinnitus on daily life; however, additional studies should be conducted to verify the effects of ACP on the neural architecture and brain function of tinnitus patients. KEY POINTS: • Efficacy of acupuncture on brain perfusion and symptoms of tinnitus patients. • Acupuncture improved the Tinnitus Handicap Inventory scores in tinnitus patients. • No significant changes in brain perfusion were observed after 12 twice-weekly sessions. • Perfusion changes would reflect changes in neuronal function.

Memory networks in tinnitus: a functional brain image study.

UNLABELLED: Tinnitus is characterized by the perception of sound in the absence of an external auditory stimulus. The network connectivity of auditory and non-auditory brain structures associated with emotion, memory and attention are functionally altered in debilitating tinnitus. Current studies suggest that tinnitus results from neuroplastic changes in the frontal and limbic temporal regions. The objective of this study was to use Single-Photon Emission Computed Tomography (SPECT) to evaluate changes in the cerebral blood flow in tinnitus patients with normal hearing compared with healthy controls. METHODS: Twenty tinnitus patients with normal hearing and 17 healthy controls, matched for sex, age and years of education, were subjected to Single Photon Emission Computed Tomography using the radiotracer ethylenedicysteine diethyl ester, labeled with Technetium 99 m (99 mTc-ECD SPECT). The severity of tinnitus was assessed using the "Tinnitus Handicap Inventory" (THI). The images were processed and analyzed using "Statistical Parametric Mapping" (SPM8). RESULTS: A significant increase in cerebral perfusion in the left parahippocampal gyrus (pFWE <0.05) was observed in patients with tinnitus compared with healthy controls. The average total THI score was 50.8+18.24, classified as moderate tinnitus. CONCLUSION: It was possible to identify significant changes in the limbic system of the brain perfusion in tinnitus patients with normal hearing, suggesting that central mechanisms, not specific to the auditory pathway, are involved in the pathophysiology of symptoms, even in the absence of clinically diagnosed peripheral changes.

Efeito do estímulo sonoro definido na plasticidade neuroquímica da via auditiva do rato. Análise das modificações na imunorreatividade de neurotransmissores

A estimulação auditiva é capaz de interferir na plasticidade neuroquímica e estrutural do sistema nervoso por meio da ativação neuronal, modificando os níveis endógenos de fatores neurotróficos e de neurotransmissores. Neste estudo analisamos as alterações químicas na via auditiva aferente de animais estimulados acusticamente. Ratos Wistar de 60 dias de idade foram submetidos ou não a um estímulo sonoro definido durante 1 hora por um período de 1 ou de 7 dias seguidos. Após a estimulação auditiva, os animais foram sacrificados e seus encéfalos e cócleas processados para imunohistoquímica para a visualização da imunorreatividade da proteína FOS e do ácido glutâmico descarboxilase (GAD) nos núcleos cocleares e da imunorreatividade do glutamato, da neurotensina e do neuropeptídeo Y nos órgãos de Corti, nos neurônios dos gânglios espirais e também nos núcleos coc1eares. O estímulo sonoro consistiu de um tom puro intermitente, na freqüência de 8KHz e na intensidade de 80 dB NPS, apresentado em caixas acústicas posicionadas acima da gaiola de cada animal. A estimulação auditiva promoveu aumento significativo na área de imunorreatividade da proteína FOS e do glutamato na região rostral do núcleo coclear dorsal. Não houve diferenças estatísticas na imunomarcação do GAD no núcleo coclear. Na cóclea, mais especificamente nas células ciliadas internas, foi observado aumento da imunorreatividade do glutamato no giro basal e diminuição da neurotensina no giro apical diante do estímulo sonoro. A análise da intensidade da imunomarcação nos neurônios do gânglio espiral revelou maior número de neurônios tipo II com forte imunorreatividade ao neuropeptídeo Y exclusivamente no giro apical da cóclea dos animais estimulados. A via auditiva periférica e o núcleo coclear respondem de forma plástica a estímulos sonoros. A estimulação auditiva específica, não prejudicial, pode ser uma estratégia para maximizar o potencial plástico das vias neurais relacionadas (AU)