Aldosterone-producing adrenocortical carcinoma without hypertension

Although adrenocortical tumors are common, adrenocortical carcinomas are rare. Moreover, aldosterone-producing adrenocortical carcinomas without hypertension are exceedingly rare, with only two previously reported cases.     

Connectivity Theory of Autism: Use of Connectivity Measures in Assessing and Treating Autistic Disorders

Background. Autism is a disorder characterized by deficits in communication, social interaction, a limited range of interests, and repetitive stereotypical behavior. Although it is believed that changes in the brain leading to Autism occur early on in prenatal and early postnatal development, there is no definitive test for a diagnosis of Autism. The diagnosis is made on the basis of behavioral signs and symptoms alone and is usually not made until age 2 or later. There have been numerous neuroanatomical abnormalities noted in Autism, some of which can be linked to neuropsychological dysfunction. Recently a new theory has become prominent which suggests the disorder may be due to aberrant neural connectivity patterns. Evidence in support of this theory has come from anatomical studies of white matter as well as functional neuroimaging studies.

Methods. Most studies have employed functional magnetic resonance imaging to investigate connectivity, or electroencephalography (EEG) coherence studies. The high temporal resolution of EEG lends itself well to the investigation of cerebral connectivity. Research suggests there may be patterns of both hyper- and hypoconnectivity between various brain regions. Seven different patterns of abnormal connectivity which can be analyzed with EEG are proposed.

Results. Patterns of hyperconnectivity may be found in frontotemporal and left hemispheric regions, whereas patterns of hypoconnectivity are often seen in frontal (orbitofrontal), right posterior (occipital/parietal-temporal), frontal-posterior, and left hemispheric regions. In addition to these patterns of hypo- and hyperconnectivity, a mu rhythm complex has been identified. Treatment goals may be based on coherence anomalies identified by quantitative EEG analysis. Increased coherence between brain regions may be downtrained, whereas decreased coherence between brain regions may be uptrained. Clinical examples of each pattern and a discussion of their neurofeedback treatment are provided.

Conclusion. A theory of autistic disorders is presented that has at its' core neural connectivity disturbances. Multivariate EEG connectivity indices are utilized to formulate a typology of connectivity anomalies or patterns that have been observed over a series of autistic patients. These represent phenotypic expressions of the underlying pathology that leads to autistic symptoms. Examples demonstrate how these connectivity metrics can be used to understand autistic disturbances and formulate neurofeedback strategies for remedying these difficulties.     

Low-Frequency Repetitive Transcranial Magnetic Stimulation Modulates Evoked-Gamma Frequency Oscillations in Autism Spectrum Disorder

Introduction. It has been reported that individuals with Autism Spectrum Disorder (ASD) have abnormal reactions to the sensory environment and visuo-perceptual abnormalities. Electrophysiological research has provided evidence that gamma band activity (30–80 Hz) is a physiological indicator of the coactivation of cortical cells engaged in processing visual stimuli and integrating different features of a stimulus. A number of studies have found augmented and indiscriminative gamma band power at early stages of visual processing in ASD; this may be related to decreased inhibitory processing and an increase in the ratio of cortical excitation to inhibition. Low frequency or “slow” (≤1HZ) repetitive transcranial magnetic stimulation (rTMS) has been shown to increase inhibition of stimulated cortex by the activation of inhibitory circuits.

Method. We wanted to test the hypothesis of gamma band abnormalities at early stages of visual processing in ASD by investigating relative evoked (i.e., ～100 ms) gamma power in 25 participants with ASD and 20 age-matched controls using Kanizsa illusory figures. In addition, we wanted to assess the effects of 12 sessions of bilateral “slow” rTMS to the dorsolateral prefrontal cortex on evoked gamma activity using a randomized controlled design.

Results. In individuals with ASD evoked gamma activity was not discriminative of stimulus type, whereas in controls early gamma power differences between target and nontarget stimuli were highly significant. Following rTMS individuals with ASD showed significant improvement in discriminatory gamma activity between relevant and irrelevant visual stimuli. We also found significant improvement in the responses on behavioral questionnaires (i.e., irritability, repetitive behavior) as a result of rTMS.

Conclusion. We propose that slow rTMS may have increased cortical inhibitory tone, which improved discriminatory gamma activity at early stages of visual processing. rTMS has the potential to become an important therapeutic tool in ASD treatment and has shown significant benefits in treating core symptoms of ASD with few, if any side effects.     

The art of gene therapy for glioma： a review of the challenging road to the bedside

Glioblastoma muhiforme （GBM） is a highly invasive brain tumour that is unvaryingly fatal in humans clesplte even aggres- sive therapeutic approaches such as surgical resection followed by chemotherapy and radiotherapy. Unconventional treatment options such as gene therapy provide an intriguing option for curbing glioma related deaths. To date, gene therapy has yielded encouraging results in preclinical animal models as well as promising safety profiles in phase I clinical trials, but has failed to demonstrate significant therapeutic efficacy in phase III clinical trials. The most widely studied antiglioma gene therapy strategies are suicide gene therapy, genetic immuno- therapy and oncolytic virotherapy, and we have attributed the challenging transition of these modalities into the clinic to four major road- blocks ： （ 1 ） anatomical features of the central nervous system, （2） the host immune system, （3） heterogeneity and invasiveness of GBM and （4） limitations in current GBM animal models. In this review, we discuss possible ways to jump these hurdles and develop new gene therapies that may be used alone or in synergy with other modalities to provide a powerful treatment option for patients with GBM.