Brain : a journal of neurology
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Multicenter Study
Structural changes in the somatosensory system correlate with tic severity in Gilles de la Tourette syndrome.
Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder characterized by multiple motor and vocal tics. Previous structural MRI studies have identified regional abnormalities in grey matter, especially in the basal ganglia. These findings are consistent with the assumption of alterations in cortico-striato-thalamo-cortical circuits and dopaminergic neurotransmission playing a major role in the pathophysiology of GTS. ⋯ These findings demonstrate, for the first time, structural alterations in somatosensory pathways in GTS. Changes of water diffusion characteristics point towards reduced branching in somatosensory pathways in GTS patients. The negative correlation between higher regional FA values and fewer tics suggests that these alterations of white matter microstructure represent adaptive reorganization of somatosensory processing in GTS.
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Social interaction is profoundly affected in the behavioural form of frontotemporal dementia (bvFTD) yet there are few means of objectively assessing this. Diagnosis of bvFTD is based on informant report, however a number of individuals with a clinical profile consistent with the disease have no imaging abnormality and seem to remain stable, with doubt about the presence of underlying neurodegenerative pathology. We aimed to quantify aspects of the behavioural disorder and link it to the underlying level of atrophy in socially relevant brain regions. ⋯ Performance on a more global test of cognitive function, the Addenbrooke's Cognitive Examination did not have a unique association with these regions. The TASIT is an objective test of social dysfunction in bvFTD which indexes the frontotemporal volume loss in bvFTD patients and provides an objective measure for separating behavioural patients who are likely to decline from those who may remain stable. These results provide additional evidence for the role of the orbitofrontal cortex and related structures in the processing of socially relevant signals, particularly those where negative emotion recognition is important.
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Mutations in the progranulin gene (GRN) are an important cause of frontotemporal lobar degeneration (FTLD) with ubiquitin and TAR DNA-binding protein 43 (TDP43)-positive pathology. The clinical presentation associated with GRN mutations is heterogeneous and may include clinical probable Alzheimer's disease. All GRN mutations identified thus far cause disease through a uniform disease mechanism, i.e. the loss of functional GRN or haploinsufficiency. ⋯ This study demonstrates that using a GRN ELISA in plasma, pathogenic GRN mutations can be accurately detected in symptomatic and asymptomatic carriers. The approximately 75% reduction in full-length GRN, suggests an unbalanced GRN metabolism in loss-of-function mutation carriers whereby more GRN is processed into granulins. We propose that plasma GRN levels could be used as a reliable and inexpensive tool to identify all GRN mutation carriers in early-onset dementia populations and asymptomatic at-risk individuals.
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Recent studies have shown that the detrimental effects of sports concussions on cognitive and motor function may persist up to a few years post-injury. The present study sought to investigate the effects of having sustained a sports concussion more than 30 years prior to testing on cognitive and motor functions. Nineteen healthy former athletes, in late adulthood (mean age = 60.79; SD = 5.16), who sustained their last sport-related concussion in early adulthood (mean age = 26.05; SD = 9.21) were compared with 21 healthy former athletes with no history of concussion (mean age = 58.89; SD = 9.07). ⋯ A rapid alternating movement task was also used to characterize motor system dysfunctions. Relative to controls, former athletes with a history of concussion had: (i) lower performance on neuropsychological tests of episodic memory and response inhibition; (ii) significantly delayed and attenuated P3a/P3b components; (iii) significantly prolonged CSP and (iv) significantly reduced movement velocity (bradykinesia). The finding that the P3, the CSP as well as neuropsychological and motor indices were altered more than three decades post-concussion provides evidence for the chronicity of cognitive and motor system changes consecutive to sports concussion.
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Endogenous pain modulation may provide facilitation or inhibition of nociceptive input by three main mechanisms. Firstly, modification of synaptic strength in the spinal dorsal horn may increase or decrease transmission of nociceptive signals to the brain. Secondly, local dorsal horn interneurons provide both feed-forward and feed-back modulation to spinothalamic and spinobulbar projection neurons. ⋯ The differences were not correlated with duration of the disease, pain intensity, autonomic or motor function scores, presence or degree of evoked pain. However, significant correlation was found with the extent of adaptation and hyperalgesia on the unaffected hand. Thus, we hypothesize that differential activity in endogenous pain modulating systems may be not only a result of CRPS, but a potential risk factor for its development.