Movement disorders in systemic autoimmune diseases: Clinical spectrum, ancillary investigations, pathophysiological considerations

With the advances in neuroimmunology especially due to the discovery of new neuronal antibodies, the recognition of treatable antibody-related movement disorders has recently received much attention. In contrast, the identification and characterisation of movement disorders associated with systemic autoimmune diseases remains a substantially unexplored area. Beyond the classic few associations such as chorea and antiphospholipid syndrome, or ataxia and coeliac disease, movement disorders have been reported in association with several systemic autoimmune diseases, however a clear image of clinical phenotypes, investigations, and treatment outcomes in these conditions has never been drawn. In this review, we analyse data from approximately 300 cases and summarise the epidemiological, clinical and diagnostic features of movement disorders associated with systemic autoimmune diseases, and the available knowledge about treatment and outcomes. We highlight that movement disorders in systemic autoimmune conditions are frequently the only or among a few presenting manifestations and are mostly treatable disorders responding to immunotherapy or dietary modifications. We point out the pertinent combination of clinical features and investigations which can suggest the underlying autoimmune nature of these movement disorders, and thus address the most appropriate treatment

Refining the Deep Brain Stimulation Target within the Limbic Globus Pallidus Internus for Tourette Syndrome

BACKGROUND: Deep brain stimulation (DBS) in patients with severe, refractory Tourette syndrome (TS) has demonstrated promising but variable results thus far. The thalamus and anteromedial globus pallidus internus (amGPi) have been the most commonly stimulated sites within the cortico-striato thalamic circuit, but an optimal target is yet to be elucidated. OBJECTIVES: This study of 15 patients with long-term amGPi DBS for severe TS investigated whether a specific anatomical site within the amGPi correlated with optimal clinical outcome for the measures of tics, obsessive compulsive behaviour (OCB), and mood. METHODS: Validated clinical assessments were used to measure tics, OCB, quality of life, anxiety, and depression before DBS and at the latest follow-up (17-82 months). Electric field simulations were created for each patient using information on electrode location and individual stimulation parameters. A subsequent regression analysis correlated these patient-specific simulations to percentage changes in outcome measures in order to identify any significant voxels related to clinical improvement. RESULTS: A region within the ventral limbic GPi, specifically on the medial medullary lamina in the pallidum at the level of the AC-PC, was significantly associated with improved tics but not mood or OCB outcome. CONCLUSIONS: This study adds further support to the application of DBS in a tic-related network, though factors such as patient sample size and clinical heterogeneity remain as limitations and replication is required

Face perception enhances insula and motor network reactivity in Tourette syndrome

Tourette syndrome is a neurodevelopmental disorder, characterised by motor and phonic tics. Tics are typically experienced as avolitional, compulsive, and associated with premonitory urges. They are exacerbated by stress and can be triggered by external stimuli, including social cues like the actions and facial expressions of others. Importantly, emotional social stimuli, with angry facial stimuli potentially the most potent social threat cue, also trigger behavioural reactions in healthy individuals, suggesting that such mechanisms may be particularly sensitive in people with Tourette syndrome. Twenty-one participants with Tourette syndrome and 21 healthy controls underwent functional magnetic resonance imaging while viewing faces wearing either neutral or angry expressions to quantify group differences in neural activity associated with processing social information. Simultaneous video recordings of participants during neuroimaging enabled us to model confounding effects of tics on task-related responses to the processing of faces. In both Tourette syndrome and control participants, face stimuli evoked enhanced activation within canonical face perception regions, including the occipital face area and fusiform face area. However, the Tourette syndrome group showed additional responses within the anterior insula to both neutral and angry faces. Functional connectivity during face viewing was then examined in a series of psychophysiological interactions. In Tourette syndrome participants, the insula showed functional connectivity with a set of cortical regions previously implicated in tic generation: the pre-supplementary motor area, premotor cortex, primary motor cortex, and the putamen. Furthermore, insula functional connectivity with the globus pallidus and thalamus varied in proportion to tic severity, while supplementary motor area connectivity varied in proportion to premonitory sensations, with insula connectivity to these regions increasing to a greater extent in patients with worse symptom severity. In addition, the occipital face area showed increased functional connectivity in Tourette syndrome participants with posterior cortical regions, including primary somatosensory cortex, and occipital face area connectivity with primary somatosensory and primary motor cortices varied in proportion to tic severity. There were no significant psychophysiological interactions in controls. These findings highlight a potential mechanism in Tourette syndrome through which heightened representation within insular cortex of embodied affective social information may impact the reactivity of subcortical motor pathways, supporting programmed motor actions that are causally implicated in tic generation. Medicinal and psychological therapies that focus on reducing insular hyper-reactivity to social stimuli may have potential benefit for tic reduction in people with Tourette syndrome

Inter and intra-Rater Reliability of Accuracy of Testicular volume Evaluation (IRRATE): a simulation study

Background: The measurement of testicular volume is a practical and inexpensive method of pubertal staging in adolescents. Traditionally, volume is measured using orchidometers or calipers, the most widely used of which is the Prader Orchidometer. However, there is conflicting evidence of its use with regards to reliability in different hands. Objectives: To determine the accuracy of the Prader orchidometer in measuring testicular volume, by comparing the resultant measurement with the actual testicular volumes. Information on inter-observer and intra-observer variation was obtained for 16 investigators. Furthermore, the effect of factors such as clinical experience, gender and training in using an orchidometer on the accuracy of testicular volume measurement were investigated. Methods: A total of 16 investigators were asked to measure a range of 4 testicular volumes, attached via prosthesis to child-sized mannequins. The volume of each testis was measured independently using the Prader Orchidometer. A proportion of investigators also repeated testicular volume measurements, blinded by measurements obtained by other investigators. Results: The mean testicular volume measured by 16 examiners for 4 sizes at 20ml, 10ml, 5ml and 3ml. There were 4 male investigators and 12 female investigators. Fischer’s exact test found males to be significantly more accurate at measuring testicular volume than females (P =0.04). Chi-squared values were measured at each volume and showed no significant difference between those with clinical paediatric endocrine experience compared with those with no experience. Inter-observer reliability was measured using coefficient of variation due to our sample size of 16. This showed no significant difference between investigators measuring each testicular volume. However, it showed that larger volume testicles were more likely to be accurately measured compared to smaller volumes. Results showed that the 20ml volume had the smallest variability of 0.109 and 0.130 for right and left respectively ad the 3ml volume had a higher variation at 0.456 and 0.559 for right and left testicles respectively. Interestingly, variation was higher at all volumes in the left testicle. Furthermore, the 5ml volume has an unexpectedly low variability which may be attributed to its link with puberty and the need for endocrinologists to be skilledat identifying this particular volume due it’s clinical relevance. 7 people were trained vs 9 untrained in using orchidometers. Orchidometer training R20 A 3 B 10 C 5 D L20 A 3 B 10 C 5 D % accuracy trained 3/7 42.9 2/7 28.6 5/7 71.4 2/7 28.6 6/7 85.7 FE: 4/7 57.1 FE: 6/7 85.7 FE: 2/7 28.6 FE: %accuracy not trained 7/9 77.8 2/9 22.2 3/9 33.3 2/9 22.2 5/9 55.6 3/9 33.3 3/9 33.3 2/9 22.2 FE 0.302 1.00 0.315 1.00 0.308 0.615 0.060 1.000 Fischer’s exact: does having orchidometer training affect accuracy of results- not significant. Conclusion In conclusion, it was found that measurement of testicular volumes on paediatric testicular models is subject to great/little inter/intra-observer variation. The data suggests that there is a clinical need for formal training in testicular volume measurement as there is currently no established training in place. As a result, the innovative, custom-made testicular models for this study could have a role in simulation training as an educational tool