Extragenetic factors and clinical penetrance of DYT1 dystonia: an exploratory study

Factors modifying the clinical penetrance of DYT1 dystonia are incompletely defined. Particularly, the contribution of extragenetic factors has been subject to only limited investigation and remains largely unexplored. A possible effect of childhood infections has been proposed, and the effect of other factors, such as perinatal adversity and trauma, has not been systematically investigated. We performed an exploratory analysis of the exposure to perinatal adversity, childhood infections, general anaesthesia and trauma comparing 39 manifesting carriers of the ?GAG mutation, 23 non-manifesting carriers and 48 non-carriers from a multi-centre European series of 28 families with DYT1 dystonia, by means of a self-completed questionnaire and clinical interview. Detailed information on perinatal adversities (pre-term birth, complications at natural delivery, urgent caesarean section), previous childhood infections, and prior general anaesthesia or physical trauma was recorded. A positive association between a history of complications of vaginal delivery and manifestation of dystonia was detected, which was not confounded by age, gender, or education level (odds ratio 8.47, 95 % confidence interval 1.45–49.4, p = 0.02). We could not observe any significant association between presence of dystonia and the other investigated variables. Comparing non-manifesting carriers to non-carriers, the presence of the ?GAG mutation per se was not associated with any of the environmental exposures explored. Perinatal adversities might modulate the clinical penetrance of DYT1 dystonia; their interaction with known genetic factors modifying penetrance of this condition should be investigated in new, larger collaborative studies.     

Defining the Epsilon‐Sarcoglycan (SGCE) Gene Phenotypic Signature in Myoclonus‐Dystonia: A Reappraisal of Genetic Testing Criteria

Mutations or exon deletions of the epsilon‐sarcoglycan (SGCE) gene cause myoclonus‐dystonia (M‐D), but a subset of M‐D patients are mutation‐negative and the sensitivity and specificity of current genetic testing criteria are unknown. We screened 46 newly enrolled M‐D patients for SGCE mutations and deletions; moreover, 24 subjects previously testing negative for SGCE mutations underwent gene dosage analysis. In our combined cohorts, we calculated sensitivity, specificity, positive and negative predictive values, and area under the curve of 2 published sets of M‐D diagnostic criteria. A stepwise logistic regression was used to assess which patients' characteristics best discriminated mutation carriers and to calculate a new mutation predictive score (“new score”), which we validated in previously published cohorts. Nine of 46 (19.5%) patients of the new cohort carried SCGE mutations, including 5 novel point mutations and 1 whole‐gene deletion; in the old cohort, 1 patient with a complex phenotype carried a 5.9‐Mb deletion encompassing SGCE. Current diagnostic criteria had a poor ability to discriminate SGCE‐positive from SGCE‐negative patients in our cohort; conversely, age of onset, especially if associated with psychiatric features (as included in the new score), showed the best discriminatory power to individuate SGCE mutation carriers, both in our cohort and in the validation cohort. Our results suggest that young age at onset of motor symptoms, especially in association with psychiatric disturbance, are strongly predictive for SGCE positivity. We suggest performing gene dosage analysis by multiple ligation‐dependent probe amplification (MLPA) to individuate large SGCE deletions that can be responsible for complex phenotypes. © 2013 Movement Disorder Society     

Failure of explicit movement control in patients with functional motor symptoms

Functional neurological symptoms are one of the most common conditions observed in neurological practice, but understanding of their underlying neurobiology is poor. Historic psychological models, based on the concept of conversion of emotional trauma into physical symptoms, have not been implemented neurobiologically, and are not generally supported by epidemiological studies. In contrast, there are robust clinical procedures that positively distinguish between organic and functional motor signs that rely primarily on distracting attention away from movement or accessing it covertly. We aimed to investigate the neurobiological principles underpinning these techniques and implications for understanding functional symptoms. We assessed 11 patients with functional motor symptoms and 11 healthy controls in three experimental set‐ups, where voluntary movements were made either with full explicit control or could additionally be influenced automatically by factors of which participants were much less aware (one‐back reaching, visuomotor transformation, and precued reaction time with variable predictive value of the precue). Patients specifically failed in those tasks where preplanning of movement could occur and under conditions of increasing certainty regarding the movement to be performed. However, they implicitly learned to adapt to a visuomotor transformation as well as healthy controls. We propose that when the movement to be performed can be preplanned or is highly predicted, patients with functional motor symptoms shift to an explicit attentive mode of processing that impairs kinematics of movement control, but movement becomes normal when such processes cannot be employed (e.g., during unexpected movement or implicit motor adaptation). © 2013 Movement Disorder Society     

Sensory tricks in primary cervical dystonia depend on visuotactile temporal discrimination

A characteristic feature of primary cervical dystonia is the presence of “sensory tricks” as well as the impairment of temporal and spatial sensory discrimination on formal testing. The aim of the present study was to test whether the amount of improvement of abnormal head deviation due to a sensory trick is associated with different performance of temporal sensory discrimination in patients with cervical dystonia. We recruited 32 patients with cervical dystonia. Dystonia severity was assessed using the Toronto Western Spasmodic Torticollis Rating Scale. Patients were rated according to clinical improvement to a sensory trick and assigned to 1 of the following groups: (1) no improvement (n = 6), (2) partial improvement (n = 17), (3) complete improvement (n = 9). Temporal discrimination thresholds were assessed for visual, tactile, and visuotactile modalities. Disease duration was shorter (P = .026) and dystonia severity lower (P = .033) in the group with complete improvement to sensory tricks compared with the group with partial improvement to sensory tricks. A significant effect for group and modality and a significant interaction between group × modality were found, with lower visuotactile discrimination thresholds in the group with complete improvement to sensory tricks compared with the other groups. In primary cervical dystonia, a complete resolution of dystonia during a sensory trick is associated with better visuotactile discrimination and shorter disease duration compared with patients with less effective sensory tricks, which may reflect progressive loss of adaptive mechanisms to basal ganglia dysfunction. © 2013 Movement Disorder Society     

Laboratory aspects of zirconia restorations

Zirconia restorations are now accepted and commonly prescribed in dentistry. However, these materials undergo hydrothermal ageing which can reduce their clinical performance. Appropriate handling is essential to limit the restorations' susceptibility to low temperature degradation/ageing. Through appropriate clinical prescribing and laboratory manufacture, an aesthetic, strong and long-lasting restoration can be fabricated. Clinical Relevance: This article will inform the reader about zirconia as a dental material as well as how best to handle a zirconia restoration.     

Percutaneous Ozone Treatment for Herniated Lumbar Discs: 1-Year Follow-up of a Multicenter Pilot Study of a Handheld Disposable Ozone-Generating Device

PurposeTo evaluate the safety and efficacy of oxygen-ozone treatment delivered via a novel, handheld ozone-generating device for improving pain and function in herniated disc patients.Materials and MethodsA total of 39 patients with contained herniated lumbar discs received oxygen-ozone treatment at 1 of 3 centers. Treatment consisted of injection of 2% ozone (10 mL): 3 mL delivered into the nucleus pulposus and 7 mL delivered into the adjacent paravertebral tissues. The first 8 patients received only ozone injections, whereas subsequent patients also received periganglionic methylprednisolone (40 mg) and 0.5% bupivacaine (1 mL) injections. Patients were evaluated at baseline and at 1 month, 6 months, and 12 months after treatment using the Oswestry Disability Index (ODI) and the Visual Analogue Scale (VAS) for leg pain and for back pain. Analgesic medication use was also assessed at each timepoint.ResultsOverall, 91% (32/35) of the per-protocol patients (those who completed follow-up and did not have significant protocol deviations) showed detectable improvement in ODI at 1-month follow-up; this increased to 93% (26/28) of patients at 12-months follow-up. At 1 month after treatment, 60% (21/35) of patients showed significant improvement in ODI scores (P = .01); 54% (19/35) showed significant improvement in VAS scores for leg pain (P = .05); and 49% (17/35) showed significant improvement in VAS scores for back pain (P = .12). At 6 months after treatment, 67% (22/33) of patients showed significant improvement in ODI scores (P = .02); 64% (21/33) showed significant improvement in VAS scores for leg pain (P = .01); and 52% (17/33) showed significant improvement in VAS scores for back pain (P = .12). At 12 months after treatment, 68% (19/28) of patients showed significant improvement in ODI scores (P < .01); 64% (18/28) showed significant improvement in VAS scores for leg pain (P < .01); and 61% (17/28) showed significant improvement in VAS scores for back pain (P = .09). Leg pain typically subsided more quickly than back pain. Use of analgesic medications also significantly decreased at all follow-up timepoints compared to baseline (P < .01). There were no adverse events or device-related issues.ConclusionsAt 1, 6, and 12 months after treatment, patients experienced significant improvements in pain and function as well as significantly decreased use of analgesic medication. Taken together with the absence of adverse events at 1-year follow-up, these data suggest that oxygen-ozone treatment is a safe and effective therapy for contained herniated discs.