Advances in the genetics of primary torsion dystonia

Knowledge about the genetics of primary torsion dystonia (PTD) has been progressing at a very slow pace compared with other movement disorders. For many years, only one causative gene was known, DYT1/TOR1A, yet the recent identification of a second PTD causative gene (DYT6/THAP1), the detection of subclinical alterations caused by mutations in PTD genes in some healthy non-penetrant individuals, and functional studies on TOR1A and THAP1 protein products have significantly improved mutation detection, genotype-phenotype correlates, and our understanding of the cellular mechanisms underlying the development of dystonia

Dystonia and Tremor: The Clinical Syndromes with Isolated Tremor

Background: Dystonia and tremor share many commonalities. Isolated tremor is part of the phenomenological spectrum of isolated dystonia and of essential tremor. The occurrence of subtle features of dystonia may allow one to differentiate dystonic tremor from essential tremor. Diagnostic uncertainty is enhanced when no features of dystonia are found in patients with a tremor syndrome, raising the question whether the observed phenomenology is an incomplete form of dystonia. Methods: Known forms of syndromes with isolated tremor are reviewed. Diagnostic uncertainties between tremor and dystonia are put into perspective. Results: The following isolated tremor syndromes are reviewed: essential tremor, head tremor, voice tremor, jaw tremor, and upper-limb tremor. Their varied phenomenology is analyzed and appraised in the light of a possible relationship with dystonia. Discussion: Clinicians making a diagnosis of isolated tremor should remain vigilant for the detection of features of dystonia. This is in keeping with the recent view that isolated tremor may be an incomplete phenomenology of dystonia

Conservative Surgical Treatment of Bisphosphonate-Related Osteonecrosis of the Jaw with Er,Cr:YSGG Laser and Platelet-Rich Plasma: A Longitudinal Study

Abstract Introduction: The management of bisphosphonate-related osteonecrosis of the jaw (BRONJ), with no evidence-based guidelines, remains controversial. We aimed to evaluate the efficiency of a conservative surgical treatment combining Er,Cr:YSGG laser and platelet-rich plasma (PRP) for the treatment of BRONJ in cancer patients.Methods:We performed a longitudinal cohort study. Inclusion criteria were (1) age 65 18 years; (2) cancer diagnosis; (3) treatment with NBP because of the underlying cancer. Results:We consecutively recruited ten patients diagnosed with BRONJ in stage I or II. These patients underwent a surgical laser-assisted therapy together with autologous PRP. At the latest follow-up at 12 months, clinical improvement was observed in eight patients. Registration Number is IRCT20180329039159N1. Conclusion:We could successfully manage the BRONJ utilizing this combined protocol to heal the 30% of surgically treated sites and to improve the 50% of patients' lesions clinically. Our findings suggest that a surgical approach combined with Er,Cr:YSGG laser and PRP benefit cancer patients with general health issues

Manual and semi-automated approaches to MIBG myocardial scintigraphy in patients with Parkinson’s disease

OBJECTIVE: This study investigates the effects of manual and semi-automatic methods for assessing MIBG semi-quantitative indices in a clinical setting. MATERIALS AND METHODS: We included (123)I-MIBG scans obtained in 35 patients with idiopathic Parkinson’s Disease. Early and late heart-to-mediastinum (H/M) ratios were calculated from (123)I-MIBG images using regions of interest (ROIs) placed over the heart and the mediastinum. The ROIs were derived using two approaches: (i) manually drawn and (ii) semi-automatic fixed-size ROIs using anatomical landmarks. Expert, moderate-expert, and not expert raters applied the ROIs procedures and interpreted the (123)I-MIBG images. We evaluated the inter and intra-rater agreements in assessing (123)I-MIBG H/M ratios. RESULTS: A moderate agreement in the raters’ classification of pathological and non-pathological scores emerged regarding early and late H/M ratio values (κ = 0.45 and 0.69 respectively), applying the manual method, while the early and late H/M ratios obtained with the semi-automatic method reached a good agreement among observers (κ = 0.78). Cohen-Kappa values revealed that the semi-automatic method improved the agreement between expert and inexpert raters: the agreement improved from a minimum of 0.29 (fair, for early H/M) and 0.69 (substantial, in late H/M) with the manual method, to 0.90 (perfect, in early H/M) and 0.87 (perfect, in late H/M) with the semi-automatic method. CONCLUSION: The use of the semi-automatic method improves the agreement among raters in classifying’ H/M ratios as pathological or non-pathological, namely for inexpert readers. These results have important implications for semi-quantitative assessment of (123)I-MIBG images in clinical routine

Dystonia Management: What to Expect From the Future? The Perspectives of Patients and Clinicians Within DystoniaNet Europe

DystoniaNet; Xarxa europea; DistoniaDytoniaNet; Red europea; DistoníaDystoniaNet; European network; DystoniaImproved care for people with dystonia presents a number of challenges. Major gaps in knowledge exist with regard to how to optimize the diagnostic process, how to leverage discoveries in pathophysiology into biomarkers, and how to develop an evidence base for current and novel treatments. These challenges are made greater by the realization of the wide spectrum of symptoms and difficulties faced by people with dystonia, which go well-beyond motor symptoms. A network of clinicians, scientists, and patients could provide resources to facilitate information exchange at different levels, share mutual experiences, and support each other's innovative projects. In the past, collaborative initiatives have been launched, including the American Dystonia Coalition, the European Cooperation in Science and Technology (COST—which however only existed for a limited time), and the Dutch DystonieNet project. The European Reference Network on Rare Neurological Diseases includes dystonia among other rare conditions affecting the central nervous system in a dedicated stream. Currently, we aim to broaden the scope of these initiatives to a comprehensive European level by further expanding the DystoniaNet network, in close collaboration with the ERN-RND. In line with the ERN-RND, the mission of DystoniaNet Europe is to improve care and quality of life for people with dystonia by, among other endeavors, facilitating access to specialized care, overcoming the disparity in education of medical professionals, and serving as a solid platform to foster international clinical and research collaborations. In this review, both professionals within the dystonia field and patients and caregivers representing Dystonia Europe highlight important unsolved issues and promising new strategies and the role that a European network can play in activating them

Development of a patient journey map for people living with cervical dystonia

BACKGROUND: Patient journey maps are increasingly used as a tool that enables healthcare providers to refine their service provision to best meet patient needs. We developed a cervical dystonia patient journey map (CDPJM) that describes the holistic patient experience from pre-diagnosis through to long-term treatment. METHODS: The CDPJM was developed in 2 stages; a patient survey (open questions and multichoice) of 15 patients with CD was conducted to inform the design of the CDPJM, which was then refined and validated by an expert-patient focus group. RESULTS: Qualitative analysis of the patient survey supported five key stages of the patient journey: symptom onset, diagnosis and therapeutic relationship with healthcare professionals, initiation of care for CD, start of CD treatment, and living with treated CD. Following symptom onset, survey respondents described having multiple visits to their family doctor who prescribed strong pain killers and muscle relaxants and referred their patient to up to 10 different specialists for diagnosis. Over half (53.3%) of respondents had received ≥ 1 misdiagnosis. Respondents reported relief at having a diagnosis but a lack of understanding of the prognosis and treatment options; 46.7% said their neurologist did not spend enough time addressing their concerns. Survey respondents reported using a variety of alternative sources of information, including the internet (86.7%), self-help groups (66.7%) and information leaflets provided by health care professionals (60.0%). While botulinum toxin (BoNT) was consistently discussed as the main treatment option, some neurologists also mentioned physiotherapy, counselling, and other complementary approaches. However, patients were often left to seek complementary services themselves. Patients reported a ‘rollercoaster’ of relief with BoNT treatment with symptoms (and subsequent impact on daily life) returning towards the end of an injection cycle. “When BoNT works well I can return to an almost normal life … when the injections stop working so well, I have to rest more and avoid going to work and experience life restrictions.” CONCLUSIONS: We present the first patient journey map for CD that can be used to guide local service mapping and to compare current provision with what patients say they want and need

Focal Cerebral Infarction in Newborn: Description of Three Cases:

We observed 3 full-term newborns with focal ischemic injury of the middle cerebral artery (MCA), in which diagnosis of MCA stroke was suspected by US and confirmed by CT scan and MRI. A four-year follow-up was carried out to study the effect of neonatal stroke on neurodevelopmental outcome. All children had a history of pre-perinatal risk factors: neonatal cerebral infarction in term infants, in fact, has many possible causes, including bacterial meningitis, inherited or acquired coagulopathies, trauma and hypoxia-ischemia. The prognosis of neonatal MCA infarction depends on early diagnosis, on the CNS plasticity mechanism and, finally, on medical therapy and neuropsychological rehabilitation

The occurrence of OCPs, PCBs, and PAHs in the soil, air, and bulk deposition of the Naples metropolitan area, southern Italy: Implications for sources and environmental processes

I am often reminded of the famous saying of Goethe: "Vedi Napoli e poi muori! - See Naples and die!". Sadly, Naples is now confronted with a number of serious, ongoing problems with a need to alleviate pressure on the worsening environment. One serious problem facing the environment is the presence of the potentially hazardous persistent organic pollutants (POPs), although few systematic studies at regional scale have been conducted. In this study, samples of soil, air, and bulk deposition were collected in Naples metropolitan area (NMA) to characterize the status of POPs, including organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs). The results obtained showed that most of these compounds are pervasive in all the studied environmental matrices, especially in some hotspot areas, such as the Bagnoli Brownfield Site and the infamous "Triangle of the Death", where unwanted ecological risk conditions for PAHs and Endosulfan were determined, respectively. The interactional complexity between urban and the surrounding rural areas was also confirmed, as is the role that urban areas play in the migration and transformation process of POPs. High urban-rural gradients for atmospheric PAHs and PCBs were observed in the NMA, and the urban areas were identified as the emission source of these contaminants. Similarly, the OCP residues, historically originated from the nearby agricultural regions, experience long-term soil re-emission and continuously influence the connected urban environment via atmospheric transport processes. Keywords: Persistent organic pollutants, Emission sources, Geochemical baseline, Atmospheric transport, Naple