Eating dysfunction associated with oromandibular dystonia: clinical characteristics and treatment considerations

BACKGROUND: In oromandibular dystonia (OMD) abnormal repetitive contractions of masticatory, facial, and lingual muscles as well as the presence of orobuccolingual (OBL) dyskinesias may interfere with the appropriate performance of tasks such as chewing and swallowing leading to significant dysphagia and weight loss. We present here the clinical characteristics and treatment variables of a series of patients that developed an OMD-associated eating dysfunction. METHODS: We present a series of patients diagnosed and followed-up at the Movement Disorders Clinic of the Department of Neurology of University of Miami, Miller School of Medicine over a 10-year period. Patients were treated with botulinum toxin injections according to standard methods. RESULTS: Five out of 32 (15.6%) OMD patients experienced symptoms of eating dysfunction associated with OMD. Significant weight loss was reported in 3/5 patients (ranged for 13–15 lbs). Two patients regained the lost weight after treatment and one was lost to follow-up. Tetrabenazine in combination with other antidystonic medication and/or botulinum toxin injections provided substantial benefit to the patients with dysphagia caused by OMD. CONCLUSION: Dystonic eating dysfunction may occasionally complicate OMD leading to weight loss. Its adequate characterization at the time of history taking and clinical examination should be part of outcome measurements of the anti-dystonic treatment in clinical practice

Case Report: Vasculitis Triggered by SIRT in a Patient With Previously Untreated Cholangiocarcinoma.

Arising from the biliary tract, cholangiocarcinoma is a rare and aggressive epithelial cancer. According to the primary site, it can be further classified into intrahepatic, perihilar and distal types. Due to the lack of symptoms early in the disease course, most patients are diagnosed at advanced stages. Being not candidates for curative surgical management, these patients are treated with palliative systemic chemotherapy, and their prognosis remains poor. Using radioisotopes like yttrium-90 -labeled microspheres ( <sup>90</sup> Y), radioembolization represents a local approach to treat primary and secondary liver tumors. In the case of intrahepatic cholangiocarcinoma, radioembolization can be used as a primary treatment, as an adjunct to chemotherapy or after failing chemotherapy. An 88-year-old man underwent radioembolization for a previously untreated stage II intrahepatic cholangiocarcinoma. One week later, he presented to our clinic with a non-pruritic maculopapular rash of the lower extremities and abdomen, worsening fatigue and low-grade fever. Laboratory exams, including hepatitis screening, were within normal limits. Showing positive immunofluorescence staining for immunoglobulin M (IgM) and complement 3 (C3) in vessel walls without IgA involvement, the skin biopsy results were compatible with leukocytoclastic vasculitis. Apart from the anticancer intervention, there have been no recent medication changes which could explain this complication. Notably, we did not observe any side effects during or after the perfusion scan with technetium-99m macroaggregated albumin (MAA) performed prior to radioembolization. The symptoms resolved quickly after a short course of colchicine and did not reappear at cholangiocarcinoma progression. In the absence of other evident causes, we conclude that the onset of leukocytoclastic vasculitis in our patient was directly linked to the administration of yttrium-90 -labeled microspheres. Our report therefore demonstrates that this condition can be a rare but manageable complication of <sup>90</sup> Y liver radioembolization

Signaling via interleukin-4, receptor alpha chain is required for successful vaccination against schistosomiasis in BALB/c mice

Radiation-attenuated (RA) schistosome larvae are potent stimulators of innate immune responses at the skin site of exposure (pinna) that are likely to be important factors in the development of Th1-mediated protective immunity. In addition to causing an influx of neutrophils, macrophages, and dendritic cells (DCs) into the dermis, RA larvae induced a cascade of chemokine and cytokine secretion following in vitro culture of pinna biopsy samples. While macrophage inflammatory protein 1 and interleukin-1 (IL-1) were produced transiently within the first few days, the Th1-promoting cytokines IL-12 and IL-18 were secreted at high levels until at least day 14. Assay of C3H/HeJ mice confirmed that IL-12 secretion was not due to lipopolysaccharide contaminants binding Toll-like receptor 4. Significantly, IL-12 p40 secretion was sustained in pinnae from vaccinated mice but not in those from nonprotected infected mice. In contrast, IL-10 was produced from both vaccinated and infected mice. This cytokine regulates IL-12-associated dermal inflammation, since in vaccinated IL-10/ mice, pinna thickness was greatly increased concurrent with elevated levels of IL-12 p40. A significant number of IL-12 p40 cells were detected as emigrants from in vitro-cultured pinnae, and most were within a population of rare large granular cells that were Ia, consistent with their being antigen-presenting cells. Labeling of IL-12 cells for CD11c, CD205, CD8, CD11b, and F4/80 indicated that the majority were myeloid DCs, although a proportion were CD11c F4/80, suggesting that macrophages were an additional source of IL-12 in the skin

Cellular and humoral immune responses and protection against schistosomes induced by a radiation-attenuated vaccine in chimpanzees

The radiation-attenuated Schistosoma mansoni vaccine is highly effective in rodents and primates but has never been tested in humans, primarily for safety reasons. To strengthen its status as a paradigm for a human recombinant antigen vaccine, we have undertaken a small-scale vaccination and challenge experiment in chimpanzees (Pan troglodytes). Immunological, clinical, and parasitological parameters were measured in three animals after multiple vaccinations, together with three controls, during the acute and chronic stages of challenge infection up to chemotherapeutic cure. Vaccination induced a strong in vitro proliferative response and early gamma interferon production, but type 2 cytokines were dominant by the time of challenge. The controls showed little response to challenge infection before the acute stage of the disease, initiated by egg deposition. In contrast, the responses of vaccinated animals were muted throughout the challenge period. Vaccination also induced parasite-specific immunoglobulin M (IgM) and IgG, which reached high levels at the time of challenge, while in control animals levels did not rise markedly before egg deposition. The protective effects of vaccination were manifested as an amelioration of acute disease and overall morbidity, revealed by differences in gamma-glutamyl transferase level, leukocytosis, eosinophilia, and hematocrit. Moreover, vaccinated chimpanzees had a 46% lower level of circulating cathodic antigen and a 38% reduction in fecal egg output, compared to controls, during the chronic phase of infection

A simple method to assess freezing of gait in Parkinson's disease patients

Freezing of gait (FOG) can be assessed by clinical and instrumental methods. Clinical examination has the advantage of being available to most clinicians; however, it requires experience and may not reveal FOG even for cases confirmed by the medical history. Instrumental methods have an advantage in that they may be used for ambulatory monitoring. The aim of the present study was to describe and evaluate a new instrumental method based on a force sensitive resistor and Pearson's correlation coefficient (Pcc) for the assessment of FOG. Nine patients with Parkinson's disease in the "on" state walked through a corridor, passed through a doorway and made a U-turn. We analyzed 24 FOG episodes by computing the Pcc between one "regular/normal" step and the rest of the steps. The Pcc reached +/- 1 for "normal" locomotion, while correlation diminished due to the lack of periodicity during FOG episodes. Gait was assessed in parallel with video. FOG episodes determined from the video were all detected with the proposed method. The computed duration of the FOG episodes was compared with those estimated from the video. The method was sensitive to various types of freezing; although no differences due to different types of freezing were detected. The study showed that Pcc analysis permitted the computerized detection of FOG in a simple manner analogous to human visual judgment, and its automation may be useful in clinical practice to provide a record of the history of FOG

Exploring Black and South Asian women's experiences of help-seeking and engagement in perinatal mental health services in the UK

Background and aims: In the United Kingdom (UK), Black and South Asian women are less likely than White British women to access support from perinatal mental health services, despite experiencing similar, or higher, levels of distress. This inequality needs to be understood and remedied. The aim of this study was to answer two questions: how do Black and South Asian women experience (1) access to perinatal mental health services and (2) care received from perinatal mental health services? Method: Semi-structured interviews were conducted with Black and South Asian women (n = 37), including four women who were interviewed with an interpreter. Interviews were recorded and transcribed line-by-line. Data were analyzed using framework analysis, by an ethnically diverse multidisciplinary team of clinicians, researchers and people with lived experience of perinatal mental illness. Results: Participants described a complex interplay of factors that impacted on seeking, and receiving help, and benefiting from services. Four themes emerged that captured the highly varied experiences of individuals: (1) Self-identity, social expectations and different attributions of distress deter help-seeking; (2) Hidden and disorganized services impede getting support; (3) The role of curiosity, kindness and flexibility in making women feel heard, accepted and supported by clinicians; (4) A shared cultural background may support or hinder trust and rapport. Conclusion: Women described a wide range of experiences and a complex interplay of factors impacting access to, and experience of, services. Women described services as giving them strength and also leaving them disappointed and confused about where to get help. The main barriers to access were attributions related to mental distress, stigma, mistrust and lack of visibility of services, and organizational gaps in the referral process. These findings describe that many women feel heard, and supported by services, reporting that services provide a high quality of care that was inclusive of diverse experiences and understandings of mental health problems. Transparency around what PMHS are, and what support is available would improve the accessibility of PMHS

Summation of reinforcement rates when conditioned stimuli are presented in compound

Three experiments used delay conditioning of magazine approach in rats to examine the summation of responding when two conditioned stimuli (CSs) are presented together as a compound. The duration of each CS varied randomly from trial-to-trial around a mean that differed between the CSs. This meant that the rats’ response rate to each CS was systematically related to the reinforcement rate of that CS, but remained steady as time elapsed during the CS (Harris & Carpenter, in press; Harris, Gharaei, & Pincham, in press). When the rats were presented with a compound of two CSs that had been conditioned separately, they responded more during the compound than during either of the CSs individually. More significantly, however, in all three experiments, the rats responded to the compound at the same rate as they responded to a third CS that had been reinforced at a rate equal to the sum of the reinforcement rates of the two CSs in compound. We discuss the implications of this finding for associative models (e.g., Rescorla & Wagner, 1972) and rate-based models (Gallistel & Gibbon, 2000) of conditioning.Grant DP1092695 from the Australian Research Counci