Treatment of primary autoimmune cerebellar ataxia with mycophenolate

Immune-mediated ataxias account for a substantial number of sporadic otherwise idiopathic ataxias. Despite some well-characterised entities such as paraneoplastic cerebellar degeneration where diagnostic markers exist, the majority of immune ataxias remained undiagnosed and untreated. We present here our experience in the treatment of suspected primary autoimmune cerebellar ataxia (PACA) using mycophenolate. All patients reported attend the Sheffield Ataxia Centre on a regular basis and had undergone extensive investigations, including genetic testing using next-generation sequencing, with other causes of ataxia excluded. The diagnosis of PACA was strongly suspected based on investigations, pattern of disease progression, and cerebellar involvement. Patients were treated with mycophenolate and monitored using MR spectroscopy of the cerebellar vermis. Thirty patients with PACA are reported here. Of these, 22 received mycophenolate (group 1). The remaining 8 were not on treatment (group 2-control group). Out of the 22 treated patients, 4 underwent serial MR spectroscopy prior to starting treatment and thus were used as controls making the total number of patients in the control group 12. The mean change of the MRS within the vermis (NAA/Cr area ratio) in the treatment group was + 0.144 ± 0.09 (improved) and in the untreated group − 0.155 ± 0.06 (deteriorated). The difference was significant. We also demonstrated a strong correlation between the spectroscopy and the SARA score. We have demonstrated the effectiveness of mycophenolate in the treatment of PACA. The results suggest that immune-mediated ataxias are potentially treatable, and that there is a need for early diagnosis to prevent permanent neurological deficit. The recently published diagnostic criteria for PACA would hopefully aid the diagnosis and treatment of this entity

Extraintestinal Manifestations of Coeliac Disease

Coeliac Disease (CD) affects at least 1% of the population. “Classical” CD refers to gastrointestinal presentations with anaemia and gastrointestinal symptoms. CD can, however, present with extraintestinal manifestations, the commonest of which are dermatitis herpetiformis and neurological presentations (e.g., ataxia, neuropathy, encephalopathy). Recognition and research into the pathophysiology of such manifestations is likely to enhance our understanding of this complex autoimmune disorder

Alcohol-related cerebellar degeneration: not all down to toxicity?

Background: Alcohol-related cerebellar degeneration is one of the commonest acquired forms of cerebellar ataxia. The exact pathogenic mechanisms by which alcohol leads to cerebellar damage remain unknown. Possible autoreactive immune mediated mechanisms have not been explored previously. In this study, we aim to investigate the potential role of alcohol-induced immune mediated cerebellar degeneration. Methods: Patients with ataxia and a history of alcohol misuse were recruited from the Ataxia and Hepatology tertiary clinics at Sheffield Teaching Hospitals NHS Trust. We determined the pattern of cerebellar involvement both on clinical (SARA score) and imaging (MRI volumetry and MR spectroscopy) parameters. In addition, HLA genotyping, serological markers for gluten-related disorders and serological reactivity on rat cerebellar tissue using indirect immunohistochemistry were assessed. Results: Thirty-eight patients were included in the study all of whom had ataxia. The gait (97 %), stance (89 %) and heel-shin slide (89 %) were the predominant SARA elements affected. MRI volumetric and spectroscopy techniques demonstrated significant structural, volumetric and functional deficits of the cerebellum with particular involvement of the cerebellar vermis. Circulating anti-gliadin antibodies were detected in 34 % patients vs. 12 % in healthy controls. Antibodies to transglutaminase 6 (TG6) were detected in 39 % of patients and 4 % of healthy control subjects. Using immunohistochemistry, Purkinje cell and/or granular layer reactivity was demonstrated in 71 % of patient sera. Conclusions: Alcohol induced tissue injury to the CNS leading to cerebellar degeneration may also involve immune mediated mechanisms, including sensitisation to gluten

Feasibility and acceptability of Lee Silverman voice treatment in progressive ataxias

Communication difficulties have considerable impact on people with progressive ataxia, yet there are currently no evidence-based treatments. LSVT LOUD® focuses on the production of healthy vocal loudness whilst also improving breath support, vocal quality, loudness and articulation in participating patients. This study aimed to investigate whether Lee Silverman Voice Treatment (LSVT LOUD®) can improve communication effectiveness in these patients. We performed a rater-blinded, single-arm study investigating LSVT LOUD® treatment in a population of patients with progressive ataxia including Friedreich’s ataxia (n = 18), spinocerebellar ataxia type 6 (n = 1), idiopathic cerebellar ataxia (n = 1), and spastic paraplegia 7 (n = 1). Twenty-one patients were recruited to the study, with 19 completing treatment. Sessions were administered via Skype in the LSVT-X format, meaning two sessions per week over a period of 8 weeks. Assessments included two baseline and two post-treatment measures and focused on outcome measures covering aspects ranging from physiological function to impact and participation. Results indicate improvements in patient-perceived outcomes for 14 of the 19 participants, in both speech and psychosocial domains. Speech data furthermore demonstrate significant improvements in prolonged vowel duration, and voice quality measures. Intelligibility and naturalness evaluations showed no change post-treatment. Patients reported high acceptability of the treatment itself, as well as administration by Skype. This is the largest treatment study for people with progressive ataxia published to date. It provides an indication that LSVT LOUD® can have a positive impact on communication in this patient group and could form the basis for larger-scale trials

Psychiatric manifestations of coeliac disease, a systematic review and meta-analysis

Background: Coeliac disease (CD) is increasingly prevalent and is associated with both gastrointestinal (GI) and extra-intestinal manifestations. Psychiatric disorders are amongst extra-intestinal manifestations proposed. The relationship between CD and such psychiatric disorders is not well recognised or understood. Aim: The aim of this systematic review and meta-analysis was to provide a greater understanding of the existing evidence and theories surrounding psychiatric manifestations of CD. Methodology: An online literature search using PubMed was conducted, the prevalence data for both CD and psychiatric disorders was extracted from eligible articles. Meta analyses on odds ratios were also performed. Results: A total of 37 articles were included in this review. A significant increase in risk was detected for autistic spectrum disorder (OR 1.53, 95% CI 1.24–1.88, p < 0.0001), attention deficit hyperactivity disorder (OR 1.39, 95% CI 1.18–1.63, p < 0.0001), depression (OR 2.17, 95% CI 2.17–11.15, p < 0.0001), anxiety (OR 6.03, 95% CI 2.22–16.35, p < 0.0001), and eating disorders (OR 1.62, 95% CI 1.37–1.91, p < 0.00001) amongst the CD population compared to healthy controls. No significant differences were found for bipolar disorder (OR 2.35, 95% CI 2.29–19.21, p = 0.43) or schizophrenia (OR 0.46, 95% CI 0.02–10.18, p = 0.62). Conclusion: CD is associated with an increased risk of depression, anxiety, eating disorders as well as ASD and ADHD. More research is required to investigate specific biological explanations as well as any effect of gluten free diet

Plus ça change...? Innovation and continuity in UK youth employment policy during the Great Recession

In response to rising youth unemployment in the context of the Great Recession, the UK introduced since 2010 numerous policy innovations in of its youth transitional labour market policy, focusing especially on Active Labour Market Policies (ALMPs) and Vocational Education and Training (VET). But is the intense reform activity indicative of a significant path-shift in policy trajectory in a direction of greater social investment, when considered against the UK’s pre-crisis institutional legacy? Focusing on key measures implemented in England between 2010 and 2015, we draw on Hall (1993) ‘degrees of change’ conceptual framework to analyse the content of recent policy innovations and assess their relative degree of continuity with the UK’s characteristic features as a ‘liberal youth transitions’ regime (Pohl and Walther, 2007). We find that despite significant changes in policy instruments’ design, the UK’s policy goals and overall youth transition model exhibit striking continuity with the pre-crisis period. In the dimension of ALMPs, we find continued emphasis on supply-side policies aimed at encouraging young people’s early labour market entry, prioritising work experience and early activation. VET shows signs of potential paradigmatic change, with numerous measures seeking to significantly transform the VET status and level of employer involvement. However, the depth of institutional change is limited, as evidence suggests continued employer resistance to stronger coordination mechanisms and a more active role as VET providers rather than consumers