Clinical Characteristics and Management of 50 Patients with Anti-GAD Ataxia: Gluten-Free Diet Has a Major Impact.

The objective of this study is to report the clinical characteristics and treatment of patients with progressive cerebellar ataxia associated with anti-GAD antibodies. We performed a retrospective review of all patients with anti-GAD ataxia managed at the Sheffield Ataxia Centre over the last 25 years. We identified 50 patients (62% females) with anti-GAD ataxia. The prevalence was 2.5% amongst 2000 patients with progressive ataxia of various causes. Mean age at onset was 55 and mean duration 8 years. Gaze-evoked nystagmus was present in 26%, cerebellar dysarthria in 26%, limb ataxia in 44% and gait ataxia in 100%. Nine patients (18%) had severe, 12 (24%) moderate and 29 (58%) mild ataxia. Ninety percent of patients had a history of additional autoimmune diseases. Family history of autoimmune diseases was seen in 52%. Baseline MR spectroscopy of the vermis was abnormal at presentation in 72%. Thirty-five patients (70%) had serological evidence of gluten sensitivity. All 35 went on gluten-free diet (GFD). Eighteen (51%) improved, 13 (37%) stabilised, 3 have started the GFD too recently to draw conclusions and one deteriorated. Mycophenolate was used in 16 patients, 7 (44%) improved, 2 stabilised, 6 have started the medication too recently to draw conclusions and one did not tolerate the drug. There is considerable overlap between anti-GAD ataxia and gluten ataxia. For those patients with both, strict GFD alone can be an effective treatment. Patients with anti-GAD ataxia and no gluten sensitivity respond well to immunosuppression.

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.

The neurobiology under the placebo effect.

The placebo effect is a phenomenon of great scientific interest that affects the response in both inactive and active treatments. It is broadly understood as the product of a central integration of positive expectations, reward learning and continuous conditioning inducing physiological changes in the brain. The placebo effect is accepted as a phenomenon which can be harnessed in clinical practice. It has emerged that there is not a single neurobiological mechanism involved in placebo responses, but many depending on the underlying disease. Molecular neuroimaging techniques with positron emission tomography and selective radiotracers have been significant in the understanding of the neurobiological systems involved in the placebo effect. The aim of this review was to summarize the key findings relating to the neurobiology behind the placebo effect.

Subspecialty preferences among neurologists of the future.

BACKGROUND AND PURPOSE: In the era of neurological subspecialization, most neurologists will have a field of specialist interest. The aim of this cross-sectional multinational study was to identify the key areas of interest among trainees or junior specialists, assess the potential influence of an interest in research and consider the results in light of population needs. METHODS: A total of 300 residents and junior neurologists who received a bursary to attend the European Academy of Neurology conference were invited to participate in this study. Demographic and work-related characteristics, as well as main subspecialty of choice, were examined via an anonymous electronic questionnaire. Participants holding a higher degree (PhD/MD) or working in research posts were considered research oriented. RESULTS: In total, 191 neurologists in training or junior specialists responded (response rate 63.7%). Full data were available for 187 participants (59.4% females). The study sample had a mean age of 30.5 ± 3.4 (range 25-45) years. The most popular subspecialty was movement disorders (18.2%), followed by multiple sclerosis (11.2%) and epilepsy (10.2%). This did not differ significantly between the participants who were or were not research oriented. CONCLUSIONS: There is a potential mismatch between the interests of trainees and the future needs of the populations they serve, which is important to identify for workforce planning.

Insufficient global health education in European neurological post-graduate training: a European Association of Young Neurologists and Trainees survey.

BACKGROUND AND PURPOSE: The awareness of and demand for neurological expertise in global health (GH) have emerged over recent years and have become more relevant due to the increasing numbers of refugees from developing countries arriving in Europe. This study aimed to assess the provision of GH education and opportunities for international exchange during neurology post-graduate training with a focus on Europe. METHODS: We developed a questionnaire covering different aspects of and interest in GH education on behalf of the European Association of Young Neurologists and Trainees. Residents in neurology and junior neurologists (RJN) were approached to complete this survey. RESULTS: Completed questionnaires were returned by 131 RJNs, of whom 65.7% were women and 84.0% were between 26 and 35 years old. In total, almost one-third (29.0%) of RJNs reported that their residency programs offered training in GH. Limited education was reported for women's or children's health and neurological disorders of immigrants and refugees, as only 22.1%, 25.2% and 22.1% of RJNs reported that such training was offered, respectively. The curriculum rarely included coverage of the global impact of neurological disorders. Definite plans to volunteer in a developing country were reported by 7.6%. The majority of the participants acknowledged the importance of GH training and international exchange during post-graduate education. CONCLUSION: This survey corroborates the interest in and appreciation of GH education by European RJNs. However, there are shortcomings in training and opportunities for international exchange. Academic neurology and international bodies, including the European Academy of Neurology, are requested to address this.

Non-motor symptoms burden in treated and untreated early Parkinson's disease patients: argument for non-motor subtypes.

BACKGROUND AND PURPOSE: Non-motor symptoms (NMSs) occurring at an early stage of Parkinson's disease (PD) may impair quality of life more than motor symptoms. This study aimed to evaluate the severity of overall NMS profile and burden of NMSs in early PD patients, treated (time since confirmed diagnosis of 5 years or less) or drug naive (DN). METHODS: Cross-sectional data from an ongoing multicentre study (16 sites) were obtained and specifically an NMS data set from validated scales was analysed in treated and DN PD patients. RESULTS: A full data set was available in 234 unique early PD patients. Of them, there were 170 treated (63.5% males, mean age 68.2 years) and 64DN patients (64.1% males, mean age 66.5 years). Compared to DN patients the time since confirmed diagnosis was significantly longer in treated PD patients (1.9 years vs. 3.7 years, P < 0.001). Fatigue (57.7%), urinary urgency (57.1%), nocturia (55.3%), memory difficulties (51.2%) and urinary frequency (48.8%) were the most prevalent NMSs amongst treated PD, whereas DN PD reported most frequently sadness (57.8%), fatigue (57.8%), lightheadedness (53.1%), memory difficulties (48.4%) and urinary urgency (46.9%). CONCLUSIONS: Our results suggest that NMSs are dominant in the untreated and early phase of PD causing a considerable burden. This warrants investigation of the issue of NMS subtyping within PD.

An association of lower serum citrulline levels within 30 days of acute rejection in patients following small intestine transplantation.

INTRODUCTION: In a prospective protocol we studied whether serum citrulline level within 30 days of an acute rejection was predictive of the episode. METHODS: An acute rejection episode was defined as the date of occurrence of any biopsy-proven rejection in which treatment was initiated until two successive biopsies showed no further rejection. We compared the mean citrulline level based on values determined within 30 days of the start of an acute rejection episode with the mean citrulline level measured on the same patient during a rejection-free period. Serum citrulline measurements were available immediately prior to the occurrence of rejection for 22 patients who experienced 37 episodes. RESULTS: For the 12 episodes of mild rejection, the mean serum citrulline level +/- SE (standard error) was 15.0 + 2.3 micromol/L prior to rejection and 18.8 +/- 2.4 micromol/L during the rejection-free periods. A paired t test of the mean differences was not significant (P = 17). For the 25 episodes of moderate or severe rejection, the mean serum citrulline level was 12.4 +/- 1.1 micromol/L before rejection and 18.8 +/- 2.0 micromol/L during the rejection-free periods. A paired t test of the mean difference was statistically significant (P = .002). CONCLUSIONS: Although further study of citrulline as a marker for the early detection of acute rejection episodes is needed, our hope is that its use will help to prevent some of these early episodes from evolving into full-blown moderate or severe grades of rejection.

Frontal lobe dysfunction in amyotrophic lateral sclerosis.

The aim of the present study was to investigate the involvement of frontal lobe dysfunction in amyotrophic lateral sclerosis (ALS) using ocular motor paradigms and neuropsychological testing. Fifty-one patients with ALS participated in the following ocular motor tasks: (1) a three-choice task and (2) a remembered saccade task. The patients underwent a clinical and neuropsychological evaluation. One-third of ALS patients presented with signs of frontal dysfunction, as determined by their high distractibility factors (DF) in the three-choice task and their performances in both the Wisconsin and Stroop tests. ALS patients exhibited longer latencies to eye movement than controls in the performance of the remembered saccade task, specifically in performance of both remembered and delayed saccades, but saccade accuracy was not impaired. Finally, performance indices of the ocular motor tasks, in particular the DF, was correlated only with the degree of dysarthria.

The epilepsy of Emperor Michael IV, Paphlagon (1034-1041 A.D.): accounts of Byzantine historians and physicians.

PURPOSE: Presentation of epilepsy suffered by Byzantine Emperor Michael IV, Paphlagon (who reigned from 1034 to 1041 A.D.) and the attitude of his contemporary society to his disorder. METHODS: Research into the accounts of Byzantine historians and chroniclers referring to the case of the emperor and Byzantine medical texts revealing the opinion of official medicine about the disorder. RESULTS: Byzantine historians and chroniclers provide detailed clinical descriptions of the seizures of Emperor Michael IV. Nearly all, expressing popular opinion, considered his disease to be demonic possession that constituted a form of divine punishment for the emperor's adultery and act of murder; his royal entourage continually attempted euphemistically to present this condition as a psychic disease. On the contrary, research into Byzantine medical texts reveals that the physicians, already from the 4th century, following Hippocratic tradition, believed that epilepsy was primarily a brain-related disorder and based their treatment on this etiological principle. CONCLUSIONS: From the study of the Byzantine histories and chronicles, it can be deduced that Emperor Michael IV, Paphlagon, suffered from generalized tonic-clonic epileptic seizures. Despite the concept then held by well-educated Byzantine doctors, who considered epilepsy a brain disorder, information indicates the deep prejudices of his social environment.