Quality of Life Changes Following the Onset of Cerebellar Ataxia: Symptoms and Concerns Self-reported by Ataxia Patients and Informants.

Semi-structured interviews of patient accounts and caregiver, or informant, perspectives are a beneficial resource for patients suffering from diseases with complex symptomatology, such as cerebellar ataxia. The aim of this study was to identify, quantify, and compare the ways in which cerebellar ataxia patients' and informants' quality of life had changed as a result of living with ataxia. Using a semi-structured interview, responses were collected from patients and informants regarding motor, cognitive, and psychosocial variables. Responses were also collected from patients and informants to open-ended questions that were subsequently categorized into 15 quality of life themes that best represented changes experienced by the patients and informants. Ataxia patients and informants agreed as to the severity of posture/gait, daily activities/fine motor tasks, speech/feeding/swallowing, and oculomotor/vision impairment. It was also demonstrated that severity ratings for specific motor-related functions strongly correlated with corresponding functions within the International Cooperative Ataxia Rating Scale (ICARS), and that this interview identified frequency associations between motor impairments and specific psychosocial difficulties, which could be useful for prognostic purposes. Overall, the information obtained from this study characterized the symptoms and challenges to ataxia patients and their caregivers, which could serve as a useful educational resource for those affected by ataxia, clinicians, and researchers.

The Cerebellum and Implicit Sequencing: Evidence from Cerebellar Ataxia.

The cerebellum recognizes sequences from prior experiences and uses this information to generate internal models that predict future outcomes in a feedforward manner [Front Hum Neurosci 8: 475, 2014; Cortex 47: 137-44, 2011; Cerebellum 7: 611-5, 2008; J Neurosci 26: 9107-16, 2006]. This process has been well documented in the motor domain, but the cerebellum's role in cognitive sequencing, within the context of implicit versus explicit processes, is not well characterized. In this study, we tested individuals with cerebellar ataxia and healthy controls to clarify the role of the cerebellum sequencing using variations on implicit versus explicit and motor versus cognitive demands across five experiments. Converging results across these studies suggest that cerebellar feedforward mechanisms may be necessary for sequencing in the implicit domain only. In the ataxia group, rhythmic tapping, rate of motor learning, and implicit sequence learning were impaired. However, for cognitive sequencing that could be accomplished using explicit strategies, the cerebellar group performed normally, as though they shifted to extra-cerebellar mechanisms to compensate. For example, when cognitive and motor functions relied on cerebellar function simultaneously, the ataxia group's motor function was unaffected, in contrast to that of controls whose motor performance declined as a function of cognitive load. These findings indicated that the cerebellum is not critical for all forms of sequencing per se. Instead, it plays a fundamental role for sequencing within the implicit domain, whether functions are motor or cognitive. Moreover, individuals with cerebellar ataxia are generally able to compensate for cognitive sequencing when explicit strategies are available in order to preserve resources for motor function.

Neuropsychiatric Symptoms as a Reliable Phenomenology of Cerebellar Ataxia.

While cerebellar ataxia (CA) is a neurodegenerative disease known for motor impairment, changes in mood have also been reported. A full account of neuropsychiatric symptomology in CA may guide improvements in treatment regimes, measure the presence and severity of sub-clinical neuropsychiatric disturbance symptomology in CA, and compare patient versus informant symptom recognition. Neuropsychiatric phenomena were gathered from CA patients with genetic and unknown etiologies and their informants (e.g., spouse or parent). Information was obtained from in-person interviews and the Center for Epidemiologic Studies Depression Scale. Responses were converted to the Neuropsychiatric Inventory-Questionnaire (NPI-Q) scores by consensus ratings. Patient NPI-Q scores were evaluated for symptom prevalence and severity relative to those obtained from healthy controls. Patient-informant NPI-Q score disagreements were evaluated. In this cohort, 95% of patients presented with at least one neuropsychiatric symptom and 51% of patients with three or more symptoms. The most common symptoms were anxiety, depression, nighttime behaviors (e.g., interrupted sleep), irritability, disinhibition, abnormal appetite, and agitation. The prevalence of these neuropsychiatric symptoms was uniform across patients with genetic versus unknown etiologies. Patient and informant symptom report disagreements reflected that patients noted sleep impairment and depression, while informants noted irritability and agitation. Neuropsychiatric disturbance is highly prevalent in patients with CA and contributes to the phenomenology of CA, regardless of etiology. Clinicians should monitor psychiatric health in their CA patients, considering that supplemental information from informants can help gauge the impact on family members and caregivers.

Visuospatial Organization and Recall in Cerebellar Ataxia.

Poor visuospatial skills can disrupt activities of daily living. The cerebellum has been implicated in visuospatial processing, and patients with cerebellar injury often exhibit poor visuospatial skills, as measured by impaired memory for the figure within the Rey-Osterrieth complex figure task (ROCF). Visuospatial skills are an inherent aspect of the ROCF; however, figure organization (i.e., the order in which the figure is reconstructed by the participant) can influence recall ability. The objective of this study was to examine and compare visuospatial and organization skills in people with cerebellar ataxia. We administered the ROCF to patients diagnosed with cerebellar ataxia and healthy controls. The cerebellar ataxia group included patients that carried a diagnosis of spinocerebellar ataxia (any subtype), autosomal dominant cerebellar ataxia, or cerebellar ataxia with unknown etiology. Primary outcome measures were organization and recall performance on the ROCF, with supplemental information derived from cognitive tests of visuospatial perception, working memory, processing speed, and motor function. Cerebellar ataxia patients revealed impaired figure organization relative to that of controls. Figure copy was impaired in the patients, but their subsequent recall performance was normal, suggesting compensation from initial organization and copying strategies. In controls, figure organization predicted recall performance, but this relationship was not observed in the patients. Instead, processing speed predicted patients' recall accuracy. Supplemental tasks indicated that visual perception was intact in the cerebellar ataxia group and that performance deficits were more closely tied to organization strategies than with visuospatial skills.

Characterization of basal ganglia volume changes in the context of HIV and polysubstance use.

HIV and psychoactive substances can impact the integrity of the basal ganglia (BG), a neural substrate of cognition, motor control, and reward-seeking behaviors. This study assessed BG gray matter (GM) volume as a function of polysubstance (stimulant and opioid) use and HIV status. We hypothesized that comorbid polysubstance use and HIV seropositivity would alter BG GM volume differently than would polysubstance use or HIV status alone. We collected structural MRI scans, substance use history, and HIV diagnoses. Participants who had HIV (HIV +), a history of polysubstance dependence (POLY +), both, or neither completed assessments for cognition, motor function, and risk-taking behaviors (N = 93). All three clinical groups showed a left-lateralized pattern of GM reduction in the BG relative to controls. However, in the HIV + /POLY + group, stimulant use was associated with increased GM volume within the globus pallidus and putamen. This surpassed the effects from opioid use, as indicated by decreased GM volume throughout the BG in the HIV-/POLY + group. Motor learning was impaired in all three clinical groups, and in the HIV + /POLY + group, motor learning was associated with increased caudate and putamen GM volume. We also observed associations between BG GM volume and risk-taking behaviors in the HIV + /POLY- and HIV-/POLY + groups. The effects of substance use on the BG differed as a function of substance type used, HIV seropositivity, and BG subregion. Although BG volume decreased in association with HIV and opioid use, stimulants can, inversely, lead to BG volume increases within the context of HIV.

Quantitative susceptibility mapping of basal ganglia iron is associated with cognitive and motor functions that distinguish spinocerebellar ataxia type 6 and type 3.

Background: In spinocerebellar ataxia type 3 (SCA3), volume loss has been reported in the basal ganglia, an iron-rich brain region, but iron content has not been examined. Recent studies have reported that patients with SCA6 have markedly decreased iron content in the cerebellar dentate, coupled with severe volume loss. Changing brain iron levels can disrupt cognitive and motor functions, yet this has not been examined in the SCAs, a disease in which iron-rich regions are affected. Methods: In the present study, we used quantitative susceptibility mapping (QSM) to measure tissue magnetic susceptibility (indicating iron concentration), structural volume, and normalized susceptibility mass (indicating iron content) in the cerebellar dentate and basal ganglia in people with SCA3 (n = 10) and SCA6 (n = 6) and healthy controls (n = 9). Data were acquired using a 7T Philips MRI scanner. Supplemental measures assessed motor, cognitive, and mood domains. Results: Putamen volume was lower in both SCA groups relative to controls, replicating prior findings. Dentate susceptibility mass and volume in SCA6 was lower than in SCA3 or controls, also replicating prior findings. The novel finding was that higher basal ganglia susceptibility mass in SCA6 correlated with lower cognitive performance and greater motor impairment, an association that was not observed in SCA3. Cerebellar dentate susceptibility mass, however, had the opposite relationship with cognition and motor function in SCA6, suggesting that, as dentate iron is depleted, it relocated to the basal ganglia, which contributed to cognitive and motor decline. By contrast, basal ganglia volume loss, rather than iron content, appeared to drive changes in motor function in SCA3. Conclusion: The associations of higher basal ganglia iron with lower motor and cognitive function in SCA6 but not in SCA3 suggest the potential for using brain iron deposition profiles beyond the cerebellar dentate to assess disease states within the cerebellar ataxias. Moreover, the role of the basal ganglia deserves greater attention as a contributor to pathologic and phenotypic changes associated with SCA.

A multimodal neuroimaging study of brain abnormalities and clinical correlates in post treatment Lyme disease.

Lyme disease is the most common vector-borne infectious disease in the United States. Post-treatment Lyme disease (PTLD) is a condition affecting 10-20% of patients in which symptoms persist despite antibiotic treatment. Cognitive complaints are common among those with PTLD, suggesting that brain changes are associated with the course of the illness. However, there has been a paucity of evidence to explain the cognitive difficulties expressed by patients with PTLD. This study administered a working memory task to a carefully screened group of 12 patients with well-characterized PTLD and 18 healthy controls while undergoing functional MRI (fMRI). A subset of 12 controls and all 12 PTLD participants also received diffusion tensor imaging (DTI) to measure white matter integrity. Clinical variables were also assessed and correlated with these multimodal MRI findings. On the working memory task, the patients with PTLD responded more slowly, but no less accurately, than did controls. FMRI activations were observed in expected regions by the controls, and to a lesser extent, by the PTLD participants. The PTLD group also hypoactivated several regions relevant to the task. Conversely, novel regions were activated by the PTLD group that were not observed in controls, suggesting a compensatory mechanism. Notably, three activations were located in white matter of the frontal lobe. DTI measures applied to these three regions of interest revealed that higher axial diffusivity correlated with fewer cognitive and neurological symptoms. Whole-brain DTI analyses revealed several frontal lobe regions in which higher axial diffusivity in the patients with PTLD correlated with longer duration of illness. Together, these results show that the brain is altered by PTLD, involving changes to white matter within the frontal lobe. Higher axial diffusivity may reflect white matter repair and healing over time, rather than pathology, and cognition appears to be dynamically affected throughout this repair process.

The association between educational attainment and SCA 3 age of onset and disease course.

BACKGROUND: The number of trinucleotide CAG repeats is inversely correlated with the age at onset (AAO) of motor symptoms in individuals with Spinocerebellar Ataxia type 3 (SCA 3) and may be responsible for 50%-60% of the variability in AAO. Drawing from a social determinants of health model, we sought to determine if educational attainment further contributes to the AAO and motor symptom progression of SCA 3. METHODS: We performed a retrospective chart review in which twenty individuals met criteria for inclusion and had been seen by an ataxia specialist at our hospital between January 2005 and July 2019. AAO of motor symptoms and Scale for Assessment and Rating of Ataxia (SARA) scores were used as primary outcome measures. RESULTS: Using a linear regression, we found that having greater CAG repeat length and greater than 16 years of education results in an earlier AAO. The importance of the CAG repeat length on AAO, however, is greater amongst individuals with lower education. Using a linear mixed model evaluating SARA score over time with AAO, we found that less than 16 years of education is associated with faster progression of the disease. CONCLUSION: In our group of SCA 3 patients, level of education correlated with both the AAO and SARA scores. Though our findings need to be confirmed with a larger cohort, our study suggests that level of education can have a strong influence on health outcomes in SCA 3 and possibly other groups of patients with ataxia.

Human visual consciousness involves large scale cortical and subcortical networks independent of task report and eye movement activity.

The full neural circuits of conscious perception remain unknown. Using a visual perception task, we directly recorded a subcortical thalamic awareness potential (TAP). We also developed a unique paradigm to classify perceived versus not perceived stimuli using eye measurements to remove confounding signals related to reporting on conscious experiences. Using fMRI, we discovered three major brain networks driving conscious visual perception independent of report: first, increases in signal detection regions in visual, fusiform cortex, and frontal eye fields; and in arousal/salience networks involving midbrain, thalamus, nucleus accumbens, anterior cingulate, and anterior insula; second, increases in frontoparietal attention and executive control networks and in the cerebellum; finally, decreases in the default mode network. These results were largely maintained after excluding eye movement-based fMRI changes. Our findings provide evidence that the neurophysiology of consciousness is complex even without overt report, involving multiple cortical and subcortical networks overlapping in space and time.

Rainfall and river flows are predictors for beta-glucuronidase positive Escherichia coil accumulation in mussels and Pacific oysters from the Dart Estuary (England).

Rainfall and river flows are environmental variables influencing the microbial status of bivalve mollusc harvesting areas. This study investigated spatial and temporal relationships between rainfall, river flows and concentrations of Escherichia coli in mussels (Mytilus spp.) and Pacific oysters (C. gigas) from three harvesting areas in the Dart Estuary over the period 1996-2009. Mussels growing on the riverbed were found to be more contaminated than oysters growing in the water column. A step change in the levels of the microbial indicator was identified in both species from all harvesting areas. The highest levels of E. coli were detected when total rainfall exceeded 2 mm and water levels in the main tributaries exceeded the mean flow. The magnitude of response in levels of E. coli to these hydrological events varied between species and monitoring points, but was consistently higher between the 3rd and 4th days after the rainfall event. This lag time is assumed to result from catchment topography and geology determining peak levels of runoff at the headwaters 12-24 h after rainfall events. It is considered that future risk management measures may include sampling targeting hydrograph events.

Inhaled nitrous oxide-induced functional B12 deficiency.

Recreational nitrous oxide (N2O) is commonly used among young people partly due to its low cost and accessibility, and awareness of its potential adverse effects is poor in this group. One such adverse effect is degeneration of the spinal cord due to its disruption of DNA synthesis by inactivating cobalamin (B12).A 19-year-old man presented to the emergency department with a 4-week history of worsening paraesthesia in his fingers and lower limbs, and weakness in the hands and lower limbs for 2 weeks. On examination, he had an ataxic gait, reduced power of grip strength and ankle movements, and impaired sensation in the lower limbs. An MRI brain and spine revealed myelopathy of the cervical and thoracic cord.On further questioning, he reported recreational N2O inhalation. His symptoms improved after stopping this and he was treated with supplementation of B vitamins. Education strategies regarding the risks of N2O misuse are indicated.

Pelvic injury is not just pelvic fracture.

Pelvic trauma is complex, most of current work centres around pelvic haemorrhage and fractures. It is important to remember that there is more anatomy in the pelvis than bones and vessels. A 29-year-old male patient was admitted after an Road Traffic Collision (RTC) where his motorbike T-boned a car. He was noted to have a traumatic dislocation of his right testicle, which spontaneously reduced in the emergency department and he was admitted for scrotal exploration and observation. Due to difficulty in mobilising postoperatively, he underwent an MRI, which showed diastasis of his pubis symphysis as well as left-sided adductor tendon rupture, not evident on his initial CT scan, and underwent pelvic fixation. Why should an emergency physician be aware of this? This case emphasises the alternate differentials with pelvic trauma in a haemodynamically stable patient, and the requirement for continuous reassessment in patients failing to improve.

How the motor system integrates with working memory.

Working memory is vital for basic functions in everyday life. During working memory, one holds a finite amount of information in mind until it is no longer required or when resources to maintain this information are depleted. Convergence of neuroimaging data indicates that working memory is supported by the motor system, and in particular, by regions that are involved in motor planning and preparation, in the absence of overt movement. These "secondary motor" regions are physically located between primary motor and non-motor regions, within the frontal lobe, cerebellum, and basal ganglia, creating a functionally organized gradient. The contribution of secondary motor regions to working memory may be to generate internal motor traces that reinforce the representation of information held in mind. The primary aim of this review is to elucidate motor-cognitive interactions through the lens of working memory using the Sternberg paradigm as a model and to suggest origins of the motor-cognitive interface. In addition, we discuss the implications of the motor-cognitive relationship for clinical groups with motor network deficits.

Risk factors for norovirus contamination of shellfish water catchments in England and Wales.

This study examines the relationships between concentrations of human noroviruses (NoV) genogroups I (GI) and II (GII) and Escherichia coli monitored in oysters from 31 commercial harvesting areas on the coast of England and Wales from May 2009 to April 2011 and demographic, hydrometric, climatic and pollution source characteristics of upstream river catchments using multiple regression techniques. The predictive environmental factors for E. coli contamination in the oysters were rainfall (cumulative 7days before sampling) while the predictive factors for NoV (GI+GII) were water temperature, catchment area and the combined volume of continuous sewage discharges in the catchment. Oysters from cold waters (<5°C) had significantly higher NoV content than those from warmer waters (>10°C). The association with water temperature may be consequential on the seasonal prevalence of the virus in the community or linked with oyster metabolic function. In a group of 10 study sites, mean concentrations of NoV increased as the number of stormwater spills at those sites also increased. The results of this study could be used to evaluate the likely impact of sewerage infrastructure improvements in catchments at risk of NoV contamination and to help identify sites suitable for shellfish farming.

International Retrovirology Association brings together scientists and clinicians to bridge discoveries about human T-lymphotropic viruses from the laboratory to clinical trials.

Human T-lymphotropic virus type 1 (HTLV-1) and HTLV-2 were among the first human retroviruses discovered in the early 1980's. The International Retrovirology Association is an organized effort that fostered the efforts of scientists and clinicians to form interdisciplinary groups to study this group of retroviruses and their related diseases. The Association promotes excellent science, patient education, and fosters the training of young scientists to promote "bench-to-bedside" research. The International Conference on Human Retrovirology: HTLV and Related Viruses sponsored by the Association supports clinicians and researchers in the exchange of research findings and stimulation of new research directions. This years conference will be held from June 22 to 25, in Montego Bay, Jamaica http://www.htlvconference.org.jm/. Since its inception in 1988, these conferences have provided a highly interactive forum for the global community of HTLV scientists. This is of particular importance as HTLV research enters its third decade and a new generation of scientists takes over this important work. Many of the scientists attending the meeting will be from developing countries where HTLV is endemic, consistent with the history of international collaborations that have characterized HTLV research. The International Conference on Human Retrovirology provides a unique opportunity for researchers of all disciplines interested in HTLV infections to meet their peers and to address the questions facing clinicians and scientists who study retroviruses, like HTLV.

Trends in the levels of Escherichia coli in commercially harvested bivalve shellfish from England and Wales, 1999-2008.

Temporal trends in Escherichia coli concentrations in bivalve shellfish were examined using data collected from 57 production areas around the coast of England and Wales during 1999-2008. Downward trends were detected in annual geometric means of E. coli in shellfish from 12% of the sampling points. The percentage of class B areas (E. coli ≤ 4600/100 g shellfish in 90% of samples) increased from 69% to 86% during the 10-year period. The improvement in the microbial quality of shellfish is associated with sewerage improvement schemes largely implemented during 2000-2005. Upward trends were detected in 9% of the points. The causes of these increases are not known. It is recommended that quantitative sanitary profiling of shellfish waters and cost-benefit appraisal over long-term planning horizons are considered as part of sewerage investment programmes under the Water Framework Directive. This would allow greater scope to secure protection and improvement of shellfish water quality.

Risk of human T-lymphotropic virus type I-associated diseases in Jamaica with common HLA types.

Human T-lymphotropic virus-I (HTLV-I) causes adult T-cell leukemia/lymphoma (ATL) and HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP). We postulated a higher disease risk for people with common human leukocyte antigen (HLA) types, due to a narrower immune response against viral or neoplastic antigens, compared to people with uncommon types. HLA class-I (A,B) and class-II (DRB1, DQB1) allele and haplotype frequencies in 56 ATL patients, 59 HAM/TSP patients and 190 population-based, asymptomatic HTLV-I-infected carriers were compared by logistic regression overall (score test) and with odds ratios (ORs) for common types (prevalence >50% of asymptomatic carriers) and by prevalence quartile. HTLV-I proviral load between asymptomatic carriers with common versus uncommon types was compared by t-test. ATL differed from asymptomatic carriers in overall DQB1 allele and class-I haplotype frequencies (p

Tuberculous encephalopathy: a rare complication of pulmonary tuberculosis

A case of tuberculous encephalopathy, a rare form of neurotuberculosis, is reported in a 16-year-old girl who had pulmonary tuberculosis and extensive cerebral demyelination. The clinical, laboratory and pathological features of this entity are highlighted and the pathogenesis discussed.

Amyotrophic lateral scherosis and antecedent poliomyelitis

Motor neurone disease may occur in patients with antecedent, sometimes remote, paralytic poliomyelitis. A Jamaican patient with this sequence is described. Research exploring the relationship between the two diseases is giving a new insight into the aetiology of motor neurone disease.