Are intravitreal injections essential during the COVID-19 pandemic? Global preferred practice patterns and practical recommendations.

Tertiary outpatient ophthalmology clinics are high-risk environments for COVID-19 transmission, especially retina clinics, where regular follow-up is needed for elderly patients with multiple comorbidities. Intravitreal injection therapy (IVT) for chronic macular diseases, is one of the most common procedures performed, associated with a significant burden of care because of the vigorous treatment regimen associated with multiple investigations. While minimizing the risk of COVID-19 infection transmission is a priority, this must be balanced against the continued provision of sight-saving ophthalmic care to patients at risk of permanent vision loss. This review aims to give evidence-based guidelines on managing IVT during the COVID-19 pandemic in common macular diseases such as age-related macular degeneration, diabetic macula edema and retinal vascular disease and to report on how the COVID-19 pandemic has affected IVT practices worldwide.To illustrate some real-world examples, 18 participants in the International Retina Collaborative, from 15 countries and across four continents, were surveyed regarding pre- and during- COVID-19 pandemic IVT practices in tertiary ophthalmic centers. The majority of centers reported a reduction in the number of appointments to reduce the risk of the spread of COVID-19 with varying changes to their IVT regimen to treat various macula diseases. Due to the constantly evolving nature of the COVID-19 pandemic, and the uncertainty about the normal resumption of health services, we suggest that new solutions for eye healthcare provision, like telemedicine, may be adopted in the future when we consider new long-term adaptations required to cope with the COVID-19 pandemic.

Dentin Staining Caused by Nano-silver Fluoride: A Comparative Study.

CLINICAL RELEVANCE: The new formulations of nano-silver fluoride caused less dentin staining than the already available commercial agents 35% silver fluoride and silver diamine fluoride at 30% and 38%. SUMMARY: The objective of this study was to evaluate the dentin staining potential of nano-silver fluoride (NSF 600 and 1500 ppm) compared with the following commercially available cariostatic agents: Advantage Arrest (Elevate Oral Care, West Palm Beach, FL, USA), Riva Star (SDI, Victoria, Australia), and Cariestop (Biodinâmica, Paraná, Brazil). Seventy-five extracted human molars were sectioned at the cementoenamel junction, and the occlusal enamel was removed for exposure of coronary dentin. The samples were divided among the five agents tested (n=15). The dentin staining (ΔE/ΔL) was analyzed with a digital spectrophotometer (VITA Easyshade, VITA Zahnfabrik, Bad Säckingen, Germany) at three different time points (before application, after two weeks, and after four weeks). Photographic images were also performed. The Kruskal-Wallis and Mann-Whitney tests compared the mean ΔE and ΔL values between groups. The NSF 600 and 1500 ppm resulted in the smallest color change (ΔE=1.02 and 1.53) and dentin staining after four weeks (ΔL=-0.76 and -1.2). The new formulations differed significantly from the commercial cariostatic agents (p<0.001). NSF might be an alternative to silver diamine fluoride since it does not compromise esthetics.

2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty

OBJECTIVE: This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence-based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA). METHODS: A panel of rheumatologists, orthopedic surgeons specializing in hip and knee arthroplasty, and methodologists was convened to construct the key clinical questions to be answered in the guideline. A multi-step systematic literature review was then conducted, from which evidence was synthesized for continuing versus withholding antirheumatic drug therapy and for optimal glucocorticoid management in the perioperative period. A Patient Panel was convened to determine patient values and preferences, and the Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence and the strength of recommendations, using a group consensus process through a convened Voting Panel of rheumatologists and orthopedic surgeons. The strength of the recommendation reflects the degree of certainty that benefits outweigh harms of the intervention, or vice versa, considering the quality of available evidence and the variability in patient values and preferences. RESULTS: The guideline addresses the perioperative use of antirheumatic drug therapy including traditional disease-modifying antirheumatic drugs, biologic agents, tofacitinib, and glucocorticoids in adults with RA, SpA, JIA, or SLE who are undergoing elective THA or TKA. It provides recommendations regarding when to continue, when to withhold, and when to restart these medications, and the optimal perioperative dosing of glucocorticoids. The guideline includes 7 recommendations, all of which are conditional and based on low- or moderate-quality evidence. CONCLUSION: This guideline should help decision-making by clinicians and patients regarding perioperative antirheumatic medication management at the time of elective THA or TKA. These conditional recommendations reflect the paucity of high-quality direct randomized controlled trial data.

2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty

OBJECTIVE: This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence-based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA). METHODS: A panel of rheumatologists, orthopedic surgeons specializing in hip and knee arthroplasty, and methodologists was convened to construct the key clinical questions to be answered in the guideline. A multi-step systematic literature review was then conducted, from which evidence was synthesized for continuing versus withholding antirheumatic drug therapy and for optimal glucocorticoid management in the perioperative period. A Patient Panel was convened to determine patient values and preferences, and the Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence and the strength of recommendations, using a group consensus process through a convened Voting Panel of rheumatologists and orthopedic surgeons. The strength of the recommendation reflects the degree of certainty that benefits outweigh harms of the intervention, or vice versa, considering the quality of available evidence and the variability in patient values and preferences. RESULTS: The guideline addresses the perioperative use of antirheumatic drug therapy including traditional disease-modifying antirheumatic drugs, biologic agents, tofacitinib, and glucocorticoids in adults with RA, SpA, JIA, or SLE who are undergoing elective THA or TKA. It provides recommendations regarding when to continue, when to withhold, and when to restart these medications, and the optimal perioperative dosing of glucocorticoids. The guideline includes 7 recommendations, all of which are conditional and based on low- or moderate-quality evidence. CONCLUSION: This guideline should help decision-making by clinicians and patients regarding perioperative antirheumatic medication management at the time of elective THA or TKA. These conditional recommendations reflect the paucity of high-quality direct randomized controlled trial data.

Maxillary unicystic ameloblastoma in a 6-week-old filly evaluated with computed tomography.

CASE REPORT: A 6-week-old Thoroughbred filly was presented for evaluation of an expansile mass overlying the right nasal passage and causing respiratory stertor. On skull radiographs, there was a loculated, soft tissue-opaque mass identified dorsal to the right upper premolars and effacing the right nasal cavity. Computed tomography (CT) revealed a locally extensive mass with relatively benign characteristics located centrally on the tooth root apices of the deciduous second premolar (506). The mass extended axially into the right nasal cavity, occluding the meatuses and causing displacement of the nasal septum to the left. CLINICAL OUTCOME & SIGNIFICANCE: Surgical excision was not deemed feasible with an athletic future in mind and the owners elected to euthanase the filly. Histopathologically, the mass was consistent with unicystic ameloblastoma and was lined intermittently with palisading, columnar basal cells (ameloblast-like cells) overlying a zone containing stellate cells in loose stroma. To the authors' knowledge this is the first report of a CT scan of an equine ameloblastoma. Although histopathology was essential for definitive diagnosis, CT clearly defined the origin of the mass and identified its locally extensive, cystic nature, which enabled informed decisions to be made.

Observation of interaction-induced modulations of a quantum Hall liquid's area.

Studies of electronic interferometers, based on edge-channel transport in the quantum Hall effect regime, have been stimulated by the search for evidence of abelian and non-abelian anyonic statistics of fractional charges. In particular, the electronic Fabry-Pérot interferometer has been found to be Coulomb dominated, thus masking coherent Aharonov-Bohm interference patterns: the flux trapped within the interferometer remains unchanged as the applied magnetic field is varied, barring unobservable modulations of the interference area. Here we report on conductance measurements indicative of the interferometer's area 'breathing' with the variation of the magnetic field, associated with observable (a fraction of a flux quantum) variations of the trapped flux. This is the result of partial (controlled) screening of Coulomb interactions. Our results introduce a novel experimental tool for probing anyonic statistics.

Robust electron pairing in the integer quantum hall effect regime.

Electron pairing is a rare phenomenon appearing only in a few unique physical systems; for example, superconductors and Kondo-correlated quantum dots. Here, we report on an unexpected electron pairing in the integer quantum Hall effect regime. The pairing takes place within an interfering edge channel in an electronic Fabry-Perot interferometer at a wide range of bulk filling factors, between 2 and 5. We report on three main observations: high-visibility Aharonov-Bohm conductance oscillations with magnetic flux periodicity equal to half the magnetic flux quantum; an interfering quasiparticle charge equal to twice the elementary electron charge as revealed by quantum shot noise measurements, and full dephasing of the pairs' interference by induced dephasing of the adjacent inner edge channel-a manifestation of inter-channel entanglement. Although this pairing phenomenon clearly results from inter-channel interaction, the exact mechanism that leads to electron-electron attraction within a single edge channel is not clear. We believe that substantial efforts are needed in order to clarify these intriguing and unexpected findings.

Impact of liver fibrosis on prognosis following liver resection for hepatitis B-associated hepatocellular carcinoma.

BACKGROUND: This study aims to evaluate the impact of liver fibrosis severity on prognosis following liver resection among HBV-HCC patients. METHODS: Data were extracted from a prospective database of 189 HBV-HCC patients treated at Mount Sinai between 1995 and 2008. Fibrosis staging of each surgical resection specimen using the modified Ishak method was performed by a single liver pathologist. RESULTS: A wide range of Ishak fibrosis stage was observed among this patient population, with 29% having established cirrhosis (Ishak stage 6). Ishak stage 6 was independently associated with poor overall and recurrence-free survival. In patients with Ishak stage 1-5, Ishak stage did not affect survival; rather, tumour size was associated with poor overall survival, and tumour size, histologic activity index and serum AFP>20 ng ml(-1) were associated with poor recurrence-free survival. In patients with Ishak stage 6, poorly differentiated histology and tumour size were associated with poor overall survival, and tumour size was associated with poor recurrence-free survival. CONCLUSION: HBV-HCC develops with varying degrees of underlying liver fibrosis; however, progressive liver fibrosis does not affect the outcomes following resection until cirrhosis is reached. Established cirrhosis, as defined histologically by Ishak stage 6, is an independent predictor of poor overall and recurrence-free survival among these patients.

Local and systemic adverse effects of imiquimod therapy for external anogenital warts in men: report of three cases.

Imiquimod is a topical immune response modifier used to treat anogenital warts. Although considered a safe drug, mild to moderate local and systemic side-effects may occasionally occur. We report three cases of local and systemic adverse effects related to imiquimod, including one case that mimicked meningitis, which promptly resolved with drug cessation.

The relationship of enamel defects and caries: a cohort study.

OBJECTIVE: Is there a relationship between enamel defects and early childhood caries? METHODS: A total of 275 children participated in a cohort study from birth to 54 months of age. Enamel defects were determined by the development defects enamel index and dental caries was registered according to the WHO criteria. Data were analyzed using descriptive, analytical techniques, multivariate analysis, and evidence-based tools as number needed to harm (NNH). RESULTS: In the follow up, 224 children were still in the study, 81.3% presented at least one tooth with enamel defect and 44.2% had dental caries. An association was found between enamel defects and dental caries (P = 0.0091). Multivariate analysis showed that night bottle-feeding, absence of fluoride and enamel defects were predictors of dental caries at 18 months (P < 0.05). Enamel defect was the only statistically significant variable to influence the development of caries at 24, 30, 36, and 42 months. At 48 months, the use of fluoride toothpaste had effect on the decrease of caries (P < 0.05). The NNH for enamel defects in relation to dental caries was 3.0, at 24 months and 5.0 at 54 months. CONCLUSION: Enamel defect is a predisposing factor for ECC.

Prevalence of enamel defects related to pre-, peri- and postnatal factors in a Brazilian population.

OBJECTIVES: The aim of this paper is to evaluate the prevalence of enamel defects in infants from a socially and economically poor population and the possible association of these defects with disturbances occurring in the pre-, peri- and postnatal periods of human development. PARTICIPANTS: 117 infants aged between 16 and 18 months old were included in four groups based on gestational age and whether part or full term pregnancy. METHOD: The data were collected in two stages: hospital-based, where gestational and birth records were examined, and home-based, where dental examinations and nutrition were evaluated. The teeth were cleaned and dried with gauze and examined in the open air, avoding direct sunlight in the knee-to-knee position. The enamel defects were coded according to the modified Developmental Defects of Enamel Index. Besides this, body weight and height were considered as anthropometric measures for the evaluation of nutritional status by the National Center for Health Statistics standards. MAIN OUTCOME MEASURES: The data were analyzed using the chi-square and Fisher Exact tests. Besides these tests, logistic regression models were used. RESULTS: The prevalence of enamel defects was 49.6%, higher in the group of male infants (p<0.001). The most frequent type of defect and the most affected surface were, respectively, diffuse opacity (9.5%) and the buccal surface (83.3%), located in the gingival half (6.7%). The logistic regression model showed that educational level, gestational age and intrauterine growth retardation (IUGR), besides a lack of breastfeeding, increased the probability of enamel defects up to level of 5%. CONCLUSIONS: The association between enamel defects and the etiologic factors shown in this study suggest the existence of social influences regarding oral health and teeth development.

Silver diamine fluoride: a caries "silver-fluoride bullet".

The antimicrobial use of silver compounds pivots on the 100-year-old application of silver nitrate, silver foil, and silver sutures for the prevention and treatment of ocular, surgical, and dental infections. Ag(+) kills pathogenic organisms at concentrations of <50 ppm, and current/potential anti-infective applications include: acute burn coverings, catheter linings, water purification systems, hospital gowns, and caries prevention. To distill the current best evidence relative to caries, this systematic review asked: Will silver diamine fluoride (SDF) more effectively prevent caries than fluoride varnish? A five-database search, reference review, and hand search identified 99 human clinical trials in three languages published between 1966 and 2006. Dual review for controlled clinical trials with the patient as the unit of observation, and excluding cross-sectional, animal, in vitro studies, and opinions, identified 2 studies meeting the inclusion criteria. The trials indicated that SDF's lowest prevented fractions for caries arrest and caries prevention were 96.1% and 70.3%, respectively. In contrast, fluoride varnish's highest prevented fractions for caries arrest and caries prevention were 21.3% and 55.7%, respectively. Similarly, SDF's highest numbers needed to treat for caries arrest and caries prevention were 0.8 (95% CI=0.5-1.0) and 0.9 (95% CI=0.4-1.1), respectively. For fluoride varnish, the lowest numbers needed to treat for caries arrest and prevention were 3.7 (95% CI=3.4-3.9) and 1.1 (95% CI=0.7-1.4), respectively. Adverse events were monitored, with no significant differences between control and experimental groups. These promising results suggest that SDF is more effective than fluoride varnish, and may be a valuable caries-preventive intervention. As well, the availability of a safe, effective, efficient, and equitable caries-preventive agent appears to meet the criteria of both the WHO Millennium Goals and the US Institute of Medicine's criteria for 21st century medical care.

Enamel defects and its relation to life course events in primary dentition of Brazilian children: a longitudinal study.

OBJECTIVE: To evaluate the cumulative incidence of enamel defects (ED) and its correlation with life course events such as malnutrition and pre- and postnatal infections, in a cohort of children of low socioeconomic status. METHODS: The children were registered at birth and examined from 12 to 36 months of age. At the baseline, 246 were examined and in the follow-up, 228. The teeth were examined under natural light and dried with gauze. ED was determined by the DDE index. RESULTS: Results show that gender was not significant. The cumulative incidence of ED at the last recall examination was 78.9%. The most prevalent type of defect was diffuse opacity, present on the gingival half of the buccal surface (p < 0.001). For logistic regression analysis maternal infections, intrauterine growth retardation (IUGR), malnutrition and postnatal infections were selected as predictor variables for the occurrence of enamel defects. CONCLUSIONS: The results indicate that life course events such as undernutrition and childhood infections during teeth development may be associated with enamel defects in socioeconomically underprivileged communities and may compromise the oral health-related quality of life.

The influence of enamel defects on the development of early childhood caries in a population with low socioeconomic status: a longitudinal study.

The purpose of this study was to evaluate the influence of enamel defects in the development of dental caries and their association with feeding practices and oral health behaviors in a cohort study of low-socioeconomic children from birth to 36 months of age in northeastern Brazil. Subjects were registered at birth and examined from 12 to 36 months of age. At baseline, 246 children were examined and at follow-up 228. The teeth were clinically examined and dried with gauze under natural light. Enamel defects were determined using the Developmental Defects of Enamel (DDE) index. Dental caries was determined using WHO criteria. Data were analyzed using descriptive and analytical techniques. At 36 months 78.9% infants presented at least one tooth with enamel defects and 25% of the children had at least one decayed tooth. A total of 16.9% teeth with enamel defects had become decayed (p = 0.0001). Opacity with enamel hypoplasia was the defect most frequently associated with dental caries (p = 0.001). Only 0.9% of the teeth without enamel defects developed caries. Multivariate analyses revealed that enamel defects, night breast-feeding and poor oral hygiene habits were predictors of dental caries at 18 and 24 months (p < 0.05). Considering the risk factors evaluated at 30 months of age, the presence of enamel defects was the single predictor of caries development at 36 months (p = 0.0001). Enamel defects are strongly associated with early childhood caries and, therefore, this correlation must be considered when focussing on low-socioeconomic communities.

The association of CAG repeat length with clinical progression in Huntington disease.

OBJECTIVE: To determine whether the rate of clinical progression in Huntington disease (HD) is influenced by the size of the CAG expansion. METHODS: The dataset consisted of 3,402 examinations of 512 subjects seen through the Baltimore Huntington's Disease Center. Subjects were seen for a mean of 6.64 visits, with mean follow-up of 6.74 years. Subjects were administered the Quantified Neurological Examination, with its subsets the Motor Impairment and Chorea Scores, the Mini-Mental State Examination, and the HD Activities of Daily Living (ADL) Scale. RESULTS: In an analysis based on the Random Effects Model, CAG length was significantly associated with the rate of progression of all measures except chorea and ADL. There was a significant interaction term between CAG length and disease duration for all measures except chorea. Further graphical exploration of the data supported these linear models and suggested that subjects at the low end of the expanded CAG repeat range may experience a more benign late course. CONCLUSIONS: CAG repeat length has a small effect on rate of progression that may be clinically important over time. Individuals with the shortest expansions appear to have the best prognosis. These effects of the CAG length may be relevant in the analysis of clinical trials.

An open-label study of escitalopram (Lexapro) for the treatment of 'Depression of Alzheimer's disease' (dAD).

BACKGROUND: Depression is a frequent neuropsychiatric complication of Alzheimer's Disease. METHODS: This study investigated the safety and effectiveness of escitalopram (LEXAPRO) for depression in AD (dAD) as defined by the NIMH consensus criteria in an 8-week, open-label treatment study. CONCLUSION: Escitalopram was efficacious and safe for the treatment of dAD in this study. Larger, controlled studies are warranted to further assess the efficacy for mood and behavioral disturbances in this medically fragile population.

Differential impairment of spatial location memory in Huntington's disease.

OBJECTIVE: To determine whether a differential impairment of spatial memory exists in Huntington's disease (HD). METHODS: Patients with HD and age matched neurologically normal subjects, as well as patients with Alzheimer's disease (AD) and Parkinson's disease (PD), learned the locations of nine items on a 3 x 3 grid over as many as 10 trials. Delayed recall of the items and their spatial locations was tested. RESULTS: Patient with HD performed worse than normal subjects on all measures, and intermediate between AD and PD patients. However, they were the only subject group in whom delayed recall of spatial locations was poorer than delayed recall of object identity. This effect was independent of the severity of dementia. CONCLUSIONS: HD patients have a differential impairment in memory for object-location information. This finding may relate to the involvement of the caudate nucleus, the primary site of pathology in HD, in corticostriatal circuits linking it with parietal association cortex. It is also consistent with views of the dorsal striatum as responsible for the acquisition over trials of specific place responses.

Ethyl-EPA in Huntington disease: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Preliminary evidence suggests beneficial effects of pure ethyl-eicosapentaenoate (ethyl-EPA) in Huntington disease (HD). METHODS: A total of 135 patients with HD were randomized to enter a multicenter, double-blind, placebo-controlled trial on the efficacy of 2 g/d ethyl-EPA vs placebo. The Unified Huntington's Disease Rating Scale (UHDRS) was used for assessment. The primary end point was outcome at 12 months on the Total Motor Score 4 subscale (TMS-4). Analysis of covariance (ANCOVA) and a chi2 test on response, defined as absence of increase in the TMS-4, were performed. RESULTS: A total of 121 patients completed 12 months, and 83 did so without protocol violations (PP cohort). Intent-to-treat (ITT) analysis revealed no significant difference between ethyl-EPA and placebo for TMS-4. In the PP cohort, ethyl-EPA proved better than placebo on the chi2 test on TMS-4 (p < 0.05), but missed significance on ANCOVA (p = 0.06). Secondary end points (ITT cohort) showed no benefit of ethyl-EPA but a significantly worse outcome in the behavioral severity and frequency compared with placebo. Exploring moderators of the efficacy of ethyl-EPA on TMS-4 showed a significant interaction between treatment and a factor defining patients with high vs low CAG repeats. Reported adverse events were distributed equally between treatment arms. CONCLUSIONS: Ethyl-eicosapentaenoate (ethyl-EPA) (purity > 95%) had no benefit in the intent-to-treat cohort of patients with Huntington disease, but exploratory analysis revealed that a significantly higher number of patients in the per protocol cohort, treated with ethyl-EPA, showed stable or improved motor function. Further studies of the potential efficacy of ethyl-EPA are warranted.

Breast-feeding and early childhood caries: an assessment among Brazilian infants.

OBJECTIVES: The purpose of the present study was to evaluate early childhood caries among 12-36-month-old children from families living in poor socio-economic conditions in the city of Recife, Brazil, its association with the type and duration of feeding (e.g. natural, sugared, bottle and glass), as well as the relationship between a supplementary diet and the occurrence of this type of caries. METHODS: The present study consisted of a visual clinical examination of teeth that had been previously cleaned with gauze. This was carried out under natural light in a waiting room. Four calibrated examiners performed the examination and the kappa test value was 8.0. The parents or guardians were interviewed for the following information: name, address, age, type of feeding, number of sugary meals, sugar intake and habitual diet. Some 468 children were included in this study. Their ages ranged from 12 to 36 months. The sample was comprised of 222 (47.4%) males and 246 females (52.6%). RESULTS: Of the 468 children included in this study, 133 (28.4%) had caries. Only 59 (12.6%) of the children examined had been breast-fed, 20 (33.9%) of whom presented with caries. Three hundred and twenty-seven (69.9%) subjects had been bottle-fed with sugared milk, 86 (26%) of whom had caries. Two hundred and eight children had five or more sugary meals per day, 70 (33.6%) of whom had caries. No statistically significant relationship was seen between breast-feeding and the prevalence of tooth decay. CONCLUSIONS: The results of the present study show that the prevalence of early childhood caries in 12-36-month-old children from poor backgrounds in Recife is in accordance with the rate found in other Brazilian cities and is extremely high compared with that of the world population as a whole. Early childhood caries was not clearly related to the type of feeding in this sample. The prevalence of early childhood caries increased with age, and the number of sugary snacks between meals and a cariogenic diet were strongly related to early childhood caries. The lack of fluoridated water and high rates of early childhood caries in lead the authors to suggest that fluoride dentifrice should be introduced at 12 months of age as a fluoride supplement and an important aid in the prevention of childhood caries. Additional studies in different cultures and societies need to be undertaken before a definitive conclusion can be drawn.

Onset and rate of striatal atrophy in preclinical Huntington disease.

BACKGROUND: Huntington disease (HD) is characterized by striatal atrophy that begins long before the onset of motor symptoms. OBJECTIVE: To determine when striatal atrophy begins, the extent and rate of atrophy before diagnosis of motor symptoms, and whether striatal atrophy can predict when symptom onset will occur. METHODS: Caudate and putamen volumes were measured on MRI scans of 19 preclinical subjects with the HD gene expansion who were very far (9 to 20 years) from estimated onset, and on serial scans from 17 preclinical subjects, six of whom were diagnosed with HD within 5 years after the initial scan. RESULTS: Striatal volumes were significantly smaller for the subjects who were very far from estimated onset than for age-matched control subjects. Statistical models fit to the longitudinal data suggest that rate of caudate atrophy becomes significant when subjects are approximately 11 years from estimated onset and rate of putamen atrophy becomes significant approximately 9 years prior to onset. In the six incident cases, caudate and putamen were approximately one-third to one-half of normal volume at diagnosis, and caudate volume alone was able to predict with 100% accuracy those subjects who would be diagnosed within 2 years of imaging. CONCLUSIONS: Striatal atrophy begins many years prior to diagnosable HD, and assessment of atrophy on MRI may be very useful in both predicting HD onset and in tracking progression in future therapeutic trials in preclinical subjects.