Digital droplet PCR (ddPCR) for the precise quantification of human T-lymphotropic virus 1 proviral loads in peripheral blood and cerebrospinal fluid of HAM/TSP patients and identification of viral mutations

An elevated human T cell lymphotropic virus 1 (HTLV)-1 proviral load (PVL) is the main risk factor for developing HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in HTLV-1 infected subjects, and a high cerebrospinal fluid (CSF) to peripheral blood mononuclear cell (PBMC) PVL ratio may be diagnostic of the condition. However, the standard method for quantification of HTLV-1 PVL—real-time PCR—has multiple limitations, including increased inter-assay variability in compartments with low cell numbers, such as CSF. Therefore, in this study, we evaluated a novel technique for HTVL-1 PVL quantification, digital droplet PCR (ddPCR). In ddPCR, PCR samples are partitioned into thousands of nanoliter-sized droplets, amplified on a thermocycler, and queried for fluorescent signal. Due to the high number of independent events (droplets), Poisson algorithms are used to determine absolute copy numbers independently of a standard curve, which enables highly precise quantitation. This assay has low intra-assay variability allowing for reliable PVL measurement in PBMC and CSF compartments of both asymptomatic carriers (AC) and HAM/TSP patients. It is also useful for HTLV-1-related clinical applications, such as longitudinal monitoring of PVL and identification of viral mutations within the region targeted by the primers and probe.     

Unexpected pathologies in patients referred for endoscopic DCR

The objective of this study is to describe a series of patients with different pathologies mimicking nasolacrimal duct obstruction (NLDO), diagnosed with the use of a computed tomography (CT) scan prior to a scheduled endoscopic dacryocystorhinostomy (DCR). This study is a retrospective report. We reviewed the medical records of 47 consecutive patients (57 sides) with long-standing epiphora between 2007 and 2012. All patients were referred to our tertiary Medical Center with a diagnosis of NLDO and were expected to undergo endoscopic dacryocystorhinostomy (DCR). They all underwent routine sinus CT scan prior to surgery. All scans, as well as the demographic and medical characteristics of these patients were reviewed. Of all 47 patients enrolled, in 4 patients (7 % of all sides), unexpected pathologies, other than nasolacrimal system distention, inflammation or infection were identified preoperatively. These included squamous cell carcinoma of the lacrimal sac and nasolacrimal duct, rhinoscleroma at Hasner’s valve region, a compressing ethmoidal mucocele and a case of dacryocystocele. These unusual pathologies mandated a different management and surgical approach. In all four cases, a preoperative CT scan helped in identifying the pathology and in localizing the lacrimal apparatus in relation to the paranasal sinuses. Different nasal, paranasal and lacrimal pathologies may mimic primary acquired NLDO. A high index of suspicion, a thorough clinical evaluation and utilizing preoperative imaging may lead to an alteration of patient management and to a completely different surgical approach.     

Vaccinations for Neuroinfectious Disease: A Global Health Priority

Vaccines for neuroinfectious diseases are becoming an ever-increasing global health priority, as neurologic manifestations and sequelae from existing and emerging central nervous system infections account for significant worldwide morbidity and mortality. The prevention of neurotropic infections can be achieved through globally coordinated vaccination campaigns, which have successfully eradicated nonzoonotic agents such as the variola viruses and, hopefully soon, poliovirus. This review discusses vaccines that are currently available or under development for zoonotic flaviviruses and alphaviruses, including Japanese and tick-borne encephalitis, yellow fever, West Nile, dengue, Zika, encephalitic equine viruses, and chikungunya. Also discussed are nonzoonotic agents, including measles and human herpesviruses, as well as select bacterial, fungal, and protozoal pathogens. While therapeutic vaccines will be required to treat a multitude of ongoing infections of the nervous system, the ideal vaccination strategy is pre-exposure vaccination, with the ultimate goals of minimizing disease associated with zoonotic viruses and the total eradication of nonzoonotic agents.     

Persistent 7-tesla phase rim predicts poor outcome in new multiple sclerosis patient lesions

BACKGROUND. In some active multiple sclerosis (MS) lesions, a strong immune reaction at the lesion edge may contain growth and thereby isolate the lesion from the surrounding parenchyma. Our previous studies suggest that this process involves opening of the blood-brain barrier in capillaries at the lesion edge, seen on MRI as centripetal contrast enhancement and a colocalized phase rim. We hypothesized that using these features to characterize early lesion evolution will allow in vivo tracking of tissue degeneration and/or repair, thus improving the evaluation of potential therapies for chronic active lesions.METHODS. Centripetally and centrifugally enhancing lesions were studied in 17 patients with MS using 7-tesla MRI. High-resolution, susceptibility-weighted, T1-weighted (before/after gadolinium), and dynamic contrast–enhanced scans were acquired at baseline and months 1, 3, 6, and 12. For each lesion, time evolution of the phase rim, lesion volume, and T1 hypointensity were assessed. In autopsies of 3 progressive MS cases, the histopathology of the phase rim was determined.RESULTS. In centripetal lesions, a phase rim colocalized with initial contrast enhancement. In 12 of 22, this phase rim persisted after enhancement resolved. Compared with centripetal lesions with transient rim, those with persistent rim had less volume shrinkage and became more T1 hypointense between months 3 and 12. No centrifugal lesions developed phase rims at any time point. Pathologically, persistent rims corresponded to an iron-laden inflammatory myeloid cell population at the edge of chronic demyelinated lesions.CONCLUSION. In early lesion evolution, a persistent phase rim in lesions that shrink least and become more T1 hypointense over time suggests that the rim might mark failure of early lesion repair and/or irreversible tissue damage. In later stages of MS, phase rim lesions continue to smolder, exerting detrimental effects on affected brain tissue.TRIAL REGISTRATION. {"type":"clinical-trial","attrs":{"text":"NCT00001248","term_id":"NCT00001248"}}NCT00001248.FUNDING. The Intramural Research Program of NINDS supported this study.     

Three brain SPECT region-of-interest templates in elderly people: normative values, hemispheric asymmetries, and a comparison of single- and multihead cameras.

The purpose of this study was to generate anatomically guided region-of-interest (ROI) brain SPECT templates based on scans of elderly healthy volunteers. We describe normal tracer uptake and hemispheric asymmetries for each of 3 camera systems and compare these characteristics among systems. METHODS: 99mTc-hexamethyl propyleneamine oxime SPECT scans were acquired from 28 elderly healthy volunteers (mean age [+/-SD], 70.3 +/- 6.5 y) on a single-head rotating gamma camera (n = 15) or on dual- (n = 18) or triple-head (n = 13) cameras. The average number of counts in each ROI was calculated and referenced to counts in a cerebellar ROI, providing semiquantitative regional cerebral blood flow (rCBF) ratios. For the templates and ROI map, base images of a healthy volunteer were obtained with each camera. Data from individuals scanned with 2 cameras on the same day (n = 15) were used to evaluate rCBF differences across cameras. For each camera, averaged SPECT templates were made using automated image registration. The base volunteer's T1-weighted MR image was converted to stereotactic space with dimensions similar to those of the SPECT templates, and 79 bilateral ROIs were defined. To obtain ROI rCBF ratios, we aligned individual images to their appropriate template and then to this modified MR image. RESULTS: The ROI coefficients of variation indicated that the fit of the ROIs was acceptable (0.07-0.35). Mean rCBF ratios ranged from 0.57 to 1.0, 0.67 to 1.01, and 0.63 to 1.00 for single-, dual-, and triple-head cameras, respectively. The cuneus, occipital cortex, occipital pole, middle temporal gyrus, and posterior middle frontal gyrus showed consistent hemispheric asymmetry (right side greater than left side in 83%-100% of individuals). Mean rCBF ratios did not differ between dual- and triple-head cameras, whereas the ratios for single- and dual-head cameras differed significantly (39 ROIs differed), even after smoothing and filtering the dual-head images to the level of the single-head images. CONCLUSION: The use of SPECT templates based on elderly healthy volunteers is an important feature of this technique because most available templates have used young individuals. Another important feature is the use of MR image-based ROIs. These procedures are versatile because they use more than 1 camera. They can easily be implemented in clinical and research settings to detect camera-specific, abnormal deviations in rCBF ROI ratios and asymmetry magnitudes in diseases associated with aging, such as stroke and dementia.     

Anatomy of Tenons capsule

Background: The microscopic and macroscopic anatomy of the anterior and posterior Tenons capsule is described. Methods: An observational anatomic study of twelve orbits of 6 cadavers (mean age 79.5 years) were examined microscopically and 8 orbits of 4 cadavers (mean age 76.8 years) were examined macroscopically. After orbital exenteration, an X‐shaped incision was made in the specimens to include the posterior part of the globe. The sections were divided into four parts: superomedial; inferomedial; superolateral; and inferolateral. In the macroscopically examined specimens, the eyelids and globes were removed from the exenterated tissues and the appearance of Tenons capsule was studied. Results: In the microscopic study, Tenons capsule covered the sclera beneath the conjunctiva and contained smooth muscle fibres in the anterior area. This anterior fascia, which had a thick appearance, reached the globe equator. From there, the capsule of the orbital fat, which contained no smooth muscle fibres, enveloped the sclera and reached the optic nerve. This was defined as the posterior capsule. In the macroscopic specimens, Tenons capsule had a thick and fibrous white appearance in the anterior area. More posteriorly, the capsule was thinner and more translucent. This thin capsular part was generally larger in the lateral area than in the medial area. Conclusions: Tenons capsule is composed of an anterior thick fibrous tissue comprising the orbital smooth muscle network and the posterior thin fibrous capsule of the orbital fat.     

Colour Doppler ultrasound imaging findings in paediatric periocular and orbital haemangiomas

Purpose: To evaluate the combined grey‐scale ultrasonography (US) and colour Doppler imaging (CDI) as the first and primary imaging modalities in diagnosing paediatric orbital haemangiomas. Methods: The charts of 20 consecutive children with a periorbital mass echographically diagnosed as a haemangioma between January 2004 and June 2009 in the Tel‐Aviv Sourasky Medical Center were reviewed. Data on demographic details, clinical findings, US and CDI characteristics, treatment and outcome were retrieved. Results: Twelve (60%) haemangiomas were located on the upper eyelid, five in the lower eyelid (25%) and three in the medial cantus (15%). The tumour resolved completely in 10 children (50%) and in 10 children (50%) partial resolution was documented. Seven (35%) patients underwent treatment (intralesional or oral steroids or propranolol). Grey‐scale US depicted a solid‐tissue mass with low internal echogenicity. Mean haemangioma volume was 1.33 cm³. Colour Doppler imaging demonstrated intralesional flow with a mean peak systolic velocity of 15.2 cm per second and a mean resistance index of 0.51. All US and CDI examinations were carried out on alert children and no sedation or general anaesthesia was needed. During mean follow‐up time of 23 months, no child required any additional imaging or diagnostic procedures to confirm the diagnosis. Conclusion: Combined US and CDI are suggested as the first imaging modalities in cases with a suspected diagnosis of periocular and orbital capillary haemangioma.     

Isotretinoin-induced adult onset Still's disease

We describe a 21-year old man who was diagnosed as having adult onset Still's disease (AOSD) in association with isotretinoin treatment for acne conglobata. The patient was febrile, with a macular salmon pink rash, arthritis, hepatosplenomegaly, and axial lymphadenopathy. Laboratory results showed leukocytosis, mild liver dysfunction and negative rheumatoid factor and antinuclear antibodies. Isotretinoin, an orally active derivative of vitamin A, has been associated with various rheumatologic conditions such as arthralgia, myalgia, vasculitis and arthritis. The etiology of rheumatic disorders associated with retinoids is still obscure; however, it is presumed that immunomodulation by several mechanisms (such as an alteration of the cytokine balance) is probably ascribable to this interesting association.     

Congestive heart failure: a current overview

Congestive heart failure (CHF), a disease seen primarily in the older patient, can be due to either systolic or diastolic dysfunction. Management is quite different if the heart failure is due to a filling abnormality as compared to poor ventricular systole. The disorder also poses many diagnostic pitfalls in the elderly. Current understanding of CHF and its influence on diagnosis and management is the focus of this review.