In multiple sclerosis (MS), retinal nerve fiber layer thickness is associated with brain parenchymal fraction and CSF volume. These data suggest that quantification of axonal thickness in the retina by optical coherence tomography (OCT) provides concurrent information about MRI brain abnormality in MS. OCT should be examined in longitudinal studies to determine if it could be used as an outcome measure in clinical trials of neuroprotective drugs.

Retinal nerve fiber layer (RNFL) is significantly decreased in multiple sclerosis (MS) optic neuritis (ON) eyes, unaffected fellow eyes of patients with MS ON, and MS eyes not affected by ON in our cohort. Macular volumes (MV) showed a significant decrease in MS ON eyes. Progressive MS cases showed more marked decreases in RNFL and MV than relapsing-remitting MS. OCT is a promising tool to detect subclinical changes in RNFL and MV in patients with MS and should be examined in longitudinal studies as a potential biomarker of retinal pathology in MS.

Background: Optical coherence tomography (OCT) is a promising new method of quantifying axon thickness in the retinal nerve fiber layer (RNFL) that has been used predominantly by ophthalmologists to monitor glaucoma. Optical coherence tomography is being considered as a potential outcome measure in multiple sclerosis (MS) clinical trials, but no data exist on the reproducibility of this technique in MS centers. Objective: To determine the reproducibility of OCT measurement of mean RNFL thickness in the undilated eyes of healthy control subjects and patients with MS. Design: Prospective analysis of 4 healthy controls to determine interrater, intrarater, and longitudinal reproducibility. Cross-sectional analysis of 3 cohorts of patients with MS (n=396) and healthy controls (n = 153). Setting: Multiple sclerosis clinics at 3 academic medical centers. Patients or Other Participants: Healthy controls and patients with MS. Main Outcome Measure: Thickness of RNFL. Results: We found excellent agreement with respect to interrater (intraclass correlation [ICC], 0.89), intrarater (ICC, 0.98), and intervisit (ICC, 0.91) results. Mean RNFL thickness did not vary significantly among research centers for patients with MS (93, 92, and 90 µm) or among healthy controls (103, 105, and 104 µm) by site. Conclusions: We demonstrate that mean RNFL thickness can be reproducibly measured by trained technicians in an MS center using the OCT-3 model. The RNFL measures from cohorts of age-matched controls and patients with MS from 3 different research centers were remarkably similar.

Dystonia is frequent in early-onset parkinsonism (EOP) and sometimes its presenting sign. 1,2 Conversely, parkinsonian signs occur in dopa-responsive dystonia (DRD), especially in later stages, and may even be the only finding in relatives of patients with clinically typical DRD. 3 Both conditions may have a similar age at onset and respond well to treatment with levodopa, and patients may report sleep benefit and diurnal variation of symptoms in both conditions. Due to this phenotypic overlap, categorization of the early-onset dystonia-parkinsonism syndromes may pose a diagnostic challenge.Dominantly, inherited mutations in the GTP cyclohydrolase I (GCHI) gene can be found in over 80% of the clinical typical cases of DRD but only when conventional screening methods and expensive gene dosage analyses are combined. 4 The most common known cause of EOP is recessively transmitted mutations in the parkin gene, the detection of which also requires comprehensive screening for small mutations and exon rearrangements. Given these technical considerations and, more importantly, because of the different prognosis of the two conditions, a fast, inexpensive marker or tool would be helpful in establishing a diagnosis of neurodegenerative EOP vs nondegenerative DRD.To date, diagnostic approaches to distinguish between the two diseases with neuroimaging (CT and MRI) have not been successful. The more recent method of transcranial sonography (TCS) of the brain parenchyma may prove a promising alternative as an easily applicable and low-cost neuroimaging technique. The substantia nigra (SN) shows a distinct hyperechogenic pattern on TCS in about 90% of patients with Parkinson disease (PD) 5 that is associated with a significant reduction of 18 F-dopa uptake in the striatum and has been related to increased tissue concentrations of iron and loss of neuromelanin. Recently, SN hyperechogenicity has been described in symptomatic and asymptomatic carriers of parkin mutations. 6 There are no published data on TCS of the midbrain in patients with DRD.To determine whether TCS can detect differences in SN echogenicity in patients with DRD vs parkin-associated EOP, we studied 5 patients with genetically proven DRD (5 women, mean age 46.0 Ϯ 12.2 years, mean disease duration 31.0 Ϯ 13.8 years), 5 patients with EOP and homozygous or compound heterozygous parkin mutations (4 men, 1 woman, mean age 59.0 Ϯ 15.4 years, mean disease duration 12.3 Ϯ 6.3 years, mean Unified Parkin-son's Disease Rating Scale-III score ["on"] 23.0 Ϯ 15.3), and 10 healthy control subjects (5 men, 5 women, mean age 52.6 Ϯ 13.2 years). TCS examination was performed through the preauricular acoustic bone window, using a phased-array ultrasound system with a 2.5-MHz sector transducer (SONOS 5500; Philips Medical System, Best, the Netherlands). A standardized axial mesencephalic plane (landmark: butterfly-shaped brainstem) with a maximum depth of 12 cm from the temporal bone window on each side was used to localize the maximum extent of the hyperechogenic signals from the i...

Background: The epidemiology of critical illness in India is distinct from high-income countries. However, limited data exist on resource availability, staffing patterns, case-mix and outcomes from critical illness. Critical care registries, by enabling a continual evaluation of service provision, epidemiology, resource availability and quality, can bridge these gaps in information. In January 2019, we established the Indian Registry of IntenSive care to map capacity and describe case-mix and outcomes. In this report, we describe the implementation process, preliminary results, opportunities for improvement, challenges and future directions. Methods: All adult and paediatric ICUs in India were eligible to join if they committed to entering data for ICU admissions. Data are collected by a designated representative through the electronic data collection platform of the registry. IRIS hosts data on a secure cloud-based server and access to the data is restricted to designated personnel and is protected with standard firewall and a valid secure socket layer (SSL) certificate. Each participating ICU owns and has access to its own data. All participating units have access to de-identified network-wide aggregate data which enables benchmarking and comparison. Results: The registry currently includes 14 adult and 1 paediatric ICU in the network (232 adult ICU beds and 9 paediatric ICU beds). There have been 8721 patient encounters with a mean age of 56.9 (SD 18.9); 61.4% of patients were male and admissions to participating ICUs were predominantly unplanned (87.5%). At admission, most patients (61.5%) received antibiotics, 17.3% needed vasopressors, and 23.7% were mechanically ventilated. Mortality for the entire cohort was 9%.  Data availability for demographics, clinical parameters, and indicators of admission severity was greater than 95%. Conclusions: IRIS represents a successful model for the continual evaluation of critical illness epidemiology in India and provides a framework for the deployment of multi-centre quality improvement and context-relevant clinical research.