Objective:
To determine whether cognitive impairments in patients with Idiopathic Intracranial Hypertension (IIH) are correlated with changes in visual processing, weight, waist circumference, mood ...or headache, and whether they change over time.
Methods:
Twenty-two newly diagnosed IIH patients participated, with a subset assessed longitudinally at 3 and 6 months. Both conventional and novel ocular motor tests of cognition were included: Symbol Digit Modalities Test (SDMT), Stroop Colour and Word Test (SCWT), Digit Span, California Verbal Learning Test (CVLT), prosaccade (PS) task, antisaccade (AS) task, interleaved antisaccade-prosaccade (AS-PS) task. Patients also completed headache, mood, and visual functioning questionnaires.
Results:
IIH patients performed more poorly than controls on the SDMT (
p
<
0.001
), SCWT (
p
=
0.021
), Digit Span test (
p
<
0.001
) and CVLT (
p
=
0.004
) at baseline, and generated a higher proportion of AS errors in both the AS (
p
<
0.001
) and AS-PS tasks (
p
=
0.007
). Further, IIH patients exhibited prolonged latencies on the cognitively complex AS-PS task (
p
=
0.034
). While weight, waist circumference, headache and mood did not predict performance on any experimental measure, increased retinal nerve fibre layer (RNFL) was associated with AS error rate on both the block
F
(3, 19)
=
3.22, B
=
0.30, p
=
0.022
and AS-PS task
F
(3, 20)
=
2.65, B
=
0.363, p
=
0.013
. Unlike ocular motor changes, impairments revealed on conventional tests of cognition persisted up to 6 months.
Conclusion:
We found multi-domain cognitive impairments in IIH patients that were unrelated to clinical characteristics. Marked ocular motor inhibitory control deficits were predicted by RNFL thickness but remained distinct from other cognitive changes, underscoring the significance of visual processing changes in IIH.
Early markers of axonal and clinical outcomes are required for early phase testing of putative neuroprotective therapies for multiple sclerosis (MS).
To assess whether early measurement of diffusion ...tensor imaging (DTI) parameters (axial and radial diffusivity) within the optic nerve during and after acute demyelinating optic neuritis (ON) could predict axonal (retinal nerve fibre layer thinning and multi-focal visual evoked potential amplitude reduction) or clinical (visual acuity and visual field loss) outcomes at 6 or 12 months.
Thirty-seven patients presenting with acute, unilateral ON were studied at baseline, one, three, six and 12 months using optic nerve DTI, clinical and paraclinical markers of axonal injury and clinical visual dysfunction.
Affected nerve axial diffusivity (AD) was reduced at baseline, 1 and 3 months. Reduced 1-month AD correlated with retinal nerve fibre layer (RNFL) thinning at 6 (R=0.38, p=0.04) and 12 months (R=0.437, p=0.008) and VEP amplitude loss at 6 (R=0.414, p=0.019) and 12 months (R=0.484, p=0.003). AD reduction at three months correlated with high contrast visual acuity at 6 (ρ = -0.519, p = 0.001) and 12 months (ρ = -0.414, p=0.011). The time-course for AD reduction for each patient was modelled using a quadratic regression. AD normalised after a median of 18 weeks and longer normalisation times were associated with more pronounced RNFL thinning and mfVEP amplitude loss at 12 months. Affected nerve radial diffusivity (RD) was unchanged until three months, after which time it remained elevated.
These results demonstrate that AD reduces during acute ON. One month AD reduction correlates with the extent of axonal loss and persistent AD reduction at 3 months predicts poorer visual outcomes. This suggests that acute ON therapies that normalise optic nerve AD by 3 months could also promote axon survival and improve visual outcomes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aims:
To retrospectively assess factors associated with John Cunningham virus (JCV) seroconversion in natalizumab-treated patients.
Background:
Natalizumab is highly effective for the treatment of ...relapsing–remitting multiple sclerosis (RRMS), but its use is complicated by opportunistic JCV infection. This virus can result in progressive multifocal leukoencephalopathy (PML). Serial assessment of JCV serostatus is mandated during natalizumab treatment.
Methods:
Patients treated with natalizumab for RRMS at six tertiary hospitals in Melbourne, Australia (n = 865) and 11 MS treatment centres in Brazil (n = 136) were assessed for change in JCV serostatus, duration of exposure to natalizumab and prior immunosuppression. Sensitivity analyses examined whether sex, age, tertiary centre, prior immunosuppression or number of JCV tests affected time to seroconversion.
Results:
From a cohort of 1001 natalizumab-treated patients, durable positive seroconversion was observed in 83 of 345 initially JCV negative patients (24.1%; 7.3% per year). Conversely, 16 of 165 initially JCV positive patients experienced durable negative seroconversion (9.7%; 3.8% per year). Forty patients (3.9%) had fluctuating serostatus. Time-to-event analysis did not identify a relationship between JCV seroconversion and duration of natalizumab exposure. Prior exposure to immunosuppression was not associated with an increased hazard of positive JCV seroconversion. Male sex was associated with increased JCV seroconversion risk adjusted hazard ratio 2.09 (95% confidence interval 1.17–3.71) p = 0.012.
Conclusion:
In this large international cohort of natalizumab-treated patients we observed an annual durable positive seroconversion rate of 7.3%. This rate exceeds that noted in registration and post-marketing studies for natalizumab. This rate also greatly exceeds that predicted by epidemiological studies of JCV seroconversion in healthy populations. Taken together, our findings support emerging evidence that natalizumab causes off-target immune changes that may be trophic for JCV seroconversion. In addition, male sex may be associated with increased positive JCV seroconversion.
ObjectiveTo determine whether cognitive impairments in patients with Idiopathic Intracranial Hypertension (IIH) are correlated with changes in visual processing, weight, waist circumference, mood or ...headache and whether they change over time.MethodsTwenty-two newly diagnosed IIH patients participated, with a subset assessed longitudinally at 3 and 6 months. Both conventional and novel ocular motor tests of cognition were included: Symbol Digit Modalities Test (SDMT), Stroop Colour and Word Test (SCWT), Digit Span, California Verbal Learning Test (CVLT), prosaccade (PS) task, antisaccade (AS) task, interleaved antisaccade-prosaccade (AS-PS) task. Patients also completed headache, mood and visual functioning questionnaires.ResultsIIH patients performed more poorly than controls on the SDMT (p<.001), SCWT (p=.021), Digit Span test (p<0.001) and CVLT (p=.004) at baseline, and generated a higher proportion of AS errors in both the AS (p<.001) and AS-PS tasks (p=.007). Further, IIH patients exhibited prolonged latencies on the cognitively complex AS-PS task (p=.034). While weight, waist circumference, headache and mood did not predict performance on any experimental measure, increased retinal nerve fibre layer (RNFL) was associated with AS error rate on both the block (F(3, 19)=3.22, B=0.30, p=0.022) and AS-PS task (F(3, 20)=2.65, B=0.363, p=0.013). Unlike ocular motor changes, impairments revealed on conventional tests of cognition persisted up to 6 months.ConclusionsWe found multi-domain cognitive impairments in IIH patients that were unrelated to clinical features. Marked ocular motor inhibitory control deficits were predicted by RNFL thickness but remained distinct from other cognitive changes, underscoring the significance of visual processing changes in IIH.
BackgroundAdherence and persistence are critical to optimising therapeutic benefit from disease-modifying therapies (DMTs) in relapsing-remitting multiple sclerosis (RRMS). This prospective, ...open-label, multicentre, observational study (AubPRO), conducted in 13 hospital-based neurology clinics around Australia, describes treatment satisfaction in patients newly initiated on teriflunomide (Aubagio) and evaluates the use of an electronic patient-reported outcome (PRO) tool.MethodsPatients (≥18 years) newly initiated on teriflunomide (14 mg/day) were followed up at 24 and 48 weeks. Patients completed questionnaires and pill counts electronically using MObile Data in Multiple Sclerosis. The primary endpoint was treatment satisfaction, measured by the Treatment Satisfaction Questionnaire for Medication (TSQM, V.1.4), at week 48. Secondary endpoints included treatment satisfaction at week 24, other PRO scales, clinical outcomes, medication adherence and safety.ResultsPatients (n=103; 54 (52.4%) treatment naive) were mostly female (n=82 (79.6%)), aged 49.5 (11.8) years, with MS duration since symptom onset of 9.1 (11.8) years and a median Expanded Disability Status Scale score of 1.0. Mean treatment satisfaction scores were high (≥60%) across all domains of the TSQM V.1.4 at week 24 and at week 48. Compared with week 24, week 48 treatment satisfaction increased for patients who were treatment naïve and for those previously on another oral or injectable DMT. Over 48 weeks, PROs remained stable across a range of measures including disability, physical health, emotional health and mobility, and there were improvements in work capacity and daily life activity. Adherence was high throughout the study with mean compliance (pill counts) of 93.2%±6.26%, and 98 of 103 (95.1%) patients remained relapse-free.ConclusionThis cohort of Australian patients with RRMS, newly initiated on teriflunomide, and treated in a real-world clinical practice setting, reported high treatment satisfaction and adherence at 24 and 48 weeks. Patient-reported measures of disability remained stably low, work capacity and daily life activity improved, and most patients remained relapse-free.
Giant cell arteritis (GCA) is the most common form of vasculitis affecting elderly people. It is one of the few true ophthalmic emergencies but symptoms and signs are variable thereby making it a ...challenging disease to diagnose. A temporal artery biopsy is the gold standard to confirm GCA, but there are currently no specific biochemical markers to aid diagnosis. We aimed to identify a less invasive method to confirm the diagnosis of GCA, as well as to ascertain clinically relevant predictive biomarkers by studying the transcriptome of purified peripheral CD4+ and CD8+ T lymphocytes in patients with GCA.
We recruited 16 patients with histological evidence of GCA at the Royal Victorian Eye and Ear Hospital, Melbourne, Australia, and aimed to collect blood samples at six time points: acute phase, 2-3 weeks, 6-8 weeks, 3 months, 6 months and 12 months after clinical diagnosis. CD4+ and CD8+ T-cells were positively selected at each time point through magnetic-assisted cell sorting. RNA was extracted from all 195 collected samples for subsequent RNA sequencing. The expression profiles of patients were compared to those of 16 age-matched controls.
Over the 12-month study period, polynomial modelling analyses identified 179 and 4 statistically significant transcripts with altered expression profiles (FDR < 0.05) between cases and controls in CD4+ and CD8+ populations, respectively. In CD8+ cells, two transcripts remained differentially expressed after 12 months; SGTB, associated with neuronal apoptosis, and FCGR3A, associatied with Takayasu arteritis. We detected genes that correlate with both symptoms and biochemical markers used for predicting long-term prognosis. 15 genes were shared across 3 phenotypes in CD4 and 16 across CD8 cells. In CD8, IL32 was common to 5 phenotypes including Polymyalgia Rheumatica, bilateral blindness and death within 12 months.
This is the first longitudinal gene expression study undertaken to identify robust transcriptomic biomarkers of GCA. Our results show cell type-specific transcript expression profiles, novel gene-phenotype associations, and uncover important biological pathways for this disease. In the acute phase, the gene-phenotype relationships we have identified could provide insight to potential disease severity and as such guide in initiating appropriate patient management.
ObjectiveQuality assurance (QA) in neuro-ophthalmology (NOPH) is often lacking. The QA registry, NODE (Neuro-ophthalmology Database), was established and implemented in tertiary NOPH clinics in ...Australia. We developed a consensus on triage categories according to Australian standardised triage categories;P1 (consult<=30 days), P2 (consult<=30-60 days) and P3 (consult>60 days).MethodsData on 410 patients at Alfred Hospital, Melbourne was collected with NODE. We developed a consensus on assignation of NOPH conditions to triage categories using recommendations from a panel of neuro-ophthalmologists with the modified Delphi approach. The average days from referral to triage and triage to the initial consultation were compared to the developed triage category standard.ResultsMost patients presenting to the service were female (n=262, 64%), aged 21 to 30 years. Common diagnoses were Idiopathic Intracranial Hypertension, IIH (24%), Optic Neuropathy, ON (17%), Headaches, (11%) Cranial Nerve Defects, CND (9%) and Eye Movement Disorders, EOMD (9%). The mean time from referral to triage was <2 days for all the common NOPH conditions. The mean time (days, +-standard deviation) from P1 category triage to initial consult for IIH was 26 (±7), ON 27 (±11), and CND was 17 (± 5). The mean time (days) from P2 triage to initial consultant for Headaches was 27 (±12), and EOMD was (±17). The mean time (days) from P3 triage to initial consultant for Myasthenia Gravis was 30 (±10).ConclusionWe have established a consensus agreement on triage categories for neuro-ophthalmological conditions. We established a QA framework for other NOPH clinics in Australia.
Screening for unsuspected visual field defects should form a part of all routine eye examinations. Here, we review a procedure for finger-counting confrontation screening that tests the periphery of ...all visual field quadrants of each eye, yet requires a total of only four responses from the patient. In addition, the test simultaneously screens for the extinction phenomenon that can accompany unilateral brain damage. Due to its efficiency, we recommend that this procedure form the standard way that screening finger-counting confrontation be performed, with abnormal findings prompting a more detailed assessment of visual fields and further neurological examination as necessary. Our paper is not intended to suggest that finger-counting confrontation is superior to other forms of visual field screening and indeed the literature suggests its sensitivity is limited.
A 47-year-old woman with postural headache, episodic stupor, and vertical gaze palsy had brain imaging findings consistent with spontaneous intracranial hypotension (SIH), including severe descent of ...the mesodiencephalic structures and diffuse pachymeningeal enhancement. The source of the cerebrospinal fluid leakage was a ruptured dorsal perineural cyst. Clinical symptoms improved after a targeted epidural blood patch was performed. Dorsal midbrain syndrome has not been reported previously as a manifestation of SIH. Perhaps distortion of structures in this brain region can occur in SIH as it does in obstructive hydrocephalus.
Leber hereditary optic neuropathy (LHON) is a neurodegenerative disorder characterised by bilateral, painless, subacute, central vision loss caused by pathogenic sequence variants in mitochondrial ...DNA (mtDNA). Over the course of 20 years, 734 people were systematically screened by our diagnostic laboratory for suspected LHON or for being at risk of LHON, with 98 found to harbour one of the three primary pathogenic mtDNA variants. Detection incidences were: 0.95% for NC_012920.1(MT-ND1):m.3460G>A; 9.4% for (MT-ND4):m.11778G>A; and 2.9% for (MT-ND6):m.14484T>C. The median age for symptomatic males was 27.3 years and for females 29.5 years, with a male to female ratio of 4.4:1 (62 males; 14 females). Most pathogenic variant carriers were propositi with the other individuals belonging to one of 14 pedigrees with noteworthy intra-family variability of clinical severity of the disease.
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