Cognitive dysfunction can be identified in patients with clinically isolated syndromes suggestive of multiple sclerosis using ocular motor testing. This study aimed to identify the functional neural ...correlates of cognitive dysfunction in patients with clinically isolated syndrome using MRI. Eighteen patients with clinically isolated syndrome and 17 healthy controls were recruited. Subjects underwent standard neurological and neuropsychological testing. Subjects also underwent functional MRI (fMRI) during a cognitive ocular motor task, involving pro-saccade (direct gaze towards target) and anti-saccade (direct gaze away from target) trials. Ocular motor performance variables (averaged response time and error rate) were calculated for each subject. Patients showed a trend towards a greater rate of anti-saccade errors (p = 0.09) compared to controls. Compared to controls, patients exhibited increased activation in the right postcentral, right supramarginal gyrus, and the right parietal operculum during the anti-saccade>pro-saccade contrast. This study demonstrated that changes in functional organisation of cognitive brain networks is associated with subtle cognitive changes in patients with clinically isolated syndrome.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Myasthenia gravis (MG) is a condition with significant phenotypic variability, posing a diagnostic challenge to many clinicians worldwide. Prolonged diagnosis can lead to reduced remission rates and ...morbidity. This study aimed to identify factors leading to a longer time to diagnosis in MG that could be addressed in future to optimize diagnosis time.
One hundred and ten patients from 3 institutions in Melbourne, Australia, were included in this retrospective cohort study. Demographic and clinical data were collected for these patients over the first 5 years from diagnosis and at 10 years. Nonparametric statistical analysis was used to identify factors contributing to a longer diagnosis time.
The median time for MG diagnosis was 102 (345) days. 90% of patients were diagnosed before 1 year. Female patients took longer than male patients to be diagnosed (
= 0.013). The time taken for first presentation after symptom onset contributed most to diagnosis time (median 17 141 days), with female patients and not working as contributory factors. Neurology referral took longer if patients had diplopia (
= 0.022), respiratory (
= 0.026) symptoms, or saw an ophthalmologist first (
< 0.001). Outpatient management compared with inpatient was associated with a longer time to be seen by a neurologist from referral (
< 0.001), for the first diagnostic result to return (
= 0.001), and for the result to be reviewed (
< 0.001). Ocular MG had a median greater time to neurologist review than generalized MG (median 5 25 days vs 1 13 days,
= 0.035). Electrophysiology tests took longer for outpatients than inpatients (median 21 35 days vs 2 8 days,
< 0.001). Outpatients were also started on treatment later than inpatients (
< 0.001). There was no association of MG severity, ethnicity, age, medical and ocular comorbidities, and public or private health service on diagnosis time. There was also no impact of time to diagnosis on Myasthenia Gravis Foundation of America outcomes, number of follow-ups or hospitalizations, or prevalence of treatments used. This study is limited by low patient numbers and its retrospective nature.
This study identified several factors that can contribute to a prolonged diagnosis time of MG. Patient and clinician education about MG and outpatient diagnostic efficiency needs emphasis. Further studies are also needed to explore the delayed presentation time of women and nonworking patients in MG.
We characterised the clinical course, treatment and outcomes in 59 patients with relapsing myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination.
We evaluated clinical ...phenotypes, annualised relapse rates (ARR) prior and on immunotherapy and Expanded Disability Status Scale (EDSS), in 218 demyelinating episodes from 33 paediatric and 26 adult patients.
The most common initial presentation in the cohort was optic neuritis (ON) in 54% (bilateral (BON) 32%, unilateral (UON) 22%), followed by acute disseminated encephalomyelitis (ADEM) (20%), which occurred exclusively in children. ON was the dominant phenotype (UON 35%, BON 19%) of all clinical episodes. 109/226 (48%) MRIs had no brain lesions. Patients were steroid responsive, but 70% of episodes treated with oral prednisone relapsed, particularly at doses <10 mg daily or within 2 months of cessation. Immunotherapy, including maintenance prednisone (P=0.0004), intravenous immunoglobulin, rituximab and mycophenolate, all reduced median ARRs on-treatment. Treatment failure rates were lower in patients on maintenance steroids (5%) compared with non-steroidal maintenance immunotherapy (38%) (P=0.016). 58% of patients experienced residual disability (average follow-up 61 months, visual loss in 24%). Patients with ON were less likely to have sustained disability defined by a final EDSS of ≥2 (OR 0.15, P=0.032), while those who had any myelitis were more likely to have sustained residual deficits (OR 3.56, P=0.077).
Relapsing MOG antibody-associated demyelination is strongly associated with ON across all age groups and ADEM in children. Patients are highly responsive to steroids, but vulnerable to relapse on steroid reduction and cessation.
Working memory (WM) impairments are common and debilitating symptoms of multiple sclerosis (MS), often emerging early in the disease. Predominantly, WM impairments are considered in a binary manner, ...with patients considered either impaired or not based on a single test. However, WM is comprised of different activated subcomponents depending upon the type of information (auditory, visual) and integration requirements. As such, unique WM impairment phenotypes occur. We aimed to determine the most frequent WM phenotypes in early MS, how they progress and which WM test(s) provide the best measure of WM impairment. A total of 88 participants (63 early relapsing-remitting MS: RRMS, 25 healthy controls) completed five WM tests (visual-spatial, auditory, episodic, executive) as well as the symbol digit modalities test as a measure of processing speed. RRMS patients were followed-up for two years. Factors affecting WM (age/gender/intelligence/mood) and MS factors (disease duration/disability) were also evaluated. Some 61.9% of RRMS patients were impaired on at least one WM subcomponent. The most subcomponents impaired were visual,-spatial and auditory WM. The most common WM phenotypes were; (1) visual-spatial sketchpad + episodic buffer + phonological loop + central executive, (2) visual-spatial sketchpad + central executive. The test of visual-spatial WM provided the best diagnostic accuracy for detecting WM impairment and progression. The SDMT did not achieve diagnostic accuracy greater than chance. Although this may be unsurprising, given that the SDMT is a measure of cognitive processing speed in MS, this does highlight the limitation of the SDMT as a general screening tool for cognitive impairment in early MS.
BACKGROUND:Many neurological disorders show deficits in ocular motor function. In the past, evaluation has been limited to assessing abnormalities largely generated by pathology of the brainstem ...andcerebellum. In disorders that primarily or substantially, affect the cerebral hemispheres, disruption of cognitive processes occur, often early in the clinical course. While neuropsychological testing traditionally is used to measure cognitive performance, the cerebral influences on the ocular motor system provides another quantitative paradigm. This review explores the relationship between cognitive sensory processing and execution of planned ocular motor tests in Parkinsonʼs disease, Huntington\x{2019}s disease and multiple sclerosis and explores areas of clinical utility.
METHODS:Review of the literature regarding cognitive and ocular motor abnormalities in neurological disease.
RESULTS:The literature indicates that in systems degeneration there are abnormalities of cognitive processing, defined both by conventional behavioural testing and by assessment of cognitive function utilizing ocular motor studies, which characterise those processes. Moreover, in diffuse disease, in processes such as multiple sclerosis, the assessment of cognitive processes involved in ocular motor function may well provide an added level of sensitivity indicating more widespread pathology than would be apparent with conventional clinical assessment.
CONCLUSIONS:Assessment of cognitive function in the ocular motor system may provide insight into cerebral function, in health and disease, and may provide both diagnostic information and permit quantification of deficit in future.
We present three cases that we suggest require a novel diagnosis and a reconsideration of current understandings of pontine anatomy. In this case series, we highlight a series of patients with ...monophasic, fully recovering inflammatory lesions in the pontine tegmentum not due to any of the currently recognized causes of this syndrome. We highlight other similar cases in the literature and suggest there may be a particular epitope for an as-yet-undiscovered antibody underlying the tropism for this area. We highlight the potential harm of misdiagnosis with relapsing inflammatory or other serious diagnoses with significant adverse impact on the patient. In addition, we propose that this would support a reinterpretation of the currently accepted anatomy of the pontine gaze inputs to the median longitudinal fasciculus and paramedian pontine reticular formation.
The development of efficient and inexpensive genome sequencing methods has revolutionized the study of human bacterial pathogens and improved vaccine design. Unfortunately, the sequence of a single ...genome does not reflect how genetic variability drives pathogenesis within a bacterial species and also limits genome-wide screens for vaccine candidates or for antimicrobial targets. We have generated the genomic sequence of six strains representing the five major disease-causing serotypes of Streptococcus agalactiae, the main cause of neonatal infection in humans. Analysis of these genomes and those available in databases showed that the S. agalactiae species can be described by a pan-genome consisting of a core genome shared by all isolates, accounting for ≈80% of any single genome, plus a dispensable genome consisting of partially shared and strain-specific genes. Mathematical extrapolation of the data suggests that the gene reservoir available for inclusion in the S. agalactiae pan-genome is vast and that unique genes will continue to be identified even after sequencing hundreds of genomes.
Hallucinogen persisting perception disorder (HPPD) is characterized by the re-emergence of perceptual symptoms experienced during acute hallucinogen intoxication following drug cessation. The ...underlying pathophysiology is poorly understood. We report the clinical characteristics and investigation findings of a series of HPPD cases with a literature review of previous case reports. We draw parallels between the features of HPPD and Visual Snow Syndrome (VSS).
Retrospective case series of 13 patients referred from neuro-ophthalmologists. Literature review with 24 HPPD case reports were identified through database search using the terms "hallucinogenic persisting perception disorder" OR "hallucinogen persisting perception disorder."
Lysergic acid diethylamide (LSD), 3,4-Methyl enedioxy methamphetamine (MDMA) and cannabinoid use was common. Cannabinoids and MDMA were mostly used in association with classical hallucinogens. The most frequent symptoms in our patients were visual snow, floaters, palinopsia, photophobia and nyctalopia. In the literature other symptoms included visual hallucinations altered motion perception, palinopsia, tracers and color enhancement. Ophthalmic and neurologic investigations were mostly normal. The majority of patients had ongoing symptoms. Two of our patients fully recovered-one after treatment with benzodiazepine and one without treatment. Twenty-five percent of cases from the literature fully recovered.
HPPD presents with heterogeneous visual phenomena on a background of previous classic and non-classic hallucinogen use. Ophthalmic investigations are typically normal. The symptoms of HPPD in our case series overlap with the typical features of Visual Snow Syndrome (VSS). Patients presenting with VSS should be screened for past recreational drug use. The DSM-5 description of HPPD does not include visual snow, nyctalopia, photophobia or floaters. A revision of the diagnostic criteria to include these symptoms may better reflect the typical clinical phenotype. Increased awareness of HPPD as a secondary cause of VSS can avoid extensive investigations. Controlled trials comparing primary and secondary VSS patients are needed to understand the pathophysiology better and optimize treatment for HPPD.
Our ability to control and inhibit behaviours that are inappropriate, unsafe, or no longer required is crucial for functioning successfully in complex environments. Here, we investigated whether a ...series of ocular motor (OM) inhibition tasks could dissociate deficits in patients with multiple sclerosis (MS), including patients with only a probable diagnosis (clinically isolated syndrome: CIS), from healthy individuals as well as a function of increasing disease duration. 25 patients with CIS, 25 early clinically definite MS patients (CDMS: ≤7 years of diagnosis), 24 late CDMS patients (>7 years from diagnosis), and 25 healthy controls participated. All participants completed a series of classic OM inhibition tasks antisaccade (AS) task, memory-guided (MG) task, endogenous cue task, and a neuropsychological inhibition task paced auditory serial addition test (PASAT). Clinical disability was characterised in CDMS patients using the Expanded Disability Severity Scale (EDSS). OM (latency and error) and PASAT performance were compared between patient groups and controls, as well as a function of disease duration. For CDMS patients only, results were correlated with EDSS score. All patient groups made more errors than controls on all OM tasks; error rate did not increase with increasing disease duration. In contrast, saccade latency (MG and endogenous cue tasks) was found to worsen with increasing disease duration. PASAT performance did not discriminate patient groups or disease duration. The EDSS did not correlate with any measure. These OM measures appear to dissociate deficit between patients at different disease durations. This suggests their utility as a measure of progression from the earliest inception of the disease.
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.
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