734 research outputs found
Brainstem involvement - frequency, presentation and outcome
Background Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) are
present in a subset of aquaporin-4 (AQP4)-IgG-negative patients with optic
neuritis (ON) and/or myelitis. Little is known so far about brainstem
involvement in MOG-IgG-positive patients. Objective To investigate the
frequency, clinical and paraclinical features, course, outcome, and prognostic
implications of brainstem involvement in MOG-IgG-positive ON and/or myelitis.
Methods Retrospective case study. Results Among 50 patients with MOG-IgG-
positive ON and/or myelitis, 15 (30 %) with a history of brainstem
encephalitis were identified. All were negative for AQP4-IgG. Symptoms
included respiratory insufficiency, intractable nausea and vomiting (INV),
dysarthria, dysphagia, impaired cough reflex, oculomotor nerve palsy and
diplopia, nystagmus, internuclear ophthalmoplegia (INO), facial nerve paresis,
trigeminal hypesthesia/dysesthesia, vertigo, hearing loss, balance
difficulties, and gait and limb ataxia; brainstem involvement was asymptomatic
in three cases. Brainstem inflammation was already present at or very shortly
after disease onset in 7/15 (47 %) patients. 16/21 (76.2 %) brainstem attacks
were accompanied by acute myelitis and/or ON. Lesions were located in the pons
(11/13), medulla oblongata (8/14), mesencephalon (cerebral peduncles; 2/14),
and cerebellar peduncles (5/14), were adjacent to the fourth ventricle in
2/12, and periaqueductal in 1/12; some had concomitant diencephalic (2/13) or
cerebellar lesions (1/14). MRI or laboratory signs of blood-brain barrier
damage were present in 5/12. Cerebrospinal fluid pleocytosis was found in
11/14 cases, with neutrophils in 7/11 (3-34 % of all CSF white blood cells),
and oligoclonal bands in 4/14. Attacks were preceded by acute infection or
vaccination in 5/15 (33.3 %). A history of teratoma was noted in one case. The
disease followed a relapsing course in 13/15 (87 %); the brainstem was
involved more than once in 6. Immunosuppression was not always effective in
preventing relapses. Interferon-beta was followed by new attacks in two
patients. While one patient died from central hypoventilation, partial or
complete recovery was achieved in the remainder following treatment with high-
dose steroids and/or plasma exchange. Brainstem involvement was associated
with a more aggressive general disease course (higher relapse rate, more
myelitis attacks, more frequently supratentorial brain lesions, worse EDSS at
last follow-up). Conclusions Brainstem involvement is present in around one
third of MOG-IgG-positive patients with ON and/or myelitis. Clinical
manifestations are diverse and may include symptoms typically seen in AQP4
-IgG-positive neuromyelitis optica, such as INV and respiratory insufficiency,
or in multiple sclerosis, such as INO. As MOG-IgG-positive brainstem
encephalitis may take a serious or even fatal course, particular attention
should be paid to signs or symptoms of additional brainstem involvement in
patients presenting with MOG-IgG-positive ON and/or myelitis
A process model of the understanding of uncertain conditionals
To build a process model of the understanding of conditionals we extract a common core of three semantics of if-then sentences: (a) the conditional event interpretation in the coherencebased probability logic, (b) the discourse processingtheory of Hans Kamp, and (c) the game-theoretical approach of Jaakko Hintikka. The empirical part reports three experiments in which each participant assessed the probability of 52 if-then sentencesin a truth table task. Each experiment included a second task: An n-back task relating the interpretation of conditionals to working memory, a Bayesian bookbag and poker chip task relating the interpretation of conditionals to probability updating, and a probabilistic modus ponens task relating the interpretation of conditionals to a classical inference task. Data analysis shows that the way in which the conditionals are interpreted correlates with each of the supplementary tasks. The results are discussed within the process model proposed in the introduction
Frontiers in Psychology / Imprecise Uncertain Reasoning : A Distributional Approach
The contribution proposes to model imprecise and uncertain reasoning by a mental probability logic that is based on probability distributions. It shows how distributions are combined with logical operators and how distributions propagate in inference rules. It discusses a series of examples like the Linda task, the suppression task, Doherty's pseudodiagnosticity task, and some of the deductive reasoning tasks of Rips. It demonstrates how to update distributions by soft evidence and how to represent correlated risks. The probabilities inferred from different logical inference forms may be so similar that it will be impossible to distinguish them empirically in a psychological study. Second-order distributions allow to obtain the probability distribution of being coherent. The maximum probability of being coherent is a second-order criterion of rationality. Technically the contribution relies on beta distributions, copulas, vines, and stochastic simulation.(VLID)311645
Frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin
Background Antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) have
been suggested to play a role in a subset of patients with neuromyelitis
optica and related disorders. Objective To assess (i) the frequency of MOG-IgG
in a large and predominantly Caucasian cohort of patients with optic neuritis
(ON) and/or myelitis; (ii) the frequency of MOG-IgG among AQP4-IgG-positive
patients and vice versa; (iii) the origin and frequency of MOG-IgG in the
cerebrospinal fluid (CSF); (iv) the presence of MOG-IgG at disease onset; and
(v) the influence of disease activity and treatment status on MOG-IgG titers.
Methods 614 serum samples from patients with ON and/or myelitis and from
controls, including 92 follow-up samples from 55 subjects, and 18 CSF samples
were tested for MOG-IgG using a live cell-based assay (CBA) employing full-
length human MOG-transfected HEK293A cells. Results MOG-IgG was detected in 95
sera from 50 patients with ON and/or myelitis, including 22/54 (40.7%)
patients with a history of both ON and myelitis, 22/103 (21.4%) with a history
of ON but no myelitis and 6/45 (13.3%) with a history of longitudinally
extensive transverse myelitis but no ON, and in 1 control patient with
encephalitis and a connective tissue disorder, all of whom were negative for
AQP4-IgG. MOG-IgG was absent in 221 further controls, including 83 patients
with AQP4-IgG-seropositive neuromyelitis optica spectrum disorders and 85 with
multiple sclerosis (MS). MOG-IgG was found in 12/18 (67%) CSF samples from
MOG-IgG-seropositive patients; the MOG-IgG-specific antibody index was
negative in all cases, indicating a predominantly peripheral origin of CSF
MOG-IgG. Serum and CSF MOG-IgG belonged to the complement-activating IgG1
subclass. MOG-IgG was present already at disease onset. The antibodies
remained detectable in 40/45 (89%) follow-up samples obtained over a median
period of 16.5 months (range 0–123). Serum titers were higher during attacks
than during remission (p < 0.0001), highest during attacks of simultaneous
myelitis and ON, lowest during acute isolated ON, and declined following
treatment. Conclusions To date, this is the largest cohort studied for IgG to
human full-length MOG by means of an up-to-date CBA. MOG-IgG is present in a
substantial subset of patients with ON and/or myelitis, but not in classical
MS. Co-existence of MOG-IgG and AQP4-IgG is highly uncommon. CSF MOG-IgG is of
extrathecal origin. Serum MOG-IgG is present already at disease onset and
remains detectable in the long-term course. Serum titers depend on disease
activity and treatment status
Age-dependent favorable visual recovery despite significant retinal atrophy in pediatric MOGAD: how much retina do you really need to see well?
Neuritis òptica; Tomografia de coherència òpticaNeuritis Ăłptica; TomografĂa de coherencia ĂłpticaOptic neuritis; Optical coherence tomographyBackground
To investigate age-related severity, patterns of retinal structural damage, and functional visual recovery in pediatric and adult cohorts of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) optic neuritis (ON).
Methods
All MOGAD patients from the 5 participating centers were included. Patients with initial manifestation <18 years were included in the pediatric (MOGADped) cohort and patients with ≥18 years in the adult (MOGADadult) cohort. For patients with MOGAD ON, examinations at least ≥6 months after ON onset were included in the analyses. Using spectral domain optical coherence tomography (SD-OCT), we acquired peripapillary retinal nerve fiber layer thickness (pRNFL) and volumes of combined ganglion cell and inner plexiform layer (GCIPL). High- and 2.5% low-contrast visual acuity (HCVA, LCVA) and visual-evoked potentials (VEP) were obtained.
Results
Twenty MOGADped (10.3±3.7 years, 30 MOGAD ON eyes) and 39 MOGADadult (34.9±11.6 years, 42 MOGAD ON eyes) patients were included. The average number of ON episodes per ON eye was similar in both groups (1.8±1.3 and 2.0±1.7). In both pediatric and adult MOGAD, ON led to pronounced neuroaxonal retinal atrophy (pRNFL: 63.1±18.7 and 64.3±22.9 μm; GCIPL: 0.42±0.09 and 0.44±0.13 mm3, respectively) and moderate delay of the VEP latencies (117.9±10.7 and 118.0±14.5 ms). In contrast, visual acuity was substantially better in children (HCVA: 51.4±9.3 vs. 35.0±20.6 raw letters, p=0.001; LCVA: 22.8±14.6 vs. 13.5±16.4, p=0.028). Complete visual recovery (HCVA-logMAR 0.0) occurred in 73.3% of MOGADped and 31% MOGADadults ON eyes, while 3.3% and 31% demonstrated moderate to severe (logMAR > 0.5) visual impairment. Independent of retinal atrophy, age at ON onset significantly correlated with visual outcome.
Conclusion
Pediatric MOGAD ON showed better visual recovery than adult MOGAD ON despite profound and almost identical neuroaxonal retinal atrophy. Age-related cortical neuroplasticity may account for the substantial discrepancy between structural changes and functional outcomes.JH is (partially) funded by the German Federal Ministry of Education and Research (Grant Numbers 01ZZ1603[A-D] and 01ZZ1804[A-H] (DIFUTURE)). Open Access funding enabled and organized by Projekt DEAL
Epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome
Background A subset of patients with neuromyelitis optica spectrum disorders
(NMOSD) has been shown to be seropositive for myelin oligodendrocyte
glycoprotein antibodies (MOG-IgG). Objective To describe the epidemiological,
clinical, radiological, cerebrospinal fluid (CSF), and electrophysiological
features of a large cohort of MOG-IgG-positive patients with optic neuritis
(ON) and/or myelitis (n = 50) as well as attack and long-term treatment
outcomes. Methods Retrospective multicenter study. Results The sex ratio was
1:2.8 (m:f). Median age at onset was 31 years (range 6-70). The disease
followed a multiphasic course in 80% (median time-to-first-relapse 5 months;
annualized relapse rate 0.92) and resulted in significant disability in 40%
(mean follow-up 75 ± 46.5 months), with severe visual impairment or functional
blindness (36%) and markedly impaired ambulation due to paresis or ataxia
(25%) as the most common long-term sequelae. Functional blindness in one or
both eyes was noted during at least one ON attack in around 70%. Perioptic
enhancement was present in several patients. Besides acute tetra-/paraparesis,
dysesthesia and pain were common in acute myelitis (70%). Longitudinally
extensive spinal cord lesions were frequent, but short lesions occurred at
least once in 44%. Fourty-one percent had a history of simultaneous ON and
myelitis. Clinical or radiological involvement of the brain, brainstem, or
cerebellum was present in 50%; extra-opticospinal symptoms included
intractable nausea and vomiting and respiratory insufficiency (fatal in one).
CSF pleocytosis (partly neutrophilic) was present in 70%, oligoclonal bands in
only 13%, and blood-CSF-barrier dysfunction in 32%. Intravenous
methylprednisolone (IVMP) and long-term immunosuppression were often
effective; however, treatment failure leading to rapid accumulation of
disability was noted in many patients as well as flare-ups after steroid
withdrawal. Full recovery was achieved by plasma exchange in some cases,
including after IVMP failure. Breakthrough attacks under azathioprine were
linked to the drug-specific latency period and a lack of cotreatment with oral
steroids. Methotrexate was effective in 5/6 patients. Interferon-beta was
associated with ongoing or increasing disease activity. Rituximab and
ofatumumab were effective in some patients. However, treatment with rituximab
was followed by early relapses in several cases; end-of-dose relapses occurred
9-12 months after the first infusion. Coexisting autoimmunity was rare (9%).
Wingerchuk’s 2006 and 2015 criteria for NMO(SD) and Barkhof and McDonald
criteria for multiple sclerosis (MS) were met by 28%, 32%, 15%, 33%,
respectively; MS had been suspected in 36%. Disease onset or relapses were
preceded by infection, vaccination, or pregnancy/delivery in several cases.
Conclusion Our findings from a predominantly Caucasian cohort strongly argue
against the concept of MOG-IgG denoting a mild and usually monophasic variant
of NMOSD. The predominantly relapsing and often severe disease course and the
short median time to second attack support the use of prophylactic long-term
treatments in patients with MOG-IgG-positive ON and/or myelitis
Deletion of the SELENOP gene leads to CNS atrophy with cerebellar ataxia in dogs.
We investigated a hereditary cerebellar ataxia in Belgian Shepherd dogs. Affected dogs developed uncoordinated movements and intention tremor at two weeks of age. The severity of clinical signs was highly variable. Histopathology demonstrated atrophy of the CNS, particularly in the cerebellum. Combined linkage and homozygosity mapping in a family with four affected puppies delineated a 52 Mb critical interval. The comparison of whole genome sequence data of one affected dog to 735 control genomes revealed a private homozygous structural variant in the critical interval, chr4:66,946,539_66,963,863del17,325. This deletion includes the entire protein coding sequence of SELENOP and is predicted to result in complete absence of the encoded selenoprotein P required for selenium transport into the CNS. Genotypes at the deletion showed the expected co-segregation with the phenotype in the investigated family. Total selenium levels in the blood of homozygous mutant puppies of the investigated litter were reduced to about 30% of the value of a homozygous wildtype littermate. Genotyping >600 Belgian Shepherd dogs revealed an additional homozygous mutant dog. This dog also suffered from pronounced ataxia, but reached an age of 10 years. Selenop-/- knock-out mice were reported to develop ataxia, but their histopathological changes were less severe than in the investigated dogs. Our results demonstrate that deletion of the SELENOP gene in dogs cause a defect in selenium transport associated with CNS atrophy and cerebellar ataxia (CACA). The affected dogs represent a valuable spontaneous animal model to gain further insights into the pathophysiological consequences of CNS selenium deficiency
Determination of some heavy metals and mineral nutrients of bay tree (Laurus nobilis L.) in Bartin city, Turkey
Concentrations of Al, Cd, Cu, Ni, and Pb in Laurus nobilis L. were examined for assessment of the impact of heavy metal exposure during winter periods, since these metals have the highest toxic potential. In this study, leaf (washed and unwashed), bark and branch samples of L. nobilis and soil samples were collected from 13 different localities, belonged to three stations. In conjunction with analyzing impact of the heavy metal exposure on the city using L. nobilis as a biomonitoring tool, the uptake and composition of mineral nutrients of L. nobilis were also investigated for determining the effects of heavy metals on mineral nutrition metabolism of the plant. The heavy metal and mineral nutrient concentrations of the collected samples were measured by using ICP-OES. The obtained data was analyzed with SPSS statistics program. As a result of measurements, the lowest and highest heavy metal accumulations and the amount of mineral nutrients measured in plants were as follows; Al (14.69-122.44 mg/kg d. wt), Cd (0.23-0.89 mg/kg d. wt), Cu (1.64-14.25 mg/kg d. wt.), Ni (0.001-0.45 mg/kg d. wt.), Pb (2.06-5.28 mg/kg d. wt.) and B (1.04- 6.67 mg/kg d. wt.), Ca (1195.34-4919.03 mg/kg d. wt.), Fe (17.13-203.25 mg/kg d. wt.), K (538.99-3778.37 mg/kg d. wt.), Mg(48.1-268.5 mg/kg d. wt.), Na (24.91-77.43 mg/kg d. wt.) and Zn (4.75-15.74 mg/kg d. wt.). According to the experimental data, the volume of the air pollution was analyzed and found significant in the city. Also, it was noticed that the metabolism of mineral nutrients of L. nobilis was altered by heavy metals. Finally, it was proved that L. nobilis is a suitable organism to be used as a biomonitoring tool for conducting research on heavy metal pollution
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