Beruflich Dokumente
Kultur Dokumente
AIM
To study the clinical and neuroradiological
features of epilepsy associated with RNFL
thinning
METHODS
Participants
454 adult patients 18-60 years with epilepsy able
to undertake OCT were consecutively included in
this cross-sectional cohort study.
Exclusion Crtieria
Clinical data
The following variables were evaluated:
Age, sex, ethnicity
Epilepsy diagnosis, duration of epilepsy (from the
time of diagnosis to the date of OCT assessment)
Handedness, intellectual disability
Antiepileptic drug (AED) history
Epilepsy surgery
Presence of VNS
Statistics
Data were analysed using Stata/IC V.11.1 soft
ware
(Stata, Texas, USA).
RESULTS
Three hundred of the 454 people with epilepsy
attending specialist clinics were included in this
study.
Their scans were analysed and compared to results
from 90 healthy controls.
Most people had drug-resistant epilepsy (210
individuals 70 %) and long disease duration (mean
23.3 years, SD 15.1)
The average RNFL thickness and the thickness of
each 90 quadrant were significantly lower in people
with epilepsy than in healthy controls
No control had abnormal RNFL thinning (<1st centile)
Discussion
People with drug-resistant epilepsy have a more
than twofold of RNFL thinning compared with
people with non-resistant epilepsy
The biological mechanisms leading to the
association between RNFL changes and
intellectual disability, lower brain parenchymal
fraction or drug resistance are unknown
In people with temporal lobe epilepsy, transsynaptic degeneration of the limbic system or
extratemporal areas has been demonstrated
using MRI, PET and SPECT
Several previous studies have suggested that
correleation between RNFL thickness and brain
parenchymal fraction in MS independent of optic
neuritis
This is the first study in epilepsy, which showed a
significant association between RNFL thinning
and lower brain volume as assessed by brain MRI.
Limitations
Though excluded participants with known glaucoma,
glaucoma might be asymptomatic or undiagnosed.
Individuals with intraocular pressure in the normal
range might still have normal-tension glaucoma and
RNFL thinning.
A cross-sectional study may not yield the strongest
correlations.
Comments
RNFL- Syndromic Epilepsy -need to be explored.
The study included fewer controls than cases.
Aim
To identify of the novel risk factors associated
with SLE/PRES
Exclusion:
Patients with another rheumatological
disease were excluded.
Persistent lymphopenia :
At least two peripheral blood lymphocyte
counts <1000 cells/mm3, at least 3 months apart.
Dyslipidemia :
Hypercholesterolaemia 5.18 mmol/L
and/or hypertriglyceridaemia 1.69 mmol/L).
Isointensity or hypointensity in T1
Hyperintensity in T2 and FLAIR sequences
No restriction on DWI
Serum markers:
Double-stranded DNA
ANA
Anticardiolipin
Anti-2-glycoprotein
C3 and C4 levels
PRES reversibility was defined on follow-up
clinical evaluation and in some cases was confirmed
by MRI.
ETHICS
The study was approved by the local ethics
committees.
STATISTICS
Data were analysed with SPSS V.21
RESULTS
PRES/SLE
P value
Serum
creatinine
304.0943.3
180.354.04
mmol/L,
0.079
Hypertension
34%,
68%
0.003
Dyslipidemia
3%
37%
0.001
Lymphocyte
count
2422398.9
77690.7
0.001
Symptom
reversibility in
less than 72 h
Mean hospital
stay
Mortality at 12
months
0.44
13.12.66
17.32.07
0.21
0.51
DISCUSSION
SLE is the most frequently associated
rheumatological disease.
The prevalence of PRES in patients with SLE
has been reported to be less than 1%
Aggressive immunosuppressive treatments
High SLEDAI scores,
Renal dysfunction
Uncontrolled hypertension
previously described as factors related to
PRES development in patients with SLE.
This study, the largest to date evaluating SLEassociated PRES, and also described two novelrisk factors:
Lymphopenia
Dyslipidemia.
limitations
Retrospective
PRES events were found by searching the
electronic clinical record systems of each
hospital, which could be associated with a lack of
complete clinical data in some of the included
subjects.
Conclusions
Aside from corroborating the conventional risk
factors for the PRES/SLE association (high SLEDAI,
renal dysfunction and hypertension), this study
also described lymphopenia as a novel risk factor
and dyslipidemia as a metabolic feature that is
strongly associated with SLE-associated PRES.
Comments
Prospective studies will be needed to confirm
these findings
Confounding factors on dyslipidemia needs to be
take into account
Introduction
Motorneuron diseases are a group of
neurodegenerative disorders, the most common form
of which is ALS.
It is characterised by degeneration of the upper and
lower motor neurons.
ALS has a median survival of 3 years from symptom
onset.
Around 7% of those initially diagnosed as ALS
ultimately turned out to have a different disease.
Aim
To determine the CSF biomarkers to differentiate
MND from its mimics.
MATERIAL/METHODS
Participants and clinical characterisation
Ethical Clearance:
Patients provided written informed consent for
the study
The study was approved by the ethics committee
of the University of Ulm
Neuromuscular
Laboratory markers
CSF was obtained by lumbar puncture,
centrifuged and stored within 2 h at 80C until
analysis.
Commercially available ELISA kits were used for
NfL and pNfH and for Tau and pTau.
RESULTS
There was no age difference between the MND
group and the control groups.
The concentrations of NfL and pNfH were
significantly higher in the CSF obtained from
patients with MND (p<0.0001)
The concentrations of Tau and pTau in the CSF
were significantly higher in AD patients than in all
patients with non-AD diagnoses taken together.
(p<0.0001).
Myopathy (n=2)
CIDP
PNP
Benign fasciculation
Encephalitis
Radiculopathy
Myositis
Endocrine myopathy
Chronic pain
Spinocerebellar ataxia
DISCUSSION
CSF levels of NfL and pNfH are elevated in MND,
thus enabling a sensitive and specific
discrimination of MND vs MND Mimics
In particular, a high positive predictive value
could be found for these biomarkers qualifying
them as confirmation markers for suspected MND.
Negative results for these markers do not rule
out MND diagnosis.
Comments
The correlation between CSF and serun NF levels
need to be studied.
INTRODUCTION
Multiple sclerosis (MS) is a chronic inflammatory disease
of the CNS affecting an estimated 2.5 million people
worldwide
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Objective
This is a double-blind, placebo-controlled, phase II
study evaluated the efficacy and safety of
ponesimod, an oral selective S1P1 receptor
modulator for the treatment of patients with
RRMS.
Study endpoints
The primary efficacy endpoint was the cumulative
number of new Gd+ lesions per patient detected
on T1-weighted MRI scans from weeks 12 to 24.
Cumulative number of new or enlarging nonenhancing T2 lesions at weeks 12, 16, 20 and 24
Cumulative number of combined unique active
lesions (CUALs; sum of all new T1 Gd+ lesions
and new or enlarging T2 lesions since previous
MRI scan) at weeks 12, 16, 20 and 24
Statistical analyses
The global null hypothesis was that none of the
three ponesimod groups differed from the placebo
group in the mean cumulative number of new T1
Gd+ lesions at weeks 12 to 24.
The alternate hypothesis was that at least one of
the ponesimod treatment groups differed from
the placebo group.
RESULTS
Patients
Of the 621 patients screened, 464 were
randomised between October 2009 and
November 2010 to receive ponesimod 10, 20 or
40 mg, or placebo.
Demographic and baseline disease characteristics
were similar across treatment groups
End Points
Mean
cumulative
number of new
T1 Gd+ lesions
The mean
reduction in new
or enlarging T2
lesions
10 Mg
3.5
31% (p=0.2194)
20 mg
1.1
56% (p=0.0208)
40 mg
1.4
34% (p=0.2194
ARR reduction
The ARR was numerically lower in each
ponesimod group
ARR was reduced by
37% - ponesimod 10 mg (p=0.1619)
21%-ponesimod 20 mg (p=0.4420)
52%- ponesimod 40 mg (p=0.0363)
K-M
Pharmacodynamics analysis
Lymphocyte counts were rapidly reduced with
ponesimod treatment in a dose-dependent
manner
Mean reductions from baseline to week 24 were
50%, 65% and 69% for ponesimod 10, 20 and 40
mg, respectively, and 3% in the placebo group.
The proportion of patients with 1 infectionassociated AEs was similar across the four groups
(placebo 45.5%; ponesimod 10 mg, 37.0%; 20
mg, 32.5%; 40 mg, 36.1%).
There were no treatment discontinuations due to
lymphopenia, nor was there a correlation
between the incidence of infections and
lymphocyte count reduction during the study.
DISCUSSION
Once-daily treatment with ponesimod 10, 20 or 40
mg for 24 weeks significantly and dose-dependently
achieved primary and secondary end points
Ponesimod was generally well tolerated at doses of
10 and 20 mg
The 40 mg dose showed signs of reduced
tolerability with no additional benefit with respect to
MRI or pharmacodynamic efficacy compared with
the 20 mg dose.
The reason for the lack of additional benefit with
ponesimod 40 mg compared with ponesimod 20 mg
is not entirely clear
Comments
The long-term safety and clinical efficacy needs
to be followed
Extension study is ongoing
Macular Hole