46 research outputs found
Serum Leptin Levels in Treatment-Naive Patients with Clinically Isolated Syndrome or Relapsing-Remitting Multiple Sclerosis
Several studies have investigated leptin levels in patients with multiple sclerosis (MS) with somewhat conflicting results. They have all focused on patients with established relapsing-remitting (RR) MS but have not specifically looked at patients with clinically isolated syndrome (CIS) suggestive of MS, in the early stages of disease. In this study, serum leptin levels were measured in 89 treatment-naïve patients with CIS (53 patients) or RRMS (36 patients) and 73 controls searching for differences between the groups and for associations with several disease parameters. The expected significant sexual dimorphism in leptin levels (higher levels in females) was observed in both MS patients and controls. Increased leptin levels were found in female patients with RRMS compared to female controls (P=.003) and female CIS patients (P=.001). Female CIS patients had comparable levels to controls. Leptin levels correlated positively to disease duration, but not to EDSS, in female patients with RRMS. The results of the present study do not indicate involvement of leptin in the early stages of MS. Normal leptin levels in patients with CIS suggest that leptin does not have a pathogenic role. The ratio leptin/BMI increases during disease course in female MS patients in a time-dependent and disability-independent manner
Pure cerebellar ataxia due to bi-allelic PRDX3 variants including recurring p.Asp202Asn
Bi-allelic variants in peroxiredoxin 3 (PRDX3) have only recently been associated with autosomal recessive spinocerebellar ataxia characterized by early onset slowly progressive cerebellar ataxia, variably associated with hyperkinetic and hypokinetic features, accompanied by cerebellar atrophy and occasional olivary and brainstem involvement. Herein, we describe a further simplex case carrying a reported PRDX3 variant as well as two additional cases with novel variants. We report the first Brazilian patient with SCAR32, replicating the pathogenic status of a known variant. All presented cases from the Brazilian and Indian populations expand the phenotypic spectrum of the disease by displaying prominent neuroradiological findings. SCAR32, although rare, should be included in the differential diagnosis of sporadic or recessive childhood and adolescent-onset pure and complex cerebellar ataxia
A study of the association of apolipoprotein gene polymorphisms with the clinical expression of multiple sclerosis
[…] Objective. To investigate the effect of polymorphisms of APOE, APOC1, APOA1 and APOC3 on susceptibility to MS, clinical expression of MS and neuropsychological parameters of MS in a population of Greek patients with the disease. […][…] Σκοπός της παρούσας μελέτης ήταν η διερεύνηση της επίπτωσης των πολυμορφισμών ε2-4 της APOE, HpaI της APOC1, MspI της APOA1, και SstI της APOC3 στην εμφάνιση, στην κλινική έκφραση, και σε νευροψυχολογικές παραμέτρους της ΣΚΠ σε δείγμα Ελλήνων ασθενών που πάσχουν από ΣΚΠ. […
The Emerging Role of microRNA in Stroke
MicroRNAs (miRNAs) are small non-coding RNAs approximately 22
nucleotides in length that play a pivotal role in post-transcriptional
gene regulation by binding to complementary sites in the 3’-untranslated
region of messenger RNAs. In the past decade, their role in several
human diseases, from cancer to cardiovascular disease, has been
established by a wealth of evidence. Stroke is responsible for 10% of
deaths worldwide and is one of the leading causes of disability. MiRNAs
are involved in stroke risk factors including hypertension,
atherosclerosis, atrial fibrillation, diabetes and dyslipidemia. The
role of miRNAs in the pathophysiology of stroke has been the subject of
more recent investigations. Animal studies, which dominate the field,
have demonstrated the differential expression of miRNAs in brain and
blood following ischemic or hemorrhagic insult and the potential use of
miRNA antagonists to reduce focal cerebral damage. In particular,
antagomirs to miR-145, -497, -181a, -1 and let-7f have been found to be
neuroprotective in vivo. The discovery of circulating miRNAs in
peripheral blood, which are unexpectedly stable, has allowed the recent
completion of several studies in human stroke patients that have
confirmed the differential expression of specific miRNAs following
stroke and have addressed their potential use as diagnostic and
prognostic markers. With miRNA research in stroke still in its infancy,
it is anticipated that in the next few years significant discoveries
that may have important therapeutic implications will emerge
Late-onset Huntington's disease: Diagnostic and prognostic considerations
Objective: To address diagnostic and prognostic issues in patients with
late-onset Huntington’s disease (HD).
Methods: We analyzed a cohort of 41 late-onset (>= 60 years) HD patients
and compared them to 39 late-onset patients referred for HD testing that
were negative for the HD-expansion and to 290 usual-onset (20-59 years)
HD patients. Disease severity was assessed by the Total Functional
Capacity Scale.
Results: Late-onset HD comprised 11.5% of our HD cohort. In total,
70.7% of late-onset HD patients had positive family history compared to
15.4% of late-onset expansion-negative patients (p < 0.001). Clinical
features at onset or presentation could not usefully distinguish between
late-onset expansion-positive and negative patients, excepting
hemichorea, which was absent from the HD group (p = 0.024). Chorea was
the first clinical feature in 53.7% and a presenting feature in 90.2%
of late-onset HD. The mutation hit rate for late-onset patients was
51.3%, lower than in usual-onset patients (p = 0.04). Frequencies of
chorea, cognitive impairment and psychiatric manifestations at onset or
presentation were not significantly different between late-onset and
usual-onset HD patients. Gait unsteadiness however was more common at
presentation in late-onset HD (p = 0.007). Late-onset HD patients
reached a severe stage of illness on average 2.8 years earlier than
usual-onset HD patients (p = 0.046).
Conclusions: A positive family history suggestive of HD, although absent
in a third of patients, remains a helpful clue in diagnosing late-onset
HD. Prognosis of late-onset HD in terms of Total Functional Capacity
appears no better and shows a trend of being somewhat less favorable
compared to usual-onset HD. (C) 2014 Elsevier Ltd. All rights reserved
The challenge of juvenile Huntington disease To test or not to test
Objective: In a cohort of patients with suspected juvenile-onset
Huntington disease (HD), we compared HD expansion-positive and -negative
cases in order to identify parameters that may allow differentiating
between them and may act as a guide to clinicians contemplating genetic
testing.
Methods: We analyzed the clinical and genetic characteristics of 76
juvenile-onset patients referred consecutively for HD genetic testing
over a 16-year period.
Results: In total, 24 patients were positive for the HD expansion (7.8%
of our HD cohort). Mean age at onset of expanded cases was similar to
unexpanded cases. All expanded cases had a family history of genetically
confirmed HD compared to only 13.5% of unexpanded cases (p = 0.000).
Clinical symptoms at onset or at presentation could not differentiate
between expanded and unexpanded patients. Although criteria suggested by
previous reports allowed statistical differentiation between the 2
groups, they were not sufficiently sensitive and specific to be used in
clinical context and performed less satisfactorily than presence of a
family history of HD alone.
Conclusions: A diagnosis of juvenile HD should be primarily contemplated
in symptomatic children with a family history of HD, although a
proportion of these will test negative. With no family history of HD,
juvenile HD is very unlikely and genetic testing should never delay
searching for other causes. The specific nature of symptoms at onset or
at presentation is of limited value in guiding the decision to test or
not to test. Neurology (R) 2013; 80: 990-99
Serum total cholesterol correlates positively to central serotonergic turnover in male but not in female subjects
Reduced central serotonergic activity and low total serum cholesterol
have been related to increased aggression, violent behavior, and
suicidality. Searching for a correlation between them, we estimated
serum total cholesterol and CSF levels of the main serotonin metabolite
5-HIAA in medication free male and female subjects for whom diagnostic
lumbar puncture was performed. To eliminate age influence, we included
in the study subjects in the age range 26 to 45 years. In a group of 62
subjects (30 males), found negative after diagnostic neurological
examination, the correlation was not significant for the whole group,
but after sex stratification, a significant positive correlation was
revealed for males but not for females. These results were replicated in
a second group of 76 subjects (31 males) with clinical and laboratory
findings suggestive of multiple sclerosis (clinically isolated
syndrome). The results link low cholesterol to low serotonergic activity
only in males, predisposing them for violent and risky behaviors. This
phenomenon could be seen as an evolutionary trait, possibly a result of
the distinct role of males in a hunter-gatherer environment of
evolutionary adaptedness, and may contribute to the understanding of the
higher incidence of violent behavior observed in males. (C) 2010
Elsevier Inc. All rights reserved
Neurochemical and neuroendocrine correlates of overactive bladder at first demyelinating episode
AimsBladder dysfunction is frequent during the course of multiple
sclerosis (MS), observed in up to 75% of patients. Urinary
symptomatology can be a feature of the first episode of MS in a minority
of cases, and most often shows characteristics of an overactive bladder
(OAB), with voiding symptoms seen less frequently, often in combination
with OAB. The neural control of micturition is complex, involving
systems located in the brain, spinal cord, and periphery, and
implicating central noradrenergic, serotonergic, and dopaminergic
activities. Urinary disorders are also linked to anxiety and depression,
conditions connected to hypothalamus-pituitary-adrenal axis activity. In
this study we aimed to investigate neurochemical and neuroendocrine
correlates of bladder dysfunction in early MS.
MethodsWe included 101 patients at first demyelinating episode
suggestive of MS that were drug-free at assessment. We evaluated the
presence of urinary symptomatology and estimated CSF levels of the main
metabolites of noradrenaline, serotonin, and dopamine, as well CSF-ACTH
and serum cortisol.
ResultsIn total, 15 patients (15%) reported urinary dysfunction
suggestive of OAB. Four of these had coexistent voiding symptomatology.
The serotonin metabolite 5-HIAA was significantly reduced (P=0.017) in
patients with OAB syndrome, while there were no differences in the
metabolites of noradrenaline (MHPG) and of dopamine (HVA). Additionally,
significantly lower serum cortisol (P=0.009) and borderline lower
CSF-ACTH (P=0.08) were found in patients with OAB.
ConclusionsMS patients with OAB syndrome at the first demyelinating
episode show reductions in central serotonergic activity and stress
hormones. Whether the same changes persist at later disease stages
remains to be investigated. Neurourol. Urodynam. 35:955-958, 2016. (c)
2015 Wiley Periodicals, Inc
Wide range of reduced penetrance alleles in spinal and bulbar muscular atrophy: a model-based approach
Background
Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy’s
disease, is an X-linked motor neuron disorder caused by an expanded CAG
repeat in the gene coding for the androgen receptor (AR). The range and
significance of reduced penetrance alleles in SBMA has not been fully
determined to date. We presently sought to determine the range of
reduced penetrance alleles in SBMA.
Methods
Through systematic literature review and meta-analysis, we collected and
analysed data from 2576 patients with SBMA and compared the
distributions of the CAG repeat number (CAG)(n) in the AR gene between
patients and 112 248 control alleles of the general population.
Results
Our analysis revealed an unexpectedly high frequency of expanded
SBMA-associated alleles, with (CAG)(n) >= 35 present in 107/100,000 and
(CAG)(n) >= 38 present in 27/100,000 of the general population.
Consequently, we suggest an updated model describing the distribution of
expanded alleles in the general population. We argue against the
established cut-off principle for the penetrance of SBMA and suggest
that penetrance gradually increases from 35 to approximately 46
(CAG)(n), above which it reaches a plateau approaching maximum value.
Conclusion
Asymptomatic men of the general population with no/unknown SBMA family
history are free of risk when carrying (CAG)(n) <= 34, are at
intermediate but increasing risk for developing SBMA when carrying
(CAG)(n) approximate to 35-46 and have close to 100% risk of developing
the disease when carrying (CAG)(n) >= 47. The above observations should
be helpful and clinically useful when providing genetic counselling to
individuals and families bearing SBMA-associated alleles