Disease progression in patients with spinal muscular atrophy (SMA) has changed dramatically within the past years due to the approval of three different disease-modifying treatments. Nusinersen was ...the first drug to be approved for the treatment of SMA patients. Clinical trials provided data from infants with SMA type 1 and children with SMA type 2, but there is still insufficient evidence and only scarcely reported long-term experience for nusinersen treatment in ambulant patients. Here, we report data from the SMArtCARE registry of ambulant patients under nusinersen treatment with a follow-up period of up to 38 months.
SMArtCARE is a disease-specific registry in Germany, Austria and Switzerland. Data are collected as real-world data during routine patient visits. Our analysis included all patients under treatment with nusinersen able to walk independently before start of treatment with focus on changes in motor function.
Data from 231 ambulant patients were included in the analysis. During the observation period, 31 pediatric walkers (27.2%) and 31 adult walkers (26.5%) experienced a clinically meaningful improvement of≥30 m in the 6-Minute-Walk-Test. In contrast, only five adult walkers (7.7%) showed a decline in walking distance≥30 m, and two pediatric walkers (1.8%) lost the ability to walk unassisted under treatment with nusinersen. HFMSE and RULM scores improved in pediatric and remained stable in adult patients.
Our data demonstrate a positive effect of nusinersen treatment in most ambulant pediatric and adult SMA patients. We not only observed a stabilization of disease progression or lack of deterioration, but clinically meaningful improvements in walking distance.
The present study aimed to investigate differences in circulating thyroid hormone levels, gender, education, depressive symptoms, and cognitive performance among patients with cognitive impairment, ...and also to examine their associations, as well as that of cognitive decline, with 5‐year mortality. Between 1998 and 2017, a hospital‐based, single‐centre (Neurology Department of the General Hospital in Vienna, Austria), retrospective follow‐up study enrolled 2102 patients with mild to severe cognitive impairment (grouped into subjective cognitive decline, mild cognitive impairment, and Alzheimer's disease). Cox proportional hazards models were used to calculate hazard ratios (HRs), with 95% confidence intervals (CIs), as well as to calculate stepwise adjustments for demographic variables (age, gender, and education), depressive symptoms (Geriatric Depression Scale, GDS‐15), and neuropsychological abilities (four domains of a neuropsychological test battery of Vienna, NTVB). In univariate analyses, total triiodothyronine (TT3) levels differed significantly between Alzheimer's disease and mild cognitive impairment patients (pdiff = .001). No other differences in cognitive impairment subgroups with any of the measured thyroid hormones were observed. Furthermore, in multivariate models, circulating TT3 was not associated with mortality (multivariable‐adjusted HR per unit increase in TT3 = 0.56; 95% CI = 0.29–1.07). In multivariate models, we observed significantly lower 5‐year mortality among women (HR = 0.56; 95% CI = 0.43–0.73) and those who scored higher on any of the four domains of the NBTV (e.g., attention and perceptual speed, HR = 0.63; 95% CI = 0.54–0.72); we also observed significantly higher 5‐year mortality among patients with depressive symptoms (HR per one point score increase in GDS‐15 = 1.06; 95% CI = 1.02–1.10), regardless of cognitive impairment subgroup. Among patients with various degrees of cognitive impairment, we found no associations of thyroid hormone levels with 5‐year mortality. Gender, neuropsychological abilities, and depressive symptoms were each significant predictors of 5‐year mortality. These results suggest that a neurocognitive test performance could serve as an important predictor of 5‐year mortality among patients with cognitive impairment, although further studies with a more complete adjustment for comorbidities are needed to confirm these findings.
Among patients with various degrees of cognitive impairment, we found little to no differences in circulating thyroid hormone levels and no associations of thyroid hormone levels with mortality. Further studies with more complete adjustment for comorbidities are needed to confirm these findings.
Summary
Objective
An association between odor and cognitive impairment has been shown in many studies. The objective of the present hospital-based, single-center retrospective study was to assess the ...impact of odor impairment on the mortality of patients with Alzheimer’s disease (AD), subjective cognitive decline (SCD), and mild cognitive impairment (MCI).
Methods
Odor function was measured by Sniffin Sticks (Burghart Messtechnik, Holm, Germany) and the assessment of self-reported olfactory functioning and olfaction-related quality of life (ASOF) test. Cognitive performance was assessed by an extensive neuropsychological test battery, symptoms of depression were diagnosed with the Geriatric Depressive Scale (GDS). The influence of demographic factors such as gender, age, and education were examined.
Results
Although the univariate analyses and pairwise post hoc comparison showed significant differences for some of the olfactory performance tests/subtests, the multivariate models showed no association between olfactory test performance and mortality among patients with cognitive impairment. “Attention,” a domain of the Neuropsychological Test Battery Vienna (NTBV), as well as depressive symptoms, gender, and age, showed a significant influence on the mortality of the patient group.
Conclusion
Lower olfactory performance showed no impact on mortality. However, decreased cognitive function of “Attention” can be considered as an influential predictor for mortality.
Abstract We performed positron emission tomography using carbonyl-11 C WAY-100635, a serotonin 1A (5-HT1A ) receptor antagonist, in 13 patients with temporal lobe epilepsy (TLE) and in 13 controls. ...5-HT1A receptor distribution mapping allowed correct lateralization of the epileptogenic temporal lobe in all patients. 5-HT1A receptor binding potential (BPND ) was significantly reduced in almost all temporal regions of the epileptogenic lobe. Compared with controls, the patients had significantly decreased BPND values in the hippocampus, parahippocampal gyrus, and amygdala. The asymmetry index (AI), which characterizes the interhemispheric asymmetry in BPND , was significantly higher in patients than in controls in most regions. Depression scores were not significantly correlated with BPND or AI values. Our data provide further evidence of functional changes in the serotonergic system in TLE. Molecular imaging of the 5-HT1A receptor may help to define the in vivo neurochemistry of TLE, and may provide a valuable tool in the noninvasive presurgical assessment of patients with medically refractory TLE.
Purpose: We systematically analyzed the lateralizing value of clinical seizure semiology in patients with frontal lobe epilepsy (FLE).
Methods: We studied the incidence, positive predictive value ...(PPV), and the lateralizing significance of various clinical symptoms in 228 seizures (s) of 31 patients (p) with medically refractory FLE (17 with left‐sided and 14 with right‐sided seizure onset). Seizures recorded during prolonged video‐EEG monitoring were assessed by two independent reviewers blinded for the patient's clinical data. Analysis was performed both for patients and seizures.
Results: Version 16 p (52%); PPV, 94%; p = 0.001; 47 s (21%); PPV, 75%; p = 0.001, unilateral clonic movements 16 p (52%); PPV, 81%; p = 0.021; 32 s (14%); PPV, 81%; p = 0.001, unilateral dystonic posturing eight p (26%); PPV, 75%; p = 0.289; 46 s (20%); PPV, 80%; p = 0.001, unilateral tonic posturing 10 p (32%); PPV, 80%; p = 0.109; 19 s (7.4%); PPV, 79%; p = 0.019, and unilateral grimacing 10 p (32%); PPV, 100%; p = 0.002; 19 s (8%); PPV, 100%; p = 0.001 were of lateralizing significance, indicating a contralateral seizure onset. Asymmetric ending five p (16%); PPV, 80%; p = 0.375; nine s (4%); PPV, 89%; p = 0.039 after secondarily generalized tonic–clonic seizures was significantly associated with an ipsilateral seizure onset. Pure ictal vocalizations occurred significantly more frequently in seizures of right hemispheric onset 13 p (42%); PPV, 62%; p = 0.581; 63 s (28%); PPV, 73%; p = 0. 001, whereas in individual patients, this symptom showed no lateralizing significance. The remaining clinical symptoms (figure 4 sign, unilateral hand automatisms, early head turning, postictal nose wiping, and unilateral eye blinking) were not of lateralizing significance in our patients. The results of clinical seizure lateralization corresponded with the final lateralization of the seizure‐onset zone in 81% of our patients.
Conclusions: Clinical seizure semiology can provide correct information on the lateralization of the seizure‐onset zone in >80% of patients with medically refractory frontal lobe epilepsy.
We characterize a consanguineous Egyptian family with an autosomal recessively inherited familial cortical myoclonic tremor and epilepsy. We used multipoint linkage analysis to map the causative ...mutation to a 12.7 megabase interval within 1q31.3-q32.2 with a log of odds score of 3.6. For further investigation of the linked region in an efficient and unbiased manner, we performed exome sequencing. Within the suspected region we identified a homozygous single base pair deletion (c.503_503delG) leading to a frameshift in the coding region of the sixth exon of CNTN2 alias TAG-1 (p.Trp168fs), which segregated in the respective family. Many studies point towards an important role of the CNTN2 product contactin 2 in neuronal excitability. Contactin 2, a glycosylphosphatidylinositol-anchored neuronal membrane protein, and another transmembrane protein called contactin associated protein-like 2 (CNTNAP2 alias CASPR2) are together necessary to maintain voltage-gated potassium channels at the juxtaparanodal region. CNTN2 knockout mice were previously reported to suffer from spontaneous seizures and mutations in the CNTNAP2 gene have been described to cause epilepsy in humans. To further delineate the role of CNTN2 in patients with epilepsy, we sequenced the coding exons in 189 Caucasian patients with epilepsy. No recessive mutation was detected and heterozygote carriers of rare CNTN2 variants do not seem to be predisposed to epilepsy. Given the severity of the mutation and the proposed function of the gene, we consider this mutation as the most likely cause for cortical myoclonic tremor and epilepsy in this family.
The aim of this study was to replicate a previously reported association between drug resistance in epilepsy patients and the 24C>T variant of the ABCC2 gene that codes for the drug efflux ...transporter MRP2.
We genotyped 381 Caucasian epileptic patients (337 drug resistant and 44 drug responsive) and 247 healthy controls for the ABCC2 gene -24C>T polymorphism (rs717620) and two other nearby SNPs in linkage disequilibrium (1249G>A and 3972C>T). Genotype, allele and three-SNP-haplotype frequencies were compared between groups. Patients were further stratified into four groups according to their degree of drug resistance (as measured by seizure frequency under medication) to perform regression analysis against genotypes and haplotpyes.
We detected no significant differences in the distribution of any of the tested alleles, genotypes or haplotypes between the investigated groups. Neither was there an association between genotypes or haplotypes and degree of drug resistance. This study was adequately powered to detect genotype relative risks of above two.
Although adequately powered to detect the previously reported effect size and although our definition of drug resistance, following the International League Against Epilepsy guidelines, was slightly stricter than in the original study, we failed to confirm an association between the 24C>T variant in the ABCC2 gene and drug resistance in epilepsy.
Dementia and pain Schmidt, Reinhold; Bach, Michael; Dal-Bianco, Peter ...
Neuropsychiatrie,
2010, Letnik:
24, Številka:
1
Journal Article
Recenzirano
Dementia has been associated with disturbed pain processing and an impaired ability to provide self-reported ratings on pain. Patients with cognitive impairment have been shown to receive pain ...treatment less frequently than cognitively unimpaired individuals. Comorbidity is common in patients with dementia and a major factor contributing to pain. This demonstrates that a structured evaluation and categorisation of pain is mandatory for the treatment of older patients and that care should be taken to note indirect signs of pain. The appropriate scales are available and we propagate their application. Multimodal pain therapy is superior to one-dimensional approaches. A discussion of the effects and interactions of the analgesics presently available for geriatric care forms an integral part of this review.
Sex differences in Alzheimer's disease Schmidt, Reinhold; Kienbacher, Eva; Benke, Thomas ...
Neuropsychiatrie,
2008, Letnik:
22, Številka:
1
Journal Article
Recenzirano
The prevalence of Alzheimer disease is higher in women than in men. In the age group 65-69 years 0.7% of women and 0.6% of men suffer from the disease with increasing frequencies of 14.2% and 8.8% in ...individuals aged 85-89 years. The incidence is also higher in demented women. In Austria 74.1% of Alzheimer patients older than 60 years are women. Several studies report more pronounced language, mnestic, semantic and orientation deficits in women, but methodological shortcomings might be responsible for this finding. The validity of results reporting a more rapid cognitive decline in women can also be questioned. Women have a broader spectrum of dementiarelated behavioural symptoms with a predominance of depression, while aggression is more frequent in men than in women. Biological explanations for gender-specific differences in the phenotype of Alzheimer s disease include different brain morphology and function with higher susceptibility for pathological lesions in women and greater cognitive reserve in men. Sex differences were also reported for expression of antioxidative enzymes and post-menopausal hormonal changes. Interactions between gender nd response to treatment, if any, are subtle and have large intra-individual variability. In Austria, two thirds of patients receiving attendance allowance are women. Care takes place in 80% by the families and is provided by women in 78%. The rate of female care-givers in partly institutionalized care units in 91% in nursing homes it is 84%.
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