Neurodegenerative diseases represent an increasing economic, social, and, above all, medical burden worldwide. The second most prevalent disease in this category is Parkinson’s disease, surpassed ...only by Alzheimer’s. It is a treatable but still incurable systemic disease with a pathogenesis that has not yet been elucidated. Several theories are currently being developed to explain the causes and progression of Parkinson’s disease. Magnesium is one of the essential macronutrients and is absolutely necessary for life as we know it. The magnesium cation performs several important functions in the cell in the context of energetic metabolism, substrate metabolism, cell signalling, and the regulation of the homeostasis of other ions. Several of these cellular processes have been simultaneously described as being disrupted in the development and progression of Parkinson’s disease. The relationship between magnesium homeostasis and the pathogenesis of Parkinson’s disease has received little scientific attention to date. The aim of this review is to summarise and critically evaluate the current state of knowledge on the possible role of magnesium in the pathogenesis of Parkinson’s disease and to outline possible future directions for research in this area.
Alzheimer's disease (AD) is an incurable neurodegenerative disease and the most frequently diagnosed type of dementia, characterized by (1) perturbed cerebral perfusion, vasculature, and cortical ...metabolism; (2) induced proinflammatory processes; and (3) the aggregation of amyloid beta and hyperphosphorylated Tau proteins. Subclinical AD changes are commonly detectable by using radiological and nuclear neuroimaging methods such as magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), and single-photon emission computed tomography (SPECT). Furthermore, other valuable modalities exist (in particular, structural volumetric, diffusion, perfusion, functional, and metabolic magnetic resonance methods) that can advance the diagnostic algorithm of AD and our understanding of its pathogenesis. Recently, new insights into AD pathoetiology revealed that deranged insulin homeostasis in the brain may play a role in the onset and progression of the disease. AD-related brain insulin resistance is closely linked to systemic insulin homeostasis disorders caused by pancreas and/or liver dysfunction. Indeed, in recent studies, linkages between the development and onset of AD and the liver and/or pancreas have been established. Aside from standard radiological and nuclear neuroimaging methods and clinically fewer common methods of magnetic resonance, this article also discusses the use of new suggestive non-neuronal imaging modalities to assess AD-associated structural changes in the liver and pancreas. Studying these changes might be of great clinical importance because of their possible involvement in AD pathogenesis during the prodromal phase of the disease.
Amyotrophic lateral sclerosis is a severe neurodegenerative disease whose exact cause is still unclear. Currently, research attention is turning to the mitochondrion as a critical organelle of energy ...metabolism. Current knowledge is sufficient to confirm the involvement of the mitochondria in the pathophysiology of the disease, since the mitochondria are involved in many processes in the cell; however, the exact mechanism of involvement is still unclear. We used peripheral blood mononuclear cells isolated from whole fresh blood from patients with amyotrophic lateral sclerosis for measurement and matched an age- and sex-matched set of healthy subjects. The group of patients consisted of patients examined and diagnosed at the neurological clinic of the University Hospital Martin. The set of controls consisted of healthy individuals who were actively searched, and controls were selected on the basis of age and sex. The group consisted of 26 patients with sporadic forms of ALS (13 women, 13 men), diagnosed based on the definitive criteria of El Escorial. The average age of patients was 54 years, and the average age of healthy controls was 56 years. We used a high-resolution O2K respirometry method, Oxygraph-2k, to measure mitochondrial respiration. Basal respiration was lower in patients by 29.48%, pyruvate-stimulated respiration (respiratory chain complex I) was lower by 29.26%, and maximal respiratory capacity was lower by 28.15%. The decrease in succinate-stimulated respiration (respiratory chain complex II) was 26.91%. Our data confirm changes in mitochondrial respiration in ALS patients, manifested by the reduced function of complex I and complex II of the respiratory chain. These defects are severe enough to confirm this disease’s hypothesized mitochondrial damage. Therefore, research interest in the future should be directed towards a deeper understanding of the involvement of mitochondria and respiratory complexes in the pathophysiology of the disease. This understanding could develop new biomarkers in diagnostics and subsequent therapeutic interventions.
Gene
(
) is localized within Parkinson's disease-(PD)-susceptibility locus
and encodes for the Na
/Mg
-exchanger. The association of several
SNPs with PD has been studied. Two, rs11240569 and ...rs823156, have been associated with reduced PD-susceptibility primarily in Asian populations. Here, we examined the association of rs11240569, rs708727, and rs823156 with PD in the Slovak population and their power to discriminate between PD patients and healthy controls. The study included 150 PD patients and 120 controls. Genotyping was performed with the TaqMan
approach. Data were analyzed by conventional statistics and Random Forest machine-learning (ML) algorithm. Individually, none of the three SNPs is associated with an altered risk for PD-onset in Slovaks. However, a combination of genotypes of SNP-triplet GG
/AG
/AA
is significantly (
< 0.05) more frequent in the PD (13.3%) than in the control (5%) cohort. ML identified the power of the tested SNPs in isolation or of their singlets (joined), duplets and triplets to discriminate between PD-patients and healthy controls as zero. Our data further substantiate differences between diverse populations regarding the association of
polymorphisms with PD-susceptibility. Lack of power of the tested SNPs to discriminate between PD and healthy cases render their clinical/diagnostic relevance in the Slovak population negligible.
The relationship between Health-Related Quality of Life (HRQoL) and MDS-UPDRS has not been fully studied so far. The aim of this study was to evaluate the relationship between all MDS-UPDRS ...components and HRQoL in a representative international cohort of PD patients.
We collected demographic and disease-related data as well as MDS-UPDRS and PDQ8 scales. Data were analyzed using correlations between PDQ8 and all MDS-UPDRS items, subsequently two hierarchical multiple regressions were performed, first between the scores of the MDS-UPDRS Parts and PDQ8 and second between individual items from those Parts demonstrating significant relationship to PDQ8 scores in the first regression. LASSO regression analyses were performed to evaluate the relationship between PDQ8 and all individual MDS-UPDRS items.
A total of 3206 PD patients were included in the study. In the first regression analysis, PDQ8 was significantly related to MDS-UPDRS parts I and II, but not to III and IV. In the second regression model, significant contributions to PDQ8 were found for Part I items Fatigue, Pain, Depressed mood, Apathy; and Part II items Dressing, Doing hobbies, Freezing, Speech and Tremor. In the LASSO analysis, six Part I, seven Part II, three Part III and one Part IV items contributed to PDQ8 scores. The five items most significantly related to the model were Depressed mood, Dressing, Apathy, Pain and Fatigue.
This is so far the largest study related to HRQoL issues in PD. Restrictions in activities of daily living and non-motor symptoms significantly contribute to HRQoL in PD.
•This is the largest study related to Quality of Life (QoL) in PD so far.•QoL is related especially to MDS-UPDRS Part II (ADLs) and Part I (NMS).•Four out of five most important independent contributors were non-motor items.
(
) SNPs rs11240569 and rs823156 are associated with altered risk for Parkinson's disease (PD), predominantly in Asian populations, and rs708727 has been linked to Alzheimer's disease (AD). In this ...study, we have examined a potential association of the three aforementioned SNPs and of rs9438393, rs56152218, and rs61822602 (all three lying in the
promoter region) with PD in the Slovak population. Out of the six tested SNPs, we have identified only rs708727 as being associated with an increased risk for PD onset in Slovaks. The minor allele (A) in rs708727 is associated with PD in dominant and completely over-dominant genetic models (OR
= 1.36 (1.05-1.77),
= 0.02, and OR
= 1.34 (1.04-1.72),
= 0.02). Furthermore, the genotypic triplet GG
+ AG
+ CC
might be clinically relevant despite showing a medium (
≥ 0.5) size difference (
= 0.522) between the PD and the control populations. RandomForest modeling has identified the power of the tested SNPs for discriminating between PD-patients and the controls to be essentially zero. The identified association of rs708727 with PD in the Slovak population leads us to hypothesize that this
polymorphism, which is involved in the epigenetic regulation of the expression of the AD-linked gene
, is also involved in the pathoetiology of PD (or universally in neurodegeneration) through the same or similar mechanism as in AD.
Once-daily treatment formulation is associated with better adherence in comparison to more complex medication regimens. The study aimed to detect the extent of adherence to pharmacotherapy in ...Parkinson disease (PD) patients who take a minimum of three daily doses of drugs, and to identify factors associated with lower levels of adherence.
The cohort was selected from non-demented PD patients. The 8-Item Morisky Medication Adherence Scale (MMAS-8), 8-Item Parkinson's Disease Questionnaire (PDQ-8), Geriatric Depression Scale (GDS), Non-Motor Symptom Assessment Scale (NMSS), 9-Item Wearing-off Questionnaire (WOQ-9), MDS-UPDRS III (motor examination), and IV (motor complications) scales were used in this study.
From a total of 124 subjects, 33.9% reported a high level of adherence, 29.8% reported a medium level of adherence, and 36.3% reported a low level of adherence to their pharmacotherapy. The level of non-adherence correlated with gender, longer disease duration, higher scores of PDQ-8, NMSS, WOQ-9, and MDS-UPDRS IV. Detailed analysis of NMSS demonstrated a correlation between the level of adherence and domains sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, and urinary symptoms. Independent risk factors for non-adherence were excessive daytime sleepiness, anhedonia, and forgetfulness.
Non-adherence to more complicated medication regimens is frequent in PD patients and is associated with gender, longer PD duration, poorer quality of life, frequency and severity of non-motor symptoms, and more severe motor and non-motor fluctuations. Non-adherence was predicted by non-motor symptoms including fatigue, mood disturbances, and subjective cognitive complaints.
Paramyotonia congenita is a non-dystrophic myotonia, in which muscle relaxation is delayed after voluntary or evoked contraction. This condition cannot be distinguished on the basis of symptoms and ...signs alone. It requires consideration of genetics as more than 100 mutations in the CLCN1 gene and at least 20 mutations in the SCN4A gene are associated with the clinical features of the non-dystrophic myotonias. Only a few families with the described features but no genetic testing have been reported in Slovakia. This prompted us to investigate genetic mutations in the SCN4A gene in 3 Slovak families clinically diagnosed with paramyotonia.
Genomic DNA of the family members was extracted from peripheral blood and amplified by polymerase chain reaction. SCN4A variants were screened by Sanger sequencing.
Our results revealed 2 potential disease-causing mutations present in the probands and affected family members - mutations c.3938C > T (p.T1313M) in two families and mutation c.2111C>T (p. T704M) in one family.
Our results may help to identify genetic determinants as well as clarify genotype-phenotype relationships in patients with paramyotonia in Slovakia.
Abstract
Background
Charcot-Marie-Tooth 1C (CMT1C) is a rare form of dominantly inherited CMT1 neuropathy caused by a mutated gene encoding lipopolysaccharide-induced tumour necrosis alpha factor ...(LITAF).
Case presentation
We report a 56-year-old patient with an atypical clinical phenotype of CMT1C, which started as progressive weakness of a single upper limb resembling acquired inflammatory neuropathy. Nerve conduction studies (NCS) and temporarily limited and partial effects of immunotherapy supported the diagnosis of inflammatory neuropathy. Significant progression of polyneuropathy, despite intensive long-lasting immunotherapy, together with repeatedly negative auxiliary investigations (CSF, MRI and antibodies) and genetic testing results finally led to the diagnosis of CMT1C neuropathy.
Conclusions
CMT1C should be added to the list of inherited neuropathies that need to be considered in suspected cases of inflammatory demyelinating neuropathy.
Improvement of adherence to pharmacotherapy in patients with Parkinson's disease (PD) is a challenge in routine clinical practice. Our study was aimed at the effect of pillbox organizers with alarms ...improving adherence to pharmacotherapy and its impact on clinical outcomes. Forty nonadherent patients with PD being treated with ≥ 3 daily doses of levodopa and/or dopamine agonists were pseudorandomized and consecutively ranked to groups A (early-start intervention) and B (delayed-start intervention). We used the following validated diagnostic instruments: MMAS-8 (adherence), PDQ-8 (quality of life, QoL), GDS (depression), NMSS (non-motor symptoms), MDS-UPDRS III (motor involvement), MDS-UPDRS IV, and WOQ-9 (motor and non-motor fluctuations and dyskinesias). We proved a significantly improved rate of adherence with the use of pillbox organizers with alarms. Moreover, after only four weeks of using the pillbox organizer, we detected an improvement in QoL scores, motor involvement, motor-, and non-motor fluctuations. Our study showed that pillbox organizers with alarms are efficient in improving adherence to pharmacotherapy in PD. It also could contribute to better motor states, less severe fluctuations, and improved QoL.
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