- Chorea Hyperglycemia Basal Ganglia Syndrome in a 63-Year-Old Male. [Journal Article]
- CRCase Rep Med 2018; 2018:9101207
- Chorea hyperglycemia basal ganglia syndrome (CHBG) is a rare condition that manifests within the setting of uncontrolled nonketotic diabetes mellitus. The objective of this case report is to present ...
Chorea hyperglycemia basal ganglia syndrome (CHBG) is a rare condition that manifests within the setting of uncontrolled nonketotic diabetes mellitus. The objective of this case report is to present a patient found to have CHBG and provide a timeline in terms of his workup and subsequent treatment. We also present a commentary on the current understanding of the pathophysiology and treatment and how this was applied to our patient. The case involves a 63-year-old poorly controlled diabetic male who presented with a one-week history of uncontrolled choreiform movements of his left upper extremity. His initial glucose level was 339 mg/dl. HbA1C was 9.9%. CT scan of the head demonstrated an abnormal increased intensity within the right lenticular nucleus and right caudate head most likely due to microcalcifications/mineralization. MRI of the brain demonstrated nonspecific T1 and T2 hyperintense abnormalities in the same area about the right basal ganglia. These findings were consistent with the movement pattern he was displaying and with a diagnosis of CHBG. Gradual control of his blood sugar levels over 48 hours led to resolution of his choreiform symptoms. After better medication adherence as an outpatient, endocrinology follow-up 6 months after discharge found his HbA1C drop to a level of 7.1%. There was no recurrence of his symptoms. CHBG is a rare manifestation of poorly controlled diabetes but is the one that clinicians should be aware of. Early recognition and gradual treatment of elevated blood glucose levels appear to lead to total resolution of choreiform symptoms.
- Complexity of the Genetics and Clinical Presentation of Spinocerebellar Ataxia 17. [Journal Article]
- FCFront Cell Neurosci 2018; 12:429
- Spinocerebellar ataxia type 17 (SCA17) is a rare autosomal dominant neurodegenerative disease caused by a CAG repeat expansion in the TATA-box binding protein gene (TBP). The disease has a varied age...
Spinocerebellar ataxia type 17 (SCA17) is a rare autosomal dominant neurodegenerative disease caused by a CAG repeat expansion in the TATA-box binding protein gene (TBP). The disease has a varied age at onset and clinical presentation. It is distinct from other SCAs for its association with dementia, psychiatric symptoms, and some patients presenting with chorea. For this reason, it is also called Huntington's disease-like 4 (HDL-4). Here we examine the distribution of SCA17 allele repeat sizes in a United Kingdom-based cohort with ataxia and find that fully penetrant pathogenic alleles are very rare (5 in 1,316 chromosomes; 0.38%). Phenotype-genotype correlation was performed on 30 individuals and the repeat structure of their TBP genes was examined. We found a negative linear correlation between total CAG repeat length and age at disease onset and, unlike SCA1, there was no correlation between the longest contiguous CAG tract and age at disease onset. We were unable to identify any particular phenotypic trait that segregated with particular CAG/CAA repeat tract structures or repeat lengths. One individual within the cohort was homozygous for variable penetrance range SCA17 alleles. This patient had a similar age at onset to heterozygotes with the same repeat sizes, but also presented with a rapidly progressive dementia. A pair of monozygotic twins within the cohort presented 3 years apart with the sibling with the earlier onset having a more severe phenotype with dementia and chorea in addition to the ataxia observed in their twin. This appears to be a case of variable expressivity, possibly influenced by other environmental or epigenetic factors. Finally, there was an asymptomatic father with a severely affected child with an age at onset in their twenties. Despite this, they share the same expanded allele repeat sizes and sequences, which would suggest that there is marked difference in the penetrance of this 51-repeat allele. We therefore propose that the variable penetrance range extend from 48 repeats to incorporate this allele. This study shows that there is variability in the presentation and penetrance of the SCA17 phenotype and highlights the complexity of this disorder.
- Enzymatic and non-enzymatic pathways of kynurenines' dimerization: the molecular factors for oxidative stress development. [Journal Article]
- PCPLoS Comput Biol 2018 Dec 10; 14(12):e1006672
- Kynurenines, the products of tryptophan oxidative degradation, are involved in multiple neuropathologies, such as Huntington's chorea, Parkinson's disease, senile dementia, etc. The major cause for h...
Kynurenines, the products of tryptophan oxidative degradation, are involved in multiple neuropathologies, such as Huntington's chorea, Parkinson's disease, senile dementia, etc. The major cause for hydroxykynurenines's neurotoxicity is the oxidative stress induced by the reactive oxygen species (ROS), the by-products of L-3-hydroxykynurenine (L-3HOK) and 3-hydroxyanthranilic acid (3HAA) oxidative self-dimerization. 2-aminophenol (2AP), a structural precursor of L-3HOK and 3HAA, undergoes the oxidative conjugation to form 2-aminophenoxazinone. There are several modes of 2AP dimerization, including both enzymatic and non-enzymatic stages. In this study, the free energies for 2AP, L-3HOK and 3HAA dimerization stages have been calculated at B3LYP/6-311G(d,p)//6-311+(O)+G(d) level, both in the gas phase and in heptane or water solution. For the intermediates, ionization potentials and electron affinities were calculated, as well as free energy and kinetics of molecular oxygen interaction with several non-enzymatically formed dimers. H-atom donating power of the intermediates increases upon the progress of the oxidation, making possible generation of hydroperoxyl radical or hydrogen peroxide from O2 at the last stages. Among the dimerization intermediates, 2-aminophenoxazinole derivatives have the lowest ionization potential and can reduce O2 to superoxide anion. The rate for O-H homolytic bond dissociation is significantly higher than that for C-H bond in non-enzymatic quinoneimine conjugate. However, the last reaction passes irreversibly, reducing O2 to hydroperoxyl radical. The inorganic ferrous iron and the heme group of Drosophila phenoxazinone synthase significantly reduce the energy cost of 2AP H-atom abstraction by O2. We have also shown experimentally that total antioxidant capacity decreases in Drosophila mutant cardinal with L-3HOK excess relative to the wild type Canton-S, and lipid peroxidation decreases in aged cardinal. Taken together, our data supports the conception of hydroxykynurenines' dual role in neurotoxicity: serving as antioxidants themselves, blocking lipid peroxidation by H-atom donation, they also can easily generate ROS upon dimerization, leading to the oxidative stress development.
- A discontinuous Galerkin model for fluorescence loss in photobleaching of intracellular polyglutamine protein aggregates. [Journal Article]
- BBBMC Biophys 2018; 11:7
- CONCLUSIONS: By directly estimating the transport parameters from live-cell image sequences using our new computational FLIP approach surprisingly fast exchange dynamics of mutant Huntingtin between cytoplasm and dim IBs could be revealed. This is likely relevant also for other polyQ diseases. Thus, our method allows for quantifying protein dynamics at different stages of the protein aggregation process in cellular models of neurodegeneration.
- Neurologic conditions and disorders of uremic syndrome of chronic kidney disease: Presentations, causes and treatment strategies. [Journal Article]
- ERExpert Rev Clin Pharmacol 2018 Dec 02
- Uremic syndrome of chronic kidney disease (CKD) is a term used to describe clinical, metabolic and hormonal abnormalities associated with progressive kidney failure. It is a rapidly growing public he...
Uremic syndrome of chronic kidney disease (CKD) is a term used to describe clinical, metabolic and hormonal abnormalities associated with progressive kidney failure. It is a rapidly growing public health problem worldwide. Nervous system complications occur in every patient with uremic syndrome of CKD. Areas covered: This review summarized central and peripheral nervous system complications of uremic syndrome of CKD and their pathogenic mechanisms. They include cognitive deterioration, encephalopathy, seizures, asterixis, myoclonus, restless leg syndrome, central pontine myelinosis, stroke, extrapyramidal movement disorders, neuropathies and myopathy. Their pathogenic mechanisms are complex and multiple. They include (1) accumulation of uremic toxins resulting in neurotoxicity, blood brain barrier injury, neuroinflammation, oxidative stress, apoptosis, brain neurotransmitters imbalance, ischemic/microvascular changes and brain metabolism dysfunction [e.g. dopamine deficiency], (2) metabolic derangement [as acidosis, hypocalcemia, hyperphosphatemia, hypomagnesemia and hyperkalemia]; (3) secondary hyperparathyroidism, (4) erythropoietin and iron deficiency anemia, (5) thiamin, vitamin D and other nutritional deficiencies, (6) hyperhomocysteinemia, and (7) coagulation problems. Expert Commentary: Nervous system complications of uremia contribute to the patients' morbidity and mortality. Optimizing renal replacement therapy, correction of associated metabolic and medical conditions and improved understanding of possible pathogenic mechanisms of these complications is a major target for their prevention and treatment.
- Treatment of psychiatric disturbances in common hyperkinetic movement disorders. [Journal Article]
- ERExpert Rev Neurother 2018 Dec 01
- This paper reviews studies that have assessed the treatment of psychiatric disturbances in dystonia, tic disorders, Tourette syndrome, Huntington's disease and essential tremor. Areas covered: We sea...
This paper reviews studies that have assessed the treatment of psychiatric disturbances in dystonia, tic disorders, Tourette syndrome, Huntington's disease and essential tremor. Areas covered: We searched for papers in English in Pubmed using the following keywords: blepharospasm, cervical dystonia, arm dystonia, laryngeal dystonia, spasmodic dysphonia, tic disorders, Tourette syndrome, Huntington's chorea, essential tremor, depression, anxiety, obsessive compulsive disorders, attention deficit hyperactivity disorders, psychosis, apathy. Expert commentary: Although psychiatric disturbances are frequent in hyperkinetic movement disorders, few controlled studies have assessed the treatment of psychiatric disturbances in such disorders. In dystonia, none of the controlled studies conducted to date have demonstrated the efficacy of drug treatment for depression or anxiety. In TS, controlled studies have demonstrated the usefulness of drug treatment on obsessive compulsive disorders and attention deficit hyperactivity disorders. Behavioral interventions may also play a role. No controlled studies have been conducted on HD nor have any studies addressed the treatment of psychiatric disturbances in ET. We conclude that there is the need of controlled studies to better evaluate pharmacological and non-pharmacological treatment of psychiatric disturbances in hyperkinetic movement disorders.
- Successful pallidotomy for post-hyperglycemic hemichorea-ballism. [Letter]
- PRParkinsonism Relat Disord 2018 Nov 28
- Molecular Pathogenesis in Huntington's Disease. [Review]
- BBiochemistry (Mosc) 2018; 83(9):1030-1039
- Huntington's disease (HD) is a severe autosomal dominant neurodegenerative disorder characterized by a combination of motor, cognitive, and psychiatric symptoms, atrophy of the basal ganglia and the ...
Huntington's disease (HD) is a severe autosomal dominant neurodegenerative disorder characterized by a combination of motor, cognitive, and psychiatric symptoms, atrophy of the basal ganglia and the cerebral cortex, and inevitably progressive course resulting in death 5-20 years after manifestation of its symptoms. HD is caused by expansion of CAG repeats in the HTT gene, which leads to pathological elongation of the polyglutamine tract within the respective protein - huntingtin. In this review, we present a modern view on molecular biology of HD as a representative of the group of polyglutamine diseases, with an emphasis on conformational changes of mutant huntingtin, disturbances in its cellular processing, and proteolytic stress in degenerating neurons. Main pathogenetic mechanisms of neurodegeneration in HD are discussed in detail, such as systemic failure of transcription, mitochondrial dysfunction and suppression of energy metabolism, abnormalities of cytoskeleton and axonal transport, microglial inflammation, decrease in synthesis of brain-derived neurotrophic factor, etc.
- Characteristics of Globus Pallidus Internus Local Field Potentials in Hyperkinetic Disease. [Journal Article]
- FNFront Neurol 2018; 9:934
- Background: Dystonia and Huntington's disease (HD) are both hyperkinetic movement disorders but exhibit distinct clinical characteristics. Aberrant output from the globus pallidus internus (GPi) is ...
Background: Dystonia and Huntington's disease (HD) are both hyperkinetic movement disorders but exhibit distinct clinical characteristics. Aberrant output from the globus pallidus internus (GPi) is involved in the pathophysiology of both HD and dystonia, and deep brain stimulation (DBS) of the GPi shows good clinical efficacy in both disorders. The electrode externalized period provides an opportunity to record local field potentials (LFPs) from the GPi to examine if activity patterns differ between hyperkinetic disorders and are associated with specific clinical characteristics. Methods: LFPs were recorded from 7 chorea-dominant HD and nine cervical dystonia patients. Differences in oscillatory activities were compared by power spectrum and Lempel-Ziv complexity (LZC). The discrepancy band power ratio was used to control for the influence of absolute power differences between groups. We further identified discrepant frequency bands and frequency band ratios for each subject and examined the correlations with clinical scores. Results: Dystonia patients exhibited greater low frequency power (6-14 Hz) while HD patients demonstrated greater high-beta and low-gamma power (26-43 Hz) (p < 0.0298, corrected). United Huntington Disease Rating Scale chorea sub-score was positively correlated with 26-43 Hz frequency band power and negatively correlated with the 6-14 Hz/26-43 Hz band power ratio. Conclusion: Dystonia and HD are characterized by distinct oscillatory activity patterns, which may relate to distinct clinical characteristics. Specifically, chorea may be related to elevated high-beta and low-gamma band power, while dystonia may be related to elevated low frequency band power. These LFPs may be useful biomarkers for adaptive DBS to treat hyperkinetic diseases.
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- Inhibition of Lithium Sensitive Orai1/ STIM1 Expression and Store Operated Ca2+ Entry in Chorea-Acanthocytosis Neurons by NF-κB Inhibitor Wogonin. [Journal Article]
- CPCell Physiol Biochem 2018; 51(1):278-289
- CONCLUSIONS: The stimulation of expression and function of Orai1/STIM1/2 by lithium in ChAc neurons are disrupted by pharmacological NFκB inhibition.