I19 Homozygosity in HD Patients - Case Reports Stepniak, I.; Witkowski, G.; Krysa, W. ...
Journal of neurology, neurosurgery and psychiatry,
09/2014, Volume:
85, Issue:
Suppl 1
Journal Article
I19Homozygosity in HD Patients - Case Reports Stepniak, I; Witkowski, G; Krysa, W ...
Journal of neurology, neurosurgery and psychiatry,
09/2014, Volume:
85, Issue:
Suppl 1
Journal Article
Peer reviewed
BackgroundThe homozygosity for CAG expansion is a very rare finding in HD patients. It is assumed, that homozygous cases show similar age at onset in comparison to the heterozygotes with the same ...expansion length but the disease progression seems to be more rapid with pronounced psychiatric symptoms, probably due to wider neuronal degeneration. We present the clinical course of two HD patients harbouring two mutant alleles, diagnosed in the Institute of Psychiatry and Neurology (IPN), Warsaw, Poland.Case historyTwo patients were clinically and genetically evaluated while being enrolled into the REGISTRY EHDN project. They showed different clinical presentation and course of the disease.The first subject (28 y.o.) with 38 and 63 CAG repeats presented with juvenile HD phenotype. Symptoms began at age of 12, with rapid development of dystonia and rigidity (Baseline TMS 74), the presence of epileptic seizures, cognitive impairment, severe irritability and obsessive-compulsive disorder.The second patient (44 y.o.) with 40 and 42 CAG repeats showed first symptoms at the age of 40. Until now the patient is affected with a mild motor symptoms (TMS 23). The depression with suicidal ideations and psychotic symptoms (delusions) seem to be the most important clinical problem. The rate of decline of cognitive abilities is not different from these observed in heterozygous patients.ConclusionsOur study on two homozygous HD cases revealed, that the clinical course of motor symptoms in them does not differ significantly from the relevant cohorts of heterozygotic subjects. However, it confirmed suggestions from other reports that the psychiatric component of HD clinical presentation may be more severe in homozygous subjects.
The methods of ultraviolet and infrared spectroscopy and quantum chemical modeling have been used to evaluate the parameters of the formation of a supramolecular inclusion complex between the ...flavonoid quercetin and the hydroxypropyl-β-cyclodextrin molecular container. The solubility of quercetin in water has been shown to increase by a factor of more than 50 when included in a supramolecular complex with 16 mM hydroxypropyl-β-cyclodextrin. It has been demonstrated that bioavailability of quercetin is improved after encapsulation with hydroxypropyl-β-cyclodextrin. The association constant for the inclusion complex of quercetin and hydroxypropyl-β-cyclodextrin (1 : 1) has been evaluated by the Higuchi-Connors method to be 3275 ± 448 М
–1
. The formation of the inclusion complex results in considerable changes in the vibrational spectra of components compared to the spectrum of the physical mixture of quercetin and hydroxypropyl-β-cyclodextrin. This difference can be explained by structural changes of the components due to hydrogen bond formation. The molecular modeling of the inclusion complex has shown that the geometry and properties of the components change after encapsulation of quercetin molecule (“guest”) inside the cavity of β-cyclodextrins (“host”). The torsion angles between the rings of the planar quercetin molecule in the complexes with β-cyclodextrin and hydroxypropyl-β-cyclodextrin have been evaluated to be 149.5° and 138.7°, respectively.
This paper presents data on wafer-fused 1550-nm vertical-cavity surface-emitting lasers (VCSELs) based on the active region and distributed Bragg reflectors (DBRs) grown by molecular beam epitaxy. ...VCSELs with a tunnel junction aperture diameter of 8 μm show lasing at a threshold current density j th <; 3 kA/cm 2 , an output optical power of ~4 mW, and a -3 dB bandwidth of approximately 7 GHz at a 10-mA bias current. The devices demonstrate single-mode continuous wave operation with the transverse side-mode suppression ratio (SMSR) varying in the range of 40-45 dB up to roll-over currents. The increase in mirror losses due to the etching of the top DBR makes the output optical power increase to 6 mW and causes the wallplug efficiency value to reach 20%, but SMSR remains in the range of 40-45 dB. This also makes it possible to reduce both the photon lifetime and, as a result, the effect of damping and increase the modulation bandwidth to 9 GHz. The observed open and clear eye diagrams indicate that non-return-to-zero operation is possible at bit rates of up to 30 Gbps without equalization or forward error correction. The high-output optical power and modulation performance pave the way for the dense wavelength division multiplexing application of wafer-fused 1550-nm VCSELs.
Claustrophobia, the well-known fear of being trapped in narrow/closed spaces, is often considered a conditioned response to traumatic experience. Surprisingly, we found that mutations affecting a ...single gene, encoding a stress-regulated neuronal protein, can cause claustrophobia. Gpm6a-deficient mice develop normally and lack obvious behavioral abnormalities. However, when mildly stressed by single-housing, these mice develop a striking claustrophobia-like phenotype, which is not inducible in wild-type controls, even by severe stress. The human GPM6A gene is located on chromosome 4q32-q34, a region linked to panic disorder. Sequence analysis of 115 claustrophobic and non-claustrophobic subjects identified nine variants in the noncoding region of the gene that are more frequent in affected individuals (P=0.028). One variant in the 3'untranslated region was linked to claustrophobia in two small pedigrees. This mutant mRNA is functional but cannot be silenced by neuronal miR124 derived itself from a stress-regulated transcript. We suggest that loosing dynamic regulation of neuronal GPM6A expression poses a genetic risk for claustrophobia.
ObjectiveStudies of TCS report changes of the echotexture of mesencephalic raphe in patients with major depression and depressive symptoms in some neurodegenerative disorders (Parkinson's disease ...(PD), Wilson's disease (WD)). The aim of this study was to test the usefulness of TCS in diagnosing of patients with genetically confirmed HD and concomitant psychiatric disorder. It is well established that the presence of reduced nucleus raphe echogenicity correlates with signs of depression in patients with affective as well as neurodegenerative disorders (Walter et al., 2010). TCS may be helpful in selection of the patients at risk of depression and can be useful in monitoring and management of HD patients.MethodsTCS was performed in 55 patients with HD. The neurological and psychiatric examination was performed using the battery of tests Unified Huntington's Disease Rating Scale (UHDRS motor, behavioural and cognitive), PBA-s (Problem Behaviours Assessment-Short), PBA-HD and HADS-SIS (Hospital Anxiety and Depression Scale combined with the Snaith Irritability Scale), the Hamilton Rating Scale for Depression, the Beck Depression Inventory and the Marin's Apathy Evaluation Scale (AES).ResultsHypoechogenicity of raphe nucleus was found in 80% of patients with depression (16/20), 22% of patients with irritability (2/9), 30% of patients with OCD (3/10 number) and 12,5% of patients without present or past history of psychiatric disturbances (2/16).Another finding, hyperechogenic substantia nigra was visualised in 45% and hyperechogenicity of lentiform nucleus was visualised in 55% of patients with genetically confirmed HD.ConclusionsOur preliminary findings seem to confirm the relationship between changes in mesencephalic raphe echogenicity and the presence of depressive symptoms also in patients with HD.
BackgroundSleep related breathing disorders (SRBD) are a risk factor for cardiovascular diseases and decrease the quality of life and performance due to nonrestorative sleep. SRBD are more frequent ...in a number of neurodegenerative disorders like multiple system atrophy or amyotrophic lateral sclerosis. According to available reports, the prevalence in Huntington's disease (HD) is not increased, however the studies included almost only presymptomatic and early symptomatic patients.AimsTo investigate the prevalence of SRBD in HD patients in moderate and advanced disease stage.Methods18 (9 women) HD patients in mean age 52.5 plus or minus 17.8 22-78 with motor UHDRS >29 and TFC <11 as well as 11 (5 women) age, gender and BMI matched healthy controls underwent the screening of nocturnal respiration with Embletta device and a questionnaire based assessment of sleep quality and daytime sleepiness.ResultsApnea hypopnea index, oxygen desaturation index and Pittsburgh Sleep Quality Index were higher in patients (5.1 plus or minus 5.1 vs 1.6 plus or minus 2.2 p = 0.031; 5.6 plus or minus 5.1 vs 1.5 plus or minus 1.9 p = 0.07; 7.9 plus or minus 4.7 vs 4.5 plus or minus 1.7 p = 0.039 respectively). Snoring Index, mean and minimal oxygen saturation and Daytime Sleepiness Scale were not different between groups. Six patients showed AHI >5 and four of them >10.ConclusionsModerate and advanced HD may be associated with significant SRBD. The data confirms also previously reported poor sleep quality in HD patients.
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