Publications by authors named "Kamila Polakova"

8 Publications

  • Page 1 of 1

Cognitive changes after methanol exposure: Longitudinal perspective.

Toxicol Lett 2021 Oct 17;349:101-108. Epub 2021 Jun 17.

Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic. Electronic address:

Background: From 2012 to 2013, there was a mass methanol poisoning outbreak in the Czech Republic. Methanol metabolites can cause specific lesions in the basal ganglia, subcortical white matter, and optic nerve. However, long-term sequelae of methanol poisoning on cognitive functioning have not yet been explored. The current study aimed to delineate the cognitive changes observed in methanol poisoning survivors in the seven years since 2012.

Methods: We conducted longitudinal research with repeated measurements in 2013, 2015, 2017 and 2019 to evaluate the development of cognitive changes after acute methanol poisoning. A complex neuropsychological battery consisted of tests of global cognitive performance, auditory and visual attention, executive functioning, learning and memory, working memory and language. Motor performance measures and depression scale were also included.

Results: Repeated measures ANOVA of four measurements with post-hoc tests showed a significant decline in the Mini-Mental State Examination (p = 0.007); however, other parameters were not significantly decreasing. In comparison to normative values, the z-scores for each test measure, in the memory domain, in particular, ranged from 43 to 60 % of participants below 1.5 SD. Mild to severe depression levels from the onset of poisoning improved during the seven years, returning to normal in up to 27 % of participants.

Conclusion: In the longitudinal perspective, methanol poisoning survivors manifest progressive global cognitive decline and overall persistent below-average cognitive performance with some improvements in the frequency of depressive symptoms.
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http://dx.doi.org/10.1016/j.toxlet.2021.06.008DOI Listing
October 2021

3D visual cueing shortens the double support phase of the gait cycle in patients with advanced Parkinson's disease treated with DBS of the STN.

PLoS One 2020 31;15(12):e0244676. Epub 2020 Dec 31.

Department of Neurology and Center of Clinical Neuroscience, 1st Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic.

Background: Gait disturbances have emerged as some of the main therapeutic concerns in late-stage Parkinson's disease (PD) treated with dopaminergic therapy and deep brain stimulation (DBS). External cues may help to overcome freezing of gait (FOG) and improve some of the gait parameters.

Aim: To evaluate the effect of 3D visual cues and STN-DBS on gait in PD group.

Methods: We enrolled 35 PD patients treated with DBS of nucleus subthalamicus (STN-DBS). Twenty-five patients (5 females; mean age 58.9 ±6.3) and 25 sex- and age-matched controls completed the gait examination. The gait in 10 patients deteriorated in OFF state. The severity of PD was evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn and Yahr (HY). The PD group filled the Falls Efficacy Scale-International (FES) and Freezing of Gait Questionnaire (FOGQ). Gait was examined using the GaitRite Analysis System, placed in the middle of the 10m marked path. The PD group was tested without dopaminergic medication with and without visual cueing together with the DBS switched ON and OFF. The setting of DBS was double-blind and performed in random order.

Results: The UPDRS was 21.9 ±9.5 in DBS ON state and 41.3 ±13.7 in DBS OFF state. HY was 2.5 ±0.6, FES 12.4 ±4.1 and FOGQ 9.4 ±5.7. In the DBS OFF state, PD group walked more slowly with shorter steps, had greater step length variability and longer duration of the double support phase compared to healthy controls. The walking speed and step length increased in the DBS ON state. The double support phase was reduced with 3D visual cueing and DBS; the combination of both cueing and DBS was even more effective.

Conclusion: Cueing with 3D visual stimuli shortens the double support phase in PD patients treated with DBS-STN. The DBS is more effective in prolonging step length and increasing gait speed. We conclude that 3D visual cueing can improve walking in patients with DBS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244676PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774936PMC
March 2021

Efficiency of I-ioflupane SPECT as the marker of basal ganglia damage in acute methanol poisoning: 6-year prospective study.

Clin Toxicol (Phila) 2021 Mar 7;59(3):235-245. Epub 2020 Aug 7.

Department of Occupational Medicine, First Faculty of Medicine, Charles University, Prague, Czech Republic.

Context: Investigate whether I-ioflupane SPECT (DaT SPECT) has the potential as a marker of basal ganglia damage in acute methanol poisoning.

Methods: Prospective, single-centre, cohort study of patients with confirmed methanol poisoning was conducted. DaT SPECT was performed twice with semi-quantification using DaTQUANT and MRI-based volumetry was calculated. Specific binding ratios (SBR) of striatum, caudate nucleus, and putamen were correlated with laboratory parameters of outcome, volumetric data, and retinal nerve fibres layer (RNFL) thickness measurements.

Results: Forty-two patients (mean age 46.3 ± 4.2 years; 8 females), including 15 with MRI-detected putamen lesions (group I) and 27 patients with intact putamen (group II), underwent DaT SPECT. Volumetry was calculated in 35 of the patients assessed. SBR values for the left putamen correlated with putamen volume ( = 0.665;  < 0.001). Decreased bilateral SBR values were determined for the striatum and the putamen, but not for the nucleus caudate, in group I ( < 0.05). Significant correlation was observed between the SBR of the posterior putamen and arterial blood pH ( = 0.574;  < 0.001) and other toxicological parameters of severity of poisoning/outcome including serum lactate, glucose, and creatinine concentrations ( < 0.05). The SBR of the posterior putamen positively correlated with the global RNFL thickness ( < 0.05). ROC analysis demonstrated a significant discriminatory ability of SBR of the posterior putamen with AUC = 0.753 (95%CI 0.604-0.902;  = 0.007). The multivariate regression model demonstrated that arterial blood pH, age, and gender were the most significant factors associated with SBR of the posterior putamen.

Conclusion: DaT SPECT demonstrates significant potential for the diagnosis of methanol-induced basal ganglia damage.
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http://dx.doi.org/10.1080/15563650.2020.1802033DOI Listing
March 2021

Agreement between the GAITRite System and the Wearable Sensor BTS G-Walk for measurement of gait parameters in healthy adults and Parkinson's disease patients.

PeerJ 2020 22;8:e8835. Epub 2020 May 22.

Department of Neurology and Center of Clinical Neuroscience, 1st Faculty of Medicine and General University Hospital in Prague, Charles University, Prague, Czech Republic.

Background: Nowadays, the most widely used types of wearable sensors in gait analysis are inertial sensors. The aim of the study was to assess the agreement between two different systems for measuring gait parameters (inertial sensor vs. electronic walkway) on healthy control subjects (HC) and patients with Parkinson's disease (PD).

Methods: Forty healthy volunteers (26 men, 14 women, mean age 58.7 ± 7.7 years) participated in the study and 24 PD patients (19 men, five women, mean age 62.7 ± 9.8 years). Each participant walked across an electronic walkway, GAITRite, with embedded pressure sensors at their preferred walking speed. Concurrently a G-Walk sensor was attached with a semi-elastic belt to the L5 spinal segment of the subject. Walking speed, cadence, stride duration, stride length, stance, swing, single support and double support phase values were compared between both systems.

Results: The Passing-Bablock regression slope line manifested the values closest to 1.00 for cadence and stride duration (0.99 ≤ 1.00) in both groups. The slope of other parameters varied between 0.26 (double support duration in PD) and 1.74 (duration of single support for HC). The mean square error confirmed the best fit of the regression line for speed, stride duration and stride length. The y-intercepts showed higher systematic error in PD than HC for speed, stance, swing, and single support phases.

Conclusions: The final results of this study indicate that the G-Walk system can be used for evaluating the gait characteristics of the healthy subjects as well as the PD patients. However, the duration of the gait cycle phases should be used with caution due to the presence of a systematic error.
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http://dx.doi.org/10.7717/peerj.8835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247524PMC
May 2020

Validation of the Freezing of Gait Questionnaire in patients with Parkinson's disease treated with deep brain stimulation.

Neurol Sci 2020 May 2;41(5):1133-1138. Epub 2020 Jan 2.

Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Katerinska 30, 128 21, Prague, Czech Republic.

Background: The Freezing of Gait Questionnaire (FoG-Q) is a fast and sensitive assessment tool for freezing (FoG).

Objective: The objective of the study is for validation of a Czech version of FoG-Q. A further, explorative aim was to examine what FoG-Q indicates about the presence and severity of gait impairment in patients treated with DBS in their full OFF state.

Design: The study was a cross-sectional validation study.

Methods: We translated FoG-Q following standardized validation protocol. We assessed 35 patients with PD and STN DBS using history taking, UPDRS, Hoehn and Yahr staging, Mini Mental State Examination, Frontal Assessment Battery, FoG-Q, Short Falls Efficacy Scale International, and Beck Depression Inventory, Second Edition. UPDRS III, clinical and instrumental gait assessment, was repeated OFF MED/DBS OFF and OFF MED/DBS ON.

Results: Internal consistency of FoG-Q was excellent (α = 0.91) as well as convergent (significant correlations with UPDRS II item 14, UPDRS III item 29, several TUG parameters, and FoG Score) and divergent validity (no association with UPDRS I). OFF MED/DBS OFF, the total FoG-Q score correlated with UPDRS III items 29, 30, and PIGD subscore, step time variability, and negatively with step length and velocity.

Limitations: Limitation of the study is a relatively small sample size.

Conclusions: In conclusion, the Czech translation of FoG-Q is valid. With respect to gait and balance, FoG-Q does, to a certain extent, reflect the native state of the disease in patients treated with high frequency STN DBS.
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http://dx.doi.org/10.1007/s10072-019-04209-3DOI Listing
May 2020

Pavement patterns can be designed to improve gait in Parkinson's disease patients.

Mov Disord 2019 12 23;34(12):1831-1838. Epub 2019 Aug 23.

Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic.

Background: Public spaces are usually designed with respect to various patient populations, but not Parkinson's disease. The objective of this study was to explore what type of easily applicable visual cueing might be used in public spaces and some interiors to improve gait in people with Parkinson's disease.

Methods: Thirty-two patients with freezing of gait walked an 8-meter track on 6 different floor patterns in single- and dual-task conditions in random sequence. The reference pattern was a virtual large transverse chessboard, and the other patterns differed either in size (small floor stones), orientation (diagonal), nature (real paving), regularity (irregular), or no pattern. Time, number of steps, velocity, step length, cadence, and dual-task effect were calculated. The number and total duration of freezing episodes were analyzed.

Results: Virtual, large, transverse floor stones improve time (P = 0.0101), velocity (P = 0.0029), number of steps (P = 0.0291), and step length (P = 0.0254) in Parkinson's disease patients compared with walking on no pattern. Virtual floor stones were superior in time and velocity to the real ones. Transverse floor stones were better than diagonal, whereas regular pattern stones were superior to irregular in some gait parameters. Subjectively, the reference pattern was preferred to the irregular one and to no pattern. No direct effect on freezing of gait was observed.

Conclusions: Parkinson's disease patients may benefit from floor patterns incorporating transverse oriented large rectangular visual cues. Because public space can be regulated with respect to people with medical conditions, the relevant legislative documents should be extended to allow for parkinsonian gait disorder. © 2019 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.27831DOI Listing
December 2019

Methanol Poisoning as an Acute Toxicological Basal Ganglia Lesion Model: Evidence from Brain Volumetry and Cognition.

Alcohol Clin Exp Res 2019 07 28;43(7):1486-1497. Epub 2019 May 28.

Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic.

Background: Acute methanol poisoning leads to optic neuropathy and necrotic lesions of basal ganglia (BG) and subcortical white matter. Survivors of methanol poisoning exhibit long-term executive and memory deficits. Associations between brain volumetry parameters and cognitive sequelae of methanol poisoning are not known. The aim of our study was to identify long-term associations between the cognitive performance of survivors of methanol poisoning and the volume of the brain structures that are selectively vulnerable to methanol.

Methods: We conducted a cross-sectional follow-up study on a sample of patients (n = 33, age 50 ± 14 years, 82% males) who survived acute methanol poisoning during methanol mass poisoning outbreak from September 2012 till January 2013 in the Czech Republic. A battery of neuropsychological tests and brain magnetic resonance imaging were included in the clinical examination protocol. Specific brain structures (putamen, globus pallidus, nucleus caudatus, and frontal white matter) were selected as regions of interest, and their volumes were estimated using the MorphoBox prototype software.

Results: In robust multiple regression models, sustained visual attention performance (as assessed by Trail Making Test and Prague Stroop Test) was positively associated with BG structures and frontal white matter volumes (Wald = 9.03 to 85.50, p < 0.01), sensitivity to interference (as assessed by Frontal Battery Assessment) was negatively associated with frontal white matter volume (Wald = 35.44 to 42.25, p < 0.001), and motor performance (as assessed by Finger Tapping Test) was positively associated with globus pallidus and frontal white matter volumes (Wald = 9.66 to 13.29, p < 0.01).

Conclusions: Our results demonstrate that smaller volumes of elements of BG-thalamocortical circuitry, namely the BG and frontal white matter, relate to attention and motor performance in methanol poisoning from a long-term perspective. Disruption of those functional circuits may underlie specific cognitive deficits observed in methanol poisoning.
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http://dx.doi.org/10.1111/acer.14077DOI Listing
July 2019

A unique de novo gain-of-function variant in associated with intellectual disability and hyperkinetic movement disorder.

Cold Spring Harb Mol Case Stud 2018 12 17;4(6). Epub 2018 Dec 17.

Institut für Neurogenomik, Helmholtz Zentrum München, Munich, 85764, Germany.

Calcium/calmodulin-dependent protein kinases (CaMKs) are key mediators of calcium signaling and underpin neuronal health. Although widely studied, the contribution of CaMKs to Mendelian disease is rather enigmatic. Here, we describe an unusual neurodevelopmental phenotype, characterized by milestone delay, intellectual disability, autism, ataxia, and mixed hyperkinetic movement disorder including severe generalized dystonia, in a proband who remained etiologically undiagnosed despite exhaustive testing. We performed trio whole-exome sequencing to identify a de novo essential splice-site variant (c.981+1G>A) in , encoding CaMKIV. Through in silico evaluation and cDNA analyses, we demonstrated that c.981+1G>A alters pre-mRNA processing and results in a stable mRNA transcript containing a 77-nt out-of-frame deletion and a premature termination codon within the last exon. The expected protein, p.Lys303Serfs*28, exhibits selective loss of the carboxy-terminal regulatory domain of CaMKIV and bears striking structural resemblance to previously reported synthetic mutants that confer constitutive CaMKIV activity. Biochemical studies in proband-derived cells confirmed an activating effect of c.981+1G>A and indicated that variant-induced excessive CaMKIV signaling is sensitive to pharmacological manipulation. Additionally, we found that variants predicted to cause selective depletion of CaMKIV's regulatory domain are unobserved in diverse catalogs of human variation, thus revealing that c.981+1G>A is a unique molecular event. We propose that our proband's phenotype is explainable by a dominant splice-disrupting mutation that acts through a gain-of-function mechanism. Our findings highlight the importance of in human neurodevelopment, provide a foundation for future clinical research of , and suggest the CaMKIV signaling pathway as a potential drug target in neurological disease.
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http://dx.doi.org/10.1101/mcs.a003293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318768PMC
December 2018
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