Zolpidem improves task-specific dystonia: A randomized clinical trial integrating exploratory transcranial magnetic stimulation and [18F] FDG-PET imaging.

BACKGROUND: Task-specific dystonia (TSFD) is a disabling movement disorder. Effective treatment options are currently limited. Zolpidem was reported to improve primary focal and generalized dystonia in a proportion of patients. The mechanisms underlying its therapeutic effects have not yet been investigated. METHODS: We conducted a randomized, double-blind, placebo-controlled, crossover trial of single-dose zolpidem in 24 patients with TSFD. Patients were clinically assessed using Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), Writers' Cramp Rating Scale (WCRS), and Visual Analogue Scale (VAS), before and after receiving placebo and zolpidem. Transcranial magnetic stimulation was conducted on placebo and zolpidem to compare corticospinal excitability - active and resting motor thresholds (AMT and RMT), resting and active input/output curves and intracortical excitability - cortical silent period (CSP), short-interval intracortical inhibition curve (SICI), long-interval intracortical inhibition (LICI) and intracortical facilitation (ICF). Eight patients underwent brain FDG-PET imaging on zolpidem and placebo. RESULTS: Zolpidem treatment improved TSFD. Zolpidem compared to placebo flattened rest and active input/output curves, reduced ICF and was associated with hypometabolism in the right cerebellum and hypermetabolism in the left inferior parietal lobule and left cingulum. Correlations were found between changes in dystonia severity on WCRS and changes in active input/output curve and in brain metabolism, respectively. Patients with lower RMT, and higher rest and active input/output curves exhibited better response to zolpidem compared to placebo. CONCLUSIONS: Zolpidem improved TSFD by reducing corticomotor output and influencing crucial nodes in higher-order sensory and motor networks.

Gait Characteristics during Dual-Task Walking in Elderly Subjects of Different Ages.

BACKGROUND: In older age, walking ability gradually decreases due to factors including impaired balance, reduced muscle strength, and impaired vision and proprioception. Further, cognitive functions play a key role during walking and gradually decline with age. There is greater variability in gait parameters when the demands during walking increase, in dual- and multiple-task situations. The aim of this study was to analyze gait parameters while performing a demanding cognitive and motor dual task in three different age-related healthy elderly subject groups. METHOD: A total of 132 healthy individuals (54 males, 78 females) were divided into three groups-55 to 65, 66 to 75, and 76 to 85 years. The subjects performed a basic walking task, dual motor task, dual mental task, and combined motor and mental task while walking. The gait parameters cycle time, stride length, swing time, and double support time were noted, as well as the variability of those parameters. RESULTS: Cycle time was longer and stride length was shorter in the >76-year-old group than in the 51-65-year-old group in all test conditions. A comparison of all three groups did not show a significant difference in swing time, while double support time was increased in the same group. CONCLUSIONS: Changes are observed when gait is performed simultaneously with an additional motor or cognitive task. Early detection of gait disorders can help identify elderly people at increased risk of falls. Employing a dual-task paradigm during gait assessment in healthy elderly subjects may help identify cognitive impairment early in the course of the disturbance.

Gait alterations in Parkinson's disease at the stage of hemiparkinsonism-A longitudinal study.

BACKGROUND: Progressive gait impairment in Parkinson's disease (PD) leads to significant disability. Quantitative gait parameters analysis provides valuable information about fine gait alterations. OBJECTIVES: To analyse change of gait parameters in patients with early PD at the stage of hemiparkinsonism and after 1 year of follow up, taking into account clinical asymmetry. METHODS: Consecutive early PD outpatients with strictly unilateral motor features underwent clinical and neuropsychological assessment at the study entry and after 1 year of follow up. Gait was assessed with GAITRite walkway using dual-task methodology. Spatiotemporal gait parameters (step time and length, swing time and double support time) and their coefficients of variation (CV), gait velocity and heel-to-heel base support were evaluated. RESULTS: We included 42 PD patients with disease duration of 1.3 years (±1.13). Progression of motor and non-motor symptoms, without significant cognitive worsening, was observed after 1 year of follow up. Significant shortening of the swing time, prolongation of the double support and increase of their CVs were observed during all task conditions similarly for most parameters on symptomatic and asymptomatic bodysides, except for CV for the swing time under the combined task. CONCLUSION: Alterations of the swing time and double support time are already present even at the asymptomatic body side, and progress similarly, or even at faster pace, at this side, despite dopaminergic treatment These parameters deserve further investigation in larger, prospective studies to address their potential to serve as markers of progression in interventional disease modifying trials with early PD patients.

Assessment of gait in patients with fibromyalgia during motor and cognitive dual task walking: a cross-sectional study.

BACKGROUND: The aim of the study was to assess gait pattern of patients diagnosed with fibromyalgia (FM) while performing demanding motor and/or cognitive dual tasks while walking. Further, idea was to explore possible correlations of dual task gait pattern alterations to patients' functional status and presence or absence of clinical symptoms associated with FM. METHODS: Twenty-four female FM patients and 24 healthy female subjects performed a basic walking task, a dual motor, a dual mental (cognitive) and a combined, dual motor and cognitive task simultaneously. Quantitative spatial (stride length) and temporal (cycle time, swing time and double support time) gait parameters were measured using GAITRite walkway system and their variability was assessed. Patients underwent clinical examination including assessment of functional status, pain and fatigue level, psychiatric and cognitive manifestations. RESULTS: The motor, cognitive and combined dual tasks affect gait performance in FM patients. Difference in tasks between FM and healthy subjects was found as double support time prolongation. Comparison of tasks showing that cycle time in FM was longer than controls and stride length was shorter in patients for all conditions, while no changes were found in any of the gait parameters variability. Further, mental/cognitive dual tasks had a larger effect than motor tasks. Correlations were also found between depression and functional status of the patients and the gait parameters. CONCLUSIONS: Gait is affected in FM patients while dual task walking. No changes in stride-to-stride variability point that patients preserve stability in complex walking situations. Analysis of gait may provide additional information for the FM identification based on presence of clinical features and cognitive status. Correlation of dual task gait alterations with occurrence of clinical symptoms and influence of cognitive changes on gait pattern could additionally define FM subgroups.

Impact of depression on gait variability in Parkinson's disease.

OBJECTIVE: The goal of this study was to analyze how depression associated with Parkinson's disease (PD) affected gait variability in these patients using a dual-task paradigm. Additionally, the dependency of the executive functions and the impact of depression on gait variability were analyzed. PATIENTS AND METHODS: Three subject groups were included: patients with PD, but no depression (PD-NonDep; 14 patients), patients with both PD and depression (PD-Dep; 16 patients) and healthy controls (HC; 15 subjects). Gait was recorded using the wireless sensors. The participants walked under four conditions: single-task, motor dual- task, cognitive dual-task, and combined dual-task. Variability of stride length, stride duration, and swing time was calculated and analyzed using the statistical methods. RESULTS: Variability of stride duration and stride length were not significantly different between PD-Dep and PD-NonDep patients. The linear mixed model showed that swing time variability was statistically significantly higher in PD-Dep patients compared to controls (p = 0.001). Hamilton Disease Rating Scale scores were significantly correlated with the swing time variability (p = 0.01). Variability of all three parameters of gait was significantly higher while performing combined or cognitive task and this effect was more pronounced in PD-Dep group of patients. CONCLUSIONS: Depression in PD was associated with swing time variability, and this effect was more prominent while performing a dual-task. SIGNIFICANCE: Diagnosing and treating depression might be important for gait improvement and fall reduction in PD patients.

Dynamics of impulsive-compulsive behaviors in early Parkinson's disease: a prospective study.

INTRODUCTION: Impulsive compulsive behaviors (ICBs) in Parkinson's disease (PD) are debilitating disorders of repetitive, excessive, and compulsive nature affecting up to one third of PD patients. Objectives are to address clinical, psychiatric, and cognitive characteristics of ICBs and to define risk factors in PD patients in the initial motor stage, followed up for 5 years. METHODS: We analyzed 106 consecutive PD outpatients at Hoehn and Yahr disease stage 1 and 125 healthy controls. The participants were assessed for the presence of any ICB using the current clinical criteria and underwent comprehensive clinical, psychiatric, and neuropsychological evaluations. The patients completed the same protocol at Years 1, 2, 3, and 5. RESULTS: ICBs were present in 21 (19.8%) PD patients and 13 (10.4%) healthy controls at baseline. Prevalence of ICBs increased to 29.2% at Year 5, significantly after Year 2. Multiple ICBs were present in 4,7% and 61.9% of PD-ICBs at the baseline and Year 5, respectively. ICBs resolved in 30% of cases (most often compulsive eating). Dopamine agonist treatment at the baseline carried five times higher risk of having or developing ICB(s) anytime during follow-up. We identified risk factors for compulsive eating (dopamine agonist treatment at baseline), hypersexuality (males), compulsive buying (depression and younger age), and punding (younger age and higher levodopa dose at baseline). Significant interaction of rate of motor progression and ICB diagnosis was shown. CONCLUSIONS: PD patients showed increasing frequency of most ICBs during the 5-year follow-up. Specific risk factors were identified for different types of ICBs.

Spatiotemporal gait characteristics of Huntington's disease during dual-task walking.

Purpose: Huntington's disease (HD) is an neurodegenerative genetic disorder with characteristic gait changes. HD also results in a range of cognitive impairments, such as difficulties to divide attention, or simultaneously monitoring two tasks.Aim: The impact of cognitive and/or motor tasks on HD gait has not been fully elucidated. The aim was to examine gait in HD patients while performing motor and/or cognitive dual-task walking.Methods: Gait was measured with and without performing concurrent cognitive and/or motor tasks. Sixteen HD patients and 24 healthy control (HC) subjects performed a self-paced basic walking task, a dual motor, a dual mental and a combined motor and mental task while walking.Results: Base walk gait parameters are significantly different between HD and HC groups. Same is true for motor, mental and combined tasks comparisons of HD and HC subjects. Gait velocity is also significantly reduced in HD compared to HC for all experimental conditions. Comparison of base walk and mental task performance showing differences in cycle time, stride length, double support time and CV of stride length, while base walk to motor task comparison is different only in stride length. No differences were found when motor and combined tasks were compared to mental task in HD patients.Conclusion: Gait pattern in HD patients while performing motor and/or cognitive dual tasks walking is remarkably preserved. Gait parameters are changed in order to reduce possible falls, and lack of differences of dual tasks gait parameters variability is attributed that patients minimizing risk of falling and preserving stability.

Selection of gait parameters for differential diagnostics of patients with de novo Parkinson's disease.

BACKGROUND: Gait disturbances are an integral part of clinical manifestations of Parkinson's disease (PD), even in the initial stages of the disease. Our goal was to identify the set of spatio-temporal gait parameters that bear the highest relevance for characterizing de novo PD patients. METHODS: Forty patients with de novo PD and forty healthy controls were recorded while walking over an electronic walkway in three different conditions: (1) base walking, (2) walking with an additional motor task, (3) walking with an additional mental task. Both groups were well balanced concerning age and gender. To select a smaller number of relevant parameters, affinity propagation clustering was applied on parameter pairwise correlation. The exemplars were then sorted by importance using the random forest algorithm. Classification accuracy of a support vector machine was tested using the selected parameters and compared to the accuracy of the model using a set of parameters derived from literature. RESULTS: Final selection of parameters included: stride length and stride length coefficient of variation (CV), stride time and stride time CV, swing time and swing time CV, step time asymmetry, and heel-to-heel base support CV. Classification performed using these parameters showed higher overall accuracy (85%) than classification using the common parameter set containing: stride time, stride length, swing time and double support time, along with their CVs (78%). CONCLUSION: In early stages of PD, double support time and its CV appear to be weak indicators of the disease. We instead found step time asymmetry and support base CV to significantly contribute to classification accuracy.

Gait pattern in patients with different multiple sclerosis phenotypes.

BACKGROUND: Gait pattern is frequently impaired in multiple sclerosis (MS), however gait characteristics in patients with different MS phenotypes have not been fully elucidated. METHODS: We analyzed spatio-temporal gait pattern characteristics in patients with relapsing-remitting (RR, n=52) and primary-progressive (PP, n=18) MS in comparison with age-matched healthy controls (HC, n=40). All subjects performed a standardized simple walking task, a dual motor- motor task, a dual motor-mental task, and a triple combined motor-mental task at a GAITRite electronic walkway of 5.5m active area. We measured: cycle time (CT), stride length (SL), swing time (ST), double support time (DST), gait velocity (GV) and calculated symmetry index (SI) for CT, SL and ST. RESULTS: With each task performed, CT and DST in the total MS group were significantly longer while SL was significantly shorter and GV significantly lower than in HC. ST was similar in the total MS patient group and HC. In both MS patients and HC, CT and DST increased and SL and GV decreased over repeated assessments. Dual and triple tasks while walking influenced walking performance in both MS patients and HC. Although patients with PPMS differed significantly from those with RRMS in the majority of gait parameters, the subgroup analysis in patients matched for age and disability (Expanded Disability Status Scale Score -EDSS, 3.0-5.0) showed similar gait performance in RRMS and PPMS patients having the same level of disability, except for CT and ST- symmetry parameters that were more impaired in the PPMS group. The EDSS score correlated significantly with CT, DST, SL and GV, but no significant correlation was found with ST except at the triple combined motor-mental task. CONCLUSION: A disturbed gait pattern in MS patients with different MS phenotypes depends on disability and reflects a cognitive-motor interference.

Influence of attention alternation on movement-related cortical potentials in healthy individuals and stroke patients.

OBJECTIVE: In this study, we analyzed the influence of artificially imposed attention variations using the auditory oddball paradigm on the cortical activity associated to motor preparation/execution. METHODS: EEG signals from Cz and its surrounding channels were recorded during three sets of ankle dorsiflexion movements. Each set was interspersed with either a complex or a simple auditory oddball task for healthy participants and a complex auditory oddball task for stroke patients. RESULTS: The amplitude of the movement-related cortical potentials (MRCPs) decreased with the complex oddball paradigm, while MRCP variability increased. Both oddball paradigms increased the detection latency significantly (p<0.05) and the complex paradigm decreased the true positive rate (TPR) (p=0.04). In patients, the negativity of the MRCP decreased while pre-phase variability increased, and the detection latency and accuracy deteriorated with attention diversion. CONCLUSION: Attention diversion has a significant influence on MRCP features and detection parameters, although these changes were counteracted by the application of the laplacian method. SIGNIFICANCE: Brain-computer interfaces for neuromodulation that use the MRCP as the control signal are robust to changes in attention. However, attention must be monitored since it plays a key role in plasticity induction. Here we demonstrate that this can be achieved using the single channel Cz.

Finger tapping analysis in patients with Parkinson's disease and atypical parkinsonism.

The goal of this study was to investigate repetitive finger tapping patterns in patients with Parkinson's disease (PD), progressive supranuclear palsy-Richardson syndrome (PSP-R), or multiple system atrophy of parkinsonian type (MSA-P). The finger tapping performance was objectively assessed in PD (n=13), PSP-R (n=15), and MSA-P (n=14) patients and matched healthy controls (HC; n=14), using miniature inertial sensors positioned on the thumb and index finger, providing spatio-temporal kinematic parameters. The main finding was the lack or only minimal progressive reduction in amplitude during the finger tapping in PSP-R patients, similar to HC, but significantly different from the sequence effect (progressive decrement) in both PD and MSA-P patients. The mean negative amplitude slope of -0.12°/cycle revealed less progression of amplitude decrement even in comparison to HC (-0.21°/cycle, p=0.032), and particularly from PD (-0.56°/cycle, p=0.001), and MSA-P patients (-1.48°/cycle, p=0.003). No significant differences were found in the average finger separation amplitudes between PD, PSP-R and MSA-P patients (pmsa-pd=0.726, pmsa-psp=0.363, ppsp-pd=0.726). The lack of clinically significant sequence effect during finger tapping differentiated PSP-R from both PD and MSA-P patients, and might be specific for PSP-R. The finger tapping kinematic parameter of amplitude slope may be a neurophysiological marker able to differentiate particular forms of parkinsonism.

Efficient neuroplasticity induction in chronic stroke patients by an associative brain-computer interface.

Brain-computer interfaces (BCIs) have the potential to improve functionality in chronic stoke patients when applied over a large number of sessions. Here we evaluated the effect and the underlying mechanisms of three BCI training sessions in a double-blind sham-controlled design. The applied BCI is based on Hebbian principles of associativity that hypothesize that neural assemblies activated in a correlated manner will strengthen synaptic connections. Twenty-two chronic stroke patients were divided into two training groups. Movement-related cortical potentials (MRCPs) were detected by electroencephalography during repetitions of foot dorsiflexion. Detection triggered a single electrical stimulation of the common peroneal nerve timed so that the resulting afferent volley arrived at the peak negative phase of the MRCP (BCIassociative group) or randomly (BCInonassociative group). Fugl-Meyer motor assessment (FM), 10-m walking speed, foot and hand tapping frequency, diffusion tensor imaging (DTI) data, and the excitability of the corticospinal tract to the target muscle [tibialis anterior (TA)] were quantified. The TA motor evoked potential (MEP) increased significantly after the BCIassociative intervention, but not for the BCInonassociative group. FM scores (0.8 ± 0.46 point difference, P = 0.01), foot (but not finger) tapping frequency, and 10-m walking speed improved significantly for the BCIassociative group, indicating clinically relevant improvements. Corticospinal tract integrity on DTI did not correlate with clinical or physiological changes. For the BCI as applied here, the precise coupling between the brain command and the afferent signal was imperative for the behavioral, clinical, and neurophysiological changes reported. This association may become the driving principle for the design of BCI rehabilitation in the future. Indeed, no available BCIs can match this degree of functional improvement with such a short intervention.

White Matter Changes in Two Leber's Hereditary Optic Neuropathy Pedigrees: 12-Year Follow-Up.

We are presenting two Leber's hereditary optic neuropathy (LHON) pedigrees with abnormal magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (H-MRS) findings but without neurological manifestation associated with LHON. The study included 14 LHON patients and 41 asymptomatic family members from 12 genealogically unrelated families. MRI showed white matter involvement and H-MRS exhibited metabolic anomalies within 12 LHON families. Main outcome measures were abnormal MRI and H-MRS findings in two pedigrees. MRI of the proband of the first pedigree showed a single demyelinating lesion in the right cerebellar hemisphere, while the proband of the second family displayed multiple supratentorial and infratentorial lesions, compatible with the demyelinating process, and both the absolute choline (Cho) concentration and Cho/creatinine ratio were increased. MRI and H-MRS profiles of both affected and unaffected mitochondrial DNA mutation carriers suggest more widespread central nervous involvement in LHON. Although even after 12 years our patients did not develop neurological symptoms, MRI could still be used to detect possible changes during the disease progression.

Gait in drug naïve patients with de novo Parkinson's disease--altered but symmetric.

BACKGROUND: Motor symptoms in Parkinson's disease (PD) are typically asymmetrical. Early stage of PD is characterised with a predominantly unilateral appearance of tremor, rigidity and bradykinesia, with or without axial involvement. Also, studies have demonstrated gait asymmetry in de novo drug naïve PD patients. Aim of this study was to investigate gait pattern, gait symmetry and gait variability in early phases of PD. METHODS: The gait was measured in 40 de novo, drug naïve PD patients and 43 healthy control subjects (HC) while performing a simple walking task. Calculated parameters were cycle time (CT), stride length (SL) and swing time (ST), and their coefficients of variation (CV). RESULTS: Considering gait parameters, PD patients and HC differed in terms of all parameters, except for the CV of CT. Analysis of gait symmetry, comparison between the gait patterns of the left and the right leg in PD patients revealed no difference for any of the assessed parameters. The majority of the gait parameters did not differ between left and right legs of HC. CONCLUSIONS: It can be concluded that even gait was already altered in de novo drug naive PD patients, gait symmetry remained preserved. The SL was the most prominent parameter of altered gait in initial stages of PD patients, while the ST heralded postural asymmetry.

Quantitative and qualitative gait assessments in Parkinson's disease patients.

BACKGROUND/AIM: Postural impairments and gait disorders in Parkinson's disease (PD) affect limits of stability, impaire postural adjustment, and evoke poor responses to perturbation. In the later stage of the disease, some patients can suffer from episodic features such as freezing of gait (FOG). Objective gait assessment and monitoring progress of the disease can give clinicians and therapist important information about changes in gait pattern and potential gait deviations, in order to prevent concomitant falls. The aim of this study was to propose a method for identification of freezing episodes and gait disturbances in patients with PD. A wireless inertial sensor system can be used to provide follow-up of the treatment effects or progress of the disease. METHODS: The system is simple for mounting a subject, comfortable, simple for installing and recording, reliable and provides high-quality sensor data. A total of 12 patients were recorded and tested. Software calculates various gait parameters that could be estimated. User friendly visual tool provides information about changes in gait characteristics, either in a form of spectrogram or by observing spatiotemporal parameters. Based on these parameters, the algorithm performs classification of strides and identification of FOG types. RESULTS: The described stride classification was merged with an algorithm for stride reconstruction resulting in a useful graphical tool that allows clinicians to inspect and analyze subject's movements. CONCLUSION: The described gait assessment system can be used for detection and categorization of gait disturbances by applying rule-based classification based on stride length, stride time, and frequency of the shank segment movements. The method provides an valuable graphical interface which is easy to interpret and provides clinicians and therapists with valuable information regarding the temporal changes in gait.

[Repetitive transcranial magnetic stimulation as an adjuvant method in the treatment of depression: preliminary results].

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) is a method of brain stimulation which is increasingly used in both clinical practice and research. Up-to-date studies have pointed out a potential antidepressive effect of rTMS, but definitive superiority over placebo has not yet been confirmed. OBJECTIVE: The aim of the study was to examine the effect of rTMS as an adjuvant treatment with antidepressants during 18 weeks of evaluation starting from the initial application of the protocol. METHODS: Four patients with the diagnosis of moderate/severe major depression were included in the study.The protocol involved 2000 stimuli per day (rTMS frequency of 10 Hz, intensity of 120% motor threshold) administered over the left dorsolateral prefrontal cortex (DLPFC) for 15 days. Subjective and objective depressive symptoms were measured before the initiation of rTMS and repeatedly evaluated at week 3, 6, 12 and 18 from the beginning of the stimulation. RESULTS: After completion of rTMS protocol two patients demonstrated a reduction of depressive symptoms that was sustained throughout the 15-week follow-up period. One patient showed a tendency of remission during the first 12 weeks of the study, but relapsed in week 18. One patient showed no significant symptom reduction at any point of follow-up. CONCLUSION: Preliminary findings suggest that rTMS has a good tolerability and can be efficient in accelerating the effect of antidepressants, particularly in individuals with shorter duration of depressive episodes and moderate symptom severity.

Gait in amyotrophic lateral sclerosis: Is gait pattern differently affected in spinal and bulbar onset of the disease during dual task walking?

Amyotrophic lateral sclerosis (ALS) is characterized by weakness, fatigue, loss of balance and coordination. The purpose of the study was to examine gait in ALS patients. Gait was compared in ALS with spinal and bulbar onset, while performing dual mental and motor tasks. Dual-task walking was performed by 27 ALS patients, 13 with spinal- and 14 with bulbar-onset disease. Twenty-nine healthy subjects were used as a control group. The subjects performed a basic, simple walking task, dual-motor task, dual-mental task, and combined motor and mental tasks. Results showed that dual-task paradigm has an effect on gait in ALS patients. Gait was differently affected in spinal and bulbar onset of ALS by some of the given tasks. Mental tasks had a larger effect than motor tasks in all gait parameters. In conclusion, both ALS forms have impaired gait in dual tasks. Simple walk in patients with spinal onset shows higher variability of certain gait parameters compared to bulbar-onset patients and controls. Differences in gait could also indicate postural instability and possible falls in complex walking situations.

Deep brain stimulation in psychiatry.

INTRODUCTION: Deep brain stimulation is a stereotactic neurosurgical method used in the treatment of Parkinson's disease and some other movement disorders. The application of deep brain stimulation in the treatment of certain psychiatric disorders has been intensively investigated taking into account the current knowledge of neurobiological basis of mood regulation, cognition, and behaviour. This paper has been aimed at presenting the available data on experience in the application of deep brain stimulation in the treatment of psychiatric disorders. It gives an overview of scientific and professional literature, bearing in mind all the contemporary approaches in the treatment of certain psychiatric disorders. Research results available so far in the treatment of treatment-resistant depression, obsessive-compulsive disorder, Gilles de la Tourette syndrome, addiction and Alzheimer's dementia, are affirmative concerning the efficacy of the method and low risk of adverse effects. Deep brain stimulation, as a relatively new neurosurgical method in the treatment of psychiatric disorders, is being intensively developed, and it is certainly going to be one of the treatments of choice, primarily of treatment-resistant disorders.

Gait characteristics in patients with major depression performing cognitive and motor tasks while walking.

Depressed patients demonstrate alterations in motor and cognitive functioning that can affect their adjustments to the variations in everyday life environment. The objective was to explore gait parameters and variability of patients with major depressive disorder in dual task walking situations. Eight patients and 20 healthy controls performed motor, mental and combined motor+mental tasks while walking. Calculated parameters were cycle time, stride length, swing time, double support time and their coefficients of variation (CV). Patients demonstrated greater gait variability (swing time CV) than controls during baseline walk (t(26)=2.64, p<0.05) and motor dual task (t(26)=3.68, p<0.05). Moreover, the transition from mental to combined task decreased stride length (M=126.48±15.35 and M=121.19±13.55, p<0.001) and increased double support time (M=0.266±0.072 and M=0.287±0.076, p<0.01) only in controls. Also, gait variability increased in controls during the combined task, while remaining the same or decreasing in patients. Tasks that required greater cognitive involvement affected gait variability in patients more than controls, but only up to a certain level, after which patients׳ stability appeared unaffected by the increase of cognitive demand. This could be explained by a tendency of patients to neglect complex cognitive tasks while walking in order to preserve stability and prevent possible falls.

Leber hereditary optic neuropathy in the population of Serbia.

BACKGROUND: Leber hereditary optic neuropathy (LHON) is the most common mitochondrial disorder. However, few countries have published their population-based findings related to this multisystemic disease. THE AIM: In order to get a better insight into the epidemiological and clinical picture of this maternally inherited disorder, we performed the first population-based clinical and molecular-genetic study of LHON in the Serbian population. METHODS: Prospective study included patients who were diagnosed with LHON after detailed medical examination and molecular-genetic confirmation. RESULTS: We identified 41 individuals from 12 genealogically unrelated families, carrying one of the three "primary" mitochondrial (mt) DNA point mutations associated with LHON. Fourteen of them were clinically affected, giving a minimum point prevalence of 1.9 per 1,000,000. The minimum point prevalence for mtDNA LHON mutations was 5.2 per 1,000,000. Male to female ratio was 6:1. Only one affected patient harboured mutant mtDNA in heteroplasmic condition. All patients were presented with common clinical findings. CONCLUSION: We observed significantly lower prevalence and higher gender ratio than expected. However, frequencies of primary mutations, incidence of heteroplasmy and clinical findings are in accordance with other studies in Caucasoid populations. Our results might be a consequence of poor recognition and misdiagnosis due to lack of diagnostic possibilities of the entity in different region of our country or less likely be in part due to specific haplotype background of Serbian population which should be further investigated.