Browsing by Author "Kostić, Vladimir S. (57189017751)"

This study was addressed to determine the presence of Parkinson disease (PD) manifestations, their distribution according to motor subtypes, and the relationships with health-related quality of life (QoL) using the recently validated European Parkinson’s Disease Association sponsored Parkinson’s Disease Composite Scale (PDCS). Frequency of symptoms was determined by the scores of items (present if >0). Using ROC analysis and Youden method, MDS-UPDRS motor subtypes were projected on the PDCS to achieve a comparable classification based on the PDCS scores. The same method was used to estimate severity levels from other measures in the study. The association between the PDCS and QoL (PDQ-39) was analyzed by correlation and multiple linear regression. The sample consisted of 776 PD patients. We found that the frequency of PD manifestations with PDCS and MDS-UPDRS were overlapping, the average difference between scales being 5.5% only. Using the MDS-UPDRS subtyping, 215 patients (27.7%) were assigned as Tremor Dominant (TD), 60 (7.7%) Indeterminate, and 501 (64.6%) Postural Instability and Gait Difficulty (PIGD) in this cohort. With this classification as criterion, the analogous PDCS-based ratio provided these cut-off values: TD subtype, ≥1.06; Indeterminate, <1.06 but >0.65; and PIGD, <0.65. The agreement between the two scales on this classification was substantial (87.6%; kappa = 0.69). PDCS total score cut-offs for PD severity were: 23/24 for mild/moderate and 41/42 for moderate/severe. Moderate to high correlations (r = 0.35–0.80) between PDCS and PDQ-39 were obtained, and the four PDCS domains showed a significant independent influence on QoL. The conclusions are: (1) the PDCS assessed the frequency of PD symptoms analogous to the MDS-UPDRS; (2) motor subtypes and severity levels can be determined with the PDCS; (3) a significant association between PDCS and QoL scores exists. © 2019, The Author(s).

This study was addressed to determine the presence of Parkinson disease (PD) manifestations, their distribution according to motor subtypes, and the relationships with health-related quality of life (QoL) using the recently validated European Parkinson’s Disease Association sponsored Parkinson’s Disease Composite Scale (PDCS). Frequency of symptoms was determined by the scores of items (present if >0). Using ROC analysis and Youden method, MDS-UPDRS motor subtypes were projected on the PDCS to achieve a comparable classification based on the PDCS scores. The same method was used to estimate severity levels from other measures in the study. The association between the PDCS and QoL (PDQ-39) was analyzed by correlation and multiple linear regression. The sample consisted of 776 PD patients. We found that the frequency of PD manifestations with PDCS and MDS-UPDRS were overlapping, the average difference between scales being 5.5% only. Using the MDS-UPDRS subtyping, 215 patients (27.7%) were assigned as Tremor Dominant (TD), 60 (7.7%) Indeterminate, and 501 (64.6%) Postural Instability and Gait Difficulty (PIGD) in this cohort. With this classification as criterion, the analogous PDCS-based ratio provided these cut-off values: TD subtype, ≥1.06; Indeterminate, <1.06 but >0.65; and PIGD, <0.65. The agreement between the two scales on this classification was substantial (87.6%; kappa = 0.69). PDCS total score cut-offs for PD severity were: 23/24 for mild/moderate and 41/42 for moderate/severe. Moderate to high correlations (r = 0.35–0.80) between PDCS and PDQ-39 were obtained, and the four PDCS domains showed a significant independent influence on QoL. The conclusions are: (1) the PDCS assessed the frequency of PD symptoms analogous to the MDS-UPDRS; (2) motor subtypes and severity levels can be determined with the PDCS; (3) a significant association between PDCS and QoL scores exists. © 2019, The Author(s).

Artificial intelligence, specifically machine learning, has found numerous applications in computer-aided diagnostics, monitoring and management of neurodegenerative movement disorders of parkinsonian type. These tasks are not trivial due to high inter-subject variability and similarity of clinical presentations of different neurodegenerative disorders in the early stages. This paper aims to give a comprehensive, high-level overview of applications of artificial intelligence through machine learning algorithms in kinematic analysis of movement disorders, specifically Parkinson's disease (PD). We surveyed papers published between January 2007 and January 2019, within online databases, including PubMed and Science Direct, with a focus on the most recently published studies. The search encompassed papers dealing with the implementation of machine learning algorithms for diagnosis and assessment of PD using data describing motion of upper and lower extremities. This systematic review presents an overview of 48 relevant studies published in the abovementioned period, which investigate the use of artificial intelligence for diagnostics, therapy assessment and progress prediction in PD based on body kinematics. Different machine learning algorithms showed promising results, particularly for early PD diagnostics. The investigated publications demonstrated the potentials of collecting data from affordable and globally available devices. However, to fully exploit artificial intelligence technologies in the future, more widespread collaboration is advised among medical institutions, clinicians and researchers, to facilitate aligning of data collection protocols, sharing and merging of data sets. © 2019 Elsevier B.V.

Autosomal recessive ataxias (ARCA) represent a complex group of diseases ranging from primary ataxias to rare and complex metabolic disorders in which ataxia is a part of the clinical picture. Small number of ARCA manifest exclusively in adulthood, while majority of typical childhood onset ARCA may also start later with atypical clinical presentation. We have systematically searched the literature for ARCA with adult onset, both in the group of primary ataxias including those that are less frequently described in isolated or in a small number of families, and also in the group of complex and metabolic diseases in which ataxia is only part of the clinical picture. We propose an algorithm that could be used when encountering a patient with adult onset sporadic or recessive ataxia in whom the acquired causes are excluded. ARCA are frequently neglected in the differential diagnosis of adult-onset ataxias. Rising awareness of their clinical significance is important, not only because some of these disorders may be potentially treatable, but also for prognostic implications and inclusion of patients to future clinical trials with disease modifying agents. © 2021, Springer-Verlag GmbH Germany, part of Springer Nature.

Autosomal recessive ataxias (ARCA) represent a complex group of diseases ranging from primary ataxias to rare and complex metabolic disorders in which ataxia is a part of the clinical picture. Small number of ARCA manifest exclusively in adulthood, while majority of typical childhood onset ARCA may also start later with atypical clinical presentation. We have systematically searched the literature for ARCA with adult onset, both in the group of primary ataxias including those that are less frequently described in isolated or in a small number of families, and also in the group of complex and metabolic diseases in which ataxia is only part of the clinical picture. We propose an algorithm that could be used when encountering a patient with adult onset sporadic or recessive ataxia in whom the acquired causes are excluded. ARCA are frequently neglected in the differential diagnosis of adult-onset ataxias. Rising awareness of their clinical significance is important, not only because some of these disorders may be potentially treatable, but also for prognostic implications and inclusion of patients to future clinical trials with disease modifying agents. © 2021, Springer-Verlag GmbH Germany, part of Springer Nature.

Objective: Differentiating Parkinson's disease (PD) from atypical parkinsonian disorders (APD) such as Multiple System Atrophy, parkinsonian type (MSA-p) or Progressive Supranuclear Palsy (PSP-RS) can be challenging. Early signs of postural Instability and gait disability (PIGD) are considered clues that may signal presence of APD. However, it remains unknown which PIGD test – or combination of tests – can best distinguish PD from APD. We evaluated the discriminative value of several widely-used PIGD tests, and aimed to develop a short PIGD evaluation that can discriminate parkinsonian disorders. Methods: In this multicentre cohort study patients were recruited by 11 European MSA Study sites. Patients were diagnosed using standardized criteria. Postural instability and gait disability was evaluated using interviews and several clinical tests. Results: Nineteen PD, 21 MSA-p and 25 PSP-RS patients were recruited. PIGD was more common in APD compared to PD. There was no significant difference in axial symptoms between PSP-RS and MSA-p, except for self-reported falls (more frequent in PSP-RS patients). The test with the greatest discriminative power to distinguish APD from PD was the ability to perform tandem gait (AUC 0.83; 95% CI 71–94; p < 0.001), followed by the retropulsion test (AUC 0.8; 95% CI 0.69–0.91; p < 0.001) and timed-up-and-go test (TUG) (AUC 0.77; 95% CI 0.64–0.9; p = 0.001). The combination of these three tests yielded highest diagnostic accuracy (AUC 0.96; 95% CI 0.92–1.0; p < 0.001). Conclusions: Our study suggests that simple “bedside” PIGD tests – particularly the combination of tandem gait performance, TUG and retropulsion test – can discriminate APD from PD. © 2018 Elsevier Ltd

Objective: Differentiating Parkinson's disease (PD) from atypical parkinsonian disorders (APD) such as Multiple System Atrophy, parkinsonian type (MSA-p) or Progressive Supranuclear Palsy (PSP-RS) can be challenging. Early signs of postural Instability and gait disability (PIGD) are considered clues that may signal presence of APD. However, it remains unknown which PIGD test – or combination of tests – can best distinguish PD from APD. We evaluated the discriminative value of several widely-used PIGD tests, and aimed to develop a short PIGD evaluation that can discriminate parkinsonian disorders. Methods: In this multicentre cohort study patients were recruited by 11 European MSA Study sites. Patients were diagnosed using standardized criteria. Postural instability and gait disability was evaluated using interviews and several clinical tests. Results: Nineteen PD, 21 MSA-p and 25 PSP-RS patients were recruited. PIGD was more common in APD compared to PD. There was no significant difference in axial symptoms between PSP-RS and MSA-p, except for self-reported falls (more frequent in PSP-RS patients). The test with the greatest discriminative power to distinguish APD from PD was the ability to perform tandem gait (AUC 0.83; 95% CI 71–94; p < 0.001), followed by the retropulsion test (AUC 0.8; 95% CI 0.69–0.91; p < 0.001) and timed-up-and-go test (TUG) (AUC 0.77; 95% CI 0.64–0.9; p = 0.001). The combination of these three tests yielded highest diagnostic accuracy (AUC 0.96; 95% CI 0.92–1.0; p < 0.001). Conclusions: Our study suggests that simple “bedside” PIGD tests – particularly the combination of tandem gait performance, TUG and retropulsion test – can discriminate APD from PD. © 2018 Elsevier Ltd

Brain calcifications may be an incidental finding on neuroimaging in normal, particularly older individuals, but can also indicate numerous hereditary and nonhereditary syndromes, and metabolic, environmental, infectious, autoimmune, mitochondrial, traumatic, or toxic disorders. Bilateral calcifications most commonly affecting the basal ganglia may often be found in idiopathic cases, and a new term, primary familial brain calcification (PFBC), has been proposed that recognizes the genetic causes of the disorder and that calcifications occurred well beyond the basal ganglia. PFBC, usually inherited in an autosomal dominant fashion, is both an intrafamilial and an interfamilial heterogeneous disorder, clinically characterized by an insidious and progressive development of movement disorders, cognitive decline, and psychiatric symptoms, but also cerebellar ataxia, pyramidal signs, and sometimes isolated seizures and headaches/migraines. Heterozygous mutations in four genes (SLC20A2, PDGFRB, PDGFB, XPR1) have recently proved to be the causes of the autosomal dominant forms of PFBC, also suggesting disrupted phosphate homeostasis as “an underlying and converging” pathophysiological mechanism. However, to date, it is not possible to anticipate with acceptable certainty any of known genetic causes of PFBC on the basis of the type, severity, pattern of distribution, or combination of movement disorders (mainly parkinsonism, with or without tremor, but also dystonia, chorea, paroxysmal kinesigenic dyskinesia, orofacial dyskinesia, and gait and speech disorders). © 2017, Springer Science+Business Media New York.

Brain calcifications may be an incidental finding on neuroimaging in normal, particularly older individuals, but can also indicate numerous hereditary and nonhereditary syndromes, and metabolic, environmental, infectious, autoimmune, mitochondrial, traumatic, or toxic disorders. Bilateral calcifications most commonly affecting the basal ganglia may often be found in idiopathic cases, and a new term, primary familial brain calcification (PFBC), has been proposed that recognizes the genetic causes of the disorder and that calcifications occurred well beyond the basal ganglia. PFBC, usually inherited in an autosomal dominant fashion, is both an intrafamilial and an interfamilial heterogeneous disorder, clinically characterized by an insidious and progressive development of movement disorders, cognitive decline, and psychiatric symptoms, but also cerebellar ataxia, pyramidal signs, and sometimes isolated seizures and headaches/migraines. Heterozygous mutations in four genes (SLC20A2, PDGFRB, PDGFB, XPR1) have recently proved to be the causes of the autosomal dominant forms of PFBC, also suggesting disrupted phosphate homeostasis as “an underlying and converging” pathophysiological mechanism. However, to date, it is not possible to anticipate with acceptable certainty any of known genetic causes of PFBC on the basis of the type, severity, pattern of distribution, or combination of movement disorders (mainly parkinsonism, with or without tremor, but also dystonia, chorea, paroxysmal kinesigenic dyskinesia, orofacial dyskinesia, and gait and speech disorders). © 2017, Springer Science+Business Media New York.

Background: The neural basis of task specificity in dystonia is still poorly understood. This study investigated gray and white matter (WM) brain alterations in patients with task-specific dystonia (TSD) and non-task-specific dystonia (NTSD). Methods: Thirty-six patients with TSD (spasmodic dysphonia, writer's cramp), 61 patients with NTSD (blepharospasm, cervical dystonia), and 83 healthy controls underwent 3D T1-weighted and diffusion tensor magnetic resonance imaging (MRI). Whole brain cortical thickness and voxel-based morphometry; volumes of basal ganglia, thalamus, nucleus accumbens, amygdala, and hippocampus; and WM damage were assessed. Analysis of variance models were used to compare MRI measures between groups, adjusting for age and botulinum toxin (BoNT) treatment. Results: The comparison between focal dystonia patients showed cortical thickness and gray matter (GM) volume differences (ie, decreased in NTSD, increased in TSD) in frontal, parietal, temporal, and occipital cortical regions; basal ganglia; thalamus; hippocampus; and amygdala. Cerebellar atrophy was found in NTSD patients relative to controls. WM damage was more severe and widespread in task-specific relative to NTSD patients. TSD patients receiving BoNT, relative to nontreated patients, had cortical thickening and increased GM volume in frontoparietal, temporal, and occipital regions. NTSD patients experiencing pain showed cortical thickening of areas involved in pain-inhibitory mechanisms. Conclusions: TSD and NTSD are characterized by opposite alterations of the main cortical and subcortical sensorimotor and cognitive-controlling brain structures, suggesting the possible presence of different pathophysiological and/or compensatory mechanisms underlying the complexity of the two clinical phenotypes of focal dystonia. © 2020 International Parkinson and Movement Disorder Society. © 2020 International Parkinson and Movement Disorder Society

Background: The neural basis of task specificity in dystonia is still poorly understood. This study investigated gray and white matter (WM) brain alterations in patients with task-specific dystonia (TSD) and non-task-specific dystonia (NTSD). Methods: Thirty-six patients with TSD (spasmodic dysphonia, writer's cramp), 61 patients with NTSD (blepharospasm, cervical dystonia), and 83 healthy controls underwent 3D T1-weighted and diffusion tensor magnetic resonance imaging (MRI). Whole brain cortical thickness and voxel-based morphometry; volumes of basal ganglia, thalamus, nucleus accumbens, amygdala, and hippocampus; and WM damage were assessed. Analysis of variance models were used to compare MRI measures between groups, adjusting for age and botulinum toxin (BoNT) treatment. Results: The comparison between focal dystonia patients showed cortical thickness and gray matter (GM) volume differences (ie, decreased in NTSD, increased in TSD) in frontal, parietal, temporal, and occipital cortical regions; basal ganglia; thalamus; hippocampus; and amygdala. Cerebellar atrophy was found in NTSD patients relative to controls. WM damage was more severe and widespread in task-specific relative to NTSD patients. TSD patients receiving BoNT, relative to nontreated patients, had cortical thickening and increased GM volume in frontoparietal, temporal, and occipital regions. NTSD patients experiencing pain showed cortical thickening of areas involved in pain-inhibitory mechanisms. Conclusions: TSD and NTSD are characterized by opposite alterations of the main cortical and subcortical sensorimotor and cognitive-controlling brain structures, suggesting the possible presence of different pathophysiological and/or compensatory mechanisms underlying the complexity of the two clinical phenotypes of focal dystonia. © 2020 International Parkinson and Movement Disorder Society. © 2020 International Parkinson and Movement Disorder Society

Introduction: Functional movement disorders (FMD) refer to a group of movement disorders that present with clinical characteristics incongruent to those due to established pathophysiologic processes, as for example in the case of neurodegeneration or lesions. The aim of this study was to assess clinical features that contribute to the specific phenotypic presentations and disease course of FMD. Methods: The study consisted of 100 patients with FMD treated at Clinic for Neurology, Clinical Center of Serbia, who were longitudinally observed. Comprehensive clinical and psychiatric assessment was performed at the baseline, when initial FMD phenotype was defined. Follow-up assessment of phenotypic pattern over the time and clinical course was done after 3.2 ± 2.5 years at average. Results: We showed that 48% of FMD patients were prone to changes of phenotypic pattern during the disease course. Dystonia had tendency to remains as single and unchanged phenotype over the time (68.2%), while patients initially presented with Tremor, Gait disorder, Parkinsonism and Mixed phenotype were more susceptible to developing additional symptoms (62.5, 50, and 100%, respectively). Higher levels of somatoform experiences (p = 0.033, Exp(B) = 1.082) and higher motor severity (p = 0.040, Exp(B) = 1.082) at baseline assessment were associated with an increased likelihood of further enriching of FMD phenotype with additional functional symptoms. Also, these patients more frequently reported pain, and had higher scores on majority of applied psychiatric scales, together with more frequent presence of major depressive disorder. Conclusion: Results from this prospective study suggested tendency for progression and enrichment of functional symptoms in FMD patients over time. Besides functional core symptoms, other key psychological and physical features (like pain or multiple somatisations) were quite relevant for chronicity and significant dysability of FMD patients. © Copyright © 2020 Tomić, Ječmenica Lukić, Petrović, Svetel, Dragašević Mišković, Kresojević, Marković and Kostić.

Introduction: Functional movement disorders (FMD) refer to a group of movement disorders that present with clinical characteristics incongruent to those due to established pathophysiologic processes, as for example in the case of neurodegeneration or lesions. The aim of this study was to assess clinical features that contribute to the specific phenotypic presentations and disease course of FMD. Methods: The study consisted of 100 patients with FMD treated at Clinic for Neurology, Clinical Center of Serbia, who were longitudinally observed. Comprehensive clinical and psychiatric assessment was performed at the baseline, when initial FMD phenotype was defined. Follow-up assessment of phenotypic pattern over the time and clinical course was done after 3.2 ± 2.5 years at average. Results: We showed that 48% of FMD patients were prone to changes of phenotypic pattern during the disease course. Dystonia had tendency to remains as single and unchanged phenotype over the time (68.2%), while patients initially presented with Tremor, Gait disorder, Parkinsonism and Mixed phenotype were more susceptible to developing additional symptoms (62.5, 50, and 100%, respectively). Higher levels of somatoform experiences (p = 0.033, Exp(B) = 1.082) and higher motor severity (p = 0.040, Exp(B) = 1.082) at baseline assessment were associated with an increased likelihood of further enriching of FMD phenotype with additional functional symptoms. Also, these patients more frequently reported pain, and had higher scores on majority of applied psychiatric scales, together with more frequent presence of major depressive disorder. Conclusion: Results from this prospective study suggested tendency for progression and enrichment of functional symptoms in FMD patients over time. Besides functional core symptoms, other key psychological and physical features (like pain or multiple somatisations) were quite relevant for chronicity and significant dysability of FMD patients. © Copyright © 2020 Tomić, Ječmenica Lukić, Petrović, Svetel, Dragašević Mišković, Kresojević, Marković and Kostić.

Geste antagonistes are usually considered typical of primary dystonia, although rarely they have been described in secondary/heredodegenerative dystonias. We have recently come across a particular geste antagoniste in 5 of 10 patients with pantothenate kinase-associated neurodegeneration (PKAN) who had prominent oromandibular involvement with severe jaw-opening dystonia. It consists of touching the chin with both hands characteristically clenched into a fist with flexion at the elbows. Because of the resemblance of this geste antagoniste with the praying-like posture of Mantis religiosa, we coined the term “mantis sign.” Reviewing videos of PKAN cases in literature, including what is considered the first cinematic depiction of a case of this disorder, 3 additional cases with akin maneuvers were identified. In contrast, examining 205 videos of non-PKAN dystonic patients from our database for the presence of a similar maneuver was unrevealing. Thus, we consider the mantis sign to be quite typical of PKAN and propose it to be added as a clinical hint toward diagnosis. © 2014 International Parkinson and Movement Disorder Society.

Geste antagonistes are usually considered typical of primary dystonia, although rarely they have been described in secondary/heredodegenerative dystonias. We have recently come across a particular geste antagoniste in 5 of 10 patients with pantothenate kinase-associated neurodegeneration (PKAN) who had prominent oromandibular involvement with severe jaw-opening dystonia. It consists of touching the chin with both hands characteristically clenched into a fist with flexion at the elbows. Because of the resemblance of this geste antagoniste with the praying-like posture of Mantis religiosa, we coined the term “mantis sign.” Reviewing videos of PKAN cases in literature, including what is considered the first cinematic depiction of a case of this disorder, 3 additional cases with akin maneuvers were identified. In contrast, examining 205 videos of non-PKAN dystonic patients from our database for the presence of a similar maneuver was unrevealing. Thus, we consider the mantis sign to be quite typical of PKAN and propose it to be added as a clinical hint toward diagnosis. © 2014 International Parkinson and Movement Disorder Society.

Background: The fixed dystonia phenotype was originally established as a prototype of functional dystonia. Nevertheless, in recent reports different functional dystonia phenotypes have been recognized with dystonic movement comprising phasic instead of tonic contraction. Objectives: To examine clinical characteristic in all patients with dystonia who fulfilled the criteria for functional movement disorders irrespective of phenotype in an attempt to determine parameters of clinical presentations that might impact the disease progression pattern and outcome. Methods: Patients presented with dystonia features incompatible with organic disease without other features required for the diagnosis of functional movement disorders were analyzed and prospectively followed-up. The two-step cluster analysis was performed to obtain the subgroups of dystonia phenotypes. Results: The two-step cluster analysis extracted two subgroup of patients. Patients of the first cluster (68.8%) presented with “mobile” dystonia (84.9%), of cranial/neck/trunk localization (90.9%), fluctuated clinical course (69.7%), with frequent additional movement or other functional neurological disorders (63.6%) during follow-up. In the second cluster (31.2%) all of the patients presented with “fixed” dystonia of extremities, and the clinical course was characterized by either the disease progression (60%), or continuous without improvement (26.7%), and rare occurrence of additional functional neurological disorders (13.3%). Conclusion: In terms of clinical and demographic features as well as pattern of disease progression there are two clinical phenotypes in patients with functional dystonia. Distinctive features of incongruence and inconstancy are characteristic for “mobile” functional dystonia subgroup of patients. © 2017, Springer-Verlag GmbH Germany, part of Springer Nature.

Background: The fixed dystonia phenotype was originally established as a prototype of functional dystonia. Nevertheless, in recent reports different functional dystonia phenotypes have been recognized with dystonic movement comprising phasic instead of tonic contraction. Objectives: To examine clinical characteristic in all patients with dystonia who fulfilled the criteria for functional movement disorders irrespective of phenotype in an attempt to determine parameters of clinical presentations that might impact the disease progression pattern and outcome. Methods: Patients presented with dystonia features incompatible with organic disease without other features required for the diagnosis of functional movement disorders were analyzed and prospectively followed-up. The two-step cluster analysis was performed to obtain the subgroups of dystonia phenotypes. Results: The two-step cluster analysis extracted two subgroup of patients. Patients of the first cluster (68.8%) presented with “mobile” dystonia (84.9%), of cranial/neck/trunk localization (90.9%), fluctuated clinical course (69.7%), with frequent additional movement or other functional neurological disorders (63.6%) during follow-up. In the second cluster (31.2%) all of the patients presented with “fixed” dystonia of extremities, and the clinical course was characterized by either the disease progression (60%), or continuous without improvement (26.7%), and rare occurrence of additional functional neurological disorders (13.3%). Conclusion: In terms of clinical and demographic features as well as pattern of disease progression there are two clinical phenotypes in patients with functional dystonia. Distinctive features of incongruence and inconstancy are characteristic for “mobile” functional dystonia subgroup of patients. © 2017, Springer-Verlag GmbH Germany, part of Springer Nature.

Introduction: Levodopa-induced dyskinesias (LID) appears in more than 50% of Parkinson’s disease patients after 5 years of treatment and clinicians always have to ensure that there is a balance between the beneficial effect of the treatment and the potential complications. Areas covered: In this review, the authors discuss the treatment of LID. Treatment can be divided into strategies for preventing their occurrence, modification of dopaminergic therapy, and providing more continuous dopaminergic stimulation as well as the use of nondopaminergic drugs. Expert opinion: Amantadine is currently considered the most effective drug for the treatment of LID. Several compounds developed to target adenosine, adrenergic, glutamatergic, and serotonergic receptors have shown to significantly decrease dyskinesias in animal models. However, despite promising preclinical results, translation to clinical practice remains challenging and majority of these compounds failed to decrease LID in randomized controlled trials with moderate–to-advanced parkinsonian patients. Despite promising results with nondopaminergic drugs, treatment of dyskinesias is still challenging and largely due to their side effects. Future research should focus on developing treatments that can provide continuous dopaminergic delivery throughout the day in a noninvasive manner. Studies on the impact of the early administration of long-acting formulations of levo-3,4-dihydroxy-phenylalanine on dyskinesias are also necessary. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.

Introduction: Levodopa-induced dyskinesias (LID) appears in more than 50% of Parkinson’s disease patients after 5 years of treatment and clinicians always have to ensure that there is a balance between the beneficial effect of the treatment and the potential complications. Areas covered: In this review, the authors discuss the treatment of LID. Treatment can be divided into strategies for preventing their occurrence, modification of dopaminergic therapy, and providing more continuous dopaminergic stimulation as well as the use of nondopaminergic drugs. Expert opinion: Amantadine is currently considered the most effective drug for the treatment of LID. Several compounds developed to target adenosine, adrenergic, glutamatergic, and serotonergic receptors have shown to significantly decrease dyskinesias in animal models. However, despite promising preclinical results, translation to clinical practice remains challenging and majority of these compounds failed to decrease LID in randomized controlled trials with moderate–to-advanced parkinsonian patients. Despite promising results with nondopaminergic drugs, treatment of dyskinesias is still challenging and largely due to their side effects. Future research should focus on developing treatments that can provide continuous dopaminergic delivery throughout the day in a noninvasive manner. Studies on the impact of the early administration of long-acting formulations of levo-3,4-dihydroxy-phenylalanine on dyskinesias are also necessary. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.

Introduction: Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive disorder with a progressive clinical course. In addition to symptomatic therapy, DBS has been increasingly recognized as a potential therapeutic strategy, especially in severe cases. Therefore, we wanted to report our experience regarding benefits of DBS in five PKAN cases in 3-year follow-up study. Methods: Five genetically confirmed PKAN patients from Serbia underwent GPi-DBS. To assess clinical outcome, we reviewed medical charts and applied: Schwab and England Activities of Daily Living Scale (S&E), EQ-5D questionnaire for quality of life, Patient Global Impression of Improvement (GPI-I), Functional Independence Measure (FIM), Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS), Barry Albright Dystonia Scale (BAD). Patients were evaluated in five visits: at the disease onset, 5 years after the onset, before surgery, 6 months and 14–36 months after the surgery. Improvement of 20% was accepted as significant. Results: Overall, dystonia significantly improved after GPi-DBS at 6 and 14–36 months postoperatively, when assessed by the BFMDRS and BAD. However, two patients failed to improve considerably. Four patients reported improvement on GPI-I, while one remained unchanged. Three patients reported significant improvement, when assessed with S&E and FIM. EQ-5D showed the most prominent improvement in the domains of mobility and pain/discomfort. Conclusion: Three out of our five patients experienced beneficial effects of the GPi-DBS, in up to 36 months follow-up. Two patients who had not reached significant improvement had longer disease duration; therefore, it might be reasonable to recommend GPi-DBS as soon as dystonia became disabling. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.