Iva Stankovic

Cognitive impairment in multiple system atrophy: a position statement by the Neuropsychology Task Force of the MDS Multiple System Atrophy (MODIMSA) study group.

Consensus diagnostic criteria for multiple system atrophy consider dementia as a nonsupporting feature, despite emerging evidence demonstrating that cognitive impairments are an integral part of the disease. Cognitive disturbances in multiple system atrophy occur across a wide spectrum from mild single domain deficits to impairments in multiple domains and even to frank dementia in some cases. Frontal‐executive dysfunction is the most common presentation, while memory and visuospatial functions also may be impaired. Imaging and neuropathological findings support the concept that cognitive impairments in MSA originate from striatofrontal deafferentation, with additional contributions from intrinsic cortical degeneration and cerebellar pathology. Based on a comprehensive evidence‐based review, the authors propose future avenues of research that ultimately may lead to diagnostic criteria for cognitive impairment and dementia associated with multiple system atrophy.

Cortico-striatal-thalamic network functional connectivity in hemiparkinsonism

Cortico-striatal-thalamic network functional connectivity (FC) and its relationship with levodopa (L-dopa) were investigated in 69 patients with hemiparkinsonism (25 drug-naïve [n-PD] and 44 under stable/optimized dopaminergic treatment [t-PD]) and 27 controls. Relative to controls, n-PD patients showed an increased FC between the left and the right basal ganglia, and a decreased connectivity of the affected caudate nucleus and thalamus with the ipsilateral frontal and insular cortices. Compared with both controls and n-PD patients, t-PD patients showed a decreased FC among the striatal and thalamic regions, and an increased FC between the striatum and temporal cortex, and between the thalamus and several sensorimotor, parietal, temporal, and occipital regions. In both n-PD and t-PD, patients with more severe motor disability had an increased striatal and/or thalamic FC with temporal, parietal, occipital, and cerebellar regions. Cortico-striatal-thalamic functional abnormalities occur in patients with hemiparkinsonism, antecede the onset of the motor symptoms on the opposite body side and are modulated by L-dopa. In patients with hemiparkinsonism, L-dopa is likely to facilitate a compensation of functional abnormalities possibly through an increased thalamic FC.

Automatic Identification and Classification of Freezing of Gait Episodes in Parkinson's Disease Patients

Alternation of walking pattern decreases quality of life and may result in falls and injuries. Freezing of gait (FOG) in Parkinsons disease (PD) patients occurs occasionally and intermittently, appearing in a random, inexplicable manner. In order to detect typical disturbances during walking, we designed an expert system for automatic classification of various gait patterns. The proposed method is based on processing of data obtained from an inertial sensor mounted on shank. The algorithm separates normal from abnormal gait using Pearsons correlation and describes each stride by duration, shank displacement, and spectral components. A rule-based data processing classifies strides as normal, short (short+) or very short (short-) strides, FOG with tremor (FOG+) or FOG with complete motor block (FOG-). The algorithm also distinguishes between straight and turning strides. In 12 PD patients, FOG+ and FOG- were identified correctly in 100% of strides, while normal strides were recognized in 95% of cases. Short+ and short- strides were identified in about 84% and 78%. Turning strides were correctly identified in 88% of cases. The proposed method may be used as an expert system for detailed stride classification, providing warning for severe FOG episodes and near-fall situations.

Circumstances of falls and fall-related injuries among patients with Parkinson's disease in an outpatient setting

Falls represent continuing, disabling and costly problem in Parkinsons disease (PD). The study was carried out at the Neurology Clinic in Belgrade from August 2011 to December 2012. As many as 180 community dwelling persons with PD aged 22-83 years who sustained a fall in past 6 months were included. Characteristics of the most recent fall were obtained through detailed interviews. Inclusion criteria were: Mini Mental State Examination (MMSE)≥24, ability to walk independently for at least 10 m and ability to statically stand for at least 90 s. Exclusion criteria were: presence of other neurologic as well as psychiatric, visual, audio-vestibular and orthopedic impairments. Falls more frequently took place outside (57.2%) and in the morning (53.9%). As much as 38.9% of persons with PD sustained an injury. Soft-tissue contusion was the most common injury (71.8%) both after indoor and outdoor falls. Fractures accounted for 5% of all fall-related injuries. All the fractures were either arm, clavicle or rib fractures. Tripping was identified as risk factor for outdoor falls (OR=7.90; 95% confidence interval [95% CI] 3.21-19.39; p=0.001). In contrast, lower extremity weakness (OR=0.20; 95% CI 0.05-0.72; p=0.015) and internal sense of sudden loss of balance (OR=0.19; 95% CI 0.05-0.73; p=0.015) were risk factors for indoor falls. To accomplish long-term results, development of particular prevention programs for persons with PD who fall at home vs. outdoors is recommended.

Episodic ataxia type 2: phenotype characteristics of a novel CACNA1A mutation and review of the literature

Episodic ataxia type 2 (EA2) is an autosomal dominant inherited neurological disorder that is characterized by paroxysmal episodes of ataxia. The causative gene for EA2 is CACNA1A which codes for the alpha 1A subunit of the voltage-gated P/Q-type calcium channel (Cav2.1). We detected a novel point mutation in the CACNA1A gene in a large Austrian family. All ten affected family members harbored a heterozygous c.3089+2T>C nucleotide exchange in intron 19. In silico modeling demonstrated a loss of the splice site of exon 19 by the mutation, which most likely results in exon skipping without frameshifting or use of an alternative splice site. Clinically, the family exhibited frequent ataxic episodes accompanied by headache in some individuals, which showed a good treatment response to acetazolamide or aminopyridine. Interictal phenotype variability was high ranging from an unremarkable clinical examination to a progressive cerebellar syndrome. Detailed cognitive testing with standardized neuropsychological tests revealed specific deficits in various domains including memory, executive functions and visual abilities. Moreover, a striking coincidence of socio-phobic behavior and anxiety disorders was detected within this family, which interfered with activities of daily living and has to be taken in consideration in EA2 patient management. We here characterize the phenotype of this novel CACNA1A mutation, review the respective literature and discuss implications on diagnosis and patient management.

Structural Brain Connectome and Cognitive Impairment in Parkinson Disease

Purpose To investigate the structural brain connectome in patients with Parkinson disease (PD) and mild cognitive impairment (MCI) and in patients with PD without MCI. Materials and Methods This prospective study was approved by the local ethics committees, and written informed consent was obtained from all subjects prior to enrollment. The individual structural brain connectome of 170 patients with PD (54 with MCI, 116 without MCI) and 41 healthy control subjects was obtained by using deterministic diffusion-tensor tractography. A network-based statistic was used to assess structural connectivity differences among groups. Results Patients with PD and MCI had global network alterations when compared with both control subjects and patients with PD without MCI (range, P = .004 to P = .048). Relative to control subjects, patients with PD and MCI had a large basal ganglia and frontoparietal network with decreased fractional anisotropy (FA) in the right hemisphere and a subnetwork with increased mean diffusivity (MD) involving similar regions bilaterally (P < .01). When compared with patients with PD without MCI, those with PD and MCI had a network with decreased FA, including basal ganglia and frontotemporoparietal regions bilaterally (P < .05). Similar findings were obtained by adjusting for motor disability (P < .05, permutation-corrected P = .06). At P < .01, patients with PD and MCI did not show network alterations relative to patients with PD without MCI. Network FA and MD values were used to differentiate patients with PD and MCI from healthy control subjects and patients with PD without MCI with fair to good accuracy (cross-validated area under the receiver operating characteristic curve [principal + secondary connected components] range, 0.75-0.85). Conclusion A disruption of structural connections between brain areas forming a network contributes to determine an altered information integration and organization and thus cognitive deficits in patients with PD. These results provide novel information concerning the structural substrates of MCI in patients with PD and may offer markers that can be used to differentiate between patients with PD and MCI and patients with PD without MCI.

Mild Cognitive Impairment in Early Parkinson's Disease Using the Movement Disorder Society Task Force Criteria: Cross-Sectional Study in Hoehn and Yahr Stage 1

Background: Mild cognitive impairment (MCI) in Parkinsons disease (PD) is common and confers a higher risk for developing dementia. Methods: In this cross-sectional study of MCI in PD conducted at a university hospital, a comprehensive neuropsychological battery covering five domains (attention/working memory, executive, verbal, and visual memory, language, and visuospatial) was administered to 111 nondemented PD patients in Hoehn and Yahr stage 1 and to 105 healthy matched control subjects (HC). MCI was diagnosed according to level 2 of the Movement Disorder Society Task Force criteria. Results: Criteria for MCI associated with PD (PD-MCI) were fulfilled by 24% of PD patients in the initial stage of the disease at the z cutoff scores of -1.5 SD in contrast to 7% of HC fulfilling criteria for MCI. Memory and visuospatial domains were the most commonly affected at -1.5 SD. PD-MCI patients mostly had a multiple-domain MCI subtype (78%). They presented a more severe bradykinesia and higher mood and apathy scores in comparison with cognitively normal PD patients. Basic motor scores predicted performance on some cognitive tests and specific cognitive-motor relationships emerged. Conclusions: MCI, predominantly of a multiple-domain subtype, was quite prevalent even in the initial stage of PD.

White matter abnormalities in Parkinson's disease patients with glucocerebrosidase gene mutations

Glucocerebrosidase gene mutations represent a genetic risk factor for the development of Parkinsons disease. This study investigated brain alterations in Parkinsons disease patients carrying heterozygous glucocerebrosidase gene mutations using structural and diffusion tensor magnetic resonance imaging. Among 360 Parkinsons disease patients screened for glucocerebrosidase gene mutations, 19 heterozygous mutation carriers (5.3%) were identified. Of these, 15 patients underwent a neuropsychological evaluation and a magnetic resonance imaging scan. Sixteen age‐ and sex‐matched healthy controls and 14 idiopathic Parkinsons disease patients without glucocerebrosidase gene mutations were also studied. Tract‐based spatial statistics was used to perform a white matter voxel‐wise analysis of diffusion tensor magnetic resonance imaging metrics. Mean fractional anisotropy values were obtained from white matter tracts of interest. Voxel‐based morphometry was used to assess gray‐matter atrophy. Cognitive deficits were found in 9 mutation carrier patients (60%). Compared with controls, Parkinsons disease patients carrying glucocerebrosidase gene mutations showed decreased fractional anisotropy in the olfactory tracts, corpus callosum, and anterior limb of the internal capsule bilaterally, as well as in the right anterior external capsule, and left cingulum, parahippocampal tract, parietal portion of the superior longitudinal fasciculus, and occipital white matter. Mutation carrier patients also had decreased fractional anisotropy of the majority of white matter tracts compared with Parkinsons disease patients with no mutations. No white matter abnormalities were found in Parkinsons disease patients without glucocerebrosidase gene mutations. No gray matter difference was found between patients and controls. In Parkinsons disease patients, verbal fluency scores correlated with white matter abnormalities. Parkinsons disease patients carrying glucocerebrosidase gene mutations experience a distributed pattern of white matter abnormalities involving the interhemispheric, frontal corticocortical, and parahippocampal tracts. White matter pathology in these patients may have an impact on the clinical manifestations of the disease, including cognitive impairment.

Fall frequency and risk factors in patients with Parkinson's disease in Belgrade, Serbia: A cross‐sectional study

The aim of the present study was to estimate fall frequency as well as demographic and clinical factors related to falling in a cohort of Serbian patients with Parkinsons disease (PD).

Validation and cross-cultural adaptation of the Falls Efficacy Scale in patients with Parkinson's disease in Serbia.

The aim of the present study was to assess the validity and reliability of the Falls Efficacy Scale (FES) in Parkinsons disease (PD) patients in Serbia.