Open-Access Electronic Diary for Motor Fluctuation and Dyskinesia Evaluation in Parkinson Disease: Comparison With Paper Diary.

OBJECTIVE: To determine the utility of an electronic diary for registering motor fluctuations and dyskinesia in Parkinson disease (PD). METHODS: Free, open-access touch screen software suitable for Android 4.4 or higher, with medication alarms, adjustable intervals, and medication dose settings was developed to evaluate ON-OFF periods and dyskinesia. Prospective evaluation included a first phase conducted to make adjustments concerning motor limitations when using the tablet, as well as for proper motor complication identification, and a second phase of 3 days of use at home with a prior diary training session comparing a modified paper version of Core Assessment Program for Surgical Interventional Therapies in PD and the electronic diary. RESULTS: All patients correctly identified ON-OFF periods and dyskinesia. Rater/patient matching ON-OFF fluctuations ranged between 94% and 100% for evaluations of different motor states. Dyskinesia matching percentage was 100% for patients with dyskinesia interfering with activities of daily living and 88% for those who reported no-interference. No significant differences between paper and electronic diaries were identified when reporting ON-OFF motor states or in the number of errors when filling the diaries. CONCLUSIONS: This electronic motor diary proved to be reliable for ON-OFF state and dyskinesia identification and classification. However, no advantage to paper diary has been observed in terms of number of erroneous entries. Based on these results, to improve home motor fluctuations, detection efforts should be directed toward the development of automatic wearable devices rather than digital versions of current available ON-OFF diaries.

A multifactorial study on nutritional status, binge eating and physical activity as main factors directly influencing body weight in Parkinson's disease.

Weight lossisa multifactorial disorder commonly affecting Parkinson's disease patients. The aim of this study was to investigate the relationship between body weight, nutritional status, physical activity, and Parkinson's disease-related factors. A total of 114 consecutive Parkinson's disease patients without dietary restrictions were evaluated prospectively with respect to: nutritional status (Mini Nutritional Assessment), physical activity level (Yale Physical Activity Survey), MDS-UPDRS score, olfactory function, depression, cognitive functionand impulse-control disorders, among other variables. Structural equation modeling was used to build multivariate models and to calculate standardized regression weights (srw) for pairs of variables, which are homologous to correlation coefficients, taking into account the effects of all other variables in the model. Sixty (53%) patients were males. Mean age was 66.1 ± 9.8 years and mean disease duration was 8.3 ± 5.6 years. Longer disease duration was negatively related to nutritional status (srw = -0.25; p = 0.01). UPDRS II + III score was associated with reduced cognitive function (srw = -0.39; p = 0.01), which was positivelyrelated to nutritional status (srw = 0.23; p = 0.01). Finally, nutritional status was positively related to body weight (srw = 0.22, p < 0.01). Binge eating and physical activity were also directly and positively related to body weight (srw = 0.32; p = 0.001 and srw = 0.23; p = 0.001). Nutritional status, binge eating and physical activity were directly and independently related to body weight in our sample of Parkinson's disease patients. Therefore, physicians should actively explore nutritional status and binge eating in Parkinson's disease patients to avoid alterations in body weight regulation. Effects of physical activity should be further explored.

Is tremor related to celiac disease?

Neurological features in celiac disease (CD) are not rare (5%-36%), but tremor is scarcely described. Subjects with CD and healthy controls completed an online survey using WHIGET tremor rating scale. One thousand five hundred and twelve subjects completed the survey, finally 674 CD patients and 290 healthy subjects were included. A higher prevalence of tremor in CD patients was observed in comparison to controls (28% vs 14%, P < 0.001). Frequency of family history of tremor in CD patients with and without tremor was 25% and 20% (P = 0.2), while in the control group it was 41% and 10% (P < 0.001). Controls with tremor showed a higher frequency of family history of tremor when compared to CD patients with tremor (41.5% vs 24.6%, P = 0.03). The results suggested that tremor in CD might be more frequent and possibly related to the disease itself and not due to associated essential tremor.

Diagnostic Value of Combined Acute Levodopa Challenge and Olfactory Testing to Predict Parkinson's Disease.

BACKGROUND: The diagnosis of Parkinson's disease (PD) can be challenging early in the disease course, when motor features are subtle. The objective of this study was to explore the diagnostic value of combining acute levodopa challenge and olfactory testing to predict PD. METHODS: Data from 210 patients with a recent onset of parkinsonism who had at least 2 years of follow-up and underwent acute levodopa challenge for the clinical prediction of long-term dopaminergic response and had olfactory testing with Sniffin' Sticks Test were evaluated. Single and combined diagnostic measures were analyzed. RESULTS: After 2 years of follow-up, a PD diagnosis was confirmed in 157 patients who fulfilled United Kingdom Parkinson's Disease Society Brain Bank criteria and was ruled out in 53. Sensitivity and specificity of acute levodopa challenge to predict PD diagnosis were 0.71 and 0.94, respectively. Sensitivity and specificity of olfactory tests were calculated according to the total olfactory score for hyposmia (0.61 and 0.77 respectively), the hyposmia identification subscore (0.63 and 0.74, respectively), and the anosmia score (0.40 and 0.85, respectively). The best combination identified was response to acute levodopa challenge together with hyposmia according to the total olfactory score (sensitivity, 0.90; specificity, 0.74; positive predictive value, 0.91; negative predictive value, 0.72; accuracy, 0.86). CONCLUSION: The combination of response to acute levodopa challenge with hyposmia according to the total olfactory score improved sensitivity for the early diagnosis of PD.

Facial tremors in patients with and without parkinsonism.

Facial (lip and jaw) tremors can be an early sign of Parkinson's disease (PD), essential tremor and other parkinsonisms. Its response to acute dopaminergic therapy and further predictive clinical diagnosis has not been previously addressed. The aim of this study was to evaluate facial tremors response to acute dopaminergic therapy and further predictive value for clinical diagnosis. A retrospective review of medical records from patients with recent onset of facial tremor, with or without parkinsonism, submitted to acute levodopa challenge for clinical prediction of sustained long-term dopaminergic response was conducted. Twenty-eight out of 559 patients (5 %) had facial tremors, which responded to levodopa in 46 % of patients. Facial tremors response to acute levodopa challenge showed 92 % sensitivity and 93 % specificity to predict a final PD diagnosis. In PD patients, facial tremor magnitude of response to levodopa was not different from that of hand rest tremor (p = 0.8). Facial tremors, although infrequent, can be an early sign of PD. Positive response to acute levodopa challenge predicts long-term PD diagnosis.

Motor features in Parkinson's disease with normal olfactory function.

BACKGROUND: Normosmic Parkinson's disease (PD) might be a unique clinical phenotype with a more benign course when compared with hyposmic PD. OBJECTIVE: The objective of this study was to evaluate motor features and the acute levodopa response according to olfactory function. METHODS: A total of 169 de novo PD patients that underwent olfactory testing and acute levodopa challenge for clinical prediction of sustained long-term dopaminergic response were evaluated. RESULTS: The overall frequency of normosmia was 33%. Normosmic PD patients scored nonsignificantly different to hyposmic/anosmic patients on motor scale and on degree of improvement with levodopa. Motor scores at follow-up were comparable among groups. CONCLUSIONS: Normal olfactory function is common in early PD and was not associated with a different motor phenotype when compared with PD patients with olfactory dysfunction. © 2016 International Parkinson and Movement Disorder Society.

Comparison of Olfactory Identification Patterns among Parkinson's Disease Patients from Different Countries.

Olfactory function assessment is an important screening tool and also may differentiate Parkinson's disease (PD) patients from other parkinsonisms, including nondegenerative ones, such as, normal pressure hydrocephalus, vascular, drug induced, or infectious parkinsonism. Several authors in different countries have reported various sets of odors that best differentiate between these conditions. It is debated if distinctive patterns of "restrictive" or "selective" hyposmia in PD may be affected by cultural aspects. To compare the olfactory identification function in PD across different countries, we analyzed Sniffin' Sticks identification task results between 112 PD patients from Argentina and previously reported data of PD patients from Brazil (106 patients), the Netherlands (400 patients), Germany (40 patients), China (110 patients), and Sri Lanka (89 patients). Categorical principal component analysis (CATPCA) was performed to find components reflecting groups of odors similarly perceived across subjects. CATPCA analysis found 2 components for each group which shared 10 out of 16 odors amongst each other. We found that only the shared items of component 2 (orange, mint, banana, garlic, coffee, cloves, and fish) showed uniform results across all of the included countries, whereas variations in component 1 (licorice, turpentine, and apple) were attributed mostly to differences across control groups.

Olfactory Dysfunction Evaluation Is Not Affected by Comorbid Depression in Parkinson's Disease.

BACKGROUND: Olfactory function assessment is an important screening tool for Parkinson's disease (PD) diagnosis. It is debated whether olfaction is affected by comorbid depression. We assessed the relationship between depression and olfaction in PD and determined whether depression may limit the usefulness of olfactory testing for PD diagnosis. METHODS: Olfaction was evaluated using the Sniffin' Sticks test and the Hyposmia Rating Scale in four groups of subjects: PD patients without depression (n = 30); PD patients with major depression (PDD; n = 30); major depressive disorder (MDD) patients (n = 29); and healthy controls (HCs; n = 30). RESULTS: No differences were found between PD and PDD patients for total Sniffin' Sticks test, threshold, discrimination or identification scores, or in Hyposmia Rating Scale, although both groups differed from HCs and MDD patients (P < 0.05), which, in turn, showed similar olfactory scores. CONCLUSIONS: Lack of differences in olfactory impairment between PD and PDD suggest that depression may not contribute to olfactory dysfunction in PD.

Neural code alterations and abnormal time patterns in Parkinson's disease.

OBJECTIVE: The neural code used by the basal ganglia is a current question in neuroscience, relevant for the understanding of the pathophysiology of Parkinson's disease. While a rate code is known to participate in the communication between the basal ganglia and the motor thalamus/cortex, different lines of evidence have also favored the presence of complex time patterns in the discharge of the basal ganglia. To gain insight into the way the basal ganglia code information, we studied the activity of the globus pallidus pars interna (GPi), an output node of the circuit. APPROACH: We implemented the 6-hydroxydopamine model of Parkinsonism in Sprague-Dawley rats, and recorded the spontaneous discharge of single GPi neurons, in head-restrained conditions at full alertness. Analyzing the temporal structure function, we looked for characteristic scales in the neuronal discharge of the GPi. MAIN RESULTS: At a low-scale, we observed the presence of dynamic processes, which allow the transmission of time patterns. Conversely, at a middle-scale, stochastic processes force the use of a rate code. Regarding the time patterns transmitted, we measured the word length and found that it is increased in Parkinson's disease. Furthermore, it showed a positive correlation with the frequency of discharge, indicating that an exacerbation of this abnormal time pattern length can be expected, as the dopamine depletion progresses. SIGNIFICANCE: We conclude that a rate code and a time pattern code can co-exist in the basal ganglia at different temporal scales. However, their normal balance is progressively altered and replaced by pathological time patterns in Parkinson's disease.

Neuronal Entropy Depends on the Level of Alertness in the Parkinsonian Globus Pallidus in vivo.

A new working hypothesis of Parkinson's disease (PD) proposes to focus on the central role of entropy increase in the basal ganglia (BG) in movement disorders. The conditions necessary for entropy increase in vivo are, however, still not fully described. We recorded the activity of single globus pallidus pars interna neurons during the transition from deep anesthesia to full alertness in relaxed, head-restrained, control, and parkinsonian (6-hydroxydopamine-lesioned group-lesioned) rats. We found that during awakening from anesthesia, the variation of neuronal entropy was significantly higher in the parkinsonian than in the control group. This implies in our view that in PD the entropy of the output neurons of the BG varies dynamically with the input to the network, which is determined by the level of alertness. Therefore, entropy needs to be interpreted as a dynamic, emergent property that characterizes the global state of the BG neuronal network, rather than a static property of parkinsonian neurons themselves. Within the framework of the "entropy hypothesis," this implies the presence of a pathological feedback loop in the parkinsonian BG, where increasing the network input results in a further increase of neuronal entropy and a worsening of akinesia.

Movement Disorders in Autosomal Dominant Cerebellar Ataxias: A Systematic Review.

Autosomal dominant cerebellar ataxias (ADCAs) are clinically heterogeneous disorders classified according to genetic subtype and collectively known as SCAs. In a few SCAs, movement disorders can be the most frequent extracerebellar sign. The aim of this article is to perform a systematic review of movement disorders frequency and characteristics in ADCAs. This work consisted of a structured search of electronic databases up to January 2013. Publications containing descriptions of ADCA clinical features written in several languages were selected initially based on title and abstract screening, followed by full-text reading of potentially relevant publications. Clinical findings and demographic data on genetically confirmed patients were extracted. Analysis of individual patient data from subjects with movement disorders was performed using the chi-square test and logistic regression. One thousand and sixty-six publications reviewing 12,151 patients from 30 different SCAs were analyzed. Individual data were available from 755 patients with at least one type of movement disorder during overall disease course. Of 422 patients in whom onset symptom data were available, one third referred a movement disorder as the initial symptom. During overall disease course, parkinsonism was common in many SCA subtypes, frequently described in the absence of ataxia and characterized as responding to dopaminergic medications. Motor complications developed occasionally in some patients as did nigrostriatal imaging alterations. Other frequent features were dystonia, chorea, and myoclonus. Rare conditions, such as akathisia, paroxysmal nonkinesigenic dyskinesia, or stiff person-like syndrome, were also reported. ADCA descriptions included a full range of movement disorders. Aside from postural or intention tremor, dopamine-responsive parkinsonism and dystonia were the most common.

Neural correlates of musical creativity: differences between high and low creative subjects.

Previous studies of musical creativity suggest that this process involves multi-regional intra and interhemispheric interactions, particularly in the prefrontal cortex. However, the activity of the prefrontal cortex and that of the parieto-temporal regions, seems to depend on the domains of creativity that are evaluated and the task that is performed. In the field of music, only few studies have investigated the brain process of a creative task and none of them have investigated the effect of the level of creativity on the recruit networks. In this work we used magnetic resonance imaging to explore these issues by comparing the brain activities of subjects with higher creative abilities to those with lesser abilities, while the subjects improvised on different rhythmic fragments. We evaluated the products the subjects created during the fMRI scan using two musical parameters: fluidity and flexibility, and classified the subjects according to their punctuation. We examined the relation between brain activity and creativity level. Subjects with higher abilities generated their own creations based on modifications of the original rhythm with little adhesion to it. They showed activation in prefrontal regions of both hemispheres and the right insula. Subjects with lower abilities made only partial changes to the original musical patterns. In these subjects, activation was only observed in left unimodal areas. We demonstrated that the activations of prefrontal and paralimbic areas, such as the insula, are related to creativity level, which is related to a widespread integration of networks that are mainly associated with cognitive, motivational and emotional processes.

Validation of a new scale to assess olfactory dysfunction in patients with Parkinson's disease.

UNLABELLED: BAKCKGROUND: Olfactory dysfunction is present in up to 90% of Parkinson's disease (PD) patients. It is usually evaluated by means of objective standardized tests; however no self-administered scales have been developed for olfactory dysfunction bedside assessment. We present validation of a new scale to assess this symptom in PD patients. METHODS: Seventy-five PD patients and 25 control subjects were evaluated using a Hyposmia Rating Scale developed in-house, combined with the extended Sniffin' Sticks test. RESULTS: Total score of the 6-item Hyposmia Rating Scale showed significant correlation with threshold, discrimination, identification and total Sniffin' Sticks test scores (r = 0.53; r = 0.60; r = 0.57; r = 0.65 respectively, p < 0.001 for all values). Area under the curve of the receiver operating curve for the ability of Hyposmia Rating Scale to discriminate patients with Sniffin' Sticks test total scores below or above the cut-off point was 80 ± 6% (p < 0.001). Considering Sniffin' Sticks test as the gold standard method for olfactory dysfunction detection, an affirmative response to a single screening question about smelling ability problems showed 35% sensitivity (95%CI = 23-47%) and 100% specificity. The best cut-off point for Hyposmia Rating Scale was 22.5 with a sensitivity of 70% (60-81%) and a specificity of 85% (65-100%). CONCLUSION: The Hyposmia Rating Scale here presented may offer a simple, cost-effective, time-saving and reliable approach to evaluate olfactory dysfunction in PD patients.

Lack of maintenance of gait pattern as measured by instrumental methods suggests psychogenic gait.

Fluctuation is a common feature of all psychogenic gait disorder (PGD) patterns. Whether this fluctuation involves only the degree of impairment or whether it affects the gait pattern itself remains an interesting question. We hypothesize that, on repeated measurements, both normal and abnormal gait may present quantitative differences while maintaining their basic underlying pattern; conversely, in psychogenic gait, the basic pattern appears not to be preserved. Using an optoelectronic system, data acquired from 19 normal subjects and 66 patients were applied to train a neural network (NN) and subsequently classify gait patterns into four different groups (normal, ataxic, spastic-paraparetic and parkinsonian). Five patients who fulfilled clinical criteria for psychogenic gait and six controls were then prospectively evaluated on two separate occasions, three months apart. Normal controls and ataxic, parkinsonian or spastic patients were correctly identified by the NN, and categorized within the corresponding groups at baseline as well as at a three-month follow-up evaluation. NN analysis showed that after three months, no PGD patient preserved the gait pattern detected at baseline, even though this finding was not clinically apparent. Modification of gait pattern detected by repeated kinematic measurement and NN analysis could suggest the presence of PGD, particularly in difficult-to-diagnose cases.

Neuronal discharge patterns in the globus pallidus pars interna in a patient with Parkinson's disease and hemiballismus secondary to subthalamotomy.

Alterations in the basal ganglia-thalamocortical "motor" circuit activity, have been proposed to explain many features associated with hypokinetic and hyperkinetic movement disorders. We describe the firing pattern of the globus pallidus pars interna in a Parkinson disease's patient who developed Hemichorea-Ballismus subsequent to ipsilateral subthalamotomy, and compare findings to those from PD patients submitted to pallidotomy while in the OFF-medication state. Single units obtained from extracellular recordings were extracted and mean discharge frequency, interspike interval and coefficient of variation (defined as Tonicity Score) were computed. Discharge density histograms, analysis of distribution and spectral analysis were also performed. Mean firing frequency showed no significant difference between PD patients in the OFF state and the patient we report. However, a significant difference in tonicity was found for this patient characterized by a regular, non-bursting firing pattern. The findings indicate that in HB caused by lesions to STN in the parkinsonian state, GPi firing rates can be similar to and firing pattern more regular than those observed in GPi of PD patients OFF-medication with intact STN.

Correlation between the Movement Disorders Society Unified Parkinson's Disease rating scale (MDS-UPDRS) and the Unified Parkinson's Disease rating scale (UPDRS) during L-dopa acute challenge.

While Movement Disorders Society Unified Parkinson's Disease rating scale (MDS-UPDRS) validation has been exhaustive; performance evaluation to detect acute changes arising after administration of a single dose of L-dopa has yet to be explored. To determine the correlation between UPDRS and MDS-UPDRS during the acute challenge with Ldopa and the MDS-UPDRS equivalent to 30% cutoff score of UPDRS for defining responsiveness, 64 patients were assessed. Consecutive assessments were performed immediately before and after administration of a single dose of L-dopa/carbidopa 250/25 mg using the motor section of the UPDRS and the MDS-UPDRS. Good diagnostic accuracy, consistent with published findings of high correlation between scales was observed. Area under the curve (AUC) was 0.99 (CI = 0.97-1.00, P < 0.001) and maximum Youden index (Y = 0.905) corresponded to a cutoff of 24.5%. In conclusion we have found an excellent correlation between UPDRS and MDS-UPDRS and that the 30% of variation in UPDRS score used for predicting sustained long term L-dopa response was equivalent to 24% in MDS-UPDRS.

Finite dimensional structure of the GPI discharge in patients with Parkinson's disease.

Stochastic systems are infinitely dimensional and deterministic systems are low dimensional, while real systems lie somewhere between these two limit cases. If the calculation of a low (finite) dimension is in fact possible, one could conclude that the system under study is not purely random. In the present work we calculate the maximal Lyapunov exponent from interspike intervals time series recorded from the internal segment of the Globus Pallidusfrom patients with Parkinson's disease. We show the convergence of the maximal Lyapunov exponent at a dimension equal to 7 or 8, which is therefore our estimation of the embedding dimension for the system. For dimensions below 7 the observed behavior is what would be expected from a stochastic system or a complex system projecting onto lower dimensional spaces. The maximal Lyapunov exponent did not show any differences between tremor and akineto-rigid forms of the disease. However, it did decay with the value of motor Unified Parkinson's Disease Rating Scale -OFF scores. Patients with a more severe disease (higher UPDRS-OFF score) showed a lower value of the maximal Lyapunov exponent. Taken together, both indexes (the maximal Lyapunov exponent and the embedding dimension) remark the importance of taking into consideration the system's non-linear properties for a better understanding of the information transmission in the basal ganglia.