Despite accumulating evidence of inter and intraindividual variability in response to theta burst stimulation, it is widely believed that in therapeutic applications, repeated sessions can have a "build-up" effect that increases the response over and above that seen in a single session. However, strong evidence for this is lacking. Therefore, we examined whether daily administration of intermittent theta burst stimulation (iTBS) over the primary motor cortex induces cumulative changes in transcranial magnetic stimulation measures of cortical excitability, above the changes induced by sham stimulation. Over five consecutive days, 20 healthy participants received either active iTBS or sham stimulation. Each day, baseline measures of cortical excitability were assessed before and up to 30 min after the intervention. There was no significant difference in the rate of response between iTBS and sham stimulation on any of the 5 days. There was no iTBS specific cumulative increase of corticospinal excitability. The likelihood that an individual would remain a responder from day-to-day was low in both groups, implying high within-subject variability of both active and sham iTBS after-effects. In contrast, we found a high within-subject repeatability of resting and active motor threshold, and baseline motor-evoked potential amplitude. In summary, sham stimulation has similar effect to active iTBS on corticospinal excitability, even when applied repeatedly for 5 days. Our results might be relevant to research and clinical applications of theta burst stimulation protocols.
COBISS.SI-ID: 5150380
Pseudodystonia represents a wide range of conditions that mimic dystonia, including disorders of the peripheral nervous system, spinal cord, brainstem, thalamus, cortex and non-neurological conditions such as musculoskeletal diseases. Here, we propose a definition of pseudodystonia and suggest a classification based on underlying pathophysiological mechanisms. We describe phenomenology of different forms of pseudodystonia and point to distinctions between dystonia and pseudodystonia as well as challenging issues that may arise in clinical practice. The term pseudodystonia can be used to describe abnormal postures, repetitive movements or both, in which results of clinical, imaging, laboratory or electrophysiological investigations provide definite explanation of symptoms which is not compatible with dystonia. Pseudodystonia can be classified into non-neurological disorders of the musculoskeletal system, disorders of sensory pathways, disorders of motor pathways and compensatory postures in other neurological diseases. Presence of associated neurological findings in the affected body part is the key towards diagnosis of pseudodystonia. Additional supporting features are the presence of fixed postures, the absence of sensory trick, acute mode of onset and severe pain. Worsening on eye closure, traditionally considered typical for pseudodystonia, is not always present and can also appear in dystonia. It is challenging to separate dystonia and pseudodystonia in patients with thalamic lesions or corticobasal syndrome, where abnormal postures coexist with sensory loss. Many cases of pseudodystonia are treatable. Therefore, it is essential to consider pseudodystonia in a differential diagnosis of abnormal postures until a detailed neurological examination rules it out.
COBISS.SI-ID: 5770668
We read with great interest the study assessing association of ß2-adrenoceptor agonists and antagonists exposure and the risk of Parkinson’s disease, by Gronich and colleagues1. Good news is that beta-receptors agonists might be protective for PD, however neurologists will be worried by data suggesting that exposure to non-selective ß2-adrenoceptor antagonists, particularly propranolol, increases the risk for PD by 2.6 time. Main concern comes from the fact that essential tremor, movement disorder frequently treated with propranolol, is itself associated with increased risk for developing PD2. Although misdiagnosis of early PD as ET may partly account for association between the two, biological basis for increased risk of PD in ET patients remains largely unclear3. The study of Gronich and colleagues logically brings to mind a possible link with propranolol treatment. But, looking from the different perspective, association between exposure to propranolol and PD in the present study, could have actually been driven by ET patients with their independent inherent risk for PD, receiving propranolol for symptomatic control of tremor. In other words, presence of ET could have distorted the association between exposure to propranolol and the risk of future PD. It is of principal importance to account, in the best possible way, for confounding biases in epidemiological studies 4. We are concerned whether ET was properly treated as confounding factor in the present study. While migraine, smoking and etc were considered in the analysis as covariates, to adjust for their possible independent association with PD, ET was neither included as a covariate, nor it was in other way controlled for its possible confounding effect in the principal analysis. In the table 1, we see how PD cases were more or less matching with controls for smoking, vascular risk factors etc. Results may nevertheless be influenced by different prevalence of ET between patients who developed PD and those who did not, but this was not taken into consideration. Authors performed a secondary analysis excluding PD patient and controls with ET diagnosis, with results showing still increased risk for PD, although lower. Possibly increased risk for PD with propranolol exposure is concerning. Lifetime risk of PD is 2 % for men and 1.3 % for women5. When considering this risk in ET patients, there is additional relative risk of 4.27, resulting in increased lifetime risk for PD in 8.5% and 5.6% of men and women with ET, respectively2. As physicians deciding on treatment, we now need to know how much, if any of the risk is related to propranolol exposure. Interestingly, data from Gronich and al. show that odds for getting PD decrease with duration of propanolol treatment, suggesting that increased occurrence of PD among propranolol users may be at least partly influenced by its use to treat “ET tremor” in patients in fact having early PD. However, one may not exclude that starting propranolol (for any indication) hasten the onset of motor symptoms in preclinical PD. Additional analysis of the data collected and further specifically designed studies should tackle this relevant issue.
COBISS.SI-ID: 5608364
PURPOSE: The purpose of this study was to identify the specific metabolic brain pattern characteristic for Parkinson's disease (PD): Parkinson's disease-related pattern (PDRP), using network analysis of [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) brain images in a cohort of Slovenian PD patients. METHODS: Twenty PD patients (age 70.1 ± 7.8 years, Movement Disorder Society Unified Parkinson's Disease Motor Rating Scale (MDS-UPDRS-III) 38.3 ± 12.2; disease duration 4.3 ± 4.1 years) and 20 age-matched normal controls (NCs) underwent FDG-PET brain imaging. An automatic voxel-based scaled subprofile model/principal component analysis (SSM/PCA) was applied to these scans for PDRP-Slovenia identification. RESULTS: The pattern was characterized by relative hypermetabolism in pallidum, putamen, thalamus, brain stem, and cerebellum associated with hypometabolism in sensorimotor cortex, posterior parietal, occipital, and frontal cortices. The expression of PDRP-Slovenia discriminated PD patients from NCs (p ( 0.0001) and correlated positively with patients' clinical score (MDS-UPDRS-III, p = 0.03). Additionally, its topography agrees well with the original PDRP (p ( 0.001) identified in American cohort of PD patients. We validated the PDRP-Slovenia expression on additional FDG-PET scans of 20 PD patients, 20 NCs, and 25 patients with atypical parkinsonism (AP). We confirmed that the expression of PDRP-Slovenia manifests good diagnostic accuracy with specificity and sensitivity of 85-90% at optimal pattern expression cutoff for discrimination of PD patients and NCs and is not expressed in AP. CONCLUSION: PDRP-Slovenia proves to be a robust and reproducible functional imaging biomarker independent of patient population. It accurately differentiates PD patients from NCs and AP and correlates well with the clinical measure of PD progression.
COBISS.SI-ID: 3642796
Background: Task specific dystonia is disabling movement disorder that includes writer’s cramp and musician dystonia. It causes impaired hand use and may lead to the termination of professional career. Currently, there is no effective treatment. Zolpidem, a short-acting hypnotic drug that binds to GABA –A receptor benzodiazepine site, has been reported to transiently improve various movement disorders, including a proportion of patients with primary focal and generalized dystonia. The mechanisms underlying its therapeutic effects has not been investigated. Methods: Six patients with writer’s cramp and one guitarist with musician dystonia underwent transcranial magnetic stimulation (TMS) and 18F-FDG-PET brain imaging after single 5 mg dose of zolpidem and placebo, in four separate sessions. We measured resting motor threshold (RMT), active motor threshold (AMT), resting and active input/output (IO) curve, short interval intracortical inhibition (SICI) curve, long interval intracortical inhibition (LICI), intracortical facilitation (ICF) and cortical silent period (CSP). Clinical improvement was rated using writer’s cramp rating scale (WCRS). Clinical and TMS measures were compared using paired sample t-test or repeated measures ANOVA; correlations were tested using Spearman analysis. Statistical parametric mapping was used to identify zolpidem effect on global brain metabolism. Eight patients with writer’s cramp and three patients with musician dystonia (1 guitarist and 2 brass musicians) underwent transcranial magnetic stimulation (TMS) and 18F-FDG-PET brain imaging after single 5 mg dose of zolpidem and placebo, in four separate sessions. We measured resting motor threshold (RMT), active motor threshold (AMT), resting and active input/output (IO) curve, short interval intracortical inhibition (SICI) curve, long interval intracortical inhibition (LICI), intracortical facilitation (ICF) and cortical silent period (CSP). Objective clinical improvement was rated using Burke-Fahn-Marsden Dystonia Rating Scale-movement (BFM-M) and writer’s cramp rating scale (WCRS). Subjective improvement was measured using the visual-analog scale (VAS). Clinical and TMS measures on zolpidem and placebo were compared using nonparametric two-related-samples Wilcoxon test or repeated measures ANOVA; correlations were tested using Spearman analysis. Statistical parametric mapping was used to identify zolpidem effect on global brain metabolism. Results: There was significant improvement on WRCS on zolpidem. Zolpidem reduced the steepness of active IO curve, while there was no difference in AMT, RMT, resting IO curve, SICI, LICI, CSP and ICF on the group level. Significant positive correlation was found between clinical improvement and enhancement of LICI on zolpidem. 18F-FDG-PET revealed that zolpidem treatment was associated with hypometabolism in primary sensori-motor cortex, cerebellum and medial temporal lobes and hypermetabolism in caput nuclei caudate, parietal cortex and frontal regions. Results: On the group level difference in improvement on WCR score between zolpidem and placebo almost achieved significance (p = 0,062) and difference in improvement on BFM scale approached significance (p = 0,08). Improvement of VAS score on zolpidem was not statistically significant from improvement on placebo. Zolpidem reduced the values of resting IO curve (p= 0,004), while there was no difference in AMT, RMT, active IO curve, SICI, LICI, CSP and ICF between zolpidem and placebo on the group level. On the group level, significant positive correlation was found between objective clinical improvement measured with BFM scale and diminishment of ICF on zolpidem (p= 0,028) and between subjective clinical improvement measured by VAS and increasement in AMT (p=0,046). In 7 out of 11 patients with focal dystonia, objective improvement of dystonia on zolpidem was shown on BFM or WRCS scale. These patients were labeled as responders. Further statistical ana
COBISS.SI-ID: 5770924