Nataša Dragašević

Therapeutic efficacy of bilateral prefrontal slow repetitive transcranial magnetic stimulation in depressed patients with Parkinson's disease: an open study.

Recent studies have suggested that both high‐ and low‐frequency repetitive transcranial magnetic stimulation (rTMS) have antidepressant effects in patients with major depression. We conducted an open study to assess the effects of slow rTMS on mood changes in patients with depression associated with Parkinsons disease (PD). Ten depressed patients with PD (four with major depression and six with dysthymia) received daily sessions of rTMS (frequency, 0.5 Hz; pulse duration, 0.1 msec; field intensity, 10% above the motor threshold) over both prefrontal regions (a total of 100 stimuli per prefrontal region daily) over 10 consecutive days. This treatment resulted in a moderate but significant decrease in scores of the Hamilton Depression Rating Scale (33–37%) and the Beck Depression Inventory (24–34%), which persisted 20 days after finishing the stimulation. In parallel, we observed mild improvement (18–20%) of motor symptoms. No significant adverse effects were reported. These preliminary results suggest the therapeutic potential of daily prefrontal low‐frequency rTMS (0.5 Hz) in depression associated with PD.

Glucose Homeostasis in Huntington Disease: Abnormalities in Insulin Sensitivity and Early-Phase Insulin Secretion

BACKGROUND Patients with Huntington disease (HD) develop diabetes mellitus more often than do matched healthy controls. Recent studies in neurodegenerative diseases suggested that insulin resistance constitutes a metabolic stressor that interacts with a preexisting neurobiological template to induce a given disorder. OBJECTIVE To investigate possible changes in insulin sensitivity and secretion, major determinants of glucose homeostasis, in a group of consecutive normoglycemic patients with HD. DESIGN Metabolic investigations. PARTICIPANTS Twenty-nine untreated, nondiabetic patients with HD and 22 control participants matched by age, sex, and socioeconomic background. MAIN OUTCOME MEASURES Glucose tolerance, assessed by means of the glucose curve during oral glucose challenge; insulin sensitivity, assessed using homeostasis model assessment and minimal model analysis based on frequent sampling of plasma glucose and plasma insulin during the intravenous glucose tolerance test; and insulin secretion, determined by means of the acute insulin response and the insulinogenic index. RESULTS The evaluation of insulin sensitivity using homeostasis model assessment demonstrated higher homeostasis model assessment insulin resistance indices, and a lower sensitivity index when the minimal model approach was used, in patients with HD compared with controls (P = .03 and P = .003, respectively). In the assessment of early-phase insulin secretion, the acute insulin response and the insulinogenic index were lower in patients with HD compared with controls (P = .02). The number of CAG repeats correlated significantly only with acute insulin response (P = .003). CONCLUSIONS Besides impairment in insulin secretion capacity, a simultaneous decrease in insulin sensitivity, with an increase in the insulin resistance level, was found in normoglycemic patients with HD compared with controls. These data imply that progression of the insulin secretion defect in HD may lead to a failure to compensate for insulin resistance.

Dystonia in Wilson's disease.

The frequency and type of dystonic movements, as well as brain abnormalities, as depicted with magnetic resonance imaging (MRI), which might correlate with dystonia, were studied in 27 consecutive patients with a neurologic form of Wilsons disease (WD) and optimized treatment. Dystonia was found in 10 patients (37%), being generalized in half of them, while two patients had segmental, two patients multifocal dystonia, and one patient bilateral foot dystonia. Dystonia was a presenting sign in four patients and developed later in the course of the disease in six patients, despite the administered therapy for WD. Putamen was the only structure significantly more frequently lesioned in dystonic (80%) in comparison to WD patients without dystonia (24%), suggesting a relation between abnormalities in this brain region and dystonic movements in WD.

Quality of life in patients with focal dystonia.

OBJECTIVES The aims of this study were to identify the clinical and demographic factors influencing health-related quality of life (HR-QoL) and to compare HR-QoL measures between various types of focal dystonia (cervical dystonia, blepharospasm, and writers cramp). METHODS We examined 157 consecutive patients with adult-onset primary focal dystonia, and HR-QoL was assessed by using the SF-36 questionnaire. Univariate and multivariate regression analyses were performed. RESULTS Patients with writers cramp scored better in all SF-36 domains, except role functioning physical (RP), while these differences were statistically significant for physical functioning (PF) (p=0.020), bodily pain (BP) (p=0.001), and general health (GH) (p=0.004). Patients with writers cramp and blepharospasm scored significantly better for BP (p=0.001) than patients with cervical dystonia. We found that each of the eight dimensions of SF-36 proved to be significantly correlated to the Hamilton depression rating scale score in patients with torticollis and blepharospasm, while vitality (VT), social functioning (SF), and mental health (MH) scales showed statistically significant correlations in patients with hand dystonia. Similar relationships were observed between anxiety and SF-36 domains. CONCLUSION Depression and anxiety are the most important predictors of poorer HR-QoL in patients with all three types of focal dystonia.

Long-Term Prognosis of Vascular Hemiballismus

Background and Purpose— The aim of this study was to prospectively evaluate the long-term prognosis of hemiballismus due to first-ever ischemic strokes. Methods— A cohort of 27 patients with hemiballismus due to first-ever ischemic strokes was followed for a mean period of 30 months (range, 5 days to 150 months). Results— During the follow-up period there were 11 deaths (44%). The survival rate was 85% (95% CI, 71% to 99%) at 6 months, 81% (95% CI, 65% to 97%) at 15 months, 51% (95% CI, 24% to 78%) at 36 months, and only 32% (95% CI, 4% to 60%) at 150 months. The survival rate free from recurrent stroke was 96% (95% CI, 87% to 100%) at 6 months, 91% (95% CI, 79% to 100%) at 12 months, 80% (95% CI, 61% to 99%) at 24 months, and 27% (95% CI, 0% to 71%) at 150 months. Conclusions— The long-term prognosis of patients with vascular hemiballismus is similar to that of other stroke patients, ie, it follows the etiologic pattern of hemiballismus.

The topography of brain damage at different stages of Parkinson's disease.

This study investigated gray matter (GM) and white matter (WM) damage in 89 patients at different clinical stages of Parkinsons disease (PD) (17 early, 46 mild, 14 moderate, and 12 severe) to differentiate the trajectories of tissue injury in this condition. PD patients had a very little GM atrophy even at the more advanced stages of the disease. Microstructural damage to the WM occurs with increasing PD severity and involves the brainstem, thalamocortical pathways, olfactory tracts, as well as the major interhemispheric, limbic, and extramotor association tracts. The most marked WM damage was found in moderate vs. mild cases. WM damage correlated with the degree of global cognitive deficits. WM abnormalities beyond the nigrostriatal system accumulate with increasing PD severity. WM damage is likely to contribute to the more severe motor and nonmotor dysfunctions occurring in patients at the later stages. Hum Brain Mapp 34:2798–2807, 2013.

Neuropsychiatric aspects of treated Wilson's disease ☆

The objective of the current cross-sectional study was to use standardized psychiatric interviews (the Structured Clinical Interview for DSM-IV Axis I Disorders and the Neuropsychiatric Inventory; NPI) in order to better characterize psychiatric symptoms in 50 consecutive, treated and clinically stable patients with Wilsons disease (WD). Nine patients (18%) had one, 7 patients (14%) had two, and 20 (40%) had >or= 3 neuropsychiatric symptoms present. The most often endosed symptoms were anxiety (62%), depression (36%), irritability (26%), as well as disinhibition and apathy (24% each). Twenty two patients (44%) had a score >or= 4 on at least one of the NPI items: again, most frequently anxiety (17 patients; 34%), depression (13 patients; 26%) and apathy (9 patients; 18%). Therefore, even among stable, long-term treated patients with WD approximately 70% experienced psychiatric symptoms.

MR imaging of the brain in patients with hepatic form of Wilson's disease

The aim of this study was to detect the sites and frequency of possible lesions by brain magnetic resonance imaging (MRI; 1,5T) in a group of 16 neurologically asymptomatic patients with hepatic form of Wilsons disease (WD; seven untreated and nine under treatment). Abnormal MR findings of the brain were found in 75% of patients. Lesions in brain parenchyma were detected in all untreated, drug‐naive patients and in 44% of treated patients. Abnormal signal in globus pallidus, putamen, and caudate nucleus was revealed in 86, 71 and 71% of treated and in 33, 33 and 22% of untreated patients, respectively. In five of eight patients with putaminal pathology (62.5%) and in four of seven patients with caudate nuclei involvement (57%), only proton density 2‐weighted sequence (PDW) exhibited sensitivity for lesion detection, with both T1W and long echo T2W sequences being insensitive. This superiority of PDW sequence was even more pronounced in the group of untreated patients in whom 80% of putaminal pathology was visible exclusively on this sequence. The lower frequency of lesions in the group of treated in comparison with untreated patients indicated that they might be reversible in the course of chronic chelating therapy.

Transcranial sonography in spinocerebellar ataxia type 2.

ObjectiveTo study the use of transcranial brain parenchyma sonography (TCS), in particular the echogenic signal in the substantia nigra (SN), in patients with spinocerebellar ataxia type 2 (SCA2), recently recognized as an uncommon cause of parkinsonism.MethodsSix consecutive and unrelated SCA2 patients without parkinsonian signs, 30 consecutive patients with Parkinson’s disease (PD), and 30 healthy, age- and sexmatched controls were prospectively studied with TCS according to a standardized protocol.ResultsFour (67 %) of the six SCA2 patients exhibited SN hyperechogenicity. In two patients, the hyperechogenicity was classified as moderate (unilateral in both) and in two as marked. Differences between the SN echogenicity of the SCA2 group or the PD group and controls were statistically significant (p < 0.001), while there was no difference between the two groups of patients.ConclusionsTranscranial brain parenchyma sonography detects SN hyperechogenicity in the majority of patients with SCA2 without parkinsonian signs. It would be important to reproduce our TCS findings in a larger number of SCA2 patients, as well as to test their possible significance in differentiating SCA2 from other types of SCA.

Clinical characteristics of paroxysmal nonkinesigenic dyskinesia in serbian family with Myofibrillogenesis regulator 1 gene mutation

The aim of this study was to describe the clinical features of a large Serbian family with paroxysmal nonkinesigenic dyskinesia (PNKD) and one of the two previously described mutations in the Myofibrillogenesis regulator 1 gene (MR‐1), which causes an alanine‐to‐valine substitution at position 9. In 5 examined out of 12 affected family members, attacks of dyskinesias appeared in the first 6 months of life. Both frequency and severity of attacks showed an age‐dependent incremental–decremental pattern with a peak between 13 to 15 years of age. They were frequently precipitated by stress, caffeine, fever, hunger, tiredness, as well as abrupt changes in temperature. Three of our patients differentiated two types of attacks: mild (120–180 minutes), with a predominance of functionally insignificant choreoathetoid movements, and severe (∼ 15–30 minutes), characterized by disabling dystonic and choreic movements of the extremities, trunk, and face. Sleep was the most reliable factor to discontinue an attack. This Serbian family further demonstrates that recurrent MR‐1 mutations are associated with PNKD worldwide, which will affect genetic testing.