Scaling analysis of bilateral hand tremor movements in essential tremor patients.

Recent evidence suggests that the dynamic-scaling behavior of the time-series of signals extracted from separate peaks of tremor spectra may reveal existence of multiple independent sources of tremor. Here, we have studied dynamic characteristics of the time-series of hand tremor movements in essential tremor (ET) patients using the detrended fluctuation analysis method. Hand accelerometry was recorded with (500 g) and without weight loading under postural conditions in 25 ET patients and 20 normal subjects. The time-series comprising peak-to-peak (PtP) intervals were extracted from regions around the first three main frequency components of power spectra (PwS) of the recorded tremors. The data were compared between the load and no-load condition on dominant (related to tremor severity) and non-dominant tremor side and with the normal (physiological) oscillations in healthy subjects. Our analysis shows that, in ET, the dynamic characteristics of the main frequency component of recorded tremors exhibit scaling behavior. Furthermore, they show that the two main components of ET tremor frequency spectra, otherwise indistinguishable without load, become significantly different after inertial loading and that they differ between the tremor sides (related to tremor severity). These results show that scaling, a time-domain analysis, helps revealing tremor features previously not revealed by frequency-domain analysis and suggest that distinct oscillatory central circuits may generate the tremor in ET patients.

Genetic heterogeneity in ten families with myoclonus-dystonia.

BACKGROUND: Myoclonus-dystonia (M-D) is a movement disorder with autosomal dominant inheritance and reduced penetrance but may also occur sporadically. Recently, mutations in the epsilon-sarcoglycan gene (SGCE) were shown to cause M-D. Furthermore, single variants in the dopamine D2 receptor (DRD2) and DYT1 genes were found in combination with SGCE mutations in two M-D families, and another M-D locus was recently mapped to chromosome 18p11 in one family. METHODS: The authors clinically and genetically characterised ten consecutive cases with myoclonus-dystonia; seven familial and three sporadic. Twenty nine M-D patients and 40 unaffected family members underwent a standardised clinical examination by a movement disorder specialist. Index cases were screened for mutations in the SGCE, DYT1, and DRD2 genes and for deletions of the SGCE gene. Suitable mutation negative families were tested for linkage to the SGCE region and to chromosome 18p11. RESULTS: Two SGCE mutations were detected among the seven familial but no mutation in the sporadic cases. Haplotype analysis at the new M-D locus was compatible with linkage in two families and excluded in another family, suggesting at least one additional M-D gene. There were no obvious clinical differences between M-D families with and without detected mutations. CONCLUSION: M-D is genetically heterogeneous with SGCE mutations accounting for the disease in only part of the clinically typical cases.

Spinocerebellar ataxia type 17 in the Yugoslav population.

OBJECTIVES: (1) Analysis of Spinocerebellar ataxia type 17 (SCA17) locus in a group of ataxic patients excluded on other known SCAs; (2) assessment of frequency distributions of SCA17 alleles in the Yugoslav population. MATERIAL AND METHODS: Study includes 115 non-related Yugoslav patients belonging to autosomal-dominant cerebellar ataxias or to sporadic idiopathic adult-onset ataxia and 115 controls. Analysis of SCA17 locus was performed using polymerase chain reaction. RESULTS: None of the analyzed patients show the presence of mutation in SCA17 locus. In the group of patients 12 different alleles in the range of 30-42 repeats were observed, while in healthy population eight alleles in the range of 30-40 repeats were detected. CONCLUSION: (1) None of 115 non-related Yugoslav ataxic patients belong to any known SCAs nor to DRPLA gene; (2) the distribution of SCA17 alleles in the Yugoslav population is consistent with the distribution in other populations and (3) the paucity of alleles with more than 39 repeats could suggest that SCA17 is very rare in the Yugoslav population.

Characteristics of dystonic movements in primary and symptomatic dystonias.

OBJECTIVE: To compare clinical characteristics of the involuntary movements in primary and symptomatic dystonias. PATIENTS AND METHODS: 132 consecutive patients with the diagnosis of primary dystonia and 51 consecutive patients with secondary dystonia caused by well defined structural lesion(s) of the central nervous system, with particular emphasis on the characteristics of involuntary movements. RESULTS: Eight variables with the highest risk contribution to either symptomatic or primary dystonias were identified: dystonic movement in secondary dystonia was much more frequently presented at rest, whereas the presence of dystonic tremor, chronic inflammatory process, or peripheral trauma located in the region that is later affected by dystonia, as well as the use of sensory tricks and development of spontaneous remissions, classified the affected patients more often in the category of those with primary dystonia. CONCLUSION: The study identified several clinical features that may be helpful in differentiating primary from secondary dystonia.

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 Wilson's 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.

SCA2 and SCA3 mutations in young-onset dopa-responsive parkinsonism.

In this study no one of our 85 patients of Serbian origin with young-onset (

Genetic and clinical analysis of spinocerebellar ataxia type 8 repeat expansion in Yugoslavia.

Spinocerebellar ataxia type 8 (SCA8) is a slowly progressive ataxia causally associated with untranslated CTG repeat expansion on chromosome 13q21. However, the role of the CTG repeat in SCA8 pathology is not yet well understood. Therefore, we studied the length of the SCA8 CTA/CTG expansions (combined repeats, CRs) in 115 patients with ataxia, 64 unrelated individuals with non-triplet neuromuscular diseases, 70 unrelated patients with schizophrenia, and 125 healthy controls. Only one patient with apparently sporadic ataxia was identified with an expansion of 100 CRs. He had inherited the expansion from his asymptomatic father (140 CRs) and transmitted the mutation to his son (92 CRs). Paternal transmission in this family produced contractions of 40 and 8 CRs, respectively. None of the subjects from other studied groups had an expansion at the SCA8 locus. In the control group the number of CRs at the SCA8 locus ranged from 14 to 34. Our findings support the notion that allelic variants of the expansion mutation at the SCA8 locus can predispose to ataxia.

[Effect of slow repetitive transcranial magnetic stimulation on depression in patients with Parkinson disease]. / Uticaj spore repetitivne transkranijumske stimulacije magnetom na depresiju kod bolesnika s Parkinsonovom bolescu.

Parkinson's disease (PD), that has usually been associated with movement disorders, is also associated with depression in about 40% of patients [1-9]. Transcranial magnetic stimulation (TMS) is a new non-invasive technique for direct stimulation of the cerebral cortical neurons [1]. Several open studies have shown that repetitive TMS (rTMS) at both rapid (rapid rTMSi > 1 Hz) and low frequencies (slow rTMSi < 1 Hz) may have antidepressant action [2-6]. The study included 8 patients diagnosed as PD fulfilling the DSM-IV criteria for major depression (5 patients) and dysthymia (3 patients). Magnetic stimulator, 200 Mag-Stim, total output 2 T and a circular coil of 90 mm, were used. For ten consecutive days, between noon and 1 p.m. the patients were stimulated with apprx. 80% of the output (1.6 T) at 0.5 Hz. The daily treatment implied stimulation of both sides of the head (first the right, then the left) at four sites (prefrontal, frontal, parietal and occipital regions) with 5 stimulations each site (20 stimulations per hemisphere). Before the beginning of the study, 2-3 hours after the last stimulation (day 10), 7 and 14 days after completion of the treatment, the patients were subjected to scoring on the Hamilton Depression Rating Scale [11] and Unified Parkinson's Disease Rating Scale (UPDRS) [12]. The HDRS values before initiation of rTMS were 19.2 +/- 3.1, with significant fall (p < 0.01) after 10 days of stimulation (14.9 +/- 3.2), 17 days (12.2 +/- 2.7) and 24 days (13.6 +/- 5.3) after the beginning of the study, suggesting that the antidepressive effect persisted even two weeks after discontinuation of stimulation. The UPDRS values were monitored concomitantly. The values on this scale failed to alter significantly. In conclusion, rTMS is a relatively safe and painless method associated with antidepressant action in PD patients. Treatment of depression in PD is of great importance, but the choice of medication is accompanied with numerous limitations [20]. Antidepressant action of rTMS and its maintenance for two weeks after discontinuation of stimulation enables usage of this method in PD in phases of exacerbation of depressive symptoms at least over the period required to reach the full effect of selected medication.

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 Wilson's 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.

Bereitschaftspotential in depressed and non-depressed patients with Parkinson's disease.

Impaired initiation and slowed execution of movements are two of the principal characteristics of Parkinson's disease (PD). A similar pattern of movement impairments (psychomotor retardation) can be seen frequently in patients with idiopathic depression. In addition, affective disorders have been frequently reported in patients with different basal ganglia disorders. The aim of this study was to determine whether there are some particularities in the cerebral electrical activity during the preparation and execution of voluntary internally paced movements (i.e., Bereitschaftspotential, BP) in depressed PD patients, which can distinguish them from non-depressed PD patients, as well as from healthy controls. The BPs were recorded in 16 patients with idiopathic PD, eight of whom were depressed (PD-D), and eight of whom were not (PD-ND). Additional recordings were taken from a group of eight age- and sex-matched healthy subjects. Depression was classified using the Research Diagnostic Criteria and the two PD groups were matched for age, disease severity, and disease duration. The amplitudes and slopes of the BPs from PD patients were generally smaller than in controls, but there was no specific pattern of BP changes that distinguished depressed from non-depressed PD patients. In addition, there was no particular association between measures of depression severity and BP parameters. The data suggest that presence of depression in PD might not have any additional deteriorating influence on already impaired preparation for self-paced spontaneous movements.

[Effect of slow repetitive transcranial magnetic stimulation on depression in patients with Parkinson 's disease]. / Uticaj spore repetitivne transkranijumske stimulacije magnetom na depresiju kod bolesnika s Parkinsonovom bolescu.

Parkinson's disease (PD), that has usually been associated with movement disorders, is also associated with depression in about 40% of patients [9]. Transcranial magnetic stimulation (TMS) is a new non-invasive technique for direct stimulation of the cerebral cortical neurons [1]. Several open studies have shown that repetitive TMS (rTMS) at both rapid (rapid rTMSi: > 1 Hz) and low frequencies (slow rTMSi: < 1 Hz) may have antidepressant action [2-6]. The study included 8 patients diagnosed as PD fulfilling the DSM-IV criteria for major depression (5 patients) and dysthymia (3 patients). Magnetic stimulator, 200 Mag-Stim, total output 2 T and a circular coil of 90 mm, were used. For ten consecutive days, between noon and 1 p.m. the patients were stimulated with apprx. 80% of the output (1.6 T) at 0.5 Hz. The daily treatment implied stimulation of both sides of the head (first the right, then the left) at four sites (prefrontal, frontal, parietal and occipital regions) with 5 stimulations each site (20 stimulations per hemisphere). Before the beginning of the study, 2-3 hours after the last stimulation (day 10), 7 and 14 days after completion of the treatment, the patients were subjected to scoring on the Hamilton Depression Rating Scale [11] and Unified Parkinson's Disease Rating Scale (UPDRS) [12]. The HDRS values before initiation of rTMS were 19.2 +/- 3.1, with significant fall (p < 0.01) after 10 days of stimulation (14.9 +/- 3.2), 17 days (12.2 +/- 2.7) and 24 days (13.6 +/- 5.3) after the beginning of the study, suggesting that the antidepressive effect persisted even two weeks after discontinuation of stimulation. The UPDRS values were monitored concomitantly. The values on this scale failed to alter significantly. In conclusion, rTMS is a relatively safe and painless method associated with antidepressant action in PD patients. Treatment of depression in PD is of great importance, but the choice of medication is accompanied with numerous limitations [20]. Antidepressant action of rTMS and its maintenance for two weeks after discontinuation of stimulation enables usage of this method in PD in phases of exacerbation of depressive symptoms at least over the period required to reach the full effect of selected medication.

Hereditary neuropathy with liability to pressure palsies associated with central nervous system myelin lesions.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder most commonly caused by a 1.5-Mb deletion in chromosome 17p11.2 which contains the peripheral myelin protein-22 (PMP22) gene. Mutations resulting in functional loss of one PMP22 gene copy are less frequent. We present a 51-year-old patient with a l.5-Mb deletion in chromosome 17p11.2 who exhibited signs of peripheral as well as central nervous system lesions. He gave a history of recurrent episodes of limb numbness and weakness with spontaneous but incomplete recovery since age 20. His father and two brothers had similar symptoms. Neurological examination revealed signs of multiple mononeuropathy associated with frontal lobe, corticospinal tract and cerebellar dysfunction, as well as signs of initial cognitive impairment. Electrophysiological investigations showed a demyelinating peripheral nerve disease with multiple conduction blocks and conduction disturbances in both optic nerves. Magnetic resonance imaging of the brain revealed multiple subcortical and periventricular foci of myelin lesions. The association of central and peripheral nervous system lesions in this patient indicates a possible role of PMP22 not only in peripheral but also in central nervous system myelin structure.

[Clinical features of essential tremor]. / Klinicke odlike esencijalnog tremora.

UNLABELLED: Essential tremor is a dominant hereditary disorder with incomplete penetration manifested in action, postural tremor with no signs of parkinsonism, cerebellar lesions or other neurological signs [1]. The diagnosis of essential tremor is established on the basis of the clinical picture, and is greatly variable and insufficiently defined [5]. MATERIAL AND METHODS: The study concerned patients with the diagnosis of essential tremor established by the International Association for Tremor Studies in 1995 where tremor was classified into definite++, possible and probable [6]. All patients were subjected to a special questionnaire including demographic and clinical characteristics of tremor. Detailed neurological examinations focusing the presence of extrapyramidal signs were carried out. Fischer's Exact test was used for statistical analysis. RESULTS: The study comprised 107 patients (55 males, 41 females), aged 17-84 years (57.3 +/- 15.6) and 7-77 (46.3 +/- 17.9) at onset of the disease. Postural tremor was present in 36% of patients, postural tremor with intentional deterioration in 16%, statopostural tremor in 21% and continuous tremor in 17% of subjects. Extrapyramidal signs were present in 31% of patients, and clumsiness in fine alternating movements was present in 17 patients. The patients with longer duration of illness were significantly more clumsy in fine alternating movements (Fischer's Exact test; p = 0.507 < 0.05), but not in the presence of extrapyramidal signs (Fischer's Exact test; p = 0.507 > 0.05). DISCUSSION: Essential tremor is described as a dominant inherited postural tremor. Koller et al. [9] describe dominantly kinetic tremor occurring with movements, while Martinelli et al. [10] describe continuous tremor manifested at rest, posture and with movements. Static tremor was considered as a result of the disease progression [8]. In our patients those with longer duration of the disease were frequently more clumsy in fine alternating movements, but not in manifestation of extrapyramidal signs. Continuous tremor is probably a subgroup of essential tremor; suggests a more pronounced role of cerebellum in its genesis.

[Buspirone in the treatment of cerebellar ataxia]. / Buspiron u lecenju cerebelarne ataksije.

Ataxia is defined as a disturbance which, quite independent of any motor weakness, alters direction and extent of voluntary movement and impairs the sustained voluntary of reflex muscle contraction necessary for maintaining postiue and equilibrium [1]. Since pathophysiological basis of cerebeller ataxia is still not completely clear, the current therapeutic attempts are mainly symptom-oriented [3]. One possible approach could be a modification of potentially involved neurotransmitter systems of the cerebellum, where particularly interesting is the serotonergic system. However, attempts with levorotatory form of tryptophan (5-HT precursors) proved to be ineffective [4, 5]. Since receptors in the cerebellum are mainly of 5-HTIA subtype, the use of specific agonists might be a more reasonable therapy [6]. The study initially involved 11 patients, but only 9 completed the protocol due to unfavorable side effects. Our open label prospective study lasted for 15 weeks. The patients were tested before the beginning of the treatment (initial visit), at 7th (first visit) and 11th week (second visit) of continuous therapy, and eventually at 15th week (final visit). The daily dose was 40 mg at the first and 60 mg at the second visit. We used the evaluation scale gurposed for cerebellar functions testing (speech, gait, coordination and ocular movements). Significant improvement of cerebellar ataxia in patients under buspiron therapy has been noted. We analyzed the results obtained from our 9 patients (4 females and 5 males), of which 6 patients suffered from cerebellar degeneration, one from multiple sclerosis, one from Ramsey-Hunt syndrome, and one from pontine myelinolysis. At the initial visit the patient score was 18.9 (SD = 7.3), subsequently, at the iirst visit the score was 15.4 (SD = 8), while the second visit yielded the score of 12.9 (SD = 8.2), and finally, after a two-weeks lasting wash-out period, it was 17.7 (SD = 7.1) (Table 1). It was found that patients exhibiting mild ataxia showed a better improvement in comparison to the patients who had marked cerebellar symptoms at the beginning of the treatment (Table 2). In conclusion, our prospective study shows that buspiron treatment improves cerebellar symptoms.

Correlation between Bereitschaftspotential and reaction time measurements in patients with Parkinson's disease. Measuring the impaired supplementary motor area function?

For a long time, reaction time (RT) testing has been used for objective assessment of characteristics of the movement impairments in patients with Parkinson's disease (PD). On the other hand, it is supposed that Bereitschaftspotential (BP) reflects CNS preparatory activity for the execution of voluntary movements, and amplitudes of BP are generally smaller in PD. In order to analyze possible correlations between two methods, we studied 15 drug-naive patients with idiopathic PD (Hoehn and Yahr stage from 1 to 2.5). BP was recorded from three scalp locations: Cz, C3, and C4, and Lateralized Potential (LP) was additionally calculated as a C3-C4 difference waveform. We recorded amplitudes of the initial part of BP (at 650 ms before movement-NS1), the maximal amplitude immediately before movement onset (N1), and the N1-NS1 difference (NS2), from the Cz and LP recordings. Two RT testing paradigms were used: Simple Reaction Time (SRT) and Choice Reaction Time (ChRT). The only significant correlation between RT parameters and BP amplitudes from Cz was negative correlation between dT (difference time between Choice Reaction Time and Simple Reaction Time), on one hand, and NS1 (P = 0.006) and N1 (P = 0.026), on the other. However, Cz-NS2 did not correlate with any of the RT parameters. Our data suggest that PD patients with smaller difference between ChRT and SRT, that is presumably caused by the lesser capacity of the movement pre-programming, have smaller (i.e., less negative) BP amplitudes. This association is especially pronounced for the earlier, NS1 amplitude that is supposed to reflect the activity of the supplementary motor area (SMA). The diminished capacity of SMA activation may be the cause of the both, smaller early BP amplitudes, and smaller ChRT-SRT difference, in PD patients.

Hemiballism: report of 25 cases.

Twenty three patients with hemiballism and two with biballism were studied. Ischaemic and haemorrhagic strokes were the cause in most patients. Other causes were encephalitis, Sydenham's chorea, systemic lupus erythematosus, basal ganglia calcifications, non-ketotic hyperglycaemia, and tuberous sclerosis. Neuroimaging studies showed a lesion of the subthalamic nucleus in only six patients. In others, different subcortical structures were involved or the results were normal. Only two patients had "pure" hemiballism. The others had other types of dyskinesias, mainly chorea, which was present in 16 patients. The prognosis was usually good.