Prevalence and evolution of spasticity in patients suffering from first-ever stroke with carotid origin: a prospective, longitudinal study.

BACKGROUND AND PURPOSE: The main aim of the study was to document the occurrence and evolution of post-stroke spasticity (PSS). The secondary goal was to identify predictors for increases and decreases in PSS rates during 12 months of subsequent follow-up. METHODS: In a longitudinal, multicenter, prospective cohort study, assessments were done at 7 days (V1), 6 months (V2), and 12 months (V3) after stroke onset. A total of 307 consecutive patients from four comprehensive stroke centers with the first-ever stroke of carotid origin and the presence of motor deficit at day 7 were included. The demographic data, baseline characteristics, Barthel index, degree and pattern of paresis and muscle tone were evaluated and recorded. Spasticity was assessed using the modified Ashworth scale. RESULTS: Spasticity was present in 45.0% of patients at V1, in 49.5% at V2, and in 43.2% at V3. A significant number of patients experienced changes in spasticity between visits: increased/new occurrence of spasticity in 32.5% (V1 and V2) and in 13.6% (V2 and V3) of patients; decreased occurrence/disappearance of spasticity in 18.5% (V1 and V2) and in 18.3% (V2 and V3) of patients. The number of patients with severe spasticity increased throughout the year, from 2.6% to 13.0% (V2) and 12.5% (V3). CONCLUSIONS: Spasticity developed in almost half of the included patients. The degree of spasticity often changed over time, in both directions. The rate of severe spasticity increased during the first year, with the maximum at 6 months following stroke onset.

The early improvement of depressive symptoms as a potential predictor of response to antidepressants in depressive patients who failed to respond to previous antidepressant treatments. Analysis of naturalistic data.

INTRODUCTION: Current studies suggest that improvement of depressive symptoms after 2 weeks of treatment could predict the subsequent response. The aim of our study was to compare the predictive effect of early improvement (EI) after 1 and 2 weeks of treatment in patients who had failed to respond to previous antidepressant treatments (≥1 unsuccessful antidepressant trial). METHOD: Seventy-one subjects were treated (≥4 weeks) with various antidepressants chosen according to the judgment of attending psychiatrists. We used three definitions of EI (MADRS reduction ≥20, 25, 30%) at both time points. Areas under curve (AUC) were calculated to compare predictive effect of EI. RESULTS: We found lower MADRS scores in weeks 1 and 2 in responders (≥50% reduction of MADRS, n=35) compared to nonresponders. AUCs of MADRS reduction for response prediction at week 1 and 2 were not significantly different (0.73 vs 0.8; p=0.24). CONCLUSION: The results indicate that improvement of depressive symptoms in the treatment of resistant patients may occur after the first week of treatment. The predictive potential might be comparable to that found after the second week of antidepressant intervention and be clinically meaningful.

The impact of avoidable mortality on life expectancy at birth in Spain: changes between three periods, from 1987 to 2001.

OBJECTIVE: To evaluate the impact of avoidable mortality on the changes in life expectancy at birth in Spain. METHODS: Standard life table techniques and the Arriaga method were used to calculate and to decompose life expectancy (LE) changes by age, effects and groups of causes of avoidable mortality among three periods (1987-91, 1992-6 and 1997-2001). A list of causes of avoidable mortality reached by consensus and previously published in Spain was used. MAIN RESULTS: Life expectancy increased in all ages and both sexes. The main contribution to the increase of LE at birth was due to people over 50. Mortality in young adults produced a reduction in LE between the first two periods, but there was an important increase in LE between the last two periods; in both cases, this was the result of factors amenable to health policy interventions. The highest improvement in LE was due to non-avoidable causes, but avoidable mortality through health service interventions showed improvements in LE in those younger than 1 year and in those aged 45-75 years. CONCLUSIONS: Making a distinction between several groups of causes of avoidable mortality and using decomposition by causes, ages and effects allowed us to better explain the impact of avoidable mortality on the LE of the whole population and gave a new dimension to this indicator that could be very useful in public health.

[Differences in disability-free life expectancy by gender and autonomous regions in Spain]. / Diferencias en la esperanza de vida libre de discapacidad por sexo y comunidades autónomas en España.

BACKGROUND: Improvement of population health is the main aim and an important challenge for the health system. To monitor the population health indicators like disability-free life expectancy (DFLE) have been implemented. The purpose of this paper was to analyze the geographical distribution of DFLE according to autonomous regions in Spain. METHODS: Data of mortality, population and disability for the year 1999, provided by the National Institute of Statistics (INE), were used. To calculate DFLE by gender and region we used the Sullivan method that weights the expected time to live according to the status of disablement of the population. The standard error of DFLE, the expectation of disability and the proportion of time lived free of disability have also been estimated. RESULTS: In 1999 the DFLE at birth in Spain was 68.5 year for men and 72.2 years in women. Men lived proportionally more time free of disability than women (91% versus 87.7%) with an expectation of disability of 6.8 and 10.1 years respectively. Variability among regions was higher in DFLE than in life expectancy (LE). The regions with highest LE are not always those with the highest proportion of time lived without disability. CONCLUSIONS: Highest life expectancy does not always mean best health as it has been assumed currently. The DFLE indicator is a useful tool to show health status differences among the Spanish population.

[Geographical distribution and time trends in avoidable mortality in Catalonia, Spain (1986-2001)]. / Distribución geográfica y evolución temporal de la mortalidad evitable en Cataluña (1986-2001).

OBJECTIVES: To analyze time trends and geographical variation in avoidable mortality by health areas in Catalonia. MATERIAL AND METHODS: Avoidable mortality was analyzed according to the classification used by the Health Department of the Regional Government of Catalonia from 1986-2001 for health areas and causes were grouped as treatable and preventable. Standardized mortality rates were calculated by the direct and indirect method and the comparative mortality figures were calculated for the treatable and preventable groups and for the 46 health areas. The mean annual change adjusted for age was also calculated using a Poisson regression of avoidable and general mortality. RESULTS: The total number of avoidable deaths was 61,261 (7.3% of overall deaths). 10,623 cases (17.34%) were classified as treatable and 50,638 (82.65%) as preventable. The mean annual change for avoidable causes was -2.43% (95% CI, -2.60 to -2.26), higher than the -1.57% (95% CI, -1.61 to -1.52) change for general mortality. The rates were higher for preventable causes than for treatable causes, although mortality decreased in both groups. The health area of Segrià was notable for its significantly higher mortality from both treatable and preventable causes in both periods. Four health areas showed a significant increase in mortality from preventable causes but none showed an increase in mortality from treatable causes. CONCLUSIONS: In Catalonia, the decrease in avoidable mortality was greater than that in general mortality from 1986 to 2001. The geographical distribution shows wide dispersion but allows areas requiring preventive interventions to be identified.

Cognitive functioning after repetitive transcranial magnetic stimulation in patients with cerebrovascular disease without dementia: a pilot study of seven patients.

AIMS: Examine whether one session of high frequency repetitive transcranial magnetic stimulation (rTMS) applied over the left dorsolateral prefrontal cortex (DLPFC) would induce any measurable cognitive changes in patients with cerebrovascular disease and mild cognitive deficits. PATIENTS AND METHOD: Seven patients with cerebrovascular disease and mild executive dysfunction entered the randomised, controlled, blinded study with a crossover design. rTMS was applied either over the left DLPFC (an active stimulation site) or over the left motor cortex (MC; a control stimulation site) in one session. Each patient participated in both stimulation sessions (days 1 and 4) and the order of stimulation sites (DLPFC or MC) was randomised. A short battery of neuropsychological tests was performed by a blinded psychologist prior to and after each rTMS session. Psychomotor speed, executive function, and memory were evaluated. RESULTS: The only mild but significant stimulation site-specific effect of rTMS was observed in the Stroop interference results (i.e. improvement) after the stimulation of DLPFC but not MC in comparison with the baseline scores (Wilcoxon, Z=-2.03, p=0.04). Patients improved in the digit symbols subtest of the Wechsler adult intelligence scale-revised after both rTMS sessions regardless of the stimulation site (DLPFC or MC; Z=-2.06, p=0.04 and Z=-2.06, p=0.04, respectively). There was no measurable effect of rTMS in any other neuropsychological test. CONCLUSION: Our pilot study results showed that one session of the high frequency rTMS applied over the left DLPFC was safe in patients with cerebrovascular disease and mild executive deficits, and may induce measurable positive effects on executive functioning.

Cognitive performance in people with Parkinson's disease and mild or moderate depression: effects of dopamine agonists in an add-on to L-dopa therapy.

In a randomized prospective multi-centre study, we evaluated the cognitive performances of a group of 41 non-demented patients, all with advanced Parkinson's disease (PD) and a current depressive episode, in whom the effects of pramipexole (PPX) and pergolide (PRG) in an add-on to l-dopa therapy were also studied and published with regard to motor symptoms of PD, motor complications and depression. The Trail Making Test, the Stroop test and four subtests (arithmetic, picture completion, digit symbols and similarities) of the Wechsler Adult Intelligence Scale-Revised were performed prior to and 8 months after the administration of either PPX or PRG. We found no statistically significant difference between the two tested drugs or between the first and the last visit in any of the above-listed neuropsychological tests. All patients' motor outcomes significantly improved and we conclusively demonstrated the anti-depressive effect of PPX. The dissociation of dopaminomimetic effects on the different tested domains indicates that there are different pathological mechanisms of cognitive, motor and affective disturbances in advanced PD patients. In our non-demented group of fluctuating depressed PD subjects, both PPX and PRG administration in combination with l-dopa were safe in terms of the effect on cognitive performance.

Pergolide mesylate can improve sexual dysfunction in patients with Parkinson's disease: the results of an open, prospective, 6-month follow-up.

One of the most disabling problems in males suffering from advanced Parkinson's disease (PD) is complex sexual dysfunction. The effect of dopamine replacement or dopaminergic stimulation on sexual dysfunction has been recently examined and described in patients treated by L-DOPA or apomorphine. Pergolide mesylate is another dopamine agonist with a known high affinity to hD(2S) subtype and a lower affinity to hD(2L) subtype of D2 dopaminergic receptors. It has been repeatedly shown to be a highly effective treatment of the complicated and advanced stages of PD. The current study has been designed to assess its efficacy in the treatment of sexual dysfunction, which frequently accompanies the complicated stage of PD in males. Fourteen male patients suffering from PD, each of whom had been treated with L-DOPA, and in whom additional treatment with peroral dopaminergic agonist (DA) was needed, were followed for a 6-month period. Pergolide mesylate (Permax) was given to each patient, and titrated to a total daily dose of 3 mg. All of the patients were taking L-DOPA. The assessments performed before the start of pergolide treatment consisted of a neurological examination, including Unified Parkinson's Disease Rating Scale (UPDRS) III and IV subscales scoring, Mini Mental State Examination (MMSE) scoring, the neuropsychological examination including Zung scale scoring to exclude depression, biochemical and haematological examinations including the examination of prolactine serum levels; and a sexological examination during which the patients filled-in the International Index of Erectile Function (IIEF) questionnaire. These examinations were repeated during the control assessments at months 1, 3 and 6. To compare the examination results, anova, Friedmann's anova (non-parametric) and Tukey post hoc tests were used. There were statistically significant differences between the values of UPDRS III motor subscale, UPDRS IV (complications of therapy) subscale and all subscales of IIEF when months 0 and 1 were compared with the results obtained at months 3 and 6. The differences between months 0 and 1 and months 3 and 6 (in these items) were virtually insignificant. In conclusion, pergolide substantially improved sexual function in the younger male patients who were still interested in sexual activities. In such cases, the introduction of pergolide might be a better choice than treatment with sildenafile, which usually meets several contraindications in common PD male population.

Intracortical inhibition and facilitation are impaired in patients with early Parkinson's disease: a paired TMS study.

Twelve patients with early Parkinson's disease (PD), none of whom had received any previous L-DOPA treatment, but using other antiparkinsonian drugs, were studied using transcranial magnetic stimulation (TMS). Contralateral and ipsilateral hemispheres were examined, with a focus on the more pronounced parkinsonian symptoms. The conditioning-test TMS paradigm (with a subthreshold conditioning stimulus and a suprathreshold test stimulus) was used through a stimulating round coil. Paired stimuli of short (3, 5 and 7 ms), medium (10, 15 and 20 ms), and long (100, 150, 200 and 250 ms) interstimulus intervals (ISI) were pseudo-randomly mixed with a single stimulus. The first interosseus muscle was used for the motor-evoked potential recordings. Ten healthy subjects (age and sex matched) were studied in the same manner to obtain normative data. When both groups were compared, the significant difference (reduction of the intracortical inhibition and facilitation) between the PD patients and the control group was found at the short and the medium ISI (3, 5, 7, 10, 15 and 20 ms) in both hemispheres (P < 0.05). The longer ISI produced non-significant differences between the two groups in intracortical excitability. There was a non-significant difference in the motor threshold. In conclusion, it can be supposed that both intracortical inhibition and facilitation are impaired in patients with early PD using other antiparkinsonian treatments than L-DOPA or dopamine agonists.

Pramipexole and pergolide in the treatment of depression in Parkinson's disease: a national multicentre prospective randomized study.

An 8-month multicentre prospective randomized study aimed at comparing the effects of dopamine receptor agonists pramipexole (PPX; Mirapexin) and pergolide (PRG; Permax) as add-on to L-dopa therapy on depression [Montgomery and Asberg Depression Rating Scale (MADRS)] in 41 non-demented patients (25 men, 16 women) suffering from both mild or moderate depression and advanced Parkinson's disease (PD). The assessment was performed by a blinded independent observer. Motor symptoms (UPDRS III), motor complications (UPDRS IV), activities of daily living (UPDRS II and VI) and depressive symptoms as measured by Self - Rating Depression Scale by Zung were evaluated in an open-label design. The average value of Zung scores decreased significantly in both groups with no statistical difference between both groups. A significant decrease in the average value of MADRS scores was present only in the PPX group. The average UPDRS scores decreased significantly with no statistical difference between both groups at the comparable average total daily dose of both preparations. In both cases, the total daily dose of L-dopa decreased significantly but the decrease was statistically more pronounced in the PRG group. Our results demonstrate the antidepressant effect of PPX in patients with PD while we can't make any conclusions with regard to antidepressant effect of PRG.

A SEEG study of ERP in motor and premotor cortices and in the basal ganglia.

OBJECTIVE: Our intention was to study the electrical activity related to the cognitive processing of simple sensory stimuli in the brain structures that participate in motor control. We focused our interest on the 250-600 ms time window, in which cognitive activity most probably provides the basis for the activity recorded. METHODS: Intracerebral stereoelectroencephalography (SEEG) recordings were made from 15 epilepsy surgery candidates. We studied potentials that were recorded in a time window in which P300 usually could be recorded on the scalp and that were directly recorded from brain structures involved in motor control: the primary motor cortex (MC, Brodmann's area 4); the lateral and mesial (SMA) premotor cortices (Brodmann's area 6); and the basal ganglia. We evaluated the first distinctive potential to occur in the 250-600 ms time window that displayed an amplitude gradient in several adjacent contacts. Four protocols were performed: an auditory oddball (aP3); a visual oddball (vP3); and contingent negative variation (CNV) protocols, in which the potentials evoked by the auditory warning (aCNV) and visual imperative (vCNV) stimuli were evaluated. In the protocols aP3, vP3, and vCNV, the tested person responded by flexing his/her thumb or hand. In the aCNV paradigm, and in a further auditory oddball paradigm (aP3c), no motor response was required. We compared the presence of an event-related potential (ERP) with an amplitude gradient to the absence of a generator. RESULTS: The frequency of P3-like potential components was statistically significantly higher in the basal ganglia when compared with the explored cortical sites. Statistically non-significant latency differences between the basal ganglia and the cortex were displayed. The differences in the distribution of the potentials in the individual cortical areas were insignificant. The mean latency of vP3 was longer than the latencies of aP3, aP3c and vCNV. There was no significant difference between the distribution and latency of aP3 and aP3c. CONCLUSIONS: (1) ERPs are generated in cortical as well as in subcortical structures. (2) The cognitive processing of sensory information in all the tested protocols occurred in the basal ganglia; the occurrence in the investigated cortical areas was less frequent and more dependent on the task. The basal ganglia may play an integrative role in cognitive information processing, in motor and non-motor tasks.

Event-related potentials, CNV, readiness potential, and movement accompanying potential recorded from posterior thalamus in human subjects. A SEEG study.

Intracranial recordings were obtained from three patients with intractable chronic pain who underwent analgesic electrical stimulation of the contralateral thalamus. Multilead electrode made it possible to record from several thalamic nuclei. The electrode was targeted into the ventroposterolateral (VPL) nucleus of the thalamus. During separate recording sessions, the following tests were performed: somatosensory evoked potentials (SEP) of the median or posterior tibial nerve, event-related cognitive potentials (auditory oddball P3 wave), readiness potential (RP) and contingent negative variation (CNV) using auditory warning (S1) and visual imperative (S2) stimuli. The movement accompanying potential (MAP), which was present in the VPL in all but one of the recordings, behaved as a far-field potential. Recordings obtained from the VPL confirmed its established role as a relay nucleus, processing somatosensory information to the primary somatosensory cortex. The VPL generated the 'thalamic' SEP, which was the only potential regularly recorded in this nucleus. In the recordings from one patient (No. 3), auditory and visual evoked potentials of the CNV protocol, peaking at approximately 300 ms, were obtained from the VPL and appeared to be generated in situ. Neither RP, CNV nor 'oddball' ERPs appeared in the VPL. From the pulvinar, only a visually evoked potential was recorded. Oddball P3, RP, CNV, and middle and long latency auditory and visual potentials (evoked in the CNV paradigm) appeared to be generated 'dorsally' to the VPL, probably in the nucleus posterolateralis (PL). This structure may therefore be involved in both the processing of afferent information and in cognitive operations.

Basal ganglia involvement in sensory and cognitive processing. A depth electrode CNV study in human subjects.

OBJECTIVE: Intracranial recordings were taken from the basal ganglia (BG) in order to explore the possible role of the BG in the cognitive processing of sensory information. METHODS: Ten patients with intractable temporal lobe epilepsy, who were candidates for epilepsy surgery, underwent intracranial recordings with depth electrodes. A frontal approach was used for the insertion of diagonal depth electrodes into the amygdalo-hippocampal complex (AH complex). These electrodes passed through the BG. The putamen was explored in 8 patients; the nucleus caudatus and pallidum were explored in two patients. The contingent negative variation (CNV) paradigm was tested using auditory warning stimuli and visual imperative stimuli followed by a hand flexion. The auditory and visual middle and late latency potentials evoked by the warning and imperative stimuli were analyzed. RESULTS: (1) Auditory evoked potentials (EPs): the amplitude potential gradient was observed with latencies of (a) 150-195ms (9 patients); (b) 215-290ms (9 patients); and (c) 350-600ms (10 patients). Negative potentials, with latencies of 100 and 110ms were observed in two patients. (2) Visual EPs: (a) 160-195ms (9 patients); (b) 210-295ms (9 patients); and (c) 330-550ms (7 patients). Negative potentials with latencies between 100 and 120ms were observed in 4 patients. CNV was obtained from the BG in 8 patients; a phase reversal was observed twice. CONCLUSIONS: (1) The BG generate middle and late latency EPs in a cognitive paradigm linked to the motor task. (2) The BG generate CNV. (3) The BG could play an integrative role in the processing of sensory, cognitive, and motor information.

Movement-related potentials in the basal ganglia: a SEEG readiness potential study.

OBJECTIVES: The brain potentials preceding and accompanying self-paced acral limb movements (Bereitschaftspotential/readiness potential (RP) paradigm) were studied in 12 patients. METHODS: Intracranial electrodes were implanted in order to explore intractable epilepsy. The electrodes were introduced into sites corresponding to the electroclinical characteristics of each patient's epileptic seizures. In 7 patients, several depth electrodes were implanted orthogonally, in the temporal, fronto-orbital and prefrontal cortex. In 4 patients, subdural strip electrodes were used for the exploration of the fronto-temporal convexity. There were no RPs recorded in these areas. No contacts were placed in the central region known to generate cortical RP. In all the patients, one or two diagonal electrodes passed through or touched the basal ganglia to reach the amygdala and the hippocampus. The putamen was explored in 11 patients (in 3 of them bilaterally); the caudate head was explored in two patients, and the pallidum was explored in two patients. RESULTS: RP with a clear amplitude gradient was present in all explored structures, however a phase reversal was never observed. RP was observed in the caudate in all recordings, and in the pallidum in one patient. It was recorded in the putamen in 8 out of the 11 explored patients. RPs were displayed contralaterally to the movement 9 times in 13 explorations, and ipsilaterally 4 times in 9 explorations. The shape of RP resembled the RP shape in the cortex and on the scalp. Movement accompanying potentials (MAPs) were also present in all 3 explored structures. The electrophysiological characteristics of MAP differed from RP, indicating separate generators. In the basal ganglia, RPs preceded the onset of movement by 500-1500 ms, at an average of 1080 (+/-330) ms. It seems that the RP in the basal ganglia starts slightly later than the RP in the motor cortices. That should be definitely demonstrated in patients with simultaneous recordings from cortical and subcortical structures. RP and MAP were displayed synchronously in the cortex and in the basal ganglia during most of the premovement period, as well as during the execution of movement. RP generators were reported by several authors in other deeply located structures, i.e. in the thalamus and in the brain-stem. CONCLUSIONS: Based on all these recordings, we presume that the RPs recorded on the scalp are generated simultaneously in several cortical as well as subcortical structures.

Intracerebral recording of readiness potential induced by a complex motor task.

While exploring 11 epileptic patients with intracerebral electrodes, we recorded readiness potential (RP) preceding a complex motor task. Multilead depth electrodes were positioned stereotactically into the cortex. In three patients, it was also possible to record RP from the putamen. The movement triggering the recording was the turning of a page in an architectural book. The movement was performed under two conditions: in the first condition, without looking at the pictures on the page (typical self-pacing); and in the second condition, following the inspection of the pictures. There were no significant differences in the appearance of RP under these two conditions, neither in duration nor in amplitude. That could be explained by the fact that "self-paced" does not mean "spontaneous," but covers the internal non-conscious program related to a given task. RP were present in the contralateral primary sensorimotor cortex and the bilateral supplementary motor area (SMA), and in the anterior caudal cingulate cortex. No difference between the cortical topography of RP preceding a simple motor task and the topography of RP occurring in connection with complex movement was observed.

Efficacy and safety of a standardised 500 unit dose of Dysport (clostridium botulinum toxin type A haemaglutinin complex) in a heterogeneous cervical dystonia population: results of a prospective, multicentre, randomised, double-blind, placebo-controlled, parallel group study.

Results from a dose-ranging study in a selected group of de novo patients with rotational cervical dystonia (CD) suggest that 500 units of Dysport (Clostridium botulinum toxin type A haemaglutinin complex) is the optimal starting dose. The present study aimed to confirm the efficacy and safety profile of this dose in a population of CD patients more representative of those seen in a typical dystonia clinic. A total of 68 patients with moderate to severe CD (Tsui score > or = 9) were randomly assigned to receive placebo or Dysport 500 units. Treatment was administered according to the clinical pattern of head deviation, using a standardised injection protocol. A total of 21 patients (11 Dysport, 10 placebo) had not previously received botulinum toxin type A (BtxA) injections, and 47 patients (24 Dysport, 23 placebo) had received BtxA more than 12 weeks previously. Assessments were performed at baseline and weeks 4, 8 and 16. Patients defined as non-responders at week 4 were re-treated in an open phase with 500 units of Dysport at week 6, and were followed up at week 10. Significant between-group differences in Tsui scores were present at weeks 4 (p=0.001) and 8 (p=0.002). Similarly, there were significant between-group differences (p < 0.001) in patient and investigator assessments of response in favour of Dysport at weeks 4 and 8. Also, more Dysport (49%) than placebo (33%) patients were pain-free at week 4 (p=0.02). Overall, 30/35 (86 %) Dysport patients and 14/33 (42%) placebo patients were classified as responders at week 4. Adverse events were reported by 15/35 Dysport patients and 9/33 placebo patients. Open phase treatment produced improvements in Tsui (p < 0.001) and pain scores (p=0.011), and 23/24 patients were classified as responders. Although individual dose titration and muscle selection is desirable, this study demonstrated that a dose of 500 units of Dysport injected into clinically identified neck muscles without electromyographic guidance is safe and effective in the treatment of patients with the major clinical types of cervical dystonia.

Amantadine infusion in treatment of motor fluctuations and dyskinesias in Parkinson's disease.

Efficiency and safety of amantadine sulfate (AMS) infusions were investigated in late stage complications of Parkinson's disease (PD). In an open-label study, 21 PD patients suffering from motor fluctuations and/or dyskinesias were administered AMS infusions (PK-Merz, 400 mg per day) during seven days. Oral AMS treatment followed. Significant improvement of UPDRS motor scores was observed between day 0 and day 7, remaining improved until day 21. Based on patients' diary notes, both severity and occurrence of hypokinetic "off" state significantly decreased (from 6.6 to 3.1 hours, p < 0.001, average "off" time per day) as well as dopaminergic-induced dyskinesias (from 2.5 to 1.3 hours, p < 0.05, average duration of dyskinesias per day). AMS infusions followed by oral administration appeared as a safe method for improvement of both motor fluctuations and dyskinesias in advanced PD. In advantage to simple oral therapy, AMS infusions allowed fast introduction of a profound and durable treatment effect.