[The new Parkinson's disease pain classification system (PD-PCS)]. / Die neue Parkinson-Schmerzklassifikation (PSK).

BACKGROUND: Chronic pain is a common non-motor symptom in patients with Parkinson's disease (PD). AIM: To facilitate the diagnosis of pain in PD, we developed a new classification system the Parkinson's disease pain classification system (PD-PCS) and translated the corresponding validated questionnaire into German. METHODS: A causal relationship of the respective pain syndrome with PD can be determined by four questions before assigning it hierarchically into one of three pain categories (neuropathic, nociceptive and nociplastic). RESULTS: In the initial validation study 77% of the patients (122/159) had PD-associated pain comprising 87 (55%) with nociceptive, 36 (22%) with nociplastic and 24 (16%) with neuropathic pain. The study revealed a high validity of the questionnaire and a moderate intrarater and interrater reliability. The questionnaire has been adapted into German and employed in 30 patients. DISCUSSION: The PD-PCS questionnaire is a valid and reliable tool to determine the relationship of a pain syndrome with PD before classifying it according to the underlying category, facilitating further diagnostics and treatment.

Correction to: Advanced Robotic Therapy Integrated Centers (ARTIC): an international collaboration facilitating the application of rehabilitation technologies.

The original article [1] contains a small mistake concerning the ARTIC Team members mentioned in the Acknowledgements. The team member, Rocco Salvatore Calabrò had their name presented incorrectly. This has now been corrected in the original article.

Chronic non-bacterial osteomyelitis is associated with impaired Sp1 signaling, reduced IL10 promoter phosphorylation, and reduced myeloid IL-10 expression.

Chronic non-bacterial osteomyelitis (CNO) is an auto-inflammatory disorder that affects the skeletal system. Interleukin (IL-)10 is an immune-modulatory cytokine that controls inflammation, and limits inflammatory cytokine responses. Dysregulation of IL-10 expression has been shown to result in autoimmune and infectious diseases. We investigated IL-10 expression by monocytic cells from CNO patients and controls. In response to stimulation with LPS, IL-10 expression from CNO monocytes was reduced (p<0.001). This was independent of IL10 promoter polymorphisms. Thus, we investigated Sp1 recruitment to the IL10 promoter and saw markedly reduced binding in CNO monocytes. This was accompanied with reduced phosphorylation of histone H3 serine 10 (H3S10), an activating epigenetic mark. Impaired recruitment of Sp1 to the IL10 promoter, and reduced H3S10 phosphorylation, may be a reflection of deficient MAPK signaling in CNO monocytes in response to LPS stimulation. Thus, we have discovered a mechanism that may be central in the pathophysiology of CNO.

IL10 promoter polymorphisms are associated with systemic onset juvenile idiopathic arthritis (SoJIA).

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is a rare, but severe cause of childhood disability. Systemic onset JIA (SoJIA) accounts for approximately 5.8% of all JIA cases and is associated with cytokine dysregulation, including interleukin (IL-)1, IL-6 and tumour necrosis factor (TNF-)α. IL-10 is an immuno-regulatory cytokine, which in part regulates inflammation by controlling inflammatory cytokine expression. Dysregulation in IL-10 expression and certain single nucleotide polymorphisms (SNPs) in the IL-10 promoter were shown to be associated with autoimmune and infectious diseases. METHODS: Genomic DNA-samples from SoJIA patients from two German Paediatric Rheumatology centres, and healthy controls were analysed for three well defined IL-10 promoter SNPs (-1082G>A, -819C>T, and -592C>A). These SNPs are in tight linkage disequilibrium, and result in three predominant (or 'classical') haplotypes: ATA, ACC, and GCC. ATA and ACC are associated with low and medium, GCC is associated with high IL-10 expression. RESULTS: Here, we show a strong association of IL-10 promoter polymorphisms with SoJIA. We demonstrate a significantly increased frequency of low IL-10 expressing -1082A/A alleles, the medium IL-10 expressing ACC haplotype (p=0.01), and an enrichment of the rare GTC haplotype (p<0.001) in patients with SoJIA. Heterozygous -1082G/A alleles (p<0.001), and the GCC haplotype (p<0.001) on one allele protect from developing SoJIA. CONCLUSIONS: This suggests a central role of the immuno-regulatory cytokine IL-10 in the pathogenesis of SoJIA.

Pain sensitivity and descending inhibition of pain in Parkinson's disease.

BACKGROUND: Patients suffering from Parkinson's disease (PD) often complain about painful sensations. Recent studies detected increased subjective pain sensitivity and increased spinal nociception, which appeared to be reversible by dopaminergic treatment. Possibly, reduced descending pain inhibition contributes to this finding. OBJECTIVE: Subjective pain thresholds as well as nociceptive reflex thresholds were investigated to isolate potential loci of the pathophysiological changes within the pain pathway. In addition, the diffuse noxious inhibitory control (DNIC) system as one form of descending control was assessed. METHOD: 15 patients with PD and 18 controls participated in the study. Electrical and heat pain thresholds as well as the nociceptive flexion reflex (NFR) thresholds were determined. Thereafter, the electrical pain thresholds were measured once during painful heat stimulation (conditioning stimulation) and twice during innocuous stimulation (control stimulation). RESULTS: Patients with PD exhibited lower electrical and heat pain thresholds as well as lower NFR thresholds. Suppression of the electrical pain thresholds during painful heat stimulation (conditioning stimulation) compared with control stimulation did not differ significantly between the groups. No differences in the thresholds between patients with PD with and without clinical pain were seen. CONCLUSIONS: Finding the NFR threshold to be decreased in addition to the decreased electrical and heat pain thresholds indicates that the pathophysiological changes either already reside at or reach down to the spinal level. Reduced activation of the DNIC system was apparently not associated with increased pain sensitivity, suggesting that DNIC-like mechanisms do not significantly contribute to clinical pain in PD.

Clinical risk-benefit assessment of dopamine agonists.

Dopamine agonists (DAs) have proven efficacy as monotherapy in early Parkinson's disease (PD) for preventing motor complications such as dyskinesia and as adjunct therapy as the disease progresses. Further, it is increasingly evident that at least some DAs may provide additional benefits, such as reduction in depressive symptoms and treatment of refractory tremor. Different side-effect profiles have been associated with levodopa and ergot or non-ergot DA treatment, such as sudden onset of sleep, reduced impulse control, hallucination, and cardiovascular fibrosis. This paper discusses the evidence for specific associations between particular treatments and side effects as well as the clinical implications for patient care. Ultimately, the choice depends on the risk-benefit assessment as it applies to the individual patient's clinical profile and the physician's preference.

Immunophenotyping in Tourette syndrome--a pilot study.

BACKGROUND AND PURPOSE: The cause of Tourette syndrome (TS) is not precisely known, although several lines of evidence point at an involvement of the immune system in its pathogenesis. RESULTS: Here, we report the results of a pilot study investigating frequently analysed lymphocyte surface markers in 20 adult patients with TS (16 males; 37.3 +/- 15.8 years) and 20 matched controls (16 males; 37.5 +/- 15.3 years). Statistical analysis revealed significant differences for the investigated lymphocyte surface markers. The difference in CD69+/CD22+-B cells (23.0 +/- 10.5% vs. 13.1 +/- 6.1%; P = 0.001) and in CD95+/CD4+-T cells (41.5 +/- 12.1% vs. 24.6 +/- 10.0%; P = 0.0001) was still significant after Bonferroni-Holm correction. CONCLUSION: Our preliminary data indicate that TS may be associated with an increased peripheral immune activity.

The prevalence of the G2019S and R1441C/G/H mutations in LRRK2 in German patients with Parkinson's disease.

BACKGROUND AND PURPOSE: The prevalence of the heterozygous G2019S and R1441C/G/H mutations in LRRK2 in patients with Parkinson's disease (PD) has shown a great variability depending on the sample population. Here we investigated the prevalence of these mutations in a large cohort of German PD patients (n = 1049). RESULTS: We observed heterozygous G2019S mutations in five patients with apparently sporadic late-onset PD (LOPD; n = 3) and young-onset PD (YOPD) (one sporadic and one familial), respectively, resulting in an overall prevalence of 0.5%. No R1441C/G/H mutation was found in our sample. DISCUSSION: In summary, the overall prevalence of the G2019S mutation in German PD patients is apparently somewhat lower than in patients from other nearby European countries. In contrast to previous reports, the G2019S mutation was also observed in apparently sporadic German LOPD patients.

Olfactory dysfunction in patients with narcolepsy with and without REM sleep behaviour disorder.

Patients with idiopathic rapid eye movement sleep behaviour disorder (RBD) frequently develop Parkinson's disease and the majority present with hyposmia, which is a potential preclinical non-motor sign of Parkinson's disease. Accordingly, it has been proposed that the clinical symptoms of hyposmia and RBD in combination have to be considered as very early symptoms of Parkinson's disease. Since not only patients with idiopathic RBD but also patients in whom RBD is associated with narcolepsy present with an olfactory dysfunction we investigated if hyposmia in RBD patients with concomitant narcolepsy is RBD specific or if narcolepsy per se is associated with olfactory dysfunction. We studied olfactory function in 20 narcoleptic patients each with RBD (9 male and 11 female; mean age 45.4 +/- 14.0 years, range 20-75 years) and without associated RBD (8 male and 12 female; mean age 44.4 +/- 13.40 years, range 20-70 years) and 40 age- and gender-matched healthy control subjects using standardized 'Sniffin' Sticks'. Both, narcoleptics with (Narc/+RBD) and without RBD (Narc/-RBD) had a significantly higher olfactory threshold (Narc/+RBD, P = 0.0001; Narc/-RBD, P = 0.0001), lower discrimination scores (P = 0.001; P = 0.014) and lower identification scores (P = 0.057; P = 0.003) than controls. There were no symptoms or signs for early parkinsonism in both patient groups. Our results show for the first time that narcolepsy per se is associated with olfactory dysfunction. In contrast to patients with idiopathic RBD, hyposmia in patients with RBD associated with narcolepsy is unlikely to be a predictor for developing parkinsonism.

Combination of 'idiopathic' REM sleep behaviour disorder and olfactory dysfunction as possible indicator for alpha-synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT.

REM sleep behaviour disorder (RBD) and olfactory dysfunction are common and very early features of alpha-synucleinopathies, in particular Parkinson's disease. To investigate the hypothesis that these two clinical features in combination are an indicator of evolving alpha-synucleinopathy, olfactory function was assessed in RBD. We studied 30 patients (18 male, 12 female; mean age 48 +/- 14 years, range 19-78 years) with clinical (idiopathic, n = 6; symptomatic, n = 13, mostly associated with narcolepsy) or subclinical (n = 11, associated with narcolepsy) RBD according to standard criteria and 30 age- and gender-matched healthy control subjects using standardized 'Sniffin' Sticks'. RBD patients had a significantly higher olfactory threshold (P = 0.0001), lower discrimination score (P = 0.003), and lower identification score (P = 0.001). Compared with normative data, 97% of the RBD patients had a pathologically increased olfactory threshold, 63% an impaired odour discrimination score, and 63% a decreased identification score. On neurological examination, signs of parkinsonism were newly found in five patients with clinical RBD (not associated with narcolepsy), who usually had a long history of 'idiopathic' RBD. Four of the five patients fulfilled the UK Brain Bank criteria for the clinical diagnosis of Parkinson's disease. The underlying nigrostriatal degeneration of clinical Parkinson's disease was confirmed by I-123-FP-CIT SPECT in one patient and early nigrostriatal degeneration was identified by SPECT in a further two patients with 'idiopathic' clinical RBD out of 11 RBD patients who agreed to undergo SPECT studies. Our study shows that RBD patients have a profound impairment of olfactory function. Five patients with clinical RBD not associated with narcolepsy had clinical or imaging signs of nigrostriatal degeneration. This new clinical finding correlates with the neuropathological staging of Parkinson's disease (stages 1-3) as proposed by Braak. In stage 1, the anterior olfactory nucleus or the olfactory bulb is affected (along with the dorsal motor nucleus of the glossopharyngeal and vagal nerves). In stage 2, additional lesions consistently remain confined to the medulla oblongata and pontine tegmentum, which are critical areas for RBD. Midbrain lesions are found only in stage 3, in particular degeneration of dopaminergic neurons in the substantia nigra pars compacta. Thus, 'idiopathic' RBD patients with olfactory impairment might present with stage 2 preclinical alpha-synucleinopathy. Since narcoleptic patients are not known to have an increased risk of developing parkinsonism, the pathophysiology and clinical relevance of hyposmia in RBD/narcolepsy patients requires further research.

The fragile X tremor ataxia syndrome in the differential diagnosis of multiple system atrophy: data from the EMSA Study Group.

The recent identification of fragile X-associated tremor ataxia syndrome (FXTAS) associated with premutations in the FMR1 gene and the possibility of clinical overlap with multiple system atrophy (MSA) has raised important questions, such as whether genetic testing for FXTAS should be performed routinely in MSA and whether positive cases might affect the specificity of current MSA diagnostic criteria. We genotyped 507 patients with clinically diagnosed or pathologically proven MSA for FMR1 repeat length. Among the 426 clinically diagnosed cases, we identified four patients carrying FMR1 premutations (0.94%). Within the subgroup of patients with probable MSA-C, three of 76 patients (3.95%) carried premutations. We identified no premutation carriers among 81 patients with pathologically proven MSA and only one carrier among 622 controls (0.16%). Our results suggest that, with proper application of current diagnostic criteria, FXTAS is very unlikely to be confused with MSA. However, slowly progressive disease or predominant tremor are useful red flags and should prompt the consideration of FXTAS. On the basis of our data, the EMSA Study Group does not recommend routine FMR1 genotyping in typical MSA patients.

Experimental pain sensitivity in multiple system atrophy and Parkinson's disease at an early stage.

BACKGROUND: Chronic spontaneous pain is a clinically relevant non-motor symptom in multiple system atrophy (MSA) and Parkinson's disease (PD). Experimental pain sensitivity, reflecting the mechanisms of nociception and pain perception leading to clinical pain, is known to be enhanced in both diseases at advanced stages. Also, this study aimed at investigating experimental pain sensitivity already at an early stage (i.e. symptom duration ≤5 years). METHODS: Experimental pain sensitivity was assessed by investigating the nociceptive flexion reflex (NFR, reflecting spinal nociception) and heat and electrical pain thresholds. 'Off-drug' MSA (n = 11) and PD (n = 14) patients selected at an early stage of the disease were compared to healthy controls (HC, n = 27). MSA patients had either parkinsonian (MSA-P, n = 5) or cerebellar (MSA-C, n = 6) subtypes. RESULTS: Compared to HC, MSA patients had lower heat pain sensitivity, whereas PD patients had reduced NFR threshold. MSA and PD patients did not differ from HC regarding other variables. MSA-P and MSA-C patients did not differ, either. CONCLUSIONS: Impaired sensory discrimination and attention deficits could contribute to the reduced perception of heat pain in MSA, whereas in PD, local changes in spinal excitability or a diminished dopaminergic descending inhibition might impact on the motor efference of the NFR to reduce its threshold to nociceptive afferent information. WHAT DOES THIS STUDY ADD?: This study investigated experimental pain sensitivity at an early stage in MSA and PD.

Pharmacotherapy of Parkinson's disease in Germany.

Treatment standards or guidelines have been developed for most features of Parkinson's disease (PD). However, data on the actual treatment that is put into practice are scarce. In 2000, a nationwide survey on the topic of sudden onset of sleep (SOS) in PD was initiated among the members of the German patient support group (deutsche Parkinson-Vereinigung, dPV). A part of this mailed questionnaire survey covering the antiparkinsonian and concomitant medication of the participants is presented here. This study analyses data sets from more than 6,500 PD patients. The mean dopaminergic dose was equivalent to 599 +/- 387 mg levodopa/die. The most frequently administered drugs were levodopa (94.2 %), dopamine agonists (DA) (71.7 %), amantadine (40.1 %), selegiline (27.6 %), entacapone (20.4 %), budipine (12.3 %), and anticholinergics (11.8 %). Costs of pharmacotherapy were estimated to be approximately 399 million/year in Germany. PD drug therapy in general strongly depended on age, disease duration, and the level of care. The treatment guidelines were apparently not consistently followed underlining the need for their continuous propagation throughout the medical community. In addition our data suggest that non-motor symptoms in PD are not adequately treated and that concomitant sedative medication contributes to the occurrence of SOS.

Microglia and the early phase of immune surveillance in the axotomized facial motor nucleus: impaired microglial activation and lymphocyte recruitment but no effect on neuronal survival or axonal regeneration in macrophage-colony stimulating factor-deficient mice.

Activation of microglia is among the first cellular changes in the injured CNS. However, little is known about their specific contribution to secondary damage or repair processes in neighboring neurons and nonneuronal cells or to the immune surveillance of the damaged tissue. Animal models with defective microglial response such as osteopetrosis provide an approach to explore these effects. Osteopetrosis (op) is an autosomal recessive mutation with a complete deficiency of the macrophage-colony stimulating factor (MCSF; CSF-1), an important mitogen for brain microglia. In the current study we examined the effects of this MCSF deficiency on the microglial reaction and the overall cellular response to nerve injury in the mouse axotomized facial motor nucleus. In the brain, MCSF receptor immunoreactivity was found only on microglia and was strongly up-regulated following injury. MCSF deficiency led to a failure of microglia to show a normal increase in early activation markers (thrombospondin, MCSF receptor, alpha M beta 2- and alpha 5 beta 1-integrins), to spread on the surface of axotomized motoneurons, and to proliferate after injury. Early recruitment of CD3(+) T-lymphocytes to the facial nucleus 24 hours after injury was reduced by 60%. In contrast, the neuronal and astrocyte response was not affected. There was a normal increase in the neuropeptides calcitonin gene-related peptide and galanin, neuronal c-JUN, and NADPH-diaphorase and a decrease in choline acetyltransferase and acetylcholinesterase. Astrocyte glial fibrillary acidic protein immunoreactivity also showed a normal increase. There was a normal influx of macrophages and granulocytes into the injured facial nerve. Synaptic stripping, neuronal survival, and speed of axonal regeneration were also not affected. The current results show a strong, selective effect of MCSF on the early activation of microglia and, indirectly, on lymphocyte recruitment. This early phase of microglial activation appears not to be involved in the process of repair following peripheral nerve injury. However, it is important in the initiation of inflammatory changes in the brain and in the interaction with the immune system.

Long-term actions of vector-derived nerve growth factor or brain-derived neurotrophic factor on choline acetyltransferase and Trk receptor levels in the adult rat basal forebrain.

Trophic factor gene therapy may provide a rational treatment strategy for neurodegenerative disease. Recombinant adeno-associated virus vectors, incorporating a neuron-specific promoter driving bicistronic expression of green fluorescent protein and either nerve growth factor or brain-derived neurotrophic factor, transduced 10,000-15,000 neurons in the medial septum for periods of at least six months. Both cholinergic and non-cholinergic neurons expressed green fluorescent protein. Nerve growth factor and brain-derived neurotrophic factor vectors produced up to 50% increases in immunohistochemical detection of the acetylcholine-synthesizing enzyme in septal neurons ipsilateral to the injection. Increased levels of this enzyme, choline acetyltransferase, persisted for six months with the brain-derived neurotrophic factor vector. The nerve growth factor vector increased Trk receptor immunoreactivity in a volume of brain exceeding that of the transduced cells. Counterstaining for the neuronal marker, NeuN, or Nissl substance did not reveal any vector toxicity at any time-point. It therefore appears that the lasting effects of vector-mediated trophic factor gene transfer will offer a new approach for modulating septal cholinergic transmission and Trk receptor activity.

Do cardiac output and serum lactate levels indicate blood transfusion requirements in anemia of prematurity?

BACKGROUND: Whether and when to transfuse in anemia of prematurity is highly controversial. Some authors suggest transfusions simply if the hemoglobin (Hb) level is below a defined normal range. Others propose the use of clinical or laboratory parameters in anemic patients to decide whether to transfuse or not. HYPOTHESIS: A decreasing amount of circulating Hb should cause a compensatory increase in cardiac output (CO) and an increase in arterial serum lactate. MATERIALS AND METHODS: In 56 anemic preterm infants (not in respiratory or hemodynamic failure) we analyzed CO after the first week of life using a Doppler sonographic method. At the same time serum lactate levels, Hb levels and oxygen saturation were registered. Nineteen of these patients were given transfusion when they demonstrated clinical signs of anemia by tachycardia > 180/min, tachypnea, retractions, apneas and centralization (group 2). The remaining 37 patients were not transfused (group 1). Serum lactate, CO, heart rate (HR), oxygen delivery, respiratory rate, capillary refill and Hb were analyzed in both groups and in group 2 before and 12-24 h after transfusion. Data between groups 1 and 2 and in group 2 before and after transfusion were compared. RESULTS: In the 56 patients studied no linear correlation between Hb and CO or between Hb and serum lactate was found. Nor could any correlation be demonstrated between the other variables studied. Examining the subgroups separately, a negative linear correlation was demonstrated between serum lactate and oxygen delivery in group 2. No other significant correlations were detected. However, when the pre- and post-transfusion data were compared in group 2 (increase of Hb from 9.45 (SD 3.44) to 12.5 (SD 3.8) g/100 ml), the CO decreased from 281.3 (SD 162.6) to 224 (SD 95.7) ml/kg per min (p < 0.01) and serum lactate decreased significantly from 3.23 mmol/l (SD 2.07) before to 1.71 (SD 0.83) after transfusion. Oxygen delivery was 35.8 (+/- 0.19) ml/kg per min group 1, 27.8 (+/- 0.05) pre- and 43.4 (+/- 0.07) post-transfusion in group 2 (p < 0.01). CONCLUSIONS: CO measurements and serum lactate levels add little information to the decision-making process for blood transfusions, as neither CO nor serum lactate levels correlate with HB levels in an otherwise asymptomatic population of preterm infants. In infants where the indication for blood transfusion is made based on traditionally accepted clinical criteria, serum lactate is an additional laboratory indicator of impaired oxygenation, as it correlates significantly with oxygen delivery. A significant lower oxygen delivery in patients in whom blood transfusion is indicated and an increase in oxygen induced by transfusion demonstrate the value of these criteria in identifying preterm infants who benefit from transfusion.

Efficacy and safety of prolonged thromboprophylaxis with a low molecular weight heparin (dalteparin) after total hip arthroplasty--the Danish Prolonged Prophylaxis (DaPP) Study.

The aim of this study was to compare the efficacy and safety of prolonged (35 days) thromboprophylaxis with a standard length (7 days) regimen of a low molecular weight heparin in patients undergoing total hip arthroplasty. The study was multicentre, randomised, double-blind, and prospective with two groups. Following seven days on a standard length regimen of dalteparin (5000 antifactor Xa units subcutaneously once daily starting 12 h before surgery), patients were randomized to continue the prophylaxis with either subcutaneous injections of dalteparin or placebo injections for a further 28 days. Efficacy was evaluated at the end of the study (day 35) in all patients with bilateral ascending phlebography to detect deep vein thrombosis. Bleeding complications and other adverse events were registered throughout the study period. Three hundred consecutive patients agreed to participate before the operation: 281 were finally randomised and 215 completed the study; two patients died before randomisation; 17 developed deep vein thrombosis; none developed pulmonary embolism; and five of 113 patients (4.4%, 95% CI 1-10%) developed deep vein thrombosis in the dalteparin group, compared with 12 of 102 (11.8%; 95% CI 6-20%) in the placebo group (p=0.039). Deep vein thrombosis in the proximal veins was diagnosed in one patient (0.9%; 95% CI 0-5%) in the dalteparin group, and in five (5.0%; 95% CI 2-11%) in the placebo group (p=0.076). Major bleeding was observed in one patient in the placebo group; minor bleeding complications and adverse events were equally distributed between the groups. We concluded that prolonged (35 days) thrombo prophylaxis with dalteparin is more effective than a standard length (7 days) regimen without increased risk of bleeding complications or other adverse events.

Potential of neurotrophic factors in therapy of Parkinson's disease.

Neurotrophic factors of dopaminergic neurons may represent a potential neuroprotective therapy for PD. This article reviews published experiments that demonstrate the effects of neurotrophic factors on dopaminergic neurons in vitro and in vivo. At present this issue is predominantly investigated in basic neuroscientific research. Its possible future clinical relevance is discussed.

Pramipexole, a nonergot dopamine agonist, is effective against rest tremor in intermediate to advanced Parkinson's disease.

We evaluated the efficacy of the nonergot dopamine receptor agonist pramipexole in 16 patients with advanced Parkinson's disease and marked rest tremor during an "on" period. The patients were drawn from a larger placebo-controlled, double-blind, randomized trial, which was not originally designed to investigate the effect of pramipexole on tremor. Eleven patients received pramipexole. The first effects were seen with a pramipexole dose of 0.75 mg/d with a reduction of the tremor item A of Unified Parkinson's Disease Rating Scale (UPDRS III, "on" state) by 25% and of rigidity and akinesia by 22%. Under the highest dose, 4.5 mg/d, the tremor score was improved by 61% over baseline (p < 0.0056, Wilcoxon signed rank) and the sum of rigidity and akinesia items by 66% (p < 0.0038, Wilcoxon signed rank). Five patients received placebo and did not improve. Based on this sample of patients, the nonergot dopamine receptor agonist pramipexole appears to have a potent anti-rest tremor action while being effective against akinesia and rigidity.

Late-onset myoclonic epilepsy in Down's syndrome (LOMEDS).

The aim of this paper is to report a patient with late-onset myoclonic epilepsy in Down's syndrome (LOMEDS) as a differential diagnosis of adult-onset progressive myoclonic epilepsies. A 55-year-old male with Down's syndrome (DS) is described who developed progressively frequent myoclonus and generalized myoclonic-tonic seizures (GMTSs) at the age of 52. EEG recordings demonstrated background slowing and generalized polyspike-wave discharges occasionally associated with myoclonic jerks, leading to the classification of primary generalized epileptic myoclonus. Descriptions of late-onset epilepsy in DS patients are rare. However, a review of the pertinent literature revealed at least two other cases of elderly DS patients developing progressive myoclonic epilepsy after the onset of dementia. We suggest that late-onset myoclonic epilepsy in Down's syndrome as characterized here should be considered in the differential diagnosis of adult-onset myoclonic epilepsies. LOMEDS apparently shares features with myoclonic epilepsy in Alzheimer's disease (AD) and Unverricht-Lundborg disease (ULD) caused by a mutation on chromosome 21. Since life expectation of DS patients has markedly increased, LOMEDS may be more frequent than currently acknowledged.