[Parasomnia and paroxysmal dyskinesia]. / Parasomnien und paroxysmale Dyskinesien.

Short involuntary paroxysmal movements or behavioral patterns are an important differential diagnosis to epileptic seizures, especially when occurring for the first time. Typically, these attacks are not witnessed by medically trained personnel and the patient anamnesis or observations by a third party are often not specific enough to differentiate between epileptic seizures and the differential diagnoses. This review presents the epidemiology, the clinical presentation, the necessary diagnostic steps and the differential diagnostic approach to parasomnias and dyskinesias. The focus is on the clinical aspects, and therapeutic principles are also briefly described.

Anticipatory postural adjustments are unaffected by age and are not absent in patients with the freezing of gait phenomenon.

In bipedal gait, the initiation of the first step is preceded by a complex sequence of movements which shift the centre of mass of the body towards the stance foot to allow for a step of the swing foot. These anticipatory postural adjustments (APAs) have been investigated in order to elucidate movement strategies in healthy and diseased persons. We studied the influence of several external parameters (age, type of step initiation) on APAs and investigated whether Parkinsonian patients may have different APAs. As a result, we found that externally elicited steps were preceded by faster and larger APAs than self-timed steps. Parkinsonian patients without the freezing of gait (FOG) phenomenon showed overall slightly reduced APAs but did not clearly differ from patients with FOG. Multiple APAs were seen in up to 25 % of the steps of the patients and in a much lower percentage of the steps of control subjects. The results indicate that APAs are significantly influenced by the timing of a step, i.e. are larger in externally elicited steps. The patients showed an overall preserved APA pattern but slowed movements and amplitude, indicating that increased bradykinesia due to progressive illness is a plausible explanation for these findings. The freezing phenomenon is not explained by a general absence or massive reduction in APA measures.

Intermediate latency evoked potentials of cortical multimodal vestibular areas: acoustic stimulation.

OBJECTIVE: Loud acoustic stimuli at 500Hz activate the vestibular system. Intermediate-latency vestibular cortical potentials of multimodal cortex regions were investigated, beyond the 20ms time range. METHODS: Eighteen healthy subjects with 32-channel EEG and one epilepsy patient with right-sided intracortical electrodes received three types of stimuli: tone bursts capable of evoking vestibular evoked myogenic potentials (VEMP) in neck muscles and sham stimuli matched for either frequency or amplitude, which cannot evoke myogenic responses. RESULTS: VEMP-capable stimuli activated anterior insula and posterior operculum bilaterally at 20, 30, 60 and 110ms, frontal brain regions at 70 and 110ms, determined by Brain Evoked Source Analysis BESA. Recordings from intracranial electrodes revealed corresponding peaks at identical latencies. Stimulus-locked high and low beta and mu band modulations were found in vestibular, parietal and occipital regions, beyond 20ms. Sham stimuli only evoked late acoustic potentials. Corresponding vestibular potentials were also seen in an eight-channel bipolar Laplacian montage. CONCLUSIONS: The sequentially appearing cortical potentials evoked by VEMP-capable stimuli co-locate with data from functional imaging studies. Frequency-specific activity (induced potentials) in these areas may reflect multimodal proprioceptive and visual sensory crosstalk. SIGNIFICANCE: Vestibular cortical evoked potentials may see clinical use in vertigo disorders.

Normative data for arm swing asymmetry: how (a)symmetrical are we?

Arm swing asymmetry during gait may be a sensitive sign for early Parkinson's disease. There is only very limited information about how much asymmetry can be considered to be physiological. To assess the normal range of arm swing asymmetry, we investigated 60 healthy subjects. The influence of age, gender, and additional mental tasks (dual-tasking) on arm swing asymmetry was assessed. Limb kinematics of 60 healthy persons in three age groups (between 40 and 75 years) were measured with an ultrasound motion capture system while subjects walked on a treadmill. Treadmill velocity was varied (3 steps) and mental loads (2 different tasks) were applied in different trials. Additionally, a group of 7 patients with early Parkinson's disease was investigated. Arm swing amplitude as well as arm swing asymmetry varied considerably in the healthy subjects. Elderly subjects swung their arms more than younger participants. Only the more demanding mental load caused a significant asymmetry, i.e., arm swing was reduced on the right side. In the patient group, asymmetry was considerably higher and even more enhanced by mental loads. Our data indicate that an asymmetry index above 50 (i.e., one side has twice the amplitude of the other) may be considered abnormal. Evaluation of arm swing asymmetry may be used as part of a test battery for early Parkinson's disease. Such testing may become even more important when disease-modifying drugs become available for Parkinson's disease.

Limited cleavage of tau with matrix-metalloproteinase MMP-9, but not MMP-3, enhances tau oligomer formation.

Tauopathies such as Alzheimer's disease or progressive supranuclear palsy are characterized by pathological deposits of aggregated protein tau. It has been shown that truncated tau is present in these deposits, and it was thus hypothesized that truncation of the protein may play a role in pathological aggregation processes. Furthermore, recent findings indicate that pro-aggregatory extracellular tau can be taken up by neurons and induce neurodegeneration. In this study, we investigated the effect of limited proteolysis by matrix-metalloproteinases 3 and 9 (MMP-3, MMP-9) as well as by the proteinases trypsine and Proteinase K (PK) on tau aggregation behavior. We applied single molecule fluorescence techniques to monitor early tau oligomer formation at nanomolar protein concentrations. We observed that tau is a substrate of both MMP-3 and MMP-9, and show that limited proteolysis by MMP-9, but not by MMP-3, PK or trypsine, increases tau oligomer formation. We further characterize tau fragments resulting from limited cleavage, demonstrating a distinct cleavage pattern for both MMP-3 and MMP-9. In summary, our data demonstrate that tau is a substrate of both MMP-3 and MMP-9, and show a differential influence of these enzymes on tau aggregation behavior, implicating a potential role in neurodegeneration.

Estudio de cohortes sobre la carga socioeconómica de la enfermedad de Parkinson en Portugal / Health-economic burden of Parkinson’s disease in Portugal: a cohort study

Introducción. La enfermedad de Parkinson (EP) es un trastorno neurodegenerativo frecuente que acarrea una considerable carga socioeconómica. Las evaluaciones económicas de la EP en los países del sur de Europa son escasas. Objetivo. Valorar los costes de la EP en una cohorte de pacientes ambulatorios de Portugal. Pacientes y métodos. Se reclutó a 49 pacientes consecutivos con EP en un centro ambulatorio de neurología adscrito a la Universidad de Lisboa entre octubre de 2004 y diciembre de 2005. El estado clínico se evaluó con la escala unificada de evaluación de la EP y la escala de Hoehn y Yahr. Los costes se evaluaron desde la perspectiva social mediante cuestionarios de economía de la salud. El cálculo de los costes indirectos se llevó a cabo aplicando el criterio del capital humano. La calidad de vida relacionada con la salud se valoró por medio del cuestionario EuroQoL (EQ-5D). Resultados. Los costes directos ascendieron a 2.717 euros (intervalo de confianza al 95%, IC 95% = 1.147-3.351) por paciente a lo largo de un semestre. Los principales contribuyentes a los costes directos fueron los medicamentos, con 544 euros (IC 95% = 426-6.940), y los ingresos hospitalarios, con 690 euros (IC 95% = 229-1.944). Los costes indirectos totalizaron 850 euros (IC 95% = 397-1.529), mientras que los gastos sufragados por el paciente constituyeron el 12% de los costes directos. La asistencia facilitada por la familia y otros allegados tuvo un papel destacado. En general, los costes resultaron inferiores a los de otros países occidentales. Conclusiones. La EP acarrea una considerable carga económica en Portugal. Entre los principales componentes del coste se encuentran la medicación y los gastos de hospitalización. Es preciso proseguir las investigaciones para describir unos patrones detallados de la utilización de los servicios sanitarios en Portugal y orientar las decisiones de política sanitaria de manera más efectiva (AU)

Introduction. Parkinson’s disease (PD) is a common neurodegenerative disorder with a considerable socioeconomic burden. Health-economic evaluations of PD in the Southern European countries are limited. Aim. To evaluate the costs of PD in an outpatient cohort in Portugal. Patients and methods. 49 consecutive PD patients were recruited at the neurological outpatient clinic of the University of Lisbon between October 2004 and December 2005. Clinical status was evaluated using the Unified Parkinson’s Disease Rating Scale and the Hoehn & Yahr stages. Costs were assessed from the societal perspective using health-economic questionnaires. Human capital approach was used to estimate indirect costs. Health-related quality of life was evaluated by means of the EQ-5D. Results. Direct costs were 2,717 euros (95% CI = 1,147-3,351) per patient for a six-month period. Main contributors to the direct costs included drugs (544 euros; 95% CI = 426-6,940) and hospitalizations (690 euros; 95% CI = 229-1,944). Indirect costs amounted to 850 euros (95% CI = 397-1,529), whereas patient expenditures constituted 12% of direct costs. Assistance by family and other relatives played a major role. In general, costs were lower than in other Western countries. Conclusions. The economic burden of PD in Portugal is considerable. Important cost components include medications and hospitalizations. More research is needed in order to describe a comprehensive health service patterns in Portugal and to guide health policy decisions more effectively (AU)

[Health-economic burden of Parkinson's disease in Portugal: a cohort study]. / Estudio de cohortes sobre la carga socioeconomica de la enfermedad de Parkinson en Portugal.

INTRODUCTION: Parkinson's disease (PD) is a common neurodegenerative disorder with a considerable socioeconomic burden. Health-economic evaluations of PD in the Southern European countries are limited. AIM: To evaluate the costs of PD in an outpatient cohort in Portugal. PATIENTS AND METHODS: 49 consecutive PD patients were recruited at the neurological outpatient clinic of the University of Lisbon between October 2004 and December 2005. Clinical status was evaluated using the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr stages. Costs were assessed from the societal perspective using health-economic questionnaires. Human capital approach was used to estimate indirect costs. Health-related quality of life was evaluated by means of the EQ-5D. RESULTS: Direct costs were 2,717 euros (95% CI = 1,147-3,351) per patient for a six-month period. Main contributors to the direct costs included drugs (544 euros; 95% CI = 426-6,940) and hospitalizations (690 euros; 95% CI = 229-1,944). Indirect costs amounted to 850 euros (95% CI = 397-1,529), whereas patient expenditures constituted 12% of direct costs. Assistance by family and other relatives played a major role. In general, costs were lower than in other Western countries. CONCLUSIONS: The economic burden of PD in Portugal is considerable. Important cost components include medications and hospitalizations. More research is needed in order to describe a comprehensive health service patterns in Portugal and to guide health policy decisions more effectively.

[Parkinson's disease: cost-of-illness in an outpatient cohort]. / Morbus Parkinson: Krankheitskosten einer ambulanten Patientenkohorte.

OBJECTIVE: The aim of this study was to evaluate the direct and indirect costs in a cohort of German outpatients with Parkinson's disease (PD) and to identify major cost drivers in PD. METHODS: 91 PD patients were consecutively enrolled in the outpatient department of the neurological clinic at the University of Marburg, Germany. Patients had to fill out a standardised questionnaire at baseline and at a 3-month follow-up and report their health service resource utilisation for the past three months, retrospectively. In addition, information on clinical parameters of PD (UPDRS, Hoehn and Yahr stage) were assessed. For 86 patients, the direct and indirect cost data were analysed. Indirect costs were calculated by the human capital approach. RESULTS: Total costs per patient and 6-month period amounted to € 8,400 [95%CI 6,768-10,302]. Of these, 30% were indirect costs (€ 2,505 [95%CI 1,541-4,047]) and 70% were direct costs (€ 5,895 [95%CI 4,846-7,376]). The major parts of the direct costs were triggered by antiparkinsonian medication (€ 2,889 [95%CI 2,392-3,655]) and inpatient stays (hospital und rehabilitation, € 1,556 [95%CI 865-2,892]). A linear multivariate model with disease severity, disease duration, sleep disorders, psychosis and dystonia explained 24% of the variance of total costs and 33% of variance of direct costs, respectively. CONCLUSION: Parkinson's disease imposes a high financial burden on both patient and society. A reduced health-related quality of life reflects the individual patient's impairment by PD.

Long-term efficacy and safety of chronic globus pallidus internus stimulation in different types of primary dystonia.

BACKGROUND: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) offers a very promising therapy for medically intractable dystonia. However, little is known about the long-term benefit and safety of this procedure. We therefore performed a retrospective long-term analysis of 18 patients (age 12-78 years) suffering from primary generalized (9), segmental (6) or focal (3) dystonia (minimum follow-up: 36 months). METHODS: Outcome was assessed using the Burke-Fahn-Marsden (BFM) scores (generalized dystonia) and the Tsui score (focal/segmental dystonia). Follow-up ranged between 37 and 90 months (mean 60 months). RESULTS: Patients with generalized dystonia showed a mean improvement in the BFM movement score of 39.4% (range 0-68.8%), 42.5% (range -16.0 to 81.3%) and 46.8% (range -2.7 to 83.1%) at the 3- and 12-month, and long-term follow-up, respectively. In focal/segmental dystonia, the mean reduction in the Tsui score was 36.8% (range 0-100%), 65.1% (range 16.7-100%) and 59.8% (range 16.7-100%) at the 3- and 12-month, and long-term follow-up, respectively. Local infections were noted in 2 patients and hardware problems (electrode dislocation and breakage of the extension cable) in 1 patient. CONCLUSION: Our data showed Gpi-DBS to offer a very effective and safe therapy for different kinds of primary dystonia, with a significant long-term benefit in the majority of cases.

[Local botulinum toxin A for treating chronic sialorrhea]. / Lokale Botulinumtoxin-A-Therapie bei chronischer Sialorrhö.

BACKGROUND: Sialorrhea and drooling interfere with oral communication and nutrition, posing problems for hygiene, nursing, and social interactions. Therapeutic efforts such as swallowing therapy, systemic medications, operations, and irradiation are often insufficient or accompanied by side effects. MATERIALS AND METHODS: Ten patients with therapy-resistant sialorrhea of various etiologies were treated between 2002 and 2007 with sonography-guided botulinum toxin A (BTA) injections into the parotid and submandibular glands bilaterally. Therapeutic success was evaluated using established symptom scores, and the glandular tissue size was sonographically measured before and 3 months after injections. RESULTS: All 10 patients benefited from the BTA therapy, as shown by significant reduction of the troublesome sialorrhea. The effect lasted 6-28 weeks. On one occasion, transient xerostomia occurred. Sonographic measurements revealed no morphologic changes. CONCLUSION: BTA is an effective and safe treatment for chronic sialorrhea. The effect is reversible. It causes no sonographically detectable changes.

[First experiences in deep brain stimulation for cervical dystonia]. / Tiefe Hirnstimulation bei zervikaler Dystonie. Erste Erfahrungen.

BACKGROUND: Cervical dystonia results in severe disability and cannot be effectively treated with medication. Repeat injections of botulinum toxin into the dystonic neck muscles can relieve the symptoms in most patients. When this treatment fails (mostly due to antibody formation), deep brain stimulation can be considered. PATIENTS AND METHODS: We report our experiences with eight patients who were treated with bilateral deep brain stimulation of the globus pallidus interna for cervical dystonia. The mean observation period was 31 months. RESULTS: Six of eight patients experienced relief from symptoms a few days after the implantation. Improvement of symptoms was a mean of 60% during the 1st year. There were no complications. CONCLUSION: In this and in other studies with small numbers of patients, deep brain stimulation has shown a good effect on cervical dystonia. According to our results, the patients who benefit most are those with no dystonic shoulder involvement and who have a tonic rather than clonic symptomatology. It seems probable that deep brain stimulation will become the therapy of choice for otherwise intractable cervical dystonia.

[Parkinson's disease--new horizons]. / Neue Erkenntnisse verändern die Therapie des Morbus Parkinson. Lässt sich der Krankheitsausbruch bald verhindern?

New information about the pathology and genetics of Parkinson's disease opens up new possibilities for treatment. A key role is played by a pathologically folded protein, the distribution of which in the brain permits new conclusions about the stage of the disease. Gene mutations in affected families provide further clues as to the pathological process. In addition to symptom control, future treatment strategies will be aimed in particular at slowing down the underlying pathological process, and will therefore go in the direction of neuroprotection and neurorestoration. Dopamine agonists that can slow cell degeneration are already the first-line treatment in patients under 70 years of age.

Postural reflexes evoked by tapping forehead and chest.

We investigated whether a tap with a reflex hammer to the forehead can elicit responses in the leg muscles and whether vestibular stimulation is the crucial prerequisite for eliciting these responses. We also measured the postural changes caused by the tap and by the compensatory, presumably reflex-like reactions of the subject. Tap-evoked activity of leg muscles was easily elicited during upright stance in normal subjects and was also seen in two subjects without vestibular function. The pattern of muscle activation clearly showed a counteraction to the tap-evoked perturbation of stance. Taps applied to the chest elicited similar reflexes. Since these two conditions imply a different activation of the vestibular apparatus, the vestibular input alone cannot account for the observed leg muscle reflexes. We suggest that multisensory reflex pathways that integrate vestibular and proprioceptive inputs account for these reflexes.

Contraversive eye deviation during deep brain stimulation of the globus pallidus internus.

Clinical signs help determine correct electrode positioning during stereotactic implantation for chronic high-frequency pallidal stimulation in Parkinson's diease (PD). The authors describe a patient who had marked, sustained, contraversive eye deviation caused by stimulation during pallidal surgery. The underlying mechanism is probably an excitation of fibers in the internal capsule by volume-conducted current spread. Such conjugate eye deviation is thus not necessarily an indication of incorrect electrode placement.

[Gliomatosis cerebri: two case reports with atypical clinical and neuroradiologic findings]. / Gliomatosis cerebri. Zwei Fallberichte mit atypischer klinischer und neuroradiologischer Befundkonstellation.

The diagnosis of the rare disease Gliomatosis cerebri requires the correlation of clinical, radiological, and pathological findings. We report on two patients with intravitally diagnosed gliomatosis cerebri. Due to the unusually high malignancy of the tumor cells, diagnosis was complicated by atypical findings such as gadolinium enhancement in MRI and raised intracranial pressure. The clinical course, differential diagnosis, and literature are summarized briefly.

Dipole source analysis in persistent mirror movements.

To elucidate the pathomechanism underlying persistent mirror movements (MM), we modelled the origin of electric brain activity associated with these movements. Movement-related cortical potentials (MRCP) in a group of subjects affected by persistent mirror movements were compared with those of a control group. The data of the normal subjects were best explained with two bilaterally active electric sources in the sensorimotor cortices with a clear preponderance of the hemisphere contralateral to the movement. In contrast, the MM subjects presented a fairly symmetric source activity in both hemispheres during unilateral intended movements. In the control group, the source representing the activity of the motor cortex ipsilateral to the moving finger reduced activity before the beginning of the movement; this was interpreted as an inhibition of the ipsilateral motor cortex during unilateral movement. In the MM group, however, this inhibition was not seen. Furthermore, while normal subjects demonstrated no relevant activity of an additional source placed near midline motor structures (supplementary motor area; SMA), subjects with MM showed considerable activity of this dipole source. These findings suggest that subjects with persistent MM have abnormal bilateral activation of the primary motor areas, probably together with an additional activation of mesial motor structures. This assumption fits well with the observation of an incomplete decussation of the pyramidal tract. The bilateral activation is then explained as a compensatory strategy in order to achieve sufficient force in the innervated target muscles.