[Practical Use of the Levodopa Pump]. / Praktische Anwendung der Levodopa-Pumpe.

Patients with advanced Parkinson's disease and motor complications undergoing optimized oral therapy can significantly benefit from continuous intrajejunal levodopa/carbidopa infusion applied by means of a medication pump. However, this requires a correctly positioned PEG-J tube and finely adjusted pump settings. Although this method is a routine procedure in specialist centers, no standard procedure has been defined up to now. For this reason, an expert recommendation regarding the practical application has been developed in order to standardize the procedure and facilitate patient access to this treatment option.

Strategies in probabilistic feedback learning in Parkinson patients OFF medication.

Studies on classification learning suggested that altered dopamine function in Parkinson's Disease (PD) specifically affects learning from feedback. In patients OFF medication, enhanced learning from negative feedback has been described. This learning bias was not seen in observational learning from feedback, indicating different neural mechanisms for this type of learning. The present study aimed to compare the acquisition of stimulus-response-outcome associations in PD patients OFF medication and healthy control subjects in active and observational learning. 16 PD patients OFF medication and 16 controls were examined with three parallel learning tasks each, two feedback-based (active and observational) and one non-feedback-based paired associates task. No acquisition deficit was seen in the patients for any of the tasks. More detailed analyses on the learning strategies did, however, reveal that the patients showed more lose-shift responses during active feedback learning than controls, and that lose-shift and win-stay responses more strongly determined performance accuracy in patients than controls. For observational feedback learning, the performance of both groups correlated similarly with the performance in non-feedback-based paired associates learning and with the accuracy of observed performance. Also, patients and controls showed comparable evidence of feedback processing in observational learning. In active feedback learning, PD patients use alternative learning strategies than healthy controls. Analyses on observational learning did not yield differences between patients and controls, adding to recent evidence of a differential role of the human striatum in active and observational learning from feedback.

Long-term evaluation of impedance levels and clinical development in subthalamic deep brain stimulation for Parkinson's disease.

BACKGROUND: This study was conducted to better understand the development of clinical efficacy and impedance levels in the long-term course of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD). METHODS: In this retrospective study of twenty PD patients, the motor part of the Unified Parkinson's Disease Rating Scale was periodically assessed i) after withdrawal of medication and inactivated stimulation, ii) after withdrawal of medication with activated stimulation and iii) after challenge with l-Dopa during activated stimulation up to 13 years after surgery. RESULTS: STN-DBS with or without medication significantly improved motor function up to 13 years after surgery. The contribution of axial symptoms increased over time. While the stimulation parameters were kept constant, the therapeutic impedances progressively declined. CONCLUSION: STN-DBS in PD remains effective in the long-term course of the disease. Constant current stimulation might be preferable over voltage-controlled stimulation, as it would alleviate the impact of impedance changes on the volume of tissue activated.

Cortical activation associated with asterixis in manifest hepatic encephalopathy.

OBJECTIVES: Severe hepatic encephalopathy gives rise to asterixis, a striking motor symptom also called flapping tremor, which is characterized by a sudden ceasing of muscle tone in all muscles of a limb. In this study, we aimed at scrutinizing the cortical activation associated with asterixis and unraveling the underlying pathophysiological mechanisms. MATERIAL AND METHODS: We recorded simultaneously neural activity with magnetoencephalography (MEG) and muscle activity with surface EMG in nine patients with manifest hepatic encephalopathy showing asterixis. Asterixis events were detected semiautomatically and served as triggers for averaging MEG signals. Evoked responses averaged time-locked to asterixis events were subjected to equivalent current dipole (ECD) modeling. Additionally, we localized the strongest cortico-muscular coherence in the frequency of the co-occurring tremulousness. RESULTS: Evoked fields averaged time-locked to asterixis events were best explained by a single dipolar source in the contralateral primary motor cortex (M1, Talairach coordinates of mean localization: -40, -20, and 64; Brodmann area 4). This dipole showed a twofold field reversal, that is biphasic wave, with frontal dipole orientation at 49 ms before flap onset and 99 ms after flap onset. Conversely, two maxima with occipital dipole orientation were observed 2 ms and 160 ms after flap onset. Cortico-muscular coherence for the tremulousness was likewise localized in the contralateral M1 confirming earlier findings in the present patient cohort. CONCLUSIONS: Our results reveal an involvement of M1 in the generation of asterixis. As also tremulousness, also called mini-asterixis, was shown to originate in M1, asterixis and mini-asterixis may share common pathophysiological mechanisms.

Motor-cortical oscillations in early stages of Parkinson's disease.

Pathophysiological changes in basal ganglia-thalamo-cortical circuits are well established in idiopathic Parkinson's disease (PD). However, it remains open whether such alterations already occur at early stages representing a characteristic neurophysiological marker of PD. Therefore, the present study aims at elucidating changes of synchronised oscillatory activity in early PD patients. In this study, we performed whole-head magnetoencephalography (MEG) in a resting condition and during steady state contraction of the more severely affected forearm in 10 drug­naive, de novo patients, in 10 early-stage patients with chronic medication and in 10 age-matched control subjects. While cortico-muscular coherence (CMC) did not differ between groups, patients showed increased sensori-motor cortical power at beta frequency (13­30 Hz) during rest as well as during isometric contraction compared to controls. In healthy control subjects the power of the contralateral hemisphere was significantly suppressed during isometric contraction. By contrast, both hemispheres were activated equally strongly in de novo patients. In medicated patients, the pattern was found to be reversed. Contralateral beta power was significantly correlated with motor impairment during isometric contraction but not during rest. The present results suggest that the reduced ability of the primary motor cortex to disengage from increased beta band oscillations during the execution of movements is an early marker of PD.

[Deep brain stimulation - expectations and doubts. A nationwide questionnaire study of patients with Parkinson's disease and their family members]. / Tiefe Hirnstimulation - Erwartungen und Bedenken. Bundesweite Fragebogenstudie mit Parkinson-Patienten und deren Angehörigen.

BACKGROUND: The aim of this questionnaire-based study was to determine the decision-making motives from Parkinson's patients and their family members for deep brain stimulation (DBS), which are crucial for the attitude towards this therapy and which should be considered during the clinical interview. MATERIAL AND METHODS: The questionnaire was sent out nationwide to members of the German Parkinson Association. Patient and family specific data as well as information sources, doubts and expectations with respect to DBS were assessed. RESULTS: A total of 582 patients and 476 family members answered the questionnaire, revealing that 96% of the patients and 91% of the family members already possessed information regarding DBS. While a large proportion of interviewees had specific expectations concerning DBS, more than two thirds expressed concerns regarding DBS; the most frequent with respect to intraoperative complications and stimulation-induced worsening of symptoms. The quantity of realistic patients and family expectations significantly correlated with a positive evaluation of DBS and doubts as well as unrealistic expectations of family members correlated with a negative attitude towards the operation. CONCLUSIONS: The findings suggest that patients and their relatives organized in support groups indeed possess detailed information regarding DBS. However, for the acceptance of the treatment a timely elucidation about DBS as well as responding to the individual concerns by the consulting physician is essential.

Motor impairment in liver cirrhosis without and with minimal hepatic encephalopathy.

AIM: Manifest hepatic encephalopathy (HE) goes along with motor symptoms such as ataxia, mini-asterixis, and asterixis. The relevance of motor impairments in cirrhotics without and with minimal HE (mHE) is still a matter of debate. PATIENTS AND METHODS: We tested three different groups of patients with liver cirrhosis: no signs of HE (HE 0), mHE, and manifest HE grade 1 according to the West Haven criteria (HE 1). All patients (n = 24) and 11 healthy control subjects were neuropsychometrically tested including critical flicker frequency (CFF), a reliable measure for HE. Motor abilities were assessed using Fahn Tremor Scale and International Ataxia Rating Scale. Fastest alternating index finger movements were analyzed for frequency and amplitude. RESULTS: Statistical analyses showed an effect of HE grade on tremor and ataxia (P < 0.01). Additionally, both ratings yielded strong negative correlation with CFF (P < 0.01, R = -0.5). Analysis of finger movements revealed an effect of HE grade on movement frequency (P < 0.03). Moreover, decreasing movement frequency and increasing movement amplitude parallel decreasing CFF (P < 0.01, R = 0.6). CONCLUSION: Our results indicate that ataxia, tremor, and slowing of finger movements are early markers for cerebral dysfunction in HE patients even prior to neuropsychometric alterations becoming detectable.

Deep brain stimulation in Parkinson's disease.

During the last 15 years deep brain stimulation (DBS) has been established as a highly-effective therapy for advanced Parkinson's disease (PD). Patient selection, stereotactic implantation, postoperative stimulator programming and patient care requires a multi-disciplinary team including movement disorders specialists in neurology and functional neurosurgery. To treat medically refractory levodopa-induced motor complications or resistant tremor the preferred target for high-frequency DBS is the subthalamic nucleus (STN). STN-DBS results in significant reduction of dyskinesias and dopaminergic medication, improvement of all cardinal motor symptoms with sustained long-term benefits, and significant improvement of quality of life when compared with best medical treatment. These benefits have to be weighed against potential surgery-related adverse events, device-related complications, and stimulus-induced side effects. The mean disease duration before initiating DBS in PD is currently about 13 years. It is presently investigated whether the optimal timing for implantation may be at an earlier disease-stage to prevent psychosocial decline and to maintain quality of life for a longer period of time.

Detection of structural changes of the human brain in longitudinally acquired MR images by deformation field morphometry: methodological analysis, validation and application.

The progression of neurodegenerative diseases as well as healthy aging is accompanied by structural changes of the brain. These changes are often only subtle when considered over time intervals of several months. Therefore morphometrical techniques for their detection in longitudinally acquired MR images must be highly sensitive, and they require a careful validation. In the present study, a novel processing chain for a longitudinal analysis based on deformation field morphometry is described. Procedures for its quantitative validation are also reported: Deformation fields were computed for the simulation of non-linear, local structural changes of human brains. Applying these deformation fields to "original" MR images yielded deformed MR images. The volume changes defined by the deformation fields represented the standard, against which the results of the longitudinal analysis of each pair of original and deformed MR image were compared. The proposed processing chain enabled to localize and to quantify simulated local atrophies near the cortex as well as in deep brain structures. An exemplary analysis of serial MR images of a patient suffering from an atypical Parkinson syndrome (cortico-basal degeneration, CBD) and healthy control subjects is presented, showing a characteristic pattern of volume changes in the brain of the patient which is strikingly different from the controls' patterns of changes.

Impaired cerebral oscillatory processing in hepatic encephalopathy.

OBJECTIVE: Hepatic encephalopathy (HE) is characterized by neuropsychological and motor deficits. The present study tested the hypothesis that worsening of motor and sensory symptoms of HE results from a common basic deficit in the cerebral oscillatory processing within the human motor and visual system. METHODS: We investigated in 32 patients with liver cirrhosis and HE grades 0-2 critical flicker frequency (CFF) and cortico-muscular (M1-EMG) coherence as a measure of coupling between the surface EMGs of hand muscles and primary motor cortex (M1) activity recorded non-invasively with magnetoencephalography (MEG) during forearm elevation. RESULTS: Patients with HE-grade 2 developed excessive M1-EMG coherence at low frequencies. In contrast, maximum M1-EMG coherence in patients with no HE showed frequency and amplitude in the physiological range. CFF was continuously reduced with worsening grades of HE. Correlation analysis revealed significant correlation between the frequency of M1-EMG coherence and CFF. CONCLUSIONS: Taken together, we demonstrate that increased grades of HE lead to a pathological M1-EMG drive which is reduced in frequency. These effects are correlated with an impaired perception of oscillatory visual stimuli. SIGNIFICANCE: The results suggest that pathological oscillatory neural processing in different human cerebral systems may represent a basic mechanism for the clinical manifestation of HE.

[Cerebral imaging for Wilson disease]. / Zerebrale Bildgebung bei Morbus Wilson.

Wilson disease is an autosomal recessive inherited copper metabolic disorder that is characterized by diminished biliary excretion of copper and a raised serum level of free copper. This leads to a toxic copper accumulation, particularly in the liver and the brain. Therefore, clinical symptoms are dominated by hepatic and extrapyramidal symptoms. Untreated Wilson disease has an unfavorable outcome. Cerebral changes are depicted most sensitively by magnetic resonance tomography. Pathological findings mainly focus on the basal ganglia, the midbrain and the brainstem. Depending on the therapy and the severity of the neurological symptoms, signal increase as well as signal decrease may be observed in T1-weighted (T1w) and T2-weighted (T2w) images and can be reversible when using an appropriate therapy. Hyperintense areas in T2-weighted images are induced by edema, gliosis, demyelinisation or cystic degeneration. Signal increase in T1-weighted images are found in patients with hepatic insufficiency and are probably due to manganese deposits. Signal decrease in T2-weighted images is probably caused by the paramagnetic effect of the copper accumulation. Furthermore, recent studies show a correlation between the clinical severity and changes in diffusion-weighted sequences. Although cross-section imaging plays a rather subordinate role in the primary diagnostics of Wilson disease, the described cerebral changes in patients with extrapyramidal disturbances should include Wilson disease in the differential. Persistent or progressive hyperintense lesions in T2-weighted images reflect therapy failure, and clinical recovery correlates to an improvement in MR images. Therefore, repeat MR imaging can be used to monitor medical therapy.

In vivo changes in the neuroforaminal size at flexion-extension and axial rotation of the cervical spine in healthy persons examined using kinematic magnetic resonance imaging.

STUDY DESIGN: In vivo flexion-extension and axial rotation magnetic resonance imaging (MRI) studies of the cervical spine were performed inside a positioning device. OBJECTIVE: To determine the functional changes of neuroforaminal size that occur during flexion-extension and axial rotation of the cervical spine in healthy persons. SUMMARY OF BACKGROUND DATA: Kinematic MRI studies of the cervical spine were performed to obtain detailed information about the functional changes that occur in neuroforaminal size during flexion-extention and axial rotation. The results were compared with published data of in vitro functional flexion-extension and axial rotation studies of the cervical spine. METHODS: Inside a positioning device, the cervical spines of 30 healthy persons were examined in a whole-body magnetic resonance scanner from 40 degrees of flexion to 30 degrees of extension at nine different angle positions. In addition, axial rotation was performed at neutral position (0 degrees ) and at 20 degrees and 40 degrees of axial rotation to both sides. The images were analyzed with respect to the neuroforaminal size at each position using a reformatted 3D-FISP sequence. RESULTS: At flexion, widening of the neuroforaminal size of up to 31% (compared with neutral position, 0 degrees ) was observed. Conversely, at extension a decrease in the size of the neuroforamen of up to 20% was recognized. At 20 degrees and 40 degrees of ipsilateral rotation of the head, a reduction in the neuroforaminal size of up to 15% and 23%, respectively, compared with the neutral position was noted. In contrast, a widening of the foraminal size was recognized on the contralateral side of 9% and 20% at 20 degrees and 40 degrees rotation. Statistically significant differences (p <== 0.05) were found in the neuroforaminal size between different degrees of flexion and extension and in addition for axial rotation compared to neutral position (0 degrees ). CONCLUSION: Compared with the results of previous biomechanical studies of human cadaver cervical spines, kinematic MRI provides additional noninvasive data concerning the physiological changes of the neuroforaminal size during flexion-extension and axial rotation in healthy individuals.