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Biomedical subjects

H M Mehdorn

Publications and source records attributed to H M Mehdorn.

At least 19 recordsLinked to original sources

Role of potassium channels in the relaxation induced by the nitric oxide (NO) donor DEA/NO in the isolated rat basilar artery.

This study investigates whether potassium ion (K+) channels are involved in the nitric oxide (NO)-induced relaxation in segments of the isolated rat basilar artery, mounted onto a wire myograph. A high extracellular K+ concentration partly inhibited the relaxant effects of the NO donors DEA/NO and SIN-1 (3-morpholino-sydnonimine). Whereas single applications of the K+ channel inhibitors tetraethyl-ammonium (10(-3) M), glibenclamide (10(-6) M), 4-aminopyridine (10(-3) M), or BaCl(2) (5 x 10(-5) M) did not affect the responses to DEA/NO, a combination of these inhibitors reduced the effects of DEA/NO. These data suggest, that the relaxant effects of NO donors are partly mediated via activation of K+channels. Different K+ channel types seem to be involved that function in a redundant manner and compensate for each other.

4-Aminopyridine↗

Effects of bilateral subthalamic nucleus stimulation on parkinsonian gait.

Gait analysis was carried out to assess the effects of L-dopa and bilateral subthalamic nucleus stimulation on gait velocity, cadence, stride length, and gait kinematics in nine patients with PD. Substantial effects of bilateral subthalamic nucleus stimulation on gait, with an increase in gait velocity and stride length comparable to that of a suprathreshold L-dopa dose, were found. Interestingly, stride length was more improved by L-dopa and cadence more by subthalamic nucleus stimulation. In two patients with freezing during the "on" period, subthalamic nucleus stimulation failed to reduce this symptom effectively.

Antiparkinson Agents↗

Granular-cell tumour: a rare suprasellar mass.

Granular-cell tumour is a rare suprasellar space occupying lesion, which usually presents with visual deterioration, endocrine deficits or headache. We present two women with extraordinarily large tumours, measuring 3.8 and 4.0 cm in diameter. In both cases the tough, vascular tumour could be removed only subtotally.

Aged↗

Malignant peripheral nerve sheath tumours--report of 8 cases and review of the literature.

BACKGROUND: Though Malignant peripheral nerve sheath tumours (MPNST) are a rare entity accounting for 5-10% of soft-tissue sarcomas they are an important differential diagnosis to benign tumours of the peripheral nervous system regarding treatment and prognosis. METHOD: We present our experience with eight patients who underwent surgery for MPNST at the Department of Neurosurgery between 10/1990 and 9/1999. The median age was 37 years [range: 13-64], the male/female ratio was 1:1. Two patients suffered from Neurofibromatosis type 1. Paraffin embedded tumour specimens were immunohistochemically stained for S-100, p53 and Ki67/MIB-1. FINDINGS: The most frequent initial symptoms were local swelling and pain followed by irritation of cranial nerves and spinal ataxia. Four tumours were localised at the head & neck region, three were found in the extremities and one tumour was located on the trunk. All patients underwent surgery with curative intent, but total resection, defined by negative surgical margins, was achieved in only 3 cases. All of these developed local recurrence with a mean disease free survival time of 10.6 months. In five cases, adjuvant radiation was given. During follow up, three patients developed distant metastases located in the lung, liver and subcutaneous tissue. Five out of eight patients died during follow-up with a mean survival time of 11.6 months after diagnosis. Results of immunohistochemical staining were as followed: S-100 (7/8), p53 (7/8). The Ki67/MIB-1 proliferation index was detectable in all tumour samples, it differed from 10-30%. INTERPRETATION: MPNST is a rare and fatal diagnosis in neurosurgery with high risk of local recurrence and occurence of distant metastases. Though mulitimodal therapy including surgical resection and adjuvant radiotherapy including brachytherapy is available, the prognosis remains dismal. Modern clinical studies and the development of effective chemotherapy is needed in order to gain control of the disease.

Adolescent↗

Olfactory event-related potentials in patients with brain tumors.

OBJECTIVE: The aim of the study was to determine how odor processing is altered in patients with unilateral supratentorial brain tumors. METHODS: Olfactory event-related potentials (OERPs) were evaluated in 10 patients with unilateral brain tumors of the frontal or temporal lobe in response to linalool and allylcaproate. Both odors were presented monorhinally by a constant-flow olfactometer. In addition, 20 healthy subjects were examined. While sniffing, the subjects were asked to discriminate the two odors. EEG was recorded from 7 electrode positions (Fz, Cz, Pz, F3/4, P3/4). Amplitudes and latencies of 3 peaks (N1, P2, P3) were measured. To control for effects of modality-non-specific alterations on the olfactory components acoustic event-related potentials (AERPs) were registered by use of an oddball paradigm. RESULTS: Patients with right-sided lesions showed distinct deficits in the discrimination task after stimulation of the right and left nostril. In contrast, patients with left-sided lesions only had an attenuation of correct reactions after left-sided stimulation. In the OERPs, patients with right-sided lesions showed P2- and P3-components with decreased amplitudes at parietal electrode positions. These alterations appeared after ipsi- and contralateral stimulation. Patients with left-sided lesions showed a significant effect of the side of stimulation. Their OERP-amplitudes were decreased after left-sided stimulation but not after right-sided stimulation. After right-sided olfactory stimulation a correlation between the olfactory and the acoustic ERP was seen in patients with right-sided lesions. CONCLUSIONS: Olfactory performance of the participating patients was markedly reduced. Patients with right-sided lesions showed bilateral impairment, which would support the importance of the right hemisphere in olfaction. The alteration of the topographic distribution of P2- and P3-amplitudes in patients with right-sided lesions might reflect an impairment of early and late olfactory processing steps.

Acyclic Monoterpenes↗

(E)-5-(2-bromovinyl)-2'-deoxyuridine potentiates ganciclovir-mediated cytotoxicity on herpes simplex virus-thymidine kinase--expressing cells.

Tumor cells expressing the thymidine kinase gene of the herpes simplex virus (HSV-tk) are rendered highly susceptible to the cytotoxic effects of different antiherpes drugs. In an attempt to enhance cytotoxicity of this therapeutic approach in glioma and other tumor cell lines transduced with the HSV-tk gene, we evaluated tumor cell killing following co-administration of two different prodrugs metabolized by HSV-tk, (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU), and ganciclovir (GCV). In 8 of 12 cell lines investigated, addition of BVDU in concentrations showing no cytotoxic effect or only limited cytotoxicity could enhance GCV-mediated cell killing by as much as one order of magnitude. In co-cultures consisting of HSV-tk(+) (9L STK) and HSV-tk(-) (9L wild-type) cells, we also observed potentiation of GCV-mediated cytotoxicity in the presence of BVDU, suggesting strongly enhanced bystander cell killing. BVDU is thought to exert its cytotoxic effect through inhibition of thymidylate synthase activity or by incorporation into replicating DNA. Both effects could be observed in all HSV-tk--expressing cells investigated, including cell lines which did not exhibit cytotoxicity after incubation with BVDU. These findings argue against current concepts of BVDU-mediated cytotoxicity in HSV-tk--expressing cells. Taken together, our data suggest that gene therapy utilizing prodrug activating enzymes may be rendered more effective by simultaneous treatment with two different prodrugs metabolized by the same enzyme.

Animals↗

Brain oedema in secretory meningiomas.

Brain oedema is usually associated with intracranial meningiomas in about 50-66%. As underlying causes, different factors like localisation, vascular supply, angiogenic growth factors and histological subtypes are discussed, and its existence is probably multifactorial. We present 11 patients with the rare subtype of secretory meningiomas. Brain oedema was observed in 82%. These tumours are localised mainly at the frontal convexity and at the sphenoid ridge. All 11 patients were female so that hormonal factors also may play a role in the production of peritumoural oedema. The postoperative outcome was good and no recurrences were seen during follow-up.

Adult↗

Cerebral autoregulation testing after aneurysmal subarachnoid hemorrhage: the phase relationship between arterial blood pressure and cerebral blood flow velocity.

OBJECTIVE: Impairment of cerebral autoregulation (CA) appears to be an important cause for secondary ischemia after subarachnoid hemorrhage (SAH). It has been shown that graded CA impairment is predictive of outcome. Little is known about whether such impairment is present, what causes CA impairment, whether it precedes vasospasm, and whether it is predictive of outcome in patients with severe aneurysmal SAH. DESIGN: Prospective, controlled study. SETTING: Neurosurgical intensive care unit. PATIENTS: Twelve patients after aneurysmal subarachnoid hemorrhage, 40 controls. INTERVENTIONS: Recording of cerebral blood flow velocities and continuous measurement of arterial blood pressure at a controlled ventilatory frequency of six per minute to standardize the influence of intrathoracic pressure changes on blood pressure. MEASUREMENTS AND MAIN RESULTS: We calculated the phase shift angles (deltaphidegrees) between slow (0.1 Hz) arterial blood pressure and cerebral blood flow velocity waves measured by transcranial Doppler ultrasound in the middle cerebral artery during a) posthemorrhage days (PHD) 1-6 (early or prevasospasm phase), and b) during PHD 7-13 (late or vasospasm phase) using a 6/min ventilation protocol, and in 40 controls spontaneously ventilating at the same rate. deltaphi <30 degrees indicated lost CA. Mean flow velocities >100 cm/sec were considered vasospasm. We combined early and late measurements to assess the CA relationship with low cerebral perfusion pressure (CPP) and/or vasospasm. We assessed the Glasgow Outcome Scale (GOS) score at discharge (1 = worst, 5 = best). The admission Hunt and Hess score was 3.6 +/- 0.7. GOS scores were n = 3 (GOS 1), n = 2 (GOS 2), n = 5 (GOS 3), n = 1 (GOS 4), and n = 1 (GOS 5). In the early phase, deltaphi was 40.4 +/- 19.8 degrees (left), and 40.4 +/- 19.2 degrees (right). CPP was 69.4 +/- 10.9, intracranial pressure (ICP) was 6.7 +/- 2.8 mm Hg. In the late phase, deltaphi worsened in six patients and none improved: 32.1 +/- 21 degrees (left), and 26.9 +/- 17.2 degrees (right); CPP was 68.1 +/- 12.1, ICP was 7.5 +/- 3.7 mm Hg. CA was significantly impaired in both phases when compared with normal subjects (deltaphi: 65.7 +/- 24.5 degrees; p < .01 for early, p < .001 for late phase). In the early phase, seven of eight patients in whom autoregulation was intact had a GOS >2 at discharge and disturbed CA on at least one side was predictive of either vegetative condition at discharge or death (p < .01). In the late phase, deltaphi was no longer predictive of outcome. Spasm was present in 8 of 17 vessels (47%) in which CA was lost; no spasm was found in 25 of 28 vessels (89%) in which CA was intact (p < .01). A low CPP was present in 6 of 17 vessels (35%) in which CA was lost; a normal CPP was found in 21 of 27 vessels (78%) in which CA was intact (p > .05, NS). However, 14 of 17 vessels (82%) with lost CA showed spasm and/or low CPP while only 8 of 27 cases (30%) with intact CA had either spasm or low CPP (p < .001). CONCLUSIONS: CA can be assessed in a graded fashion in SAH patients. CA impairment precedes vasospasm; ongoing vasospasm worsens CA. CA assessment early after subarachnoid hemorrhage, within PHD 1-6, is predictive of outcome whereas late assessment is not. CA impairment is associated with cerebral vasospasm and low CPP.

Adult↗

Secretory meningiomas: clinical and immunohistochemical observations.

OBJECTIVE: Secretory meningiomas are a rare histological subtype of these benign intracranial tumors. Few reports have been published regarding their tendency to develop peritumoral edema. METHODS: Between July 1994 and February 1999, 11 patients with secretory meningiomas underwent operations in the Department of Neurosurgery, University of Kiel, Kiel, Germany. The clinical notes and radiological data (computed tomographic and magnetic resonance imaging scans) were reviewed. Immunohistochemistry was used to examine the expression of carcinoembryonic antigen and epithelial membrane antigen as well as progesterone and estrogen receptors. RESULTS: Secretory meningiomas were found in 11 (5%) of 214 patients with intracranial meningiomas who were operated on in that period. All 11 patients were women. These patients' mean age was 65 years (range, 51-87 yr). The localization of these tumors was at the convexity in seven patients, at the sphenoid ridge in two patients, and in the olfactory groove and petroclival region in one patient each. Two meningiomas had no edema surrounding them, two meningiomas had a small amount of edema, two had moderate edema, and five had severe edema. No recurrences were observed during the mean follow-up period of 26 months (range, 8-65 mo). Immunohistochemically, all tumors contained pseudopsammoma bodies and reacted with epithelial membrane antigen and carcinoembryonic antigen. The MIB-1 antibody staining index showed a mean of 2% (range, 0-7%). CONCLUSION: Secretory meningiomas are rare tumors, and they are mainly localized at the frontal convexity and the sphenoid ridge. They are surrounded by more edema than usual. The preponderance of female patients with this presentation is striking. The expression of carcinoembryonic antigen and epithelial membrane antigen is a characteristic feature of secretory meningiomas. These meningiomas are also positive for progesterone receptors, which has been shown to be a good prognostic factor.

Aged↗

Stroke pattern interpretation: the variability of hypertensive versus amyloid angiopathy hemorrhage.

INTRODUCTION: It is commonly felt that cerebral amyloid angiopathy (CAA) related intracerebral hemorrhage (ICH) can be distinguished from hypertension (HTN)-related ICH by certain typical features on computerized tomography (CT) and magnetic resonance imaging (MRI). The purpose of this study was to investigate the performance of clinicians who were asked to differentiate between CAA and HTN based on hemorrhage pattern interpretation and to assess the feasibility of such classification. METHODS: The admission scans from 83 patients who were admitted to our service with an acute ICH were presented to 5 clinicians in a randomized and blinded fashion (1 junior, and 1 senior neurosurgical resident, 1 attending neurosurgeon, and 2 neurosurgeon-neuroradiologists). There were no patients who received oral anticoagulants other than low-dose aspirin, or who suffered from vascular malformations or tumors. Scans from 41 patients with a histologically proven diagnosis of CAA and from 42 patients with a clear history of HTN were investigated. Hematoma evacuation was done in all CAA patients and in 59% of HTN patients (n = 25). RESULTS: The overall average classification accuracy was 66.8% (range: 62.7-69.9). For correct HTN classification it was 69.5% (range: 64.3-81), and 63.9% for CAA, respectively (range: 48.9-75.6). There were negligible differences in classification accuracy among all observers. Patients with a CAA-related ICH were significantly older than patients with a HTN-related ICH (74 vs. 66.5 years, p < 0.05). There was a significantly higher number of hematomas >30 ml in CAA (85.3%) when compared with HTN (59.5%). No basal ganglionic hemorrhage was seen in CAA, but in 40.5% in HTN. Intraventricular hemorrhage was seen in 24.4% in CAA, and in 26.2% in HTN. Two patients (4.9%) with CAA, and 7 patients with HTN (16.7%) presented with cerebellar hematomas. CONCLUSIONS: Three of 10 scans were not correctly diagnosed regardless of the examiner's level of training. This calls into question the reliability of classifying the underlying pathological condition based on hemorrhage pattern interpretation on CT or MRI. The definite diagnosis of CAA- versus HTN-related hemorrhage requires a histopathological confirmation and should not be based solely on hemorrhage pattern interpretation.

Adult↗

Giant cystic craniopharyngiomas with extension into the posterior fossa.

Between 1991 and 1998, 24 patients underwent surgery for a craniopharyngioma in our department. This group included two patients who had tumors with extensive growth along the midline, and along the posterior fossa in particular. In both cases suprasellar calcifications were typical features on magnetic resonance imaging (MRI) and computed tomography (CT). A 7-year-old boy presented with a 6-month history of headache, nausea, and progressive unilateral hearing loss. With a suboccipital approach it was possible to remove the main part of the tumor. In a 13-year-old boy headache and visual deterioration led to the diagnosis of a craniopharyngioma, which was removed with a pterional approach. For the neuroimaging work-up in such cases of atypically growing craniopharyngiomas MRI is the method of choice. Additional CT scanning is recommended, which provides valuable information about bony changes at the skull base due to space-occupying growth. CT substantiates the differential diagnosis if typical calcifications are seen.

Adolescent↗

Spontaneous intracranial haematomas caused by neoplasms.

We report about 50 patients with spontaneous intracerebral haematomas (ICH) caused by intracranial neoplasms to assess the underlying histological condition, their presentation on admission, diagnostic work-up, treatment, histological diagnosis, and clinical outcome. These patients were identified in a prospective series of 2041 patients with intracranial neoplasms and 692 patients with spontaneous ICH, which were both consecutively collected over a nine-year-period. The frequency of ICH in patients with intracranial neoplasms was 2.4%. The frequency of tumour related ICH in the ICH group was 7.2%. The leading cause of tumour related ICH were metastases of extracranial origin (n = 18; 36%), followed by glioblastoma multiforme (n = 15; 30%). Nine patients (18%) had benign primary intracranial neoplasms. On admission 18 patients were somnolent (36%) and 14 patients (28%) were comatose. In 29 cases (58%) ICH was the first clinical sign of neoplastic disease, while in 21 patients (42%) a malignant tumour was already known. We operated on 45 patients (90%), four patients (8%) were not operated on because of poor clinical condition and died, one patient refused surgical treatment. Six patients (12%) died despite surgery. This series confirms the importance of a proper neuroradiological and clinical work-up of patients with suspected tumour related ICH followed by operative treatment and histological confirmation of the diagnosis. This is supported by the fact that 18% of patients had prognostically favourable intracranial tumours which would not otherwise have been adequately treated.

Acute Disease↗

Results in the operative treatment of elderly patients with intracranial meningioma.

With life expectancy in the industrial nations increasing during recent years, the number of patients older than 70 years with intracranial tumours and, especially, meningiomas is rising. To evaluate the indications for operative treatment, we reviewed 66 patients older than 70 years who were operated upon for intracranial meningioma in our department between 1991 and 1997. The mean age was 75 years. The oldest patients were 86 years old. Thirteen patients with recurrent meningiomas were operated upon. The mortality rate was 7.6%. Neurological symptoms improved in 38 patients (57.6%), were unchanged in 11 (16.6%), and deteriorated in 12 (18.2%). Patients with recurrent meningiomas seem to have a higher operative risk and their outcome is worse than after a primary operation. In general, there were good postoperative results in patients with few concomitant diseases, small meningiomas, small edema, short time of operation, and accessible location (convexity rather than skull base). Age in general is not a contraindication for operation. In cases of incidental findings of small meningiomas, we recommend observation and MRI follow-up. Symptomatic meningiomas should be removed whenever there is an acceptable risk from an internal or anaesthesiological point of view.

Aged↗

Gait analysis in idiopathic normal pressure hydrocephalus--which parameters respond to the CSF tap test?

OBJECTIVES: Normal pressure hydrocephalus (NPH) is an often underestimated cause of hypokinetic gait disorders in the elderly. Diagnosing NPH is a complex problem, since many symptoms overlap with other neurological diseases. The purpose of the present study was to characterize the gait pattern in NPH quantitatively. Additionally, we analyzed the improvement of gait parameters following tapping of cerebrospinal fluid (CSF). METHODS: Gait analysis was performed in 10 patients and 12 age-matched healthy controls during overground and treadmill locomotion. RESULTS: Compared to healthy controls, patients with NPH walked significantly slower, with shorter and more variable strides and a somewhat lower cadence. The feet were not lifted to a normal height and the dorsal extension of the forefoot prior to heel-strike was insufficient. Balance-related gait parameters such as step width and the foot rotation angles were significantly increased in NPH, while their variability was lower. Only some gait parameters improved after tapping 30 ml CSF. Gait velocity increased by about 23% due to an increased stride length, while the cadence remained unchanged. Balance-related gait parameters and the foot-to-floor clearance during swing were not affected by the treatment. CONCLUSIONS: In conclusion, we found a triad of decreased stride length, decreased foot-to-floor clearance and a broad-based gait to be the typical features of the gait abnormality in NPH. Only the stride length improved following a diagnostic spinal tap. These results may help to more reliably diagnose the condition of NPH in a routine clinical setting.

Aged↗

[Neuronavigation in the region of the skull base].

Neuronavigation (computer-aided surgery planning and performance) has proven to be helpful in performing neurosurgical operations. The experiences of our department gained on more than 500 patients operated upon will be presented, with special focus on more than 100 operations for lesions on the skull base. Navigation is one of several modern surgical tools, its value cannot be defined without observing other improvements e.g. in the area of preoperative diagnostics, intraoperative monitoring, microsurgical instruments and microsurgical approaches.

Adenoma↗

Effects of potassium channel inhibitors on the relaxation induced by the nitric oxide donor diethylamine nitric oxide in isolated human cerebral arteries.

OBJECT: The goal of this study was to investigate whether K+ channels are involved in nitric oxide (NO)-induced relaxation of isolated human cerebral arteries. METHODS: Successive concentration-response curves relating to the use of the NO donor diethylamine NO (DEA/NO) were established in the absence and presence of different K+ channel inhibitors after mounting human cerebral arteries onto a wire myograph. The arteries were obtained from macroscopically intact tissue that had been removed during brain tumor operations. A high K+ concentration partially inhibited the relaxant effects of DEA/NO. Different K+ channel inhibitors (tetraethylammonium [TEA], 10(-3) M; charybdotoxin, 10(-7) M; glibenclamide, 10(-6) M; 4-aminopyridine [4-AP], 10(-3) M; BaCl2, 5 x 10(-5) M; and apamin, 10(-6) M) alone failed to affect the responses to DEA/NO. However, a combination of TEA, glibenclamide, 4-AP, and BaCl2 partially blocked the relaxant effects of DEA/NO. In addition, the effects of DEA/NO were inhibited by the thromboxane A2 analog U46619 (3 x 10(-7) M). CONCLUSIONS: Inhibitors of the large-conductance or small-conductance Ca++-activated K+ channels, the adenosine triphosphate-sensitive K+ channels, and the delayed-rectifier or inward-rectifier K+ channels failed to alter the effects of DEA/NO when only one K+ channel blocker was used. However, a regimen of a combination of K+ channel blockers that possess selectivity for different channels demonstrated that different K+ channel types are involved; these channels may function in a redundant manner and compensate for each other. Selective thromboxane A2 agonists are capable of inhibiting the relaxant response to the NO donor.

Cerebral Arteries↗

Spontaneous oscillations of arterial blood pressure, cerebral and peripheral blood flow in healthy and comatose subjects.

Slow and rhythmic spontaneous oscillations of cerebral and peripheral blood flow occur within frequencies of 0.5-3 min-1 (0.008-0.05 Hz, B-waves) and 3-9 min-1 (0.05-0.15 Hz, M-waves). The generators and pathways of such oscillations are not fully understood. We compared the coefficient of variance (CoV), which serves as an indicator for the amplitude of oscillations and is calculated as the percent standard deviation of oscillations within a particular frequency band from the mean, to study the impairment of generators or pathways of such oscillations in normal subjects and comatose patients in a controlled fashion. With local ethic committee approval, data were collected from 19 healthy volunteers and nine comatose patients suffering from severe traumatic brain injury (n = 3), severe subarachnoid hemorrhage (n = 3), and intracerebral hemorrhage (n = 3). Cerebral blood flow velocities were measured by transcranial Doppler ultrasound (TCD), peripheral vasomotion by finger tip laser Doppler flowmetry (LDF), and ABP by either non-invasive continuous blood pressure recordings (Finapres method) in control subjects, or by direct radial artery recordings in comatose patients. Each recording session lasted approximately 20-30 min. Data were stored in the TCD device for offline analysis of CoV. For CoV in the cerebral B-wave frequency range there was no difference between coma patients and controls, however there was a highly significant reduction in the amplitude of peripheral B-wave LDF and ABP vasomotion (3.8 +/- 2.1 vs. 28.2 +/- 16.1 for LDF, p < 0.001; and 1.2 +/- 0.7 vs. 4.6 +/- 2.8 for ABP, p < 0.001). This observation was confirmed for spontaneous cerebral and peripheral oscillations in the M-wave frequency range. The CoV reduction in peripheral LDF and ABP oscillations suggest a severe impairment of the proposed sympathetic pathway in comatose patients. The preservation of central TCD oscillations argues in favor of different pathways and/or generators of cerebral and peripheral B- and M-waves.

Adult↗

Surgical treatment of Parkinson's disease.

Ablative surgery and deep brain stimulation for Parkinson's disease can be performed in the thalamus, the pallidum and the subthalamic nucleus. The efficacy and safety of unilateral pallidotomy is well established. Deep brain stimulation has a lower morbidity and is preferred for bilateral surgery. The subthalamic nucleus presently seems to be the most promising target in advanced stage Parkinson's disease.

Electric Stimulation↗