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ABSTRACT: In this review we discuss the position of electrical neuromodulation as a safe and reversible adjuvant therapy for treatment of patients with chronic cardiac diseases who have become refractory to conventional strategies. In patients with chronic refractory angina, electrical neuromodulation, independent of the applied modality, has shown to reduce complaints of angina, to enhance exercise capacity, to improve quality of life and to employ anti-ischaemic effects. To date, electrical neuromodulation seems to be one of the best adjuvant therapies for these patients. In addition, neuromodulation in the treatment of heart failure and resistant arrhythmias is the subject of several ongoing studies.
Netherlands heart journal: monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 11/2012; · 1.44 Impact Factor
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ABSTRACT: Pilot study.
To study the effect of pulsatile bolus infusion of intrathecal baclofen (ITB) on daily ITB dose, in patients showing dose increases, probably due to tolerance.
Department of neurology and neurosurgery, University Medical Center Groningen, the Netherlands.
Data on dosages and clinical efficacy were gathered from four patients who were switched from continuous to pulsatile bolus infusion of ITB, because of the probable diagnosis of tolerance to ITB.
Switching from continuous to pulsatile bolus infusion resulted in a decrease of the daily ITB dose, while the clinical effect could be kept stable, without introducing adverse events.
Pulsatile bolus infusion of ITB seems to be an effective and safe treatment strategy to reverse the need for increasing ITB dosages in patients with the probable diagnosis of tolerance to ITB.
Spinal Cord 11/2009; 48(6):483-6. · 1.80 Impact Factor
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ABSTRACT: Retrospective study.
To study the incidence and management of tolerance in patients treated with intrathecal baclofen (ITB) therapy.
Department of neurology and neurosurgery, University Medical Center Groningen, The Netherlands.
Medical records of all patients who had received an implantable ITB pump at our clinic during 1991-2005 were reviewed.
A total of 37 patients (representing 116 pump years) were included. Mean follow-up time was 38 months (range 3-120 months). Baclofen dose increased in the first 18 months after implantation (P<0.05), and then stabilized around a mean dose of 350 microg per day. Eight patients (22%) developed tolerance, defined as a dose increase of >100 microg per year. No predictive factors for development of tolerance could be determined. Three different treatment regimens for tolerant patients were analyzed. Altering the infusion mode from simple to complex continuous (n=6) had no effect on the development of tolerance. Pulsatile bolus infusion (n=1) and a drug holiday (n=2) were both effective in reducing the daily baclofen dose. Patients who needed surgical revision of the pump system because of mechanical failures (n=11) showed a significant dose decrease during the first month after revision, indicating that the preoperative dose increase most likely had been caused by the pump failure. Pump-related complications occurred once per 10.5 years of ITB treatment. Drug-related side effects had an annual risk of 13.8%. The reported events were mostly mild.
ITB therapy is effective and safe, also in the long term and causes tolerance in only 22% of the treated patients.
Spinal Cord 04/2009; 47(10):751-6. · 1.80 Impact Factor
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ABSTRACT: Neurophysiological assessment can provide quantitative measures for the selected motor signs that have been targeted for surgery and may be helpful in predicting the therapeutic effects of deep brain stimulation (DBS) on pathological tremor, motor performance, and rigidity.
To present a survey and demonstrate the contribution of neurophysiological assessment of side effects and effects on disabling motor symptoms at various steps of DBS surgery, and to confirm its role for optimal target localization, as an adjuvant to anatomic imaging.
The data result from 192 nuclei in 118 procedures on patients with Parkinson's disease (84), essential tremor (24), Hallenvorder Spatz dystonia (4), multiple sclerosis (4), and Holmes tremor (2). The intraoperative neurophysiological monitoring (IOM) protocol consists of semimicroelectrode recording (for subthalamic nuclei), whereas accelerotransducers and spectral analysis allow assessment of tremor, finger tapping (FT), diadochokinesis (DDK), and determination of the distance between DBS electrodes and internal capsule (IC). Rigidity is assessed by surface EMG recordings in combination with a goniometer.
The determination of the functional distance between the DBS electrode and the IC is based on the activation functions of axons in the IC. We show the high sensitivity of accelerometers for tremor over a large part of the body, the relationship between clinical scores and spectral frequencies of FT and DDK. Parkinsonian rigidity can be assessed from surface EMG (sEMG) by means of a balance coefficient, which can detect negative rigidity, for low unified Parkinson's disease rating scale (UPDRS) scores (0-2) and quantified EMG when negative rigidity is excluded.
Accelerometer and sEMG recording have shown their value for intraoperative assessment of disabling motor symptoms and side effects during surgery, to optimize the target position electrodes for DBS. The combination with contemporary signal analyzing techniques permit intraoperative monitoring without a significant delay. IONM improves sensitivity and adds objective neurophysiological data.
Neurophysiologie Clinique/Clinical Neurophysiology 01/2008; 37(6):467-75. · 1.98 Impact Factor
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ABSTRACT: Long-term evaluation of treatment of chronic, therapeutically refractory tinnitus by means of chronic electrical stimulation of the vestibulocochlear nerve.
Inclusion criteria were severe, chronic, therapeutically refractory, unilateral tinnitus and severe hearing loss at the ipsilateral site. Out of 6 patients, 4 patients were selected for long-term evaluation. Two patients were not evaluated because of premature dropout.
A stimulation electrode was placed around the vestibulocochlear nerve through a retrosigmoid approach and connected to a subcutaneously positioned pulse generator via an extension cable. Follow-up was performed 3 months and 42.5 months after implantation. Three measures for treatment outcome were used. First, effect sizes were determined by means of the total Tinnitus Handicap Inventory (THI) score using Cohen's formula. Second, general and tinnitus-specific audiometric tests were performed in on and off conditions of the neurostimulation system. Third, recordings were noted for tinnitus severity and treatment success on a visual analogue scale.
All 4 patients reported successful treatment with neurostimulation. The effect size after 3 months was 0.7, indicating an average effect, while the effect size measured during long-term follow-up was 1.75, indicating a substantial effect with major clinical implications. No changes in hearing level for both ears were measured. The neurostimulation system did not change the tinnitus pitch in any of the patients, and resulted in a minimal reduction of tinnitus loudness in only 2 patients. In all 4 patients the original tinnitus sound was replaced by another, pleasantly perceived sound. The average VAS score of perceived tinnitus severity was reduced from 8 to 3.25. The average VAS score for treatment success was 7.25.
The long-term follow-up of neurostimulation treatment for chronic tinnitus shows promising results. Long-term results were better than those determined after a 3-month follow-up. In all patients the tinnitus was replaced by another sound, which was perceived as pleasant. Further studies are needed before accepting neurostimulation as a treatment modality for chronic, therapeutically refractory tinnitus.
Stereotactic and Functional Neurosurgery 02/2007; 85(4):150-7. · 1.85 Impact Factor
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ABSTRACT: Ischemic disease (ID) is now an important indication for electrical neuromodulation (NM), particularly in chronic pain conditions. NM is defined as a therapeutic modality that aims to restore functions of the nervous system or modulate neural structures involved in the dysfunction of organ systems. One of the NM methods used is chronic electrical stimulation of the spinal cord (spinal cord stimulation: SCS). SCS in ID, as applied to ischemic heart disease (IHD) and peripheral vascular disease (PVD), started in Europe in the 1970s and 1980s, respectively. Patients with ID are eligible for SCS when they experience disabling pain, resulting from ischaemia. This pain should be considered therapeutically refractory to standard treatment intended to decrease metabolic demand or following revascularization procedures. Several studies have demonstrated the beneficial effect of SCS on IHD and PVD by improving the quality of life of this group of severely disabled patients, without adversely influencing mortality and morbidity. SCS used as additional treatment for IHD reduces angina pectoris (AP) in its frequency and intensity, increases exercise capacity, and does not seem to mask the warning signs of a myocardial infarction. Besides the analgesic effect, different studies have demonstrated an anti-ischemic effect, as expressed by different cardiac indices such as exercise duration, ambulatory ECG recording, coronary flow measurements, and PET scans. SCS can be considered as an alternative to open heart bypass grafting (CABG) for patients at high risk from surgical procedures. Moreover, SCS appears to be more efficacious than transcutaneous electrical nerve stimulation (TENS). The SCS implantation technique is relatively simple: implanting an epidural electrode under local anesthesia (supervised by the anesthesist) with the tip at T1, covering the painful area with paraesthesia by external stimulation (pulse width 210, rate 85 Hz), and connecting this electrode to a subcutaneously implanted pulse generator. In PVD the pain may manifest itself at rest or during walking (claudication), disabling the patient severely. Most of the patients suffer from atherosclerotic critical limb ischemia. All patients should be therapeutically refractory (medication and revascularization) to become eligible for SCS. Ulcers on the extremities should be minimal. In PVD the same implantation technique is used as in IHD except that the tip of the electrode is positioned at T10-11. In PVD the majority of the patients show significant reduction in pain and more than half of the patients show improvement of circulatory indices, as shown by Doppler, thermography, and oximetry studies. Limb salvage studies show variable results depending on the stage of the trophic changes. The underlying mechanisms of action of SCS in PVD require further elucidation.
Advances and technical standards in neurosurgery 02/2007; 32:63-89.
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ABSTRACT: We assessed the efficacy of chronic stimulation of the subthalamic nucleus (STN-DBS) in 20 patients with Parkinson's disease (PD) by means of clinical assessments and patient diaries 12 months after surgery. STN-DBS reduced the UPDRS part III off-medication score by 33%, and successively improved complete daily on-time without dyskinesia at 12 months significantly. In conclusion, our study demonstrates the efficacy of chronic STN-DBS on motor features in a selected population of advanced PD patients. In addition to clinical assessments, patients' diaries serve as an essential tool to evaluate the functional motor status after STN-DBS.
Parkinsonism & Related Disorders 05/2006; 12(3):143-8. · 3.80 Impact Factor
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R Hilker,
A T Portman,
J Voges, M J Staal,
L Burghaus,
T van Laar,
A Koulousakis,
R P Maguire,
J Pruim,
B M de Jong,
K Herholz,
V Sturm,
W-D Heiss,
K L Leenders
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ABSTRACT: Glutamate mediated excitotoxicity of the hyperactive subthalamic nucleus (STN) has been reported to contribute to nigral degeneration in Parkinson's disease (PD). Deep brain stimulation of the STN (STN DBS), in its role as a highly effective treatment of severe PD motor complications, has been thought to inhibit STN hyperactivity and therefore decrease progression of PD.
In a prospective two centre study, disease progression was determined by means of serial (18)F-fluorodopa (F-dopa) positron emission tomography (PET) in 30 patients with successful STN DBS over the first 16 (SD 6) months after surgery.
Depending on the method of PET data analysis used in the two centres, annual progression rates relative to baseline were 9.5-12.4% in the caudate and 10.7-12.9% in the putamen.
This functional imaging study is the first to demonstrate a continuous decline of dopaminergic function in patients with advanced PD under clinically effective bilateral STN stimulation. The rates of progression in patients with STN DBS were within the range of previously reported data from longitudinal imaging studies in PD. Therefore this study could not confirm the neuroprotective properties of DBS in the STN target.
Journal of Neurology Neurosurgery & Psychiatry 10/2005; 76(9):1217-21. · 4.76 Impact Factor
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ABSTRACT: Tinnitus is an uncomfortable symptom for the patient and an embarrassing one for the consulted physician. So far, there is no treatment that can be considered well established in terms of providing long-term reduction of tinnitus in excess of placebo effects. There is considerable evidence of pathophysiological similarity between tinnitus and chronic pain. Some forms of chronic pain can be treated by neurostimulation.
This study was designed to investigate the feasibility of neurostimulation of the cochlear nerve in order to reduce tinnitus.
Pilot study.
Tertiary referral center.
Five patients with therapeutically refractory tinnitus were selected for this study.
Placing a stimulation lead around the cochlear nerve through the suboccipital approach and connecting the stimulation lead to a pulse generator.
The patients experienced 1) an absence of major or minor complications, such as death, meningitis, cranial nerve deficit, and vestibular problems; 2) tolerance of the procedure as considered by the patient; 3) relief of tinnitus in at least one patient.
Implantation of the neurostimulation system was accomplished in each patient without any difficulty. None of the patients considered the treatment unbearable. No major or minor complications occurred in this study. Subjective tinnitus reduction was accomplished in four patients.
Our preliminary data show that neurostimulation of the cochlear nerve is feasible, is bearable for the patient, and is a safe treatment modality without major complications. The effects on tinnitus are promising.
Ontology & Neurotology 06/2005; 26(3):425-8; discussion 428. · 1.90 Impact Factor
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ABSTRACT: To compare the efficacy of unilateral pallidotomy and bilateral subthalamic nucleus (STN) stimulation in patients with advanced Parkinson disease (PD) in a randomized, observer-blind, multicenter trial.
Thirty-four patients with advanced PD were randomly assigned to have unilateral pallidotomy or bilateral STN stimulation. The primary outcome was the change from baseline to 6 months in the motor part of the Unified PD Rating Scale (motor UPDRS) in the off phase. Secondary outcomes were parkinsonian symptoms in the on phase (motor UPDRS), dyskinesias (Clinical Dyskinesia Rating Scale and dyskinesias UPDRS), functional status (activities of daily living UPDRS and Schwab and England scale), PD Quality of Life questionnaire, changes in drug treatment, and adverse effects.
The off phase motor UPDRS score improved from 46.5 to 37 points in the group of pallidotomy patients and from 51.5 to 26.5 in the STN stimulation patients (p = 0.002). Of the secondary outcome measures, on phase motor UPDRS and dyskinesias UPDRS improved significantly in favor of the STN stimulation patients. Reduction of antiparkinsonian drugs was greater after STN stimulation than after pallidotomy. One patient in each group had a major adverse effect.
Bilateral STN stimulation is more effective than unilateral pallidotomy in reducing parkinsonian symptoms in patients with advanced PD.
Neurology 02/2004; 62(2):201-7. · 8.31 Impact Factor
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ABSTRACT: Human fetal ventral mesencephalon tissue has been used as dopaminergic striatal implants in Parkinsonian patients, so far with variable effects. Fetuses from animals that breed in large litters, e.g., pigs, have been considered as alternative donors of dopaminergic tissue. The optimal gestational age of the porcine fetal donors has not been studied systematically. We collected ventral mesencephalic (VM) tissue from fetal pigs, embryonal ages E21, E28, E42, and E70, and examined the viability of the fetal VM cells after dissociation, the expression of tyrosine hydroxylase (TH) in culture, the presence of catecholamines, and the cellular survival and outgrowth up to 10 months after intrastriatal implantation in rats. The highest viability was found in suspensions prepared from E28 fetuses. The highest number of TH-positive cells was found in cell cultures prepared from E28 VM tissue. Explants with a gestational age of 28 and 42 days contained the largest amount of dopamine. Only E28-derived grafts showed TH-cell survival after implantation in rat striatum. Our results show that a gestational age of 28 days must be considered to be the optimal age for dopaminergic tissue derived from pig fetuses for therapeutic use as intrastriatal grafts in Parkinsonian patients.
Experimental Brain Research 07/2000; 132(3):345-50. · 2.39 Impact Factor
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ABSTRACT: The subacute effect of thalamotomy and pallidotomy on regional cerebral metabolism was studied by means of Positron Emission Tomography (PET). In this way we aimed to identify the pattern of functional deafferentiation following a specific lesion in the basal ganglia. The cerebral distribution of 2-[18F]fluoro 2-deoxy-D-glucose (FDG) uptake at 1-2 weeks after operation was compared with the uptake before operation. Analysis of the changes was done by statistical parametric mapping (SPM). Thalamotomy resulted in a reduction of FDG uptake in predominantly the lateral prefrontal- and the parietal cortex, whereas pallidotomy affected only uptake in the (pre)frontal cortex. The absence of change in the primary sensory-motor cortex after either surgical procedure may suggest that, in man, the motor portions of the thalamus exert a predominantly indirect influence on the human motor cortex.
Clinical Neurology and Neurosurgery 07/2000; 102(2):84-90. · 1.58 Impact Factor
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ABSTRACT: Human fetal ventral mesencephalon tissue has been used as dopaminergic striatal implants in Parkinsonian patients, so far
with variable effects. Fetuses from animals that breed in large litters, e.g., pigs, have been considered as alternative donors
of dopaminergic tissue. The optimal gestational age of the porcine fetal donors has not been studied systematically. We collected
ventral mesencephalic (VM) tissue from fetal pigs, embryonal ages E21, E28, E42, and E70, and examined the viability of the
fetal VM cells after dissociation, the expression of tyrosine hydroxylase (TH) in culture, the presence of catecholamines,
and the cellular survival and outgrowth up to 10months after intrastriatal implantation in rats. The highest viability was
found in suspensions prepared from E28 fetuses. The highest number of TH-positive cells was found in cell cultures prepared
from E28 VM tissue. Explants with a gestational age of 28 and 42days contained the largest amount of dopamine. Only E28-derived
grafts showed TH-cell survival after implantation in rat striatum. Our results show that a gestational age of 28 days must
be considered to be the optimal age for dopaminergic tissue derived from pig fetuses for therapeutic use as intrastriatal
grafts in Parkinsonian patients.
Experimental Brain Research 01/2000; 132(3):345-350. · 2.39 Impact Factor
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R M de Bie,
R J de Haan,
P C Nijssen,
A W Rutgers,
G N Beute,
D A Bosch,
R Haaxma,
B Schmand,
P R Schuurman, M J Staal,
J D Speelman
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ABSTRACT: The results of several cohort studies suggest that patients with advanced Parkinson's disease would benefit from unilateral pallidotomy. We have assessed the efficacy of unilateral pallidotomy in a randomised, single-blind, multicentre trial.
We enrolled 37 patients with advanced Parkinson's disease who had, despite optimum pharmacological treatment, at least one of the following symptoms: severe response fluctuations, dyskinesias, painful dystonias, or bradykinesia. Patients were randomly assigned to unilateral pallidotomy within 1 month or to pallidotomy after the primary outcome assessment (6 months later). The primary outcome was the difference between the groups in median changes on the motor examination section of the unified Parkinson's disease rating scale (UPDRS 3) score done in the off phase. Secondary outcome measures included levodopa-induced dyskinesias (dyskinesia rating scale [DRS]) and extent of disability (UPDRS 2).
The median UPDRS 3 off score of the pallidotomy patients improved from 47 to 32.5, whereas that of control patients slightly worsened from 52.5 to 56.5 (p<0.001). In the on phase the median DRS score improved 50% in pallidotomy patients compared with no change in controls. The UPDRS 2 off score improved with a median of 7 in the pallidotomy group. Two treated patients had major adverse effects.
Unilateral pallidotomy is an effective treatment in patients with advanced Parkinson's disease, who have an unsatisfactory response to pharmacological treatment.
The Lancet 11/1999; 354(9191):1665-9. · 38.28 Impact Factor
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ABSTRACT: To determine morbidity and mortality characteristics in patients treated with electrical neuromodulation for refractory angina pectoris.
A retrospective multicentre study of patients treated with spinal cord stimulation between 1987 and 1997; 21 centres were contacted and 14 responded.
Specialist centres worldwide.
Questionnaires were returned on 517 patients, of whom 71% were male. One was lost to follow up. Mean (SD) age was 63.9 (10.1) years. Duration of angina pectoris was 8.1 (6.3) years.
Before spinal cord stimulation, 66% of the patients had experienced myocardial infarction, 68% had three vessel disease, and in 24% the left ventricular ejection fraction (LVEF) was </= 40%. Percutaneous transluminal coronary angioplasty and bypass surgery were performed in 17% and 58% of the subjects, respectively. During a median follow up of 23 months (range 0 to 128), 103 patients died (52 from a cardiac cause, 25 from a non-cardiac cause, and 26 from an unknown cause). Annual all cause mortality was 7-8%; annual cardiovascular fatality was 3.5-5%. Mortality was univariately related to sex, number of diseased vessels, number of revascularisation procedures, previous myocardial infarction, LVEF, insulin dependent diabetes, beta blocking agents, and angiotensin converting enzyme inhibitors. Multiple variate analysis showed that LVEF, sex, beta blockers, and age >/= 71 years were independent predictors of mortality. During spinal cord stimulation, New York Heart Association functional class improved from 3.5 to 2.1 (p < 0.01); 25 of the deceased patients (24%) and 32 survivors (8%) experienced myocardial infarction; hospital admissions were significantly (p < 0.001) more common in the deceased group (66% v 37%).
The clinical outcome of patients with intractable angina is not adversely affected by the chronic use of neurostimulation.
Heart (British Cardiac Society) 08/1999; 82(1):82-8. · 4.22 Impact Factor
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ABSTRACT: The purpose of our study was to analyse and evaluate the costs of continuous intrathecal baclofen administration as a modality in the treatment of severe spasticity in the Netherlands.
A cost analysis was conducted as part of a prospective, multicentre, multidisciplinary, randomised and placebo-controlled clinical trial. The study covered the period from December 1991 to September 1995. The data on medical consumption and costs were collected over a 3-year period from different sources: administrative databases of health insurance companies, hospital registries and a patient survey. These data were structured by means of a flowchart analysis of the medical decision-making by specialists and general practitioners (GPs). They included data on in- and outpatient care, home care and care in nursing homes. The cost analysis was conducted using data from 18 patients included in the trial and from 15 so-called 'match' patients. The latter group are patients with comparable diseases leading to spasticity and living in comparable circumstances. Next to absolute costs (direct and indirect) of care and treatment for the 2 groups of patients, cost differences between the 2 groups were considered (differential cost analysis).
Per patient cost data, collected prospectively for 2 years during the phase of clinical evaluation, and retrospectively 1 year before implantation. The data were collected on patients from in- and outpatient care, home care and care in nursing home settings.
The trial patients (8 men) had a mean age of 46 years; 11 patients had multiple sclerosis and 7 patients had spinal cord injuries. The match patients (7 men) had a mean age of 48 years; 9 patients had multiple sclerosis and 6 patients had spinal cord injuries.
Trial patients were treated with a subcutaneously implanted programmable continuous infusion pump (SynchroMed, Medtronic), filled with baclofen (a muscle relaxant) to treat patients with chronic disabling spasticity who did not respond to a maximum dose of oral baclofen, dantrolene and tizanidine.
An analysis of hospital stay between both groups showed a significant difference during the implantation year. The average number of hospital days per patient in the year in the treated group was 31.5 days and in the match group was 18.7 days. Significant cost differences between both groups in the year that started with pump implantation and the following year can be attributed mostly to the costs of implantation of the pump and related hospitalisation days. The total costs of patient selection, testing, implanting the pump and follow-up amounted to $US28,473 for the first year. Savings must be taken into consideration as well. The savings of direct costs were due to withdrawal of oral medication (estimated annual total of between $US1950 and $US2800 per patient). Indirect savings on employment and nursing home costs, amounted annually to $US1047 and $US5814, respectively. Scenarios make it possible to consider policy consequences. The case of 'extending' the indications for this treatment to a larger population has been calculated and visualised.
The costs of the therapy (continuous intrathecal infusion of baclofen) can be attributed mostly to implantation of the pump and related hospitalisation days. Savings originated from withdrawal of oral medication, job preservation and avoidance or delay of admission to a nursing home.
PharmacoEconomics 05/1999; 15(4):395-404. · 2.66 Impact Factor
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ABSTRACT: Spinal cord stimulation is known to be a successful treatment for chronic intractable angina pectoris. Its effect may be anti-ischemic. It is uncertain if the clinical effect is partly caused by a placebo effect of surgery for implantation of a stimulator. In this study, clinical efficacy is investigated, together with a possible placebo effect.
Efficacy of spinal cord stimulation as a treatment for chronic intractable angina pectoris was studied for 6 weeks in 13 treated patients and 12 control patients with chronic angina. Assessments were exercise capacity and ischemia, daily frequency of anginal attacks and nitrate tablet consumption, and quality of life (perceived quality of life and pain). Compared with control, exercise duration (P =.03) and time to angina (P =.01) increased; anginal attacks and sublingual nitrate consumption (P =.01) and ischemic episodes on 48-hour electrocardiogram (P =.04) decreased. ST-segment depression on the exercise electrocardiogram decreased at comparable workload (P =.01). Anginal attacks and consumption of sublingual nitrates decreased (P =.01), perceived quality of life increased (P =.03), and pain decreased (P =.01).
Spinal cord stimulation is effective in chronic intractable angina pectoris, and its effect is exerted through anti-ischemic action. Efficacy is unlikely to be explained as a placebo effect from surgery.
American Heart Journal 01/1999; 136(6):1114-20. · 4.65 Impact Factor
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ABSTRACT: Spinal cord stimulation (SCS) has been used for more than 30 years now, and although it has shown to be effective under certain well-described conditions of chronic pain, conclusive evidence on its effectiveness is still sparse. There is a need for more prospective and methodological good studies, in order to prove SCS efficacy for new or still questionable indications and to reveal prognostic factors for successful application. Especially at this moment, when governments are trying to control and reduce their health care expenses, studies on the cost-effectiveness of SCS are important. In contrast to the early years when SCS was applied by independent physicians exploring the field of neurostimulation, the importance of information exchange and coordination of studies has now been recognized. Recent technical improvements of SCS devices may positively influence clinical outcome.
Spinal Cord 11/1998; 36(10):671-82. · 1.80 Impact Factor
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ABSTRACT: We determined dopamine (DA), noradrenaline (NA), and adrenaline (A), as well as immunohistochemically stained tyrosine hydroxylase (TH) and DA in dissected rat ventral mesencephalon (VM) tissue from Embryonic Day (ED) 14 to Postnatal Day (P) 17. Whole VM tissue DA, NA, and A contents increased with advancing age. VM DA/protein increased from ED15 to ED16, whereas NA/protein increased from ED15 to ED16 and from ED20 to P4. VM DA/NA ratio increased from ED14 to ED15 and decreased from ED18 to P4. VM cell suspensions exhibited higher DA/NA ratios than whole VM tissue. Washed cell suspensions had higher DA/NA than unwashed counterparts. We conclude that data from both VM immunohistochemistry and catecholamine assays relate to VM development. VM DA is contained mainly in cells, whereas VM NA is located in fibers that channel at the dorsal side of the VM. Determination of tissue catecholamine contents may be helpful for the biochemical characterization of tentatively identified VM grafts.
Experimental Neurology 07/1997; 145(2 Pt 1):434-41. · 4.70 Impact Factor
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ABSTRACT: Human fetal neural dopaminergic tissue can be transplanted and can ameliorate neurological deficiencies in patients with Parkinson's disease (PD). Donor tissue from other species has been used experimentally for several years in animal experiments and is now being considered an attractive alternative, particularly from a donor species that breeds in large litters, e.g., the pig. We have studied the early ontogenetic development of the mesencephalic dopaminergic system in the pig, utilising an anti-tyrosine hydroxylase (TH) immunocytochemical technique, and demonstrated the earliest appearance of its cell bodies at embryonic day 20 (E20). We compared the porcine data with those of human fetal development, as revealed by the same technique. Embryonic dopaminergic cell groups resembling the A8, A9, and A10 of the rat are present in the pig and differentiate into the homologous cell groups of human, although interesting quantitative differences are apparent. In the pig, prolonged presence of immature characteristics of TH-immunoreactive (TH-i.r.) cell bodies was observed, notwithstanding the early outgrowth of TH-i.r. axons into the ganglionic eminence. In the human, on the other hand, cell divisions and maturation of dendrites have progressed to a further degree than in the pig, before such distinct outgrowth of axons takes place. In pig embryos of 28 days, cells in the ventral mesencephalon had differentiated into TH containing neurons, which indicates their potential to synthesize dopamine. In spite of their differentiation, these cells still showed immature morphological features (rounded cell bodies with undifferentiated, short processes). Dopamine synthesis by these cells was demonstrated in previous studies by the high performance liquid chromatographic technique (HogenEsch et al. [1993] Can. J. Neurol. Sci. 20(suppl. 4):P.S. 235). In a separate paper, we have described that these porcine 28-day dopaminergic cells retain their potential for development and outgrowth in culture (van Roon et al. [1995] Res. Neurol. Neurosci. 7:199-205). We conclude that the ventral mesencephalon in pig embryos of 28 days is a potential source of dopaminergic neurons to be used as a xenograft in PD.
The Journal of Comparative Neurology 06/1997; 382(1):19-28. · 3.81 Impact Factor
