Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The two principle targets for deep brain stimulation or lesioning in patients with Parkinson's disease, the subthalamic nucleus (STN) and the globus pallidus internus (GPi), reveal a high degree of individual variability which is relevant to the planning of stereotactic operations. Both nuclei can clearly be delineated in T2WI spin echo MRI which was acquired under stereotactic conditions in general anesthesia before surgery. Such images of 35 patients served for retrospective morphometric analysis of different basal ganglia nuclei (STN, GP, red nucleus, and substantia nigra) and several anatomical landmarks (anterior and posterior commissure, maximum width of third ventricle, brain length and width). The average AC-PC distance was 25.74 mm (range 21 to 29 mm) and is in agreement with previous studies. On average, the center of the STN was located 12.65 mm (+/-1.3) lateral from the midline as determined 3 mm ventral to the intercommissural plane. The average width of the third ventricle was 7.05 mm (+/-2.41). The width of the third ventricle correlated with the laterality of the STN (r(right)=.78; r(left)=.83) and GP (r(right)=.76; r(left)=.68). Although to a lesser extent, significant correlations were also observed between the laterality of the STN and brain width, improving prediction of STN laterality by multiple linear regression analysis (r(right)=.82; r(left)=.87). Similarly, the laterality of GP correlated with brain width. In addition, gender-specific differences were detected. The STN and GP was located farther lateral in males which may be due to overall brain anatomy as gender-specific differences were also observed for brain width and length and AC-PC distance. MRI-based in vivo-localization of different basal ganglia nuclei extend statistical information from common histological brain atlases which are based on a limited number of brains. The correlations observed between different basal ganglia nuclei, i.e. the STN and GPi, and anatomical landmarks may be useful for surgical planning.
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PMID:Magnetic resonance imaging-based morphometry and landmark correlation of basal ganglia nuclei. 1238 23

Parkinson's disease patients are known to have not only motor but also urinary autonomic disorders, suggesting central dopaminergic pathways being involved in the micturition function. However, there is little evidence that the substantia nigra pars compacta (SNC) and the ventral tegmental area (VTA), the major dopamine-containing nuclei in the midbrain, should participate in regulating micturition. We investigated micturition-related electrophysiological properties in the SNC and VTA. In 20 male cats under ketamine anaesthesia, in which spontaneous isovolumetric micturition reflex was generated, we performed electrical stimulation and extracellular single-unit recording in the SNC and the VTA, and correlation analysis of the neuronal firings and antidromic stimulation between the SNC/VTA and the pontine storage centre (PSC). Electrical stimulations in the SNC elicited termination of the micturition reflex, whereas those in the VTA elicited both termination and facilitation of the reflex. Forty-nine neurons in the SNC/VTA showed firing in response to the bladder storage/micturition cycles. The major neurons were tonic storage (55%) and phasic storage neurons (22%), which were found diffusely in th e SNC/VTA. The rest were tonic micturition (16%) and phasic micturition neurons (6%), which were concentrated in the caudal part (A2-4 in the Horsley-Clarke coordinates). These neuronal types were further subclassified into augmenting, constant, binary and decrementing neurons according to their temporal discharge rate change. The decrementing neurons were concentrated in the caudal part (A2-4), whereas the augmenting neurons in the rostral part (A4-6). Some of the recorded neurons had preceding firing pattern, which was more frequently found in the tonic type than in the phasic-type neurons. Twenty-four of the neuronal firings in the SNC/VTA were recorded simultaneously with those in the PSC. However, there was no apparent time-correlation between both sets of neuronal firings. In 15 of the simultaneous recording sites, electrical stimulation was applied to one site to see if antidromic response might be evoked in another site. However, there was no orthodromic or antidromic response in either SNC/VTA or PSC. In conclusion, the present study indicates that neurons in the SNC and the VTA are involved in supra-pontine control of micturition, particularly of urinary storage phase. It is also likely that the major role of the SNC is inhibition of the micturiton reflex, whereas that of the VTA is both facilitation and inhibition of the micturition reflex.
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PMID:Micturition-related electrophysiological properties in the substantia nigra pars compacta and the ventral tegmental area in cats. 1249 33

The subthalamic nucleus (STN) is now regarded as the optimal surgical target for the treatment of medically refractory idiopathic Parkinson's disease. In our center, a predominantly MRI-directed method has been developed for targeting the STN. The STN is localized on T2-weighted images from a 1.5-T MRI scanner. Long acquisition, high-resolution images are acquired in both the axial and coronal planes under strict stereotactic conditions with the patient under general anesthesia. The boundary of STN is co-registered in both planes to give optimal 3-dimensional target definition. Stereotactic coordinates of the dorsolateral STN are recorded and the trajectory is planned down the axis of the nucleus in the coronal plane. Initially, per-operative macrostimulation was used for adjustment at the target prior to unilateral subthalamotomy in 26 patients. Five patients were lost to follow-up. Assessments of the lesions in post-operative images confirmed successful localisation of the lesions within the dorsolateral STN in all of the remaining 21 cases. In a subsequent series of 19 patients treated by deep brain stimulation (DBS), unilateral in 1 patient and bilateral in 18, the STN was targeted using the same MRI-directed method, guide tubes and radio-opaque stylettes were implanted, and target verification was entirely MRI-based. Following implantation of the guide tubes and stylettes, assessments of the per-operative MRI images for the 37 STN targetings confirmed a mean target error, between the stylette and the desired target in the axial plane, of 0.3 mm mediolaterally (SD = 0.4) and 0.4 mm anteroposteriorly (SD = 0.4), with median errors of 0.5 mm. This study demonstrates that MRI-directed targeting of the STN through guide tubes is accurate, and allows direct verification and corrections as necessary. Cumulative frequencies predict that the majority of DBS electrodes placed in this manner will be within 0.5 mm of the planned target. Because physiological methods are not required, the whole procedure can be performed under general anesthesia. We feel that planning with reference to a standard atlas is unreliable and not significantly helped by the addition of microelectrode recording, the accuracy of which in the axial plane is dependent upon the distance between the recording trajectories, which is typically 2 mm.
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PMID:MRI-directed subthalamic nucleus surgery for Parkinson's disease. 1265 38

Dystonia is a neurological syndrome involving sustained contractions of opposing muscles leading to abnormal movements and postures. Recent studies report abnormally low pallidal neuronal activity in patients with generalized dystonia, suggesting hyperkinetic disorders result from underactive basal ganglia output. We examined this hypothesis in 11 patients with segmental and generalized dystonia undergoing microelectrode exploration of the internal globus pallidus (GPi) before pallidotomy or deep brain stimulation (DBS) implantation. The mean firing rates and firing patterns were compared with those in six patients with Parkinson's disease (PD). In seven patients who underwent surgery under local anesthesia, the mean GPi firing rate was 77 Hz, similar to the 74 Hz observed in the PD patients. However, in three dystonic patients under propofol anesthesia, GPi mean firing rate was much reduced (31 Hz), and the firing pattern was distinguished by long pauses in activity, as reported by others. Low-dose propofol in one other dystonia patient also seemed to suppress GPi firing. These results indicate that an abnormally low basal ganglia output is not the sine qua non of dystonia. The widely accepted pathophysiological models of dystonia that propose global decreases in basal ganglia output need to be viewed with caution in light of these findings.
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PMID:Pallidal neuronal activity: implications for models of dystonia. 1266 15

1. This study was undertaken to elucidate dopaminergic mechanisms underlying bladder hyperactivity in a rat model of Parkinson's disease (PD) induced by a unilateral 6-OHDA injection into the substantia nigra pars compacta. 2. In 6-OHDA-lesioned rats, voided volume per micturition (0.41+/-0.04 ml, mean+/-s.e.m.) measured during 24 h in a metabolic cage was significantly smaller than in sham-operated rats (0.67+/-0.07 ml). 3. Cystrometrograms (CMG) in conscious animals revealed significantly smaller bladder capacity (BC) (0.46+/-0.03 ml) in 6-OHDA-lesioned rats than in sham rats (0.72+/-0.06 ml). 4. SKF38393 (D1/D5 receptor agonist, i.v.) significantly increased BC in 6-OHDA rats without apparent effects in sham rats. SKF38393 applied intracerebroventricularly (i.c.v.) under urethane anesthesia also increased BC in 6-OHDA-lesioned rats and by a smaller increment in sham rats. 5. In contrast, quinpirole (D2/D3/D4 receptor agonist, i.v.) significantly reduced BC in sham and 6-OHDA-lesioned rats. Intrathecal injection of quinpirole similarly reduced BC in sham and 6-OHDA-lesioned rats. 6. PD128907 (D(3)-receptor agonist) did not have significant effects on BC in 6-OHDA-lesioned rats. 7. These results indicate that a rat model of PD exhibited bladder hyperactivity as observed in patients with PD, and that stimulation of D1/D5 dopamine receptors at a supraspinal site can suppress bladder hyperactivity in PD, whereas stimulation of D2/D4, but not D3, dopamine receptors had the opposite effect to reduce bladder capacity. Thus, D1/D5 dopamine receptor agonists might be effective in treating neurogenic bladder hyperactivity in PD.
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PMID:Dopaminergic mechanisms underlying bladder hyperactivity in rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway. 1292 29

A patient with Parkinson's disease refused both anti-Parkinson medication and general anaesthesia. Low dose remifentanil infusion suppressed her otherwise severe tremor, and the operation was performed uneventfully under local anaesthesia.
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PMID:[Temporary suppression of tremor by remifentanil in a patient with Parkinson's disease during cataract extraction under local anesthesia]. 1450 5

Neurodegenerative diseases are increasingly common in elderly patients, who present a particular anaesthetic challenge. The majority of people over the age of 70 years have some degree of cerebral atrophy. The pathogenesis of neurodegenerative diseases is due to alterations in the transport, degradation and aggregation of proteins. Alterations in physiology that occur with advancing age affect both the pharmacokinetics and pharmacodynamics of drugs used in the elderly. Changes in pharmacokinetics result in either increased or reduced drug concentrations depending on the variable contributions of absorption, metabolism and elimination. The distribution of a drug depends on its protein binding, cardiac output and blood volume, which are all altered in the elderly. Metabolism and excretion of drugs are also affected due to changes in hepatic and renal mass and blood flow in the elderly. A number of drugs are used in neurodegenerative disorders including antidepressants, benzodiazepines, antipsychotics, acetylcholinesterase inhibitors and levodopa. Polypharmacy is a common problem, which can lead to adverse drug interactions and an exacerbation of dementia. Levodopa, bromocriptine and tricyclic antidepressants are known to cause orthostatic hypotension in patients with neurodegenerative disease. Elderly patients are liable to excessive sedation from benzodiazepines in both the pre- and postoperative period; therefore these drugs should be prescribed in low doses. For induction of general anaesthesia propofol is a suitable agent in patients with neurodegenerative disease due to its rapid metabolism, but may not be suitable in patients with Parkinson's disease as it can induce spontaneous involuntary movements. Volatile inhalational agents should be administered carefully in the elderly, as they are more sensitive to the depressant cerebral and cardiovascular effects. Levodopa should be avoided in conjunction with halothane, which sensitises the heart to catecholamines. Co-administration of monoamine oxidase inhibitors and opioids should be avoided as it can cause agitation, muscular rigidity, sweating and hyperpyrexia. If an anticholinergic agent is required, then glycopyrronium bromide is the drug of choice in this group of patients, as it does not cross the blood brain barrier. Patients should continue to take their usual medications in hospital and do not let the change in routine alter the times at which treatments are administered. This is particularly relevant to the timing of levodopa in Parkinson's disease, as missed treatment can be detrimental. Regional anaesthesia may, however, have significant advantages in patients with Parkinson's disease, who can continue to take oral levodopa preoperatively, during surgery, if required, and early in the postoperative period. Anti-emetic drugs such as phenothiazines, butyrophenones and metoclopramide should be used carefully in the postoperative period in these patients as their antidopaminergic effects may induce or exacerbate parkinsonian effects.
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PMID:Anaesthesia in elderly patients with neurodegenerative disorders: special considerations. 1501 69

A 72-year-old male patient with Parkinson's disease referred to the Dental Hospital of Kyushu University, Fukuoka, Japan, presented with movement of an implant-supported prosthesis, slight pain, and purulent drainage from the gingiva in the anterior region of the maxilla, where implants had been placed more than 20 years earlier. He requested that the mobile implant and prosthesis be removed and was in need of implant therapy in his maxilla. In addition to Parkinson's disease the patient had a severe gag reflex, which made treatment difficult. A total of 6 treatments were required. New implants were successfully placed while the patient was under anesthesia (a combination of intravenously administered 3% prilocaine hydrochloride and vasopressin); midazolam was also administered intravenously. The results of this case indicate that use of regional anesthesia in combination with midazolam can be recommended for implant surgery in patients with Parkinson's disease. Intravenous midazolam can be considered the sedative of choice for the surgical treatment of patients suffering from systemic disease.
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PMID:Implant surgery for a patient with Parkinson's disease controlled by intravenous midazolam: a case report. 1510 2

Functional surgery for movement disorders is a recent stereotactic neurosurgical operation, restricted yet to patients with advanced Parkinson's disease or with generalized primary dystonia. One or two electrodes are implanted in the basal ganglia, namely in the globus pallidus pars interna or in the subthalamic nucleus, to realize a deep brain stimulation at high frequency. While this approach needs additional data to demonstrate clinical benefits, first results observed after short and long-term follow up are encouraging. Perioperative problems in patients with Parkinson's disease are possible respiratory disorders, a postoperative miss in medication doses and potential drug interactions with anaesthesia. The objectives of anaesthesia will be to allow stereotactic neurosurgical procedure, to maintain the upper airway patency and to be quickly reversible.
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PMID:[Functional surgery for movement disorders: implications for anaesthesia]. 1512 Jul 92

Spatial distribution of the clinical effects induced by deep brain stimulation during the intraoperative investigation of the subthalamic nucleus (STN) for Parkinson's disease (PD) was analysed in 17 patients under local anesthesia. The stimulation parameters were 130 hertz, 100 micros, and voltage ranged from 0.05 to 5 volts. Optimal motor response was assessed as the total and lasting disappearance of wrist rigidity on the side opposite to stimulation. Among the adverse effects induced by stimulation, special attention was given to frequently observed autonomic effects (AE). Full motor response was achieved in 49.2% of the 301 points evaluated,with a mean voltage (MV) of 0.94 volts; paresthesiae occurred in 6.6% (MV: 2 volts), dystonia in 10.6% (MV: 3.4 volts), autonomic effects in 19.6% (MV: 3.1 volts) and oculomotor effects in 31.6% (MV: 3 volts). The motor target was located in the posterodorsal part of the nucleus and the optimal point for motor response was close to the superior limit of the nucleus. Whereas other adverse effects occurred relatively far from the motor target, AE occurred with statistic significance near this point. Their neural substrates, such as limbic system and their relationship with postoperative behavioral disorders, are discussed.
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PMID:Motor and non motor effects during intraoperative subthalamic stimulation for Parkinson's disease. 1572 57


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