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Biomedical subjects

J Vitek

Publications and source records attributed to J Vitek.

At least 19 recordsLinked to original sources

Normalizing motor-related brain activity: subthalamic nucleus stimulation in Parkinson disease.

OBJECTIVE: To test whether therapeutic unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson disease (PD) leads to normalization in the pattern of brain activation during movement execution and control of movement extent. METHODS: Six patients with PD were imaged off medication by PET during performance of a visually guided tracking task with the DBS voltage programmed for therapeutic (effective) or subtherapeutic (ineffective) stimulation. Data from patients with PD during ineffective stimulation were compared with a group of 13 age-matched control subjects to identify sites with abnormal patterns of activation. Conjunction analysis was used to identify those areas in patients with PD where activity normalized when they were treated with effective stimulation. RESULTS: For movement execution, effective DBS caused an increase of activation in the supplementary motor area (SMA), superior parietal cortex, and cerebellum toward a more normal pattern. At rest, effective stimulation reduced overactivity of SMA. Therapeutic stimulation also induced reductions of movement related "overactivity" compared with healthy subjects in prefrontal, temporal lobe, and basal ganglia circuits, consistent with the notion that many areas are recruited to compensate for ineffective motor initiation. Normalization of activity related to the control of movement extent was associated with reductions of activity in primary motor cortex, SMA, and basal ganglia. CONCLUSIONS: Effective subthalamic nucleus stimulation leads to task-specific modifications with appropriate recruitment of motor areas as well as widespread, nonspecific reductions of compensatory or competing cortical activity.

Adult↗

Bilateral subthalamotomy in Parkinson's disease: initial and long-term response.

We conducted an open label pilot study of the effect of bilateral subthalamotomy in 18 patients with advanced Parkinson's disease. In seven patients, the first subthalamotomy pre-dated the second by 12-24 months ('staged surgery'). Subsequently, a second group of 11 patients received bilateral subthalamotomy on the same day ('simultaneous surgery'). Patients were assessed according to the CAPIT (Core Assessment Program for Intracerebral Transplantation) protocol, a battery of timed motor tests and neuropsychological tests. Evaluations were performed in the 'off' and 'on' drug states before surgery and at 1 and 6 months and every year thereafter for a minimum of 3 years after bilateral subthalamotomy. Compared with baseline, bilateral subthalamotomy induced a significant (P < 0.001) reduction in the 'off' (49.5%) and 'on' (35.5%) Unified Parkinson's Disease Rating Scale (UPDRS) motor scores at the last assessment. A blind rating of videotape motor exams in the 'off' and 'on' medication states preoperatively and at 2 years postoperatively also revealed a significant improvement. All of the cardinal features of Parkinson's disease as well as activities of daily living (ADL) scores significantly improved (P < 0.01). Levodopa-induced dyskinesias were reduced by 50% (P < 0.01), and the mean daily levodopa dose was reduced by 47% at the time of the last evaluation compared with baseline (P < 0.0001). Dyskinesias occurred intraoperatively or in the immediate postoperative hours in 13 patients, but were generally mild and short lasting. Three patients developed severe generalized chorea that gradually resolved within the next 3-6 months. Three patients experienced severe and persistent postoperative dysarthria. In two, this coincided with the patients exhibiting large bilateral lesions also suffering from severe dyskinesias. No patient exhibited permanent cognitive impairment. The motor benefit has persisted for a follow-up of 3-6 years. This study indicates that bilateral subthalamotomy may induce a significant and long-lasting improvement of advanced Parkinson's disease, but the clinical outcome was variable. This variability may depend in large part on the precise location and volume of the lesions. Further refinement of the surgical procedure is mandatory.

Activities of Daily Living↗

The subthalamic nucleus in Parkinson's disease: somatotopic organization and physiological characteristics.

Single-cell recording of the subthalamic nucleus (STN) was undertaken in 14 patients with Parkinson's disease submitted to surgery. Three hundred and fifty neurones were recorded and assessed for their response to passive and active movements. Thirty-two per cent were activated by passive and active movement of the limbs, oromandibular region and abdominal wall. All neurones with sensorimotor responses were in the dorsolateral region of the STN. Arm-related neurones were lateral (> or =14 mm plane) to leg-related neurones, which were found more medially (< or =12 mm). Representation of the oromandibular musculature was in the middle of the sensorimotor region (approximately 13 mm plane) and ventral to the arm and leg. Two hundred neurones were adequately isolated for 'off-line' analysis. The mean frequency of discharge was 33 +/- 17 Hz (13-117 Hz). Three types of neuronal discharges were distinguished: irregular (60.5%), tonic (24%) and oscillatory (15.5 %). They were statistically differentiated on the basis of their mean firing frequency and the coefficient of variation of the interspike interval. Neurones responding to movement were of the irregular or tonic type, and were found in the dorsolateral region of the STN. Neurones with oscillatory and low frequency activity did not respond to movement and were in the ventral one-third of the nucleus. Thirty-eight tremor-related neurones were recorded. The majority (84%) of these were sensitive to movement and were located in the dorsolateral region of the STN. Cross power analysis (n = 16) between the rhythmic neuronal activity and tremor in the limbs showed a peak frequency of 5 Hz (4-8 Hz). Neuronal activity of the substantia nigra pars reticulata was recorded 0.5-3 mm below the STN. Eighty neurones were recorded 'on-line' and 27 were isolated for 'off-line' analysis. A tonic pattern of discharge characterized by a mean firing rate of 71 +/- 28 Hz (35-122 Hz) with a mean coefficient of variation of the interspike interval of 0.85 +/- 0.29 ms was found. In only three neurones (11%) was there a response to sensorimotor stimulation. The findings of this study indicate that the somatotopic arrangement and electrophysiological features of the STN in Parkinson's disease patients are similar to those found in monkeys.

Action Potentials↗

Pathophysiologic basis of surgery for Parkinson's disease.

Dopamine depletion induces a series of changes in the basal ganglia motor circuit that underlie the origin of the cardinal features of Parkinson's disease. It has now been established that hyperactivity of the subthalamic nucleus (STN) is an essential feature of the parkinsonian state. This leads to increased excitatory driving onto the globus pallidum internum (GPi) and substantia nigra reticulata (SNr) which, in turn, overinhibits the motor projections to the thalamus and brainstem. The STN and GPi have become the preferred targets for surgery to treat PD. In keeping with the classic pathophysiologic model, physiologic and neuroimaging studies in patients have shown that lesioning or functional blockades (by deep brain stimulation, or DBS) of these nuclei increased cortical activation, in parallel with clinical improvements of bradykinesia. Neuronal recording during surgery has also shown tremor-related activity in both the STN and GPi. However, the pathophysiologic model of the basal ganglia needs further refinement to provide a more detailed explanation of the origin of both tremor and rigidity in Parkinson's disease and to explain the antidyskinetic effect of surgery of the GPi and STN.

Basal Ganglia↗

Extracranial vertebral artery stent placement: in-hospital and follow-up results.

OBJECT: The authors summarize their experience with stent deployment in the treatment of vertebrobasilar artery (VBA) insufficiency. This is an underdiagnosed condition, and the incidence of significant vertebral artery (VA) stenosis has been underappreciated. Medical therapy has been the mainstay of treatment because of the high rate of morbidity associated with surgical correction of VA stenosis. Recently, some authors have reported acceptable results with the use of percutaneous transluminal angioplasty, but this technique has significant weaknesses such as elastic recoil and problems in achieving safe treatment of dissections. METHODS: The authors investigated the feasibility, safety, and outcome of VA stent placement in 50 patients in whom 55 vessels were treated using stents. Technical success was achieved in 54 (98%) of 55 vessels, with no procedure-related complications. However, one patient (2%) died of nonneurological causes, and one (2%) suffered a stroke that occurred within the 30-day postprocedural period and was related to a complicated coronary intervention. Clinical follow-up review performed at a mean of 25 +/- 10 months revealed two patients (4%) with recurrence of VBA symptoms. Six-month angiographic follow up was completed in 90% of eligible patients, with a 10% incidence of restenosis as defined by greater than 50% luminal narrowing. CONCLUSIONS: Vertebral artery stent placement is feasible in patients who have significant VA stenosis, with predictably good angiographically demonstrated and clinical results. The 6-month angiographically confirmed restenosis rate appears to be low, as does the clinical recurrence rate. This technique solves the problems of elastic recoil and the treatment of angioplasty-induced dissections. Further prospective comparison with medical preventive strategies is warranted.

Adult↗

The subthalamic nucleus and tremor in Parkinson's disease.

The role of the subthalamic nucleus (STN) in the origin of parkinsonian tremor is discussed. Previous studies in monkeys made parkinsonian by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) administration suggested a direct participation of the STN in the pathophysiology of tremor. We recorded tremor-related activity in the STN in 12 patients with Parkinson's disease (PD) and found that microstimulation of the sensorimotor region of the nucleus, where these neurons are present, stopped the tremor with a very short latency. Long-term treatment by means of bilateral deep-brain stimulation (DBS) in the same 12 patients led to a significant reduction of tremor as well as other cardinal features of PD. This effect was blindly assessed at 3 months after implantation. In another group of seven patients, a unilateral lesion of the STN was performed. Both postural and resting tremor were significantly improved on the limbs contralateral to the lesion side. In three patients, tremor disappeared completely after 12 months of follow up. The electrophysiologic data and therapeutic effect of inactivating the STN strongly indicated that this structure is directly involved in the origin of parkinsonian tremor, as suggested by the MPTP model.

Adult↗

Phase II study of intracarotid or selective intracerebral infusion of cisplatin for treatment of recurrent anaplastic gliomas.

PURPOSE: To assess the response of patients with recurrent malignant gliomas to intra-arterial (IA) cisplatin. METHODS: Eligibility criteria included patients with recurrent supratentorial malignant gliomas and measurable, unilateral contrast-enhancing tumor located within the territory of one or two major cerebral arteries. Patients received 75 mg/m2 IA cisplatin every four weeks. Depending on individual patients' tumor topography, cisplatin was infused either into the cervical internal carotid artery (ICA) (15 patients), or into one or two major cerebral arteries (26 patients), most often the M1 segment of the middle cerebral artery. RESULTS: Of 40 patients evaluable for tumor response, four patients (10%) were responders and nine patients (22%) had disease stabilization. The median time to tumor progression among the 13 patients with tumor response or stable disease was 23.7 weeks. The response rate did not significantly differ between patients receiving ICA versus selective intracerebral infusion, although the latter group contained a higher proportion of glioblastoma. Tumor progression occurred solely as local failure in 33 patients (82%), with all enhancing tumor still located within the vascular territory infused with IA cisplatin. Ipsilateral vision loss occurred in two patients after ICA cisplatin but in none of the selective infusion patients. Seizures and/or transient or permanent neurologic deterioration occurred in four patients (27%) after ICA cisplatin and in 11 patients (44%) after selective intracerebral infusion. CONCLUSIONS: Although this was not a randomized comparison, selective intracerebral artery cisplatin infusion in this group of patients reduced the risk of eye toxicity, but did not produce a better tumor response rate, and carried a higher risk of neurotoxicity relative to ICA infusion.

Adult↗

Elective stenting of the extracranial carotid arteries.

BACKGROUND: Surgical endarterectomy has been shown to be superior to medical management in the management of severe carotid stenosis in both symptomatic and asymptomatic patients. Endarterectomy, although effective, does have limitations, and percutaneous techniques may offer an alternative method of treatment. METHODS AND RESULTS: The feasibility and safety of percutaneous carotid angioplasty and elective (primary) stenting was evaluated prospectively in a consecutive series of 107 patients. One hundred twenty-six carotid arteries with significant stenosis were treated. This series represented a high-risk subset that included patients with previous ipsilateral endarterectomy and severe medical comorbidity. Forty-five percent of the patients were referred by surgeons. Patients had independent neurological examinations before and after the procedure and follow-up cerebral angiography at 6 months. The mean (+/- SD) stenosis was reduced from 78 +/- 14% to 2 +/- 5%. There were 7 minor strokes, 2 major strokes, and 1 death during the initial hospitalization and first 30 days after the procedure. For the combined end point of all strokes and death, the incidence was 7.9%. For ipsilateral major stroke and death, the incidence was 1.6%. There were no strokes during the follow-up period. Mean angiographic stenosis at 6 months in 81 patients was 18 +/- 16% (range, -21% to 57%). Four (4.9%) of these 81 patients had asymptomatic restenosis. Five asymptomatic patients had repeat intervention: 2 had angioplasty for restenosis, 2 had angioplasty for stent deformation, and 1 had endarterectomy for restenosis. CONCLUSIONS: In a high-risk group of patients, percutaneous carotid angioplasty and stenting are feasible and can be performed with low restenosis and repeat intervention rates.

Aged↗

Combined coronary and bilateral carotid stenting: a case report.

We describe a patient who underwent stenting of both internal carotid arteries and two coronary arteries. Two combined carotid and coronary procedures were done 4 wk apart to revascularize the patient. The first procedure was complicated by a minor stroke with good recovery. At 6 mo of follow-up, he is asymptomatic and without angiographic restenosis.

Aged↗

Brain edema in meningiomas is associated with increased vascular endothelial growth factor expression.

OBJECTIVE: Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF), an endothelial cell-specific cytokine, induces proliferation of endothelial cells and increases vascular permeability dramatically. All gliomas secrete significant amounts of VEGF, whereas meningiomas are variable in expression. Thus, we sought to determine whether the extent of VPF/VEGF expression in meningiomas correlated with differences in brain edema associated with these tumors. METHODS: Meningioma tissue samples from 37 patients (15 men, average age 65 +/- 13 yr; 22 women, average age 60 +/- 10 yr) who underwent surgery at or were referred to the University of Alabama Hospital were examined retrospectively for the extent of expression of immunoreactive VPF/VEGF. Additionally, peritumoral edema was assessed on a blinded basis radiographically from preoperative magnetic resonance imaging scans. Selected specimens were examined by in situ hybridization to document the source of VPF/VEGF. RESULTS: The predominant meningioma subclassifications were transitional (57%) or meningothelial (27%) subtypes. VPF/VEGF immunoreactivity ranged from 0 to 3.5, with a median value of 2 on a subjective 5-point scale; magnetic resonance imaging-assessed edema ranged in extent from 0 to 4 (subjective 5-point scale), with a median value of 2.5. The correlation of determination (R2) of magnetic resonance imaging-assessed tumor edema rating and VPF/VEGF staining intensity rating was 0.6087 (r = 0.78; P = 0.0001). In situ hybridization localized VPF/VEGF messenger ribonucleic acid in meningioma cells and not in normal parenchymal brain cells. CONCLUSION: These data suggest that meningioma-associated edema may be a result of the capacity of meningioma cells to produce VPF/VEGF locally, leading to increased tumor neovascularization and enhanced vascular permeability.

Adult↗

Carotid endarterectomy performed after progressive carotid stenosis following angioplasty and stent placement. Case report.

Carotid endarterectomy (CEA) is the treatment of choice for asymptomatic and symptomatic disease causing greater than 60% internal carotid artery (ICA) stenosis. Recently, percutaneous transluminal angioplasty (PTA) with stent placement has been investigated as a therapeutic option for the treatment of ICA stenosis. In this report the authors document CEA performed after PTA with stent placement and describe the pathological findings. A standard CEA was performed. The surgical intervention was more difficult secondary to the following variables: the length of the exposure necessary to dissect out the metallic stent, the difficulty with opening and cutting the artery, and the care required to remove the stent to avoid vessel wall perforation. Pathological examination of the specimen demonstrated classic atherosclerotic changes revealing persistence of native disease. The metallic stent was embedded within the plaque. Many questions remain unanswered regarding the physiological and biological changes that occur in the carotid vessel wall after PTA with stent placement. It is concluded that CEA of a stent-containing carotid artery is feasible and should be considered as an alternative when recurrent stenosis occurs after PTA.

Angioplasty, Balloon↗

Carotid stent-supported angioplasty: a neurovascular intervention to prevent stroke.

Obstructive carotid artery disease is responsible for 60% of strokes in the United States and is the third major cause of death. Stent-supported carotid artery angioplasty has the potential to prevent stroke in thousands of patients and offers a number of potential advantages over surgical revascularization (carotid endarterectomy). Results of the prospective observational study at the University of Alabama at Birmingham indicate that carotid stent-supported angioplasty is safe and probably effective in reducing stroke in patients with high-risk cerebrovascular disease. Technical success was achieved in 99% of 146 procedures; 210 stents were placed in 152 vessels, with only 1 instance of stent thrombosis. The rate of major in-hospital complications was unexpectedly low-only 1 death and 2 major strokes. Seven patients suffered minor strokes, but only 2 were left with minor weakness. When compared with a projected complication rate of 6% had these patients undergone carotid endarterectomy, stenting resulted in fewer major events. At 6-month follow-up, 69 of 74 patients were evaluated by angiography or ultrasound, which detected 8 cases of stent deformation and a restenosis rate of < 5%. Because of these instances of stent deformation, use of the Palmaz (biliary) stent was discontinued. Although 1 patient had a transient ischemic attack, no strokes occurred during follow-up. To date, carotid stenting is an investigational procedure. Cardiovascular interventionalists, industry, and the FDA are encouraged to validate this approach through clinical testing. However, improvements in technique, devices, and adjunctive therapies are needed before the method can be tested in randomized trials.

Adult↗

Angioplasty and stenting for restenosis after carotid endarterectomy. Initial experience.

BACKGROUND AND PURPOSE: Endarterectomy for recurrent carotid stenosis after endarterectomy has a significantly higher complication rate than the original operation. Angioplasty and stenting may offer a useful alternative treatment for these patients. METHODS: Between September 1994 and April 1996, 22 patients had 25 carotid arteries treated with angioplasty and stenting for postendarterectomy restenosis. All patients had an independent neurological examination and National Institutes of Health Stroke Scale evaluation before and after the procedure. Patients were treated with aspirin and ticlopidine. All patients were requested to return at 6 months for follow-up angiography. The mean patient age was 69 +/- 7 years, and the mean elapsed time from endarterectomy was 73 +/- 69 months. Seventy-seven percent of the patients were symptomatic. RESULTS: Mean stenosis was reduced from 79 +/- 13% before the procedure to 1.8 +/- 3.6% after stenting. One patient had a minor stroke, for a complication rate of 4% per treated artery. In the eight patients who returned for 6-month angiography, mean stenosis was 19.4 +/- 4.4% and restenosis (> or = 50% stenosis) did not occur. CONCLUSIONS: In a small series, angioplasty and stenting appear to be safe and well tolerated for the treatment of postendarterectomy restenosis.

Aged↗

Mutations in the CYP11B1 gene causing congenital adrenal hyperplasia and hypertension cluster in exons 6, 7, and 8.

Steroid 11 beta-hydroxylase deficiency (failure to convert 11-deoxycortisol to cortisol) is the second most common cause of congenital adrenal hyperplasia and results in a hypertensive form of the disease. The 11 beta-hydroxylase enzyme is encoded by the CYP11B1 gene on chromosome 8q22. Two mutations in CYP11B1 have previously been reported in patients with 11 beta-hydroxylase deficiency--Arg-448-->His and a 2-bp insertion in codon 394. We now report eight previously uncharacterized mutations causing this disorder. Seven are point mutations (three nonsense and four missense) and one is a single base pair deletion causing a frameshift. We have used an in vitro transfection assay to show that all five known missense mutations causing 11 beta-hydroxylase deficiency abolish enzymatic activity. In principle, deletions of CYP11B1 could be generated by unequal crossing-over between CYP11B1 and the adjacent CYP11B2 gene, but no such deletions were found among the deficiency alleles in this study. Seven of the 10 known mutations are clustered in exons 6-8, a nonrandom distribution within the gene. This may reflect the location of functionally important amino acid residues within the enzyme or an increased tendency to develop mutations within this region of the gene.

Adrenal Hyperplasia, Congenital↗

Polymorphism in the RD (D6S45) gene.

The RD (D6S45) gene in the class III region of the HLA major histocompatibility complex encodes a protein normally containing 24 consecutive basic-acidic dipeptide repeats. We determined the frequency of variations in the number of repeats by use of the polymerase chain reaction. Of 107 subjects 7 (3.3%) carried genes encoding 22 or 23 repeats. There was no difference in the frequency of such polymorphisms between normal individuals and those with systemic lupus erythematosus, a disease associated with other polymorphisms in the class III region of HLA. The frequency of polymorphisms in proteins with oligopeptide repeats may provide useful information concerning functional constraints on repeat number.

Base Sequence↗