Stimulation of the rat subthalamic nucleus is neuroprotective following significant nigral dopamine neuron loss.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is efficacious in treating the motor symptoms of Parkinson's disease (PD). However, the impact of STN-DBS on the progression of PD is unknown. Previous preclinical studies have demonstrated that STN-DBS can attenuate the degeneration of a relatively intact nigrostriatal system from dopamine (DA)-depleting neurotoxins. The present study examined whether STN-DBS can provide neuroprotection in the face of prior significant nigral DA neuron loss similar to PD patients at the time of diagnosis. STN-DBS between 2 and 4 weeks after intrastriatal 6-hydroxydopamine (6-OHDA) provided significant sparing of DA neurons in the SN of rats. This effect was not due to inadvertent lesioning of the STN and was dependent upon proper electrode placement. Since STN-DBS appears to have significant neuroprotective properties, initiation of STN-DBS earlier in the course of PD may provide added neuroprotective benefits in addition to its ability to provide symptomatic relief.

Intracranial metastatic parathyroid carcinoma: case report.

OBJECTIVE AND IMPORTANCE: Parathyroid carcinoma is a rare entity, and fewer than 200 cases have been described. It is a slowly progressive disease characterized by frequent recurrences and local metastases. Most patients with parathyroid carcinoma die from metabolic complications of hyperparathyroidism. Five-year survival rates range from 25 to 50%. Functional parathyroid carcinoma is a rare cause of hyperparathyroidism that affects only 0.32 to 5% of all patients who undergo surgery for hypercalcemia. A review of the literature revealed only one other reported case of metastatic intracranial parathyroid carcinoma, in a patient who experienced local recurrence and metastatic disease when she was diagnosed with an intracranial lesion. CLINICAL PRESENTATION: We report the case of a 44-year-old African-American man with recent-onset, right lower-extremity weakness and hypercalcemia 4 years after he underwent a parathyroidectomy for parathyroid carcinoma. At presentation, his parathyroid level was 467 pg/ml, and his serum calcium level was 15.2 mg/dl. Imaging studies revealed an isolated enhancing left mesial frontoparietal mass. A systemic Cardiolite study demonstrated a single focus of radiotracer uptake in this region. No abnormal uptake was demonstrated in the neck or elsewhere. INTERVENTION: The patient underwent a frameless stereotactic interventional magnetic resonance imaging-guided resection via a parasagittal interhemispheric approach. Pathological findings were consistent with parathyroid carcinoma. After resection, his right lower-extremity weakness and secondary hyperparathyroidism resolved. CONCLUSION: The typical natural history of parathyroid carcinoma concludes with death from complications of hyperparathyroidism. This case report supports aggressive surgical management to eliminate all parathyroid hormone-secreting malignant tissue and prevent metabolic complications. In this patient, intraoperative magnetic resonance imaging was helpful to ensure complete resection.

Dorsal midline proboscis associated with diastematomyelia and tethered cord syndrome. Case report.

There have been sporadic reports on tail proboscis, a vestigial appendage, as part of sacrococcygeal dysraphism. The case the authors present, different from the tail proboscis, is the first report linking a proboscis containing a hemilipomyelomeningocele with tethered cord syndrome, associated with diastematomyelia. Tethering was caused by the diastematomyelia that anchored the split spinal cord. The authors emphasize the importance of prompt diagnostic and therapeutic measures for treatment of this condition.

Biological significance of tissue plasminogen activator content in brain tumors.

Fresh brain-tumor samples were obtained at operation and analyzed for their content of tissue type plasminogen activator (tPA) using an activity assay (gel chromatography zymogram) and an enzyme-linked immunospecific assay. The specimens were taken from 23 glioblastomas, 35 metastatic tumors, 42 meningiomas, 16 low-grade gliomas, and seven acoustic neurinomas; seven specimens were from normal brain. A strong correlation was found between the results of the two assays (r = 0.77, p less than 0.0001). There was a threefold difference in the tPA content of the benign tumors as compared to malignant tumors (p = 0.0006), the latter having less tPA. Histologically benign meningiomas contained higher tPA than malignant meningiomas (p = 0.01); however, the difference between low-grade gliomas and high-grade gliomas was less evident. Overall regression analysis data have shown an inverse relationship between the tissue content in tPA and the presence and degree of tumor necrosis and peritumoral brain edema (p = 0.004 and p = 0.0004, respectively). This finding was most consistent in the glioblastoma group where the correlation coefficient values were r = 0.53 and r = -0.55, respectively. There was no significant correlation between the tissue tPA content and the age and sex, steroid use, or plasma tPA of the patients or the duration of symptoms. In summary, this is the first demonstration of tPA in a large series of human brain tumors and in normal brain. The differences observed have clear biological significance and, although the source of tPA in tumor tissue is still unknown, a relative reduction in tPA in tumor tissue may play an integral role in the development of tissue necrosis and tissue edema. The lack of tPA in tumor necrosis was not due to tissue destruction and cell death since urokinase was readily detectable in that tissue.

Bloody cerebrospinal fluid alters contractility of cultured arteries.

The pathogenesis of cerebral vasospasm that follows aneurysmal subarachnoid hemorrhage (SAH) is poorly understood. Multiple methods have been used to clarify the mechanism of spasmogen-induced vasospasm, however, each method has its own limitations. Cultured cells lose their phenotype and inter-cellular interactions, and animal models are expensive and can be used only in some established centers. Isolated cerebral arteries have been used extensively to study the contractility by transient exposure to spasmogens that, however, can hardly represent cerebral vasospasm that occurs 2-4 days after SAH. In this study, we cultured arteries with bloody cerebrospinal fluid (CSF) from patients of cerebral vasospasm and studied the contractility of the arteries 1, 3 and 4 days later. This method preserves artery wall structure, prolongs exposure of artery to bloody CSF, and is simple and inexpensive. Cultured rat aorta showed enhanced contractile response to 5-HT (p < 0.001) but reduced response to KCl (p < 0.05) 4 days after culturing with bloody CSF. We concluded that the contractility of arteries was modified by prolonged incubation with bloody CSF. Our observations in this study could be important and may explain some aspects of pathogenesis of cerebral vasospasm.

Stereotactic pallidotomy results for Parkinson's exceed those of fetal graft.

Fetal graft research and renewed interest in Leksell's postero-ventral pallidotomy (PVP) stimulated reconsideration of surgical therapy for Parkinson's disease (PD), particularly with regard to improving akinetic symptoms previously thought resistant to surgical lesions. Review of our series and other published results of PVP and fetal graft show that PVP has beneficial effects on both akinetic and hyperkinetic symptoms that better the results reported for fetal graft implantation and other conventional stereotactics. Presented are the results of 60 consecutive patients, 55 of whom underwent PVP, and 5 who underwent fetal graft implantation. Using the Unified Parkinson's Disease Rating Scale (UPDRS), we found that PVP gave significant (P < 0.05) reductions in akinetic symptomatology including freezing, arising from a chair, posture, gait, postural instability, and bradykinesia. Fetal graft patients had significant reductions in two akinetic symptoms: bradykinesia and postural instability. PVP's dramatic therapeutic effects on akinesia may be explained by interruption of amplified collateral inhibitory output from the pallidum to brain stem locomotor centers such as the pedunculopontine nucleus, whereas interruption of collaterals to ventral lateral thalamus by PVP may account for the elimination of hyperkinesia. The excellent results of PVP represent a significant advance in the surgical treatment of PD.

Pathophysiology of tethered cord syndrome.

Tethered cord syndrome, manifested by motor and sensory dysfunction and incontinence, is caused by excessive tension in the lumbosacral cord. The underlying mechanism is related to impairment of oxidative metabolism in this region. This theory is derived from redox changes of cytochrome a, a3, and supported by spinal cord blood flow, evoked potential, and histological studies. The well-known finding of elongated spinal cord attached to the tight filum or a tumor is not always demonstrated in imaging studies, and understanding of pathophysiology allows physicians to correctly diagnose and treat patients with tethered cord syndrome.

Language representation in the human brain: evidence from cortical mapping.

The manner in which the human brain processes grammatical-syntactic and lexical-semantic functions has been extensively debated in neurolinguistics. The discreteness and selectivity of the representation of syntactic-morphological properties in the dominant frontal cortex and the representation of the lexical-semantics in the temporo-parietal cortex have been questioned. Three right-handed adult male neurosurgical patients undergoing left craniotomy for intractable seizures were evaluated using various grammatical and semantic tasks during cortical mapping. The sampling of language tasks consisted of trials with stimulation (experimental) and without stimulation (control) from sites in the dominant fronto-temporo-parietal cortex The sampling of language implicated a larger cortical area devoted to language (syntactic-morphological and lexical-semantic) tasks. Further, a large part of the fronto-parieto-temporal cortex was involved with syntactic-morphological functions. However, only the parieto-temporal sites were implicated with the ordering of lexicon in sentence construction. These observations suggest that the representation of language in the human brain may be columnar or multilayered.

Endoscopic procedures for resection of arteriovenous malformations.

BACKGROUND: Resection of arteriovenous malformations (AVMs), particularly those located in functional areas, requires precision. To enhance that precision, endoscope-assisted microsurgery has been employed at Loma Linda University. METHODS: Twenty-five consecutive cases of AVM were treated microsurgically with endoscopic assistance. Patients were divided into two groups: (1) those having AVMs in functional areas, and (2) those whose AVMs extended into the ventricle, either in the trigonal area or the capsulocaudatothalamic area. The endoscope was inserted into the subarachnoid space to interrupt communicating venules around the major draining vein and into the cleavage developed between the AVM venous loops and surrounding brain tissue as shunting arterioles and communicating venules were interrupted. For surgery of intraventricular AVMs, the curved endoscope was inserted into the ventricle, providing visualization of the AVM core, which was dissected from the ventricular side. RESULTS: AVMs were totally resected in all cases except for two patients with capsulocaudatothalamic AVMs, which were decreased in size sufficiently to receive radiosurgery. CONCLUSION: Endoscope-assisted microsurgery enhances magnification, illumination, and technical precision while the surgeon is dissecting the AVM core vessels and while operating on AVMs extending into the ventricle.

Interventional MRI-guided stereotactic aspiration of acute/subacute intracerebral hematomas.

Surgical interventions for hypertensive intracerebral hematomas are still controversial. Many believe only hyperacute intervention is of any real utility. The majority of present interventions require a formal craniotomy with standard neurosurgical techniques. There are, however, a few reports on CT-guided stereotactic aspiration of these hematomas with favorable results. We report 10 patients treated with frameless fiduciless stereotactic means using an intraoperative MRI scanner (GE 0.5 T Signa SP). These patients were initially diagnosed as having hypertensive intracerebral hematoma and operated on within 1-34 days after hemorrhage. The actual operating time averaged less than 120 min, including intraoperative imaging. Clot volumes ranged from 2.5 to 75 cm(3) with a mean of 31 cm(3). There were 2 thalamic hematomas and 8 basal gangliar hematomas. Three patients had intraventricular hematoma extension and all 3, as well as an additional patient, required extraventricular drainage. However, no patients required permanent posthemorrhage ventriculoperitoneal shunting. Aspiration was successful in all cases to 70-90% of clot removal. Two cases utilized intrahematoma t-PA infusion with subsequent 80-90% clot removal. There were no complications or rehemorrhages. All patients showed some form of improvement that included either improved blood pressure control, speech or cognitive abilities. We conclude that using an intraoperative MRI scanner to perform frameless, fiduciless stereotactic aspiration of acute/subacute intracerebral hematoma is a safe and potentially effective means of treating intracerebral hematomas.

Comparison of MRI and ventriculographic target acquisition for posteroventral pallidotomy.

The true accuracy of MRI scanners utilized for target acquisition in functional stereotaxis remains undefined. We have performed pallidotomies at the Loma Linda University Medical Center using both MRI and MRI concomitant with positive contrast ventriculography. A retrospective study of 33 cases revealed significant differences in coordinates obtained by MRI alone and MRI concomitant with ventriculography (antero-posterior coordinates, mean error: 2.6 mm, range 0.5-6.8 mm; Z coordinates: mean error 4.6 mm, range 0-19 mm). While MRI promises excellent target identification, the generated target coordinates significantly stray from the optimal target. Ventriculography corrects the MRI coordinates and demonstrates the position of the radiofrequency probe with respect to the target and anatomic reference points.

Stereotactic posterioventral pallidotomy improves balance control as assessed by computerized posturography.

Postural instability is arguably the most debilitating symptom of Parkinson's disease (PD). Recently, posterioventral pallidotomy/pallidoansotomy (PVP) has been advocated to improve a multitude of symptoms associated with PD. Dyskinesias, rigidity and bradykinesia are the most talked about improved symptoms, but posture and gait are also affected after PVP. To analyze the effect of PVP on postural control, 14 patients with PD were prospectively studied using a computerized dynamic posturography machine. Seven males and 7 females underwent a total of 18 procedures, 6 left PVP, 6 right PVP, 2 bilateral and 2 had Vim thalamotomies in addition to PVP. Data were collected pre- and postoperatively after a 12-hour drug-free interval ('off' period) and 1-2 h after medications ('on' period). Postoperative analyses were performed between 1 and 3 months postoperatively. As a group, patients' balance, in the off period, improved after surgery in a dynamic setting. Prior to surgery, patients' anterior-posterior sway exceeded their stability limits (patient fell) on 31% of the trials. After surgery, the fall rate decreased to 23%. Anterior-posterior sway decreased significantly (p < 0.05) postoperatively when the platform was sway referenced. In comparing the effect of surgery in decreasing sway with that of medication preoperatively, improvement after surgery (off period) was better than the preoperative on period (p < 0.05). Patients also improved in ostoperative off state when compared to preoperative off state with the platform sway referenced (p < 0.05), controlling for improvement in dyskinesia-induced imbalance. In conclusion, PVP improves standing balance performance better than that achieved with medications preoperatively. Since central input parameters were improved, the mechanism of PVP may be centralized.

Stimulation of the globus pallidus in Parkinson's disease.

In 62 patients undergoing posteroventral pallidotomy (PVP) for the treatment of Parkinson's disease, we have demonstrated significant (p < 0.01) elimination of akinetic features and other symptoms during intraoperative stimulation trials in areas anterior to the PVP target (n = 30). Stimulation in anterior pallidal regions frequently resulted in an immediate reversal of akinetic states despite enforced abstinence of medications. The beneficial effects were achieved with as little as 0.25 V at 100 Hz. Stimulation at the PVP target site (n = 32) resulted in insignificant changes (p > 0.05).

Chronic anterior pallidal stimulation for Parkinson's disease.

We present the case of a 51-year-old female who had a four-year history of Parkinson's disease with severe "on-off' and disabling progression of symptoms on chronic levodopa therapy. After obtaining FDA approval, we implanted a Medtronic deep brain stimulation lead stereotactically into the right anterior pallidum contralateral to her most symptomatologic side. Intra-operative stimulation trials at 100 Hz caused reproducible reversal of akinetic symptoms and simultaneous microelectrode recording of the posteroventral pallidum revealed decreased neural activity during anterior pallidal stimulation. The patient was evaluated pre-operatively and postoperatively using the Hoehn and Yahr Staging Scale, the Unified Parkinson's Disease Rating Scale (UPDRS), videotape, and a computerized data glove. Six months after implantation, the total UPDRS score was decreased from 68 to 8 and Hoehn and Yahr Staging improved from 3.0 to 1.5 during periods of chronic high frequency stimulation. Dramatic improvements in tremor, dystonia, bradykinesia, and akinesia were noted within seconds of stimulator activation and were also objectively measured using a computerized data glove. This case reveals the potential for therapeutic pallidal stimulation for Parkinson's akinetic symptomatology.