Update on deep brain stimulation for Parkinson's disease.

Deep brain stimulation (DBS) has evolved from an experimental procedure to a major treatment option for Parkinson's disease (PD). Although its underlying mechanism is still not fully understood, a growing body of evidence supports the role of DBS as an effective treatment option for carefully selected patients. Over time, the ever-expanding DBS patient cohort has also revealed the risks and challenges of the surgery. Major goals of this approach include identifying and reaching the correct target of stimulation, as well as delivering electrical current to the appropriate location in an appropriate manner. The safety concerns and adverse outcomes continue to be addressed with ever-improving operative strategies. Imminent developments in biomedical engineering hold the promise of more sophisticated and intelligent DBS devices, and improved imaging technology is providing unprecedented anatomical and functional resolution. Further advances in our understanding of physiology and pathology of the deep brain structures--guided not in small part by experience and access gained with DBS surgery in PD--will shape the future of this field.

Spatio-spectral characterization of local field potentials in the subthalamic nucleus via multitrack microelectrode recordings.

Deep brain stimulation of the subthalamic nucleus (STN) is a highly effective treatment for motor symptoms of Parkinson's disease. However, precise intraoperative localization of STN remains a procedural challenge. In the present study, local field potentials (LFPs) were recorded from three tracks during microelectrode recording-based (MER) targeting of STN, in five patients. The raw LFP data were preprocessed in original recording setup and then data quality was compared to data with common average derivation. The depth-frequency maps were generated according to preprocessing results for each patient and spectral characteristics of LFPs were explored at each depth across different tracks and different subjects. Spatio-spectral analysis of LFP was investigated to see whether LFP activity can be used for optimal track selection and STN border identification. Analysis show that monopolar derivation suffer from various artifacts and/or power line noise which makes the interpretation of target localization very difficult in most of the subjects. Unlikely, bipolar derivation helps to recover the neurological signals and investigation of signal characteristics. The frequency-vs-depth maps using a modified Welch periodogram with robust statistics, demonstrated that a median-based spectrum estimation approach eliminates outliers pretty well by preserving band-specific LFP activity. The results indicate that there is a clear oscillatory beta activity around 20 Hz in all subjects. 1/f normalization reveals the high frequency oscillations (HFOs) between 200-to-350 Hz in two subjects. It's noted that the optimal track selection is not consistent with the track having highest beta band oscillations in two out of five subjects. In conclusion, microelectrode-derived LFP recordings may provide an alternative approach to single unit activity (SUA)-based MER, for localizing the target STN borders during DBS surgery. Despite the small number of subjects, the present study adds to existing knowledge about LFP-based pathophysiology of PD and its target-based spectral activities.

Transsphenoidal microsurgery for growth hormone-secreting pituitary adenomas: initial outcome and long-term results.

Treatment of acromegaly has long been recognized as necessary to relieve symptoms, halt progression of deformities, and decompress the sella turcica. More recently, treatment strategies have focused on decreasing GH levels to a point at which mortality rates normalize, thereby redefining previous concepts of a cure. No surgical series to date has investigated the long-term effect of treatment on mortality rates. We retrospectively reviewed 254 consecutive patients with acromegaly who underwent transsphenoidal microsurgery of GH-secreting adenomas between 1974-1992. Seventy-six percent of these patients had basal GH levels <5 ng/mL within 30 days of surgery, and 24% had persistent disease. Multivariate analysis revealed that higher stage, grade, and preoperative GH levels were all predictive of persistence (P < 0.01). Long-term follow-up was obtained on 129 of the patients in initial remission. Of these, 9 (7%) had disease recurrence and 120 remained in remission. The incidence of major postoperative complications was 8% (2% permanent diabetes insipidus, 2% cerebrospinal fluid leaks requiring surgery, 2% meningitis, and 2% hypopituitarism), with no mortality. In contrast to the 2.4- to 4.8-fold increased mortality among untreated acromegalics, the mortality rate among patients with posttherapy GH levels <5 ng/mL was equivalent to that of age- and sex-matched controls. Aggressive therapy to normalize GH levels should therefore be instituted at diagnosis.

Spontaneous intracranial hypotension resulting in stupor caused by diencephalic compression.

A 51-year-old man had a 4-month history of progressive headache and gradual onset of somnolence. MRI suggested spontaneous intracranial hypotension (SIH) with diencephalic compression, but he did not improve after three epidural blood patches. He became alert following intrathecal saline infusion that normalized his CSF pressure. A CSF leak was noted on spinal MRI and confirmed with CT contrast myelography. Surgical ligation of a torn dural root sleeve isolating a ruptured Tarlov's cyst resulted in permanent cure.

Oxidant defense enzymes of Plasmodium falciparum.

We have measured and characterized three oxidant defense enzymes in early and late intraerythrocytic stages of the human malarial parasite, Plasmodium falciparum. Isolated early intraerythrocytic stages contain catalase (24.1 mumol min-1 (mg protein)-1) and superoxide dismutase (SOD; 6.3 units (mg protein)-1) but little or no glutathione peroxidase (GPX; less than 2 mumol min-1 (mg protein)-1). Isolated late intraerythrocytic stages of P. falciparum contain slightly less catalase (17.0 mumol min-1 (mg protein)-1) but significantly more GPX (7.7 mumol min-1 (mg protein)-1) and SOD (25.1 units (mg protein)-1). P. falciparum, like P. berghei, probably acquires most of its SOD from its host, since parasite-associated SOD is predominantly cyanide-sensitive, and has the same pI as host SOD. Unlike P. berghei, however, late stages of P. falciparum contain an additional SOD isozyme which is not cyanide-sensitive and may represent an endogenous enzyme. Parasites grown in red cells that have been partially depleted of SOD are more sensitive to exogenously generated superoxide, suggesting some dependence of the parasite on host SOD.

Intraoperative fiber-optic endoscopy for ventricular catheter insertion.

OBJECTIVE: Ventricular catheter placement is a common neurosurgical procedure often resulting in inaccurate intraventricular positioning. We conducted a comparison of the accuracy of endoscopic and conventional ventricular catheter placement in adults. METHODS: A retrospective analysis of data was performed on 37 consecutive patients undergoing ventriculo-peritoneal shunt (VPS) insertion with endoscopy and 40 randomly selected, unmatched patients undergoing VPS insertion without endoscopy, for the treatment of hydrocephalus of varied etiology. A grading system for catheter tip position was developed consisting of five intraventricular zones, V1 -V5, and three intraparenchymal zones, A, B, C. Zones V1 for the frontal approaches and V1 or V2 for the occipital approaches were the optimal catheter tip locations. Postoperative scans of each patient were used to grade the accuracy of ventricular catheter placement. RESULTS: Seventy-six percent of all endoscopic ventricular catheters were in zone V1 and 100% were within zones V1-V3. No endoscopically inserted catheters were observed in zones V4, V5 or intraparenchymally. Thirty-eight percent of the conventionally placed catheters were in zone V1, 53% in zones V1-3 and 15% intraparenchymally. There was a statistically significant difference in the percentage of catheters in optimal location versus in any other location, favoring endoscopic guidance (p<0.001). CONCLUSION: We conclude that endoscopic ventricular catheter placement provides improved positioning accuracy than conventional techniques.

Localization of subthalamic nucleus borders using macroelectrode local field potential recordings.

Deep brain stimulation of the subthalamic nucleus (STN) is a highly effective treatment for motor symptoms of Parkinson's disease. However, precise intraoperative localization of STN remains a procedural challenge. In the present study, local field potentials (LFPs) were recorded from DBS macroelectrodes during trajectory to STN, in six patients. The frequency-vs-depth map of LFP activity was extracted and further analyzed within different sub-bands, to investigate whether LFP activity can be used for STN border identification. STN borders identified by LFPs were compared to border predictions by the neurosurgeon, based on microelectrode-derived, single-unit recordings (MER-SUA). The results demonstrate difference between MER-SUA and macroelectrode LFP recording with respect to the dorsal STN border of -1.00 ±0.84 mm and -0.42 ±1.07 mm in the beta and gamma frequency bands, respectively. For these sub-bands, RMS of these distances was found to be 1.26 mm and 1.06 mm, respectively. Analysis of other sub-bands did not allow for distinguishing the caudal border of STN. In conclusion, macroelectrode-derived LFP recordings may provide an alternative approach to MER-SUA, for localizing the target STN borders during DBS surgery.

Sensitivity of neurite outgrowth to microfilament disruption varies with adhesion molecule substrate.

Interactions between the cytoskeleton and cell adhesion molecules are presumed responsible for neurite extension. We have examined the role of microfilaments in neurite outgrowth on the cell adhesion molecules L1, P84, N-CAM, and on laminin. Cerebellar neurons growing on each substrate exhibited differing growth cone morphologies and rates of neurite extension. Growth of neurites in the presence of cytochalasin B (CB) was not inhibited on substrates of L1 or P84 but was markedly inhibited on N-CAM. Neurons on laminin were initially unable to extend neurites in the presence of CB but recovered this ability within 9 h. These studies suggest that neurite outgrowth mediated by different cell adhesion molecules proceeds via involvement of distinct cytoskeletal interactions.

Colocalization and coassembly of two human brain M-type potassium channel subunits that are mutated in epilepsy.

Acetylcholine excites many central and autonomic neurons through inhibition of M-channels, slowly activating, noninactivating voltage-gated potassium channels. We here provide information regarding the in vivo distribution and biochemical characteristics of human brain KCNQ2 and KCNQ3, two channel subunits that form M-channels when expressed in vitro, and, when mutated, cause the dominantly inherited epileptic syndrome, benign neonatal familial convulsions. KCNQ2 and KCNQ3 proteins are colocalized in a somatodendritic pattern on pyramidal and polymorphic neurons in the human cortex and hippocampus. Immunoreactivity for KCNQ2, but not KCNQ3, is also prominent in some terminal fields, suggesting a presynaptic role for a distinct subgroup of M-channels in the regulation of action potential propagation and neurotransmitter release. KCNQ2 and KCNQ3 can be coimmunoprecipitated from brain lysates. Further, KCNQ2 and KCNQ3 are coassociated with tubulin and protein kinase A within a Triton X-100-insoluble protein complex. This complex is not associated with low-density membrane rafts or with N-methyl-d-aspartate receptors, PSD-95 scaffolding proteins, or other potassium channels tested. Our studies thus provide a view of a signaling complex that may be important for cognitive function as well as epilepsy. Analysis of this complex may shed light on the unknown transduction pathway linking muscarinic acetylcholine receptor activation to M-channel inhibition.