Role of Functional neurosurgery in Improving Patient Outcomes in Epilepsy, Movement Disorders, and Chronic Pain.

Functional neurosurgery encompasses surgical procedures geared towards treating movement disorders (such as Parkinson's disease and essential tremor), drug-resistant epilepsy, and various types of pain disorders. It is one of the most rapidly expanding fields within neurosurgery and utilizes both traditional open surgical methods such as open temporal lobectomy for epilepsy as well as neuromodulation-based treatments such as implanting brain or nerve stimulation devices. This review outlines the role functional neurosurgery plays in treatment of epilepsy, movement disorders, and pain, and how it is being implemented at the University of Missouri by the Department of Neurosurgery.

Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy.

PURPOSE: We report a multicenter, double-blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization-related epilepsy. METHODS: Participants were adults with medically refractory partial seizures, including secondarily generalized seizures. Half received stimulation and half no stimulation during a 3-month blinded phase; then all received unblinded stimulation. RESULTS: One hundred ten participants were randomized. Baseline monthly median seizure frequency was 19.5. In the last month of the blinded phase the stimulated group had a 29% greater reduction in seizures compared with the control group, as estimated by a generalized estimating equations (GEE) model (p = 0.002). Unadjusted median declines at the end of the blinded phase were 14.5% in the control group and 40.4% in the stimulated group. Complex partial and "most severe" seizures were significantly reduced by stimulation. By 2 years, there was a 56% median percent reduction in seizure frequency; 54% of patients had a seizure reduction of at least 50%, and 14 patients were seizure-free for at least 6 months. Five deaths occurred and none were from implantation or stimulation. No participant had symptomatic hemorrhage or brain infection. Two participants had acute, transient stimulation-associated seizures. Cognition and mood showed no group differences, but participants in the stimulated group were more likely to report depression or memory problems as adverse events. DISCUSSION: Bilateral stimulation of the anterior nuclei of the thalamus reduces seizures. Benefit persisted for 2 years of study. Complication rates were modest. Deep brain stimulation of the anterior thalamus is useful for some people with medically refractory partial and secondarily generalized seizures.

The falcine trigeminocardiac reflex: case report and review of the literature.

BACKGROUND: Trigeminocardiac reflex (TCR), the reproducible hypotension and bradycardia upon stimulation of the trigeminal nerve, has been reported during craniofacial surgery and during surgery within the cerebellopontine angle, petrosal sinus, orbit, and trigeminal ganglion. Whereas the falx cerebri is known to be innervated by the nervus tentorii, a recurrent branch of V1, there have been no reports to date of this response upon mechanical stimulation of the falx. CASE DESCRIPTION: We report a case of immediate, reproducible, and reflexive response of asystole upon stimulation of the falx cerebri during operative resection of a parafalcine meningioma in a 53-year-old woman. Upon recognition of the reproducible relationship between falcine stimulation and increased vagal tone, the patient was given glycopyrrolate in an effort to block cholinergic hyperactivity. After glycopyrrolate was given, no further dysrhythmias occurred. CONCLUSION: In this patient, mechanical stimulation of the falx likely resulted in the hyperactivity of the trigeminal ganglion, thereby triggering TCR. The dorsal region of the spinal trigeminal tract includes neurons from hypoglossal and vagus nerves, and projections have been seen between the vagus and trigeminal nuclei. The vagus provides parasympathetic innervation to the heart, vascular smooth muscle, and abdominal viscera. Vagal stimulation via these connections after trigeminal nerve activation likely accounts for the reflexive response of asystole seen in this patient. This is confirmed by the observation that the reflex was inhibited by the anticholinergic effects of glycopyrrolate. Awareness of TCR allows for early detection and appropriate treatment.

Mxi1-0, an alternatively transcribed Mxi1 isoform, is overexpressed in glioblastomas.

The c-Myc transcription factor regulates expression of genes related to cell growth, division, and apoptosis. Mxi1, a member of the Mad family, represses transcription of c-Myc-regulated genes by mediating chromatin condensation via histone deacetylase and the Sin3 corepressor. Mxi1 is a c-Myc antagonist and suppresses cell proliferation in vitro. Here, we describe the identification of Mxi1-0, a novel Mxi1 isoform that is alternatively transcribed from an upstream exon. Mxi1-0 and Mxi1 have different amino-terminal sequences, but share identical Max- and DNA-binding domains. Both isoforms are able to bind Max, to recognize E-box binding sites, and to interact with Sin3. Despite these similarities and in contrast to Mxi1, Mxi1-0 is predominantly localized to the cytoplasm and fails to repress c-Myc-dependent transcription. Although Mxi1-0 and Mxi1 are coexpressed in both human and mouse cells, the relative levels of Mxi1-0 are higher in primary glioblastoma tumors than in normal brain tissue. This variation in the levels of Mxi1-0 and Mxi1 suggests that Mxi1-0 may modulate the Myc-inhibitory activity of Mxi1. The identification of Mxi1-0 as an alternatively transcribed Mxi1 isoform has significant implications for the interpretation of previous Mxi1 studies, particularly those related to the phenotype of the mxi1 knockout mouse.

Characterization of gene expression profiles associated with glioma progression using oligonucleotide-based microarray analysis and real-time reverse transcription-polymerase chain reaction.

Diffuse astrocytoma of World Health Organization (WHO) grade II has an inherent tendency to spontaneously progress to anaplastic astrocytoma (WHO grade III) and/or glioblastoma (WHO grade IV). The molecular basis of astrocytoma progression is still poorly understood, in particular with respect to the progression-associated changes at the mRNA level. Therefore, we compared the transcriptional profile of approximately 6800 genes in primary WHO grade II gliomas and corresponding recurrent high-grade (WHO grade III or IV) gliomas from eight patients using oligonucleotide-based microarray analysis. We identified 66 genes whose mRNA levels differed significantly (P < 0.01, > or =2-fold change) between the primary and recurrent tumors. The microarray data were corroborated by real-time reverse transcription-polymerase chain reaction analysis of 12 selected genes, including 7 genes with increased expression and 5 genes with reduced expression on progression. In addition, the expression of these 12 genes was determined in an independent series of 43 astrocytic gliomas (9 diffuse astrocytomas, 10 anaplastic astrocytomas, 17 primary, and 7 secondary glioblastomas). These analyses confirmed that the transcript levels of nine of the selected genes (COL4A2, FOXM1, MGP, TOP2A, CENPF, IGFBP4, VEGFA, ADD3, and CAMK2G) differed significantly in WHO grade II astrocytomas as compared to anaplastic astrocytomas and/or glioblastomas. Thus, we identified and validated a set of interesting candidate genes whose differential expression likely plays a role in astrocytoma progression.