Hypersynchronous neuronal firing is a hallmark of epilepsy, but the mechanisms underlying simultaneous activation of multiple neurons remains unknown. Epileptic discharges are in part initiated by a local depolarization shift that drives groups of neurons into synchronous bursting. In an attempt to define the cellular basis for hypersynchronous bursting activity, we studied the occurrence of paroxysmal depolarization shifts after suppressing synaptic activity by TTX and voltage-gated Ca 2+ channel blockers. Here we report that paroxysmal depolarization shifts can be initiated by release of glutamate from extrasynaptic sources or by photolysis of caged Ca 2+ in astrocytes. Two-photon imaging of live exposed cortex revealed that several anti-epileptics, including valproate, gabapentin and phenytoin, reduced the ability of astrocytes to transmit Ca 2+ signaling. Our results reveal an unanticipated key role for astrocytes in seizure activity. As such, these findings identify astrocytes as a proximal target for the treatment of epileptic disorders.Epilepsy is a neurological disorder in which normal brain function is disrupted as a consequence of intensive burst activity from groups of neurons1. Epilepsies result from long-lasting plastic changes in the brain affecting the expression of receptors and channels, and involve sprouting and reorganization of synapses, as well as reactive gliosis2 ,3 . Several lines of evidence suggest a key role of glutamate in the pathogenesis of epilepsy. Local or systemic administration of glutamate agonists triggers excessive neuronal firing, whereas glutamate receptor (GluR) antagonists have anticonvulsant properties 4 . The observation that astrocytes release glutamate via a regulated Ca 2+ dependent mechanism 5-8 prompted us to hypothesize that glutamate released by astrocytes plays a causal role in synchronous firing of large populations of neurons.Paroxysmal depolarization shifts (PDSs) are abnormal prolonged depolarizations with repetitive spiking and are reflected as interictal discharges in the electroencephalogram 2, 3. We report here that glutamate released by astrocytes can trigger PDSs in several models of experimental seizure. A unifying feature of seizure activity was its consistent association Corresponding author: Guo-Feng Tian (Guo-Feng_Tian@URMC.Rochester.edu). * These authors contributed equally to this work. NIH Public Access RESULTS PDSs can be triggered by an action potential-independent mechanismTo examine the cellular mechanism underlying PDSs, we patched CA1 pyramidal neurons in rat hippocampal slices exposed to 4-aminopyridine (4-AP). 4-AP is a K + channel blocker that induces intense electrical discharges in slices9 and seizure activity in experimental animals 10 . All slices exposed to 4-AP (61 slices from 23 rats) exhibited epileptiform bursting activity expressed as transient episodes of neuronal depolarizations eliciting trains of action potentials (Fig. 1a). Bath application of TTX promptly eliminated neuronal firing (Fig. 1b). Unexpectedly, the...

Movement disorders, such as Parkinson's disease, tremor, and dystonia, are among the most common neurological conditions and affect millions of patients. Although medications are the mainstay of therapy for movement disorders, neurosurgery has played an important role in their management for the past 50 years. Surgery is now a viable and safe option for patients with medically intractable Parkinson's disease, essential tremor, and dystonia. In this article, we provide a review of the history, neurocircuitry, indication, technical aspects, outcomes, complications, and emerging neurosurgical approaches for the treatment of movement disorders.

Therapeutic/care management, level III.

Objective: We examine the effect of intracranial air on stereotactic accuracy during bilateral deep brain stimulation (DBS) surgery for Parkinson’s disease (PD). We also assess factors that may predict an increased risk of intracranial air during these surgeries. Methods: 32 patients with PD underwent bilateral DBS surgery. The technique used for implantation of the leads has been standardized in over 800 subthalamic nucleus (STN) implantations. For lead implantation, the goal of the neurophysiological technique is identification of the STN and its borders with 3 microelectrode recording (MER) tracks. We examined the number of tracks and the degree of deviation from the planned target on each side. Total intracranial air (TIA) was then compared in these groups. We also examined the relationship between the TIA and length of surgery, ventricular volume and the degree of atrophy. Results: Side 2 in this series required more MER tracks. The TIA was larger in patients with more than 3 MER tracks on side 2 of surgery. There was more deviation from the target on side 2. In addition, the TIA in patients with >1 mm of vector deviation on side 2 was more than in those without. The TIA correlated with the number of tracks on side 2 as well as with the degree of the second euclidean deviation on side 2. There was a correlation of degree of atrophy with TIA. Conclusion: In bilateral STN DBS for PD, intracranial air may contribute to error in stereotactic accuracy especially on the second side. In addition, there is a correlation between the accumulated volume of intracranial air and the degree of cerebral atrophy.

BACKGROUND Patients with Parkinson disease (PD) admitted to the hospital for any reason are at a higher risk of hospital-related complications. Frequent causes include delays in administering PD medications or use of contraindicated medications. The Joint Commission Disease-Specific Care (DSC) program has been used to establish a systematic approach to the care of specific inpatient populations. Once obtained, this certification demonstrates a commitment to patient care and safety, which is transparent to the public and can improve quality of care. METHODS We formalized our efforts to improve the care of hospitalized patients with PD by pursuing Joint Commission DSC. An interprofessional team was assembled to include nurses, therapists, physicians, pharmacists, performance improvement specialists, and data analysts. The team identified quality metrics based on clinical guidelines. In addition, a large educational campaign was undertaken. Application to the Joint Commission for DSC resulted in a successful June 15, 2018 site visit. To our knowledge, this is the first DSC program in PD in an acute care hospital. CONCLUSION Using the established platform of DSC certification from the Joint Commission, we developed a program based on relevant metrics that aims to address medication management of patients with PD admitted to the hospital. Our hope is to improve the care of this vulnerable patient population.

Anterior cervical decompression and fusion has gained popularity because of its applicability to a variety of cervical spine disorders. The authors of long-term follow-up studies have demonstrated the development of degenerative changes in segments adjacent to fusion. So-called adjacent-segment disease causes symptomatic deterioration in up to 25% of the patients who have undergone anterior cervical decompression and fusion for cervical spondylotic myelopathy. The causes of this condition are debated in the literature. The authors provide a review of the available literature on the pathogenesis, prevention, and treatment of postarthrodesis adjacent-segment degenerative disease.

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Background: Functional magnetic resonance imaging (fMRI) has been used for preoperative planning and intraoperative surgical navigation. However, most experience to date has been with preoperative images acquired on high-field echoplanar MRI units. We explored the feasibility of acquiring fMRI of the motor cortex with a dedicated low-field intraoperative MRI (iMRI). Methods: Five healthy volunteers were scanned with the 0.12-tesla PoleStar N-10 iMRI (Odin Medical Technologies, Israel). A finger-tapping motor paradigm was performed with sequential scans, acquired alternately at rest and during activity. In addition, scans were obtained during breath holding alternating with normal breathing. The same paradigms were repeated using a 3-tesla MRI (Siemens Corp., Allandale, N.J., USA). Statistical analysis was performed offline using cross-correlation and cluster techniques. Data were resampled using the ‘jackknife’ process. The location, number of activated voxels and degrees of statistical significance between the two scanners were compared. Results: With both the 0.12- and 3-tesla imagers, motor cortex activation was seen in all subjects to a significance of p < 0.02 or greater. No clustered pixels were seen outside the sensorimotor cortex. The resampled correlation coefficients were normally distributed, with a mean of 0.56 for both the 0.12- and 3-tesla scanners (standard deviations 0.11 and 0.08, respectively). The breath holding paradigm confirmed that the expected diffuse activation was seen on 0.12- and 3-tesla scans. Conclusions: Accurate fMRI with a low-field iMRI is feasible. Such data could be acquired immediately before or even during surgery. This would increase the utility of iMRI and allow for updated intraoperative functional imaging, free of the limitations of brain shift.