Albert J. Fenoy

Risks of common complications in deep brain stimulation surgery: management and avoidance

OBJECT Deep brain stimulation (DBS) surgery is increasingly prominent in the treatment of various disorders refractory to medication. Despite the procedures efficacy, the community at large continues to be hesitant about presumed associated risks. The main object of this study was to assess the incidence of various surgical complications occurring both during and after DBS device implantation in a large population of patients with movement disorders in an effort to better quantify patient risk, define management plans, and develop methods for risk avoidance. A second aim was to corroborate the low procedural complication risk of DBS reported by others, which in light of the procedures efficacy is needed to promote its widespread acceptance. METHODS All patients who had undergone new DBS device implantation surgery between 2002 and 2010 by a single surgeon were entered into a database after being verified by cross-referencing manufacturer implantation records. All surgical records and charts were reviewed to identify intraoperative, perioperative, and long-term surgical complications, including any characteristics predictive of an adverse event. RESULTS Seven hundred twenty-eight patients received 1333 new DBS electrodes and 1218 new internal pulse generators (IPGs) in a total of 1356 stereotactic procedures for the treatment of movement disorders. Seventy-eight percent of the patients had staged lead and IPG implantations. Of the 728 patients, 452 suffered from medically refractory Parkinson disease; in the other patients, essential tremor (144), dystonia (64), mixed disease (30), and other hyperkinetic movement disorders (38) were diagnosed. Severe intraoperative adverse events included vasovagal response in 6 patients (0.8%), hypotension in 2 (0.3%), and seizure in 2 (0.3%). Postoperative imaging confirmed asymptomatic intracerebral hemorrhage (ICH) in 4 patients (0.5%), asymptomatic intraventricular hemorrhage in 25 (3.4%), symptomatic ICH in 8 (1.1%), and ischemic infarction in 3 (0.4%), associated with hemiparesis and/or decreased consciousness in 13 (1.7%). Long-term complications of DBS device implantation not requiring additional surgery included hardware discomfort in 8 patients (1.1%) and loss of desired effect in 10 (1.4%). Hardware-related complications requiring surgical revision included wound infections in 13 patients (1.7%), lead malposition and/or migration in 13 (1.7%), component fracture in 10 (1.4%), component malfunction in 4 (0.5%), and loss of effect in 19 (2.6%). CONCLUSIONS The authors confirmed that the overall risk of both procedure- and hardware-related adverse events is acceptably low. They offer advice on how to avoid the most common complications.

Craniocervical junction fusions in patients with hindbrain herniation and syringohydromyelia

OBJECT Patients with hindbrain herniation or the so-called Chiari malformation Type I (CM-I) and/or syringohydromyelia are treated with dorsal decompression alone; however, a small percentage of patients with other associated abnormalities require concomitant dorsal craniocervical junction (CCJ) fusion. The authors surveyed the indications for CCJ fusions in this population. METHODS A retrospective review of University of Iowa medical records and radiographs obtained between 1996 and 2005 was performed. Inclusion criteria encompassed patients with diagnoses of CM-I and/or syringohydromyelia requiring dorsal CCJ fusions, and others with CCJ abnormalities who had CM-I and/or syringohydromyelia. RESULTS Two hundred thirty-four patients were identified, all of whom were symptomatic at presentation. Their ages ranged from 2.5 to 86 years; 33% of the patients were < 16 years of age. Patients were categorized as follows, with some being assigned to > 1 category: Group I, congenital or acquired CCJ abnormalities with reducible bone compression (25% of patients); Group II, previous anterior CCJ/upper brainstem decompression (44%); Group III, occipitocervical complex instability with CM-I and/or syringohydromyelia but without CCJ bone abnormalities requiring adjunctive posterior fossa decompression (26%); and Group IV, musculoligamentous instability, either from pathological states or from muscle dehiscence from repeated posterior fossa procedures (14%). Instrumentation was used in 96% of patients, with all 96% receiving semirigid fixation with titanium loop and sublaminar cables; all fusion constructs incorporated autologous bone. At last follow-up evaluation, fusion was radiographically complete in 97%, and symptom improvement was seen in 92%. CONCLUSIONS Dorsal CCJ fusions are required in patients with CM-I and/or syringohydromyelia who have concomitant CCJ abnormalities (Groups I and II). A definite group (CM-I and/or syringohydromyelia) without bone abnormality exists (Groups III and IV). This may be due to muscle weakness secondary to a high syrinx.

Management of device-related wound complications in deep brain stimulation surgery

OBJECT Wound complications are uncommon following deep brain stimulation (DBS) surgery. However, certain key technical steps can be performed in each procedure to minimize this still troublesome risk. The authors reviewed the incidence and management of all hardware-related wound dehiscences and infections in a large patient series. METHODS All patients undergoing new DBS hardware implantation surgery between 2002 and 2010 by a single surgeon (R.K.S.) were entered into a database after undergoing verification by cross-referencing manufacturer implantation records. All hardware-related complications such as wound dehiscence, erosions, and/or infections were identified, and wound location, time of incidence, and mechanism were categorized. Charts were reviewed to evaluate the success of conservative treatment versus partial or total hardware removal. RESULTS Seven hundred twenty-eight patients received 1333 new DBS leads and 1218 new implantable pulse generators (IPGs) in a total of 1356 stereotactic procedures for movement disorders. Seventy-eight percent of patients underwent staged lead and IPG implantations. Sixteen patients presented with atraumatic device-related infection and/or dehiscence within 12 months from original implantation; 9 of these patients (1.24%) required additional surgery after antibiotic failure. All 8 patients presenting with cranial wound complications were treated initially by debridement in an attempt to salvage the leads; debridement followed by intravenous antibiotics was only successful in 2 patients presenting with dehiscence alone. One of 2 lead-only removals was successful in infections originating in the cranium; the only IPG-originating infection was treated by partial hardware removal and intravenous antibiotics. Two of 637 IPG replacements resulted in infections within 12 months after revision, requiring either partial or total hardware removal, while 1 dehiscence in this group was treated by debridement alone. CONCLUSIONS In a large series of new DBS hardware implantations, the incidence of postoperative wound dehiscence and/or infections requiring further surgery was 1.24%. Standard practice for all implantations was a short procedural duration, copious povidone-iodine irrigation, and postoperative antibiotic administration. Partial hardware removal should be initially attempted for infection. Debridement alone is successful in treating dehiscence without infection.

Functional localization of auditory cortical fields of human: Click-train stimulation

Averaged auditory evoked potentials (AEPs) to bilaterally presented 100 Hz click trains were recorded from multiple sites simultaneously within Heschls gyrus (HG) and on the posterolateral surface of the superior temporal gyrus (STG) in epilepsy-surgery patients. Three auditory fields were identified based on AEP waveforms and their distribution. Primary (core) auditory cortex was localized to posteromedial HG. Here the AEP was characterized by a robust polyphasic low-frequency field potential having a short onset latency and on which was superimposed a smaller frequency-following response to the click train. Core AEPs exhibited the lowest response threshold and highest response amplitude at one HG site with threshold rising and amplitude declining systematically on either side of it. The AEPs recorded anterolateral to the core, if present, were typically of low amplitude, with little or no evidence of short-latency waves or the frequency-following response that characterized core AEPs. We suggest that this area is part of a lateral auditory belt system. Robust AEPs, with waveforms demonstrably different from those of the core or lateral belt, were localized to the posterolateral surface of the STG and conform to previously described field PLST.

Subthalamic Neuronal Firing in Obsessive- Compulsive Disorder and Parkinson Disease

Although electrophysiologic dysfunction of the subthalamic nucleus is putative, deep brain stimulation of this structure has recently been reported to improve obsessions and compulsions. In Parkinson disease, sensorimotor subthalamic neurons display high‐frequency burst firing, which is considered as an electrophysiologic signature of motor loop dysfunction. We addressed whether such neuronal dysfunction of the subthalamic nucleus also exists in the nonmotor loops involved in patients with obsessive‐compulsive disorder.

Expression of nitric oxide synthase in the cerebral microvasculature after traumatic brain injury in the rat

Reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPHd) histochemistry and nitric oxide synthase (NOS) immunocytochemistry were performed on sections of brain after moderate traumatic brain injury. There was a pronounced increase in NADPHd reactivity and an induction of the endothelial NOS (eNOS) isoform in microvessels surrounding the cortical contusion by 24 h post-injury. This altered microvascular state may contribute to barrier breakdown and hyperemia which characterize traumatic brain injury.

Deep brain stimulation: are astrocytes a key driver behind the scene?

Despite its widespread use, the underlying mechanism of deep brain stimulation (DBS) remains unknown. Once thought to impart a “functional inactivation”, there is now increasing evidence showing that DBS actually can both inhibit neurons and activate axons, generating a wide range of effects. This implies that the mechanisms that underlie DBS work not only locally but also at the network level. Therefore, not only may DBS induce membrane or synaptic plastic changes in neurons over a wide network, but it may also trigger cellular and molecular changes in other cells, especially astrocytes, where, together, the glial–neuronal interactions may explain effects that are not clearly rationalized by simple activation/inhibition theories alone. Recent studies suggest that (1) high‐frequency stimulation (HFS) activates astrocytes and leads to the release of gliotransmitters that can regulate surrounding neurons at the synapse; (2) activated astrocytes modulate synaptic activity and increase axonal activation; (3) activated astrocytes can signal further astrocytes across large networks, contributing to observed network effects induced by DBS; (4) activated astrocytes can help explain the disparate effects of activation and inhibition induced by HFS at different sites; (5) astrocytes contribute to synaptic plasticity through long‐term potentiation (LTP) and depression (LTD), possibly helping to mediate the long‐term effects of DBS; and (6) DBS may increase delta‐opioid receptor activity in astrcoytes to confer neuroprotection. Together, the plastic changes in these glial–neuronal interactions network‐wide likely underlie the range of effects seen, from the variable temporal latencies to observed effect to global activation patterns. This article reviews recent research progress in the literature on how astrocytes play a key role in DBS efficacy.

Calcium pyrophosphate dihydrate crystal deposition in the craniovertebral junction.

OBJECT Calcium pyrophosphate dihydrate (CPPD) deposition is a rare cause of retroodontoid mass lesions in elderly individuals. However, this condition may be severely underdiagnosed if sufficient attention is not paid to imaging characteristics and clinical presentation. The authors sought to evaluate the decision-making process in both the diagnosis and surgical treatment of CPPD. METHODS A retrospective review of University of Iowa medical records and radiographs accumulated between 1977 and 2006 was performed. The inclusion criterion was histopathological findings consistent with pseudogout at the craniovertebral junction (CVJ). Twenty-one patients with a mean age of 70.3 years and a mean symptom duration prior to presentation of 17.5 months were identified and included in this study. RESULTS The patients presented most frequently with occipital and neck pain (85%) and numbness or paresthesias (61%). Lower cranial nerve deficits were seen in 29%. Calcification of the mass or transverse ligament was seen on computed tomography in all included patients. Gross-total resection was achieved in all patients: 19 of 21 patients underwent transoral-transpalatopharyngeal resection, with only 16 requiring concomitant dorsal occipital-cervical fusion. The mean follow-up duration was 15 months. Eighteen patients (86%) had improvement or resolution of symptoms after treatment, and 3 were lost to follow-up. CONCLUSIONS Although rare, CPPD deposition at the CVJ should be suspected on finding calcification of and around the transverse ligament on neuroimaging. Transoral-transpalatopharyngeal resection is preferred to halt the progression of neurological deterioration; dorsal fusion is not always mandatory as concomitant ligamentous calcification and atlantoaxial joint ankylosis may provide added stability.

Hearing suppression induced by electrical stimulation of human auditory cortex

In the course of performing electrical stimulation functional mapping (ESFM) in neurosurgery patients, we identified three subjects who experienced hearing suppression during stimulation of sites within the superior temporal gyrus (STG). One of these patients had long standing tinnitus that affected both ears. In all subjects, auditory event related potentials (ERPs) were recorded from chronically implanted intracranial electrodes and the results were used to localize auditory cortical fields within the STG. Hearing suppression sites were identified within anterior lateral Heschls gyrus (HG) and posterior lateral STG, in what may be auditory belt and parabelt fields. Cortical stimulation suppressed hearing in both ears, which persisted beyond the period of electrical stimulation. Subjects experienced other stimulation-evoked perceptions at some of these same sites, including symptoms of vestibular activation and alteration of audio-visual speech processing. In contrast, stimulation of presumed core auditory cortex within posterior medial HG evoked sound perceptions, or in one case an increase in tinnitus intensity, that affected the contralateral ear and did not persist beyond the period of stimulation. The current results confirm a rarely reported experimental observation, and correlate the cortical sites associated with hearing suppression with physiologically identified auditory cortical fields.

Deep brain stimulation of the medial forebrain bundle: Distinctive responses in resistant depression

BACKGROUND Treatment resistant depression (TRD) is a serious, disabling disease. Deep brain stimulation (DBS) to the superolateral branch of the medial forebrain bundle (MFB), as proposed by Schlaepfer et al. (2013), has led to rapid anti-depressant response but has not been replicated. METHODS In this interim analysis of an ongoing pilot study of ten subjects, we assessed the efficacy of MFB-DBS in a cohort of four TRD patients over a 52-week period using the Montgomery-Åsberg Depression Rating Scale (MADRS) as the primary assessment tool. Implanted patients entered a 4-week single-blinded sham stimulation period prior to stimulation initiation. Deterministic fiber tracking analysis was performed to compare modulated fiber tracts between patients. RESULTS Intraoperatively, responder patients displayed immediate increased signs of energy and motivation upon stimulation at target. There was no significant mean change in mood during sham stimulation phase. Three of 4 patients had >50% decrease in MADRS scores at 7 days post-stimulation initiation relative to baseline. One patient withdrew from study participation. At 26 weeks, two of 3 remaining patients continue to have >80% decrease in MADRS scores. One patient failed to have response; evaluation of modulated fiber tracts revealed reduced frontal connectivity to the target region. LIMITATIONS This is an interim report, with limited conclusions. CONCLUSION This study of MFB-DBS shows similar rapid anti-depressant effects within the first week of stimulation as initially reported by Schlaepfer et al. (2013). Implementation of anhedonia measurements would greatly augment characterization of the striking motivational effects observed. We urge others to pursue this target to further prove efficacy. ClinicalTrials.gov (identifier: NCT02046330) https://clinicaltrials.gov/ct2/show/NCT02046330.