Shape-constrained deformable brain segmentation: Methods and quantitative validation.

MRI-guided neuro interventions require rapid, accurate, and reproducible segmentation of anatomical brain structures for identification of targets during surgical procedures and post-surgical evaluation of intervention efficiency. Segmentation algorithms must be validated and cleared for clinical use. This work introduces a methodology for shape-constrained deformable brain segmentation, describes the quantitative validation used for its clinical clearance, and presents a comparison with manual expert segmentation and FreeSurfer, an open source software for neuroimaging data analysis. ClearPoint Maestro is software for fully-automatic brain segmentation from T1-weighted MRI that combines a shape-constrained deformable brain model with voxel-wise tissue segmentation within the cerebral hemispheres and the cerebellum. The performance of the segmentation was validated in terms of accuracy and reproducibility. Segmentation accuracy was evaluated with respect to training data and independently traced ground truth. Segmentation reproducibility was quantified and compared with manual expert segmentation and FreeSurfer. Quantitative reproducibility analysis indicates superior performance compared to both manual expert segmentation and FreeSurfer. The shape-constrained methodology results in accurate and highly reproducible segmentation. Inherent point based-correspondence provides consistent target identification ideal for MRI-guided neuro interventions.

MRI-guided laser interstitial thermal thalamotomy for medically intractable tremor disorders.

INTRODUCTION: Medically intractable tremors are a common, difficult clinical situation. Deep brain stimulation decreases Parkinson's disease resting tremor and essential tremor, but not all patients are candidates from a diagnostic, medical, or social standpoint, prompting the need for alternative surgical strategies. METHODS: We describe 13 patients with medically intractable tremor treated with laser interstitial thermal thalamotomy performed under general anesthesia using live MRI-guidance and the Clearpoint stereotactic system. RESULTS: All patients had a dramatic decrease in tremor immediately postoperatively, which has been sustained through follow-up (3-17 months) in all but 1 patient (mean tremor score reduction of 62%; 10.33 ± 2.69 to 3.89 ± 3.1). Objective side effects were transient and included imbalance and paresthesia. CONCLUSION: Medically intractable tremor treated with laser interstitial thermal thalamotomy may be a useful addition to the treatment armamentarium for medically intractable tremor disorders. © 2018 International Parkinson and Movement Disorder Society.

Factors predictive of improved overall survival following stereotactic radiosurgery for recurrent glioblastoma.

The currently accepted standard of care for primary glioblastoma (GBM) consists of maximal surgical resection followed by fractionated external beam radiotherapy (EBRT) with concomitant temozolomide chemotherapy. The role of stereotactic radiosurgery (SRS) in the treatment of GBM is not well defined, but SRS has typically been applied as a salvage therapy for GBM recurrence. This paper reviews our single institution experience using gamma knife radiosurgery (GKRS) for the treatment of GBM. Thirty-six patients treated with GKRS for pathologically proven GBM at LSU Health in Shreveport from February 2000 to December 2013 were identified and analyzed. Patient characteristics, treatment variables, and survival were correlated. Seven patients received GKRS in the immediate postoperative period for an average tumor volume of 10.9 cm(3), and 29 patients were treated for a recurrent average tumor volume of 11.4 cm(3) with a prescribed dose ranging from 10 to 20 Gy at the 50 % isodose line. The median overall survival was significantly higher in recurrence group compared to up-front group [7.9 months (0.77-32.1 months) vs. 3.5 months (range 0.23-11.7 months) respectively, (p = 0.018)]. The predictive factors for improved survival in the patients with GBM were as follows: Karnofsky performance scale (KPS) > 70 (p = 0.026), age ≤ 50 years (p = 0.006), absence of neurodeficits (p = 0.01), and initial postoperative treatment with EBRT (p = 0.042). Adjuvant therapy with GKRS following GBM recurrence demonstrates statistical superiority over immediate postoperative boost therapy.

Predictors of unfavorable outcomes following deep brain stimulation for movement disorders and the effect of hospital case volume on outcomes: an analysis of 33, 642 patients across 234 US hospitals using the National (Nationwide) Inpatient Sample from 2002 to 2011.

OBJECT: With limited data available on association of risk factors and effect of hospital case volume on outcomes following deep brain stimulation (DBS), the authors attempted to identify these associations using a large population-based database. METHODS: The authors performed a retrospective cohort study involving patients who underwent DBS for 3 primary movement disorders: Parkinson's disease, essential tremor, and dystonia from 2002 to 2011 using the National (Nationwide) Inpatient Sample (NIS) database. Using national estimates, the authors identified associations of patient demographics, clinical characteristics, and hospital characteristics on short-term postoperative outcomes following DBS. Additionally, effect of hospital volume on unfavorable outcomes was investigated. RESULTS: Overall, 33, 642 patients underwent DBS for 3 primary movement disorders across 234 hospitals in the US. The mean age of the cohort was 63.42 ± 11.31 years and 36% of patients were female. The inpatients' postoperative risks were 5.9% for unfavorable discharge, 10.2% for prolonged length of stay, 14.6% for high-end hospital charges, 0.5% for wound complications, 0.4% for cardiac complications, 1.8% for venous thromboembolism, and 5.5% for neurological complications, including those arising from an implanted nervous system device. Compared with low-volume centers, odds of having an unfavorable discharge, prolonged LOS, high-end hospital charges, wound, and cardiac complications were significantly lower in the high-volume and medium-volume centers. CONCLUSIONS: The authors' study provides individualized estimates of the risks of postoperative complications based on patient demographics and comorbidities and hospital characteristics, which could potentially be used as an adjunct for risk stratification for patients undergoing DBS.

Cocaine influences alcohol-seeking behavior and relapse drinking in alcohol-preferring (P) rats.

BACKGROUND: The results of several studies suggest that there may be common neurocircuits regulating drug-seeking behaviors. Common biological pathways regulating drug-seeking would explain the phenomenon that seeking for 1 drug can be enhanced by exposure to another drug of abuse. The objective of this study was to assess the time course effects of acute cocaine administration on ethanol (EtOH) seeking and relapse. METHODS: Alcohol-preferring (P) rats were allowed to self-administer 15% EtOH and water. EtOH-seeking was assessed through the use of the Pavlovian spontaneous recovery (PSR) model, while EtOH-relapse drinking was assessed through the use of the alcohol-deprivation effect. RESULTS: Cocaine (0, 1, or 10 mg/kg), injected immediately, 30 minutes, or 4 hours prior to the first PSR testing session, dose-dependently increased responding on the EtOH lever compared to extinction responses and responding by saline controls. Under relapse conditions, cocaine given immediately prior to the relapse session had no effect (1 mg/kg) or reduced responding (10 mg/kg). In contrast, cocaine given 4 hours prior to the relapse session markedly enhanced EtOH responding compared to saline. CONCLUSIONS: The enhanced expression of EtOH-seeking and EtOH-relapse behaviors may be a result of a priming effect of cocaine on neuronal circuits mediating these behaviors. The effect of cocaine on EtOH-relapse drinking is indicative of the complex interactions that can occur between drugs of abuse; production of conflicting behaviors (immediate), and priming of relapse/seeking (4-hour delay).

Regional trends and the impact of various patient and hospital factors on outcomes and costs of hospitalization between academic and nonacademic centers after deep brain stimulation surgery for Parkinson's disease: a United States Nationwide Inpatient Sample analysis from 2006 to 2010.

OBJECT: The aim of this study was to analyze the incidence of adverse outcomes, complications, inpatient mortality, length of hospital stay, and the factors affecting them between academic and nonacademic centers after deep brain stimulation (DBS) surgery for Parkinson's disease (PD). The authors also analyzed the impact of various factors on the total hospitalization charges after this procedure. METHODS: This is a retrospective cohort study using the Nationwide Inpatient Sample (NIS) from 2006 to 2010. Various patient and hospital variables were analyzed from the database. The adverse discharge disposition and the higher cost of hospitalization were taken as the dependent variables. RESULTS: A total of 2244 patients who underwent surgical treatment for PD were identified from the database. The mean age was 64.22 ± 9.8 years and 68.7% (n = 1523) of the patients were male. The majority of the patients was discharged to home or self-care (87.9%, n = 1972). The majority of the procedures was performed at high-volume centers (64.8%, n = 1453), at academic institutions (85.33%, n = 1915), in urban areas (n = 2158, 96.16%), and at hospitals with a large bedsize (86.6%, n = 1907) in the West or South. Adverse discharge disposition was more likely in elderly patients (OR > 1, p = 0.011) with high comorbidity index (OR 1.508 [95% CI 1.148-1.98], p = 0.004) and those with complications (OR 3.155 [95% CI 1.202-8.279], p = 0.033). A hospital with a larger annual caseload was an independent predictor of adverse discharge disposition (OR 3.543 [95% CI 1.781-7.048], p < 0.001), whereas patients treated by physicians with high case volumes had significantly better outcomes (p = 0.006). The median total cost of hospitalization had increased by 6% from 2006 through 2010. Hospitals with a smaller case volume (OR 0.093, p < 0.001), private hospitals (OR 11.027, p < 0.001), nonteaching hospitals (OR 3.139, p = 0.003), and hospitals in the West compared with hospitals in Northeast and the Midwest (OR 1.885 [p = 0.033] and OR 2.897 [p = 0.031], respectively) were independent predictors of higher hospital cost. The mean length of hospital stay decreased from 2.03 days in 2006 to 1.55 days in 2010. There was no difference in the discharge disposition among academic versus nonacademic centers and rural versus urban hospitals (p > 0.05). CONCLUSIONS: Elderly female patients with nonprivate insurance and high comorbidity index who underwent surgery at low-volume centers performed by a surgeon with a low annual case volume and the occurrence of postoperative complications were correlated with an adverse discharge disposition. High-volume, government-owned academic centers in the Northeast were associated with a lower cost incurred to the hospitals. It can be recommended that the widespread availability of this procedure across small, academic centers in rural areas may not only provide easier access to the patients but also reduces the total cost of hospitalization.

Strategies to maximize resection of complex, or high surgical risk, low-grade gliomas.

OBJECT: Early and aggressive resection of low-grade gliomas (LGGs) leads to increased overall patient survival, decreased malignant progression, and better seizure control. This case series describes the authors' approach to achieving optimal neurological and surgical outcomes in patients referred by outside neurosurgeons for stereotactic biopsy of tumors believed to be complex or a high surgical risk, due to their diffuse nature on neuroimaging and their obvious infiltration of functional cortex. METHODS: Seven patients underwent individualized neuroimaging evaluation preoperatively, which included routine brain MRI with and without contrast administration for intraoperative neuronavigation, functional MRI with speech and motor mapping, diffusion tensor imaging to delineate white matter tracts, and MR perfusion to identify potential foci of higher grade malignancy within the tumor. Awake craniotomy with intraoperative motor and speech mapping was performed in all patients. Tumor removal was initiated through a transsylvian approach for insular lesions, and through multiple corticotomies in stimulation-confirmed noneloquent areas for all other lesions. Resection was continued until neuronavigation indicated normal brain, cortical or subcortical stimulation revealed functional cortex, or the patient began to experience a minor neurological deficit on intraoperative testing. RESULTS: Gross-total resection was achieved in 1 patient and subtotal resection (> 80%) in 6 patients, as assessed by postoperative MRI. Over the average follow-up duration of 31 months, no patient experienced a progression or recurrence. Long-term seizure control was excellent in 6 patients who achieved Engel Class I outcomes. Neurologically, all 7 patients experienced mild temporary deficits or seizures that completely resolved, and 1 patient continues to have mild expressive aphasia. CONCLUSIONS: Significant resection of diffuse, infiltrating LGGs is possible, even in presumed eloquent cortex. Aggressive resection maximizes seizure control and does not necessarily cause permanent neurological deficits. Individualized preoperative neuroimaging evaluation, including tractography and awake craniotomy with intraoperative speech and motor mapping, is an essential tool in achieving these outcomes.

A Modified Technique for Interventional MRI-Guided Deep Brain Stimulation Using the ClearPoint System.

BACKGROUND: Deep brain stimulation (DBS) is increasingly performed using imaging-based techniques, which are rapidly evolving to minimize invasiveness and use limited resources efficiently. OBJECTIVE: To describe a modified surgical technique for interventional MRI-guided stereotactic procedures using ClearPoint. METHODS: A total of 160 consecutive DBS cases for Parkinson disease (48%), essential tremor (44%), dual essential tremor/Parkinson disease (3%), and dystonia (5%) were studied. Technique modifications included (1) preplanning the target/trajectory, (2) adoption of a smaller incision and new stereotactic frame, (3) changing the sequence of surgical steps, aiming to final target PRIOR to drilling, (4) reducing burr hole size, (5) minimizing dural opening, and (6) anchoring leads with a bio cement/plate combination in lieu of commercial devices. Demographic data, radial error, number of passes, and case time were prospectively collected while complications and clinical outcomes were retrospectively assessed. RESULTS: One hundred and forty seven DBS patients had 262 total leads placed. Average radial error was 0.41 mm bilaterally. Seventy nine leads had error <0.2 mm; 6 leads had error >1 mm. Pin-to-stylet insertion time, pin-to-frame removal time, and pin-to-room departure time were 2 hours 1 minute, 2 hours 48 minutes, and 3 hours 16 minutes, respectively, and were significantly shorter than those obtained with the original ClearPoint technique for our first 150 DBS cases ( P < .0001). Complications included infection with hardware removal (2.5%) and superficial hemorrhage without permanent neurological sequelae (1.9%). CONCLUSION: The modified ClearPoint technique maintains accuracy while reducing invasiveness and MRI time. This workflow can be expanded to other applications, including laser interstitial thermal therapy and gene delivery.

Evaluation of first nonfebrile seizures.

Nonfebrile seizures may indicate underlying disease or epilepsy. The patient history can often distinguish epileptic seizures from nonepileptic disorders by identifying the events directly preceding the convulsion, associated conditions, and details of the seizure, including triggers, length, and type of movements. Laboratory testing, lumbar puncture, and neuroimaging may be indicated depending on the presentation, suspected etiology, and patient's age. Electroencephalography should be performed 24 to 48 hours after a first seizure because of its substantial yield and ability to predict recurrence. Neuroimaging is recommended for adults, infants, and children who have cognitive or motor developmental delay or a focal seizure. Neuroimaging may be scheduled on an outpatient basis for patients with stable vital signs who are awake and have returned to neurologic baseline. Emergent neuroimaging should be performed in patients with persistent decreased mental status or a new focal neurologic abnormality. Although magnetic resonance imaging is generally preferred to head computed tomography because of its greater sensitivity for intracranial pathology, computed tomography should be performed if intracranial bleeding is suspected because of recent head trauma, coagulopathy, or severe headache. Treatment with an antiepileptic drug after a first seizure does not prevent epilepsy in the long term, but it decreases the short-term likelihood of a second seizure. Adults with an unremarkable neurologic examination, no comorbidities, and no known structural brain disease who have returned to neurologic baseline do not need to be started on antiepileptic therapy. Treatment decisions should weigh the benefit of decreased short-term risk of recurrence against the potential adverse effects of antiepileptic drugs.

Iatrogenic paraplegia in 2 morbidly obese patients with ankylosing spondylitis undergoing total hip arthroplasty.

The authors describe 2 cases of intraoperative thoracic vertebral body extension fractures in morbidly obese patients with ankylosing spondylitis (AS), undergoing total hip arthroplasty, with resultant acute traumatic paraplegia. The pathophysiology with regard to the surgical positioning and the associated risks of obesity and AS are reviewed. Additionally, strategies for avoiding these types of injuries are discussed.

Results of vascularized rib grafts in complex spinal reconstruction. Surgical technique.

BACKGROUND: The application of vascularized rib grafts in spine surgery has been limited to the treatment of kyphosis with anterior placement of the rib graft to facilitate anterior spine arthrodesis. The outcomes following use of vascularized rib grafts in complex spinal reconstruction have not been adequately evaluated. The purpose of this study was to determine the results, including the time to osseous union and complications, following anterior or posterior placement of pedicled vascularized rib grafts for complex spinal reconstruction. METHODS: The medical records and images of all patients in whom a vascularized rib graft had been used for a multisegmental spine reconstruction at a single institution between 1994 and 2004 were retrospectively reviewed. Eighteen patients (mean age, 45.3 years) who had been followed for an average of 31.8 months were identified. Details regarding indications, the levels that were spanned, the graft length, the time to union, and complications were evaluated. RESULTS: The preoperative diagnoses included metastatic or primary tumor (thirteen patients) and progressive kyphosis secondary to chronic osteomyelitis (two), injury (one), congenital anomalies (one), or implant failure (one). On the average, 4.4 levels were fused and 1.9 vertebral bodies were excised. All eighteen arthrodeses included various forms of allograft and/or autograft material, and instrumentation was used, in addition to the vascularized rib graft, in twelve patients. The mean rib length was 16.1 cm, and a rib between the fifth and eleventh ribs, inclusive, was used, depending on the location of the spinal reconstruction. The average time to union was 6.8 months, and all rib grafts united. There were no complications specific to the rib-harvesting procedure. CONCLUSIONS: The use of a vascularized rib graft in complex spinal reconstruction adds little time to the overall procedure, is associated with low morbidity, and appears to offer substantial benefits to the patient.

Intermittent bilateral deep brain stimulation of the nucleus accumbens shell reduces intravenous methamphetamine intake and seeking in Wistar rats.

OBJECTIVE There is increasing interest in neuromodulation for addiction. Methamphetamine abuse is a global health epidemic with no proven treatment. The objective of this study was to examine the effects of intermittent nucleus accumbens shell (AcbSh) deep brain stimulation (DBS) on operant methamphetamine intake and on methamphetamine seeking when stimulation is delivered in an environment different from that of drug use. METHODS Eighteen rats were implanted with intravenous (IV) catheters and bilateral AcbSh electrodes and subsequently underwent daily sessions in 2-lever (active/methamphetamine and inactive/no reward) operant chambers to establish IV methamphetamine self-administration. After stable responding was achieved, 3 hours of DBS or sham treatment was administered (sham: 0 µA, n = 8; active: 200 µA, n = 10) in a separate nondrug environment prior to the daily operant sessions for 5 consecutive days. Immediately following each DBS/sham treatment, rats were placed in the operant chambers to examine the effects of remote stimulation on methamphetamine intake. After the 5 days of therapy were finished, rats reestablished a posttreatment baseline, followed by extinction training, abstinence, and 1 day of relapse testing to assess methamphetamine-seeking behavior. RESULTS There was a decrease in total methamphetamine intake in rats receiving active DBS versus sham on Days 1 (42%) and 2 (44%). Methamphetamine administration returned to baseline levels following the cessation of DBS therapy. Compared with baseline drug responding, methamphetamine seeking was reduced (57%) in the DBS group but not in the sham group. CONCLUSIONS It is feasible to deliver noncontinuous DBS outside of the drug use environment with a resultant decrease in IV methamphetamine intake and seeking. The AcbSh is a neuroanatomical substrate for psychostimulant reinforcement and may be a target for intermittent neuromodulatory therapies that could be administered during brief periods of sobriety.

Results of vascularized rib grafts in complex spinal reconstruction.

BACKGROUND: The application of vascularized rib grafts in spine surgery has been limited to the treatment of kyphosis with anterior placement of the rib graft to facilitate anterior spine arthrodesis. The outcomes following use of vascularized rib grafts in complex spinal reconstruction have not been adequately evaluated. The purpose of this study was to determine the results, including the time to osseous union and complications, following anterior or posterior placement of pedicled vascularized rib grafts for complex spinal reconstruction. METHODS: The medical records and images of all patients in whom a vascularized rib graft had been used for a multisegmental spine reconstruction at a single institution between 1994 and 2004 were retrospectively reviewed. Eighteen patients (mean age, 45.3 years) who had been followed for an average of 31.8 months were identified. Details regarding indications, the levels that were spanned, the graft length, the time to union, and complications were evaluated. RESULTS: The preoperative diagnoses included metastatic or primary tumor (thirteen patients) and progressive kyphosis secondary to chronic osteomyelitis (two), injury (one), congenital anomalies (one), or implant failure (one). On the average, 4.4 levels were fused and 1.9 vertebral bodies were excised. All eighteen arthrodeses included various forms of allograft and/or autograft material, and instrumentation was used, in addition to the vascularized rib graft, in twelve patients. The mean rib length was 16.1 cm, and a rib between the fifth and eleventh ribs, inclusive, was used, depending on the location of the spinal reconstruction. The average time to union was 6.8 months, and all rib grafts united. There were no complications specific to the rib-harvesting procedure. CONCLUSIONS: The use of a vascularized rib graft in complex spinal reconstruction adds little time to the overall procedure, is associated with low morbidity, and appears to offer substantial benefits to the patient.

A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration.

Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people. There is a need for novel, effective and practical treatment strategies that are validated in animal models. Neuromodulation, including deep brain stimulation (DBS) therapy, refers to the use of electricity to influence pathological neuronal activity and has shown promise for psychiatric disorders, including drug dependence. DBS in clinical practice involves the continuous delivery of stimulation into brain structures using an implantable pacemaker-like system that is programmed externally by a physician to alleviate symptoms. This treatment will be limited in methamphetamine users due to challenging psychosocial situations. Electrical treatments that can be delivered intermittently, non-invasively and remotely from the drug-use setting will be more realistic. This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence. Methamphetamine dependence is rapidly developed in rodents using an operant paradigm of intravenous (IV) self-administration that incorporates a period of extended access to drug and demonstrates both escalation of use and high motivation to obtain drug.

Percutaneous retrieval of an intrathecal foreign body: technical note.

A 58-year-old man had an intrathecal baclofen pump implanted. A guidewire used during removal of a previously placed lumbar drain catheter fractured, and a fragment was left within the thecal sac. Using fluoroscopic guidance, a loop snare device was used to retrieve the intrathecal foreign body successfully and without complication. The pump was placed without any difficulty, and the patient's hospital course was uneventful.

Ethanol and nicotine interaction within the posterior ventral tegmental area in male and female alcohol-preferring rats: evidence of synergy and differential gene activation in the nucleus accumbens shell.

RATIONALE: Ethanol and nicotine are frequently co-abused. The biological basis for the high co-morbidity rate is not known. Alcohol-preferring (P) rats will self-administer EtOH or nicotine directly into the posterior ventral tegmental area (pVTA). OBJECTIVE: The current experiments examined whether sub-threshold concentrations of EtOH and nicotine would support the development of self-administration behaviors if the drugs were combined. METHODS: Rats were implanted with a guide cannula aimed at the pVTA. Rats were randomly assigned to groups that self-administered sub-threshold concentrations of EtOH (50 mg%) or nicotine (1 µM) or combinations of ethanol (25 or 50 mg%) and nicotine (0.5 or 1.0 µM). Alterations in gene expression downstream projections areas (nucleus accumbens shell, AcbSh) were assessed following a single, acute exposure to EtOH (50 mg%), nicotine (1 µM), or ethanol and nicotine (50 mg% + 1 µM) directly into the pVTA. RESULTS: The results indicated that P rats would co-administer EtOH and nicotine directly into the pVTA at concentrations that did not support individual self-administration. EtOH and nicotine directly administered into the pVTA resulted in alterations in gene expression in the AcbSh (50.8-fold increase in brain-derived neurotrophic factor (BDNF), 2.4-fold decrease in glial cell line-derived neurotrophic factor (GDNF), 10.3-fold increase in vesicular glutamate transporter 1 (Vglut1)) that were not observed following microinjections of equivalent concentrations/doses of ethanol or nicotine. CONCLUSION: The data indicate that ethanol and nicotine act synergistically to produce reinforcement and alter gene expression within the mesolimbic dopamine system. The high rate of co-morbidity of alcoholism and nicotine dependence could be the result of the interactions of EtOH and nicotine within the mesolimbic dopamine system.

Percutaneous retrieval of an intrathecal foreign body: technical note.

A 58-year-old man had an intrathecal baclofen pump implanted. A guidewire used during removal of a previously placed lumbar drain catheter fractured, and a fragment was left within the thecal sac. Using fluoroscopic guidance, a loop snare device was used to retrieve the intrathecal foreign body successfully and without complication. The pump was placed without any difficulty, and the patient's hospital course was uneventful.

Reduced ethanol consumption by alcohol-preferring (P) rats following pharmacological silencing and deep brain stimulation of the nucleus accumbens shell.

OBJECT: There is increasing interest in deep brain stimulation (DBS) for the treatment of addiction. Initial testing must be conducted in animals, and the alcohol-preferring (P) rat meets the criteria for an animal model of alcoholism. This study is composed of 2 experiments designed to examine the effects of 1) pharmacological inactivation and 2) DBS of the nucleus accumbens shell (AcbSh) on the consumption of alcohol by P rats. METHODS: In the first experiment, the effects of reversible inactivation of the AcbSh were investigated by administering intracranial injections of γ-aminobutyric acid (GABA) agonists. Bilateral microinjections of drug were administered to the AcbSh in P rats (8-10 rats/group), after which the animals were placed in operant chambers containing 2 levers--one used to administer water and the other to administer 15% EtOH--to examine the acquisition and maintenance of oral EtOH self-administration. In the second experiment, a DBS electrode was placed in each P rat's left AcbSh. The animals then received 100 or 200 µA (3-4 rats/group) of DBS to examine the effect on daily consumption of oral EtOH in a free-access paradigm. RESULTS: In the first experiment, pharmacological silencing of the AcbSh with GABA agonists did not decrease the acquisition of EtOH drinking behavior but did reduce EtOH consumption by 55% in chronically drinking rats. Similarly, in the second experiment, 200 µA of DBS consistently reduced EtOH intake by 47% in chronically drinking rats. The amount of EtOH consumption returned to baseline levels following termination of therapy in both experiments. CONCLUSIONS: Pharmacological silencing and DBS of the AcbSh reduced EtOH intake after chronic EtOH use had been established in rodents. The AcbSh is a neuroanatomical substrate for the reinforcing effects of alcohol and may be a target for surgical intervention in cases of alcoholism.

Elucidating the biological basis for the reinforcing actions of alcohol in the mesolimbic dopamine system: the role of active metabolites of alcohol.

The development of successful pharmacotherapeutics for the treatment of alcoholism is predicated upon understanding the biological action of alcohol. A limitation of the alcohol research field has been examining the effects of alcohol only and ignoring the multiple biological active metabolites of alcohol. The concept that alcohol is a "pro-drug" is not new. Alcohol is readily metabolized to acetaldehyde within the brain. Acetaldehyde is a highly reactive compound that forms a number of condensation products, including salsolinol and iso-salsolinol (acetaldehyde and dopamine). Recent experiments have established that numerous metabolites of alcohol have direct CNS action, and could, in part or whole, mediate the reinforcing actions of alcohol within the mesolimbic dopamine system. The mesolimbic dopamine system originates in the ventral tegmental area (VTA) and projects to forebrain regions that include the nucleus accumbens (Acb) and the medial prefrontal cortex (mPFC) and is thought to be the neurocircuitry governing the rewarding properties of drugs of abuse. Within this neurocircuitry there is convincing evidence that; (1) biologically active metabolites of alcohol can directly or indirectly increase the activity of VTA dopamine neurons, (2) alcohol and alcohol metabolites are reinforcing within the mesolimbic dopamine system, (3) inhibiting the alcohol metabolic pathway inhibits the biological consequences of alcohol exposure, (4) alcohol consumption can be reduced by inhibiting/attenuating the alcohol metabolic pathway in the mesolimbic dopamine system, (5) alcohol metabolites can alter neurochemical levels within the mesolimbic dopamine system, and (6) alcohol interacts with alcohol metabolites to enhance the actions of both compounds. The data indicate that there is a positive relationship between alcohol and alcohol metabolites in regulating the biological consequences of consuming alcohol and the potential of alcohol use escalating to alcoholism.

Role of dynamic CT myelography in identifying the etiology of superficial siderosis.

The authors report three cases of superficial siderosis with a fluid-filled spinal canal cavity communicating with the subarachnoid space. The site of communication was identified with dynamic CT myelography and the defect was surgically repaired.