Bilateral amygdala stimulation reduces avoidance behavior in a predator scent posttraumatic stress disorder model.

OBJECTIVE The predator scent model of posttraumatic stress disorder (PTSD) produces prolonged abnormal anxiety and avoidance-like behaviors. Increased basolateral amygdala activity has been shown to correlate with severity of PTSD symptoms in human studies. Modulation of this increased amygdala activity by deep brain stimulation led to improved symptoms in prior studies that used a foot shock model of inducing PTSD. The predator scent model is a different technique that induces long-lasting avoidance behavioral responses by exposing the animal to an inescapable scent of one of its predators. The authors hypothesize that high-frequency stimulation of the bilateral basolateral amygdala will decrease avoidance and anxiety-like behaviors in a predator scent rodent model of PTSD. METHODS Rodents underwent cat urine exposure in a place preference protocol. Avoidance in the place preference paradigm and anxiety-like behavior in the elevated plus maze were measured before and after high-frequency stimulation. RESULTS Predator scent exposure resulted in long-term significant avoidance behavior in rodents. Bilateral stimulation significantly decreased avoidance behavior in rodents compared to no stimulation following predator scent exposure. There were no significant differences in anxiety behaviors on the elevated plus maze between stimulated and unstimulated cohorts. CONCLUSIONS Bilateral stimulation of the basolateral amygdala leads to decreased avoidance behavior compared to controls in a predator scent model of PTSD.

Traumatic brain injury among female veterans: a review of sex differences in military neurosurgery.

The impact of traumatic brain injury (TBI) has been demonstrated in various studies with respect to prevalence, morbidity, and mortality data. Many of the patients burdened with long-term sequelae of TBI are veterans. Although fewer in number, female veterans with TBI have been suggested to suffer from unique physical, mental, and social challenges. However, there remains a significant knowledge gap in the sex differences in TBI. Increased female representation in the military heralds an increased risk of TBI for female soldiers, and medical professionals must be prepared to address the unique health challenges in the face of changing demographics among the veteran TBI population. In this review, the authors aimed to present the current understanding of sex differences in TBI in the veteran population and suggest directions for future investigations.

Deep brain stimulation for psychiatric disorders: where we are now.

Fossil records showing trephination in the Stone Age provide evidence that humans have sought to influence the mind through physical means since before the historical record. Attempts to treat psychiatric disease via neurosurgical means in the 20th century provided some intriguing initial results. However, the indiscriminate application of these treatments, lack of rigorous evaluation of the results, and the side effects of ablative, irreversible procedures resulted in a backlash against brain surgery for psychiatric disorders that continues to this day. With the advent of psychotropic medications, interest in invasive procedures for organic brain disease waned. Diagnosis and classification of psychiatric diseases has improved, due to a better understanding of psychiatric patho-physiology and the development of disease and treatment biomarkers. Meanwhile, a significant percentage of patients remain refractory to multiple modes of treatment, and psychiatric disease remains the number one cause of disability in the world. These data, along with the safe and efficacious application of deep brain stimulation (DBS) for movement disorders, in principle a reversible process, is rekindling interest in the surgical treatment of psychiatric disorders with stimulation of deep brain sites involved in emotional and behavioral circuitry. This review presents a brief history of psychosurgery and summarizes the development of DBS for psychiatric disease, reviewing the available evidence for the current application of DBS for disorders of the mind.

Spinal cord stimulation failure: evaluation of factors underlying hardware explantation.

OBJECTIVE: Spinal cord stimulation has been shown to improve pain relief and reduce narcotic analgesic use in cases of complex refractory pain syndromes. However, a subset of patients ultimately undergoes removal of the spinal cord stimulator (SCS) system, presumably because of surgical complications or poor efficacy. This retrospective study addresses the paucity of evidence regarding risk factors and underlying causes of spinal cord stimulation failures that necessitate this explantation. METHODS: In this retrospective single-center review, 129 patients underwent explantation of SCS hardware during a 9-year period (2005-2013) following initial placement at the authors' institution or elsewhere. Medical history, including indication of implantation, device characteristics, revision history, and reported reasons for removal of hardware, were reviewed. RESULTS: The 74 (57%) women and 55 (43%) men were a median of 49 years old (IQR 41-61 years) at explantation; the median time to explantation was 20 months (IQR 7.5-45.5 months). Thoracic or upper lumbar leads were placed in 89.9% of patients primarily for the diagnosis of postsurgical failed-back surgery syndrome (70.5%), chronic regional pain syndrome (14.7%), and neuropathic pain (8.5%). More than half of patients were legally disabled. Initial postoperative reduction in pain was reported in 81% of patients, and 37.8% returned to work. Among 15 patients with acute postsurgical complications (12 infections, 2 hemorrhages, 1 immediate paraplegia), the median time to removal was 2 months. Primary reasons for hardware removal were lack of stimulation efficacy (81%), electrode failure due to migration (14%), and allergic reactions to implanted hardware in 2 patients. The 72 patients who underwent formal psychiatric evaluation before implantation were affected by high rates of major depression (64%), anxiety (34%), posttraumatic stress disorder (PTSD) (12%), drug or alcohol abuse (12%), and physical or sexual abuse (22%). CONCLUSIONS: The authors' findings provide insight regarding the mechanisms of spinal cord stimulation failure that resulted in total removal of the implanted system. The relationship between spinal cord stimulation failure and certain psychiatric disorders, such as PTSD, depression, and anxiety, is highlighted. Ultimately, this work may shed light on potential avenues to reduce morbidity and improve patient outcomes.

Current and future directions of deep brain stimulation for neurological and psychiatric disorders.

Deep brain stimulation (DBS) has evolved considerably over the past 4 decades. Although it has primarily been used to treat movement disorders such as Parkinson's disease, essential tremor, and dystonia, recently it has been approved to treat obsessive-compulsive disorder and epilepsy. Novel potential indications in both neurological and psychiatric disorders are undergoing active study. There have been significant advances in DBS technology, including preoperative and intraoperative imaging, surgical approaches and techniques, and device improvements. In addition to providing significant clinical benefits and improving quality of life, DBS has also increased the understanding of human electrophysiology and network interactions. Despite the value of DBS, future developments should be aimed at developing less invasive techniques and attaining not just symptom improvement but curative disease modification.

Postconcussion syndrome: demographics and predictors in 221 patients.

OBJECTIVE The objective of this study was to determine the demographics and predictors of postconcussion syndrome (PCS) in a large series of patients using a novel definition of PCS. METHODS The authors conducted a retrospective cohort study of 284 consecutive concussed patients, 221 of whom had PCS on the basis of at least 3 symptoms persisting at least 1 month. This definition of PCS was uniformly employed and is unique in accepting an expanded list of symptoms, in shortening the postconcussion interval to 1 month from 3 months, and in excluding those with focal injuries such as hemorrhages and contusions. RESULTS The 221 cases showed considerable heterogeneity in clinical features of PCS. They averaged 3.3 concussions, with a range of 0 to 12 or more concussions, and 62.4% occurred during sports and recreation. The median duration of PCS was 7 months at the time of examination, with 11.8% lasting more than 2 years, and 23.1% with PCS had only 1 concussion. The average patient age was 27 years (range 10-74 years). The average number of persistent symptoms was 8.1; 26.2% had a previous psychiatric condition, attention-deficit disorder/attention-deficit hyperactivity disorder, a learning disability, or previous migraine headaches. The prevalence of arachnoid cysts and Chiari malformation in PCS exceeded the general population. Additionally, involvement in litigation, presence of extracranial injuries, amnesia and/or loss of consciousness, and female sex were predictive of reporting a high number of symptoms. A prior history of psychiatric conditions or migraines, cause of injury, number of previous concussions, and age did not significantly predict symptom number. Only the number of symptoms reported predicted the duration of PCS. To predict the number of symptoms for those who fulfilled PCS criteria according to the International Classification of Diseases, 10th Revision (ICD-10), and the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), the number of previous concussions was significant. CONCLUSIONS PCS is commonly associated with multiple concussions, but 23.1% in the present series occurred after only 1 concussion. Most patients with PCS had multiple symptoms persisting for months or years. The median duration of PCS was 7 months, with a range up to 26 years. In only 11.3%, the PCS had ended at the time of consultation. Not all predictors commonly cited in the literature align with the findings in this study. This is likely due to differences in the definitions of PCS used in research. These results suggest that the use of ICD-10 and DSM-IV to diagnose PCS may be biased toward those who are vulnerable to concussions or with more severe forms of PCS. It is thus important to redefine PCS based on evidence-based medicine.

Structural and biochemical abnormalities in the absence of acute deficits in mild primary blast-induced head trauma.

OBJECTIVE: Blast-induced neurotrauma (BINT), if not fatal, is nonetheless potentially crippling. It can produce a wide array of acute symptoms in moderate-to-severe exposures, but mild BINT (mBINT) is characterized by the distinct absence of acute clinical abnormalities. The lack of observable indications for mBINT is particularly alarming, as these injuries have been linked to severe long-term psychiatric and degenerative neurological dysfunction. Although the long-term sequelae of BINT are extensively documented, the underlying mechanisms of injury remain poorly understood, impeding the development of diagnostic and treatment strategies. The primary goal of this research was to recapitulate primary mBINT in rodents in order to facilitate well-controlled, long-term investigations of blast-induced pathological neurological sequelae and identify potential mechanisms by which ongoing damage may occur postinjury. METHODS: A validated, open-ended shock tube model was used to deliver blast overpressure (150 kPa) to anesthetized rats with body shielding and head fixation, simulating the protective effects of military-grade body armor and isolating a shock wave injury from confounding systemic injury responses, head acceleration, and other elements of explosive events. Evans Blue-labeled albumin was used to visualize blood-brain barrier (BBB) compromise at 4 hours postinjury. Iba1 staining was used to visualize activated microglia and infiltrating macrophages in areas of peak BBB compromise. Acrolein, a potent posttraumatic neurotoxin, was quantified in brain tissue by immunoblotting and in urine through liquid chromatography with tandem mass spectrometry at 1, 2, 3, and 5 days postinjury. Locomotor behavior, motor performance, and short-term memory were assessed with open field, rotarod, and novel object recognition (NOR) paradigms at 24 and 48 hours after the blast. RESULTS: Average speed, maximum speed, and distance traveled in an open-field exploration paradigm did not show significant differences in performance between sham-injured and mBINT rats. Likewise, rats with mBINT did not exhibit deficits in maximum revolutions per minute or total run time in a rotarod paradigm. Short-term memory was also unaffected by mBINT in an NOR paradigm. Despite lacking observable motor or cognitive deficits in the acute term, blast-injured rats displayed brain acrolein levels that were significantly elevated for at least 5 days, and acrolein's glutathione-reduced metabolite, 3-HPMA, was present in urine for 2 days after injury. Additionally, mBINT brain tissue demonstrated BBB damage 4 hours postinjury and colocalized neuroinflammatory changes 24 hours postinjury. CONCLUSIONS: This model highlights mBINT's potential for underlying detrimental physical and biochemical alterations despite the lack of apparent acute symptoms and, by recapitulating the human condition, represents an avenue for further examining the pathophysiology of mBINT. The sustained upregulation of acrolein for days after injury suggests that acrolein may be an upstream player potentiating ongoing postinjury damage and neuroinflammation. Ultimately, continued research with this model may lead to diagnostic and treatment mechanisms capable of preventing or reducing the severity of long-term neurological dysfunction following mBINT.