Jean-Philippe Langevin

Deep brain stimulation of the amygdala alleviates post-traumatic stress disorder symptoms in a rat model

Post-traumatic stress disorder (PTSD) is an anxiety disorder triggered by a life-threatening event causing intense fear. Recently, functional neuroimaging studies have suggested that amygdala hyperactivity is responsible for the symptoms of PTSD. Deep brain stimulation (DBS) can functionally reduce the activity of a cerebral target by delivering an electrical signal through an electrode. We tested whether DBS of the amygdala could be used to treat PTSD symptoms. Rats traumatized by inescapable shocks, in the presence of an unfamiliar object, develop the tendency to bury the object when re-exposed to it several days later. This behavior mimics the symptoms of PTSD. 10 Sprague-Dawley rats underwent the placement of an electrode in the right basolateral nucleus of the amygdala (BLn). The rats were then subjected to a session of inescapable shocks while being exposed to a conspicuous object (a ball). Five rats received DBS treatment while the other 5 rats did not. After 7 days of treatment, the rats were re-exposed to the ball and the time spent burying it under the bedding was recorded. Rats treated with BLn DBS spent on average 13 times less time burying the ball than the sham control rats. The treated rats also spent 18 times more time exploring the ball than the sham control rats. In conclusion, the behavior of treated rats in this PTSD model was nearly normalized. We argue that these results have direct implications for patients suffering from treatment-resistant PTSD by offering a new therapeutic strategy.

The amygdala as a target for behavior surgery

The amygdala was a popular target during the era of psychosurgery, specifically for the treatment of intractable aggression. This mesiotemporal structure was thought to primarily mediate fear and anger. However, recent evidence suggests that the amygdala is part of a complex network that mediates the formation of a larger repertoire of positive and negative emotions. Dysfunctions within the network or the amygdala itself can lead to various mental illnesses. In those cases, deep brain stimulation (DBS) applied focally may treat the symptoms. This review presents data supporting the potential therapeutic role of DBS of the amygdala in the treatment of anxiety disorders, addiction, and mood disorders. The success of DBS for psychiatric conditions will likely depend on our ability to precisely determine the optimal target for a specific case.

Treatment-refractory posttraumatic stress disorder (TRPTSD): a review and framework for the future☆

Post-traumatic stress disorder (PTSD) is a serious psychiatric consequence of trauma that occurs in a proportion of individuals exposed to life-threatening events. Trauma-focused psychotherapy is often recommended as first choice for those who do not recover spontaneously. But many individuals require medications. In the US, only paroxetine (PRX) and sertraline (SRT) are FDA approved for PTSD. But response and remission rates with these medications are low, so numerous other pharmacologic interventions have been tried. To date, there has not been a systematic review of the data on what are the best next-step pharmacologic strategies for individuals who fail standard treatments. To that end, we review 168 published trials of medications other than PRX or SRT and provide a detailed analysis of the 88/168 studies that describe alternative pharmacologic interventions in patients refractory to other treatment. We also review clinical factors relevant to treatment-refractory PTSD; the neurobiology of extinction, as well as evidence-based psychotherapy and neuromodulation strategies for this condition.

Deep Brain Stimulation of the Basolateral Amygdala: Targeting Technique and Electrodiagnostic Findings

The amygdala plays a critical role in emotion regulation. It could prove to be an effective neuromodulation target in the treatment of psychiatric conditions characterized by failure of extinction. We aim to describe our targeting technique, and intra-operative and post-operative electrodiagnostic findings associated with the placement of deep brain stimulation (DBS) electrodes in the amygdala. We used a transfrontal approach to implant DBS electrodes in the basolateral nucleus of the amygdala (BLn) of a patient suffering from severe post-traumatic stress disorder. We used microelectrode recording (MER) and awake intra-operative neurostimulation to assist with the placement. Post-operatively, the patient underwent monthly surveillance electroencephalograms (EEG). MER predicted the trajectory of the electrode through the amygdala. The right BLn showed a higher spike frequency than the left BLn. Intra-operative neurostimulation of the BLn elicited pleasant memories. The monthly EEG showed the presence of more sleep patterns over time with DBS. BLn DBS electrodes can be placed using a transfrontal approach. MER can predict the trajectory of the electrode in the amygdala and it may reflect the BLn neuronal activity underlying post-traumatic stress disorder PTSD. The EEG findings may underscore the reduction in anxiety.

Limbic Neuromodulation: Implications for Addiction, Posttraumatic Stress Disorder, and Memory

Deep brain stimulation, a technique whereby electrodes are implanted into specific brain regions to modulate their activity, has been mainly used to treat movement disorders. More recently this technique has been proposed for the treatment of drug addiction, posttraumatic stress disorder (PTSD), and dementia. The nucleus accumbens, amygdala, and hippocampus, central nuclei within the limbic system, have been studied as potential targets for neuromodulation for the treatment of drug addiction, PTSD, and dementia, respectively. As the scope of neuromodulation grows to include disorders of mood and thought, new ethical and philosophic challenges that require multidisciplinary discussion and cooperation are emerging.

Waldenström's macroglobulinemia and large B-cell central nervous system lymphoma: a case report

BACKGROUND Waldenströms macroglobulinemia is a low-grade B-cell lymphoma characterized by monoclonal synthesis and secretion of IgM antibodies [3]. The classic symptoms of WM result from blood hyperviscosity. Neurologic symptoms, such as fatigue, dizziness, and blurred vision, are common. The metastatic spread to the CNS, which rarely has been reported, can occur either diffusely or in the form of a mass lesion. CASE DESCRIPTION We present the case of a 73-year-old woman with intracerebral large B-cell lymphoma and concurrent WM. CONCLUSION This case illustrates the importance of histopathologic diagnosis by brain biopsy despite an existing diagnosis of systemic neoplasm.

Charting the road forward in psychiatric neurosurgery: proceedings of the 2016 American Society for Stereotactic and Functional Neurosurgery workshop on neuromodulation for psychiatric disorders

Objective Refractory psychiatric disease is a major cause of morbidity and mortality worldwide, and there is a great need for new treatments. In the last decade, investigators piloted novel deep brain stimulation (DBS)-based therapies for depression and obsessive–compulsive disorder (OCD). Results from recent pivotal trials of these therapies, however, did not demonstrate the degree of efficacy expected from previous smaller trials. To discuss next steps, neurosurgeons, neurologists, psychiatrists and representatives from industry convened a workshop sponsored by the American Society for Stereotactic and Functional Neurosurgery in Chicago, Illinois, in June of 2016. Design Here we summarise the proceedings of the workshop. Participants discussed a number of issues of importance to the community. First, we discussed how to interpret results from the recent pivotal trials of DBS for OCD and depression. We then reviewed what can be learnt from lesions and closed-loop neurostimulation. Subsequently, representatives from the National Institutes of Health, the Food and Drug Administration and industry discussed their views on neuromodulation for psychiatric disorders. In particular, these third parties discussed their criteria for moving forward with new trials. Finally, we discussed the best way of confirming safety and efficacy of these therapies, including registries and clinical trial design. We close by discussing next steps in the journey to new neuromodulatory therapies for these devastating illnesses. Conclusion Interest and motivation remain strong for deep brain stimulation for psychiatric disease. Progress will require coordinated efforts by all stakeholders.

Deep brain stimulation of a patient with psychogenic movement disorder.

Background: The long-term safety of deep brain stimulation (DBS) is an important issue because new applications are being investigated for a variety of disorders. Studying instances where DBS was inadvertently implanted in patients without a movement disorder may provide information about the safety of the therapy. We report the case of a patient with a psychogenic movement disorder treated with deep brain stimulation (DBS). Case Description: The patient presented at our clinic after 5 years of chronic DBS of the subthalamic nucleus (STN) for presumed Parkinsons disease. A dopamine transporter (DAT) scan (DaTscan) showed normal DAT distribution in the striatum. A positron emission tomography (PET) scan showed no abnormal metabolic patterns. Further psychiatric and neurological evaluations revealed that the patient was suffering from a psychogenic movement disorder. The patient displayed no sign or symptom from the stimulation, and DBS did not lead to any benefits or side effects for this patient. Conclusion: We argue that the absence of side effects, the normal DaTscan, and PET scan after 5 years of chronic stimulation illustrate the safety of DBS on neural tissue.

Poster 393 C5 Palsy After Cervical Laminectomy and Fusion: 2 Case Reports

Disclosures: Alexander Tucker: I Have No Relevant Financial Relationships To Disclose Case/Program Description: Proximal upper extremity weakness is a poorly understood complication of cervical spine surgery. The cause of this complication is unknown, although most patients recover completely over weeks to months with conservative treatment. We present two cases of postoperative, transient C5 palsy after laminectomy and fusion. Electrodiagnostic (EDX) studies performed after surgery revealed active denervation of the deltoid and biceps muscles on the symptomatic side, however the rhomboid muscles appeared unaffected. Setting: Tertiary care hospital. Results: By 6 months postoperatively, both patients had clinically improved strength in all previously affected muscle groups. We suggest that the current models of postoperative C5 palsy pathogenesis may be inadequate to explain our findings and propose an alternative theory of watershed ischemia distal to the origin of the dorsal scapular nerve as a contributing factor to the etiology of this surgical complication. Discussion: The cases described above illustrate postoperative C5 palsy, a notorious and under-recognized complication of cervical decompressive surgery, that was diagnosed clinically and correlated with EDX evidence. This description is the first to present the results of preoperative and postoperative electrophysiological studies; confirming deltoid and biceps weakness with rhomboid sparing. Conclusions: Serial EDX studies, as were performed on the patients presented here, may be used to assist with diagnosis, confirmation of involved root levels, prognostication, to follow recovery or to offer clues into the pathophysiology of the condition. Level of Evidence: Level V

Eyelid apraxia associated with deep brain stimulation of the periaqueductal gray area

We report a patient with eyelid apraxia following deep brain stimulation of the periaqueductal gray area. Based on the position of our electrode, we argue that the phenomenon is linked to inhibition of the nearby central caudal nucleus of the oculomotor nucleus by high frequency stimulation.