Breast-conserving surgery with whole breast radiation therapy has a subsequent lower mood disorder incidence rate than total mastectomy in early-stage breast cancer patients: a nationwide population-based longitudinal study.

PURPOSE: Breast-conserving surgery (BCS) followed by whole breast radiation therapy (BCS-WBRT) or total mastectomy without WBRT (TM-no-WBRT) is the primary treatment for early stage breast cancer patients. Our study aimed to identify which early stage breast cancer treatment strategies had a subsequent lower incidence rate of mood disorder over a period of 10 years after the primary treatment. METHODS: This retrospective cohort study consisted of newly diagnosed early stage breast cancer patients in Taiwan from 2000 to 2013 using the National Health Insurance Research Database in Taiwan. We used a 1:1 propensity score matching by age to enrol patients into the BCS-WBRT and TM-no-WBRT groups. Statistical analyses were performed to calculate the hazard ratio and cumulative incidence rate. RESULTS: Our study consisted of 876 BCS-WBRT patients and 1949 TM-no-WBRT patients. After propensity score matching, each study group included 876 patients. The results showed that the mood disorder incidence rate was lower in the BCS-WBRT group than in the TM-no-WBRT group. Multivariate Cox regression analysis revealed that the BCS-WBRT group had a decreased risk of developing mood disorder (adjusted hazard ratio 0.69, 95% CI 0.53-0.90, p < 0.01). Furthermore, the Kaplan-Meier analysis showed that the BCS-WBRT group had a lower cumulative incidence rate of mood disorder, especially depression, after undergoing 10 years of primary treatment (p = 0.004). CONCLUSION: Our results indicated that BCS-WBRT was associated with a lower risk of development of mood disorder over a 10-year period compared to TM-no-WBRT in early stage breast cancer patients. Our findings may provide helpful information, along with other clinical data, for breast cancer patients as they choose the type of appropriate surgery for treatment.

The effects of insular and mesiotemporal lesions on affective information processing: Preliminary evidence from patients with epilepsy surgery.

Depressive symptoms and anxiety are common complaints in patients who have had epilepsy surgery. Recent studies have reported disturbances in emotional memory, facial and vocal emotion recognition, and affective learning after temporal lobe and/or insular resection for drug-resistant seizures, suggesting that these regions may be involved in emotional processes underlying psychological symptoms. The insula is a core component of the salience network and is thought to be involved in processing emotions such as disgust, and the role of mesial temporal lobe structures in affective processing is well established. However, to our knowledge, no study has yet investigated whether attentional processing of affective information is altered when these structures are resected as part of an epilepsy surgery. The present study examined the interference control capacity and attentional biases for emotional information in adult patients with epilepsy who underwent temporal lobe resections including the amygdala and hippocampus (n = 15) and/or partial or complete insular resections (n = 16). Patients were tested on an Emotional Stroop test and on a Dot-Probe task using fearful and disgusting pictures and were compared with a healthy control group (n = 30) matched for age, gender, and education. Repeated-measures analyses of variances revealed a significant effect of emotional words on color naming speed in the Emotional Stroop task among insular patients, which was not observed in the other groups. By contrast, the groups did not differ on Dot-Probe task performance. These preliminary findings suggest that insular damage may alter emotional interference control.

Hippocampal injury-induced cognitive and mood dysfunction, altered neurogenesis, and epilepsy: can early neural stem cell grafting intervention provide protection?

Damage to the hippocampus can occur through many causes including head trauma, ischemia, stroke, status epilepticus, and Alzheimer's disease. Certain changes such as increased levels of neurogenesis and elevated concentrations of multiple neurotrophic factors that ensue in the acute phase after injury seem beneficial for restraining hippocampal dysfunction. However, many alterations that arise in the intermediate to chronic phase after injury such as abnormal migration of newly born neurons, aberrant synaptic reorganization, progressive loss of inhibitory gamma-amino butyric acid positive interneurons including those expressing reelin, greatly declined neurogenesis, and sustained inflammation are detrimental. Consequently, the net effect of postinjury plasticity in the hippocampus remains inadequate for promoting significant functional recovery. Hence, ideal therapeutic interventions ought to be efficient for restraining these detrimental changes in order to block the propensity of most hippocampal injuries to evolve into learning deficits, memory dysfunction, depression, and temporal lobe epilepsy. Neural stem cell (NSC) grafting into the hippocampus early after injury appears alluring from this perspective because several recent studies have demonstrated the therapeutic value of this intervention, especially for preventing/easing memory dysfunction, depression, and temporal lobe epilepsy development in the chronic phase after injury. These beneficial effects of NSC grafting appeared to be mediated through considerable modulation of aberrant hippocampal postinjury plasticity with additions of new inhibitory gamma-amino butyric acid positive interneurons and astrocytes secreting a variety of neurotrophic factors and anticonvulsant proteins. This review presents advancements made in NSC grafting therapy for treating hippocampal injury in animal models of excitotoxic injury, traumatic brain injury, Alzheimer's disease, and status epilepticus; potential mechanisms of functional recovery mediated by NSC grafts placed early after hippocampal injury; and issues that need to be resolved prior to considering clinical application of NSC grafting for hippocampal injury.

History of psychosurgery: a psychiatrist's perspective.

Interest in using neuromodulation to treat psychiatric disorders is rapidly increasing. The development of novel tools and techniques, such as deep brain stimulation (DBS), increases precision and minimizes risk. This article reviews the history of psychosurgical interventions and recent developments of DBS to provide a framework for understanding current options and future goals. We begin by discussing early approaches to psychosurgery, focusing on the widespread use of lobotomy and the subsequent backlash from the public and professionals in the field. Next, we discuss the development of stereotaxis. This technique allows for more targeted, precise interventions that produce discrete subcortical lesions. We focus on four stereotactic procedures that were developed using this technique: cingulotomy, capsulotomy, subcaudate tractotomy, and limbic leucotomy. We subsequently review contemporary theory and approaches with relevance to psychosurgery. We discuss the systems and neurocircuitry that are thought to be involved in psychiatric illness and provide targets for intervention. This discussion includes presentation of basal ganglia thalamocortical pathophysiology including cortico-striato-thalamo-cortical loops. We focus the discussion on two psychiatric disorders that have been targets of neurosurgical interventions: obsessive-compulsive disorder and mood disorders such as major depressive disorder. Evidence from studies of DBS in psychiatric disorders, including efficacy and tolerability, is reviewed. Finally, we look to the future, exploring the possibilities for these approaches to increase understanding, transform societal views of mental illness, and improve treatment.

Lesion procedures in psychiatric neurosurgery.

OBJECTIVE: Lesion procedures for psychiatric indications have a history that spans more than a century. This review provides a brief history of psychiatric surgery and addresses the most recent literature on lesion surgery for the treatment of anxiety and mood disorders. METHODS: Relevant data described in publications from the early 1900 s through the modern era regarding lesion procedures for psychiatric indications, both historical and current use, are reported. RESULTS: The early procedures of Burkhardt, Moniz, and Freeman are reviewed, followed by descriptions of the more refined techniques of Leksell, Knight, Foltz, White, and Kelly. The application of lesion procedures to obsessive-compulsive disorder, mood disorders, and addiction are discussed. CONCLUSIONS: Lesioning procedures have informed modern deep brain stimulation targets. Recent lesioning studies demonstrate the efficacy and durability of these procedures in severely disabled patients. Judicious application of these techniques should continue for appropriately selected patients with severe, refractory psychiatric disorders.

Surgery of the mind, mood, and conscious state: an idea in evolution.

Since the beginning of recorded history, humans have sought a physical means of altering disordered behavior and consciousness. This quest has spawned numerous innovations in neurosurgery and the neurosciences, from the earliest prehistoric attempts at trepanation to the electrocortical and anatomic localization of cerebral function that emerged in the 19th century. At the start of the 20th century, the overwhelming social impact of psychiatric illness intersected with the novel but imperfect understanding of frontal lobe function, establishing a decades-long venture into the modern origin of psychosurgery, the prefrontal lobotomy. The subsequent social and ethical ramifications of the widespread overuse of transorbital lobotomies drove psychosurgery to near extinction. However, as the pharmacologic treatment of psychiatric illness was established, numerous concomitant technical and neuroscientific innovations permitted the incremental development of a new paradigm of treating the disordered mind. In this article, we retrospectively examine these early origins of psychosurgery and then look to the recent past, present, and future for emerging trends in surgery of the psyche. Recent decades have seen a revolution in minimalism, noninvasive imaging, and functional manipulation of the human cerebrum that have created new opportunities and treatment modalities for disorders of the human mind and mood. Early contemporary efforts were directed at focal lesioning of abnormal pathways, but deep-brain stimulation now aims to reversibly alter and modulate those neurologic activities responsible for not only psychiatric disorders, but also to modulate and even to augment consciousness, memory, and other elements of cerebral function. As new tools become available, the social and medical impact of psychosurgery promises to revolutionize not only neurosurgery, but also humans' capability for positively impacting life and society.

Neurosurgical treatment of mood disorders: traditional psychosurgery and the advent of deep brain stimulation.

PURPOSE OF REVIEW: From its peak in the 1940s and 1950s, psychosurgery (or, neurosurgery for psychiatric disorders) has had a gradual decline, with only a few centers around the world continuing with the procedure into the 1980s and 1990s. With recent developments in brain stimulation techniques, the continuing relevance of psychosurgery in the treatment of psychiatric disorders is worthy of examination. RECENT FINDINGS: A review of databases (PubMed, Medline, Current Contents and Embase) suggests that psychosurgery in the form of stereotactic focal ablation is still practiced in a few centers, although the number has decreased further from the 1990s. Procedures have not changed substantively, although modern imaging and stereotaxy have made them more precise. No good predictors of treatment response have been identified. There is a major shift in interest to deep brain stimulation (DBS) instead of ablative surgery. Studies of DBS in resistant depression and obsessive-compulsive disorder have been few and have involved small numbers, but this field is growing rapidly. SUMMARY: Although ablative psychosurgery using stereotactic procedures continues to be used to a small extent, psychiatrists remain ambivalent about this procedure. The baton of psychosurgery, however, appears to have been passed on to DBS, but more data are needed on technical details and outcomes before the possible therapeutic role of DBS can be established.

Pain and psycho-affective disorders.

The subject of human pain can be subdivided into two broad categories: physical pain and psychological pain. Since the dawn of human consciousness, each of these two forms of pain-one clearly physical, the other having more to deal with the mind-have played a central role in human existence. Psychological pain and suffering add dimensions that go far beyond the boundaries of its physical counterpart. In the past 50 years, one of the more remarkable accomplishments of medical science has been to increasingly enable the clinician to impact, as never before, each of these critical realms of human existence. Our intention is, therefore, to initially describe a few of the many exciting neuroscientific and neurosurgical advances that have been made in the treatment of various types of pain and to speculate on some of the emergent questions that we believe need to be addressed. After this is accomplished, we will then use this information as a kind of two-pronged philosophical entrance into questions of the mind, brain, and soul that we feel are necessary to bring back into the sphere of the modern physician's practice. The goal of this article is two-fold: 1) to share some of our exciting research and 2) to renew the interest in timeless questions, such as that of the mind-brain and the brain-mind, in the conversation of the modern neurosurgeon. The International Association for the Study of Pain divides pain into two broad functions and anatomical categories. In this framework, "nociceptive" pain is defined as the kind of physical pain that results when the tissue is damaged. Given this perspective, such pain is usually considered a consequence of one's defense against one's environment. The other pain is the "neuropathic" one resulting from a lesion or a dysfunction of the human nervous system. As such, we will take the risk of crossing beyond the boundaries of neurosurgery and venture into boundaries that, at another time, might seem more natural to the discipline of psychiatry for two reasons. The first is that psychiatry seems to be so focused on the brain-its biochemistry and pharmacology--that questions of mind and soul have become rare and almost negligible. The second is to follow the course of the results of our own clinical investigations that have taken us into that very human world where questions of physical pain, psychological pain, and the experience of suffering abound. Today, however, the strategy of neuromodulation offers the advantage of being precisely tailored in neuroanatomical terms and, even more importantly, of being altogether reversible. At both our own Istituto Neurologico C. Besta and many other neurosurgical centers worldwide, many procedures have been reported in which implant neuromodulation devices successfully treat pain. For example, long-term stimulation of the spinal cord has been fairly effective in the treatment of neuropathic pain, multiple sclerosis, and various other forms of pain. Good results have been obtained in treating peripheral vascular diseases and sympathetic reflex dystrophy syndrome. Good results have also been achieved in trigeminal nerve stimulation and peripheral nerve stimulation. In the case of thalamic stimulation, there has also been an improvement of symptoms, but a long-term degree of tolerance was noticed. Hypothalamic stimulation has also been seen to be effective in controlling trigeminal autonomic cephalalgic pain, as well as the facial pain that is known to occur in multiple sclerosis. Motor cortex stimulation was found to occasionally have good results in treating neuropathic pain, whereas occipital nerve stimulation was found to achieve good results in controlling chronic cluster headache and other chronic headaches, although with only short-term follow-up so far. Recent reports of functional magnetic resonance imaging have prompted us to propose exciting new neurosurgical targets that may be effective in treating psychoaffective disorders. Our results appear to be more than promising so far. It appears that neuropathic pain and psychoaffective disorders seem to be sharing an anatomophysiological common background at the Brodmann Area 25 of the anterior cingulated gyrus. On the basis of these exciting findings, we believe that it is reasonable to suggest that neuropathic pain and psychoaffective disorders may ultimately be managed with complementary or, at least, similar, therapeutic strategies, each of which lie within the domain of the neurosurgeon.

Ablative neurosurgery for mental disorders: is there still a role in the 21st century? A personal perspective.

OBJECT: The author presents his personal perspective on ablative neurosurgical techniques used to perform bilateral anterior cingulotomy (BACI) and bilateral anterior capsulotomy (BACA) for ameliorating the symptoms of refractory obsessive-compulsive disorder (OCD) and treatment refractory depression (TRD). With depression predicted to be the second most common cause of disability in the world by the year 2020 and the birth of electric neurostimulation representing an attractive alternative treatment option for TRD and OCD, it is desirable to revisit the pros and cons of these treatment options. METHODS: The author reviewed the surgical methods and outcome (including neuroimaging findings) in all cases in which ablative neurosurgery was performed at Ninewells Hospital and Medical School over the last 2 decades. RESULTS: The advantages of ablative procedures (BACI and BACA) from patients' and psychiatrists' perspectives are that the ablative procedures are one-off procedures that do not require lifelong commitment to program the stimulation devices, fix hardware failures, or change exhausted batteries. From the perspective of healthcare funding bodies, the relatively low cost of these treatments is an advantage. The main disadvantages of BACI and BACA are the perceived higher complication rates, the irreversibility of the surgical lesions, and the stigma associated with brain destruction in psychiatric patients that are still unpalatable in the community at large. However, some patients still choose a one-off procedure in preference to any other options presented to them. CONCLUSIONS: There is still place for BACI and BACA in modern neurosurgery for mental disorders, at least in the short term for those who do not want to commit to lifelong device programming and maintenance.

Limbic leukotomy for intractable major affective disorders: a 7-year follow-up study using nine comprehensive psychiatric test evaluations.

Surgical treatment of psychiatric disease can be effective for some patients with severe, intractable disorders. However, few long-term studies using comprehensive psychiatric test evaluation of patients who have undergone surgery have been carried out. Stereotactic limbic leukotomy (subcaudate tractotomy and cingulotomy) was performed via radiofrequency thermocoagulation on 16 patients with intractable major affective disorders (bipolar). Patients were followed for 7 years, and nine complete psychiatric test evaluations were conducted before and after the procedure. Clinical outcomes were evaluated using the Current Global Psychiatric-Social Status Scale (CGPSS). In the 7-year follow-up, mean scores on the Hamilton Depression Rating Scale and the Beck Depression Inventory declined significantly from 42+/-5.76 to 20+/-11.98 (p<0.01) and from 32+/-9.13 to 19 +/- 14.29 (p<0.05), respectively. Also, mean scores on the Hamilton Anxiety Rating Scale and Negative Symptom Scale declined significantly from 104+/-53.62 to 57+/-36.41 (p<0.01) and from 57+/-15.38 to 33+/-18.8 (p<0.05), respectively. There were no statistical differences before and after surgery for Young's Mania Rating Scale, p>0.1. Using the CGPSS, 68.8% of patients had a marked response (CGPSS of >or=3), 18.9% of patients had a possible response (CGPSS of 2), and 12.6% did not improve or became worse (CGPSS of 0 or 1). There was no surgical mortality and only three patients experienced temporary minor complications. Based on these nine comprehensive psychiatric test evaluations, limbic leukotomy is an effective procedure for long-term treatment of severe, intractable major affective disorders, with no significant side effects. The results of the psychiatric tests carried out during the 7 years of follow-up were constant and stable. The current findings demonstrate that depression, anxiety, and negative symptoms are significantly reduced by limbic leukotomy, but mania and active symptoms are not. Surgical intervention remains an important therapeutic option for the treatment of major affective disorders, and is probably underused.

[Stereotactic multi-target operation for patients with affective disorder].

OBJECTIVE: To explore the efficacy and complication of bilateral multi-target radiofrequency lesion operation in patients with affective disorder. METHODS: One hundred and eighty-two cases with affective disorder were treated with unstaged bilateral multi-target radiofrequency thermocoagulation. The efficacy was evaluated with the method established in 1990 by the National Psychosurgery Cooperative Group. RESULTS: After 2 weeks of operation, 86 cases with remarkable improvements, 81 cases with improvements, 15 case with no improvements, no case with progression, total efficient ratio was 91.76%. With 6-54 months of follow-up to all of 166 cases, 38 cases with recovery, 59 cases with remarkable improvements, 52 cases with improvements, 17 cases with no improvements, no case with progression, total efficient ratio was 89.76%. Except for early temporal complication of stereotaxic operation, the long-term complication ratio was less than 1%. CONCLUSION: CT-guided bilateral multi-target operation is prominent in treatment of affective disorder with high efficacy and safety.

Practical management of treatment-resistant affective disorders.

The Geoffrey Knight National Unit was set up in 1970 exclusively for psychosurgery. In recent years it has become increasingly concerned with the development of medication regimens that might avoid the need for surgery. This has offered a unique pharmacotherapeutic opportunity because all the referrals have severe, persistent and treatment-resistant disorders. The scheme of high-dose and combined medication devised is presented and discussed.

Neurosurgery for affective disorders at Atkinson Morley's Hospital 1948-1994.

Neurosurgical practice in the treatment of affective disorders has changed dramatically over the last 40 years. This paper traces the changes which have occurred in one institution, namely Atkinson Morley's Hospital, Wimbledon, London, UK from 1948 to the present day. Freehand operations designed by McKissock and performed on large numbers of patients disappeared as better non-surgical treatments became available and long term complications and treatment failures became dearer. In the 1970's stereotactic limbic leucotomy, a much more focal and accurate operation, was devised and became popular. The present day practice utilises precisely the same techniques as the original stereotactic limbic leucotomy but is employed on small numbers of patients. The procedure continues to have a role for those few patients with severe psychiatric illness, particularly obsessive compulsive disorder, which has proved refractory to other therapeutic modalities.

Neuropsychological correlates of stereotactic subcaudate tractotomy. A prospective study.

Stereotactic subcaudate tractotomy is a surgical procedure performed for the alleviation of intractable affective disorders. It involves the destruction of bifrontal pathways located beneath and in front of the head of the caudate nucleus. We report the first prospective study of the neuropsychological correlates of this operation in 23 patients. Tests of general intelligence, speed and attention, as well as a wide range of focal cognitive tests, including tasks which have been reported in the literature to be sensitive to frontal lobe dysfunction, were administered 1 wk before the operation, 2 wks after the operation and approximately 6 mths after the operation. The results indicated that this operation does not cause any significant, long-term adverse, cognitive deficits. In the post-operative assessment, however, patients show a significant deterioration in their performance on recognition memory tests and a large proportion of them present with a marked tendency to confabulate on recall tasks. In addition, their performance on some of the tasks which are considered to be sensitive to frontal lobe dysfunction is found to be significantly impaired. These deficits are interpreted to reflect frontal lobe dysfunction due to widespread post-operative oedema rather than damage to the subcaudate pathways. The potential for research on these transient effects of the operation for the advancement of our understanding of frontal lobe functions is discussed.

Treatment of psychiatric illness by stereotactic cingulotomy.

The treatment of 198 psychiatrically disabled patients with stereotactic cingulotomy was evaluated prospectively for a mean follow-up of 8.6 years. Patients with major affective disorders and anxiety disorders fared the best, with a return to normal functioning in the majority. Patients with obsessive-compulsive disorders, schizophrenia, and personality disorders improved less predictably, with an uneven improvement in functioning that required active ongoing psychiatric treatment. Low mortality and morbidity, a reduction of violent behavior, a possible reduction of suicidal risk, and a lessening of the intractable suffering of chronic psychiatric illness all indicate that cingulotomy can be an effective, safe treatment for patients with affective disorders that are unresponsive to all other forms of therapy.

The stalemate position.

The psychosurgical operation of stereotactic subcaudate tractotomy can be a highly effective treatment for chronic and intractable affective disorders. We have lately given increasing attention to cases where the depressed mood appears to lift although there is little improvement in social function. In these cases there has been a failure of rehabilitation and the complexities of this process post-operatively are discussed. In addition, relatives report in some 10% of cases "personality changes" after the operation which are not perceived in this way by an independent medical assessor and these observations seem to depend upon relatives mis-interpreting the resumption of pre-morbid personality function after long illnesses as undesirable side-effects. Case histories illustrating the problems are described. Treatment and rehabilitation strategies are outlined.