Rare Case of Managing and Evaluating Viability after Replantation of a Serial Self-Amputated Bilateral Testis by a Patient with Schizophrenia: A Case Report.

Amputation of the testis is very rare in clinical situations; therefore, most surgeons have no experience with an amputated testis. In this case, a 31-year-old male with schizophrenia amputated both testes due to self-mutilation. We performed replantation surgery via microscopy. On postoperative day 1, he removed his right testis by using his hand, even though his hands were restrained. The second attack disrupted the viability of the right testis. However, after proper management, we checked the normal sex hormone level by preserving the replanted left testis. We evaluated the viability of the replanted testis by performing five examinations, namely, intraoperative indocyanine green injection, testicular scan with technetium pertechnetate, contrast-enhanced computerized tomography, Doppler ultrasonography, and serum testosterone level. In this report, we aimed to describe our rare experience about management with replantation of the amputated testes and evaluation of their viability.

Schizophrenia and neurosurgery: systematic review and theories.

OBJECTIVE: Despite its relatively low prevalence, schizophrenia has a high burden of illness due to its lifelong effects and the fact that it is often refractory to psychotropic treatment. This review investigated how neurosurgical interventions, primarily neuromodulation through deep brain stimulation (DBS), can mitigate treatment-refractory schizophrenia. Pathophysiological data and ongoing clinical trials were reviewed to suggest which targets hold promise for neurosurgical efficacy. METHODS: A systematic review of the literature was conducted via an electronic search of the PubMed, Scopus, and Web of Science databases. Included papers were human or animal studies of neurosurgical interventions for schizophrenia conducted between 2012 and 2022. An electronic search of ClinicalTrials.gov and the International Clinical Trials Registry Platform was conducted to find ongoing clinical trials. The ROBINS-I (Risk of Bias in Nonrandomized Studies of Interventions) assessment tool was used to evaluate risk of bias in the study. RESULTS: Eight human and 2 rat studies were included in the review. Of the human studies, 5 used DBS targeting the nucleus accumbens, subgenual anterior cingulate cortex, habenula, and substantial nigra pars reticulata. The remaining 3 human studies reported the results of subcaudate tractotomies and anterior capsulotomies. The rat studies investigated DBS of the nucleus accumbens and medial prefrontal cortex. Overall, human studies demonstrated long-term reduction in Positive and Negative Syndrome Scale scores in many participants, with a low incidence of surgical and psychological side effects. The rat studies demonstrated improved prepulse and latent inhibition in the targeted areas after DBS. CONCLUSIONS: As identified in this review, recent studies have investigated the potential effects of therapeutic DBS for schizophrenia, with varying results. DBS targets that have been explored include the hippocampus, subgenual anterior cingulate cortex, habenula, substantia nigra pars reticulata, and medial prefrontal cortex. In addition to DBS, other neuromodulatory techniques such as neuroablation have been studied. Current evidence suggests that neuroablation in the subcaudate tract and anterior capsulotomy may be beneficial for some patients. The authors recommend further exploration of neuromodulation for treatment-refractory schizophrenia, under the condition that rigorous standards be upheld when considering surgical candidacy for these treatments, given that their safety and efficacy remain to be determined.

Gamma Knife capsulotomy for correction of obsessive-compulsive symptoms in a patient with schizophrenia: Case report.

The treatment of mental illnesses that are resistant to conservative therapy poses a serious problem. Surgical methods with proven efficacy have been proposed for only a small group of psychiatric diseases, while in practice non-classical clinical situations are seen rather often. A 36-year-old man with a 18-year history of "schizophrenia with a predominant obsessive-compulsive syndrome" was referred to the Burdenko National Medical Research Center of Neurosurgery for consideration of neurosurgical treatment. Based on results of longitudinal independent evaluations of the patient in several specialized clinical centers the disease was considered resistant to medical therapy. Radiosurgical procedure was performed by means of Leksell Gamma Knife Perfexion™ (Elekta AB; Stockholm, Sweden). Ventral portion of the anterior limb of internal capsule was targeted with two 4-mm isocenters on each side, with prescription dose at 50% isodose line of 80 Gy and a maximal dose of 160 Gy. No obvious complications or side effects were noted during 13-month follow-up after radiosurgery. Gradual clinical improvement was observed with 25% reduction of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score at 13 months after treatment. Similarly, the Hospital Anxiety and Depression Scale (HADS) anxiety and depression scores decreased by 24% and 58%, respectively. This is the first published case of radiosurgical treatment of a psychiatric disorder in Russia. It demonstrates the potential efficacy of Gamma Knife capsulotomy for non-classical forms of obsessive-compulsive disorder comorbid with schizophrenia. Nevertheless, definitive conclusions about the reliability of this radiosurgical indication can only be made based on the results of larger studies.

Use of Stereoelectroencephalography Beyond Epilepsy: A Systematic Review.

BACKGROUND: Stereoelectroencephalography (sEEG) is an increasingly popular surgical technique used clinically to study neural circuits involved in medication-refractory epilepsy, and it is concomitantly used in the scientific investigation of neural circuitry underlying behavior. METHODS: Using PRISMA guidelines, the U.S. National Library of Medicine at the National Institutes of Health PubMed database was queried for investigational or therapeutic applications of sEEG in human subjects. Abstracts were analyzed independently by 2 authors for inclusion or exclusion. RESULTS: The study search identified 752 articles, and after exclusion criteria were applied, 8 studies were selected for in-depth review. Among those 8 studies, 122 patients were included, with indications ranging from schizophrenia to Parkinson disease. All the included studies were single-institution case series representing level IV scientific evidence. CONCLUSIONS: sEEG is an important method in epilepsy surgery that could be applied to other neurologic and psychiatric diseases. Information from these studies could provide additional pathophysiologic information and lead to further development and refinement of neuromodulation therapies for such conditions.

Deep brain stimulation in treatment resistant schizophrenia: A pilot randomized cross-over clinical trial.

BACKGROUND: Up to 30% of patients with schizophrenia are resistant to antipsychotic drug treatment, with 60% of such cases also failing to respond to clozapine. Deep brain stimulation (DBS) has been used in treatment resistant patients with other psychiatric disorders, but there is a lack of trials in schizophrenia, partly due to uncertainties over where to site the electrodes. This trial aimed to examine the effectiveness of nucleus accumbens (NAcc) and subgenual anterior cingulate cortex (subgenual ACC) targeted DBS; the primary outcome measure was PANSS total score, as assessed fortnightly. METHODS: Eight patients with schizophrenia, who met criteria for treatment resistance and were also resistant to/intolerant of clozapine, were randomly assigned using central allocation to receive DBS in the NAcc or subgenual ACC. An open stabilization phase lasting at least six months was followed by a randomized double-blind crossover phase lasting 24 weeks in those who met symptomatic improvement criteria. The primary end-point was a 25% improvement in PANSS total score. (ClinicalTrials.gov Identifier: NCT02377505; trial completed). FINDINGS: One implanted patient did not receive DBS due to complications of surgery. Of the remaining 7 patients, 2/3 with NAcc and 2/4 with subgenual ACC electrode placements met the symptomatic improvement criteria (58% and 86%, and 37% and 68% improvement in PANSS total score, respectively). Three of these patients entered the crossover phase and all showed worsening when the stimulation was discontinued. The fourth patient worsened after the current was switched off accidentally without her or the investigators' knowledge. Physical adverse events were uncommon, but two patients developed persistent psychiatric adverse effects (negative symptoms/apathy and mood instability, respectively). INTERPRETATION: These preliminary findings point to the possibility of DBS having therapeutic effects in patients with schizophrenia who do not respond to any other treatment. Larger trials with careful attention to blinding will be necessary to establish the extent of the benefits and whether these can be achieved without psychiatric side-effects.

Reduced rate of revascularization in schizophrenic patients with acute myocardial infarction: A systematic review and meta-analysis.

IMPORTANCE: It has been suggested that patients with schizophrenia have higher than expected mortality following acute coronary events. However, the in-hospital revascularization rate in patients with schizophrenia and acute myocardial infarction (AMI) compared to mentally healthy patients remains unknown. OBJECTIVE: To evaluate the revascularization rate in schizophrenic patients after AMI with a meta-analysis of observational studies. DATA SOURCES: PubMed and Embase electronical databases. STUDY SELECTION: Observational studies that evaluate the likelihood of revascularization in AMI patients with schizophrenia compared to those without schizophrenia, after adjustment for potential influencing factors. DATA EXTRACTION AND SYNTHESIS: Data regarding study design, characteristics of the AMI patients and schizophrenic patients, and strategies of revascularization were extracted. Results were pooled and analyzed with a random effect model to incorporate the potential heterogeneity. MAIN OUTCOME AND MEASURES: The likelihood of revascularization in AMI patients with schizophrenia compared to those without schizophrenia, after adjustment for potential influencing factors. RESULTS: Overall, 3,260,754 hospitalized AMI patients from six follow-up studies were included, of which 17,875 patients had a prior diagnosis of schizophrenia. Results of this meta-analysis suggest that revascularization was significantly lower in AMI patients with schizophrenia compared to those without schizophrenia (odds ratio [OR]: 0.48, 95% confidence interval [CI]: 0.38 to 0.62, p < .001; I2 = 93%), after adjustment for demographic characteristics, comorbidities, and hospital and regional factors. Specifically, AMI patients with schizophrenia had significantly fewer percutaneous coronary interventions (OR: 0.48, 95% CI: 0.41 to 0.56, p < .001; I2 = 49%) and coronary artery bypass grafts (OR: 0.61, 95% CI: 0.53 to 0.70, p < .001; I2 = 20%) compared to those without schizophrenia. CONCLUSIONS AND RELEVANCE: Patients with schizophrenia and AMI have a lower rate of coronary revascularization as compared with patients without schizophrenia, which is an important cause of higher-than-expected mortality rate in this population.

Schizo-obsessive disorder and neurosurgery for schizophrenia.

Schizophrenia likely represents a cluster of diseases presenting with delusions, hallucinations, disorganised behaviour and disorganised thought. Currently, medical therapy struggles to treat a substantial portion of patients, but with improved stratification of component diseases, it may be possible to better understand and treat schizophrenia. The overlap between schizophrenia, schizo-obsessive disorder and obsessive-compulsive disorder is discussed within the context of a clinical case and neuroimaging data. Furthermore, the use of obsessive-compulsive disorder deep brain stimulation protocols for schizo-obsessive disorder is discussed and may yield an advance in neurosurgical treatment of psychiatric conditions.

Laitinen's Subgenual Cingulotomy: Anatomical Location and Case Report.

BACKGROUND: The widespread use of deep brain stimulation (DBS) for movement disorders has renewed the interest in DBS for psychiatric disorders. Lauri Laitinen was a pioneer of stereotactic psychosurgery in the 1950s to 1970s, especially by introducing the subgenual cingulotomy. Our aim here was to verify the anatomical target used by Laitinen, to report on a patient who underwent this procedure, and to review the literature. MATERIALS AND METHODS: The records of Helsinki University Hospital were searched for psychosurgical cases performed between 1970 and 1974. Alive consenting patients were interviewed and underwent a brain MRI. RESULTS: We found 1 patient alive who underwent subgenual cingulotomy in 1971 for obsessive thoughts, anxiety, and compulsions, diagnosed at that time as "schizophrenia psychoneurotica." MRI showed bilateral subgenual cingulotomy lesions (254 and 160 mm3, respectively). The coordinates of the center of the lesions in relation to the midcommissural point for the right and left, respectively, were: 7.1 and 7.9 mm lateral; 0.2 mm inferior and 1.4 mm superior, and 33.0 and 33.9 anterior, confirming correct subgenual targeting. The patient reported retrospective satisfactory results. CONCLUSIONS: The lesion in this patient was found to be in the expected location, which gives some verification of the correct placement of Laitinen's subgenus cingulotomy target.

Surgical Resection of Pineal Epidermoid Cyst Contributed to Relieving Schizophrenia Symptoms.

BACKGROUND: The pineal gland has been demonstrated to be involved in the development of mood and psychotic disorders. However, few studies have looked at the relationship between pineal region tumors and psychiatric disorders. Intracranial epidermoid cysts usually arise in the cerebellopontine angle area and are extremely rare in the pineal region. The case of pineal epidermoid cyst presenting as schizophrenia has never been reported before. CASE PRESENTATION: We described the case of a 23-year-old man who presented to the hospital with symptoms suggestive of schizophrenia. During work-up, he was found to have a pineal lesion on brain magnetic resonance imaging. Total resection of the tumor was subsequently performed, and pathology confirmed an epidermoid cyst. One month after surgery, the patient's psychotic symptoms significantly improved free of drug and fully returned to work 3 months postoperatively. CONCLUSIONS: This case highlights the importance of including mass lesions of the pineal region in the differential diagnosis of psychotic disorders. It also provides further support that the pineal region may play a role in the pathophysiology of psychiatric diseases, although more studies will be needed to elucidate this interesting connection.

Moderate effects of noninvasive brain stimulation of the frontal cortex for improving negative symptoms in schizophrenia: Meta-analysis of controlled trials.

BACKGROUND: Negative symptoms in schizophrenia concern a clinically relevant reduction of goal-directed behavior that strongly and negatively impacts daily functioning. Existing treatments are of marginal effect and novel approaches are needed. Noninvasive neurostimulation by means of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are novel approaches that may hold promise. OBJECTIVES: To provide a quantitative integration of the published evidence regarding effects of rTMS and tDCS over the frontal cortex on negative symptoms, including an analysis of effects of sham stimulation. METHODS: Meta-analysis was applied, using a random effects model, to calculate mean weighted effect sizes (Cohen's d). Heterogeneity was assessed by using Cochrans Q and I2 tests. RESULTS: For rTMS treatment, the mean weighted effect size compared to sham stimulation was 0.64 (0.32-0.96; k = 22, total N = 827). Studies with younger participants showed stronger effects as compared to studies with older participants. For tDCS studies a mean weighted effect size of 0.50 (-0.07 to 1.07; k = 5, total N = 134) was found. For all frontal noninvasive neurostimulation studies together (i.e., TMS and tDCS studies combined) active stimulation was superior to sham, the mean weighted effect size was 0.61 (24 studies, 27 comparisons, 95% confidence interval 0.33-0.89; total N = 961). Sham rTMS (baseline - posttreatment comparison) showed a significant improvement of negative symptoms, d = 0.31 (0.09-0.52; k = 16, total N = 333). Whereas previous meta-analyses were underpowered, our meta-analysis had a power of 0.87 to detect a small effect. CONCLUSIONS: The available evidence indicates that noninvasive prefrontal neurostimulation can improve negative symptoms. This finding suggests a causal role for the lateral frontal cortex in self-initiated goal-directed behavior. The evidence is stronger for rTMS than for tDCS, although this may be due to the small number of studies as yet with tDCS. More research is needed to establish moderator variables that may affect response to neurostimulation and to optimize treatment parameters in order to achieve stable and durable (and thus clinically relevant) effects.

Schizophrenia and anaesthesia.

Administering anaesthesia for elderly patients with chronic schizophrenia has always been a great challenge to anaesthetists. These patients will usually be on multiple antipsychotic drugs for many years and may lead to delayed awakening, cardiovascular instability, arrhythmias and sudden cardiac death during general anaesthesia. This case report is about the perioperative anaesthetic management of an elderly schizophrenic patient undergoing removal of femur implant. This article will explore important drug interactions and available options for a successful anaesthesia.

Dr. Robert G. Heath: a controversial figure in the history of deep brain stimulation.

The history of psychosurgery is filled with tales of researchers pushing the boundaries of science and ethics. These stories often create a dark historical framework for some of the most important medical and surgical advancements. Dr. Robert G. Heath, a board-certified neurologist, psychiatrist, and psychoanalyst, holds a debated position within this framework and is most notably remembered for his research on schizophrenia. Dr. Heath was one of the first physicians to implant electrodes in deep cortical structures as a psychosurgical intervention. He used electrical stimulation in an attempt to cure patients with schizophrenia and as a method of conversion therapy in a homosexual man. This research was highly controversial, even prior to the implementation of current ethics standards for clinical research and often goes unmentioned within the historical narrative of deep brain stimulation (DBS). While distinction between the modern practice of DBS and its controversial origins is necessary, it is important to examine Dr. Heath's work as it allows for reflection on current neurosurgical practices and questioning the ethical implication of these advancements.

Neurosurgery of the future: Deep brain stimulations and manipulations.

Important advances are afoot in the field of neurosurgery-particularly in the realms of deep brain stimulation (DBS), deep brain manipulation (DBM), and the newly introduced refinement "closed-loop" deep brain stimulation (CLDBS). Use of closed-loop technology will make both DBS and DBM more precise as procedures and will broaden their indications. CLDBS utilizes as feedback a variety of sources of electrophysiological and neurochemical afferent information about the function of the brain structures to be treated or studied. The efferent actions will be either electric, i.e. the classic excitatory or inhibitory ones, or micro-injection of such things as neural proteins and transmitters, neural grafts, implants of pluripotent stem cells or mesenchymal stem cells, and some variants of gene therapy. The pathologies to be treated, beside Parkinson's disease and movement disorders, include repair of neural tissues, neurodegenerative pathologies, psychiatric and behavioral dysfunctions, i.e. schizophrenia in its various guises, bipolar disorders, obesity, anorexia, drug addiction, and alcoholism. The possibility of using these new modalities to treat a number of cognitive dysfunctions is also under consideration. Because the DBS-CLDBS technology brings about a cross-fertilization between scientific investigation and surgical practice, it will also contribute to an enhanced understanding of brain function.

Schizophrenia and neurosurgery: A dark past with hope of a brighter future.

Schizophrenia is a chronic and progressive psychiatric disease that remains difficult to manage in the 21st century. Current medical therapies have been able to give reprieve and decrease incidence of psychotic episodes. However, as the disease progresses, patients can become ever more refractory to current pharmaceutical agents and the polypharmacy that is attempted in treatment. Additionally, many of these drugs have significant adverse effects, leaving the practitioner in a difficult predicament for treating these patients. The history of neurosurgery for schizophrenia, among other psychiatric diseases, has a very dark past. Therefore, this review examines peer-reviewed studies on the history of schizophrenia, its medical and surgical therapies, financial costs, and future directions for disease management. We highlight the historically poor relationship between neurosurgery and psychiatric disease and discuss current research in the understandings of schizophrenia. Guided by a strong code of ethics and new technology, including the use of stereotaxis and deep brain stimulation (DBS), the medical communities treating psychiatric disease are beginning to overcome the horrors of the past. DBS is currently being used with moderate success in the treatment of depression, obsessive compulsive disorder, Tourette's syndrome, and anorexia nervosa. With greater understanding of the neural circuitry of schizophrenia and the evolving role for DBS in psychiatric disease, the authors believe that schizophrenia, like other psychiatric diseases, can be treated with DBS.

Disorder-related risk factors for revision total hip arthroplasty after hip hemiarthroplasty in displaced femoral neck fracture patients: a nationwide population-based cohort study.

BACKGROUND: The choice of primary hip hemiarthroplasty or total hip arthroplasty for displaced femoral neck fracture is still controversial. Revision hip arthroplasty not only increases risk and cost but also could result in worse outcome. Determining the risk factors for revision can help inform medical decision-making and aid in risk stratification of publicly reported outcomes. Therefore, we conducted a nationwide population-based study to identify the disease-related risk factors and construct a risk score nomogram to predict revision surgery. METHODS: Records of all 68,030 femoral neck fracture patients receiving partial hemiarthroplasty (HA) in 2000-2010, with no total hip arthroplasty (THA) or revision HA history, were collected from the National Health Insurance Research Database. Cox proportional hazard regression was used to estimate the risk of revision hip replacement (RHA). The score of each risk factor was the quotient of the regression coefficient of the variable by the regression coefficient for a 10-year increase in age. The predictive accuracy was tested using the area under the receiver operating characteristic curve (AUROC). RESULTS: The revision risk for hemiarthroplasty increased in male, those with schizophrenia and end-stage renal disease patients had 1.58-, 1.88-, and 1.74-fold revision HA risk (95 % confidence interval (CI) = 1.40-1.78, 1.26-2.79, and 1.29-2.34, respectively). In a predictive model, the cumulative risk score ranged from 0 to 13 with a 5.08 to 91.82 % 10-year predicted RHA risk. The percentage of AUROC for 10-year RHA risk in nomogram was 61.9 (95 % CI = 60.0-63.4). CONCLUSIONS: Males, schizophrenia and end-stage renal disease patients have higher risk of revision surgery after hemiarthroplasty for femoral neck fracture.

Neurosurgery for schizophrenia: an update on pathophysiology and a novel therapeutic target.

The main objectives of this review were to provide an update on the progress made in understanding specific circuit abnormalities leading to psychotic symptoms in schizophrenia and to propose rational targets for therapeutic deep brain stimulation (DBS). Refractory schizophrenia remains a major unsolved clinical problem, with 10%-30% of patients not responding to standard treatment options. Progress made over the last decade was analyzed through reviewing structural and functional neuroimaging studies in humans, along with studies of animal models of schizophrenia. The authors reviewed theories implicating dysfunction in dopaminergic and glutamatergic signaling in the pathophysiology of the disorder, paying particular attention to neurosurgically relevant nodes in the circuit. In this context, the authors focused on an important pathological circuit involving the associative striatum, anterior hippocampus, and ventral striatum, and discuss the possibility of targeting these nodes for therapeutic neuromodulation with DBS. Finally, the authors examined ethical considerations in the treatment of these vulnerable patients. The functional anatomy of neural circuits relevant to schizophrenia remains of great interest to neurosurgeons and psychiatrists and lends itself to the development of specific targets for neuromodulation. Ongoing progress in the understanding of these structures will be critical to the development of potential neurosurgical treatments of schizophrenia.

Bayard Holmes (1852-1924) and Henry Cotton (1869-1933): Surgeon-psychiatrists and their tragic quest to cure schizophrenia.

Early 20th-century medicine was dominated by the infectious theory of disease. Some leading physicians believed that infection or the accumulation of toxic substances from bacterial stasis caused a wide range of diseases, including schizophrenia. In the case of schizophrenia, one theory held that intestinal stasis lead to the bacterial production of toxins that affected brain function, resulting in psychotic illness. This theory predicted that clearing the stasis by drainage or by removal of the offending organ would be curative. Bayard Holmes and Henry Cotton, surgeon-psychiatrists, achieved notoriety for their efforts to cure schizophrenia surgically. Their endeavours were not only a failure but resulted in tragedy to their families and to a wider population. Treatment of their own sons also represented a violation of the ethics of their time. This account describes the life and career of Holmes and Cotton and reappraises their work in the light of recent developments.