Device-Based Modulation of Neurocircuits as a Therapeutic for Psychiatric Disorders.

Device-based neuromodulation of brain circuits is emerging as a promising new approach in the study and treatment of psychiatric disorders. This work presents recent advances in the development of tools for identifying neurocircuits as therapeutic targets and in tools for modulating neurocircuits. We review clinical evidence for the therapeutic efficacy of circuit modulation with a range of brain stimulation approaches, including subthreshold, subconvulsive, convulsive, and neurosurgical techniques. We further discuss strategies for enhancing the precision and efficacy of neuromodulatory techniques. Finally, we survey cutting-edge research in therapeutic circuit modulation using novel paradigms and next-generation devices.

Temporal effects of barbiturate coma on intracranial pressure and compensatory reserve in children with traumatic brain injury.

BACKGROUND: The aim was to study the effects of barbiturate coma treatment (BCT) on intracranial pressure (ICP) and intracranial compensatory reserve (RAP index) in children (< 17 years of age) with traumatic brain injury (TBI) and refractory intracranial hypertension (RICH). METHODS: High-resolution monitoring data were used to study the effects of BCT on ICP, mean arterial pressure (MAP), cerebral perfusion pressure (CPP), and RAP index. Four half hour long periods were studied: before bolus injection and at 5, 10, and 24 hours thereafter, respectively, and a fifth tapering period with S-thiopental between < 100 and < 30 µmol/L. S-thiopental concentrations and administered doses were registered. RESULTS: Seventeen children treated with BCT 2007-2017 with high-resolution data were included; median age 15 (range 6-17) and median Glasgow coma score 7 (range 3-8). Median time from trauma to start of BCT was 44.5 h (range 2.5-197.5) and from start to stop 99.0 h (range 21.0-329.0). Median ICP was 22 (IQR 20-25) in the half hour period before onset of BCT and 16 (IQR 11-20) in the half hour period 5 h later (p = 0.011). The corresponding figures for CPP were 65 (IQR 62-71) and 63 (57-71) (p > 0.05). The RAP index was in the half hour period before onset of BCT 0.6 (IQR 0.1-0.7), in the half hour period 5 h later 0.3 (IQR 0.1-0.7) (p = 0.331), and in the whole BCT period 0.3 (IQR 0.2-0.4) (p = 0.004). Eighty-two percent (14/17) had favorable outcome (good recovery = 8 patients and moderate disability = 6 patients). CONCLUSION: BCT significantly reduced ICP and RAP index with preserved CPP. BCT should be considered in case of RICH.

Magnetic seizure therapy is efficacious and well tolerated for treatment-resistant bipolar depression: an open-label clinical trial

Background: Treatment-resistant bipolar depression can be treated effectively using electroconvulsive therapy, but its use is limited because of stigma and cognitive adverse effects. Magnetic seizure therapy is a new convulsive therapy with promising early evidence of antidepressant effects and minimal cognitive adverse effects. However, there are no clinical trials of the efficacy and safety of magnetic seizure therapy for treatment-resistant bipolar depression. Methods: Participants with treatment-resistant bipolar depression were treated with magnetic seizure therapy for up to 24 sessions or until remission. Magnetic seizure therapy was applied over the prefrontal cortex at high (100 Hz; n = 8), medium (50 or 60 Hz; n = 9) or low (25 Hz; n = 3) frequency, or over the vertex at high frequency (n = 6). The primary outcome measure was the 24-item Hamilton Rating Scale for Depression. Participants completed a comprehensive battery of neurocognitive tests. Results: Twenty-six participants completed a minimally adequate trial of magnetic seizure therapy (i.e., ≥ 8 sessions), and 20 completed full treatment per protocol. Participants showed a significant reduction in scores on the Hamilton Rating Scale for Depression. Adequate trial completers had a remission rate of 23.1% and a response rate of 38.5%. Per-protocol completers had a remission rate of 30% and a response rate of 50%. Almost all cognitive measures remained stable, except for significantly worsened recall consistency on the autobiographical memory inventory. Limitations: The open-label study design and modest sample size did not allow for comparisons between stimulation parameters. Conclusion: In treatment-resistant bipolar depression, magnetic seizure therapy produced significant improvements in depression symptoms with minimal effects on cognitive performance. These promising results warrant further investigation with larger randomized clinical trials comparing magnetic seizure therapy to electroconvulsive therapy. Clinical trial registration: NCT01596608; clinicaltrials.gov

New directions in the rational design of electrical and magnetic seizure therapies: individualized Low Amplitude Seizure Therapy (iLAST) and Magnetic Seizure Therapy (MST).

Electroconvulsive therapy remains a key treatment option for severe cases of depression, but undesirable side-effects continue to limit its use. Innovations in the design of novel seizure therapies seek to improve its risk benefit ratio through enhanced control of the focality of stimulation. The design of seizure therapies with increased spatial precision is motivated by avoiding stimulation of deep brain structures implicated in memory retention, including the hippocampus. The development of two innovations in seizure therapy-individualized low-amplitude seizure therapy (iLAST) and magnetic seizure therapy (MST), are detailed. iLAST is a method of seizure titration involving reducing current spread in the brain by titrating current amplitude from the traditional fixed amplitudes. MST, which can be used in conjunction with iLAST dosing methods, involves the use of magnetic stimulation to reduce shunting and spreading of current by the scalp occurring during electrical stimulation. Evidence is presented on the rationale for increasing the focality of ECT in hopes of preserving its effectiveness, while reducing cognitive side-effects. Finally, the value of electric field and neural modelling is illustrated to explain observed clinical effects of modifications to ECT technique, and their utility in the rational design of the next generation of seizure therapies.

Neuromodulation Treatments for Geriatric Mood and Cognitive Disorders.

There is increasing evidence for the efficacy of neuromodulation in the treatment of resistant mood disorders and emerging data supporting the use of neuromodulation in cognitive disorders. A significant minority of depressed elders do not respond to pharmacotherapy and/or psychotherapy. This has led clinicians to recommend the increasing use of electroconvulsive therapy (ECT) in the treatment of medication-resistant or life-threatening geriatric depression. Multiple studies have supported the safety and efficacy of ECT in the elderly, yet ECT is associated with side effects including cardiovascular and cognitive side effects. Neuromodulation therapies have the potential for providing effective treatment for treatment-resistant older adults with reduced side effects and this review will outline the risks and benefits of neuromodulation treatment in geriatric psychiatry. There is also emerging evidence of the efficacy of neuromodulation devices in the treatment of cognitive disorders. Pharmacotherapy has been largely ineffective in changing the course of neurodegenerative diseases causing dementia and other treatments are clearly needed. This review will outline the available evidence for neuromodulation in the treatment of mood and cognitive disorders in the elderly.

Magnetic seizure therapy in treatment-resistant depression: clinical, neuropsychological and metabolic effects.

BACKGROUND: Magnetic seizure therapy (MST), despite being in an early phase of clinical research, has been demonstrated to be associated with antidepressant efficacy. However, safety, tolerability and efficacy data in connection with functional brain activity from larger samples are lacking. The aim of this study was to determine clinical and cognitive effects of MST and the influence of MST on regional brain glucose metabolism. METHOD: Twenty-six patients suffering from treatment-resistant depression (TRD) underwent MST. Ten patients underwent a randomized trial and 16 patients an open-label study design. The primary outcome criterion was the severity of depressive symptoms assessed with the Hamilton Depression Rating Scale (HAMD). Depressive symptoms, tolerability and cognitive safety, along with social functioning and quality of life parameters, were assessed using various rating scales. A clinical follow-up visit 6 months following the completion of a course of MST and [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) scans of 12 patients were analysed. RESULTS: A significant response to MST was demonstrated by 69% of the patient sample, with 46% meeting remission criteria. Anxiety ratings were significantly reduced in responders and their quality of life was improved. Half of the responders relapsed within 6 months. No cognitive side-effects were observed. FDG-PET scans showed a metabolic increase in the frontal cortex bilaterally and a decrease in the left striatum. CONCLUSIONS: Robust antidepressant and anti-anxiety efficacy of MST was demonstrated, and found to be associated with localized metabolic changes in brain areas that are strongly implicated in depression. Thus, MST presents an effective, well-tolerated and safe treatment option for patients unable to respond to other forms of therapy for depression.

Extracorporeal shock wave therapy for the treatment of poststroke plantar-flexor muscles spasticity: a prospective open-label study.

OBJECTIVES: To assess the use of extracorporeal shock wave therapy (ESWT) for the treatment of equinus foot after stroke and to correlate the ESWT effect on spastic plantar-flexor muscles with echo intensity on the Heckmatt scale. METHODS: The prospective open-label study examined 23 patients with poststroke lower limb spasticity. Adults with spastic equinus foot after stroke received one ESWT session on hypertonic plantar-flexor muscles. The effect on spasticity, degree of passive ankle dorsiflexion, and neurophysiological values were evaluated. Before treatment, participants underwent a sonography evaluation of calf muscles to identify echo intensity on the Heckmatt scale. RESULTS: Immediately after the session, ESWT induced a statistically significant reduction in muscle tone, increasing passive ankle dorsiflexion motion. At 30 days of follow-up, the effect persisted only in patients with echo intensity of spastic plantar-flexor muscles graded I, II, or III on the Heckmatt scale without any action related to spinal excitability. Mild adverse events were reported after the treatment but were resolved in a few days. CONCLUSIONS: ESWT is safe and efficacious for the treatment of poststroke plantar-flexor muscles spasticity, reducing muscle tone and improving passive ankle dorsiflexion motion. The effect was long lasting in subjects with echo intensity of calf muscles graded I, II, or III but was brief for echo intensity graded IV on the Heckmatt scale. The ESWT effect did not appear to be related to spinal excitability.

The seizure, not electricity, is essential in convulsive therapy: the flurothyl experience.

BACKGROUND: For more than 50 years, research in convulsive therapy has been focused on the impact of electricity and seizures on memory and not on brain chemistry or neurophysiology. Brief pulse and ultra-brief pulse currents replaced sinusoidal currents. Electrode placements were varied, energy dosing was altered, and electricity was replaced by magnetic currents. METHOD: The published experiences and archival records of seizures induced by camphor, pentylenetetrazol, and flurothyl are reviewed and compared with the changes induced by electricity. FINDINGS: The clinical efficacy of chemically induced seizures is equal to that of electrical inductions. Seizure durations are longer, and impairment of cognition and memory is less. Electroconvulsive therapy replaced chemical treatments for ease of use, not for greater efficacy or safety. CONCLUSIONS: The brain seizure, not the method of induction, is the essential element in the efficacy of convulsive therapy. Seizure induction with chemicals avoids the direct effects of electricity on brain functions with lesser effects on cognition. Reexamination of chemical inductions of seizures as replacements for electricity is encouraged.

The emerging use of brain stimulation treatments for psychiatric disorders.

OBJECTIVE: The aim of this study was to review the current state of development and application of a wide range of brain stimulation approaches in the treatment of psychiatric disorders. METHOD: The approaches reviewed include forms of minimally invasive magnetic and electrical stimulation, seizure induction, implanted devices and several highly novel approaches in early development. RESULTS: An extensive range of brain stimulation approaches are now being widely used in the treatment of patients with psychiatric disorders, or actively investigated for this use. Both vagal nerve stimulation (VNS) and repetitive transcranial magnetic stimulation (rTMS) have been introduced into clinical practice in some countries. A small body of research suggests that VNS has some potentially long-lasting antidepressant effects in a minority of patients treated. rTMS has now been extensively investigated for over 15 years, with a large body of research now supporting its antidepressant effects. Further rTMS research needs to focus on defining the most appropriate stimulation methods and exploring its longer term use in maintenance protocols. Very early data suggest that magnetic seizure therapy (MST) has promise in the treatment of patients referred for electroconvulsive therapy: MST appears to have fewer side effects and may have similar efficacy. A number of other approaches including surgical and alternative forms of electrical stimulation appear to alter brain activity in a promising manner, but are in need of evaluation in more substantive patient samples. CONCLUSIONS: It appears likely that the range of psychiatric treatments available for patients will grow over the coming years to progressively include a number of novel brain stimulation techniques.

The beginnings of modern psychiatric treatment in Europe. Lessons from an early account of convulsive therapy.

Convulsive therapy (COT) is a major European contribution to the psychiatric armamentarium and biological psychiatry. COT was introduced in psychiatry by László Meduna, a Hungarian neuropsychiatrist. All subsequent publications about the first patient treated with COT, Zoltán L (ZL), were based on Meduna's papers and autobiography. After 4 years of catatonic stupor, ZL received camphor-induced COT which resulted in full remission and discharge from the institution. The aim of this paper is to reconstruct ZL's case history from the original case notes--partly written by Meduna himself--which were recovered from the archives of the National Institute of Psychiatry and Neurology. The case notes show that ZL repeatedly received COT between 1934 and 1937, first with camphor and then with cardiazol induction. After the first course of COT the catatonic stupor was resolved and the psychotic symptoms subsided. However, the remission lasted for only a few months and was followed by a relapse. Despite repeated courses of COT, ZL never became symptom free again, was never discharged and died in the Institute in 1945. This historical case is discussed from both the diagnostic and therapeutic points of view, and an attempt is made to explain the possible reasons for the discrepancies found between Meduna's account and ZL's case notes.

[The birth of convulsive therapy]. / A görcskezelés születése.

The history of the first convulsive treatment is summarized here in commemoration of its 75th anniversary. The neuropathological and clinical findings underlying the theoretical basis of the method are reviewed, together with the case histories of the first batch of patients who underwent convulsive therapy. The early indications and effectiveness of convulsive therapy are also discussed. Finally, in a broader context, the role of convulsive treatment in the development of modern biological psychiatry and Laszlo Meduna's contribution to this development touched upon.

Estratégias de educação em saúde a pacientes com diabetes mellitus em insulinoterapia: revisão integrativa / Estrategias de educación en salud a pacientes con diabetes mellitus en insulinoterapia: revisión integradora / Health education strategies for patients with diabetes mellitus in insulin therapy: integrative review

RESUMO Objetivo: avaliar a utilização de diferentes estratégias de educação em saúde destinadas ao cuidado das pessoas com diabetes em tratamento de insulinoterapia. Métodos: revisão integrativa da literatura, com busca realizada no período de junho de 2021 e março de 2022, com recorte temporal de dez anos, nas bases eletrônicas Science Direct, Cumulative index to nursing and Allied Health Literature, portal PubMed, Web of Science, Scopus, Scientific Electronic Library Online e Biblioteca Virtual em Saúde, com descritores controlados indexados no Descritores em Ciências da Saúde e no Medical Subject Headings. Resultados: nos oito estudos selecionados a partir dos critérios de inclusão, as estratégias encontradas foram o uso de material impresso, a orientação verbal individual e em grupo, o emprego de recurso audiovisual e a simulação clínica. Conclusão: a análise dos estudos permitiu verificar que diferentes modalidades de educação em saúde são eficazes para auxiliar no gerenciamento do diabetes. Entretanto, os métodos de ensino passivos ainda são maioria, o que torna necessário que novos estudos explorem outras formas de preparo para o cuidado em saúde, como as metodologias ativas de ensino-aprendizagem.

RESUMEN Objetivo: evaluar la utilización de diferentes estrategias de educación en salud dirigidas al cuidado a las personas con diabetes en tratamiento de insulinoterapia. Métodos: revisión integradora de la literatura, con búsqueda realizada en el período de junio de 2021 y marzo de 2022, con recorte temporal de diez años, en las bases electrónicas Science Direct, Cumulative index to Nursing and Allied Health Literature, portal PubMed, Web of Science, Scopus, Scientific Electronic Library Online y Biblioteca Virtual em Salud, con descriptores controlados indexados en el Descritores em Ciências da Saúde y en el Medical Subject Headings. Resultados: en los ocho estudios seleccionados a partir de los criterios de inclusión, las estrategias encontradas fueron el uso de material impreso, la orientación verbal individual y en grupo, el empleo de recurso audiovisual y la simulación clínica. Conclusión: el análisis de los estudios permitió verificar que diferentes modalidades de educación en salud son eficaces para ayudar en el manejo de la diabetes. Sin embargo, los métodos de enseñanza pasivos todavía son mayoría, lo que hace necesario que nuevos estudios exploren otras formas de preparación para el cuidado en salud, como las metodologías activas de enseñanza-aprendizaje.

ABSTRACT Objective: to evaluate the use of different health education strategies aimed at the care of people with diabetes undergoing insulin therapy treatment. Methods: integrative literature review, with a search conducted in June 2021 and March 2022, with a ten-year time frame, in the electronic bases Science Direct, Cumulative index to nursing and Allied Health Literature, PubMed portal, Web of Science, Scopus, Scientific Electronic Library Online and Virtual Health Library, with controlled descriptors indexed in Descriptors in Health Sciences and Medical Subject Headings. esults: in the eight studies selected based on the inclusion criteria, the strategies found were the use of printed material, individual and group verbal guidance, the use of audiovisual resources and clinical simulation. Conclusion: the analysis of the studies allowed us to verify that different modalities of health education are effective to assist in the management of diabetes. However, passive teaching methods are still majority, which makes it necessary for further studies to explore other forms of preparation for health care, such as active teaching-learning methodologies.

Fatores associados a anormalidades na cintilografia de perfusão miocárdica de pacientes diabéticos / Factors associated with abnormalities on myocardial perfusion scintigraphy in diabetic patients

O diabetes melito é o maior fator de risco para doença arterial coronariana. Além da longa duração de diabetes, outros fatores, como presença de doença arterial periférica e tabagismo são fortes preditores para anormalidades na cintilografia de perfusão do miocárdio. O objetivo deste estudo foi avaliar o impacto dos fatores de risco de pacientes diabéticos nos resultados da cintilografia de perfusão do miocárdio e comparar com os resultados de pacientes não diabéticos em uma clínica de medicina nuclear. Foi realizado um estudo transversal retrospectivo por meio da análise de prontuários de pacientes que realizaram cintilografia miocárdica no período de 2010 a 2019. Foram avaliados 34.736 prontuários. Analisando a fase de estresse da cintilografia de perfusão do miocárdio, os portadores de diabetes melito precisaram receber estímulo farmacológico duas vezes mais que os não diabéticos para sua realização. Também foram avaliados fatores que tivessem impacto negativo no resultado da cintilografia de perfusão do miocárdio, e foi visto que o diabetes melito (33,6%), a insulinoterapia (18,1%), a hipertensão arterial sistêmica (69,9%), a dislipidemia (53%), o sedentarismo (83,1%), o uso de estresse farmacológico (50,6%), a dor torácica típica (8,5%) e a angina limitante durante o teste (1,7%) estiveram associados significativamente (p<0,001) a anormalidades neste exame. (AU)

Diabetes mellitus (DM) is the greatest risk factor for coronary artery disease. In addition to a long duration of diabetes, the presence of peripheral arterial disease and smoking are strong predictors of abnormalities on myocardial perfusion scintigraphy (MPS). This study aimed to assess the impact of risk factors in diabetic patients on MPS results and compare them with those of non-diabetic patients in a nuclear medicine clinic. A retrospective cross-sectional study was performed through the analysis of the medical records of patients who underwent MPS in 2010­2019. A total of 34,736 medical records were evaluated. Analyzing the stress phase of MPS, DM patients required two-fold more pharmacological stimulation than non-diabetic patients for MPS. Factors that negatively impact the MPS results were also evaluated, and DM (33.6%), insulin therapy (18.1%), systemic arterial hypertension (69.9%), dyslipidemia (53%), sedentary lifestyle (83.1%), use of pharmacological stress (50.6%), typical chest pain (8.5%), and limiting angina during the test (1.7%) were significantly associated (p < 0.001) with test abnormalities. (AU)

Time related changes in reversible MRI findings after prolonged hypoglycemia.

Diffusion weighted magnetic resonance images (DWI) in hypoglycemic coma show more definite and earlier findings than do T1-weighted images, or even fluid-attenuated inversion recovery (FLAIR). However, there has been limited information on the time related changes of such MRI images. We report here the time related changes of MRI findings after prolonged hypoglycemia in a diabetic 62-year-old man without hypoxia. We found in the patient that hyperintensities in DWI, T2-weighted and FLAIR images disappeared on the 14th day along with normalization of the apparent diffusion coefficient (ADC). Single photon emission computed tomography (SPECT) showed no low perfusion findings throughout the course. Since the day when the hyperintensities disappeared, the patient became to open his eyes in response to verbal command. This paper demonstrates serial alterations in reversible DWI findings after prolonged hypoglycemia and we need to define its mechanisms in the future.

Outcome of Extracorporeal Shock Wave Therapy for Insertional Achilles Tendinopathy with and without Haglund's Deformity.

Purpose. To compare the results of extracorporeal shock wave therapy (ESWT) for insertional Achilles tendinopathy (IAT) with or without Haglund's deformity. Methods. Between September 2014 and May 2015, all patients who underwent ESWT were retrospectively enrolled in this study. A total of 67 patients were available for follow-up and assigned into nondeformtiy group (n = 37) and deformtiy group (n = 30). Clinical outcomes were evaluated by VISA-A Score and 6-point Likert scale. Results. The VISA-A score increased in both groups, from 49.57 ± 9.98 at baseline to 83.86 ± 8.59 at 14.5 ± 7.2 months after treatment in nondeformity group (P < 0.001) and from 48.70 ± 9.38 at baseline to 67.78 ± 11.35 at 15.3 ± 6.7 months after treatment in deformity group (P < 0.001). However, there was a greater improvement in VISA-A Score for the nondeformity group compared with deformity group (P = 0.005). For the 6-point Likert scale, there were decreases from 3.92 ± 0.80 at baseline to 1.57 ± 0.73 at the follow-up time point in nondeformity group (P < 0.001) and from 4.0 ± 0.76 at baseline to 2.37 ± 1.03 at the follow-up time point in deformity group (P < 0.001). There was no significant difference in improvement of the 6-point Likert scale between both groups (P = 0.062). Conclusions. ESWT resulted in greater clinical outcomes in patients without Haglund's deformity compared with patients with Haglund's deformity.

Sudden death in epilepsy: can any lessons be learned from convulsive therapy?

Convulsive therapy (chemically or electrically induced) has been used since the mid-1930s. Initially it had a high mortality rate, but this has been falling slowly in response to refinements in technique (introduction of muscle paralysis during the seizure, brief intravenous general anesthesia and, more recently, the acceptance that adequate ventilation and oxygenation are necessary during the procedure). Mortality during convulsive therapy has been ascribed to both cardiac and respiratory causes (particularly acute arrhythmias and pulmonary edema). There is some evidence that supporting respiration during and after the convulsion has reduced mortality significantly, such that electrical convulsive therapy is now a very low-risk procedure, even in the very elderly. This gives tenuous support for the view that death in epileptic seizures may be of respiratory origin.

[Forced method of insulin-coma therapy (methodology, effects)]. / Forsirovannyi sposob insulinokomatoznoi terapii (metodika, osobennosti deistviia).

A study of a new regimen of insulin comatose therapy by intravenous instillation has shown the feasibility of determining the minimal comatose dose of insulin and achieving the comatose state in the first days of insulin therapy. This method makes it possible to utilize the advantages of insulin comatose treatment (a more marked arresting antipsychotic action and the remission persistence). At the same time insulin comatose therapy by intravenous instillation permits the physicians to overcome one of the major drawbacks of this treatment, namely the time lag of the therapeutic response associated with the period of time needed to select the minimal comatose dose which was characteristic of the old method.