Electrically evoked and spontaneous neural activity in the subthalamic nucleus under general anesthesia

OBJECTIVE Deep brain stimulation (DBS) surgery is commonly performed with the patient awake to facilitate assessments of electrode positioning. However, awake neurosurgery can be a barrier to patients receiving DBS. Electrode implantation can be performed with the patient under general anesthesia (GA) using intraoperative imaging, although such techniques are not widely available. Electrophysiological features can also aid in the identification of target neural regions and provide functional evidence of electrode placement. Here we assess the presence and positional variation under GA of spontaneous beta and high-frequency oscillation (HFO) activity, and evoked resonant neural activity (ERNA), a novel evoked response localized to the subthalamic nucleus. METHODS ERNA, beta, and HFO were intraoperatively recorded from DBS leads comprising four individual electrodes immediately after bilateral awake implantation into the subthalamic nucleus of 21 patients with Parkinson’s disease (42 hemispheres) and after subsequent GA induction deep enough to perform pulse generator implantation. The main anesthetic agent was either propofol (10 patients) or sevoflurane (11 patients). RESULTS GA reduced the amplitude of ERNA, beta, and HFO activity (p < 0.001); however, ERNA amplitudes remained large in comparison to spontaneous local field potentials. Notably, a moderately strong correlation between awake ERNA amplitude and electrode distance to an “ideal” therapeutic target within dorsal STN was preserved under GA (awake: ρ = −0.73, adjusted p value [padj] < 0.001; GA: ρ = −0.69, padj < 0.001). In contrast, correlations were diminished under GA for beta (awake: ρ = −0.45, padj < 0.001; GA: ρ = −0.13, padj = 0.12) and HFO (awake: ρ = −0.69, padj < 0.001; GA: ρ = −0.33, padj < 0.001). The largest ERNA occurred at the same electrode (awake vs GA) for 35/42 hemispheres (83.3%) and corresponded closely to the electrode selected by the clinician for chronic therapy at 12 months (awake ERNA 77.5%, GA ERNA 82.5%). The largest beta amplitude occurred at the same electrode (awake vs GA) for only 17/42 (40.5%) hemispheres and 21/42 (50%) for HFO. The electrode measuring the largest awake beta and HFO amplitudes corresponded to the electrode selected by the clinician for chronic therapy at 12 months in 60% and 70% of hemispheres, respectively. However, this correspondence diminished substantially under GA (beta 20%, HFO 35%). CONCLUSIONS ERNA is a robust electrophysiological signal localized to the dorsal subthalamic nucleus subregion that is largely preserved under GA, indicating it could feasibly guide electrode implantation, either alone or in complementary use with existing methods.

Update on Intravenous Immunoglobulin in Neurology: Modulating Neuro-autoimmunity, Evolving Factors on Efficacy and Dosing and Challenges on Stopping Chronic IVIg Therapy

In the last 25 years, intravenous immunoglobulin (IVIg) has had a major impact in the successful treatment of previously untreatable or poorly controlled autoimmune neurological disorders. Derived from thousands of healthy donors, IVIg contains IgG1 isotypes of idiotypic antibodies that have the potential to bind pathogenic autoantibodies or cross-react with various antigenic peptides, including proteins conserved among the “common cold”-pre-pandemic coronaviruses; as a result, after IVIg infusions, some of the patients’ sera may transiently become positive for various neuronal antibodies, even for anti-SARS-CoV-2, necessitating caution in separating antibodies derived from the infused IVIg or acquired humoral immunity. IVIg exerts multiple effects on the immunoregulatory network by variably affecting autoantibodies, complement activation, FcRn saturation, FcγRIIb receptors, cytokines, and inflammatory mediators. Based on randomized controlled trials, IVIg is approved for the treatment of GBS, CIDP, MMN and dermatomyositis; has been effective in, myasthenia gravis exacerbations, and stiff-person syndrome; and exhibits convincing efficacy in autoimmune epilepsy, neuromyelitis, and autoimmune encephalitis. Recent evidence suggests that polymorphisms in the genes encoding FcRn and FcγRIIB may influence the catabolism of infused IgG or its anti-inflammatory effects, impacting on individualized dosing or efficacy. For chronic maintenance therapy, IVIg and subcutaneous IgG are effective in controlled studies only in CIDP and MMN preventing relapses and axonal loss up to 48 weeks; in practice, however, IVIg is continuously used for years in all the aforementioned neurological conditions, like is a “forever necessary therapy” for maintaining stability, generating challenges on when and how to stop it. Because about 35-40% of patients on chronic therapy do not exhibit objective neurological signs of worsening after stopping IVIg but express subjective symptoms of fatigue, pains, spasms, or a feeling of generalized weakness, a conditioning effect combined with fear that discontinuing chronic therapy may destabilize a multi-year stability status is likely. The dilemmas of continuing chronic therapy, the importance of adjusting dosing and scheduling or periodically stopping IVIg to objectively assess necessity, and concerns in accurately interpreting IVIg-dependency are discussed. Finally, the merit of subcutaneous IgG, the ineffectiveness of IVIg in IgG4-neurological autoimmunities, and genetic factors affecting IVIg dosing and efficacy are addressed.

Organic electrolytic photocapacitors for stimulation of the mouse somatosensory cortex

Objective. For decades electrical stimulation has been used in neuroscience to investigate brain networks and been deployed clinically as a mode of therapy. Classically, all methods of electrical stimulation require implanted electrodes to be connected in some manner to an apparatus which provides power for the stimulation itself. Approach. We show the use of novel organic electronic devices, specifically organic electrolytic photocapacitors (OEPCs), which can be activated when illuminated with deep-red wavelengths of light and correspondingly do not require connections with external wires or power supplies when implanted at various depths in vivo. Main results. We stimulated cortical brain tissue of mice with devices implanted subcutaneously, as well as beneath both the skin and skull to demonstrate a wireless stimulation of the whisker motor cortex. Devices induced both a behavior response (whisker movement) and a sensory response in the corresponding sensory cortex. Additionally, we showed that coating OEPCs with a thin layer of a conducting polymer formulation (PEDOT:PSS) significantly increases their charge storage capacity, and can be used to further optimize the applied photoelectrical stimulation. Significance. Overall, this new technology can provide an on-demand electrical stimulation by simply using an OEPC and a deep-red wavelength illumination. Wires and interconnects to provide power to implanted neurostimulation electrodes are often problematic in freely-moving animal research and with implanted electrodes for long-term therapy in patients. Our wireless brain stimulation opens new perspectives for wireless electrical stimulation for applications in fundamental neurostimulation and in chronic therapy.

Organic electrolytic photocapacitors for stimulation of the mouse somatosensory cortex

Objective: For decades electrical stimulation has been used in neuroscience to investigate brain networks and been deployed clinically as a mode of therapy. Classically, all methods of electrical stimulation require implanted electrodes to be connected in some manner to an apparatus which provides power for the stimulation itself. Approach: We show the use of novel organic electronic devices, specifically organic electrolytic photocapacitors (OEPCs), which can be activated when illuminated with deep-red wavelengths of light and correspondingly do not require connections with external wires or power supplies when implanted at various depths in vivo. Main results: We stimulated cortical brain tissue of mice with devices implanted subcutaneously, as well as beneath both the skin and skull to demonstrate a wireless stimulation of the whisker motor cortex. Devices induced both a behavior response (whisker movement) and a sensory response in the corresponding sensory cortex. Additionally, we showed that coating OEPCs with a thin layer of a conducting polymer formulation (PEDOT:PSS) significantly increases their charge storage capacity, and can be used to further optimize the applied photoelectrical stimulation. Significance: Overall, this new technology can provide an on-demand electrical stimulation by simply using an OEPC and a deep-red wavelength illumination. Wires and interconnects to provide power to implanted neurostimulation electrodes are often problematic in freely-moving animal research and with implanted electrodes for long-term therapy in patients. Our wireless brain stimulation opens new perspectives for wireless electrical stimulation for applications in fundamental neurostimulation and in chronic therapy.

DRUG REVIEW OF KUSHAMOOLA CHURNA WITH TANDULODOK IN ASRUGDARA MANAGEMENT

In Ayurveda, menstruation has been described in 3 phases as rajahkala (menstrual period) rutukala (fertile period) and rutuvyatitkal (premenstrual period) & Do’s and Don’ts regarding this has also been explained in detail. Due to so much physical and emotional stress women are suffering from so many menstrual problems, Asrugdara (menorrhagia) is one of them and in Samhitas its causes, Etiopathogenesis, treatment and complications are ex- plained in detail. Menorrhagia is being treated with hormonal combination have so many side effects in acute as well as chronic therapy. Kushamool churna with tandulodak (Rice water) as explained by Bhaishajya Ratnawali treats Asrugdara in 3 days. Due to its pharmacological properties, it breaks down the pathology of Asrugdara in the acute stage. So, we can formulate this combination for the acute condition of menorrhagia. Keywords: Rajahkala, Rutukala, Rutuvyatitkal, Asrugdara, Menorrhagia, Etiopathogenesis.

Improvement in Medication Adherence Using TV Programmes as Reminders

According to WHO only 50% patients adhere to chronic therapy. The problem of non-adherence has persisted over decades. Over 197 million Indian households have TV sets and on an average Indian’s spend 3 hours, 44 minutes watching television. TV programme is used as intervention by patients to improve medication adherence rates. The objective of the research is to find the effect of TV programme as a form of reminder in improving medication adherence. With the help of a structured questionnaire the information about medication adherence behaviour was obtained from patients suffering from different types of diseases in the state of Sikkim, India. It has been found that when patients use TV programme as a form of reminder the odds of missing the medication consciously reduces by 45.9%. At a personal level the probability that a person will not miss the time of medication is 42.3% higher compared to when it is not used and if the total population is considered, 15.6% less people would not be missing the medication at all when the reminder is used.

Improvement in Medication Adherence using TV Programme as Reminder

According to WHO only 50% patients adhere to chronic therapy. The problem of non-adherence has persisted over decades. Over 197 million Indian households have TV sets and on an average Indian’s spend 3 hours, 44 minutes watching television. TV programme is used as intervention by patients to improve medication adherence rates. The objective of the research is to find the effect of TV programme as a form of reminder in improving medication adherence. With the help of a structured questionnaire the information about medication adherence behaviour was obtained from patients suffering from different types of diseases in the state of Sikkim, India. It has been found that when patients use TV programme as a form of reminder the odds of missing the medication consciously reduces by 45.9%. At a personal level the probability that a person will not miss the time of medication is 42.3% higher compared to when it is not used and if the total population is considered, 15.6% less people would not be missing the medication at all when the reminder is used.

Improvement in Medication Adherence Using TV Programmes as Reminders

According to WHO, only 50% of patients adhere to chronic therapy. The problem of non-adherence has persisted over decades. Over 197 million Indian households have TV sets, and on average Indians spend 3 hours, 44 minutes watching television. A TV programme is used as intervention by patients to improve medication adherence rates. The objective of the research is to find the effect of TV programmes as a form of reminder in improving medication adherence. With the help of a structured questionnaire, the information about medication adherence behaviour was obtained from patients suffering from different types of diseases in the state of Sikkim, India. It has been found that when patients use TV programmes as a form of reminder, the odds of missing the medication consciously reduces by 45.9%. At a personal level, the probability that a person will not miss the time of medication is 42.3% higher compared to when it is not used, and if the total population is considered, 15.6% fewer people would not be missing the medication at all when the reminder is used.

Clinical characteristics and outcomes of 1,331 patients with COVID-19: HM Spanish Cohort

Background. Spain is one of the European countries most affected by the COVID-19 pandemic. Epidemiologic studies are warranted to improve the disease understanding, evaluate the care procedure and prepare for futures waves. The aim of the study was to describe epidemiologic characteristics associated with hospitalized patients with COVID-19. Methods. This real-world, observational, multicenter and retrospective study screened all consecutive patients admitted to 8 Spanish private hospitals. Inclusion criteria: hospitalized adults (age≥18 years old) with clinically and radiologically findings compatible with COVID-19 disease from March 1st to April 5th, 2020. Exclusion criteria: patients presenting negative PCR for SARS-CoV-2 during the first 7 days from hospital admission, transfer to a hospital not belonging to the HM consortium, lack of data and discharge against medical advice in emergency departments. Results. One thousand and three hundred thirty-one COVID-19 patients (medium age 66.9 years old; males n= 841, medium length of hospital stayed 8 days, non-survivors n=233) were analyzed. One hundred and fifteen were admitted to intensive care unit (medium length of stay 16 days, invasive mechanical ventilation n= 95, septic shock n= 37 and renal replacement therapy n= 17). Age, male gender, leukocytes, platelets, oxygen saturation, chronic therapy with steroids and treatment with hydroxychloroquine/azithromycin were independent factors associated with mortality. The proportion of patients that survive and received tocilizumab and steroids were lesser and higher respectively than those that die, but their association was not significant. Conclusions. Overall crude mortality rate was 17.5%, rising up to 36.5% in the subgroup of patients that were admitted to the intensive care unit. Seven factors impact in hospital mortality. No immunomodulatory intervention were associated with in-hospital mortality.