Neuromodulation for the treatment of Prader-Willi syndrome - A systematic review.

Prader-Willi syndrome (PWS) is a complex, genetic disorder characterized by multisystem involvement, including hyperphagia, maladaptive behaviors and endocrinological derangements. Recent developments in advanced neuroimaging have led to a growing understanding of PWS as a neural circuit disorder, as well as subsequent interests in the application of neuromodulatory therapies. Various non-invasive and invasive device-based neuromodulation methods, including vagus nerve stimulation (VNS), transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and deep brain stimulation (DBS) have all been reported to be potentially promising treatments for addressing the major symptoms of PWS. In this systematic literature review, we summarize the recent literature that investigated these therapies, discuss the underlying circuits which may underpin symptom manifestations, and cover future directions of the field. Through our comprehensive search, there were a total of 47 patients who had undergone device-based neuromodulation therapy for PWS. Two articles described VNS, 4 tDCS, 1 rTMS and 2 DBS, targeting different symptoms of PWS, including aberrant behavior, hyperphagia and weight. Multi-center and multi-country efforts will be required to advance the field given the low prevalence of PWS. Finally, given the potentially vulnerable population, neuroethical considerations and dialogue should guide the field.

Responsive deep brain stimulation for the treatment of Tourette syndrome.

To report the results of 'responsive' deep brain stimulation (DBS) for Tourette syndrome (TS) in a National Institutes of Health funded experimental cohort. The use of 'brain derived physiology' as a method to trigger DBS devices to deliver trains of electrical stimulation is a proposed approach to address the paroxysmal motor and vocal tic symptoms which appear as part of TS. Ten subjects underwent bilateral staged DBS surgery and each was implanted with bilateral centromedian thalamic (CM) region DBS leads and bilateral M1 region cortical strips. A series of identical experiments and data collections were conducted on three groups of consecutively recruited subjects. Group 1 (n = 2) underwent acute responsive DBS using deep and superficial leads. Group 2 (n = 4) underwent chronic responsive DBS using deep and superficial leads. Group 3 (n = 4) underwent responsive DBS using only the deep leads. The primary outcome measure for each of the 8 subjects with chronic responsive DBS was calculated as the pre-operative baseline Yale Global Tic Severity Scale (YGTSS) motor subscore compared to the 6 month embedded responsive DBS setting. A responder for the study was defined as any subject manifesting a ≥ 30 points improvement on the YGTSS motor subscale. The videotaped Modified Rush Tic Rating Scale (MRVTRS) was a secondary outcome. Outcomes were collected at 6 months across three different device states: no stimulation, conventional open-loop stimulation, and embedded responsive stimulation. The experience programming each of the groups and the methods applied for programming were captured. There were 10 medication refractory TS subjects enrolled in the study (5 male and 5 female) and 4/8 (50%) in the chronic responsive eligible cohort met the primary outcome manifesting a reduction of the YGTSS motor scale of ≥ 30% when on responsive DBS settings. Proof of concept for the use of responsive stimulation was observed in all three groups (acute responsive, cortically triggered and deep DBS leads only). The responsive approach was safe and well tolerated. TS power spectral changes associated with tics occurred consistently in the low frequency 2-10 Hz delta-theta-low alpha oscillation range. The study highlighted the variety of programming strategies which were employed to achieve responsive DBS and those used to overcome stimulation induced artifacts. Proof of concept was also established for a single DBS lead triggering bi-hemispheric delivery of therapeutic stimulation. Responsive DBS was applied to treat TS related motor and vocal tics through the application of three different experimental paradigms. The approach was safe and effective in a subset of individuals. The use of different devices in this study was not aimed at making between device comparisons, but rather, the study was adapted to the current state of the art in technology. Overall, four of the chronic responsive eligible subjects met the primary outcome variable for clinical effectiveness. Cortical physiology was used to trigger responsive DBS when therapy was limited by stimulation induced artifacts.

The blink reflex and its modulation - Part 2: Pathophysiology and clinical utility.

The blink reflex (BR) is integrated at the brainstem; however, it is modulated by inputs from various structures such as the striatum, globus pallidus, substantia nigra, and nucleus raphe magnus but also from afferent input from the peripheral nervous system. Therefore, it provides information about the pathophysiology of numerous peripheral and central nervous system disorders. The BR is a valuable tool for studying the integrity of the trigemino-facial system, the relevant brainstem nuclei, and circuits. At the same time, some neurophysiological techniques applying the BR may indicate abnormalities involving structures rostral to the brainstem that modulate or control the BR circuits. This is a state-of-the-art review of the clinical application of BR modulation; physiology is reviewed in part 1. In this review, we aim to present the role of the BR and techniques related to its modulation in understanding pathophysiological mechanisms of motor control and pain disorders, in which these techniques are diagnostically helpful. Furthermore, some BR techniques may have a predictive value or serve as a basis for follow-up evaluation. BR testing may benefit in the diagnosis of hemifacial spasm, dystonia, functional movement disorders, migraine, orofacial pain, and psychiatric disorders. Although the abnormalities in the integrity of the BR pathway itself may provide information about trigeminal or facial nerve disorders, alterations in BR excitability are found in several disease conditions. BR excitability studies are suitable for understanding the common pathophysiological mechanisms behind various clinical entities, elucidating alterations in top-down inhibitory systems, and allowing for follow-up and quantitation of many neurological syndromes.

Blink reflex excitability in patients with Hemifacial spasm exhibiting different abnormal discharge patterns: from early isolated discharges to later grouped bursts or tonic spasms.

OBJECTIVE: We studied blink reflex (BR) and BR excitability recovery (BRER) in patients with hemifacial spasm (HFS) exhibiting different abnormal discharge patterns. We hypothesized that patients with groups of clonic or tonic burst activities appear later in the disease course and may have more excitability of the BR circuit at the brainstem compared to patients with isolated twitchings, which occur earlier. METHODS: We included 124 patients with botulinum toxin-naive HFS (mean age 50.6 ± 13.3 years) and 40 healthy subjects. We performed surface polymyography on facial muscles in patients and classified them according to the abnormal discharge pattern: isolated discharges, grouped bursts forming random sequences, tonic spasms, and a combination of these activities. Then, we recorded BR and BRER at 200, 600, and 1000 ms interstimulus intervals. We compared disease duration, R1 and R2 latencies, R2 area-under-the-curve (AUC), and BRER% (i) between healthy subjects and patients and (ii) among groups of patients with different abnormal discharge patterns. RESULTS: There were isolated discharges in 28 patients, grouped bursts forming random sequences in 42, and continuous muscle activity with tonic spasms in one. The remaining patients had combinations. Mean R1 and R2 latencies were significantly longer, and mean R2 AUC was significantly higher on the symptomatic side of patients compared to healthy subjects. The mean BRER was enhanced on both sides in patients than in healthy subjects (p < 0.001). However, it was similar among patient groups with different abnormal discharge patterns (p > 0.05). The mean disease duration in patients with isolated discharges was shorter (3.3 ± 2.0 years) than those with grouped bursts or tonic spasms (p = 0.002; Kruskal-Wallis test). CONCLUSION: Our study observed that excitability at the brainstem was similar in HFS patients with different abnormal discharge patterns, suggesting that the difference in discharge patterns in HFS may be due to a reason other than the difference in BR excitability.

Electrodiagnostic methods to verify Guillain-Barré syndrome subtypes in Istanbul: A prospective multicenter study.

BACKGROUND AND AIMS: This study aimed to identify the clinical characteristics and electrodiagnostic subtypes of Guillain-Barré syndrome (GBS) in Istanbul. METHODS: Patients with GBS were prospectively recruited between April 2019 and March 2022 and two electrodiagnostic examinations were performed on each patient. The criteria of Ho et al., Hadden et al., Rajabally et al., and Uncini et al. were compared for the differentiation of demyelinating and axonal subtypes, and their relations with anti-ganglioside antibodies were analyzed. RESULTS: One hundred seventy-seven patients were included, 69 before the coronavirus disease 2019 pandemic (April 2019-February 2020) and 108 during the pandemic (March 2020-March 2022), without substantial changes in monthly frequencies. As compared with the criteria of Uncini et al., demyelinating GBS subtype diagnosis was more frequent according to the Ho et al. and Hadden et al. criteria (95/162, 58.6% vs. 110/174, 63.2% and 121/174, 69.5%, respectively), and less frequent according to Rajabally et al.'s criteria (76/174, 43.7%). Fourteen patients' diagnoses made using Rajabally et al.'s criteria were shifted to the other subtype with the second electrodiagnostic examination. Of the 106 analyzed patients, 22 had immunoglobulin G anti-ganglioside antibodies (14 with the axonal subtype). They had less frequent sensory symptoms (54.5% vs. 83.1%, p = 0.009), a more frequent history of previous gastroenteritis (54.5% vs. 22.9%, p = 0.007), and a more severe disease as compared with those without antibodies. INTERPRETATION: Serial electrodiagnostic examinations are more helpful for accurate subtype diagnosis of GBS because of the dynamic pathophysiology of the disease. We observed no significant increase in GBS frequency during the pandemic in this metropolis.

Rasmussen's syndrome treated with anakinra.

BACKGROUND AND OBJECTIVE: Rasmussen's encephalitis (RE) is a rare chronic neurological disorder, characterized by unilateral inflammation of the cerebral cortex, refractory focal epilepsy or epilepsia partialis continua, hemiparesis, and progressive cognitive decline. Interleukin-1 (IL-1) plays an important role in neuroinflammation as a key element in the activation of the inflammatory IL-1ß-IL-1 receptor type 1 (IL-1R1) axis. Anakinra, an IL-1 inhibitor, is successfully used in patients with new onset refractory status epilepticus and febrile infection-related epilepsy syndrome. METHODS AND RESULTS: We present 38-year-old male with RE having right-sided hemiparesis and continuous spasms being unresponsive to immune modulatory therapies like pulse steroid, intravenous immunoglobulin and anti-seizure drugs. After treatment with anakinra for three weeks, the continuous spasms almost completely subsided, and his muscle strength returned to normal. DISCUSSION: Anakinra may be considered as a treatment option in patients with RE and refractory seizures.

Impulse control disorders in Parkinson's disease: a retrospective analysis of 1824 patients in a 12-year period.

OBJECTIVE: This study aims to clinically evaluate the impulse control disorders (ICDs) encountered in treating Parkinson's disease. METHOD: This is a retrospective analysis between 2010 and 2022. We retrieved the medical records of all patients diagnosed with idiopathic Parkinson's disease. The demographic and clinical findings were recorded. ICDs constituted a specific item in the examination, and each one (compulsive shopping, compulsive eating, pathological gambling, hypersexuality, punding, dopamine dysregulation syndrome, and hobbyism) was noted separately. RESULTS: In the study period, we identified 1824 patients (56.2% men, n = 1025). The mean age was 70.5 ± 11.9 years. In the cohort, 128 (7%) patients with Parkinson's disease had one or more ICDs. The ICDs were compulsive shopping, punding/hobbyism, compulsive eating, hypersexuality, pathological gambling, and dopamine dysregulation syndrome. When we compared patients with and without ICDs, patients with ICDs were younger (p ≤ 0.001), and the men/women ratio was higher in this group with ICDs. Although the mean daily pramipexole dose was higher in patients with ICDs, mean daily long-acting pramipexole dose was only 1.4 ± 0.92 mg/day. CONCLUSION: The significant findings in this study were (i) the lower frequency of ICDs (7%); (ii) the common occurrence of compulsive shopping, punding/hobbyism, and compulsive eating; and (iii) the development of ICDs under relatively lower doses of pramipexole. We suggest that ICDs in Parkinson's disease should be associated with a personal trait with dopamine agonists, and potential electrophysiological or genetic markers of this trait warrant further analysis to avoid treatment in these patients.

Increased prevalence of mild myopathic changes in the post-COVID-19 duration.

OBJECTIVE: There are reports of peripheral nerve and muscle involvement during or after coronavirus disease 2019 (COVID-19), even following a mild infection. Here, we aimed to analyze the objective findings regarding peripheral nerve, neuromuscular junction, and muscle function using electrophysiology in patients with a previous COVID-19 infection. METHODS: All consecutive patients with a history of COVID-19 were questioned for post-COVID-19 duration-related neurological complaints via Composite Autonomic Symptom Score-31 (COMPASS-31), modified Toronto Neuropathy score (mTORONTO), and Fatigue Severity Scale (FSS). Patients were dichotomized into two groups based on their scores in the questionnaire. Group 1 (patients with high scores in any area of the questionnaire) and Group 2 (patients with normal scores in all sections of the questionnaire). In the second step, Group 1 was invited to a preplanned hospital visit for electrophysiological analysis, including nerve conduction studies, repetitive nerve stimulation, needle electromyography (EMG), quantitative motor unit potential analysis (qMUP), and single fiber EMG. We included 106 patients in the study. According to the questionnaire, 38 patients constituted Group 1, and 68 formed Group 2. RESULTS: Of the 38 patients, 14 accepted and underwent preplanned electrophysiological examinations. Needle EMG revealed small, short, polyphasic MUPs with early recruitment, and qMUP analysis demonstrated an increased percentage of polyphasic potentials in three patients. The examinations in other patients were unremarkable. CONCLUSIONS: The high prevalence of complaints and objective myopathic findings in our cohort implicated the role of muscle involvement in the post-COVID-19 duration. Considering the socioeconomic and psychological burden of the post-COVID-19 duration among individuals and societies, a better understanding of the symptoms and myopathy is warranted.

Perspectives of Implementation of Closed-Loop Deep Brain Stimulation: From Neurological to Psychiatric Disorders.

BACKGROUND: Deep brain stimulation (DBS) is a highly efficient, evidence-based therapy to alleviate symptoms and improve quality of life in movement disorders such as Parkinson's disease, essential tremor, and dystonia, which is also being applied in several psychiatric disorders, such as obsessive-compulsive disorder and depression, when they are otherwise resistant to therapy. SUMMARY: At present, DBS is clinically applied in the so-called open-loop approach, with fixed stimulation parameters, irrespective of the patients' clinical state(s). This approach ignores the brain states or feedback from the central nervous system or peripheral recordings, thus potentially limiting its efficacy and inducing side effects by stimulation of the targeted networks below or above the therapeutic level. KEY MESSAGES: The currently emerging closed-loop (CL) approaches are designed to adapt stimulation parameters to the electrophysiological surrogates of disease symptoms and states. CL-DBS paves the way for adaptive personalized DBS protocols. This review elaborates on the perspectives of the CL technology and discusses its opportunities as well as its potential pitfalls for both clinical and research use in neuropsychiatric disorders.

A comparative transcranial magnetic stimulation study: Assessing cortical excitability and plasticity in Alzheimer's disease, dementia with Lewy bodies and Frontotemporal dementia.

BACKGROUND: Here, we aimed to investigate the roles of long-term potentiation-like (LTP-like) plasticity using intermittent theta burst (iTBS) protocol and resting motor threshold (rMT) in the differential diagnosis of Alzheimer's disease (AD), diffuse dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). METHOD: We enrolled 21 subjects with AD, 28 subjects with DLB, 14 subjects with FTD, and 33 elderly subjects with normal cognitive functions into the study. We recorded rMT and percentage amplitude change of motor evoked potentials (MEPs) after the iTBS protocol in each group. RESULTS: In patients with AD and DLB, the percentage amplitude change of MEPs, and rMTs were significantly lower than in healthy subjects. However, no significant difference was observed in individuals with FTD. CONCLUSION: Our findings showed that transcranial magnetic stimulation measures, particularly rMTs and LTP-like plasticity, may be potential biomarkers to distinguish between different dementia subtypes. Impaired motor cortical excitability and synaptic plasticity were more prominent in AD and DLB than in FTD. This aligns with the evidence that cortical motor networks are usually spared in FTDs in early-to-middle stages.

Segmental Reflex, Long Latency Reflex, and Mixed Nerve Silent Period in Dystonia.

We hypothesized that "long latency reflexes" (LLRs), associated segmental reflex (SR), and mixed nerve silent periods (MnSPs) recorded on the distal upper extremity muscles would behave differently in patients with cervical dystonia and focal hand dystonia. We enrolled patients with cervical dystonia, generalized dystonia, focal hand dystonia, and healthy individuals. We recorded SR, LLRs, and MnSPs. The mean amplitude of SR on the affected side of focal hand dystonia was significantly lower (p = 0.010). The parameters related to LLRs and MnSPs were not different between groups. We suggest, using SR, LLRs, and MnSPs, we could not show an electrophysiological signature specific to dystonia.

A cross-sectional study on restless legs syndrome (RLS) in polycythemia vera (PV): is iron deficiency the only culprit?

INTRODUCTION: In polycythemia vera (PV) patients undergoing phlebotomy, iron deficiency (ID) may develop. ID has been linked to restless legs syndrome (RLS), and in one study, 29.6% of PV patients had RLS. We aimed to evaluate the frequency of RLS in PV and to evaluate factors that might play a role in RLS development among PV and essential thrombocythemia (ET) patients. METHODS: We consecutively included PV cases as the patient group, and ET and ID patients and healthy subjects (HSs) were included as controls. Those with conditions that could lead to RLS were excluded. All subjects were questioned according to the diagnostic criteria of the International Restless Legs Syndrome Study Group. RESULTS: Twenty-seven PV, 23 ET, and 22 ID patients and 23 HSs were included. RLS was detected in 25.9%, 34.8%, and 45.5% of PV, ET, and ID patients, respectively. None of the HSs had RLS. In univariate analysis, interferon-α and anagrelide use, magnesium levels, and the Leeds assessment of neuropathic symptoms and signs (LANSS) scores had a significant impact on RLS in PV and ET patients (p = 0.014, p = 0.032, p = 0.036, and p = 0.003, respectively). CONCLUSION: RLS was more common among PV and ET patients than HSs, which was irrespective to the iron status. RLS was more frequent in ET patients than that observed in PV cases, indicating that ID may not be the only causative factor for RLS development in PV. Further prospective studies are needed to determine the prevalence and risk factors of RLS developing in PV and ET.

Weight and survival after deep brain stimulation for Parkinson's disease.

BACKGROUND: Weight loss in Parkinson's disease (PD) is common and associated with increased mortality. The clinical significance of weight changes following deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) is unclear. OBJECTIVES: To address (1) whether PD patients exhibit progressive weight loss, (2) whether staged DBS surgery is associated with weight changes, and (3) whether survival after DBS correlates with post-DBS weight. METHODS: This is a single-center, longitudinal, retrospective cohort study of 1625 PD patients. We examined trends in weight over time and the relationship between weight and years survival after DBS using regression and mixed model analyses. RESULTS: There was a decline in body weight predating motor symptom onset (n = 756, 0.70 ± 0.03% decrease per year, p < 0.001). Weight decline accelerated in the decade preceding death (n = 456, 2.18 ± 0.31% decrease per year, p < 0.001). DBS patients showed a weight increase of 2.0 ± 0.33% at 1 year following the first DBS lead implant (n = 455) and 2.68 ± 1.1% at 3 years if a contralateral DBS lead was placed (n = 249). The bilateral STN DBS group gained the most weight after surgery during 6 years of follow up (vs bilateral GPi, 3.03 ± 0.45% vs 1.89 ± 0.31%, p < 0.01). An analysis of the DBS cohort with date of death available (n = 72) revealed that post-DBS weight (0-12 months after the first or 0-36 months after the second surgery) was positively associated with survival (R2 = 0.14, p < 0.001). DISCUSSION: Though PD is associated with significant weight loss, DBS patients gained weight following surgery. Higher post-operative weight was associated with increased survival. These results should be replicated in other cohorts.

Atypical findings: Atypical parkinsonian syndromes or Atypical parkinsonian syndromes look-alikes.

OBJECTIVE: In parkinsonian syndromes, presentations other than current diagnostic criteria are considered atypical findings. Our goal was to identify and describe the frequency and features of uncommon manifestations of atypical parkinsonian syndromes within our group. METHODS: We retrospectively retrieved the medical records of all patients admitted to our clinic with parkinsonism between January 2011 and January 2022. We only included patients with atypical parkinsonian syndromes, in which the diagnosis was based on current clinical criteria. We retrospectively analyzed neurological, psychiatric, radiological, and electrophysiological characteristics. Typical and atypical features were classified according to the current clinical criteria and previous reports. RESULTS: We determined 51 patients with atypical parkinsonian syndromes; 46 were included, whereas five were excluded due to insufficient follow-up. The probable diagnoses were multiple system atrophy (MSA, n = 19), dementia with Lewy bodies (DLB, n = 10), frontotemporal dementia (FTD, n = 10), corticobasal syndrome (CBS, n = 3), progressive supranuclear palsy (PSP, n = 4). The prevalence of atypical findings was similar among different types of atypical parkinsonian syndromes (p = 0.847). Atypical findings were eyelid myoclonus, double vision in MSA; ataxia, myoclonus, and a typical hummingbird sign on MRI in DLB; pyramidal findings and family history in FTD; early onset, family history, and onset with psychiatric findings in PSP-like phenotype. Genetic causes were identified in the FTD-like phenotype with pyramidal findings, whereas symptom onset was early with myoclonus in the PSP-like phenotype. CONCLUSION: Atypical findings such as abnormal saccades, myoclonus, and ataxia may be a part of degenerative syndromes. However, family history, onset at an earlier age, and specific neurological findings suggest genetic syndromes.

Music can be reconstructed from human auditory cortex activity using nonlinear decoding models.

Music is core to human experience, yet the precise neural dynamics underlying music perception remain unknown. We analyzed a unique intracranial electroencephalography (iEEG) dataset of 29 patients who listened to a Pink Floyd song and applied a stimulus reconstruction approach previously used in the speech domain. We successfully reconstructed a recognizable song from direct neural recordings and quantified the impact of different factors on decoding accuracy. Combining encoding and decoding analyses, we found a right-hemisphere dominance for music perception with a primary role of the superior temporal gyrus (STG), evidenced a new STG subregion tuned to musical rhythm, and defined an anterior-posterior STG organization exhibiting sustained and onset responses to musical elements. Our findings show the feasibility of applying predictive modeling on short datasets acquired in single patients, paving the way for adding musical elements to brain-computer interface (BCI) applications.

Late Component of the Trigemino-Cervical Reflex: Clinical and Neuroradiological Correlations.

INTRODUCTION: The authors aimed to analyze the possible relationship of the late response of trigemino-cervical reflex (TCR) with various clinical conditions having brainstem lesions and lesion localizations in the brainstem. METHODS: The authors enrolled 30 healthy subjects, 16 patients with stroke, 14 patients with multiple sclerosis (MS), and 9 patients with neuro-Behçet disease. All patients had at least one MRI, and lesion localization was classified into midbrain, pons, medulla oblongata, or their combinations. The TCR was recorded simultaneously from bilateral sternocleidomastoid and splenius capitis muscles. RESULTS: There was no significant difference based on lesion localization within the brainstem. Trigemino-cervical reflex latency was significantly longer in patients with MS compared with all other groups (P < 0.005 for each comparison). The Receiver Operating Characteristic curve analysis of sternocleidomastoid showed a cut-off value of 76.9 ms with 44% sensitivity and 92.7% specificity to predict MS. Similarly, the authors determined a cut-off value of 61.5 ms of splenius capitis latency with 38.5% sensitivity and 91.5% specificity to predict MS. CONCLUSIONS: This study showed that TCR might be abnormal in a given patient with one brainstem lesion, independently from the lesion localization. This may be attributed to a broad network of TCR at the brainstem. Thus, abnormally delayed TCR responses can be used as a tool for the discrimination of MS among other brainstem lesions.

Participant perceptions of changes in psychosocial domains following participation in an adaptive deep brain stimulation trial.

BACKGROUND: There has been substantial controversy in the neuroethics literature regarding the extent to which deep brain stimulation (DBS) impacts dimensions of personality, mood, and behavior. OBJECTIVE/HYPOTHESIS: Despite extensive debate in the theoretical literature, there remains a paucity of empirical data available to support or refute claims related to the psychosocial changes following DBS. METHODS: A mixed-methods approach was used to examine the perspectives of patients who underwent DBS regarding changes to their personality, authenticity, autonomy, risk-taking, and overall quality of life. RESULTS: Patients (n = 21) who were enrolled in adaptive DBS trials for Parkinson's disease, essential tremor, obsessive-compulsive disorder, Tourette's syndrome, or dystonia participated. Qualitative data revealed that participants, in general, reported positive experiences with alterations in what was described as 'personality, mood, and behavior changes.' The majority of participants reported increases in quality of life. No participants reported 'regretting the decision to undergo DBS.' CONCLUSION(S): The findings from this patient sample do not support the narrative that DBS results in substantial adverse changes to dimensions of personality, mood, and behavior. Changes reported as "negative" or "undesired" were few in number, and transient in nature.

Nociceptive flexion reflex in small fibers neuropathy and pain assessments†.

BACKGROUND: The nociceptive flexion reflex (NFR) is a polysynaptic and multisegmental spinal reflex that develops in response to a noxious stimulus and is characterized by the withdrawal of the affected body part. The NFR possesses two excitatory components: early RII and late RIII. Late RIII is derived from high-threshold cutaneous afferent A-delta fibers, which are prone to injury early in the course of diabetes mellitus (DM) and may lead to neuropathic pain. We investigated NFR in patients with DM with different types of polyneuropathies to analyze the role of NFR in small fiber neuropathy (SFN). METHODS: We included 37 patients with DM and 20 healthy participants of similar age and sex. We performed the Composite Autonomic Neuropathy Scale-31, modified Toronto Neuropathy Scale, and routine nerve conduction studies. We grouped the patients into large fiber neuropathy (LFN), SFN, and no overt neurological symptom/sign groups. In all participants, NFR was recorded on anterior tibial (AT) and biceps femoris (BF) muscles after train stimuli on the sole of the foot, and NFR-RIII findings were compared. RESULTS: We identified 11 patients with LFN, 15 with SFN, and 11 with no overt neurological symptoms or signs. The RIII response on the AT was absent in 22 (60%) patients with DM and 8 (40%) healthy participants. The RIII response on the BF was absent in 31 (73.8%) patients and 7 (35%) healthy participants (P = .001). In DM, the latency of RIII was prolonged, and the magnitude was reduced. Abnormal findings were seen in all subgroups; however, they were more prominent in patients with LFN compared to other groups. CONCLUSIONS: The NFR-RIII was abnormal in patients with DM even before the emergence of the neuropathic symptoms. The pattern of involvement before neuropathic symptoms was possibly related to an earlier loss of A-delta fibers.

Future directions in psychiatric neurosurgery: Proceedings of the 2022 American Society for Stereotactic and Functional Neurosurgery meeting on surgical neuromodulation for psychiatric disorders.

OBJECTIVE: Despite advances in the treatment of psychiatric diseases, currently available therapies do not provide sufficient and durable relief for as many as 30-40% of patients. Neuromodulation, including deep brain stimulation (DBS), has emerged as a potential therapy for persistent disabling disease, however it has not yet gained widespread adoption. In 2016, the American Society for Stereotactic and Functional Neurosurgery (ASSFN) convened a meeting with leaders in the field to discuss a roadmap for the path forward. A follow-up meeting in 2022 aimed to review the current state of the field and to identify critical barriers and milestones for progress. DESIGN: The ASSFN convened a meeting on June 3, 2022 in Atlanta, Georgia and included leaders from the fields of neurology, neurosurgery, and psychiatry along with colleagues from industry, government, ethics, and law. The goal was to review the current state of the field, assess for advances or setbacks in the interim six years, and suggest a future path forward. The participants focused on five areas of interest: interdisciplinary engagement, regulatory pathways and trial design, disease biomarkers, ethics of psychiatric surgery, and resource allocation/prioritization. The proceedings are summarized here. CONCLUSION: The field of surgical psychiatry has made significant progress since our last expert meeting. Although weakness and threats to the development of novel surgical therapies exist, the identified strengths and opportunities promise to move the field through methodically rigorous and biologically-based approaches. The experts agree that ethics, law, patient engagement, and multidisciplinary teams will be critical to any potential growth in this area.