Aggregation-Induced Modulation of Ground and Excited State Photophysics of 5-(tert-Butyl)-2-Hydroxy-1,3-Isophthalaldehyde (5-tBHI).

5-(tert-Butyl)-2-hydroxy-1,3-isophthalaldehyde (5-tBHI) is a photochromic material susceptible to either excited state proton transfer or excited state intramolecular proton transfer, depending upon the solvent. However, it has also been found to aggregate in the presence of sodium dodecyl sulfate. In this current study, based on the steady-state and time-resolved spectroscopy, supported by crystallography, quantum chemical density functional theory calculation, and molecular dynamics (MD) simulation, we report on the aggregation of this potential single benzene-based emitter (SBBE) in neat solvents as well as solid phase to modulate its photophysics. It has been found that 5-tBHI forms mixed aggregates of different orders, owing to the presence of both enolic and tautomeric forms, to yield tunable emission, although the emission intensity is quenched. These findings suggest that the intramolecular hydrogen bonding of 5-tBHI not only limits intermolecular interactions but also promotes nonradiative deactivation pathways. Hence, designing and structural engineering, with a focus to suppressing intramolecular hydrogen bonding as well as increasing through space conjugation by replacing the aldehydic moieties with bulky aliphatic or aromatic ketonic groups, can be a plausible approach to yielding improved probes with tunable emission and higher fluorescence quantum yields.

Rhythmic Jaw Movements in Amyotrophic Lateral Sclerosis: Is It Clonus or Tremor?

Background: Jaw clonus refers to involuntary, rhythmic jaw contractions induced by a hyperactive trigeminal nerve stretch reflex; however, the movements, when triggered without a stretch, can be confused with a tremor. Phenomenology Shown: This video demonstrates a patient with amyotrophic lateral sclerosis presenting with rapid rhythmic jaw movements seen at rest, alongside a power spectrum analysis revealing a narrow high-frequency peak of 10 Hz. Educational Value: Rhythmic jaw movements are seen in many disorders such as Parkinson's disease, essential tremor, tardive syndromes, and cranial myorhythmias; however, a high-frequency movement, regardless of clonus or tremor, can indicate amyotrophic lateral sclerosis when accompanied by typical upper and lower motor neuron signs. Highlights: The presented video abstract shows a patient with amyotrophic lateral sclerosis with rhythmic jaw movements seen at rest. A power spectrum analysis of the rhythmic movements revealed a 10 Hz peak, a frequency higher than those seen in patients with Parkinson's disease, essential tremor, myorhythmia, and tardive syndromes.

Current opinions and practices in post-stroke movement disorders: Survey of movement disorders society members.

BACKGROUND: Post-stroke movement disorders (PSMD) encompass a wide array of presentations, which vary in mode of onset, phenomenology, response to treatment, and natural history. There are no evidence-based guidelines on the diagnosis and treatment of PSMD. OBJECTIVES: To survey current opinions and practices on the diagnosis and treatment of PSMD. METHODS: A survey was developed by the PSMD Study Group, commissioned by the International Parkinson's and Movement Disorders Society (MDS). The survey, distributed to all members, yielded a total of 529 responses, 395 (74.7%) of which came from clinicians with experience with PSMD. RESULTS: Parkinsonism (68%), hemiballismus/hemichorea (61%), tremor (58%), and dystonia (54%) were by far the most commonly endorsed presentation of PSMD, although this varied by region. Basal ganglia stroke (76% of responders), symptoms contralateral to stroke (75%), and a temporal relationship (59%) were considered important factors for the diagnosis of PSMD. Oral medication use depended on the phenomenology of the PSMD. Almost 50% of respondents considered deep brain stimulation and ablative surgeries as options for treatment. The lack of guidelines for the diagnosis and treatment was considered the most important gap to address. CONCLUSIONS: Regionally varying opinions and practices on PSMD highlight gaps in (and mistranslation of) epidemiologic and therapeutic knowledge. Multicenter registries and prospective community-based studies are needed for the creation of evidence-based guidelines to inform the diagnosis and treatment of patients with PSMD.

The Vocal Flutter of Multiple System Atrophy: A Parkinsonian-Type Phenomenon?

BACKGROUND: Early features of multiple system atrophy (MSA) are similar to those in Parkinson's disease (PD), which can challenge differential diagnosis. Identifying clinical markers that help distinguish MSA from forms of parkinsonism is essential to promptly implement the most appropriate management plan. In the context of a thorough neurological evaluation, the presence of a vocal flutter might be considered a potential feature of MSA-parkinsonian type (MSA-P). CASES: This case series describes clinical histories of 3 individuals with MSA-P. In each case, vocal flutter was detected during neurological and motor speech evaluations. It seemed to be a concomitant feature with the constellation of other signs and symptoms that led to the clinical diagnosis. LITERATURE REVIEW: The vocal flutter may be described as pitch and loudness fluctuations during phonation. Different from a vocal tremor, the flutter phenomenon has higher oscillation frequencies. The neuropathological underpinnings of vocal flutter may be related to generalized laryngeal dysfunction that is commonly described in MSA-P. CONCLUSION: Vocal flutter may be a unique speech feature in some individuals who have MSA-P. Future studies using perceptual and acoustic measures of speech are warranted to quantify these observations and directly compare to other MSA variants, PD, and a control group.

Roussy-Lévy Syndrome: Pes Cavus, Tendon Areflexia, Amyotrophy, Gait Ataxia, and Upper Limb Tremor in a Patient with CMT Neuropathy.

Background: Roussy-Lévy syndrome (RLS) is characterized by postural hand tremor seen in patients with familial autosomal dominant Charcot-Marie-Tooth (CMT) neuropathy. Phenomenology Shown: This video demonstrates irregular, jerky bilateral kinetic, postural, rest tremor affecting the right > left hand, along with pes cavus and gait ataxia in a patient with CMT disease. Educational Value: Pes cavus, tendon areflexia, sensory ataxia, and upper limb tremor should prompt consideration of CMT neuropathy. Highlights: This video abstract depicts a bilateral hand tremor characteristic of Roussy-Lévy syndrome seen in patients with Charcot-Marie-Tooth disease neuropathy. The significance of the abstract lies in the phenomenology and the physiology of the tremor seen in patients with genetically confirmed duplication of PMP22 gene.

Non-trivial ground and excited state photophysics of a substituted phenol.

5-(tert-Butyl)-2-hydroxy-1,3-isophthalaldehyde (5-tBHI) shows solvent dependent single or dual emission. The photophysics of 5-tBHI has been studied in a variety of solvents and the results were compared with that of the methyl derivative of the probe as well as the 5-tBHI anion. It has been found that the intramolecular H-bonded conformer of 5-tBHI predominantly exists in non-polar solvents, and undergoes facile excited state intramolecular proton transfer (ESIPT). On the other hand, a dynamic equilibrium can be found in polar, protic solvents, even in the ground state, except in water. NMR analyses confirm the loss of aromaticity of the probe in the ground state via anion formation, in equilibrium with the solvent mediated intermolecularly H-bonded state, in neat polar protic solvents like methanol. The proton transfer process, either intramolecularly or intermolecularly, was found to be of the order of 1 ps, and even faster than the instrumental resolution in the case of water. The current finding provides important insights on the photophysics of this small, substituted phenol.

Longitudinal predictors of health-related quality of life in isolated dystonia.

OBJECTIVE: To determine longitudinal predictors of health-related quality of life (HR-QoL) in an international multicenter cohort of patients with isolated dystonia. METHODS: Out of 603 dystonia patients prospectively enrolled in the Natural History Dystonia Coalition study, 155 were assessed three times within 2 years for HR-QoL, symptoms of depression, generalized anxiety disorder (GAD), and social anxiety disorder (SAD), as well as dystonia severity and dystonic tremor. In addition, the impact of botulinum neurotoxin (BoNT) injections on HR-QoL was evaluated after 1 year. RESULTS: Depressive symptoms at baseline predicted lower HR-QoL on all subscales after 2 years (all p ≤ 0.001). Higher GAD scores at baseline predicted lower HR-QoL related to general health, pain and emotional well-being, whereas higher SAD scores predicted higher pain-related QoL after 2 years (all p ≤ 0.006). Dystonia severity at baseline predicted social functioning (p = 0.002). Neither dystonic tremor, age, or sex predicted HR-QoL at 2 years. Two latent categories were revealed across the three-time points: Category 1 with higher total HR-QoL scores (mean HR-QoL = 74.4% ± 16.1), susceptible to symptoms of depression and SAD, and Category 2 with lower total HR-QoL scores (mean HR-QoL = 45.5% ± 17.6), susceptible to symptoms of GAD. HR-QoL improved over the course of 1 year irrespective of the use of BoNT. CONCLUSION: The longitudinal impact of psychiatric symptoms on HR-QoL emphasizes the importance of incorporating mental health treatment, in particular also the therapy of anxiety disorders, into treatment regimens for dystonia.

Basis of movement control in dystonia and why botulinum toxin should influence it?

Dystonia is a network disorder involving multiple brain regions, such as the motor cortex, sensory cortex, basal ganglia, and cerebellum. Botulinum toxin (BoNT) is the first-line therapy for treating focal dystonia and is a potent molecule that blocks the release of acetylcholine at the peripheral neuromuscular junction. However, the clinical benefits of BoNT are not solely related to peripheral muscle relaxation or modulation of afferent input from the muscle spindle. An increasing body of evidence, albeit in smaller cohorts, has shown that BoNT leads to distant modulation of the pathological brain substrates implicated in dystonia. A single treatment session of BoNT has been observed to reduce excessive motor excitability and improve sensory processing. Furthermore, owing to plasticity effects that are induced by botulinum, neural reorganization of pathological networks occurs, presumably leading to defective motor programs of dystonia replaced with normal movement patterns. However, longitudinal studies investigating the effects of multiple treatment sessions in large, well-characterized homogenous cohorts of dystonia will provide further compelling evidence supporting central botulinum mechanisms.

An Empirical Comparison of Commonly Used Universal Rating Scales for Dystonia.

Background: There are several widely used clinical rating scales for documenting the severity and distribution of various types of dystonia. Objectives: The goal of this study was to evaluate the performance of the most commonly used scales in a large group of adults with the most common types of isolated dystonia. Methods: Global Dystonia Rating Scale (GDRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFM) scores were obtained for 3067 participants. Most had focal or segmental dystonia, with smaller numbers of multifocal or generalized dystonia. These scales were also compared for 209 adults with cervical dystonia that had Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) scores and 210 adults with blepharospasm that had Blepharospasm Severity Scale (BSRS) scores. Results: There were strong correlations between the GDRS and BFM total scores (r = 0.79) and moderate correlations for their sub scores (r > 0.5). Scores for both scales showed positive skew, with an overabundance of low scores. BFM sub-scores were not normally distributed, due to artifacts caused by the provoking factor. Relevant sub-scores of the GDRS and BFM also showed moderate correlations with the TWSTRS (r > 0.5) for cervical dystonia and the BSRS (r > 0.5) for blepharospasm. Conclusions: The BFM is more widely used than the GDRS, but these results suggest the GDRS may be preferable for focal and segmental dystonias. The overabundance of very low scores for both scales highlights challenges associated with discriminating very mild dystonia from other abnormal movements or variants of normal behavior.

Visual Dysfunction and Occupational Performance in Persons With Parkinson's Disease.

IMPORTANCE: Visual function is critical to support occupational performance for persons with Parkinson's disease (PwP), yet it can be adversely affected by the disease. OBJECTIVE: To evaluate the prevalence and general awareness of visual dysfunction and identify the association between visual dysfunction and occupational performance in PwP. DESIGN: Self-reported cross-sectional electronic survey. PARTICIPANTS: PwP, identified from a registered database at a neurological institute, were invited to complete the survey through emails and newsletters. OUTCOMES AND MEASURES: The survey contained items of self-reported visual difficulties, diagnosed eye conditions, and about general awareness about disease-related visual dysfunction. Ophthalmological symptoms and occupational performance were measured with the Visual Impairment Parkinson's disease Questionnaire and the Revised Self-Reported Functional Visual Performance Scale, respectively. RESULTS: Data from PwP (n = 92; Mage = 69 yr) were analyzed. Nearly half were unaware that their disease could affect vision. Awareness was not associated with disease duration. Individuals reporting awareness tended to report difficulties with vision. Functional activities requiring vision were mildly impaired, and the frequency of ophthalmologic symptoms (commonly related to ocular surface disorder) was low. Nevertheless, a higher frequency of ophthalmologic symptoms was positively associated with a higher degree of disability in activities of daily living (Spearman's ρ = .49, p < .01). CONCLUSIONS AND RELEVANCE: Visual dysfunction related to Parkinson's disease may affect occupational performance. Screening for changes in vision in these individuals may aid occupational therapists in addressing functional independence and activity engagement. What This Article Adds: People with Parkinson's disease may not have a general awareness that the disease can adversely affect visual function. Those individuals with awareness tend to notice changes in vision, and this disease-related visual dysfunction may limit engagement and participation in everyday activities. Active evaluation of visual function in people with Parkinson's disease is recommended. Occupational therapists could play a key role by screening for visual dysfunction and providing patient education in the clinic.

Tremor Induced by Cyclosporine, Tacrolimus, Sirolimus, or Everolimus: A Review of the Literature.

Calcineurin inhibitors such as cyclosporine and tacrolimus are immunosuppressant drugs that are known to induce tremors. Non-calcineurin inhibitors such as sirolimus and everolimus have also reportedly been accompanied by tremors, albeit less likely. However, the prevalence rates reported in the literature are notably wide, and the risk profiles for these drug-induced tremors are less understood. We searched PubMed to extract data on the risk of tremors with these drugs when prescribed for various transplant and non-transplant indications. We ascertained whether the risk of drug-induced tremor is influenced by the underlying diagnosis, dosing formulations, drug concentrations, and blood monitoring. We extracted data on treatment strategies and outcomes for tremors. Articles were primarily screened based on English language publications, abstracts, and studies with n ≥ 5, which included case series, retrospective studies, case-controlled studies, and prospective studies. We found 81 eligible studies comprising 33 cyclosporine, 43 tacrolimus, 6 sirolimus, and 1 everolimus that discussed tremor as an adverse event. In the pooled analysis of studies with n > 100, the incidence of tremor was 17% with cyclosporine, 21.5% with tacrolimus, and 7.8% with sirolimus and everolimus together. Regarding the underlying diagnosis, tremor was more frequently reported in kidney transplant (cyclosporine 28%, tacrolimus 30.1%) and bone marrow transplant (cyclosporine 40%, tacrolimus 41.9%) patients compared with liver transplant (cyclosporine 9%, tacrolimus 11.5%) and nontransplant indications (cyclosporine 21.5%, tacrolimus 11.3%). Most studies did not report whether the risk of tremors correlated with drug concentrations in the blood. The prevalence of tremors when using the twice-daily formulation of tacrolimus was nearly the same as the once-daily formulation (17% vs 18%). Data on individual-level risk factors for tremors were lacking. Except for three studies that found some benefit to maintaining magnesium levels, there were minimal data on treatments and outcomes. A large body of data supports a substantive and wide prevalence of tremor resulting from tacrolimus use followed by cyclosporine, especially in patients receiving a kidney transplant. However, there is little reporting on the patient-related risk factors for tremor, risk relationship with drug concentrations, treatment strategies, and outcomes.

Non-channeled Video Laryngoscopy as an Alternative to Conventional Laryngoscopy for Intubating Adult Patients in the Intensive Care Unit.

Background Endotracheal intubation in the intensive care unit (ICU) is often a risky procedure due to the emergency situation, unstable condition of the patient, and technical problems such as inadequate positioning. Several new techniques, such as video laryngoscopy, have been developed recently to improve the success rate of first-pass intubations and reduce complications. We conducted this study to compare a non-channeled reusable video laryngoscope BPL VL-02 (manufactured by BPL Medical Technologies, Bangalore, India) with a conventional laryngoscope for intubation of adult patients in the ICU. Methodology A total of 72 ICU patients were randomly allocated to be intubated with either conventional direct laryngoscopy via Macintosh blade (group A) or video laryngoscopy with BPL VL-02 (group B). All patients were intubated by the primary investigator and the assistant noted the following parameters: the total number of intubation attempts, total duration of intubation, assistance or alternative technique required, Cormack Lehane grading, and any complications. Results There was no significant difference in the Cormack Lehane grading, number of attempts, or complications between the two groups. On comparing the assistance required during intubation in patients, it was observed that four (11.11%) patients in group A and seven (19.44%) patients in group B needed backward, upward, and rightward pressure on the larynx assistance during intubation. In five (13.89%) patients in group B, Stylet was required during intubation. The difference was statistically significant (p = 0.0308). The video laryngoscopy group (group B) had a longer mean duration of intubation (64.36 ± 6.28 seconds) compared to group A (45.72 ± 11.45 seconds), and the difference was statistically significant (p < 0.0001). Conclusions Non-channeled video laryngoscope (BPL VL-02) is not a suitable alternative to conventional direct laryngoscopy with a Macintosh blade in terms of successful first-pass intubation, total duration of intubation, and assistance required.

Utilization, surgical populations, centers, coverages, regional balance, and their influential factors of deep brain stimulation for Parkinson's disease: a large-scale multicenter cross-sectional study from 1997 to 2021.

BACKGROUND: Deep brain stimulation (DBS) is an emerging and effective therapy for Parkinson's disease (PD). However, little is known about its utilization, surgical populations, centers, coverages, regional balance, and influential factors. MATERIALS AND METHODS: This large-scale multicenter cross-sectional study was conducted using a national census involving 74 Chinese centers. National DBS populations and centers for PD were investigated in 1997-2021, and regional sociodemographic features, surgical populations, related resources, and insurance policies in 2020 were explored. RESULTS: Since the first DBS surgery in 1997, a total of 38 122 PD patients from 349 centers underwent DBS by 2021, which covered 1.118% (1.108-1.129) of patients and 0.954% (0.933-0.976) of centers. Significant upward trends in the annual surgical population and coverages were observed with rapid climbing rates, while the annual surgical centers and their coverage showed two growth peaks in 2002-2006 and 2010-2018, correlating with clinical approvals and new technologies. A total of 103 070 (51 165-154 975) PD patients [2.088% (1.351-2.825) coverage] and 603 (72-1134) centers [1.356% (1.126-1.586) coverage] are predicted to conduct DBS by 2030. The new remotely programmed DBS technology was recoded as the first application in 2015 and rapidly increased to 2771 (47.39%, 46.11-48.67) patients with 10 507 remote programming sessions annually in 2021. Provinces in the eastern and central regions had better economic status, more surgical patients, higher insurance affordability, and more related resources than those in the western and northeastern regions. Higher gross domestic product per capita ( ß =5.041, 3.324-6.758 and ß =0.008, 0.004-0.012; all P <0.001) and more functional neurosurgery doctors ( ß =3.596, 0.353-6.839; P =0.031 and ß =0.010, 0.002-0.017; P =0.013) positively influenced surgical populations and coverages, while higher insurance levels ( ß =128.888, 64.702-193.075; P <0.001) positively influenced surgical coverages. CONCLUSION: Although surgical populations, centers, and coverages of DBS for PD have rapidly improved and are predicted to show future increases, this is still insufficient to cover potential eligible patients. Regionally imbalanced health coverage should be given attention to promote coordinated development.

Improvement in Patient Satisfaction and Anxiety With Perioperative Music Therapy in Patients Undergoing Total Abdominal Hysterectomy: A Single-Blind Prospective Study.

Introduction Listening to music is a safe and low-cost way to reduce preoperative anxiety among patients, but more research is needed to evaluate its effectiveness fully. Aims The aim of the study is to identify the effect of intraoperative music therapy on the visual analogue scale for anxiety (VASA) scores (VASA 1 and VASA 2) and patient satisfaction score (PSS) perioperatively. Methods In a study of 188 patients aged 40-70, those in group A (94 patients) listened to pre-approved music during their surgery for abdominal hysterectomy, while group B (94 patients) did not. Both groups wore noise-cancelling earphones. VASA was recorded before (VASA 1) and after (VASA 2) the surgery. PSS was recorded in the postoperative ward. Music preferences were kept confidential from the investigator recording the scores. Result The two groups of patients had similar demographic profiles and baseline characteristics. The VASA 1 of both groups was similar, with a mean value of 4.36 ± 1.13 for group A and 4.23 ± 1.05 for group B (p = 0.606). However, group A had lower VASA 2 (1.79 ± 0.83) than group B (3.77 ± 0.98). The difference was statistically significant (p < 0.001). The patient satisfaction score in group A was notably higher than those in group B. A total of 52 patients were highly satisfied in group A as compared to none in group B (p < 0.001), and a total of 42 patients were moderately satisfied as compared to eight patients in group B (p < 0.001). Eighty-six patients in group B were unsatisfied. Conclusion According to our research, playing specific music at the right volume can significantly lower anxiety levels and increase patients' satisfaction scores for those who have had abdominal hysterectomy surgeries.

Applications of Transcranial Magnetic Stimulation for Understanding and Treating Dystonia.

Transcranial magnetic stimulation (TMS)-based studies have led to an advanced understanding of the pathophysiology of dystonia. This narrative review summarizes the TMS data contributed to the literature so far. Many studies have shown that increased motor cortex excitability, excessive sensorimotor plasticity, and abnormal sensorimotor integration are the core pathophysiological substrates for dystonia. However, an increasing body of evidence supports a more widespread network dysfunction involving many other brain regions. Repetitive TMS pulses (rTMS) in dystonia have therapeutic potential as they can induce local and network-wide effects through modulation of excitability and plasticity. The bulk of rTMS studies has targeted the premotor cortex with some promising results in focal hand dystonia. Some studies have targeted the cerebellum for cervical dystonia and the anterior cingulate cortex for blepharospasm. We believe that therapeutic potential could be leveraged better when rTMS is implemented in conjunction with standard-of-care pharmacological treatments. However, due to several limitations in the studies conducted to date, including small samples, heterogeneous populations, variability in the target sites, and inconsistencies in the study design and control arm, it is hard to draw a definite conclusion. Further studies are warranted to determine optimal targets and protocols yielding the most beneficial outcomes that will translate into meaningful clinical changes.

Hematoma-induced Twiddler-like phenomenon as a presentation of DBS hardware failure: Case report.

Deep brain stimulators (DBS) may fail for a multitude of reasons. We present a 79-year-old Parkinson's disease patient who suffered a DBS failure following impulse generator (IPG) replacement surgery due to the IPG flipping within an expanded capsular pocket. This creation of the pocket was unintentional, and the pocket formed around an undiagnosed postoperative hemorrhage. The syndrome could be considered "Twiddler-like" because it resulted in device flipping. There were, however, many characteristic differences between our case and classical Twiddler's syndrome. DBS neurostimulator failure due to hematoma induced device flipping should be suspected when device interrogation is impossible or there are abnormally high impedances across multiple DBS lead contacts. A plain film X-ray series should be ordered and can be useful in providing radiological evidence of device flipping. In cases like ours the extensive braiding encountered in Twiddler's syndrome may be absent. Anchoring the IPG to a deep fascial layer as well as the use of an antimicrobial pouch are two methods that may be employed to prevent or to treat this complication.

Globus pallidus internus deep brain stimulation evokes resonant neural activity in Parkinson's disease.

Globus pallidus internus deep brain stimulation is an established therapy for patients with medication-refractory Parkinson's disease. Clinical outcomes are highly dependent on applying stimulation to precise locations in the brain. However, robust neurophysiological markers are needed to determine the optimal electrode location and to guide postoperative stimulation parameter selection. In this study, we evaluated evoked resonant neural activity in the pallidum as a potential intraoperative marker to optimize targeting and stimulation parameter selection to improve outcomes of deep brain stimulation for Parkinson's disease. Intraoperative local field potential recordings were acquired in 22 patients with Parkinson's disease undergoing globus pallidus internus deep brain stimulation implantation (N = 27 hemispheres). A control group of patients undergoing implantation in the subthalamic nucleus (N = 4 hemispheres) for Parkinson's disease or the thalamus for essential tremor (N = 9 patients) were included for comparison. High-frequency (135 Hz) stimulation was delivered from each electrode contact sequentially while recording the evoked response from the other contacts. Low-frequency stimulation (10 Hz) was also applied as a comparison. Evoked resonant neural activity features, including amplitude, frequency and localization were measured and analysed for correlation with empirically derived postoperative therapeutic stimulation parameters. Pallidal evoked resonant neural activity elicited by stimulation in the globus pallidus internus or externus was detected in 26 of 27 hemispheres and varied across hemispheres and across stimulating contacts within individual hemispheres. Bursts of high-frequency stimulation elicited evoked resonant neural activity with similar amplitudes (P = 0.9) but a higher frequency (P = 0.009) and a higher number of peaks (P = 0.004) than low-frequency stimulation. We identified a 'hotspot' in the postero-dorsal pallidum where stimulation elicited higher evoked resonant neural activity amplitudes (P < 0.001). In 69.6% of hemispheres, the contact that elicited the maximum amplitude intraoperatively matched the contact empirically selected for chronic therapeutic stimulation by an expert clinician after 4 months of programming sessions. Pallidal and subthalamic nucleus evoked resonant neural activity were similar except for lower pallidal amplitudes. No evoked resonant neural activity was detected in the essential tremor control group. Given its spatial topography and correlation with postoperative stimulation parameters empirically selected by expert clinicians, pallidal evoked resonant neural activity shows promise as a potential marker to guide intraoperative targeting and to assist the clinician with postoperative stimulation programming. Importantly, evoked resonant neural activity may also have the potential to guide directional and closed-loop deep brain stimulation programming for Parkinson's disease.

Phenomenology and Physiology of Tacrolimus Induced Tremor.

Background: Tacrolimus is a potent immunosuppressant drug commonly used after solid organ transplant surgery. The use of this drug is frequently associated with the emergence of tremors. There is little information on the clinical and physiological characteristics of tacrolimus-induced tremors. Characterizing these tremors is essential as they can promote the development of specific therapies. Methods: We describe four patients placed on tacrolimus immunosuppressant therapy following kidney transplant surgery and who developed tremors impacting their daily functional activities. We describe the clinical and physiological characteristics of the tremor and the response generated after a limb cooling test. Results: A postural and kinetic tremor mainly involving the distal hands was observed in our cohort. In the accelerometer-based assessment, the tremor amplitude was noted to be mild to moderate, and the frequency was 5-6 Hz. Cooling the forearm and the hand led to a temporary albeit significant reduction of tremor amplitude (p = 0.03). Limb cooling lowered the tremor frequency by 1 Hz in two patients with no change in the other two patients, and the statistical comparison was not significant (p > 0.05). Conclusions: Limb cooling may be pursued as a therapeutic option for addressing tacrolimus-induced tremor, as the patients in our cohort benefitted from temporary tremor suppression.

On periodic growth and shrinkage of glaciers in the Warwan sub-basin, western Himalaya, between 1990 and 2020.

Knowledge about glacier extent, dynamics, and characteristics are important for climate change attribution and prediction. Understanding on long-term dynamics and glacier inventory is crucial, particularly for the melt-dominated and latitudinally-diverse western Himalayan glacier basins. In this study, a temporal inventory is prepared for Warwan-sub basin (WSB), utilizing satellite imageries since the 1993 (Landsat TM: 1993; ETM+: 2001, 2008; OLI: 2020) and elevation model (SRTM DEM: 2000). The base inventory was generated for the year 2001 and systematically adjusted to the glacier situations in 1993, 2008, and 2020. Results indicate that in the year 2001, WSB in the western Himalaya included 84 glaciers (> 0.02 km2) covering an area of 187.9 ± 5.8 km2. The mapping (2001) further revealed a supraglacial debris cover of 15% of the glacierized area (28.2 ± 0.9 km2). Overall, the debris cover increased by 6% between 1993 and 2020. Temporal analyses clearly suggest a period of gain in the glacierized area (2001-2008) interspersed by the two phases of decline (1993-2001 and 2008-2020). Results specify a stronger decline in the glacierized area during 1993 to 2001 (197.03 ± 6.1 to 187.9 ± 5.8 km2) than between 2008 and 2020 (188.4 ± 5.9 to 182.8 ± 5.66 km2). Remarkably, the glacierized area increased from 187.9 ± 5.8 to 188.4 ± 5.8 km2 during 2001 to 2008. In view of widespread recession of regional glaciers, the gain in the area between 2001 and 2008 represents a peculiar characteristic of WSB that needs further detailed investigation. Further analyses suggest that low-altitude, east-facing, debris-free, steep-sloped, and small glaciers experienced greater loss in the area than large, debris-covered, north-facing, gently sloped, and high-altitude glaciers. Overall, the study at the sub-basin scale reveals inherent glacier dynamics with periodic increase and decrease in the glacierized area and a notable influence of non-climatic factors in regulating spatial heterogeneity and the rate of glacier changes.