Subcortical tau is linked to hypoperfusion in connected cortical regions in 4-repeat tauopathies.

Four-repeat (4R) tauopathies are neurodegenerative diseases characterized by cerebral accumulation of 4R tau pathology. The most prominent 4R tauopathies are progressive supranuclear palsy (PSP) and corticobasal degeneration characterized by subcortical tau accumulation and cortical neuronal dysfunction, as shown by PET-assessed hypoperfusion and glucose hypometabolism. Yet, there is a spatial mismatch between subcortical tau deposition patterns and cortical neuronal dysfunction, and it is unclear how these two pathological brain changes are interrelated. Here, we hypothesized that subcortical tau pathology induces remote neuronal dysfunction in functionally connected cortical regions to test a pathophysiological model that mechanistically links subcortical tau accumulation to cortical neuronal dysfunction in 4R tauopathies. We included 51 Aß-negative patients with clinically diagnosed PSP variants (n = 26) or corticobasal syndrome (n = 25) who underwent structural MRI and 18F-PI-2620 tau-PET. 18F-PI-2620 tau-PET was recorded using a dynamic one-stop-shop acquisition protocol to determine an early 0.5-2.5 min post tracer-injection perfusion window for assessing cortical neuronal dysfunction, as well as a 20-40 min post tracer-injection window to determine 4R-tau load. Perfusion-PET (i.e. early window) was assessed in 200 cortical regions, and tau-PET was assessed in 32 subcortical regions of established functional brain atlases. We determined tau epicentres as subcortical regions with the highest 18F-PI-2620 tau-PET signal and assessed the connectivity of tau epicentres to cortical regions of interest using a resting-state functional MRI-based functional connectivity template derived from 69 healthy elderly controls from the ADNI cohort. Using linear regression, we assessed whether: (i) higher subcortical tau-PET was associated with reduced cortical perfusion; and (ii) cortical perfusion reductions were observed preferentially in regions closely connected to subcortical tau epicentres. As hypothesized, higher subcortical tau-PET was associated with overall lower cortical perfusion, which remained consistent when controlling for cortical tau-PET. Using group-average and subject-level PET data, we found that the seed-based connectivity pattern of subcortical tau epicentres aligned with cortical perfusion patterns, where cortical regions that were more closely connected to the tau epicentre showed lower perfusion. Together, subcortical tau-accumulation is associated with remote perfusion reductions indicative of neuronal dysfunction in functionally connected cortical regions in 4R-tauopathies. This suggests that subcortical tau pathology may induce cortical dysfunction, which may contribute to clinical disease manifestation and clinical heterogeneity.

Precision Balance Assessment in Parkinson's Disease: Utilizing Vision-Based 3D Pose Tracking for Pull Test Analysis.

Postural instability is a common complication in advanced Parkinson's disease (PD) associated with recurrent falls and fall-related injuries. The test of retropulsion, consisting of a rapid balance perturbation by a pull in the backward direction, is regarded as the gold standard for evaluating postural instability in PD and is a key component of the neurological examination and clinical rating in PD (e.g., MDS-UPDRS). However, significant variability in test execution and interpretation contributes to a low intra- and inter-rater test reliability. Here, we explore the potential for objective, vision-based assessment of the pull test (vPull) using 3D pose tracking applied to single-sensor RGB-Depth recordings of clinical assessments. The initial results in a cohort of healthy individuals (n = 15) demonstrate overall excellent agreement of vPull-derived metrics with the gold standard marker-based motion capture. Subsequently, in a cohort of PD patients and controls (n = 15 each), we assessed the inter-rater reliability of vPull and analyzed PD-related impairments in postural response (including pull-to-step latency, number of steps, retropulsion angle). These quantitative metrics effectively distinguish healthy performance from and within varying degrees of postural impairment in PD. vPull shows promise for straightforward clinical implementation with the potential to enhance the sensitivity and specificity of postural instability assessment and fall risk prediction in PD.

[Pathological Lesions and Fractures of the Proximal Femur]. / Patologická loziska a zlomeniny proximálního femuru.

PURPOSE OF THE STUDY The aim of the study was to determine the incidence of primary malignancies metastasizing to the area of the proximal femur, to evaluate the localization of the lesions and fractures, to compare the results of the selected surgical therapy, survival time of the patients and postoperative complications. MATERIAL AND METHODS We retrospectively evaluated the group of patients operated on from 2012 to 2021. The study included 45 patients (24 women and 21 men) with a pathological lesion or a pathological fracture in the area of the proximal femur. The average age was 67 years (38-90). There were 30 (67%) cases of pathological fracture and 15 (33%) cases of pathological lesions in the cohort. In each patient, the perioperative biopsy or resected sample was sent for histological examination. The type of primary malignancy with the localization of lesions and fractures was assessed. Furthermore, we evaluated the outcomes of the surgical method chosen and its complications. We monitored the patients' functional score using the Karnofsky performance status and survival interval. RESULTS The most common primary malignancy was multiple myeloma in 10 cases (22%), followed by seven cases (16%) of breast and lung cancer and 6 cases (13%) of clear cell renal cell carcinoma. Internal fixation was used in 15 cases (33%). Tumor resection with hip joint replacement was performed in 29 patients (64%). One patient was treated with percutaneous femoroplasty. Out of a total of 45 patients, 10 patients (22%) survived for less than three months. The survival rate of more than one year was observed in 21 patients (47%). A total of seven complications occurred in six patients (15%). Fewer complications occurred in the group of patients with a pathological fracture compared to the group with an impending fracture. DISCUSSION Pathological lesions in the bone or an already existing pathological fracture are signs of advanced cancer. Better outcomes are reported in patients who underwent prophylactic surgery, which was, however, not confirmed by our study. The incidence of individual primary malignancies, the postoperative complications and the patient survival corresponded to the statistical data reported by the other authors. CONCLUSIONS In patients with a pathological lesion of the proximal femur, operative treatment will increase the quality of life, either when choosing osteosynthesis or joint replacement, while prophylactic treatment is usually associated with a better prognosis. As a less invasive procedure with lower blood loss, osteosynthesis is indicated for palliative therapy in patients with a limited expected survival time or in patients with a prognosis of healing of the lesion. Reconstruction of the joint with an arthroplasty is indicated in patients with a better prognosis or in cases excluding safe osteosynthesis. Our study confirmed good outcomes with the use of an uncemented revision femoral component. Key words: metastasis, osteolysis, pathological fracture, proximal femur.

Interactions of dopamine, iron, and alpha-synuclein linked to dopaminergic neuron vulnerability in Parkinson's disease and Neurodegeneration with Brain Iron Accumulation disorders.

Dopamine metabolism, alpha-synuclein pathology, and iron homeostasis have all been implicated as potential contributors to the unique vulnerability of substantia nigra dopaminergic neurons which preferentially decline in Parkinson's disease and some rare neurodegenerative disorders with shared pathological features. However, the mechanisms contributing to disease progression and resulting in dopaminergic neuron loss in the substantia nigra are still not completely understood. Increasing evidence demonstrates that disrupted dopamine, alpha-synuclein, and/or iron pathways, when combined with the unique morphological, physiological, and metabolic features of this neuron population, may culminate in weakened resilience to multiple stressors. This review analyzes the involvement of each of these pathways in dopamine neuron physiology and function, and discusses how disrupted interplay of dopamine, alpha-synuclein, and iron pathways may synergize to promote pathology and drive the unique vulnerability to disease states. We suggest that elucidating the interactions of dopamine with iron and alpha-synuclein, and the role of dopamine metabolism in driving pathogenic phenotypes will be critical for developing therapeutics to prevent progression in diseases that show degeneration of nigral dopamine neurons such as Parkinson's disease and the rare family of disorders known as Neurodegeneration with Brain Iron Accumulation.

The impact of occlusive vs non-occlusive application of 5-aminolevulinic acid (BF-200 ALA) on the efficacy and tolerability of photodynamic therapy for actinic keratosis on the scalp and face: A prospective within-patient comparison trial.

BACKGROUND: Photodynamic therapy (PDT) is an effective treatment for actinic keratoses (AK). PDT is usually performed with occlusion of the photosensitizer prior to subsequent illumination. OBJECTIVES: This study aimed to compare the efficacy and tolerability of occlusive versus non-occlusive application of a 5-aminolevulinic gel (BT-200 ALA) for PDT of multiple AK on the scalp or face. METHODS: Prospective, investigator-blinded, within-patient comparison study on 45 patients. PDT with occlusion of ALA was performed in a target area on one randomized side of the scalp or face. One week later a contralateral target area received the same treatment except that no occlusion of the ALA gel was performed. 3 and 6 months after PDT, the clearance rate of a predetermined target lesion and the total clearance rate of all AK within the treated areas were determined. PDT-induced pain and skin phototoxicity and cosmetic outcome were also recorded. RESULTS: Clearance rate of the target AK and total AK clearance rate at 3 months after PDT was 88.4% and 90.6% for occlusive PDT and 58.1% (P = .001) and 70.4% (P = .04) for non-occlusive PDT. The corresponding values at 6 months after PDT were 69.7% and 72.1% for occlusive PDT and 30.2% (P < .001) and 35.6% (P = .001) for non-occlusive PDT. Pain score and skin phototoxicity were significantly higher after occlusive ALA application. No difference was observed with respect to cosmetic outcome. CONCLUSIONS: Occlusive application of ALA significantly improves the efficacy of PDT but is associated with more pain and increased phototoxicity.

[Validation of a French version of the 16-item Prodromal Questionnaire (fPQ16) in adolescents and young adults seeking help]. / Validation d'une version française du 16-items Prodromal Questionnaire (fPQ16) chez des adolescents et jeunes adultes consultant en psychiatrie.

INTRODUCTION: The duration of untreated psychosis has been largely associated with poor outcomes in psychosis. Actual diagnostic tools may be used by very specialized teams and need sustained evaluation. We present a French version of a self-report questionnaire: the 16-item Prodromal Questionnaire (fPQ16). Our objective was to evaluate its predictive value for an ultra-high-risk state (UHR) or psychosis. The population enrolled was consulting in a young adults and adolescents center in Sainte-Anne hospital, Paris, France. METHODS: PQ16 had first been translated into French and independently back translated and validated by the original authors. Between November 2016 and May 2018, every C'JAAD consulting patient was proposed to fill in the fPQ16. Each patient was next evaluated with the French version of the comprehensive assessment of at-risk mental state (CAARMS), which detects UHR or psychosis. Statistical analysis of fPQ16 concurrent validity was performed using ROC curves. fPQ16 acceptability was studied by four additional questions especially designed for that purpose. RESULTS: One hundred participants were included. Mean age was 19.85years (SD 3.3 y). Fifty-eight percent of patients included were diagnosed with UHR (40%) or psychotic (18%) state after CAARMS evaluation. Mean score at fPQ16 was 5.7 (SD 3.8). Best cut-off score was 4 positive items, with excellent sensibility (91%) and correct specificity (60%). Positive predictive value of fPQ16 was 76%. Area under the curve was 0.85 (P<0.0001). fPQ16 showed good acceptability. DISCUSSION: fPQ16 had good screening performances in our population. Cut-off score was lower than in previous studies, but performances were equal or better. As a well-accepted and short questionnaire, the fPQ16 could be a great screening tool in primary care. A version with 18-items, including two items focused on thought content and disorganization that are missing in PQ16, is under evaluation.

Interrelation between Sarcopenia and the Number of Motor Neurons in Patients with Parkinsonian Syndromes.

INTRODUCTION: Pathogenesis in a subgroup of sarcopenic patients seems to be based on a reduced number of motor neurons. This study aimed at investigating the overlap between sarcopenia and neurodegeneration, as reflected by a low number of motor neurons in patients with Parkinsonian syndromes (PS). METHODS: The motor unit number index (MUNIX) of the hypothenar muscle was used to assess the number and size (MUSIX) of motor units (MUs) in patients with idiopathic Parkinson disease (iPD, n = 53), patients with atypical Parkinsonian syndrome (aPS, n = 21), and a control group (n = 30). Mean age of participants was 70.3 years and 54.1% were female. Skeletal muscle mass by bioelectrical impedance analysis, hand-grip strength and gait speed were measured. Based on these assessments, sarcopenia was diagnosed according to the criteria of the European Working Group on Sarcopenia in Older People. RESULTS: Sarcopenia criteria were met by 10 patients with PS (13.5%). The study group had significantly lower MUNIX values than the control group (109 [SD ±39.1] vs. 129 [SD ±45.1]; p = 0.020) even after adjustment for age and sex. Three of the 5 sarcopenic iPD patients (75%) had pathological low MUNIX values (<80). DISCUSSION/CONCLUSION: Sarcopenia is a frequent comorbidity in PS. The pathologically low MUNIX values found in 75% of our sarcopenic iPD patients provides further support for the existence of a neurodegenerative overlap syndrome with a reduced number of MUs potentially leading to sarcopenia. This finding warrants further evaluation.

A simplified ultrasonography-guided approach for neurotoxin injection into the obliquus capitis inferior muscle in spasmodic torticollis.

The obliquus capitis inferior (OCI) muscle may be crucially involved in generating the tremulous component of spasmodic torticollis. This study was undertaken to evaluate the efficacy of a simplified ultrasonography-guided approach of botulinum neurotoxin injection into the OCI in the management of spasmodic torticollis. Here, a novel off-plane technique of ultrasonography-guided botulinum neurotoxin injection into the OCI is demonstrated on video. We investigated its effect in five patients with tremulous torticollis with only partial response to conventional injection technique not injecting OCI. On ultrasonography the OCI and its neighboring structures (greater occipital nerve, vertebrae C1 and C2) were clearly displayed. Unlike the previously proposed approach with axial OCI imaging and in-plane medio-lateral needle insertion, we applied here an off-plane needle insertion technique. With this, the ultrasonography guidance of needle insertion was easier using the sagittal imaging plane rather than the axial plane. Compared to botulinum neurotoxin injection into more superficial neck muscles only, additional ultrasonography-guided botulinum neurotoxin injection into the OCI led to a higher benefit (self-rated improvement of cervical dystonia, p = 0.026, Mann-Whitney test), especially of the tremulous component (p = 0.007), even though the total botulinum neurotoxin dose was not changed. We conclude that selected patients with tremulous torticollis may benefit from botulinum neurotoxin injection into the OCI.

Body height loss characterizes camptocormia in Parkinson's disease.

Axial deformities such as camptocormia or Pisa syndrome in people with Parkinson's disease (PwP) are poorly understood. The scarcity of information may result from the shortage of reliable and responsive evaluation instruments. We evaluated the body height loss (BHL) as a new measure for PwP with axial deformities. 50 PwP with axial deformity defined by an UPDRS item 28 value of at least 2 were included in this mono-center study. We measured body height while lying supine and after 1 min of standing, providing a percentage value of BHL, and compared this measure to other clinical variables. BHL depended on the Hoehn and Yahr clinical stage and correlated with clinical scales for function and mobility, but not with timely measures of the axial disorder such as age at diagnosis or duration of disease. ANOVA showed that only lumbar flexion explained the variability of BHL (F = 21.0, p < 0.0001), but not kyphosis (F = 0.4, p = 0.74) or lateroflexion (F = 0.6, p = 0.6). Re-test reliability of BHL was good with к = 0.76 (p < 0.0001). BHL resulted from the lumbar spine and the hip joint and not from the thoracic spine or lateroflexion. This observation conforms to the concept of upper-type and lower-type camptocormia with only the latter leading to a BHL. The assessment of the BHL is shown to be a well defined, easy to perform, and reliable measure for the clinical evaluation of lower-type camptocormia.

The enantioselective addition of 1-fluoro-1-nitro(phenylsulfonyl)methane to isatin-derived ketimines.

An asymmetric organocatalytic addition of fluorinated phenylsulfonylnitromethane to isatin-derived ketimines was developed. The reaction was efficiently catalyzed by a chiral tertiary amine, cinchonine. This methodology provides a new type of optically active compound with two adjacent quaternary carbon stereocenters in good yield (up to 96%), with moderate diastereoselectivity (up to 5.7 : 1 dr) and excellent enantioselectivity (up to 98/96% ee).

The Influence of Asthma Exacerbations on Health-Related Quality of Life.

The purpose of this study was to determine the influence of asthma on the quality of life (QoL) of patients hospitalized for an exacerbation of the disease and those with controlled asthma receiving outpatient treatment, and to establish the patients' somatic status and the level of health care utilization. This study involved 239 adults with asthma (123 hospitalized patients and 116 outpatients of family physicians). The authors used: WHOQOL-BREF questionnaire and a questionnaire measuring health care utilization. There were no differences in QoL levels between the patients with severe and controlled asthma. The psychological domain was assessed higher by hospitalized patients (p = 0.02). QoL levels correlated negatively with age, place of residence, and marital status, and positively with education. The general QoL level was most strongly influenced by gender, age, education, the number of home visits and interventions of a district nurse, and the somatic index (p < 0.05). Somatic symptoms were more severe in hospitalized patients. The QoL assessment of asthma patients in relation to somatic symptoms, health care services and socio-demographic variables allows better understanding of the complex health situation of patients at various stages of the disease, and tailoring the therapy to individual needs. Patients receiving outpatient treatment require professional psychotherapeutic support.

Does health status influence acceptance of illness in patients with chronic respiratory diseases?

The level of illness acceptance correlates positively with compliance to the doctor's recommendations, and negatively with the frequency and intensity of complications of chronic diseases. The purpose of this study was to determine the influence of the clinical condition on the level of illness acceptance, and to find variables which would have the most profound effect on the level of illness acceptance in patients with chronic respiratory diseases. The study group consisted of 594 adult patients (mean age: 60 ± 15 years) with mixed chronic respiratory diseases, recruited from patients of 136 general practitioners. The average score in the Acceptance of Illness Scale was 26.2 ± 7.6. The low level of illness acceptance was noted in 174 (62.6 %) and high in 46 (16.6 %) patients. Analysis of multiple regressions was used to examine the influence of explanatory variables on the level of illness acceptance. The variables which shaped the level of illness acceptance in our patients included: improvement of health, intensity of symptoms, age, marital status, education level, place of residence, BMI, and the number of chronic diseases. All above mentioned variables should be considered during a design of prevention programs for patients with mixed chronic respiratory diseases.

Subacute peripheral neuropathy under duodopa therapy without cobalamin deficiency and despite supplementation.

Continuous jejunal levodopa infusion is an increasingly used therapy option in patients with Parkinson's disease who experience severe fluctuations from oral levodopa. In a number of recent reports polyneuropathy in patients receiving jejunal levodopa infusion was referenced to cobalamin (vitamin B12) deficiency. We describe one of three cases from our hospital with severe subacute polyneuropathy that developed during jejunal levodopa infusion, and occurred despite vitamin substitution therapy and normal vitamin B12 and holotranscobalamin serum levels.

CCSD(T) calculations of confined systems: in-crystal polarizabilities of F⁻, Cl⁻, O²â», and S²â».

We explore dipole polarizabilities of the singly and doubly charged anions F(-), Cl(-), O(2-), and S(2-) in an external, harmonic oscillator (HO) confining potential ∑(i)½ω(2)r(i)(2). We find that in contrast to F(-) and Cl(-) those for O(2-) and S(2-) are unrealistically high due to the instability of the corresponding restricted Hartree-Fock (RHF) solutions. Yet, already a relatively weak HO confining potential stabilizes their RHF solutions and eliminates any possible broken-symmetry solutions. The coupled-cluster theory with single, double and noniterative triple excitations (CCSD(T)) then yields considerably reduced polarizabilities for O(2-) and S(2-) relative to their unconfined values. We showed that polarizabilities of O(2-) and S(2-) are more sensitive to the strength of a confinement potential than are those for F(-) and Cl(-). This enables us to relate the confining parameter ω with the known experimental polarizabilities for selected crystals (our "training set") and to find a specific confining parameter ω for which the CCSD(T) polarizability equals the experimental in-crystal polarizability of an anion in the training set. The latter may then be used as an alternative approach for determining the in-crystal polarizabilities of anions by exploiting the fact that the characteristic ω values depend linearly on the ionic radius of a cation participating in specific crystals containing these anions. Using this method we then calculate the isotropic dipole polarizabilities for F(-), Cl(-), O(2-), and S(2-) embedded in the LiF, LiCl, NaF, NaCl, KF, KCl, ZnO, ZnS, MgO, MgS, CaO, CaS, SrO, SrS, BaO, BaS, and other crystals containing halogen, oxygen, or sulphur anions. We compare our results with those obtained via alternative models of the in-crystal anionic polarizabilities.

Randomized cross-over trial to investigate the efficacy of a two-week physiotherapy programme with repetitive exercises of cueing to reduce the severity of freezing of gait in patients with Parkinson's disease.

OBJECTIVE: To investigate the efficacy of a two-week programme of repetitive exercise with cueing and movement strategies upon freezing of gait in people with Parkinson's disease. DESIGN: Randomized cross-over trial. SETTING: Specialist clinic for Parkinson's disease. SUBJECTS: A total of 22 patients with Parkinson's disease and freezing while other symptoms had favorably responded to dopaminergic treatment. INTERVENTION: Patients were randomized into a four-week cross-over trial, and received either treatment (Group 1) or no treatment (Group 2) during Period 1, and switched during Period 2. Treatment consisted of a two-week programme during which the patients exercised cueing, and movement strategies together with a physiotherapist. MAIN MEASURE: The primary outcome measure was a freezing score assessed from blinded and random ratings of video recordings. The secondary outcome measure was a patient-reported freezing questionnaire. Mean differences between the treatment periods (treatment arms) were evaluated for treatment (period) effects. Sums of treatment periods were evaluated for carry-over effects. RESULTS: The programme led to a significant treatment effect in the freezing score of 3.0 improvement (95% confidence interval 0.9-5.0; p < 0.01). No carry-over or period effects were detected. The questionnaire revealed a period effect, so groups were compared after Period 1, where a significant difference was found (15.0 vs. 11.7; p < 0.05). CONCLUSIONS: The two-week physiotherapy programme reduced the severity of freezing in patients with Parkinson's disease.

Changes in Candida spp., mutans streptococci and lactobacilli following treatment of early childhood caries: a 1-year follow-up.

Early childhood caries (ECC) is closely related to high numbers of mutans streptococci, lactobacilli and Candida albicans. Oral colonization of these microorganisms was monitored in a prospective clinical study in order to investigate the effect of comprehensive treatment under general anesthesia and the sustainability of microbial changes. Saliva samples were collected from 50 healthy infants with ECC before and in regular intervals up to 12 months after treatment. Microorganisms were detected by cultivation on selective agars (CRT® bacteria and Sabouraud/CandiSelect™) and scored. Additionally, plaque on upper front teeth and the dmft were recorded. Parents were repeatedly interviewed regarding the children's diet and oral hygiene, accompanied by corresponding advice. Plaque frequency and the numbers of mutans streptococci, lactobacilli and yeasts were significantly reduced as a result of treatment (p < 0.0001, Wilcoxon test). Nevertheless, this effect was not permanent. An ordinal regression model on the follow-up period revealed that the odds for bacteria and yeasts to reach a higher score increased linearly over time (p < 0.01) with an odds ratio of 2.244 per year. One third (34%) of the children developed new dentinal lesions within 1 year postoperatively. High scores of lactobacilli before treatment predicted caries relapse (p < 0.05). Nutritional and oral hygiene habits changed only slightly despite advising. Elimination and restoration of ECC lesions under general anesthesia proved to be an effective procedure in reducing cariogenic bacteria and yeasts. A satisfactory and sustainable success, however, could be achieved neither regarding microbiologic parameters nor with respect to the relapse rate. More suitable strategies are needed.

Tezepelumab in a case of severe asthma exacerbation and influenza-pneumonia on VV-ECMO.

We present a case of 43-year-old male patient with broadly by Omalizumab, Mepolizumab and Benralizumab pretreated allergic asthma, who suffered a near fatal exacerbation, triggered by an influenza A infection. Due to massive bronchoconstriction with consecutive hypercapnic ventilatory failure veno-venous ECMO therapy had to be implemented. Hence, guideline directed asthma therapy a substantial bronchodilatation could not be achieved. After administration of a single dose Tezepelumab, a novel TLSP-inhibitor, and otherwise unchanged therapy we documented a significant reduction in intrinsic PEEP measured via a naso-gastric balloon catheter and a narrowing in the expiratory flow curve of the ventilator within 24 hours. The consecutive ventilatory improvement allowed the successful weaning from veno-venous ECMO therapy and invasive ventilation.

No evidence for effects of low-intensity vestibular noise stimulation on mild-to-moderate gait impairments in patients with Parkinson's disease.

BACKGROUND: Gait impairment is a key feature in later stages of Parkinson's disease (PD), which often responds poorly to pharmacological therapies. Neuromodulatory treatment by low-intensity noisy galvanic vestibular stimulation (nGVS) has indicated positive effects on postural instability in PD, which may possibly be conveyed to improvement of dynamic gait dysfunction. OBJECTIVE: To investigate the effects of individually tuned nGVS on normal and cognitively challenged walking in PD patients with mild-to-moderate gait dysfunction. METHODS: Effects of nGVS of varying intensities (0-0.7 mA) on body sway were examined in 32 patients with PD (ON medication state, Hoehn and Yahr: 2.3 ± 0.5), who were standing with eyes closed on a posturographic force plate. Treatment response and optimal nGVS stimulation intensity were determined on an individual patient level. In a second step, the effects of optimal nGVS vs. sham treatment on walking with preferred speed and with a cognitive dual task were investigated by assessment of spatiotemporal gait parameters on a pressure-sensitive gait carpet. RESULTS: Evaluation of individual balance responses yielded that 59% of patients displayed a beneficial balance response to nGVS treatment with an average optimal improvement of 23%. However, optimal nGVS had no effects on gait parameters neither for the normal nor the cognitively challenged walking condition compared to sham stimulation irrespective of the nGVS responder status. CONCLUSIONS: Low-intensity nGVS seems to have differential treatment effects on static postural imbalance and continuous gait dysfunction in PD, which could be explained by a selective modulation of midbrain-thalamic circuits of balance control.

Low-intensity vestibular noise stimulation improves postural symptoms in progressive supranuclear palsy.

BACKGROUND: Postural imbalance and falls are an early disabling symptom in patients with progressive supranuclear palsy (PSP) of multifactorial origin that may involve abnormal vestibulospinal reflexes. Low-intensity noisy galvanic vestibular stimulation (nGVS) is a non-invasive treatment to normalize deficient vestibular function and attenuate imbalance in Parkinson's disease. The presumed therapeutic mode of nGVS is stochastic resonance (SR), a mechanism by which weak sensory noise stimulation can enhance sensory information processing. OBJECTIVE: To examine potential treatment effects of nGVS on postural instability in 16 patients with PSP with a clinically probable and [18F]PI-2620 tau-PET-positive PSP. METHODS: Effects of nGVS of varying intensity (0-0.7 mA) on body sway were examined, while patients were standing with eyes closed on a posturographic force plate. We assumed a bell-shaped response curve with maximal sway reductions at intermediate nGVS intensities to be indicative of SR. An established SR-curve model was fitted on individual patient outcomes and three experienced human raters had to judge whether responses to nGVS were consistent with the exhibition of SR. RESULTS: We found nGVS-induced reductions of body sway compatible with SR in 9 patients (56%) with optimal improvements of 31 ± 10%. In eight patients (50%), nGVS-induced sway reductions exceeded the minimal clinically important difference (improvement: 34 ± 5%), indicative of strong SR. CONCLUSION: nGVS yielded clinically relevant reductions in body sway compatible with the exhibition of SR in vestibular sensorimotor pathways in at least half of the assessed patients. Non-invasive vestibular noise stimulation may be thus a well-tolerated treatment strategy to ameliorate postural symptoms in PSP.