Impact of rhythmic auditory stimulation on gait disturbances in individuals with progressive supranuclear palsy

Atypical parkinsonism in the French West Indies

To the Editor: A woman in her 60s was referred to a memory disorders clinic with a 1-year history of memory loss. She also had multiple falls, mostly backward falls. Other problems included urinary incontinence, toe dystonia, depression, and behavioral abnormalities. She was originally diagnosed with atypical Parkinson's disease (PD) and had some response to levodopa with carbidopa. Examination found fluent speech with decreased content and slow irregular prosody, mild vertical gaze deficit, ptosis, and forward head tilt when gazing down. Review of the clinical presentation and brain magnetic resonance image (MRI) changed the diagnosis to progressive supranuclear palsy (PSP). PSP is an uncommon neurological disorder that clinically may resemble PD, but the pathophysiology is distinct from PD. PSP is a tauopathy, while PD is a ubiquitinopathy. PSP is in the same family as frontotemporal lobe degeneration. In PSP, abnormal tau is present in brain areas that are consistent with the clinical signs. One estimate of PSP prevalence in the United States is 1.39 per 100,000.1 This woman at first was felt to be a routine case of falling and memory loss, a common presentation in a geriatrics clinic. The lower extremity stiffness and tremor led to a preliminary diagnosis of atypical Parkinson's disease, but the brain MRI results led to the presumptive diagnosis of PSP. MRI showed mild to moderate cerebral volume loss, more prominent in the frontal lobes, and mild deformity and narrowing of the midbrain due to atrophy in a shape that suggested a bird, particularly a hummingbird, consistent with PSP (Figure 1). An expert committee defined criteria for the diagnosis of PSP. Major criteria are a gradual progressive disorder with onset after age 40, vertical supranuclear palsy (weakness in up-down gaze, especially down gaze) or slowing of vertical saccades (normal eye jerking when changing point of gaze), and postural instability with falls within the first year of disease onset.2 There is clinical similarity between PSP and PD. Both conditions include postural instability with falls,3 axial and limb rigidity, tremors, autonomic dysfunction, mood disorders,4, 5 and ophthalmic symptoms,6 but there are clinical differences that help separate the conditions. Eye signs are a cornerstone sign of PSP. Typically, downward gaze difficulty occurs early in the disease.7 Other distinguishing eye signs are slow blink rate and lid retraction, which produces a facial worried expression, different from PD's “masked face” or hypomimia countenance.7 Falls are more likely in the first 3 years with PSP, whereas the median for falls onset in PD is 9 years.3 The falling in PSP is more likely to be backward, probably because of retrocollis (tendency to tilt the head backward). Olfactory dysfunction is relatively specific for PD and can differentiate it from PSP.8 Therapeutic response to levodopa is more likely in PD.5, 9 The Food and Drug Administration has not approved any medication for PSP. Clinical trials of coenzyme Q10 have not been published. No evidence has been found of efficacy of any nondrug therapy. A combination of eye and balance rehabilitation was shown to have some positive effect in gaze control, gait, and general mobility in one study, but the effect was not shown to have benefit in terms of number of falls, quality of life, or mortality.10 One year after the examination, the woman was found to have fewer falls, presumably due to education about rising and sitting, safety measures (wheelchair seat belt), and compensating for neck rigidity. When she did fall, she was reported to have less injury, presumably due to padding of the floor and sharp edges. Her care burden had increased, and she was being moved to a facility with a higher level of care. Levodopa with carbidopa was believed to help reduce her tremors. Botulinum toxin was used for her toe dystonia. Memory loss and falling may be due to PSP. The diagnosis of PSP has a poor prognosis. There are no evidence-based therapies available, although physical therapy with balance training and family education may be helpful. The clinical picture of PSP overlaps with that of PD. Certain characteristics can help separate them, including the unique PSP brain MRI, eye signs, and falling history. Conflict of Interest: Dr. Hajjar receives salary support from a grant from Taibah University, Saudi Arabia. Author Contributions: The authors wrote the manuscript jointly. Sponsor's Role: Taibah University had no role in preparation of this paper.

Atypical parkinsonism in the French West Indies

BackgroundTraumatic brain injury (TBI) has been repeatedly shown to be a risk factor for several neurodegenerative diseases. However, no studies have yet examined TBI as a risk factor for corticobasal degeneration (CBD) or corticobasal syndrome (CBS), and few have examined progressive supranuclear palsy (PSP) in relation to TBI.MethodThis is a retrospective observational study using the National Alzheimer’s Coordinating Centers (NACC) database. TBI status was assessed based on self‐reported history. Clinicians estimate was used for determining age at onset (AAO) of cognitive decline and autopsy examination was used for neuropathological diagnosis of CBD and PSP. The most recent assessment of participants was used as of June 2018, including participant visits which occurred between 2005 and 2018. The NACC dataset includes a total of 38,249 participants. 101 (14 TBI+) participants were included with clinical (antemortem) diagnoses of PSP and 137 (16 TBI+) with CBS. 2,743 autopsy samples were also included, including 120 (14 TBI+), 58 (7 TBI+), and 11 (1 TBI+) with neuropathological (autopsy) diagnoses of PSP, CBD, or both, respectively. 181 (21 TBI+) of the participants with autopsy diagnosed PSP or CBD had antemortem cognitive decline.ResultTBI is associated with a significant 4‐year earlier AAO of cognitive decline among participants with an antemortem diagnosis of CBS and a 6‐year earlier AAO in participants with autopsy diagnosed PSP. Additionally, TBI among participants with autopsy diagnosed CBD without concomitant Alzheimer’s disease (AD) neuropathology was associated with a 7‐year earlier AAO of cognitive decline (p=.066). History of TBI was not significantly associated with the prevalence of PSP and/or CBD pathology postmortem.ConclusionThis is the first report linking TBI with an earlier onset of cognitive decline in CBS and in neuropathologically defined PSP.

To enhance the sensitivity and specificity of the clinical diagnosis of progressive supranuclear palsy (PSP), neuroradiological parameters established in pathologically proven cases are needed. We examined brainstem atrophy in five pathologically confirmed PSP patients (three men, mean age at death 77 years, range 64-84 years). Time interval between symptom onset and MRI ranged from 1 to 5 years, and between MRI and death from 33 to 52 months. Only one patient had clinical diagnosis of PSP at the time of MRI. Control group consisted of 19 age- and gender-matched healthy subjects. Seventeen morphometric parameters of the midbrain and pons were measured on T1-weighted midsagittal and T2-weighted axial MRI scans with Image Analyzer. Measurements of superior cerebellar peduncle (SCP) width were performed on PSP autopsy specimens. Mean SCP width on MRI in PSP (2.7 +/- 0.8 mm, 95%CI: 2.1-3.3) was smaller than in controls (3.7 +/- 0.5 mm, 95%CI: 3.5-3.9). Mean SCP width at autopsy was 8% smaller than mean SCP width on MRI. Midsagittal midbrain area in PSP (99.1 +/- 6.9 mm(2), 95%CI: 90.5-107.6) was smaller than in controls (141.0 +/- 18.1 mm(2), 95%CI: 132.2-149.7). Midbrain/pons area ratio in PSP was 1:5 and in controls was 1:4 (p < 0.01). Repeat MRI 17 months later in one PSP case revealed 30% decrease of SCP width. MR imaging with quantitative analysis may be useful in the diagnosis of early PSP and in monitoring disease course.

Parkinson’s disease (PD) is a debilitating neurodegenerative disorder causing many physical limitations. Rhythmic auditory stimulation (RAS) influences motor complications not alleviated by medicine and has been used to modify straight line walking in this population. However, motor complications are exacerbated during more complex movements including those involving direction changes. Thus immediate RAS effects on direction switch duration (DSD) and other kinematic measures during a multi-directional step task were investigated in PD patients. Long term RAS application was also explored by evaluating functional gait and balance and kinematic step measures before and after 6 weeks of multi-directional stepping either with (Cue, C group) or without (No cue, NC group) RAS use. Evaluations were also administered 1, 4 and 8 weeks after training termination. Kinematic measures were collected during stepping without, then with RAS for the C group and without RAS for the NC group. Step testing/training was performed at slow, normal and fast speeds in forward, back and side directions. Participants with PD switched step direction during the stepping task faster with RAS use before training. Like straight line walking RAS application influenced the more complex task of direction switching and counteracted the well-known bradykinesia in PD. After training both groups improved their functional gait and balance measures and maintained balance improvements for at least 8 weeks. Only the C group retained gait improvements for at least 8 weeks after training termination. Adding RAS resulted in functional benefits not observed in training without it. Kinematic measures compared before and after step training clarified the underlying contributors to functional performances. Both groups reduced the variability of DSD. The C group participants maintained this alteration longer. DSD reduction also occurred after training and was retained for at least 8 weeks for this group. These outcomes further support the advantages of adding RAS to training regiments for those with PD. The current results indicate that RAS effects are not limited to simple activities like straight line walking. Moreover, RAS can be used for improving and maintaining improvements longer in activities involving various forms of transition which present most difficulties for those with PD.

Background and purposeThis study presents a secondary analysis of a quasi-randomized clinical trial exploring the effects of immersive virtual reality (VR) rehabilitation alone versus in combination with Neurologic Music Therapy (NMT) in individuals with Parkinson's disease (PD).MethodsTwenty participants with idiopathic Parkinson's disease were allocated to two groups using a quasi-randomized procedure. One group received immersive VR-based gait training using the CAREN system (CAREN group), while the other received the same training protocol with the addition of NMT sensory-motor techniques delivered by a certified NMT therapist (CAREN-M group). Participants attended 12 rehabilitation sessions (three sessions per week over four weeks), each lasting approximately 45 min. Both groups underwent the same number, duration, and intensity of rehabilitation sessions. Clinical outcomes (BBS, Tinetti Scale, Barthel Index, 10-meter walking test, Timed-Up-Go) and biomechanical gait parameters (kinematic, kinetic, and electromyography data) were assessed for pre- and post-treatment.ResultsBoth interventions led to significant improvements in motor function, but group-specific patterns emerged. The CAREN group showed greater gains in spatial parameters, such as gait speed and stride length, alongside increased muscle activation and improved joint kinematics. The CAREN-M group exhibited superior improvements in temporal parameters (e.g., cycle and swing duration), trunk stability, and postural control, suggesting that rhythmic auditory stimulation (RAS) may enhance motor timing and coordination. Between-group comparisons showed a greater reduction in Time Up and Go (TUG) times in the CAREN-M group.Discussion and conclusionThese findings support the hypothesis that combining immersive VR (e.g., CAREN system) with NMT offers additive benefits by targeting distinct components of motor control through multisensory stimulation. The integration of rhythmic auditory cues into immersive VR environments can represent a promising direction for neurorehabilitation in PD, with the potential to improve functional mobility and gait quality.Trial Registration NumberNCT07066137.

Introduction: Parkinson’s Disease (PD) is a neurological illness characterised by impairments in movement, balance, coordination and gait caused by the absence or deficiency of dopamine and it is progressive in nature. The absence or decreased arm swing is a prodromal sign that may lead to gait impairments. Aim: To assess and analyse the effect of Rhythmic Auditory Stimulation (RAS) on arm swing and spatiotemporal gait parameters in conjunction with Cura Swing and Nordic Walking (NW). Materials and Methods: A quasi-experimental study was conducted at the Krupanidhi Group of Institutions, Bengaluru, Karnataka, India, which recruited 30 subjects based on specific inclusion criteria; the study duration was six months, from June 2022 to December 2022. After obtaining informed consent, participants were randomly divided into two groups, groups A and B, each consisting of 15 subjects, with interventions provided for five days each week over three weeks. The pre- and post-treatment evaluation included a 3D analysis using Kinovea and the Functional Gait Assessment (FGA). Group A, the control group, received 20 minutes of NW along with conventional physiotherapy, whilst group B received 20 minutes of RAS training through Cura Swing, followed by 20 minutes of NW. Results: After analysing the data using an Independent t-test, the results for Kinovea post forward swing and Kinovea post backward swing for both the right and left sides revealed a substantial difference between the two groups. Additional variables such as Timed Up and Go (TUG), cadence, stride length and FGA indicated significant differences between groups, with p-values of 0.01, 0.03, 0.009 and 0.02, respectively. Based on intergroup comparison analysis using a Paired t-test, there was a significant improvement in both groups independently regarding the measures of Kinovea forward and backward swing for both the right and left arms, TUG, cadence, stride length and FGA. Conclusion: RAS and NW programmes have shown beneficial effects on arm swing and balance. The lack of research in the literature concerning the therapeutic advantages of NW in conjunction with RAS as a holistic treatment contributes to the uniqueness of this study

Background. Rhythmic auditory stimulation (RAS) can influence movement during straight line walking and direction transition in individuals with Parkinson disease (PD). Objective. The authors studied whether multidirectional step training with RAS would generalize to functional gait conditions used in daily activities and balance. Methods. In a matched-pairs design, 8 patients practiced externally paced (EP) stepping (RAS group), and 8 patients practiced internally paced (IP) stepping (no RAS group) for 6 weeks. Participants were evaluated on the first and last days of practice, and 1 week, 4 weeks, and 8 weeks after practice termination. Evaluations included a primary measurement—the Dynamic Gait Index (DGI)—and secondary measurements—the Unified Parkinson’s Disease Rating Scale (UPDRS), Tinetti-gait and balance tests, Timed-Up-and-Go (TUG), and Freezing of Gait Questionnaire (FOGQ). Results. The RAS group significantly improved performance on the DGI and several secondary measures, and they maintained improvements for the DGI, Tinetti, FOGQ, and balance and gait items of the UPDRS above pretraining values at least 4 weeks after practice termination. The no RAS group revealed several improvements with training but could not maintain these improvements for as long as the other group. Conclusions. Individuals with PD can generalize motor improvements achieved during multidirectional step training to contexts of functional gait and balance. Training with RAS is advantageous for enhancing functional gait improvements and the maintenance of functional gait and balance improvements over 8 weeks.

Neuropathology of progressive supranuclear palsy after treatment with tilavonemab

We present the case of a 54-year-old male, without any significant medical history, who insidiously developed speech disturbances and walking difficulties, accompanied by backward falls. The symptoms progressively worsened over time. The patient was initially diagnosed with Parkinson's disease; however, he failed to respond to standard therapy with Levodopa. He came to our attention for worsening postural instability and binocular diplopia. A neurological exam was highly suggestive of a Parkinson-plus disease, most likely progressive supranuclear gaze palsy. Brain MRI was performed and revealed moderate midbrain atrophy with the characteristic "hummingbird" and "Mickey mouse" signs. An increased MR parkinsonism index was also noted. Based on all clinical and paraclinical data, a diagnosis of probable progressive supranuclear palsy was established. We review the main imaging features of this disease and their current role in diagnosis.

OBJECTIVE. Progressive supranuclear palsy (PSP) is listed as a core clinical feature in the Movement Disorder Society 2017 criteria, along with ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction. Imaging evidence shows predominant mid-brain atrophy and postsynaptic striatal dopaminergic degeneration as two supportive features. The purpose of this study was to investigate the diagnostic performance of 123I-N- ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (123I-FP-CIT) SPECT by comparing it with evaluation of core clinical features and MRI in the diagnosis of PSP. MATERIALS AND METHODS. The study included 53 patients with clinically suspected PSP who had undergone 123I-FP-CIT SPECT and MRI examinations. MR parkinsonism index (MRPI) was used as the MRI index. For the 123I-FP-CIT SPECT index, specific binding ratio (SBR) was calculated as the average of the right and left SBRs. RESULTS. In regard to core clinical features, ocular motor dysfunction was present in 15 of 20 (75.0%) patients with the diagnosis of probable PSP (p < 0.0001). Calculation of the diagnostic performance of the imaging parameters showed that MRPI (cutoff > 11.6) had 85.0% sensitivity, 100% specificity, and 94.3% accuracy. SBR (cutoff < 3.7) had 95.0% sensitivity, 36.4% specificity, and 58.5% accuracy. CONCLUSION. Iodine-123-labeled FP-CIT SPECT has high sensitivity, and MRI has high specificity in the diagnosis of PSP. Because these tools have complementary roles, reach ing a more confident clinical diagnosis of PSP may be possible when both are used.

Determine the prevalence, incidence, and clinical diagnostic accuracy for neuropathologically-diagnosed PSP.

IntroductionThe diagnosis of progressive supranuclear palsy (PSP) is often challenging since PSP may clinically resemble other neurodegenerative disorders. Recently, the tau PET tracer [18F]RO948, a potential new biomarker for PSP, was developed. The aim of this study was to determine the ability of three different biomarkers, including [18F]RO948 PET, to distinguish PSP patients from healthy controls and from patients with α-synucleinopathies. MethodsPatients with PSP (n = 23), α-synucleinopathies (n = 47) and healthy controls (n = 61) were included from the BioFINDER-2 study. [18F]RO948 standardized uptake value ratios (SUVR), magnetic resonance imaging midbrain/pons ratio, and cerebrospinal fluid neurofilament light (NfL) levels were compared between diagnostic groups individually and in combination. Results[18F]RO948 PET SUVR in the globus pallidus, NfL, and midbrain/pons area ratios were all able to differentiate PSP patients from controls and from patients with α-synucleinopathies ([18F]RO948 [mean ± SD]: controls 1.24 ± 0.22; PSP 1.47 ± 0.4; PD 1.18 ± 0.2; DLB 1.25 ± 0.24, p < 0.05), (NfL pg/mL [mean ± SD]: controls 1055 ± 569; PSP 2197 ± 1010; PD 1038 ± 416; DLB 1548 ± 687, p < 0.001) and (midbrain/pons ratio [mean ± SD]: controls 0.46 ± 0.07; PSP 0.34 ± 0.09; PD 0.43 ± 0.06; DLB 0.40 ± 0.07, p < 0.01). Receiver operating characteristic (ROC) analyses indicated that combining the three biomarkers resulted in the highest area under the ROC values (0.94 [0.88–1.00]) for separating controls from PSP and (0.92 [0.85–0.99]) for separating PSP from α-synucleinopathies. ConclusionsAll studied biomarkers could individually separate PSP from controls and α-synucleinopathies patients at a group level. The optimal prediction models included NfL and midbrain/pons ratio for separating controls from PSP and all three biomarkers for separating PSP from α-synucleinopathies.

Background/Aims Children with severe acquired brain injury frequently have walking rehabilitation goals. The aim of this study was to investigate if rhythmic auditory stimulation would improve walking speed and gait quality in children with acquired brain injury. Methods A total of four children were included in this study (age 10–12 years; mean time since acquired brain injury 12.75 weeks). A multiple baseline single case experimental study design was followed. The baseline phase (phase A) consisted of standard rehabilitation (10 physiotherapy sessions a week) and for the intervention phase (phase B), two out of the 10 sessions were replaced with rhythmic auditory stimulation. A 10-metre walk test and the Edinburgh Visual Gait Score was completed twice a week at the beginning and end of the session. Visual analysis of level, slope and trend, and statistical analysis of effect size (Tau-U) was conducted across phases. Descriptive analysis of within-session change was completed. Results All children showed improvement. In the 10-metre walk test, three children demonstrated a steeper trendline in phase A and one child demonstrated consistent trendlines between phases A and B. Tau-U indicated a small effect size (−0.207 (z =−1.32, P=0.1853)) that was not statistically significant for the Edinburgh Visual Gait Score; one child showed a steeper trendline in phase A and one in phase B, while others were consistent. One child’s Edinburgh Visual Gait Score improved greatly in phase B. Tau-U indicated a large effect size (−0.6235 (z=−3.9981, P=0.0001)) that was statistically significant. Within session changes indicated that, overall, children showed greater immediate changes with the Edinburgh Visual Gait Score and 10-metre walk test with the rhythmic auditory stimulation than with standard physiotherapy. Conclusions In addition to standard physiotherapy, rhythmic auditory stimulation may be of benefit to children relearning to walk after an acquired brain injury, potentially having a greater effect on gait biomechanics than walking speed. Rhythmic auditory stimulation can be considered alongside other gait interventions, but more research is required.