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Demencia/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Enfermedades Neurodegenerativas/diagnóstico por imagen , Neuroimagen/métodos , Trastornos Parkinsonianos/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Demencia/patología , Demencia/fisiopatología , Humanos , Enfermedades Neurodegenerativas/patología , Enfermedades Neurodegenerativas/fisiopatología , Trastornos Parkinsonianos/patología , Trastornos Parkinsonianos/fisiopatologíaRESUMEN
Introduction: Concussion is a growing public health concern. No uniformly established therapy exists; neurofeedback studies report treatment value. We use infralow frequency neuromodulation (ILF) to remediate disabling neurological symptoms caused by traumatic brain injury (TBI) and noted improved outcomes with a novel concussion protocol. Postconcussion symptoms (PCS) and persistent postconcussion symptoms (PPCS; >3 months post head injury) are designated timelines for protracted neurological complaints following TBI. We performed a retrospective study to explore effectiveness of ILF in PCS/PPCS and investigated the value of using this concussion protocol. Method: Patients with PCS/PPCS seen for their first neurology office visit or received their first neurofeedback session between 1 August 2018 and 31 January 2021 were entered. Outcomes were compared following treatment as usual (TAU) vs. TAU with ILF neurotherapy (TAU+ILF). The study cohort was limited to PPCS patients; the TAU+ILF group was restricted further to PPCS patients receiving at least 10 neurotherapy sessions. Within the TAU+ILF group, comparisons were made between those who trained at least 10 sessions using concussion protocol (TAU+ILF+CP) and those who trained for at least 10 sessions of ILF regardless of protocol (TAU+ILF-CP). Results: Among our resultant PPCS cohort (n = 59) leading persistent neurological complaints were headache (67.8%), memory impairment (57.6%), and brain fog (50.8%). PPCS patients in TAU+ILF+CP (n = 25) demonstrated greater net (p = 0.004) and percent (p = 0.026) improvement of symptoms compared to PPCS subjects in TAU (n = 26). PPCS patients in TAU+ILF-CP (n = 8) trended toward significant symptom improvements compared to TAU, and TAU+ILF+CP trended toward greater efficacy than TAU+ILF-CP. Conclusion: PPCS patients who received TAU+ILF+CP demonstrated significantly greater improvement as a group when compared to TAU. When used as an integrative modality to treatment as usual in managing patients with PPCS, ILF neuromodulation with use of concussion protocol provided significant symptom improvements.
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BACKGROUND: Progressive supranuclear palsy (PSP) is a neurodegenerative disease without approved therapies, and therapeutics are often tried off-label in the hope of slowing disease progression. Results from these experiences are seldom shared, which limits evidence-based knowledge to guide future treatment decisions. OBJECTIVES: To describe an open-label experience, including safety/tolerability, and longitudinal changes in biomarkers of disease progression in PSP-Richardson's syndrome (PSP-RS) patients treated with either salsalate or young plasma and compare to natural history data from previous multicenter studies. METHODS: For 6 months, 10 PSP-RS patients received daily salsalate 2,250 mg, and 5 patients received monthly infusions of four units of young plasma. Every 3 months, clinical severity was assessed with the Progressive Supranuclear Palsy Rating Scale (PSPRS), and MRI was obtained for volumetric measurement of midbrain. A range of exploratory biomarkers, including cerebrospinal fluid levels of neurofilament light chain, were collected at baseline and 6 months. Interventional data were compared to historical PSP-RS patients from the davunetide clinical trial and the 4-Repeat Tauopathy Neuroimaging Initiative. RESULTS: Salsalate and young plasma were safe and well tolerated. PSPRS change from baseline (mean ± standard deviation [SD]) was similar in salsalate (+5.6 ± 9.6), young plasma (+5.0 ± 7.1), and historical controls (+5.6 ± 7.1), and change in midbrain volume (cm3 ± SD) did not differ between salsalate (-0.07 ± 0.03), young plasma (-0.06 ± 0.03), and historical controls (-0.06 ± 0.04). No differences were observed between groups on any exploratory endpoint. CONCLUSIONS: Neither salsalate nor young plasma had a detectable effect on disease progression in PSP-RS. Focused open-label clinical trials incorporating historical clinical, neuropsychological, fluid, and imaging biomarkers provide useful preliminary data about the promise of novel PSP-directed therapies.
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Progressive supranuclear palsy (PSP) is associated with a variety of cognitive deficits, as well as motor and psychiatric disturbances. As clinical trials for PSP evolve, briefer screening instruments will be needed to determine cognitive effects of interventions. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) may fill this gap. Three hundred four participants diagnosed with Richardson's syndrome of PSP were evaluated with the RBANS, as well as other scales typically used in PSP. RBANS performances for these participants fell significantly below expectations for the Total Scale score and all five Indexes. Cognitive scores on the RBANS were also significantly related to other markers of PSP (e.g., motor and functional abilities, depression, global cognition). Compared to other clinical conditions from the literature, patients with PSP show impairment on tests of visuospatial perception and construction and attention. Although additional research is needed, the current study supports the clinical applicability of the RBANS in patients with PSP, as well as its potential for future clinical trials.
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Trastornos del Conocimiento/diagnóstico , Cognición/fisiología , Pruebas Neuropsicológicas , Parálisis Supranuclear Progresiva/complicaciones , Anciano , Atención , Trastornos del Conocimiento/complicaciones , Trastornos del Conocimiento/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Parálisis Supranuclear Progresiva/psicologíaRESUMEN
BACKGROUND: Progressive supranuclear palsy (PSP) -Richardson's Syndrome and Corticobasal Syndrome (CBS) are the two classic clinical syndromes associated with underlying four repeat (4R) tau pathology. The PSP Rating Scale is a commonly used assessment in PSP clinical trials; there is an increasing interest in designing combined 4R tauopathy clinical trials involving both CBS and PSP. OBJECTIVES: To determine contributions of each domain of the PSP Rating Scale to overall severity and characterize the probable sequence of clinical progression of PSP as compared to CBS. METHODS: Multicenter clinical trial and natural history study data were analyzed from 545 patients with PSP and 49 with CBS. Proportional odds models were applied to model normalized cross-sectional PSP Rating Scale, estimating the probability that a patient would experience impairment in each domain using the PSP Rating Scale total score as the index of overall disease severity. RESULTS: The earliest symptom domain to demonstrate impairment in PSP patients was most likely to be Ocular Motor, followed jointly by Gait/Midline and Daily Activities, then Limb Motor and Mentation, and finally Bulbar. For CBS, Limb Motor manifested first and ocular showed less probability of impairment throughout the disease spectrum. An online tool to visualize predicted disease progression was developed to predict relative disability on each subscale per overall disease severity. CONCLUSION: The PSP Rating Scale captures disease severity in both PSP and CBS. Modelling how domains change in relation to one other at varying disease severities may facilitate detection of therapeutic effects in future clinical trials.
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Enfermedades de los Ganglios Basales/fisiopatología , Progresión de la Enfermedad , Enfermedades Neurodegenerativas/fisiopatología , Índice de Severidad de la Enfermedad , Parálisis Supranuclear Progresiva/fisiopatología , Anciano , Anciano de 80 o más Años , Enfermedades de los Ganglios Basales/diagnóstico , Visualización de Datos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Neurológicos , Enfermedades Neurodegenerativas/diagnóstico , Pronóstico , Parálisis Supranuclear Progresiva/diagnóstico , SíndromeRESUMEN
This paper considers how parents are affected by and play a role in the lives of their young adult children. The years during which young people make the transition to adulthood has changed significantly in recent years--this transition now takes place over a longer period of time. We describe how young people experience these years; how they affect their parents and parent-child relationships; and how this time period is experienced by vulnerable youth.