-
Current Neurology and Neuroscience... Jul 2023Apraxia of speech (AOS) is a motor speech disorder that has long been recognized to occur secondary to acute neurologic insults and, more recently, to neurodegenerative... (Review)
Review
PURPOSE OF REVIEW
Apraxia of speech (AOS) is a motor speech disorder that has long been recognized to occur secondary to acute neurologic insults and, more recently, to neurodegenerative diseases as a harbinger for progressive supranuclear palsy and corticobasal syndrome. This article reviews recent findings regarding the clinic phenotypes of AOS, neuroimaging correlates, and the underlying disease processes.
RECENT FINDINGS
Two clinical subtypes of AOS map onto two underlying 4-repeat tauopathies. New imaging techniques have recently been applied to the study of progressive AOS. There is no data on the impact of behavioral intervention, although studies of nonfluent/agrammatic primary progressive aphasia that include patients with AOS suggest some benefit in speech intelligibility and maintenance. While recent findings suggest subtypes of AOS exist that are linked to molecular pathology and have important implications for disease progression, further research is needed to assess outcome of behavioral and other types of intervention.
Topics: Humans; Speech; Apraxias; Supranuclear Palsy, Progressive; Neuroimaging; Neurodegenerative Diseases
PubMed: 37269450
DOI: 10.1007/s11910-023-01275-1 -
Nature Aug 2023Speech brain-computer interfaces (BCIs) have the potential to restore rapid communication to people with paralysis by decoding neural activity evoked by attempted speech...
Speech brain-computer interfaces (BCIs) have the potential to restore rapid communication to people with paralysis by decoding neural activity evoked by attempted speech into text or sound. Early demonstrations, although promising, have not yet achieved accuracies sufficiently high for communication of unconstrained sentences from a large vocabulary. Here we demonstrate a speech-to-text BCI that records spiking activity from intracortical microelectrode arrays. Enabled by these high-resolution recordings, our study participant-who can no longer speak intelligibly owing to amyotrophic lateral sclerosis-achieved a 9.1% word error rate on a 50-word vocabulary (2.7 times fewer errors than the previous state-of-the-art speech BCI) and a 23.8% word error rate on a 125,000-word vocabulary (the first successful demonstration, to our knowledge, of large-vocabulary decoding). Our participant's attempted speech was decoded at 62 words per minute, which is 3.4 times as fast as the previous record and begins to approach the speed of natural conversation (160 words per minute). Finally, we highlight two aspects of the neural code for speech that are encouraging for speech BCIs: spatially intermixed tuning to speech articulators that makes accurate decoding possible from only a small region of cortex, and a detailed articulatory representation of phonemes that persists years after paralysis. These results show a feasible path forward for restoring rapid communication to people with paralysis who can no longer speak.
Topics: Humans; Amyotrophic Lateral Sclerosis; Brain-Computer Interfaces; Cerebral Cortex; Microelectrodes; Paralysis; Speech; Vocabulary; Neural Prostheses
PubMed: 37612500
DOI: 10.1038/s41586-023-06377-x -
Nature Aug 2023Speech neuroprostheses have the potential to restore communication to people living with paralysis, but naturalistic speed and expressivity are elusive. Here we use...
Speech neuroprostheses have the potential to restore communication to people living with paralysis, but naturalistic speed and expressivity are elusive. Here we use high-density surface recordings of the speech cortex in a clinical-trial participant with severe limb and vocal paralysis to achieve high-performance real-time decoding across three complementary speech-related output modalities: text, speech audio and facial-avatar animation. We trained and evaluated deep-learning models using neural data collected as the participant attempted to silently speak sentences. For text, we demonstrate accurate and rapid large-vocabulary decoding with a median rate of 78 words per minute and median word error rate of 25%. For speech audio, we demonstrate intelligible and rapid speech synthesis and personalization to the participant's pre-injury voice. For facial-avatar animation, we demonstrate the control of virtual orofacial movements for speech and non-speech communicative gestures. The decoders reached high performance with less than two weeks of training. Our findings introduce a multimodal speech-neuroprosthetic approach that has substantial promise to restore full, embodied communication to people living with severe paralysis.
Topics: Humans; Cerebral Cortex; Clinical Trials as Topic; Communication; Deep Learning; Face; Gestures; Movement; Neural Prostheses; Paralysis; Speech; Vocabulary; Voice
PubMed: 37612505
DOI: 10.1038/s41586-023-06443-4 -
Alternative Therapies in Health and... Oct 2023To investigate water exercise therapy's effect on lower limb function rehabilitation in patients with the first stroke. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To investigate water exercise therapy's effect on lower limb function rehabilitation in patients with the first stroke.
METHOD
160 patients with the first stroke and lower limb dysfunction who received rehabilitation treatment in the Geriatric Hospital of Hainan, China, from May 2020 to June 2021 were randomly divided into two groups, the control group, and the hydrotherapy group. Each group comprises 80 cases in each group. The control group received conventional drug therapy and traditional rehabilitation training, while the hydrotherapy group received underwater exercise training in combination with the routine group treatment plan. The National Health Center Stroke Scale (NIHSS), the modified Rankin scale (MRS), the limb motor function score table (Fugl-Meyer assessment, FMA), Functional Walking Scale (functional ambulation category scale, FAC), Berg Balance Scale (BBS) and the modified Barthel index (MBI) were respectively used to evaluate the neurological function, lower limb motor function, walking function, balance function and daily living ability before and after treatment.
RESULT
There was no significant difference in NIHSS, MRS, FMA, FAC, BBS, and MBI scores between the two groups before treatment (P > .05). However, after 8 weeks of treatment, there was a significant difference in FMA, FAC, BBS, and MBI scores between the two groups (P = .00035). The FMA scores in control group was 16.60 ± 4.49, while 21.45 ± 2.96 after treatment. The FAC scores in control group was 1.45 ± 0.68, while 1.95 ± 0.783 after treatment.
CONCLUSION
Early water exercise training in hemiplegic patients with the first stroke can significantly enhance the balance ability, walking ability as well as limb coordination of patients.
Topics: Humans; Aged; Stroke Rehabilitation; Aquatic Therapy; Hemiplegia; Stroke; Lower Extremity; Treatment Outcome
PubMed: 37573592
DOI: No ID Found -
Proceedings of the National Academy of... Oct 2023Despite much effort, antibody therapies for Alzheimer's disease (AD) have shown limited efficacy. Challenges to the rational design of effective antibodies include the...
Despite much effort, antibody therapies for Alzheimer's disease (AD) have shown limited efficacy. Challenges to the rational design of effective antibodies include the difficulty of achieving specific affinity to critical targets, poor expression, and antibody aggregation caused by buried charges and unstructured loops. To overcome these challenges, we grafted previously determined sequences of fibril-capping amyloid inhibitors onto a camel heavy chain antibody scaffold. These sequences were designed to cap fibrils of tau, known to form the neurofibrillary tangles of AD, thereby preventing fibril elongation. The nanobodies grafted with capping inhibitors blocked tau aggregation in biosensor cells seeded with postmortem brain extracts from AD and progressive supranuclear palsy (PSP) patients. The tau capping nanobody inhibitors also blocked seeding by recombinant tau oligomers. Another challenge to the design of effective antibodies is their poor blood-brain barrier (BBB) penetration. In this study, we also designed a bispecific nanobody composed of a nanobody that targets a receptor on the BBB and a tau capping nanobody inhibitor, conjoined by a flexible linker. We provide evidence that the bispecific nanobody improved BBB penetration over the tau capping inhibitor alone after intravenous administration in mice. Our results suggest that the design of synthetic antibodies that target sequences that drive protein aggregation may be a promising approach to inhibit the prion-like seeding of tau and other proteins involved in AD and related proteinopathies.
Topics: Humans; Animals; Mice; Alzheimer Disease; tau Proteins; Single-Domain Antibodies; Neurofibrillary Tangles; Supranuclear Palsy, Progressive; Antibodies; Brain
PubMed: 37801475
DOI: 10.1073/pnas.2300258120 -
Cell May 2024Tauopathies are age-associated neurodegenerative diseases whose mechanistic underpinnings remain elusive, partially due to a lack of appropriate human models. Here, we...
Tauopathies are age-associated neurodegenerative diseases whose mechanistic underpinnings remain elusive, partially due to a lack of appropriate human models. Here, we engineered human induced pluripotent stem cell (hiPSC)-derived neuronal lines to express 4R Tau and 4R Tau carrying the P301S MAPT mutation when differentiated into neurons. 4R-P301S neurons display progressive Tau inclusions upon seeding with Tau fibrils and recapitulate features of tauopathy phenotypes including shared transcriptomic signatures, autophagic body accumulation, and reduced neuronal activity. A CRISPRi screen of genes associated with Tau pathobiology identified over 500 genetic modifiers of seeding-induced Tau propagation, including retromer VPS29 and genes in the UFMylation cascade. In progressive supranuclear palsy (PSP) and Alzheimer's Disease (AD) brains, the UFMylation cascade is altered in neurofibrillary-tangle-bearing neurons. Inhibiting the UFMylation cascade in vitro and in vivo suppressed seeding-induced Tau propagation. This model provides a robust platform to identify novel therapeutic strategies for 4R tauopathy.
Topics: Humans; Induced Pluripotent Stem Cells; tau Proteins; Tauopathies; Neurons; Animals; Mice; Alzheimer Disease; Brain; Supranuclear Palsy, Progressive; Cell Differentiation; Mutation; Autophagy
PubMed: 38582079
DOI: 10.1016/j.cell.2024.03.015 -
Annual Review of Physiology Feb 2024Mitochondria play a key role in kidney physiology and pathology. They produce ATP to fuel energy-demanding water and solute reabsorption processes along the nephron.... (Review)
Review
Mitochondria play a key role in kidney physiology and pathology. They produce ATP to fuel energy-demanding water and solute reabsorption processes along the nephron. Moreover, mitochondria contribute to cellular health by the regulation of autophagy, (oxidative) stress responses, and apoptosis. Mitochondrial abundance is particularly high in cortical segments, including proximal and distal convoluted tubules. Dysfunction of the mitochondria has been described for tubulopathies such as Fanconi, Gitelman, and Bartter-like syndromes and renal tubular acidosis. In addition, mitochondrial cytopathies often affect renal (tubular) tissues, such as in Kearns-Sayre and Leigh syndromes. Nevertheless, the mechanisms by which mitochondrial dysfunction results in renal tubular diseases are only scarcely being explored. This review provides an overview of mitochondrial dysfunction in the development and progression of kidney tubulopathies. Furthermore, it emphasizes the need for further mechanistic investigations to identify links between mitochondrial function and renal electrolyte reabsorption.
Topics: Humans; Kidney Tubules; Bartter Syndrome; Kearns-Sayre Syndrome; Kidney Diseases; Mitochondria
PubMed: 38012047
DOI: 10.1146/annurev-physiol-042222-025000 -
Cleveland Clinic Journal of Medicine Jun 2024Gastroparesis is a heterogeneous motility disorder characterized by nausea, vomiting, and postprandial fullness. Its diagnosis requires objective documentation of... (Review)
Review
Gastroparesis is a heterogeneous motility disorder characterized by nausea, vomiting, and postprandial fullness. Its diagnosis requires objective documentation of delayed gastric emptying of solid food and exclusion of mechanical obstruction. Its epidemiology is unclear, and the main causes are diabetes mellitus and idiopathic disease. Cardinal symptoms often co-occur. Management involves nutritional assessment, dietary changes, drug evaluation, glycemic control (for patients with diabetes mellitus), and symptom relief. In this review, we explore challenges nongastroenterologists may encounter and how they can use current recommendations to manage patients with gastroparesis.
Topics: Gastroparesis; Humans; Gastric Emptying
PubMed: 38830702
DOI: 10.3949/ccjm.91a.23078 -
Current Opinion in Neurology Jun 2024Anti-IgLON5 disease is characterized by a distinctive sleep disorder, associated with a heterogeneous spectrum of neurological symptoms. Initial autopsies showed a novel... (Review)
Review
PURPOSE OF REVIEW
Anti-IgLON5 disease is characterized by a distinctive sleep disorder, associated with a heterogeneous spectrum of neurological symptoms. Initial autopsies showed a novel neuronal tauopathy predominantly located in the tegmentum of the brainstem. Recently, new diagnostic red flags, biomarkers predictors of response to immunotherapy, and novel insights into the autoimmune pathogenesis of the disease have been reported.
RECENT FINDINGS
Patients with diagnosis of neurodegenerative dementia, progressive supranuclear palsy (PSP) or with motor-neuron disease (MND)-like syndrome have been reported to have IgLON5 antibodies, which are the hallmark of anti-IgLON5 disease. Second, low levels of neurofilament light chain in serum and cerebrospinal fluid of patients at disease onset could be a predictor of immunotherapy response. Recent neuropathological studies indicate that the neuronal tau deposits occur late in the course of the disease. Moreover, IgLON5 antibodies induce cytoskeletal changes in cultured hippocampal neurons suggesting that the tauopathy could be secondary of the IgLON5 antibody effects.
SUMMARY
Anti-IgLON5 disease can mimic and should be considered in atypical presentations of MND, neurodegenerative dementia and PSP. Neurofilament light chain levels seem promising biomarker for disease prognosis. Finally, the neuropathological and in vitro experimental studies strengthen the autoimmune hypothesis of the disease.
Topics: Animals; Humans; Autoantibodies; Biomarkers; Cell Adhesion Molecules, Neuronal; Neurofilament Proteins; Supranuclear Palsy, Progressive; Motor Neuron Disease; Neurodegenerative Diseases
PubMed: 38563128
DOI: 10.1097/WCO.0000000000001271 -
Ugeskrift For Laeger Feb 2024Butterfly vertebra anomaly is a rare condition where the vertebral body fails to fuse during embryogenesis. In this case report, we present a 32-year-old male with...
Butterfly vertebra anomaly is a rare condition where the vertebral body fails to fuse during embryogenesis. In this case report, we present a 32-year-old male with progressive lower back pain and paralysis in both lower extremities. CT- and MR-scan showed an isolated L3 butterfly vertebra with a fusion of L2 and L3 discus through the defect and a discus prolapse compressing the spinal canal. The patient underwent successful decompressive surgery and experienced relief in symptoms post-operatively.
Topics: Male; Humans; Adult; Intervertebral Disc Displacement; Low Back Pain; Lower Extremity; Lumbar Vertebrae; Paralysis
PubMed: 38445324
DOI: 10.61409/V09230590