-
Brain Communications 2024Progressive supranuclear palsy is a neurodegenerative disease characterized by the deposition of four-repeat tau in neuronal and glial lesions in the brainstem,...
Progressive supranuclear palsy is a neurodegenerative disease characterized by the deposition of four-repeat tau in neuronal and glial lesions in the brainstem, cerebellar, subcortical and cortical brain regions. There are varying clinical presentations of progressive supranuclear palsy with different neuroimaging signatures, presumed to be due to different topographical distributions and burden of tau. The classic Richardson syndrome presentation is considered a subcortical variant, whilst progressive supranuclear palsy with predominant speech and language impairment is considered a cortical variant, although the pathological underpinnings of these variants are unclear. In this case-control study, we aimed to determine whether patterns of regional tau pathology differed between these variants and whether tau burden correlated with neuroimaging. Thirty-three neuropathologically confirmed progressive supranuclear palsy patients with either the Richardson syndrome ( = 17) or speech/language ( = 16) variant and magnetic resonance imaging were included. Tau lesion burden was semi-quantitatively graded in cerebellar, brainstem, subcortical and cortical regions and combined to form neuronal and glial tau scores. Regional magnetic resonance imaging volumes were converted to -scores using 33 age- and sex-matched controls. Diffusion tensor imaging metrics, including fractional anisotropy and mean diffusivity, were calculated. Tau burden and neuroimaging metrics were compared between groups and correlated using linear regression models. Neuronal and glial tau burden were higher in motor and superior frontal cortices in the speech/language variant. In the subcortical and brainstem regions, only the glial tau burden differed, with a higher burden in globus pallidus, subthalamic nucleus, substantia nigra and red nucleus in Richardson's syndrome. No differences were observed in the cerebellar dentate and striatum. Greater volume loss was observed in the motor cortex in the speech/language variant and in the subthalamic nucleus, red nucleus and midbrain in Richardson's syndrome. Fractional anisotropy was lower in the midbrain and superior cerebellar peduncle in Richardson's syndrome. Mean diffusivity was greater in the superior frontal cortex in the speech/language variant and midbrain in Richardson's syndrome. Neuronal tau burden showed associations with volume loss, lower fractional anisotropy and higher mean diffusivity in the superior frontal cortex, although these findings did not survive correction for multiple comparisons. Results suggest that a shift in the distribution of tau, particularly neuronal tau, within the progressive supranuclear palsy network of regions is driving different clinical presentations in progressive supranuclear palsy. The possibility of different disease epicentres in these clinical variants has potential implications for the use of imaging biomarkers in progressive supranuclear palsy.
PubMed: 38660629
DOI: 10.1093/braincomms/fcae113 -
MedRxiv : the Preprint Server For... Apr 2024Apraxia is a core feature of Alzheimer's disease, but the pathomechanism of this characteristic symptom is not well understood. Here, we systematically investigated...
OBJECTIVES
Apraxia is a core feature of Alzheimer's disease, but the pathomechanism of this characteristic symptom is not well understood. Here, we systematically investigated apraxia profiles in a well-defined group of patients with Alzheimer's disease (AD; N=32) who additionally underwent PET imaging with the second-generation tau PET tracer [18F]PI-2620. We hypothesized that specific patterns of tau pathology might be related to apraxic deficits.
METHODS
Patients (N=32) with a biomarker-confirmed diagnosis of Alzheimer's disease were recruited in addition to a sample cognitively unimpaired controls (CU ; N=41). Both groups underwent in-depth neuropsychological assessment of apraxia (Dementia Apraxia Screening Test; DATE and the Cologne Apraxia Screening; KAS). In addition, static PET imaging with [18F]PI-2620 was performed to assess tau pathology in the AD patients. To specifically investigate the association of apraxia with regional tau-pathology, we compared the PET-data from this group with an independent sample of amyloid-negative cognitively intact participants (CU N=54) by generation of z-score-deviation maps as well as voxel- based multiple regression analyses.
RESULTS
We identified significant clusters of tau-aggregation in praxis-related regions (e.g., supramarginal gyrus, angular gyrus, temporal, parietal and occipital regions) that were associated with apraxia. These regions were similar between the two apraxia assessments. No correlations between tau-tracer uptake in primary motor cortical or subcortical brain regions and apraxia were observed.
CONCLUSIONS
These results suggest that tau deposition in specific cortical brain regions may induce local neuronal dysfunction leading to a dose-dependent functional decline in praxis performance.
PubMed: 38645131
DOI: 10.1101/2024.04.09.24305535 -
International Journal of Yoga Therapy Apr 2024A previous study discovered that two speakers with moderate apraxia of speech increased their sequential motion rates after unilateral forced-nostril breathing (UFNB)...
A previous study discovered that two speakers with moderate apraxia of speech increased their sequential motion rates after unilateral forced-nostril breathing (UFNB) practiced as an adjunct to speech-language therapy in an AB repeated-measures design. The current study sought to: (1) delineate possible UFNB plus practice effects from practice effects alone in motor speech skills; (2) examine the relationships between UFNB integrity, participant-reported stress levels, and motor speech performance; and (3) sample a participant-led UFNB training schedule to contribute to the literature's growing understanding of UFNB dosage. A single-subject (n-of-1 trial), ABAB reversal design was used across four motor speech behaviors. A 60-year-old female with chronic, severe apraxia of speech participated. The researchers developed a breathing app to assess UFNB practice integrity and administer the Simple Aphasia Stress Scale after each UFNB session. The participant improved from overall severe to moderate apraxia of speech on the Apraxia Battery for Adults. Visual inspection of graphs confirmed robust motor speech practice effects for all variables. Articulatory-kinematic variables demonstrated sensitivity to the UFNB-plus-practice condition and correlated to stress scale scores but not UFNB integrity scores. The participant achieved 20-minute UFNB sessions 4 times per week. Removal of UFNB during A2 (UFNB withdrawal) and after a 10-day break during B2 (UFNB full dosage) revealed UFNB practice effects on stress scale scores. UFNB with motor speech practice may benefit articulatory-kinematic skills compared to motor speech practice alone. Regular, cumulative UFNB practice appeared to lower self-perceived stress levels. These findings, along with prior work, provide a foundation to further explore yoga breathing and its use with speakers who have apraxia of speech.
Topics: Adult; Female; Humans; Middle Aged; Yoga; Speech; Apraxias; Respiration; Aphasia
PubMed: 38640400
DOI: 10.17761/2024-D-22-00077 -
Cerebral Cortex (New York, N.Y. : 1991) Apr 2024Apraxia localization has relied on voxel-based, lesion-symptom mapping studies in left hemisphere stroke patients. Studies on the neural substrates of different...
Apraxia localization has relied on voxel-based, lesion-symptom mapping studies in left hemisphere stroke patients. Studies on the neural substrates of different manifestations of apraxia in neurodegenerative disorders are scarce. The primary aim of this study was to look into the neural substrates of different manifestations of apraxia in a cohort of corticobasal syndrome patients (CBS) by use of cortical thickness. Twenty-six CBS patients were included in this cross-sectional study. The Goldenberg apraxia test (GAT) was applied. 3D-T1-weighted images were analyzed via the automated recon-all Freesurfer version 6.0 pipeline. Vertex-based multivariate General Linear Model analysis was applied to correlate GAT scores with cortical thickness. Deficits in imitation of meaningless gestures correlated with bilateral superior parietal atrophy, extending to the angular and supramarginal gyri, particularly on the left. Finger imitation relied predominantly on superior parietal lobes, whereas the left angular and supramarginal gyri, in addition to superior parietal lobes, were critical for hand imitation. The widespread bilateral clusters of atrophy in CBS related to apraxia indicate different pathophysiological mechanisms mediating praxis in neurodegenerative disorders compared to vascular lesions, with implications both for our understanding of praxis and for the rehabilitation approaches of patients with apraxia.
Topics: Humans; Corticobasal Degeneration; Cross-Sectional Studies; Apraxias; Magnetic Resonance Imaging; Neurodegenerative Diseases; Atrophy; Imitative Behavior
PubMed: 38629797
DOI: 10.1093/cercor/bhae154 -
Cureus Mar 2024Apraxia of eyelid opening (AEO) is occasionally seen in Parkinson's disease (PD) or related diseases. However, many clinicians have trouble with the management of AEO by...
Apraxia of eyelid opening (AEO) is occasionally seen in Parkinson's disease (PD) or related diseases. However, many clinicians have trouble with the management of AEO by Parkinsonism. In this report, we describe a case of AEO in Parkinsonism improved by trihexyphenidyl (THP). The patient was a 64-year-old woman, who was previously healthy but developed bradykinesia. She was clinically diagnosed as PD due to an L-dopa challenge test, but no other detailed tests were performed. She started antiparkinsonian medications and her symptoms were improved at an early phase. However, her motor symptoms were gradually exacerbated over time, and antiparkinsonian medications were dosed up. At 69 years old, blepharospasm and AEO developed. Although other antiparkinsonian medications did not improve her AEO, THP cured AEO dramatically at 73 years old. In this report, we discuss a mechanism of AEO by Parkinsonism and the pathway of THP for the improvement of AEO.
PubMed: 38618350
DOI: 10.7759/cureus.56232 -
Eye and Brain 2024This review delineates the ocular motor disturbances across a spectrum of neurodegenerative disorders, including Alzheimer's Disease (AD) and related disorders (ADRD),... (Review)
Review
This review delineates the ocular motor disturbances across a spectrum of neurodegenerative disorders, including Alzheimer's Disease (AD) and related disorders (ADRD), Parkinson's Disease (PD), atypical parkinsonism, and others, leveraging advancements in eye-tracking technology for enhanced diagnostic precision. We delve into the different classes of eye movements, their clinical assessment, and specific abnormalities manifesting in these diseases, highlighting the nuanced differences and shared patterns. For instance, AD and ADRD are characterized by increased saccadic latencies and instability in fixation, while PD features saccadic hypometria and mild smooth pursuit impairments. Atypical parkinsonism, notably Progressive Supranuclear Palsy (PSP) and Corticobasal Syndrome (CBS), presents with distinct ocular motor signatures such as vertical supranuclear gaze palsy and saccadic apraxia, respectively. Our review underscores the diagnostic value of eye movement analysis in differentiating between these disorders and also posits the existence of underlying common pathological mechanisms. We discuss how eye movements have potential as biomarkers for neurodegenerative diseases but also some of the existing limitations.
PubMed: 38617403
DOI: 10.2147/EB.S384769 -
Case Reports in Oncological Medicine 2024Immune checkpoint inhibitors (ICIs) are a group of drugs that have improved outcomes for patients with various cancers. Generally considered safe and well tolerated,...
Immune checkpoint inhibitors (ICIs) are a group of drugs that have improved outcomes for patients with various cancers. Generally considered safe and well tolerated, these drugs are occasionally linked to immune-mediated or immune-related adverse events. Among these, autoimmune neurological events are rare, displaying varying incidence rates across different studies. Peripheral neuropathy, although one of the more common neurological immune-related events, is at times underestimated. This case report highlights an adult patient diagnosed with metastatic intrahepatic cholangiocarcinoma. Initially, the patient underwent chemoimmunotherapy with gemcitabine, cisplatin, and durvalumab for eight cycles, achieving partial response without significant toxicity. Following this, the patient continued with maintenance monotherapy with durvalumab every 28 days. After completing six cycles of maintenance therapy, the patient suddenly experienced paresthesia and hypoesthesia in four limbs, accompanied by apraxia in the hands that was more pronounced on the right side. Additionally, the patient reported neuropathic pain in the right arm and encountered limitations in certain instrumental activities of daily living. Diagnostic studies, including laboratory and electrophysiological studies, combined with the clinical presentation, identified immune-related peripheral polyneuropathy. Durvalumab was suspended and prednisolone therapy was initiated, resulting in a rapid resolution of all neuropathic symptoms. In addition to the clinical case, this article reviews the literature on immunotherapy-associated peripheral neuropathy.
PubMed: 38596399
DOI: 10.1155/2024/8212943 -
International Journal of Pediatric... Apr 2024Velocardiofacial syndrome, a prevalent microdeletion syndrome occurring in 1 in 2000-4000 live births, is marked by speech and language disorders, notably velopharyngeal...
OBJECTIVES
Velocardiofacial syndrome, a prevalent microdeletion syndrome occurring in 1 in 2000-4000 live births, is marked by speech and language disorders, notably velopharyngeal dysfunction. This study investigates speech outcomes, nasometric and videofluoroscopic results before and after primary repair of cleft palate using the Sommerlad intravelar veloplasty (SIVV) technique within the Isfahan cleft care team for patients with velocardiofacial syndrome.
METHODS
Employing a quasi-experimental design, 19 participants with velocardiofacial syndrome, who underwent primary cleft palate repair by the Isfahan cleft care team, were included through convenience sampling. Perceptual and instrumental outcomes were assessed pre-and post-operatively. Statistical analysis encompassed paired t-tests and the non-parametric Wilcoxon signed-rank test (p < 0.05).
RESULTS
The study identified no statistically significant differences between pre-and post-surgical speech outcome parameters and nasalance scores. Nonetheless, a significant distinction emerged in the velopharyngeal closure ratio based on fluoroscopic evaluation (p = 0.038).
CONCLUSION
The efficacy of the SIVV technique in treating velopharyngeal dysfunction in velocardiofacial syndrome patients is inconclusive, demanding further research. Post-surgical speech outcomes are influenced by surgical technique, hypotonia, apraxia of speech, and surgery timing. Notably, an elevated velopharyngeal valve closure ratio, though anatomically indicative, does not exclusively predict surgical success.
Topics: Humans; Cleft Palate; DiGeorge Syndrome; Plastic Surgery Procedures; Velopharyngeal Insufficiency; Treatment Outcome; Retrospective Studies; Speech; Palate, Soft
PubMed: 38588634
DOI: 10.1016/j.ijporl.2024.111940