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Geriatrics (Basel, Switzerland) Mar 2024Intravenous thrombolysis and mechanical thrombectomy are the first-line reperfusion therapies for acute ischemic stroke. Here, we describe the utility of diffusion...
Diffusion MRI Fiber Tractography and Benzodiazepine SPECT Imaging for Assessing Neural Damage to the Language Centers in an Elderly Patient after Successful Reperfusion Therapy.
BACKGROUND
Intravenous thrombolysis and mechanical thrombectomy are the first-line reperfusion therapies for acute ischemic stroke. Here, we describe the utility of diffusion magnetic resonance imaging (MRI) fiber tractography and I-iomazenil benzodiazepine receptor single-photon emission computed tomography to estimate the prognosis of post-stroke aphasia after successful reperfusion therapy.
CASE REPORT
An 81-year-old man was admitted to the hospital approximately 3.5 h after the onset of symptoms, including decreased consciousness, right hemiparesis, and aphasia. An MRI revealed acute cerebral infarction due to M1 segment occlusion. Intravenous alteplase thrombolysis followed by endovascular thrombectomy resulted in recanalization of the left middle cerebral artery territory. A subsequent MRI showed no new ischemic or hemorrhagic lesions. Although the patient's motor hemiparesis gradually recovered, motor aphasia persisted. Diffusion MRI fiber tractography performed 2 weeks after admission revealed partial injury to the left arcuate fasciculus, indicated by lower fractional anisotropy values than on the contralateral side. A decreased benzodiazepine receptor density was also detected in the left perisylvian and temporoparietal cortices. The patient showed no clear signs of further improvement in the chronic stage post-stroke and was discharged to a nursing home after 3 months.
CONCLUSIONS
The application of functional neuroimaging techniques to assess neuronal damage to the primary brain regions 2 weeks after reperfusion therapy for large-vessel occlusion may allow for an accurate prognosis of post-stroke aphasia. This may have a direct clinical implication for navigating subacute-to-chronic phases of rehabilitative care.
PubMed: 38525747
DOI: 10.3390/geriatrics9020030 -
Clinical Neurophysiology : Official... May 2024We investigated the feasibility of recording cortico-cortical evoked potentials (CCEPs) in patients with low- and high-grade glioma. We compared CCEPs during awake and...
OBJECTIVE
We investigated the feasibility of recording cortico-cortical evoked potentials (CCEPs) in patients with low- and high-grade glioma. We compared CCEPs during awake and asleep surgery, as well as those stimulated from the functional Broca area and recorded from the functional Wernicke area (BtW), and vice versa (WtB). We also analyzed CCEP properties according to tumor location, histopathology, and aphasia.
METHODS
We included 20 patients who underwent minimally invasive surgery in an asleep-awake-asleep setting. Strip electrode placement was guided by classical Penfield stimulation of positive language sites and fiber tracking of the arcuate fascicle. CCEPs were elicited with alternating monophasic single pulses of 1.1 Hz frequency and recorded as averaged signals. Intraoperatively, there was no post-processing of the signal.
RESULTS
Ninety-seven CCEPs from 19 patients were analyzed. There was no significant difference in CCEP properties when comparing awake versus asleep, nor BtW versus WtB. CCEP amplitude and latency were affected by tumor location and histopathology. CCEP features after tumor resection correlated with short- and long-term postoperative aphasia.
CONCLUSION
CCEP recordings are feasible during minimally invasive surgery. CCEPs might be surrogate markers for altered connectivity of the language tracts.
SIGNIFICANCE
This study may guide the incorporation of CCEPs into intraoperative neurophysiological monitoring.
Topics: Humans; Glioma; Male; Female; Brain Neoplasms; Middle Aged; Adult; Aged; Evoked Potentials; Language; Minimally Invasive Surgical Procedures; Electric Stimulation; Intraoperative Neurophysiological Monitoring; Cerebral Cortex; Wakefulness
PubMed: 38521679
DOI: 10.1016/j.clinph.2023.12.136 -
Neurology. Genetics Apr 2024To introduce the first case in which primary progressive apraxia of speech (PPAOS) is associated with TAR DNA-binding protein 43 (TDP-43) instead of 4-repeat tau.
OBJECTIVES
To introduce the first case in which primary progressive apraxia of speech (PPAOS) is associated with TAR DNA-binding protein 43 (TDP-43) instead of 4-repeat tau.
METHODS
This patient was identified through a postmortem autopsy. Following an initial diagnostic evaluation, he participated in 3 annual research visits during which speech, language, cognitive, and neurologic assessments were administered. Neuroimaging was also acquired.
RESULTS
Apraxia of speech was diagnosed at his initial visit with a comprehensive neurologic examination further revealing subtle motor findings in the right hand. At subsequent visits, agrammatic aphasia and motor symptoms consistent with corticobasal syndrome were evident. Cognition and behavior remained relatively intact until advanced stages. FDG-PET revealed hypometabolism in the right temporoparietal cortex and left premotor and motor cortices. There was also low-level signal in the right temporoparietal cortex on tau-PET. A sequence variation in the progranulin gene was identified (GRN c.1A>C, p.Met1). Pathologic diagnosis was TDP-43 Type A with an atypical distribution of inclusions in premotor and motor cortices.
DISCUSSION
This case report demonstrates that TDP-43 Type A inclusions in an atypical distribution can present clinically as PPAOS. The sequence variation in the progranulin gene and asymmetric temporoparietal cortex involvement were the strongest indications of the unusual neuropathophysiology prior to autopsy.
PubMed: 38515991
DOI: 10.1212/NXG.0000000000200134 -
Journal of Neurology, Neurosurgery, and... Mar 2024Primary progressive aphasia (PPA) defines a group of neurodegenerative disorders characterised by language decline. Three PPA variants correlate with distinct underlying...
BACKGROUND
Primary progressive aphasia (PPA) defines a group of neurodegenerative disorders characterised by language decline. Three PPA variants correlate with distinct underlying pathologies: semantic variant PPA (svPPA) with transactive response DNA-binding protein of 43 kD (TDP-43) proteinopathy, agrammatic variant PPA (agPPA) with tau deposition and logopenic variant PPA (lvPPA) with Alzheimer's disease (AD). Our objectives were to differentiate PPA variants using clinical and neuroimaging features, assess progression and evaluate structural MRI and a novel 18-F fluorodeoxyglucose positron emission tomography (FDG-PET) image decomposition machine learning algorithm for neuropathology prediction.
METHODS
We analysed 82 autopsied patients diagnosed with PPA from 1998 to 2022. Clinical histories, language characteristics, neuropsychological results and brain imaging were reviewed. A machine learning framework using a -nearest neighbours classifier assessed FDG-PET scans from 45 patients compared with a large reference database.
RESULTS
PPA variant distribution: 35 lvPPA (80% AD), 28 agPPA (89% tauopathy) and 18 svPPA (72% frontotemporal lobar degeneration-TAR DNA-binding protein (FTLD-TDP)). Apraxia of speech was associated with 4R-tauopathy in agPPA, while pure agrammatic PPA without apraxia was linked to 3R-tauopathy. Longitudinal data revealed language dysfunction remained the predominant deficit for patients with lvPPA, agPPA evolved to corticobasal or progressive supranuclear palsy syndrome (64%) and svPPA progressed to behavioural variant frontotemporal dementia (44%). agPPA-4R-tauopathy exhibited limited pre-supplementary motor area atrophy, lvPPA-AD displayed temporal atrophy extending to the superior temporal sulcus and svPPA-FTLD-TDP had severe temporal pole atrophy. The FDG-PET-based machine learning algorithm accurately predicted clinical diagnoses and underlying pathologies.
CONCLUSIONS
Distinguishing 3R-taupathy and 4R-tauopathy in agPPA may rely on apraxia of speech presence. Additional linguistic and clinical features can aid neuropathology prediction. Our data-driven brain metabolism decomposition approach effectively predicts underlying neuropathology.
PubMed: 38514176
DOI: 10.1136/jnnp-2023-332862 -
Neurological Sciences : Official... Mar 2024Most stroke patients suffer from an imbalance in blood supply, which causes severe brain damage leading to functional deficits in motor, sensory, swallowing, cognitive,...
BACKGROUND
Most stroke patients suffer from an imbalance in blood supply, which causes severe brain damage leading to functional deficits in motor, sensory, swallowing, cognitive, emotional, and speech functions. Repetitive transcranial magnetic stimulation (rTMS) is thought to restore functions impaired during the stroke process and improve the quality of life of stroke patients. However, the efficacy of rTMS in treating post-stroke function impairment varies significantly. Therefore, we conducted a meta-analysis of the number of patients with effective rTMS in treating post-stroke dysfunction.
METHODS
The PubMed, Embase, and Cochrane Library databases were searched. Screening and full-text review were performed by three investigators. Single-group rate meta-analysis was performed on the extracted data using a random variable model. Then subgroup analyses were performed at the levels of stroke acuity (acute, chronic, or subacute); post-stroke symptoms (including upper and lower limb motor function, dysphagia, depression, aphasia); rTMS stimulation site (affected side, unaffected side); and whether or not it was a combination therapy.
RESULTS
We obtained 8955 search records, and finally 33 studies (2682 patients) were included in the meta-analysis. The overall analysis found that effective strength (ES) of rTMS was 0.53. In addition, we found that the ES of rTMS from acute/subacute/chronic post-stroke was 0.69, 0.45, and 0.52. We also found that the ES of rTMS using high-frequency stimulation was 0.56, while the ES of rTMS using low-frequency stimulation was 0.53. From post-stroke symptoms, we found that the ES of rTMS in sensory aspects, upper limb functional aspects, swallowing function, and aphasia was 0.50, 0.52, 0.51, and 0.54. And from the site of rTMS stimulation, we found that the ES of rTMS applied to the affected side was 0.51, while the ES applied to the unaffected side was 0.54. What's more, we found that the ES of rTMS applied alone was 0.53, while the ES of rTMS applied in conjunction with other therapeutic modalities was 0.53.
CONCLUSIONS
By comparing the results of the data, we recommend rTMS as a treatment option for rehabilitation of functional impairment in patients after stroke. We also recommend that rehabilitation physicians or clinicians use combination therapy as one of the options for patients.
PubMed: 38512529
DOI: 10.1007/s10072-024-07455-2 -
International Journal of Stroke :... Apr 2024Three large randomized controlled trials of fluoxetine for stroke recovery have been performed. We performed an individual patient data meta-analysis (IPDM) on the...
BACKGROUND
Three large randomized controlled trials of fluoxetine for stroke recovery have been performed. We performed an individual patient data meta-analysis (IPDM) on the combined data.
METHODS
Fixed effects meta-analyses were performed on the combined data set, for the primary outcome (modified Rankin scale (mRS) at 6 months), and secondary outcomes common to the individual trials. As a sensitivity analysis, summary statistics from each trial were created and combined.
FINDINGS
The three trials recruited a combined total of 5907 people (mean age 69.5 years (SD 12.3), 2256 (38%) females, 2-15 days post-stroke) from Australia, New Zealand, United Kingdom, Sweden, and Vietnam; and randomized them to fluoxetine 20 mg daily or matching placebo for 6 months. Data on 5833 (98.75%) were available at 6 months. The adjusted ordinal comparison of mRS was similar in the two groups (common OR 0.96, 95% CI 0.87 to 1.05, p = 0.37). There were no statistically significant interactions between the minimization variables (baseline probability of being alive and independent at 6 months, time to treatment, motor deficit, or aphasia) and pre-specified subgroups (including age, pathological type, inability to assess mood, proxy or patient consent, baseline depression, country). Fluoxetine increased seizure risk (2.64% vs 1.8%, p = 0.03), falls with injury (6.26% vs 4.51%, p = 0.03), fractures (3.15% vs 1.39%, p < 0.0001) and hyponatremia (1.22% vs 0.61%, p = 0.01) but reduced new depression (10.05% vs 13.42%, p < 0.0001). At 12 months, there was no difference in adjusted mRS (n = 5760; common OR 0.98, 95% CI 0.89 to 1.07). Sensitivity analyses gave the same results.
INTERPRETATION
Fluoxetine 20 mg daily for 6 months did not improve functional recovery. It increased seizures, falls with injury, and bone fractures but reduced depression frequency at 6 months.
PubMed: 38497332
DOI: 10.1177/17474930241242628 -
International Journal of Molecular... Mar 2024The L1 cell adhesion molecule (L1) has demonstrated a range of beneficial effects in animal models of spinal cord injury, neurodegenerative disease, and ischemia;...
The L1 cell adhesion molecule (L1) has demonstrated a range of beneficial effects in animal models of spinal cord injury, neurodegenerative disease, and ischemia; however, the role of L1 in TBI has not been fully examined. Mutations in the gene affecting the extracellular domain of this type 1 transmembrane glycoprotein have been identified in patients with L1 syndrome. These patients suffer from hydrocephalus, MASA (mental retardation, adducted thumbs, shuffling gait, aphasia) symptoms, and corpus callosum agenesis. Clinicians have observed that recovery post-traumatic brain injury (TBI) varies among the population. This variability may be explained by the genetic differences present in the general population. In this study, we utilized a novel mouse model of L1 syndrome with a mutation at aspartic acid position 201 in the extracellular domain of L1 (L1-201). We assessed the impact of this specific single nucleotide polymorphism (SNP) localized to the X-chromosome gene on recovery outcomes following TBI by comparing the L1-201 mouse mutants with their wild-type littermates. We demonstrate that male L1-201 mice exhibit significantly worse learning and memory outcomes in the Morris water maze after lateral fluid percussion (LFP) injury compared to male wild-type mice and a trend to worse motor function on the rotarod. However, no significant changes were observed in markers for inflammatory responses or apoptosis after TBI.
Topics: Humans; Male; Animals; Mice; Neural Cell Adhesion Molecule L1; Neurodegenerative Diseases; Polymorphism, Single Nucleotide; Hydrocephalus; Brain Injuries, Traumatic; Intellectual Disability; Spastic Paraplegia, Hereditary; Genetic Diseases, X-Linked
PubMed: 38474289
DOI: 10.3390/ijms25053043 -
Cerebral Cortex (New York, N.Y. : 1991) Mar 2024Speech disorders are associated with different degrees of functional and structural abnormalities. However, the abnormalities associated with specific disorders, and the... (Meta-Analysis)
Meta-Analysis
Speech disorders are associated with different degrees of functional and structural abnormalities. However, the abnormalities associated with specific disorders, and the common abnormalities shown by all disorders, remain unclear. Herein, a meta-analysis was conducted to integrate the results of 70 studies that compared 1843 speech disorder patients (dysarthria, dysphonia, stuttering, and aphasia) to 1950 healthy controls in terms of brain activity, functional connectivity, gray matter, and white matter fractional anisotropy. The analysis revealed that compared to controls, the dysarthria group showed higher activity in the left superior temporal gyrus and lower activity in the left postcentral gyrus. The dysphonia group had higher activity in the right precentral and postcentral gyrus. The stuttering group had higher activity in the right inferior frontal gyrus and lower activity in the left inferior frontal gyrus. The aphasia group showed lower activity in the bilateral anterior cingulate gyrus and left superior frontal gyrus. Across the four disorders, there were concurrent lower activity, gray matter, and fractional anisotropy in motor and auditory cortices, and stronger connectivity between the default mode network and frontoparietal network. These findings enhance our understanding of the neural basis of speech disorders, potentially aiding clinical diagnosis and intervention.
Topics: Humans; Dysarthria; Stuttering; Likelihood Functions; Dysphonia; Speech Disorders; Auditory Cortex; Aphasia
PubMed: 38466117
DOI: 10.1093/cercor/bhae075 -
Cureus Feb 2024There is a complex link between tuberculous meningitis (TBM) and aphasia, in which a language impairment is caused by an injury to the cortical language centre. The...
There is a complex link between tuberculous meningitis (TBM) and aphasia, in which a language impairment is caused by an injury to the cortical language centre. The parts of the brain that function for speech and language production are the Wernicke's, Broca's, and arcuate fasciculus regions. This case report mainly highlights the neurological consequences of TBM, and how it affects language and speech functioning. It outlines a comprehensive physiotherapy rehabilitation program that targets a range of issues for the patient, such as verbal output, weakness, motor deficits, articulation issues in speech, and coordination issues. Various treatment modalities can help correct weakness, improve balance and coordination, increase flexibility and range of motion (ROM), and make speech more fluent. The case report emphasizes the necessity of using an integrated approach that combines speech-language therapy (SLT), melodic intonation therapy (MIT), constraint-induced aphasia therapy (CIAT), medication treatments, and physical therapy to address the multifaceted impacts of TBM-induced aphasia on a patient's quality of life (QOL).
PubMed: 38465188
DOI: 10.7759/cureus.53793 -
Frontiers in Human Neuroscience 2024Over one-third of stroke survivors develop aphasia, and language dysfunction persists for the remainder of their lives. Brain language network changes in patients with...
Case report: An N-of-1 study using amplitude modulated transcranial alternating current stimulation between Broca's area and the right homotopic area to improve post-stroke aphasia with increased inter-regional synchrony.
Over one-third of stroke survivors develop aphasia, and language dysfunction persists for the remainder of their lives. Brain language network changes in patients with aphasia. Recently, it has been reported that phase synchrony within a low beta-band (14-19 Hz) frequency between Broca's area and the homotopic region of the right hemisphere is positively correlated with language function in patients with subacute post-stroke aphasia, suggesting that synchrony is important for language recovery. Here, we employed amplitude-modulated transcranial alternating current stimulation (AM-tACS) to enhance synchrony within the low beta band frequency between Broca's area and the right homotopic area, and to improve language function in a case of chronic post-stroke aphasia. According to an N-of-1 study design, the patient underwent short-term intervention with a one-time intervention of 15 Hz-AM-tACS with Broca's and the right homotopic areas (real condition), sham stimulation (sham condition), and 15 Hz-AM-tACS with Broca's and the left parietal areas (control condition) and long-term intervention with sham and real conditions (10 sessions in total, each). In the short-term intervention, the reaction time and accuracy rate of the naming task improved after real condition, not after sham and control conditions. The synchrony between the stimulated areas evaluated by coherence largely increased after the real condition. In the long-term intervention, naming ability, verbal fluency and overall language function improved, with the increase in the synchrony, and those improvements were sustained for more than a month after real condition. This suggests that AM-tACS on Broca's area and the right homotopic areas may be a promising therapeutic approach for patients with poststroke aphasia.
PubMed: 38454909
DOI: 10.3389/fnhum.2024.1297683