Publications by authors named "Mana Higashihara"
Age-related trends in amyloid positivity in Parkinson's disease without dementia.
Aging (Albany NY)
August 2025
Amyloid-beta (Aβ) plays a pivotal role in cognitive decline in Parkinson's disease (PD). The prevalence of amyloid positivity, evaluated using the cerebrospinal fluid (CSF) of patients with PD without dementia in their sixties, is lower than that in individuals with normal cognition without PD diagnosis in the same age range. However, it is unclear whether this is also the case in patients with PD without dementia in their eighties.
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- α-synuclein seed amplification assays (α-syn SAA) show promise but may have reduced sensitivity due to variations among patients with Lewy body disease (LBD).
- In a study of 34 Parkinson's disease (PD) patients and 7 with dementia with Lewy bodies (DLB), 85.2% of those with abnormal cardiac MIBG scans tested positive for α-syn SAA, while only 14.3% of those with normal scans did.
- MIBG cardiac scintigraphy was identified as a significant factor influencing α-syn SAA positivity, indicating that while α-syn SAA can be sensitive for LBD in specific cases, its effectiveness may be diminished in patients with normal M
Article Synopsis
- Cortical hyperexcitability in amyotrophic lateral sclerosis (ALS) is linked to complex interactions between cortical interneurons, with this study examining GABA-ergic dysfunction via a combination of transcranial magnetic stimulation (TMS) and EEG.
- In 21 ALS patients, TMS-EEG results showed significant differences in the transcranial evoked potential (TEP) components compared to healthy controls, indicating impaired cortical inhibitory function.
- Notably, changes in TEP components correlated with muscle weakness and longer disease duration, highlighting the role of disrupted GABA-ergic circuits in the progression of ALS.
Associations of cerebrospinal fluid monoamine metabolites with striatal dopamine transporter binding and I-meta-iodobenzylguanidine cardiac scintigraphy in Parkinson's disease: Multivariate analyses.
Parkinsonism Relat Disord
November 2024
Article Synopsis
- In Parkinson's disease patients, levels of cerebrospinal fluid metabolites homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA), which are linked to dopamine and serotonin, are found to be decreased.
- A study involving 57 drug-naïve PD patients indicated significant differences in 5-HIAA levels between those with positive vs negative cardiac MIBG imaging, suggesting a direct association.
- Additionally, a correlation was found between HVA levels and striatal dopamine transporter binding, confirming that both HVA and 5-HIAA have important roles in PD pathology and imaging outcomes.
Cortical inexcitability in ALS: correlating a clinical phenotype.
J Neurol Neurosurg Psychiatry
March 2025
Background: Cortical inexcitability, a less studied feature of upper motor neuron (UMN) dysfunction in amyotrophic lateral sclerosis (ALS), was identified in a large cross-sectional cohort of ALS patients and their demographic and clinical characteristics were contrasted with normal or hyperexcitable ALS cohorts to assess the impact of cortical inexcitability on ALS phenotype and survival.
Methods: Threshold-tracking transcranial magnetic stimulation (TMS) technique with measurement of mean short interval intracortical inhibition (SICI) differentiated ALS patients into three groups (1) inexcitable (no TMS response at maximal stimulator output in the setting of preserved lower motor neuron (LMN) function), (2) hyperexcitable (SICI≤5.5%) and (3) normal cortical excitability (SICI>5.
An 81-year-old woman presented with statin-induced anti-HMGCR immune-mediated necrotizing myopathy. Treatment was successful without complications with a reduced oral steroid dosage from the current consensus for all ages and backgrounds. This case suggests the importance of early diagnosis and the possibility of steroid dosage adjustment considering the patient's age, disease severity, and comorbidities.
View Article and Find Full Text PDFIdentifying upper motor neuron (UMN) dysfunction is fundamental to the diagnosis and understanding of disease pathogenesis in motor neuron disease (MND). The clinical assessment of UMN dysfunction may be difficult, particularly in the setting of severe muscle weakness. From a physiological perspective, transcranial magnetic stimulation (TMS) techniques provide objective biomarkers of UMN dysfunction in MND and may also be useful to interrogate cortical and network function.
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- Argyrophilic grain disease (AGD) is linked to senile dementia, particularly cases where it is the sole pathological cause, also associated with parkinsonism.
- The study presents two autopsy cases of dementia with grains, highlighting distinct clinical features such as parkinsonism in one patient and pure amnestic dementia in another.
- Using cryo-electron microscopy, the researchers found a similar three-dimensional structure of tau protein in both cases and noted the presence of argyrophilic grains and tau structures in specific brain regions, suggesting a potential connection between AGD and parkinsonism.
Background And Purpose: Cortical hyperexcitability has been identified as a diagnostic and pathogenic biomarker of amyotrophic lateral sclerosis (ALS). Cortical excitability is assessed by transcranial magnetic stimulation (TMS), a non-invasive neurophysiological technique. The TMS biomarkers exhibiting highest sensitivity for cortical hyperexcitability in ALS remain to be elucidated.
View Article and Find Full Text PDFUtility of split hand index with different motor unit number estimation techniques in ALS.
Clin Neurophysiol
December 2023
Objective: Utility of the split hand index (SI) in amyotrophic lateral sclerosis (ALS) has been reported when using the compound muscle action potential (CMAP) amplitude method (SI). A motor unit number index (MUNIX) based SI method (SI) was purported to exhibit higher sensitivity. The present study assessed the clinical utility of SI, derived by CMAP amplitude, MUNIX and MScan-MUNE (SI) methods, in ALS.
View Article and Find Full Text PDFBackground: 18F-THK5351 PET is used to image ongoing astrogliosis by estimating monoamine oxidase B levels. 18F-THK5351 preferentially accumulates around the substantia nigra (SN) and periaqueductal gray (PG) in the midbrain under healthy conditions and exhibits a "trimodal pattern." In progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), the midbrain 18F-THK5351 uptake can be increased by astrogliosis, collapsing the "trimodal pattern.
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- Corticobasal syndrome (CBS) involves asymmetric symptoms due to issues in the cerebral cortex and basal ganglia, making early detection of imaging abnormalities difficult.
- Previous studies found asymmetric F-THK5351 PET abnormalities in CBS patients, but their effectiveness in larger early-stage groups needed further exploration.
- In a study of 15 CBS patients, 100% exhibited asymmetric tracer uptake on imaging, with F-THK5351 PET showing high sensitivity for identifying these abnormalities compared to other imaging techniques.
Introduction/aims: Reliable neurophysiological markers in amyotrophic lateral sclerosis (ALS) are of great interest. The compound muscle action potential (CMAP) amplitude has been a conventional marker, although it is greatly influenced by the electrode position. We propose the far-field potential of the CMAP (FFP-CMAP) as a new neurophysiological marker in ALS.
View Article and Find Full Text PDFEarly diagnosis of spinal cord subacute combined degeneration (SCD) is difficult, especially in pre-existing lower extremity impairment cases. We report a case of progressive SCD diagnosed after severe anemia. The peripheral symptoms of SCD other than gait disturbance should also be well understood and given close attention.
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- The study examines the relationship between cerebrospinal fluid (CSF) homovanillic acid (HVA) and striatal dopamine transporter (DAT) binding in patients with various neurological conditions, focusing on Parkinson's disease (PD) and progressive supranuclear palsy (PSP).
- Results indicate a significant correlation between CSF HVA levels and DAT binding, especially in patients with PD (r = 0.34) and PSP (r = 0.77), suggesting that lower DAT binding may be linked to dopamine levels in the brain.
- Findings reveal that patients with PSP had the lowest DAT binding compared to those with PD, indicating that striatal DAT reduction is more pronounced in PSP, potentially reflecting
Article Synopsis
- Autoantibodies to MuSK proteins are linked to severe cases of generalized myasthenia gravis (MG), often resulting in issues like breathing difficulties.
- Research shows that MuSK is present in the blood of both humans and mice, with levels rising significantly in cases of nerve damage and MG models.
- The release of MuSK into the bloodstream seems to be triggered by muscle issues at the neuromuscular junction, which may explain the difficulty in treating MuSK-related MG and highlight its potential use as a diagnostic biomarker for neuromuscular diseases.
Article Synopsis
- CSF p-tau181 is a key biomarker for Alzheimer's disease (AD) and the study aimed to see if it changes in patients with Neuronal Intranuclear Inclusion Disease (NIID), a neurodegenerative disorder.
- The research compared CSF biomarker levels, including p-tau181, across 12 NIID patients, 120 confirmed AD patients, and various other neurocognitive disorder patients.
- Results showed significantly elevated CSF p-tau181 levels in NIID patients compared to others, indicating that NIID might share some biochemical features with AD despite the differences in other biomarkers like Aβ42.
Article Synopsis
- A 52-year-old woman developed Wallenberg syndrome after experiencing upper respiratory symptoms, leading to CT and MRI scans that showed nodular lesions in both her lungs and brain.
- A lung biopsy confirmed a diagnosis of low-grade lymphomatoid granulomatosis.
- PET scans indicated varying levels of tracer uptake, suggesting inflammation and reactive astrogliosis in the brain lesions, highlighting the importance of PET studies in understanding this condition's diagnosis and underlying mechanisms.
Background: 18F-THK5351 PET estimates the concentrations of monoamine oxidase B (MAO-B) that are preferentially located in astrocytes and can be used to visualize and quantify ongoing astrogliosis. To study images of astrogliosis in neurological disorders, it is essential to understand the detailed binding sites of 18F-THK5351 as the MAO-B ligand under normal conditions. In this study, we examined the detailed distribution pattern of 18F-THK5351 in the healthy brain by comparing 18F-THK5351 uptake between subjects taking and not taking the MAO-B inhibitor.
View Article and Find Full Text PDFThe split-elbow index: A biomarker of the split elbow sign in ALS.
Clin Neurophysiol Pract
December 2021
Objective: The split elbow sign is a clinical feature of amyotrophic lateral sclerosis (ALS), characterised by preferential weakness of biceps brachii muscle compared to triceps. A novel neurophysiological index, termed the , was developed to quantify the split-elbow sign, and assess its utility in ALS.
Methods: Clinical and neurophysiological assessment was prospectively undertaken on 34 ALS patients and 32 ALS mimics.
Objective: The split-hand index (SI), a reliable diagnostic marker of amyotrophic lateral sclerosis (ALS), was prospectively assessed for differences across ALS subtypes and between the onset side of clinical symptoms or the dominant and contralateral sides. In addition, the prognostic utility of the SI was longitudinally assessed.
Methods: Two hundred and forty-five ALS patients underwent measurement of SI on both sides compared with 126 neuromuscular mimic disorders (NMD).
Article Synopsis
- Two patients with different forms of ALS underwent an 18F-THK5351 PET scan to examine areas of the brain affected by astrogliosis, which is related to disease progression.
- Patient 1 had flail leg syndrome, showing increased PET uptake in the motor cortex linked to the leg area.
- Patient 2, with ALS-frontotemporal dementia, displayed increased uptake in the left anterior temporal lobe, aligning with their neurological symptoms.
- This study suggests that 18F-THK5351 PET is an effective method for visualizing ALS-related brain lesions and understanding the disease's pathology.
Objective: To determine whether cortical hyperexcitability was more prominent in cognitively impaired patients with amyotrophic lateral sclerosis (ALS).
Methods: Threshold tracking transcranial magnetic stimulation (TMS) was used to assess cortical excitability and cognitive function was determined by the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Cognitive impairment was defined by ECAS < 105.