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1.
Neurology ; 103(3): e209606, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-38976821

RESUMEN

BACKGROUND AND OBJECTIVES: Neural computations underlying gait disorders in Parkinson disease (PD) are multifactorial and involve impaired expression of stereotactic locomotor patterns and compensatory recruitment of cognitive functions. This study aimed to clarify the network mechanisms of cognitive contribution to gait control and its breakdown in patients with PD. METHODS: Patients with PD were instructed to walk at a comfortable pace on a mat with pressure sensors. The characterization of cognitive-motor interplay was enhanced by using a gait with a secondary cognitive task (dual-task condition) and a gait without additional tasks (single-task condition). Participants were scanned using 3-T MRI and 123I-ioflupane SPECT. RESULTS: According to gait characteristics, cluster analysis assisted by a nonlinear dimensionality reduction technique, t-distributed stochastic neighbor embedding, categorized 56 patients with PD into 3 subpopulations. The preserved gait (PG) subgroup (n = 23) showed preserved speed and variability during gait, both with and without additional cognitive load. Compared with the PG subgroup, the mildly impaired gait (MIG) subgroup (n = 16) demonstrated deteriorated gait variability with additional cognitive load and impaired speed and gait variability without additional cognitive load. The severely impaired gait (SIG) subgroup (n = 17) revealed the slowest speed and highest gait variability. In addition, group differences were found in attention/working memory and executive function domains, with the lowest performance in the SIG subgroup than in the PG and MIG subgroups. Using resting-state functional MRI, the SIG subgroup demonstrated lower functional connectivity of the left and right frontoparietal network (FPN) with the caudate than the PG subgroup did (left FPN, d = 1.21, p < 0.001; right FPN, d = 1.05, p = 0.004). Cortical thickness in the FPN and 123I-ioflupane uptake in the striatum did not differ among the 3 subgroups. By contrast, the severity of Ch4 density loss was significantly correlated with the level of functional connectivity degradation of the FPN and caudate (left FPN-caudate, r = 0.27, p = 0.04). DISCUSSION: These findings suggest that the functional connectivity of the FPN with the caudate, as mediated by the cholinergic Ch4 projection system, underlies the compensatory recruitment of attention and executive function for damaged automaticity in gait in patients with PD.


Asunto(s)
Trastornos Neurológicos de la Marcha , Imagen por Resonancia Magnética , Enfermedad de Parkinson , Tomografía Computarizada de Emisión de Fotón Único , Humanos , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/complicaciones , Masculino , Femenino , Anciano , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/fisiopatología , Trastornos Neurológicos de la Marcha/diagnóstico por imagen , Persona de Mediana Edad , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/fisiopatología , Cuerpo Estriado/diagnóstico por imagen , Cuerpo Estriado/fisiopatología , Lóbulo Parietal/diagnóstico por imagen , Lóbulo Parietal/fisiopatología , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiopatología , Vías Nerviosas/fisiopatología , Vías Nerviosas/diagnóstico por imagen , Núcleo Basal de Meynert/fisiopatología , Núcleo Basal de Meynert/diagnóstico por imagen , Nortropanos
2.
Ann Neurol ; 92(1): 110-121, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35428994

RESUMEN

OBJECTIVE: The motor severity in Parkinson disease (PD) is believed to parallel dopaminergic terminal degeneration in the striatum, although the terminal was reported to be virtually absent by 4 years postdiagnosis. Meanwhile, neuromelanin-laden dopamine neuron loss in the substantia nigra (SN) elucidated a variability at early stages and gradual loss with less variability 10 years postdiagnosis. Here, we aimed to clarify the correlation between motor impairments and striatal dopaminergic terminal degeneration and nigral neuromelanin-laden dopamine neuron loss at early to advanced stages of PD. METHODS: Ninety-three PD patients were divided into early and advanced subgroups based on motor symptom duration and whether motor fluctuation was present. Striatal dopaminergic terminal degeneration was evaluated using a presynaptic dopamine transporter tracer, 123 I-ioflupane single photon emission computed tomography (SPECT). Nigral neuromelanin-laden dopamine neuron density was assessed by neuromelanin-sensitive magnetic resonance imaging (NM-MRI). RESULTS: In patients with early stage PD (motor symptoms for ≤8 or 10 years), motor dysfunction during the drug-off state was paralleled by a decline in 123 I-ioflupane uptake in the striatum despite the absence of a correlation with reductions in NM-MRI signals in SN. Meanwhile, in patients with advanced stage PD (motor symptoms for >8 or 10 years and with fluctuation), the degree of motor deficits during the drug-off state was not correlated with 123 I-ioflupane uptake in the striatum, despite its significant negative correlation with NM-MRI signals in SN. INTERPRETATION: We propose striatal dopaminergic terminal loss measured using 123 I-ioflupane SPECT and nigral dopamine neuron loss assessed with NM-MRI as early stage and advanced stage motor impairment biomarkers, respectively. ANN NEUROL 2022;92:110-121.


Asunto(s)
Enfermedad de Parkinson , Cuerpo Estriado/metabolismo , Dopamina , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Neuronas Dopaminérgicas/patología , Humanos , Imagen por Resonancia Magnética/métodos , Degeneración Nerviosa/diagnóstico por imagen , Degeneración Nerviosa/patología , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagen , Sustancia Negra/patología , Tomografía Computarizada de Emisión de Fotón Único/métodos
3.
Clin Neurophysiol Pract ; 6: 191-193, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34307969

RESUMEN

BACKGROUND: Multifocal motor neuropathy (MMN) occasionally presents with cranial nerve involvement. However, no MMN cases with visual pathway impairment demonstrated by visual evoked potential (VEP) have been reported. CASE REPORT: A 36-year-old man was admitted to our hospital with progressive muscular weakness. On admission, neurological findings revealed bilateral muscle weakness and atrophy of the distal upper limbs. The blood tests were positive for GM-1 ganglioside antibodies. Nerve conduction studies revealed bilateral conduction block in the median nerve. He was diagnosed with MMN. Intravenous immunoglobulin treatment improved muscle weakness and blurred vision, which was not a complaint when he was first seen. Moreover, VEP showed a post-treatment shortening of P100 latency. These treatment effects were consistently observed for 3.5 years. SIGNIFICANCE: Our findings suggested that MMN could affect the visual pathway through autoimmune mechanisms.

4.
Mov Disord Clin Pract ; 8(1): 126-132, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33426168

RESUMEN

BACKGROUND: Mutations in the tau gene linked to chromosome 17 cause frontotemporal dementia and parkinsonism (FTDP-17). OBJECTIVE: This study presents 3 Japanese familial cases diagnosed with N279K tau gene mutation, including 1 autopsy-confirmed case. METHODS: We compared the clinical presentations, cognitive functions, and images between the 3 familial cases diagnosed with N279K mutation. RESULTS: All 3 patients presented symptoms in their early 40s. One patient showed severe cognitive dysfunction and died in his sixth year after onset. The remaining 2 cases presented with parkinsonism-dominant clinical features. Among the 2 cases, 1 presented the characteristic symptoms of progressive supranuclear palsy. The pathological features of the dementia-dominant case showed frontal and temporal lobe-dominant neuronal loss and gliosis. Tau-positive neuronal and glial inclusions were found throughout. Further, tufted astrocytes and globose tangles were present whereas there were no Pick bodies and astrocytic plaques, compatible with pathology-confirmed frontotemporal lobar degeneration (FTLD) -tau subtypes. CONCLUSIONS: Patients with FTDP-17 can be classified into the following 2 major groups: dementia and parkinsonism-plus predominant phenotypes. Among our 3 cases, 1 showed dementia predominance whereas the other 2 showed parkinsonism predominance. Mutations in the microtubule-associated protein tau (MAPT) present with several pathological features. Clinically, our case presented a behavioral variant frontotemporal dementia (bvFTD). However, morphologically, the observed glial and neuronal pathology met the criteria for progressive supranuclear palsy (PSP). This study highlights the clinical heterogeneity within and between families with same MAPT mutation. Few pathologically confirmed PSP cases have been reported with mutations in MAPT.

5.
Intern Med ; 56(24): 3347-3351, 2017 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-29021436

RESUMEN

Autoimmune autonomic ganglionopathy is an autonomic disorder that occurs as a symptom of paraneoplastic neurological syndrome. To date, there have been no reports on multiple myeloma with autoimmune autonomic ganglionopathy. A 37-year-old Japanese woman suffered from orthostatic hypotension was diagnosed with multiple myeloma (IgG kappa type), and a serological examination revealed the presence of anti-ganglionic nicotinic acetylcholine receptor (anti-gAChR) antibodies. She was treated for multiple myeloma, as a result, the autonomic disturbance improved and her anti-gAChR antibody titer decreased to undetectable levels, despite the fact that she only achieved a partial remission of multiple myeloma. Treatment for multiple myeloma may improve autoimmune autonomic ganglionopathy.


Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/complicaciones , Ganglios Autónomos/patología , Mieloma Múltiple/complicaciones , Adulto , Autoanticuerpos/inmunología , Femenino , Humanos , Receptores Nicotínicos/inmunología
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