RESUMO
OBJECTIVES: Cholinergic projections to cerebral cortical and subcortical regions are decreased in Parkinson disease (PD), but not evaluated in the parkinsonian syndromes of multiple system atrophy (MSA-P) and progressive supranuclear palsy (PSP). We studied cholinergic innervation in these disorders as compared to age-appropriate normal control subjects. METHODS: We used PET with [(11)C]PMP to measure acetylcholinesterase (AChE) activity in multiple cerebral cortical and subcortical regions. We studied 22 normal controls, 12 patients with PD, 13 patients with MSA-P, and 4 patients with PSP. RESULTS: We found significantly decreased AChE activity in most cerebral cortical regions in PD and MSA-P, and a similar but nonsignificant decrease in PSP. No differences were found between PD and MSA-P. Significantly decreased AChE activity was found in PD in striatum, cerebellum, and thalamus, with a marginally significant decrease in mesencephalon and no change in pons. Significantly greater declines in AChE activity in all subcortical regions were seen in MSA-P and PSP vs in PD. Decreased AChE activity in brainstem and cerebellum of all 3 disorders correlated with disturbances of balance and gait. CONCLUSIONS: Cerebral cortical cholinergic activity is decreased to a similar level in Parkinson disease (PD), parkinsonian syndromes of multiple system atrophy (MSA-P), and progressive supranuclear palsy (PSP) as compared to normal controls. Subcortical cholinergic activity is significantly more decreased in MSA-P and PSP than in PD. The more substantial decrease reflects greater impairment in the pontine cholinergic group, which is important in motor activity, particularly gait. These differences may account for the greater gait disturbances in the early stages of MSA-P and PSP than in PD.
Assuntos
Acetilcolinesterase/metabolismo , Atrofia de Múltiplos Sistemas/diagnóstico por imagem , Atrofia de Múltiplos Sistemas/fisiopatologia , Transtornos Parkinsonianos/diagnóstico por imagem , Transtornos Parkinsonianos/fisiopatologia , Paralisia Supranuclear Progressiva/diagnóstico por imagem , Paralisia Supranuclear Progressiva/fisiopatologia , Acetilcolina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Encéfalo/anatomia & histologia , Encéfalo/enzimologia , Encéfalo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/patologia , Vias Neurais/anatomia & histologia , Vias Neurais/patologia , Vias Neurais/fisiologia , Vias Neurais/fisiopatologia , Transtornos Parkinsonianos/patologia , Tomografia por Emissão de Pósitrons , Traçadores Radioativos , Paralisia Supranuclear Progressiva/patologiaRESUMO
OBJECTIVE: To explore the neurochemical basis of REM sleep behavior disorder (RBD) in multiple-system atrophy (MSA). METHODS: In 13 patients with probable MSA, nocturnal, laboratory-based polysomnography was used to rate the severity of REM atonia loss by the percentage of REM sleep with tonically increased electromyographic (EMG) activity and the percentage of REM sleep with phasic EMG bursts. PET with (+)-[11C]dihydrotetrabenazine ([11C]DTBZ) was employed to measure the density of striatal monoaminergic terminals and SPECT with (-)-5-[123I]iodobenzovesamicol ([123I]IBVM) to measure the density of 123I]IBVM. RESULTS: Age and gender distributions were similar in patient and normal control groups. The MSA subjects showed decreased mean [11C]DTBZ binding in the striatum (p < 0.0001) and decreased [123I]IBVM binding in the thalamus (p < 0.001). Moreover, in the MSA group, striatal [11C]DTBZ binding was inversely correlated with the severity of REM atonia loss (p = 0.003). Thalamic [123I]IBVM binding, however, was not correlated to the severity of REM atonia loss. CONCLUSION: Decreased nigrostriatal dopaminergic projections may contribute to RBD in MSA.
Assuntos
Monoaminas Biogênicas/metabolismo , Corpo Estriado/metabolismo , Atrofia de Múltiplos Sistemas/fisiopatologia , Transtorno do Comportamento do Sono REM/diagnóstico , Transtorno do Comportamento do Sono REM/metabolismo , Tetrabenazina/análogos & derivados , Adulto , Distribuição por Idade , Idoso , Ligação Competitiva , Radioisótopos de Carbono , Corpo Estriado/diagnóstico por imagem , Eletromiografia , Feminino , Humanos , Radioisótopos do Iodo , Masculino , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/complicações , Atrofia de Múltiplos Sistemas/metabolismo , Piperidinas , Polissonografia , Valor Preditivo dos Testes , Transtorno do Comportamento do Sono REM/etiologia , Valores de Referência , Distribuição por Sexo , Tetra-Hidronaftalenos , Tálamo/diagnóstico por imagem , Tálamo/metabolismo , Tomografia Computadorizada de Emissão , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
OBJECTIVE: To explore the neurochemical basis of obstructive sleep apnea (OSA) in multiple-system atrophy (MSA). METHODS: In 13 patients with probable MSA, nocturnal, laboratory-based polysomnography was used to rate the severity of OSA using the apnea-hypopnea index during sleep. SPECT with (-)-5-[123I]iodobenzovesamicol ([123I]IBVM) was utilized to measure the density of thalamic cholinergic terminals, which project from the brainstem pedunculopontine and laterodorsal tegmental nuclei. PET with (+)-[11C]dihydrotetrabenazine ([11C]DTBZ) was also used to measure the density of striatal monoaminergic terminals, which project from the brainstem. Findings in the patient group were compared with data from 12 normal control subjects scanned utilizing [123I]IBVM and 15 normal control subjects utilizing [11C]DTBZ. RESULTS: Age and gender distributions were similar in patient and control groups. The MSA subjects showed decreased [123I]IBVM binding in the thalamus (p < 0.001) and decreased mean [11C]DTBZ binding in the striatum (p < 0.0001) in comparison with the control subjects. In the MSA group, thalamic [123I]IBVM binding was inversely correlated with the severity of OSA (p = 0.011). Striatal [11C]DTBZ binding was not correlated with the severity of OSA (p = 0.19). CONCLUSION: Decreased pontine cholinergic projections may contribute to OSA in MSA.
Assuntos
Corpo Estriado/metabolismo , Proteínas de Membrana Transportadoras , Atrofia de Múltiplos Sistemas/fisiopatologia , Neuropeptídeos , Receptores Colinérgicos/deficiência , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/metabolismo , Tetrabenazina/análogos & derivados , Tálamo/metabolismo , Proteínas de Transporte Vesicular , Adulto , Distribuição por Idade , Idoso , Ligação Competitiva , Proteínas de Transporte/metabolismo , Corpo Estriado/diagnóstico por imagem , Feminino , Humanos , Radioisótopos do Iodo , Masculino , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/complicações , Atrofia de Múltiplos Sistemas/diagnóstico por imagem , Projetos Piloto , Piperidinas , Ponte/fisiopatologia , Receptores Colinérgicos/metabolismo , Valores de Referência , Análise de Regressão , Distribuição por Sexo , Apneia Obstrutiva do Sono/etiologia , Tetra-Hidronaftalenos , Tálamo/diagnóstico por imagem , Tomografia Computadorizada de Emissão , Tomografia Computadorizada de Emissão de Fóton Único , Proteínas Vesiculares de Transporte de Acetilcolina , Proteínas Vesiculares de Transporte de Aminas BiogênicasRESUMO
REM sleep behavior disorder (RBD) is a possible herald of neurodegenerative disorders with parkinsonism. The authors determined the density of striatal dopaminergic terminals with [11C]dihydrotetrabenazine PET in six elderly subjects with chronic idiopathic RBD and 19 age-appropriate controls. In subjects with RBD, there were significant reductions in striatal [11C]dihydrotetrabenazine binding, particularly in the posterior putamen.