Preserved acetylcholinesterase activity in aged cerebral cortex.
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Acetylcholinesterase↗
Biomedical subjects
H Shinotoh
Publications and source records attributed to H Shinotoh.
Brain muscarinic receptors in progressive supranuclear palsy and Parkinson's disease: a positron emission tomographic study.
OBJECTIVES: To assess muscarinic acetylcholine receptors (mAChRs) in the brains of patients with progressive supranuclear palsy and Parkinson's disease, and to correlate the cholinergic system with cognitive function in progressive supranuclear palsy and Parkinson's disease. METHODS: Positron emission tomography (PET) and [11C]N-methyl-4-piperidyl benzilate ([11C]NMPB) was used to measure mAChRs in the brain of seven patients with progressive supranuclear palsy, 12 patients with Parkinson's disease, and eight healthy controls. All of the patients with progressive supranuclear palsy were demented. The Parkinson's disease group consisted of 11 non-demented patients and one demented patient. The mini mental state examination (MMSE) was used to assess the severity of cognitive dysfunction in all of the subjects. The modified Wisconsin card sorting test (WCST) was used to evaluate frontal cognitive function in the non-demented patients with Parkinson's disease and controls. RESULTS: The mean K3 value, an index of mAChR binding, was significantly higher for the frontal cortex in the patients with Parkinson's disease than in the controls (p<0.01). By contrast, the patients with progressive supranuclear palsy had no significant changes in the K3 values of any cerebral cortical regions. The mean score of the MMSE in the progressive supranuclear palsy group was significantly lower than that in the control group. Although there was no difference between the Parkinson's disease and control groups in the MMSE, the non-demented patients with Parkinson's disease showed significant frontal lobe dysfunction in the WCST. CONCLUSIONS: The increased mAChR binding in the frontal cortex of the patients with Parkinson's disease may reflect denervation hypersensitivity caused by loss of the ascending cholinergic input to that region from the basal forebrain and may be related to frontal lobe dysfunction in Parkinson's disease. The cerebral cortical cholinergic system may not have a major role in cognitive dysfunction in progressive supranuclear palsy.
Aged↗
Herpes zoster ophthalmicus and delayed contralateral hemiparesis: a case of ipsilateral midbrain involvement.
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Adult↗
Measurement of acetylcholinesterase by positron emission tomography in the brains of healthy controls and patients with Alzheimer's disease.
BACKGROUND: Acetylcholinesterase activity, a marker for degeneration of the central cholinergic system, has consistently been reported, in necropsy brain studies, to be reduced in the cerebral cortex of patients with Alzheimer's disease. We have shown regional acetylcholinesterase activity in vivo in rodent and primate brains with radioactive acetylcholine analogues. In the present study, we used one of the analogues to map acetylcholinesterase activity in the brains of living people. METHODS: Positron emission tomography (PET) and a radiolabelled acetylcholine analogue with high hydrolytic specificity to acetylcholinesterase [11C]N-methyl-4-piperidyl acetate (MP4A), was used in eight elderly healthy controls and five patients with Alzheimer's disease who had mild dementia. All participants were given an intravenous injection of [11C]MP4A and then sequential patterns of radioactivity in various brain regions were obtained by PET. Time courses of [11C]MP4A concentration in arterial blood were also measured to obtain an input function. A three-compartment model was used to estimate regional acetylcholinesterase activity in the brain. FINDINGS: The estimated acetylcholinesterase distribution in the brain of the control participants agreed with the acetylcholinesterase distribution at necropsy. All patients with Alzheimer's disease had multiple cortical regions with a reduced estimated acetylcholinesterase activity in comparison with control participants. The reduction was more pronounced in the parietotemporal cortex, with an average reduction rate of 31% in temporal and 38% in parietal cortex, and less pronounced in other cortical lesions (19% in frontal, 24% in occipital, and 20% in sensorimotor cortex). Each patient was found to have at least two cortical regions with significantly reduced acetylcholinesterase activity. INTERPRETATION: The method we describe for non-invasive in-vivo detection of regional acetylcholinesterase changes in the living human brain that is feasible for biochemical assessment of Alzheimer's disease.
Acetylcholinesterase↗
"Familial Parkinson's disease"--a case-control study of families.
BACKGROUND: Parkinson's disease (PD) patients frequently report a family history of PD and this may provide etiological clues to PD. It has also been suggested that a report of a negative family history is reliable. We studied the prevalence of PD in relatives of PD patients to assess the reliability of family history and to evaluate possible explanations of "familial PD" (fPD). METHODS: 81 of 650 (12.5%) PD probands (all PD patients seen at clinic in 4 years) reported a positive family history of PD. Each fPD proband was matched with non-familial PD (nfPD) proband by gender and year of birth. Screening and follow-up questionnaires were mailed to relatives to obtain information concerning pedigree and presence of neurodegenerative disease. Available family members (regardless of disease status) were examined. RESULTS: On examination, 8 persons, said to be "normal" by probands, relatives and themselves, had definite or possible PD (5 fPD, 3 nfPD). The prevalence rate of PD among first and second degree living relatives of probands varied significantly between fPD and nfPD groups (6269/100,000 versus 1190/100,000; p < 0.001). The weighted prevalence (taking into account the proportions of fPD and nfPD within the clinic) was 1822/100,000, a value more than 5 times higher than reported prevalence rates of PD in the general population (p < 0.001). The prevalence rate was greater in first degree relatives than second degree. CONCLUSIONS: "Familial parkinsonism" cannot be explained merely by size of or advanced age within families. Significant numbers of previously unrecognized PD patients may be identified despite a "negative" family history. That is, the patient's report of an absence of familial parkinsonism is frequently inaccurate. The prevalence rate in relatives of PD patients appears to be higher than the general population-regardless of the family history reported by a PD patient. We believe our study suggests that genetic influences or early life environmental exposures are likely to be of etiological importance in PD.
Adult↗
High signal intensity on T1 weighted MRI of the anterolateral column of the spinal cord in amyotrophic lateral sclerosis.
OBJECTIVE: To investigate MRI abnormalities in patients with amyotrophic lateral sclerosis. METHODS: Fourteen patients with amyotrophic lateral sclerosis underwent MRI of the head and spinal cord using T1 and T2 weighted images. Forty age matched controls (29 with other neurological diseases, 11 with non-neurological diseases) underwent MRI of the cervical spinal cord using T1 and T2 weighted images. RESULTS: In all the control patients, the signal intensity of the posterior column was equal or slightly hypointense compared with the anterolateral column of the cervical spinal cord on T1 weighted images. However, eight of 14 patients with amyotrophic lateral sclerosis showed pronounced high signal intensity in the anterolateral column of the spinal cord on T1 weighted MRI, which also disclosed high signal intensity of the intracranial corticospinal tract in two of the 14 patients. T2 weighted MRI demonstrated high signal intensity of the lateral corticospinal tract of the spinal cord in two, high signal intensity of the intracranial corticospinal tract in five, and low signal intensity of the motor cortex in six of the 14 patients. Two of the 14 patients showed no abnormal findings on MRI. CONCLUSIONS: High signal intensity of the anterolateral column of the spinal cord of patients with amyotrophic lateral sclerosis is a new imaging abnormality and may be useful for the diagnosis of this disease.
Adult↗
Presynaptic and postsynaptic striatal dopaminergic function in patients with manganese intoxication: a positron emission tomography study.
We performed PET on four patients with chronic industrial Mn intoxication; presynaptic and postsynaptic dopaminergic function were measured with [18F]6-fluoro-L-dopa (6FD) and [11C]raclopride (RAC). All patients had a rigid-akinetic syndrome; they had no sustained benefit from L-dopa. Influx constants (Ki) of 6FD were normal in the caudate and putamen. RAC binding was mildly reduced in the caudate and normal in the putamen. We conclude that nigrostriatal dopaminergic dysfunction is not responsible for the parkinsonism caused by chronic Mn intoxication. The pathology is likely to be downstream of the dopaminergic projection.
Adult↗
Lamotrigine trial in idiopathic parkinsonism: a double-blind, placebo-controlled, crossover study.
Increased glutamatergic transmission in the basal ganglia is implicated in the pathophysiology of idiopathic parkinsonism (IP). We investigated the effects of lamotrigine (LTG), a glutamate-release inhibitor, in the symptomatic treatment of IP in two double-blind, placebo-controlled studies. Single doses of L-dopa/carbidopa (equal to 50% of the usual morning dose) were administered together with either LTG (100, 200, or 400 mg) or two random placebo doses in 14 patients with IP. The patients were assessed using the Modified Columbia Rating Scale (MCRS) and the Purdue Pegboard Test (PPBT) at multiple intervals over 8 hours. There were no significant differences between the placebo doses and the three doses of LTG on the MCRS and PPBT scores. In a 3-month study, 12 patients took LTG titrated up to 400 mg or placebo with their antiparkinsonian medication for 3 months and were then crossed over. Nine of 12 patients did not complete the study because of dyskinesia (n = 2), hallucinations (n = 3), and deterioration of parkinsonian symptoms (n = 4) on LTG. There was no significant difference between placebo and LTG on the MCRS and PPBT in the three patients who completed the study. The results failed to demonstrate any symptomatically beneficial effects of LTG in IP.
Adult↗
Fluorodopa and raclopride PET analysis of patients with Machado-Joseph disease.
We performed [18F]6-fluoro-L-dopa (6-FD) and [11C]raclopride (RAC) PET studies in six patients with Machado-Joseph disease (MJD) (age, 17 to 61 years; duration of illness, 3 to 10 years), normal controls (n = 10 in 6-FD-PET, n = 8 in RAC-PET), and patients with idiopathic parkinsonism (n = 15 in 6-FD-PET). The youngest patient with MJD had prominent dystonia and pyramidal features (type 1 MJD), whereas the remainder were prominently ataxic (types 2 and 3 MJD). Striatal RAC binding was normal in patients with MJD. Striatal 6-FD influx constants (Ki) were low in the range of idiopathic parkinsonism in two patients with MJD (youngest and oldest patients), whereas striatal Ki were normal in the remaining patients with MJD. The impairment of the nigrostriatal dopaminergic pathway did not correlate with the phenotype, CAG repeat length, disease duration, or age of onset of patients with MJD. Our results suggest that striatal D2 receptors are normal and the nigral damage is diverse in MJD.
Adolescent↗
[Shy-Drager syndrome and multiple system atrophy].
Shy-Drager syndrome (SDS) is a subtype of multiple system atrophy (MSA) with the clinical predominance of autonomic failure. The differential diagnosis between SDS and Parkinson's disease (PD) can sometimes be difficult clinically. The features favoring a clinical diagnosis of SDS are marked orthostatic hypotension, erectile impotence in males, urinary symptoms, nocturnal stridor, rigidity and akinesia without tremors, levodopa unresponsiveness, cerebellar signs, cerebellar atrophy on brain CT scans and MRI.
Diagnosis, Differential↗
[Muscarinic cholinergic receptor imaging of parkinsonian brain using 11C-NMPB and PET].
11C-NMPB is a useful ligand which is used to measure brain muscarinic cholinergic receptors (mAChRs) for its high affinity and high brain uptake. PET images of 11C-NMPB uptake had the highest accumulations in the cerebral cortex and striatum and the lowest in the cerebellum, both in patients with Parkinson's disease (PD) and normal subjects. 11C-NMPB uptake was homogeneous throughout the cerebral cortex in the normal subjects but greater in the frontal cortex of about one half of the PD patients as compared with other cerebral cortical areas. Quantitative analysis showed that the PD patients had high K3 values, an index of mAChR binding, in the frontal cortex. In PD, increased mAChR binding in the frontal cortex may be related to frontal lobe dysfunction. This technique should prove useful for detecting subclinical impairment of the central cholinergic system in PD.
Animals↗
[Magnetic resonance spectroscopy in Parkinson's disease and multiple system atrophy].
Recent advances in magnetic resonance spectroscopy(MRS) allow to assay noninvasively key molecules of brain metabolism in living patients. There are several reports of MRS in Parkinson's disease(PD) and multiple system atrophy(MSA). 1H-MRS of the striatum revealed the reduced NAA/Cr and Cho/Cr ratio in MSA patients and the preserved NAA/Cr and Cho/Cr ratio in PD patients. The reduced NAA/Cr ratio probably reflects striatal neuronal loss. 1H-MRS of the striatum showed increased Cho/Cr ratio in the "on" state compared with that in the "off" state in the PD patients. The increased Cho/Cr ratio may reflect some membrane alteration or change of choline metabolism in PD with the "wearing-off" phenomena. Although studies are still preliminary, MRS shows great possibility for aiding in the differential diagnosis of parkinsonism and it will contribute to a better understanding of the pathogenesis of PD and MSA.
Aspartic Acid↗
[L-dopa/benserazide during pregnancy in a patient with juvenile parkinsonism].
We report a 34-year-old woman with juvenile parkinsonism who had been treated with five tablets daily of l-dopa/benserazide (100 mg/25 mg). She became pregnant in May 1995 and continued the same treatment. She delivered a healthy boy (3,798 g, 52 cm) with Apgar scores of 9 at 38 weeks gestation by normal delivery. In animal study, there is a report of teratogenicity (bone abnormality) of l-dopa/benserazide in rabbits at doses of 30 mg/kg and 120 mg/kg. However, there have been several reports of uneventful delivery of normal children in patients with juvenile parkinsonism who had been treated with l-dopa/decarboxylase inhibitor (DCI) during pregnancy. There seems to be no firm reason to avoid pregnancy during the treatment of l-dopa/DCI or to withhold l-dopa/DCI during pregnancy.
Adult↗
Manganese intoxication in the rhesus monkey: a clinical, imaging, pathologic, and biochemical study.
We gave three adult rhesus monkeys seven IV injections of manganese chloride at approximately 1-week intervals. We evaluated neurologic status by serial clinical examinations and performed a levodopa test if the animal developed features of basal ganglia dysfunction. After the animals were killed, we performed neuropathologic, neurochemical, and laser microprobe mass analysis (LAMMA) studies. Two of three animals developed a parkinsonian syndrome characterized by bradykinesia, rigidity, and facial grimacing suggestive of dystonia but not tremor. Neither animal responded to levodopa. Autopsy demonstrated gliosis primarily confined to the globus pallidus (GP) and the substantia nigra pars reticularis (SNr). We detected focal mineral deposits throughout the GP and SNr, particularly in a perivascular distribution. LAMMA studies noted that mineral deposits were primarily comprised of iron and aluminum. The severity of pathologic change correlated with the degree of clinical dysfunction. These studies demonstrate that, in contrast to Parkinson's disease (PD) and MPTP-induced parkinsonism, manganese primarily damages the GP and SNr and relatively spares the nigrostriatal dopaminergic system. Further, the results suggest that Mn-induced parkinsonism can be differentiated from PD and MPTP-induced parkinsonism by the clinical syndrome and response to levodopa. The accumulation of iron and aluminum suggests that iron/aluminum-induced oxidant stress may contribute to the damage associated with Mn toxicity.
Animals↗
[Difficulty in eye opening following left hemispheric infarction-- causative lesion and pathophysiology of abnormalities of the eye and eyelids movements].
We reported a patient suffering from difficulty in eye opening following left hemispheric infarction. A 78-year-old left-handed woman with atrial fibrillation had an acute onset of right hemiparesis and difficulty in eye opening. On admission, mild disorientation, vertical gaze palsy, right homonymous hemianopia, anosognosia of right hemiparesis, agnosia of right side of the body and forced grasping reflex of the left hand were seen. She was aware of her difficulty in opening her eyelids. Vertical saccadic eye movements were absent to command but when her head was free to move, the vertical saccadic eye movements improved that may suggest oculomotor apraxia. Bell's phenomenon was absent, and optokinetic responses were normal. Aphasia and facial apraxia were not seen. Brain CT and MRI demonstrated infarction in the territory of the anterior divisions of the left middle cerebral artery which includes the inferior frontal gyrus, middle frontal gyrus, fronto-parietal operculum and temporal operculum. SPECT disclosed hypoperfusion area in the left frontal lobe. No lesion was seen in the midbrain and pons. On the basis of these findings, cerebral emboli of the divisions of the left middle cerebral artery were diagnosed. Until about 11th days from onset, she could not open her eyelids by our verbal commands or even voluntarily, and showed paradoxical contraction of the bilateral orbicularis oculi muscles by verbal commands to open her eyes or when her eyes were forcedly opened by hands. After the 12th days from the onset, she became to be able to open her eyes voluntarily when she was asked to count the number of fingers presented in front of her face and when her families called her, but she could not open her eyes by verbal commands, which may be characteristic of apraxia of eyelid opening. She also had bilateral blephaloptosis when she opened her eyes. Considering this case together with previous reports, embolic lesion of the left cerebral hemisphere including the frontal eye field area and its adjacent areas which may be involved in higher control of eye lid movements and supranuclear vertical gaze movements was thought to cause difficulties in eye opening and vertical gaze palsy.
Aged↗
[Neurotransmitter systems in the human brain studied by positron emission tomography].
Positron emission tomography with appropriate tracers provides unique opportunity to study neurotransmitter systems in the living human brain. PET with [18F] 6-fluoro-L-dopa (FD) provides an index of the integrity of nigrostriatal pathway, and striatal FD uptake correlates linearly with the density of nigral neurons. PET allows us to assess the progression of the nigral lesions in Parkinson's disease (PD). A 68-year-old normal female volunteer was scanned by FD-PET. Subsequently, she developed parkinsonism 3.7 years after the scan. A repeated FD-PET scan revealed a significant reduction of FD uptake by 20% over the 5.2 year interval. The results suggest a relatively short presymptomatic period with fast initial losses of nigral neurons in PD. FD-PET has been used to determine the viability of fetal graft implanted in the striatum for the treatment of PD. PET imaging of dopamine D1 and D2 receptors may be useful for the differential diagnosis of PD and striatonigral degeneration. PET reveals significant reduction of dopamine D1 and D2 receptor binding in the putamen of patients with SND, while D1 and D2 receptor binding is normal or slightly upregulated in PD. We found hypersensitivity of muscarinic cholinergic receptors in the frontal cortex of patients with PD by using PET. The result suggests a loss of ascending cholinergic system in the frontal cortex in PD, which may cause the frontal lobe dysfunction in PD. Recently, acetylcholine analogs labelled with positron emitter have been developed for measurement of brain acetylcholinesterase activity in vivo. These tracers may be useful for the assessment of ascending cholinergic system in Alzheimer's disease and PD.
Aged↗
The use of PET in Parkinson's disease.
Activation studies with positron emission tomography (PET) have provided an understanding of the pathophysiology of akinesia and tremor in Parkinson's disease (PD). [18F]6-fluoro-L-dopa (FD)-PET and dopamine receptor imaging by PET can assist in the differential diagnosis of various forms of parkinsonism. FED-PET is capable of detecting subclinical dopaminergic deficits. This allows not only the early or preclinical detection of PD but also the investigation of subclinical lesions of the substantia nigra in PD-related disorders. Longitudinal studies of PD and MPTP induced parkinsonism have provided new insight into the pathogenesis of PD.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Hypersensitivity of cortical muscarinic receptors in Parkinson's disease demonstrated by PET.
The status of muscarinic receptors (mAChRs) is not clear in Parkinson's disease (PD). We measured mAChR binding in the brain of eight patients with PD and eight, age-matched, healthy controls by positron emission tomography (PET) and [11C]N-methyl-4-piperidyl benzilate ([11C]NMPB). PD patients were not demented according to DSM III criteria but showed significant frontal lobe dysfunction in the Modified Wisconsin Card Sorting Test. A mean K3 value, which is an index of mAChR binding calculated by a graphical method, was 20% higher in the frontal cortex of PD patients than controls (p < 0.05). Hypersensitivity of mAChRs in the frontal cortex of PD patients may be a response to a loss of ascending cholinergic input to that region, and may relate to frontal lobe dysfunction in PD.
Aged↗