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J O Rinne

Publications and source records attributed to J O Rinne.

At least 19 recordsLinked to original sources

A quantitative morphometrical study of neuron degeneration in the substantia nigra in Parkinson's disease.

We studied the pigmented neurons of the substantia nigra (SN) from 8 controls and 20 patients with Parkinson's disease (PD) using a computerized morphometric methodology. On the basis of neuronal topography, several anatomic regions were outlined in the SN. In these subregions the area, perimeter, diameter of the cell bodies and cell numbers were measured and were counted in the controls and PD patients. The measurements were made at the level of the exit of the third cranial nerve from the brain stem. In PD patients, when the whole SN was considered, the mean area, mean perimeter and diameter of the pigmented cell bodies were significantly reduced by 35%, 20% and 21% respectively from the control mean values. Regionally, the pigmented neuron area in the medial ventral part (VM), medial dorsal part (DM), lateral ventral part (VL), lateral dorsal part (DL) and pars lateralis part (PL) showed a significant reduction of 33-41% as compared to controls. In these subregions, a significant decrease in PD patients from the control mean values was seen both in the pigmented neuron perimeter, by 19-26%, and the diameter by 19-25%. This decrease in cell size suggests that, in PD patients, the remaining pigmented neurons in the SN are in a process of degeneration and atrophy. In PD patients the number of pigmented neurons in the whole SN decreased about 76% from control values. Evaluation of the influence of cell size on the apparent quantity of cells in sections indicates, however, that in PD patients the impact of true loss of pigmented neurons is far more dramatic than the impact of their decrease in size.

Aged

Positron emission tomography studies on the dopaminergic system and striatal opioid binding in the olivopontocerebellar atrophy variant of multiple system atrophy.

Ten patients with sporadic olivopontocerebellar atrophy and autonomic failure were studied with positron emission tomography. Subjects underwent both an [11C]diprenorphine and an [18F]fluorodopa scan. The mean caudate-occipital uptake ratio for [11C]diprenorphine was significantly reduced to 88% and the putamen-occipital uptake ratio to 85% of the control values. Individually, 4 of the 10 patients had significantly reduced opioid binding in the putamen. Mean putamen [18F]fluorodopa uptake was significantly diminished (to 71% of the control mean); individually 7 patients had significantly reduced uptake. There was a significant positive correlation between putamen-occipital uptake ratios for [11C]diprenorphine and putamen uptake of [18F]fluorodopa. Our results suggest that subclinical nigrostriatal dysfunction is present in the majority of patients with sporadic olivopontocerebellar atrophy, in accordance with it being part of the spectrum of multiple system atrophy.

Autonomic Nervous System Diseases

PET examination of the monoamine transporter with [11C]beta-CIT and [11C]beta-CFT in early Parkinson's disease.

The monoamine transporter was studied in 4 healthy controls and 5 patients with early Parkinson's disease (PD), who had not received any antiparkinsonian medication, by means of positron emission tomography (PET) using two novel ligands, [11C]beta-CIT and [11C]beta-CFT. Both ligands showed highest uptake in the striatum. There was intermediate accumulation of activity in the thalamus and midbrain, which was more marked for [11C]beta-CIT than for [11C]beta-CFT. In the cortical areas, uptake of both ligands was not different from that seen in the cerebellum. In the controls, the putamen-to-cerebellum and caudate-to-cerebellum ratios for [11C]beta-CFT were higher than those for [11C]beta-CIT (putamen: 3.15 +/- 0.39 for [11C]beta-CFT, and 1.84 +/- 0.10 for [11C]beta-CIT; caudate: 3.15 +/- 0.31 for [11C]beta-CFT, and 1.95 +/- 0.17 for [11C]beta-CIT). Reduction from mean control value in PD patients was greater for [11C]beta-CFT (45% in the putamen contralateral to the predominant symptoms, P < 0.001) than for [11C]beta-CIT (20%, P > 0.05). [11C]beta-CFT uptake in the caudate nucleus was also diminished in PD patients (to 80% of the control mean, P < 0.05), whereas [11C]beta-CIT was within normal range (reduced to 90% of the control mean). These results indicate that both [11C]beta-CIT and [11C]beta-CFT are useful PET ligands to study brain monoamine transporter in healthy controls and in patients with PD. However, [11C]beta-CFT seems superior to [11C]beta-CIT in this respect.

Adult

Effects of monoamine uptake inhibitors given early postnatally on monoamines in the brain stem, caudate/putamen and cortex, and on dopamine D1 and D2 receptors in the caudate/putamen.

Rats were treated with desipramine 5 mg/kg, nomifensine 10 mg/kg, zimelidine 25 mg/kg or with 0.9% sodium chloride once a day during the second and third weeks after birth, and brain stem, caudate/putamen and cortical monoamines, and caudate/putamen dopamine D1 (3[H]SCH 23390) and D2 (3[H]spiroperidol) receptor binding were measured when rats were at two months of age. In the brain stem, the concentration of 3-methoxy-4-hydroxy-phenyl glycol was increased in nomifensine rats and the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in zimelidine rats. In the caudate/putamen, the concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid and the ratio of homovanillic acid to dopamine were increased in desipramine rats; neither 3[H]SCH 23390 nor 3[H]spiroperidol binding were affected by any of the three monoamine uptake inhibiting antidepressants studied. In the cortex, the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in desipramine and zimelidine rats. The findings suggest that desipramine but not nomifensine increases the metabolism of dopamine in the caudate/putamen and nomifensine but not desipramine increases the metabolism of norepinephrine in the brain stem, and furthermore that the metabolism of serotonin is affected by desipramine as well as by zimelidine. It is possible that also treatment of women with these drugs during late pregnancy causes long-lasting changes in the brain of human fetus.

Animals

Increased density of dopamine D2 receptors in the putamen, but not in the caudate nucleus in early Parkinson's disease: a PET study with [11C]raclopride.

Striatal dopamine D2 receptors were studied, using positron emission tomography (PET), in 10 patients with early Parkinson's disease without any antiparkinsonian medication and in 14 healthy controls. [11C]Raclopride was used as ligand and an equilibrium method was applied. The maximum count of receptors (Bmax) and their dissociation constant (Kd) were calculated according to the Scatchard principle. In parkinsonian patients, the Bmax of D2 receptors was increased in the putamen contralateral to the predominant symptoms, as compared to the opposite putamen, by 33% (p = 0.0008). In the caudate nucleus no significant side to side differences was noted. On comparison with age-matched healthy controls, Bmax values in the putamen (p = 0.0012) but not in the caudate nucleus contralateral to the side of predominant clinical symptoms were increased in PD patients. The Kd values were unchanged. The difference in putaminal Bmax values between the opposite hemispheres correlated with the difference in the severity of parkinsonian motor symptoms between the two body sides (r = 0.69, p = 0.03). The present results show that there is both a relative and absolute increase in the number of dopamine D2 receptors in the putamen, but not in the caudate nucleus in early Parkinson's disease.

Carbon Radioisotopes

Striatal opioid receptor binding in Parkinson's disease, striatonigral degeneration and Steele-Richardson-Olszewski syndrome, A [11C]diprenorphine PET study.

The clinical differentiation of Parkinson's disease from the striatonigral degeneration (SND) type of multiple system atrophy (MSA) and Steele-Richardson-Olszewski syndrome (SRO) may be difficult. This is reflected by a 20-25% misdiagnosis rate in clinicopathological series of cases labelled as 'Parkinson's disease' in life. The caudate and putamen contain a high density of opioidergic neurons and receptors which have a close anatomical and physiological relationship with the dopaminergic system. We used [11C]diprenorphine with PET to investigate striatal opioid receptor binding in groups of patients with clinically defined Parkinson's disease (n = 8), SND (n = 7) and SRO (n = 6), compared with normal controls (n = 8). There was no significant difference between mean ligand binding in the putamen and caudate of Parkinson's disease cases when compared with normals. Mean putamen, but not caudate, opioid receptor binding was significantly reduced in the SND group, when compared with normals. By contrast, in the SRO group, both mean caudate and putamen opioid receptor binding was significantly reduced when compared with both normal and Parkinson's disease groups. When considering the individual patients, none of the eight Parkinson's disease cases (0%), none of the seven SND cases (0%), but four of the six SRO cases (67%) had caudate opioid receptor binding that was > 2.5 SDs below the normal mean. Corresponding figures for putamen opioid receptor binding were: none of the Parkinson's disease cases (0%); three of the SND cases (43%); and all of the SRO cases (100%). We conclude that there are differences in the pattern of opioid receptor binding in the striatum of Parkinson's disease, SND and SRO patients, as determined by [11C]diprenorphine PET. The different binding patterns may help to differentiate these akinetic-rigid syndromes in life.

Adult

Cell counts in the substantia nigra: a comparison of single section counts and disector counts in patients with Parkinson's disease and in controls.

The disector (DS) is a method by which it is possible to estimate the density of cells in a volume of tissue, and when associated with Cavalieri's principle, the total number of cells of a neural nucleus. Since the introduction of this method, there has been some uncertainty about the value of cell counts estimated using single section (SS). To compare these two methods, we counted the pigmented neurons in the pars compacta of the substantia nigra (SNpc) in seven normal controls and in four patients with Parkinson's disease (PD), using both single histological sections and the DS. The calculations were performed at two different levels of the substantia nigra. Level I was cut through the colliculus superior and caudal red nucleus, and level II showed the exit of the third cranial nerve in all cases. As methods, the two counts were in close agreement (Pearson's correlation coefficient at levels I and II were r = 0.97 and r = 1.00, respectively, P < 0.001). The correspondence was different in the controls and in the parkinsonian patients, however, as can be judged from the slopes of the average regression lines (0.20 for controls, 0.31 for parkinsonian patients). It is nevertheless evident that once the regression line has been defined. DS counts can be estimated from SS counts when the pigmented neuron numbers are counted in the SNpc. The results suggest that comparisons of pigmented neuron counts made from SS are relevant if the cutting level of the section is well defined, and if section thickness is kept constant.

Adult

Single section and disector counts in evaluating neuronal loss from the substantia nigra in patients with Parkinson's disease.

In order to investigate the correlation between single section (SS) and disector (DS) counts for estimating the pigmented neurons in the pars compacta of the substantia nigra (SNpc), 12 patients with Parkinson's disease (PD) and seven controls were studied. The SS counts were obtained at the level of the exit of the third cranial nerve in the SNpc. The DS counts were made from the whole volume of the SNpc. There was a significant correlation between SS and DS counts (r = 0.94, P < 0.001), suggesting that the methods closely agree. Comparison of SS and DS counts in controls and PD patients showed that the pigmented neurons in PD were decreased by 75% (P < 0.001) and 55% (P < 0.001) in the SS and DS counts, respectively. This study suggests that loss of pigmented neurons from the SNpc in PD can be estimated by either method.

Aged

Positron emission tomography study of human narcolepsy: no increase in striatal dopamine D2 receptors.

We investigated dopamine D2 receptors in the caudate nucleus and putamen with positron emission tomography in seven patients with narcolepsy and seven healthy controls by using [11C]raclopride as a ligand. We applied an equilibrium method and Scatchard principle to give a quantitative estimation of the number (Bmax) and dissociation constant (Kd) of the receptors. Both the Bmax and Kd were within the normal range in the caudate nucleus and putamen in narcoleptic patients. We found no evidence for increased D2 receptor binding in narcolepsy.

Adolescent

PET studies on brain monoamine transporters with carbon-11-beta-CIT in Parkinson's disease.

UNLABELLED: The cocaine analog 2 beta-carbomethoxy-3 beta-[4-iodophenyl]tropane (beta-CIT) labeled with 11C was used to study dopamine reuptake sites with PET. METHODS: Three normal subjects and nine patients with Parkinson's disease were investigated. Each of them underwent a dynamic PET scan (25 timeframes over 80 min) with [11C]-beta-CIT. A dose of 102.5-211.3 MBq (2.77-5.71 mCi) of this ligand was administered intravenously and a PET examination with an ECAT 931/08 PET camera was carried out. Ratios between the striatal/cortical/thalamic/midbrain and cerebellar uptake of this radioligand were calculated. RESULTS: The highest accumulation of [11C]beta-CIT was observed in the caudate and putamen, though there was some uptake in the thalamus and the midbrain. Cortical uptake was negligible. Carbon-11-beta-CIT accumulated significantly less in the putamen of the Parkinson's patients than in the normal subjects. The putamen-to-cerebellum ratio in the Parkinson's patients was 1.59 +/- 0.04 and 1.80 +/- 0.13s (p = 0.028) in the normal subjects. In the caudate, there was no significant difference between the Parkinson's patients and the normal subjects. CONCLUSION: These results imply that [11C]beta-CIT is a useful compound for carrying out a PET examination of the function of the presynaptic monoaminergic neurons both in normal and pathological brains.

Adult

The neuropathological features of neuroacanthocytosis.

In this article we describe the neuropathological changes in three patients with neuroacanthocytosis and review the neuropathology of the other eight cases reported in the literature. Macroscopically the brains showed enlargement of the lateral ventricles, especially the frontal horns. The most severely and consistently affected brain areas were the caudate nucleus and putamen, which were atrophic and showed by light microscopy marked neuronal loss and gliosis. Small and medium-sized striatal neurons were particularly depleted. The globus pallidus was almost as severely involved as the striatum. In some cases the thalamus, substantia nigra, and anterior horns of the spinal cord showed pathology, mainly neuronal loss and mild gliosis. Brain areas with no pathology included the subthalamic nucleus, cerebral cortex, cerebellum, pons, and medulla. The preservation of these areas may help in the neuropathological distinction of neuroacanthocytosis from Huntington's disease.

Acanthocytes

Lyme borreliosis associated with complete flaccid paraplegia.

We report the case of a patient with concomitant Lyme borreliosis and acute paraplegia. The paraplegia was complete, flaccid and of upper motor neurone type. The diagnosis of borreliosis was based on the detection of large amounts of IgM and IgG borrelia antibodies in the acute phase serum and on the complete disappearance of IgM antibody during the review period. IgG borrelia antibodies were also detected in the CSF, but leakage of antibodies from the blood to the intrathecal space could not be ruled out. Lymphocytosis and increased total protein concentration in the CSF were signs compatible with neuroborreliosis. Ceftriaxone therapy effected dramatic recovery of the patient. This case suggests that borreliosis should be considered a possible cause of acute flaccid paraplegia.

Acute Disease

Corticobasal degeneration. A clinical study of 36 cases.

The presenting features and their subsequent evolution in 36 patients with pathologically proven or clinically probable corticobasal degeneration are described. The most common initial complaint was of a unilateral 'clumsy, stiff or jerky arm' (n = 20). Typically the arm was akinetic, rigid and apraxic. In about a third of these the arm was held in a striking and characteristic fixed dystonic posture. Jerking of the arm, due to action and stimulus-sensitive myoclonus accompanied these symptoms in about a third of the cases. The next most common presentation (n = 10) was difficulty walking due to clumsiness and loss of fine motor control of one leg due to apraxia or dysequilibrium, or a combination of both. Sensory symptoms in the affected arm heralded the onset of illness in three and accompanied a motor disturbance in two cases. Presentation with dysarthria or a behavioural syndrome were rare. The symptoms progressed slowly, usually involving first the ipsilateral arm and leg, but gradually spread to affect all four limbs. After a mean follow-up of 5.2 years (range 2-8 years) gait difficulties and a supranuclear ophthalmoplegia had emerged in most patients and dysarthria and pyramidal signs were common. Higher mental function was relatively preserved in most and a cortical sensory loss was evident in a quarter of cases.

Adult

Dystonia after head trauma.

Dystonia is a rare consequence of head trauma. We describe 10 such cases and review 19 similar patients reported in the literature. Twenty-two of the 29 patients suffered head injury during the first or second decade of life. There was a variable delay between the head trauma and the onset of dystonia. In 18 cases with severe head injury, this interval (median, 18 months; range, 1 month to 9 years) was longer than in 11 cases with mild head injury (median, 14 days; range, 3 days to 5 years). In our series, nine of the 10 cases started as a focal dystonia and one as a hemidystonia. The dystonia progressed and spread over several months or years. Two cases remained as focal dystonias, but the others developed segmental, hemi-, multifocal, or generalized dystonia. On brain imaging studies (CT or MRI), the most frequent lesion site was in the contralateral basal ganglia or thalamus, but two cases had normal brain scans. Dysfunction of the lenticulothalamic neuronal circuit seems to be related to the development of dystonia following head trauma.

Adolescent

Nigral degeneration in neuroacanthocytosis.

We counted nerve cells in different subregions of the substantia nigra in three patients with neuroacanthocytosis and compared the results with those of age-matched Parkinson's disease and control patients. Two patients with neuroacanthocytosis and clinical parkinsonism in life had a reduced neuronal density in the substantia nigra, while in a third patient without parkinsonism, this number was at the lower limit of the control range. In neuroacanthocytosis with parkinsonism and in Parkinson's disease, the ventrolateral region of the substantia nigra was most severely affected, although in neuroacanthocytosis cases, nigral neuronal loss was more widespread.

Aged

PET studies on dopamine D1 receptors in the human brain with carbon-11-SCH 39166 and carbon-11-NNC 756.

UNLABELLED: PET studies were carried out on brain dopamine D1 receptors using two new ligands, [11C]SCH 39166 and [11C]NNC 756. METHODS: Four normal subjects and eight predominantly unilateral patients with early Parkinson's disease were investigated. Each of them underwent both a PET scan with [11C]SCH 39166 and one with [11C]NNC 756. A dose of about 185 MBq (5 mCi) of these ligands was administered intravenously and a dynamic PET scan with an ECAT 931/08 PET camera was carried out. Ratios between the striatal and cerebellar uptake of these compounds were calculated. RESULTS: Both [11C]SCH 39166 and [11C]NNC 756 accumulated in the striatum. There was also some neocortical binding; 75% of the striatal value in the case of [11C]SCH 39166 and 60% with [11C]NNC 756 which displayed higher (p < 0.01) uptake in the striatum than [11C]SCH 39166. There were no significant side-to-side differences in the controls nor in the parkinsonian patients. CONCLUSIONS: These results imply that both [11C]SCH 39166 and [11C]NNC 756 can be used in PET studies for the visualization and quantification of dopamine D1 receptors. Since [11C]NNC 756 has a significantly better signal-to-noise ratio in the striatum than [11C]SCH 39166, it seems to offer definite advantages for studies of D1 receptors.

Adult

Brain methionine- and leucine-enkephalin receptors in patients with dementia.

Brain [3H]Met- and [3H]Leu-enkephalin binding was studied in patients with Alzheimer's disease (AD) and vascular dementia (VD), and in age-matched controls. Brain areas investigated were the internal and external globus pallidus, amygdala, hippocampus and temporal cortex. In AD, the binding of both enkephalins decreased in all brain areas examined, except in the external globus pallidus for both enkephalins and in the internal globus pallidus for leucine-enkephalin. Scatchard analysis of amygdaloid samples showed a decrease in the number of receptors (Bmax) without any change in their affinity (Kd). In patients with VD, no significant changes in enkephalin binding were seen. Thus, in AD, enkephalin binding (mainly reflecting delta opioid receptor subtype) is decreased, especially in limbic areas.

Aged

Human brain methionine- and leucine-enkephalins and their receptors during ageing.

Brain Met- and Leu-enk levels were investigated with radioimmunoassay and their binding to enkephalin receptors was studied with [3H]Met- and [3H]Leu-enkephalin in 56 human subjects (4-93 yr). Of the brain areas investigated, the head of the caudate nucleus and pallidum showed an age-associated decline for both Met- and Leu-enk content. In the substantia nigra and in putamen, no significant age-effect was seen. Binding of the enkephalins, which was studied in the head of the caudate nucleus and hippocampus, did not show significant age dependency. In conclusion, ageing affects human brain enkephalin levels but not their receptor binding, at least in brain areas investigated in the present study.

Adolescent