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G Defer

Publications and source records attributed to G Defer.

At least 19 recordsLinked to original sources

Relationships between striatal dopamine denervation and frontal executive tests in Parkinson's disease.

Indirect evidence from human and monkey investigations supports the idea that impaired frontal tasks in Parkinson's disease (PD) may result from striato-frontal disruption caused by dopamine (DA) denervation of the caudate nucleus. To directly investigate this hypothesis, we used PET with 11C-S-Nomifensine (11C-S-NMF), a sensitive marker of striatal DA denervation, in 10 non-demented PD patients in whom two frontal executive tests, the object alternation (OA) and the conditional associative learning (CAL) tasks, thought to reflect mainly set-shifting/inhibition and planning, respectively, were given. In addition, the central executive function of verbal working memory was assessed with the Brown Peterson paradigm (BPP). We found a highly significant correlation between right caudate 11C-S-NMF specific binding and OA performance, less significant and reverse-direction correlations between CAL performance and putamen 11C-S-NMF binding, and no significant correlation with BPP performance. Thus, caudate DA denervation may subtend poor set-shifting/inhibition process in PD. Our results also point to distinct and complex relationships between striatal DA and specific frontal tasks.

Adult

Cluster headache-like attack as an opening symptom of a unilateral infarction of the cervical cord: persistent anaesthesia and dysaesthesia to cold stimuli.

A 54 year old man experienced excruciating left retro-orbital pain with lacrimation and redness of the eye representative of a cluster headache attack. This was followed by left hemiparesis with plegia of the lower limb and left Horner's syndrome. Five days later the hemiparesis recovered while the patient developed hypoanaesthesia to cold stimuli that evoked painful burning dysaesthesia on the right side below the C4 level. MRI disclosed a discrete infarct in the left lateral aspect of the cord at C2 level concomitant to a left vertebral artery thrombosis. This limited infarct and the clinical symptoms suggest a hypoperfusion in the peripheral arterial system of the left hemicord, supplied both by the anterior and posterior spinal arteries. Cluster headache-like attack and persistent dysaesthesia to cold stimuli are discussed respectively in view of the central sympathetic involvement and partial spinothalamic system dysfunction.

Anesthesia

Paraneoplastic cerebellar syndrome and optic neuritis with anti-CV2 antibodies: clinical response to excision of the primary tumor.

OBJECTIVE: To describe a patient with a paraneoplastic cerebellar syndrome and optic neuritis with circulating anti-CV2 antibodies and clinical improvement after excision of a small cell lung carcinoma. DESIGN: Report of a case. SETTING: A 62-year-old man simultaneously developed a severe cerebellar syndrome and a bilateral optic neuritis predominantly in the left eye (visual acuity, 20/25 in the right eye; < 20/400 in the left eye; and bilateral swelling of the optic discs). MAIN OUTCOME AND RESULTS: Anti-CV2 antibodies, recently described as associated with paraneoplastic neurological syndrome, were detected in the patient's serum sample. These antibodies were demonstrated to react with the cytoplasm of a subpopulation of oligodendrocytes in the white matter of rat brain in the cerebellum, brainstem, spinal cord, and optic chiasm. The patient was found to have a small cell lung carcinoma, which was removed. After excision of the tumor, the cerebellar syndrome improved dramatically and the papilledema disappeared despite aftereffects of the optic neuritis. CONCLUSIONS: These findings were consistent with the diagnosis of a paraneoplastic neurological syndrome, although both optic neuritis and remission of the cerebellar syndrome are uncommon patterns of paraneoplastic syndromes. CV2 antigen expression by the oligodendrocytes of the cerebellum, brainstem, spinal cord, and optic chiasm correlated with the clinical syndrome observed in our patient. However, the precise pathophysiological role of anti-CV2 antibodies is still unknown.

Autoantibodies

[Gesture apraxia disclosing carbon monoxide poisoning].

A seventy year old right handed woman presented progressive limb apraxia and headache due to carbon monoxide poisoning. Thereafter, when in hospital for one week, she developed akinetic mutism, coma and died. Limb apraxia has been rather uncommonly reported in carbon monoxide poisoning. The akinetic mutism observed after the patient had been removed from intoxication could be analysed as a delayed encephalopathy related to a chronic carbon monoxide poisoning.

Aged

[Neuropsychological testing of 5 patients with Parkinson's disease before and after neuron graft].

Five patients with idiopathic PD were followed by neuropsychological tests after brain fetal neuronal transplantation. The following tests were used in order to assess memory as well as visuospatial and frontal functions: MMSE, Mattis Scale, Wisconsin Card Sorting Test, Stroop task, word fluency tasks, 15-objects test, WAIS-R (Digit span, Arithmetic, Block design, Pictures completion, Pictures arrangement), learning of 15 words of Rey, WMS-R (Logical memory) and Visual memory of L. Israël. The same tests were performed before, then one year following the transplantation. Pooled data did not show any significant difference between pre and post-operative tests. Individual results varied among patients: 2 remained unchanged, 1 had a pathological deterioration which increased after one year, 1 had some frontal symptoms whereas the last patient improved. Our data confirm that this surgical procedure do not induce permanent neuropsychological deficits, but do not indicate at the present time any clear effect of dopamine reinnervation on cognitive functions.

Aged

Clinical correlates of [18F]fluorodopa uptake in five grafted parkinsonian patients.

To assess the efficacy of fetal mesencephalic grafts in Parkinson's disease, it is important to know if the grafted cells survive and are functional. Positron emission tomography (PET) and [18F]fluorodopa ([18F]dopa) have been used to demonstrate the survival of the grafted cells, but the relationship of [18F]dopa uptake changes in the grafted striatum to motor function remains unclear. We investigated this question with 16 serial PET scans in 5 severe parkinsonian patients unilaterally grafted in whom we found a significant and progressive increase of the [18F]dopa uptake in the grafted putamen. The number of patients was too small to assess the sensitivity of [18F]dopa PET scans in individual patients. Yet, by analyzing the 16 serial PET scans we found a correlation between the [18F]dopa uptake (Ki) in the grafted putamen and the percentage of daily time spent "on," suggesting that Ki changes have a functional meaning. In addition, the Ki values were correlated with the contralateral finger dexterity to the same extent in both the grafted and nongrafted putamen. These results indicate that [18F]dopa uptake reflects the motor function of the opposite side of the body, similarly in the grafted and ungrafted putamen, at least in terms of these tasks. Finally, extrapolating from these correlations offers the suggestion that clinical optimal results of the graft could be achieved if the graft brings the Ki values in the putamen to about two standard deviations of mean control values.

Brain

Peduncular 'rubral' tremor and dopaminergic denervation: a PET study.

Lesions causing so-called rubral tremors frequently involve the substantia nigra or the nigrostriatal fibers, suggesting dopaminergic denervation as possibly contributory. We examined this hypothesis using PET and [18F]-fluorodopa in six patients with a contralateral tremor following a peduncular lesion. The denervation revealed by PET was even more marked than in severe parkinsonian patients. All patients showed partial to complete improvement with levodopa therapy. PET evaluation of D2-receptors with [76Br]bromolisuride showed no asymmetry of the D2 binding despite the important asymmetry of 18F-fluorodopa uptake. Our results indicate an important involvement of the nigral dopaminergic system in peduncular tremors that appears to be independent of postsynaptic dopamine receptors.

Adult

Non-matched images with 123I-IMP and 99mTc-bicisate single-photon emission tomography in the demonstration of focal hyperaemia during the subacute phase of an ischaemic stroke.

Focal hyperaemia is a fairly common phenomenon in the subacute phase of an ischaemic stroke. This has rarely been reported with iodine-123 iodoamphetamine (IMP) and has never been identified using technetium-99m bicisate (99mTc-ECD). In this report, we present the case of a patient suffering from a left cerebral posterior stroke. 123I-IMP single-photon emission tomography (SPET) images showed a large area of significantly increased IMP activity located in the left occipital region whereas 99mTc-bicisate SPET displayed hypoactivity in the same area.

Amphetamines

Bilateral motor improvement and alteration of L-dopa effect in two patients with Parkinson's disease following intrastriatal transplantation of foetal ventral mesencephalon.

Several recent reports have suggested that foetal ventral mesencephalic transplants could alleviate motor symptoms in patients with Parkinson's disease. Expectations of future success must be clarified by precise analysis of the extent and limitation of recovery associated with an assessment of function of the graft using [18F]fluorodopa (18F-dopa) PET. Two patients with idiopathic Parkinson's disease, severely impaired despite optimal medication, have been followed 10 and 17 months after stereotaxic unilateral intrastriatal transplantation of neural cells dissociated from human foetal ventral mesencephalon. Analysis of the clinical evolution complied with the protocol established in the 'Core Assessment Program for Intracerebral Transplantation'. Both patients have benefited from the transplantation in their daily activities and in motor timed tests, although they still exhibit parkinsonian symptoms and require L-dopa therapy. This is associated with a gradual increase in 18F-dopa uptake at the site of grafting. There are two major clinical changes: (i) a bilateral motor improvement for the speed of movements (the quality of movements improved almost exclusively on the side contralateral to the graft); (ii) a change in the outcome of the L-dopa treatment as exemplified by a postoperative transient period of heavy dyskinesias and subsequent additive actions of the two treatments. These results confirm that neural transplantation may be useful for patients with Parkinson's disease. The improvement recorded on the side ipsilateral to the graft does not match that observed on the contralateral side and it is proposed that bilateral transplantation may be necessary. The existence of a transient postoperative period of heavy dyskinesias suggests that the patients may benefit from a controlled decrease of L-dopa intake after grafting.

Adult

Kinetics of a new iodolabeled MAO-B inhibitor in the rat brain and in cultured astrocytes.

3-Bromobenzyloxy phenyloxy hydroxymethyl propanol was labelled with iodine-125. Labeling yield was approximately 92%. Using HPLC and an RP18 column, Iodo*MD (MW = 412) was obtained at no-carrier-added conditions (specific activity 125 Ci/mmole). Biochemical experiments were carried out in vitro and showed a Ki for MAO-B of 5.4 nM and of 5000 for MAO-A (RA/B = 926). Using ex vivo kinetic inhibition in rat (dose: 5 mg/kg p.o.), the results demonstrated a strong similarity of action with BromoMD and IodoMD, with an inhibition percentage that decreased with time (91% at 1 hour, 48% at 8 hours, 2% at 24 hours). The rat brain Iodo*MD concentration was maximal after the first pass and inhibition decreased slowly with time (T1/2 = 1.8 hours). Uptake and wash-out of Iodo*MD was studied on two-day-old rat astrocytes in culture. Half-times of uptake and efflux were respectively 2.5 minutes and 7.5 minutes. The use of metabolic inhibitors (KCN and Digoxin) suggested the absence of any active transport. Binding studies with various concentration of cold MD 360194 showed that at 10(-8) M the uptake decreased significantly. Rats were dissected at different times post i.v. injection (0-2 hours), and the principal organs and brain were obtained (the brain was separated into 7 pieces). Radioactivity was concentrated mainly in the liver (24.6 +/- 4%), fat (12.4 +/- 3.4%) and muscles (18.4 +/- 3%). In the brain the concentration was approximately 1.2 +/- 0.3% within 30 minutes post i.v. injection and 0.84 +/- 0.15% thereafter. The hypothalamus and striatum were two-fold more active than the cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Propanol

Early and delayed brain SPECT with technetium-99m-ECD and iodine-123-IMP in subacute strokes.

UNLABELLED: The brain distribution of 99mTc-ECD versus 123I-IMP was compared in patients with subacute stroke in order to compare diagnostic accuracy. METHODS: A total of 25 patients with subacute stroke underwent early and delayed SPECT imaging with 99mTc-ECD and 123I-IMP. Washout of 99mTc-ECD was calculated and a differential percentage of activity (DPA) of ischemic versus normal zones was assessed. Images were analyzed twice by five independent observers. RESULTS: Technetium-99m-ECD clearance was 12.5% from the whole brain during early imaging. Ischemic parietal zones had higher clearance than normal parietal zones. Technetium-99m-ECD images showed larger differences between abnormal and normal brain activity than 123I-IMP images. Detection accuracy was slightly, but not significantly, higher for 99mTc-ECD and 123I-IMP (sensitivity: 73.8% as 66.6%; specificity: 81.7% as 81.6%). Reproducibility among observers was similar for 99mTc-ECD and early 123I-IMP. CONCLUSION: Technetium-99m-ECD demonstrates high diagnostic accuracy during subacute stroke, similar to 123I-IMP, but with more intense, better delineation of the perfusion defects.

Adult