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Biomedical subjects

E Broussolle

Publications and source records attributed to E Broussolle.

At least 37 records · Page 2Linked to original sources
PubMed2001

Contributions of PET and SPECT to the understanding of the pathophysiology of Parkinson's disease.

Positron emission tomography (PET) and single photon emission computed tomography (SPECT) provide the means to studying in vivo the neurochemical, hemodynamic or metabolic consequences of the degeneration of the nigrostriatal dopaminergic system in Parkinson's disease (PD). The extent of striatal dopaminergic denervation can be quantified with radiotracers as [18F]FDopa for PET and [123I]tropanes for SPECT. There are other radiotracers such as [11C]Dopa and meta-tyrosines as well as PET tracers for uptake sites. Striatal uptake of [18F]FDopa and [123I]tropanes is markedly decreased in PD, more in the putamen than in the caudate nucleus, and inversely correlates with the severity of motor signs and with duration of disease. PET and SPECT make possible the assessment by noninvasive means of the changes in dopamine receptor density, the effect of neuronal transplants or neuroprotective treatments in PD patients, or the nigrostriatal dopaminergic function in at-risk subjects. Activation studies using cerebral blood flow and metabolism measurements during a motor task reveal an impaired ability to activate the supplementary motor area and dorsolateral prefrontal cortex in PD. This functional disability is reversed by the use of dopaminergic medication or by surgical treatment by pallidotomy or deep brain stimulation. The differential diagnosis between PD and multiple system atrophy, progressive supranuclear palsy or corticobasal degeneration is not yet clearly established by PET and SPECT, even though these syndromes have some particular neurochemical and metabolic profiles. On the other hand, PET and SPECT are useful for distinguishing PD from Dopa-responsive dystonia, or for assessing the integrity of the nigrostriatal dopaminergic pathway in atypical cases of postural tremor or iatrogenic parkinsonian syndromes.

Aging↗
PubMed2001

Glial toxicity in urine and multiple sclerosis.

The biochemical and biological characterization of a cytotoxic activity targeting macroglial cells (oligodendrocytes and astrocytes), in moncyte cultures and in CSF of a patient with multiple sclerosis, has previously been described. In further studies, cell-based tests have shown a good correlation between this glial cytotoxic (gliotoxic) activity, in CSF or in urine, and MS. We now present results obtained with urine samples from 102 MS patients, 51 patients with other neurological disease and 35 healthy subjects using a bioassay set up for the detection of an apoptosis-like effect induced in a glial cell-line. Significant gliotoxicity was detected in urine from 74/102 MS patients while only 4/51 neurological controls (P>0.001) and never in healthy subjects (P>0.001). Given the statistical tendency provided by this bioassay and its technical limitations for routine testing, it is now used for monitoring the molecular characterization of this 'gliotoxic factor'. Its replacement by a specific immunoassay could provide more accurate routine techniques for the detection of this biological marker in MS.

Adult↗
PubMed2000

Motor imagery in normal subjects and in asymmetrical Parkinson's disease: a PET study.

OBJECTIVE: To investigate, using PET and H2(15)O, brain activation abnormalities of patients with PD during motor imagery. To determine whether motor imagery activation patterns depend on the hand used to complete the task. BACKGROUND: Previous work in PD has shown that bradykinesia is associated with slowness of motor imagery. METHODS: The PET study was performed in eight patients with PD with predominantly right-sided akinesia, and in eight age-matched control subjects, all right-handed. Regional cerebral blood flow was measured by PET and H2(15)O while subjects imagined a predetermined unimanual externally cued sequential movement with a joystick with either the left or the right hand, and during a rest condition. RESULTS: In normal subjects, the prefrontal cortex, supplementary motor area (SMA), superior parietal lobe, inferior frontal gyrus, and cerebellum were activated during motor imagery with either the left or the right hand. Contralateral primary motor cortex activation was noted only when the task was imagined with the right (dominant) hand, whereas activation of the dorsolateral prefrontal cortex was observed only during imagery with the left hand. In patients with PD, motor imagery with the right ("akinetic") hand was characterized by lack of activation of the contralateral primary sensorimotor cortex and the cerebellum, persistent activation of the SMA, and bilateral activation of the superior parietal cortex. Motor imagery with the left ("non-akinetic") hand was also abnormal, with lack of activation of the SMA compared with controls. CONCLUSIONS: In patients with PD with predominantly right-sided akinesia, brain activation during motor imagery is abnormal and may appear even with the less affected hand. In normal subjects, brain activation during motor imagery depends on the hand used in the imagined movement.

Adult↗
PubMed2000

[18 F]-dopa PET study in patients with juvenile-onset PD and parkin gene mutations.

+Parkin gene mutations cause a form of early-onset autosomal recessive PD with neuronal loss in the substantia nigra and no Lewy bodies. The authors present a PET [18F]-dopa study of one familial and two sporadic cases with juvenile-onset PD resulting from parkin gene mutations. They found a profound decrease of [18F]-dopa uptake, representing 28% of putamen and 44% of caudate nucleus control subject values. PD caused by parkin gene mutations is distinct from idiopathic PD on molecular grounds but has similar clinical and PET findings.

Adult↗
PubMed2000

Overactivation of primary motor cortex is asymmetrical in hemiparkinsonian patients.

Regional cerebral blood flow (rCBF) was measured using PET and H2(15)O in Parkinson's disease (PD) patients with predominantly right-sided akinetic-rigid symptoms and in control subjects during the execution of an externally cued motor task either with the left or the right hand. During the execution of the task with the left, non-akinetic, hand, cerebral activation in PD patients appeared similar to that of controls. Activated areas were the primary motor cortex, premotor cortex, parietal cortex and cerebellum. When the task was executed with the right, akinetic, hand cerebral activation in PD patients differed from that of controls subjects. The most important change was a bilateral activation of the primary motor cortex. We conclude that overactivation of primary motor cortex is asymmetrical in hemiparkinsonian patients.

Adult↗
PubMed2000

Clinical report of three patients with hereditary hemochromatosis and movement disorders.

Neurologic manifestations are rarely described in hereditary hemochromatosis (HH). We describe three patients with HH and movement disorders. Patient 1, a 69-year-old man, had a 13-year history of disabling cerebellar syndrome, action tremor and myoclonus, and secondary dementia. Patient 2 was a 40-year-old man with a 9-year history of cerebellar syndrome, head and arm tremor, and cervical dystonia. Patient 3, a 75-year-old woman, had a 5-year history of rapidly disabling parkinsonian syndrome unresponsive to levodopa. The diagnosis of HH was established in the three patients by iron tests, evidence of a C282Y mutation, and, in two patients, by liver biopsy. High-field T2-weighted magnetic resonance imaging showed hyperintense signals in hemispheric white matter in patient 1, cerebellar atrophy in patient 2, and cerebellar and cerebral atrophy in patient 3 and no significant hypointense signals in the three patients. Phlebotomies and symptomatic treatments did not change the course of the disease. Our cases are compared with the five previously reported observations of HH with movement disorders. This rare association is one cause of the chronic acquired non-Wilsonian hepatocerebral degeneration syndromes and represents a separate entity from aceruloplasminemia. The pathophysiologic mechanism of movement disorders in HH is unresolved. No hepatic insufficiency and portosystemic encephalopathy is evidenced in our cases, whereas the putative role of abnormal iron load remains to be ascertained. HH should be investigated more systematically in patients with movement disorders.

Adult↗
PubMed1999

The relation of putamen and caudate nucleus 18F-Dopa uptake to motor and cognitive performances in Parkinson's disease.

The contribution of striatal (caudate nucleus-putamen) dopaminergic deficiency to the severity of motor signs is well established in Parkinson's disease (PD), while its role in the occurrence of cognitive and mood changes remains unresolved. We therefore measured in 27 non-demented PD patients and 10 age-matched controls striatal uptake of [18F]-6-fluoro-L-Dopa (F-Dopa) with PET, and mood (Beck depression), memory (Grober-Buschke), frontal executive functions (verbal fluency and Wisconsin card sorting), and attentional processing of sensory stimuli (N2-P3 auditory event-related potentials--ERPs). Locomotor disability of patients was assessed by Hoehn and Yahr score and Unified Parkinson's Disease Rating Scale (UPDRS). ANOVA showed that memory, but neither frontal lobe functions nor ERPs, was significantly altered in PD patients, whereas indices of depression were found only in advanced PD. The F-Dopa rate constant Ki was significantly reduced in the striatum, more in putamen than caudate nucleus, and inversely correlated with disease duration. A significant inverse correlation was found between both putamen and caudate nucleus Ki and Hoehn and Yahr score, and between putamen--but not caudate nucleus Ki --and UPDRS motor score. Principal components analysis (PCA) of PD patients Ki values and mood, cognitive and ERP parameters gave a three-factor solution. Variables contributing to factor 1 were memory score and N2-P3 ERP latencies, those to factor 2 were striatal Ki values, and those to factor 3 frontal executive performances. Depression did not segregate with any variable. Our findings suggest that unlike locomotor disability, cognitive abilities and mood state of non-demented PD patients are for the most part unrelated to striatal dopaminergic depletion and may result from dysfunction of extra-striatal dopaminergic or from non-dopaminergic systems.

Adult↗
PubMed1999

Phosphorus and proton magnetic resonance spectroscopy in episodic ataxia type 2.

Localized phosphorus (31P) and proton (1H) magnetic resonance spectroscopy was performed in the cerebellum and the occipital lobe of 6 patients with episodic ataxia type 2. From use of 31P magnetic resonance spectroscopy, untreated patients showed decreased high-energy phosphate ratios in the cerebrum, and increased pH in the cerebellum and cerebrum, which normalized under acetazolamide. 1H magnetic resonance spectra demonstrated high lactate peaks in 3 of the 6 patients. These metabolic alterations, probably induced by the calcium channelopathy, may characterize episodic ataxia type 2.

Acetazolamide↗
PubMed1999

A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe. French Parkinson's Disease Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson's Disease.

Autosomal recessive juvenile parkinsonism (AR-JP, PARK2; OMIM 602544), one of the monogenic forms of Parkinson's disease (PD), was initially described in Japan. It is characterized by early onset (before age 40), marked response to levodopa treatment and levodopa-induced dyskinesias. The gene responsible for AR-JP was recently identified and designated parkin. We have analysed the 12 coding exons of the parkin gene in 35 mostly European families with early onset autosomal recessive parkinsonism. In one family, a homozygous deletion of exon 4 could be demonstrated. By direct sequencing of the exons in the index patients of the remaining 34 families, eight previously undescribed point mutations (homozygous or heterozygous) were detected in eight families that included 20 patients. The mutations segregated with the disease in the families and were not detected on 110-166 control chromosomes. Four mutations caused truncation of the parkin protein. Three were frameshifts (202-203delAG, 255delA and 321-322insGT) and one a nonsense mutation (Trp453Stop). The other four were missense mutations (Lys161Asn, Arg256Cys, Arg275Trp and Thr415Asn) that probably affect amino acids that are important for the function of the parkin protein, since they result in the same phenotype as truncating mutations or homozygous exon deletions. Mean age at onset was 38 +/- 12 years, but onset up to age 58 was observed. Mutations in the parkin gene are therefore not invariably associated with early onset parkinsonism. In many patients, the phenotype is indistinguishable from that of idiopathic PD. This study has shown that a wide variety of different mutations in the parkin gene are a common cause of autosomal recessive parkinsonism in Europe and that different types of point mutations seem to be more frequently responsible for the disease phenotype than are deletions.

Binding Sites↗
PubMed1998

A de novo missense mutation (R1623Q) of the SCN5A gene in a Japanese girl with sporadic long QT sydrome. Mutations in brief no. 140. Online.

Two missense mutations and a nine-nucleotide deletion of the cardiac sodium channel (SCN5A) gene have been shown to cause long QT syndrome (LQTS) in several familial cases. We identified a novel missense mutation (R1623Q) of the SCN5A gene in a Japanese girl with sporadic LQTS. We used polymerase chain reaction, single-strand conformation polymorphism analysis and DNA sequence analysis to identify a mutation of the SCN5A gene in the patient. A single nucleotide substitution of guanine to adenine, in codon 1612, changed the coding sense of the SCN5A from arginine to glutamine (R1623Q) in the S4 segment of domain IV which is a highly conserved region of the SCN5A. This mutation was not identified in the unaffected biological parents and brother of the patient, and 100 normal, unrelated individuals. This finding is the first evidence of a de nova mutation in SCN5A associated with LQTS.

Amino Acid Substitution↗
PubMed1998

Course of valvular strands in patients with stroke: cooperative study with transesophageal echocardiography.

BACKGROUND: Native valve strands might be related to the acute stage of thrombosis or might suggest a long-term valvular change. We aimed to estimate changes in the strands in patients with stroke through a serial transesophageal echocardiographic (TEE) study. METHODS AND RESULTS: A study was conducted among patients who were referred for TEE for stroke or cardiac pathology. Patients had TEE examinations with a 5-MHz multiplane TEE probe. Echocardiography was repeated 3 months later in patients with stroke. TEE was performed in 180 patients admitted to cardiology units and in 160 patients referred to neurology units. Among 34 patients with valvular strands, 30 were referred to neurology for stroke, whereas 4 patients were admitted to cardiology (18.8% versus 2.2%, difference 16.5%, 95% confidence interval 10% to 22.9%, P =.001). Strands were located on the mitral valve in 16 patients, the aortic valve in 6 patients, and both left heart valves in 8 patients. Among the 38 valves with strands, 17 (44. 7%) were morphologically normal, 4 (10.5%) were thickened, 7 (18.4%) were redundant, and 10 (26.3%) had both abnormalities. TEE showed other abnormalities in 16 (53.3%) patients, whereas 14 patients had only strands. Twenty-six (86.6%) patients had a second TEE study 3 months later. Strands were not found in 4 (15.4%) patients (95% confidence interval 4.3% to 34.9%). CONCLUSIONS: Valvular thickening or redundancy may predispose valves to strand formation. Native valve strands usually persist and thus reflect a chronic valvular change.

Adolescent↗
PubMed1998

Gliomatosis cerebri: a rare cause of progressive headache.

A 49-year-old right-handed woman was admitted for an 8-month history of unusual headache and transient diplopia. Clinical examination and brain CT scan were normal. Two months later, symptoms of raised intracranial pressure developed and a brain CT scan showed small lateral ventricles and sulci without any abnormal contrast enhancement or tumor mass. Brain MRI with T2-weighted spin echo sequences revealed a hyperintense signal in the right temporoparietal region, whereas only a slight enlargement of this region was noted on T1 spin echo. The patient deteriorated rapidly and died with uncontrollable raised cerebrospinal fluid pressure. The diagnosis of gliomatosis cerebri was made at necropsy. Gliomatosis cerebri is a rare intracranial neoplasm of neuroepithelial origin. Spread of this tumor is particularly fast in the white matter compared with the gray matter and nuclei. Clinical symptoms are not specific. The diagnosis can be suspected by MFU showing an isointense or hypointense signal in the deep white matter on T1-weighted images, and largely a hyperitense signal on T2-weighted sequences. The diagnosis is confirmed by stereotactic biopsy or necropsy. No curative treatment is currently available. Radiotherapy can delay the rapidly fatal outcome. Our case illustrates the possible onset of this rare disease by isolated cephalgia with normal early CT scan.

Brain Neoplasms↗
PubMed1998

Chromosome 6-linked autosomal recessive early-onset Parkinsonism: linkage in European and Algerian families, extension of the clinical spectrum, and evidence of a small homozygous deletion in one family. The French Parkinson's Disease Genetics Study Group, and the European Consortium on Genetic Susceptibility in Parkinson's Disease.

The gene for autosomal recessive juvenile Parkinsonism (AR-JP) recently has been mapped to chromosome 6q25.2-27 in Japanese families. We have tested one Algerian and 10 European multiplex families with early-onset Parkinson disease for linkage to this locus, with marker D6S305. Homogeneity analysis provided a conditional probability in favor of linkage of >.9 in eight families, which were analyzed further with eight microsatellite markers spanning the 17-cM AR-JP region. Haplotype reconstruction for eight families and determination of the smallest region of homozygosity in two consanguineous families reduced the candidate interval to 11.3 cM. If the deletion of two microsatellite markers (D6S411 and D6S1550) that colocalize on the genetic map and that segregate with the disease in the Algerian family is taken into account, the candidate region would be reduced to <1 cM. These findings should facilitate identification of the corresponding gene. We have confirmed linkage of AR-JP, in European families and in an Algerian family, to the PARK2 locus. PARK2 appears to be an important locus for AR-JP in European patients. The clinical spectrum of the disease in our families, with age at onset <=58 years and the presence of painful dystonia in some patients, is broader than that reported previously.

Age of Onset↗