Biomedical subjects

Pierre Brugières

Publications and source records attributed to Pierre Brugières.

13 recordsLinked to original sources

PubMed2006

Bilateral periventricular heterotopias in an X-linked dominant transmission in a family with two affected males.

We report on the case of dizygotic twin boys, born prematurely to an asymptomatic mother. Bilateral periventricular heterotopias with enlarged ventricles were discovered at birth in both twins. One of the twins died prematurely of bronchopulmonary complications, and was shown to have several neuropathological anomalies (microgyria, thin corpus callosum, and reduced white matter). The surviving twin had mental retardation, without epilepsy. MRI of the mother showed asymptomatic periventricular heterotopias without ventricular enlargement. She had two affected daughters also with asymptomatic periventricular heterotopias. A point mutation in the last coding exon 48 of the Filamin A (FLNA) gene (7922c > t) was discovered on sequencing and segregated with the affected individuals. This family has a classical X-linked dominant BPNH pathology, with greater severity in males than females. The location of the FLNA mutation is discussed in light of the neuropathological anomalies and mental retardation in male patients.

Amino Acid Sequence↗

PubMed2006

Effect of fetal neural transplants in patients with Huntington's disease 6 years after surgery: a long-term follow-up study.

BACKGROUND: Although we have shown in three out of five patients with Huntington's disease that motor and cognitive improvements 2 years after intracerebral fetal neural grafts are correlated with recovery of brain metabolic activity in grafted striatal areas and connected regions of the cerebral cortex, neural grafts are not known to have protective effects on the host brain per se. We undertook long-term follow-up of previously reported patients with the disease to ascertain the nature and extent of any secondary decline after grafting. METHODS: Five patients with Huntington's disease from our pilot study were assessed annually with the unified Huntington's disease rating scale, neuropsychological tests, and MRI, for up to 6 years after neural grafting. Resting cerebral activity was recorded at 2 and 6 years. FINDINGS: Clinical improvement plateaued after 2 years and then faded off variably 4-6 years after surgery. Dystonia deteriorated consistently, whereas chorea did not. Cognitive performance remained stable on non-timed tests, whereas progression of motor disability was shown by deterioration on timed tests. Hypometabolism also affected the brain heterogeneously, sparing the benefits in the frontal cortex and at the precise location of the grafts, but showing a progressive deterioration in other areas. Two patients who had no benefit from grafting at 2 years continued to decline in the same way as non-grafted patients. INTERPRETATION: Neuronal transplantation in Huntington's disease provides a period of several years of improvement and stability, but not a permanent cure for the disease. Improvement of the surgical procedure and in patient selection could improve the therapeutic value, but neuroprotective treatment seems to be unavoidable in the disease.

Adult↗

PubMed2006

Posterior cervical spinal cord infarction complicating the treatment of an intracranial dural arteriovenous fistula embolization. Case report.

Acute ischemic infarction of the posterolateral bulbomedullary junction occurred in a 28-year-old man who underwent arterial embolization for the treatment of an intracranial dural arteriovenous malformation. The migration of the embolic agent in the posterior spinal artery via a peripheral anastomosis between the middle meningeal artery and the posterior meningeal artery was responsible for this complication. The cast of glue in the radiculopial system at the upper cervical level was visible on computed tomography scanning, and magnetic resonance imaging demonstrated circumscribed signal changes and restricted diffusion in the arterial territory of the bulbomedullary junction. The authors discuss the anatomical, clinical, and technical issues of this rare complication.

Adult↗

PubMed2005

The role of the striatum in rule application: the model of Huntington's disease at early stage.

The role of the basal ganglia, and more specifically of the striatum, in language is still debated. Recent studies have proposed that linguistic abilities involve two distinct types of processes: the retrieving of stored information, implicating temporal lobe areas, and the application of combinatorial rules, implicating fronto-striatal circuits. Studies of patients with focal lesions and neurodegenerative diseases have suggested a role for the striatum in morphological rule application, but functional imaging studies found that the left caudate was involved in syntactic processing and not morphological processing. In the present study, we tested the view that the basal ganglia are involved in rule application and not in lexical retrieving in a model of striatal dysfunction, namely Huntington's disease at early stages. We assessed the rule-lexicon dichotomy in the linguistic domain with morphology (conjugation of non-verbs and verbs) and syntax (sentence comprehension) and in a non-linguistic domain with arithmetic operations (subtraction and multiplication). Thirty Huntington's disease patients (15 at stage I and 15 at stage II) and 20 controls matched for their age and cultural level were included in this study. Huntington's disease patients were also assessed using the Unified Huntington's Disease Rating Scale (UHDRS) and MRI. We found that early Huntington's disease patients were impaired in rule application in the linguistic and non-linguistic domains (morphology, syntax and subtraction), whereas they were broadly spared with lexical processing. The pattern of performance was similar in patients at stage I and stage II, except that stage II patients were more impaired in all tasks assessing rules and had in addition a very slight impairment in the lexical condition of conjugation. Finally, syntactic rule abilities correlated with all markers of the disease evolution including bicaudate ratio and performance in executive function, whereas there was no correlation with arithmetic and morphological abilities. Together, this suggests that the striatum is involved in rule processing more than in lexical processing and that it extends to linguistic and non-linguistic domains. These results are discussed in terms of domain-specific versus domain-general processes of rule application.

Adult↗

PubMed2005

Long-term follow-up of pediatric sickle cell disease patients with abnormal high velocities on transcranial Doppler.

Cerebral arteriopathy can be detected in children with sickle cell disease (SCD) by transcranial Doppler (TCD). Abnormally high velocities are predictive of high stroke risk, which can be reduced by transfusion therapy. We report the results of the screening of 291 SCD children followed in our center, including the clinical and imaging follow-up of 35 children with abnormal TCDs who were placed on transfusion therapy. We postulated that patients with normal MRA findings and abnormal TCD velocities that normalized on a transfusion program could be safely treated with hydroxyurea (HU). We report their outcome (median follow-up of 4.4 years). Of 13 patients with normalized velocities on transfusion, 10 had normal MRAs, and transfusion therapy was stopped and HU begun. Four of these ten patients redeveloped high velocities off transfusion, so currently only six remain transfusion-free. Six other transplanted patients remain transfusion-free. Abnormal TCD velocities detect a high-risk group, justifying the research for suitable transplant donors. Multicenter studies comparing HU therapy to long-term transfusion might help identify which patients can avoid transfusion and its complications while avoiding vasculopathy.

Adolescent↗

PubMed2004

Neurofibromatosis 1-associated neuropathies: a reappraisal.

Neurofibromatosis 1 (NF1) is a common disease which is a source of various multisystemic manifestations related either to the accumulation of neurofibromas or to specific developmental abnormalities. The neurofibroma is the hallmark lesion of NF1 and develops from peripheral nerves. However, to date, the description of peripheral neuropathies of NF1 has not been investigated. To examine this question, we have evaluated 688 NF1 patients for the presentation, prognosis and associated morbidity of peripheral neuropathies in two hospital-based series. We collected 18 patients (four women and 14 men) with diffuse peripheral neuropathy (2.3%). Eight patients had a paucisymptomatic or an asymptomatic neuropathy detected only on electrophysiological study, two had minor sensory manifestations, five had moderate motor and sensory manifestations and three had severe motor and sensory manifestations. Superimposed radicular changes were observed in seven cases. Two patients had a subacute and 16 a chronic polyneuropathy. Fourteen patients had a demyelinating neuropathy with either severe axonal changes (three), moderate or minor axonal changes (four) or no axonal changes (seven). Four patients had axonal neuropathies. There was a strong association between the presence of a peripheral neuropathy and large root diffuse neurofibromas (P < 0.03) and subcutaneous neurofibromas (P < 0.0001). Severe morbidity and mortality of patients with NF1 and peripheral neuropathies was 50%, much higher than what is observed in the general population of patients with NF1, and 100% in patients with the most severe symptoms and electrophysiological changes (demyelination with severe axonal features). Four patients out of 18 (22%) developed a malignant peripheral nerve sheath tumour (MPNST), a much higher proportion than in the whole population of NF1. Two patients died. Peripheral neuropathy constitutes a potentially severe complication in patients with NF1 associated with a frequent morbidity related to spinal complications and MPNSTs. Association of proximal large neurofibromas, peripheral neuropathies and subcutaneous neurofibromas may constitute a phenotype of NF1 with a severe prognosis.

Adolescent↗

PubMed2004

Comparison of in vitro and in vivo MRI of the spine using parallel imaging.

OBJECTIVE: The purpose of this study was to compare the image quality of two parallel-imaging methods applied to standard turbo spin-echo T2-weighted imaging of the lumbar spine. MATERIALS AND METHODS: Phantom imaging and lumbar spine studies of 15 healthy subjects were performed using T2-weighted turbo spin-echo sequences obtained with and without parallel imaging (generalized autocalibrating partially parallel acquisition [GRAPPA] and modified sensitive encoding [mSENSE]) on a 1.5-T magnet. The signal-to-noise ratio (SNR) and uniformity were measured in the phantom, and SNR and signal difference-noise ratio were evaluated in cerebrospinal fluid, vertebral bodies, and subcutaneous fat of the volunteers, using both techniques sequentially. Aliasing artifacts on GRAPPA and mSENSE images were visually evaluated. SNRs were compared using the Student's paired t test, with p values less than 0.05 considered significant. RESULTS: In the phantom study, when the same number of coil elements were used (n = 3), SNR and uniformity values obtained with standard T2-weighted turbo spin-echo sequences were higher than those obtained with parallel sequences. The GRAPPA SNR obtained with three coil elements was higher than the standard T2-weighted SNR obtained with one coil element. Similar findings were noted regarding uniformity. In the lumbar spine, GRAPPA SNR values for fat, cerebrospinal fluid, and vertebral bodies were significantly higher than mSENSE SNR values, with a p value less than 0.01, but were not significantly different from T2-weighted turbo spin-echo SNR values. GRAPPA signal difference-noise ratio values were significantly higher than mSENSE signal difference-noise ratio values, with a p value less than 0.01, but were not significantly different from T2-weighted turbo spin-echo signal difference-noise ratio values. GRAPPA produced fewer aliasing artifacts than mSENSE. CONCLUSION: In spine MRI, GRAPPA may be used to reduce scanning time and yields a higher SNR than mSENSE without any increase in aliasing artifacts and with an SNR similar to that obtained with standard T2-weighted turbo spin-echo.

Artifacts↗

PubMed2004

Water diffusion compartmentation at high b values in ischemic human brain.

BACKGROUND AND PURPOSE: We studied the evolution of brain water compartments during the early stage of ischemic stroke. METHODS: Diffusion-weighted imaging was performed at 1.5 T in 10 volunteers and 14 patients with stroke. We used a single-shot echo-planar technique with 11 b values of 0-5000 s/mm(2). Regions of interest were selected in the white matter (WM) and striatum of the volunteers and in the ischemic core of the patients. Measurements were fitted on the basis of a biexponential decay with the b factor as follows: S(b) = S(0)[(f(slow) x exp(-b x ADC(slow)) + (f(fast) x exp(-b x ADC(fast))] where S(b) is the signal intensity in the presence of a diffusion gradient, S(0) is the signal intensity without diffusion sensitization, ADC(slow) and ADC(fast) are the respective apparent diffusion coefficients (ADCs) of slow diffusing compartments (SDCs) and fast diffusing compartments (FDCs), and f(slow) and f(fast) the respective contributions to the signal intensity of SDC and FDC. RESULTS: In healthy subjects, FDC represents 74.3 +/- 3.1% of brain water, with ADC(fast) = (124.6 +/- 12.0) x 10(-5) mm(2)/s and ADC(slow) = (15.5 +/- 3.9) x 10(-5) mm(2)/s. In stroke, decreased FDC (49.1% +/- 10.9%; P = 1.05 x10(-5)) and increased ADC(slow) ([22.4 +/- 8.1] x 10(-5) mm(2)/s; P = 8.07 x 10(-3)) were observed, but ADC(fast) was not significantly changed ([135.6 +/- 25.7] x 10 (-5) mm(2)/s; P =.151). CONCLUSION: The restricted diffusion observed in the early stroke is mainly related to a redistribution of water from the FDC to the SDC.

Body Water↗

PubMed2003

Striatal neural grafting improves cortical metabolism in Huntington's disease patients.

Huntington's disease is a hereditary disease in which degeneration of neurons in the striatum leads to motor and cognitive deficits. Foetal striatal allografts reverse these deficits in phenotypic models of Huntington's disease developed in primates. A recent open-label pilot study has shown some clinical improvement or stabilization in three out of five Huntington's disease patients who received bilateral striatal grafts of foetal neurons. We show here that the clinical changes in these three patients were associated with a reduction of the striatal and cortical hypometabolism, demonstrating that grafts were able to restore the function of striato-cortical loops. Conversely, in the two patients not improved by the grafts, striatal and cortical hypometabolism progressed over the 2-year follow-up. Finally, detailed anatomical-functional analysis of the grafted striata, enabled by the 3D fusion of MRI and metabolic images, revealed considerable heterogeneity in the anatomic and metabolic profiles of grafted tissue, both within and between Huntington's disease patients. Our results demonstrate the usefulness of PET measurements of brain glucose metabolism in understanding the effects of foetal grafts in patients with Huntington's disease.

Adult↗

PubMed2003

Antiangiogenic therapy against experimental glioblastoma using genetically engineered cells producing interferon-alpha, angiostatin, or endostatin.

Inhibition of angiogenesis has been considered among the most promising approaches to treat highly vascularized solid tumors such as glioblastoma. In this study, we designed and validated a new in vitro assay system based on the implantation of tumor cells into organotypic brain slice cultures. We evaluated the effects of local production of three endogenous inhibitors of angiogenesis, angiostatin, endostatin, and interferon (IFN)-alpha(1), using stably transfected rat (9L) and human (GL15) glioblastoma cells on tumor vascularization and growth. Despite similar effectiveness of the three proteins in a classic in vitro endothelial cell migration assay, IFN-alpha(1) demonstrated the most potent antiangiogenic effect in organotypic brain slice cultures. In vivo, after intracerebral implantation of such genetically modified glioblastoma cells, IFN-alpha(1) caused a dramatic decrease in tumor volume revealed by magnetic resonance imaging and by postmortem histology. The mechanisms of this antitumor effect were most likely caused by the major antiangiogenic action of the cytokine, because IFN-alpha(1) expression provoked a pronounced decrease in blood vessel density, which was accompanied by extensive necrosis in the body mass of the tumors. The median survival time of rats implanted intracerebrally with IFN-alpha-expressing 9L cells tripled, and was still significantly increased when these constituted only 1% of transplanted tumor cells. A similar effect was seen when 50% of the transplanted cells were replaced by IFN-alpha-expressing bone marrow stromal cells. These data point to the local delivery of IFN-alpha(1) using cell vectors as a potent tool for the inhibition of tumor-induced angiogenesis.

Angiogenesis Inhibitors↗

PubMed2003

Hydrocephalus due to idiopathic stenosis of the foramina of Magendie and Luschka. Report of three cases.

Idiopathic stenosis of the foramina of Magendie and Luschka is a rare cause of obstructive hydrocephalus involving the four ventricles. Like other causes of noncommunicating hydrocephalus, it can be treated with endoscopic third ventriculostomy (ETV). Three patients who were 21, 53, and 68 years of age presented with either headaches (isolated or associated with raised intracranial pressure) or vertigo, or a combination of gait disorders, sphincter disorders, and disorders of higher functions. In each case, magnetic resonance (MR) imaging demonstrated hydrocephalus involving the four ventricles (mean transverse diameter of third ventricle 14.15 mm; mean sagittal diameter of fourth ventricle 23.13 mm; and mean ventricular volume 123.92 ml) with no signs of a Chiari Type I malformation (normal posterior fossa dimensions, no herniation of cerebellar tonsils). The diagnosis of obstruction was confirmed using ventriculography (in two patients) and/or MR flow images (in two patients). All patients presented with marked dilation of the foramen of Luschka that herniated into the cisterna pontis. All patients were treated using ETV. No complications were observed. All three patients became asymptomatic during the weeks following the surgical procedure and remained stable at a mean follow-up interval of 36 months. Postoperative MR images demonstrated regression of the hydrocephalus (mean transverse diameter of third ventricle 7.01 mm; mean sagittal diameter of fourth ventricle 16.6 mm; and mean ventricular volume 79.95 ml), resolution of dilation of the foramen of Luschka, and good patency of the ventriculostomy (flow sequences). These results confirm the existence of hydrocephalus caused by idiopathic fourth ventricle outflow obstruction without an associated Chiari Type I malformation, and the efficacy of ETV for this rare indication.

Adult↗

PubMed2002

An 8-y-old boy with acute stroke and radiological signs of cerebral vasculitis after recent Mycoplasma pneumoniae infection.

A young boy was admitted to hospital for acute stroke. Cerebral angiography showed a pattern suggestive of vasculitis and a recent Mycoplasma pneumoniae infection was detected. The absence of microorganisms in cerebrospinal fluid, the pattern of vasculitis and previous reports supporting a post-infectious immunological mechanism for certain complications of M. pneumoniae infection suggest this mechanism as the cause of the stroke.

Cerebral Angiography↗

PubMed1999

Chronic motor cortex stimulation in the treatment of central and neuropathic pain. Correlations between clinical, electrophysiological and anatomical data.

Thirty-two patients with refractory central and neuropathic pain of peripheral origin were treated by chronic stimulation of the motor cortex between May 1993 and January 1997. The mean follow-up was 27.3 months. The first 24 patients were operated according to the technique described by Tsubokawa. The last 13 cases (eight new patients and five reinterventions) were operated by a technique including localisation by superficial CT reconstruction of the central region and neuronavigator guidance. The position of the central sulcus was confirmed by the use of intraoperative somatosensory evoked potentials. The somatotopic organisation of the motor cortex was established peroperatively by studying the motor responses at stimulation of the motor cortex through the dura. Ten of the 13 patients with central pain (77%) and ten of the 12 patients with neuropathic facial pain had experienced substantial pain relief (75%). One of the three patients with post-paraplegia pain was clearly improved. A satisfactory result was obtained in one patient with pain related to plexus avulsion and in one patient with pain related to intercostal herpes zooster. None of the patients developed epileptic seizures. The position of the stimulating poles effective on pain corresponded to the somatotopic representation of the motor cortex. The neuronavigator localisation and guidance technique proved to be most useful identifying the appropriate portion of the motor gyrus. It also allowed the establishment of reliable correlations between electrophysiological-clinical and anatomical data which may be used to improve the clinical results and possibly to extend the indications of this technique.

Adult↗