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Biomedical subjects

J Honnorat

Publications and source records attributed to J Honnorat.

At least 55 records · Page 3Linked to original sources
PubMed2001

Thrombolytic therapy in acute ischemic stroke patients with cardiac thrombus.

The authors describe the outcome of five patients with a cardiac thrombus selected among 183 patients with stroke (2.7 %) who were given IV tissue plasminogen activator (tPA). No early systemic or cerebral embolism occurred. Two patients made a complete recovery at 3 months. Two patients had a moderate outcome. One patient had late recurrent cerebral embolism and died. These data suggest that the presence of a cardiac thrombus is not associated with a high risk of recurrent embolism in patients with stroke who are given IV tPA.

Aged↗
PubMed2001

Isolation and expression pattern of human Unc-33-like phosphoprotein 6/collapsin response mediator protein 5 (Ulip6/CRMP5): coexistence with Ulip2/CRMP2 in Sema3a- sensitive oligodendrocytes.

The Unc-33-like phosphoprotein/collapsin response mediator protein (Ulip/CRMP) family consists of four homologous phosphoproteins considered crucial for brain development. Autoantibodies produced against member(s) of this family by patients with paraneoplastic neurological diseases have made it possible to clone a fifth human Ulip/CRMP and characterize its cellular and anatomical distribution in developing brain. This protein, referred to as Ulip6/CRMP5, is highly expressed during rat brain development in postmitotic neural precursors and in the fasciculi of fibers, suggesting its involvement in neuronal migration/differentiation and axonal growth. In the adult, Ulip6/CRMP5 is still expressed in some neurons, namely in areas that retain neurogenesis and in oligodendrocytes in the midbrain, hindbrain, and spinal cord. Ulip2/CRMP2 and Ulip6/CRMP5 are coexpressed in postmitotic neural precursors at certain times during development and in oligodendrocytes in the adult. Because Ulip2/CRMP2 has been reported to mediate semaphorin-3A (Sema3A) signal in developing neurons, in studies to understand the function of Ulip6/CRMP5 and Ulip2/CRMP2 in the adult, purified adult rat brain oligodendrocytes were cultured in a Sema3A-conditioned medium. Oligodendrocytes were found to have Sema3A binding sites and to express neuropilin-1, the major Sema3A receptor component. In the presence of Sema3A, these oligodendrocytes displayed a dramatic reduction in process extension, which was reversed by removal of Sema3A and prevented by anti-neuropilin-1, anti-Ulip6/CRMP5, anti-Ulip2/CRMP2 antibodies, or VEGF-165, another neuropilin-1 ligand. These results indicate the existence in the adult brain of a Sema3A signaling pathway that modulates oligodendrocyte process extension mediated by neuropilin-1, Ulip6/CRMP5, and Ulip2/CRMP2, and they open new fields of investigation of neuron/oligodendrocyte interactions in the normal and pathological brain.

Animals↗
PubMed2001

Cerebellar ataxia with anti-glutamic acid decarboxylase antibodies: study of 14 patients.

BACKGROUND: Antibodies to glutamic acid decarboxylase (GAD-Ab) are described in patients with insulin-dependent (type 1) diabetes mellitus (IDDM), in stiff-man syndrome, and, recently, in a few patients with cerebellar ataxia. OBJECTIVES: To show a link between GAD-Ab and some patients with cerebellar ataxia and to clarify their clinical and immunologic profiles. METHODS: Serum samples were selected from 9000 samples of 4 laboratories. The selection criterion was an immunohistochemical pattern compatible with GAD-Ab that was confirmed by radioimmunoassay. We identified 22 patients with stiff-man syndrome and 14 with cerebellar ataxia and GAD-Ab. RESULTS: Thirteen of the 14 patients with cerebellar ataxia and GAD-Ab were women, and 11 had late-onset IDDM. Patients did not have clinical or radiologic evidence of brainstem involvement. Ten patients had oligoclonal IgG bands in the cerebrospinal fluid, and intrathecal GAD-Ab synthesis was observed in 5 of the 6 patients studied. The level of GAD-Ab of these patients was similar to those with stiff-man syndrome and significantly higher than those with IDDM or with polyendocrine autoimmunity (P<.001). However, the GAD-Ab levels of 6 of the 9 patients with polyendocrine autoimmunity overlapped with those of patients with cerebellar ataxia. CONCLUSIONS: These results suggest a link between high level of GAD-Ab and some cases of cerebellar ataxia, particularly women with IDDM. If high serum levels of GAD-Ab are detected, the cerebrospinal fluid should be evaluated for the presence of oligoclonal IgG bands and intrathecal synthesis of GAD-Ab to further prove an autoimmune origin of the syndrome.

Adult↗
PubMed2001

Paraneoplastic anti-CV2 antibodies react with peripheral nerve and are associated with a mixed axonal and demyelinating peripheral neuropathy.

Subacute sensory neuronopathy with anti-Hu antibodies is the best-characterized paraneoplastic peripheral neuropathy associated with carcinoma. Anti-CV2 antibodies, another group of paraneoplastic antibodies, react with a 66-kd brain protein belonging to the family of Ulip/CRMP proteins. The manifestations associated with anti-CV2 antibodies include cerebellar degeneration, uveitis, and peripheral neuropathy. Some of these patients also have anti-Hu antibodies. We have compared the clinical, electrophysiological, and pathological characteristics of the peripheral neuropathy in 9 patients with anti-CV2 antibodies (3 of whom also had anti-Hu antibodies) and 12 patients with only anti-Hu antibodies. Data for patients with anti-Hu antibodies alone indicated subacute sensory neuronopathy. Patients with anti-CV2 antibodies had a mixed axonal and demyelinating sensory motor neuropathy that was sometimes superimposed on subacute sensory neuronopathy when both anti-CV2 and anti-Hu antibodies were present. Unlike anti-Hu antibodies, anti-CV2 antibodies reacted with peripheral nerve antigens, as shown by their ability to bind to a 66-kd protein in human and rat nerve on Western blot analysis and to immunolabel peripheral nerve axons and sensory neurons on immunohistochemical study.

Aged↗
PubMed2001

Redifferentiation therapy in brain tumors: long-lasting complete regression of glioblastomas and an anaplastic astrocytoma under long term 1-alpha-hydroxycholecalciferol.

PURPOSE: Classical and new therapies in anaplastic astrocytomas and glioblastomas do not yield sufficient results. Agents able to redifferentiate neoplastic cells in vitro are known. We proposed alfacalcidol, a vitamin D analog able to bind to nuclear receptors regulating mitotic activity, in the treatment of malignant gliomas. PATIENTS AND METHODS: Patients with glioblastomas and anaplastic astrocytomas were enrolled in a phase II trial involving surgery or biopsy, radiotherapy (64 Gy), chemotherapy with VM26-CCNU or fotemustine, and alfacalcidol at the daily dose of 0.04 microg/kg. MRI took place every 6 months. RESULTS: Eleven patients were included and completed the study. The series involved 10 glioblastomas and 1 anaplastic astrocytoma. Three patients out of 11 patients (27%), 2 glioblastomas and 1 astrocytoma grade III, exhibited a particular response, consisting in the progressive regression of the radiological lesion, with a decrease of the gadolinium-enhanced area. Simultaneously, the patients showed a complete clinical remission, observed respectively for 7, 5 and 4 years. In the series of 10 patients with glioblastomas, 2 cases showed this response; after 4 years, 2 of 10 patients with glioblastomas (20%) were alive; the median survival time is 21 months. Normal or subnormal calcemia was observed, at the dose proposed, so that no interruption of the drug was necessary. CONCLUSIONS: Alfacalcidol, an in vitro agent of redifferentiation, is safe and seems able to induce in some patients, in synergy with classical surgery-radiotherapy-chemotherapy treatments, a particular progressive and durable regression of the tumor. The responders might represent about 20% of malignant gliomas.

Adjuvants, Immunologic↗
PubMed2001

Early diagnosis of hemorrhagic transformation: diffusion/perfusion-weighted MRI versus CT scan.

UNLABELLED: Standard magnetic resonance imaging (MRI) techniques failed to image adequately acute hemorrhagic transformation (HT). Therefore, computed tomography (CT) is still needed to exclude intracerebral hemorrhage. New MRI techniques such as diffusion- and perfusion-weighted imaging (DWI and PWI) may improve the early detection of HT. The utility of this approach requires a direct comparison of the sensitivity of CT with these MRI techniques. METHODS: Nine patients experienced an acute carotid artery territory ischemic stroke diagnosed on a first CT performed 3.8 +/- 2 h after the onset of stroke. They underwent a second CT 12 +/- 4 h after the onset of stroke, followed 35 +/- 10 min later by an MRI protocol including: (1) an axial isotropic DWI SE echo-planar imaging (EPI) sequence; (2) time of flight MR angiography (TOF MRA); (3) PWI with an axial T(2)*-weighted gradient echo EPI sequence using 20 ml gadolinium contrast agent (Gd-DTPA); HT was characterized on DWI SE EPI as a heterogeneous area of signal loss within the ischemic area; (4) at day 7, CT was also performed in all patients who had an early suspicion of bleeding according to MRI. RESULTS: An HT was detected exclusively with CT in 1 out of 9 patients, while an MRI pattern of HT was found in 6 out of 9 patients. In 5 of these 6 patients, the CT scan did not show an obvious pattern of HT. Day 7 CT confirmed HT in all patients who had early suspicion of bleeding according to DWI criteria. CONCLUSION: This study suggests that new MRI techniques may allow an early detection of HT, thus improving the management of stroke.

Adult↗
PubMed2000

Intravenous tPA in acute ischemic stroke related to internal carotid artery dissection.

The authors describe the outcomes in 11 patients who had acute ischemic stroke related to internal carotid artery (ICA) dissection and were treated with IV tissue plasminogen activator (tPA). One symptomatic intracerebral hemorrhage occurred 36 hours after tPA was given. The mean day 90 modified Rankin Scale (m-RS) score was 2.4 (+/-1.6). No death was observed at 3 months. Four patients of 11 (36.4%) made an excellent recovery (day 90 m-RS score: 0 to 1). This study demonstrates the feasibility of IV thrombolysis with tPA (0.8 mg/kg) in ischemic stroke related to ICA dissection within the first 7 hours.

Adult↗
PubMed2000

rtPA intravenous thrombolysis in anterior choroidal artery territory stroke.

OBJECTIVE: To study the possible specific response to recombinant tissue plasminogen activator (rtPA) thrombolysis of anterior choroidal artery (AChA) stroke. BACKGROUND: Outcome and response after rtPA thrombolysis are possibly better in small-vessel infarcts, but a specific study of AChA stroke has not yet been performed. METHODS: The authors proposed an open trial of IV rtPA within 7 hours in patients age 20 and 81 years with all types of internal carotid artery territory stroke if the baseline Scandinavian Stroke Scale (SSS) score was less than 48. A dose of rtPA 0.8 mg/kg was infused over 90 minutes. Of 114 consecutive patients, 9 patients (7.9%) exhibited hypodensity in the AChA territory on day 1 brain CT. RESULTS: Seven of nine patients with AChA infarct had a primary early recovery within 6 hours after the initiation of rtPA infusion. In addition, recovery was complete in five patients and partial in two patients. No intracerebral hematoma was observed. Three patients had a "reinfarct syndrome" at 12, 25, and 48 hours respectively. However, in the two latter patients treated with IV heparin, the deficit disappeared again with the increase of heparin dose in one patient and disappeared spontaneously in the other patient. The overall outcome at day 90 was six total recoveries in nine patients (66%). Patients with a final good outcome had a slight "unstructured" hypodensity in the AChA territory on day 1 brain CT, whereas patients with a bad outcome had the classic "structured" hypodensity of AChA territory stroke. CONCLUSION: These data support a specific quick response of AChA territory stroke to IV rtPA thrombolysis, probably due to the small size of the artery and of the "clot." The high frequency of the reinfarct syndrome is a clinical fact that is difficult to explain. Efficient heparin treatment after 24 hours may control the reinfarct syndrome in some patients.

Aged↗
PubMed2000

Collapsin response mediator protein-3/unc-33-like protein-4 gene: organization, chromosomal mapping and expression in the developing mouse brain.

CRMPs (collapsin response mediator proteins)/ULIPs (unc-33-like proteins) are a family of intracytoplasmic proteins that are expressed mainly in the brain. The involvement of CRMP/ULIP members in neuronal differentiation, growth cone motility and axonal collapse has been suggested. We recently found that a member of this family, CRMP3/ULIP4, corresponds to POP66 (paraneoplastic oligodendrocyte protein of 66 kDa), a protein which may be associated with auto-immune induced-neuronal degeneration in paraneoplastic neurological syndromes. However, the physiological functions of these proteins remain to be elucidated. Further studies, including the generation of cell lines and of animals with modified/disrupted CRMP/ULIP gene expression, are necessary to explore the functions of this protein. We have cloned and determined the organization and chromosomal localization of the mouse gene encoding CRMP3/ULIP4. The gene is composed of 14 exons and spans more than 20 kb. We assigned the mouse CRMP3/ULIP4 gene to the distal end of chromosome 7. In mouse brain, in situ hybridization showed that CRMP3/ULIP4 mRNA is expressed mainly in the dentate gyrus of hippocampus, in the granular layers of cerebellum and in the inferior olive of the pons, the nucleus which controls movement and posture, and adjusts the major output of descending motor system.

Amino Acid Sequence↗
PubMed2000

Differential expression of collapsin response mediator proteins (CRMP/ULIP) in subsets of oligodendrocytes in the postnatal rodent brain.

The family of collapsin response mediator protein/Unc-33-like protein (CRMP/Ulip), composed of four homologous members, is specifically and highly expressed in the nervous system during embryonic neuronal development and dramatically down-regulated in the adult. Members of this family have been proposed to be part of the semaphorins signal transduction pathway involved in axonal outgrowth. Here, we show by in situ hybridization and immunohistochemistry that CRMP2/Ulip2, and to a lesser extent CRMP3/Ulip4, are expressed in immature and mature oligodendrocytes, but not in astrocytes. Transcripts encoding the other CRMP/Ulip members are also detectable by RT-PCR in highly purified mature oligodendrocytes. Interestingly, in the adult, the protein CRMP2/Ulip2 is mainly detectable in subsets of oligodendrocytes distributed according to an increasing rostrocaudal gradient, with the largest number of positive cells being present in the brain stem and spinal cord. In cultures of highly purified oligodendrocytes, however, CRMP2/Ulip2 was detectable in all the cells. Addition of Sema3A in the culture medium completely inhibited the emergence of oligodendrocyte processes suggesting that, as in neurons, a Sema3A signaling pathway mediated via CRMP2/Ulip2 may be involved in the regulation of oligodendroglial process outgrowth.

Animals↗
PubMed2000

Treatment of paraneoplastic neurological syndromes with antineuronal antibodies (Anti-Hu, anti-Yo) with a combination of immunoglobulins, cyclophosphamide, and methylprednisolone.

OBJECTIVES: To evaluate the effect of a combination of immunoglobulins (IVIg), cyclophosphamide (CTX), and methylprednisolone (MP) on the clinical course of patients with paraneoplastic neurological syndrome (PNS) and antineuronal antibodies (Abs). METHODS: Seventeen patients with paraneoplastic encephalomyelitis/sensory neuropathy (PEM/SN) with anti-Hu Abs (n = 10) or cerebellar degeneration (PCD) with anti-Yo Abs (n = 7) received one to nine cycles (mean 3.5) of a combination of IVIg (0.5 g/kg/day from days 1 to 5), CTX (600 mg/m2 at day 1) and MP (1g/day from day 1 to 3). The Rankin scale (RS) was used to evaluate the response. A positive response was considered as either improvement or stabilisation in patients who were still ambulatory (RS< or =3) at the onset of treatment, whereas only improvement, and not stabilisation, was considered a therapeutic benefit in bedridden patients (RS> or =4). RESULTS: Tolerance was good and no patient experienced grade 3/4 toxicity (World Health Organisation). Sixteen patients were evaluable for response. Of the seven patients with RS> or =4, none improved. Of the nine patients with RS< or =3, none improved but three (two SN and one PCD) stabilised for 4, 35, and 16 months. CONCLUSIONS: This study suggests that vigorous immunosuppressive treatment is not useful in severely disabled PNS patients with antineuronal Abs. In a minority of patients (mainly with SN) who are not severely disabled at the onset of treatment, a transient stabilisation is possible and deserves further evaluation.

Aged↗
PubMed2000

[Anti-neuronal antibodies and central nervous system diseases: contribution to diagnosis and pathophysiology].

Antibodies against antigens found in the central nervous system have been evidenced in several neurological diseases. The most well-known are associated with paraneoplastic neurological diseases (Anti-Hu, Yo, Ri amphiphysin, Tr, CV2 and Ta antibodies). Some of these antibodies are specific for certain types of cancer or neurological syndromes and are highly useful diagnostic tools for the clinician. They have contributed to the hypothesis that these paraneoplastic neurological syndromes involve autoimmune cross reactions between tumoral and nervous system antigens. They are however most unlikely pathogenic on their own. Anti voltage-dependent calcium channel antibodies associated with Lambert-Eaton syndrome which is paraneoplastic in only 60 p. 100 of the cases are also observed in cases of paraneoplastic cerebellar atrophy. Anti-GAD antibodies are seen in non-paraneoplastic stiff man syndrome and in certain progressive cerebellar atrophies. Antibodies reacting with different glutamate receptors are detected in different neurological diseases including Rasmussen's encephalitis. Finally, antibodies are described in diverse conditions such as amyotrophic lateral sclerosis, Sydeham chorea or Gilles de la Tourette syndrome. The significance of the antibodies observed outside the context of paraneoplastic syndromes is not well understood, but the anti-GAD antibodies associated with progressive cerebellar disorders and autoimmune polyendocrinopathies could be an expression of the autoimmune nature of certain neurological degenerative processes affecting the central nervous system.

Antibodies↗
PubMed2000

[18F]fluorodeoxyglucose positron emission tomography in the diagnosis of cancer in patients with paraneoplastic neurological syndrome and anti-Hu antibodies.

The diagnosis of cancer is often difficult in patients with paraneoplastic neurological syndrome and anti-Hu antibodies. Fluorodeoxyglucose 18 positron emission tomography scanning is a highly sensitive and specific method to detect lung tumors. We investigated 15 patients with paraneoplastic neurological syndrome and anti-Hu antibodies. Radiological methods led to the diagnosis of cancer in 12 patients, and test results were negative in 3. Whole-body [18F]fluorodeoxyglucose positron emission tomography showed abnormal uptake in the mediastinum in these 3 patients in accordance with the expected location of the malignancy.

Aged↗
PubMed2000

[Primary lateral sclerosis with breast cancer, a potential paraneoplastic neurological syndrome].

Few reports indicate that motor neuron diseases may have paraneoplastic origin. A 70 year-old woman suffering from progressive upper motor neuron disease is presented. Laboratory, radiological and neurophysiologic studies were compatible with primary lateral sclerosis. Six years later a routine screening led to the discovery of a breast cancer, suggesting that the upper motor neuron syndrome could be paraneoplastic. So, in female patients with primary lateral sclerosis, a mammography should be recommended to search for breast cancer.

Aged↗
PubMed1999

Antiamphiphysin antibodies are associated with various paraneoplastic neurological syndromes and tumors.

BACKGROUND: Antiamphiphysin antibodies react with a 128-kd protein found in synaptic vesicles. They were first described in patients with paraneoplastic stiff-man syndrome and breast cancer, but studies suggest that they can also occur in patients with other tumors and neurological disorders. OBJECTIVE: To determine if antiamphiphysin antibodies are associated with various paraneoplastic neurological syndromes and tumors. PATIENTS AND METHODS: Of 2800 serum samples tested by routine immunohistochemical procedures on sections of paraformaldehyde-fixed rat brain for the detection of autoantibodies associated with paraneoplastic neurological syndromes, 5 were selected because of labeling suggestive of antiamphiphysin antibodies and subsequently confirmed by the results of Western blot analysis using recombinant amphiphysin protein. Controls consisted of 40 patients with various nonparaneoplastic neurological diseases; 101 patients with cancer but without paraneoplastic neurological syndrome; 9 patients with small cell lung cancer, anti-Hu antibodies, and paraneoplastic neurological syndrome; 3 patients with M2-type antimitochondrial antibodies but no neurological disorder; and 30 normal subjects. RESULTS: Of the 5 patients with antiamphiphysin antibodies, patient 1 had sensory neuronopathy, encephalomyelitis, and breast cancer; patient 2 had limbic encephalitis, and small cell lung cancer was detected in the mediastinum after 24 months of follow-up; patient 3 had encephalomyelitis and ovarian carcinoma; and patients 4 and 5 had Lambert-Eaton myasthenic syndrome and small cell lung cancer (patient 4 subsequently developed cerebellar degeneration). None of the 5 had stiffness. Two patients (Nos. 2 and 4) had antimitochondrial antibodies. The two patients (Nos. 4 and 5) with Lambert-Eaton myasthenic syndrome had antibodies directed against the voltage-gated calcium channel, and patient 2 subsequently developed anti-Hu antibodies. In the controls, antiamphiphysin antibodies were detected by Western blot analysis in 3 of 8 patients with anti-Hu antibodies, but in none of the other groups. CONCLUSIONS: These data indicate that antiamphiphysin antibodies are not specific for one type of tumor or one neurological syndrome and can be associated with other neural and nonneural antibodies. The simultaneous association of several antibodies in some patients suggests multimodal autoantibody production.

Aged↗
PubMed1999

[Mechanisms of paraneoplastic neurologic syndromes].

INTRODUCTION: Paraneoplastic neurological syndromes (PNS) refer to a set of neurological disorders associated with neuronal degeneration in some patients with systemic cancers. These disorders are not related to the tumor mass or metastasis. CURRENT KNOWLEDGE AND KEY POINTS: Evidence argues for an autoimmune reaction against tumor cells which expresses antigens normally present in neurons. A high percentage of patients with PNS harbors high titers of anti-neuronal autoantibodies in their serum and cerebrospinal fluid. In addition to their clinical interest in diagnosis and pathophysiology, these autoantibodies provide a unique opportunity to identify genes encoding previously undiscovered neuronal proteins which are also expressed by tumor cells. These "onconeural" antigens have been classified in four groups: neuromuscular junction proteins, nerve terminal/vesicle-associated proteins, neuronal RNA binding proteins, or neuronal signal transduction proteins. FUTURE PROSPECTS AND PROJECTS: All of these proteins would play a major role in the neuronal maturation and homeostasis, and for some of them in cellular proliferation. Better understanding of the exact role of these proteins would in turn permit better understanding of the mechanisms of neuronal degeneration and tumor cell proliferation in PNS.

Autoantibodies↗