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F Graus

Publications and source records attributed to F Graus.

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

The impact of the introduction of the 14-3-3 protein assay in the surveillance of sporadic Creutzfeldt-Jakob disease in Catalonia.

The 14-3-3 assay in the CSF has a high predictive value for the diagnosis of sporadic Creutzfeldt-Jakob disease (CJD). Our objective was to analyse the trends in mortality and incidence rates of CJD in Catalonia, an autonomous community of Spain, setting the cut off point the date when the 14-3-3 assay was incorporated to our CJD surveillance system. Only definite and probable cases according to the criteria adapted from Masters and colleagues were included for the analysis. Familial cases were excluded after genetic analysis of the PrP gen. We found a quasi threefold increase in the incidence and mortality rates for CJD after introduction of the 14-3-3 assay in our surveillance system in 1997 as compared with the period 1993-1996. Our findings suggest an improvement of case ascertainment in part due to the introduction of the 14-3-3 assay in the surveillance system.

14-3-3 Proteins↗
PubMed2001

Dramatic improvement of POEMS syndrome following autologous haematopoietic cell transplantation.

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, serum monoclonal protein and skin changes) is a rare plasma cell disorder of unknown pathogenesis and is diagnosed by the demonstration of a plasma cell proliferation at the biopsy of an osteoesclerotic lesion. When the lesions are in a limited area, radiation therapy is usually highly effective. Patients with disseminated disease require systemic chemotherapy, which is not effective in most cases. A patient with severe widespread POEMS syndrome resistant to melphalan who experienced a dramatic improvement after high-dose melphalan followed by autologous haematopoietic cell transplantation (AHCT) is reported. We believe that this is the first reported case of POEMS syndrome treated with AHCT, a procedure that could be considered in similarly affected patients.

Adult↗
PubMed2001

Clinical outcome in adult onset idiopathic or paraneoplastic opsoclonus-myoclonus.

We analysed a series of 24 adult patients with idiopathic (10 cases) and paraneoplastic (14 cases) opsoclonus-myoclonus syndrome (OMS) to ascertain possible differences in clinical course and response to immunotherapies between both groups. Associated tumours were small-cell lung cancer (SCLC) (nine patients), non-SCLC (one patient), breast carcinoma (two patients), gastric adenocarcinoma (one patient) and kidney carcinoma (one patient). Patients with paraneoplastic OMS were older [median age: 66 years versus 40 years (P = 0.006) of those with idiopathic OMS] and had a higher frequency of encephalopathy (64% versus 10%; P = 0.02). Serum from 10/10 idiopathic and 12/14 paraneoplastic OMS patients showed no specific immunoreactivity on rat or human brainstem or cerebellum, lacked specific antineuronal antibodies (Hu, Yo, Ri, Tr, glutamic acid decarboxylase, amphiphysin or CV2) and did not contain antibodies to voltage-gated calcium channels. The two paraneoplastic exceptions were a patient with SCLC, whose serum contained both anti-Hu and anti-amphiphysin antibodies and a patient with breast cancer who had serum anti-Ri antibodies. The clinical course of idiopathic OMS was monophasic except in two elderly women who had relapses of the opsoclonus and mild residual ataxia. Most idiopathic OMS patients made a good recovery, but residual gait ataxia tended to persist in older patients. Immunotherapy (mainly intravenous immunoglobulins or corticosteroids) seemed to accelerate recovery. Paraneoplastic OMS had a more severe clinical course, despite treatment with intravenous immunoglobulins or corticosteroids, and was the cause of death in five patients whose tumours were not treated. By contrast the eight patients whose tumours were treated showed a complete or partial neurological recovery. We conclude that idiopathic OMS occurs in younger patients, the clinical evolution is more benign and the effect of immunotherapy appears more effective than in paraneoplastic OMS. In patients aged 50 years and older with OMS who develop encephalopathy, early diagnosis and treatment of a probable underlying tumour, usually SCLC, is indicated to increase the chances of neurological recovery. At present, there are no immunological markers to identify the adult patients with paraneoplastic OMS.

Adrenal Cortex Hormones↗
PubMed2001

Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients.

We reviewed 200 patients with paraneoplastic encephalomyelitis (PEM) and anti-Hu antibodies to show possible clinical differences with respect to previous series, and to identify patient, tumour and treatment-related characteristics associated with neurological disability and survival. The median age of the 200 patients was 63 years (range 28-82 years) and 75% were men. The predominant neurological syndromes were sensory neuropathy (54%), cerebellar ataxia (10%), limbic encephalitis (9%) and multifocal involvement (11%). Sensorimotor neuropathies with predominant motor involvement were observed in only 4% of the patients. Pathological or X-ray evidence of a tumour was obtained in 167 patients (83%) and was a small-cell lung cancer (SCLC) in 74% of those with histological diagnosis. Coexistence of extrathoracic tumours with SCLC was rare (0.5%). Positive Hu immunoreactivity was observed in the extrathoracic tumours of six out of seven patients in whom autopsy or long-term follow-up ruled out a coexisting SCLC. PEM preceded the diagnosis of the tumour in 71% of patients (mean delay +/- SD 6.5 +/- 7.0 months; range 0.1-47 months). In the 24 patients in whom the tumour diagnosis was the initial event, PEM predicted the progression or relapse of the tumour in 87% of them. No tumour was found in 33 patients, including four who had a post-mortem study and four with >5 years of follow-up. In a logistic regression analysis, treatment of the tumour, associated or not with immunotherapy, was an independent predictor of improvement/stabilization of PEM [odds ratio 4.56; 95% confidence interval (CI) 1.62-12.86]. Cox multivariate analysis indicated that the variables independently associated with mortality were: age >60 years [relative risk (RR) 1.49; 95% CI 1.05-2.12], Rankin score at diagnosis >3 (RR 1.60; 95% CI 1.12-2.28), more than one area of the nervous system affected (RR 1.61; 95% CI 1.08-2.40), and absence of treatment (RR 2.56; 95% CI 1.76-3.71). We conclude that, unlike previous series, the majority of our patients were male, and there was a low occurrence of predominantly motor neuropathies and extrathoracic tumours coexisting with SCLC. When the diagnosed extrathoracic tumour expresses Hu antigens, further tests to rule out a coexisting SCLC are probably unnecessary. Finally, the predictors of mortality and PEM evolution found in the study may be important in the design of future therapeutic protocols, and emphasize the importance of early diagnosis and treatment of the underlying tumour.

Adult↗
PubMed2001

Chronic idiopathic sensory ataxic neuropathy: immunological aspects of a series of 17 patients.

Sensory ataxic neuropathies (SANs) are characterized by loss of proprioceptive sensations and preservation of muscle strength. They may be idiopathic or associated with different toxic, infectious or autoimmune causes. Reactivity against gangliosides containing disialosyl groups, particularly GD1b, has been reported in isolated cases of acute and chronic idiopathic ataxic neuropathies (iSAN) and different experimental findings (in vivo animal models and in vitro preparations) suggest that antidisialosyl or antiGD1b antibodies could play a role in the pathogenesis of some ataxic neuropathies. We present the clinical, immunological and immunohistochemical characteristics of 17 patients who had a chronic iSAN without gammopathy. Patients were selected from a large group of 130 subjects with SAN: 93 with known etiology and 37 with iSAN. IgM and IgG antibodies to GM1, GM2, GM3, aGM1, GD1a, GD1b, GD3, GT1b and GQ1b were investigated by ELISA (INCAT protocol) and thin layer chromatography. Immunohistochemistry, using biotinylated Ig extracted from the patientś serum, was performed on human dorsal root ganglia (DRG), spinal cord, anterior and posterior roots, sural nerve and muscle tissue. The mean age of the 17 patients was 62 (37-80 years). The most disabling features were unsteadiness and severe ataxia of gait. Only one patient of this group was wheelchair-bound. The clinical data of these 17 patients were similar to those of the other patients with SAN, except that progression was slower. Antibodies to GD1b, GD3 and GT1b were found in 1/17. Two more patients (one with an acute iSAN and one with chronic iSAN and gammopathy), also had antibodies to disialosyl or GD1b. No immunohistochemical pattern of reactivity was found in any of the tissues tested with the 17 sera. In summary, this study demonstrates antidisialosyl or anti GD1b antibodies only in 3/37 (8.1p. cent) of patients with iSAN, either acute, chronic, or with gammopathy. However, their value seems to be reinforced by the negativity of antiganglioside antibodies in the large group of patients with SAN of known etiology (0/93). Further studies will be necessary to confirm the importance of target antigens containing disialosyl moieties in a subset of iSAN patients. However, the negativity of antiganglioside antibodies in most cases suggests that the pathology of the sensory neurons and/or axons is probably not humorally mediated in the majority of patients with iSAN.

Adult↗
PubMed2000

Long-term clinical outcome of paraneoplastic cerebellar degeneration and anti-Yo antibodies.

The outcome of 34 women with anti-Yo-associated paraneoplastic cerebellar degeneration was reviewed. Three patients had not developed cancer after more than 4 years of follow-up. The only independent predictor for survival was the type of associated tumor (risk ratio, 1.79; 95% CI, 1.02 to 3.12). Median survival was 100 months for patients with breast cancer and 22 for those with gynecologic cancer. Although paraneoplastic cerebellar degeneration leads to the diagnosis of cancer in 63% of the patients, cancer progression was the cause of death in 52%.

Adult↗
PubMed2000

Autoantibodies to glutamic acid decarboxylase in patients with therapy-resistant epilepsy.

BACKGROUND: Autoantibodies to glutamic acid decarboxylase (GAD-A) are present in type 1 diabetes and stiff man syndrome (SMS), and have also been reported in cerebellar ataxia. Epilepsy was present in 4 of 19 patients with SMS and GAD-A, implying that epilepsy sometimes is associated with anti-GAD autoimmunity. METHODS: The authors investigated the prevalence of GAD-A in patients with therapy-resistant localization-related epilepsy (n = 51) and generalized epilepsy (n = 49) by a radiobinding assay. The positive samples were confirmed by immunohistochemistry and immunoblotting of recombinant human GAD65. RESULTS: GAD-A were found in eight patients with localization-related epilepsy, whereas none of the patients with generalized epilepsy, other neurologic disorders (n = 38), or the control subjects (n = 48) had GAD-A. Two patients had high levels of GAD-A, similar to SMS, whereas six patients had significantly lower titers, characteristic of type 1 diabetes. The two patients with high levels of GAD-A had GAD-A both in serum and CSF by immunohistochemistry and immunoblotting. Both of them had longstanding therapy-resistant temporal lobe epilepsy but did not have diabetes. One had a history of autoimmune disease, whereas the other had serologic evidence of multiple autoantibodies without any clinical signs of autoimmune disease. CONCLUSIONS: GAD autoimmunity may be associated with refractory localization-related epilepsy.

Adolescent↗
PubMed2000

EFNS task force report: a questionnaire-based survey on the service provision and quality assurance for determination of diagnostic autoantibody tests in European neuroimmunology centres. European Federation of Neurological Societies.

Autoantibodies to a wide variety of neural components are frequently sought in the sera of patients with neurological diseases suspected to have an antibody-associated autoimmune basis. Variations in assay methodology and availability are likely to exist throughout European diagnostic immunology centres, and interlaboratory discrepancies in performance for some assays have been reported. The availability of quality assurance is largely unknown. In this questionnaire-based EFNS task force, all 18 national representatives of the Neuroimmunology Panel within the EFNS were invited to estimate the service provision within their country; 12 panel members responded. From these responses, it emerged that a range of assays are being performed throughout European centres, involving over 20 separate antigens, using a broad array of immunodetection techniques. With the exception of the estimation of anti-AChR antibodies for the diagnosis of myasthenia gravis, no systematic quality assurance schemes are available, this being conducted on an ad hoc basis, or not at all. Since quality is a central component of assay sensitivity and specificity, we conclude that there is an urgent need to introduce pan-European quality assurance schemes, based on provision of positive and negative test sera from a central source, and in which all neuroimmunology laboratories should participate.

Autoantibodies↗
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↗
PubMed1999

Clinical outcome of patients with anti-Hu-associated encephalomyelitis after treatment of the tumor.

OBJECTIVE: To evaluate 1) the effect of the tumor treatment on the clinical course of paraneoplastic encephalomyelitis (PEM) with anti-Hu antibodies, 2) the impact of immunotherapy on the tumor evolution, and 3) the outcome of the small cell lung cancer (SCLC) of PEM patients compared with that of patients without PEM. METHODS: The authors retrospectively analyzed 51 PEM patients (42 with SCLC, 9 with other tumors) who received antineoplastic treatment with (25 patients) or without (26) concomitant immunotherapy. Tumor response was assessed at the end of the antineoplastic treatment. Progression of PEM was defined as a change of at least 1 point in the Rankin scale measured at the onset and at the end of the tumor treatment. To evaluate the outcome of SCLC, 27 PEM patients with SCLC were matched one-to-one with SCLC patients without PEM for age, performance status, tumor stage, and type of antineoplastic treatment. RESULTS: Thirty-six (70%) patients were neurologically stable at the end of the tumor treatment. In a logistic regression analysis, tumor complete response was the only predictor of PEM stabilization (OR 7.07; 95% CI 1.68 to 29.76; p = 0.006). Immunotherapy did not modify the outcome of the tumor and PEM. Median survival was similar in SCLC patients with and without PEM, but the probability of survival at 30 months was higher in PEM patients with SCLC (OR 5.26; 95% CI 1.0004 to 27.6902; p = 0.03). CONCLUSIONS: Complete response of the tumor seems to have a favorable influence on the course of paraneoplastic encephalomyelitis (PEM). Concomitant immunotherapy does not adversely affect the tumor outcome. The small cell lung cancer of PEM patients may have a slightly better evolution than that of patients without PEM.

Adult↗
PubMed1999

Acute quadriplegic myopathy with myosin-deficient muscle fibres after liver transplantation: defining the clinical picture and delimiting the risk factors.

BACKGROUND: In the last few years, rare cases of acute quadriplegic myopathy (AQM*) with myosin-deficient muscle fibres occurring after solid organ transplantation has been reported. The aim of the present study was to review all cases of AQM with myosin deficient fibres seen at our institution among a large series of patients after orthotopic liver transplants (OLT), with special attention to clinical aspects and associated risk factors. Additionally, an extensive review of all ultrastructurally demonstrated cases of AQM in transplant recipients is also included. PATIENTS AND METHODS: Among patients involved in 281 consecutive liver transplant procedures performed in a 4-year period, 3 men and 1 woman developed an arreflexic, flaccid quadriplegia in the immediate postoperative period of OLT. After ruling out other causes of weakness, a muscle biopsy was performed and a loss of thick (myosin) filaments was confirmed by ultrastructural analysis in all cases. Accurate clinical, epidemiological, and evolutive data were recorded. RESULTS: Corticosteroids had been used at usual dosage given to liver transplant recipients; all four patients had several intra- and postoperative complications leading to receiving significantly higher amounts of hemoderivates, to develop renal failure in all cases, and to require a significantly higher number of reoperations within a few days after transplantation than our contemporaneous global series of liver transplant recipients. AQM patients required a significantly longer intensive care unit and hospital stay. Muscular recovery was the rule, but currently a mild myopathic gait remains in three patients. These and other reported cases of AQM do not histologically and clinically differ from AQM seen in other critically ill patients who have not had transplants. CONCLUSIONS: Patients with a complicated intra- and postoperative course of OLT who develop newly acquired acute muscle weakness should be suspected as having acute AQM with myosin-deficient muscle fibres. In this setting, differential diagnosis with other causes of weakness should be carried out, because the prognosis of this myopathy is good with early muscle rehabilitation therapy.

Acute Disease↗
PubMed1999

Central motor conduction time in patients with multifocal motor conduction block.

The finding of conduction block (CB) within short consecutive segments along a motor nerve is a key feature of multifocal motor neuropathy (MMN). Despite their different pathogenesis, this may be the only clinical difference between some cases of MMN and the pure spinal muscular atrophy form of motor neuron disease (MND). In 12 patients with distal atrophy and fasciculations and electrophysiological evidence of CBs in the upper limbs, we measured the peripheral and central motor conduction times (PMCT and CMCT) to hand muscles. We reasoned that patients with MMN should show an abnormally prolonged PMCT with normal CMCT, whereas an increased CMCT would suggest MND. All patients had delayed F-wave latency and increased PMCT. Three patients had increased CMCT. Follow-up showed little clinical and electrophysiological change in 7 of the 9 patients with normal CMCT, and a progressive motor deficit leading ultimately to death in 1 of the 3 patients with increased CMCT. This patient's electrophysiological follow-up showed a significant decrement of the compound motor action potential to both proximal and distal stimulation points, with disappearance of earlier CBs. Autopsy revealed loss of anterior horn cells and axons of the ventral root, and degeneration of large myelinated fibers. We conclude that determining the CMCT may help in differentiating MND from MMN. Persistence of a stable clinical picture over a span of at least 1 year and lack of electrophysiological signs of involvement of upper motor neurons should both be required before establishing the diagnosis of MMN even with electrophysiological evidence of CB.

Adult↗
PubMed1999

Epilepsia partialis continua: a new manifestation of anti-Hu-associated paraneoplastic encephalomyelitis.

We report on 3 anti-Hu-positive patients who presented with clinical and electroencephalographic (EEG) features of epilepsia partialis continua (EPC). Two of the patients had an associated small cell carcinoma. Magnetic resonance imaging (MRI) disclosed a hyperintense nonenhancing focal lesion in T2-weighted images in the sensorimotor area in 2 patients. Histopathological analysis of the lesion revealed inflammatory infiltrates and neuronal cell loss. In the patient who had a postmortem study, these neuropathological changes were not observed in other areas of the nervous system. This study emphasizes that the possibility of an anti-Hu-associated paraneoplastic disorder must be considered in patients with cortical encephalitis presenting with EPC when a brain tumor can be excluded.

Adult↗