T Sharshar

Hôpital Raymond-Poincaré – Hôpitaux universitaires Paris Ile-de-France Ouest, Garches, Ile-de-France, France

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Publications (30)102.96 Total impact

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    Article: A prospective multicenter study of ICU acquired paralysis
    Critical Care 04/2012; 5:1-1. · 4.93 Impact Factor
  • Article: Tongue weakness is associated with respiratory failure in patients with severe Guillain-Barré syndrome.
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    ABSTRACT: Swallowing impairment may worsen respiratory weakness and conduct to respiratory complications such as aspiration pneumonia in Guillain-Barré syndrome (GBS). We prospectively evaluate how tongue weakness could be associated to bulbar dysfunction and respiratory weakness in severe GBS patients. Tongue strength, dysphagia and respiratory parameters were measured in 16 GBS patients at intensive care unit (ICU) admission and discharge and in seven controls. Tongue strength was decreased in the GBS patients compared with the controls. At admission, patients with dysphagia and those requiring mechanical ventilation (MV) had greater tongue weakness. All the patients with initial tongue strength <150 g required MV during ICU stay. Tongue strength correlated significantly with respiratory parameters. This study confirms the strong association between bulbar and respiratory dysfunction in GBS admitted to ICU. Tongue weakness may be present in GBS, especially during the phase of increasing paralysis, and resolves during the recovery phase. Tongue strength and indices of global and respiratory strength vary in parallel throughout the course of GBS. Further studies are needed to assess if, when used in combination with other respiratory tests, tongue strength measurement could contribute to identify patients at high risk for respiratory complications.
    Acta Neurologica Scandinavica 10/2008; 119(6):364-70. · 2.47 Impact Factor
  • Article: [Neuromuscular abnormalities in critical illness].
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    ABSTRACT: Critical illness neuromuscular abnormalities (CINMA) are found in 25 percent of ITU patients who recover consciousness and are characterized by a bilateral and symmetric weakness that involves the four limbs but spares the facial muscles. Electrophysiological testing shows an axonal sensory motor polyneuropathy and/or myopathy. The main risk factors of CINMA are prolonged durations of multiple organ failure and mechanical ventilation, use of corticosteroids and hyperglycaemia. CINMA contribute also to increase the duration of mechanical ventilation, this effect being mediated by diaphragm weakness. The median duration of limb weakness is 21 days, although it can exceed several months in some patients. Few preventive measures have been assessed. Whether the benefit of strict blood glucose control in ITU patients recovering from heart surgery on CINMA incidence can be extended to medical ICU patients needs to be determined.
    Revue Neurologique 01/2006; 161(12 Pt 1):1267-71. · 0.49 Impact Factor
  • Article: [Long term domiciliary mechanical ventilation in patients with neuromuscular disease (indications, establishment and follow up)].
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    ABSTRACT: Neuromuscular diseases represent a heterogeneous group of pathologies which common feature is the development of a restrictive ventilatory failure. Respiratory insufficiency of neuromuscular origin manifests itself by functional symptoms that must be carefully searched for in the history, such as headaches, sleep disorders, or dyspnoea of effort, sometimes very mild, or in severe cases associated with orthopnoea. Follow up should be multi-disciplinary. On the respiratory level regular measurement of blood gases, vital capacity, maximum inspiratory and expiratory pressures as well as sleep studies, will detect the criteria for mechanical ventilation (hypercarbia > 45 mm Hg, nocturnal desaturation < 88%, vital capacity < 60%, PImax < 60 cm H2O). The establishment of mechanical ventilation is a major decision for patients with neuromuscular disease because of the important physical, psychological, social and sometimes financial consequences. The patients and their family must be instructed precisely in order to obtain the best possible observation and compliance. The establishment requires a stay in hospital of several days to optimise the choice of ventilator, its settings, and connections. The link with the organisation managing the domiciliary ventilation is fundamental in ensuring follow up after discharge from hospital. Techniques of cough assistance must be taught to each neuromuscular patient requiring mechanical ventilation. Ventilation of neuromuscular patients requires careful evaluation of the indications and rigorous follow up by a multidisciplinary team with wide experience of this type of disease.
    Revue des Maladies Respiratoires 12/2005; 22(6 Pt 1):1021-30. · 0.59 Impact Factor
  • Article: Significance of phrenic nerve electrophysiological abnormalities in Guillain-Barré syndrome.
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    ABSTRACT: The authors investigated whether the amplitude and latency of diaphragm compound muscle action potential helped predict respiratory failure in Guillain-Barré syndrome. Both variables were significantly but weakly correlated with vital capacity (VC) and were similar in unventilated (n = 60) and ventilated (n = 10) patients. In ventilated patients, motor loss severity, progression, and VC reduction were significantly greater, and bulbar dysfunction was more common. Predicting respiratory failure must rely on clinical features and VC.
    Neurology 12/2005; 65(10):1646-9. · 8.31 Impact Factor
  • Article: Limitations of sniff nasal pressure in patients with severe neuromuscular weakness.
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    ABSTRACT: Inspiratory muscle strength in patients with neuromuscular disorders can be assessed using sniff inspiratory nasal pressure (Pn(sn)) and maximum inspiratory mouth pressure (PI(max)). However, the relative merits of Pn(sn) against PI(max) are not known in patients with severe neuromuscular disease. To investigate whether severity of disease modifies the relation between Pn(sn) and PI(max). Vital capacity (VC), Pn(sn), and PI(max) were measured in 258 patients with neuromuscular disorders. Data were analysed from 241 patients, 17 being unable to perform PI(max) or Pn(sn) manoeuvres. The correlation between Pn(sn) and PI(max) was +0.94 (p<0.0001), with a mean (SD) difference between Pn(sn) and PI(max) of -4.8 (21.2) cm H(2)O (the limits of agreement were 37.6 and -47.2 cm H(2)O). VC (% predicted) was positively correlated with Pn(sn)/PI(max) (r = +0.86; p<0.0001), with a lower Pn(sn)/PI(max) value in patients with a VC <40% of predicted than in those with a VC >40% (0.80 (0.35) v 1.04 (0.41); p<0.0001). PI(max) is greater than Pn(sn) in patients with a severe restrictive ventilatory defect caused by neuromuscular disease. Pn(sn) may not accurately reflect inspiratory muscle strength in such patients and it is thus advisable to use both tests.
    Journal of Neurology Neurosurgery &amp Psychiatry 01/2004; 74(12):1685-7. · 4.76 Impact Factor
  • Article: Standards of measurements in myasthenia gravis.
    P Gajdos, T Sharshar, S Chevret
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    ABSTRACT: Valid and reliable measurements of muscle impairment are needed to assess therapeutic efficacy in patients with generalized myasthenia gravis. Several muscle scoring systems have been proposed for assessing muscle strength in such patients. The aim of the present study is to assess the validity and interobserver agreement of these muscle scores.
    Annals of the New York Academy of Sciences 10/2003; 998:445-52. · 3.15 Impact Factor
  • Article: Electrophysiology to predict mechanical ventilation in Guillain-Barré syndrome.
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    ABSTRACT: To determine whether electrophysiological features predict endotracheal mechanical ventilation (ETMV) in Guillain-Barré syndrome (GBS). Non-ventilated GBS patients admitted to an ICU underwent standard electrophysiological testing. Endotracheal mechanical ventilation was decided by physicians who were unaware of electrophysiological results. Sixty consecutive patients underwent electrophysiological testing within 17 days of GBS onset; based on Hadden's criteria, 37 (62%) had primary demyelinating, 18 (30%) equivocal and five (8%) axonal disease. Time at electrophysiological testing and proportions of patients treated by plasma exchange and intravenous immunoglobulins were similar in the three groups, whereas primary demyelinating patients had worse results for disability grade and arm grade. The ETMV was required within 20 days of electrophysiological testing in 20 patients, 17 (46%) in the primary demyelinating group, three (17%) in equivocal group and none in the axonal group (P = 0.02). This prospective study suggests that electrophysiological demyelination may predict a need for ETMV in GBS.
    European Journal of Neurology 02/2003; 10(1):39-44. · 3.69 Impact Factor
  • Article: Monocyte chemoattractant protein 1 and chemokine receptor CCR2 productions in Guillain-Barré syndrome and experimental autoimmune neuritis.
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    ABSTRACT: Infiltration of activated lymphocytes and monocytes is a key phenomenon in the pathogenesis of Guillain-Barré syndrome (GBS) and experimental autoimmune neuritis (EAN). To investigate the role of chemokines, we determined the blood and nerve tissue expression of monocyte chemoattractant protein 1 (MCP-1), a major chemoattractant of monocytes and activated lymphocytes, and its receptor CCR2 in GBS and EAN. MCP-1 circulating levels (ng/ml) in GBS were increased at the time of progression, peaked at the time of plateau and normalized with recovery. MCP-1 circulating levels were the highest in the most disabled patients. The number of circulating CCR2 positive cells was lower in patients with GBS than in healthy subjects (p<0.004). In GBS, MCP-1 expression was observed in epineurial and endoneurial vessels, on infiltrating cells, Schwann cells and in the endoneurial extracellular matrix. Some CCR2 positive cells were observed in nerve biopsies of GBS patients. In EAN, a slight positivity for MCP-1 was observed in the sciatic nerve. There was no circulating CCR2 positive cells. However, at the time of plateau, a conspicuous infiltration of CCR2 positive cells was observed in the sciatic nerve that was no longer observed at the time of recovery. These results suggest that MCP-1 and CCR2 may participate to the recruitment of circulating mononuclear cells in nerve tissue in EAN and GBS.
    Journal of Neuroimmunology 01/2003; 134(1-2):118-27. · 2.96 Impact Factor
  • Article: MMP-9 correlates with electrophysiologic abnormalities in Guillain-Barré syndrome.
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    ABSTRACT: To investigate the role of MMP-9 in Guillain-Barré syndrome, the authors correlated electrophysiologic abnormalities and MMP-9 plasma levels in a series of 21 patients. MMP-9 plasma levels were higher in the demyelinating group than in the nondemyelinating group, and in patients with high CSF protein level. Increase of MMP-9 circulating levels correlated with the increase of F waves latencies, reduction of CMAP amplitude, and decrease of nerve conduction velocities. Circulating MMP-9 may contribute to the peripheral nerve dysfunction of demyelinating Guillain-Barré syndrome.
    Neurology 12/2002; 59(10):1649-51. · 8.31 Impact Factor
  • Article: Neuropathology of septic shock
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    ABSTRACT: Introduction: Septic shock is the most frequent cause of death in intensive care units. It is often complicated by an encephalopathy and there is increasing evidence that central autonomic nervous system (CANS) dysfunction plays a crucial role in the onset and persistance of the haemodynamic failure. However, only a few neuropathological studies are available; they are always retrospective and often disagree.Material and methods: Twenty consecutive patient who died from septic shock were examined and compared with eight patients who died from nonseptic shock in the same unit and five ‘normal’ controls collected from the Forensic Medicine Service.Results and conclusion: A variety of lesions, including microabscesses, multifocal necrotizing leukoencephalopathy, haemorrhages and disseminated intravascular coagulation, were found, and were most probably related to the biological disturbances associated with sepsis. These lesions may contribute to the ‘septic encephalopathy’. Ischaemic changes in ‘susceptible’ areas were comparable in septic shock and in nonseptic shock. In contrast, ischaemic changes in the nuclei of the CANS were significantly more severe in septic shock than in nonseptic shock. Neuronal apoptosis in these nuclei was significantly more frequent and more severe in septic shock; apoptosis did not correlate exactly with neuronal ischaemia and was associated with only mild microglial activation suggesting that circulating factors may also play a role in its causation.
    Neuropathology and Applied Neurobiology 03/2002; 28(2):159 - 159. · 3.80 Impact Factor
  • Article: [Cellular aspect of neuroinflammation in Guillain-Barré syndrome: a key to a new therapeutic option?].
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    ABSTRACT: Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating neuropathy associated with long-lasting morbidity and substantial risk of mortality. The two reference treatments (plasma exchange-PE and intravenous immunoglobulins-IVIGs) do not change the functional prognosis in patients with very severe disease. Pathogenesis of GBS associates recently characterized humoral and cellular immune dysfunctions. Antibodies against nerve antigens may participate in complement activation, antibody-dependent macrophage cytotoxicity, and reversible conduction failure. Cellular immune reaction is associated with an increase of proinflammatory cytokines (for exemple TNF-alpha), a decrease of anti-inflammatory cytokines (such as TGF-B1), an increase of matrix metalloproteinases (MMP-9-gelatinase B), all abnomalities favoring adhesion to and transmigration across endothelium of immune cells, a key phenomenon in GBS. Recovery of GBS is characterized by the normalization of these abnormalities. Experimental allergic neuritis (EAN), the experimental model of GBS has strikingly similar immunological abnormalities. The treatments of GBS, PE and IVIGs, mainly target the humoral component of the immune response. IFN-B is a cellular immunomodulator that inhibits antigen presentation, TNF-alpha production and binding, modulates macrophages properties. IFN-B increases anti-inflammatory T cell functions and cytokines, such as TGF-B1. IFN-B has important properties on leukodiapedesis by modulating expression of cell adhesion molecules and the MMP-9 proteinase. IFN-B has been used with success in EAN, in some patients with acute exacerbation of chronic inflammatory demyelinating polyneuropathy, and in one patient with GBS. Pathophysiology of GBS, IFN-B properties, and experimental studies support the initiation of a trial of IFN-B in GBS.
    Revue Neurologique 02/2002; 158(1):15-27. · 0.49 Impact Factor
  • Article: IFN-beta decreases adhesion and transmigration capacities of lymphocytes in Guillain-Barré syndrome.
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    ABSTRACT: The adhesion capacities, transmigration capacities, and integrin expression of lymphocytes from patients with Guillain-Barré syndrome incubated with interferon-beta were studied. Interferon-beta induced a dose-dependent inhibition of lymphocyte adhesion to recombinant vascular adhesion molecule-1 (p < 0.0001) and recombinant intercellular adhesion molecule-1 (rICAM-1) (p < 0.01) without modulation of very late activation molecule-4 and lymphocyte function-associated antigen-1 expressions and a dose-dependent decrease of lymphocyte transmigration across fibronectin (p < 0.0001). Inhibition of adhesion to rICAM-1 was similar after long (18 hours) or short (5 minutes) incubation time. These results support the potential therapeutic benefit of interferon-beta in Guillain-Barré syndrome.
    Neurology 11/2001; 57(9):1704-6. · 8.31 Impact Factor
  • Article: Cardiac variability in critically ill adults: influence of sepsis.
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    ABSTRACT: To evaluate, in critically ill adults, factors associated with impaired sympathovagal balance. One-month inception cohort study. Twenty-six-bed medical intensive care unit of a teaching hospital. Critically ill adults with an expected duration of intensive care unit stay of > or =48 hrs were enrolled. Patients with permanent arrhythmia or cardiac pacing were not included. None. Sympathovagal balance was assessed on the day after intensive care unit admission by the low-frequency/high-frequency ratio obtained from spectral components of heart rate signal: overall variability, low frequency, and high frequency. Forty-one patients, 13 with sepsis and 28 without sepsis, were assessed. Predictors of low-frequency/high-frequency ratio with the automatic interaction detection method were sepsis and age. Binary logit analysis adjusted for age showed that sepsis remained a strong and independent factor of a low-frequency/high-frequency ratio of <1.50, with an odds ratio of 3.63 (95% confidence interval, 1.47-9.01, p =.005). Use of mechanical ventilation, catecholamines, or sedation did not add any information. The use of the low-frequency/high-frequency ratio in diagnosing sepsis may be supported by a likelihood ratio for low frequency/high frequency <1 at 6.47. This work suggests that impaired cardiac variability and notably sympathovagal balance (i.e., a low-frequency/high-frequency ratio <1.0) may be a diagnostic test for sepsis.
    Critical Care Medicine 08/2001; 29(7):1380-5. · 6.33 Impact Factor
  • Article: Inhibition of the adhesion step of leukodiapedesis: a critical event in the recovery of Guillain-Barré syndrome associated with accumulation of proteolytically active lymphocytes in blood.
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    ABSTRACT: Intraneural inflammation, that reflects emigration of immune cells from blood to nerve tissue, is a critical event in Guillain-Barré syndrome pathogenesis. To investigate the adhesion and transmigration phases of leukodiapedesis, we determined in a series of patients with GBS: (1) circulating levels of soluble forms of adhesion molecules (sICAM-1 and sVCAM-1); (2) attachment capacities of circulating lymphocytes to rICAM-1 and rVCAM-1; (3) fibronectin-penetrating capacities of circulating lymphocytes; and (4) lymphocyte intracellular concentrations of MMP-9 at the different phases of GBS and in healthy controls. Circulating levels of sVCAM-1 and sICAM-1 were above normal values at the time of progression, markedly increased at the time of plateau (sVCAM-1: P<0.03; sICAM-1: P<0.02), and tended to normalize during recovery. The percentage of cells with attachment capacities to rVCAM-1 and to rICAM-1 decreased from progression to recovery by 30 and 31%, respectively (P<0.02). The number of circulating lymphocytes with fibronectin penetrating capacities was lower than controls at the time of progression (P<0.01), then progressively increased to reach values higher than controls at the time of late recovery (P<0.02). Cellular concentrations of MMP-9 in circulating lymphocytes paralleled their fibronectin penetrating capacities. These results suggest early emigration of lymphocytes into nerve, followed by shedding of adhesion molecules from endothelium, and late decrease of lymphocyte adhesion capacities. Plateau and recovery are associated with accumulation in the vascular compartment of still proteolytically active lymphocytes that can no longer adhere to endothelial cells. Modulation of the adhesion step of leukodiapedesis may be crucially involved in the switch from progression to plateau of GBS.
    Journal of Neuroimmunology 04/2001; 114(1-2):188-96. · 2.96 Impact Factor
  • Article: [Guillain-Barré syndrome: epidemiological, clinical and therapeutic insight].
    J C Raphaël, T Sharshar
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    ABSTRACT: The average annual incidence of Guillain-Barré syndrome is 1.5 per 100 000. Mortality was about 5% in a recent clinical trial. Ten percent of patients have severe neurological sequelae one year after onset. For these patients, general care is essential and should be provided in appropriate hospital units. Corticosteroids, administered orally or intravenously are ineffective. Plasma exchange (PE) was the first treatment to demonstrate efficacy in randomized clinical trials. Indications have been recently specified. Patients who can walk must be given two PEs and two additional PEs in case of aggravation. Four plasma exchanges are sufficient in patients unable to walk unaided (intermediate form) or who are mechanically ventilated (severe form). No further PE is required if the patient fails to improve. High-dose intravenous immunoglobulins (0.4 g /kg daily for 5 days) and PE have equivalent efficacy in intermediate and severe forms. The optimal dose of IVIg and the number of Pes in the different severity forms are being assessed in an ongoing study.
    Annales de medecine interne 06/2000; 151 Suppl 1:1S35-40.
  • Article: Association of herpes simplex virus encephalitis and paraneoplastic encephalitis - a clinico-pathological study.
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    ABSTRACT: A 57 year-old woman developed acute limbic encephalitis and brainstem dysfunction. Anti-HU antibodies were repeatedly detected in serum and CSF. Postmortem examination showed necrotic and hemorrhagic lesions in the temporal lobes characteristic of herpes simplex virus encephalitis, which was confirmed by immunocytochemistry, and Purkinje cell loss with proliferation of Bergman glia and myelin loss in the external aspect of the dentate nuclei characteristic of paraneoplastic encephalitis. PCR-assay performed on temporal tissue extracts was positive for HSV-1. There was no identifiable neoplasm. This unusual association raises the possibility of a link between the two diseases.
    Annales de Pathologie 06/2000; 20(3):249-52. · 0.25 Impact Factor
  • Article: Validity and reliability of two muscle strength scores commonly used as endpoints in assessing treatment of myasthenia gravis.
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    ABSTRACT: Valid and reliable measurements of muscle impairment are needed to assess therapeutic efficacy in patients with generalized myasthenia gravis (MG). In 22 patients we compared the validity and interobserver reliability of two scoring methods commonly used as main endpoints in clinical trials, i.e., the Myasthenic Muscle Score (MMS) ranging from 0 to 100 (normal) and the Quantified Myasthenia Gravis Strength Score (QMGSS) ranging from 0 (normal) to 39. Each score is correlated more with functional scale and less with the patient's self-evaluation. Using intraclass correlation we found strong agreement between observers for both the MMS (r = 0.906) and the QMGSS (r = 0.905). The correlation between MMS and QGMSS was high (r = 0.87). The reliability of neither score depended on any specific item, since the removal of individual items did not significantly alter the intraclass correlation coefficient (ranging from 0.86 to 0.93).
    Journal of Neurology 05/2000; 247(4):286-90. · 3.47 Impact Factor
  • Article: [Corticotherapy in severe infectious states].
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    ABSTRACT: Septic shock is one of the leading cause of death in modern countries. Scientists have made huge improvement in the understanding of mechanisms of inflammation, and the sequence of activation of the various pro and anti-inflammatory markers is now well known. By contrary, physicians have failed to improve survival from septic shock, in spite of the development of specific targets of the various points of the cytokine cascade sought to have a key role in host survival to sepsis. Corticosteroids were among the first anti-inflammatory drugs, which have been tested in high quality randomised controlled trials. These trials clearly showed that patients with septic shock are unlikely to benefit from a short course of a large dose of an anti-inflammatory steroid. More recent findings highlighting the role of the integrity of the hypothalamic-pituitary -adrenal axis to appropriately respond to a septic insult, have led to a reappraisal of the use of steroids in septic shock. Several high quality randomised controlled trials have evaluated the efficacy and safety of a prolonged treatment with low dose hydrocortisone in severe sepsis. These trials strongly suggested that this strategy of corticotherapy reduced the morbidity of septic shock and may favourably affect survival from septic shock.
    Bulletin de l'Académie nationale de médecine 02/2000; 184(8):1631-40; discussion 1640-2. · 0.25 Impact Factor
  • Article: Matrix metalloproteinase-9 is increased and correlates with severity in Guillain-Barré syndrome.
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    ABSTRACT: To study the expression and activity of matrix metalloproteinases (MMPs) MMP-2 (72-kd type IV collagenase, gelatinase A), MMP-3 (58-kd stromelysin-1), and MMP-9 (92-kd type IV collagenase, gelatinase B) and tissue inhibitors of MPs (TIMP) in patients with Guillain-Barre syndrome (GBS). Background: MMPs are able to proteolysis of basement membranes and other matrix components, promoting transmigration of inflammatory cells from circulation to nerve tissue. Twenty-five patients with GBS were analyzed according to the phase of the disease, i.e., progression, plateau, early recovery, and late recovery. Determinations of MMP-2, MMP-3, MMP-9, and TIMP-1 were performed using ELISA, zymography, and immunocytochemistry in circulation or peripheral nerve. MMP-9 plasma levels were increased in 67% of patients on admission and decreased from progression to late recovery (p < 0.002). During the course of GBS, MMP-9 was progressively balanced by its inhibitor TIMP-1, as assessed by the MMP-9/TIMP-1 ratio. MMP-9 and TIMP-1 plasma levels and the MMP-9/TIMP-1 ratio correlated positively with disability. MMP-2 expression was similar to controls. MMP-3 activity was not detected, and plasma levels were not different from those in controls. Positive MMP-9 immunolabeling was 51 +/- 11% of circulating lymphocytes. It was observed in some endothelial cells and mononuclear cells adherent to the endothelium and close to myelinated fibers. Circulating matrix metalloproteinases (MMP-9) correlates with disease severity in Guillain-Barré syndrome (GBS). MMP-9 likely represents an important molecule in the pathogenesis of GBS and therefore could represent an interesting therapeutic target.
    Neurology 11/1999; 53(8):1683-91. · 8.31 Impact Factor