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Biomedical subjects

Gavin Giovannoni

Publications and source records attributed to Gavin Giovannoni.

45 records · Page 3Linked to original sources
PubMed2003

Serum gelatinase B/MMP-9 in primary progressive multiple sclerosis patients treated with interferon-beta-1a.

BACKGROUND: Interferon- beta (IFNbeta) acts by a variety of mechanisms in relapsing-remitting multiple sclerosis (MS). One of these is a cellular down-regulation of gelatinase B or matrix metalloproteinase-9 (MMP-9), which is known from biochemical, biological and immunohistochemical evidences to play a disease-promoting role in MS. AIMS: a) To investigate the influence of IFNbeta-1a (30 or 60 micro g I. M./week) on serum MMP-9 levels in patients with primary progressive MS (PPMS). b) To correlate serum MMP-9 levels with clinical and magnetic resonance imaging (MRI) findings. METHODS: Serial blood samples were collected every 3 months from 49 patients participating in a phase II trial of IFNbeta-1a in PPMS. Serum MMP-9 was quantified by ELISA and correlations with clinical (EDSS) as well as MRI findings (brain and spinal cord atrophy, ventricular volume, T1 and T2 lesion load) were calculated. RESULTS: No significant differences were found between serial serum MMP-9 levels in IFNbeta-treated versus placebo-treated patients. MMP-9 levels did not differ between patients who progressed or did not progress during the study interval. Although mean absolute serum MMP-9 levels over the study period correlated with an increase in T2 lesion load (relative T2 change: r=0.51, p<0.001; absolute T2 change: r=0.30, p=0.038), absolute increase in brain ventricular volume (r=0.29, p=0.05) and increased brain atrophy (r=0.35, p=0.02), only the correlation with T2 lesion load was sustained throughout the study period. No correlations were found between MMP-9 levels and relative changes in ventricular volume or with relative/absolute changes in T1 lesion load and in spinal cord atrophy. None of the MRI measures correlated with MMP-9 changes between baseline levels and those on treatment. CONCLUSION: Although some evidence suggests a down-regulating effect of IFNbeta on MMP-9, this was not confirmed for a once weekly intramuscular dose of IFNbeta-1a in patients with PPMS. The sustained correlation between serum MMP-9 and changes in T2 volumes, and the lack of correlation with clinical or MRI measures of disease progression may suggest that MMP-9 is more directly related to non-specific central nervous system damage than to axonal loss.

Adult↗
PubMed2003

CSF and serum immune parameters in Sydenham's chorea: evidence of an autoimmune syndrome?

Previous investigations have suggested that Sydenham's chorea (SC) may be an autoantibody mediated disorder. We examined this autoimmune hypothesis by measuring Th1 (IFN-gamma, IL-12) and Th2 (IL-4, IL-10) cytokines, oligoclonal bands (OCB) and anti-basal ganglia antibodies (ABGA). CSF IL-4 was elevated in 31% of acute SC and 50% of persistent SC. CSF IL-10 was also elevated in 31% of acute SC but 0% of persistent SC. CSF IFN-gamma was undetectable in all patients. Serums IL-4, IL-10 and IL-12 were elevated in acute compared to persistent SC. OCB were found in 46% of acute SC, ABGA were in 93% of acute SC and 50% of persistent SC was of IgG(1) and IgG(3) subclass. These findings support an autoantibody pathogenesis.

Adolescent↗
PubMed2003

The therapeutic potential of cannabis.

Research of the cannabinoid system has many similarities with that of the opioid system. In both instances, studies into drug-producing plants led to the discovery of an endogenous control system with a central role in neurobiology. Few compounds have had as much positive press from patients as those of the cannabinoid system. While these claims are investigated in disorders such as multiple sclerosis spasticity and pain, basic research is discovering interesting members of this family of compounds that have previously unknown qualities, the most notable of which is the capacity for neuroprotection. Large randomised clinical trials of the better known compounds are in progress. Even if the results of these studies are not as positive as many expect them to be, that we are only just beginning to appreciate the huge therapeutic potential of this family of compounds is clear.

Cannabinoids↗
PubMed2002

Decreased level of kynurenic acid in cerebrospinal fluid of relapsing-onset multiple sclerosis patients.

The present study was undertaken to measure cerebrospinal fluid (CSF) levels of kynurenic acid (KYNA) in patients with relapsing-onset multiple sclerosis (MS) during remission or not progressing for at least 2 months. In these patients the levels of CSF KYNA were found to be significantly lower compared with subjects with non-inflammatory neurological diseases, as well as those with inflammatory disease (median (interquartile range): 0.41 (0.3-0.5) pmol/ml, n=26 vs. 0.67 (0.5-1.1), n=23, P<0.01 and 1.7 (1.5-2.6), n=16, P<0.001, respectively). These results provide further evidence of the alterations in the kynurenine pathway during remitting-onset MS.

Adult↗
PubMed2002

Post-streptococcal autoimmune neuropsychiatric disease presenting as paroxysmal dystonic choreoathetosis.

Paroxysmal dystonic choreoathetosis (PDC) is an episodic, non-kinesogenic, extrapyramidal movement disorder. It is postulated that PDC is an ion channel disorder. We describe a sporadic case of paroxysmal dystonic choreoathetosis occurring after streptococcal pharyngitis. The episodes were characterized by abrupt-onset dystonic posturing, choreoathetosis, visual hallucinations and behavioral disturbance. Each episode lasted between 10 minutes and 4 hours, and occurred up to 4 times per day. In between attacks, examination was normal. The episodes waxed and waned in frequency during a 6-month illness. Magnetic resonance imaging of the brain was normal. Post-streptococcal neuropsychiatric disease has a proposed autoimmune etiology, which is supported by the presence of serum antibasal ganglia antibodies. Western immunoblotting of this case's serum demonstrated antibody binding to a basal ganglia antigens of molecular weight 80 kDa and 95 kDa. Immunohistochemistry examination demonstrated specific antibody binding to large striatal neurones. We propose that autoantibodies produced in post-streptococcal neuropsychiatric disease cause alteration in neurotransmission, possibly secondary to ion channel binding.

Antibody Specificity↗
PubMed2002

Post-streptococcal autoimmune dystonia with isolated bilateral striatal necrosis.

Infantile bilateral striatal necrosis (IBSN) is characterized by a dystonic movement disorder and basal ganglia imaging abnormalities. Acute IBSN often occurs after upper respiratory tract infections although no specific micro-organism which may cause IBSN has been identified. We present 2 children (1 year 2 months and 4 years) with acute IBSN after clinical pharyngitis. Both IBSN patients had serological evidence of recent beta-haemolytic streptococcal infection. Due to the association of post-streptococcal disorders with anti-basal ganglia antibodies (ABGA), we examined both patients for anti-neuronal antibodies. For comparison, 20 children with dystonia (9 females, 11 males; mean age 4 years 1 month), and 20 children with uncomplicated streptococcal infection (12 females, 8 males; mean age 5 years 9 months) were examined. Both IBSN patients had antibodies reactive against basal ganglia constituents of molecular weight 40 kDa. Immunohistochemistry showed antibody reactivity against large striatal neurons only. Other anti-neuronal antibodies were negative, supporting striatal specificity. All controls were negative for ABGA. Acute IBSN is part of the poststreptococcal autoimmune neuropsychiatric spectrum. An autoimmune aetiology should be considered in this phenotype, as immunomodulatory therapies may reduce morbidity and mortality.

Antibody Specificity↗