Quantitative methods for tracking cognitive change 3 years after coronary artery bypass surgery: a comparison of on-pump CABG and non-surgical controls

The analysis and interpretation of change in cognitive function test scores after coronary artery bypass grafting (CABG) present considerable statistical challenges. Application of hierarchical linear statistical models can estimate the effects of a surgical intervention on the time course of multiple biomarkers. We use an "analyze then summarize" approach whereby we estimate the intervention effects separately for each cognitive test and then pool them, taking appropriate account of their statistical correlations. The model accounts for dropouts at follow-up, the chance of which may be related to past cognitive score, by implicitly imputing the missing data from individuals' past scores and group patterns. We apply this approach to a study of the effects of CABG on the time course of cognitive function as measured by 16 separate neuropsychological test scores, clustered into 8 cognitive domains. The study includes measurements on 140 CABG patients and 92 nonsurgical controls at baseline, and at 3, 12, and 36 months. Our "analyze then summarize" method allows us to identify differences between the treatment groups in individual tests as well as in aggregate measures. It takes into account the correlation structure of the data and thereby produces more precise results than summarizing before analyzing. The methods used have application to a wide range of intervention studies in which multiple biomarkers are followed over time to quantify health effects. Software to implement the methods in the R statistical package is available from the authors at http://www.biostat.jhsph.edu/sbarry/software/ATSrcode.pdf

Motor nerve terminal degeneration provides a potential mechanism for rapid recovery in acute motor axonal neuropathy after <i>Campylobacter</i> infection

We investigated the possible mechanisms of paralysis and recovery in a patient with the acute motor axonal neuropathy (AMAN) pattern of the Guillain-Barré syndrome. The AMAN pattern of GBS is characterized clinically by acute paralysis without sensory involvement and electrodiagnostically by low compound motor action potential amplitudes, suggesting axonal damage, without evidence of demyelination. Many AMAN patients have serologic or culture evidence of recent Campylobacter jejuni infection. Pathologically, the most severe cases are characterized by wallerian-like degeneration of motor axons affecting the ventral roots as well as peripheral nerves, but some fatal cases have only minor changes in the roots and peripheral nerves, and some paralyzed patients with the characteristic electrodiagnostic findings of AMAN recover rapidly. The mechanism of paralysis and recovery in such cases has been uncertain. A 64-year-old woman with culture-proven Campylobacter upsaliensis diarrhea developed typical features of AMAN. She improved quickly following plasmapheresis. Her serum contained IgG anti-GM1 antibodies. The lipopolysaccharide of the organism bound peanut agglutinin. This binding was blocked by cholera toxin, suggesting that the organism contained the Gal(beta1-3)GalNAc epitope of GM1 in its lipopolysaccharide. Motor-point biopsy showed denervated neuromuscular junctions and reduced fiber numbers in intramuscular nerves. In contrast, the sural nerve biopsy was normal and skin biopsy showed normal dermal and epidermal innervation. In AMAN the paralysis may reflect degeneration of motor nerve terminals and intramuscular axons. In addition, the anti-GM1 antibodies, which can bind at nodes of Ranvier, might produce failure of conduction. These processes are potentially reversible and likely to underlie the capacity for rapid recovery that characterizes some cases of AMAN

<i>Campylobacter jejuni</i> lipopolysaccharides in Guillain-Barré syndrome: molecular mimicry and host susceptibility

&lt;p&gt;&lt;b&gt;Objective:&lt;/b&gt; This study was designed to determine if the presence of specific ganglioside-like moieties in &lt;i&gt;Campylobacter&lt;/i&gt; lipopolysaccharides(LPSs) is related to the development of Guillain-Barré syndrome (GBS), and to discover how frequently such moieties, including GM1, are present in these LPSs.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; We studied &lt;i&gt;Campylobacter&lt;/i&gt; isolates and sera from seven patients with GBS (five acute motor axonal neuropathy, one acute inflammatory demyelinating polyneuropathy, and one Fisher's syndrome), and compared them with similar specimens from patients with &lt;i&gt;Campylobacter&lt;/i&gt; enteritis alone.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; All GBS patients had antiganglioside antibodies. Anti-GM1 and anti-GD1a titers were significantly elevated in post-&lt;i&gt;Campylobacter&lt;/i&gt; GBS, both axonal and demyelinating, compared with normal control subjects or those with uncomplicated Campylobacter diarrhea. &lt;i&gt;Campylobacter&lt;/i&gt; isolated from patients with GBS and with enteritis alone had similar ganglioside-like moieties.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; These results indicate that patients who develop GBS respond differently to the ganglioside-like epitopes on Campylobacter than do non-GBS diarrhea patients. Our findings support a role for host susceptibility as a determinant for the outcome following &lt;i&gt;Campylobacter&lt;/i&gt; infection. These findings have important implications for the development of vaccines against &lt;i&gt;Campylobacter jejuni&lt;/i&gt;.&lt;/p&gt