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Ref Number = PITIKA-ASPR0005
INVOLVEMENT OF KYNURENINE PATHWAY IN THE PATHOPHYSIOLOGY OF SUBACUTE SCKEROSING PANENCEPHALITIS
Hirofumi Inoue, Takeshi Matsushige, Takashi Ichiyama, Alato Okuno, Osamu Takikawa, Shozo Tomonaga, Banu Anlar, Deniz YĆ¼ksel, Yasushi Otsuka, Fumitaka Kohno, Madoka Hoshide, Shouichi Ohga, and Shunji Hasegawa
OBJECT: Subacute sclerosing panencephalitis (SSPE) is a slowly progressive neurodegenerative disorder caused by a persistent infection of aberrant measles virus. Increased kynurenine pathway (KP) metabolism has been implicated in the etiology of acute encephalopathy and neurodegenerative diseases. Indoleamine-2, 3-dioxygenase (IDO) initiates the increased production of quinolinic acid (QUIN), which is one of KP metabolites, and has an excitotoxic effect for neurons. We investigated serum IDO activity and cerebrospinal fluid (CSF) QUIN levels in patients with SSPE to clarify whether KP modifies the pathogenesis of SSPE.
METHOD: Serum and CSF samples were obtained at diagnostic procedure from 20 and 24 patients with SSPE, respectively. The age- and sex-matched control subjects were 40 afebrile and noninfectious children with relevant medical conditions. We measured the ratio between serum kynurenine and tryptophan concentration as the systemic IDO activity by high-performance liquid chromatographic analysis. We also measured CSF QUIN concentrations to evaluate the condition of KP in central nervous system by gas chromatography/mass spectrometry. We evaluated the relationship between serial CSF QUIN concentrations and neurological disability index (NDI) in a patient. Differences between SSPE patients and controls were analyzed with Mann-Whitney U test. P-values less than 0.05 were taken to be significant. 
RESULT: The CSF QUIN levels were significantly higher in patients with SSPE than in controls (p < 0.001), although serum IDO activities showed no significant differences between the two groups. In a patient with SSPE, CSF QUIN level was 31.6 pmol/ml at the diagnosis (NDI score 8%), and increased to 1002.4 pmol/ml at 8 months later (NDI score 91%), when his deterioration progressed rapidly.
CONCLUSION: SSPE patients had high levels of CSF QUIN, which increased with a deterioration of neurological disability. We suggest that KP might modify the pathogenesis of SSPE.
Keywords: Subacute sclerosing panencephalitis, CSF QUIN, neurological disability index, kynurenine pathway
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