title: Mycobacterium leprae in neurons of the medulla oblongata and spinal cord in leprosy.
abstract: Peripheral neuropathy has been extensively studied in leprosy, a chronic disease caused by Mycobacterium leprae, but the central nervous system (CNS) is thought to be free from bacilli. Involvement of the CNS was explored in autopsy cases of clinically cured lepromatous leprosy (n = 67) and in non-leprosy cases (n = 15). Paraffin sections of the medulla oblongata and spinal cord were subjected to hematoxylin and eosin staining, Fite acid-fast staining, and anti-phenolic glycolipid-I (PGL-I) immunostaining. PGL-I-positive areas were microdissected from selected cases and nested polymerase chain reaction (PCR) targeting the M. leprae-specific repetitive sequence was performed. Of the 67 cases of leprosy, 44 (67%) had vacuolar changes of motor neurons either in medulla oblongata (nucleus ambiguous or hypoglossal nucleus) or spinal cord. Fite staining was negative, but PGL-I was positive in vacuolated areas. PCR revealed M. leprae-specific genomic DNA in 18 of 19 cases (95%) with vacuolated changes and 5 of 8 (63%) without vacuolated changes. All of above findings were negative in control cases. Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining did not show a significant increase of apoptosis in the neurons. The PCR positivity had a significant correlation with PGL-I immunostaining (p < 0.05). The presence of vacuolar changes in the spinal cord was correlated with hand and feet deformity grades (p = 0.04). This study provides significant additional evidence to indicate that M. leprae is present in the CNS in a subset of patients. Further investigation is required to correlate this finding to motor dysfunction and silent neuropathy in leprosy.
authors.affiliation: Department of Human Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Thida
authors.initials: T
authors.lastname: Aung
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kitajima
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Nomoto
authors.forename: Junichiro
authors.initials: J
authors.lastname: En
authors.forename: Suguru
authors.initials: S
authors.lastname: Yonezawa
authors.forename: Isao
authors.initials: I
authors.lastname: Arikawa
authors.forename: Masamichi
authors.initials: M
authors.lastname: Goto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000378:metabolism; D005260:Female; D006017:Glycolipids / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D007918:Leprosy / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008526:Medulla Oblongata / Q000473:pathology*; D008875:Middle Aged; D009166:Mycobacterium leprae / Q000302:isolation & purification*; D009474:Neurons / Q000382:microbiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013116:Spinal Cord / Q000473:pathology*; D013223:Statistics as Topic
chemical_list: D000942:Antigens, Bacterial; D006017:Glycolipids; C045169:phenolic glycolipid I, Mycobacterium leprae