The value of csf analysis for the differential diagnosis of HTLV-I associated myelopathy and multiple sclerosis

Abstract

SUMMARY -Cerebrospinal fluid (CSF) and serum of 17 patients with HAM/TSP (HTLV-I associated myelopathy/ tropical spastic paraparesis), six with multiple sclerosis and six with idiopathic epilepsy (non inflammatory control) from Brazil were analysed for the presence of intrathecal synthesis of virus-specific antibodies against measles, rubella, varicella zoster virus and herpes simplex virus by enzyme-linked immunosorbent assay (ELISA). All HAM/TSP and multiple sclerosis cases had an intrathecal immune response (oligoclonal IgG). In HAM/TSP, only 1/17 case showed a polyspecific intrathecal immune response against measles and rubella virus. In multiple sclerosis, specific antibodies against measles and rubella (MRZ response) were observed in all patients but not in the control with idiopathic epilepsy. The diagnostic and theoretical relevance of mono-and polyspecific immune responses is discussed for these chronic neurological diseases. KEY WORDS: HTLV-I, HAM/TSP, cerebrospinal fluid, antibody indexValor da análise do LCR para o diagnóstico diferencial de mielopatia associada ao HTLV-I e esclerose múltipla RESUMO -Amostras de líquido cefalorraquidiano (LCR) e soro de 17 pacientes brasileiros com HAM/TSP, seis com esclerose múltipla e seis com epilepsia idiopática (controle não-inflamatório) foram analisadas para a presença de anticorpos para os vírus do sarampo, rubéola, varicela zoster e herpes simples pelo método de ELISA. Todos os casos de HAM/TSP e esclerose múltipla tinham resposta imune intratecal (IgG oligoclonal). Somente 1/17 casos de HAM/TSP apresentavam resposta imune poliespecifica intratecal para sarampo e rubéola. Anticorpos específicos para sarampo e rubeola (resposta MRZ) foram observados em todos os pacientes com esclerose múltipla, mas não nos controles com epilepsia idiopática. A relevância das respostas poliespecifica e monoespecifica é discutida para essas doenças neurológicas crônicas. PALAVRAS-CHAVE: HTLV-I, HAM/TSP, líquido cefalorraquidiano, índice de anticorpos.The sensitive detection of intrathecally synthesized antibodies increased the relevance of CSF analysis for diagnosis of neurological diseases 17 . The sucessful concepts for discrimination of blood derived and brain derived CSF fractions 16 of immunoglobulin could be extended to the detection of brain defined specific antibodies exceeding the theoretical upper concentration of blood derived antibody species in CSF. An immune response against virus antigens within the central nervous system (CNS) has been demonstrated in different neurological diseases 1 " 4 -6,7 . This reaction may be

Polyspecific, antiviral immune response distinguishes multiple sclerosis and neuromyelitis optica

“…This would be well in line with the recent proposal of a specific antigen in some NMO patients (ie, aquaporin-4) 14 15. Consistently, MRZR is also negative in patients with other CNS disorders characterised by well defined antibody targets such as paraneoplastic neurological syndromes associated with antibodies against Hu, Ri, Yo, Ma, Ta or amphiphysin (personal observation in 34 patients, SJ, RV), viral encephalitis or myelitis,6 8 and neuroborreliosis 16. The hypothesis of differential ways of B cell involvement is further supported by the finding that MRZR was also negative in OCB positive NMO patients.…”

The intrathecal, polyspecific antiviral immune response: Specific for MS or a general marker of CNS autoimmunity?

“…MRZR was previously found to be missing also in patients with infectious inflammatory disorders of the CNS such as chronic neuroborreliosis [15] or viral encephalomyelitis [4,16]. These findings underscore the significance of MRZR as a possible disease marker for MS, especially when the very rarity of CNS vasculitis, the only condition besides MS shown to be associated with the marker thus far, is taken into account.…”

“…As simultaneous infection with several neurotropic viruses is unlikely and PCR for measles, rubella, and varicella zoster virus was shown to be negative in MRZR positive MS patients, MRZR is thought to represent non-specific activation (so called 'bystander' activation) of B cells within the CNS in the absence of viral replication, whereas in MRZR negative patients a more targeted humoral immune response is discussed [3,19]. Consistently, all inflammatory disorders in which MRZR was found to be negative so far such as NMO [11], neuroborreliosis [15], viral encephalitis and myelitis [4,16], and now PND, are characterized by well defined target antigens.…”

Cerebrospinal fluid data compilation and knowledge-based interpretation of bacterial, viral, parasitic, oncological, chronic inflammatory and demyelinating diseases. Diagnostic patterns not to be missed in neurology and psychiatry

“…All antibodies for which the MS patient had a former systemic infection or immunization 26 can be found synthesized in brain with frequencies between 10% and 30% (see complementary review 4 and references 35,36,37,38,39 ). But the frequencies are extraordenary high for measles antibodies (up to 80%), rubella antibodies ( up to 67%) and VZV antibodies (up to 63%) with a combined frequency for one to three of them, with up to 96% and for the more specific frequency of the diagnostic relevant combination of two to three increased antibody Index values up to 75% of the MS cases individually depending on the total amount of intrathecal IgG 36,39 .…”