Dan B, Christiaens F, Christophe C, Dachy B
Pediatr Neurol 2000 Feb;22(2):136-8
Hopital Universitaire des Enfants Reine Fabiola, Dept of Neurologie, Brussels, Belgium
PMID# 10738920; UI# 20201499
In children, Multiple Sclerosis is rare and has some clinical and paraclinical differences compared with adults. The assessment of CorticoSpinal Motor Tracts is expected to be relevant because of their frequent early involvement in this disease.
Reported are the results of TransCranial Magnetic Stimulation in two children who presented at 12 and 9 years of age with Clinically Probable and Definite Multiple Sclerosis, respectively.
In Patient 1 the excitatory Cortical threshold for the upper limbs was abnormally raised.
In Patient 2 the latency of the Motor-Evoked Potentials was considerably increased for the right Tibialis Anterior Muscle, with a slowing of the Central Conduction Time.
Although these abnormalities may be consistent with Central Conduction Impairment, they may alternatively suggest early Axonal Damage, because irreversible Axonal lesions occurring at the onset of the disease have recently been reported.
Testing of Central Motor Tracts, in addition to Visual, Auditory, and SomatoSensory Pathways, therefore appears appropriate in the multimodal assessment of pediatric patients with suspected Multiple Sclerosis.
Rio J, Barbera N, Tintoré M, Brieva L, Montalban X
Med Clin (Barc) 2000 Feb 12;114(5):169-70
Unidad de NeuroInmunologia Clinica, Hospital General Universitario Vall d'Hebron, Barcelona
PMID# 10738721; UI# 20203208
Neutrailzing AntiBodies (NABs) against Interferon-ß have been described in one third of patients with Multiple Sclerosis treated with Interferon-ß. We have analyzed the frequency of NABs and their clinical consequences.
Patients And Methods
We have studied 68 patients. NABs were determined by protein A MyxoVirus assay.
Positive NABs were detected in 13% of the patients after 2 years of treatment.
It does not seem to exist a relationship between presence of NABs and a poor evolution of the disease in our patients with Multiple Sclerosis treated with Interferon-ß.
Theiler's Murine EncephaloMyelitis Virus (TMEV): The Role Of A Small Out-of-Frame Protein In Viral Persistence And DeMyelination
Obuchi M, Ohara Y
Jpn J Infect Dis 1999 Dec;52(6):228-233
Kanazawa Medical University, Dept of Microbiology, Ishikawa 920-0293, Japan
Theiler's Murine EncephaloMyelitis Virus (TMEV) belongs to the genus CardioVirus of the family PicornaViridae and is divided into two subgroups on the basis of different biological activities.
GDVII subgroup strains produce acute and fatal PolioEncephaloMyelitis in mice with no Virus persistence. In contrast, DA or TO subgroup strains cause an early nonfatal PolioEncephaloMyelitis.
TMEV is thought to be an excellent animal model for the human DeMyelinating Disease, Multiple Sclerosis.
Data suggest that Macrophages are a major reservoir harboring the Virus. A small out-of-frame protein designated L* is synthesized in DA subgroup strains from an alternative, out-of-frame, initiation site.
Studies of a DA mutant virus, having an ACG rather than an AUG and therefore does not synthesize L* protein, demonstrate that this protein is important for Virus growth in particular cell types and is critical for DA-induced DeMyelinating disease and Virus persistence.
In addition, TMEV can be used as a vector for delivering foreign sequences into the Central Nervous System.
Frequent HHV-6 Reactivation In Multiple Sclerosis (MS) And Chronic Fatigue Syndrome (CFS)
Ablashi DV, Eastman HB, Owen CB, Roman MM, Friedman J, Zabriskie JB, Peterson DL, Pearson GR, Whitman JE
J Clin Virol 2000 May 1;16(3):179-191
Georgetown University, School of Medicine, Dept of Microbiology and Immunology, Washington, DC, USA
HHV-6 is a ubiquitous Virus and its infection usually occurs in childhood and then becomes a latent infection. HHV-6 reactivation has been shown to play a role in the PathoGenesis of AIDS and several other diseases.
To determine what role HHV6 infection or reactivation plays in the PathoGenesis of Multiple Sclerosis (MS) and Chronic Fatigue Syndrome (CFS).
Twenty-one MS and 35 CFS patients were studied and followed clinically. In these patients, we measured HHV-6 IgG and IgM AntiBody levels and also analyzed their Peripheral Blood MonoNuclear Cells (PBMCs) for the presence of HHV-6, using a short term culture assay.
In both MS and CFS patients, we found higher levels of HHV-6 IgM AntiBody and elevated levels of IgG AntiBody when compared to healthy controls.
Seventy percent of the MS patients studied contained IgM AntiBodies for HHV-6 late Antigens (capsid), while only 15% of the Healthy Donors (HD) and 20% of the patients with Other Neurological Disorders (OND) had HHV-6 IgM AntiBodies.
Higher frequency of IgM AntiBody was also detected in CFS patients (57.1%) compared to HD (16%).
Moreover, 54% of CFS patients exhibited AntiBody to HHV-6 early protein (p41/38) compared to only 8.0% of the HD. Elevated IgG AntiBody titers were detected in both the MS and the CFS patients.
PBMCs from MS, CFS and HD were analyzed in a short term culture assay in order to detect HHV-6 Antigen expressing cells and to characterize the Viral isolates obtained as either Variant A or B.
Fifty-four percent of MS patients contained HHV-6 early and late Antigen producing cells and 87% of HHV-6 isolates were Variant B.
Isolates from CFS, patients were predominately Variant A (70%) and isolates from HD were predominately Variant B (67%).
Moreover, one isolate from OND was also Variant B. Persistent HHV-6 infection was found in two CFS patients over a period of 2.5 years and HHV-6 specific Cellular Immune Responses were detected in PBMCs from ten CFS patients.
In both MS and CFS patients, we found increased levels of HHV-6 AntiBody and HHV-6 DNA. A decrease in Cellular Immune Responses was also detected in CFS patients. These data suggest that HHV-6 reactivation plays a role in the PathoGenesis of these disorders.
Blumberg BM, Mock DJ, Powers JM, Ito M, Assouline JG, Baker JV, Chen B, Goodman AD
J Clin Virol 2000 May 1;16(3):159-178
VA Bio-Medical Research Institute, Building 7, East Orange VA Medical Center, 385 Tremont Avenue, East Orange, NJ, USA
Progressive Multifocal Leukoencephalopathy (PML) and Multiple Sclerosis (MS) are DeMyelinative Diseases of the Central Nervous System (CNS).
PML occurs mostly in individuals with AIDS-impaired immunity and is thought to be caused by JC polyoma virus (JCV). In MS a NeuroTrophic Virus trigger is suspected, but the precise etiology remains unknown.
Human HerpesVirus 6 (HHV6) is a ubiquitous, commensal and usually benign beta-HerpesVirus. Some researchers have found evidence for HHV6 infection in MS plaques and sera.
We recently demonstrated a high frequency of cells containing HHV6 Genome in PML lesions, as well as co-infection of Oligodendrocytes by JCV and HHV6.
This suggests that HHV6 may be a co-factor in the etiology of PML, and raises questions about its role in other DeMyelinative Diseases.
To determine the prevalence and cellular localization of HHV6, JCV and HIV-1 infected cells in PML, MS, AIDS and control CNS tissues, and their potential relationship with disease.
An unconventional, sensitive two-step In Situ Polymerase Chain Reaction (ISPCR) procedure was used to amplify and detect HHV6, JCV and HIV-1 genomic DNAs in formalin fixed, paraffin-embedded archival CNS tissues.
HHV6, JCV and HIV-1 Gene expression was detected by ICC for HHV6 p41 and gp101, JCV large T, and HIV-1 p24 gag and NEF proteins.
A high frequency of HHV6 genome was consistently detected in both PML and MS White Matter lesional cells; a Peri-Lesional concentration was notable.
HHV6 was found mainly in Oligodendrocytes, but Neurons were also infected. HHV6 was present in larger amounts than JCV in PML lesions, while more HIV-1 than HHV6 was present in AIDS.
Variable amounts of HHV6 genome were detected in normal, AIDS and other control brains; the frequency of infected cells tended to increase with patient age.
High concentrations of HHV6 genome in association with PML and MS lesions, open the possibility that HHV6 activation may play a role in the PathoGenesis of these DeMyelinative diseases.