Autoimmune causes of encephalitis syndrome in Thailand: prospective study of 103 patients

Background: Data on encephalitis in Thailand have not been completely described. Etiologies remain largely unknown. We prospectively analyzed 103 Thai patients from 27 provinces for the causes of encephalitis using clinical, microbiological and neuroimaging indices; caseswithout a diagnosis were evaluated for autoimmune causes of encephalitis. Methods: Patients with encephalitis and/or myelitis were prospectively studied between October 2010 and August 2012. Cases associated with bacterial, rickettsial and mycobacterial diseases were excluded. Herpes viruses 1-6 and enteroviruses infection was diagnosed using PCR evaluation of CSF; dengue and JE viruses infection, by serology. The serum of test-negative patients was evaluated for the presence of autoantibodies. Results: 103 patients were recruited. Fifty-three patients (52%) had no etiologies identified. Twenty-five patients (24%) were associated with infections. Immune encephalitis was found in 25 (24%); neuropsychiatric lupus erythematosus (4), demyelinating diseases (3), Behcet’s disease (1) and the remaining had antibodies to NMDAR (5), ANNA-2 (6), Yo (2), AMPA (1), GABA (1), VGKC (1) and NMDA coexisting with ANNA-2 (1). Presenting symptoms in the autoimmune group included behavioral changes in 6/25 (versus 12/25 in infectious and 13/53 in unknown group) and as psychosis in 6/25 (versus 0/25 infectious and 2/53 unknown). Seizures were found in 6/25 autoimmune, 4/25 infectious and 19/53 unknown group. Two patients with anti-ANNA-2 and one anti-Yo had temporal lobe involvement by magnetic resonance imaging. Two immune encephalitis patients with antibodies to NMDAR and ANNA-2 had ovarian tumors. Conclusions: Autoantibody-associated encephalitis should be considered in the differential diagnosis and management algorithm regardless of clinical and neuroimaging features

LINE-1 methylation patterns of different loci in normal and cancerous cells

This study evaluated methylation patterns of long interspersed nuclear element-1 (LINE-1) sequences from 17 loci in several cell types, including squamous cell cancer cell lines, normal oral epithelium (NOE), white blood cells and head and neck squamous cell cancers (HNSCC). Although sequences of each LINE-1 are homologous, LINE-1 methylation levels at each locus are different. Moreover, some loci demonstrate the different methylation levels between normal tissue types. Interestingly, in some chromosomal regions, wider ranges of LINE-1 methylation levels were observed. In cancerous cells, the methylation levels of most LINE-1 loci demonstrated a positive correlation with each other and with the genome-wide levels. Therefore, the loss of genome-wide methylation in cancerous cells occurs as a generalized process. However, different LINE-1 loci showed different incidences of HNSCC hypomethylation, which is a lower methylation level than NOE. Additionally, we report a closer direct association between two LINE-1s in different EPHA3 introns. Finally, hypermethylation of some LINE-1s can be found sporadically in cancer. In conclusion, even though the global hypomethylation process that occurs in cancerous cells can generally deplete LINE-1 methylation levels, LINE-1 methylation can be influenced differentially depending on where the particular sequences are located in the genome

Mechanisms of escape phenomenon of spinal cord and brainstem in human rabies

BACKGROUND: Rabies virus preferentially involves brainstem, thalamus and spinal cord in human furious and paralytic rabies beginning in the early stage of illness. Nevertheless, rabies patient remains alert until the pre-terminal phase. Weakness of extremities develops only when furious rabies patient becomes comatose; whereas peripheral nerve dysfunction is responsible for weakness in paralytic rabies. METHODS: Evidence of apoptosis and mitochondrial outer membrane permeabilization in brain and spinal cord of 10 rabies patients was examined and these findings were correlated with the presence of rabies virus antigen. RESULTS: Although apoptosis was evident in most of the regions, cytochrome c leakage was relatively absent in spinal cord of nearly all patients despite the abundant presence of rabies virus antigen. Such finding was also noted in brainstem of 5 patients. CONCLUSION: Cell death in human rabies may be delayed in spinal cord and the reticular activating system, such as brainstem, thus explaining absence of weakness due to spinal cord dysfunction and preservation of consciousness

LINE-1 methylation patterns of different loci

in normal and cancerous cell

Human rabies: neuropathogenesis, diagnosis, and management.

International audienceRabies is an almost invariably fatal disease that can present as classic furious rabies or paralytic rabies. Recovery has been reported in only a few patients, most of whom were infected with bat rabies virus variants, and has been associated with promptness of host immune response and spontaneous (immune) virus clearance. Viral mechanisms that have evolved to minimise damage to the CNS but enable the virus to spread might explain why survivors have overall good functional recovery. The shorter survival of patients with furious rabies compared with those with paralytic rabies closely corresponds to the greater amount of virus and lower immune response in the CNS of patients with the furious form. Rabies virus is present in the CNS long before symptom onset: subclinical anterior horn cell dysfunction and abnormal brain MRI in patients with furious rabies are evident days before brain symptoms develop. How the virus produces its devastating effects and how it selectively impairs behaviour in patients with furious rabies and the peripheral nerves of patients with paralytic rabies is beginning to be understood. However, to develop a pragmatic treatment strategy, a thorough understanding of the neuropathogenetic mechanisms is needed

Postoperative radiotherapy timing, molecular subgroups and treatment outcomes of Thai pediatric patients with medulloblastoma.

IntroductionMedulloblastoma (MB) is the most common childhood malignant brain tumor worldwide. Recently, molecular classification was established and started to play a role in the management of MB; however, studies involving molecular defined MB in Southeast Asia have been limited. We aimed to describe, and correlate clinical characteristics and molecular subgroups with therapeutic outcomes of Thai pediatric patients with MB.Materials and methodsPediatric MB patients treated at King Chulalongkorn Memorial Hospital in Thailand from 2006 to 2018 were recruited. Patients were classified by clinical characteristics into standard- and high-risk groups, which determined treatment regimen. Retrospectively, available tumor tissues were classified into 3 molecular subgroups using immunohistochemistry: 1) WNT, 2) SHH, and 3) non-WNT/non-SHH. The primary outcome was 5-year overall survival (OS). Risk factors associated with OS were analyzed using cox regression analysis.ResultsFifty-three Thai pediatric patients with MB were enrolled. The median follow-up time was 60 months. The 5-year OS for all patients, and patients with standard-risk and high-risk were 74.2%, 76.3% and 71.4%, respectively. Tumor tissues of 24 patients were available, of which 23 could be molecularly classified. Two, one and 20 were in the WNT, SHH and non-WNT/non-SHH subtypes with 5-year OS of 100%, 100% and 78.9%, respectively. Using multivariate analysis, the interval of more than 8 weeks between surgery and radiotherapy was significantly correlated with a decrease in the 5-year OS.ConclusionInterval between surgery and radiotherapy within 8 weeks was associated with good therapeutic outcomes among Thai pediatric patients with MB. Simplified molecular subtyping combined with clinical characteristics is practical in risk classification of patients with MB in institutes with limited resources

Intracellular Spread of Rabies Virus Is Reduced in the Paralytic Form of Canine Rabies Compared to the Furious Form.

Studies of the furious and paralytic forms of canine rabies at the early stage of disease have shown a more rapid viral colonization of the cerebral hemispheres in the furious form, as measured by viral antigen within neuronal cell bodies and viral RNA levels. Measurement of cellular processes separate from neuronal cell body provides a visual record of the spread of rabies virus which occurs across synapses. In this study, the amount of rabies viral antigen within cell processes was quantitatively assessed by image analysis in a cohort of naturally rabies infected non-vaccinated dogs (5 furious and 5 paralytic) that were sacrificed shortly after developing illness. Measurements were taken at different levels of the spinal cord, brain stem, and cerebrum. Results were compared to the amount of rabies viral antigen in neuronal cell bodies. Generally, the amount of rabies viral antigen in cell processes decreased in a rostral direction, following the pattern for the amount of rabies viral antigen in neuronal cell bodies and the percentage of involved cell bodies. However, there was a delay in cell process involvement following cell body involvement, consistent with replication occurring in the cell body region and subsequent transport out to cell processes. Greater amounts of antigen were seen in cell processes in dogs with the furious compared to paralytic form, at all anatomic levels examined. This difference was even evident when comparing (1) neurons with similar amounts of antigen, (2) similar percentages of involved neurons, and (3) anatomic levels that showed 100% positive neurons. These findings suggest that intracellular transport of the virus may be slower in the paralytic form, resulting in slower viral propagation. Possible mechanisms might involve host-specific differences in intracellular virus transport. The latter could be cytokine-mediated, since previous studies have documented greater inflammation in the paralytic form