Sasitorn Siritho

Myelin injury without astrocytopathy in neuroinflammatory disorders with MOG antibodies

Objective To compare myelin and astrocyte injury in patients with antibodies against myelin oligodendrocyte glycoprotein (anti-MOG) or aquaporin-4 (anti-AQP4), and multiple sclerosis (MS). Methods Myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) levels were measured in the cerebral spinal fluid (CSF) from anti-MOG+ or anti-AQP4+ patients tested in both sera and CSF by cell-based assays with live transfected cells. Results In total, 75.6% (68/90) of the patients were positive for either anti-MOG or anti-AQP4 antibodies in both serum and CSF; 74.2% (23/31) were anti-MOG+, and 76.3% (45/59) were anti-AQP4+. No patients were only CSF positive or were positive for both anti-MOG and anti-AQP4 antibodies, and none of the MS patients or controls had these autoantibodies in the serum or CSF. MBP levels were elevated in the anti-MOG+ cases compared to the multiple sclerosis (MS) patients, and the levels found were similar between anti-MOG+ cases and anti-AQP4+ neuromyelitis optica spectrum disorder (NMOSD) cases. Meanwhile, GFAP was only elevated in the anti-AQP4+ NMOSD. Moreover, CSF pleocytosis, high protein levels, and oligoclonal IgG band negativity distinguished the anti-MOG+ cases from MS patients. Conclusions Myelin injury was more severe in the anti-MOG+ cases than in the MS cases, and anti-MOG+ cases have differences in the CSF characteristics compared to MS. GFAP elevation in anti-AQP4+ cases was absent in anti-MOG+ patients (even in cases with NMOSD phenotype), indicating that immune-mediated astrocytopathy is unique to anti-AQP4+ patients. Our study suggests that anti-MOG+ cases are distinct from MS and anti-AQP4+ NMOSD.

A retrospective study of multiple sclerosis in Siriraj Hospital, Bankok, Thailand.

OBJECTIVE To determine the demographic and clinical data of Thai multiple sclerosis (MS) patients. METHODS A retrospective study of 72 patients attending the MS clinic at Siriraj Hospital, Mahidol University, Thailand between January 1997 and June 2004. RESULTS Fifty-eight patients (81%) were classified as clinically definite MS, 5 (7%) as Devics syndrome, and 9 (13%) as possible MS. There were 62 females (86%) and 10 males (14%). Age at onset was 33 +/- 12 years with a mean relapse rate of 1.2 +/- 1.0 attacks per annum. None had a family history of MS. Visual impairment (53%) was the most common manifestation. Only 16% had classic (western) form of MS. Positive oligoclonal bands were found in 21%, visual evoked potentials with a typical delayed latency in 28%. MRI brain lesions compatible with McDonalds criteria were seen in only 24%, and spinal MRI brain longer than 2 vertebral bodies in 62%. The mean Kurtzkes Expanded Disability Status Scale (EDSS) was 3.0. CONCLUSIONS Thai MS patients had much more female occurrence, no family history, common optico-spinal form, long spinal MRI lesions and low positive CSF oligoclonal bands.

The clinical spectrum associated with myelin oligodendrocyte glycoprotein antibodies (anti-MOG-Ab) in Thai patients.

Background: Myelin oligodendrocyte glycoprotein (anti-MOG) antibody was reported in anti-aquaporin-4 (anti-AQP4) seronegative neuromyelitis optica spectrum disorders (NMOSD) patients. Objectives: To describe clinical phenotypes associated with anti-MOG. Methods: Seventy consecutive Thai patients with inflammatory idiopathic demyelinating central nervous system disorders (IIDCD) who were previously anti-AQP4 seronegative were tested for anti-MOG. Results: Anti-MOG was positive in six patients, representing 20.7% of the IIDCD anti-AQP4 seronegative patients with a non-multiple sclerosis phenotype, and most had relapses. All first presented with optic neuritis with good visual recovery after treatment. Conclusions: Anti-MOG positive patients may have manifestations that mimic NMOSD but differ in their course and prognosis from anti-AQP4 positive NMOSD.

Features of anti-aquaporin 4 antibody-seronegative Thai patients with neuromyelitis optica spectrum disorders: a comparison with seropositive cases.

OBJECTIVE The aim of this study is to investigate the unique features of seronegative neuromyelitis optica spectrum disorders (NMOSD) in Thailand. BACKGROUND It remains unknown whether seronegative NMOSD patients possess clinical and paraclinical features that are distinct from those with seropositivity. METHODS In a Thai cohort of idiopathic inflammatory CNS disorders (n=122), 52 patients fulfilled the Wingerchuk 2007 criteria for NMOSD. We determined anti-AQP4 antibody statuses using three different assays (an in-house cell-based assay [CBA], a commercially available CBA and a tissue-based indirect immunofluorescence [IIF] assay). RESULTS Among the NMOSD patients, the percentage of seropositive cases was 54.5% based on the in-house and commercial CBAs and 30.8% based on the IIF assay. Using the in-house CBA, seronegative NMOSD patients exhibited distinct features compared with seropositive patients, such as a lack of female preponderance (F/M=1.2 vs. 6.0), frequent simultaneous bilateral optic involvement (33.3% vs. 0.04%), a lower annual relapse rate (0.4 ± 0.3 vs. 0.7 ± 0.6), fewer spinal cord lesions (1.0 ± 4.3 vs. 1.4 ± 0.6), and lower CSF cell counts (20 ± 72 vs. 80 ± 285). Use of the commercial CBA yielded essentially similar results, but some of these differences were not significant using IIF. CONCLUSIONS Sensitive anti-AQP4 antibody assays reveal features of seronegative NMOSD patients that differ from those of seropositive patients from Thailand.

Efficacy and safety of beta-interferon in Thai patients with demyelinating diseases

Background: The efficacy of beta-interferon (IFN-β) treatment in Thai patients with demyelinating diseases has not been reported. Objectives: To evaluate the efficacy and any adverse drug reactions of IFN-β therapy in Thai patients, for each group of demyelinating diseases. Methods: We retrospectively reviewed data of Thai patients with multiple sclerosis (MS), neuromyelitis optica (NMO) and NMO spectrum disorders (NMOSDs) who attended the MS Clinic at Siriraj Hospital, Thailand from March 2000 to October 2011. We reviewed those 73 patients who received IFN-β. We evaluated the drug’s efficacy over 2 years and any adverse drug reactions among these patients. Results: Of the 40 MS patients who received IFN-β, 26 adhered to the medication for at least 2 years. In addition, 27 NMO/NMOSDs patients who had been diagnosed with MS were treated as such with IFN-β. In the true MS group, the pre- and post-treatment annualized relapse rates (ARR) were 1.25 and 0.59, respectively, so there was a reduction of 52.8% (p = 0.004). In addition, in 69.2% of the patients, IFN-β also showed beneficial effects by prolonging the time to first relapse to 15.9 months and stabilizing or decreasing progression of the disease. In contrast, no significant benefit was seen in the NMO/NMOSDs group. On the contrary, an increase in EDSS was seen in 53.3 % of them. The most common side effects seen were local skin reactions and flu-like symptoms. Conclusions: Treatment with IFN-β was effective in reducing both ARR and disability progression in Thai patients with MS. In contrast, we observed that giving IFN-β treatment to NMO/NMOSDs patients may lead to a worsening of symptoms.

Vitamin D level status in Thai neuromyelitis optica patients

Vitamin D status of Thai clinically isolated syndrome (CIS), multiple sclerosis (MS) and NMO/neuromyelitis optica spectrum disorders (NMOSD) patients were prospectively collected (N=130). Its associations with disability score, and disease activity were sought. Mean vitamin D levels were not significantly different (CIS, 22.18±8.2; MS, 23.41±11.9; NMO/NMOSD, 23.54±9.3ng/mL; p=0.857). Prevalence of vitamin D insufficiency and deficiency (≤30ng/mL) was 73-80%. Neither disability score nor disease activity was associated with vitamin D level. Vitamin D insufficiency was common in Thai CIS, MS, and NMO/NMOSD patients without association with disability or disease activity.

The characteristics of spinal imaging in different types of demyelinating diseases

BACKGROUND Transverse myelitis is the common presentation in demyelinating conditions. OBJECTIVE To determine the characteristics of spinal lesions among each type of demyelinating diseases. METHODS Medical records and spinal imaging of patients who were [1] older than 18years, [2] had at least one attack of TM, [3] had available spinal MRI data and [4] were tested for aquaporin-4 antibody were included. RESULTS One hundred and fifty-eight patients were eligible (27 clinically isolated syndrome [CIS], 38 MS, 55 seropositive neuromyelitis optica spectrum disorders [NMOSD], 9 seronegative NMOSD, and 29 idiopathic transverse myelitis [IDD-TM]). All groups showed female preponderance and no difference of age at onset. In each patient group, no significant difference in the mean number of spinal lesions was found. The most common levels of involvement were thoracic in IDD-TM, cervical in CIS and MS, as well as cervico-thoracic in both NMOSD groups. Long extensive TM was the most common finding in both the seropositive and seronegative NMOSD groups compared to the other groups. Peripheral location and <30% of spinal cord area involvement were the characteristic findings in CIS and MS. Central location and intermediately involved of the cross-sectional cord area were the determinants for the seropositive and seronegative NMOSD groups, respectively. CONCLUSION Spinal MRI findings can help to differentiate among demyelinating diseases in who presented with TM.

Severe Headache with Eye Involvement from Herpes Zoster Ophthalmicus, Trigeminal Tract, and Brainstem Nuclei

A 43-year-old female presented with severe sharp stabbing right-sided periorbital and retroorbital area headache, dull-aching unilateral jaw pain, eyelid swelling, ptosis, and tearing of the right eye but no rash. The pain episodes lasted five minutes to one hour and occurred 10–15 times per day with unremitting milder pain between the attacks. She later developed an erythematous maculopapular rash over the right forehead and therefore was treated with antivirals. MRI performed one month after the onset revealed small hypersignal-T2 in the right dorsolateral mid-pons and from the right dorsolateral aspect of the pontomedullary region to the right dorsolateral aspect of the upper cervical cord, along the course of the principal sensory nucleus and spinal nucleus of the right trigeminal nerve. No definite contrast enhancement of the right brain stem/upper cervical cord was seen. Orbital imaging showed no abnormality of bilateral optic nerves/chiasm, extraocular muscles, and globes. Slight enhancement of the right V1, V2, and the cisterna right trigeminal nerve was detected. Our findings support the hypothesis of direct involvement by virus theory, reflecting rostral viral transmission along the gasserian ganglion to the trigeminal nuclei at brainstem and caudal spreading along the descending tract of CN V.

Beneficial effect of plasma exchange in acute attack of neuromyelitis optica spectrum disorders

BACKGROUND Plasma exchange (PLEX) is routinely performed in neuromyelitis optica spectrum disorders (NMOSD) patients with an acute attack who do not respond to corticosteroids treatment. OBJECTIVE To compare treatment outcomes in NMOSD patients with an acute attack between the two groups. METHODS We retrospectively studied 67 attacks from 52 NMOSD patients. Outcome measurements using Expanded Disability Status Scale (EDSS), modified Rankin Scale (mRS) were compared. RESULTS There were 23 IVMP responders, 16 IVMP non-responders refusing PLEX, 12 IVMP non-responders/PLEX responders, and 16 IVMP/PLEX non-responders. The IVMP-responders showed faster improvement since the time of discharge but seemed to have less treatment benefit over time. However, IVMP non-responders/PLEX responders showed continuous and maximum improvement at 6 months (ΔEDSS from nadir: 1 for IVMP-responders vs 0.5 for IVMP non-responders without PLEX vs 2.75 IVMP non-responders/PLEX-responders vs 0.5 IVMP/PLEX non-responders; p = 0.49) and had comparable outcomes to the IVMP-responders (nadir EDSS 8.0 to 5.25 [ΔEDSS = 2.75] vs nadir EDSS 6.5 to 5.0; [ΔEDSS = 1.5], respectively). CONCLUSION Add - on PLEX treatment in NMOSD patients with an acute attack should be considered in those not responding to IVMP alone.

How long does it take to diagnose patients with neuromyelitis optica (NMO) using the 2006 diagnostic criteria

BACKGROUND AND PURPOSE A few reports studied the time use to diagnose patient with neuromyelitis optica (NMO). The Aim of the study is to evaluate the interval from disease onset to the time when patients fulfilled the NMO diagnostic criteria 2006 in Thai. METHOD A retrospective study of the NMO patients visiting the MS clinic and related disorders at Siriraj hospital was reviewed. RESULTS There were 42 definite NMO. All were female. The most common first presentations were optic neuritis (ON) (45.2%), transverse myelitis (TM) (35.7%), ON and TM (9.5%) and brainstem symptoms (9.5%), respectively. The mean age at onset of their ON and TM attack was 33.4 and 38.4 years, respectively. Anti-AQP4 antibody was presented in 82% using cell based assay. For those presented with ON, 7.1% reported painful eye movements and 33.3% had bilateral involvement. Brain MRI not compatible with MS was found in 94.87%. In who presented with TM, 87.8% revealed long extensive transverse myelitis (LETM) in spinal MRI. The presence of CSF-oligoclonal band (CSF-OCB) was found in 14.6%. Our NMO patients had the average number of the attack of 1.5 times before the diagnosis could be made. Nearly fifty-five percent of NMO patients fulfilled the NMO diagnostic criteria 2006 within 1 year after disease onset and 90.5% within 5 years CONCLUSION About half of Thai patients with definite NMO were diagnosed within 1 year and approximately 90% within 5 years from their disease onset.