"NMDA receptor spectrum disorder" in the differential diagnosis of demyelinating disorders of the CNS: optic neuritis and myelitis.

OBJECTIVE: The aim of this study was to investigate the frequency of anti-N-methyl-D-aspartate receptor (anti-NMDAR) antibody positivity in patients presenting with transverse myelitis (TM) and/or optic neuritis (ON), to describe their neurologic and radiological characteristics, and to compare these characteristics with those reported in previous studies. MATERIAL AND METHODS: This study included 179 patients (ON: 96, TM: 74, ON and TM: 9) who visited Isfahan Multiple Sclerosis Center from January 2017 to September 2019, for approximately 32 months. The respective neurological examinations were performed. Demographic data of the patients, as well as findings from radiological and serological investigations were obtained. RESULTS: Frequencies of anti-NMDAR seropositivity in patients with TM, ON, and concurrent TM and ON were approximately 3.4%, 1.4%, and 11.1%, respectively. None exhibited any psychiatric symptoms. CONCLUSION: Based on the frequency of seropositivity for anti-NMDAR antibody in our patients, positivity for this antibody appears to be more frequent than previously anticipated in patients presenting with these conditions. We recommend that the anti-NMDAR antibody presence in CSF/serum be checked and considered in addition to the routine examinations performed upon confronting demyelinating conditions such as TM and ON. We suggest considering the term "NMDAR spectrum disorder" to more clearly distinguish the potentially overlapping conditions with different etiologies in patients with CNS disorders.

The prominence of Oligoclonal Bands for clinical conversion in Radiologically isolated syndrome: 10-year follow-up study in Isfahan, Iran.

BACKGROUND: Since data is limited on radiologically isolated syndrome (RIS) subjects in certain regions like the Middle East, we aimed to further explore the replicability and generalizability of previously suggested predictors among a cohort of Iranian RIS subjects and report the long-term clinically definite MS (CDMS) conversion rate in this cohort. METHODS: We conducted a prospective 10-year cohort on our RIS participants, during which we collected the MRI, paraclinical, and demographic data of the subjects, and identified those who converted to CDMS. RESULTS: Out of 35 participants, 10 (28.5 %) developed CDMS during an average of 5.58 ± 3.08 years (range: 4 months to 10.33 years). OCB positivity was the only definitive predictor for conversion to CDMS in this cohort (P-value = 0.006), but other previously reported risk factors such as spinal cord lesions or age lacked statistical significance (P-values > 0.05). We also reported the median survival time as 114 months, the proportion surviving after 14 months as 96.9 % ± 3.1 %, and the overall conversion rate as 0.05 cases per year. CONCLUSION: Our results highlight OCB as an important predictive factor of clinical conversion in RIS. The prominence of OCB suggests a need for routine CSF analysis in RIS subjects and could guide clinicians in deciding which RIS subjects benefit from DMTs.

Centrally-located transverse myelitis would facilitate the differentiation of NMOSD and MOG-AD from MS.

OBJECTIVES: Differentiating neuromyelitis optica spectrum disorder (NMOSD) and Myelin oligodendrocyte glycoprotein antibody disease (MOG-AD) from multiple sclerosis (MS) is important since MS therapies might result in progression and relapse of the former diseases. Evidence of long extending transverse myelitis (LETM) in magnetic resonance imaging (MRI) is one of the requirements to make an NMOSD diagnosis. However, centrally located lesions on spinal MRI may bring higher sensitivity and specificity to the NMOSD and MOG-AD diagnosis. METHODS: We aimed to assess the association between NMOSD diagnosis and the presence of centrally located lesions at disease onset. We reviewed 102 medical records from the Isfahan MS clinic who presented with cervical cord lesions and 17 MS, 23 NMOSD, and 6 MOG-AD patients were selected. We collected demographic, clinical, and MRI data of patients who had clinical presentations of cervical cord lesion at disease onset, and the characteristics of the lesion were studied. RESULTS: There was an association between NMOSD diagnosis and presence of a centrally located lesion (CLTM) (P < 0.001), presence of an LETM (P < 0.001), and an intermediate to high axial cord expansion (P < 0.001). CLTM and LETM can also be found in MOG-AD patients. The presence of CLTM (sensitivity and specificity: 95.65% and 69.56%), possessed higher sensitivity and specificity for NMO diagnosis than LETM presence (sensitivity and specificity: 78.26% and 43.47%). CONCLUSION: A diagnostic criteria including the centrality, location, and expansion of the transverse myelitis lesions, in addition to LETM, may be more accurate in the diagnosis of NMOSD and MOG-AD and their distinction from MS.

Dorsal midbrain involvement in MRI as a core clinical manifestation for NMOSD diagnosis.

BACKGROUND: Few data are available on the prevalence of midbrain lesions among NMOSD patients. The study aimed to address the frequency of midbrain lesions, especially dorsal midbrain involvement, among a group of NMOSD patients. METHODS: The medical records of 108 NMOSD patients were reviewed, who were registered at the Al-Zahra MS Clinic, Isfahan, Iran. The patients´ information including sex, age, first recorded chief complaint, and midbrain lesion presence in the first brain MRI was collected. RESULTS: Out of the 108 NMOSD patients, eight had midbrain lesions in their first brain MRI (7.4%). Of these patients, 50% were male and 50% were female, with the mean age being 35.25 ± 12.17 years. The most frequent first chief complaints included diplopia due to incomplete third nerve palsy and vertigo. The brain MRIs of the patients showed symmetric dorsal midbrain involvement in all the patients, and enhancement was discovered in only one of the brain MRIs. CONCLUSION: Among the patients, 7.4% presented midbrain involvement at onset. Therefore, midbrain lesions should also be considered as a possible core clinical manifestation in the NMOSD diagnostic criteria.

Paraneoplastic neuromyelitis optica associated with fever of unknown origin as an early manifestation: A case report.

Tumors have been frequently reported to be associated with neuromyelitis optica (NMO). Here we review a case of a 34-year-old woman who presented with complaint of one-sided visual loss. All Lab tests exhibited negative results which decreased the possibility of Auto-immune or neuro-inflammatory disorders. Magnetic resonance imaging (MRI) of the brain and spinal cord was done as a part of work up, which showed Meningioma in anterior fossa without any other findings supporting neuro-demyelinating disorders. After complete surgical removal of the meningioma, patient's visual loss was completely resolved. 4 weeks later, she was admitted to the hospital for the second time with fever fulfilling the Fever of Unknown Origin (FUO) criteria. One week after she was discharged, she came back with paraplegia. MRI with Gadolinium showed an enhancing lesion involving T6-T9 segments of the thoracic spine. In order to rule in NMO, we checked for antibody to aquaporin-4 (AQP4-Ab) and the result was positive. This is the first report showing a probable association between FUO and NMO. Our case also demonstrates how variable the clinical presentations of NMO can be. We suggest that the diagnosis of NMO should be considered in the appropriate clinical setting despite of the presence of unconventional manifestations.

Anti-HSV-2 antibody in patients with MS and NMO.

BACKGROUND: Multiple sclerosis (MS) and neuromyelitis optica (NMO) are demyelinating disorders of the central nervous system. There is growing evidence that viruses may play a causal role in these diseases. Human herpes viruses have been of special attention since their DNA have been detected in many of MS patients' samples. Human herpes simplex virus 2 (HSV-2) is a member of this family which has not been investigated thoroughly in MS and NMO. METHODS: We took blood samples from 90 subjects including 30 RRMS patients, 30 NMO patients and 30 healthy controls. After serum isolation, all serum samples were frozen at -70 °C to be used for enzyme linked immunosorbent assay (ELISA) for detection of specific antibodies against HSV-2. Presence or absence of antibodies against HSV-2 was determined based on the cut-off calibrator and index values were then determined. A value of <0.9: negative, between 0.9 and 1.1: equivocal and <1.1: positive. RESULTS: Mean age of all subjects was 33.36 and female to male ratio was 4.3/1. None of the subjects were seropositive for anti-HSV-2 antibody. Analysis indicated no significant differences (P-value >0.05) among antibody levels between MS (0.19 ±â€¯0.08), NMO (0.22 ±â€¯0.16) and control (0.21 ±â€¯0.09) groups. There were also no correlations between mean antibody index or O.D. and subjects' sex, family history, blood group, smoking history, age and presence of visual-motor-sensory or other forms of disability in any of the three MS, NMO and control groups (P-value >0.05). CONCLUSION: We found no associations between patients' diagnosis of MS or NMO and mean anti-HSV-2 antibody index and O.D. levels.