Longitudinally Extensive Spinal Cord Lesions Research Articles

Myelopathies in patients older than 50: not to miss inflammatory etiologies.

Background: Inflammatory myelopathies are primarily associated with younger age, and there are few studies in the elderly. Longitudinally extensive spinal cord lesions (LECL) are common in inflammatory myelopathies, but when the first event occurs in older age may have a broader differential diagnosis.Objectives: To identify all non-traumatic myelopathies' etiologies in patients older than 50 years in a tertiary care hospital and to evaluate characteristics that differentiate inflammatory from non-inflammatory etiologies, focusing on the late-onset (≥50 years old) longitudinally extensive spinal cord lesions (LO-LECL) group.Methods: Retrospective study of patients admitted between 2008 to 2019. Demographic, clinical, laboratory, and magnetic resonance imaging (MRI) data of all patients were analyzed to identify predictors that could more easily identify inflammatory from non-inflammatory etiologies and further identify the etiologies of LO-LECL.Results: One hundred and three patients 50 years or older diagnosed with non-traumatic myelopathy were included, despite the lesion extension. Five were vascular (5%), 10 spondylotic (10%), 16 other etiologies (16%), 22 inflammatory (21%) and 50 neoplastic myelopathies (49%). Among 23 LO-LECL, 3 were vascular (13%), 4 neoplastic (17%), 7 other etiologies (30%) and 9 inflammatory (39%). The inflammatory LO-LECL had the median time to nadir significantly different from the neoplastic and the other etiologies groups and had the median EDSS at last visit (3.5) significantly lower than the non-inflammatory LO-LECL (7.0-7.5).Conclusions: Inflammatory etiologies are not to be disregarded in older adults with non-traumatic myelopathies. The symptoms' temporal profile is critical to differentiate inflammatory LO-LECL from other etiologies and it has better functional recovery after adequate treatment.

The Prevalence of Anti-Aquaporin 4 Antibody in Patients with Idiopathic Inflammatory Demyelinating Diseases Presented to a Tertiary Hospital in Malaysia: Presentation and Prognosis.

Background. There have been inconsistent reports on the prevalence and pathogenicity of anti-Aquaporin 4 (AQP4) in patients presented with idiopathic inflammatory demyelinating diseases (IIDDs). Objective. To estimate the prevalence of anti-AQP4 antibody in patients with IIDDs presented to University Malaya Medical Centre in terms of patients' clinical and radiological presentations and prognoses. Methods. Retrospective data review of IIDDs patients presented from 2005 to 2015. Patients were classified into classical multiple sclerosis (CMS), opticospinal (OS) presentation, optic neuritis (ON), transverse myelitis (TM), brainstem syndrome (BS), and tumefactive MS. Anti-Aquaporin 4 antibody was tested using the Indirect Immunofluorescence Test (IIFT) cell-based assay. Statistical analysis was done using the SPSS version 20. Results. Anti-AQP4 antibody was detected in 53% of patients presented with IIDDs. CMS was more common in the seronegative group, 27/47 (57.45%; p < 0.001). Conversely, OS involvement was more common in the seropositive group, 26/53 (49.06%; p < 0.001). Longitudinally extensive spinal cord lesions (LESCLs) on MRI were also more common in the seropositive group, 29/40 (72.50%; p = 0.004). Only 2/40 (5.00%) had MRI evidence of patchy or multiple short-segment spinal cord lesions in the AQP4-positive group (p = 0.003). The relapse rate and Expanded Disability Status Scale (EDSS) were also higher in the seropositive group (5.43 versus 3.17, p = 0.005; 4.07 versus 2.51, p = 0.006, resp.). Typical clinical presentations that defined NMO were also seen in the seronegative patients, but in a lower frequency. Conclusion. Our cohort of patients had a higher prevalence of seropositivity of anti-AQP4 antibody as compared to those in Western countries. This was also associated with a more typical presentation of opticospinal involvement with LESCLs on MRI, a higher rate of relapse, and EDSS.

Early and extensive spinal white matter involvement in neuromyelitis optica.

Studies of longitudinally extensive spinal cord lesions (LESCLs) in neuromyelitis optica (NMO) have focused on gray matter, where the relevant antigen, aquaporin-4 (AQP4), is abundant. Because spinal white matter pathology in NMO is not well characterized, we aimed to clarify spinal white matter pathology of LESCLs in NMO. We analyzed 50 spinal cord lesions from eleven autopsied NMO/NMO spectrum disorder (NMOSD) cases. We also evaluated LESCLs with three or fewer spinal cord attacks by 3-tesla MRI in 15 AQP4 antibody-positive NMO/NMOSD patients and in 15 AQP4 antibody-negative multiple sclerosis (MS) patients. Pathological analysis revealed seven cases of AQP4 loss and four predominantly demyelinating cases. Forty-four lesions from AQP4 loss cases involved significantly more frequently posterior columns (PC) and lateral columns (LC) than anterior columns (AC) (59.1%, 63.6%, and 34.1%, respectively). The posterior horn (PH), central portion (CP), and anterior horn (AH) were similarly affected (38.6%, 36.4% and 31.8%, respectively). Isolated perivascular inflammatory lesions with selective loss of astrocyte endfoot proteins, AQP4 and connexin 43, were present only in white matter and were more frequent in PC and LC than in AC (22.7%, 29.5% and 2.3%, Pcorr = 0.020, and Pcorr = 0.004, respectively). MRI indicated LESCLs more frequently affected PC and LC than AC in anti-AQP4 antibody-seropositive NMO/NMOSD (86.7%, 60.0% and 20.0%, Pcorr = 0.005, and Pcorr = 0.043, respectively) and AQP4 antibody-seronegative MS patients (86.7%, 73.3% and 33.3%, Pcorr = 0.063, and Pcorr = 0.043, respectively). PH, CP and AH were involved in 93.3%, 86.7% and 73.3% of seropositive patients, respectively, and in 53.3%, 60.0% and 40.0% of seronegative patients, respectively. NMO frequently and extensively affects spinal white matter in addition to central gray matter, especially in PC and LC, where isolated perivascular lesions with astrocyte endfoot protein loss may emerge. Spinal white matter involvement may also appear in early NMO, similar to cerebral white matter lesions.

Linear lesions may assist early diagnosis of neuromyelitis optica and longitudinally extensive transverse myelitis, two subtypes of NMOSD

Purpose: To investigate the relationship between linear lesions (LL) and the development of longitudinally extensive spinal cord lesions (LESCL) in Chinese patients with neuromyelitis optica or longitudinally extensive transverse myelitis.Method: The clinical records of 143 patients with these conditions were reviewed. Forty-one patients with LL were divided into three groups according to the order of appearance of LL and LESCL (simultaneously [n=10], LL first [n=26], or LESCL first [n=5]). The remaining 102 patients without LL were used as a control group.Results: Patients who developed LL first demonstrated a lower annualized relapse rate than those in the simultaneous group (1.00 [0.23–10.00] vs. 4.38 [0.60–6.67], p=0.017) and the control group (1.00 [0.23–10.00] vs. 2.00 [0.24–10.00], p=0.007). Among all patients with LL, there were significantly more who developed them before LESCL than those who developed them after LESCL (p<0.001) or at the same time (p=0.008). The mean time before the appearance of LESCL was 9.0months (2–35months) in the ‘LL-first’ group, which was shorter than that in the control group (12months [1–60months], p=0.010). The rate of positivity for anti-aquaporin 4 IgG antibodies was higher in patients with LL compared with controls (90.24% vs. 64.71%, p=0.002).Conclusion: LL may be a precursor to LESCL and assist early diagnosis of neuromyelitis optica and longitudinally extensive transverse myelitis.

Longitudinally extensive spinal cord lesion: etiology and imaging features

To explore the etiologies and imaging features of longitudinally extensive spinal cord lesion (LESCL). The etiologies and magnetic resonance (MR) imaging features of 51 hospitalized LESCL patients from January 2011 to August 2013 were reviewed and retrospectively analyzed. Among them, the causes were neuromyelitis optica spectrum disorder (NMOSD, n = 25), isolated longitudinally extensive transverse myelitis (n = 6), subacute combined degeneration (n = 4), multiple sclerosis (MS, n = 3), paraneoplastic myelopathy (n = 3), anterior spinal artery syndrome (n = 3), acute disseminated encephalomyelitis (n = 2), spinal dural arteriovenous fistula (n = 2), intramedullary spinal cord metastasis (n = 1), myelopathic leukemia (n = 1) and syringomyelus (n = 1). For MR imaging, at least one lesion of each patient presented continuously longitudinal profile and whole-length spinal cord was involved in 11 patients. LESCL may be caused by various diseases. And the imaging features may aid its diagnosis despite a lack of specificity.

What we know and do not know about fingolimod: Outline and interpretation of results from the Japanese fingolimod core and extension studies

AbstractMultiple sclerosis (MS) is an idiopathic demyelinating disease of the central nervous system (CNS). Autoreactive T cells that recognize undetermined CNS antigens are assumed to mediate the disease. Fingolimod or FTY720, a sphingosine 1‐phosphate receptor (S1PR) modulator, downmodulates S1PR on lymphocytes causing retention of circulating lymphocytes in the lymph nodes, including the CNS antigen‐autoreactive lymphocytes that invade the CNS. Fingolimod has recently been approved in several countries as a once‐daily, oral, disease‐modifying drug for relapsing–remitting MS. Recently, the Japanese fingolimod core and extension studies showed the efficacy of fingolimod in terms of brain magnetic resonance imaging criteria and clinical activities in Japanese patients with relapsing MS without longitudinally extensive spinal cord lesions (LESCL). These results were consistent with the effects of fingolimod in Caucasian MS patients. No new safety issues were observed except for severe exacerbations that occurred in four anti‐aquaporin‐4 antibody‐positive cases in whom LESCL were absent at the time of the entry. Thus, fingolimod is regarded as efficacious and safe for Asian MS patients, although Asian neuromyelitis optica cases in the early course of the disease should be excluded from fingolimod treatment.

Differentiation of neuromyelitis optica from multiple sclerosis in a cohort from the mainland of China.

Although there were criteria for diagnosis of neuromyelitis optica (NMO) and multiple sclerosis (MS), it is still difficult to differentiate NMO from MS, due to the overlapping clinical manifestations. Therefore it is necessary to characterize clinical features of NMO and MS patients in the mainland of China, to simplify the process of disease diagnosis, and to identify criteria for the differential diagnosis of NMO and MS. A total of 138 Chinese Han patients from the mainland of China including 73 NMO, 60 MS and 5 MS-like patients with positive NMO-IgG were included in the study. Clinical records were reviewed retrospectively and the results of clinical examination, laboratory experiments, magnetic resonance imaging (MRI) and evoked potentials (EPs) were compared between NMO and MS patients. In addition, the relationship between the NMO-IgG serologic status and clinical characteristics were analyzed. Compared with MS patients (1.3: 1.0), more female prevalence was observed in NMO patients (4.2: 1.0; P = 0.003). There were also statistically significant differences in visual EPs, oligoclonal bands, brainstem lesions in MRI and longitudinally extensive spinal cord lesions (LESCLs) between NMO and MS patients. Brainstem lesions observed in brain MRI were found in 17.9% of MS patients, over 3.7 times higher than in NMO patients (4.8%, P = 0.024). When stratified NMO patients by NMO-IgG, LESCLs were found in 42.1% of NMO-IgG-negative NMO patients, over 3.5 times higher than in NMO-IgG-positive patients (11.9%, P = 0.008). Statistical difference was also observed in CD4+/CD8+ ratios between NMO-IgG-positive and -negative NMO patients. Comprehensive analysis of MRI, laboratory and EPs data can facilitate differential diagnosis of MS and NMO. In addition, the combination of LESCLs and brain MRI findings failing to satisfy MRI criteria for MS is highly sensitive and specific for NMO.

Spinal cord lesions and disability in Hispanics with multiple sclerosis

Longitudinally extensive spinal cord lesions (LESCLs) are believed to occur predominantly with opticospinal multiple sclerosis (OSMS) and are associated with disability. The purpose of this study is to describe the prevalence and patterns of spinal cord lesions in Hispanics with multiple sclerosis (MS) and OSMS and their association with disability. A cross-sectional study of 164 patients with complete MRIs was used. In each case the spinal cord was classified: LESCLs, scattered spinal cord lesions (sSCLs) or no spinal cord lesions (noSCLs). Clinical course was defined as classical MS or OSMS. Risk of disability (Expanded Disability Status Scale≥4.0) was adjusted for age, disease duration and sex using logistic regression.A total of 125/164 (73%) MS patients had spinal cord lesions (sSCLs, 57%; LESCLs, 19%), but only 11 (7%) had OSMS. LESCLs were associated with disability (p<0.0001), longer disease duration (p<0.0001) and MS (n=21 vs. n=10 OSMS; p<0.0001). LESCLs were also associated with the greatest risk to disability (OR 7.3, 95% CIs 1.9-26.5; p=0.003; sSCLs OR 2.5, 95% CIs 0.9-7.1; p=0.09) compared with noSCLs. LESCLs are more common than OSMS and are associated with worse disability even in patients with MS. These results suggest that LESCLs are a more important marker of disability in MS than OSMS and may be an early indicator of more aggressive disease in this population.

Clinical Features and Sera Anti‐Aquaporin 4 Antibody Positivity in Patients with Demyelinating Disorders of the Central Nervous System from Tianjin, China

To investigate the clinical characteristics and sera anti-aquaporin 4 (AQP4) antibody positivity in patients with inflammatory demyelinating disorders (IDDs) of the central nervous system (CNS) in Tianjin, China. We retrospectively evaluated 234 patients with IDDs including neuromyelitis optica (NMO), recurrent optic neuritis (rON), longitudinally extensive transverse myelitis (LETM), clinically isolated syndrome (CIS), and multiple sclerosis (MS) groups. Sera from 217 patients were determined for AQP4-Ab. The clinical characteristics and sera anti-AQP4 positivity were compared. The IDDS comprised 63 MS, 51 NMO, 56 LETM, 10 rON, and 54 CIS. Compared with MS, NMO had a higher frequency of occurrence in women, intractable hiccup and nausea (IHN), medullospinal lesion, longitudinally extensive spinal cord lesions (LESCL) and bilateral ON, disease onset at a later age, and worsening residual disability. AQP4-Ab-positive rates were 84.1% and 69% in NMO and NMO spectrum disorders (NMOSD), respectively, whereas it was undetectable in all of the MS sera samples. We comprehensively contrast the distinct clinical features of MS, NMO, and NMOSD in our center. A sensitive AQP4-Ab assay is necessary for the early diagnosis of NMOSD in our patients. Neither medullospinal lesion nor IHN is unique in NMO.

“Bright spotty lesions” on spinal magnetic resonance imaging differentiate neuromyelitis optica from multiple sclerosis

Background: Spinal magnetic resonance imaging (MRI) finding of longitudinally extensive spinal cord lesions (LESCL) extending over three vertebral segments and involvements of spinal central gray matter have been reported in patients with neuromyelitis optica (NMO). Objectives: We aimed to review spinal MRI findings in NMO and multiple sclerosis (MS), and to determine whether the “bright spotty lesions” (BSLs) are a discriminative finding of NMO. Methods: For this study, 24 consecutive patients with NMO and 34 patients with MS were enrolled. BSLs were defined as very hyperintense spotty lesions on axial T2WI. We also studied the length, distribution, signal homogeneity, size, and presence of contrast-enhanced lesions. Results: BSLs were more frequently found in patients with NMO (54%) than in those with MS (3%; p < 0.01). LESCL were found in 67% of the NMO patients. BSLs were seen in 63% of the patients without LESCL. BSLs or LESCL were found in 88% of the NMO patients. Inhomogeneous lesions, transversally extensive lesions, and central lesions were more frequently seen in NMO than in MS. Conclusions: BSLs are a newly defined spinal MRI finding specifically seen in NMO. In combination with LESCL, BSLs can help differentiate patients with NMO from those with MS with higher sensitivity than LESCL alone.

Month of birth in multiple sclerosis with and without longitudinally extensive spinal cord lesions: A study of a Japanese national survey

ObjectivesMonth of birth has been associated with the environmental factors for multiple sclerosis (MS). This study aimed to investigate whether individuals with MS had significantly different frequencies of birth in a particular month of the year, and whether month-of-birth patterns were influenced by the longitudinally extensive spinal cord lesions (LESCL) status relative to the general population in the same Japanese birth cohort. MethodsIn this study, performed as a part of the fourth Japanese nationwide survey of MS, patients were divided into two groups according to the presence (n=307) or absence (n=906) of LESCLs that were diagnosed on the basis of magnetic resonance imaging findings. The number of births in every month was counted for both groups. Control data were obtained from birth records of the Japanese general population of the median years of birth of each group. Differences in the month-of-birth distributions between the patients and the general population were assessed using the chi-square test. ResultsIn MS patients without LESCLs, significantly more patients were born in January and June, whereas significantly fewer patients were born in May, compared to the general population. The seasonal patterns of birth were not in association with those of ambient ultraviolet (UV) radiation. No significant differences were found for the month-of-birth distributions between MS patients with LESCLs and the general population. ConclusionsA different distribution of month of birth in Japanese MS patients without LESCLs from the general population, but not in those with LESCLs, suggests some role for environmental factors in the pathogenesis of the former group. Environmental factors other than UV radiation should be further elucidated in Japanese and other Asian MS cohorts.

Comparison of clinical, immunological and neuroimaging features between anti-aquaporin-4 antibody-positive and antibody-negative Sjögren’s syndrome patients with central nervous system manifestations

Background and objective: The objective of this study is to clarify clinical, immunological, and neuroimaging features in anti-aquaporin-4 (AQP4) antibody-positive and antibody-negative Sjögren’s syndrome (SS) patients with central nervous system (CNS) involvement. Methods: Medical records and MRI scans were retrospectively analyzed in 22 consecutive SS patients with CNS manifestations. Results: Seven (31.8%) patients were positive for anti-AQP4 antibodies. The frequency of visual impairment was higher in anti-AQP4 antibody-positive patients than in antibody-negative patients (71.4% vs. 0.0%, p = 0.0008). Brain MRI showed that discrete lesions were more commonly found in the cerebrum, brainstem, and optic nerve in anti-AQP4 antibody-positive patients than in antibody-negative patients (p = 0.002, p = 0.006, and p = 0.004, respectively), while spinal cord MRI showed that posterior column lesions in the cervical spinal cord were more frequent in anti-AQP4 antibody-positive patients than in antibody-negative patients (71.4% vs. 14.3%, p = 0.01). SS-A antibody titers were higher in anti-AQP4 antibody-positive patients than in antibody-negative patients (p = 0.012) and were also higher in patients with longitudinally extensive spinal cord lesions (LESCLs) than in those without LESCLs (p = 0.019). Conclusions: In SS, the presence of anti-AQP4 antibodies is associated with involvement of the optic nerve, cerebrum and brainstem, and with cervical posterior column lesions in the spinal cord.

Seroprevalence of NMO-IgG among patients with neuromyelitis optica and opticospinal multiple sclerosis

Objectives In this study we sought to compare the seropositivity of NMO-IgG in patients presenting with demyelinative involvement of optic nerve and spinal cord with and without longitudinally extensive spinal cord lesion (LESCL). Methods Patients who were referred to Isfahan Multiple Sclerosis Clinic and Isfahan Devic's Disease Clinic at Al-Zahra Hospital in Iran were screened for this study. Patients with signs and symptoms indicating the demyelinating involvement of optic nerve(s) and spinal cord were included. Patients were evaluated by a neurologist and spinal cord and brain magnetic resonance imaging (MRI) were obtained. Patients with normal first brain MRI and with spinal cord demyelinative lesions visible on spinal MRI were included. Patients were then put into two groups: (i) patients with LESCL [neuromyelitis optica (NMO)] and (ii) patients with spinal plaques which do not extend over three vertebrae [opticospinal multiple sclerosis (OSMS)]. NMO-IgG was measured in the serum of the included patients. Results Totally we recruited 33 patients with LESCL and 32 patients without LESCL. The mean age of patients without LESCL was 34.61 ± 10.98 and it was 33.48 ± 11.93 for the NMO patients. In both groups there were 24 females and the rest were males. Among the NMO patients 16 (48.5%) were positive for NMO-IgG, while in the OSMS group there were none. Conclusion The results of this study are in line with previous observations, and imply that the presence of LESCL is associated with the presence of NMO-IgG and thus an indicator of NMO.

Acute transverse myelitis in demyelinating diseases among the Chinese

The aim of the study was to characterize the demographic, clinical, and prognostic features of Chinese patients with acute transverse myelitis (ATM). The clinical data from ATM patients in a demyelinating disease database were analyzed retrospectively. Sixty-seven ATM patients with a follow-up duration longer than 2 years were identified. The frequency of neuromyelitis optica-related ATM (NMO-ATM) was high in our cohort (40.3%). Recurrent ATM (R-ATM), with a female predominance, was common in total idiopathic ATM (69.0%, 20/29). In R-ATM with longitudinally extensive spinal cord lesions (LESCLs), the high seropositivity of NMO-IgG, spinal cord lesions mostly involved the central gray matter and severer long-term disability were similar to NMO-ATM. In RTM without LESCLs, low seropositivity of NMO-IgG, preferentially involvement of the peripheral white matter and relative better neurological recovery were consistent with multiple sclerosis-related ATM (MS-ATM). The transition rates to MS in patients with acute partial transverse myelitis (APTM) and acute complete transverse myelitis (ACTM) were not significant (16.7 vs. 6.3%, P = 0.753), while LESCLs (OR = 11.4, P = 0.028) were significantly correlated with transition to NMO. The presence of LESCLs was the only variable showing a higher risk for reaching Rankin 3 (hazard ratio: 2.5, 95% CI: 1.0-6.1). Chinese patients with ATM had demographic, clinical, and prognostic features different from those in Western populations. Idiopathic R-ATM, common in Chinese, is a heterogeneous entity that shares partial clinical, spinal MRI and prognostic features with MS-ATM and NMO-ATM. The length of spinal cord lesion, rather than APTM/ACTM, may be a prognostic factor associated with clinical outcome and long-term disability in our population.

Intravascular lymphoma presenting as a longitudinally-extensive myelitis: Diagnostic challenges and etiologic clues

Intravascular lymphoma is a rare disorder that commonly involves the central nervous system. Neurologic involvement may be the presenting and only manifestation. Identifying intravascular lymphoma as the cause of neurologic disease is diagnostically challenging. We report an elderly woman presenting with subacute onset paraparesis due to spinal cord involvement by an intravascular lymphoma. Progressive worsening was associated with extension of a longitudinally-extensive thoracic intramedullary spinal cord lesion. Extensive investigations failed to provide a diagnosis in life and repeated empiric therapeutic trials were unsuccessful. Diagnostic confirmation was postmortem. A longitudinally-extensive spinal cord lesion has a broad differential diagnosis. Intravascular lymphoma should be considered particularly in older individuals. The presence of coexisting hematologic abnormalities should prompt consideration of a bone marrow biopsy. Early diagnosis may direct therapy and lead to a more favorable prognosis.

Characteristic linear lesions and longitudinally extensive spinal cord lesions in Chinese patients with neuromyelitis optica

ObjectiveTo investigate the characteristics of the linear lesions and longitudinally extensive spinal cord (LESC) lesions in Chinese patients with neuromyelitis optica (NMO). MethodsThe medical records and magnetic resonance imaging (MRI) scans of 29 patients with NMO were reviewed. The frequencies and distributions of linear and LESC lesions were compared against those displayed by 22 multiple sclerosis (MS) patients. Furthermore, the association of lesions with aquaporin-4 IgG (AQP4-IgG) antibody was investigated. ResultsThe NMO patients had significantly more linear lesions than MS patients (48.3 vs 0%, p<0.001). In the NMO group, linear lesions were found in the medulla in 34.5% (10/29) of patients, across the medullospinal region in 10.3% (3/29) and in the spinal cord in 13.8% (4/29). LESC lesions can be seen more frequently in NMO than MS (72.4 vs 22.7%, p<0.001). In 93.1% (27/29) of the NMO cases, the axial section of the spinal MRI showed lesions on the central gray matter only, whilst the spinal lesions in MS were usually located in the peripheral white matter (72.7%, 16/22). The AQP4-IgG antibody was found to be associated with both linear and LESC lesions in NMO cases. ConclusionsHigh frequency of linear lesions and LESC lesions were found in Chinese patients with NMO and linear lesions were correlated with AQP4-IgG antibody.

急性発症のｌｏｎｇｉｔｕｄｉｎａｌｌｙ ｅｘｔｅｎｓｉｖｅ ｓｐｉｎａｌ ｃｏｒｄ ｌｅｓｉｏｎを呈した転移性脊髄髄内腫瘍

A 34-year-old previously healthy man presented with acute transverse lumbar myelopathy and MRI evidence of a longitudinally extensive spinal cord lesion (LESCL) from the upper thoracic cord extending down to the conus medullaris. Gadolinium-DTPA enhancement revealed a clearly demarcated enhanced nodule confined to the level of the 11th thoracic vertebral body (T11), which might have caused longitudinally extensive edema in the spinal cord. Histopathological appearance of adenocarcinoma of the nodule led to the ultimate diagnosis of lung cancer. Intramedullary spinal cord metastasis in a young patient without previously-diagnosed malignancy is a rare disorder, but should be listed up as a cause of LESCL.

Heterogeneity and continuum of multiple sclerosis phenotypes in Japanese according to the results of the fourth nationwide survey

There are two distinct phenotypes of multiple sclerosis (MS) in Asians, optic-spinal MS (OSMS) and conventional MS (CMS). In 2004, we performed the fourth nationwide epidemiological survey of MS. The epidemiological features were reported elsewhere; here we report the characteristic features of patients with each MS phenotype, classified according to the clinically estimated sites of involvement and MRI findings. Among 1493 MS patients collated, 57.7% were classified as having CMS and 16.5% were classified as having OSMS. Based on MRI findings, MS patients were further subdivided into those with OSMS with or without longitudinally extensive spinal cord lesions (LESCLs) and those with CMS with or without LESCLs. Although disease duration did not differ significantly among the four groups, EDSS scores were significantly higher in patients with LESCLs than in those without LESCLs, irrespective of OSMS or CMS phenotype. Similar trends were found for the frequencies of bilateral visual loss, transverse myelitis, and marked CSF pleocytosis and neutrophilia. Increased IgG index, brain lesions fulfilling the Barkhof criteria and secondary progression were more commonly found in CMS patients than in OSMS patients, while negative brain MRIs were more commonly encountered in OSMS patients than CMS patients, irrespective of the presence of LESCLs. These findings suggest that demographic features not only vary based on CMS or OSMS phenotype, but also with the presence or absence of LESCLs, and that nonetheless, these four phenotypes constitute a continuum.

229. Low Sensitivity of AQP4 IgG in MS, LESCL and NMO in Australians

We investigated the prevalence of AQP4 IgG in classical multiple sclerosis (MS), Neuromyelitis optica (NMO) and MS with longitudinally extensive spinal cord lesions (LESCL) from a Western Australian MS cohort. There were only two cases (2%) found to be seropositive in a total of 96 samples. One positive case was found among 52 MS patients (1.9%), the other among the 18 LESCL or NMO patients (5.6%). Twenty three PPMS were all seronegative. There were 14 LESCL cases in this MS cohort with one AQP4 IgG positive (7.1%).

Association of the HLA-DRB1 alleles with characteristic MRI features of Asian multiple sclerosis

Background In Asian patients with multiple sclerosis (MS), a paucity of brain lesions and longitudinally extensive spinal cord lesions (LESCLs) extending three or more vertebral segments are characteristic findings on magnetic resonance imaging (MRI). We aimed to disclose possible factors contributing to the development of such MRI features. Method Genotyping of HLA-DRB1 and -DPB1 alleles was performed in 121 consecutive Japanese patients with clinically definite MS based on the Poser criteria and 125 healthy controls. Possible factors associated with MRI features were determined by multiple logistic analysis. Patients with MS were classified based on the presence or absence of brain lesions fulfilling the Barkhof criteria (Barkhof brain lesions) and LESCLs. Barkhof brain lesion–negative (−) patients had a markedly lower frequency of HLA-DRB1*0901 than controls (P corr < 0.05), whereas the frequency of DRB1*1501 was increased in the Barkhof brain lesion–positive (+) group, although this increase was not significant after correction. No Barkhof(−)LESCL(+) patients carried DRB1*0901 (P corr < 0.05), despite this being the most common allele in Japanese. The Barkhof(−)LESCL(−) group showed a significant increase in the frequency of DRB1*0405 compared with controls (P corr < 0.05). None of the DPB1 alleles were significantly different among the groups. Using multiple logistic analysis, the absence of oligoclonal bands was positively associated with an absence of Barkhof brain lesions, whereas a higher EDSS score was positively associated with the presence of LESCLs; however, the presence of anti-aquaporin-4 antibodies was not associated with either feature. Conclusion The characteristic MRI features in Asians are partly related to distinct HLA-DRB1 gene alleles and an absence of oligoclonal bands.