Prominent brainstem symptoms/signs in patients with neuromyelitis optica in a Taiwanese population

Neuromyelitis optica (NMO) is a severe demyelinating disease defined principally by its selective effect on the optic nerves and spinal cord. Contemporary diagnostic criteria require an absence of any clinical disease outside the optic nerve or spinal cord. However, we frequently encounter patients with NMO who have previously undetected symptomatic brainstem lesions. We investigated the brainstem symptoms/signs in patients with NMO and their corresponding MRI findings in a Taiwanese population. We evaluated the clinical symptoms/signs, anti-aquaporin-4 antibody titer and corresponding brain MRI of 49 patients with NMO; results were obtained from chart reviews and during clinical visits. A total of 18 (37%) patients with NMO had brainstem symptoms/signs, including diplopia (n = 9, 50%), prolonged hiccup and poor appetite (n = 9, 50%). For these patients, most of their brainstem events occurred during the first demyelinating attack in their NMO course. A higher percentage (77.8%) of patients with brainstem NMO had brain lesions with specific NMO patterns, including lesions involving the hypothalamus (n = 6, 33.3%), midbrain or pons (n = 8, 44.4%), periaqueductal regions (n = 5, 27.7%), and medulla (n = 10, 55.6%). Brainstem symptoms/signs and characteristic NMO imaging findings are common in Taiwanese patients with NMO, and should be considered a part of the illness in addition to optic neuritis and myelitis.     

The spectrum of neuromyelitis optica: a case of NMO with extensive brain stem involvement

Neuromyelitis optica (NMO), regarded as a distinct clinical entity from multiple sclerosis (MS), is generally characterized by demyelinating lesions involving optic nerves and spinal cord with sparing of the brain. We report a case with initial clinical, radiological and serological features consistent with NMO, but with concomitant extensively clinical and radiological involvement of the brain stem. Although there are well defined criteria for NMO that restricts the lesions to optic nerves and spinal cord, the case presented here and the review of literature support the idea that NMO may present as a spectrum of clinical and radiological entities rather than the confining clinical criteria that has been hitherto applied.     

视神经脊髓炎MRI诊断

视神经脊髓炎为一种自身免疫性炎性疾病,主要累及视神经和脊髓,脑组织也可出现病灶,但其MRI表现与经典的多发性硬化有所不同.常规MRI可以发现视神经炎和脊髓炎病灶.MRI新技术中以扩散张量成像、磁共振波谱分析及磁化传递成像的研究较多.     

视神经脊髓炎患者33例脑部磁共振分析

目的 探讨视神经脊髓炎(neuromyelitis optica,NMO)患者脑部MRI影像学表现.方法 收集满足最新NMO诊断标准且脑部MRI表现不符合多发性硬化诊断标准的患者33例,均行脑部和脊髓MRI检查,分析其MRI影像学特点.结果 33例NMO中,脑部正常表现者5例(15.2%),异常表现28例(84.8%),其中脑内实质有明确病灶22例(66.7%),另6例(18.2%)脑内虽未见明确病灶,但深部脑白质显示了肉眼可视的对称性弥漫性脱髓鞘高信号影.22例明确病灶中,15例病灶数≥2个,7例为单个病灶.幕上近皮质、皮质下和深部脑白质区的点状非特异性病灶最多,少数为非典型的斑片状融合病灶.幕下脑干是易受累的部位(14/33,42.4%),特别是延髓(7/33,21.2%).结论 NMO患者出现脑内异常较为常见,有脑部的异常不能排除NMO的诊断.认识NMO脑内病灶对完善NMO诊断标准有帮助.     

视神经脊髓炎MRI诊断

视神经脊髓炎为一种自身免疫性炎性疾病,主要累及视神经和脊髓,脑组织也可出现病灶,但其MRI表现与经典的多发性硬化有所不同.常规MRI可以发现视神经炎和脊髓炎病灶.MRI新技术中以扩散张量成像、磁共振波谱分析及磁化传递成像的研究较多.     

Neuromyelitis optica with clinical and histopathological involvement of the brain

Diagnostic criteria for neuromyelitis optica (NMO) state that there should be no active disease outside the optic nerves and spinal cord. However, several cases have been described with symptomatic brain involvement. We describe an autopsy case of a patient with NMO and symptomatic involvement of the brain. The histopathology of the brain lesions is typical for NMO, with extensive macrophage infiltration, including perivascular accumulation of large numbers of eosinophils. This is the first case that clearly shows that in NMO, the histopathology of the brain lesions is identical to that of the lesions in the optic nerves and spinal cord.     

Brain magnetic resonance imaging abnormalities in neuromyelitis optica

Objective – Brain abnormalities in neuromyelitis optica (NMO) attracted much attention. Our study was to identify the brain magnetic resonance imaging (MRI) abnormalities in Chinese NMO patients. Methods – Patients who fulfilled the latest diagnostic criteria of NMO proposed by Wingerchuk et al. [Neurology 66 (2006) 1485] and whose brain MRI did not meet the multiple sclerosis (MS) criteria of McDonald et al. [Ann Neurol 50 (2001) 121] were selected to perform MRI scanning of the brain, spinal cord and optic nerves. Results – Twenty‐eight of 33 patients (84.8%) had abnormal MRI findings. Twenty‐two patients (66.7%) presented with well‐defined brain parenchymal lesions and the other six patients (18.2%) with macroscopic symmetrical diffuse hyperintensities in deep white matter. Fifteen of 22 patients had more than one lesion (≥2 lesions) and the other seven patients had single lesion. In the supratentorium, most lesions were punctate or small round dot and non‐specific in juxtacortical, subcortical and deep white matter regions, a few were patchy atypical confluent lesions. Brainstem was easily involved (14/33, 42.4%) especially in medulla (7/33, 21.2%). Conclusions – This study demonstrates the characteristics of brain MRI abnormalities in Chinese NMO patients, which are helpful to the revision of diagnostic criteria for NMO.     

Spinal cord MRI in clinically isolated optic neuritis

BACKGROUND/METHODS: One hundred and fifteen patients with clinically isolated optic neuritis underwent magnetic resonance imaging (MRI) of the brain and spinal cord within 3 months of the onset of symptoms. RESULTS: Eighty one (70%) patients had brain lesions and 31 (27%) had cord lesions. Cord lesions were seen in 12% with a normal brain MRI, 21% with between one and eight brain lesions, and 45% with nine or more brain lesions. When the new diagnostic criteria for MS were applied, MRI cord imaging used for evidence of dissemination in time and space allowed a diagnosis of MS in only one additional asymptomatic patient at 1 year, two additional asymptomatic patients at 3 years. CONCLUSIONS: Using existing criteria, spinal cord imaging rarely contributes to the diagnosis in patients with clinically isolated optic neuritis.     

视神经脊髓炎患者头颅磁共振成像特点

目的 分析视神经脊髓炎(neuromyelitis optica,NMO)患者头颅MRI特点.方法 对27例NMO患者的头颅MRI进行回顾性分析.结果 22例(81.5%)NMO患者存在不同类型的头部病灶,并可分为非特异性(7例)、非典型性(1例)、多发性硬化样(MS-like,3例)及脑室-导水管-中央管周围型(11例),但以脑室-导水管-中央管周围型最为常见(40.7%),且NMO患者颅内的病灶数与最后一次MRI检查的时间呈正相关(r=0.475,P=0.025).结论 NMO患者脑内病灶类型多样,但以脑室-导水管-中央管周围型最为常见,可能存在不同机制.对疑似病例早期进行头颅MRI检查相当必要.     

Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression

BACKGROUND: Neuromyelitis optica (NMO)-IgG is a specific autoantibody marker for NMO. It binds selectively to aquaporin 4 (AQP4), which is highly concentrated in astrocytic foot processes at the blood-brain barrier and is not restricted to optic nerve and spinal cord. Although it is conventionally believed that the brain is spared, brain imaging abnormalities are not uncommon in patients with NMO. OBJECTIVE: To investigate the location of brain lesions that are distinctive for NMO with respect to the localization of AQP4 in mammalian brain. DESIGN: Observational, retrospective case series. SETTING: Clinical serologic cohort of patients tested for NMO-IgG for whom brain MRI images were available. PATIENTS: We identified 120 patients seropositive for NMO-IgG for whom brain magnetic resonance images were available. MAIN OUTCOME MEASURE: Magnetic resonance imaging abnormalities. RESULTS: In 8 patients we observed recurring and distinctive magnetic resonance imaging abnormalities in the hypothalamic and periventricular areas that corresponded to brain regions of high AQP4 expression. CONCLUSION: The distribution of NMO-characteristic brain lesions corresponds to sites of high AQP4 expression.     

视神经脊髓炎诊断进展

视神经脊髓炎是主要累及视神经和脊髓的中枢神经系统自身免疫性疾病,既往被认为是多发性硬化的一种亚型.自发现NMO-IgG以来,越来越多的证据提示视神经脊髓炎为一独立疾病.脊髓MRI所显示的长节段横贯性脊髓炎是其最具特征性的影像学改变,Wingerchuk诊断标准和美国国立多发性硬化协会推荐的诊断标准为目前常用标准.随着对视神经脊髓炎认识的加深,对视神经炎、脊髓炎及其脑部表现等临床症状的鉴别诊断水平也有所提高.     

Intractable pruritus in neuromyelitis optica

Neuromyelitis optica (NMO) is an immune-mediated disease of the central nervous system. Pruritus in patients with NMO has rarely been reported. We aimed to explore the characteristics and underlying mechanisms of pruritus in NMO patients. We reviewed the case records of 64 NMO patients who visited the Department of Neurology at the Third Hospital of Sun Yat-sen University between 2009 and 2015. Of the 64 aquaporin-4 antibody-positive NMO patients, 18 had pruritus. Spinal magnetic resonance imaging (MRI) showed lesions in all of these patients. A total of 13 patients presented with brain lesions, and four had lesions in the periaqueductal gray matter on cerebral MRI. However, the anatomical distribution of pruritus did not always correspond to the dermatomal distributions of the involved spinal cord segments. Pruritus was completely or partially relieved after treatment. Pruritus is not a rare occurrence and may be a characteristic feature of NMO.     

Neuromyelitis optica-IgG in idiopathic inflammatory demyelinating disorders amongst Hong Kong Chinese

Background:  Idiopathic inflammatory demyelinating disorders (IIDD) affect the central nervous system. In classical multiple sclerosis (CMS), brain, optic nerves [optic neuritis (ON)] and spinal cord [acute transverse myelitis (ATM)] are affected. In neuromyelitis optica (NMO), optic nerves and spinal cord are predominantly affected. NMO-IgG, an autoantibody targeting aquaporin-4, is a marker for NMO. We studied the frequency and clinical relevance of NMO-IgG seropositivity in IIDD patients.
Methods:  Neuromyelitis optica-IgG was detected by indirect immunofluorescence using primate cerebellum.
Results:  Neuromyelitis optica-IgG was detected in six of 10 NMO patients (60%), six of 10 idiopathic relapsing transverse myelitis (IRTM) patients (60%), two of nine idiopathic relapsing ON patients (22%), one of 11 patients (9%) having single ON attack, one of 30 CMS patients (3%), and none of patients having single ATM attack or controls. Comparing NMO-IgG seropositive ( n  = 12) with NMO-IgG seronegative ( n  = 8) patients having NMO or IRTM, NMO-IgG seropositivity was associated with a higher relapse rate in first 2 years, 1.5 and 0.6 attacks/year for seropositive and seronegative groups respectively ( P  = 0.006), and non-significant trend towards more severe ON and myelitis with poorer clinical outcome.
Conclusion:  Neuromyelitis optica -IgG facilitates diagnosis of NMO spectrum disorders. NMO-IgG seropositivity is associated with higher relapse rate in first 2 years.     

Neuroradiological aspects of Devic's neuromyelitis optica

INTRODUCTION: Neuromyelitis optica (NMO) is a rare inflammatory and demyelinating disorder of the central nervous system, restricted to optical nerves and spinal cord. The main neuroradiological aspects, now summarized into a complete set of diagnosis criteria, are a normal cerebral MRI at onset and longitudinal involvement of the spinal cord concerning more than 3 vertebral segments. The clinical course and frequency of typical lesions remain unknown. OBJECTIVE: We here report neuroradiological data from patients suffering from NMO. METHODS: Brain and spinal cord MRI were systematically reviewed for 32 afro-Caribbean patients. RESULTS: A typical longitudinal spinal lesion was seen in 44.7 percent with or without edema; a lesion involving less than 3 vertebral segments in 26.3 percent and no lesion in 21.1 percent. Longitudinal study of a few bouts suggested a progressive normalisation of spinal cord appearance. Atrophy was negatively correlated with immunosuppressive treatment. Cerebral lesions usually absent at onset were correlated to the follow-up. In a non-recursive condition, patients completed diagnostic criteria for encephalic and spinal lesions in 82.8 percent and 48.1 percent. CONCLUSION: Radiology of spinal bouts showed multiple aspects besides the typical form. The notion of multiple bouts must be added to the spinal criteria to achieve good sensitivity. A typical extensive spinal lesion is usual in the follow-up, but seen after less then half of the bouts. Requiring such a lesion would delay the diagnosis.     

Neuromyelitis optica: brain abnormalities in a Brazilian cohort

Neuromyelitis optica (NMO) is a demyelinating disease consisting of relapsing-remitting optic neuritis and myelitis with a more severe course than Multiple Sclerosis. Recently, it has been shown that almost 50% of patients with NMO can have brain magnetic resonance imaging (MRI) abnormalities. We report on six Brazilian patients with NMO, fulfilling the 1999 Wingerchuck criteria for this disease, with abnormal brain MRI and discuss their clinical and radiological features.     

Aquaporin-4 autoantibody: a neurogenic cause of anorexia and weight loss

Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disease often associated with a highly specific autoantibody, aquaporin-4 antibody. Although the classic syndrome involves the optic nerves and spinal cord, aquaporin-4 antibody has been important in defining the true spectrum of NMO, which now includes brain lesions in areas of high aquaporin-4 expression. Brainstem involvement, specifically area postrema involvement in the medulla, has been associated with intractable vomiting in some patients with NMO. We describe a 14-year-old female with positive aquaporin-4 antibody whose clinical course was dominated by severe anorexia with associated weight loss (from 68-41kg; body mass index 25.2-15.6). Magnetic resonance imaging showed lesions in the medulla, pons, and thalami. Although she had asymptomatic radiological longitudinally extensive transverse myelitis, she never had symptoms or signs referable to the spinal cord or the optic nerves. We propose that anorexia and weight loss should be considered part of the NMO spectrum, probably related to area postrema involvement.     

Neuromyelitis Optica Preceded by Brain Demyelinating Episode

Neuromyelitis optica (NMO) is considered a distinct disease from multiple sclerosis (MS) because of its pathogenesis. It is well accepted that NMO selectively affects the spinal cord and optic nerve and is not associated with brain lesions at the onset of the disease, unlike MS. We present a unique case where the patient's initial lesion was in the brain, and optic neuritis and myelitis were revealed 6 years after the brain lesion. In addition, the patient's serum antiaquaporin 4 (AQP4) antibody was positive. We consider the brain lesion to precede abnormal lesion of NMO, and the AQP4 measurement is important for diagnostics, even if it occurs with brain lesions.     

Is Devic's neuromyelitis optica a separate disease? A comparative study with multiple sclerosis

Devic's neuromyelitis optica (NMO) associates optic neuritis and myelopathy without other neurological signs. Many patients with NMO may be diagnosed as having multiple sclerosis (MS). However, there have been no previous studies comparing these two pathologies and it is still unclear if NMO is a separate entity or a subtype of MS. In the present study, we compared a series of NMO patients with a series of MS patients for whom optic neuritis or myelopathy was the presenting symptom, in order to determine the place of NMO in the spectrum of MS. We retrospectively studied 30 patients diagnosed with NMO and we compared these patients with 50 consecutive MS cases revealed by optic neuritis or acute myelopathy. MS patients were only included if a relapse occurred demonstrating time and space dissemination. We compared the two groups in terms of clinical presentation, laboratory findings (MRI and CSF) and clinical outcome. NMO patients were older and more frequently women than MS patients but the difference was not significant. CSF and MRI data were clearly different: oligoclonal bands (OCB) were found in 23% of NMO cases and 88% of MS (P < 0.001), abnormal brain MRI data were observed in 10% of NMO cases and 66% of MS (P < 0.001) and a large spinal cord lesion was observed in 67% of NMO cases and 7.4% of MS cases (P < 0.001). Clinical outcome was evaluated as more severe in the NMO group (P < 0.001). On the basis of clinical data, all NMO patients but three had dissemination in time and space. When we included MRI parameters, only two of the NMO patients met criteria for MS and one of the MS patients met criteria for NMO. Our study demonstrates that NMO and MS should be considered as two different entities. The respective criteria for NMO and MS were able to distinguish these two pathologies but only when MRI data were applied. This finding could have implications for future therapeutic trials.     

Prevalence of neuromyelitis optica spectrum disorder and phenotype distribution

Neuromyelitis optica spectrum disorder (NMOsd) is a group of demyelinating disorders recently redefined and associated with NMO-IgG/anti-aquaporin 4 antibodies. Because NMOsd is of unknown prevalence worldwide, we conducted a retrospective, cross-sectional study of 850 patients with demyelinating disorders hospitalized in North East Tuscany from 1998 to 2006 to examine the prevalence of NMO and related disorders among unselected consecutive neurological patients with inflammatory CNS diseases and to evaluate the clinical phenotype spectrum of identified cases. Clinical data were updated after at least 2 years of follow-up. An immunofluorescence technique was used to detect NMO-IgG on rat brain tissue. Sera from other 828 neurological patients, 65 non-neurological patients and 50 healthy donors served as controls. The prevalence of NMOsd was 1.5%, with a MS:NMOsd ratio of 42.7. Among 13 NMOsd patients, 77% had long spinal cord lesions, 38% had severe optic neuritis and 23% had brain or brainstem lesions. Only 56% had clinically definite NMO at follow-up. The final EDSS score ranged from 1 to 10, mainly depending on brainstem involvement occurrence. Our findings confirm a low prevalence of NMO and related disorders among demyelinating inflammatory diseases in a Caucasian population. Moreover, this study demonstrates an unexpectedly high prevalence of limited and atypical variants of this disease, not previously documented.     

Magnetic resonance imaging of Asians with multiple sclerosis was similar to that of the West

Magnetic resonance imaging (MRI) of the brain is the most important paraclinical diagnostic test in multiple sclerosis (MS). The appearance of MRI in Asians with MS is not well defined. We retrospectively surveyed the first brain and spinal cord MRI in patients diagnosed to have MS, according to Poser's criteria in seven regions throughout Asia to define the MRI changes among Asians with MS. There were 101 patients with first brain, and 86 with first spinal cord MRI, 66 of whom had both. The brain MRI showed a mean of 17 lesions per patient in T2 weighted images, mostly asymptomatic. Almost all the lesions were in the white matter, particularly in the juxtacortical, deep and periventricular white matter. A third of the lesions were greater than 5 mm, 14% enhanced with gadolinium. There were more supratentorial than infratentorial lesions at a ratio of 7.5: 1. Ninety five percent of the spinal cord lesions were in cervical and thoracic regions, 34% enhanced with gadolinium. The lesions extended over a mean of 3.6 +/- 3.3 vertebral bodies in length. Fifty (50%) of the brain and 54 (63%) of the spinal MRI patients had the optic-spinal form of MS. The MRI of the optic-spinal and classical groups of patients were similar in appearance and distribution, except that the optic-spinal MS patients have fewer brain but longer and more severe spinal cord lesions. In conclusion, the brain and spinal cord MRI of Asian patients with MS was similar to that of the West, although, in this study, Asian MS patients had larger spinal cord lesions.