Occurrence of ankylosing spondylitis and multiple sclerosis-like syndrome in a HLA-B27 positive patient

Occurrence of multiple sclerosis (MS) in patients with ankylosing spondylitis (AS) has been reported in isolated cases. We describe a white 33-year-old male with a definite familial HLAB27 positive AS and MS-like syndrome. The patient developed acute onset of gait difficulty, postural unsteadiness, dysarthria and right side weakness that resolved within 1 month; after 6 months he presented right-sided face sensory loss, disappeared after 2 weeks. Brain and cervical MRI was performed twice and showed disseminated lesions in space (multiple foci of increased signal intensity in the periventricular white matter, in the corpus callosum, in the hypothalamus, in the brainstem and in the cervical spinal cord) and in time (a new enhancing lesion >3 months after the onset of the clinical event). Visual evoked potentials were markedly altered. Cerebrospinal fluid examination was negative for intrathecal production of oligoclonal bands. Differential diagnosis was considered and other pathologies were excluded.     

Coexistence of ankylosing spondylitis and multiple sclerosis

Ankylosing spondylitis is reported to involve not only the joints but neurologic systems as well. The association of MS and AS has rarely been reported in the literature and epidemiological studies did not prove a definite relationship between these two conditions at present. We here describe a HLA-B 27 positive AS patient with MS symptoms and review the literature on the association of two diseases.     

Clustering of organ-specific autoimmunity: a case presentation of multiple sclerosis and connective tissue disorders

Multiple sclerosis (MS) is the most common demyelinating disease caused by an autoimmune inflammatory process in the central nervous system (CNS) and is associated with aberrant immune response to myelin selfantigens. Coexistence of MS with other autoimmune disorders, including connective tissue disorders including systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome and scleroderma have been reported previously. In the present article we report the coexistence of MS, familial mediterranean fever and ankylosing spondylitis in a patient and review the clinical presentation, neurologic findings, cerebrospinal fluid and radiologic characteristics and treatment options. We further discuss the immunopathogenetic mechanisms for a possible association between MS and autoimmune disorders.     

HLA and multiple sclerosis in Italy: a review of the literature

Summary HLA antigens of locus A, C, B, DR and DQ were typed in 104 Italian multiple sclerosis patients and in 905 healthy controls; the results have been compared with those published in the Italian literature. The Italian studies have been reviewed regarding the ethnic origin of the typed population and the corresponding prevalence of the disease. The data suggest a lack of association between A3 and B7 antigens and Italian multiple sclerosis and a relevance of other DR locus antigens (mainly DR4 and DR5), in addition to DR2, in the susceptibility to the disease.     

Headaches and multiple sclerosis: a clinical study and review of the literature

Summary Whether multiple sclerosis (MS) can cause headaches is controversial. To clarify the association between headaches and MS we prospectively analyzed 104 consecutive MS patients using detailed headache evaluations. Fifty-four patients (52%) reported headaches, compared with 5 of 35 (14%) patients initially suspected to have MS but subsequently proven to have other disorders, and 18 of 100 (18%) matched general neurology patients. The MS patients had tension headaches or vascular headaches of the migraine type; there was no distinctive MS headache. Seven of these patients had headaches with their first MS symptoms, but in only one did headaches recur with disease activity. Headaches did not correlate with any clinical features of MS. We conclude that an association between headaches and MS may exist.     

The immunopathophysiology of multiple sclerosis

This review explores the principle features of the immunopathology of multiple sclerosis (MS), particularly relapsing-remitting MS. It highlights the emerging concepts in the pathogenesis of MS in the context of known features of pathology, including the characterization of cytokine networks promoting inflammatory damage of the central nervous system, B-cell involvement, and inflammatory damage of axons and neurons. This article preferentially focuses on MS rather than animal models of the disease, such as experimental autoimmune encephalomyelitis.     

Effect of bisphosphonates on ankylosing spondylitis: A meta-analysis

This study aimed to compare outcomes between ankylosing spondylitis (AS) treated with and without bisphosphonate (BP; non-BP) through a meta-analysis. The Medline (via PubMed), Cochrane, Scopus, and Embase databases were searched for studies that evaluated the outcomes of AS, including patient age, disease duration, disease activity, and bone mineral density (BMD), published between January 2000 and March 2020. Two authors extracted the data independently. Any discrepancies were resolved by a consensus. Six comparative studies were identified. No significant differences were found between the BP and non-BP groups in terms of demographic characteristics, disease activity, and BMD, except for follow-up erythrocyte sedimentation rate (ESR). The follow-up ESR was higher in the BP than in the non-BP group. A literature review identified six comparative studies reporting the outcomes of BP and non-BP treatments for AS. Despite the heterogeneity, a limited number of meta-analyses reported that BP treatment was not clearly better than non-BP treatment. Hence, further large-scale multicenter studies are required to validate our results.     

Spreading of autoimmunity from central to peripheral myelin: two cases of clinical association between multiple sclerosis and chronic inflammatory demyelinating polyneuropathy

Abstract Demyelinating inflammatory diseases of central and peripheral myelin share similar aetiopathogenesis but rarely occur simultaneously in the same individual. Here we report two clinical cases of temporal association between multiple sclerosis (MS) and chronic inflammatory demyelinating polyneuropathy (CIDP). Our finding supports the hypothesis that clinically manifested central and peripheral demyelinating diseases could result from a common pathogenic event characterised by T-cell autoimmunity spreading from central to peripheral myelin.     

The dynamics of multiple sclerosis

The history of our understanding of the pathogenesis and pathophysiology of multiple sclerosis are reviewed in the context of Charcot's contribution. The implications for treatment of the new knowledge gained from studies during life of pathology and pathogenesis (by MRI) and pathophysiology (by evoked potentials) are reviewed.Based on the Charcot lecture given to the International Federation of Multiple Sclerosis Societies, Amsterdam, October 1991     

Recent insights into the pathology of multiple sclerosis and neuromyelitis optica

Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system. Traditionally, demyelinating lesions in the white matter have been regarded as the most important pathological feature in MS, but recent pathological and imaging studies confirmed substantial changes in grey matter and normal-appearing white matter. MS lesions are characterized by inflammation, demyelination, axonal damage and astrogliosis. During early MS lesion formation acute axonal injury is extensive and correlates with inflammation. In addition to focal lesions, diffuse wide-spread changes including neuroaxonal degeneration and compartmentalized inflammation are likely to contribute to increasing disability in progressive MS. Neuromyelitis optica (NMO) is classically characterized by severe transverse myelitis and optic neuritis, but brain lesions are also present in the majority of NMO patients. The discovery of the NMO-specific antibody demonstrated that NMO is a disease entity distinct from MS. This antibody binds to aquaporin-4 expressed in astrocytes and ependymal cells. NMO lesions are characterized by inflammation, demyelination, axonal damage and a marked loss of aquaporin-4. Early NMO lesions demonstrate a pronounced humoral inflammatory response and astrocytic cell death with loss of aquaporin-4, followed by inflammatory demyelination and axonal damage. These recent findings contribute to a better understanding of different mechanisms leading to inflammatory demyelination.     

Rationale for off-label treatments use in primary progressive multiple sclerosis: A review of the literature

BackgroundUntil recently, few therapeutic options, other than symptomatic treatment, were available for patients with primary progressive multiple sclerosis (PPMS). Ocrelizumab is the only approved treatment in this indication, and only since 2017. However, many patients in France are receiving off-label treatments for PPMS, mainly rituximab, mycophenolate mofetil, methotrexate, cyclophosphamide, and azathioprine.ObjectiveTo evaluate published data concerning the efficacy of these five treatments frequently used as off-label disease-modifying therapies.MethodsWe reviewed and summarized the studies published in Pubmed since the inception of the database.ResultsEvidence from randomized controlled trials is lacking to support the use of these treatments as disease-modifying therapies in PPMS.ConclusionThe literature lacks dedicated studies to support the off-label use of these disease-modifying therapies in PPMS. However, some limited data are available in the literature suggesting that the use of rituximab and cyclophosphamide could potentially be of some interest in specific subpopulations.     

The significance of perivascular infiltrations in multiple sclerosis

Summary 143 autopsy cases of multiple sclerosis (19 acute and 124 chronic cases) were analysed histologically for the extent of active demyelination and the degree of infiltration within and outside the demyelinating lesions and in the leptomeninges. The results were compared with the duration of the illness. Infiltrations were found in 60% of all cases but more often (74%) in those with active demyelination. Inflammatory lesions outside demyelinating foci were observed in 27% of the total, and in 80% of them active demyelination was present. Inflammatory lesions in the meninges were present in 41% of the total and in 80% of these were accompanied by active demyelination.The duration of illness correlated with decreasing severity of active demyelination and of perivascular infiltration. Patients treated with cortico-steroids and/or immunosuppressive substances showed no or only moderate inflammatory lesions. The duration of illness in both these groups was significantly longer than the average of untreated patients. The significance of these pathological findings for the CSF cytology in multiple sclerosis is discussed.Fellow of the Bundesministerium für Wissenschaft und Forschung der Bundesrepublik Österreich.     

多发性硬化413例患者的临床表现特点

目的 总结多发性硬化(MS)患者的临床特点。方法 用临床病例分析统计方法，对413例MS患者的发病规律和临床特点进行归纳、分析。结果 MS好发于青壮年，以急性和亚急性起病为主；首发症状以视力障碍(128例，31．O％)最常见；肢体无力(325例)、感觉障碍(246例)、视力障碍(243例)是MS患者最常见的症状，Lhermitte征较多见；发作性症状多见，以痛性痉挛发作和癫疴发作常见；可合并周围神经系统损害；临床定位以脊髓(256例)和视神经(244例)受累最多见。结论本组MS临床特点不同于西方人。     

Tumefactive multiple sclerosis requiring emergency craniotomy: Case report and literature review

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system, characterized by focal neurological dysfunction with a relapsing and remitting course. Tumor-like presentation of MS (or “tumefactive”/“pseudotumoral” presentation) has been described before with a certain frequency; it consists of a large single plaque (>2 cm) with presence of edema and mass effect and it is hard to distinguish from a brain tumor. However, we present a very rare case of a 53-year-old woman with a right temporal mass that turned out to be a MS plaque, who deteriorated within hours (brain herniation with loss of consciousness and unilateral mydriasis) and required an emergency craniotomy. We also present a review of the literature. It appears that only 4 cases of emergency craniotomy/craniectomy required in a patient with a tumor-like MS plaque have been reported before.     

Evoked potentials for evaluation of multiple sclerosis

The role of evoked potentials (EP) in the assessment of multiple sclerosis (MS) has changed over the last decade. This is largely due to progress in imaging techniques. But while MRI has a greater diagnostic sensitivity, EP remain a useful diagnostic tool in many clinical situations. Moreover, recent studies demonstrate the utility of EP for monitoring and predicting the course of the disease in patient groups, although not yet in individuals. For these purposes, EP show better results than conventional MRI. In the near future, new developments in electrophysiology, immunology and imaging may allow to differentiate between different subtypes of MS early in the course, and consequently to tailor therapeutic measures more precisely to the individual patients.     

干扰素-β治疗复发-缓解型多发性硬化系统评价

目的评价干扰素-β(IFN-β)治疗复发-缓解型多发性硬化的有效性和安全性。方法检索Cochrane临床对照试验中心注册库、美国国立医学图书馆、荷兰医学文摘、CINAHL、LILACS、PEDRO、中国生物医学文献数据库、临床试验注册中心和世界卫生组织国际临床试验注册平台(检索截止时间:2014年6月);并通过阅读相关论文参考文献,联系参与IFN-β治疗多发性硬化临床试验的研究者和企业,进一步获取研究信息或未发表的数据。由两名评价人员独立筛选研究、提取研究信息和数据、评价偏倚风险。应用Review Manager软件(Version 5.3.3)进行Meta分析,GRADEpro软件评价研究设计和实施过程中的局限性(偏倚风险)、结果的不一致性和不精确性、证据的间接性和发表偏倚对主体证据质量的影响。结果共检索相关文献576篇,阅读标题和摘要后初步筛选出26项研究;进一步阅读全文后纳入5项研究(共2129例复发-缓解型多发性硬化患者:高剂量IFN-β组1076例、安慰剂组1053例)。所有纳入的研究均为IFN-β单药治疗且随访时间≥1年的随机双盲安慰剂对照平行临床试验。大多数研究存在方法学局限性,主要缺陷为随访偏倚风险较高,且数据分析未使用意向治疗原则,仅919例受试者(43.17%)的数据可用于分析随访2年时的主要结局。Meta分析显示,IFN-β可轻微减少随访2年时复发病例数(RR=0.810,95%CI:0.740~0.890;P=0.000)和残疾进展病例数(RR=0.700,95%CI:0.550~0.880;P=0.002);敏感性分析(最差情况的演示分析)显示,IFN-β治疗无效(RR=1.110,95%CI:0.730~1.680,P=0.620;RR=1.310,95%CI:0.600~2.890,P=0.500)。共1581例患者(74.26%)的数据可用于分析随访1年时至少复发1次的病例数(RR=0.740,95%CI:0.590~0.930;P=0.010),绝对危险降低率为13.24%,需治疗的病例数为8例,表明需要治疗8例患者才可防止1例在第1年内复发。但在年复发率方面,IFN-β治疗无效。IFN-β常导致注射部位局部反应、寒颤、发热、肌肉疼痛、流感样症状、头痛、血清丙氨酸转氨酶和天冬氨酸转氨酶水平升高等不良事件,但并不增加外周血淋巴细胞和中性粒细胞减少、抑郁、自杀行为或自杀观念的发生。结论高质量证据显示,IFN-β治疗复发-缓解型多发性硬化可轻微降低第1年内的复发病例数,但超过1年的疗效尚不能确定。目前尚无足够证据证明IFN-β在减少残疾进展病例数方面的疗效,尚待高质量的随机对照临床试验评价其长期有效性。     

Gelatinase in the cerebrospinal fluid of patients with multiple sclerosis and other inflammatory neurological disorders

A substrate conversion assay was used to detect gelatinase activity in the cerebrospinal fluid (CSF) of patients with various neurological disorders. Two main forms of gelatinase with an apparent molecular mass of 65 and 85 kDa, respectively, could be discerned. The high molecular mass gelatinase was detectable only in samples of patients with multiple sclerosis or other inflammatory neurological disorders. A statistically significant correlation was found between the level of the 85-kDa gelatinase and the CSF cytosis. This protease could play a role in the process of demyelination and breakdown of the blood-brain barrier in certain neurological disorders, such as multiple sclerosis.     

Hypoxia-like tissue injury as a component of multiple sclerosis lesions

Recent data suggest that the mechanisms of demyelination and tissue damage in multiple sclerosis (MS) are heterogenous. In this review, evidence is discussed, which show that in a subset of multiple sclerosis patients the central nervous system (CNS) lesions show profound similarities to tissue alterations found in acute white matter stroke, thus suggesting that a hypoxia-like metabolic injury is a pathogenetic component in a subset of inflammatory brain lesions. Both, vascular pathology as well as metabolic disturbances induced by toxins of activated macrophages and microglia may be responsible for such lesions in multiple sclerosis.     

High cervical neurinoma (C1/C2) diagnosed falsely as multiple sclerosis because of trigeminal neuralgia

Summary Remitting paresis of the left leg accompanied by left trigeminal neuralgia led to the diagnosis of multiple sclerosis in a 46-year-old woman.Over the following 6 years, an incomplete syndrome of the spinal cord developed along with bilateral trigeminal pain. Neuroradiological and neurosurgical exploration revealed a neurinoma located ventrolaterally at C1/C2 on the left side.It is emphasized that since trigeminal fibres descend as far as the upper part of the C2 segment, trigeminal neuralgia should not be considered as an exclusively supraspinal symptom.