Psychotic onset of multiple sclerosis

A case is reported of a woman in whom acute manic attacks were followed later in life by neurological signs of multiple sclerosis, thus suggesting a possible correlation between the two clinical entities.

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Sommario è descritto il caso di una donna in cui la sclerosi multipla fu preceduta da attacchi acuti di tipo psicotico (maniacale).

     

HLA-antigens and the prognosis of multiple sclerosis

Summary The histocompatibility pattern of 160 patients with multiple sclerosis (MS) living in the epidemiological area of Southern Lower Saxony was determined and compared to a control population. The only significant difference was the more frequent occurrence of DW2 in the patient group (44% vs. 21%). Taking a progression index (grade of disability divided by the duration of the disease) as a measure for prognosis no difference could be found between the DW2 positive and the DW2 negative patients. The reason why we could not confirm the worse prognosis for DW2 positive patients found by Jersild et al. (1973) and Raun et al. (1980) remains to be investigated.This work was supported by the Deutsche Forschungsgemeinschaft in the frame of the Schwerpunktprogramm: Etiology and Pathogenesis of Multiple Sclerosis and Related Diseases     

Physiopathology and treatment of fatigue in multiple sclerosis

Fatigue is a common symptom of patients with multiple sclerosis (MS). It is reported by about one-third of patients, and for many fatigue is the most disabling symptom. Fatigue may be associated with motor disturbances and/or mood disorders, which makes it very difficult to determine whether the fatigue is an aspect of these features or a result per se of the disease. Although peripheral mechanisms have some role in the pathogenesis of fatigue, in MS there are clear indications that the more important role is played by “central” abnormalities. Neurophysiological studies have shown that fatigue does not depend on involvement of the pyramidal tracts and implicate impairment of volitional drive of the descending motor pathways as a physiopathological mechanism. Metabolic abnormalities of the frontal cortex and basal ganglia revealed by positronemission tomography and correlations between fatigue and magnetic resonance imaging lesion burden support this hypothesis. Some recent studies also suggest that pro-inflammatory cytokines contribute to the sense of tiredness. No specific treatments are available. Management strategies include medications, exercise, and behavioural therapy; in most cases a combined approach is appropritate. Received: 26 September 2000, Accepted: 28 September 2000     

Magnetic resonance in monitoring the natural history of multiple sclerosis and the effects of treatment

In this review the main contributions of magnetic resonance (MR) techniques in the monitoring of multiple sclerosis (MS) course, both natural or modified by treatments, are presented. MR measures well correlate with short-term disease evolution and therefore their use is appropriate as primary end-points in preliminary clinical trials evaluating the effects of new treatments. In contrast, the correlation between MR measures and long-term clinical evolution in clinically definite MS is less clear, thus indicating that such measures can be used at present only as a secondary end-point in large scale definitive trials. The results coming from the clinical application of newer MR techniques with higher pathological specificity are also presented and their possible future roles in monitoring treatment aimed at preventing development of disability in MS are discussed.

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Sommario In questo articolo vengono presi in esame i principali contributi che le tecniche di risonanza magnetica (RM) forniscono per il monitoraggio del decorso della sclerosi multipla (SM), sia esso naturale o modificato da interventi terapeutici. Le correlazioni riscontrate tra parametri di RM ed attività a breve termine della malattia rendono appropriato l'uso di tali misure come end-point primari in trial di fase II volti ad esplorare la efficacia di nuovi trattamenti. Le correlazioni tra parametri di RM ed evoluzione clinica a lungo termine sono invece modeste nelle forme clinicamente definite di malattia e pertanto tali misure sono attualmente utilizzate esclusivamente come end-point secondari nei trial di fase III. In questo articolo vengono inoltre presentati i risultati ottenuti dall'applicazione clinica di nuove tecniche non convenzionali di RM, nonché il loro possibile ruolo futuro nel monitorare l'efficacia dei trattamenti volti a prevenire lo sviluppo di disabilità in pazienti con SM.

     

多发性硬化交感神经皮肤反应的研究

对３８例多发性硬化（ＭＳ）患者和４１例正常人的交感神经皮肤反应（ＳＳＲ）与多方式诱发电位进行研究。结果：３８例确诊和近似确诊的ＭＳ患者ＳＳＲ异常率（８１．６％）比异常的诱发电位更为常见。在伴有自主神经症状的２１例ＭＳ患者中１９例ＳＳＲ异常（９０．５％），１７例无自主神经症状的ＭＳ患者中１２例ＳＳＲ异常（７０．６％）。提示：ＳＳＲ能客观有效地反映自主神经功能状态，检出ＭＳ的亚临床异常。将ＳＳＲ与多方式诱发电位联合评估ＭＳ中枢神经系统损害，具有更高的敏感性，有助于ＭＳ的早期诊断。     

多发性硬化血清麻疹、风疹和水痘-带状疱疹病毒IgG抗体水平及临床意义

目的通过检测多发性硬化(Multiple sclerosis,MS)患者血清中麻疹病毒、风疹病毒和水痘-带状疱疹病毒的免疫球蛋白G(Immunoglobulin G,IgG)抗体浓度,并进行扩展残疾状态量表(Expanded disability status scale,EDSS)评分,探讨上述病毒在MS发病中的临床意义及其与临床神经功能缺失的相关性。方法收集2013年9月-2015年2月郑州大学第一附属医院神经内科收治的50例MS患者急性期(复发期)的血清标本,其中临床孤立综合征(CIS亚组)22例,复发-缓解型MS(RRMS亚组)28例,对照组收集同一时期我院体检结果正常的37例健康志愿者的血清标本。采用双抗体夹心酶联免疫吸附方法(Enzyme linked immunosorbent assay,ELISA)测定并比较血清中3种病毒IgG抗体的浓度,分析血清中各病毒抗体水平与EDSS评分的相关性。结果 (1)MS病例组麻疹病毒、风疹病毒、水痘-带状疱疹病毒IgG抗体的血清浓度高于对照组,差异具有统计学意义(P0.05);(2)CIS亚组患者血清中麻疹病毒、风疹病毒、水痘-带状疱疹病毒IgG抗体水平低于RRMS亚组,EDSS评分亦低于RRMS亚组,差异均具有统计学意义(P0.05);(3)MS病例组血清中麻疹病毒、风疹病毒、水痘-带状疱疹病毒IgG抗体与EDSS评分无相关性(P0.05)。结论 MS患者血清中的麻疹病毒、风疹病毒和水痘-带状疱疹病毒可能不仅与MS的发病相关,而且与疾病的复发有关。     

Prolonged dynamic clinico-immunological observation of 85 patients with definite multiple sclerosis: First steps towards monitoring process activity

Prolonged clinico-immunological observation of 85 patients with definite multiple sclerosis (MS) was performed in order to elucidate the connections between the clinical and immune state. A battery of immunological investigations was performed, including estimation of T-cell subpopulations in blood and cerebrospinal fluid (CSF); proliferative responses of circulating lymphocytes to mitogens, recombinant interleukin-2 (rIL2) and myelin basic protein levels in different culture conditions; levels of immunoglobulin (Ig) in sera and CSF, and of Ig production in vitro; indices of IL2 synthesis and IL2 sensitivity; production of prostaglandin E2 and tumour necrosis factor (TNF) alpha by monocytes and levels of -endorphin in sera and supernatants phytohaemagglutinin of (PHA)-activated cells. Clinical observation was performed periodically using Kurtzke scales and was supplemented by repeated recording of evoked potentials and magnetic resonance imaging. Initial investigations showed specific differences between patients with MS and the control groups (donors and patients with other neurological disorders of the same age). Correlative and regressive analyses showed no association between immunological and clinical parameters at the initial investigation, although immunological indexes were inter-related, and indicated specific alterations in immuno-regulation in MS. Retrospective analysis revealed associations between the clinical status of patients with MS and their previous immune status. Evidence of cell activation — including a decreased percentage of circulating cells with differential antigens, lower cell mitogen-induced proliferative responses in vitro, with restoration following the addition of autoserum, greater IL2 sensitivity, and increased TNF-alpha production by macrophages — often predicted the clinical manifestation of deterioration. It is proposed that the immunopathological process in MS has a number of stages with characteristic features, and that progression from one stage to another can be subclinical. No single immunological index can be used to determine stage. Only systemic alterations reflect the real situation, whilst every patient has some abnormalities. A system of clinico-immunological monitoring could severe as the basis for a new approach to the dynamic treatment of MS.     

A clinico-pathoanatomical study of multiple sclerosis diagnosis

The diagnosis of multiple sclerosis (MS) is clinical and verifiable at post mortem. Neuropathological examination of 518 consecutive patients with clinically definite MS revealed a correct diagnosis in 485 cases (94%). Clinical diagnosis had been established by a neurologist in all cases. Erroneous diagnosis included a variety of other neurological disorders. Also investigated was a randomly selected series of 33 patients with a clinical diagnosis of probable MS: post mortem confirmation of MS was obtained in circa 66%, for the remainder the error pattern was similar to the above. Clinical diagnosis of definite MS was correct in 94% cases. Laboratory tests and examinations have not radically improved diagnosis. Neuropathological examination may occasionally fail to demonstrate MS plaques if the optic nerves are not investigated.     

Biochemical findings in multiple sclerosis

Summary Lymphocyte stimulation tests with human basic protein of myelin were performed on patients with multiple sclerosis, with other neurological diseases and on normal subjects. In both MS and OND group, a hypersensitization to basic protein was seen in about one third of the cases. All normal subjects, except one, had negative responses. In the MS group, a positive correlation could be found with some features of the disease: significantly more positive responses were found in independent patients with a short duration of illness and in those with an oligoclonal distribution in the CSF. The authors compare their results with those of the literature. The possible role of BP in pathogeny of MS and OND is discussed.Supported by grant No. 76/4 from the Belgian Centre for MS     

Short-term intensive cyclophosphamide treatment in multiple sclerosis

Summary The effect of short-term intensive cyclophosphamide therapy upon 21 patients with moderately advanced multiple sclerosis is compared with a non-treated control group of 21 patients retrospectively matched for global disability. The progression of the disease was evaluated by regular disability scoring, and the results were analyzed by non-parametric statistical tests. No significant differences in the progression of the disability could be detected during a follow-up period of 2 years.

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Zusammenfassung Die Wirksamkeit von kurzzeitiger intensiver Cyclophosphamid-Therapie bei 21 Multiple-Sklerose-Kranken wurde im Vergleich zu 21 Kranken mit ähnlichen Funktionsausfällen in einer retrospektiven Studie untersucht. Der Krankheitsverlauf wurde mit regelmäßigen Untersuchungen registriert und nach einem Punktsystem bewertet. Diese Ergebnisse wurden mit nicht-parametrisch statistischen Tests analysiert. Die mittlere Krankheitsprogression war während der Nachbeobachtungszeit von 24 Monaten in beiden Therapiegruppen niemals signifikant verschieden.

     

Real-world challenges in the diagnosis of primary progressive multiple sclerosis

Background and purpose

Despite the 2017 revisions to the McDonald criteria, diagnosing primary progressive multiple sclerosis (PPMS) remains challenging. To improve clinical practice, the aim was to identify frequent diagnostic challenges in a real-world setting and associate these with the performance of the 2010 and 2017 PPMS diagnostic McDonald criteria.

Methods

Clinical, radiological and laboratory characteristics at the time of diagnosis were retrospectively recorded from designated PPMS patient files. Possible complicating factors were recorded such as confounding comorbidity, signs indicative of alternative diagnoses, possible earlier relapses and/or incomplete diagnostic work-up (no cerebrospinal fluid examination and/or magnetic resonance imaging brain and spinal cord). The percentages of patients fulfilling the 2010 and 2017 McDonald criteria were calculated after censoring patients with these complicating factors.

Results

A total of 322 designated PPMS patients were included. Of all participants, it was found that n = 28/322 had confounding comorbidity and/or signs indicative of alternative diagnoses, n = 103/294 had possible initial relapsing and/or uncertainly progressive phenotypes and n = 73/191 received an incomplete diagnostic work-up. When applying the 2010 and 2017 diagnostic PPMS McDonald criteria on n = 118 cases with a full diagnostic work-up and a primary progressive disease course without a better alternative explanation, these were met by 104/118 (88.1%) and 98/118 remaining patients (83.1%), respectively (p = 0.15).

Conclusion

Accurate interpretation of the initial clinical course, consideration of alternative diagnoses and a full diagnostic work-up are the cornerstones of a PPMS diagnosis. When these conditions are met, the 2010 and 2017 McDonald criteria for PPMS perform similarly, emphasizing the importance of their appropriate application in clinical practice.     

105例多发性硬化临床特点及治疗分析

目的 探讨多发性硬化的临床发病特点及临床治疗疗效.方法 从2005-01至2010-10月间收治的多发性硬化患者105例为研究对象.结果 105例患者中以20-40岁女性多见,以急性、亚急性起病,以肢体无力为首发症状最常见,病变部位多以脑和脊髓多见,脑脊液蛋白升高、IgG增高及寡克隆区带阳性常见,核磁共振较计算机断层扫...     

Neurochemical and morphological studies on demyelination in multiple sclerosis with special reference to etiological aspects

Summary Light microscopic studies were used as control for neurochemical studies and these showed that some micro plaques could be found also in areas which were normal on visual inspection. Also foreign cell infiltrates were found outside any clear plaque material. The number of these cells did not correlate with other findings like lipid or enzyme chemistry. In electronmicroscopic studies astrocytes demonstrated most lysosomes and phagocytosis of myelin. This increased lysosomal reaction was demonstrated also in biochemical analyses performed on MS biopsy specimens. Occasional nuclear changes like inclusion bodies and protrusion of inner nuclear membrane were observed suggesting some exogenous, possibly viral factor as an origin of the disease. Neurochemical studies showed that demyelination as a sense of decrease in myelin lipid and phosphohydrolase activity is only a later phenomenon and increased lysosomal activities possibly originating from various glial cells are found before demyelination. However myelin-like material found inside lysosomes suggests the early moderate demyelination before classical plaques can be found. Acid hydrolases were mostly increased at areas around plaques and encephalitogenic protein was not demonstrable at plaque areas. Our combined study suggests early changes of glial cells as a basic mechanism of the disease. However, the clarification of the basic course of these changes remains to be seen although nuclear changes may suggest a slow viral infection.Aided by a grant from Sigrid Juselius' Foundation.     

Lipid composition of myelin in multiple sclerosis

Summary Myelin was isolated from histologically normal white matter and plaques from MS patients and from white matter of neurologically normal controls. No difference was found in the total lipid content. There were no detectable deficits in MS myelin of phosphoglycerides, plasmalogens or sphingolipids. Gangliosides and lysolecithin were not detected. Analysis of the fatty aldehyde composition of the phosphoglycerides and the fatty acid composition of the cholesteryl esters, phosphoglycerides and sphingolipids did not show any differences between the normal and MS myelin.This investigation was supported by Grant 484 from the National Multiple Sclerosis Society and by USPHS Grants HD 04575, NB 05464, GM-K6-19177.The postmortem specimens were provided from the International Tissue Bank supported by the National Multiple Sclerosis Society and administered by Wallace W. Tourtellotte, M.D., Ph.D.     

多发性硬化的周围神经系统损害

目的 探讨多发性硬化（MS）患者合并周围神经系统（PNS）损害的临床及肌电图特点。方法 回顾性分析14例MS合并PNS损害的临床及肌电图资料。结果 MS合并PNS损害的发生率为12．5％,其临床表现主要为末梢型或神经型根型感觉障碍、根性疼痛、肌肉萎缩,周围神经受损较神经根受损常见。PNS损害并不是每次发病都出现,出现时间较早、持续时间较短,不影响的疾病的病程及患者的功能障碍。肌电图上表现为存在纤颤波、正锐波,轻收缩时波幅增高、时限延长,感觉神经传导速度减慢,末端运动潜伏期延长,神经电位波幅降低,F波潜伏期延长等。结论 MS患者确实可能有PNS损害,出现PNS损害不影响患者的预后,常随着病情的好转很快恢复。     

损害大脑灰质的多发性硬化的临床和影像学特征

目的分析损害大脑灰质的多发性硬化病例的临床和MRI特点。方法收集2004年1月～2006年6月期间住院并经多发性硬化专科门诊进行临床和MRI动态观察确诊[采用McDonald(2001)诊断标准]的多发性硬化患者共54例,将其中13例损害大脑灰质的多发性硬化患者的临床和MRI资料进行回顾性对比分析。结果损害大脑灰质的多发性硬化病例13例,占多发性硬化总病例数的24%(13/54),其中5例初诊时根据脑CT报告误诊为多发性脑梗死,3例初诊时误诊为病毒性脑炎和脑病,5例首诊为多发性硬化的患者得益于多系列的脑MR扫描、VEP和脑脊液IgG指数的帮助;损害大脑灰质的多发性硬化患者症状、体征较重,复发次数多,预后较差;大脑灰质的损害主要在大脑深部灰质(丘脑和基底节)。结论初次诊断多发性硬化相当困难,建议使用McDonald(2001)诊断标准,并参考脑/脊髓功能MRI,诱发电位及脑脊液IgG指数/OB;多发性硬化损害大脑灰质可能与神经元变性有关。     

Contribution to the histoenzymatic changes in multiple sclerosis

Summary The activities of acP, alkP, ATP-ase, TPP-ase, non-specific esterase, ASS, AChE and ChE have been investigated by histochemical methods, in the brain of 2 cases of multiple sclerosis.A decrease in the activity of ASS, AChE, ChE and alkP was noticed in the demyelinated white matter of the plaques. Inside the plaques also a loss of ChE activity in the oligodendroglia was observed, whereas the activity of ATP-ase, TPP-ase and acP was increased.The significance of the changes found of the neuroglia hyperactivity in demyelination is discussed.

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Zusammenfassung Histochemische Untersuchungen der Aktivität der sauren und alkalischen Phosphatase, der ATP-ase, der TPP-ase, der unspezifischen Esterase, der Arylsulfatase, der Acetylcholinesterase und der Cholinesterase im Gehirn von 2 Multiple Sklerosefällen. Die Aktivität der Arylsulfatase, der Acetylcholinesterase, der Cholinesterase und der alkalischen Phosphatase verschwindet in den Entmarkungsherden beinahe vollkommen. Im Bereich der Entmarkungsherde war die Cholinesteraseaktivität der Oligodendrogliazellen völlig gewichen, während die Aktivität der ATP-ase, TPP-ase und der sauren Phosphatase erhöht erschien. Die Bedeutung der festgestellten Hyperaktivität der Neurogliazellen in den Entmarkungsprozessen wird diskutiert.

     

多发性硬化患者血清性激素水平变化及其意义

目的:探讨多发性硬化(MS)患者血清性激素(E2,TSTO)水平的变化及其临床意义。方法:采用放射免疫法对31例活动期MS患者、22例缓解期MS患者和40例健康对照者的血清性激素水平进行检测。结果:活动期MS患者血清雌二醇(E2)水平显著高于缓解期MS患者和对照组(P<0.01),而睾酮(TST0)水平明显降低(P<0.01);经过糖皮质激素治疗后活动期MS患者血清E2水平明显升高(P<0.01),TST0水平降低(P<0.01),且血清性激素水平变化与疗效相关。结论:活动期MS患者血清性激素水平紊乱。雌激素水平升高可能与MS的活动性相关,适当的雄激素替代治疗可能对MS有益。     

Treatment of multiple sclerosis with mitoxantrone

Summary Ten multiple sclerosis patients, all with a rapid deteriorating disease profile, were treated with 12 mg/m² of the cytostatic agent mitoxantrone, administered every 3 months. This dosage is only 25% of what a patient with a solid tumour would normally receive during the same time period. In all treated patients the deterioration was stopped following the initial dosage; in four out of ten patients there was even an immediate improvement of the neurological status. Eight out of nine patients showed an improvement after 1 year as compared with their enrolment status; the other one remained stabile. In correlation with the clinical improvement, the mean P100 latencies of visual evoked potentials showed a reduction after 1 year. However, the changes identified through magnetic resonance imaging were even clearer than those seen clinically. At admission, this group of patients presented with a total of 169 gadolinium (Gd)-enhancing lesions. Only 10 lesions were enhancing in nine patients 12 months after the initiation of treatment. It appears that mitoxantrone accelerates the disappearance of Gd-enhancing lesions and prevents the development of new ones. Minimal side effects such as mild nausea and a slight faintness were evident in six patients and then for only 1–2 days.