The thymus in seronegative myasthenia gravis patients

Summary In 5–10% of all patients with typical generalised myasthenia gravis (MG), serum antibody to the acetylcholine receptor (AChR) is undetectable. To determine whether these represent a distinct subgroup, we have compared the thymuses of 14 seronegatives, 70 seropositives and 12 non-myasthenic controls. By quantitative immunohistology on coded sections, the 7 seronegative samples were clearly distinguishable from the controls by the pronounced lymph node-type T-cell areas in the medulla. While these closely resembled those in the seropositive cases, germinal centres were significantly sparser, and total in vitro IgG production was disproportionately low (per B cell) in the 12 cases tested. Furthermore, specific anti-AChR production was never detected in any of these cultures. The data support the view that the medullary T-cell areas are the most consistent abnormalitiy in the MG thymus (though it may not be primary), and they strongly imply that seronegative and seropositive MG are distinct entities.     

重症肌无力患者泼尼松治疗前后免疫学指标的变化

探讨泼尼松治疗重症肌无力（MG）免疫学机制。对382例MG患者在漏尼松中剂量冲击，小剂量维持疗法治疗前后，检测酰胆碱受体抗炎（AchRab)，突触前膜抗体（PsMab)，单个核细胞亚群（PBMC），肿瘤坏死因子（TNF），可溶性白介素－2受体（SIL－2R），β2－微球蛋白（β2－m)，以及红细胞免疫功能的变化。结果表明：MG患者在泼尼松治疗前后多项免疫指标有显著性的变化。为泼尼松治疗MG提供了评定疗效的免疫学指标，进一步阐明了MG发病的免疫学机制。     

Plasma C3c in immune-mediated neurological diseases: a preliminary report

Plasma C3c levels were examined in 56 patients with immune (27) and non-immune (29) mediated neurological diseases by crossed immunoelectrophoresis. Plasma samples were collected during the active phase of illness in both groups, usually within 7 days of admission. 11 patients (4 Guillain-Barré Syndrome-GBS, 3 chronic inflammatory demyelinating polyneuropathy-CIDP, 4 myasthenia gravis-MG) had their plasma saved sequentially during the active and the recovery phase. Plasma C3c levels were elevated in the group with immune mediated diseases when compared with those of non-immune mediated diseases. The sensitivity and specificity of C3c as a diagnostic test for immune mediated neurological diseases were 61.4 and 100% respectively with a positive and negative predictive value of 100 and 41%. the C3c levels in plasma correlated well with disease severity in MG and GBS patients. Such a correlation was also evident in all CIDP patients except one that had persistent elevation in the presence of clinical improvement. Results suggest that the plasma C3c level may be useful for differentiating immune from non-immune mediated neurological diseases. Plasma C3c may also be used for monitoring disease severity, particularly in myasthenia gravis.     

Exacerbation of myasthenia gravis after removal of thymomas

It appeared from this prospective and non-randomized study, that the removal of thymomas in myasthenia gravis (MG) patients resulted in rapid exacerbation of the clinical severity of the disease and of anti-acetylcholine receptor antibodies titres, which peaked after about 300 days and continued for up to 2 years. Long-term follow-up after thymomectomy (mean duration ± SEM after surgery 5.5 ± 0.8 years) showed that the immunological and clinical state observed prior to surgery was eventually restored, but long-term benefit attributable to surgery could not be demonstrated. Non-thymoma MG cases, however, exhibited post-operative amelioration in clinical course and decreasing antibodies titres, both of which were already significant one year after surgery, and additional improvement was observed at the time of long-term follow-up (mean 4.3 ± 0.5 years). Furthermore, the prognosis for MG patients not operated on was also favourable. It is suggested that the occurrence of thymomas is linked to genetic factors and that neoplasia of the thymus may be part of immunoregulatory mechanisms with predominance of inhibition.     

Myasthenia gravis developing after discovery of thymoma

We report 4 cases of myasthenia gravis in which myasthenic symptoms developed after a thymoma was known to be present. They include 3 invasive thymomas and one thymoma. In 3 of them, myasthenic symptoms developed 2–7 months after removal of the thymoma; in 1 case, myasthenic symptoms developed 11 years after the thymoma was known to be present. We also discuss here the possible pathogenetic mechanism of post-thymomectomic myasthenia gravis, and propose that it is due to the natural course of the disease.     

Thymus in myasthenia gravis: a light and electron microscopic study of a case with thymic follicular hyperplasia

The present study has focused mainly on microenvironmental aspects of the thymus from a 17-year-old female patient suffering from myasthenia gravis. The most striking lightmicroscopic feature was again the well known presence of lymphoid follicular hyperplasia. Ultrastructurally, the configuration, cellular composition and fine structure were to a large extent the same as in other, peripheral lymphoid organs. Cells showing the typical morphologic characteristics of fibroblastic reticulum cells, which are most probably precursors of dendritic reticulum cells, were observed within germinal centers. Additionally the morphology of the unaffected medulla and corticomedullary region was studied, thereby paying particular attention to the structural changes of interdigitating cells. These contained frequently Birbeck granules, which have not been described before in human thymus.     

Die Bedeutung der Bestimmung von Antikörpern gegen Acetylcholinreceptoren in der Diagnostik der Myasthenia gravis

Zusammenfassung Bei 65 Patienten mit Myasthenia gravis (MG) wurden Antikörper gegen Acetylcholin-Receptoren (ACh-R) in der IgG-Fraktion des Patienten-Serums bestimmt (Immunpräzipitations-Assay mit¹²⁵Jod--Bungarotoxin und menschlichem ACh-R als Antigen). Bei 91% der Patienten zeigte sich eine erhöhte Antikörper-Konzentration bis zum 500fachen des oberen Referenzbereichs. Eine Kontrollgruppe von 77 Patienten mit anderen gesicherten Autoimmunerkrankungen oder positiven Antikörpern gegen Muskulatur wies in keinem Fall erhöhte ACh-R-Antikörper-Konzentrationen auf. Damit ist der in-vitro Nachweis von ACh-R-Antikörpern ein empfindlicher und hochspezifischer Test für die Diagnostik der MG. Der Test eignet sich ebenfalls für die Verlaufskontrolle unter Therapie mit Immunsuppressiva oder Plasmapherese. Immunfluoreszenz-Untersuchung auf Antikörper gegen Muskelgewebe ist für die MG-Diagnostik weniger empfindlich und nicht spezifisch.Herrn Prof. Dr. A. Struppler zum 60. Geburtstag gewidmet     

Treatment of myasthenia gravis

Summary In the treatment of myasthenia gravis (MG) considerable progress has recently been achieved. Our experience is based on the observation of 139 patients with an average follow-up of 3 years and 4 months.A treatment plan and results are presented.Indications for thymectomy: all cases of MG in adult life, apart from ocular myasthenia without radiological thymoma and without electrophysiological and pharmacological signs of generalization; before puberty only cases with radiological thymoma and severely incapacitating or life-threatening signs.Median sternotomy is preferable for thymoma, the transcervical approach with a sternal split for non-neoplastic thymus. Mediastinal radiotherapy is indicated after removal of an invasive or adhesive thymoma.Indications for corticosteroids: 1) before thymectomy: respiratory weakness; 2) soon after thymectomy: life-threatening signs; 3) later after thymectomy: incapacitating or life-threatening signs; 4) as an alternative to thymectomy: when surgery cannot be performed or it is not indicated. Oral Prednisone was nearly always preferred: alternate-day high single dose (75 to 115 mg) has given good results in most cases even if in some cases a small dose was required in the off day; inversely a lower alternate-day or daily dose was often sufficient.Long-term results: following this schedule for adult patients good results were scored in 67% of thymomas, in 94% of hyperplasias, and in 62% of unthymectomized patients: in prepuberal life the few cases of severe MG have all shown a favorable evolution.

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Zusammenfassung Bei der Behandlung der Myasthenie wurden in letzter Zeit beachtliche Fortschritte erzielt. Wir teilen hier unsere Erfahrungen anhand von 139 Patienten mit einer durchschnittlichen Katamnese von 3 Jahren und 4 Monaten mit.Wir betrachten als Indikationen für eine Thymektomie: alle Fälle von Myasthenie beim Erwachsenen mit Ausnahme der rein okulären Formen ohne radiologisch nachweisbares Thymom und ohne elektrophysiologische oder pharmakologische Zeichen einer Generalisierung; bei Kindern vor der Pubertät empfehlen wir die Thymektomie nur in Fällen mit radiologisch nachweisbarem Thymom und mit schwerer Beeinträchtigung oder gar Lebensgefährdung durch die Symptome.Die mediane Sternotomie ist beim Thymom vorzuziehen, der transzervikale Zugang mit Spaltung des Sternums für die nicht neoplastischen Thymusvergrößerungen. Mediastinale Strahlentherapie ist nach Exstirpation eines invasiven Thymoms oder eines Thymoms mit Adhäsionen angezeigt.Als Indikation für die Corticosteroidtherapie betrachten wir: 1. wenn vor der Thymektomie Atemstörungen bestehen; 2. wenn bald nach der Thymektomie lebensbedrohliche Symptome auftreten; 3. wenn später nach Thymektomie nennenswert behindernde oder lebensbedrohliche Symptome in Erscheinung treten; 4. als Alternative zur Thymektomie, wenn diese nicht durchgeführt werden kann oder nicht indiziert ist. Die orale Prednisontherapie wurde fast immer vorgezogen: wir gaben an alternierenden Tagen jeweils hohe Einzeldosen (75–115 mg) mit gutem Erfolg in den meisten Fällen. In gewissen Fällen war eine kleine Dosis an den Tagen zwischen der Hauptdose aber genügend, ebenso in Einzelfällen eine allgemein niedrigere Dosierung. Die Langzeiterfolge mit diesem therapeutischen Vorgehen betrugen 67% gute Ergebnisse bei Thymomen und 94% bei Thymushyperplasie. Unter den nicht thymektomierten Patienten wiesen 62% ein gutes Ergebnis auf. Vor der Pubertät zeigten die allerdings wenigen Fälle schwerer Myasthenie alle ein gutes Ansprechen auf die Therapie.

     

Laparoscopic assisted colectomy and myasthenia gravis

Summary

Myasthenia gravis is an auto-immune disorder posing particular challenges in the anaesthesia of patients requiring laparotomy. This report describes how a laparoscopic approach may overcome these difficulties.