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A woman with acute myelopathy in pregnancy: case outcome

BMJ 2009; 339 doi: https://doi.org/10.1136/bmj.b4026 (Published 10 December 2009) Cite this as: BMJ 2009;339:b4026
  1. Reinhard Reuß, physician 1,
  2. Paulus S Rommer, researcher 1,
  3. Wolfgang Brück, professor2,
  4. Friedemann Paul, head of research group 39,
  5. Michael Bolz, senior physician4,
  6. Sven Jarius, neuroimmunologist5,
  7. Tobias Boettcher, clinical neurologist6,
  8. Annette Großmann, senior physician7,
  9. Alexander Bock, senior physician8,
  10. Frauke Zipp, professor9,
  11. Reiner Benecke, professor1,
  12. Uwe K Zettl, professor1
  1. 1Department of Neurology, University of Rostock, 18147 Rostock, Germany
  2. 2Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany
  3. 3NeuroCure Clinical Research Center, Charité Universitätsmedizin Berlin, Berlin, Germany
  4. 4Department of Gynaecology, University of Rostock
  5. 5Division of Molecular Neuroimmunology, Department of Neurology, University of Heidelberg, Heidelberg, Germany
  6. 6Neurology Division, Dietrich-Bonhoeffer Klinikum Neubrandenburg, Neubrandenburg, Germany
  7. 7Department of Radiology, University of Rostock
  8. 8Neuroradiology Division, Dietrich-Bonhoeffer Klinikum Neubrandenburg
  9. 9Cecilie-Vogt Clinic for Neurology, Charité-Universitätsmedizin, Berlin
  1. Correspondence to: R Reuß reinhard.reuss{at}neuro.med.uni-giessen.de
  • Accepted 14 August 2009

Four weeks ago (BMJ 2009;339:b3862) we described the case of 23 year old Andrea G, who presented with progressive transverse spinal cord syndrome in early pregnancy. Her symptoms recurred during a subsequent pregnancy (BMJ 2009;339:b4025).

We considered many possible causes, including autoimmune inflammatory disorders such as multiple sclerosis or systemic lupus erythematosus and acute rubella infection, but these were excluded by the combination of clinical presentation and the results of laboratory tests or magnetic resonance imaging (MRI). Since the most striking feature was the vertical extension of the spinal cord lesion on MRI, we considered recurrent relapses of longitudinally extensive transverse myelitis to be the most likely diagnosis. This condition is characterised by transverse myelitis with spinal cord lesions extending over three or more vertebral segments.1 Tests showed anti-aquaporin 4 (AQP4) antibodies in our patient’s serum, confirming the diagnosis.2 Oligoclonal bands were not detected. These are often present in patients with central nervous system infection or autoimmune disease, including 85-95% of those with multiple sclerosis but only 15-30% of patients with longitudinally extensive transverse myelitis.

We treated Mrs G with eight courses of plasma exchange. Her clinical symptoms improved immediately, and her spinal cord lesions had reduced in size on subsequent MRI scans. Plasma exchange, alongside intravenous immunoglobulin, is also effective in other immune system mediated disorders such as Guillain-Barré syndrome and myasthenia gravis.

In the 21st week of her second pregnancy Mrs G had a spontaneous miscarriage. Macroscopically and microscopically the fetus was normal. Histological investigation of the placenta showed multiple infarcts mainly located in the maternal part of the placenta. AQP4 immunostaining showed a complete loss of immunoreactivity. In a normal placenta AQP4 is expressed in specific cell types depending on the stage of pregnancy.3 In addition, diffuse, mainly perivascular, deposits of membrane attack complexes of the complement system were clearly detectable in the syncytiotrophoblasts and to a moderate degree in the perivasal layers of the fetal vessels (figure).

Figure1

Diffuse, mainly perivascular deposits (red staining) of the membrane attack complex of the complement system detected with an antibody to the C9neo epitope. Fetal vessels show moderate markings (a) and the phagocytic syncytiotrophoblast (a crucial interface for maternal-fetal placental transfer processes) is clearly marked (b)

The fact that Mrs G experienced both episodes during pregnancy suggests a pathogenic relevance of immunological changes during gestation in the development of her condition and to an increased risk of relapse in pregnancy. Animal studies showed an up-regulation of AQP4 in the central nervous system during mid-pregnancy.4 An up-regulation of AQP4, together with a shift in the mediator of the immune response from T helper cell 1 to T helper cell 2 during pregnancy, may have led to increased antigen stimulation and subsequent production of antibodies to AQP4 in our patient. We therefore believe that increased antibody production may have been responsible for both the myelitis and the miscarriage.

During the next seven months, Mrs G’s myelitis recurred four times, including a first instance of optical neuritis in July 2007. This led to the diagnosis of neuromyelitis optica, for which longitudinal extensive transverse myelitis is often a precursor.

Because of the likely association with pregnancy and repeated relapses, Mrs G had no desire to become pregnant again immediately. In August 2007 she began off-label immunosuppressive treatment with rituximab (2×1 g administered intravenously), an anti-CD20 antibody that depletes B cells.5 This stabilised her condition, and she had no further relapses until May 2008. She was given a second cycle of rituximab at the end of May. In October 2008, no CD19 or CD20 positive cells were detected in her peripheral blood, and she remains well.

Notes

Cite this as: BMJ 2009;339:b4026

Footnotes

  • doi:10.1136/bmj.b5177
  • doi:10.1136/bmj.b5178
  • doi:10.1136/bmj.b5179
  • doi:10.1136/bmj.b5180
  • doi:10.1136/bmj.b5250
  • This is the final part of a three part case report that describes the outcome and summarises the comments made by readers during the presentation of a real patient’s story. Further responses are welcome through bmj.com

  • We thank W Brück for the figure, C F Lucchinetti for aquaporin 4 immunostaining, and M Vieth for discussion of placental pathology.

  • Competing interests None declared.

  • Patient consent obtained.

  • Provenance and peer review: Not commissioned; externally peer reviewed.

References

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