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Adult paraneoplastic opsoclonus-myoclonus syndrome associated with antimitochondrial autoantibodies
  1. F Blaes1,
  2. M Jauss1,
  3. J Kraus1,
  4. P Oschmann1,
  5. I Krasenbrink1,
  6. M Kaps1,
  7. B Teegen2
  1. 1Department of Neurology, Justus-Liebig-University, 35385 Giessen, Germany
  2. 2Euroimmun GmbH, 23560 Lübeck, Germany
  1. Correspondence to:
 Dr F Blaes, Department of Neurology, Justus-Liebig-University, Am Steg 14, 35385 Giessen, Germany;

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Adult paraneoplastic opsoclonus-myoclonus syndrome associated with antimitochondrial autoantibodies

Paraneoplastic opsoclonus-myoclonus syndrome (OMS) is a rare complication of cancer characterised by chaotic, synchronous eye movements (opsoclonus), spontaneous muscle jerks (myoclonus), and ataxia. In children OMS is almost exclusively associated with neuroblastoma, whereas in adults small cell lung cancer (SCLC) and breast cancer are the most frequent tumours associated with OMS.1,2 Some breast cancer patients with OMS have an antineuronal antibody called anti-Ri in the serum and CSF.1,2 In most patients with SCLC-associated OMS, antineuronal antibodies are not detected.1 Here we report the first case of SCLC-associated OMS with high titre antimitochondrial antibodies (AMA) in serum and CSF.

A 58 year old Caucasian woman developed a flu like syndrome, followed by eye movement disturbances three days later. On admission to our hospital, physical examination revealed disorientation, opsoclonus, myoclonus predominantly of the upper limbs, and severe limb and trunk ataxia. The deep tendon reflexes were normal and no paresis or sensory deficit could be found. Cranial CT and MRI scans and routine laboratory tests were normal. CSF examination revealed lymphocytic pleiocytosis, normal total protein, and positive oligoclonal bands. In serum and CSF no antineuronal antibodies but high titre AMA could be detected. High dose steroid therapy was started one week after onset of symptoms, and the patient experienced significant improvement of the OMS within one week of commencing steroid treatment. By four weeks the opsoclonus and myoclonus had disappeared, and there was only a mild trunk ataxia: the patient could walk unassisted.

CT scan of the thorax showed a mediastinal mass. Bronchoscopy was normal, but a mediastinoscopic biopsy was positive for SCLC cells. Starting at the fourth week after admission, the patient received chemotherapy followed by a complete remission of the SCLC. At present, after a 2 year follow up, the patient is in good health (under intermittent chemotherapy without signs of tumour relapse) and, with exception of a mild ataxia, the neurological status is normal. The patient did not have clinical or laboratory signs of primary biliary cirrhosis (PBC) or any other liver disease at any time.

Using frozen sections of primate cerebellum, cortex, gut, Hep-2 cells, liver, and kidney (Euroimmun, Lübeck) for routine autoantibody tests, no antineuronal antibody was found, but strong staining of the mitochondria could be detected in all tissues by indirect immunofluorescence. The initial serum titre of the AMA was 1/1000 and CSF titre was 1/640. Antibody specificity index ASI (ASI = [AMA(CSF)/IgG(CSF)]/[AMA(serum)/IgG(serum)]) was calculated. ASI was 18.9 (normal value <3), indicating intrathecal synthesis of the AMA.

Western blot analysis, using pyruvate dehydrogenase (PDH), cerebellum, liver, and kidney as well as protein homogenates of neuroblastoma (SKN-SH) and SCLC cell lines (N417), was performed as previously described.3 No reactivity against PDH or any neuronal specific reactivity was found. However, the patient’s serum showed a reactivity to 18 and 21 kD protein expressed in all the above tissues and cell lines. Using the EUROASSAY® technique (Euroimmun, Lübeck), the serum showed no reactivity to the mitochondrial M2, M4 or M9 antigens. Western blot on recombinant HuD and NOVA-1/2 proteins showed no reactivity for anti-Hu or anti-Ri antibodies.

Adult paraneoplastic OMS has been described as a rare syndrome mostly associated with SCLC or breast cancer.1,2 Similar to other adult paraneoplastic syndromes, a variety of different underlying tumours has been reported. In patients with SCLC and paraneoplastic encephalomyelitis/subacute sensory neuropathy anti-Hu antibodies are detectable in a majority of the patients. In contrast, only in some breast cancer associated OMS a specific antineuronal antibody (anti-Ri) has been described, whereas OMS patients with SCLC rarely have antineuronal autoantibodies.1

AMA has been described in patients with PBC, and high titre anti-M2, a subspecificity of AMA, is highly specific for this disease.4 Other AMA specificities can occur in autoimmune liver or bile diseases.4 However, our patient did not have any liver or bile disease, but rather a paraneoplastic OMS with high titre AMA in both serum and CSF. Moreover, ASI revealed intrathecal synthesis of the AMA. Thus it seems unlikely that the AMA in our patient was a non-specific immune activation. Antoine and colleagues have reported patients with a paraneoplastic neurological syndrome associated with AMA.5 In contrast to our case, their patients had antineuronal antibodies and AMA, and the AMA specificity was anti-M2. More recently, AMA has been described in some patients with cancer without neurological disturbances, most AMA being anti-M2 specific.4 We could not identify the exact specificity of the AMA in our case, but the underlying antigen was not PDH or one of the known mitochondrial antigens (M2, M4 or M9). However, this mitochondrial antigen was expressed in all tested tissues including SCLC tumour cell lines.

Although an OMS patient with steroid responsive paraneoplastic OMS has been reported, the clinical course of our patient, with an almost complete remission after steroid therapy, is unusual. Previous studies described paraneoplastic OMS in adults as very resistant to steroids, plasmapheresis, or intravenous immunoglobulins.1 However, tumour therapy led to a marked improvement of the OMS in most of these patients.1 The good response to treatment may have been the result of a very short delay between the start of the syndrome and beginning of treatment.

In conclusion, adult paraneoplastic OMS can be associated with non-neuronal autoantibodies, and antimitochondrial autoantibodies in some patients without PBC may suggest an underlying tumour.


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