A 30-year-old woman with relapsed acute myeloid leukaemia (AML) underwent allogeneic haematopoietic stem cell transplantation (HSCT) in second complete remission, from a male matched unrelated donor in August 2004. There was a single mismatch at the DQB1 allele. The patient was conditioned with total body irradiation 14.4 Gy in six fractions, cyclophosphamide 120 mg/kg and CAMPATH 1H, with short-course methotrexate and cyclosporin A for graft-versus-host disease prophylaxis. She was readmitted at day 60 post transplant complaining of a week history of vague abdominal pain and diarrhoea, as well as feeling ‘shaky’. On examination, she had a coarse jerking tremor, ataxia, dysdiadochokinesis and a marked inability to follow movement with her eyes. Abdominal examination was normal. The cyclosporin level was acceptable at 122 nmol/l, and brief discontinuation made no improvement in her symptoms. CT and MRI brain were normal, as was CSF taken at lumbar puncture. There was marked further deterioration in both speech and tremor, and the empirical use of foscarnet to cover the possibility of HHV 6 infection was also of no benefit. Bone marrow examination showed her to still be in morphological remission, although chimerism was 83% donor. A neurology opinion was sought, and a clinical diagnosis of opsoclonus myoclonus (OM) was made. Anti-Hu antibody was tested and was negative. A slow spontaneous recovery in symptoms occurred over the next 4 weeks and the patient was transferred to a neurological rehabilitation unit. Unfortunately, she suffered a frank haematological relapse of her AML a month later and ultimately died of her disease.
OM (Dancing eye syndrome/Kinsbourne syndrome) is a rare neurological condition of subacute onset. It is characterised by disturbed motor control of limbs, trunk and head with features of cerebellar damage, as well as irregular saccadic eye movement in horizontal and vertical planes, along with irritability or disturbed sleep. There is considerable variation in clinical severity. Onset is usually between 10 months and 3 years of age, and is very rare in adults. There is usually no preceding neurological illness.1, 2 OM is associated with a neuroblastoma in 10–90% of paediatric cases, which tend to have a T-cell infiltrate. Removal of the neuroblastoma has no effect on subsequent outcome of the OM. In adults, OM has been shown to be a paraneoplastic phenomenon in greater than 50% of cases, most commonly small-cell lung carcinoma, although there are case reports in non-small-cell lung carcinoma, as well as breast, kidney, gastric and ovarian carcinoma.3 The immune system is implicated in view of the disease response to immunomodulatory agents and the association of relapse with infection. Anti-Hu antibodies are IgG antibodies to neurofilament in cerebellar/peripheral nerves, albeit with no common antigen, and are associated with OM. Around 50% of patients have preceding viral infections, although with the average age of the patients there is no clear role for a causative infectious agent, and there is no evidence for a genetic basis to the disease. The exact sites of damage in the disease are not clear, although the ataxic limb and trunk movements are consistent with cerebellar damage. The abnormal eye movements may be due to damage to ‘pause’ neurones within the parapontine reticular formation of the brain. It is unclear whether the characteristic irritability and disturbed sleep are due to damage to further specific neurones or are secondary consequences. If there are no associated neuroblastomas, then most patients will have a normal CT/MRI brain, CSF and EEG. There is no long-term cure for the disease and the effect of treatment on outcome is unclear. Symptoms may fluctuate or relapse, often triggered by minor intercurrent illnesses. Motor and cognitive effects persist and may worsen with age. Steroids and ACTH are useful in controlling acute symptoms, and are regarded as standard treatment. IVIG has been shown to be of use, and there are several case reports of other immunomodulatory agents being of use including azathioprine, rituximab and plasma exchange.1
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