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A case of stiff limb syndrome responsive to plasma exchange
  1. A COLES
  1. Department of Neurology, Norfolk and Norwich Health Care NHS Trust, Brunswick Road
  2. Norwich Norfolk NR1 3SR, UK
  3. Department of Neurology, Addenbrooke's NHS Trust, Hills Road, Cambridge CB2 2QQ, UK
  1. Dr R Barker, Cambridge Centre for Brain Repair, Forvie Site, Robinson Way, Cambridge CB2 2PY, UK
  1. A COLES,
  2. R BARKER
  1. Department of Neurology, Norfolk and Norwich Health Care NHS Trust, Brunswick Road
  2. Norwich Norfolk NR1 3SR, UK
  3. Department of Neurology, Addenbrooke's NHS Trust, Hills Road, Cambridge CB2 2QQ, UK
  1. Dr R Barker, Cambridge Centre for Brain Repair, Forvie Site, Robinson Way, Cambridge CB2 2PY, UK

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Stiff limb syndrome is a recently described, rare condition that is characterised by rigidity within the limbs that progresses in a relapsing and remitting fashion, often with involvement of the sphincters and brain stem.1 2 The axial muscles are spared in the early stages of the illness, which helps distinguish it from stiff man syndrome, although it may still represent a similar pathogenic mechanism to that proposed in stiff man syndrome, in which anti-GAD antibodies are typically seen in about 60% of patients.3 However, patients with stiff limb syndrome seem to have different neurophysiological abnormalities from stiff man syndrome2 and fewer of these patients have anti-GAD antibodies; they also typically show a poorly sustained response to baclofen and diazepam. The response to immunotherapy in stiff limb syndrome is not known, whereas patients with stiff man syndrome may respond to intravenous immunoglobulin4 5 as well as possibly plasma exchange.6-8 We now report on a patient with stiff limb syndrome who responded dramatically to plasma exchange and in whom an antiaxonal antibody was isolated, suggesting that this condition may have an immunological basis.

A 50 year old retired auxiliary nurse presented with a 10 year history of progressive pain, stiffness, and flexion contractures in her hands, followed by increasing immobility. Her neurological problems began at 24 years of age when she developed viral meningitis based on a headache, fever, and a CSF lymphocytosis, that resolved after a week. At the age of 28 she complained of back and leg pain with urinary retention but displayed no abnormal neurological signs and had a myelogram that was normal. Her leg symptoms resolved, but she continued to complain of urinary retention and frequency, for which no cause was found. She went on to have a urethrotomy which did not relieve her symptoms. At the age of 40 she started to develop stiffness and pain in the hands, which slowly clawed, after which her arms and neck became progressively stiffer and her trunk became increasingly stooped on walking, with additional difficulty raising her arms above her head. Five years after the onset of her symptoms she was incapacitated, required assistance with all activities of daily living, and was permanently catheterised. At this stage a seronegative polyarthritis was diagnosed and she was treated with hydroxychloroquine, prothiaden, and corticosteroids, all without effect. She subsequently had some spontaneous remission but at the time of her referral to us she could only walk 10 yards with one stick and continued to complain of heaviness, pain, and stiffness in the limbs especially the left arm. In addition she had developed an intermittent tremor of the right arm and leg, which sometimes affected her jaw and she had difficulty swallowing large boluses of food.

Examination at this time showed her to have flexion contractures of all fingers. She had irregular jerking movements of her right arm and leg that were accentuated by moving the limb or walking a few steps. She had difficulty standing up from a chair without assistance and although she was not weak on formal examination, all limb movements were accompanied by pain. No reflex or sensory abnormalities were found and her plantar responses were flexor.

Investigations showed normal nerve conduction studies as well a normal CSF examination including negative oligoclonal bands; brain and spine MRI, and routine hematological and biochemical tests were also normal. Her autoantibody screen was negative as were her anti-GAD and anti-neuronal antibodies although an antiaxonal antibody was detected in her serum which is currently being further characterised. More extensive neurophysiology showed her to have an abnormal hypersegmented EMG pattern during muscle spasms although no continuous motor unit activity was recorded at rest. The latency of responses to magnetic stimulation of the motor cortex was normal.

The diagnosis of stiff limb syndrome was made and she was initially treated with diazepam and baclofen, but continued to deteriorate and gradually lost all useful function of her arms. There was a similar lack of response to intravenous methylprednisolone, so she was given intravenous immunoglobulin, to which she developed an anaphylactic reaction. Her disorder progressed and she developed prominent rigidity and spasms of the face, trunk and limbs. Her speech developed a strangled quality and she had episodes of involuntary tachypnoea apparently due to spasm of respiratory muscles. She was bed bound and totally dependent for all activities of daily living, needing constant nursing. As a result it was decided to give her empirical treatment with two courses of plasma exchange in November and December 1996. After the first exchange, the spasms of her facial and respiratory muscles ceased and after the second there was a slow sustained improvement in limb power, so that after 6 months she had regained independence. For the next 18 months she walked and lived normally, even travelling on holiday. This improvement was punctuated by two admissions with chest infections and impaired respiratory function, which responded well to antibiotics.

Unfortunately the stiffness and tremor of her limbs returned in June 1998 and by November of that year, she was once again immobile and dependent such that she could barely wash herself and was unable to walk at all. Any attempt to move her limbs caused disabling tremor and stiffness. Again, reflexes and plantars were normal. She had a further course of plasma exchange and again responded slowly, such that 3 months later she was able to walk on two sticks. This improvement was initially sustained although she has required a further course of plasma exchange in February 2000 and has now been started on oral cyclophosphamide with notable benefit. The patient has not had further neurophysiological investigations.

This case has all the features of stiff limb syndrome with the novel finding of antiaxonal antibodies detected in the serum. The patient failed to respond to baclofen and diazepam and could not tolerate intravenous immunoglobulin but did have a dramatic and sustained response to plasma exchange, although the need for repeated courses of this treatment has led to her being started on cyclophosphamide. This has not been reported before for this condition and whereas this case illustrates the possible therapeutic effect of this treatment, it also raises the possibility that stiff limb syndrome may have an immunological basis.

Acknowledgments

We thank John Pilling for permission to present his case, Peter Brown for performing the detailed neurophysiology on this patient, and Angela Vincent for the serological testing and detection of the antiaxonal antibody.

References

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