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Pure Motor Demyelinating Neuropathy: Deterioration After Steroid Treatment and Improvement with Intravenous Immunoglobulin

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Pure Motor Demyelinating Neuropathy: Deterioration After Steroid Treatment and Improvement with Intravenous Immunoglobulin 77878ournal ofNeurology, Neurosurgery, and Psychiatry 1994;57:778-783 PAPERS J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.57.7.778 on 1 July 1994. Downloaded from Pure motor demyelinating neuropathy: deterioration after steroid treatment and improvement with intravenous immunoglobulin Michael Donaghy, K R Mills, S J Boniface, J Simmons, I Wright, Norman Gregson, Jean Jacobs Abstract In recent years, various subtypes of MFMN Within one month of starting oral pred- have been characterised and associated with nisolone treatment weakness unexpect- high titres of antiganglioside antibodies in edly increased in four patients aged 34 to 1 1% to 84% of cases depending on the clini- 75 years with purely motor forms of cal subtype.9 10 This motor neuropathy is most acquired chronic demyelinating neuro- commonly multifocal and associated with pathy. By contrast, steroids produced the motor nerve conduction block. Less often expected improvement in 11 other patients show symmetric weakness with dif- patients with symmetric sensorimotor fusely slowed motor conduction velocities. chronic inflammatory demyelinating These pure motor neuropathies have usually polyneuropathy. Two of the patients with failed to respond to treatment with pred- purely motor demyelinating neuropathy nisolone. Indeed, progression of weakness were subsequently treated with high dose seems to be common despite the use of high IVIg (0.4 glkglday for five days) with dose steroid treatment in MFMN.91 In one prompt improvements in strength mea- report, eight of nine patients improved with surements and motor nerve conduction. cyclophosphamide treatment" but the pros- Thus IVIg seems to be the treatment of pect of serious side effects makes this an unat- choice and steroids should be used with tractive long term treatment for such a extreme caution, if at all, in patients with chronic disease. Improved strength has been purely motor forms of acquired demyeli- reported recently after high dose IVIg treat- nating polyneuropathy. ment.12-'5 In some cases IVIg or cyclophos- phamide treatment had been started while the ( Neurol Neurosurg Psychiatry 1994;57:778-783) patient was already taking or had recently taken prednisolone and these reports of bene- ficial treatments must be seen in the light of http://jnnp.bmj.com/ This communication highlights unpredicted the unexpected steroid induced weakness we Department of differences in the response to steroid treat- report here. Clinical Neurology, ment of different types of acquired chronic Radcliffe Infirmary, demyelinating neuropathy. These differences Woodstock Road, Oxford OX2 6HE, UK have important practical implications con- Methods M Donaghy cerning the choice of appropriate treatment PATIENT POPULATION K R Mills for patients with chronic inflammatory The study is based on retrospective analysis of on September 24, 2021 by guest. Protected copyright. S J Boniface J Simmons demyelinating sensorimotor neuropathy 12 patients with CIDP and four with MFMN I Wright (CIDP), by contrast with those with purely referred consecutively over a three year period Department of motor demyelinating neuropathy or multifo- to a peripheral neuropathy clinic run by one Anatomy, Guy's cal motor neuropathy (MFMN). physician (MD). Diagnosis, decisions to treat, Hospital, St Thomas CIDP was first recognised as a treatable and monitoring of treatment were all under- Street, London SE1 9RT, UK cause of neurological disability over 20 years taken by MD. Because the need for formal N Gregson ago after reports of steroid responsiveness, study of different neuropathy subgroups was Department of subsequently confirmed by a controlled trial.5 not anticipated, there were no standard proto- Neuropathology, Azathioprine is often added to prednisolone, cols for assessing the degree of weakness, the Institute ofNeurology, causes nature of the studies Queen Square, and occasionally improvement in electrophysiological (per- London WClN 3BG, patients who failed to respond to prednisolone formed by three different neurophysiologists), UK alone.67 Plasma exchange is effective in CIDP the necessity for sural nerve biopsy, or the J Jacobs and is often used to initiate improvement in estimation of serum ganglioside antibodies. Correspondence to: to steroids.8 Routine serum was Dr Michael Donaghy, patients initially unresponsive protein electrophoresis Department of Clinical Two follow up studies of a total of 152 undertaken on all patients and no parapro- Neurology, Radcliffe with that between 85% was detected. Patients were Infirmary, Woodstock Road, patients CIDP suggest teinaemia diag- Oxford OX2 6HE, UK. and 95% of patients respond favourably to nosed as having CIDP according to standard Received 5 July 1993 and varying regimens of immunosuppressive treat- guidelines'6; all had symmetric distributions of in final revised form ment on absence or reduced 18 October 1993. based prednisolone, azathioprine, weakness, tendon Accepted 27 October 1993 and plasma exchange.67 reflexes, large fibre modality sensory loss, and Treatment ofpure motor neuropathy 779 absent or reduced sensory nerve action poten- flow was used in with CIDP patients taking J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.57.7.778 on 1 July 1994. Downloaded from tials (SAPs). more than two months to improve, and in the Pure MFMN was diagnosed on the follow- four patients with MFMN whose weakness ing grounds: seemed to increase after initiation of steroid (a) Purely motor features with normal treatment. sensation. Patients 1 and 2 with MFMN were given (b) Arm(s) affected at onset. IVIg (0 4 g/kg/day for five days) 33 months (c) Progression over more than two and 26 months respectively after they had last months. received any other immunomodulatory (d) (Multi-) focal onset. treatment (for example, steroids, plasma (e) Relative preservation of tendon exchange, or cyclophosphamide). Before and reflexes even in affected limbs. after treatment, these two patients were (f) Motor nerve conduction block assessed by myometry, a timed walk over a (defined as a proximal/distal CMAP ampli- fixed distance, stamina tests of upper and tude ratio of 60% or less), absent or pro- lower limbs, and by electrophysiology. longed F waves, or motor conduction velocities (MCVs) reduced to 38 m/s in the upper limb and 30 m/s in the lower limb. Results (g) Preserved SAPs or lack of demyelina- PATIENTS WITH SENSORIMOTOR CIDP tion or remyelination on the sural nerve biopsy. Patient profile The 12 patients were aged 10 to 75 years. All SURAL NERVE BIOPSY had a mixed sensorimotor polyneuropathy; Subtotal sural nerve biopsy was undertaken at sensory ataxia was the predominant feature in the ankle in the four patients with MFMN one patient who also had mild weakness and (1-4) to seek evidence of demyelination or electrophysiological evidence of motor nerve remyelination. Plastic embedded semithin demyelination. Immunosuppressive treatment sections and teased fibre preparations were was started in 11 patients; one was not treated analysed morphometrically."7 because of a combination of mild disability, diabetes mellitus, and low intelligence. GANGLIOSIDE ANTIBODIES Frozen stored serum samples from the Response to steroids patients with MFMN (1-4) were analysed. After steroid treatment in the eight patients GM1 and sialo GM1 antibodies were with CIDP aged 10 to 50 years, six regained detected by enzyme linked immunosorbent normal or near normal limb muscle power assay (ELISA).'5 This protocol has been vali- within six months. One had mild pretreat- dated in an international comparative study ment symptoms, barely sufficient to alter gait, organised by Dr Zielasek (Wurzburg). and he improved only slightly. The patient Further ganglioside antibody reactivity was with prominent sensory ataxia regained the detected by thin layer chromatography over- ability to walk briskly without a stick, layer with a total ganglioside extract from although some residual ataxia remained. human brain and cauda equina.'8 Three older patients, aged 66 to 75 years, responded notably less promptly and com- http://jnnp.bmj.com/ IMMUNOSUPPRESSANT REGIMEN pletely to steroid treatment. The two patients All patients with CIDP or MFMN were in their eighth decade were initially unable to treated with oral prednisolone (60 mg/daily) bear weight or walk but, after a combination for the first two to four weeks, then with 45 of steroids, azathioprine, and plasma mg/day until their neuropathic symptoms sta- exchange, both made sustained improvements bilised or improved. Treatment was then after four and eight months respectively, and gradually converted to 25-45 mg on alternate eventually walked with walking frames. days for maintenance treatment. Azathioprine None of the patients with CIDP deterio- on September 24, 2021 by guest. Protected copyright. (2-5 mg/kg/day) was added in 10 of the 11 rated while taking steroids. treated patients with CIDP, and in all four patients with purely motor neuropathy. PURE MOTOR DEMYELINATING NEUROPATHY Plasma exchange (5 x 4 litres) by continuous (TABLE) Patient profile The duration of symptoms in four male MFMNpatients: summary ofinvestigations patients with MFMN ranged from five months to six years. Three patients (1, 3, and Sural nerve biopsy Electrophysiology Ganglioside 4) had a noticeably asymmetric pattern of MF antibodies muscle weakness. The weakness in patient 2 MCV CB density (normal Patient (mis) (%o) F(ms) (/mm2) range) GMI GDlb GM2 had started asymmetrically, but had later become symmetric.
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