A patient with Guillain-Barré syndrome is reported on who responded favourably to a short course treatment with the novel immunosuppressant sodium fusidate (Fucidin), given at a daily dose of 1.5 g for one week. Along with prompt and clear cut clinical improvement, treatment with Fucidin was associated with a rapid decline in the blood concentrations of inflammatory cytokines presumably implicated in the pathogenesis of Guillain-Barré syndrome such as interleukin-2, interferon-γ, and tumor necrosis factor-α. The ex vivo production of these cytokines was also markedly diminished compared with pretreatment values. Fucidin was well tolerated and no clinical or biochemical side effects were seen.
- Guillain-Barré syndrome
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Guillain-Barré syndrome is a heterogeneous syndrome which may be due to a demyelinating or axonal neuropathy probably autoimmune in nature, that is clinically characterised by acute progressive and symmetric motor weakness of the limbs and of bulbar and facial musculature1 2 We report on a patient with severe Guillain-Barré syndrome who responded favourably to a short course of treatment with the novel immunosuppressant sodium fusidate (Fucidin; see Nicoletti et al 3 for a review.
A 46 year old woman developed progressive weakness in the legs and after few days in the arms. Two weeks after the onset of symptoms the patient was admitted to hospital. Neurological examination showed severe weakness of the lower limbs and less marked weakness in the upper limbs, with the absence of deep tendon reflexes. She was unable to walk 5 m with a walking frame. No cranial nerve involvement was noticed.
Examination by EMG disclosed reduced motor conduction velocity in all limbs, particularly in the lower limbs (median nerve 44 m/s; ulnar nerve 53 m/s; right exterior sciatic popliteal (ESP) 32 m/s, left ESP 33 m/s, posterior tibial nerve 32 m/s). The sensory conduction was normal. Needle EMG showed fibrillation and positive sharp waves in all muscles examined. Brain and spinal MRI were normal: Chest radiography and abdominal echography were performed to exclude neoplasms and showed no abnormalities. Analysis of CSF showed an abnormal total protein concentration (111 mg/dl), a high concentration of albumin (65.2 mg/dl), IgG 11.3 mg/dl, and a cell count of 0.8/mm3.
At immunological analysis, the patient showed raised blood concentrations of interferon (IFN)-γ, interleukin (IL)-2, and tumour necrosis factor (TNF-α). These cytokines are usually not detectable in the blood of normal healthy subjects.4 5
The diagnosis of Guillain-Barré syndrome was made according to the Asbury diagnostic criteria.6
The degree of motor function was expressed on a seven point functional scale as used in previous trials: 0=healthy; 1=minor signs or symptoms but fully capable of manual work; 2=able to walk>10 m without assistance; 3=able to walk>10 m with a walker or support; 4=bedridden or chairbound (unable to walk 10 m with a walker or support); 5, requiring assisted ventilation for at least part of the day; and 6, dead. At entrance our patient was assigned a 4 disability grade.
After obtaining informed consent from the patient, she was treated orally with sodium fusidate (Fucidin, Sigma-Tau, Pomezia, Rome, Italy). at a dose of 1.5 g (two tablets before each of the main meals) for one week. No other treatment or rehabilitation was previously performed.
Three days after the start of treatment the patient was able to stand up from her bed and to maintain a standing position without assistance. After 10 days she was able to walk (grade 2) and presented a progressive improvement in the motor deficits of the arms. The patient was discharged at grade 1 and rehabilitative treatment was started. These clinical effects were accompanied by a progressive and marked reduction in the circulating concentrations of IFN-γ, IL-2, and TNF-α; the values were reduced>50% in each patient after three days of treatment and further declined below the threshold of detection of the assays at the end of treatment with Fucidin (figure). The ex vivo production of these cytokines from peripheral blood mononuclear cells was also strongly diminished compared with pretreatment values; phytohaemagglutinin induced IFN-γ and IL-2 production declined from 321 to 109 pg/ml and 201 to 56 pg/ml respectively, and lypopolysaccharide induced TNF-α release diminished from 476 to 137 pg/ml. Treatment with Fucidin was well tolerated and no clinical, biochemical, or haematological side effects were noticed.
At clinical follow up, performed after 6 months, the patient showed no modification of the clinical grade. All deep tendon reflexes were normal except for the bilateral achilles reflexes. A neurophysiological study showed an improvement of the motor conduction velocity (median nerve 52 m/s; right ESP 44 m/s and left ESP 44 m/s). Neurological examination at the 1 year follow up showed a slightly distal muscular strength deficit of the left arm, but all the deep tendon reflexes were normal. She reported frequent night cramps. Motor conduction velocities were normal. The patient was able to perform normal daily activities.
Proinflammatory cytokines such as IL-2, IFN-γ ,and TNF-α may play an important part in the pathogenesis of Guillain-Barré syndrome.2 Because Fucidin suppresses IL-2, IFN-γ ,and TNF-α production in vitro and in vivo7-12 we tested its effects in one patient with Guillain-Barré syndrome. The prompt beneficial clinical response was associated with a rapid decline of IL-2, IFN-γ ,and TNF-α blood concentrations as well as with their diminished ex vivo secretion. This suggests, but does not prove, that an inhibitory effect of Fucidin on the production of these cytokines might have favoured recovery.
Although most patients spontaneously recover from Guillain-Barré syndrome, the course of the disease might be severe, leading to severe tetraparesis which requires artificial ventilation in about 20% of the patients, with a long lasting and costly stay in intensive care units, and with residual deficits occurring in 5%-10% of the patients.1 2 The course of the disease is favourably modulated by plasmapheresis13 and high dose intravenous gammaglobulin.14 However, these approaches are expensive and, in the case of plasma exchange, technically difficult, and alternative therapies are much needed.
Because Fucidin was only tested in a single case of Guillain-Barré syndrome, and in view of the autoremitting course of the disease, no firm conclusion can be drawn on the utility of this drug in the treatment of Guillain-Barré syndrome. None the less, evidence for a possible therapeutic effect is strenghtened by previously noted beneficial effects of Fucidin in the treatment of other immunoinflammatory diseases in rodents and humans.8 10 11 15-19 Moreover, that recovery of our Fucidin treated patient occurred much earlier than usual (2–4 weeks after cessation of progression2), also suggests a causal relation to treatment with Fucidin. Along with the rare and reversible side effects of Fucidin,3 this case report warrants larger studies on use of this drug in Guillain-Barré syndrome.
This work was partly supported by grant No 96.03102.04 from the Italian National Council of Research.
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