Christa Walgaard, MD
Pieter A. van Doorn, MD, PhD
Introduction, course of the disease
Guillain-Barré syndrome (GBS) is an important cause of acute neuromuscular paralysis. Rapidly progressive weakness is the most striking clinical feature of GBS. By definition, maximum weakness is reached within four weeks, but most patients reach their maximal weakness within two weeks1, 2. A plateau phase of varying length follows the progressive phase. The plateau phase is followed by the recovery phase which can take months to years. About 20% of severely affected patients remain unable to walk after six months and many patients remain otherwise disabled or severely fatigued3-5.
General care
GBS patients need multidisciplinary care to prevent and manage complications6. Immobilization is a risk factor for the development of deep vein thrombosis (DVT), in addition thrombo-embolic complications may more frequently occur during intravenous immunoglobulin (IVIg) treatment. Subcutaneous fractionated heparin and support stockings are recommended for nonambulant adult patients6. Autonomic dysfunction is a common and potentially lethal feature of GBS, therefore recognition of autonomic dysfunction is important; heart rate (ECG), pulse and blood pressure should be monitored regularly5. Respiratory dysfunction occurs in 20-30% of patients and respiratory function (vital capacity, respiratory frequency) should be monitored frequently in GBS patients, especially during the progressive phase. Recently, a prognostic model to predict respiratory insufficiency has been developed, which can be used already at hospital admission (Walgaard et al, accepted Ann. Neurol.). Pain has been described in up to 89% of patients, and can be present already before the onset of weakness7-9. The pain can be severe and recognition is important, especially in patients who are hindered in communication due to endotracheal intubation. Acute nociceptive pain should be treated according to the WHO guidelines and chronic neuropathic pain with amitriptyline or anti-epileptic drugs5.
Beneficial effects of immunotherapy
The North American Plasma Exchange (PE) study was the first large trial which established the positive effect of immunotherapy10. PE is most effective when started within the first two weeks of the illness11. In 1992 a randomized controlled trial (RCT) on the use of IVIg proved that IVIg and PE are equally effective12. Since the publication of these results, IVIg, in a regimen of 0.4 g/kg bodyweight daily for 5 consecutive days, has replaced PE as the preferred treatment in many centers, mainly because of its greater convenience and availability. The combination of PE followed by IVIg was not significantly better than PE or IVIg alone13. The addition of methylprednisolon to IVIg was not beneficial in GBS, although there might be a short-term effect of this combined treatment when a correction is made for known prognostic factors14. Mycophenolate mofetil added to IVIg was also not beneficial according to a pilot study in 25 GBS patients15.
Treatment of mildly affected patients
‘Mildly affected’ is arbitrarily defined as being able to walk without assistance16. The effects of IVIg have not been studied in those patients. One randomized trial studied the effect of PE in patients who could walk with or without aid, but could not run17. Onset of motor recovery was faster in patients who received two PE sessions than in those who received no PE.
Treatment of patients who continue to deteriorate
A proportion of patients continue to deteriorate after standard treatment with a single course of IVIg3. Until now it is unknown what is the best strategy for those patients; wait and see or start additional IVIg treatment. RCT’s are required to establish the best treatment strategy in those patients who have a highly variable disease course. The pathophysiological reason why some patients continue to deteriorate and could be paralyzed for months is not known. A recent study suggests that GBS patients who have a limited IgG rise after standard IVIg treatment (0.4 g/kg bodyweight for 5 days) have a poorer prognosis18. The prognosis of GBS can be determined already early in the course of disease19. An RCT evaluating the effect of a second IVIg course in patients with a poor prognosis (SID-GBS study) will start early 2010.
Treatment of patients who deteriorate after initial improvement
About 5-10% of GBS patients deteriorate after initial improvement or stabilization after IVIg therapy, a condition which is called a ‘Treatment Related clinical Fluctuation’ (TRF)20. It is common practice to treat those patients with a second IVIg course, because patients are likely to improve after re-initiating this treatment.
Rehabilitation and management of fatigue
Patients with previous GBS seem to have a persistent long-term impact on quality of life and functioning, this is relatively independent from various variables at onset21, 22. This knowledge should encourage the development of training and disease adaptation courses for GBS patients. Long-term outcome studies on rehabilitation or studies that compare different rehabilitation methods in GBS patients were not conducted. Early start of physiotherapy for hospitalized GBS patients and provision of rehabilitation during and after hospital admission are recommended23.
Although the neurological recovery is often relatively good, the majority of patients with GBS remain severely fatigued4. The cause and contributing factors of fatigue are not well known, but fatigue appears in part to be sequel of forced inactivity and general muscle deconditioning6, 24 Amantadine appeared to be ineffective in relieving fatigue25, however physical training resulted in a 20% fatigue severity reduction in a small prospective observational study26. Additional studies to improve neurological outcome and to relieve fatigue and pain in patients with GBS are urgently required.
References
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