Friday, October 20, 2017

Treatment dilemmas in Guillain-Barré syndrome

Verboon C, van Doorn PA, Jacobs BC. Treatment dilemmas in Guillain-Barré syndrome. J Neurol Neurosurg Psychiatry. 2017 Apr;88(4):346-352.

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy with a highly variable clinical course and outcome. Intravenous immunoglobulin (IVIg) and plasma exchange are proven effective treatments, but the efficacy has been demonstrated mainly on motor improvement in adults with a typical and severe form of GBS. In clinical practice, treatment dilemmas may occur in patients with a relatively mild presentation, variant forms of GBS, or when the onset of weakness was more than 2 weeks ago. Other therapeutic dilemmas may arise in patients who do not improve or even progress after initial treatment. We provide an overview of the current literature about therapeutic options in these situations, and additionally give our personal view that may serve as a basis for therapeutic decision-making.

From the article

Despite the proven effectiveness of these treatments in GBS, the care of patients in clinical practice is often complex. First, outcome in many patients is still poor: 2–10% may die, 20% are still unable to walk after 6 months and many patients suffer from residual symptoms, including pain and severe fatigue. Second, the patients in whom the therapeutic effects have been demonstrated frequently represent a selected proportion of the patients (symptoms <2 weeks and who are walking with aid, bed bound or in need of artificial ventilation (GBS disability grade ≥3,).

Third, the efficacy of PE and IVIg has primarily been demonstrated related to improvement on the GBS disability scale 4 weeks after the start of treatment. However, this scale focuses on walking and does not take into account other consequences of GBS that are important in daily life, such as arm function, facial weakness, sensory deficits, pain and fatigue. Finally, as a consequence of this, the Cochrane reviews about treatment of GBS are restricted to the specific inclusion and outcome criteria of the trials being focused on the GBS disability scale….

Current personal view: Based on limited evidence we recommend to start treatment as soon as possible in patients who walk with aid, are bedbound or ventilated (level of evidence: 3). In patients who are still able to walk unaided but show rapid progression of symptoms one likely should aim to prevent further nerve damage and not wait for further clinical deterioration (level of evidence: 4)….

Current personal view: There is no information available on the effect of treatment in patients with GBS presenting 4 weeks or later after the onset of weakness. Subacute GBS or A-CIDP should be considered in patients who present after 4 weeks of onset. We suggest to start IVIg when there is clear clinical progression or a 'wait and see' policy in case of relatively mild and stable disease (level of evidence: 4)….

Current personal view: Patients with mild GBS may have long-term functional impairment, but only a beneficial effect of treatment with PE has been demonstrated (level of evidence: 2). This effect has not been demonstrated for IVIg in adult patients. Based on the effect of PE in mild cases and of IVIg in severe cases, IVIg likely may be effective in mild GBS too. We propose that treatment (either PE or IVIg) should be considered especially in mildly affected patients who develop additional features such as autonomic dysfunction, bulbar or facial weakness (level of evidence: 4). New treatment trials preferentially should study the effect of treatment not only restricted to severely affected patients with GBS…

Current personal view: Based on the results of four retrospective studies with small numbers of patients, we consider to recommend IVIg over PE in patients with pure motor GBS (level of evidence: 3). Patients with PCB, ataxic and sensory GBS might never become eligible for treatment when only the GBS disability scale is taken into account and therefore treatment should be initiated when symptoms are seriously disabling or rapidly progressing (level of evidence: 4)….
Current personal view: No RCT has been performed exclusively in patients with axonal forms of GBS, until such studies have demonstrated otherwise, we recommend to treat these patients similarly as the patients with a demyelinating form of GBS (level of evidence: 4)…

Current personal view: There currently is no indication to treat children with GBS differently than adults. IVIg seems to be effective in children with GBS (level of evidence: 2) and is preferred over PE because it is easier to administer and possibly better tolerated in small children (level of evidence: 3)…

One randomised trial compared the efficacy of PE, IVIg, and PE followed immediately by IVIg in 379 severely affected patients, but did not find significant differences between the three treatment modalities in any of the outcome measures. Thus IVIg after PE was not significantly better than IVIg or PE alone. However, all patients receiving the combination switched to IVIg regardless of recovery after PE. No trial has been conducted to show whether patients who truly do not respond to one of these two treatments, may respond after switching to the other treatment.

Whether PE after IVIg should be considered remains unclear. One small retrospective study in 46 patients reported that treatment with IVIg followed by PE was not better than IVIg alone. On the contrary, the patients who received both treatments had a worse GBS disability grade at discharge and were longer hospitalised.  The researchers conclude that this could reflect a more severe disease course in patients receiving two treatments, but it could also suggest that PE washes out IVIg, thus preventing the therapeutic effects of IVIg.

Another option for patients who continue to deteriorate after initial treatment is to repeat the same regimen of treatment, being either PE or IVIg. Most studies on PE have investigated the effect of five exchanges. One trial showed that six PEs were not superior over four in already ventilated patients but the sixth course was given as part of the study protocol and not because of lack of
improvement. A second course of IVIg may be beneficial in patients who rapidly metabolise the administered IgG. Previous studies showed that a low-serum IgG increase 2 weeks after treatment is associated with more a severe disease course and poor outcome in comparison with patients who have a high IgG increase after treatment…

Current personal view: At present there is no evidence that outcome is improved by repeating treatment (either IVIg or PE) or switch to another type of treatment (level of evidence: 2). PE after IVIg should probably be avoided (level of evidence: 4).

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