High-Dose Intravenous Immunoglobulin Treatment and Cerebral Vasospasm: A Possible Mechanism of Ischemic Encephalopathy?

Abstract

A 46-year-old woman with a severe polyradiculoneuropathy treated with high-dose intravenous immunoglobulin (IVIg) presented an encephalopathy with increased blood flow velocities of the middle cerebral arteries (MCAs) detected by transcranial Doppler (TCD) studies. The similitude between this observation and another case recently reported of a patient suffering from Guillain-Barré syndrome (GBS) and cerebral blood flow abnormalities after IVIg treatment prompted us to investigate the responsibility of the IVIg therapy in the genesis of these blood flow alterations. We studied therefore by TCD 10 consecutive patients who underwent this treatment for different reasons. In 1 case we observed an asymptomatic, spontaneously reversible increase in the blood flow velocities of the MCAs consistent with a vasospasm and occurring 3–10 days after completion of the therapy. Stroke and ischemic encephalopathy have been reported as possible complications of IVIg treatment. In the case under discussion, clinical events appeared shortly after the administration of the IVIg therapy and responded favorably to a treatment with nimodipine. Other etiopathogenic mechanisms, in particular a CNS vasculopathic process related to the GBS itself, have to be considered as well. Further studies, with a larger number of patients, are therefore needed to evaluate the underlying mechanisms of blood flow abnormalities occurring sometimes in GBS patients after IVIg treatment.

Intravenous immunoglobulins contain naturally occurring antibodies that mimic antineutrophil cytoplasmic antibodies and activate neutrophils in a TNFα-dependent and Fc-receptor–independent way

“…Despite considerable improvements in the generation of IVIg preparations, a variety of adverse effects have been reported. [9][10][11][12][13][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]41,[54][55][56] Some of these side effects have been ascribed to the low content of IgG oligomers (aggregates) and dimers in the preparations that increase upon storage. Activation of the respiratory burst, generation of PAF, and degranulation of neutrophils can be triggered by IgG dimers and oligomers via Fc␥ RIIa receptors 57,58 without complexation to antigens and are thus believed to trigger some of the known clinical side effects.…”

“…[9][10][11][12] There are some mild common side effects like headache, fever, and chills, which are mainly transitory in nature and often related to the speed of infusion. 4,[13][14][15] However, potentially serious side effects such as ischemic encephalopathy, [16][17][18][19] cerebral infarction, [20][21][22][23][24][25][26][27] and aseptic meningitis [28][29][30][31][32][33] have been reported in patients treated with IVIg. These side effects are not uncommon.…”

“…These side effects are not uncommon. Sekul et al 28 reported aseptic meningitis to occur in up to 11% of patients treated with high-dose (2 g/kg) IVIg, and Sztajzel et al 19 found subclinical cerebral vasospasm to occur in 1 of 10 patients treated with IVIg. Frequently, these IVIg side effects are associated with an aseptic neutrophilic pleocytosis in cerebrospinal fluid (CSF), suggesting a neutrophil-mediated pathogenic mechanism.…”

Strokes after intravenous gamma globulin: Thrombotic phenomenon in patients with risk factors or just coincidence?

“…Other components may cause activation of thrombosis: elevated platelet counts [15], activation of platelets by IVIG [14], and increased fibrinogen levels [8]. Hyperviscosity induced acute ischemia and vasospasm of cerebral arteries [6][7][8]20] as well as the thrombogenic effects of the stabilizing agent used in the IG preparations (glucose, sucrose, maltose, or sorbitol) have the potential to trigger thrombosis [19].…”

“…Symptoms are usually transitory and related to the speed of the infusion, and they usually occur during the first or second infusion [3]. Aseptic meningitis with a self-limiting course [4] and severe headaches [5] may also occur, while transient encephalopathy was observed in 3 published cases [6][7][8]. More recently, cases of acute myocardial infarctions [9][10][11][12][13] and thrombotic events, some fatal [14][15][16][17][18][19], have also been observed.…”