A rare case of Miller Fisher variant of Guillain-Barré Syndrome (GBS) induced by a checkpoint inhibitor.

With the recent development of novel, more potent cancer treatment, in particular, immune 'checkpoint inhibitors', cases of neurological immune-related adverse events are on the rise. Although rare, this includes Guillain-Barré Syndrome (GBS). We present the case of a 68-year-old male who was admitted with sudden onset of worsening neurological symptoms following immunotherapy treatment. These symptoms progressed quickly to respiratory failure requiring intubation and admission to the intensive care unit. He was thoroughly investigated and is believed to have an axonal neuropathy in the form of Miller Fisher Syndrome (MFS) variant of GBS, secondary to immunotherapy treatment. He was initially treated with intravenous immunoglobulin, and later, perhaps more effectively, with high dose steroids which significantly improved his symptoms. This case of checkpoint inhibitor-induced MFS is one of few in the literature and is an important reminder of the potential for new immunotherapeutic agents to cause significant neurotoxic effects. These should be promptly and thoroughly investigated, in particular, as the management of these patients can differ from standard treatments used in these conditions.

[Neurological complications during treatment of the tumor necrosis alpha inhibitors]. / Powiklania neurologiczne w przebiegu leczenia inhibitorami przeciwcial monoklonalnych.

Medications with TNF-alpha inhibitors family are successfully applicable in rheumatology, gastroenterology, dermatology and neurology. Still, the ongoing research on the safety assessment of their application, also due to neurological complications. The vast majority of these complications is associated with an increased risk of serious virus (Herpes simplex--JC) and bacterial (Listeria monocytogenes) neuroinfections. They can cause the occurrence of progressive multifocal leukoencephalopathy--PML with a severe clinical course and poor prognosis or herpes simplex encephalitis--HSE. Meta-analysis revealed a number of cases of PML and the HSE in the first 6 months of treatment with natalizumab, efalizumab, rituximab, abatacept and infliximab. Common complication occasionally turning on this biologics is chronic demyelinating polyneuropathy or Lewis-Sumner syndrome. Described are cases of central and peripheral demyelination typical of multiple sclerosis (MS). Are also reported cases of motor multifocal neuropathy with conduction block acute encephalithis with polyneuropathy or mononeuropathy in the form of anterior optic neuropathy Guillen-Barre' syndrome and its variant, Miller-Fisher syndrome have been confirmed as adverse events following treatment with infliximab. Also revealed several cases of myasthenia gravis after using etanercept. In the few cases of systemic lupus CNS involvement caused by treatment with TNF inhibitors, the mechanism of these disorders is still considered too vague. Due to the emerging reports on the number of neurological adverse events of TNF antagonists, significantly higher than those described in the literature, the safety of their use requires further monitoring and multicenter studies.

Guillain-Barré and Miller Fisher syndromes occurring with tumor necrosis factor alpha antagonist therapy.

OBJECTIVE: Diverse neurologic syndromes have been described in association with tumor necrosis factor alpha (TNFalpha) antagonist therapy for inflammatory arthritides and Crohn's disease. The objective of this study was to review the occurrence and clinical features of Guillain-Barré syndrome and its variant, the Miller Fisher syndrome, during TNFalpha antagonist therapy. METHODS: The postmarketing database of the US Food and Drug Administration (FDA) was searched, following our experience with a patient with rheumatoid arthritis in whom the Miller Fisher syndrome variant of the Guillain-Barré syndrome developed while he was receiving infliximab therapy. RESULTS: Our index patient had a neurologic illness defined initially by ataxia and dysarthria, which fluctuated in relation to each subsequent infliximab infusion and, after 6 months, culminated in areflexic flaccid quadriplegia. In addition, 15 patients in whom Guillain-Barré syndrome developed following TNFalpha antagonist therapy were identified from the FDA database. Guillain-Barré syndrome developed following infliximab therapy in 9 patients, following etanercept therapy in 5 patients, and following adalimumab therapy in 1 patient. Among the 13 patients for whom followup data were available, 1 patient experienced no resolution, 9 patients had partial resolution, and 3 patients had complete resolution of Guillain-Barré syndrome following therapy. CONCLUSION: An association of Guillain-Barré syndrome with TNFalpha antagonist therapy is supported by the worsening of neurologic symptoms that occurred in our index patient following each infusion of infliximab, and by the temporal association of this syndrome with TNFalpha antagonist therapy in 15 other patients. An acute or subacute demyelinating polyneuropathy should be considered a potential adverse effect of TNFalpha antagonist therapy.