Annotation for CIBERNED
Spinal nerve involvement in early Guillain-Barré syndrome: the Haymaker and Kernohan’s legacy
José Berciano, MD, PhD
Service of Neurology, University Hospital “Marqués de Valdecilla (IDIVAL)”, Department of Medicine and Psychiatry, University of Cantabria (UC), “Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED)”, Santander, Spain
Journal of the Neurological Sciences 2017; 382: 1-9
Guillain-Barré syndrome (GBS) is an immune-mediated cause of acute neuromuscular paralysis, which encompasses acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal and motor-sensory axonal neuropathy (AMAN and AMSAN) and Fisher syndrome. Diagnosis of early GBS, defined as of 10 days of disease onset, may be challenging. Furthermore, autopsy studies of early GBS are scanty. This review paper is focused on the seminal contribution by Haymaker and Kernohan [Medicine (Baltimore) 1949; 28: 59-141], which is essential to understand the mechanisms of ascending paralysis and nerve conduction failure in any early GBS subtype.
Webb Haymaker and James Kernohan reported 50 clinico-pathological studies of fatal GBS cases, 32 of them having died between days 2 and 10 after onset. They established that the brunt of initial lesions, consisting of endoneurial oedema interpreted as degenerative, relied on spinal nerves. That this oedema was inflammatory was soon thereafter recognized. Two decades later, however, the pathogenic role of endoneurial oedema was disputed. In experimental allergic neuritis (EAN), considered an animal model of GBS, the initial lesion appearing on day 4 post-inoculation is marked inflammatory oedema in the sciatic nerve and lumbosacral nerve roots. Additional detailed clinico-pathological studies corroborated that the appearance of epi-perineurium at the subarachnoid angle, where anterior and posterior roots join to form the spinal nerve, is a pathological hotspot in early GBS, there developing inflammatory oedema, incipient demyelination and endoneurial ischemic zones with axonal degeneration. Furthermore, nerve ultrasonography has demonstrated predominant spinal nerve changes in early GBS, either AIDP or AMAN/AMSAN. Other outstanding Haymaker and Kernohan’s contributions were to clarify the complex nosology of the syndrome bringing under the same rubric Landry’s paralysis, acute febrile polyneuritis and GBS, and critically analyzing GBS exclusion criteria by then prevailing.
It is concluded that the authors’ legacy remains as relevant as ever, their pathological contributions to early GBS playing an irreplaceable role to understanding its physiopathology. Accepting the pathogenic role of endoneurial oedema in the first few days of the clinical course, there is a pressing need for new therapeutic strategies to stop its rapid impact on the axons, which in EAN appears at the height of the inflammatory process at 7 days post-inoculation.
Professor emeritus, University of Cantabria and CIBERNED
Santander, September 20, 2017