Pathophysiology
The etiology of RPON is still unknown and remains controversial - some scientists believe that RPON is a subtype of migraine, while others believe that it is a neuropathic disorder. As such, different potential etiologic mechanisms have been proposed based on case reports, including migrainous and neuropathic mechanisms. Yet, the renaming of RPON from OM indicates that the neuropathic cause may play a more important role than the migrainous cause in the pathophysiology of RPON. Migrainous mechanism
RPON was previously thought to be having a migrainous origin since it shares some common characteristics with migraine, and their only differences are the intensity and duration of headaches. Therefore, it was postulated that migraine caused ophthalmoplegia in RPON. However, the major argument against a migrainous origin is the long latency period between the onset of headache and ophthalmoplegia (up to 14 days), which is not consistent with a typical migraine. Nevertheless, several migrainous mechanisms have been proposed. Nerve compression
Compression mechanism is the first theory postulated regarding the pathophysiology of RPON. It is proposed that headache is caused by direct pressure on CNIII (compression neuropathy) within the cavernous sinus due to edema of the walls of the internal carotid artery (ICA) or posterior cerebral artery (PCA) during migraine episodes. Ischemia
Cavernous section of the ICA and a perforating vessel from the proximal PCA are responsible for supplying CNIII, CNIV, and CNVI. During migraine attacks, vasoconstriction of the ICA and PCA may lead to a reversible and ischemic breakdown of the blood-brain barrier.
Cranial nerve enhancement resulted from RPON would gradually disappear as the symptoms subside after an episode, but spontaneous resolution of nerve enhancement is very unlikely to be seen in neoplastic (e.g. schwannoma), inflammatory and infectious diseases. Contrast-enhanced MRI results can also reveal the location of nerve inflammation for disease diagnosis. Although Tolosa–Hunt syndrome (THS) and RPON share many clinical features, THS can be identified by the presence of granulomatous inflammation in the cavernous sinus, superior orbital fissure, or orbit in MRI scans.Magnetic resonance angiography (MRA) or CT angiography (CTA) can be used to examine cerebral blood vessels and to rule out vascular abnormalities, such as an aneurysm. In cases where intracranial vascular lesions, for example, subarachnoid hemorrhage cannot be completely ruled out after performing MRA or CTA, physicians may consider using traditional digital subtraction angiography (DSA) for more detailed investigation. Laboratory tests
Lumbar punctures and blood tests might be performed on those with RPON to identify other possible causes of cranial neuropathy, including diabetes, inflammatory diseases, infections, tumors, and other systemic diseases that involve either the central nervous system or the peripheral nervous system. The detection of abnormalities in these tests suggests that RPON is highly unlikely to be the culprit in cranial neuropathy, and more diagnostic tests should be done to find out the underlying condition. Treatment
To date, no clinical trials or treatment guidelines for RPON have been published.