MR Imaging Evaluation of Inferior Olivary Nuclei: Comparison of Postoperative Subjects with and without Posterior Fossa Syndrome

Discussion

As previously stated, damage to the bilateral pECPs is the most widely accepted cause of postoperative PFS and cerebellar mutism.^{5,8⇓⇓⇓–12} Because of the anatomic overlap between the first segments of the dentatorubrothalamocortical pathway and the Guillain-Mollaret triangle, damage to the pECP leads to contralateral HOD.^{23⇓⇓⇓⇓–28} Therefore, damage to the bilateral pECPs should lead to the development of bilateral HOD on MR imaging, which may serve as a delayed surrogate imaging indicator of PFS. Indeed, the 100% positive predictive value yields a high confidence that a positive result (obtained by using bilateral HOD as a classifier) is truly indicative of PFS.

Although bilateral HOD has previously been associated with linguistic pathway abnormalities,^{29⇓⇓–32} we could not find any report of cerebellar mutism and linguistic abnormalities attributed to bilateral damage of the pECPs and with subsequent HOD in the ION. Most of the described cases in which unilateral HOD was observed on imaging did not have associated linguistic category findings,^{33⇓⇓⇓–37} though this was described in at least 1 study.³⁸

Bilateral HOD was not present in every case of clinically diagnosed PFS in our cohort. This divergence could be due to inconsistencies in the clinical diagnostic criteria because despite all ongoing effort and research, the diagnosis of PFS is sometimes still a judgment call, dependent on the investigator's experience. Our criteria of prolonged mutism and severe associated cerebellar syndrome with ataxia were used to differentiate PFS from other causes of postoperative speech disorders, including damage to the lower cranial nerves,¹³ psychological issues,³⁹ and medication-induced deficits. Indeed, at least one of our patients with PFS without bilateral HOD on MR imaging was described in the medical records as having immediate mutism following anesthesia recovery, a presentation that is not typical of cerebellar mutism, which generally appears an average of 1.7 days after surgery.^3,5,40 In fact, the immediate onset of mutism may indicate a bulbar abnormality from direct, inadvertent surgical injury to the lower cranial nerve nuclei¹³ rather than true cerebellar mutism in the context of PFS. We, therefore, recognize the challenges of differentiating cerebellar mutism from other forms of transient speech arrests in these patients during the postoperative period when other compounding clinical considerations occur concurrently.

Another reason that bilateral HOD was not always present in patients with PFS is that surgical damage is not necessarily a binary, all-or-none phenomenon. In other words, the magnitude of damage to the pECP that is needed to cause a critical drop of cerebellar input to the supratentorial brain may be different from the amount of damage leading the later to visible MR imaging changes of HOD. For example, one may hypothesize that most of the bilateral pECP fibers need to be destroyed to result in bilateral HOD, but somewhat less damage may be sufficient to cause a global frontal lobe dysfunction and resultant speech apraxia (ie, cerebellar mutism). Indeed, the 2 mechanisms causing PFS and HOD are likely different: one leading to frontal lobe dysfunction and mutism through reversed cerebellocerebral diaschisis; the other, to a peculiar form of degeneration associated with initial hypertrophy through a trans-synaptic mechanism with as yet poorly understood neurologic correlates.

Another unique clinical aspect of bilateral HOD in our patient cohort was the absence of palatal myoclonus in all patients, though this neurologic sign is commonly seen associated with HOD. The reason for this discrepancy is unclear. However, given that our cohort's lesions occurred in the specific circumstance of posterior fossa surgery and consistently in a specific location (ie, pECP) but other lesions in the literature often involved injury to the second, descending (rubro-olivary) segment of the Guillain-Mollaret triangle, an unidentified anatomic explanation may exist, such as involvement of brain stem structures immediately adjacent to the descending tegmental tracts in the development of palatal myoclonus.

The MR imaging signs and evolution of HOD-type changes are well-described, with pathologic evaluation first revealing 6 distinct stages after destruction of the central tegmental tracts: no olivary changes (within 24 hours), olivary amiculum degeneration (typically 2–7 days), olivary hypertrophy (approximately 3 weeks), culminant olivary enlargement (approximately 8.5 months), olivary pseudohypertrophy (9.5 months), and olivary atrophy (after a few years).²⁸ These findings were later classified into 3 stages on the basis of MR imaging of other cases and analysis of cases in the literature.^27,34 The first is seen with T2 and proton attenuation signal hyperintensity without hypertrophy and may occur as early as 4 weeks after injury. The second stage demonstrates hypertrophy starting approximately 4 months after injury extending until hypertrophy resolves approximately 3–4 years later. The third and final stage exhibits resolved hypertrophy with persistent high T2 and proton attenuation signal intensity and is noted to persist indefinitely. These concur with our observations.

We were fortunate that our retrospective analysis was performed on patients whose clinical imaging protocol had included both axial T2 and proton attenuation imaging. The proton attenuation sequence was often the most conclusive imaging sequence, especially on the earlier postoperative follow-up studies, as previously reported by others.⁴¹ However, our imaging protocol was not optimized to evaluate the ION, an area that is somewhat difficult to visualize on routine imaging and is often prone to artifacts. Our protocol was also limited by section thickness, which was routinely 5 mm. Because the olivary body measures approximately 1.25 cm, with the ION being in the bottom portion, only 1 or 2 sections could generally be obtained to evaluate the region of interest on traditional 5-mm imaging, with the possibility of significant partial volume averaging effects.

Our finding of unilateral HOD in patients with and without PFS may be due to the proposed process of 1 cerebellar hemisphere normally providing asymmetric input toward speech. There is no consensus in the literature as to which side provides more input, with an earlier article implicating the left cerebellar hemisphere⁴² and more recent articles implicating the right.^{43⇓⇓⇓–47} In cases in which we detected unilateral HOD, patients with PFS had unilateral right HOD, and patients without PFS had unilateral left HOD. Other articles described inconclusive findings.^38,48 Given the inconsistency between literature reports, it is possible that interindividual variations determine the dominant cerebellar hemisphere for speech and language production. Alternatively, complete damage to the dominant side may lead to PFS, even if damage to the subdominant pECP is partial, hence insufficient to cause corresponding HOD. This result would explain the few exceptions of clinical-imaging discrepancies (ie, clinical PFS syndrome in conjunction with unilateral HOD only).

Although bilateral HOD is not 100% sensitive for detecting PFS, these findings suggest that a threshold of damage to the pECPs is required for both MR imaging and clinical perceptibility. Future studies evaluating the degree of damage to the pECPs and defining PFS diagnostic criteria in a larger patient cohort with detailed clinical evaluation will be the next step in understanding this complex syndrome. Our data demonstrate that changes of HOD on MR imaging may be used in the future as an objective though a posteriori criterion in the diagnosis of PFS and may help clarify the definition of the clinical syndrome. Future evaluation will include prospective analysis of a larger cohort of patients with posterior fossa surgery who have PFS, with more robust diagnostic information (optimized imaging of the Guillain-Mollaret triangle and pECPs) and structured clinical information acquired and evaluated by experienced investigators to formulate standardized clinical and imaging diagnostic criteria for this complex, challenging syndrome.