Published ahead of print on July 8, 2010
doi: 10.3174/ajnr.A2198

American Journal of Neuroradiology 31:E82, October 2010
© 2010 American Society of Neuroradiology

P. Mariën^a
aDepartment of Neurology
Ziekenhuisnetwerk Antwerpen Middelheim General Hospital
Antwerp, Belgium

H.J. De Smet^b
bDepartment of Experimental Psychology
University of Ghent
Ghent, Belgium

P.F. Paquier^c
cDepartment of Neurology and Neuropsychology
University Hospital Erasme, Université Libre de Bruxelles
Brussels, Belgium

J. Verhoeven^d
dDepartment of Language and Communication Science
City University London
London, United Kingdom

We read the article of Miller et al¹ with great interest. In this retrospective study, the neuroimaging data of a group of 11 children with postoperative posterior fossa syndrome (PFS) and an age- and gender-matched control population who did not develop the syndrome were analyzed to evaluate whether pediatricpatients with postoperative PFS present with a consistent pattern of surgical damage and perfusion alterations at the supratentorial level as reflected by cerebellocerebral diaschisis (CCD). A consistent pattern of bilateral structural damage to the proximal efferent cerebellar pathway (pECP) was found in association with a significant decrease of cerebral blood flow, mainly within the frontal brain regions. Based on these findings, the authors concluded that bilateral surgical damage to the pECP is the primary cause of PFS and that predominantly frontal CCD acts as the underlying pathophysiologic mechanism.

We fully agree that the study of Miller et al¹ adds important evidence to current insights in the possible cause and pathophysiologic mechanism underlying the PFS, but we would like to point out that CCD has already been reported on several previous occasions as a possible explanation for transient postoperative mutism^2,3 and for the constellation of neurobehavioral and affective symptoms characterizing PFS in the pediatric population.^4–6 For instance, Mariën et al (2001, 2003)^4,6 reported the preliminary results of a prospective study in which the pathophysiologic role of CCD in PFS was explored. An illustrative patient was described who, in the preoperative phase, already presented with mild dysexecutive symptoms reflected on technetium 99m hexamethylpropyleneamine oxime single-photon emission CT (SPECT) by perfusional changes in the anatomo-clinically suspected prefrontal brain regions. After surgical resection of a posterior fossa medulloblastoma, full-blown PFS was associated with a significant aggravation and extension of the preoperative supratentorial perfusional deficits on repeat SPECT. When akinetic mutism receded and behavioral and affective distortions started to ameliorate after a 5-week period, a marked improvement of regional cerebral blood flow was objectified bilaterally in the prefrontal areas. By sharp contrast, no pre- and postoperative supratentorial perfusion alterations were observed in a child who did not develop PFS after posterior fossa tumor resection.

On the basis of the close parallelism between the development and course of neurobehavioral symptoms and perfusional changes on SPECT in the anatomo-clinically suspected supratentorial brain regions, we concluded that CCD might be intrinsically implicated in the pathophysiology of the PFS. As consistently reflected by CCD, the distant metabolic impact of surgical damage to the cerebellum via the dentatorubrothalamic tract on the supratentorial brain regions crucially involved in language dynamics and behavioral and affective regulation was later confirmed in an adolescent patient as well as in a larger study of 5 children with PFS.^7,8

The authors infer from the correlation between PFS symptoms and perfusional changes within the frontal lobe regions that”mutism in PFS is probably a speech apraxia rather than a simple dysarthria, dysphasia, or other cerebellar speech disorder.”¹ Although we are strongly inclined to support the view that patients with PFS, in addition to subsequent cerebellar dysarthria, may also present with higher level nonmotor speech and language disorders such as apraxia of speech or even aphasia, there still are no studies that substantiate the view of the apractogenic nature of the verbal output disorder following the phase of postoperative mutism.⁹ Given the fact that apraxic speech symptoms have already been described as CCD phenomena in adult patients after focal cerebellar damage, more systematic studies are needed to elucidate the exact nature and pathophysiologic substrate of speech and language phenomena following the phase of mutism in PFS.^10,11

References

1. Miller NG, Reddick WE, Kocak M, et al.Cerebellocerebral diaschisis is the likely mechanism of postsurgical posterior fossa syndrome in pediatric patients with midline cerebellar tumors. ANJR Am J Neuroradiol2010;31:288–94.Epub 2009 Oct 1[Abstract/Free Full Text]
2. Germano A, Baldari S, Caruso G, et al.Reversible cerebral perfusion alterations in children with transient mutism after posterior fossa surgery. Childs Nerv Syst 1998;14:114–19[CrossRef][Medline]
3. Sagiuchi T, Ishii K, Aoki Y, et al.Bilateral crossed cerebello-cerebral diaschisis and mutism after surgery for cerebellar medulloblastoma. Ann Nucl Med 2001;15:157–60[Medline]
4. Mariën P, Engelborghs S, Fabbro F, et al.The lateralized linguistic cerebellum: a review and new hypothesis. Brain Lang 2001;79:580–600[CrossRef][Medline]
5. Clerico A, Sordi A, Ragni G, et al.Brief report: transient mutism following posterior fossa surgery studied by single photon emission computed tomography (SPECT). Med Pediatr Oncol 2002;38:445–48[CrossRef][Medline]
6. Mariën P, Engelborghs S, Michiels E, et al.Cognitive and linguistic disturbances in the posterior fossa syndrome in children: a diaschisis phenomenon? Brain Lang 2003;87:162[CrossRef]
7. Baillieux H, De Smet HJ, Lesage G, et al.Neurobehavioral alterations in an adolescent following posterior fossa tumor resection. Cerebellum 2006;5:289–95[CrossRef][Medline]
8. De Smet HJ, Baillieux H, Wackenier P, et al.Long-term cognitive deficits following posterior fossa tumor resection: a neuropsychological and functional neuroimaging follow-up study. Neuropsychology 2009;23:694–704[CrossRef][Medline]
9. Riva D, Giorgi C.The cerebellum contributes to higher cognitive functions during development: evidence from a series of children surgically treated for posterior fossa tumors. Brain 2000;123:1051–61[Abstract/Free Full Text]
10. Mariën P, Verhoeven J, Engelborghs S, et al.A role for the cerebellum in motor speech planning? Evidence from a case with the foreign accent syndrome. Clin Neurol Neurosurg 2006;108:518–22.Epub 2005 Aug 1[CrossRef][Medline]
11. Cohen DA, Kurowski K, Steven MS, et al.Paradoxical facilitation: the resolution of foreign accent syndrome after cerebellar stroke. Neurology 2009;73:566–67[Free Full Text]

Reply

Published ahead of print on July 8, 2010
doi: 10.3174/ajnr.A2229

American Journal of Neuroradiology 31:E83, October 2010
© 2010 American Society of Neuroradiology

N.G. Miller^a, W.E. Reddick^a, M. Kocak^a, J.O. Glass^a, U. Löbel^a, B. Morris^a,A. Gajjar^a and Z. Patay^a
aSt. Jude Children’s Research Hospital
Memphis, Tennessee

We greatly appreciated the insightful comments of Mariën et al regarding our retrospective case-control study on posterior fossa syndrome (PFS).¹ We are aware of and recognize the significant work and contribution of our colleagues to the domain. The authors of the letter rightfully pointed out that cerebellocerebral diaschisis (CCD) has previously been proposed as a likely explanation for the pathomechanism of PFS, mostly in the context of sporadiccase studies of patients with PFS by using single-photon emissiontomography (SPECT) studies. For example, in 1998, 2 case studies used SPECT to demonstrate reversible hypoperfusion in the frontal cerebral cortex in patients who developed PFS.² In 2001, this was reiterated in a single case study demonstrating the same phenomenon.³ The authors of the letter also pointed out a review study on cerebellar function that appeared to link PFS to adiaschisis phenomenon via right-sided cerebellar damage.⁴ There was also a talk at the 41st Annual Meeting of the Academy of Aphasia on this topic.⁵

It is reassuring that there appears to be a growing consensus in the literature regarding this matter. As mentioned previously, the idea of CCD as a potential cause of PFS has been previously proposed from the interpretation of case observations, but the phenomenon had not yet been scientifically tested. Because of our study design, we can quite confidently state that patients who developed postsurgical PFS had specific changes in cerebral blood flow (very likely global, but dominantly frontal hypoperfusion) compared with those who did not develop this syndrome and that patients who developed PFS had a specific damage pattern to the proximal efferent cerebellar pathways compared with those who did not develop the syndrome. Additionally, our study appears to be the first to use dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging techniques to approach the matter. It is our hope that our contribution can be used by others to further characterize the manifestations of this disorder.

We inferred from the conclusions of our study and the clinical signs of acute PFS that the acute manifestation of PFS appeared to be a speech apraxia rather than a dysarthria or cerebellar ataxia. Mariën et al cited an article related to the behavioral disorders and other manifestations in patients undergoing posterior fossa surgery.⁶ The description in the study of acute PFS is very similar to our own experience: “All had normal involuntary palatal, lip, and tongue movements, but none of them could imitate tongue or lip movements on command.”⁶ The inability to perform a task while the motor functions required to do that task are intact seems to indicate apraxic dysfunction. As Mariën et al astutely mentioned, this applies to the initial mutism and not the subsequent verbal output disorder. Our study did not evaluate the long-term sequelae of PFS, and we have no comment on the etiology of subsequent disorders.

Our esteemed colleagues will be pleased to learn that since the submission of our manuscript, we have continued our research and found further evidence to validate the emerging concept of the development of postoperative PFS, which we intend to publish in the near future.

References

1. Miller NG, Reddick WE, Kocak M, et al. Cerebellocerebral diaschisis is the likely mechanism of postsurgical posterior fossa syndrome in pediatric patients with midline cerebellar tumors.ANJR Am J Neuroradiol 2010;31:288–94. Epub 2009 Oct 1[Abstract/Free Full Text]
2. Germano A, Baldari S, Caruso G, et al. Reversible cerebral perfusion alterations in children with transient mutism after posterior fossa surgery. Childs Nerv Syst 1998;14:114–19[CrossRef][Medline]
3. Sagiuchi T, Ishii K, Aoki Y, et al. Bilateral crossed cerebello-cerebral diaschisis and mutism after surgery for cerebellar medulloblastoma. Ann Nucl Med 2001;15:157–60[Medline]
4. Mariën P, Engelborghs S, Fabbro F, et al. The lateralized linguistic cerebellum: a review and new hypothesis. Brain Lang 2001;79:580–600[CrossRef][Medline]
5. Mariën P, Engelborghs S, Michiels E, et al. Cognitive and linguistic disturbances in the posterior fossa syndrome in children: a diaschisis phenomenon? Brain Lang 2003;87:162[CrossRef]
6. Riva D, Giorgi C. The cerebellum contributes to higher cognitive functions during development: evidence from a series of children surgically treated for posterior fossa tumors. Brain 2000;123:1051–61[Abstract/Free Full Text]