Acta Neurochir (2013) 155:469–476 DOI 10.1007/s00701-012-1567-y
CLINICAL ARTICLE - VASCULAR
Hypertrophic olivary degeneration following surgical resection or gamma knife radiosurgery of brainstem cavernous malformations: an 11-case series and a review of literature Jung-Ho Yun & Jae Sung Ahn & Jung Cheol Park & Do Hoon Kwon & Byung Duk Kwun & Chang Jin Kim
Received: 6 August 2012 / Accepted: 13 November 2012 / Published online: 6 December 2012 # Springer-Verlag Wien 2012
Abstract Background We describe 11 patients with hypertrophic olivary degeneration (HOD) after surgical resection or gamma knife radiosurgery for brainstem cavernous malformations. In addition, we statistically analyzed the predicting factors associated with the development of HOD. Methods From January 2001 to May 2011, a total of 73 patients (30 in the surgical group and 43 in the radiosurgery group) with brainstem cavernous malformations were treated in our institute. Of them, 11 patients (incidence: 15 %) developed HOD with high signal intensity on T2-weighted MRI during follow-up. The predicting factors (location, size, age, and treatment method) associated with the development of HOD were statistically analyzed. Results Among the 11 HOD patients, seven patients received surgical resection and four patients received gamma knife radiosurgery. Six patients had bilateral HOD and the remaining five patients had unilateral HOD. Overall HODassociated symptoms presented in four patients, including three palatal tremors and one ataxia. In all four patients with symptoms, these symptoms disappeared incompletely within the clinical follow-up period. The size of the cavernous malformation, age of patient, and treatment methods were not significantly correlated with the development of HOD. A significantly higher incidence of HOD was associated with midbrain cavernous malformations than with pontine or medulla cavernous malformations.
J.-H. Yun : J. S. Ahn (*) : J. C. Park : D. H. Kwon : B. D. Kwun : C. J. Kim Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, 388-1, Pungnap-2 dong, Songpa-gu, Seoul 138-736, South Korea e-mail:
[email protected]
Conclusions HOD should be recognized as a noninfrequent complication of surgical resection or gamma knife radiosurgery within the brainstem, especially for midbrain cavernous malformations. In addition, to the best of our knowledge, this is the first report on HOD development after radiosurgery. Keywords Hypertrophic olivary degeneration . Brainstem cavernous malformation . Surgical resection . Gamma knife radiosurgery
Introduction Hypertrophic olivary degeneration (HOD) is an unusual neuronal degenerative condition involving inferior olivary nuclei with increased T2-weighted signal intensity on magnetic resonance imaging (MRI). The first description of HOD was by Oppenheim [16] in 1887, but the development of HOD was described widely by Guillain and Mollaret [10] in 1931, who showed that this condition occurs by injury of the anatomical dentato–ruburo–olivary connections, which is referred to as the Guilllain-Mollaret Triangle (GMT). The GMT is composed of the contralateral dentate nucleus (DN) of the cerebellum, the ipsilateral red nucleus (RN) of the mesencephalon, and the inferior olivary nucleus (ION) of the medulla. Injuries to these connections are most commonly caused by cerebrovascular events, including infarction or hemorrhage, but can also include traumatic head injury, direct manipulation, neoplastic disease and demyelinative or infectious disease. There are various brainstem diseases, but we have experience with HOD following treatment for brainstem cavernous malformation (BSCM). We were therefore interested in
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understanding the causes and clinical course of HOD. Although limited HOD cases have been reported after surgical resection of BSCM (Table 1), we present 11 patients who had HOD after surgical resection or gamma knife radiosurgery for BSCM and analyzed the predicting factors associated with the development of HOD. In addition, we report the first study on four cases of HOD that developed after gamma knife radiosurgery (GKRS).
Materials and methods Patient population The medical records of patients who underwent surgical resection or GKRS for BSCM from January 2001 through May 2011 were retrospectively reviewed. A total of 73 patients (30 in the surgical group and 43 in the radiosurgery group) with BSCM were treated in our institute. Among these 73 patients with BSCM, 11 cases (15 %) showing HOD in follow-up MRI with or without symptom were selected for this study. The multiplicity of BSCM, time interval between symptom onset and treatment, bleeding after treatment, HOD-associated symptoms, and last HOD symptom states were reviewed retrospectively. Clinical and radiological follow-up of HOD We investigated HOD-associated symptoms in all patients, and reviewed each case until the last follow-up period. Clinical follow-up ranged from 2 to 36 months with a mean of 21 months. Radiologic follow-up was performed by T2weighted and fluid-attenuated inversion recovery (FLAIR)
MRI. If patients complained of HOD-related symptoms, we immediately performed a follow-up MRI. If the patients had no HOD-associated symptoms or had improved symptoms, we undertook a follow–up MRI at a mean of 12 months (range, 3–15 months) after treatment. The predicting factors associated with the occurrence of HOD In this study, we assumed that possible factors associated with the development of HOD are the following: location, size, age, and treatment method. In all 73 patients, these possible factors were compared between the HOD and non-HOD groups. The correlation of each factor with the occurrence of HOD was analyzed statistically by univariate regression analysis using the chi-square test (SPSS 17.0). P values of less than 0.05 were considered statistically significant.
Results The characteristics of the 11 HOD cases are summarized in Table 2. HOD cases were divided into two groups based on treatment method: seven cases in the surgical group and four cases in the GKRS group (Table 3). Patients 3 and 8 received surgical resection followed by GKRS. In these cases, we performed partial resection of the cavernous malformation by surgery. No evidence of HOD was seen by brain MRI in both cases for radiosurgical planning; therefore, these patients were enrolled in the radiosurgery group. The time interval from HOD diagosis to treatment was a mean of 7.7 months (range, 1–12 months) in the surgical group and 9.5 months (range, 3–15 months) in the radiosurgery group. Bilateral
Table 1 Summary of previous eight cases of HOD that developed after surgical resection of the brainstem cavernous malformation Reference
Age/sex
Lesion/CM site
Time To Dx HOD (months)
Size of lesion (mm)
HOD site
Surgical approach
Symptom associated HOD
Phatouros and McConchie [17] Tsui et al. [21]
14/F
Pontine/Lt
13
25
–
–
–
43/F
Pontine/Rt
7
–
–
SOC
PT
Harter and Davis [12]
32/M
3
20
Lt
SOC/transvermian
–
Hornyak and Osborn [13]
44/M
Ponto-mesencephalic junction/Lt Pontine/Lt
4
12
Lt
PT
50/F
Pontine/Lt
17
14
Lt
53/M
6
8
Both
47/F
Ponto-mesencephalic junction/Midline Mesencephalic/Lt
6
25
Both
35/F
Pontine/Lt
7
–
Lt
Midline SOC/ transvermian Midline SOC/ transvermian Midline SOC/ transvermian Frontal craniotomy transcallosal –
Gatlin and Wineman [7]
PT – PT –
M male, F female, CM cavernous malformation, Lt left, Rt right, Dx diagnosis, HOD hypertrophic olivary degeneration, SOC suboccipital craniotomy, PT palatal tremor
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Table 2 Summary of the characteristics of the eleven cases of HOD in this study Case no.
Age Location (years)/ of CM sex
Size of Time To Site of Tx/resection lesion (mm) Dx HOD HOD state (months)
Case 1
51/M
Lt MB
13×15
5
Both
Para-median SOC/total
Case 2
56/F
Lt MB pons
14×15
7
Both
Midline SOC/total –
Case 3
29/F
Lt MB-dorsal
13×14 10×6
3
Lt
Lt STC/subtotal 5 months After op GKRS
Case 4
22/M
Lt pons
12×15
7
Lt
Midline SOC/total –
Case 5
57/F
Rt pons
14×17
12
Rt
Midline SOC/total –
Case 6
37/F
Rt pons
32×26
10
Rt
Midline SOC/total –
Case 7
9/F
Rt pons
14×15
1–12
Both
Case 8
60/F
Rt pons dorsal
16×17
6
Both
Midline SOC/ subtotal Midline SOC/ subtotal 7 months after op GKRS
10×8 Case 9
67/M
Case 10 25/F Case 11 34/M
Lt pons-mid Lt MBventral Rt pons
6×5
14
Lt
GKRS
10×8
15
Both
GKRS
18×15
1
Both
Midline SOC/ subtotal
Reference dose/ Initial Sx/Sx prescription dose of HOD (isodose level)
Follow-up duration (months)/ final Sx
Hmr (recent months)
– –
Lt motor Ataxia/none
36/Sx free
None
Lt facial numbness/PT Rt side weakness/PT
18/Sx persist Yes (1)
– 28 Gy/14 Gy (50 %)
22/Sx persist Yes (1)
Rt facial numbness/none lt side weakness/none Dysarthria & diplopia/none Rt 6th nerve palsy/none Lt side weakness/PT
– –
27/Sx persist None 12/Sx free
None
38/Sx persist Yes (1) 24/Sx free
Yes (2)
7/Sx persist
Yes (8)
26/Sx free
None
27/Sx free
Yes (1)
24 Gy/12 Gy (50 %) 28 Gy/14 Gy (50 %) 21 Gy/12 Gy (57 %) –
Rt side weakness/none Lt diplopia/none
Lt side 2/Sx persist weakness/ataxia
Yes (8)
M male, F female, CM cavernous malformation, MB midbrain, Lt left, Rt right, Dx diagnosis, Imp improve, Tx treatment, HOD hypertrophic olivary degeneration, Sx symptom, SOC suboccipital craniotomy, STC subtemporal craniotomy, PT palatal tremor, Hmr hemorrhage
HOD was seen in four of seven patients in the surgery group and two of four in the radiosurgery group. HOD-associated symptoms occurred in four of 11 patients, and included one palatal tremor and one ataxia in the surgery group and two palatal tremors in the radiosurgery group. The time interval between symptom onset and treatment was a mean of 4 months in the surgical group and a mean of
3.5 months in the radiosurgery group; there were no significant statistically differences between the two groups. In the four patients with symptoms, these symptoms had resolved incompletely until the last clinical follow-up period. Potential factors associated with the development of HOD in all BSCM patients showed no significant differences in terms of the size of the BSCM, treatment methods, and patient
Table 3 Summary of two HOD groups according to treatment methods
Surgical HOD group (total number07)
Gamma knife HOD group (total number04)
Location Midbrain (%)
1 (14 %)
2 (50 %)
Pons (%)
6 (86 %)
2 (50 %)
Medulla (%)
0 (0 %)
0 (0 %)
Time interval between symptom onset and treatment (months) Time interval between HOD diagnosis and treatment (months) HOD-associated symptoms
Mean 4 (range 1–13)
Mean 3.5 (range 1–8)
Mean 7.7 (range 1–12)
Mean 9.5 (range 3–15)
Number (%)
2 (28 %)
2 (50 %)
Symptom detail
1 palatal tremor, 1 ataxia
2 palatal tremor
Symptom onset after treatment (month)
4 and 6
1 and 5
Number of bilateral HODs (%)
4 (57 %)
2 (50 %)
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age. There was only a significant statistical difference in the location of the BSCM (Table 4). A higher incidence of midbrain cavernous malformation was seen in the HOD group than in the pontine or medulla cavernous malformation group.
Case descriptions Case 1: surgical group A 51-year-old man with a 5-month history of a slowly developed paresthesia of the right upper extremity was admitted to our institute. An initial MRI showed a 4 mm× 3 mm sized, hyperintense lesion in the midbrain (left side tectal area), which was diagnosed as a BSCM. After follow– up for 5 months with close observation, the patient’s symptoms had deteriorated. MRI demonstrated an acute hemorrhage and hemosiderin staining within the left midbrain (Fig. 1a, b). Neurological evaluation at that time revealed dysarthria without tough tremor or palsy, paresthesia of the right upper extremity, and gait ataxia without other cranial nerve palsy. We performed microsurgical resection of the BSCM via a paramedian suboccipital craniotomy with a transtentorial approach-assisted brain navigation system. Intraoperatively, the lesion did not extend into other structures other than the midbrain on the left tectal area, and the cavernoma was seen at the surface of the midbrain. Surgery with gross total removal was performed without any complications, and cavernous malformation was confirmed histopathologically. At discharge, the patient showed remarkable improvement in dysarthria and mild improvement in initial ataxia and paresthesia of the right upper extremity. Five months after surgery,
the patients visited our hospital again due to progressive ataxia and dysarthria with soft palate tremor that was not found in the initial admission. Laryngoscopy examination of the involuntary tremor localized it to the vocal cord and pharynx. MRI showed hypertrophy of the contralateral side olivary lesion on T2-weighted MRI (Fig. 1c). In 13 months follow-up T2weighted MRI image showed bilateral high signal intensity and hypertrophy in both inferior olivary nuclei (Fig. 1d). There was no abnormal contrast enhanced lesion with intravenous gadolinium. The patient’s palatal tremor improved with the administration of the clonazepam. At the last follow-up examination 3 years after the operation, his tremor was well controlled, but ataxia and paresthesia persisted. Case 9: radiosurgery group A 67-year-old man presented with new onset diplopia and headache. Physical examination revealed a right sixth nerve palsy and grade 4 hemiparesis. MRI showed a 6 mm×5 mm sized hemosiderin-stained lesion with an acute hemorrhage at the left dorsal pons. The diagnosis was BSCM. Conservative treatment was commenced, and after 4 months, surpassing the acute hemorrhage period, the treatment of the lesion was accomplished using GKRS with a 14-Gy prediscription dose of 50 %. The patient recovered well and had a significant gradual improvement in diplopia and right side weakness. Fifteen months after radiosurgery, follow-up MRI showed a decrease in the area of the lesion and a new lesion in the inferior olivary nucleus, which had high signal change in T2-weighted MRI (Fig. 2a, b). At that time, the patient no longer complained of diplopia and right side weakness. The MRI findings supported the diagnosis of bilateral HOD.
Table 4 The predicting factors associated with the development of HOD Total
HOD, number (%)
Non-HOD, number (%)
73
11 (15)
62 (85)
midbrain
9
3 (33)
pons
51
8 (16)
43 (84)
medulla
13
0 (0)
13 (100)
20 mm
34 12
8 (24) 2 (17)
26 (76) 10 (83)
60 years
26 5
4 (15) 1 (20)
22 (85) 4 (80)
surgical resection
30
7 (23)
23 (77)
radiosurgery
43
4 (9)
39 (91)
Total number
P value
Location 6 (67) 0.031
Size 0.079
Age 0.786
Treatment method 0.182
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Fig. 1 Initial MRI scans of case 1. a Axial T1-weighted, preoperative MRI revealed a cavernous malformation in the left dorsal mesencephalon with recent bleeding. b Coronal unenhanced T1-weighted MRI detected a cavernous malformation with recent bleeding at the left mesencephalon. Follow–up MRI scans of case 1. c Five months after surgery, axial T2-weighted image showed unilateral high signal lesions in the right inferior olivary nucleus (broken arrow), and (d) 18 months after surgery, axial T2-weighted imagery showed bilateral high signal lesions in both inferior olivary nuclei (arrow)
One year later, repeated MRI showed no interval changes of the bilateral HOD and significantly diminished cavernous malformation lesion (Fig. 2c, d).
Discussion HOD is associated with pathological changes occurring due to injury of the anatomical dentato–ruburo–olivary connection and caused by trans-synaptic degeneration with neuronal vacuolization and hypertrophy, including increased gliotic reaction [8]. Degenerative patterns of neurons can also be observed in many regions, such as the optic pathway, the dorsal root ganglion and the dentate nucleus [1]. However, it is very unusual that the size of the neuron cell increases rather than decreases [3]. Electron microscopy has shown marked proliferation of mitochondria and increased neuronal size due to neurofilamentous proliferation and cytoplasmic vacuolization through the formation of rough endoplasmic reticulum vesicles [14]. Consequentially, the main pathological findings of inferior olivary hypertrophy are hypertrophic vacuolization, hypertrophy of the astrocyte, and gliotic reaction.
Birbamer et al. [4] described the evolution of olivary changes after acute lesion onset by assessing MRI data. These authors suggested three stages: (1) the acute stage without olivary changes, (2) olivary enlargement and increased signal on T2-weighted and proton densityweighted MRI, and (3) the persistence stage of increased signal on T2-weighted and proton density-weighted MRI with disappearance of the hypertrophic olivary nucleus. Goto et al. [8] have reported that general radiographic changes in HOD correlate with its pathological findings [8]. MRI showed high signal intensity in T2-weighted imaging within about 3 weeks after an insult. Although olivary hypertrophic changes on pathological investigation typically vanish in 10–16 months, olivary hyperintensity on T2weighted images can persist for years after resolution of the hypertrophy. However, Goyal et al. [9] identified increased olivary signal on T2-weighted images first appearing 1 month after the inciting lesion and persisting for at least 3–4 years. On the other hand, the authors showed that olivary hypertrophy initially developed 6 months after the acute event and resolved by 3–4 years. In our current study, the period from onset to MRI of the HOD ranged from 1 to 15 months; these findings would
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Fig. 2 Initial and follow-up MRI scans of case 9. a, b Axial T2-weighted preoperative MRI revealed a cavernous malformation in the left pontine lesion. c At 14 months after gamma knife procedure, axial T2-weighted image showed ipsilateral high signal lesions in the inferior olivary nucleus (broken arrow). d At 2 years after the gamma knife procedure, a high signal lesion on an axial T2-weighted image persisted without any structure changes (arrow)
correspond to the second stage as described by Birbamer et al. [4]. Case 1 showed a unilateral HOD 4 months after an insult, but a bilateral lesion occurred 1 year later. This means that imaging of that lesion may persist even after pathological changes. However, as in our case 1, radiologically abnormal lesion and clinical symptom do not necessarily coincide. The patient’s symptom can be improved even if the lesion progressed in radiological study. When the primary lesion is involved only in the central tegmental tract (CTT), olivary hypertrophy occurs on the ipsilateral side. When the primary lesion is contained within the DN or in the superior cerebellar peduncle (SCP), olivary hypertrophy occurs on the contralateral side. However, when the lesion affects both the CTT or affects both the SCP, olivary hypertrophy is bilateral. Tsui et al. [21] also presented a case of bilateral HOD after involvement of the ipsilateral CTT as well as the surrounding areas of the ipsilateral SCP, which may have disrupted the ipsilateral CTT and the dentato-rubral fibers ascending to the contralateral RN. This is due to decussation of the dentate-rubral fibers [23].
In this study, we can predict if a one-sided BSCM simultaneously involved in the ipsilateral CTT and contralateral SCP, HOD developed bilaterally (Fig. 3b). On the other hand, in midline BSCM, bilateral HOD developed if both CTTs and SCPs were involved simultaneously (Fig. 3a, c). A primary insult in the brain stem lesion is the most common factor underpinning cerebrovascular events, including infarction or hemorrhage. In addition, traumatic head injury [3], malignant tumor [18] (astrocytoma, metastasis, lymphoma), demyelination (multiple sclerosis), infectious or inflammatory disease [11] (tuberculosis, acquired immune deficiency syndrome, sarcoidosis), and surgical manipulation during the operation can contribute to this insult [22]. We found that 4 of 43 of our present patient subjects developed HOD following GKRS. HOD occurrence after surgical resection is very rare. In addition, to the best of our knowledge, this is the first report of HOD occurrences after radiosurgery. Therefore, we can postulate that HOD can develop due to radiation effects of indirect surgical treatment similar to cerebrovascular events including hemorrhage or
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Fig. 3 Illustration of the Guilllain-Mollaret Triangle (GMT) involved in bilateral HOD. Bilateral HODs can develop when ipsilateral central tegmental tract and contralateral superior cerebellar peduncles are simultaneously involved in ipsilateral BSCM (b). In midline BSCM, bilateral HOD develops when both superior cerebellar peduncles (a) are involved, or both central tegmental tracts (c) are involved. Insult of the both inferior olivary nuclei (ION) is less likely to occur to HOD. A circle indicates red nucleus (RN), square dentate nucleus (DN), triangle inferior olivary nucleus (ION); a red line indicates superior cerebellar peduncle (SCP), blue line central tegmental tract (CTT), gray line inferior cerebellar peduncle (ICP)
infarction, although the exact underlying mechanism is unknown. The differential diagnosis of HOD is often difficult because of the similarity of radiological results as like infarction and neoplastic disease. If the lesion is strictly restricted to only one or both inferior olive, with preserving surrounding structures, HOD should be strongly suspected. Macht et al. [15] documented that the most important diagnostic point for hypertrophic olivary degeneration is in the detection of an initiating pathological change in the GMT, separated from the inferior olivary nucleus. Therefore, this remote primary lesion from the inferior olivary nucleus is the most important clue to distinguishing HOD from other cerebrovascular events. In addition, the time interval between HOD diagnosis and insult onset is also indicative of HOD. However, this diagnostic clue may not be seen immediately after brainstem insult, as this typically occurs in a delayed fashion. Hypertrophy of the olive reaches its maximum around the same time (approximately 8.5 months after the injury) as the peak of olivary enlargement demonstrated on MRI [2]. Also, the default of contrast enhancement limited to the inferior olivary nucleus, and typical symptoms such as palatal tremor or ocular myoclonus may help in the diagnosis. Considering these important points for a successful differential diagnosis, HOD after injury to any component of the GMT should not be confused with typical
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cerebrovascular events (infarction or hemorrhage), neoplastic disease, or other primary pathological conditions of the medulla. The clinical presentation of HOD is palatal tremor, dentatorubral tremor (Holmes tremor), and ocular myoclonus. Palatal tremor has been described as an involuntary movement of the oropharynx, including the soft palate, tongue, and uvula. The pathogenesis of palatal tremor is known; the failure of ascending gamma-aminobutyric acid control induces excessive simultaneous expression of the olivary nuclei [19]. Although almost all cases of palatal tremor are seen together with HOD, not all cases of HOD are accompanied by palatal tremor [20]. As a typical but not essential clinical manifestation, palatal tremor usually develops within 10– 11 months following initial onset and often persists throughout life [6]. Other symptoms most commonly detailed in association with HOD are paresthesia, ataxia, dysarthria, diplopia, hemiparesis, low limb spasticity, hypoesthesia and dysmetria [5]. In our current study, HOD-associated symptoms were detected in four patients with clinical follow-up ranging from 2 to 36 months (mean, 21 months). Three palatal tremors and one ataxia developed in our HOD group. Despite medical and conservative treatment, the symptoms of all four patients did not completely improve until last clinical follow-up period. Generally, the incidence of HOD following surgery is unknown, but Hornyak et al. [13] reported four cases of HOD following surgical resection in BSCM. They suggested that HOD developed in a delayed manner in most of these cases, and symptomatic HOD accounted for 75 % (3 of 4) of those cases. In our study cohort, the incidence of HOD was 15 % (11 of 73), but that of symptomatic HOD indicating the importance of the clinical course was only 5.4 % (4 of 73). Although the incidence of HOD is very low in the entire disease group, it is not an infrequent complication in the treated BSCM group. In addition, this can be explained by missing the HOD if patient symptoms are absent and a follow-up radiological study is not performed. The incidence of HOD in our surgery group was higher than that of the radiosurgery group, which may be due to selection bias, i.e. patients with an exacerbation of clinical symptoms were more likely to be candidates for surgical treatment. Our current study has some noteworthy limitations, mostly stemming from its small number of cases and short follow-up period. In addition, two patients underwent combined treatment (surgical resection and radiosurgery), rather than sole treatment. Although we took the last treatment to underlie the etiology of HOD, we cannot exclude the possibility of an effect of combined treatment in the development of HOD in those two cases. Lastly, we used univariate regression analysis, not multivariate analysis, to analyze the factors associated with the occurrence of HOD because of small number of cases.
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No previous report exists on radiation-induced HOD, and we propose that the indirect insult of radiation treatment can lead to the development of HOD although the mechanism remains unknown. Further studies will be required to ascertain the long-term follow-up results of HOD-induced symptoms (palatal tremor, ataxia, ocular myoclonus, and Holmes tremor) and the mechanism of radiation-induced HOD as the final course of this degenerative disease remains unknown.
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10.
11.
12.
13.
Conclusions We describe 11 patients who presented with HOD after surgical resection or GKRS for BSCM. Our report suggests that both surgical trauma and the radiation effect of GKRS could lead to the development of HOD. Especially, location of BSCM was the only predictive factor leading to HOD. We conclude that HOD should be recognized as a potential and not infrequent complication of surgical resection or radiosurgery within the brainstem, especially in midbrain cavernous malformation. Therefore, it is important not to confuse HOD with an infarction, hemorrhage, malignancy, and inflammatory or infectious diseases and we should be able to suspect this degenerative phenomenon and avoid unnecessary further investigations.
14.
15.
16. 17. 18.
19.
20. Conflicts of interest None. 21.
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Comment This is a very interesting article. Brain stem lesions have been considered untouchable by many for a long time, but with advances in microsurgery and the development of less invasive radiosurgical tools, there is an increased willingness to enter this region and treat/operate upon different pathologies. Given the relatively benign course of cavernomas, post-surgical or radiosurgical effects are observable and their course possible to follow. It is of note that whichever is the intervention, the likelihood of development of hypertrophic olivary degeneration is the same, and it is reassuring to note that the changes are not always permanent. Andras Kemeny Sheffield, UK
