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Hypertrophic olivary degeneration after cerebellar hemorrhage
Journal of Clinical Neuroscience xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Case report
Hypertrophic olivary degeneration after cerebellar hemorrhage Gregory Walker, Kaustubh Limaye, Brian T. Jankowitz, Ashutosh P. Jadhav ⇑ University of Pittsburgh Medical Center, United States
a r t i c l e
i n f o
Article history: Received 15 March 2017 Accepted 22 May 2017 Available online xxxx Keywords: Intracerebral hemorrhage Hypertrophic olivary degeneration Dural arteriovenous malformation
a b s t r a c t We present a striking example of hypertrophic olivary degeneration after cerebellar hemorrhage. This case highlights some important teaching points: unique response of the inferior olivary nucleus to deafferentation, anatomy of Mollaret’s triangle and clinical manifestations of disruption in Mollaret’s triangle. The purpose of this teaching case is to highlight a rare but important post-stroke complication. Ó 2017 Elsevier Ltd. All rights reserved.
1. Case description An obese 57 year old man with no other significant past medical history presented with acute onset of vomiting, severe bi-frontal headache, vertigo and gait instability. On initial evaluation, he additionally complained of photophobia and a vertiginous sensation which was worse on standing and improved with eye closing. Initial physical exam was notable for hypertension (170/90 mmHg), truncal ataxia and somnolence with normal language, cranial nerve, motor and sensory function. Hematologic and coagulation profile was normal. Electrolytes, renal functions and liver functions were unremarkable. The initial computed topography of the head demonstrated an 8 cubic centimeter hemorrhage with involvement of the vermis, bilateral superior cerebella as well as the left dentate nucleus (Fig. 1A). There was compression of the cerebral aqueduct and 4th ventricle as well as mild mass effect and resultant enlargement of both lateral ventricles. There were no other foci of hemorrhage and notably, there was no hemorrhage within the parenchyma of the brainstem. The patient was intubated for neurologic deterioration and an extra-ventricular drain was then placed for concern of symptomatic hydrocephalus. Further workup included a catheter based angiogram which revealed the presence of a 2 cm 2 cm 1 cm superior vermian arteriovenous malformation (AVM) fed by both superior cerebellar arteries (SCA) with note of a feeding artery aneurysm measuring 4 mm (Fig. 1B). The venous drainage was deep via the vein of Galen and straight sinus (Fig. 1B). The patient
⇑ Corresponding author at: University of Pittsburgh Medical Center, 200 Lothrop St, Suite C-400, Pittsburgh, PA 15213, United States. Fax: +1 412 647 8445. E-mail address: [email protected] (A.P. Jadhav).
subsequently underwent coil embolization of the right SCA feeding artery aneurysm followed by Onyx liquid embolization of the AVM. Post procedure angiography runs demonstrated obliteration of the AVM (Fig. 1D). Patient was discharged to rehab two weeks after initial presentation. His neurological exam at that time was notable for moderate dysarthria, broken saccades, moderate truncal and upper extremity ataxia as well as cognitive injury involving attention, executive function, working and procedural memory. Extraocular movements, facial motor and sensory functions, hearing and all other lower cranial nerve functions were intact. A follow up MRI head at one month post presentation revealed evolution of the hemorrhage and persistent obliteration of the AVM. T2-weighted/ FLAIR sequence now revealed new hyper-intensity and hypertrophy of the inferior olivary nucleus, consistent with hypertrophic olivary degeneration (Fig. 1C). 2. Discussion We highlight a case of hypertrophic olivary degeneration (HOD), a rare condition which presents with a unique constellation of findings. Our case of left dentate nucleus hemorrhage allows us to revisit the instructive anatomical, histopathological and clinical features of this entity and discuss a novel element, as our case likely represents the most rapid onset of HOD reported to date. The condition of hypertrophic olivary degeneration was first reported by the German physiologist Oppenheim in 1887; however, it was not until 1931 that French physicians Guillain and Mollaret described the anatomy of this condition, providing a better understanding of the disease process. Hypertrophic olivary degeneration results from a disruption in the dentatorubro-olivary pathway (triangle of Guillain-Mollaret),
http://dx.doi.org/10.1016/j.jocn.2017.05.035 0967-5868/Ó 2017 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Walker G et al. Hypertrophic olivary degeneration after cerebellar hemorrhage. J Clin Neurosci (2017), http://dx.doi.org/ 10.1016/j.jocn.2017.05.035
2
Case report / Journal of Clinical Neuroscience xxx (2017) xxx–xxx
Fig. 1. (A) Non contrast CT head reveals a parenchymal hemorrhage involving the vermis, bilateral cerebella as well as the left dentate nucleus (blue arrow) (B) Cerebral angiogram reveals a superior cerebellar arterio venous malformation (AVM, purple arrow) fed by both superior cerebellar arteries with feeding artery aneurysm (red star). Venous drainage is deep and occurs via the Vein of Galen and straight sinus (blue arrows). (C) T2-weighted/FLAIR sequence on MRI brain performed in 1 month after initial presentation reveals hypertrophic olivary degeneration. (D) Cerebral angiogram which shows post embolization complete obliteration of the aneurysm (red star) and AVM (purple arrow). There is no early venous drainage.
a neuronal pathway represented bilaterally in the cerebellar hemispheres and the brainstem. A lesion of this triangle classically presents with delayed palatal myoclonus, a cyclic movement disorder of the soft palate. It may also present with ocular myoclonus, a rubral tremor and a variety of cranial neuropathies or cerebellar syndromes depending on the location of the lesion. Anatomically, the triangle begins in the dentate nucleus, deep in the superior cerebellar hemisphere. This nucleus then sends efferent fibers which exit through the superior cerebellar peduncle, decussate in the brachium conjunctivum and project to the contralateral red nucleus in the midbrain. The full range of functions of the red nucleus is not well characterized however it does provide basic flexor tone to the upper extremities through the descending motor rubrospinal tract. This dentato-rubral tract is thought to have complementary fine motor control [1]. From the red nucleus, the triangle continues down through the pons in the central tegmental tract and synapses on the inferior olivary nucleus (ION) of the ipsilateral ventrolateral medulla. From here there is a connection, the olivocerebellar tract, which runs from the ION, back over midline, into the cerebellum through the inferior cerebellar peduncle ending as communicating afferents onto the dentate nucleus. The unique pathophysiology of HOD is characterized by transsynaptic degeneration associated with proximal hypertrophy rather than atrophy. Six pathophysiologic phases have been proposed using work from a post mortem case series by Groto et al. The series tracked histopathological changes of HOD patients who had suffered pontine hemorrhages and expired at various
stages post ictus from 16.5 h to 10 months. The paradoxical hypertrophy of the ION is thought to be due to a result of de-afferentiation of the triangle causing neuronal cell body enlargement, vacuolation of the nerve cells, fibrillary gliosis and ION astrocyte proliferation [1–3]. Wallerian degeneration may play a role in this pathophysiology. Wallerian degeneration, however, is typically characterized by high signal intensity on MRI of the corticospinal tract as opposed to the inferior olivary nucleus. There are three typical patterns of hypertrophic olivary degeneration. In HOD, involvement is usually unilateral, as lesions are more commonly unilateral thus affecting only one triangle. In the ipsilateral pattern, a lesion anywhere from the red nucleus through the central tegmental tract will cause the ipsilateral ION to hypertrophy. In the second pattern, a lesion at the dentate nucleus or along the dentado-rubral tract will involve the contralateral ION. Lesions of the afferent olivo-cerebellar tract and its connections with the dentate nucleus are not felt to cause HOD [4]. Bilateral HOD is the least common pattern and can be caused by a larger lesion involving both triangles or multiple lesions [1–3]. One report exists of a unilateral lesion causing bilateral HOD [5]. In our case, we observed a unilateral left-sided dentate hemorrhage resulting in right sided HOD with normal MRI structure and signal on the left side. This fits the classical ‘‘contralateral” pattern. While not observed in this case, an interesting feature which is considered a hallmark of injury to the dentatorubro-olivary pathway (triangle of Guillain-Mollaret) is symptomatic palatal tremor. Symptomatic palatal myoclonus occurs in up to 25% of patients with HOD [5]. Compared with essential palatal tremor, symp-
Please cite this article in press as: Walker G et al. Hypertrophic olivary degeneration after cerebellar hemorrhage. J Clin Neurosci (2017), http://dx.doi.org/ 10.1016/j.jocn.2017.05.035
Case report / Journal of Clinical Neuroscience xxx (2017) xxx–xxx
tomatic palatal tremor can present with disruption of brainstem reflexes, cerebellar signs and lower cranial neuropathies. Classic distinguishing features also include the absence of an ‘‘ear clicking” sound and the tremor’s persistence in sleep. The exact mechanism underlying the tremor remains unclear but the accepted hypothesis involves interruption of GABAergic descending inhibition of the dentate-olivary tract during de-afferentiation of the triangle. These descending GABAergic inhibitory fibers synapse onto the gap junctions of the olivary neurons. Decreased tonic inhibition leads to hypersynchronous discharge which spreads across the ventrolateral medulla, at times exciting motor output to the palate. Olivary neurons are believed to have intrinsic oscillator property and the hypersynchronous discharge can therefore manifest as a symptomatic palatal tremor. Positron emission tomography studies in HOD patients have demonstrated an increase in medullary metabolism further strengthening the hypothesis that hyperactivity in the medulla may link hyper-synchrony in the inferior olive to olivary hypertrophy and eventually symptomatic palatal tremor [5– 7]. The delay in appearance of hypertrophy of the olive and of the palatal tremor can be due to the variable location of the lesion and the distance as well as the rate of de-afferentiation of the triangle. Radiographically, HOD is characterized initially by the presence of T2 hyper-intensity followed eventually by enlargement of the olivary nuclei. Hyperintensity on T2 has been reported to occur as early as 1 month, with hypertrophy reported at 4–6 months post ictus and commonly within 10 months [7,8]. The hypertrophy may resolve within 16 months, however the T2 hyper intensity which typically predates hypertrophy, can persist for years [6–8]. 3. Take home points
3
HOD occurs after disruption of the dentatorubro-olivary pathway (triangle of Guillain-Mollaret). T2 hyper-intensity of the inferior olivary nucleus is typically seen on brain MRI in a delayed fashion followed by hypertrophy. The hypertrophy then typically resolves but the hyperintensity can persist for years. HOD can occur in three different patterns: ipsilateral, contralateral or bilateral. Disruption of the Mollaret’s triangle can lead to palatal myoclonus, which occurs in approximately 25% of cases. Disclosure The authors report no relevant financial disclosures. References [1] Asal N, Yilmaz O, Turan A, et al. Hypertrophic olivary degeneration after pontine hemorrhage. Neuroradiology 2012;54:413–5. [2] Goto N, Kaneko M. Olivary enlargement: chronological and morphometric analysis. Acts Neuropthol (Berl) 1981;54:275–82. [3] Goto N, Kakimi S, Kaneko M. Olivary enlargement: stage of initial astrocytic changes. Cain Neuropathol 1988;7:39–43. [4] Salamon-Murayama N, Russell EJ, Rabin B. Diagnosis please. Case 17: hypertrophic olivary degeneration secondary to pontine hemorrhage. Radiology 1999;213:814–7. [5] Nishie Makoto, Yoshida Yasuji, Hirata Yutaka, et al. Generation of symptomatic palatal tremor is not correlated with inferior olivary hypertrophy. Brain 2002;125(6):1348–57. [6] Uchino A, Hasuo K, Uchida S. Olivar degeneration after cerebellar or brainstem hemorrhage. MRI Neuroradiol 1993;35:335–8. [7] Gerace C, Fele M, Luna R, et al. Neurological picture. Bilateral hypertrophic olivary degeneration. J Neurol Neurosurg Psychiatry 77:73. [8] Uchino A, Takase Y, Nomiyama K, et al. Brainstem and cerebellar changes after cerebrovascular accidents: magnetic resonance imaging. Eur Radiol 2006;16:592–7.
HOD is a rare type of de-afferentation resulting in hypertrophy of the affected structure.
Please cite this article in press as: Walker G et al. Hypertrophic olivary degeneration after cerebellar hemorrhage. J Clin Neurosci (2017), http://dx.doi.org/ 10.1016/j.jocn.2017.05.035
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Case report
Hypertrophic olivary degeneration after cerebellar hemorrhage Gregory Walker, Kaustubh Limaye, Brian T. Jankowitz, Ashutosh P. Jadhav ⇑ University of Pittsburgh Medical Center, United States
a r t i c l e
i n f o
Article history: Received 15 March 2017 Accepted 22 May 2017 Available online xxxx Keywords: Intracerebral hemorrhage Hypertrophic olivary degeneration Dural arteriovenous malformation
a b s t r a c t We present a striking example of hypertrophic olivary degeneration after cerebellar hemorrhage. This case highlights some important teaching points: unique response of the inferior olivary nucleus to deafferentation, anatomy of Mollaret’s triangle and clinical manifestations of disruption in Mollaret’s triangle. The purpose of this teaching case is to highlight a rare but important post-stroke complication. Ó 2017 Elsevier Ltd. All rights reserved.
1. Case description An obese 57 year old man with no other significant past medical history presented with acute onset of vomiting, severe bi-frontal headache, vertigo and gait instability. On initial evaluation, he additionally complained of photophobia and a vertiginous sensation which was worse on standing and improved with eye closing. Initial physical exam was notable for hypertension (170/90 mmHg), truncal ataxia and somnolence with normal language, cranial nerve, motor and sensory function. Hematologic and coagulation profile was normal. Electrolytes, renal functions and liver functions were unremarkable. The initial computed topography of the head demonstrated an 8 cubic centimeter hemorrhage with involvement of the vermis, bilateral superior cerebella as well as the left dentate nucleus (Fig. 1A). There was compression of the cerebral aqueduct and 4th ventricle as well as mild mass effect and resultant enlargement of both lateral ventricles. There were no other foci of hemorrhage and notably, there was no hemorrhage within the parenchyma of the brainstem. The patient was intubated for neurologic deterioration and an extra-ventricular drain was then placed for concern of symptomatic hydrocephalus. Further workup included a catheter based angiogram which revealed the presence of a 2 cm 2 cm 1 cm superior vermian arteriovenous malformation (AVM) fed by both superior cerebellar arteries (SCA) with note of a feeding artery aneurysm measuring 4 mm (Fig. 1B). The venous drainage was deep via the vein of Galen and straight sinus (Fig. 1B). The patient
⇑ Corresponding author at: University of Pittsburgh Medical Center, 200 Lothrop St, Suite C-400, Pittsburgh, PA 15213, United States. Fax: +1 412 647 8445. E-mail address: [email protected] (A.P. Jadhav).
subsequently underwent coil embolization of the right SCA feeding artery aneurysm followed by Onyx liquid embolization of the AVM. Post procedure angiography runs demonstrated obliteration of the AVM (Fig. 1D). Patient was discharged to rehab two weeks after initial presentation. His neurological exam at that time was notable for moderate dysarthria, broken saccades, moderate truncal and upper extremity ataxia as well as cognitive injury involving attention, executive function, working and procedural memory. Extraocular movements, facial motor and sensory functions, hearing and all other lower cranial nerve functions were intact. A follow up MRI head at one month post presentation revealed evolution of the hemorrhage and persistent obliteration of the AVM. T2-weighted/ FLAIR sequence now revealed new hyper-intensity and hypertrophy of the inferior olivary nucleus, consistent with hypertrophic olivary degeneration (Fig. 1C). 2. Discussion We highlight a case of hypertrophic olivary degeneration (HOD), a rare condition which presents with a unique constellation of findings. Our case of left dentate nucleus hemorrhage allows us to revisit the instructive anatomical, histopathological and clinical features of this entity and discuss a novel element, as our case likely represents the most rapid onset of HOD reported to date. The condition of hypertrophic olivary degeneration was first reported by the German physiologist Oppenheim in 1887; however, it was not until 1931 that French physicians Guillain and Mollaret described the anatomy of this condition, providing a better understanding of the disease process. Hypertrophic olivary degeneration results from a disruption in the dentatorubro-olivary pathway (triangle of Guillain-Mollaret),
http://dx.doi.org/10.1016/j.jocn.2017.05.035 0967-5868/Ó 2017 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Walker G et al. Hypertrophic olivary degeneration after cerebellar hemorrhage. J Clin Neurosci (2017), http://dx.doi.org/ 10.1016/j.jocn.2017.05.035
2
Case report / Journal of Clinical Neuroscience xxx (2017) xxx–xxx
Fig. 1. (A) Non contrast CT head reveals a parenchymal hemorrhage involving the vermis, bilateral cerebella as well as the left dentate nucleus (blue arrow) (B) Cerebral angiogram reveals a superior cerebellar arterio venous malformation (AVM, purple arrow) fed by both superior cerebellar arteries with feeding artery aneurysm (red star). Venous drainage is deep and occurs via the Vein of Galen and straight sinus (blue arrows). (C) T2-weighted/FLAIR sequence on MRI brain performed in 1 month after initial presentation reveals hypertrophic olivary degeneration. (D) Cerebral angiogram which shows post embolization complete obliteration of the aneurysm (red star) and AVM (purple arrow). There is no early venous drainage.
a neuronal pathway represented bilaterally in the cerebellar hemispheres and the brainstem. A lesion of this triangle classically presents with delayed palatal myoclonus, a cyclic movement disorder of the soft palate. It may also present with ocular myoclonus, a rubral tremor and a variety of cranial neuropathies or cerebellar syndromes depending on the location of the lesion. Anatomically, the triangle begins in the dentate nucleus, deep in the superior cerebellar hemisphere. This nucleus then sends efferent fibers which exit through the superior cerebellar peduncle, decussate in the brachium conjunctivum and project to the contralateral red nucleus in the midbrain. The full range of functions of the red nucleus is not well characterized however it does provide basic flexor tone to the upper extremities through the descending motor rubrospinal tract. This dentato-rubral tract is thought to have complementary fine motor control [1]. From the red nucleus, the triangle continues down through the pons in the central tegmental tract and synapses on the inferior olivary nucleus (ION) of the ipsilateral ventrolateral medulla. From here there is a connection, the olivocerebellar tract, which runs from the ION, back over midline, into the cerebellum through the inferior cerebellar peduncle ending as communicating afferents onto the dentate nucleus. The unique pathophysiology of HOD is characterized by transsynaptic degeneration associated with proximal hypertrophy rather than atrophy. Six pathophysiologic phases have been proposed using work from a post mortem case series by Groto et al. The series tracked histopathological changes of HOD patients who had suffered pontine hemorrhages and expired at various
stages post ictus from 16.5 h to 10 months. The paradoxical hypertrophy of the ION is thought to be due to a result of de-afferentiation of the triangle causing neuronal cell body enlargement, vacuolation of the nerve cells, fibrillary gliosis and ION astrocyte proliferation [1–3]. Wallerian degeneration may play a role in this pathophysiology. Wallerian degeneration, however, is typically characterized by high signal intensity on MRI of the corticospinal tract as opposed to the inferior olivary nucleus. There are three typical patterns of hypertrophic olivary degeneration. In HOD, involvement is usually unilateral, as lesions are more commonly unilateral thus affecting only one triangle. In the ipsilateral pattern, a lesion anywhere from the red nucleus through the central tegmental tract will cause the ipsilateral ION to hypertrophy. In the second pattern, a lesion at the dentate nucleus or along the dentado-rubral tract will involve the contralateral ION. Lesions of the afferent olivo-cerebellar tract and its connections with the dentate nucleus are not felt to cause HOD [4]. Bilateral HOD is the least common pattern and can be caused by a larger lesion involving both triangles or multiple lesions [1–3]. One report exists of a unilateral lesion causing bilateral HOD [5]. In our case, we observed a unilateral left-sided dentate hemorrhage resulting in right sided HOD with normal MRI structure and signal on the left side. This fits the classical ‘‘contralateral” pattern. While not observed in this case, an interesting feature which is considered a hallmark of injury to the dentatorubro-olivary pathway (triangle of Guillain-Mollaret) is symptomatic palatal tremor. Symptomatic palatal myoclonus occurs in up to 25% of patients with HOD [5]. Compared with essential palatal tremor, symp-
Please cite this article in press as: Walker G et al. Hypertrophic olivary degeneration after cerebellar hemorrhage. J Clin Neurosci (2017), http://dx.doi.org/ 10.1016/j.jocn.2017.05.035
Case report / Journal of Clinical Neuroscience xxx (2017) xxx–xxx
tomatic palatal tremor can present with disruption of brainstem reflexes, cerebellar signs and lower cranial neuropathies. Classic distinguishing features also include the absence of an ‘‘ear clicking” sound and the tremor’s persistence in sleep. The exact mechanism underlying the tremor remains unclear but the accepted hypothesis involves interruption of GABAergic descending inhibition of the dentate-olivary tract during de-afferentiation of the triangle. These descending GABAergic inhibitory fibers synapse onto the gap junctions of the olivary neurons. Decreased tonic inhibition leads to hypersynchronous discharge which spreads across the ventrolateral medulla, at times exciting motor output to the palate. Olivary neurons are believed to have intrinsic oscillator property and the hypersynchronous discharge can therefore manifest as a symptomatic palatal tremor. Positron emission tomography studies in HOD patients have demonstrated an increase in medullary metabolism further strengthening the hypothesis that hyperactivity in the medulla may link hyper-synchrony in the inferior olive to olivary hypertrophy and eventually symptomatic palatal tremor [5– 7]. The delay in appearance of hypertrophy of the olive and of the palatal tremor can be due to the variable location of the lesion and the distance as well as the rate of de-afferentiation of the triangle. Radiographically, HOD is characterized initially by the presence of T2 hyper-intensity followed eventually by enlargement of the olivary nuclei. Hyperintensity on T2 has been reported to occur as early as 1 month, with hypertrophy reported at 4–6 months post ictus and commonly within 10 months [7,8]. The hypertrophy may resolve within 16 months, however the T2 hyper intensity which typically predates hypertrophy, can persist for years [6–8]. 3. Take home points
3
HOD occurs after disruption of the dentatorubro-olivary pathway (triangle of Guillain-Mollaret). T2 hyper-intensity of the inferior olivary nucleus is typically seen on brain MRI in a delayed fashion followed by hypertrophy. The hypertrophy then typically resolves but the hyperintensity can persist for years. HOD can occur in three different patterns: ipsilateral, contralateral or bilateral. Disruption of the Mollaret’s triangle can lead to palatal myoclonus, which occurs in approximately 25% of cases. Disclosure The authors report no relevant financial disclosures. References [1] Asal N, Yilmaz O, Turan A, et al. Hypertrophic olivary degeneration after pontine hemorrhage. Neuroradiology 2012;54:413–5. [2] Goto N, Kaneko M. Olivary enlargement: chronological and morphometric analysis. Acts Neuropthol (Berl) 1981;54:275–82. [3] Goto N, Kakimi S, Kaneko M. Olivary enlargement: stage of initial astrocytic changes. Cain Neuropathol 1988;7:39–43. [4] Salamon-Murayama N, Russell EJ, Rabin B. Diagnosis please. Case 17: hypertrophic olivary degeneration secondary to pontine hemorrhage. Radiology 1999;213:814–7. [5] Nishie Makoto, Yoshida Yasuji, Hirata Yutaka, et al. Generation of symptomatic palatal tremor is not correlated with inferior olivary hypertrophy. Brain 2002;125(6):1348–57. [6] Uchino A, Hasuo K, Uchida S. Olivar degeneration after cerebellar or brainstem hemorrhage. MRI Neuroradiol 1993;35:335–8. [7] Gerace C, Fele M, Luna R, et al. Neurological picture. Bilateral hypertrophic olivary degeneration. J Neurol Neurosurg Psychiatry 77:73. [8] Uchino A, Takase Y, Nomiyama K, et al. Brainstem and cerebellar changes after cerebrovascular accidents: magnetic resonance imaging. Eur Radiol 2006;16:592–7.
HOD is a rare type of de-afferentation resulting in hypertrophy of the affected structure.
Please cite this article in press as: Walker G et al. Hypertrophic olivary degeneration after cerebellar hemorrhage. J Clin Neurosci (2017), http://dx.doi.org/ 10.1016/j.jocn.2017.05.035