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Pure upbeat nystagmus in association with bilateral internuclear ophthalmoplegia
Journal of the Neurological Sciences 317 (2012) 148–150
Contents lists available at SciVerse ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Short communication
Pure upbeat nystagmus in association with bilateral internuclear ophthalmoplegia☆ Jae-Hwan Choi a, Na-Yeon Jung a, Min-Ji Kim a, Kwang-Dong Choi a,⁎, Ji Soo Kim b, Dae-Soo Jung a a b
Department of Neurology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Republic of Korea Department of Neurology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Republic of Korea
a r t i c l e
i n f o
Article history: Received 27 December 2011 Received in revised form 27 February 2012 Accepted 29 February 2012 Available online 24 March 2012 Keywords: Upbeat nystagmus Internuclear ophthalmoplegia Medial longitudinal fasciculus
a b s t r a c t A 66-year-old man developed primary position upbeat nystagmus and bilateral internuclear ophthalmoplegia (INO). Video-oculography showed primary position upbeat nystagmus with exponentially decreasing slow phases, which disappeared in darkness. Brain MRI disclosed enhancing lesions involving bilateral dorsomedial pons extending from the middle to upper portion. Upbeat nystagmus in association with bilateral INO may be attributed by the damage of the cell groups of the paramedian tracts (PMT), the projections from the interstitial nucleus of Cajal (INC) to PMT, or the connections between INC and the nucleus of Roller. © 2012 Elsevier B.V. All rights reserved.
1. Introduction
2. Report of a case
Upbeat nystagmus mostly occurs in brainstem lesions [1,2]. In ventral pontine tegmental lesions, upbeat nystagmus has been attributed to damage of the ventral tegmental tract (VTT) that carries a signal for upward vestibulo-ocular reflex (VOR) while in caudal medullary lesions, it has been ascribed to involvement of the nucleus Roller, one of the perihypoglossal nuclei which might contribute to vertical oculomotor integration [1]. However, pure upbeat nystagmus in straight ahead position of gaze has not been described in association with bilateral internuclear ophthalmoplegia (INO) from pontine tegmental lesion involving the medial longitudinal fasciculus (MLF). Although upbeat nystagmus has been reported in a few patients with unilateral INO [3,4], recent three-dimensional recordings of eye movements documented torsional-vertical nystagmus (jerky seesaw nystagmus) in all 33 patients with unilateral INO, which may be caused by a disruption of neural pathway from the contralateral vertical semicircular canals with or without concomitant damage to the fibers from the contralateral utricle in or near the MLF [5]. We report pure upbeat nystagmus in the primary position in a patient with bilateral INO due to dorsomedial pontine tegmental lesions.
This study protocol was approved by the Institutional Review Board at Pusan National University Medical School and informed consent was obtained from the patient.
☆ This study was supported by a grant of the Korean Heath Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A070001). ⁎ Corresponding author at: Department of Neurology, College of Medicine, Pusan National University, Pusan National University Hospital, 1-10 Ami-dong, Seo-gu, Busan, 602-739, Republic of Korea. Tel.: + 82 51 240 7317; fax: + 82 51 245 2783. E-mail address: [email protected] (K.-D. Choi). 0022-510X/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2012.02.036
A 66-year-old man presented with horizontal diplopia and oscillopsia for 3 weeks. He had no associated headache or ocular pain, and denied any preceding illnesses. Neurological examination showed pure upbeat nystagmus in the primary position with fixation (Video). The nystagmus disappeared in darkness. It was enhanced during upgaze and convergence, and decreased in downward gaze. He had adduction paresis with dissociated abducting nystagmus in both lateral gazes, which were consistent with bilateral INO. Impaired adduction was similar for saccades, smooth pursuit, the VOR, and convergence. Vertical head impulse tests did not reveal any catch-up saccades. Other neurological examinations were unremarkable. Three-dimensional videooculography (SMI, Germany) disclosed pure upbeat nystagmus with exponentially decreasing slow phases (Fig. 1). It was not modified by vibratory stimulations on both mastoids, hyperventilation, horizontal and vertical head-shaking, or varying head positions. Upward smooth pursuit was continuously interrupted by the upbeat nystagmus while the gain of downward smooth pursuit was normal. Results from complete blood counts, serum chemistry, autoimmune antibody screening, and chest radiography were normal. CSF analyses were normal with negative Gram staining and oligoclonal bands. CSF cultures were negative for bacterial, viral, Mycobacterium tuberculosis, or fungal growth. Brain MRI showed hyperintensities in bilateral dorsomedial pons extending from the middle to upper portion on T2- and diffusionweighted images, and apparent diffusion coefficient map (Fig. 2A–H). Gadolinium-enhanced T1-weighted images revealed enhancement in
J.-H. Choi et al. / Journal of the Neurological Sciences 317 (2012) 148–150
149
Fig. 1. Video-oculography (SMI, Teltow, Germany) shows primary position upbeat nystagmus with exponentially decreasing slow phases. Upward deflection in each tracing indicates upward movements of the eyes. LV—vertical position of the left eye; RV—vertical position of the right eye.
the corresponding lesions on T2-weighted images (Fig. 2I–L). Evaluation for underlying cancers was unremarkable. With a suspicion of focal brainstem encephalitis or vasculitis we tried intravenous dexamethasone administration. Upbeat nystagmus and bilateral INO markedly improved. 3. Comment Our patient developed pure upbeat nystagmus in association with bilateral INO from dorsomedial pontine lesions affecting the MLF. Since the MLF contains the pathways involved in the generation of vertical VOR, the upbeat nystagmus may be ascribed to selective damage to the upward VOR pathways [2]. However, the decreasing slow phase velocities of the nystagmus, disappearance in darkness, and normal head impulse tests in the vertical plane are more consistent with deficient neural integrator function rather than imbalance in the vertical VOR. The major contributor for vertical gaze holding is the interstitial nucleus of Cajal (INC) in the midbrain. The cell groups of the paramedian tracts (PMT) between the MLFs, both rostral and caudal to the abducens nuclei are also involved in the gaze holding by receiving
inputs from all premotor structures involved in horizontal and vertical eye movements, and by projecting to the flocculus [6]. One PMT cell group in the medulla is the nucleus pararaphales, which receives inputs from INC, and projects to the flocculus and ventral paraflocculus [7]. Such signals could be important for vertical gaze-holding. The projections from INC are known to descend to PMT in MLF [8]. Accordingly, upbeat nystagmus in our patient may be attributed to the damage of PMT or the projections from INC to PMT. However, pharmacological inactivation of the rostral PMT subgroup produces downbeat nystagmus with vertical gaze-holding impairment rather than pure upbeat nystagmus [1]. Alternatively, the disruption of connections between INC and the nucleus of Roller may generate upbeat nystagmus in MLF lesions. Patients with caudal medullary lesions showed upbeat nystagmus by affecting the paramedian part of bilateral posterior tegmentum [1,2]. The nucleus of Roller appears to play a role in upward vestibular eye movements and vertical oculomotor integration since it receives projections from SVN and INC, and projects strongly to the flocculus [8]. The projections from INC also terminate within the nucleus of Roller via MLF [9].
Fig. 2. Brain MRIs disclose hyperintensities in bilateral dorsomedial pons extending from the middle to upper portion on T2- (A–D) and diffusion-weighted (E and F) images, and apparent diffusion coefficient map (G and H) (arrow heads). (I–L) Gadolinium-enhanced T1-weighted images reveal enhancement in the corresponding lesions on T2-weighted images (arrows).
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J.-H. Choi et al. / Journal of the Neurological Sciences 317 (2012) 148–150
Supplementary materials related to this article can be found online at doi:10.1016/j.jns.2012.02.036. References [1] Pierrot-Deseilligny C, Milea D. Vertical nystagmus: clinical facts and hypotheses. Brain 2005;128:1237–46. [2] Kim JS, Yoon B, Choi KD, Oh SY, Park SH, Kim BK. Upbeat nystagmus: clinicoanatomical correlations in 15 patients. J Clin Neurol 2006;2:58–65. [3] Troost BT, Martinez J, Abel LA, Heros RC. Upbeat nystagmus and internuclear ophthalmoplegia with brainstem glioma. Arch Neurol 1980;37:453–6. [4] Tilikete C, Milea D, Pierrot-Deseilligny C. Upbeat nystagmus from a demyelinating lesion in the caudal pons. J Neuroophthalmol 2008;28:202–6.
[5] Jeong SH, Kim EK, Lee J, Choi KD, Kim JS. Patterns of dissociated torsional-vertical nystagmus in internuclear ophthalmoplegia. Ann N Y Acad Sci 2011;1233:271–8. [6] Büttner-Ennever JA, Horn AK. Pathways from cell groups of the paramedian tracts to the floccular region. Ann N Y Acad Sci 1996;781:532–40. [7] Büttner-Ennever JA, Horn AKE, Schmidtke K. Cell groups of the medial longitudinal fasciculus and paramedian tracts. Rev Neurol 1989;145:533–9. [8] Langer T, Fuchs AF, Scudder CA, Chubb MC. Afferents to the flocculus of the cerebellum in the rhesus macaque as revealed by retrograde transport of horseradish peroxidase. J Comp Neurol 1985;235:1–25. [9] Aldes LD, Boone TB. Does the interstitial nucleus of cajal project to the hypoglossal nucleus in the rat? J Neurosci Res 1984;12:553–61.
Contents lists available at SciVerse ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Short communication
Pure upbeat nystagmus in association with bilateral internuclear ophthalmoplegia☆ Jae-Hwan Choi a, Na-Yeon Jung a, Min-Ji Kim a, Kwang-Dong Choi a,⁎, Ji Soo Kim b, Dae-Soo Jung a a b
Department of Neurology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Republic of Korea Department of Neurology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Republic of Korea
a r t i c l e
i n f o
Article history: Received 27 December 2011 Received in revised form 27 February 2012 Accepted 29 February 2012 Available online 24 March 2012 Keywords: Upbeat nystagmus Internuclear ophthalmoplegia Medial longitudinal fasciculus
a b s t r a c t A 66-year-old man developed primary position upbeat nystagmus and bilateral internuclear ophthalmoplegia (INO). Video-oculography showed primary position upbeat nystagmus with exponentially decreasing slow phases, which disappeared in darkness. Brain MRI disclosed enhancing lesions involving bilateral dorsomedial pons extending from the middle to upper portion. Upbeat nystagmus in association with bilateral INO may be attributed by the damage of the cell groups of the paramedian tracts (PMT), the projections from the interstitial nucleus of Cajal (INC) to PMT, or the connections between INC and the nucleus of Roller. © 2012 Elsevier B.V. All rights reserved.
1. Introduction
2. Report of a case
Upbeat nystagmus mostly occurs in brainstem lesions [1,2]. In ventral pontine tegmental lesions, upbeat nystagmus has been attributed to damage of the ventral tegmental tract (VTT) that carries a signal for upward vestibulo-ocular reflex (VOR) while in caudal medullary lesions, it has been ascribed to involvement of the nucleus Roller, one of the perihypoglossal nuclei which might contribute to vertical oculomotor integration [1]. However, pure upbeat nystagmus in straight ahead position of gaze has not been described in association with bilateral internuclear ophthalmoplegia (INO) from pontine tegmental lesion involving the medial longitudinal fasciculus (MLF). Although upbeat nystagmus has been reported in a few patients with unilateral INO [3,4], recent three-dimensional recordings of eye movements documented torsional-vertical nystagmus (jerky seesaw nystagmus) in all 33 patients with unilateral INO, which may be caused by a disruption of neural pathway from the contralateral vertical semicircular canals with or without concomitant damage to the fibers from the contralateral utricle in or near the MLF [5]. We report pure upbeat nystagmus in the primary position in a patient with bilateral INO due to dorsomedial pontine tegmental lesions.
This study protocol was approved by the Institutional Review Board at Pusan National University Medical School and informed consent was obtained from the patient.
☆ This study was supported by a grant of the Korean Heath Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A070001). ⁎ Corresponding author at: Department of Neurology, College of Medicine, Pusan National University, Pusan National University Hospital, 1-10 Ami-dong, Seo-gu, Busan, 602-739, Republic of Korea. Tel.: + 82 51 240 7317; fax: + 82 51 245 2783. E-mail address: [email protected] (K.-D. Choi). 0022-510X/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2012.02.036
A 66-year-old man presented with horizontal diplopia and oscillopsia for 3 weeks. He had no associated headache or ocular pain, and denied any preceding illnesses. Neurological examination showed pure upbeat nystagmus in the primary position with fixation (Video). The nystagmus disappeared in darkness. It was enhanced during upgaze and convergence, and decreased in downward gaze. He had adduction paresis with dissociated abducting nystagmus in both lateral gazes, which were consistent with bilateral INO. Impaired adduction was similar for saccades, smooth pursuit, the VOR, and convergence. Vertical head impulse tests did not reveal any catch-up saccades. Other neurological examinations were unremarkable. Three-dimensional videooculography (SMI, Germany) disclosed pure upbeat nystagmus with exponentially decreasing slow phases (Fig. 1). It was not modified by vibratory stimulations on both mastoids, hyperventilation, horizontal and vertical head-shaking, or varying head positions. Upward smooth pursuit was continuously interrupted by the upbeat nystagmus while the gain of downward smooth pursuit was normal. Results from complete blood counts, serum chemistry, autoimmune antibody screening, and chest radiography were normal. CSF analyses were normal with negative Gram staining and oligoclonal bands. CSF cultures were negative for bacterial, viral, Mycobacterium tuberculosis, or fungal growth. Brain MRI showed hyperintensities in bilateral dorsomedial pons extending from the middle to upper portion on T2- and diffusionweighted images, and apparent diffusion coefficient map (Fig. 2A–H). Gadolinium-enhanced T1-weighted images revealed enhancement in
J.-H. Choi et al. / Journal of the Neurological Sciences 317 (2012) 148–150
149
Fig. 1. Video-oculography (SMI, Teltow, Germany) shows primary position upbeat nystagmus with exponentially decreasing slow phases. Upward deflection in each tracing indicates upward movements of the eyes. LV—vertical position of the left eye; RV—vertical position of the right eye.
the corresponding lesions on T2-weighted images (Fig. 2I–L). Evaluation for underlying cancers was unremarkable. With a suspicion of focal brainstem encephalitis or vasculitis we tried intravenous dexamethasone administration. Upbeat nystagmus and bilateral INO markedly improved. 3. Comment Our patient developed pure upbeat nystagmus in association with bilateral INO from dorsomedial pontine lesions affecting the MLF. Since the MLF contains the pathways involved in the generation of vertical VOR, the upbeat nystagmus may be ascribed to selective damage to the upward VOR pathways [2]. However, the decreasing slow phase velocities of the nystagmus, disappearance in darkness, and normal head impulse tests in the vertical plane are more consistent with deficient neural integrator function rather than imbalance in the vertical VOR. The major contributor for vertical gaze holding is the interstitial nucleus of Cajal (INC) in the midbrain. The cell groups of the paramedian tracts (PMT) between the MLFs, both rostral and caudal to the abducens nuclei are also involved in the gaze holding by receiving
inputs from all premotor structures involved in horizontal and vertical eye movements, and by projecting to the flocculus [6]. One PMT cell group in the medulla is the nucleus pararaphales, which receives inputs from INC, and projects to the flocculus and ventral paraflocculus [7]. Such signals could be important for vertical gaze-holding. The projections from INC are known to descend to PMT in MLF [8]. Accordingly, upbeat nystagmus in our patient may be attributed to the damage of PMT or the projections from INC to PMT. However, pharmacological inactivation of the rostral PMT subgroup produces downbeat nystagmus with vertical gaze-holding impairment rather than pure upbeat nystagmus [1]. Alternatively, the disruption of connections between INC and the nucleus of Roller may generate upbeat nystagmus in MLF lesions. Patients with caudal medullary lesions showed upbeat nystagmus by affecting the paramedian part of bilateral posterior tegmentum [1,2]. The nucleus of Roller appears to play a role in upward vestibular eye movements and vertical oculomotor integration since it receives projections from SVN and INC, and projects strongly to the flocculus [8]. The projections from INC also terminate within the nucleus of Roller via MLF [9].
Fig. 2. Brain MRIs disclose hyperintensities in bilateral dorsomedial pons extending from the middle to upper portion on T2- (A–D) and diffusion-weighted (E and F) images, and apparent diffusion coefficient map (G and H) (arrow heads). (I–L) Gadolinium-enhanced T1-weighted images reveal enhancement in the corresponding lesions on T2-weighted images (arrows).
150
J.-H. Choi et al. / Journal of the Neurological Sciences 317 (2012) 148–150
Supplementary materials related to this article can be found online at doi:10.1016/j.jns.2012.02.036. References [1] Pierrot-Deseilligny C, Milea D. Vertical nystagmus: clinical facts and hypotheses. Brain 2005;128:1237–46. [2] Kim JS, Yoon B, Choi KD, Oh SY, Park SH, Kim BK. Upbeat nystagmus: clinicoanatomical correlations in 15 patients. J Clin Neurol 2006;2:58–65. [3] Troost BT, Martinez J, Abel LA, Heros RC. Upbeat nystagmus and internuclear ophthalmoplegia with brainstem glioma. Arch Neurol 1980;37:453–6. [4] Tilikete C, Milea D, Pierrot-Deseilligny C. Upbeat nystagmus from a demyelinating lesion in the caudal pons. J Neuroophthalmol 2008;28:202–6.
[5] Jeong SH, Kim EK, Lee J, Choi KD, Kim JS. Patterns of dissociated torsional-vertical nystagmus in internuclear ophthalmoplegia. Ann N Y Acad Sci 2011;1233:271–8. [6] Büttner-Ennever JA, Horn AK. Pathways from cell groups of the paramedian tracts to the floccular region. Ann N Y Acad Sci 1996;781:532–40. [7] Büttner-Ennever JA, Horn AKE, Schmidtke K. Cell groups of the medial longitudinal fasciculus and paramedian tracts. Rev Neurol 1989;145:533–9. [8] Langer T, Fuchs AF, Scudder CA, Chubb MC. Afferents to the flocculus of the cerebellum in the rhesus macaque as revealed by retrograde transport of horseradish peroxidase. J Comp Neurol 1985;235:1–25. [9] Aldes LD, Boone TB. Does the interstitial nucleus of cajal project to the hypoglossal nucleus in the rat? J Neurosci Res 1984;12:553–61.