Case Reports / Journal of Clinical Neuroscience 19 (2012) 1597–1599 1597 Downbeat nystagmus due to a paramedian medullary lesion ⇑ Kiyotaka Nakamagoe a, , Kotone Shimizu a, Tadachika Koganezawa b, Akira Tamaoka a a Department of Neurology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan b Department of Cardiovascular Physiology, Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan article info abstract

Article history: Cell groups of the paramedian tract, which are located in the paramedian region of the lower brainstem, Received 14 March 2012 are eye-movement-related neurons that project to the cerebellar flocculus. Their inactivation produces Accepted 17 March 2012 downbeat nystagmus, which resembles eye movement disorders resulting from lesions of the cerebellar flocculus in animal experiments. Therefore, paramedian tract cells are assumed to fulfill an important function in ocular movement control, such as gaze-holding and maintaining vestibular balance. This Keywords: paper presents a 50-year-old female who manifested downbeat nystagmus due to damage to the para- Cerebellum median tract cells caused by a localized ischemic lesion in the medulla oblongata. We found that a par- Cerebral infarction amedian medullary lesion-induced nystagmus, similar to that observed following floccular lesions, Downbeat nystagmus Flocculus clearly indicates that a subgroup of paramedian tract cells projecting to the flocculus was impaired. This Brainstem finding has important implications in considering a brainstem–cerebellar feedback loop involved in ves- Neural integrator tibulo-oculomotor controls, such as vestibular balance. Although there have been a few reports of down- Paramedian tract neuron beat nystagmus caused by lesions in the midline region of the lower brainstem, to our knowledge none report the occurrence of nystagmus due to a strictly localized medullar lesion, such as the one described here. Ó 2012 Elsevier Ltd. All rights reserved.

1. Introduction 2. Case report

Vertical nystagmus due to small lesions in the lower brainstem We present a 50-year-old female who, at 42 years of age, mani- often manifests as upbeat nystagmus. Downbeat nystagmus, how- fested right-sided lateral medullary syndrome caused by occlusion ever, is often caused by cerebellar floccular lesions.1 Groups of cells of the right posterior inferior cerebellar artery. Her brain MRI in the paramedian tract (PMT) occur in and around the medial lon- showed a small, new ischemic lesion in the right lateral portion of gitudinal fasciculus in the paramedian region of the lower brain- the medulla oblongata. However, she led a normal life afterwards stem. These PMT cells project to the cerebellar flocculus and are without symptoms of nystagmus. At 47 years of age she manifested involved in ocular movement.2,3 Although PMT cells have long dizziness and oscillopsia and visited our clinic with persistent oscil- been suggested to have an important role in eye movement con- lopsia on lateral gaze 3 months after the onset of symptoms. Her trol, the mechanism and clinical relevance are poorly understood. neurological examinations revealed downbeat nystagmus during Only limited evidence is available from animal experiments3 and fixation, and mild, crossed sensory deficits in the right part of the clinical studies4–6 on downbeat nystagmus associated with im- face, left extremities, and trunk, but she had no ataxia or paralysis. paired PMT cells. Previous right-sided lateral medullary syndrome was suspected to We present a patient with downbeat nystagmus due to a dam- be responsible for the crossed sensory disturbances. Her downbeat aged subgroup of PMT cells caused by a localized lesion in the par- nystagmus lasted more than 3 years from the onset of symptoms. amedian region of the medullary tegmentum. An ischemic lesion in the right dorsal paramedian portion

Fig. 1. (A) Midsagittal brain T1-weighted MRI showing low-intensity lesions in the medulla oblongata (arrow); and (B) axial brain T2-weighted MRI showing punctate, high- intensity lesions in the tegmentum and the right paramedian region of the dorsal medulla oblongata (arrow). These lesions, which are probably small infarctions, are believed to be responsible for nystagmus.

⇑ Corresponding author. Tel./fax: +81 29 853 3224. E-mail address: [email protected] (K. Nakamagoe). 1598 Case Reports / Journal of Clinical Neuroscience 19 (2012) 1597–1599 of the medulla oblongata was shown in thin-slice brainstem MRI by the upward and downward eye positions of the eyes in the or- (Fig. 1). bit, or the position of the head. The patient’s eye movements were also recorded with electro- nystagmography (First, Tokyo, Japan), using a direct current (DC) recording technique. Downbeat nystagmus was observed in the 3. Discussion light and in the dark, and in the absence of fixation (rapid phase: velocity, 61.7°/s; amplitude, 4.7°; and slow phase: velocity, 14.9°/ The MRI revealed an ischemic lesion in the paramedian tegmen- s; amplitude, 4.4°; frequency, 2.1/s) (Fig. 2). Downbeat nystagmus tal region of the medulla oblongata after nystagmus, the lesion was was accentuated in the lateral eye position and was not influenced in the paramedian region in which cell groups of PMT are located;

Fig. 2. Electronystagmography recording (direct current) of eye movement in the absence of fixation (eyes open in the dark): upper – vertical eye position; lower – corresponding eye movement velocity. Downbeat nystagmus lowering in the fast-phase and rising in the slow-phase was noted.

Fig. 3. Schematic of the pathogenesis of downbeat nystagmus showing how vertical eye movement might be generated by events starting with cell groups of paramedian tract (PMT) neurons impaired by lesions in the lower brainstem, attenuating the activity of floccular Purkinje cells. Upward eye movements are induced that constitute the slow phase of nystagmus, which is then followed by the compensatory fast-phase beating in a downward direction, resulting in downbeat nystagmus. G = cerebellar granule cells, P = Purkinje cells. Case Reports / Journal of Clinical Neuroscience 19 (2012) 1599–1601 1599 hence, the lesion was suspected to be responsible for the observed be responsible for central vestibular imbalance in the vertical downbeat nystagmus. direction, suggesting that a PMT–flocculus–vestibular nucleus PMT cell groups are important in gaze holding and in the main- pathway might be important in maintaining vestibular balance. tenance of vestibular balance. Impaired PMT cells have been shown This patient is unusual in that downbeat nystagmus was caused to induce downbeat nystagmus in an animal model.3 In the present by vestibular imbalance as a result of damage caused to PMT cells patient, the medullary lesion was much lower than the location of by small brainstem infarctions. PMT cells that control eye movement. In the animal model,3 as also 6 suggested by a previously reported human lesion, the PMT cells Disclosure are supposed to be at the medullary–pontine junction. However, the PMT cell groups spread from the pons to the lower medulla The authors report no conflicts of interest. oblongata and project to the cerebellar flocculus.2 Furthermore, the eye movement disorders seen in our patient resembled those Acknowledgments observed in the floccular lesions.7 According to previous reports, the cerebellar flocculus and paraflocculus are important in main- This study was funded by a Scientific Research Grant (C) (No. taining gaze holding and vestibular balance, and the impairment 23590869) from the Ministry of Education, Culture, Sports, Science, 1,7 of these regions induces downbeat nystagmus. In the present pa- and Technology of Japan. tient, the impairment of PMT cells might have induced a disorder similar to those resulting from floccular lesions. This finding sug- References gests that feedback from the brainstem might influence the control of ocular movement in the cerebellum. 1. Pierrot-Deseilligny C, Milea D. Vertical nystagmus: clinical facts and hypotheses. Fig. 3 presents a summary of the pathogenesis of downbeat nys- Brain 2005;128:1237–46. 3 2. Büttner-Ennever JA, Horn AK. Pathways from cell groups of the paramedian tagmus caused by lesions in PMT cell groups. Lesions in PMT cells tracts to the floccular region. Ann N Y Acad Sci 1996;781:532–40. attenuate the activity of floccular Purkinje cells, which, in turn, re- 3. Nakamagoe K, Iwamoto Y, Yoshida K. Evidence for brainstem structures duce the inhibition of secondary vestibular nucleus neurons that participating in oculomotor integration. Science 2000;288:857–9. receive input from the anterior semicircular canals. However, the 4. de Jong JM, Cohen B, Matsuo V, et al. Midsagittal pontomedullary brain stem section: effects on ocular adduction and nystagmus. Exp Neurol 1980;68: neuronal activity of the posterior canal-related secondary vestibu- 420–42. lar nucleus neurons remains unaffected because the neurons do 5. Yeow YK, Tjia TL. The localizing value of downbeat nystagmus. Singapore Med J not receive inhibitory regulation from the flocculus.8 As a result, 1989;30:273–6. 6. Wagner J, Lehnen N, Glasauer S, et al. Downbeat nystagmus caused by a only the anterior canal-related secondary vestibular nucleus neu- paramedian ponto-medullary lesion. J Neurol 2009;256:1572–4. rons are activated, which induces upward eye movement that con- 7. Zee DS, Yamazaki A, Butler PH, et al. Effects of ablation of flocculus and stitute the slow phase of nystagmus. This is then followed by paraflocculus on eye movements in primate. J Neurophysiol 1981;46: 878–99. compensatory fast-phase downward beating, resulting in down- 8. Sato Y, Kawasaki T. Operational unit responsible for plane-specific control of eye beat nystagmus. It is suspected that lesions in PMT cells might movement by cerebellar flocculus in cat. J Neurophysiol 1990;64:551–64. doi:http://dx.doi.org/10.1016/j.jocn.2012.03.017

Abnormalities of neuromuscular transmission in patients with Miller–Fisher syndrome ⇑ Parvathi Menon a,b, Neil Mahant a,b, Steve Vucic b,c, a Department of Neurology, Westmead Hospital, Cnr Hawkesbury and Darcy Road, Westmead, New South Wales 2145, Australia b Sydney Medical School, Westmead, University of Sydney, Australia c Neuroscience Research Australia, Sydney, Australia article info abstract

Article history: The mechanism of motor weakness in patients with Miller–Fisher syndrome (MFS) remains to be fully Received 12 March 2012 elucidated. We performed stimulated single fibre electromyography (sSFEMG) in a clinically weak fron- Accepted 17 March 2012 talis muscle in a patient with MFS. Stimulate single fiber EMG revealed increased jitter in over 50% of the apparent single fibre action potentials from the frontalis muscle in addition to increased mean jitter. The findings in the present study suggest dysfunction of neuromuscular transmission in patients with MFS. Keywords: Ó 2012 Elsevier Ltd. All rights reserved. Miller–Fisher Syndrome Neuromuscular transmission dysfunction Single fibre EMG

1. Introduction

MFS is clinically characterised as a syndrome of ataxia, areflexia, and ophthalmoplegia 1 but the phenotype may be varied and include 2 ⇑ Corresponding author. Tel.: +61 2 9845 6097; fax: +61 2 9635 6684. facial and bulbar weakness. MFS is typically associated with an E-mail address: [email protected] (S. Vucic). antecedent infection, particularly with Campylobacter jejuni, and