Ocular Flutter

Ocular FlutterBlurred VisionThis patient was seen in the Neurovisual Clinic for evaluation of a monocular attack of optic neuritis which completely resolved. Six months later, she became unsteady walking and was found to have bilateral ataxia. She was given a diagnosis of multiple sclerosis (MS). Neuro-ophthalmological examination: The examination was normal apart from the eye movements which showed, in central gaze, episodic bursts of horizontal back-to-back saccades without an intersaccadic interval characteristic of ocular flutter. The patient was seen prior to the availability of neuroimaging by MRI. In 1954 Cogan first used the term "ocular flutter" to describe a rare disorder of horizontal eye movements characterized by rapid bursts of synchronous back-to-back horizontal oscillatory movements usually seen in the primary position of gaze. Since then, there have been over 50 reports, usually single cases or small series, linking the phenomenon to a wide variety of brainstem and cerebellar conditions, e.g. post enteroviral infection, cerebral malaria, cyclosporine treatment and meningitis, but perhaps most frequently associated with parainfectious states or, with opsoclonus, as a paraneoplastic manifestation of occult malignancy.This patient with MS has ocular flutter characterized by: • Horizontal saccadic oscillations without an intersaccadic interval. • The frequency of oscillations is usually high, typically 10 to 25 cycles per second, as evident in this case. • Ocular flutter is intermittent and mainly associated with voluntary saccades - flutter dysmetria. • When the amplitude is very small, the oscillation can only be detected with an ophthalmoscope or on eye movement recordings, and then the term microflutter is used to describe the disorder. Ocular flutter occurs in: 1. Paraneoplastic opsoclonus/flutter due to an occult neoplasm 2. Multiple sclerosis 3. Side effects of drugs: lithium, amitriptyline, cocaine and phenytoin with diazepam. 4. Toxins: chlordecone, thallium, strychnine, toluene, and organophosphates or 5. Complication of pregnancy In three reported cases from Japan of the opsoclonus-myoclonus syndrome (OMS) during pregnancy, the neurologic symptoms were entirely similar to those of OMS unrelated to pregnancy with opsoclonus/flutter, trunkal ataxia and myoclonic jerks of the neck and limbs. The condition of the fetuses were good, except in the one case that miscarried. In all three cases the OMS occurred in the middle to late stages of pregnancy. Whether the symptoms improved because the pregnancy ended or because of corticosteroid therapy remains unclear. However, the OMS gradually improved after spontaneous miscarriage in one case. Taken together, the authors suggested that these results raise the possibility that pregnancy influences the appearance of OMS. Table 10-8 Etiology of Ocular Flutter and Opsoclonus. Pg 525 (12). When agents with a variety of potential effects on neurotransmitters have been excluded, a patient with ocular flutter warrants a careful evaluation for an occult neoplasm, and long-term follow-up. In filming this short clip, the patient was asked to try and hold her gaze steady fixating on the camera. You will see that she is unable to do this because of bursts of spontaneous back-to-back horizontal saccades without a saccadic interval - this abnormality is characteristic of ocular flutter. Ocular flutter in the absence of other neurological signs implies a paraneoplastic syndrome due to an occult neoplasm, most frequently cancer of the breast.Ocular flutter has been hypothesized to be caused by loss of "pause" neuronal inhibition of burst neuron function in the paramedian pontine reticular formation (PPRF). However, there has only been one imaging study confirming this anatomical localization. The report is of a young woman with a definite relapse of her MS who developed prominent ocular flutter without any obvious ophthalmoplegia or nystagmus. (15) An axial MRI FLAIR sequence through the pons and medulla showed a single prominent midline high signal lesion in the region of the PPRF. A sagittal midline section showing the same lesion demonstrated its cranio-caudal distribution and its subventricular localization. Repeat axial and sagittal images through the same region months later showed the disappearance of the midline pontine lesion. The disappearance of the lesion followed acute treatment with a 3-day course of intravenous methylprednisolone and the ocular flutter dramatically improved. The authors of this case referred to the MRI atlas by Kretschman and Weinrich and confirmed that the brainstem lesion was at the level of the sixth nerve nuclei and to be virtually exactly occupying the position of the PPRF. There were other far less obvious small areas of abnormal signal in the posterior fossa, including two in the left cerebellar hemisphere, one each in the right cerebellar hemisphere and the superior medulla. As she recovered from the MS attack, both the midline pontine lesion and the ocular flutter dramatically improved. This case is the first clear evidence that at least some cases of ocular flutter are due to lesions involving the PPRF. (Schon F, Hodgson TL, Mort D, Kennard C. Ocular flutter associated with a localized lesion in the paramedian pontine reticular formation. Ann Neurol 2001;50:413-416).In 1979, Zee and colleagues studied a single patient with ocular flutter and related their findings to what was known about the anatomy and physiology of saccade generation in the monkey. They proposed that "pause" neurons normally prevent saccadic oscillations during fixation by inhibiting "bursts" neuron firing and that this mechanism is disturbed in ocular flutter. They later proposed a similar disturbance in both voluntary and blink-induced saccadic oscillations. They hypothesized that the anatomical site involved in this group of eye movement disorders, which also includes opsoclonus, would be in the medial region of the PPRF, which is the human equivalent of the pontine raphe interpositus nucleus (RIN), in which pause neurons are located in the monkey. In humans, it lies adjacent to the midline and in the upper pons at the level of the sixth nerve nucleus but slightly ventral to it. However, experimental lesions of the omnipause region with excitotoxins caused slow saccades rather than oscillations. One possible explanation is that burst neurons may also have been affected. The only comparable case to Schon et al's MS patient, is one reported by Averbuch-Heller and colleagues. Their patient developed macrosaccadic oscillations five years after a head injury. The MRI in this patient showed a lesion in the right side of the pons extending upward from the level of the sixth nerve nucleus into the tegmentum and basis pontis. It was proposed that the eye movement abnormality was caused by damage to the adjacent omnipause neuron projections.Multiple sclerosisTable 10-8 Etiology of Ocular Flutter and Opsoclonus. Pg 525 (12)Ocular flutter ceased when the acute MS attack went into remission.1. Apsner R, Schulenburg A, Steinhoff N. Keil F, Janata K, Kalhs P, Greinix H. Cyclosporin A induced ocular flutter after marrow transplantation. Bone Marrow Transplantation 1997;20:255-256. http://www.ncbi.nlm.nih.gov/pubmed/9257896 2. Averbuch-Heller L, Kor AA, Rottach KG, Dell'Osso LF, Remler BF, Leigh RJ. Dysfunction of pontine ominipause neurons causes impaired fixation: macrosaccadic oscillations with a unilateral pontine lesion. Neuroophthalmology 1996;16:99-106. http://www.ncbi.nlm.nih.gov/pubmed/11539873 3. Buttner U. Straube A, Handke V. Opsoclonus and ocular flutter. Nervenarzt 1997;68:633-637. http://www.ncbi.nlm.nih.gov/pubmed/9380208 4. Buttner-Ennever JA, Pause M. Neuroanatomic identification of the raphe nucleus in the pons associated with omnipause neurons of the oculomotor system in the monkey. J Comp Neurol 1988;267:307-321. http://www.ncbi.nlm.nih.gov/pubmed/2830321 5. Cogan DG. Ocular dysmetria: flutter like oscillations of the eyes, and opsoclonus. Arch Ophthalmol 1954;51:318-335. http://www.ncbi.nlm.nih.gov/pubmed/13123617 6. Francis DA, Heron JR, Ocular flutter in suspected multiple sclerosis: a presenting paroxysmal manifestation. Postgrad Med J 1985; 61:333-334. http://www.ncbi.nlm.nih.gov/pubmed/4022865 7. Gotot T, Yonemitsu M, Araki Y et al. Case of opsoclonus-myoclonus syndrome (OMS) developing during pregnancy. Nippon Naika Gakkai Zasshi 1999;88:344-346. http://www.ncbi.nlm.nih.gov/pubmed/10341601 8. Gresty MA, Findley LJ, Wade P. Mechanism of rotary eye movements in opsoclonus. Br J Ophthalmol 1980; 62:533-535. http://www.ncbi.nlm.nih.gov/pubmed/7448146 9. Idris MNA, Sokrab TEO. Post malaria cerebellar ataxia and ocular flutter: report of two cases. East Afr Med J 1999;7:417-418. http://www.ncbi.nlm.nih.gov/pubmed/10520374 10. Kaneko CRS, Effect of ibotinic acid lesions of the omnipause neurons on saccadic eye movements in rhesus macaques. J Neurophysiol 1996;75:2229-2242. http://www.ncbi.nlm.nih.gov/pubmed/8793737 11. Kretschmann HJ, Weinrich W. Cranial neuroimaging and clinical neuroanatomy. Stuttgart: Thieme Verlag, 1992. 12. Leigh RJ, Zee DS. Diagnosis of Nystagmus and Saccadic Intrusion. Chp 10:475-558. In: The Neurology of Eye Movements, Fourth Edition. Oxford University Press, NY. 2006. 13. Orimo S, Sato H, Ozawa E et al. An autopsied case of purulent meningitis associated with ocular flutter. Brain Nerve 1998;50:469-472. http://www.ncbi.nlm.nih.gov/pubmed/9621372 14. Reiji K, Sakamoto M, Tanaka K, Hayashi H. Opsoclonus-myoclonus syndrome during pregnancy. J Neuroophthalmol 2004;24:273. http://www.ncbi.nlm.nih.gov/pubmed/15348998 15. Schon F, Hodgson TL, Mort D, Kennard C. Ocular flutter associated with a localized lesion in the paramedian pontine reticular formation. Ann Neurol 2001;50:413-416. http://www.ncbi.nlm.nih.gov/pubmed/11558800 16. Wiest G, Safoshnik G, Schnarberth G, Mueller C. Ocular flutter and trunkal ataxia may be associated with enterovirus infection. J Neurol 1997;244:288-292. http://www.ncbi.nlm.nih.gov/pubmed/9178152 17. Zee DS, Robinson DA. A hypothetical explanation of saccadic oscillations. Ann Neurol 1979;5:405-414. http://www.ncbi.nlm.nih.gov/pubmed/111605MTndosocularflutte