Upbeat Nystagmus

Upbeat Nystagmus; Horizontal Gaze Evoked Nystagmus; OpsoclonusPowerPoint Presentation: Upbeat Nystagmus: http://library.med.utah.edu/NOVEL/Wray/PPT/Upbeat_Nystagmus.ppt Shirley H. Wray, M.D., Ph.D., FRCP, Harvard Medical SchoolNausea and vomitingThe patient is a 36 year old Korean doctor who arrived from Korea in November 1994. On 12/25/94 she developed a painful erythematous eruption along her upper back extending toward her right shoulder. A physician diagnosed herpes zoster and prescribed a five day course of Acyclovir with good resolution of her pain and vescicles. On 1/1/95, she developed low grade fever, nausea and vomiting. She was seen at an outside hospital, had a KUB and chest x-ray, received intravenous hydration and was discharged after three days with a diagnosis of gastritis. She was able to return to work at the Massachusetts General Hospital where she was a neuropathology fellow. On 1/16/95 with almost complete resolution of her gastrointestinal symptoms, she complained of generalized weakness and the day prior to admission developed difficulty swallowing, moving her tongue, and double vision. She had a "spinning sensation" which she found difficult to characterize. Initially she had no weakness or difficulty with her gait but on the following day she felt generally weak and dizzy. Nevertheless, she went to work. That evening she had increasing vertigo and came to the emergency room. In the ER she complained of difficulty speaking and swallowing but no difficulty breathing. Past Medical History: Only significant for the previous episode of herpes zoster. Family History: Father has myasthenia gravis Physical Examination: Ill appearing patient. BP 100-150/60, temperature 97.5, pulse 76, respiration rate 20. Neck supple,full movements No Kernig's or Brudzinsky's sign Skin, hyperpigmented macules over the left shoulder consistent with post-inflammatory hyperpigmentation. Neurological Examination: Alert, oriented. Respiratory capacity decreased, range 1.5 to 1 liter Comprehension normal Speech dysarthric Bulbar palsy with brisk jaw jerk and facial jerks Good gag Pupils 4 mm OU, reacting to light and near Fundus examination normal Ocular Motility: Upbeat nystagmus in primary and vertical gaze Full horizontal and vertical gaze Horizontal gaze evoked nystagmus Normal convergence No facial weakness Motor System: Full strength throughout Symmetrical 1+ to 2+ reflexes Plantar response flexor Sensory Examination: Normal Coordination: No ataxia Lumbar Puncture day 2: Cerebrospinal fluid (CSF) protein 35 mg/dl Glucose 56 mg/dl 3 red blood cells, 73 white cells, 96% lymphocytes. Blood Studies: White blood count 5,400, 80% polymorphonuclear Erythrocyte sedimentation rate 22 mm/hr Liver Function/Electrolytes: Normal liver function Serum potassium, low 2.7 mmol/L Sodium 142 mmol/L Normal renal function Brain CT: Normal Electrocardiogram: Normal sinus rhythm, no ST-T wave changes Electromyography: Studies performed on right upper and lower extremity normal F and H reflexes, normal. Repetitive stimulation normal. Impression: No electrophysiological evidence of a neuromuscular junction disorder, or neuropathy. Brain MRI: Showed a large diffuse area of inflammation in the brainstem and a second focus in the cervical spinal cord. Laryngoscopy: Revealed paralyzed vocal cords. Infectious Disease Consult: Negative RPR, Lyme and heterophil antibody. Elevated IgG Negative studies for herpes Negative CSF viral studies Rheumatology Consult: Strongly positive ANA in a speckled pattern. Diagnosis: Post infectious brainstem encephalitis Bulbar palsy Cervical myelitis Hospital Course: The patient was admitted to the ICU and intubated as her vital capacity was low and she was unable to handle secretions. She developed increasing bilateral facial weakness and her condition progressed with the development of dysesthesias, hyperesthesia and weakness of the left arm and leg and bilateral ataxia. She was intubated for less than a week and appeared to be improving but shortly after being extubated she requested re-intubation due to extreme fatigue and occasional respiratory distress. Lumbar Puncture day 9: CSF protein down to 27 mg/dl Glucose 64 mg/dl White cell count down to 22, 95% lymphocytes. Treatment: The patient received a 14-day course of intravenous acyclovir and antibiotics. Over this time there was slow improvement in her strength and she was able to be extubated and transferred to the floor. On 1/29/95 Cervical Spine MRI: Sagittal T1, T2 and post contrast T1 spin echo images, axial T2 and gradient echo images, showed an abnormal T2 bright signal in the brainstem and cervical cord from the level of the 4th ventricle, near the level of the alae, down to cervical level C4 where it became more patchy in distribution down to level C7 and T1. This was a new finding. The T2 hyperintensity was not present on the previous study done several days earlier. There was no enhancement post gadolinium and no expansion of the cord. Impression: Post-infectious brainstem encephalitis. Hospital Course: On 2/2/95, at approximately 9 a.m., a physician found her lying supine in bed, all limbs flaccid, eyes open and staring up. She failed to respond to voice. The pupils were equal and reactive. Respirations were regular and then paradoxical and intermittent. Oxygen saturation dropped to the 60's She was immediately admitted to respiratory ICU and intubated. BP dropped and she was started on pressors Respiratory ICU: The patient recovered consciousness approximately half an hour later and was able to follow commands. She became worried about her respiratory status and requested a tracheostomy as she felt that she would be unable to control her secretions and needed to protect her airway. On 2/10/95 a tracheostomy was performed. Repeat Brain CT: Normal Chest X-ray: Consolidation of the left lower lobe. Medication: Broad spectum antibiotics. Hospital Course: She remained in the respiratory ICU. The tracheostomy was changed to a fenestrated one to enable her to talk and make her needs known. She remained stable for five days, and was then transferred to the floor to start more active physiotherapy. She made slow progress, regained strength on the left side. The bilateral ataxia gradually decreased and resolved. Upbeat nystagmus in primary position persisted. On 2/13/95 MRI Brainstem: The previous lesions in the brainstem and cervical spinal cord appeared more distinct but smaller. They extended from the pontomedullary junction to the lower medulla. The cervical spinal cord lesion extended to C4 level. On 2/13/95 MRI Cervical Spinal Cord: Minimal to no change in increased T2 signal in the inferior medulla and superior cervical cord. No enhancement with gadolinium. On 2/13/95 Brain MRI: Slight worsening in the increased T2 hyperintensity in the inferior brainstem and superior cervical cord extending to C4 level, consistent with acute myelitis. On 2/24/95 the tracheostomy was removed. She regained normal swallowing and was able to eat and control her secretions without difficulty. On 2/24/95 whilst on oral steroids, she was discharged home instead of rehab, at her request. Medications: Prednisone 80 mg q.d. Dilantin 100 mg b.i.d. She tolerated a dysphagia-2 diet and was allowed to advance her diet as she tolerated the feedings. Diagnosis: Post Infectious brainstem encephalitis Bulbar Palsy Cervical myelitis On 2/27/95, on follow-up, she was able to walk with 2 sticks. Her speech had almost completely recovered Her gag reflex remained a little weak. She was able to eat solids without difficulty. Upbeat nystagmus persisted and produced disturbing oscillopsia which made it difficult for her to walk. Neuro-ophthalmic Examination: Visual acuity J1 OU with good fixation stabilizing her eyes. Pupils equal, normal reflexes Ocular Motility: Upbeat nystagmus Horizontal gaze nystagmus, right greater than left Full vertical gaze with upbeat nystagmus on upgaze No nystagmus on downgaze Suppression of nystagmus on fixation and on convergence The new observation on this visit was the presence of opsoclonus with frequent obtrusive multi-directional saccades in all directions. Palate normal. No involuntary movements of the face. On 3/3/95 she presented with a drug rash secondary to Dilantin Neuro-ophthalmological signs were unchanged and opsoclonus was still present. Medication: High dose prednisone. On 3/17/95, she appeared Cushionoid from steroid side effects. She was still taking prednisone 80 mg. daily and Baclofen 10 mg t.i.d. On 11/19/95 Brain MRI: The study compared to 2/13/95 showed the areas of T2 signal intensity in the cervicomedullary junction were improving and much smaller. On 11/28/95 Follow-Up: She complained on this occasion of vertical diplopia Visual acuity 20/25 OU, normal pupils and fundi Ocular Motility: Full eye movements No upbeat nystagmus, oscillopsia or opsoclonus Horizontal gaze evoked nystagmus On left gaze, downbeating and slight torsional component On right gaze, downbeating New Finging: A skew deviation with mild left head tilt and left hypotropia indicative of a left ocular tilt reaction (OTR) She was seen again on 12/19/95 and for the last time on 1/19/96 prior to returning home to Korea. On this occasion she was 99% back to her normal baseline except for persistent vertical diplopia due to skew deviation. This prevented her from driving unless she patched one eye. Glasses with Fresnel prisms corrected her diplopia and she returned to Korea. Final Diagnosis: Post herpes zoster brainstem encephalitis Cervical myelitisThis 36 year old Korean doctor with severe post infectious brainstem encephalitis allowed us to film her on three separate occasions. On day 8, she had oscillopsia Upbeat nystagmus in primary gaze Full eye movements, Horizontal gaze evoked nystagmus Impaired convergence and Bilateral facial weakness Difficulty gripping her lips together Unable to whistle Impaired gag and cough At 3 weeks she had started to recover, her voice was stronger and she was able to pronounce words and swallow solids. Ocular Motility: Upbeat nystagmus in primary gaze Square wave jerks Vertical and horizontal saccadic hypermetria Saccadic pursuit in all directions of gaze At 10 months she had chills, fever, anorexia and hiccups lasting over one hour. Ocular Motility: Upbeat nystagmus in primary gaze Vertical and horizontal saccadic hypermetria Saccadic pursuit Downbeat nystagmus on gaze right, left and down. The clinical features of upbeat nystagmus illustrated by this case are: • Nystagmus is present in central gaze and increases on looking up • Nystagmus is partially suppressed by convergence • It is associated with abnormal smooth pursuit and • Saccadic intrusions (square wave jerks) • Horizontal gaze evoked downbeat nystagmus and • Late in the course of her illness by episodic opsoclonus Upbeat nystagmus may convert to downbeat with convergence. Upbeat may occasionally get worse on downgaze which means an unstable neural gaze holding integrator. Additional cases of upbeat nystagmus alongside this case: ID917-5 Post resection of a cerebellar astrocytoma ID941-5 Cavernous angioma of the medulla with hemorrhage ID906-4 Multiple Sclerosis ID208-1 Wernicke's encephalopathy post stomach stapling for morbid obesity Saccadic hypermetria: Lesions of the dorsal vermis and fastigial nuclei cause saccadic dysmetria. Typically hypometria if the vermis alone is involved and typically hypermetria if the fastigial nuclei are involved. I asked Dr. Zee to explain why this patient had both vertical and horizontal hypermetria post operatively, with no cerebellar lesion. Dr. Zee suggested that it may be due to the same mechanism that accounts for saccadic dysmetria in Wallenberg's syndrome, with a lesion of the inferior olive or inferior cerebellar peduncle leading to a functional lesion of the fastigial nucleus. (Due to climbing fiber activity decrease producing an increase in Purkinje cell inhibition on that side creating a functional fastigial nucleus lesion.) Square wave jerks: Are pairs of small horizontal saccades typically less than 2° that take the eye away from the target and then return it within 200 msec. In certain cerebellar syndromes, square wave jerks may occur almost continuously and have been called square wave oscillations. These oscillations maybe mistaken for nystagmus but in this patient they are seen in addition to upbeat nystagmus on upgaze. Skew Deviation: For a discussion of skew deviation review ID169-37.There are no imaging studies available in this patient.Upbeat nystagmus is reported most commonly with lesions in the caudal medulla, which variably involve the peri-hyperglossal group of nuclei, including the nucleus intercalates, the nucleus of Roller and the nucleus pararaphales.Post herpes zoster encephalitisAcyclovir, antibiotics and steroids1. Baloh RW, Yee RD. Spontaneous vertical nystagmus. Rev Neurol (Paris). 1989;145:527-532. http://www.ncbi.nlm.nih.gov/pubmed/2682931 2. Benjamin EE, Zimmerman CF, Troost BT. Lateropulsion and upbeat nystagmus are manifestations of central vestibular dysfunction. Arch Neurol. 1986;43:962-964. http://www.ncbi.nlm.nih.gov/pubmed/3488729 3. Elliott AJ, Simpson EM, Oakhill A, Decock R. Nystagmus after medulloblastoma. Developmental Medicine and Child Neurology 1989;391:43-46. http://www.ncbi.nlm.nih.gov/pubmed/2920872 4. Fisher A, Gresty M, Chambers B, Rudge P. Primary position upbeating nystagmus. A variety of central positional nystagmus. Brain. 1983;106:949-64. http://www.ncbi.nlm.nih.gov/pubmed/6606479 5. Furman JM, Brownstone PK, Baloh RW. Atypical brainstem encephalitis: magnetic resonance imaging and oculographic features. Neurology. 1985;35:438-440. http://www.ncbi.nlm.nih.gov/pubmed/3871923 6. Gilman N. Baloh RW. Primary position upbeat nystagmus. Neurology 1977;27:294-297. http://www.ncbi.nlm.nih.gov/pubmed/557768 7. Glasauer S. Kalla R, Büttner U, Strupp M, Brandt T. 4-aminopyridine restores visual ocular motor function in upbeat nystagmus. J Neurol Neurosurg Psychiatry 2005;76:451-453. http://www.ncbi.nlm.nih.gov/pubmed/15716550 8. Keane JR, Itabashi HH. Upbeat nystagmus: clinicopathologic study of two patients. Neurology. 1987;37:491-497. http://www.ncbi.nlm.nih.gov/pubmed/3822146 9. Leigh RJ, Zee DS. Diagnosis of Nystagmus and Saccadic Intrusion. Chp 10:475-558. In: The Neurology of Eye Movements 4th Edition. Oxford University Press, New York 2006. 10. Nakada T, Remler MP. Primary position upbeat nystagmus; another central vestibular nystagmus? J Clin Neuroophthalmol 1981;1:181-185. http://www.ncbi.nlm.nih.gov/pubmed/6213659 11. Pierrot-Deseilligny C, Milea D. Vertical nystagmus: clinical facts and hypotheses. Brain 2005;128:1237-1246. http://www.ncbi.nlm.nih.gov/pubmed/15872015 12. Tilikete C, Hermier M, Pelisson D, Vighetto A. Saccadic lateropulsion and upbeat nystagmus: disorders of caudal medulla. Ann Neurol. 2002;52:658-662. http://www.ncbi.nlm.nih.gov/pubmed/12402267curriculum_fellow; MTndosupbeatnystagmus; VBmeningoencephaliti