Palatal Tremor

Pendular Vertical Oscillations; Full Vertical GazePowerPoint presentations: http://library.med.utah.edu/NOVEL/Wray/PPT/Palatal Tremor: Palatal_Tremor.ppt Shirley H. Wray, M.D., Ph.D., FRCP, Harvard Medical School Pendular Vertical Oscillations: http://library.med.utah.edu/NOVEL/Wray/PPT/Pendular_Vertical_Oscillations.ppt Shirley H. Wray, M.D., Ph.D., FRCP, Harvard Medical SchoolConstant movement of the eyes.The patient is a 60 year old woman with insulin dependent diabetes mellitus. She was legally blind as a result of diabetic retinopathy and bilateral vitreous hemorrhage. In 1987, she was admitted to her local hospital with slurred speech and a right hemiparesis progressing over a period of three days. Investigations revealed: Hypertension Cerebrovascular disease with 30% stenosis of the left internal carotid artery A small infarct in the left substantia nigra extending inferiorly into the left cerebral peduncle. She made an excellent recovery from her stroke and was treated with coumadin for six months. Coumadin was stopped when she developed progressive diabetic retinopathy. She lost vision in her left eye from a vitreous hemorrhage and unsuccessful vitreous surgery. In the right eye, she had a successful cataract extraction and vitrectomy for a small vitreous hemorrhage. This was followed, however, by a recurrent vitreous hemorrhage which reduced her vision to light perception only. In 1991, four years after her stroke, she became aware that her eyes were constantly moving. Her daughter commented on her eyes "oscillating" and when the patient touched her eyeball she could feel her eyes moving up and down. Symptomatic inquiry: Negative for vertigo, headache or difficulty in swallowing. Past History: Diabetic peripheral neuropathy Thyroid disease, on replacement synthyroid Neuro-ophthalmological examination: Visual acuity OD light perception, OS NLP Pupil OD oval and fixed OS distorted and fixed The eye movements showed: • Constant low amplitude pendular vertical oscillations (PVOs) with eyes open and closed • Lid nystagmus • Normal horizontal saccades • Normal vertical saccades • Poor convergence • No suppression of the PVOs on attempted convergence to look at her finger held at near. The presence of PVOs prompted an examination of the palate which showed: Palatal tremor (myoclonus) with rhythmic movement of the soft palate at 3 to 4 Hz synchronous with the ocular PVOs. Neurological examination: Speech normal Minimal drift of the right upper extremity with hyperreflexia. Flexor plantar responses Peripheral motor-sensory neuropathy, absent ankle jerks, Co-ordination intact. Normal gait Investigations: Brain MRI: 1. Small cavitary infarct in the left substantia nigra extending inferiorly in the left cerebral peduncle. 2. Ill-defined signal abnormalities involving the pons bilaterally and a small (1-2 mm) lacune in the posterior limb of the internal capsule/thalamus on the right. 3. Extensive bilateral periventricular white matter signal abnormalities, and T2 bright signal in the right external capsule. These findings were non-specific and probably related to microangiopathic leukoencephalopathy. Brainstem MRI: A gradient echo volume acquisition through the brainstem with T1 weighting was obtained and the data reformatted in the axial plane with 1 mm sections. This study showed asymmetry of the ventral medulla at the level of the olives. The left olivary nucleus appeared smaller than the right. No other abnormality of the brainstem was detected. Impression: Asymmetry of the medullary olivary complexes with probable degenerative hypertrophy of the right inferior olivary nucleus. Chest fluoroscopy, at the time of intermittent hiccups, ruled out diaphragmatic myoclonus. Diagnosis: Brainstem infarction in the left substantia nigra/left cerebral peduncle Palatal tremor Pendular vertical oscillationsThis patient with palatal tremor had striking pendular vertical oscillations (PVOs) in central gaze. The eye movements show: • Constant low amplitude PVOs with eyes open and closed • Lid nystagmus • Normal horizontal saccades • Normal vertical saccades • Poor convergence • No suppression of the PVOs on attempted convergence to look at her finger held at near. The palatal tremor filmed in the same frame as her face and eyes can be seen to be synchronous with the PVOs. The term ‘tremor' is more accurate than "myoclonus", since the movements of affected muscles are to-and-fro, and are approximately synchronized, typically at a rate of about two cycles per second. PVOs are characterized by: • Smooth, pendular movements occurring at a frequency of 1 to 3 Hz (typically 2 Hz). • PVOs are accentuated under closed lids • PVOs are synchronized with movements of the palate, facial muscles, pharynx, tongue, larynx and diaphragm. Conclusions from the analysis of eye movement recordings 1. PVOs are smooth rather than saccadic and have the velocity characteristics of normal convergence and divergence eye movements. Despite the absence of other components of the near triad (miosis and accommodation), the disorder retains certain features characteristic of normal vergence movements. 2. The eye movements are disjunctive, and furthermore the peak velocities achieved for various amplitudes are typical of normal vergence movements. 3. The pathological alterations resulting in PVO implicate a separately functioning, physiologically normal vergence system within the brainstem. 4. The continuous nature of PVOs distinguishes them from the nystagmus that occurs with Parinaud's syndrome, which is episodic and provoked by voluntary saccadic eye movements, especially attempted upgaze. 5. In cerebral Whipple's disease the abnormal eye movements have been ascribed to oscillations of the vergence system; hence the term pendular vergence oscillations.MRI in two cases of palatal tremor are illustrated: Case 1: Figure 1. Axial NECT scan shows a large pontine hemorrhage extending to the midbrain in patient (ID936-4), who survived this massive hypertensive intracranial hemorrhage and 2 years later developed palatal tremor. Case 2: Figure 2. Axial T2WI in a patient who developed palatal tremor 6 months after a midbrain bleed from a cavernous malformation shows a small mixed signal intensity lesion in the dorsal midbrain tegmentum. Figure 3. Axial T2WI (same case as Fig. 2) shows enlarged olives with striking hyperintensity characteristic for classic hypertrophic olivary degeneration. Courtesy Anne Osborn, M.D.According to Guillain and Mollaret the crucial location for the lesion(s) producing palatal tremor is one that involves the dentato-olivary pathway through the superior cerebellar peduncle. This pathway is an interconnecting circuit connecting three brainstem nuclei - the dentate, the red nucleus and the inferior olivary nucleus. The lesion can be located in one of four places: 1. The dentate nucleus 2. The dentate outflow through the superior cerebellar peduncle 3. At the level of the red nucleus where the pathway passes dorsally and inferior to the contralateral red nucleus or 4. In the descending central tegmental tract to the contralateral inferior olivary nucleus. More recent studies have implicated interruption of a pathway from the deep cerebellar nuclei through the superior cerebellar peduncle, which then loops caudally through the central tegmental tract to the inferior olive. When the syndrome is due to unilateral infarction of the dentate nucleus and superior cerebellar peduncle, hypertrophic changes in the inferior olivary nucleus appear on the contralateral side, as in this patient with a cavitary infarct in the left brainstem and contralateral hypertrophy of the right inferior olivary nucleus.Histologically, the olivary nucleus is enlarged, due to hypertrophy of neurons that contain increased acetylcholinesterase reaction product. Such changes begin within a month of the stroke and maximize in about six months, and are accompanied by astrocytosis, and synaptic and axonal remodeling. At the same time, the number of olivary neurons progressively declines, so that after six years, they are less than 10% of control brains. Also, both the myelin and the axons of efferent fibers from olivary neurons are severely degenerated in patients with persistent palatal tremor who survive several years. Despite the anatomic demonstration of atrophy, functional imaging studies suggest increased metabolism of the inferior olive.Pontine infarctionOnly rarely does palatal tremor resolve spontaneously. Gabapentin, ceruletide, memantine, and anticholinergic agents may help some patients. Drugs that block connexin channels and there by reduce synchronized discharge of electronically coupled olivary neurons might provide a new therapeutic approach.1. Averbuch-Heller L, Tusa RJ, Fubry L, Rottach KG, Ganser GL, Heide W, Büttner U, Leigh RJ. A double-blind controlled study of gabapentin and baclofen as treatment for acquired nystagmus. Ann Neurol 1997;41:818-825. http://www.ncbi.nlm.nih.gov/pubmed/9189045 2. Barton JJ, Cox TA. Acquired pendular nystagmus in multiple sclerosis: clinical observations and the role of optic neuropathy. J Neurol Neurosurg Psychiatry. 1993 Mar;56(3):262-267. http://www.ncbi.nlm.nih.gov/pubmed/8459242 3. Dehaene I., Van Zandycke M, Appel B. Acquired pendular nystagmus. Neuro-ophthalmol 1987;7(5);297-300. 4. Deuschl G, Toro C, Valls-Solé J, Zeffiro T, Zee DS, Hallett M. Symptomatic and essential palatal tremor. 1. Clinical, physiological and MRI analysis. Brain. 1994 Aug;117 ( Pt 4):775-788. http://www.ncbi.nlm.nih.gov/pubmed/7922465 5. Dubinsky RM, Hallett M, Di Chiro G, Fulham M, Schwankhaus J. Increased glucose metabolism in the medulla of patients with palatal myoclonus. Neurology. 1991 Apr;41(4):557-562. http://www.ncbi.nlm.nih.gov/pubmed/2011257 6. Gautier JC, Blackwood W. Enlargement of the inferior olivary nucleus in association with lesions of the central tegmental tract or dentate nucleus. Brain 1961;84(3):342-361. http://www.ncbi.nlm.nih.gov/pubmed/13897315 7. Goyal M, Versnick E, Tuite P, Saint Cyr J, Kucharczyk W, Montanera W, Willinsky R, Mikulis D. Hypertrophic olivary degeneration: meta-analysis of the temporal evolution of MR findings. Am J Neuroradiol 2000; 21:1073-1077. http://www.ncbi.nlm.nih.gov/pubmed/10871017 8. Guillain G, Mollaret P. Deux cas myoclonies synchrones et rhythmées vélo-pharyngo-laryngo-oculodiaphragmatiques: Le problèm anatomique et physiolopathologique de ce syndrome. rev. Neurol (Paris) 1931;2:545-566. 9. Katz B, Hoyt W, Townsend J. Ocular Bobbing and Unilateral Pontine Hemorrhage. Report of a Case. J Clin Neuro-ophthalmol 1982;2:193-195. http://www.ncbi.nlm.nih.gov/pubmed/6217223 10. Keane JR. Acute vertical ocular myoclonus. Neurology 1986;36:86-89. http://www.ncbi.nlm.nih.gov/pubmed/3941790 11. Koeppen AH. Olivary hypertrophy; histochemical demonstration of hydrolytic enzymes. Neurology 1980;30:471-480. http://www.ncbi.nlm.nih.gov/pubmed/6245389 12. Leigh RJ, Hong S, Zee DS, Optican LM. Oculopalatal tremor: clinical and computational study of a disorder of the inferior olive. Soc Neurosci Abstr 2005; 933.8. 13. Leigh RJ, Zee DS. Diagnosis of Nystagmus and Saccadic Intrusions. Chp 10:475-558. In: The Neurology of Eye Movements, 4th Edition. Oxford University Press, New York 2006. 14. Lopez LI, Bronstein AM, Gresty MA, Du Boulay EP, Rudge P. Clinical and MRI correlates in 27 patients with acquired pendular nystagmus. Brain. 1996 Apr;119 ( Pt 2):465-472. http://www.ncbi.nlm.nih.gov/pubmed/8800942 15. Nishie M, Yoshida Y, Hirata Y, Matsunaga M. Generation of symptomatic palatal tremor is not correlated with inferior olivary hypertrophy. Brain. 2002 Jun;125(Pt 6):1348-1357. http://www.ncbi.nlm.nih.gov/pubmed/12023323 16. Ruigrok TJ, deZeeuw CI, Vogel J. Hypertrophy of inferior olivary neurons : a degenerative regenerative or plasticity phenomenon. Eur J Morphol 1990 ;28 :224-239. http://www.ncbi.nlm.nih.gov/pubmed/2245132 17. Samuel M, Torun N, Tuite PJ, Sharpe JA, Lang AE. Progressive ataxia and palatal tremor (PAPT): clinical and MRI assessment with review of palatal tremors. Brain. 2004 Jun;127(Pt 6):1252-1268. Epub 2004 Apr 16. http://www.ncbi.nlm.nih.gov/pubmed/15090471 18. Yokota T, Hirashima F, Furukawa T, Tsukagoshi H, Yoshikawa H. MRI findings of inferior olives in palatal myoclonus J Neurol 1989;236:115-116. http://www.ncbi.nlm.nih.gov/pubmed/270905