Slow Saccade Syndrome

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Identifier 924-2
Title Slow Saccade Syndrome
Ocular Movements Supranuclear Paralysis of Up and Down Gaze; Slow Hypometric Horizontal Saccades; Vertical Oculocephalic Reflex Intact; Lid Retraction
Creator Shirley H. Wray, M.D., Ph.D., FRCP, Professor of Neurology Harvard Medical School, Director, Unit for Neurovisual Disorders, Massachusetts General Hospital
Contributor Primary Shirley H. Wray, MD, PhD, FRCP, Professor of Neurology, Harvard Medical School; Director, Unit for Neurovisual Disorders, Massachusetts General Hospital
Subject Lid Retraction; Supranuclear Paralysis of Up and Downgaze Degeneration; Slow Hypometric Horizontal Saccades; Vertical Oculocephalic Reflex Intact; Progressive Supranuclear Palsy - Tauopathy; Steele Richardson Olszewski Syndrome; CNS - Degeneration
Supplementary Materials PowerPoint Presentations: Tauopathies: A contemporary way to consider a set of neurodegenerative diseases based on their molecular signature: http://library.med.utah.edu/NOVEL/Wray/PPT/Tauopathies_guest_lecture.ppt John Growdon, M.D. Massachusetts General Hospital Progressive Supranuclear Palsy: http://library.med.utah.edu/NOVEL/Wray/PPT/Progressive_Supranuclear_Palsy.ppt Shirley H. Wray, M.D., Ph.D., FRCP, Harvard Medical School
Presenting Symptom Unsteady walking
History The patient is a 62 year old woman referred from Ireland with a one year history of unsteadiness walking which she first noted following a fall from a chair. Her gait disorder was insidious in onset and may have pre-dated the fall. Since then she had become increasingly unsteady with a tendency to fall backwards and she now walks with a cane. In the past 6 months because of episodic diplopia when looking straight ahead, she closes her right eye to focus a single image. During a recent admission in April 1990 to Galway Regional Hospital, she realized that she could no longer look upwards without tilting her head. She denied any disturbance in her speech but her relatives noted it had become increasingly slurred and of nasal quality. Neurological examination at that time showed: Patient rather emotionally labile Minimal dysarthria Paralysis of upgaze with normal doll's eye movements Abnormal saccades on horizontal gaze Hyperreflexia throughout with flexor plantar responses Broad based gait, ataxic on heel/toe walking Positive Romberg's test MRI showed: Cerebral brainstem and vermal atrophy in addition to white matter changes. Diagnosis: Pontine cerebellar degeneration Family History: Her mother is alive and well at age 90. No family history of neurological disease. As the patient intended to visit the United States in the summer she was referred for re-evaluation to the Neurovisual Clinic at the Massachusetts General Hospital. Diagnosis: Progressive supranuclear palsy
Clinical This patient with Progressive Supranuclear Palsy (PSP) has a constellation of eye signs: 1. Supranuclear saccadic and pursuit paralysis of up and downgaze 2. Slow hypometric horizontal saccades 3. Gaze evoked nystagmus to right and left Confirmation that the vertical gaze disorder is supranuclear and localized to the rostral interstitial nucleus of the MLF (riMLF) in the midbrain is the presence of : 1. Upward deviation of the eyes on forced eye closure (intact Bell's) and 2. Full upward eye movements when the head is bent. forward, the oculocephalic or doll's eye reflex At the onset of PSP: • Vertical saccades are slow • Vertical saccadic range is progressively reduced • Difficulty with initiation of vertical saccades • Vertical smooth pursuit impaired (reduced range) • Vertical optokinetic stimulation causes gaze to tonically deviate in the direction of the stripe movement (Personal communication Zee DS 2005) Additional PSP signs are: 1. Positive glabella tap, (inability to inhibit a blink when the forehead is tapped) 2. Myerson's Sign (inability to inhibit a blink to a bright pen light shown in the eyes) 3. Blepharoclonus (tremor of the lids on gentle eye closure) 4. Square wave jerks 5. Bilateral ophthalmoparesis in the late stages of the disease Box 12-14 Clinical features of PSP. Pg. 639 (5).
Neuroimaging The patient's MRI showed cerebral, brainstem and cerebellar vermis atrophy in addition to non-specific white matter disease. PSP has characteristic changes on neuroimaging. A sagittal T2-weighted MR scan in another patient with PSP shows the tectal plate (arrow) is markedly thinned and atrophic. (Figure 1) Functional MRI reveals global metabolic reduction most pronounced in the frontal lobes, anterior cingulate gyrus, the basal ganglia, the ventrolateral and dorsomedial nuclei of thalamus and the upper brainstem. PET scans using fluorodopa demonstrate diminished striatal dopamine formation and storage. In addition to hypometabolism in the putamen, severe caudate involvement on PET scanning distinguishes PSP from Parkinson's disease (Figures 2 and 3).
Anatomy Supranuclear paralysis of vertical gaze localizes to the midbrain and to the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF). The riMLF is a wing-shaped structure that lies dorsomedial to the red nucleus and rostral to the interstitial nucleus of Cajal. The riMLF contains burst neurons for vertical and torsional saccades. The riMLF projects predominantly to the ipsilateral oculomotor (third nerve) and trochlear (fourth nerve) nuclei.
Pathology In an autopsy case of PSP, a pale locus ceruleus and substantia nigra are two typical gross features on inspection of the brainstem. (Figure 4) Neuronal loss, granulovacuolar degeneration and fibrillary gliosis are present in areas of neuronal change. There is widespread neuronal and glial tau accumulation in the cortex, basal ganglia, in periaqueductal gray matter, subthalamic nucleus, red nucleus, substantia nigra, pedunculopontine nucleus, superior colliculus, and in the dentate nucleus of the cerebellum. Microscopically, globose neurofibrillary tangles are observed on LHE stain. (Figure 5) The neuronal cytoplasmic inclusions are strongly immunoreactive for tau. (Figure 6A) Tufted astrocytes are a specific finding in PSP. They are often binucleate and have long tau reactive processes. (Figure 6B) The intracellular aggregation of tau in PSP may be sufficient to cause nerve cell degeneration.
Etiology PSP is a "tauopathy" . Studies suggest that it is a recessive disorder in linkage disequilibrium with the tau gene. Rare familial forms of PSP exist including an autosomal dominant transmission with incomplete penetrance. The relationship to the tau gene further suggests a relationship to frontotemporal dementia/Pick's Disease (FTDP) and some families carrying the FTDP-17 mutation (chromosome 17) have affected members with PSP-type phenotypes.
Disease/Diagnosis Progressive Supranuclear Palsy - Tauopathy
Treatment There is no cure for PSP. Once the disease has begun its course is relentlessly progressive.<br><br>
References 1. Buttner-Ennever JA, Horn AK. Pathways from cell groups of the paramedian tracts to the floccular region. Ann N Y Acad Sci. 1996 Jun 19;781:532-40. http://www.ncbi.nlm.nih.gov/pubmed/8694442 2. Daniel SE, de Bruin VM, Lees AJ. The clinical and pathological spectrum of Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy): a reappraisal. Brain 1995, Jun;118 ( Pt 3):759-70. http://www.ncbi.nlm.nih.gov/pubmed/7600092 3. Friedman DI, Jankovic J, McCrary JA 3rd. Neuro-ophthalmic findings in progressive supranuclear palsy. J Clin Neuroophthalmol. 1992 Jun;12(2):104-9. http://www.ncbi.nlm.nih.gov/pubmed/1629370 4. Growdon JH, Rossor MN. The Dementias. Blue Books of Practical Neurology. Butterworth-Heinemann 1998; Vol 19. 5. Leigh RJ, Zee DS. Diagnosis of Central Disorders of Ocular Motility. Chp 12:598-718. In: The Neurology of Eye Movements, Fourth Edition. Oxford University Press, NY. 2006. 6. Mendez MG, Cummings JL. Dementia A Clinical Approach. Third Edition. Butterworth Heinemann 2003. 7. Richardson JC, Steele J, Olszewski J. Supranuclear ophthalmoplegia, pseudobulbar palsy, nuchal dystonia and dementia. a clinical report on eight cases of heterogenous system degeneration. Trans Am Neurol Assoc. 1963;88:25-9. http://www.ncbi.nlm.nih.gov/pubmed/14272249 8. Stanford PM, Halliday GM, Brooks WS, Kwok JBJ, Storey CE, Creasey H, Morris JGL, Fulham MJ, Schofield PR. Progressive supranuclear palsy pathology caused by a novel silent mutation in exon 10 of the tau gene: expansion of the disease phenotype caused by tau gene mutations. Brain 2000;123(Pt 5):880-893. http://www.ncbi.nlm.nih.gov/pubmed/10775534 9. Sir Charles Bell (http://www.whonamedit.com/doctor.cfm/2103.html
Relation is Part of 166-18, 924-2, 932-3, 936-5, 939-3
Contributor Secondary Tessa Hedley-Whyte, MD, Massachusetts General Hospital, Pathology; Anne Osborn, MD, University of Utah, Neuroimaging; Steve Smith, Videographer; Ray Balhorn, Digital Video Compressionist
Reviewer David Zee, M.D. Johns Hopkins University, 2005.
Publisher Spencer S. Eccles Health Sciences Library, University of Utah
Date 1990
Type Image/MovingImage
Format video/mp4
Source 3/4" Umatic master videotape
Rights Management Copyright 2002. For further information regarding the rights to this collection, please visit: https://NOVEL.utah.edu/about/copyright
Holding Institution Spencer S. Eccles Health Sciences Library, University of Utah, 10 N 1900 E, SLC, UT 84112-5890
Collection Neuro-ophthalmology Virtual Education Library: NOVEL http://NOVEL.utah.edu
Language eng
ARK ark:/87278/s6b30rwd
Setname ehsl_novel_shw
Date Created 2005-08-22
Date Modified 2017-11-22
ID 188543
Reference URL https://collections.lib.utah.edu/ark:/87278/s6b30rwd
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