| Identifier |
939-3 |
| Title |
Slow Saccade Syndrome |
| Creator |
Shirley H. Wray, MD, PhD, FRCP |
| Contributors |
Tessa Hedley-Whyte, MD; Anne Osborn, MD; David Zee, MD; Steve Smith, Videographer; Ray Balhorn, Video Compressionist |
| Affiliation |
(SHW) Professor of Neurology, Harvard Medical School; Director, Unit for Neurovisual Disorders, Massachusetts General Hospital; (THW) Massachusetts General Hospital, Boston, Massachusetts; (AO) Professor of Radiology, University of Utah, Salt Lake City, Utah; (DZ) Johns Hopkins Hospital, Baltimore, Maryland |
| Subject |
Supranuclear Paralysis of Upward Gaze; Slow Hypometric Horizontal Saccades; Square Wave Jerks; Convergence Insufficiency; Positive Glabella Tap; Progressive Supranuclear Palsy - Tauopathy; Steele-Richardson-Olszewski Syndrome; CNS - Degeneration Supranuclear Paralysis of Upgaze Degeneration |
| History |
In 1992, this 60 year old woman realized that she was "slowing up", dragging her right foot and walking slowly, and her speech became slurred. She saw a number of physicians and was given the diagnosis of Parkinson's disease and started on Sinemet 50/200 t.i.d. In January 1994, she was seen by a neurologist who noted the following findings. Dysarthria Flattened facies Mild resting tremor of the hands Significant limitation of upgaze with normal downgaze No nystagus No fibrillations of the tongue No bulbar weakness Mild decrease in spontaneous movements with diminished arm swing and a stooped forward gait Mild decrease in strength bilaterally Marked Hyperreflexia 3+ throughout with ankle clonus Plantar responses flexor No cerebellar ataxia Again a diagnosis of Parkinson's disease was made and her medication changed to Permax. The patient failed to improve on Permax and was referred for a third opinion. When seen in October 1994, she had noted progressive difficulty reading with the print running into each other. She would then rest from reading and start again and occasionally noted double vision with horizontal separation of the image. She had no diplopia watching TV. She was afraid to go for her driving license exam for fear that she would fail it. With regard to her memory she felt her memory was slipping. She forgot the names of people and some numbers and could not remember distant events. She had no problem calculating her checkbook. The neurological examination was unchanged. Dysarthric Flattened akinetic face Brisk jaw and facial jerk consistent with a mild pseudo-bulbar palsy Eyelids: 1. Infrequent blinking 2. Mild blepharoclonus 3. Positive glabella tap Ocular motility exam showed: Supranuclear paralysis of upward gaze with intact Bell's Slow saccades on full downgaze Slow horizontal saccades Saccadic pursuit in all directions Absent convergence with exophoria at near No nystagmus Diagnosis: Progressive supranuclear palsy |
| 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. The intracellular aggregation of tau in PSP may be sufficient to cause nerve cell degeneration. (Figure 6B) |
| Disease/Diagnosis |
Progressive Supranuclear Palsy - tauopathy |
| Clinical |
This 60 year old woman with Progressive Supranuclear Palsy (PSP) has: • Supranuclear saccadic paresis of upward gaze • Slow vertical downgaze saccades • Intact vertical pursuit • Slow hypometric horizontal saccades (a mixture of extreme hypometria and slowing - Slow Saccade Syndrome) • Square wave horizontal jerks looking up • Slow blink rate • Slow eyelid opening - mild apraxia • Convergence insufficiency with an exophoria at near • Accurate performance of the anti-saccade test (frontal lobe function) - when asked to look to the side opposite to the presentation of a visual target - the examiner's hand. 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 • Impaired initiation of vertical saccades • Vertical smooth pursuit impaired (reduced range) • Vertical optokinetic stimulation can cause gaze to tonically deviate in the direction of the stripe movement (Personal communication Zee DS 2005) Additonal signs in her case are: • An expressionless face with her mouth half open • Head hyperextended (nuchal dystonia) • 1+ jaw jerk and facial jerks • Tongue moves normally • Disinhibited behavior - inappropriate laugh Box 12-14 Clinical features of PSP. Pg. 639(5). |
| Presenting Symptom |
Difficulty reading |
| Ocular Movements |
Supranuclear Saccadic Paralysis of Upward Gaze; Slow Hypometric Horizontal Saccades; Square Wave Jerks; Convergence Insufficiency; Positive Glabella Tap |
| Neuroimaging |
PSP has characteristic changes on neuroimaging. In another case a sagittal T2-weighted MR scan shows the tectal plate 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) |
| Treatment |
There is no cure for PSP and once the disease has begun, its course is relentlessly progressive. |
| 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. |
| Supplementary Materials |
Tauopathies: A contemporary way to consider a set of neurodegenerative diseases based on their molecular signature: https://collections.lib.utah.edu/details?id=2174238 Progressive Supranuclear Palsy: https://collections.lib.utah.edu/details?id=2174233 |
| Date |
1995 |
| 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;781:532-540. 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):759-770. 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):104-109. 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;88:25-29. 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) |
| Language |
eng |
| Format |
video/mp4 |
| Type |
Image/MovingImage |
| Source |
3/4" Umatic master videotape |
| Relation is Part of |
166-18,168-3, 924-2, 932-3, 936-5 |
| Collection |
Neuro-Ophthalmology Virtual Education Library - Shirley H. Wray Neuro-Ophthalmology Collection: https://novel.utah.edu/Wray/ |
| Publisher |
North American Neuro-Ophthalmology Society |
| Holding Institution |
Spencer S. Eccles Health Sciences Library, University of Utah |
| Rights Management |
Copyright 2002. For further information regarding the rights to this collection, please visit: https://NOVEL.utah.edu/about/copyright |
| ARK |
ark:/87278/s6b885pf |
| Setname |
ehsl_novel_shw |
| ID |
188512 |
| Reference URL |
https://collections.lib.utah.edu/ark:/87278/s6b885pf |
