| Identifier |
166-18 |
| Title |
Supranuclear Paralysis of Up and Downgaze |
| Creator |
Shirley H. Wray, MD, PhD, FRCP |
| Affiliation |
(SHW) Professor of Neurology, Harvard Medical School; Director, Unit for Neurovisual Disorders, Massachusetts General Hospital, Boston, Massachusetts |
| Subject |
Positive Glabella Tap; Slow Hypometric Horizontal Saccades; Supranuclear Paralysis of Up and Downgaze Degeneration; Progressive Supranuclear Palsy - Tauopathy; Steele Richardson Olszewski Syndrome; CNS - Degeneration |
| History |
This patient presented to the Dementia Clinic for evaluation of forgetfulness, impaired recall memory, lack of attentiveness and spontaneity and progressive impairment of mobility over a period of one year. Neurological examination: The patient was found to have multisystem involvement with: 1. Mild dementia 2. Extrapyramidal signs of neck rigidity, reduced blink rate, positive glabella tap and mask-like face. 3. Mild pseudobulbar palsy with slurred speech, no spasticity of the tongue, but brisk jaw and facial jerks 4. Supranuclear paralysis of vertical up and downgaze 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. (Figure 6B) The intracellular aggregation of tau in PSP may be sufficient to cause nerve cell degeneration. |
| Disease/Diagnosis |
Progressive Supranuclear Palsy - Tauopathy |
| Clinical |
This patient with Progressive Supranuclear Palsy (PSP) has a constellation of eye signs: 1) Reduced blink rate 2) Slow hypometric horizontal saccades 3) Supranuclear saccadic and pursuit paralysis of up and downgaze 4) Intact vertical oculocephalic reflex 5) Intact Bell's 6) Positive glabella tap 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). |
| Presenting Symptom |
Impaired Memory |
| Ocular Movements |
Slow Hypometric Horizontal Saccades; Supranuclear Paralysis of Up and Downgaze; Vertical Oculocephalic Reflex Intact |
| 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" of unknown etiology. 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 |
1976 |
| 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 Neuro-ophthalmol. 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 |
16 mm Film |
| Relation is Part of |
168-3, 924-2, 932-3, 936-5, 939-3. |
| Collection |
Neuro-Ophthalmology Virtual Education Library: Shirley H. Wray 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/s60c7sbz |
| Setname |
ehsl_novel_shw |
| ID |
188623 |
| Reference URL |
https://collections.lib.utah.edu/ark:/87278/s60c7sbz |
