Apraxia of Eyelid Opening

Apraxia of Eyelid Opening; Impaired Initiation of Horizontal Saccades; Slow Hypometric Horizontal Saccades; Supranuclear Paralysis of Up and Downgaze; Square Wave JerksPowerPoint Presentation: 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 SchoolFrequent fallsIn January 1997, This 73 year old patient was referred to the Neurovisual Clinic. At that time his speech was slurred and he stated that his eyes were his "biggest" complaint due to: 1. Impaired focusing "close up" 2. His eyes shut spontaneously much of the time 3. Bright sunlight provoked eye closure 4. The frequent closure of his eyes made it difficult for him to hold a conversation with anybody. 5. With his eyes open his vision was clear Neuro-ophthalmological examination documented: Visual acuity: 20/40 OU Eyelids: Age related bilateral ptosis Infrequent blinking Positive glabella tap Able to close his eyes but very slow opening his eyes Mild blepharoclonus Ocular motility: Slow hypometric horizontal saccades Slow vertical saccades Absent convergence Saccadic pursuit in all directions Convergence insufficiency with exophoria at near Within six months his wife noted that his condition had deteriorated in that he: Seemed to have lost his motivation Rarely spoke unless spoken to Tended to sit longer without moving Did not appear to wish to read anything More difficulty feeding himself and dressing Much slower in all his movements Neurological examination at that time showed: Striking paucity of movements Rigidity of the neck Difficulty getting up out of a chair, toppling backwards Slowness walking and he needed to make several small steps in order to turn Speech had become dysphonic more than dysarthric Tongue moved well Jaw jerk and facial jerks absent Diagnosis: Progressive supranuclear palsyThis patient with progressive supranuclear palsy (PSP) has: • Supranuclear saccadic and pursuit paralysis of upward gaze. • Square wave jerks looking up • Slow hypometric horizontal saccades • Slow eyelid closure and impaired voluntary eyelid opening with striking inability to open his eyes on command (aparaxia) • His speech is dysphonic and dysarthric Comment: The inability to initiate eyelid opening is a dysfunction of voluntary lid control due, in this patient, to disease of the extrapyramidal system. The patient can close his eyes slowly on command and reopen them normally after blinking. But, the major problem was a difficulty in voluntarily opening his eyes on command (eyelid apraxia). The term "eyelid apraxia" is a misnomer and should not be used to describe the eyelid dysfunction in this case of PSP because the motor system is affected. 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) 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).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)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.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.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-like phenotypes.There is no cure for PSP. Once the disease has begun, its course is relentlessly progressive.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)curriculum_fellow; GVSapraxiaofeyelidopenin