Neuro-Ophthalmic Disease Cases
Kelly A. Malloy, OD, FAAO, Diplomate
Clinical cases will be used to demonstrate the varied presentations related to neuro-ophthalmic disease. These will include both afferent and efferent manifestations of neuro-ophthalmic disease, as well as associated ocular health and neurologic manifestations. Conditions that may be demonstrated through clinical cases are included in the outline below.
Course Learning Objectives:
1. To emphasize the importance of the optometrist’s role in identifying signs and symptoms which suggest a neuro-ophthalmic disease process.
2. To understand how to conduct an examination oriented to the detection of neuro-ophthalmic disease.
3. To discern the differential diagnoses for a variety of clinical neuro-ophthalmic presentations.
4. To become familiar with the necessary diagnostic testing for a variety of neuro-ophthalmic presentaions.
5. To emphasize the need to promptly identify and refer patients presenting with emergent neuro-ophthalmic disease conditions.
6. To have a better understanding of the work-up, management, and treatment of neuro-ophthalmic disease conditions.
Neuro – Ophthalmic Disease Cases - OUTLINE
Conditions that may be demonstrated through actual clinical cases are included in the outline below.
PAPILLEDEMA
Papilledema - Bilateral/Asymmetric (anatomic difference in lamina) RARELY Unilateral
ICP (Intracranial pressure) greater than 200 - 250 mm H2O
Features of edema
Axoplasmic stasis in pre-laminar optic nerve
Obscuration of retinal vessels coursing over the disc margin
Paton’s lines temporally
Symptoms of Increased Intra-Cranial Pressure
Headache
Nausea
Vomiting
Diplopia (Abduction deficit – CN VI)
Pulsatile tinnitus
Transient Visual Obscurations (TVOs) Last few seconds (uni or bi-lateral) Transient optic nerve ischemia
Pattern of Edema
Corresponds with NFL thickness
Superior, Inferior > Nasal > Temp
Superior and Inferior NFL swell first
Last to swell is Temporal NFL
NFL swelling blurs disc margins and obscures underlying vessels
Spontaneous Venous Pulsation
Presence of SVP means ICP normal (at that moment - can fluctuate)
10-20 % of normals may not have SVP
PSEUDOTUMOR CEREBRI IMPOSTERS
Tumor Cerebri
Anomalous Discs, Obesity, Migraine
Venous Sinus Thrombosis
Arteriovenous Malformation
Spinal Cord Tumors
PSEUDOTUMOR CEREBRI IS A SYNDROME BASED UPON:
MODIFIED DANDY’S DIAGNOSTIC CRITERIA
PATIENT MUST BE AWAKE & ALERT
SIGNS & SYMPTOMS OF INCREASED ICP
NO NEUROLOGIC SIGNS EXCEPT CN VI PARESIS
CSF OPENING PRESSURE > 200MM. H20 & NORMAL COMPOSITION
NORMAL MRI, CT
PSEUDOTUMOR CEREBRI - EPIDEMIOLOGY
92% Women
Ages 11-58
No Racial Bias
13/100,000 In Women - 10% Above Ideal Body Weight
19/100,000 - 20% Above Ideal Body Weight
PSEUDOTUMOR CEREBRI INVESTIGATIONS
MRI and MRV (MRA)
LUMBAR PUNCTURE with opening pressure and analysis of CSF
TREATMENT
WEIGHT LOSS (6%)
CARBONIC ANHYDRASE INHIBITORS
acetazolamide (diamox); up to 1000 mg.
reduces CSF by 50% but may be unsustained!
Contraindicated in renal disease
SURGICAL TREATMENT
Lumboperitoneal Shunt
Optic Nerve Sheath Fenestration
Gastric Bypass Surgery
PROGNOSIS
49% Have Some Visual Loss (Corbett 1982; Orcutt 1984)
25% Severe & Permanent Visual Loss (Folley 1955; Boddle 1974)
80% Improve In 8 Months (Corbett 1982)
10% Recurrence Rate
CRANIAL NERVE III PALSY
Hyper Deviation Which Increases In Upgaze And Reverses In Downgaze
Exo Which Increases Across From The Vertically Limited Eye
DEATH FROM SUBARACHNOID HEMORRHAGE (SAH) (LOCKSLEY 1969)
20% Of Patients With SAH Die Within 48 Hours
need to consider aneurysm in all CN III palsy
ANSWER BY PUPIL
INVOLVED=ANEURYSM
SPARED=VASCULOPATHIC
DOES NOT APPLY IF:
Complicated CNIII
Incomplete CNIII
Relative Sparing
20-50 Years Of Age
ABERRANT REGENERATION OF CN III
Pseudo Graefe Sign
Eyelid Synkinesia
ABERRANT REGENERATION OF CN III - CAUSES
COMMON CAUSES: Aneurysm, Tumor, Trauma
UNUSUAL: Inflammation
NEVER: Diabetes Mellitus
ISOLATED CN III PALSY IN ADULTS
Undetermined 24%
Aneurysm 21%
Ischemia 18%
Trauma 13%
Neoplasm 12%
CN III PALSY Work-up ADULTS
20-50 YEARS
CT, MRI, MRA, Arteriogram
50+ YEARS (pupil, palsy, pain)
Neuroimaging
Vasculopathic Evaluation
CNIV PALSY
Vertical Diplopia , Worse at Near, Object Tilting, Relief With Head Position
A Hypertropia That Increases Across From The Vertically Limited Eye And On Ipsilateral Head Tilt
MEASURING EXCYCLOTORSION
Subjective, Maddox Rod, Bagolini Striated Lenses, Fundus, Plot Blindspot
OBJECTIVE vs. SUBJECTIVE EXCYCLOTORSION
Objective = Subjective - Acute
Objective > Subjective - Longstanding
Objective Without Subjective - Congenital
“CHECKLIST” EXAMINATIONwhat to look for: anatomic localization:
CONTRA HORNER’S LOCUS CERULEUS (Copetto 1983)
CONTRA INO MLF (Vanooteghem 1992)
IPSI RAPD BRACHIUM SUP COLL (Elliot 1991)
DMS ANT MEDULLARY VELUM
BILATERAL CNIV ANT MEDULLARY VELUM
TRUNCAL ATAXIA & IPSI DYSMETRIA SUP CEREBELLAR PEDUNCLE
IPSI CN III, V1, VI, OSP CAVERNOUS SINUS
BILATERAL CNIV
R HYPER> IN L GAZE & RHT, L HYPER> IN R GAZE & LHT
V PATTERN ESO > 25 PD, EXCYCLOTORSION > 10 deg
(LOOK FOR THE DORSAL MIDBRAIN SYNDROME)
ISOLATED CN IV IN KIDS (CAUSE)
Trauma, Congenital
ISOLATED CN IV IN ADULTS
10% Aneurysm, 20% Ischemic, 30% Undetermined, 40% Trauma
TRAUMATIC CNIV PROGNOSIS (SYDNOR 1982)
SPONTANEOUS RECOVERY:
UNILATERAL: 65%
BILATERAL: 25%
WHAT DO I DO?
History Of Trauma?, Old Photos, Vertical Vergences, Neuro-Imaging, Vasculopathic Eval, MG?, Graves?, Skew?
CNIV: MANAGEMENT?
Segmental Prisms & Patches X 9-12 Months
Monitor For Secondary Contracture - Surgical Intervention
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ABDUCTION DEFICIT/ CN VI PALSY
F ABDUCTION DEFICIT
CN VI PALSY KEY POINTS - Measure At Distance
Imposters – Abduction Deficits
Graves Disease / Thyroid Orbitopathy, Myasthenia Gravis, Loss Of Fusional Reserves, Spasm Of The Near Reflex, Duane’s Retraction Syndrome
“THE SIGNATURE OF CN VI PARESIS”
At Distance: Eso Which Increases In The Action Of The Palsied Eye
CN VI PALSY - ANSWER BY MOTILITY
Duction > Version, “Glissades” (Slowed Saccades), Asymmetric OKN (Optokinetic Nystagmus), Negative Forced Duction
ANATOMIC LOCALIZATION
FASICULAR
CN VI +
Contralateral Hemiplegia = (Raymond’s)
VII + Contralateral Hemiplegia = (Millard-Gubler)
Etiology: Infarction, Demyelination, Tumor
SUBARACHNOID
Increased Intracranial Pressure (Papilledema), AICA Aneurysm, Subarachnoid Hemorrhage, Trauma, Meningitis, Clivus Tumor, Post Infectious, Neurosurgical
PETROUS
Petrous Apex/ Mastoid Infection, Inferior Petrosal Sinus Infection, Petrous Bone Fracture, Trigeminal Schwannoma, Lumbar Puncture, Myelography, Spinal/ Epidural Anesthesia
CAVERNOUS SINUS/ SOF
Aneurysm, Thrombosis, CCF (Carotid Cavernous Fistula), Dural AVM (Arterio-venous Malformation), Tumor, Tolossa-Hunt, Herpes Zoster
WORK-UP?
CBC (Complete Blood Count), BS (Blood Sugar) / HEMOGLOBIN A1c, LYME TITER, RPR/ FTA-ABS (tests for syphilis), ANA (Anti-Nuclear Antibody), ESR (Erythrocyte Sedimentation Rate), C-REACTIVE PROTEIN, PLATELETS, & HEMOGLOBIN (tests for Giant Cell Arteritis), Exclude Trauma, MRI With Gadolinium, Lumbar Puncture
CHRONIC CNVI PALSY (= OR > 6 months) – Harbingers of Serious Intracranial Disease
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HORNER SYNDROME
MIOSIS, PTOSIS, ANHYDROSIS
Anisocoria > Dim “Lazy Dilator” (Dilation Lag) Anisocoria > 5 Sec Than 12 Sec
Measure in bright AND dim - Greater anisocoria in dim illumination
Pancoast’s Tumor (Apical lung tumor)
TRIAD: Ptosis, Miosis, Arm Pain
CAROTID ARTERY DISSECTION
CLASSIC TRIAD: Pain On Side Of Face, Head Or Neck, Oculosympathetic Paresis Without Anhydrosis, Delayed Retinal Or Cerebral Ischemia (50-95% Of Patients)
SYMPTOMS
Exploding, Ipsilat Headache
Transient Monocular Blindness
Diplopia
Orbital, Facial, Neck, Jaw Pain
Dysguesia
Facial Numbness
Neck Swelling
SIGNS
Horner’s Syndrome
Neck Bruit Or Swelling
CN VI, IX-XII
CRAO
Cerebral Ischemia
Need to consider CAROTID DISSECTION in EVERY PAINFUL HORNER SYNDROME
Can occur with or without trauma
Medical Emergency
Horner’ s with eye, head, neck pain - Pt to hospital (MRI, MRA, CTA, angiogram)
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OPTIC NEURITIS
Most common acute monocular vision loss in young and middle-aged
3rd and 4th decades, Females
Association with Multiple Sclerosis
Typical ON
Unilateral
Painful (with eye movements)
Visual loss progressing over one week
Young / middle age adult
Normal fundus or minimal ON edema
Atypical ON
NLP vision
Optic disc or retinal hemes
Severe disc swelling
Macular exudates
No pain
Uveitis
Bilateral vision loss (adults)
DDX of Optic Neuritis
Inflammatory / Autoimmunine Diseasesn ( SLE, Antiphospholipid Syndrome, Primary Sjogren’s Syndrome, Neurosarcoidosis, Neuro-Bechet’s Disease, Wegener’s Granulomatosis)
Infectious Etiologies ( Lyme , Neurosyphilis, HIV-related disorders of the CNS)
Genetic / Hereditary Disorders
Demyelinating Disorders
50% of MS pts develop ON at some point
ON is 1st clinical symptom of MS in 20%
Work-Up
lab testing to R/O other etiologies
ACE, ANA, Lyme titer, FTA-ABS, RPR
MRI of brain and orbits with contrast
Spinal tap ?
Recommended ON Tx
IV Methylprednisolone
250 mg q 6 hr x 3 days
Oral prednisone taper
1 mg/kg/day x 11 days, 4 day taper [20 mg day 1; 10 mg days 2 and 4]
MS treatments
High-risk
ON and 2 or more lesions on MRI
Immunomodulators
Copaxone
Interferons
Interferon beta-1a (Avonex or Rebif)
Interferon beta-1b (Betaseron)
Lower risk of further demyelinating events
Reduce MRI activity
OPTIC NEURITIS (CLINICAL PROFILE)
F (77.2%) M (22.8%)
CAUCASION (85%) > BLACK (15%)
AGES 15-40 YEARS (MEDIAN 31.8)
92.2% PAIN!
VISUAL NADIR: 4.7 DAYS
RECOVERY: 2-3 MONTHS
FELLOW EYE: 20% (68.8%, 33.2%, 31.4%)
IDIOPATHIC OPTIC NEURITIS SYMPTOMS
92.2% PAINFUL, BLURRED VISION
DISCOMFORT ON EYE MOVEMENT
IDIOPATHIC OPTIC NEURITIS FUNDUS EXAM
RETROBULBAR OPTIC NEURITIS 65%
PAPILLITIS 35%
IDIOPATHIC OPTIC NEURITIS VISUAL RECOVERY
RECOVERY BEGINS WITHIN 3 WEEKS OF ONSET OF SYMPTOMS
PLATEAU’S @ 6 WEEKS; IMPROVES UP TO 1 YEAR
@ 5 YEARS: 87%: > 20/25 94%:> 20/40
VISUAL RECOVERY IS WORSE IN PATIENTS WITH FC/LP
RECURRING OF 20% IN 5 YEARS
ONTT(Beck 1992)
Optic Neuritis= MS (Relapsing/ remitting)
DxMS: Clinical Diagnosis + MRI findings
Oral steroids double risk of recurrence (30%)
Treatment affects course of disease (IV sol medrol halves risk of CDMS at 2 years in patients with + MRI). IV steroids speed visual recovery
MRI can predict CDMS
ONTT TREATMENT RECOMMENTATIONS FOR IDIOPATHIC OPTIC NEURITIS
8 DAYS OF ONSET
MRI SHOULD BE PERFORMED
ASSESS CRITICAL NUMBER OF WHITE MATTER LESIONS
IV METHYLPREDNISOLONE X 3 DAYS (short course of prednisone)
ONTT – 10 year results
Overall risk of MS in 10 yrs = 38% CDMS
One or more brain lesions = 56% CDMS
> 40% with one or more lesions did NOT develop CDMS in 10 yrs
No brain lesions = 22% CDMS
78% with no lesions did NOT develop CDMS in 10 yrs
Risk significantly higher with 1 lesion
No increased risk with greater number of lesions
Mean time to DX = 3 years
Almost 75% of Dx occurred in 5 years
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GIANT CELL ARTERITIS
ELDERLY - Mean age :72 years
Consider in patients over age 50
Preference for Caucasians (2/3)
Preference for women (2/3)
27% men
73% women
Attacks medium and large sized arteries
Specifically targets arteries with ILM
Elastin likely is inciting antigen (auto-immune)
Thrombosis and Occlusion
SYSTEMIC SYMPTOMS OF GCA
Fever , Headache, Anorexia/Weight Loss, Malaise, Myalgia
GCA SYMPTOMS(Keltner 1982)
HEADACHE 4-100%
TENDER TEMPORAL ARTERY 28-91%
MYALGIA/ ARTHRALGIA 28-86%
FEVER 30-100%
WEIGHT LOSS 16-76%
JAW CLAUDICATION 4-67%
ANOREXIA 14-69%
MALAISE 12-97%
LEG 2-43%
OCCULT GCA
Ocular involvement
No systemic symptoms / signs
21% of GCA cases
Have LOWER values of ESR and CRP
May be a more localized disease process
OCULAR INVOLVEMENT
50% of GCA pts. present with ocular involvement
Characteristics of pts with ocular involvement
OLDER, LOWER ESR (&CRP)
LESS SYSTEMIC SYMPTOMS
VISUAL LOSS
The fellow eye can be affected (28-31%):
Simultaneously
Within days to weeks
BILATERAL ischemic visual loss – CONSIDER GCA!
AMAUROSIS FUGAX
Transient monocular blindness
Most often caused by ON ischemia, can be light-induced
Present in 31-46% of GCA pts.
Precedes permanent visual loss 50-63% of time
Prodrome to AAION
OCULAR SIGNS OF GCA
Arteritic Anterior Ischemic Optic Neuropathy (AAION) (81%)
Central Retinal Artery Occlusion (9 - 14%)
Cilioretinal Artery Occlusion
Posterior Ischemic Optic Neuropathy
Ocular Ischemia (CWS, Choroidal Hypoperfusion, Chorioretinal Degen.)
Ocular Motility Restrictions / Cranial Neuropathies
Nystagmus / Internuclear Ophthalmoplegia
AAION
81% of GCA pts
Most common cause of severe vision loss in GCA
Poor visual prognosis
Fellow eye commonly involved (65% if untreated)
Simultaneously or within weeks (usually)
More severe visual dysfunction than N-AION (usually!)
Extremely poor visual prognosis
“Chalky white” disk swelling
Cupping & parapapillary atrophy (Hayreh et al.2001)
LAB TESTING / WORK-UP
Westergren Sedimentation Rate (ESR)
C-Reactive Protein (CRP)
Platelet count
CBC c differential
Erythrocyte Sedimentation Rate Westergren / STAT
A normal ESR does NOT R/O GCA
Normal in 12-13% of GCA patients
NON-SPECIFIC FOR GCA
Indicator of inflammatory and neoplastic disease
Non-specific marker of an acute phase reaction
ESR High Normal Cut-Off
MEN: Age / 2 WOMEN:{Age + 10} / 2
C-Reactive Protein
Immunoassay
Normal Value: <2.54 mg/dL
Elevated in GCA
One of major Acute Phase Reactants
Independent risk factor for coronary artery disease
Returns to normal more rapidly than ESR with resolution of disease process
Elevated CRP and ESR : 97% specific for GCA
CBC with Differential
Anemia associated with GCA (normochromic, normocytic)
Platelet Count
Thrombocytosis: platelet count (>400x109/L)
Marker of systemic inflammatory response
Linked with increased cerebral ischemic events
Severe thrombocytosis (> 600x109)
associated with risk of permanent visual loss
If suspicion remains, get GSTA Biopsy!
BIOPSY OF Greater Superficial Temporal Artery
PERFORMED WITHIN 14 days
SKIP LESIONS in 28 % (17/60), BIOPSY 3-7 mm. SEGMENT
DO NOT WAIT UNTIL AFTER BIOPSY TO TREAT
Try to perform biopsy within 2 weeks of treatment
TEMPORAL ARTERY BIOPSY
2cm sample (preferably more)
Ipsilateral side of any ocular invovement
Skip Lesions (4 - 5% false negatives)
TREATMENT
Visual Involvement: PROTECT OTHER EYE
STAT IV Methylprednisolone
(Solumedrol 250mg IV q 6 hrs x 3 days)
Followed by Oral Prednisone
No Visual Involvement: PROTECT VISION
Oral Prednisone (60-80 mg daily)
PROGNOSIS
UNTREATED: 30-40% BILATERAL BLIND
(highest risk of vision loss within 10 days)
5-10% GO BLIND DESPITE TREATMENT
15-34% HAVE SLIGHT IMPROVEMENT WITH TREATMENT
26% RELAPSE RATE
ANY NEW-ONSET NEUROLOGIC DEFICIT IN A PATIENT OVER 50 YRS. SHOULD BE INVESTIGATED FOR GCA!
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MYASTHENIA GRAVIS
NEUROMUSCULAR DISORDER
WEAKNESS & FATIGABILITY OF VOLUNTARY MUSCLE
DECREASE OF Ach RECEPTORS
AUTOIMMUNE ATTACK
PEAK INCIDENCE
YOUNGER WOMEN (15-20)
OLDER MEN (50-60)