An Organized Approach to the Patient with Papilledema and IIH
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1 An Organized Approach to the Patient with Papilledema and IIH Leonard V. Messner, OD, FAAO James L. Fanelli, OD, FAAO Please silence all mobile devices and remove items from chairs so others can sit. Unauthorized recording of this session is prohibited. 1
2 Disclosures There are no disclosures to be made that affect the content of this presentation 2
3 Please remember to complete your session evaluations online. 3
4 Papilledema - Key Points Papilledema vs Pseudopapilledema Pathogenesis of papilledema Staging of papilledema Causes of papilledema 4
5 Papilledema Definition: Optic disc edema and elevation owing to elevated intracranial pressure Differentiated from Disc Edema Swelling of the optic disc of unknown etiology 5
6 SAS, ICP, and CSF CSF flows in SAS ON sheath houses ON and SAS Extends to the Lamina Increased ICP Orbital portion ON compressed Compression transmitted forward to the lamina Tourniquet like compression Axonal transport blocked at lamina 6
7 SAS, ICP and CSF 7
8 SAS, ICP and CSF 8
9 Pathogenesis - Neurogenic Elevated ICP Axoplasmic stasis & arrest (lamina cribrosa) Intra axonal edema/cytotoxic edema Leakage of axoplasmic fluid (extracellular edema) Increased extra-axonal osmolarity (extracellular edema) 9
10 Disc and Edema Intra and extracellular swelling Microtubule distortion 10
11 Pathogenesis Tumors/space occupying lesions IIH Increased CSF production Decreased CSF resorption DVST, inflammation, meningitis, SAH Dural venous sinus obstruction Cerebral edema Medications 11
12 Pathogenesis - Vasogenic Obstructed venous outflow Capillary dilation & leakage Capillary nonperfusion / ischemia 12
13 13
14 Histologic Edema: 2 Sources Cytotoxic edema Intracellular edema secondary to Direct cellular injury Vasogenic edema Extracellular edema secondary to Vessel leakage 14
15 Clinical Features - Ocular Bilateral Symmetric Transient diplopia (CN VI) TVO s (+/-) 15
16 Clinical Features - Ocular Vision preservation early in disease process (As opposed to other causes of optic nerve edema) Develops over hours to weeks Progressive deterioration of visual fields Visual recovery is related to management of underlying causes 16
17 Visual Loss VF VA Early Developed Chronic Atrophic 17
18 Clinical Features - Non-ocular Headaches (upon awakening & head movement, cough, Valsalva) Pulsatile intracranial noises Seizure Emesis (+/- nausea) Neurologic dysfunction 18
19 Ocular Signs Blurring of disc margins Elevation of disc Obscuration of the cup Edema of the peripapillary RNFL Retinal and choroidal folds Hyperemic discs Vascular congestion Hemorrhages, exudates and infarcts 19
20 Differentiating Papilledema Optic disc edema secondary to increased intracranial pressure PseudoPapilledema Optic disc edema not related to increased ICP 20
21 Disc Edema NOT ICP Related Ischemic Optic Neuropathies AION NAION Disc Drusen Optic Neuritis Vascular Etiologies Diabetic disc edema C/BRVO Hypertensive disc edema Unilateral disc edema 21
22 Pseudopapilledema- Ophthalmoscopy Venous pulsations + Absence of physiological cupping Vascular anomalies No NFL exudates No NFL infarcts 22
23 Disc Edema-NO ICP elevation VOs Tilted disc ION PPCNVM Drusen 23
24 78 Y/O White Male AMD yearly visit No complaints 20/30 OD, OS, OU 24
25 78 Y/O White Male 25
26 Disc Drusen May be seen on fundoscopy Buried drusen not visible 26
27 52 Y/O Caucasian Pediatrician No complaints 20/20 OD, OS, OU 27
28 Pseudopapilledema-OCT Findings Elevation of the optic nerve head with.. Minimal increase in RNFL thickness Minimal central cup Increased reflectance of hyaline Shadowing near hyaline Separation of deeper retina from RPE Neutral/Negative RPE and BM deflection 28
29 Disc Drusen-OCT findings Elevation Normal RNFL No/minimal cup Increased reflectance Shadowing Separation of outer retina 29
30 Disc Drusen- Shadowing & Separation of Outer Retinal Layers 30
31 Pseudopapilledema-OCT Findings Neutral/Negative RPE and BM deflection 31
32 OCT Findings- Papilledema 32
33 Forward Bowing of RPE/BM 33
34 14 Y/O New Patient Headaches worsening 20/20 20/
35 14 Y/O NP 35
36 36
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39 39
40 Stages of Papilledema Jackson Hoyt & Beeston Frisen
41 Early (Grade 1-2) Mild disc elevation Halo of edema - early temporal sparing Circumpapillary retino-choroidal folds (Paton s lines) Loss of SVP 41
42 C-Shaped Edema 42
43 C-Shaped Edema 43
44 42 y/o woman c/o headaches VA = 20/20 OD, 20/20 OS 62 inches tall 260 pounds 44
45 45
46 46
47 Developed (Grade 3-4) Marked disc elevation & hyperemic edema Obscuration of major vessels - halo expansion- around to on disc Microvascular disruption capillary telangiectasis collaterals infarcts hemorrhage Grade 3 Grade 4 47
48 48
49 49
50 Chronic (Grade 5) Marked dome-shaped disc elevation ( champagne cork ) Resolution of hemorrhage & infarcts Less hyperemia, more pallor Obscuration of vessels Obliteration of optic cup Refractile bodies 50
51 51
52 52
53 Refractile Bodies Seen fundoscopically Represent lipid exudates from chronic microvascular leakage 53
54 54
55 Frisen Staging Summary 55
56 Atrophic (Post-Papilledema Optic Atrophy) Flattening of disc Resolution of edema Residual collaterals Generalized disc pallor 56
57 Sometimes Bad Outcome 57
58 Other Times Good Outcome Longterm 58
59 Causes of Papilledema Intracranial mass Structural abnormality / Hydrocephalus Vascular (e.g. CVT, AVM) Iatrogenic Idiopathic intracranial hypertension Corbett JJ
60 15 Y/O Female Headaches Recent increase HA x 2 months Blurred vision, difficulty focusing Waxing and waning? Tinnitus 20/25 20/25- ERRLA APD Neuroimaging and biopsy: Astrocytoma 60
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63 1 month post surgery 63
64 64
65 August
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69 Causes of Papilledema Intracranial mass Structural abnormality / Hydrocephalus Vascular (e.g. CVT, AVM) Iatrogenic Idiopathic intracranial hypertension Corbett JJ
70 17 y/o AA Male Six week hx of vision loss, OS > OD Worse at near than distance Previous spectacle Rx (not sure of last exam) Occasional stress headaches Increasing problems with dizziness passed out one year earlier while getting off bus 70
71 Neuro-ophthalmic Examination BCVA: 20/200 OD 20/400 OS Sluggish pupils OU (? LAPD) Downbeat nystagmus (greater down left & down right) Visual fields: Bitemporal hemianopia denser below than above 71
72 72
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77 Hydrocephalus and kids shunts Shunt failure 77
78 Sometime, big things come in small packages 78
79 35 y/o Woman c/o headaches VA = 20/20, OU 79
80 80
81 81
82 Sagital Sinus Obstruction 82
83 CSF Production and Drainage CSF produced from arterial blood in the choroidal plexus in lateral and 4 th ventricles Exits 4 th ventricles Into SAS 83
84 84
85 T1 Weighted T2 Weighted 85
86 CSF Production and Drainage CSF is absorbed into the dural venous sinuses by the arachnoid villi 86
87 CSF Production and Drainage About 650 cc of CSF is produced per day Normal CSF pressure mm H2O (8-15 mmhg) Normal CSF pressure is LOW Normal Dural Venous sinus pressure is LOWER! Therefore, anything that impedes dural venous sinus drainage will result in impaired CSF drainage 87
88 Dural Venous Sinus Thrombosis Imaging: MRV/CTV International Study of Cerebral Venous and Dural Venous Sinus Thrombosis (ISCVT) 88
89 Papilledema - Key Points Neuroimaging studies for neuro-ophthalmic disorders Pathogenesis of papilledema Papilledema vs Pseudopapilledema Staging of papilledema Causes of papilledema 89
90 Idiopathic Intracranial Hypertension (Pseudotumor Cerebri) 90
91 IIH - Key Points Defining pseudotumor cerebri & IIH Pathogenesis of IIH Clinical features and neuroradiology Prognostic factors and management OCT analysis of papilledema Visual fields! 91
92 34 y/o Woman VA = 20/20, OU + HA x 2 yrs. Normal neuro exam BMI: 39 92
93 93
94 Pseudotumor Cerebri & Idiopathic Intracranial Hypertension 94
95 Pseudotumor Cerebri elevated ICP no mass No known cause Identifiable cause Idiopathic Intracranial Hypertension Iatrogenic Hypervitaminotosis Inflammatory Venous sinus thrombosis 95
96 Dandy WE Ann Surg
97 Smith JL J Clin Neuro-ophthalmol
98 Dandy Criteria for IIH (Modified) Signs & symptoms of elevated ICP (e.g. papilledema, headaches) No localizing neurologic signs (except CN VI paresis) ICP >250 mm H2O (normal CSF) No evidence of mass/structural lesion on MRI Empty sella No ventriculomegaly No secondary cause of elevated ICP Smith JL. J Clin Neuro-ophthalmol
99 Revised Diagnostic Criteria for the Pseudotumor Cerebri Syndrome in Adults and Children Wall M, et al. Neurology
100 Neuroradiology Findings with IIH Empty sella Posterior scleral flattening Optic nerve distension Ectopic displacement of cerebellar tonsils Dural venous sinus stenosis 100
101 Neuroradiology Findings with IIH Empty sella Posterior scleral flattening Optic nerve distension Ectopic displacement of cerebellar tonsils Dural venous sinus stenosis 101
102 102
103 Neuroradiology Findings with IIH Empty sella Posterior scleral flattening Optic nerve distension Ectopic displacement of cerebellar tonsils Dural venous sinus stenosis 103
104 104
105 Neuroradiology Findings with IIH Empty sella Posterior scleral flattening Optic nerve distension Ectopic displacement of cerebellar tonsils Dural venous sinus stenosis Aiken AH, et al. Am J Neuroradiol
106 106
107 Neuroradiology Findings with IIH Empty sella Posterior scleral flattening Optic nerve distension Ectopic displacement of cerebellar tonsils Dural venous sinus stenosis Farb RI, et al. Neurology
108 28 y/o AA Woman c/o moderate, progressive headaches x 1 month Normal neurologic exam BVA: 20/20 OD 20/20 OS BMI:
109 109
110 110
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116 27 y/o AA Woman c/o moderate, progressive headaches x 1-2 month Normal neurologic exam BVA: 20/20 OD 20/20 OS BMI:
117 117
118 118
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120 120
121 Epidemiology of IIH % female 15 to 44 years Obesity MAI = /100, /100,000 if obese female yrs. Giuseffi V, et al. Neurology 1991 Ireland B, et al. Arch Neurol 1990 Radhakrishnan K. et al. Arch Neurol
122 Pathogenesis of IIH (???) Increased cerebral blood volume - Raichle 1978 Increased arachnoid resistance to CSF drainage - Aisenberg 1980 Increased intra-abdominal pressure with cerebral venous hypertension - Sugerman 2001 Reduced CSF absorption by extracranial lymphatics Johnston
123 Baseline Clinical Profile (IIHTT) Headache (84%) Back pain (53%) Tinnitus (52%) Vision loss Transient vision loss (68%) Symptomatic vision loss (32%) Visual fields (86% {5% > 15db}) Enlarged blind spot Inferior arcuate defects Wall M JAMA Neurol
124 The rest of the story 20/20 20/20 124
125 -2.54 db db 125
126 12 mos later db db 126
127 19 mos later 20/20 20/30 127
128 19 mos later HVF db db 128
129 Risk Factors for Poor Visual Prognosis Male gender African American Morbid obesity Marked weight gain Obstructive sleep apnea Concomitant medications Acute onset of signs and symptoms of elevated ICP (fulminant IIH) High-grade papilledema Lack of headaches Lack of ophthalmic oversight Biousse V. NANOS
130 Gender Men represent approx 10% of all IIH Less likely to have headache ( estrogen factor ) Less likely to seek care Digre & Corbett Arch Neurol 1989 Bruce BB, et al. Neurology
131 Race No strong influence on development of IIH African Americans = more aggressive disease: 3X more likely to have severe vision loss 5X more likely to develop blindness Bruce BB, et al. Neurology
132 Obesity NORDIC ave. BMI = 39 Increased severity of papilledema and visual loss if BMI 40 Recent weight gain (5-15%) even in non-obese patients Szewka AJ, et al. J Neuroophthalmol 2013 Wall & George. Brain
133 Medications Many meds proposed to induce IIH, few testretest data Tetracycline derivatives (minocycline) cyclosporine, lithium, nalidixic acid, nitrofurantoin, oral contraceptives, levonorgestrel, danaxol, and tamoxifen Friedman DI. Am J Clin Dermatol 2005 Fraser CL, et al. Arch Neurol
134 14 y/o Girl HAs x 2-3 weeks Rx minocycline x 1 month for acne VA: 20/20 OU BMI:
135 135
136 136
137 137
138 138
139 MRI / MRV normal D/C minocycline Follow-up x 3 weeks 139
140 Reduction in RNFL: 32 microns OD 142 microns OS 140
141 By 4 mos: Reduction in RNFL: 109 microns OD 196 microns OS 141
142 Co-Morbidities Anemia Hypertension Obstructive sleep apnea Biousse V, et al. Am J Ophthalmol 2003 Wall M. Neurol Clin
143 Pregnancy Independent of weight gain, not a risk factor for IIH Beware of cerebral venous sinus thrombosis (end of pregnancy & post partum period) Biousse V, et al. Neurology
144 35 y/o woman c/o progressive & severe HA s, emesis & nausea 2 weeks post partum VA = 20/20, OD & OS 144
145 145
146 146
147 Clinical Findings Predictive of Poor Outcomes Absence of headaches Severity of papilledema (+/-) Marked visual field defects at presentation Fulminant course (malignant IIH) Biousse V. NANOS
148 Management of IIH Observation CAI s / diuretics? value Surgery VP shunt ONSF Weight loss 5-10% BMI Visual Fields 148
149 149
150 Acetazolamide for IIH (?) (The IIH Pilot Trial) UK prospective study 50 IIH patients: ½ Rx acetazolamide ½ observation All patients advised to lose weight No benefit to acetazolamide (12 mos.) Matthews T, et al. NANOS
151 NORDIC IIH Treatment Trial Specific Aim 1: The trial is focused on determining the efficacy of low sodium diet with or without acetazolamide to reduce or reverse visual loss. Specific Aim 2: (a) To identify proteomic and genetic risk factors for IIH by screening a large cohort of IIH patients and controls. 151
152 Mild IIH 152
153 IIHTT 6-Month Results Acetazolamide better than diet alone for visual field improvement (PMD reduction of 1.43 vs db) Acetazolamide arm showed better weight reduction than diet alone Acetazolamide arm showed better resolution of papilledema & improvement of QOL scores vs. diet alone Wall M, et al. JAMA Neurol
154 25 y/o AA Woman c/o progressive vision loss OU h/o recurrent headaches (am > pm) BVA: 20/30 OD 20/40 OS 154
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161 38 y/o AA Woman Medical history = SLE Tx with po prednisone Approx. 200 lb weight gain (>400 lbs.) BVA: 20/20 OD 20/20 OS 161
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165 OD 165
166 OS 166
167 Cont. MRI / MRV normal Coordinated care through HMO PCP Nothing done IEI 5 mos. later complaining of progressive severe HA (10/10) BVA: 20/20 OD 20/20 OS 167
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170 OD 170
171 OS 171
172 32 y/o Hispanic Woman c/o progressive, debilitating headaches x 2 mos. Normal neurologic exam BVA: 20/20 OD 20/20 OS BMI:
173 173
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181 F/U x 6 mos Rx Diamox (500 mg BID) Weight loss (approx. 25 lbs.) Improvement in headaches 181
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187 F/U x 14 mos D/C Diamox x 3 months Weight loss (BMI reduction from 38 to 30) Headache free 187
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190 Total RNFL Reduction OD: 386 to 97 OS: 442 to
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194 IIH - Key Points Defining pseudotumor cerebri & IIH Pathogenesis of IIH Clinical features and neuroradiology Prognostic factors and management OCT analysis of papilledema Visual fields! 194
195 Thank you! 195
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