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9. Lepori D, Capasso P, Fournier D, et al.

High-resolution ultra-
sound evaluation of internal jugular venous valves. Eur Radiol No Correlation between
1999;9:1222–1226.
10. Akkawi NM, Agosti C, Rozzini L, et al. Transient global am- Intraocular Pressure and
nesia and venous flow patterns. Lancet 2001;357:639.
11. Maalikjy Akkawi N, Agosti C, Anzola GP, et al. Transient Intracranial Pressure
global amnesia: a clinical and sonographic study. Eur Neurol
2003;49:67–71. Ying Han, MD, PhD,1 Timothy J. McCulley, MD,1
12. Ishikawa M. Clinical guidelines for idiopathic normal pressure and Jonathan C. Horton, MD, PhD1,2
hydrocephalus. Neurol Med Chir (Tokyo) 2004;44:222–223.
13. Relkin N, Marmarou A, Klinge P, et al. Diagnosing idiopathic
normal-pressure hydrocephalus. Neurosurgery 2005;57(3 A recent study has reported an excellent correlation between
suppl):S4 –S16. intraocular pressure (IOP) and intracranial pressure (ICP),
14. Marmarou A, Bergsneider M, Klinge P, et al. The value of sup- suggesting that measurement of IOP may serve as a nonin-
plemental prognostic tests for the preoperative assessment of id- vasive means to determine ICP. To reexamine the relation
iopathic normal-pressure hydrocephalus. Neurosurgery 2005;
between IOP and ICP, we reviewed the medical records of
57(3 suppl):S17–S28.
15. Akkawi NM, Agosti C, Borroni B, et al. Jugular valve all patients who underwent lumbar puncture between 1991
incompetence: a study using air contrast ultrasonography on a and 2007 in the neuro-ophthalmology clinic at the Univer-
general population. J Ultrasound Med 2002;21:747–751. sity of California San Francisco. Data for IOP and ICP were
16. Malm J, Eklund A. Idiopathic normal pressure hydrocephalus. available for 55 patients. There was no correlation between
Pract Neurol 2006;6:14 –27. IOP and ICP (Pearson correlation coefficient, r ⫽ 0.07; p ⫽
17. Welch K, Friedman V. The cerebrospinal fluid valves. Brain 0.59). IOP measurement is not a useful substitute for ICP
1960;83:454 – 469. measurement.
18. Di Chiro G. Observations on the circulation of the cerebrospi-
nal fluid. Acta Radiol Diagn (Stockh) 1966;5:988 –1002. Ann Neurol 2008;64:221–224
19. Greitz D. Cerebrospinal fluid circulation and associated intracra-
nial dynamics. A radiologic investigation using MR imaging and
radionuclide cisternography. Acta Radiol Suppl 1993;386:1–23.
An accurate noninvasive way to measure intracranial
20. Zmajevic M, Klarica M, Varda R, et al. Elimination of phenol-
sulfonphthalein from the cerebrospinal fluid via capillaries in pressure (ICP) has long been sought, with little success.
central nervous system in cats by active transport. Neurosci Lett If intraocular pressure (IOP) were a faithful reflection
2002;321:123–125. of ICP, it would offer an easy solution. In rhesus mon-
keys, an increase in IOP has been reported after exper-
imental increase of ICP.1 In this study, however, IOP
rarely increased to more than the reference range, lead-
ing the authors to predict that the value of isolated
IOP measurements would be limited, if applied to the
evaluation of patients with intracranial hypertension.
In another macaque study, IOP and ICP were varied
by manipulation of PaCO2.2 Again, IOP remained
within the reference range, even at the maximum re-
corded ICP. In a human study, a correlation was found
between ICP and IOP with repeated measurements in
single patients, but no consistent relation prevailed
from patient to patient.3 Another study found a corre-
lation across patients, but concluded that “enough vari-
ability. . . exists to preclude using IOP to precisely de-

From the 1Department of Ophthalmology, Beckman Vision Center;


and 2Departments of Neurology and Physiology, University of Cal-
ifornia San Francisco, San Francisco, CA.
Received Feb 5, 2008, and in revised form Mar 25. Accepted for
publication Apr 4, 2008.
Published online June 20, 2008, in Wiley InterScience
(www.interscience.wiley.com). DOI: 10.1002/ana.21416
Address correspondence to Dr Horton, Department of Ophthalmol-
ogy, 10 Koret Way, Box 0730, San Francisco, CA 94143.
E-mail: hortonj@vision.ucsf.edu

Han et al: IOP and ICP are uncorrelated 221


termine ICP.”4 Finally, one study found no correlation
Table. Clinical Diagnoses of the Study Group
between IOP and ICP.5
In contrast, Sajjadi and colleagues6 reported a tight Diagnosis Cases, n
correlation (r ⫽ 0.955) between IOP and ICP. They (%)
proposed that IOP may be used instead of frequent Pseudotumor cerebri 38 (69%)
lumbar punctures in follow-up of patients with benign
intracranial hypertension and in patients with impaired Anterior ischemic optic neuropathy 5 (9%)
consciousness after head trauma. Puzzled by the dis- Headache 4 (7%)
crepancy between Sajjadi and colleagues’ study6 and Idiopathic optic disc swelling 2 (4%)
most prior reports in the literature,1–5 we examined the Optic neuritis 2 (4%)
correlation between ICP and IOP in our patients to
determine whether IOP can be used as a reliable sur- Acute disseminated encephalomyelitis 1 (2%)
rogate for ICP. Posterior uveitis 1 (2%)
Dural sinus occlusion 1 (2%)
Subjects and Methods Unknown 1 (2%)
This retrospective study was approved by the Institutional Re-
view Board at the University of California San Francisco.
Cases were identified by searching the entire patient database The average of the IOP in the two eyes for each
of a single neuro-ophthalmologist (J.C.H.), who has main- patient ranged from 10 to 21 mmHg, with a mean of
tained electronic medical records since 1991. The search term 14.4 ⫾ 2.7mm Hg. No patient showed a pressure dif-
lumbar puncture yielded records of 77 patients older than 18
ference between the two eyes of more than 2mm Hg.
years who had undergone a spinal tap in the neuro-
ophthalmology clinic between 1991 and 2007, usually for the
ICP ranged from 70 to 550mm H2O, with a mean of
evaluation of bilateral optic disc edema. Data from 22 patients 274.2 ⫾ 102.4mm H2O (Fig). There was no signifi-
were excluded for the following reasons: IOP was not recorded cant correlation between the ICP and the average IOP
(n ⫽ 13), the IOP was not measured the same day (n ⫽ 7), (Pearson’s product-moment correlation coefficient, r ⫽
or the patient was being treated with acetazolamide (n ⫽ 2). 0.07, p ⫽ 0.59).
No patient had a history of glaucoma, use of topical medica- We also broke the comparison down by eye, testing
tions to reduce IOP, or recent prior lumbar puncture. the correlation between ICP/left eye pressure and ICP/
The IOP was measured in each eye by Goldmann contact right eye pressure. Neither eye pressure showed a signif-
tonometry, usually by a resident or fellow. The accuracy of the icant correlation with ICP. Finally, we selected which-
tonometer in our clinic is calibrated every 3 months, requiring ever eye pressure yielded the best correlation with ICP.
an adjustment of less than 1mm Hg. The subarachnoid open-
However, this comparison still did not produce a statis-
ing pressure was measured in the left lateral decubitus position
using a manometer after a spinal puncture at L3-4 or L4-5
tically significant correlation between IOP and ICP.
under local anesthesia. The procedure was performed by the
same physician (J.C.H.) in every patient. The lumbar punc- Discussion
ture was always done after measurement of the IOP. Typically, Numerous studies have assessed the relation between
the IOP was measured by an ophthalmology resident during IOP and ICP, in the hope of finding a noninvasive
the course of a neuro-ophthalmological examination in an af- method of determining ICP. Although a few studies,
ternoon clinic. The patient then waited until the end of the both animal and human, have found a slight effect of
clinic, when the lumbar puncture was performed. The maxi- ICP on IOP, they have concluded uniformly that IOP
mum time between Goldmann tonometry and lumbar punc- provides no clinically useful estimate of ICP.1–5
ture was 5 hours. The exact time between IOP measurement The findings of Sajjadi and colleagues6 are inconsis-
and ICP measurement was not documented in each patient
tent with previous reports, as well as our data, and are
but averaged 2 to 3 hours for the cohort.
The main objective of this study was to examine the cor-
difficult to explain. They reported a close correlation
relation between mean IOP and ICP. Statistical significance (r ⫽ 0.955), with a nearly 1:1 relation between IOP
was assessed by calculating the Pearson’s product-moment and ICP. Their IOP measurements were performed
correlation coefficient, using Igor Pro statistics software with a Schiotz tonometer, which is a notoriously inac-
(WaveMetrics, Lake Oswego, OR). curate instrument. In a comparison of five portable
tonometers, the Schiotz tonometer was found to have
Results the poorest correlation (r ⫽ 0.66) with the gold stan-
After the above-mentioned exclusions, there were 55 dard, the Goldmann tonometer.7 Therefore, even if an
patients in whom IOP and ICP were recorded within a excellent correlation did exist between IOP and ICP, it
5-hour time window. There were 42 female and 13 would be hard to demonstrate with a Schiotz tonom-
male patients, with a mean age of 37.6 years. The fe- eter. Moreover, Sajjadi and colleagues6 used the
male predominance reflected the fact that the majority Schiotz tonometer incorrectly, by averaging values ob-
of patients had pseudotumor cerebri (Table). tained with the 5.5 and 10.0 gm weights. The instru-

222 Annals of Neurology Vol 64 No 2 August 2008


and physiological connections between the intracranial
fossa and orbit,” noting that compression of the poste-
rior globe is seen by neuroimaging in some patients with
increased ICP.11,12 It is true that globe compression, by
any means, can cause a transient increase in IOP. How-
ever, IOP is dependent on numerous factors, including
aqueous production, episcleral venous pressure, and flow
resistance through the trabecular meshwork. The eye
eventually compensates for external pressure by adjusting
these parameters to restore IOP to its baseline level. This
compensation explains why glaucoma is not a frequent
finding in patients with an orbital neoplasm that com-
presses the globe.
Sajjadi and colleagues6 also state, “other possible
mechanisms include the increase in ophthalmic venous
pressure. . ., which would be transmitted directly to the
ocular fluid. . .” Although episcleral venous pressure
does influence aqueous outflow, it does not have a di-
rect connection with ocular fluid. The trabecular mesh-
Fig. Graph showing mean intraocular pressure (IOP) plotted work and Schlemm’s canal are interposed between the
against intracranial pressure (ICP) for our subjects and for intraocular fluid and the episcleral veins, buffering any
Sajjadi and colleagues’ 6 report. Our data show no correlation effect caused by a change in episcleral venous pressure.
between IOP and ICP (r ⫽ 0.07), whereas Sajjadi and col- Moreover, the orbit is richly anastomotic with venous
leagues found a strong correlation (r ⫽ 0.955). The fits are outflow through the inferior orbital fissure (via the in-
linear regressions through the data points. ferior ophthalmic vein to the venous plexus of the
pterygopalatine fossa) and through the eyelids both
ment performs most accurately when the plunger medially (via the angular vein) and laterally (via the
makes a minimal impression on the cornea. Instruc- superficial temporal vessels). We agree that pressure
tions provided with the Shiotz tonometer specify that within the cavernous sinus would result in an increased
the appropriate weight should be chosen to give a scale superior ophthalmic vein pressure, as evidenced by
reading of 2 to 5 units. It is not recommended to av- ophthalmodynamometry readings.13 However, this
erage two readings, one obtained with the correct would not necessarily produce an increase in IOP.
weight and the other with weight that gives a reading In summary, no correlation was present between
outside 2 to 5 scale units. Such a technique would fur- IOP and ICP in our patients. IOP should not be relied
ther reduce the accuracy of the Shiotz tonometer. on as a means to infer ICP.
There are several potential weakness of our study. Up
to 5 hours elapsed between IOP and ICP measurement,
This work was supported by Research to Prevent Blindness.
with an average of about 2.5 hours. IOP is known to
fluctuate diurnally, with a peak in the morning followed
by a plateau in the afternoon.8,9 Between 1:00 and 5:30 References
PM, the mean decline in IOP is less than 2mm Hg. In- 1. Lehman RA, Krupin T, Podos SM. Experimental effect of in-
dividual subjects show little short-term pressure variation tracranial hypertension upon intraocular pressure. J Neurosurg
on repeated measurements during this time interval. 1972;36:60 – 66.
2. Smith RB, Aass AA, Nemoto EM. Intraocular and intracranial
Therefore, it is doubtful that the time lag between the pressure during respiratory alkalosis and acidosis. Br J Anaesth
two pressure measurements we made could have ob- 1981;53:967–972.
scured any correlation between IOP and ICP in our pa- 3. Sheeran P, Bland JM, Hall GM. Intraocular pressure changes
tients. Another point is that the IOP was measured by a and alterations in intracranial pressure. Lancet 2000;355:899.
different physician in each patient. It would have been 4. Lashutka MK, Chandra A, Murray HN, et al. The relationship
of intraocular pressure to intracranial pressure. Ann Emerg Med
ideal had the same person checked the IOP in every pa- 2004;43:585–591.
tient, but Goldmann tonometry readings show little in- 5. Czarnik T, Gawda R, Latka D, et al. Noninvasive measurement
terobserver variation, with 95% limits of agreement of intracranial pressure: is it possible? J Trauma 2007;62:
of ⫾ 2.6 mm Hg.10 Therefore, the fact that tonometry 207–211.
data were obtained by different observers introduced 6. Sajjadi SA, Harirchian MH, Sheikhbahaei N, et al. Correlation
of ICP and IOP. Ann Neurol 2006;59:867– 870.
only a minor source of error. 7. Wingert TA, Bassi CJ, McAlister WH, Galanis JC. Clinical
Sajjadi and colleagues6 attribute the correlation be- evaluation of five portable tonometers. J Am Optom Assoc
tween ICP and IOP that they found to “the anatomical 1995;66:670 – 674.

Han et al: IOP and ICP are uncorrelated 223


8. Hamilton KE, Pye DC, Aggarwala S, et al. Diurnal variation of Imbalance and gait ataxia are major causes of func-
central corneal thickness and Goldmann applanation tonometry tional disability and falls in patients with cerebellar
estimates of intraocular pressure. J Glaucoma 2007;16:29 –35.
9. David R, Zangwill L, Briscoe D, et al. Diurnal intraocular pres-
ataxia. The mechanisms underlying these deficits re-
sure variations: an analysis of 690 diurnal curves. Br J Ophthal- main uncertain, but impaired vestibular reflexes are
mol 1992;76:280 –283. likely to play an important role, because the vestibular
10. Tonnu P-A, Ho T, Sharma E, et al. A comparison of four system provides the brain with essential information re-
methods of tonometry: method agreement and interobserver garding motion and the body’s orientation relative to
variability. Br J Opthalmol 2005;89:847– 850.
11. Brodsky MC, Vaphiades M. Magnetic resonance imaging in
gravity.
pseudotumor cerebri. Ophthalmology 1998;105:1686 –1693. Most prior studies of vestibular function in patients
12. Madill SA, Connor SE. Computed tomography demonstrates with cerebellar disease have focused on the rotational
short axial globe length in cases with idiopathic intracranial hy- vestibuloocular reflex (rVOR). Occasionally, the rVOR
pertension. J Neuroophthalmol 2005;25:180 –184. is absent1; most often it is present, although it may
13. Firsching R, Schutze M, Motschmann M, Behrens-Baumann W.
Venous ophthalmodynamometry: a noninvasive method for as-
have an abnormal amplitude or direction.2,3 Responses
sessment of intracranial pressure. J Neurosurg 2000;93:33–36. to linear motion (translation) and gravity, which are
mediated by the otolith organs, are likely to be of par-
ticular importance to balance and walking. In fact, it
has been shown that the horizontal (side-to-side) trans-
lational VOR (tVOR) is commonly impaired by cere-
bellar disease.4,5 The response to vertical head motion
Abnormal Vestibular (bob), however, has not previously been studied in
ataxic individuals, although this motion is prominent
Responses to Vertical Head during natural human locomotion.6 In a prior study,7
we found that the vertical tVOR is impaired in pa-
Motion in Cerebellar Ataxia tients with progressive supranuclear palsy, another neu-
Ke Liao, MS,1–3 Mark F. Walker, MD,1,2 rodegenerative disease, in which gait and balance defi-
and R. John Leigh, MD1–3 cits are prominent and occur early. Here, we
investigated the vertical tVOR in patients with cerebel-
lar ataxia.
Falls pose an important problem to neurologists caring for pa-
tients with cerebellar disorders. Normal human gait is charac- Subjects and Methods
terized by prominent up-and-down linear head movements
We studied vestibuloocular reflexes in a group of eight pa-
(vertical translations). Thus, we asked whether patients with
tients (age range, 27–79 years; median age, 57 years; Table)
cerebellar gait ataxia showed abnormal responses of otolithic
who presented with gait ataxia as a component of one of a
vestibuloocular reflexes to this motion. Compared with
range of cerebellar disorders. Twenty healthy subjects (8
healthy subjects, all cerebellar patients showed impaired
women; age range, 25–72 years; median age, 55 years) served
otolith-ocular responses. Neurologists often test the rotational
as the comparison group.8 Experiments were performed in
vestibuloocular reflexes in cerebellar patients, but our results
ambient light, so that natural visual cues were available, and
indicate that vestibular responses to vertical linear motion are
the safety of the subject on the platform could be monitored
severely affected. Impairment of the corresponding otolith-
by one of the investigators who stood by the platform with
spinal reflexes may contribute substantially to falls.
an emergency stop switch. All subjects gave informed, writ-
Ann Neurol 2008;64:224 –227 ten consent, in accordance with the Declaration of Helsinki,
under a protocol approved by the Institutional Review Board
of the Cleveland Veterans Affairs Medical Center.

Stimuli
Experimental methods have been described in detail in a
prior report.8 Subjects sat in a chair on a Moog
From the 1Neurology Service and Daroff-Dell’Osso Laboratory, 6DOF2000E electric motion platform (Moog, East Aurora,
Veterans Affairs Medical Center; and Departments of 2Neurology
and 3Biomedical Engineering, Case Western Reserve University, NY). Belts were used to secure the subject’s torso, and a
Cleveland, OH. snugly fitting skate-board helmet, inlaid with foam, stabilized
Received Jan 10, 2008, and in revised form Mar 6, 2008. Accepted the subject’s head. Any head movements that were decoupled
for publication Mar 28, 2008. from chair or platform motion were measured, as described
later. The tVOR stimulus consisted of 2Hz bob (typical am-
Published online in Wiley InterScience (www.interscience.wiley.com).
DOI: 10.1002/ana.21407 plitude ⫾ 2.3cm), and the rVOR stimulus was 1Hz yaw
(typical amplitude ⫾ 6 degrees), each for a duration of 12
Address correspondence to Dr Walker, Department of Neurology,
Case Western Reserve University, Cleveland VAMC, 10701 seconds. In one patient (P8), only bob stimuli were applied.
East Boulevard, 127-W, Cleveland, OH 44106. Data from two visual conditions, each used for one exper-
E-mail: mark.walker@case.edu imental run, are presented here: (1) subjects binocularly

224 Annals of Neurology Vol 64 No 2 August 2008