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Hi guys, sorry for the delay but work has been busy. Here's the next case, thought we would do one that involves the eyes a little bit

A 14-year-old boy presented to our emergency department because of neck stiffness, diplopia, and blurred vision. He reported that the symptoms had begun 2 weeks earlier with a stiff neck after he had slept in a chair. Four days before presentation, he had noted mildly blurred vision, a headache, and neck stiffness. The headache was relieved with acetaminophen. The morning before presentation, he complained of intermittent diplopia, and his parents took him to an optometrist for evaluation. On funduscopic examination, the optometrist observed blurred disk margins bilaterally. The patient was then referred to an ophthalmologist, who obtained a head CT, findings of which were normal. The patient was subsequently referred to our institution for evaluation.

On presentation, the patient’s only complaint was diplopia on right and left lateral gazes. He denied having headache, neck tenderness, change in visual acuity, nausea, or emesis. The general examination revealed an obese adolescent male in no distress, with normal vital signs. Funduscopic examination showed indistinct optic disk margins bilaterally, retinal hemorrhages at the nasal margin of the left optic disk, and an absence of spontaneous venous pulsations. Diplopia was present on right and left lateral gazes, with an inability of the patient’s left eye to abduct fully on left lateral gaze. On the cover test, the lateral-most image on both right and left lateral gaze was eliminated by covering the abducting eye. Findings on the rest of the neurologic examination were normal, including visual fields, visual acuity, deep tendon reflexes, motor strength, sensory function, and cerebellar function. After the neurologic examination, the patient had a single episode of emesis but continued to deny having nausea.

1. Which one of the following best explains the physical findings in this patient?
a. Papilledema
b. Optic neuritis
c. Papilledema and a left cranial nerve (CN) III palsy
d. Optic neuritis and a left CN III palsy
e. Papilledema and bilateral CN VI palsies

Thanks eyemd for taking us through these cases.  I have had very little pathology and no eye pathology, but I would like to make a guess on this.  I'll try to write out all of my thought process and if it's incorrect at any stage, please correct me.  Thank you.

papilledema = swelling of optic disc
optic neuritis = inflammation of optic nerve, can this also lead to papilledema? hm...
neck stiffness = mechanical or infectious
diplopia = could be CN III or CNVI
blurred vision = optic neuritis or papilledema
headache = could be anything, could be increased ocular pressure
normal head Ct = no tumor
indistinct optic disk margins = papilledema (probably not optic neuritis ?)
retinal hemorrhage = papilledema
inability of left eye abduction = CN VI, problematic left lateral rectus
cover test: not sure what this tells me, isn't this normal?  If I cover my abducting eye during lateral gaze, my peripheral vision will definitely diminish on that side
visual acuity normal: not sure what this tells me, if papilledema or optic neuritis does not affect your visual acuity, then what does?  CN II defect?

So I think I would choose E. Papilledema and bilateral CN VI palsies

The answer should be E.

- Patient has symptoms of papilledema (blurred disk margins bilaterally) then option B and D are unlikely.

- Patient also manifests with ocular motor palsy---> exclude option A.

- Although the patient has diplopia, which could be seen in CN III paralysis, he does not have other features of CN III  (ptosis, pupil dilation), in addition, diplopia in CN III appears in more than one direction rather than only the horizontal diplopia in this patient. Therefore, option C is inappropriate.

- The patient has a typical symptom of CN VI palsy: lateral rectus muscle paralysis (inability of the patient’s left eye to abduct)


@ngqvu: hi, nice to meet you.

Question 1: e (nicely done by ngqvu and ducicu)

By definition, papilledema describes swelling of the optic disk and is caused by increased intracranial pressure (ICP). Papilledema would not explain the diplopia or ocular palsy noted on examination. A swollen optic nerve head that is indistinguishable from mild papilledema characterizes optic neuritis. Patients with optic neuritis often describe pain with eye movement as well as pronounced impairment of visual acuity, and a scotoma can be found on visual field testing, but not diplopia. A left CN III palsy would manifest as weakness of the left eye on gaze in all directions, except abduction. Diplopia on lateral gaze is due to the inability of the eyes to maintain appropriate conjugate alignment when moving in the horizontal direction. This can be due to a CN III (medial rectus) palsy, a CN VI (lateral rectus) palsy, or dysfunction of the brain-stem systems that coordinate CN III and CN VI. Our patient was unable to abduct his left eye fully, an outcome indicating a left CN VI palsy. Thus, papilledema or optic neuritis with left CN III palsy cannot explain the symptoms in this patient. Detecting subtle abnormalities in eye movement associated with mild CN VI palsies is often difficult. A simple rule in horizontal diplopia is that the most-lateral image is the abnormal image. The eye responsible can be identified by covering each eye separately and noting when the most-lateral image disappears. In this patient, only the left CN VI was noticeably weak on examination, but the fact that on right lateral gaze the lateral-most image disappeared when the right eye was covered indicates a coexisting right CN VI palsy. Therefore, papilledema and bilateral CN VI palsies best characterize the findings in this patient.

The patient was admitted to the hospital for further investigation.

2. Which one of the following diagnoses is least likely in this patient?
a. Acute bacterial meningitis
b. Increased intracranial pressure
c. Brain tumor
d. Subdural hematoma
e. Intracranial venous sinus thrombosis

question 2: d. Subdural hematoma

All of the given options here can cause papilledema due to increase intracranial pressure and CN VI paralysis.
If the patient suffer from subdural hemorrhage, the hematoma should be seen on CT scan image and patient usually has a history of trauma. However, the CT of the patient is normal and no history of trauma  ---> subdural hematoma is least likely.

Question 2: a

A child with acute bacterial meningitis usually is sick and irritable with fever, severe headache, nausea, and nuchal rigidity; therefore, this is the least likely diagnosis in our patient. Chronic smoldering meningitis, however, can manifest as described in our patient because of dysfunction of cerebrospinal fluid (CSF) absorption, but it is uncommon. The best pathophysiologic explanation for the neurologic findings is increased ICP. In the presence of increased ICP, the axoplasmic flow from the optic nerve is impeded, an outcome resulting in congestion of the optic disc and the characteristic appearance of papilledema on the funduscopic examination. An intracranial lesion, such as a tumor or subdural hematoma, frequently produces signs and symptoms of increased ICP. Venous sinus thrombosis can also cause an increase in ICP because of the increase in venous pressure and resultant reduction in CSF absorption.

In a young patient, evidence of increased ICP with bilateral CN VI palsies is suggestive of an intracranial tumor.

3. Which one of the following diagnostic procedures is most appropriate at this point?
a. Electroencephalography (EEG)
b. Magnetic resonance imaging (MRI) with use of contrast medium
c. CT
d. Lumbar puncture (LP)
e. Fluorescein angiography of the retina

Thanks eyemd.  Your explanation about the cover test is very interesting.

a. EEG: record electrical activity of brain: not helpful in diagnosing a tumor
b. MRI with contrast: standard protocol in for detecting brain tumor
c. CT: negative CT earlier, repeat CT would probably not be high yield in this case unless a contrast is added
d. LP: good test for infection but all signs in this case point to increased ICP due to tumors or hemorrhage
e. Retina angiography: can test for abnormal blood vessels or tumor in the eye

I'm a bit torn between b and e.  Although b can help detect brain tumor and CN VI palsies, but I'm more concerned with the retina hemorrhage and absence of venous pulsation so I would order a retina angiography first followed by a MRI.  I pick E.

Hello ducicu.  Thanks for the Pharmacology book.

I hope everyone has had a great weekend.

Question 3: b

The initial diagnostic study in evaluating a patient with suspected increased ICP is an imaging study of the brain. An EEG would not be expected to provide any useful additional information. To evaluate the posterior fossa adequately, MRI with contrast medium is the study of choice. In this patient, magnetic resonance angiography would also be important to rule out sagittal (or other) sinus thrombosis. CT does not provide adequate imaging of the posterior fossa and is inferior to MRI for evaluation of a suspected neoplasm. An LP could result in catastrophic cerebral hemiation and is absolutely contraindicated until the presence of non-communicating hydrocephalus or an intracranial lesion has been ruled out by brain imaging. Fluorescein angiography of the retina is useful in distinguishing true papilledema from pseudopapilledema. In true papilledema, the fundus vessels leak dye because of the abnormal retinal vascular permeability. Although fluorescein angiography of the retina is useful in establishing the presence of true papilledema, it is an unnecessary study in this patient because of the other neurologic findings.

In our patient, MRI and magnetic resonance angiography with gadolinium contrast showed normal findings; in particular there was no evidence of meningeal enhancement to suggest chronic meningitis, no change in ventricular size to suggest hydrocephalus, and no evidence of a lesion or venous sinus thrombosis. An LP performed subsequently yielded the following results (reference ranges shown parenthetically): opening pressure, 47 mm Hg (5-15 mm Hg); glucose, 68 mg/dL (45-80 mg/dL); protein, 36 mg/dL (65-195 mg/dL); leukocytes, 2/mm3 (<5/mm3); erythrocytes, 5/mm3; and negative Gram stain and culture.

4. On the basis of the physical, radiological, and laboratory findings, which one of the following diagnostic possibilities is most likely in this patient?
a. Chronic meningitis
b. Subdural hematoma
c. Brain tumor
d. Normal-pressure hydrocephalus
e. Pseudotumor cerebri (PTC)

Question 4: E

- Imaging of CNS in this patient revealed normal ----> exclude option b and c
- Cerebrospinal fluid is normal ----> exclude option a
- Normal-pressure hydrocephalus ---> patient usually has symptoms of dementia. urinary incontinent and ataxia. This patient does not manifest those symptoms.
- Pseudotumor cerebri can explain the symptoms in our patient: headache, diplopia, CN VI paralysis, increase pressure of CSF.

@eyemd: question 2: I agree that meningitis is unlikely in this patient but at least it is more likely than subdural hemorrhage. Because if pupilledema and CN VI paralysis result from subdural hemorrhage the hematoma would have occupied a definite space. Therefore, the hematoma should be large enough to be observed by CT, but in this patient, CT scan is normal. How can you explain it?

Question 4: e

The LP showed an increased opening pressure with decreased protein and normal glucose, cell count, and Gram stain. Thus, no laboratory evidence supports the diagnosis of meningitis. Normal findings on MRI with gadolinium contrast rule out subdural hematoma, brain tumor, and normal-pressure hydrocephalus. After performing a thorough history, physical examination, MRI, and LP, we diagnosed PTC. Pseudotumor cerebri describes the syndrome of increased ICP in the absence of a structural central nervous system lesion or other identifiable cause of increased ICP.

5. Which one of the following management options is least appropriate in our patient?
a. Removal of CSF
b. Treatment with acetazolamide
c. No treatment because there is no risk associated with this disorder
d. Careful follow-up to include visual field and funduscopic evaluation
e. Weight reduction in an obese patient

ducicu: regarding question 2, I agree with you. I apologize that the question was not well written because both meningitis and SDH could have been the answer. Thanks for not letting me get away with it 

a. CSF drainage should help alleviate the elevated pressure.  I don't see anything that might send a red flag contraindicated for the procedure so it should be safe.
b. I think this should help with ICP.
c. From the patient's history, it seems like there are plenty of risks.
d. Sounds good.
e. I think this should help with just about everything.

I go with C for this one.

Question 5: C

- In this patient, high ICP causes papillary edema and CN paralysis. Do nothing is definitely inappropriate.

- Removal of CSF and using diuresis (option A and B) help to decrease ICP then they are benefit for the patient

- Overweight also plays a role in the etiology of pseudotumor cerebri, therefore weight reduction in an obese patient (option E) is recommended.

- Careful follow-up to include visual field and funduscopic evaluation (option D) is necessary to decide interventions if required in order to prevent blindness

Question 5: C

The treatment goals are to preserve vision and relieve symptoms. The benefit of CSF removal to lower the ICP is well established, and patients often report rapid resolution of their symptoms. Acetazolamide is a carbonic anhydrase inhibitor that reduces the secretion of CSF by the choroid plexus and is often helpful. The natural history of PTC is variable, and the major complication is vision loss. Obviously, treatment is recommended for a patient with PTC and abnormalities on CN testing. Thorough evaluation by an ophthalmologist, including quantitative visual fields, visual acuity testing, and funduscopic photographs, is recommended. In an obese patient, weight reduction is recommended.

In our patient, a therapeutic LP was performed, and CSF fluid was withdrawn to a closing pressure of 35 mm Hg. The intensity of the patient’s headache diminished within a week. Use of acetazolamide was instituted. The patient is scheduled to return for reevaluation in the neurology and ophthalmology clinics in 1 month.

Discussion

Pseudotumor cerebri is a syndrome of increased ICP in the absence of other identifiable causes. In adults, PTC occurs most commonly in women who are often obese and have menstrual irregularities. In children, representation of males and females is equal and obesity is less of a factor, although some data suggest a pattern similar to the adult epidemiology, ie, occurring more commonly in adolescent females. Familial cases have been described. The cardinal symptom of PTC is headache; however, in 1 study only 75% of patients had headache. Other common complaints include neck stiffness, ataxia, nausea, diplopia, and disturbance of vision (blurring, obscuration, and scotoma). Papilledema is the most common physical finding, followed by CN VI palsies and visual field defects. Diplopia due to CN VI palsies is common in the presence of increased ICP. The intracranial course of CN VI makes this nerve susceptible to stretch injuries in the presence of increasing ICP. Increased ICP causes a downward shift of the brain stem and stretches the CN VI as it passes over the petrous ridge of the skull base. Thus, a CN VI palsy is a poor localizing sign because any pathology resulting in increased ICP can produce unilateral or bilateral CN VI palsies. Rather than headache and papilledema, infants and children may have irritability, apathy, somnolence, dizziness, or ataxia. Papilledema is unlikely if the fontanelles are open. The characteristic radiological feature of PTC is normal findings. Clinicians frequently cite small “slitlike” ventricles as a radiographic characteristic of PTC, but this finding was recently disputed.

The signs and symptoms of PTC are due to the chronic increase in ICP, generally with opening pressures between 25 and 45 mm Hg. In general, the causes of increased ICP can be classified by the underlying physiology: (1) increase in intracranial volume associated with a lesion, such as a subdural hematoma or a tumor; (2) increase in intracranial venous pressure that results in an increase in venous volume and a decrease in CSF absorption, eg, as occurring with venous sinus thrombosis; and (3) abnormalities in CSF production, absorption, and circulation. The mechanism producing the increased ICP in PTC is unknown, but current thinking suggests 3 primary mechanisms may be involved: sluggish intracranial venous circulation with increased cerebral blood volume, slowed CSF absorption, and onset of cerebral (vasogenic) edema. The literature on PTC describes a long list of possible causes in adults; however, a critical review of the literature found supportive evidence for only corticosteroid withdrawal, nalidixic acid, tetracycline, thyroid replacement therapy, vitamin A, nitrofurantoin, iron deficiency anemia, and hypoparathyroidism.

Of importance, PTC is a diagnosis of exclusion. Several disorders present with papilledema because of increased ICP with no localizing signs. A thorough history, physical examination, imaging study, and LP can rule out most factors known to cause increased ICP. In large studies assessing the presentation of increased ICP with no localizing signs, approximately 30% of patients are found to have a lesion, structural defect, or identifiable cause of abnormal CSF dynamics, such as chronic meningitis. Four criteria have been proposed for the diagnosis of PTC: ICP increased higher than 15 mm Hg, normal CSF composition, symptoms and signs that are associated with increased ICP alone, and normal findings on radiological studies.
The treatment goals are to preserve vision and relieve symptoms. The natural history of PTC is variable, and the major complication is severe vision loss. In the 4 series of patients reviewed by Ahlskog and O’Neill (total, 210 patients), remission was noted in a high percentage of patients (80% to 100%), but recurrent episodes were also frequent (6% to 37%). Severe vision loss was between 4% and 12%.

Careful observation by a neurologist and ophthalmologist is recommended for patients with PTC. The patient should have quantitative visual field and funduscopic photographs to guide therapy. Removal of CSF to lower the ICP and relieve symptoms is effective and has been reported to reverse the pathologic process. If symptoms recur, LP should be repeated, and CSF removed. Repeated LP every 2 days to every week has been used in the treatment of pseudotumor, with good results. The mechanism for the resolution of symptoms after LP is unknown, and because CSF is produced at a rate of about 0.35 mL/min, only hours are needed to replenish the CSF withdrawn. One possibility is that, in the presence of increased ICP, the LP makes a relative CSF leak that produces prolonged relief. The therapeutic LP is frequently combined with acetazolamide, 10 mg/kg per day. Acetazolamide acts to reduce the secretion of CSF by the choroid plexus. In instances in which patients continue to have increased ICP and subsequent optic nerve atrophy, a 2-week course of dexa-methasone is indicated.

The decision to proceed to surgery for a shunt or optic nerve fenestration is best determined by the status of quantitative visual fields and visual acuity testing. When visual field defects enlarge despite medical therapy or visual acuity decreases, surgical treatment should be considered.

This case demonstrates the importance of a thorough neurologic examination, in particular the eye examination, in a patient with minimal symptoms.