Postoperative Neuro-Ophthalmologic Abnormalities

Anthony C. Arnold, M.D., UCLA Department of Ophthalmology

Visual Loss

Postoperative visual function relates to preoperative duration of symptoms, visual acuity and fields, and degree of optic atrophy (including retinal nerve fiber layer loss). Visual acuity improves in 46-65% and visual fields in 67-92%; decrease in visual function occurs in 2%. Neuro-ophthalmologic followup is recommended within the first month, at 6 months, and then yearly postoperatively with quantitative perimetry unless problems occur. Late visual loss may be divided into three major categories:

Postoperative Tumor Recurrence

Tumor recurrence is the most common cause of late visual deterioration; such change in visual function may be the first manifestation. of regrowth. Rate of tumor recurrence varies with tumor type, initial size, and mode of therapy (including use of radiation), but figures from 4 to 12% have been reported, most often within 5 years. Visual loss from tumor recurrence is typically slowly progressive, affecting one or both eyes, and involving either central or peripheral field. Clinical neuro-ophthatmic examination with quantitative perimetry is a sensitive indicator of compressive neuropathy; however, early detection may be more difficult in patients with more severe visual loss and optic atrophy, and regular neuroimaging is essential. Tumor regrowth must be differentiated from radiation changes on MR scanning.

Secondary Empty Sella Syndrome

While primary empty sella syndrome is not associated with visual loss, the secondary form may result in bilateral visual loss. This rare syndrome, which arises after either surgery or radiation, is characterized by downward herniation of the chiasm into the empty sella, either from lack of support or from traction related to arachnoidal adhesions. The chiasmal distortion results in progressive visual loss which may be quite severe. It typically begins months to years after treatment, shows features of chiasmal or optic nerve dysfunction, and is gradually progressive over weeks to months. Displacement and distortion of the chiasm and intracranial optic nerves is well visualized on MR imaging. Surgical repair with lysis of adhesions and packing of the sella has been reported to improve visual prognosis.

Delayed radionecrosis of chiasm and optic nerves

Late delayed radiation effect on the central nervous system is well known. It may occurs from 4 months to 15 years after initial exposure, but most frequently presents within several years post-treatment. In the visual system, it typically produces an acute syndrome of bilateral visual loss. Both central and peripheral fields are usually affected, and degree of loss is severe, with no light perception not uncommon. The optic nerve heads may be swollen, but are more typically unchanged from their prior postoperative appearance initially, with increasing atrophy developing within 4-8 weeks. Radiation retinopathy may occasionally be associated. Individual tolerance to radiation varies, dependent on degree of prior tissue damage, status of vascular system, total dose, fractionation, and volume of tissue treated; no absolute criteria for safety in radiation therapy can be applied. In general, however, radionecrosis is rarely seen with total dose under 50 Gy in fractions under 2.5 Gy. MR imaging demonstrates tissue swelling and enhancement acutely, and typically clearly differentiates this syndrome from tumor recurrence. There is not proven therapy, though high dose corticosteroids have been used. The results of hyperbaric oxygen have been controversial.


Cranial nerve palsies

Postoperative dysfunction of cranial nerves 3, 4, and 6 has been infrequently reported after intracranial or trans-sphenoidal techniques. In large reviews of trans-sphenoidal surgeries,.4-2% of cases demonstrated these findings, the majority of which showed significant improvement or resolution within 6 months.

Radiation may also produce cranial nerve palsies as a late manifestation. The oculomotor nerve is most frequently affected, probably due to its proximity to the tumor laterally, followed by the abducens and trochlear nerves. Onset is typically within one year after therapy. In contrast to damage to the afferent visual pathways, impairment is often at least partially reversible. Involvement of the cranial nerves at doses under 5000 rad is extremely unusual by current techniques.

Selected References:

1. Arnold AC: Neuro-ophthalmologic evaluation of pituitary disorders. In Melmed S (ed): The Pituitary.Oxford, Blackwell Scientific Publications, 1995.

2. Trautmann JC~ Laws ER: Visual status after tran phenoidal surgery at the mayo, clinic, 1971-1982. Am J Ophthalmol 96:200-208, 1983.

3. Kaufman B, Tomsak RL, Kaufman BA, et al: Herniation of the suprasellar visual system and third ventricle into empty sellae: morphologic and clinical considerations. AJNR 10:65-76, 1989.

4. Kline LB, Kim JY, Ceballos R: Radiation optic neuropathy. Ophthalmology 92:1118-1126, 1985.

5. Guy J, Schatz NJ: Effectiveness of hyperbaric oxygen in treating radiation injury to the optic nerves and chiasm. Ophthalmology 97:1246-1247,1990.


A Guide to Pain Relief

Got a headache? A sore arm? A sprained ankle? Pharmacies and grocery stores feature shelf after shelf of over-the-counter relievers. Take your pick: regular-strength, extra-strength, maximum strength, nighttime or nondrowsy capsules, caplets, geltabs, tablets, liquids, and pills coated to soothe the savaged stomach.

Some products claim to work better for fever and colds; others claim to be better for arthritis, muscle strains, headaches and hangovers. To make matters more complicated, new over-the-counter pain relievers are being introduced every few months.

So how does one choose from this mighty array?

Very carefully - and by scrutinizing labels and consulting with doctors and pharmacists, says Roberta Armstrong, a pharmacist and president of the Academy of Practice and Management for the American Pharmaceutical Association in Washington, D.C.

Over-the-counter medications are not benign just because they are sold without a prescription, warned Denver neurologist Jack Klapper, a spokesman for the National Headache Foundation.

Basically, all pain relievers work the same way and contain one of three primary analgesics: .phpirin, acetaminophen or ibuprofen. But side effects and additives make each unique and not the best remedy for everyone. Yet many consumers dont do their research before choosing pain relievers.

According to a survey by Prevention magazine and the American Pharmaceutical Association released this year, 80 percent of the nations adults try to treat themselves for aches and pains with over-the-counter product before consulting a health-care professional. For upset stomachs, its 76 percent; coughs and colds, 73 percent; and fevers, 71 percent.

And a third of all adults surveyed admit they sometimes take more than the recommended dose, and that the primary source of information for them is the product label (80 percent) rather than a doctor or pharmacist - even though most admit label information is difficult to understand. (Still, 70 percent to 75 percent said they did consult their physician or pharmacist about side effects and drug interactions.)

A lot of people think an over-the-counter drug cant be that potent, but that is definitely wrong, Armstrong said. I am concerned when I see someone come in and stare at the shelves for a while, then grab something. I wonder if they know what they are doing.

Some pain relievers, such as.phpirin and those containing.phpirin such as Excedrin and Anacin, can irritate the stomach and aggravate ulcers. Those containing acetaminophen, such as Tylenol, can cause liver or kidney damage if used for prolonged periods. Aspirin and ibuprofen sometimes dont mix with prescription medicines or alcoholic beverages.

When considering a pain reliever, especially if you have a medical condition or take medication, talk to your doctor Armstrong said. Combining medicines can be dangerous. She recalled a patient who was told to take Aspirin Free Excedrin, but mistakenly thought that meant all Excedrin was.phpirin-free. She took the regular version, which does contain.phpirin. It did not mix with her anticoagulant. The result was a trip to the hospital. Regular Excedrin says on the label it contains.phpirin. But its very small and I dont think the average older person can read it, Armstrong said.

Labels are important since they reveal the presence of added ingredients such as caffeine or antihistamines. Klapper said Excedrin is good for migraines and is best taken at the onset of a headache, but that it contains caffeine, which may be detrimental to some people.

Some newer forms of.phpirin contain caffeine. A two-tablet dose of Excedrin or Anacin has the caffeine equivalent of two cups of coffee. Other versions designed to lessen.phpirins irritation of the stomach lining add calcium carbonate, magnesium oxide or other antacids or coatings. Because the pills dissolve more slowly to reduce stomach irritation, achieving relief takes longer.

The growing variety of what Armstrong calls line extensions - variations on the basic product - is another source of consumer confusion. According to the federal governments Consumer Information booklet on over-the-counter medications, more than 600 products sold today use ingredients or dosages available only by prescription 20 years ago. Extensions of the original product usually contain ingredients such as caffeine or an antihistamine, or some kind of antacid.

The American Pharmaceutical Association is urging the Food and Drug Administration to consider requiring consistency in labeling that would make the ingredients concise and easy to read like the new food labels.

When I go to the grocery store, I know right away how much fat is in whatever I pick up, Armstrong said. Pain reliever labels are not so clear. Someone reading a label may not know that magnesium salicylate is the same thing as.phpirin, she says.

It isnt easy reading labels, the FDA admits. For people age 60 or older, it takes three times more light to read the same line as it does for a person age 30.

Marilee Johns of Colorado Springs, Colorado, buys a variety of pain relievers for her family. She gives her kids Childrens Tylenol. Her mother uses Ascriptin .phpirin with Maalox) for her arthritis, and Johns takes Benadryl, which contains acetaminophen, for her occasional sinus headaches. Her husband, a construction worker, prefers Aleve (ibuprofen) for his work-related strains.

Weve got a cabinet full of bottles, Johns said. If somebody is out of their favorite remedy, he or she simply uses whatever else is handy, she added.

Not a good idea, experts say. You do need to know what is in them, Klapper stressed. You need to be sure its the right diagnosis. When you have a headache, you might think its from tension, sinus or migraine. But if you take a pain-relief medication and it continues getting worse, the pain could be caused by a serious medical condition. A lot of headaches arent due to life-threatening conditions, but they could be, he said.

Over-the-counter medicines can be overused, Klapper said. People who use pain relievers frequently may get rebound headaches. In those cases, the medication may prolong the headache or the person may suffer withdrawal headaches when he stops taking the tablets, particularly those that include caffeine.



Article appeared in the Ventura County Star. Reprinted with permission.


Pseudo Cushings

Things may not always be what they seem.

By Ted Friedman, M.D., Ph.D., Cedars-Sinai Medical Center

Cushings syndrome is a rare disorder which can severely affect the patient. Symptoms of patients with Cushings syndrome include weight gain, easy bruising, menstrual irregularities, increased appetite, trouble sleeping, depression or mood swings, anxiety, fatigue and altered mentation (trouble concentrating or decreased memory).

Physical abnormalities include new onset obesity (primarily in the abdominal and buttock regions), buffalo hump, filling in of the regions above the collarbone, thinning of the extremities, rounding and reddening of the face, thin skin, decreased muscle strength, high blood pressure, stretch marks and excess hair growth in women. Although some patients may have most or all of these signs and symptoms so that the diagnosis of Cushings syndrome may be easy to make, other patients may have mild Cushings syndrome and come to their health care providers at an early stage of the disease. These patients may have trouble being diagnosed with Cushings syndrome. Furthermore, other medical conditions may also result in some of the signs, symptoms and laboratory abnormalities seen in patients with Cushings syndrome, although the patient doesnt actually have Cushings syndrome. These conditions are called pseudo-Cushings states and include conditions such as severe stresses (illness or emotional stress), alcoholism or alcohol withdrawal and psychiatric conditions such as depression, panic disorders and psychotic conditions.

The psychiatric conditions, such as depression, which lead to a high production of the hormone, cortisol, are quite common and a patient with one of these conditions may appear similar to a patient with Cushings syndrome.

It is quite important to determine if the patient has Cushings syndrome or a pseudo-Cushings state because if a patient with a pseudo-Cushings state is incorrectly diagnosed as having Cushings syndrome, that patient could undergo needless and potentially harmful testing and also unnecessary surgery which would permanently impair the patients health. On the other hand, if a patient truly has Cushings syndrome, it would be important to confirm the diagnoses and eliminate the possibility of a pseudo-Cushings state so that the cause of the Cushings syndrome can be determined.

The most common cause of Cushings syndrome is a pituitary tumor (Cushings disease). Other causes of Cushings syndrome include adrenal tumors or cancers and tumors in other parts of the body, such as the lung, thymus or pancreas making the hormone ACTH (ectopic ACTH syndrome). It is important to determine that the patient has Cushings syndrome before the type of Cushings syndrome is investigated.

What should your health care provider do if you have a few of the signs and symptoms of Cushings syndrome? The first thing she/he should do is a careful history and physical looking for the items discussed above. Attention should be directed to the time course of the symptoms (new, sudden onset of weight gain and other symptoms suggest Cushings syndrome, while long-standing, non-progressing symptoms suggest pseudo-Cushings states).

Comparison with old pictures is often very helpful. I would then recommend that your health care provider obtain between one and three 24-hour urine samples and have them measured for urinary free cortisol (UFC). This test is a good screen to help determine if you have Cushings syndrome, are completely normal, or have intermediate values which require further testing to distinguish between pseudo-Cushings states and Cushings syndrome. If all your UFCs are in the normal range (usually less than 50 or 90 mg/day, depending on the assay), it is very unlikely that you have Cushings syndrome. If some of your UFCs are more than 3.5 times the upper limit of normal (usually more than 175 or 315 mg/day, depending on the assay), you probably have Cushings syndrome and you should have a work-up to determine the etiology of the Cushings syndrome.

If your UFCs fall in the range between the upper limit of normal and 3.5 times the upper limit of normal, you need to have further tests to distinguish between Cushings syndrome and pseudo-Cushings states. If your UFCs are either clearly high or mildly high, you should be referred to an Endocrinologist who specializes in Cushings syndrome for further work-up.

There are two good tests to help the Endocrinologist distinguish between mild Cushings syndrome and pseudo-Cushings states in those patients with a mildly elevated UFC. One test is called a diurnal cortisol test and takes advantage of the fact that normal patients and patients with pseudo-Cushings states have high plasma cortisol levels in the morning and much lower levels in the evening and at night, while patients with Cushings syndrome have high cortisol levels in both the morning and at night. The diurnal cortisol test takes advantage of this by having a blood sample drawn at midnight which is sent for plasma cortisol. Because of the timing of the required blood draw, this test may require a hospital admission. A plasma cortisol level of greater than 7.5 mg/dl probably means that you have Cushings syndrome, while a value less than 7.5 mg/dl probably indicates that you dont have Cushings syndrome. This test is quite accurate, but it requires blood collection at an inconvenient time. Because of the difficulty in obtaining blood at midnight, Endocrinologists are evaluating whether cortisol in a saliva sample can be used to distinguish between Cushings syndrome and pseudo-Cushings states. This test looks promising, however, it is still too early to recommend it instead of the diurnal plasma cortisol test.

The other test to help Endocrinologists distinguish between mild Cushings syndrome and pseudo-Cushings states in those patients with a mildly elevated UFC is the dexamethasone-CRH test. This test combines two tests, the dexamethasone suppression test and the CRH test which individually are good but not great at distinguishing between pseudo-Cushings states and Cushings syndrome. The dexamethasone test uses a drug called dexamethasone which in normal people and those with pseudo-Cushings states, suppresses the production of ACTH by the pituitary leading to low cortisol levels. In patients with Cushings syndrome, dexamethasone is ineffective and the cortisol usually doesnt decrease to low levels. CRH is a hormone which stimulates the pituitary to make more ACTH which leads to an increase in cortisol levels. Patients with Cushings syndrome have a larger increase in plasma ACTH and cortisol levels than in normal individuals or those patients with pseudo-Cushings states. Although these tests individually are helpful to diagnose Cushings syndrome, many patients with pseudo-Cushings states also respond to them in a similar manner as those with Cushings syndrome, making them not the ideal test to use individually. However, when these tests are combined, the distinction between Cushings syndrome and pseudo-Cushings states is almost always made. In the combined test, you take dexamethasone 4 times a day for 2 days and then get a injection of CRH. Your cortisol is measured 20 minutes after the CRH injection and a value of greater than 1.4 mg/dl means that you probably have Cushings syndrome. The main drawbacks to this test is that it requires a lot of steps and the drug (CRH) is expensive.

There are other tests (listed in Table) that may help your Endocrinologist determine if you have Cushings syndrome or pseudo-Cushings states. There are also tests (Table) that are not helpful in making the distinction between these two conditions and may actually confuse both you and your Endocrinologist if done at this time. One test called inferior petrosal sinus sampling (IPSS) is very good to determine what type of Cushings syndrome you have, but not good to determine if you have Cushings syndrome or pseudo-Cushings states and should not be done at this stage. Pituitary MRI is also very good for localizing a pituitary tumor once the diagnosis of Cushings syndrome is made, however it is not recommended to distinguish between Cushings syndrome and pseudo-Cushings states. This is because up to 10% of normal individuals have what radiologists read as a pituitary tumor on MRI (incidentalomas).

The distinction between Cushings syndrome and pseudo-Cushings states is often difficult leading to frustration for both patient and physician. To prevent this frustration, working closely with a good Endocrinologist who sees many patients with Cushings syndrome is needed. Patience is also needed. With time, most patients will declare themselves and develop a clearer picture consistent with either Cushings syndrome or a pseudo-Cushings state. While waiting, treating the underlying psychiatric condition (if present) is often helpful. The tincture of time is the best cure!


Two Alternatives for Obstructive Sleep Apnea

Published: May 18, 2009

By Todd Neale, Staff Writer, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine

LITTLE FALLS, N.J., May 18 -- For patients with obstructive sleep apnea, surgery and treatment with an oral device that adjusts the jaw appear to be effective alternatives to continuous positive airway pressure (CPAP), two retrospective studies showed.

In the first study, transpalatal advancement pharyngoplasty, a surgical procedure to enlarge the retropalatal area of the oropharynx, produced a success rate of 63%, according to Neville Patrick Shine, F.R.C.S., of St. John's Hospital in Edinburgh, and Richard Hamilton Lewis, F.R.A.C.S., of Royal Perth Hospital in Australia.

In the second study, application of a mandibular advancement device, which moves the lower jaw forward to prevent airway obstruction, was associated with a success rate of 74%, according to Jeong-Whun Kim, M.D., Ph.D., of Seoul National University Bundang Hospital in Seongnam, South Korea, and colleagues.

Both studies were published in the May Archives of Otolaryngology -- Head & Neck Surgery.

Although CPAP is the standard treatment for obstructive sleep, it has drawbacks, including discomfort from the mask, a dry or stuffy nose, and eye irritation, according to Shine and Lewis.

Because of these issues, compliance is low, ranging from 40% to 70%, according to Dr. Kim and colleagues.

So the two groups of researchers explored the major alternatives to CPAP, surgery and application of oral appliances.

Shine and Lewis conducted a review of the records of 60 patients (92% male; mean age 47.5) who underwent transpalatal advancement pharyngoplasty.

Polysomnography was performed three to six months after surgery.

Following treatment, the mean number of respiratory disturbances per hour of sleep decreased from 37.2 to 15.4 (P<0.001).

The mean minimum arterial oxygen saturation improved from 83.9% to 87.4% (P<0.001).

Treatment success -- defined as fewer than 20 respiratory disturbances per hour of sleep and a 50% reduction from baseline -- occurred in 63% of the patients.

Nearly three-quarters (72%) showed some improvement, and 35% were "cured," the researchers reported.

There were no significant associations between any presurgical patient characteristics and outcome.

Five patients had oronasal fistulae, all of which closed spontaneously. Two had secondary tonsillar hemorrhages, and one developed airway obstruction during recovery that required an emergency tracheostomy.

Transpalatal advancement pharyngoplasty "should be considered in patients in whom conservative management has failed and who are willing to undergo surgery to improve the retropalatal airway," Shine and Lewis concluded.

The study by Dr. Kim and colleagues involved 50 Korean patients (92% male; mean age 50.2) who received a mandibular advancement device.

Polysomnography was performed at least three months after application.

The mean number of respiratory disturbances per hour of sleep was reduced from 36.6 to 12.3 (P<0.001) after treatment.

Treatment success was defined the same way as in the study by Shine and Lewis and was achieved in 74% of patients, including 43% of those with mild disease, 82% of those with moderate disease, and 75% of those with severe disease.

In addition, the duration of the apnea and hypopnea episodes, the percentage of patients with snoring, and sleep quality were all significantly improved.

Minimum oxygen saturation did not change with treatment.

No patient characteristics were associated with treatment outcome.

Two patients developed mild temporomandibular joint pain.

The researchers concluded that "the mandibular advancement device is a simple, noninvasive, easy-to-manufacture, and easy-to-use device and showed good treatment outcome in nocturnal respiratory function and sleep quality in Korean patients with obstructive sleep apnea."

Because the device worked well for patients with all degrees of disease severity, they said, "mandibular advancement device application can be used as a good alternative option in patients with obstructive sleep apnea, without patient selection, and could be used in patients with severe obstructive sleep apnea."

Shine and Lewis acknowledged that their study was limited by the retrospective design, restricted generalization outside their practice, selection bias, short follow-up, lack of data on quality of life, and nonrandom loss to follow-up.

Dr. Kim and colleagues said the size of their study limited the interpretation of prognostic factors. The study also may have been limited by selection bias.


ASCO: Cymbalta Tames Post-Chemo Pain

Published: Jun 4, 2012

By Crystal Phend, Senior Staff Writer, MedPage Today
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco

CHICAGO -- The antidepressant duloxetine (Cymbalta) appears to cut down on the numbness and tingling associated with taxane or platinum-based chemotherapy, according to clinical trial results.

Pain from chemotherapy-induced peripheral neuropathy and its interference with daily life fell significantly with the drug, Ellen Lavoie Smith, PhD, of the University of Michigan School of Nursing in Ann Arbor, and colleagues found.

A clinically significant 30% or greater reduction in pain scores occurred in 33% of duloxetine-treated patients compared with 17% of placebo-treated patients, they reported here at the American Society of Clinical Oncology meeting.

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