158 Chapter 10: Over-reliance on negative test results

Table 10.2 Causes of vitamin B12 deficiency

Nutritional deficiency strict vegan diet alcoholism

elderly institutionalized

Gastric disorders

absence of intrinsic factors (pernicious anemia) gastroplasty/gastrectomy

food-cobalamin malabsorption syndrome gastritis with achlorhydria

gastric atrophy (Sjogren’s syndrome, idiopathic) decreased acid (antacids, vagotomy) pancreatic disease (surgical, exocrine failure)

Small-bowel disorders intestinal surgery

ileal disease (Crohn’s, amyloid, lymphoma) infections (Diphylloboturium latum)

effects are indigestion and a smooth tongue (Hunter’s glossitis). Neuropsychiatric changes are widespread, including combined sclerosis of the spinal cord, peripheral neuropathy, cognitive impairment, depression, parkinsonism and optic neuropathy. The visual loss of B12 deficiency is bilateral and symmetric, painless and gradually progressive. Loss of color vision, decreased acuity and central or ceco-central scotomas are characteristic. The optic discs may be normal or hyperemic acutely, pale and atrophic later.

Visual loss and other neurologic manifestations of B12 deficiency can occur well in advance of hematologic changes and therefore a CBC is not an adequate screening test for such vitamin deficiency. Furthermore, the official normal values provided by many laboratories indicate a rather broad range and occasional patients are symptomatically deficient even at levels that are technically within this normal range. This patient’s visual loss was consistent with nutritional deficiency and she was therefore treated with parental hydroxycobalamin even though her B12 serum level was “officially” normal. Her positive response to treatment confirmed this as the mechanism of visual loss.

Diagnosis: Pernicious anemia with normal serum B12 level

Tip: The possibility of B12 deficiency should be entertained in patients with characteristic clinical features even in the presence of low-normal serum vitamin levels.

Twinkling after embolic stroke

Case: An 82-year-old woman was hospitalized for treatment of new-onset atrial fibrillation. At some point during her hospital course she developed difficulty seeing to the right side and a brain MRI revealed a left occipital infarct (Figure 10.2A). Soon after returning home she noticed continuous “sparkling and twinkling”, along with mild photosensitivity. Over the next four months her sparkles persisted, especially in bright light, prompting neuro-ophthalmic consultation. On examination, visual acuity, pupillary responses and ophthalmoscopic appearance were normal. Goldmann perimetry showed a right homonymous superior quadrantanopic defect consistent with her left occipital infarct (Figure 10.2B).

Now we understand the basis of this patient’s visual field defect. But what is causing her persistent photopsias?

This patient has suffered an embolic stroke secondary to atrial fibrillation. We would consider that the infarct may have produced cortical irritability, i.e. focal seizures, accounting for her positive visual symptoms. The continuous nature of her photopsias, however, would be extremely unusual, and an EEG was normal. Dilated examination of the fundi showed no retinal cause for her symptom.

It was noted that during her hospitalization the patient had been started on digoxin for persistent atrial fibrillation and had been on the same dose (0.25 mg/day) since discharge. The possibility of digitalis toxicity was considered, however her serum digoxin level was only 1.9 ng/ml (therapeutic

range 0.8–2.0 ng/ml). Despite her therapeutic level, this possibility was further pursued. Following discussion with her cardiologist, the digoxin dose was decreased to 0.125 mg per day and within one week her photopsias and light sensitivity completely resolved. She has since remained stable from a cardiovascular standpoint.

Discussion: Digitalis toxicity causes changes in many tissues, including the eye and brain. Visual dysfunction is probably due to its effects on photoreceptors, especially cones. While full-blown digitalis toxicity produces systemic effects including nausea, malaise, confusion and cardiac conduction abnormalities, visual manifestations may occur in the absence of other symptoms and signs. The classic description of digitalis toxicity emphasizes altered color vision, specifically the perception of a yellow-green tinge. In fact, there is a wide spectrum of visual disturbance associated with toxicity from cardiac glycosides, the most common of which is not yellow-green vision but white or “frosty” vision (see Table 10.3). Consistent with a predilection for causing cone dysfunction, visual symptoms from

Table 10.3 Visual symptoms of digitalis toxicity

Blurred or hazy vision Alterations of color

frosted or snowy vision xanthopsia

less commonly red, blue or brown Positive phenomena

flashes, sparkles flickering, shimmering glare or dazzle scintillating scotoma

digitalis are most prominent in bright light and are often accompanied by positive visual phenomena and photosensitivity. Objective findings on examination include decreased acuity, abnormal color vision and central scotomas that are bilateral and symmetric.

Toxicity from cardiac glycosides may occur without a change in the dose or the addition of another medication. Furthermore, symptoms of toxicity may occur even with doses that are within the therapeutic range, as illustrated by this case. Abnormalities of color vision are demonstrable on the Farnsworth