manifestations of these disorders and the limitations of the tests that we use to diagnose them.

serum B12 level was 240 pg/mL (normal 220–1000). An MRI of brain and orbits with and without contrast was normal.

Unexplained visual loss

Case: A 59-year-old accountant developed difficulty with near vision during her busy taxpreparation season. Along with blurring of vision in both eyes, she noticed that colors appeared less bright. There were no other focal deficits and no systemic symptoms. She was generally healthy and on no medications, had a normal diet, was a non-smoker and consumed occasional alcohol.

Examination showed best corrected visual acuity of 20/50 OD and 20/40 OS. She identified 7 of 15 Ishihara color plates in each eye and pupillary responses were normal. Goldmann perimetry revealed a relative ceco-central scotoma in each eye (Figure 10.1) and the fundus examination was completely normal. Laboratory testing showed a normal hemoglobin of 14 g/dL but elevated mean corpuscular volume (MCV) of 120 fL (normal 81–99). The

In the absence of any objective abnormalities, would you consider that this might be non-organic visual loss, perhaps due to job-related stress?

While this might be a consideration, the visual field pattern in this case (bilateral ceco-central scotomas) would be most unusual for functional visual loss. This particular visual field pattern usually indicates a disease process involving the papillomacular bundle. Specific forms of optic neuropathy that produce bilateral ceco-central scotomas include certain toxins, nutritional deficiencies, hereditary optic neuropathies and demyelinating disease (see Table 10.1). It is extremely unusual for this pattern of visual loss to be produced by a mass lesion; optic nerve or chiasmal compression can cause central loss but when it does there is almost always paracentral and/or peripheral field loss as well.

Table 10.1 Optic neuropathies that produce bilateral ceco-central scotomas

Toxins ethambutol isoniazide disulfiram

chloramphenicol linezolide

chemotherapy (cisplatin, vincristine, 5-FU) Nutritional deficiency

B-vitamins (B12, B6, B1) folate

Hereditary disorders

Leber’s hereditary optic neuropathy dominant optic atrophy

Demyelinating disease multiple sclerosis neuromyelitis optica

Visual loss due to nutritional deficiency was suspected based on her macrocytosis, however her serum B12 level was within the normal range. What would you like to do next?

There are other methods for investigating the possibility of B12 deficiency which might be helpful in this case. Because vitamin B12 is an important co-factor in the metabolism of homocysteine and methylmalonic acid, altered levels of these metabolites can be used as supportive evidence of a deficiency state. A comitant elevation of serum homocysteine (≥13 µmol/L) or methylmalonic acid (≥0.4 µmol/L) in the absence of renal failure, folate deficiency or insufficient level of B6 lends support to a diagnosis of B12 deficiency. A Schilling test is the standard method for demonstrating B12 malabsorption, but at many institutions this cumbersome test is no longer unavailable. Anti-parietal cell antibody assay is a useful test for the diagnosis of pernicious anemia although it is not helpful for identifying other mechanisms of B12 deficiency.

This patient’s serum demonstrated a high titer of anti-parietal cell antibodies consistent with pernicious anemia. She was treated with 1000 micrograms of intramuscular hydroxycobalamin each

week for one month followed by monthly injections. At her two-month follow-up visit, visual acuities had improved to 20/25 OU with normal color vision in each eye and the visual fields had returned to normal. She has been well on monthly maintenance B12 injections since.

Discussion: Vitamin B12 (cobalamin) deficiency is an important cause of optic neuropathy because visual loss is preventable and, to some extent, reversible with treatment. Important dietary sources of B12 are meat, liver, fish, cheese and eggs. The typical western diet contains 3–30 µg of B12 daily and hepatic reserves are sufficient for 5 to 10 years, thus symptoms of deficiency typically develop years after the causative event. Absorption of B12 requires gastric acid, pancreatic enzymes, intrinsic factor and intact mucosal cells in the ileum.

Those at risk for insufficient dietary intake of B12 are strict vegans, alcoholics, institutionalized patients and the elderly. The prevalence of cobalamin deficiency in the elderly population has been estimated at about 20%. A number of conditions can interfere with the normal absorption process of B12 and eventually lead to a deficiency state. These include gastrectomy, pernicious anemia, food-cobalamin malabsorption syndrome, pancreatectomy, and a variety of intestinal disorders (see Table 10.2). Food-cobalamin malabsorption syndrome is an increasingly recognized cause of B12 deficiency in patients with normal dietary intake and a normal Schilling test. The malabsorption stems from an inability to release cobalamin from ingested food so that it is unavailable for intrinsic factor-mediated absorption. The release of food cobalamin requires stomach pepsin and acid, so the main risk for this form of malabsorption is gastric dysfunction due to a number of underlying conditions (see Table 10.2).

The clinical sequelae of B12 deficiency can be divided into hematologic, neuropsychiatric and gastrointestinal manifestations. Hematologic changes consist of macrocytosis, hypersegmented neutrophils and anemia. Typical gastrointestinal