Both Mr. A and Mr. B presented with a typical picture of latent scurvy and the additional finding of parkinsonism. These cases are important for 2 reasons. First, the swift and full response of these patients’ parkinsonism to vitamin C replacement underscores the importance of considering a vitamin C deficiency when confronted with EPS. And second, both patients lacked signs of bleeding or of impaired collagen synthesis. This differs from the classic presentation of scurvy as a disorder primarily of collagen metabolism.4
Lind described the onset of scurvy as one in which striking emotional and behavior changes developed and later were followed by abnormal bleeding and even death.2 These early changes also were recognized by Shapter in 1847.5 Furthermore, the evidence that exists about the time-course of scurvy’s development suggests that neuropsychiatric findings precede the hemorrhagic.6 Indeed, classic skin findings, such as petechiae or corkscrew hairs, may develop years after the onset of neuropsychiatric changes.7,8
Despite WHO characterizing it as latent scurvy, the distinct syndromal presentation of hypovitaminosis C with parkinsonism along with the rapid response to vitamin C replacement argues for its recognition as a distinct clinical entity and not just a prelude to the hemorrhagic state. To assist in recognizing neuropsychiatric scurvy, the author suggests the operationalized approach described in Table 1.9
Vitamin C has an intimate role in the normal functioning of the basal ganglia. It is involved in the synthesis of catechecholamines, the regulation of the release and postsynaptic activities of various neurotransmitters, and managing the oxyradical toxicity of aerobic metabolism. Table 2 outlines some of the normal brain functions of vitamin C and the potential consequences of inadequate central vitamin C.9,10 Risk factors for vitamin C deficiency include those affecting the uptake, response to, and elimination of this vitamin (Table 3).11-14
The potential role of alcohol use by both patients also warrants mention. Current data suggest a nonlinear relationship between alcohol use and neurotoxicity. Epidemiologic data show that moderate alcohol consumption protects against the development of such neurodegenerative processes as Parkinson disease and Alzheimer disease.15,16 But the cases here reflect excessive use of alcohol. In this situation, a variety of progressive insults, such as those caused by oxyradical toxicity as well as malnutrition may foster the development of basal ganglia dysfunction.17
A deficiency of vitamin C may be determined in several ways. The most frequently used laboratory measure of vitamin C status is the serum vitamin C level. This level is included in the WHO’s recommendations for diagnosis.3 However, this assay is limited because when facing total body depletion, the kidneys may restrict the elimination of vitamin C and tend to maintain serum vitamin C levels even as target tissue levels fall. An interesting example of this is the 0.2 mg/dL value that each patient registered. In Mr. A’s case, this reflected a systemic deficit of vitamin C, while in Mr. B’s case it correlated with the onset of effective repletion of body’s stores.
A fall in urinary output of vitamin C is another marker of hypovitaminosis C. When available, this laboratory test can be used with the serum level to assess total body stores of vitamin C. Lymphocytes, neutrophils, and platelets also store vitamin C. These target tissues tend to saturate when the oral intake ranges between 100 mg to 200 mg a day. This is the same point at which serum vitamin C levels peak and level off in normal, healthy adults.18,19 Once again, the limited availability of target-tissue assays puts these studies out of reach for most clinicians.
No evaluation is complete without some assurance of what the disease is not. Deficiencies of biotin, zinc, folate, and B12 all may affect the function of the basal ganglia.20 The biotin deficiencies literature is particularly robust. Biotin deficiencies affecting basal ganglia function are best known as inherited disorders of metabolism.21 Manganese intoxication also may present as a movement disorder.22
Treatment of neuropsychiatric scurvy has relied on IV administration of vitamin C. Although the bioavailability of oral vitamin C among healthy adult volunteers is nearly complete up to about 200 mg a day, a patient with neuropsychiatric scurvy may need substantially more than that amount to accommodate total body deficiencies and increased demands.23 The IV route allows serum vitamin C levels up to 100 times higher than by the oral route.24 Mr. B is, in fact, the first person reported in the literature with neuropsychiatric scurvy to respond to oral vitamin C replacement alone. Once repletion of vitamin C is complete, it is useful to consider a maintenance replacement dose based on a patient’s risk factors and needs.