Psychosomatics 2014:55:82–86
Published by Elsevier Inc. on behalf of The Academy of Psychosomatic Medicine.
Case Reports Ectopia Lentis, “The Sign of the Tremulous Iris,” and Hypovitaminosis C: A Classic Eye Finding with a Neuropsychiatric Twist Holly Volz, M.S3., Margit Gerardi, Ph.D., Thomas M. Brown, M.D., David W. Carroll, D.N.P.
Introduction Iridodonesis, tremulousness of the iris, is a striking physical examination finding. It is caused by inherited or acquired disorders of connective tissue. Common causes include trauma and cataract surgery. Wellestablished inherited causes include Marfan syndrome, Ehlers-Danlos syndrome, and homocystinuria, all of which can cause ectopia lentis, and subsequently iridodonesis. Indeed, ectopia lentis is among the findings used to help identify patients with Marfan syndrome.1 Among the acquired causes of ectopia lentis and iridodonesis may be nutritional disorders, such as hyperhomocysteinemia.2 We propose that vitamin C deficiency may be another acquired disorder of collagen that can cause ectopia lentis and iridodonesis. Furthermore, vitamin C deficiency is increasingly recognized as a cause of neuropsychiatric problems. As the clinician attempts to knit a diagnosis from clinical data, iridodonesis may offer another clue that a nutritional deficiency is present.
with 2 items of 4 recalled after 5 minutes. Because Mr. V was markedly weak, apathetic, and irritable, further cognitive testing was not pursued. The authors turned next to the physical examination. Mr. V had abnormal nystagmus on extreme horizontal gaze, diffuse hypotonia, and dysarthria. He also had palatal petechiae, multiple traumatic lesions on both feet extending up to his knees, friable nails, and left iridodonesis. He had no resting tremor, cogwheeling, or abnormal involuntary movements. He did not exhibit arachnodactyly, inexplicable stretch marks, cardiovascular abnormalities, hypermobile joints, or personal or family history of connective tissue disease. Mr. V smoked 2 packs per day of tobacco for many years. He had no history of inherited connective tissue disease, head trauma, heart disease, eye trauma, or cataract surgery. He did report a weight loss of 55 lb over the past year, which was confirmed by review of medical records and thought to be due to neglect. Mr. V's malnutrition and cerebellar findings satisfied operationalized criteria for a diagnosis of Wernicke encephalopathy.3 The World Health Organization operationalized the diagnosis of scurvy as a constellation of findings consistent with a vitamin C
Case Report Mr. V, a 66-year-old white male veteran with a history of schizophrenia was brought to the hospital for severe selfneglect and wandering. Since he had bilateral lower extremity cellulitis and foot ulcerations, he was admitted to the medicine service. He was alert and oriented in all spheres. He endorsed his usual delusion that he had a bubble in his head that contained demons, and on which he did not act. Short-term memory was marginally intact 82
www.psychosomaticsjournal.org
Received July 16, 2013; revised August 15, 2013; accepted August 16, 2013. From School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX; School of Nursing, University of Texas Health Science Center at San Antonio, San Antonio, TX; Department of Psychiatry, Audie L. Murphy Memorial VAMC, San Antonio, TX. Send correspondence and reprint requests to Thomas M. Brown, M.D., Department of Psychiatry, Audie L. Murphy Memorial VAMC, 7400 Merton Minton Blvd, San Antonio, TX 78229; e-mail: [email protected] Published by Elsevier Inc. on behalf of The Academy of Psychosomatic Medicine.
Psychosomatics 55:1, January/February 2014
Volz et al. deficiency, in the setting of inadequate vitamin C intake, and ideally confirmed by laboratory studies.4 The concern that Mr. V might have both Wernicke’s encephalopathy and scurvy led the authors to request serum levels of vitamin C, zinc, and thiamine. Mr. V's serum vitamin C level was returned at 0.0 mg/dL (normal range: 0.4–2.0 mg/dL), along with a normal serum zinc level of 81 mcg/dL (normal range: 70– 150 mcg/dL), and a low serum thiamine level of 79 nmol/L (normal range: 87–280 nmol/L). Further micronutrient laboratory studies were not requested in part because stigmata of other nutritional deficiencies were not present, such as lesions in a “farmer's tan” distribution that may have suggested pellagra. In addition, the authors recommended drawing relevant laboratory studies but not waiting for the results to return before initiating micronutrient replacement. The laboratory studies were intended to help confirm diagnoses and track response to treatment, though not to determine whether Mr. V should receive replacement therapy. But though vitamin replacement was recommended, this was not immediately provided by the primary ward team. A formal ophthalmologic examination was planned to complement the bedside
examination. An electroencephalogram and neuroimaging were also requested. However, later on the day of assessment, before vitamin replacement, Mr. V experienced a refeeding syndrome with heightened confusion and pulseless ventricular tachycardia and died. Discussion Ocular findings in scurvy have long been regarded as rare and hemorrhagic, and they are found only in advanced cases of scurvy.5 Vitamin C is essential in collagen synthesis. The role of collagen in creating and maintaining the structural and functional integrity of the ciliary body and lens is well-described.6 The lens is tethered to the ciliary muscles by the fibrils that form the zonule of Zinn. These fibrils insert into the collagenous capsule of the lens and thereby anchor the lens to the ciliary body. When the ciliary muscles contract or relax, the fibrils pull on the lens capsule and cause the lens to change shape and focus. Any damage to these fibrils or the lens capsule may affect not just the function of the lens, but even the secureness of its attachment to the surrounding structures. In ectopia
FIGURE.
Psychosomatics 55:1, January/February 2014
www.psychosomaticsjournal.org
83
Case Reports lentis, a portion of the lens becomes detached from the zonule of Zinn. The result is a lens that trembles when the eye moves (Figure). We propose that, just as is true for other disorders of collagen formation, vitamin C deficiency may increase the risk of ectopia lentis. This may be discovered on physical examination by the presence of iridodonesis, which is easily recognized. The possibility that Mr. V had an inherited connective tissue disease was considered. Although Mr. V failed to meet diagnostic criteria for Marfan syndrome, this was an especially important consideration as a weak association may exist between this disorder and TABLE.
schizophrenia. Psychosis occurs slightly more commonly among patients with Marfan syndrome than in the general population.7 What may distinguish a vitamin C deficiency most from Marfan syndrome and other collagen disorders associated with ectopia lentis is that vitamin C deficiency is much more common and more easily treated. The table below outlines various disorders that may cause ectopia lentis8–10 (Table). Vitamin C deficiency is not rare. In a study of otherwise healthy European adults, Roman Viñas et al.11 found that 10%–20% had deficient intake of vitamin C and 11% consumed too little zinc. Other
Comparative Findings Among Collagen Disorders that Cause Ectopia Lentis
Disease
Eye
Neuropsychiatric Skin
Joint and bone
Scurvy
Hemorrhages— most reported finding
Apathy, weakness, irritability, and EPS
Subperiosteal None bleeding and pain; hips and knees kept in classic flexed position
Marfan syndrome
Ectopia lentis is a “major” diagnostic criterion
Weak association with schizophrenia
Easy bruising: Rumpel-Leede phenomenon; gingival and periungual bleeding; corkscrew hairs Appearance of stretch marks with no explanation
Arachnodactyly, dolichostenomelia; pectus excavatum; scoliosis; flat feet; hypermobile joints; dural ectasia Ehlers-Danlos Ectopia lentis is a Chronic pain Joint hypermobility Easy bruising. syndrome minor finding. leads to anxiety Skin may stretch —a major or depression in remarkably. Myopia, diagnostic feature strabismus, and most patients Papyraceous, easy eversion of atrophic, and upper eyelids hemosiderotic (Metenier sign) changes more common common Osteoporosis Homocystinuria Ectopia lentis seen Risk of dementia There may be present brittle, common; pectus in most untreated increased excavatum, sparse hair, a cases and is one of malar flush, and scoliosis and pes the earliest findings livedo reticularis planus may occur
Osteogenesis imperfecta
Blue sclera most distinctive eye finding
No routine findings
Fragile skin that Frequent fractures scars easily and low bone density
WeillMarchesani (brachydactyly) syndrome
Structural eye abnormalities common and ectopia lentis in over 60%
No routine findings
Thick skin
84
www.psychosomaticsjournal.org
Short stature and brachydactyly typical
Cardiovascular
Aortic root dilatation; Mitral valve prolapse
Laboratory and study findings Decreased serum vitamin C
No specific test Although fibrillin-1 gene mutation on chromosome 15 occurs in many cases
Arterial rupture No specific may be seen in the laboratory test, vascular subtype although microscopy may reveal collagen fibrils in loose or disorganized arrays
Increased urine and Peripheral and serum homocysteine cerebrovascular thromboembolism levels; increased serum methionine levels; decreased serum cysteine levels; nonexistent serum cystathionine level Mitral and aortic Abnormal type I valve procollagen synthesis regurgitation in cultured cells. common Abnormal COL1A1 and COL1A2 genes Occasional heart Gene sequence findings, including analysis positive for patent ductus ADAMTS10 arteriosus and pulmonary stenosis
Psychosomatics 55:1, January/February 2014
Volz et al. authors report even higher rates of vitamin C deficiency among otherwise healthy adults.12 Besides inadequate intake, enhanced elimination or consumption can also lower serum vitamin C levels. For example, diuretics and hemodialysis enhance vitamin C losses. And though nonsmoking adults require about 60 mg daily of oral vitamin C, for smokers the need rises to 140 mg daily.13 Besides inadequate intake and enhanced elimination, patients may experience resistance to the actions of, or increased demand for, vitamin C. This may occur in infection, diabetes, and burns, postoperatively, and in other catabolic states.14 Mr. V was a malnourished smoker with bilateral lower extremity cellulitis and was thus a “set-up” for hypovitaminosis C. His case reflects several important issues in consultation-liaison psychiatry. These include the importance of the physical examination, the neuropsychiatric features of scurvy, and the peril faced by the malnourished patient. The idea that ectopia lentis and iridodonesis may be linked to scurvy is new. As is true for the association of nystagmus and ophthalmoplegia with Wernicke encephalopathy, this striking eye finding may help guide the clinician toward a specific physiologic explanation for at least some components of the mental status examination. And in the case of scurvy, the association with hypovitaminosis C and mental status changes is both old and evolving. James Lind15 identified the sentinel symptoms of scurvy as a change in behavior, with a “lazy, inactive disposition” and an ill “countenance” developing in the affected individual. Shapter16 in 1847 described the onset of scurvy as marked by “feelings of weakness, of listlessness, and a disinclination to exertion,” and noted that “the patient is nervous.” The most common symptoms of scurvy are indeed central. Irritability, psychomotor retardation, and weakness are seen in nearly all patients with scurvy. Classic symptoms, such as gingival bleeding, may occur in less than half.17 More recently, extrapyramidal symptoms (EPS) have been linked with vitamin C deficiency.14,18 The
association between hypovitaminosis C and EPS is important to psychiatrists for at least two reasons. Firstly, it suggests a readily treatable cause of EPS in at least some patients. Secondly, this association may help to guide other aspects of treatment, such as whether a drug is responsible for a patient's movement disorder. Iridodonesis may thus warn of potential sensitivity to antipsychotic agents. Such associations underscore the importance of the physical examination in consultation-liaison psychiatry. Unfortunately, in the case of Mr. V, the evidence of micronutrient deficiency did not prevent him from dying of what was thought to be a refeeding syndrome. After assessment by the psychiatric consultants, Mr. V was started on supplemental protein and carbohydrate feeds to increase his weight toward a calculated ideal. These feeds were given without the micronutrient replacement that his physical and mental status examinations suggested he would need. Within hours, Mr. V became highly confused and died. Delirium alone, and delirium accompanied by arrhythmias, is a hallmark of the refeeding syndrome.19–21 Mr. V's case is thus a stark reminder of the need to consider a refeeding syndrome when a patient becomes delirious. This is true both because of the relatively high prevalence of micronutrient deficiencies, as well as the swift lethality of some refeeding syndromes.11,22 Conclusions Mr. V's case includes what we believe to be a first report of iridodonesis due to scurvy. His death precluded a more complete evaluation of his iridodonesis. And yet his death also emphasizes the importance as well as the urgency of recognizing the potential role of nutritional deficiencies in psychiatric presentations and course. It is hoped that the case of Mr. V may inspire more inquiry into possible reversible nutritional causes of the tremulous iris.
References 1. Yang JH, Han H, Jang SY, Moon JR, Sung K, Chung TY, et al: A comparison of the Ghent and revised Ghent nosologies for the diagnosis of Marfan syndrome in an adult Korean population. Am J Med Genet A 2012; 158A (5):989–995
Psychosomatics 55:1, January/February 2014
2. Krumdieck CL, Prince CW: Mechanisms of homocysteine toxicity on connective tissues: implications for the morbidity of aging. J Nutr 2000; 130(2S Suppl):365S–368S 3. Caine D, Halliday GM, Kril JJ, Harper CG: Operational criteria for the classification of chronic alcoholics: identification
www.psychosomaticsjournal.org
85
Case Reports
4. 5. 6. 7.
8.
9.
10.
11.
12. 13.
86
of Wernicke's encephalopathy. J Neurol Neurosurg Psychiatry 1997; 62:51–60 World Health Organization: http://whqlibdoc.who.int/hq/ 1999/WHO_NHD_99.11.pdf Accessed 07.08.13. Hood J, Hodges RE: Ocular lesions in scurvy. Am J Clin Nutr 1969; 22(5):559–567 Reis LM, Semina EV: Genetics of anterior segment dysgenesis disorders. Curr Opin Ophthalmol 2011; 22(5):314–324 Lemberg M, Thompson AW: Marfan syndrome and schizophrenia: a case report and literature review. Gen Hosp Psychiatry 2010 (32(2):228.e9-228.e10) Lumley MA, Jordan M, Rubenstein R, Tsipouras P, Evans MI: Psychosocial functioning in the Ehlers-Danlos syndrome. Am J Med Genet 1994; 53(2):149–152 Van Den Bossche MJ, Van Wallendael KL, Strazisar M, Sabbe B, Del-Favero J: Co-occurrence of Marfan syndrome and schizophrenia: what can be learned? Eur J Med Genet 2012; 55(4):252–255 Werder SF: Cobalamin deficiency, hyperhomocysteinemia, and dementia. Neuropsychiatr Dis Treat 2010; 6: 159–195 Roman Viñas B, Ribas Barba L, Ngo J, et al: Projected prevalence of inadequate nutrient intakes in Europe. Ann Nutr Metab 2011; 59(2-4):84–95 Ben-Zvi GT, Tidman MJ: Be vigilant for scurvy in high-risk groups. Practitioner 2012; 256(1755):23–25 Berger MM: Vitamin C requirements in parenteral nutrition. Gastroenterology 2009; 137(5 Suppl):S70–S78
www.psychosomaticsjournal.org
14. Shavit I, Brown TM: Simultaneous scurvy and Wernicke's encephalopathy in a patient with an ascorbate-responsive dyskinesia. Psychosomatics 2013; 54(2):181–186 15. James Lind: The Diagnostics, or Symptoms, in A Treatise on the Scurvy, in Three Parts, 3rd Ed. S. Crowder, D. Wilson and G. Nicholls, T. Cadell, T. Becket and Co., G. Pearch and W. Woodfall. 1752, pp 98-129; available via Google Books at http://books.google.com/books?id=T1OT3tYmh5wC &printsec=frontcover#v=onepage&q&f=false 16. Shapter T: On the recent occurrence of scurvy in Exeter and the neighbourhood. Prov Med Surg J 1847; 11:281–285 17. Fouron JC, Chicoine L: Le scorbut: aspects particuliers de l'association rachitisme-scorbut. Can Med Assoc J 1962; 86: 1191–1196 18. Noble M, Healey CS, McDougal-Chukwumah LD, Brown TM: Old disease, new look? A first report of parkinsonism due to scurvy, and of refeeding-induced worsening of scurvy Psychosomatics 2013; 54(3):277–283 19. Brown TM: A case of shoshin beriberi: lessons old and new for the psychiatrist. Psychosomatics 2013; 54:175–180 20. Caplan JP: Too much too soon? Refeeding syndrome as an iatrogenic cause of delirium Psychosomatics 2008; 49:249–251 21. Caplan JP, Chang G: Refeeding syndrome as an iatrogenic cause of delirium: a retrospective pilot study. Psychosomatics 2010; 51:419–424 22. Khan LU, Ahmed J, Khan S, Macfie J: Refeeding syndrome: a literature review. Gastroenterol Res Pract 2011. 10.1155/2011/410971. Epub 2010 Aug 2
Psychosomatics 55:1, January/February 2014
Published by Elsevier Inc. on behalf of The Academy of Psychosomatic Medicine.
Case Reports Ectopia Lentis, “The Sign of the Tremulous Iris,” and Hypovitaminosis C: A Classic Eye Finding with a Neuropsychiatric Twist Holly Volz, M.S3., Margit Gerardi, Ph.D., Thomas M. Brown, M.D., David W. Carroll, D.N.P.
Introduction Iridodonesis, tremulousness of the iris, is a striking physical examination finding. It is caused by inherited or acquired disorders of connective tissue. Common causes include trauma and cataract surgery. Wellestablished inherited causes include Marfan syndrome, Ehlers-Danlos syndrome, and homocystinuria, all of which can cause ectopia lentis, and subsequently iridodonesis. Indeed, ectopia lentis is among the findings used to help identify patients with Marfan syndrome.1 Among the acquired causes of ectopia lentis and iridodonesis may be nutritional disorders, such as hyperhomocysteinemia.2 We propose that vitamin C deficiency may be another acquired disorder of collagen that can cause ectopia lentis and iridodonesis. Furthermore, vitamin C deficiency is increasingly recognized as a cause of neuropsychiatric problems. As the clinician attempts to knit a diagnosis from clinical data, iridodonesis may offer another clue that a nutritional deficiency is present.
with 2 items of 4 recalled after 5 minutes. Because Mr. V was markedly weak, apathetic, and irritable, further cognitive testing was not pursued. The authors turned next to the physical examination. Mr. V had abnormal nystagmus on extreme horizontal gaze, diffuse hypotonia, and dysarthria. He also had palatal petechiae, multiple traumatic lesions on both feet extending up to his knees, friable nails, and left iridodonesis. He had no resting tremor, cogwheeling, or abnormal involuntary movements. He did not exhibit arachnodactyly, inexplicable stretch marks, cardiovascular abnormalities, hypermobile joints, or personal or family history of connective tissue disease. Mr. V smoked 2 packs per day of tobacco for many years. He had no history of inherited connective tissue disease, head trauma, heart disease, eye trauma, or cataract surgery. He did report a weight loss of 55 lb over the past year, which was confirmed by review of medical records and thought to be due to neglect. Mr. V's malnutrition and cerebellar findings satisfied operationalized criteria for a diagnosis of Wernicke encephalopathy.3 The World Health Organization operationalized the diagnosis of scurvy as a constellation of findings consistent with a vitamin C
Case Report Mr. V, a 66-year-old white male veteran with a history of schizophrenia was brought to the hospital for severe selfneglect and wandering. Since he had bilateral lower extremity cellulitis and foot ulcerations, he was admitted to the medicine service. He was alert and oriented in all spheres. He endorsed his usual delusion that he had a bubble in his head that contained demons, and on which he did not act. Short-term memory was marginally intact 82
www.psychosomaticsjournal.org
Received July 16, 2013; revised August 15, 2013; accepted August 16, 2013. From School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX; School of Nursing, University of Texas Health Science Center at San Antonio, San Antonio, TX; Department of Psychiatry, Audie L. Murphy Memorial VAMC, San Antonio, TX. Send correspondence and reprint requests to Thomas M. Brown, M.D., Department of Psychiatry, Audie L. Murphy Memorial VAMC, 7400 Merton Minton Blvd, San Antonio, TX 78229; e-mail: [email protected] Published by Elsevier Inc. on behalf of The Academy of Psychosomatic Medicine.
Psychosomatics 55:1, January/February 2014
Volz et al. deficiency, in the setting of inadequate vitamin C intake, and ideally confirmed by laboratory studies.4 The concern that Mr. V might have both Wernicke’s encephalopathy and scurvy led the authors to request serum levels of vitamin C, zinc, and thiamine. Mr. V's serum vitamin C level was returned at 0.0 mg/dL (normal range: 0.4–2.0 mg/dL), along with a normal serum zinc level of 81 mcg/dL (normal range: 70– 150 mcg/dL), and a low serum thiamine level of 79 nmol/L (normal range: 87–280 nmol/L). Further micronutrient laboratory studies were not requested in part because stigmata of other nutritional deficiencies were not present, such as lesions in a “farmer's tan” distribution that may have suggested pellagra. In addition, the authors recommended drawing relevant laboratory studies but not waiting for the results to return before initiating micronutrient replacement. The laboratory studies were intended to help confirm diagnoses and track response to treatment, though not to determine whether Mr. V should receive replacement therapy. But though vitamin replacement was recommended, this was not immediately provided by the primary ward team. A formal ophthalmologic examination was planned to complement the bedside
examination. An electroencephalogram and neuroimaging were also requested. However, later on the day of assessment, before vitamin replacement, Mr. V experienced a refeeding syndrome with heightened confusion and pulseless ventricular tachycardia and died. Discussion Ocular findings in scurvy have long been regarded as rare and hemorrhagic, and they are found only in advanced cases of scurvy.5 Vitamin C is essential in collagen synthesis. The role of collagen in creating and maintaining the structural and functional integrity of the ciliary body and lens is well-described.6 The lens is tethered to the ciliary muscles by the fibrils that form the zonule of Zinn. These fibrils insert into the collagenous capsule of the lens and thereby anchor the lens to the ciliary body. When the ciliary muscles contract or relax, the fibrils pull on the lens capsule and cause the lens to change shape and focus. Any damage to these fibrils or the lens capsule may affect not just the function of the lens, but even the secureness of its attachment to the surrounding structures. In ectopia
FIGURE.
Psychosomatics 55:1, January/February 2014
www.psychosomaticsjournal.org
83
Case Reports lentis, a portion of the lens becomes detached from the zonule of Zinn. The result is a lens that trembles when the eye moves (Figure). We propose that, just as is true for other disorders of collagen formation, vitamin C deficiency may increase the risk of ectopia lentis. This may be discovered on physical examination by the presence of iridodonesis, which is easily recognized. The possibility that Mr. V had an inherited connective tissue disease was considered. Although Mr. V failed to meet diagnostic criteria for Marfan syndrome, this was an especially important consideration as a weak association may exist between this disorder and TABLE.
schizophrenia. Psychosis occurs slightly more commonly among patients with Marfan syndrome than in the general population.7 What may distinguish a vitamin C deficiency most from Marfan syndrome and other collagen disorders associated with ectopia lentis is that vitamin C deficiency is much more common and more easily treated. The table below outlines various disorders that may cause ectopia lentis8–10 (Table). Vitamin C deficiency is not rare. In a study of otherwise healthy European adults, Roman Viñas et al.11 found that 10%–20% had deficient intake of vitamin C and 11% consumed too little zinc. Other
Comparative Findings Among Collagen Disorders that Cause Ectopia Lentis
Disease
Eye
Neuropsychiatric Skin
Joint and bone
Scurvy
Hemorrhages— most reported finding
Apathy, weakness, irritability, and EPS
Subperiosteal None bleeding and pain; hips and knees kept in classic flexed position
Marfan syndrome
Ectopia lentis is a “major” diagnostic criterion
Weak association with schizophrenia
Easy bruising: Rumpel-Leede phenomenon; gingival and periungual bleeding; corkscrew hairs Appearance of stretch marks with no explanation
Arachnodactyly, dolichostenomelia; pectus excavatum; scoliosis; flat feet; hypermobile joints; dural ectasia Ehlers-Danlos Ectopia lentis is a Chronic pain Joint hypermobility Easy bruising. syndrome minor finding. leads to anxiety Skin may stretch —a major or depression in remarkably. Myopia, diagnostic feature strabismus, and most patients Papyraceous, easy eversion of atrophic, and upper eyelids hemosiderotic (Metenier sign) changes more common common Osteoporosis Homocystinuria Ectopia lentis seen Risk of dementia There may be present brittle, common; pectus in most untreated increased excavatum, sparse hair, a cases and is one of malar flush, and scoliosis and pes the earliest findings livedo reticularis planus may occur
Osteogenesis imperfecta
Blue sclera most distinctive eye finding
No routine findings
Fragile skin that Frequent fractures scars easily and low bone density
WeillMarchesani (brachydactyly) syndrome
Structural eye abnormalities common and ectopia lentis in over 60%
No routine findings
Thick skin
84
www.psychosomaticsjournal.org
Short stature and brachydactyly typical
Cardiovascular
Aortic root dilatation; Mitral valve prolapse
Laboratory and study findings Decreased serum vitamin C
No specific test Although fibrillin-1 gene mutation on chromosome 15 occurs in many cases
Arterial rupture No specific may be seen in the laboratory test, vascular subtype although microscopy may reveal collagen fibrils in loose or disorganized arrays
Increased urine and Peripheral and serum homocysteine cerebrovascular thromboembolism levels; increased serum methionine levels; decreased serum cysteine levels; nonexistent serum cystathionine level Mitral and aortic Abnormal type I valve procollagen synthesis regurgitation in cultured cells. common Abnormal COL1A1 and COL1A2 genes Occasional heart Gene sequence findings, including analysis positive for patent ductus ADAMTS10 arteriosus and pulmonary stenosis
Psychosomatics 55:1, January/February 2014
Volz et al. authors report even higher rates of vitamin C deficiency among otherwise healthy adults.12 Besides inadequate intake, enhanced elimination or consumption can also lower serum vitamin C levels. For example, diuretics and hemodialysis enhance vitamin C losses. And though nonsmoking adults require about 60 mg daily of oral vitamin C, for smokers the need rises to 140 mg daily.13 Besides inadequate intake and enhanced elimination, patients may experience resistance to the actions of, or increased demand for, vitamin C. This may occur in infection, diabetes, and burns, postoperatively, and in other catabolic states.14 Mr. V was a malnourished smoker with bilateral lower extremity cellulitis and was thus a “set-up” for hypovitaminosis C. His case reflects several important issues in consultation-liaison psychiatry. These include the importance of the physical examination, the neuropsychiatric features of scurvy, and the peril faced by the malnourished patient. The idea that ectopia lentis and iridodonesis may be linked to scurvy is new. As is true for the association of nystagmus and ophthalmoplegia with Wernicke encephalopathy, this striking eye finding may help guide the clinician toward a specific physiologic explanation for at least some components of the mental status examination. And in the case of scurvy, the association with hypovitaminosis C and mental status changes is both old and evolving. James Lind15 identified the sentinel symptoms of scurvy as a change in behavior, with a “lazy, inactive disposition” and an ill “countenance” developing in the affected individual. Shapter16 in 1847 described the onset of scurvy as marked by “feelings of weakness, of listlessness, and a disinclination to exertion,” and noted that “the patient is nervous.” The most common symptoms of scurvy are indeed central. Irritability, psychomotor retardation, and weakness are seen in nearly all patients with scurvy. Classic symptoms, such as gingival bleeding, may occur in less than half.17 More recently, extrapyramidal symptoms (EPS) have been linked with vitamin C deficiency.14,18 The
association between hypovitaminosis C and EPS is important to psychiatrists for at least two reasons. Firstly, it suggests a readily treatable cause of EPS in at least some patients. Secondly, this association may help to guide other aspects of treatment, such as whether a drug is responsible for a patient's movement disorder. Iridodonesis may thus warn of potential sensitivity to antipsychotic agents. Such associations underscore the importance of the physical examination in consultation-liaison psychiatry. Unfortunately, in the case of Mr. V, the evidence of micronutrient deficiency did not prevent him from dying of what was thought to be a refeeding syndrome. After assessment by the psychiatric consultants, Mr. V was started on supplemental protein and carbohydrate feeds to increase his weight toward a calculated ideal. These feeds were given without the micronutrient replacement that his physical and mental status examinations suggested he would need. Within hours, Mr. V became highly confused and died. Delirium alone, and delirium accompanied by arrhythmias, is a hallmark of the refeeding syndrome.19–21 Mr. V's case is thus a stark reminder of the need to consider a refeeding syndrome when a patient becomes delirious. This is true both because of the relatively high prevalence of micronutrient deficiencies, as well as the swift lethality of some refeeding syndromes.11,22 Conclusions Mr. V's case includes what we believe to be a first report of iridodonesis due to scurvy. His death precluded a more complete evaluation of his iridodonesis. And yet his death also emphasizes the importance as well as the urgency of recognizing the potential role of nutritional deficiencies in psychiatric presentations and course. It is hoped that the case of Mr. V may inspire more inquiry into possible reversible nutritional causes of the tremulous iris.
References 1. Yang JH, Han H, Jang SY, Moon JR, Sung K, Chung TY, et al: A comparison of the Ghent and revised Ghent nosologies for the diagnosis of Marfan syndrome in an adult Korean population. Am J Med Genet A 2012; 158A (5):989–995
Psychosomatics 55:1, January/February 2014
2. Krumdieck CL, Prince CW: Mechanisms of homocysteine toxicity on connective tissues: implications for the morbidity of aging. J Nutr 2000; 130(2S Suppl):365S–368S 3. Caine D, Halliday GM, Kril JJ, Harper CG: Operational criteria for the classification of chronic alcoholics: identification
www.psychosomaticsjournal.org
85
Case Reports
4. 5. 6. 7.
8.
9.
10.
11.
12. 13.
86
of Wernicke's encephalopathy. J Neurol Neurosurg Psychiatry 1997; 62:51–60 World Health Organization: http://whqlibdoc.who.int/hq/ 1999/WHO_NHD_99.11.pdf Accessed 07.08.13. Hood J, Hodges RE: Ocular lesions in scurvy. Am J Clin Nutr 1969; 22(5):559–567 Reis LM, Semina EV: Genetics of anterior segment dysgenesis disorders. Curr Opin Ophthalmol 2011; 22(5):314–324 Lemberg M, Thompson AW: Marfan syndrome and schizophrenia: a case report and literature review. Gen Hosp Psychiatry 2010 (32(2):228.e9-228.e10) Lumley MA, Jordan M, Rubenstein R, Tsipouras P, Evans MI: Psychosocial functioning in the Ehlers-Danlos syndrome. Am J Med Genet 1994; 53(2):149–152 Van Den Bossche MJ, Van Wallendael KL, Strazisar M, Sabbe B, Del-Favero J: Co-occurrence of Marfan syndrome and schizophrenia: what can be learned? Eur J Med Genet 2012; 55(4):252–255 Werder SF: Cobalamin deficiency, hyperhomocysteinemia, and dementia. Neuropsychiatr Dis Treat 2010; 6: 159–195 Roman Viñas B, Ribas Barba L, Ngo J, et al: Projected prevalence of inadequate nutrient intakes in Europe. Ann Nutr Metab 2011; 59(2-4):84–95 Ben-Zvi GT, Tidman MJ: Be vigilant for scurvy in high-risk groups. Practitioner 2012; 256(1755):23–25 Berger MM: Vitamin C requirements in parenteral nutrition. Gastroenterology 2009; 137(5 Suppl):S70–S78
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14. Shavit I, Brown TM: Simultaneous scurvy and Wernicke's encephalopathy in a patient with an ascorbate-responsive dyskinesia. Psychosomatics 2013; 54(2):181–186 15. James Lind: The Diagnostics, or Symptoms, in A Treatise on the Scurvy, in Three Parts, 3rd Ed. S. Crowder, D. Wilson and G. Nicholls, T. Cadell, T. Becket and Co., G. Pearch and W. Woodfall. 1752, pp 98-129; available via Google Books at http://books.google.com/books?id=T1OT3tYmh5wC &printsec=frontcover#v=onepage&q&f=false 16. Shapter T: On the recent occurrence of scurvy in Exeter and the neighbourhood. Prov Med Surg J 1847; 11:281–285 17. Fouron JC, Chicoine L: Le scorbut: aspects particuliers de l'association rachitisme-scorbut. Can Med Assoc J 1962; 86: 1191–1196 18. Noble M, Healey CS, McDougal-Chukwumah LD, Brown TM: Old disease, new look? A first report of parkinsonism due to scurvy, and of refeeding-induced worsening of scurvy Psychosomatics 2013; 54(3):277–283 19. Brown TM: A case of shoshin beriberi: lessons old and new for the psychiatrist. Psychosomatics 2013; 54:175–180 20. Caplan JP: Too much too soon? Refeeding syndrome as an iatrogenic cause of delirium Psychosomatics 2008; 49:249–251 21. Caplan JP, Chang G: Refeeding syndrome as an iatrogenic cause of delirium: a retrospective pilot study. Psychosomatics 2010; 51:419–424 22. Khan LU, Ahmed J, Khan S, Macfie J: Refeeding syndrome: a literature review. Gastroenterol Res Pract 2011. 10.1155/2011/410971. Epub 2010 Aug 2
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