General Hospital Psychiatry 37 (2015) 273.e5–273.e7

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Case Report

Pernicious anemia presenting as catatonia: correlating vitamin B12 levels and catatonic symptoms Damien Bram, M.D. a,c,⁎, Maxime Bubrovszky, M.D., Ph.D. b,c, Jean-Paul Durand, M.D. a, Guillaume Lefevre, M.D. b,d, Sandrine Morell-Dubois, M.D. b,d, Guillaume Vaiva, M.D., Ph.D. b,c a

EPSM des Flandres, Bailleul, France Université Lille Nord de France, Lille, France Department of Psychiatry, CHU Lille, Lille, France d Department of Internal Medicine, National Reference Center for Rare Autoimmune and Systemic Diseases, CHRU Lille, Lille, France b c

a r t i c l e

i n f o

Article history: Received 14 August 2014 Revised 12 February 2015 Accepted 17 February 2015 Keywords: Catatonia Vitamin B12 deficiency Psychiatry Vitamins

a b s t r a c t Pernicious anemia has been associated with various psychiatric manifestations, such as depression, mania and psychosis. Psychiatric symptoms can sometimes occur without hematological and neurological abnormalities and can be prodromal of vitamin B12 deficiency. We report a case of autoimmune B12 deficiency presenting as catatonia without signs of anemia or macrocytosis, in which a correlation was found between the patient's B12 blood levels and catatonic symptoms over time. This catatonic episode was successfully treated with only lorazepam and adequate doses of cyanocobalamin. © 2015 Elsevier Inc. All rights reserved.

1. Case report The patient was a retired 60-year-old woman who was brought to the Emergency Department (ED) by her husband because of sudden mental status deterioration for 4 days. The patient's medical past history was significant for Biermer disease with positive parietal cell antibodies controlled with cyanocobalamin one im injection of 1000 μg/month. She had a chronic atrophic gastritis and slight intestinal atrophy without metaplasia complicating her Biermer disease. Other aspects of the patient's medical history included hypertension (controlled with valsartan 40 mg/day), sleep apnea, premature menopause at the age of 40 years (treated with a hormone replacement therapy during 10 years) and allergy to iodine. She also had hypothyroidism (controlled with levothyroxine 87.5 μg/day) for which she had a regular endocrinological follow-up with closely monitored thyroid function tests. Furthermore, a serology analysis (HIV, hepatitis B and C, CMV infection, Epstein Barr virus, parvovirus B19) had been performed prior to her ED admission and revealed no abnormalities. The patient did not have any family history of psychiatric illness.

⁎ Corresponding author. 85 rue Massena, 59800 Lille, France. Tel.: +33-783400199. E-mail addresses: [email protected] (D. Bram), [email protected] (M. Bubrovszky), Jean-Paul.Durand@epsm-des-flandres.com (J.-P. Durand), [email protected] (G. Lefevre), [email protected] (S. Morell-Dubois), [email protected] (G. Vaiva). http://dx.doi.org/10.1016/j.genhosppsych.2015.02.003 0163-8343/© 2015 Elsevier Inc. All rights reserved.

At intake, she reported general slowing, insomnia and anxiety. The patient's husband described 4 or 5 short and mild self-limiting episodes of abnormal still sitting and hypoactivity during the 5 years preceding examination at the ED. Mental status examination showed that the patient had general psychomotor slowing, apathy, minimal changes of facial expression, anxiety, a perplexed look, flat affect, poor spontaneous movements, waxy flexibility and facial and manual stereotypies. A catatonia challenge with 10 mg of zolpidem [1] was made at the ED, and after 30 min, the patient recovered from all her symptoms. The presence of 5 catatonic symptoms (immobility/stupor, mutism, staring, waxy flexibility, stereotypies) leads to the diagnosis of catatonia with a great diagnostic power [2]. Neurological examination did not reveal any abnormalities, apart from overresponsive reflexes that were already known. Computed tomography scan of the head without contrast was reported as normal as well as biological testing (complete blood count, prothrombin time, activated partial thromboplastin time, toxic chemical analysis, blood electrolytes, liver chemistry, blood ammonia and blood glucose). However, vitamin B12 was tested and revealed a mild vitamin B12 deficiency at 176 pg/ml (normal values: 200–950 pg/ml). The patient returned home asymptomatic with a prescription of lorazepam 4 mg/day and a psychiatric follow-up. Fig. 1 shows the relationship between the patient's catatonic symptoms and B12 levels over time. The patient progressively relapsed (showing once again immobility, apathy, staring and a waxy flexibility) between day 36 and day 51 after tapering off lorazepam while her B12 levels were still below 200 pg/ml. Therefore, lorazepam was introduced again at day 51 and the deadlines between the cyanocobalamin

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Fig. 1. Catatonic symptoms and B12 levels over time.

injections were shortened at day 80 (once every 3 weeks instead of once a month). After tapering lorazepam at day 60 and this dosage adjustment and while vitamin B12 levels were kept normal, the patient did not present any catatonic relapse during 1 year of follow-up. After these catatonic episodes, during asymptomatic periods with vitamin B12 levels above 200 pg/ml, no psychiatric disorder was revealed at the Mini International Neuropsychiatric Interview. The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis II Personality Disorders did not reveal any personality disorder. The hypomania checklist as well as the Hamilton Depression Rating Scale revealed no signs of mood disorder. Furthermore, the Beck Anxiety Inventory and the Hamilton Anxiety Scale were negative, ruling out any anxiety disorder. 2. Discussion Catatonia has been observed in a wide variety of general medical, neurological and psychiatric disorders, as well as associated with drugs and toxic substances, making it sometimes difficult to make the etiological diagnosis [3]. In this case, there is no supporting evidence for a neurological, toxic or psychiatric origin of this catatonic syndrome. Despite a wide hematological and biochemical screening, the only abnormality found was the low vitamin B12 level, suggesting that the patient's Biermer disease was the most likely etiology of this catatonic episode. Although the B12 levels were not very low — and although the normal range remains quite unclear, as most authors agree on 200 pg/ml as the lower limit — the B12 deficiency was confirmed [4]. Indeed, psychiatric symptoms can precede the onset of anemia or neurological features and can sometimes be seen in the absence of macrocytosis and while levels of B12 are not dramatically low [5,6]. To date, three cases of vitamin B12 deficiency presenting as catatonia have been reported, one during pernicious anemia (with a vitamin B12 level of 159 pg/ml) and two others due to dietary intake deficiencies (1.07 and 150 pg/ml) [6–8]. This woman's case of pernicious anemia presenting as catatonia without signs of anemia or macrocytosis adds to the existing data a clinical-biological parallelism between catatonic symptoms and B12 levels over time. It also tends to strengthen the fact that catatonia can occur even with moderately decreased vitamin B12 levels (between 150 and 200 pg/ml). Furthermore, she was

successfully treated by lorazepam only and did not receive any antipsychotics, unlike the previous case reports. At day 73 and day 80, though, the levels of B12 were below 200 pg/ ml without any catatonic relapse. A strictly linear relationship between B12 levels and the patient's symptoms was unlikely, as catatonia has various etiologies and can break out under the influence of multifactorial stressors [3]. However, the absence of relapse after shortening the deadlines between the cyanocobalamin injections — therefore increasing the B12 levels over 200 pg/ml — supports the accountability of the B12 deficiency in the patient's catatonic symptoms. B12 deficiency can be responsible for irreversible symptoms in cases of delayed diagnosis [9]. The frequent absence of hematological signs in the early onset of the B12 deficiency may contribute to this delay [5]. In at-risk population such as elderly patients in institutions, patients suffering from neuropsychiatric symptoms, autoimmune diseases, intestinal malabsorption, decreased intakes, malnutrition or hereditary cobalamin metabolism diseases, the early detection of B12 deficiency (by annual cobalamin levels screening) and treatment (po or im administration) are important to prevent structural and irreversible damages [10]. Therefore, in cases of catatonia of unknown etiology, B12 level screening could be useful for etiological diagnosis and early treatment especially in at-risk population of B12 deficiency. Acknowledgments We thank the patient for giving permission to publish this case report. References [1] Thomas P, Rascle C, Mastain B, Maron M, Vaiva G. Test for catatonia with zolpidem. Lancet 1997;349(9053):702. [2] Peralta V, Cuesta MJ. Motor features in psychotic disorders. II: development of diagnostic criteria for catatonia. Schizophr Res 2001;47(2–3):117–26. [3] Jaimes-Albornoz W, Serra-Mestres J. Catatonia in the emergency department. Emerg Med J 2012;29(11):863–7. [4] Snow CF. Laboratory diagnosis of vitamin B12 and folate deficiency: a guide for the primary care physician. Arch Intern Med 1999;159:1289–98. [5] Lindenbaum J, Healton EB, Savage DG, Brust JCM, Garrett TJ, Podell ER, et al. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med 1988;318(26):1720–8. [6] Berry N, Sagar R, Tripathi BM. Catatonia and other psychiatric symptoms with vitamin B12 deficiency. Acta Psychiatr Scand 2003;108(2):156–9.

D. Bram et al. / General Hospital Psychiatry 37 (2015) 273.e5–273.e7 [7] Catalano G, Catalano MC, Rosenberg EI, Embi PJ, Embi CS. Catatonia: another neuropsychiatric presentation of vitamin B12 deficiency? Psychosomatics 1998;39(5):456–60. [8] Jauhar S, Blackett A, Srireddy P, McKenna PJ. Pernicious anaemia presenting as catatonia without signs of anaemia or macrocytosis. BJP 2010;197(3):244–5.

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[9] Andrès E, Loukili NH, Noel E, Kaltenbach G, Abdelgheni MB, Perrin AE, et al. Vitamin B12 (cobalamin) deficiency in elderly patients. CMAJ 2004;171(3):251–9. [10] Lachner C, Steinle NI, Regenold WT. The neuropsychiatry of vitamin B12 deficiency in elderly patients. J Neuropsychiatry Clin Neurosci 2012;24(1):5–15.

Pernicious anemia presenting as catatonia: correlating vitamin B12 levels and catatonic symptoms.

Pernicious anemia has been associated with various psychiatric manifestations, such as depression, mania and psychosis. Psychiatric symptoms can somet...
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