Neurosciences

E. Andrès1, G. Kaltenbach2

1. Departments of Internal Medicine, Diabetes and Metabolic Disorders, 2. Internal Medicine and Geriatrics, Hôpitaux Universitaires de Strasbourg, France. Correspondence: Prof. E. ANDRES, Service de Médicine Interne, Clinique Médicale B, Hôpitaux Universitaires de Strasbourg, 1 place de l'Hôpital à 67 091 STRASBOURG, cedex, FRANCE

Dear Sir,

We read with interest the paper of A. Abyad on the prevalence of vitamin B12 deficiency among demented patients and cognitive recovery with cobalamin replacement (1). It is an exciting paper on a very interesting topic. As main results, the authors reported that 40 of their 56 patients (71.5%) had a frank cognitive improvement on Folstein Minimental Status Examination with cyanocobalamin intramuscularly.
To our knowledge, it is first well-designed and documented study with such topic. However, we have several comments or questions.
First to our opinion and in accordance with the current literature, the definition of cobalamin deficiency requires at least a confirmation of the low serum vitamin B12 levels (on 2 samples) or an elevation of the serum methyl malonic acid and homocysteine levels (functional cobalamin deficiency) (2, 3). Thus, we think that the patients of the present study had low serum vitamin B12 and not "true" vitamin B12 deficiency.
Second, the authors don't explain or hypothesize the mechanism of the cobalamin deficiency in their patients: nutritional deficiency, pernicious anemia or food-cobalamin malabsorption (see definition in table 1)? To our experience (cohort study of cobalamin deficiency in the Hôpitaux Universitaires de Strasbourg), this later mechanism was prominent in elderly patients (4, 5). In fact, elderly patients had several underlying conditions or diseases or often take drugs that may favor food-cobalamin malabsorption (see table 1).

Table 1
Food-cobalamin malabsorption (adapted from (6)).

*: To fulfill the criteria of food-cobalamin malbsorption patients had to meet at least the first 4 criteria. ;**: Derived Schilling tests used food-bound cobalamin (e.g.: egg yolk].

Thirst, we have previously demonstrated that oral cyanocobalamin therapy (with doses between 500 and 1000 µg per day) may be an adequate therapy to cure cobalamin deficiency [6-8]. To our opinion, the benefit of an oral administration of cyanocobalamin is multiple, especially in elderly patients: avoiding painful intra-muscular injections by patients, avoiding side effects of intra-muscular injection in case of anticoagulation and decreasing the cost of therapy (no monthly by a nurse) [8].

References

1. Abyad A. Prevalence of vitamin B12 deficiency among demented patients and cognitive recovery with cobalamin replacement. The Journal of Nutrition Health & Aginig 2002; 6: 254-260.
2. Andrès E, Noel E, Kaltenbach G, Noblet-Dick M et le Groupe d'étude des carences en vitamine B12 des Hôpitaux Universitaires de Strasbourg. Carences en vitamine B12 chez l'adulte: données actuelles. Ann Biol Clin 2002; 60: 744-745.
3. Snow C. Laboratory Diagnosis of vitamin B12 and folate deficiency. A guide for the primary cares physician. Arch Intern Med 1999; 159: 1289-1298.
4. Andrès E, Perrin AE, Kraemer JP, Goichot B, Demangeat C, Ruellan A et al. Anémies par carence en vitamine B12 chez le sujet âgé de plus de 75 ans: nouveaux concepts. A propos de 20 observations. Rev Med Interne 2000: 21: 946-955.
5. Andrès E, Kaltenbach G, Perrin AE, Kurtz JE, Schlienger JL. Food-cobalamin malabsorption in the elderly. Am J Med 2002; 113: 351-352.
6. Andrès E, Kurtz JE, Perrin AE, Maloisel F, Demangeat C, Goichot B et al. Oral cobalamin therapy for the treatment of patients with food-cobalamin malabsorption. Am J Med 2001; 111: 126-129.
7. Andrès E, Kaltenbach G, Noel E, Noblet-Dick M, Perrin AE. Short-term oral cobalamin therapy for food-related cobalamin malabsorption. Ann Pharmacother 2003; 37: 301-302.
8. Kaltenbach G, Noblet-Dick M, Barnier-Figue G, Berthel M, Kuntzmann F, Andrès E. Early normalization of low vitamin B12 levels by oral cobalamin therapy in three older patients with pernicious anemia. J Am Geriatr Soc 2002; 50: 1914-1915.

A.Abyad

Director, Abyad Medical Center & Middle-East Longevity Institute , Coordinator, Ain WaZein Elderly Care Center, Abyad Medical Center, Tripoli-Lebanon, PObox 618, Tel &
Fax : 961-6-443684/5/6, Mobile : 961-3-201901, E-mail : aabyad@cyberia.net.lb

Thank you for your comments , I agree with you that serum methyl malonic acid and homocysteine levels is the ideal standard. However we relied on the literature where Allen and colleagues propose that the appropriate lower limit of normal serum Cbl level is approximately 300 pg/ml (26-28). The current RIA (Radioimmunoassays) for determining Cbl is sensitive, fairly inexpensive, and extensively accessible (9). We did not have the money or the facility to be able to do the serum methyl malonic acid.
The objective of the study is to find out the prevalence of vitamin B12 deficiency among demented patients and to look at the effects of cobalamin repletion on cognition in elderly, subjects with low serum cobalamin and evidence of cognitive dysfunction. Therefore we did not look at the mechanism of B12 deficiency, however I believe that the mechanism is multiple as you mentioned.
As for the management we elected the I M route since I thing strongly that this route is faster and more effective. I am starting to use the oral route , however a good number of my patient prefer the IM route, it may to do with the cultural differences

References

1. Stabler SP, Allen RH, Savage DG, Lindenbaum J. Clinical spectrum and diagnosis of cobalamin deficiency. Blood 1990;76:871-881
2. Lindenbaum J. Savage DG, Stabler SP, Allen RH. Diagnosis of cobalamin deficiency. II. Relative sensitivities of serum cobalamin, MMA and total homocysteine concentrations. Am J Hematol 1990;34:99-107
3. Allen RH, Stabler SP, Savage DG, Lindenbaum J. Diagnosis of cobalamin deficiency. I: usefiilness of serum methylmalonic acid and total homocysteine concentrations. Am J Hematol 1990; 34(2): 90-8
4. Allen RH. Megaloblastic anemia. In Wyngaarden JB, Smith LH Jr, Bernnett JC, eds. Cecil textbook of medicine. 19th ed. Philadelphia: WB Saunders, 1992:846-54