Abstract
Orthostatic hypotension in patients with cobalamin (Cbl) deficiency has been reported
previously in isolated cases but we are not aware of detailed systematic studies of
hemodynamic and autonomic nervous system function in patients with cobalamin deficiency.
We investigated hemodynamic and autonomic responses to 60° passive head up tilt (HUT)
in 21 patients with vitamin B12 deficiency, 21 healthy age-matched control subjects and 9 age-matched patients with
diabetes mellitus (DM) and established diabetic neuropathy. To systematically assess
hemodynamic and autonomic nervous system function, we performed measurements of heart
rate, beat-to-beat systolic and diastolic blood pressure, stroke index, cardiac index,
total peripheral resistance index, total power, low (LF) and high (HF) frequency oscillatory
component of heart rate variability, LF/HF ratio and spontaneous baroreflex sensitivity.
As compared to controls, we found a significant fall of systolic blood pressure during
60 consecutive beats directly after head up tilt; furthermore, a significantly blunted
fall of stroke index, cardiac index and a lack of increase of total peripheral resistance
index for the duration of tilt in patients with diabetes mellitus and in patients
with vitamin B12 deficiency. As compared to controls, we observed an altered response of spectral
indices of sympathetic activation and vagal withdrawal and an impaired modulation
of baroreflex sensitivity during head up tilt suggestive of a complex modification
in the neural control activities in patients with cobalamin deficiency, which was
comparable to that observed in patients with diabetes mellitus and established autonomic
neuropathy. The results suggest that vitamin B12 deficiency causes autonomic dysfunction with similar hemodynamic consequences and
patterns of autonomic failure as seen in diabetic autonomic neuropathy. Defective
sympathetic activation may be the cause for orthostatic hypotension, which is occasionally
seen in patients with vitamin B12 deficiency. It is concluded that patients with orthostatic hypotension should be
screened for cobalamin deficiency.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Autonomic Neuroscience: Basic and ClinicalAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Power spectrum analyses of heart rate fluctuation: a quantitative probe of beat to beat cardiovascular control.Science. 1981; 213: 220-222
- Beat to beat variability in cardiovascular variables: noise or music?.J. Am. Coll. Cardiol. 1989; 14: 1139-1148
- Assessment of autonomic nervous system functions in patients with vitamin B12 deficiency by power spectral analyses of heart rate variability.Pacing Clin. Electrophysiol. 2000; 23: 975-978
- Power spectral analyses of heart rate variation improves assessment of diabetic cardiac autonomic neuropathy.Diabetes. 1992; 41: 633-640
- Tilt table testing for assessing syncope.J. Am. Coll. Cardiol. 1996; 28: 263-275
- Neuropathic bladder in setting of severe vitamin B12 deficiency: a case report.J. Urol. 1995; 154: 199-200
- Pernicous anemia: the expected findings of very low serum cobalamin levels, anemia, and macrocytosis are often lacking.Arch. Intern. Med. 1988; 148: 1712-1714
- Diabetic autonomic neuropathy.Diabetologia. 1979; 17: 195-212
- Comparing spectra of a series of point events, particularly for heart rate variability data.IEEE Trans. Biomed. Eng. 1984; 31: 384-387
- Orthostatic hypotension in pernicious anemia.Acta Haematol. 1988; 80: 230
- Deficient catecholamine release as the basis of orthostatic hypotension in pernicious anemia.J. Neurol., Neurosurg. Psychiatry. 1982; 45: 1053-1055
- Cardiovascular reflexes and autonomic neuropathy.Clin. Sci. Mol. Med. 1978; 55: 321-327
- Assessment of cardiovascular effects in diabetic autonomic neuropathy and prognostic implications.Ann. Intern. Med. 1980; 92: 308-311
- Real-time monitor for hemodynamic beat-to-beat parameters and power spectra analyses of the biosignals.in: Proceedings of the 20th Annual International Conference of the IEEE Engineering in Medicine and Biology Society. vol. 20. 1998: 360-363
- Time and frequency domain estimates of spontaneous baroreflex sensitivity provide early detection of autonomic dysfunction in diabetes mellitus.Diabetologia. 1997; 40: 1470-1475
- Cardiac autonomic patterns preceding occasional vasovagal reactions in healthy humans.Circulation. 1998; 98: 1756-1761
- A software package for non-invasive, real-time beat-to-beat monitoring of total peripheral resistance and for assessment of autonomic function.Comp. Biol. Med. 1998; 28: 121-142
- Beta-2 adrenergic receptor variants affect resting blood pressure and agonist-induced vasodilation in young adult Caucasians.Hypertension. 1999; 33: 1425-1430
- Neurologic aspects of cobalamin deficiency.Medicine (Baltimore). 1991; 70: 229-245
- Reversible orthostatic hypotension of pernicious anemia.JAMA. 1987; 257: 1084-1086
- Orthostatic hypotension associated with pernicious anemia: report of a case with complete recovery following vitamin B12 therapy.JAMA. 1962; 182: 196-198
- Neurologic and evoked potential abnormalities in subtle cobalamin deficiency states, including deficiency without anemia and with normal absorption of free cobalamin.Arch. Neurol. 1990; 47: 1008-1012
- Comparison of electrophysiologic and autonomic tests in sensory diabetic neuropathy.Clin. Auton. Res. 1998; 8: 213-220
- Development and evaluation of an impedance cardiac output system.Aerosp. Med. 1966; 37: 1208-1212
- Complete cure of urinary and faecal incontinence after intravenous vitamin B12 therapy in a patient with post-gastrectomy megaloblastic anemia.J. Intern. Med. 1992; 231: 313-315
- Spectral analyses of heart rate: interpretational limitations.Arch. Neurol. 1998; 55: 264
- Neuropsychiatric disorders caused by cobalamin deficiency in the absents of anemia or macrocytosis.N. Engl. J. Med. 1988; 318: 1720-1728
- Sural nerve morphometry in diabetic autonomic and painful sensory neuropathy: a clinicopathological study.Brain. 1991; 114: 867-892
- Orthostatic hypotension induced by vitamin B12 deficiency.J. Am. Geriatr. Soc. 1991; 39: 601-602
- The sympathetic nervous system in diabetic neuropathy: a clinical and pathological study.Brain. 1975; 98: 341-356
- Cardiovascular neural regulation explored in the frequency domain.Circulation. 1991; 84: 482-492
- The peripheral neuropathy of vitamin B12 deficiency.J. Neurol. Sci. 1984; 66: 117-126
- Power spectrum analyses of heart rate variability to assess the changes in sympathovagal balance during graded orthostatic tilt.Circulation. 1994; 90: 1826-1831
- A positive feedback sympathetic pressor reflex during stretch of the thoracic aorta in conscious dogs.Circ. Res. 1982; 50: 125-132
- Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympathovagal interaction in man and conscious dog.Circ. Res. 1986; 59: 178-193
- Spectral analyses of heart rate variability in assessment of diabetic autonomic neuropathy.J. Auton. Nerv. Syst. 1988; 23: 143-153
- Changes in autonomic regulation induced by physical training in mild hypertension.Hypertension. 1988; 12: 600-610
- Cardiorespiratory arrest and diabetic autonomic neuropathy.Lancet. 1978; 1: 14-16
- Daily-life baroreflex modulation: new perspectives from computer analyses of cardiovascular signals.in: Di Rienzo M Mancia G Parati G Pedotti A Zanchetti A Computer Analyses of Cardiovascular Signals. IOS Press, Amsterdam1995: 209-218
- Photoelectric measurement of blood pressure, volume and flow in the finger.(Digest of the)in: 10th International Conference on Medical and Biological Engineering, Dresden1973
- Assessment of autonomic function in humans by heart rate spectral analyses.Am. J. Physiol. 1985; 248: H151-H153
- Pathophysiological basis of orthostatic hypotension in autonomic failure.J. Physiol. (London). 1999; 519: 1-10
- Autonomic dysfunction in vitamin B12 deficiency: a heart rate variability study.J. Auton. Nerv. Syst. 1998; 71: 25-27
- Autonomic nervous function in asymptomatic diabetic patients with signs of peripheral neuropathy.Diabetes Care. 1981; 4: 529-534
- A quantitative method of assessing baroreflex sensitivity.Circ. Res. 1969; 24: 109-121
- Heart rate variability. Standards of measurement, physiological interpretation, and clinical use.Circulation. 1996; 93 (Special report): 1043-1065
- Autonomic dysfunction and orthostatic hypotension caused by vitamin B12 deficiency.J. Neurol., Neurosurg. Psychiatry. 1999; 66: 804-805
- Reproducibility of hemodynamic measurements by impedance cardiography.Cardiovasc. Res. 1983; 17: 728-734
- Pernicious anemia seen initially as orthostatic hypotension.Arch. Intern. Med. 1981; 141: 1543-1544
Article info
Publication history
Accepted:
December 4,
2001
Received in revised form:
July 12,
2001
Received:
February 12,
2001
Identification
Copyright
© 2002 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.
