Original Articles

By Dr. Derrick Lonsdale , Dr. Raymond J Shamberger , Dr. Mark E Obrenovich
Corresponding Author Dr. Derrick Lonsdale
Preventive Medicine Group Private Practice, 24700 Center Ridge Road - United States of America OH 44145
Submitting Author Dr. Derrick Lonsdale
Other Authors Dr. Raymond J Shamberger
King James Medical Laboratory, - United States of America

Dr. Mark E Obrenovich
Dept of Pathology,School of Medicine, Case Western Reserve University, Cleveland, Ohio, - United States of America


Dysautonomia, Asymmetric Blood Pressures, Erythrocyte Transketolase

Lonsdale D, Shamberger RJ, Obrenovich ME. Exaggerated Autonomic Asymmetry: A Clue to Nutrient Deficiency Dysautonomia. WebmedCentral ALTERNATIVE MEDICINE 2011;2(4):WMC001854
doi: 10.9754/journal.wmc.2011.001854
Submitted on: 13 Apr 2011 01:36:31 PM GMT
Published on: 15 Apr 2011 08:30:42 AM GMT


Seventeen adult Caucasian subjects were diagnosed clinically with dysautonomia, based on symptoms. Sixteen had asymmetrically different blood pressures measured simultaneously in both arms. Fourteen admitted to craving for sweets, salt or reactions to ingestion of sugar. Of these, 9 had abnormal erythrocyte transketolase changes indicating loss of thiamine homeostasis. Beriberi is the prototype for functional dysautonomia in its early stages.  It is hypothesized that excessive ingestion of simple carbohydrates results in defective oxidative metabolism in autonomic nervous system control mechanisms, resulting in exaggeration of normal asymmetric reflex action, an effect similar to that induced by mild chronic hypoxia. Abnormal thiamine homeostasis and dysautonomia have been reported in a number of degenerative brain diseases.

Running title:

Nutrient deficiency dysautonomia with asymmetric brachial pulse pressures


Dysautonomia is a broad term that describes any disease or malfunction of the autonomic nervous system. This includes postural orthostatic tachycardia syndrome (POTS), inappropriate sinus tachycardia (IST), vasovagal syncope, mitral valve prolapse dysautonomia, pure autonomic failure, neurocardiogenic syncope (NCS), neurally mediated hypotension (NMH), autonomic instability and a number of lesser-known disorders such as cerebral salt-wasting syndrome. Dysautonomia is associated with Lyme disease, primary biliary cirrhosis, multiple system atrophy (Shy-Drager syndrome) Ehlers-Danlos syndrome, and Marfan syndrome for reasons that are not fully understood (Köllensperger, M., et al. 2007). Quinn (Quinn, N., 1989) emphasized the diagnostic confusion surrounding a constellation of brain diseases where there is autonomic dysfunction in common and questioned how autonomic failure is defined, particularly in its milder form.
Blood pressure is usually performed on one arm only. Sixteen of seventeen patients with dysautonomia were found to have widely different blood pressures in the two arms when measured simultaneously by two operators. One patient was lost to follow up. Asymmetric action of the autonomic nervous system (ANS) is normal (Shannahof-Kalsa, D. S., 2007). Exaggeration of ANS reflexes may result from marginal oxidative dysfunction induced by thiamine deficiency (TD), other non caloric nutrients (Lonsdale, D.. 2009) or hypoxia, an example being partial hanging (paraphilia). (Ueno, Y., et al. 2003). Acute and chronic hypoxia induces sympathoadrenal responses (Johnson, T. S., et al. 1983) similar to those induced by TD (Voltmeyer, H. O., et al. 1993). Wernicke-Korsakoff syndrome, often associated with dysautonomia, is the most frequent manifestation of TD and other non caloric nutrient deficiencies in Western society (Kril, J. J., 1996) Dysautonomia is associated with a number of degenerative brain diseases (Quinn, N.,1989) and abnormal thiamine homeostasis (Gibson, G. E., Blass J P. 2007). Mitochondrial disruption from TD (Bettendorff L, et al. 1995) would curtail synthesis of thiamine triphosphate (TTP), an unknown factor in TD (Gandolf, M., et al. 2009).
Beriberi is the classic prototype for dysautonomia (Lonsdale, D., 2006). Death from Wernicke disease occurred in a woman receiving parenteral nutrition in spite of 24 mg of thiamine a day (Lonsdale, D., 1978). Increasing carbohydrate relative to total calories caused a decrease of plasma and urine concentrations of thiamine (Elmadfa, I., et al. 2001). Beriberi heart disease was reported in 23 Japanese patients, including 17 teenagers consuming soft drinks and carbohydrate foods (Kawai C, et al. 1980). TD is common in elderly patients (O’Keefe, H. O., et al. 1994)

Patients and Methods

The patient population consisted of 9 females and 8 males. Their ages ranged from 14 to 76 years, with an averaged of 44.2. Thirteen controls were healthy individuals consisting of 12 females and one male with an age range of 24 to 66 years and an average of 51.8 The symptoms of the 17 patients, all of which have been reported in dysautonomia (Lonsdale, D., 1987., 2009), are shown in Illustration 1. Illustration 1 - attached
Erythrocyte transketolase activity and thiamine pyrophosphate effect were performed in all 17 patients (Massod, M. F., et al 1971). The study first measures the baseline activity of the enzyme (TKA) and the percentage acceleration over baseline after in vitro addition of thiamine pyrophosphate (TPPE)
Many of these patients had a lifelong history of polysymptomatic illness, one having begun at the age of 7 years after falling from a second floor window. Thirteen had either undiagnosed daily headaches or migraine. Thirteen experienced constant and/or recurrent alternating unilateral recumbent nasal congestion, indicating exaggeration of the normal ANS controlled nasal cycle (Shannahof-Kalsa, D. S., 2008). Two had received a proven diagnosis of sleep apnea, two with Lyme disease, one of whom had proven deficient esophageal peristalsis, two with mononucleosis and 3 women had a history of recurrent vaginal yeast infections. Four patients, one of whom had been found elsewhere to be homozygous for the MTHFR C677T mutation, had elevated blood homocysteine, (data not shown) one of whom had melanin pigmentation on both arms suggesting vitamin B 12 deficiency (Mori, K., et al. 2001. (Hoffman, C. F., et al. 2003). This individual, in whom the TPPE was repeatedly in the thiamine deficiency range, was addicted to sugar in any form, experiencing a severe reaction after consumption of blackstrap molasses taken as a “health food”. Sweet and/or salt craving was admitted in 14 of these patients and appeared to be an important etiologic component. One patient with a lifelong history of daily headaches, had a previous diagnosis of membranous glomerulo nephritis, myelodysplasia and esophageal ulceration. Echocardiography revealed mild tricuspid insufficiency. One male patient had a 20-year history of alternating urgency diarrhea and constipation, panic attacks and bipolar symptomology. One woman had experienced 12 PAP smears, each of which had been positive for HPV infection. One woman had a hysterectomy at age 38 years for endometriosis. Echocardiograms had shown mitral valve prolapse in one patient and mitral regurgitation without prolapse in another. A 38-year old man had mild aortic and tricuspid regurgitation and a 14-year old boy had an “insignificant patent foramen ovale”. A 38-year old man had migraine headaches and had passed 6 renal calculi. A man of 38 years of age presented with an 18 month history of chest pain, extreme fatigue and tinnitus Studies elsewhere had shown that he had Complex IV deficiency marked by repeatedly low blood levels of thiamine, even after the administration of 600 mg of a water soluble thiamine salt daily for an extended period.
Subject # 4 had been reported elsewhere to have elevations of anti-DNA and ASO titres. Subject # 9 had been found elsewhere to be infected with Blastocystis Hominis and Subjects # 1, 2 and 10 all had suffered recurrent yeast infections of the vagina. There are many instances of an association between organic disease and dysautonomia (Lonsdale, D., 2009). The blood pressures of 17 patients and 13 healthy individuals acting as controls are shown in Illustrations 2 and 3.
Illustrations 2 and 3 - attached


Blood pressure asymmetry calculations were performed, using Chi square analysis. Each increase or decrease was assigned a value of 1. If the increase or decrease was the same value in both groups a value of 0.5 was assigned to each group. This calculation was done as a ratio and proportion statistic. Positives or negatives were squared and all became positive. The systolic, diastolic and pulse pressure increases or decreases were observed in the patient and control groups. indicating that the asymmetry was greater in the patients (Group 1) than in the controls (Group 2) (Illustration 4).
Illustration 4 - attached
One patient had a TKA that was below the laboratory norm. Ten, in some of whom there were multiple tests performed, had a TPPE of 18% or above, indicating thiamine deficiency or abnormal homeostasis Of the sixteen patients who had simultaneous blood pressures measured, there were 13 measurements of TKA in which the TPPE indicated abnormal thiamine homeostasis. The pulse pressures in these patients were compared with the 7 patients in whom the TPPE indicated thiamine sufficiency. The pulse pressures in those with abnormal TPPE were higher than those with acceptable TPPE (Illustration 5).
Illustration 5 -attached


Asymmetry of the autonomic nervous system (ANS)
Asymmetry of the ANS is well known and three yogi techniques for selectively activating one half of the ANS are known (Shannahof-Kalsa, D. S., 2007). Simultaneously measured blood pressure asymmetry has not been reported to our knowledge. Other manifestations of asymmetry in these patients appear to be exaggeration of otherwise normal reflex activity. Autonomic asymmetry has been demonstrated in migraineurs (Aynon, Y., et al. 2004). The frontal and temporal lobes have a division of responsibility in regulation of heart rate and blood pressure (Foster, P. S., et al. 2006). Midbrain activity, resulting in right-left asymmetry in sympathetic drive, predisposes to cardiac arrhythmia (Critchley, H. D., et al. 2005). Asymmetric innervation of the ureter and fallopian tubes has been demonstrated (Lychkova, A. E., 2005). Autonomic nose innervation is asymmetrical and oscillates in a regular nasal cycle. The authors concluded that hypothalamic instability results in marked autonomic asymmetry (Eccles, R., Eccles, K. S., 1981). Dysfunctional esophageal peristalsis in one of the patients indicated failure of parasympathetic drive, since the esophagus lacks sympathetic innervation. Reduced parasympathetic activity in autism has been published (Ming, X., et al 2005).
Whether the asymmetric blood pressures in these patients are exaggeration of normal ANS asymmetry, anatomical difference in the origin of the right brachial artery from that of the left, heart valve deficiencies as revealed in some of our patients, or a combination of these variables is unknown. Pulse pressures are known to be wide in thiamine deficient beriberi (Inouye, K., Katsura, E., 1965) Dysautonomia
Familial Dysautonomia (Riley-Day syndrome) has many symptoms (Lonsdale, D., 1987, 1990). A case report of a woman with asymmetric functional dysautonomia revealed that the pulse pressures reduced with dietary correction and nutrient supplements that included thiamine and magnesium (Lonsdale, D., 1990). Combination of hypertension and orthostatic hypotension (OT) in older individuals (Lee, T., et al. 2005) was found in 13.4% of hypertensive and 5.5% normotensive subjects (Fedorowski, A., et al. 2009). If asymmetric blood pressures are relatively common, it may depend on which arm is used for diagnostic purposes.
Neural reflexes regulate immunity, involving the nicotinic acetylcholine receptor that inhibits innate immune responses (Rosas-Ballina, M., Tracey, K. J., 2009). Failure might create a greater susceptibility to opportunist infection as in several of our patients. It has been hypothesized that dysfunctional oxidative metabolism provides the underlying etiology for dysautonomia and its association with a number of diseases. (Lonsdale, D., 2009).
Bruxism, common in sleep, was reported in the awake state in multiple system atrophy (MSA) (Wali, G. M., 2004). McKeon and associates found that one per cent of 15,000 patients evaluated for paraneoplastic neurological autoimmunity were seropositive for the nicotinic ganglionic acetylcholine receptor autoantibody (alpha3-AChR), many of whom had dysautonomia (McKeon, A., et al. 2009). One of our patients had a diagnosis of Sjogren syndrome, reported in dysautonomia due to acetylcholine receptor antibodies (Bourcier, M. E., Vanik, A. L., 2008). She had also been diagnosed with Lyme disease, itself associated with Holmes-Adie syndrome (Stricker, R. B., Winger, E. E., 2001).. Two of our patients had a history of undiagnosed daily headaches, sometimes associated with autonomic dysfunction ( Montagna, P., 2006).
Oxidative Dysfunction
Evidently asymmetry can become symptomatic, as in alternating recumbent nasal congestion and exaggerated asymmetric blood pressures. Chronic hypoxia in the rat stimulated sympathoadrenal system functions, dependent on the degree and duration of hypoxic exposure (Johnson, T. S., et al. 1983).
Thiamine Homeostasis
Altered thiamine homeostasis in many neurodegenerative diseases (Gibson, G. E., Blass, J. P., 2007) and defective acetyl choline metabolism (Barclay, L. L., et al. 1981), represents a model system for exploring the pathological mechanisms (Hazell, A. S., Butterworth, R. F., 2009).
Ten of our patients had a TPPE over 18%, indicating abnormal thiamine homeostasis. Some had repeated TPPE (Illustration 5) in or out of range. In only two patients was a zero TPPE recorded, indicating full TPP enzyme saturation. A marginal TPPE, (1-18%) may represent a graded transition from cofactor sufficiency to deficiency symptoms.
TD in mice reduced transketolase activity in cortex and hippocampus, without significantly affecting thiamine dependent enzymes. Pentose-phosphate dysfunction, a pathway dependent on transketolase, contributed to impaired hippocampal neurogenesis (Zhao, Y., et al. 2009), Magnetic resonance mapping in TD rats demonstrated no lesions in the frontal cortex in the early stages of deficiency (Dror, V., et al. 2009). Striking preservation of intellect, with severe motor disability was noted in MSA (Quinn, N., 1989), suggesting that any form of relatively mild oxidative dysfunction particularly affects the lower brain. Peters, who did the early classic experiments with thiamine after its synthesis, noted that no certain difference between the respiration of normal and thiamine deficient pigeon’s brain had been observed. “With glucose present, there was no doubt that the respiration was lowered and, as in the case of the lactate accumulation, especially in the lower parts of the brain” (Peters, R. A., 1936). Panic attacks in 15 patients suggested fragmented fight-or-flight reflexes as occurred after CO2 inhalation (Blechert, J., et al. 2010). One of our patients, a woman of 38 years, began her symptoms at the age of 7 years after a fall from a second floor window. Physical stress can initiate intermittent symptoms in a marginal metabolic state (Lonsdale, D., 2009).
Twenty adolescent patients with abnormal erythrocyte transketolase were treated successfully by nutritional correction (Lonsdale, D., Shamberger, R. J.,1980), suggesting that our 17 patients may represent these adolescents in their later years. Although treated by appropriate nutritional counseling and supplements that included thiamine tetrahydrofurfuryl disulfide, results have been variable as in thiamin treatment of other neurological diseases (Gibson, G. E., Blass, J. P., 2007).
Brain thiamine deficiency
Brain TD mechanisms have remained elusive. TTP is known to have some connection with the function of chloride channels (Bettendorff, L., et al. 1994) and has long been known to be important in brain metabolism (Pincus, J. H., et al. 1973.Cooper, J. R., Pincus, J. H., 1979). It is synthesized in rat brain mitochondria from TPP, using energy for the reaction coupled to the respiratory chain (Gangolf, M., et al. 2009) but its role is unclear. Deficiency might occur from mitochondrial disruption. It is twice more abundant in brainstem than in cortex or cerebellum (Gangolf, M., et al. 2010) and is in high concentration in the electric organ of the Electrophorus electricus and Torpedo marmorata (Bettendorff, L., et al. 1987). The electric organ is an adaptation of a neuromuscular junction. The potential actions of TTP may be similar to ATP, recently found to be an extracellular messenger (Khakh, S., Burnstock, G., 2009).
Thiamine may be involved in acetylcholine release (Eder, L., et al. 1976) and its synthesis is dependent on adequate action of the citric acid cycle and acetyl CoA. Mitochondria are uncoupled and their cristae disorganized with experimental TD. Respiratory control and morphology are restored with thiamine (Bettendorff, L., et al. 1995).

Conclusion and Hypothesis

The symptoms in our patients are often considered to be psychiatric or psychosomatic. A biochemical classification for disease has been proposed (Quinn, N., 1989). Dysautonomia may be the connecting link to organic disease through loss of efficiency in oxidative metabolism, the central control mechanisms being affected first (Lonsdale, D., 2009). We hypothesize that mild to moderate hypoxia and/or thiamine deficiency both give rise to exaggeration of centrally controlled mechanisms involved in all survival reflexes, mediated normally through a balanced reaction of the ANS and endocrine system. The sympathoadrenal system is evolutionally designed for short term action when energy is consumed at an accelerated rate, as in fight-or-flight. Automatically initiated, it is our response to stress, the nature of which has changed radically from the situations encountered by our ancestors. That, together with dietary excesses, particularly in the universal ingestion of sugar, appears to be responsible for initiating long term disease related to the synthesis and use of cellular energy. Failure of ANS cholinergic neurotransmission might follow from TD and/or other cofactors involved in glucose metabolism, exposing the organism to adrenal medullary release of epinephrine.  


1.Aynon, Y., Nitzen, M., Sprecher, E., Rogowski, C,. Yamitsky, D., 2004. Autonomic asymmetry in migraine: augmented parasympathetic activation in left unilateral migraineurs. Brain.127(Pt 9),2099-2108.
2.Barclay, L. L., Gibson, G. E., Blass, J. P., 1981. Impairment of behavior and acetylcholine metabolism in thiamine deficiency. J. Pharmacol. Exp. Ther.217, 537-543.
3.Barker, J. N., Jordan, F., 1982. Phrenic thiamin and neuropathy in sudden infant deaths. In: Sable, H. Z.,  Gubler   .           C.J. (Eds.),  Thiamine:Twenty Years of Progress. Ann. NY. Acad. Sci. 378,440-452.
4.Bettendorff, L., Michel-Cahay, C, Grandfils, C., De Rycher, C., Schoffeniels, E., 1987. Thiamine triphosphate and membrane-associated thiamine phosphatases in the electric organ of Electrophorus Electricus. J. Neurochem. 49, 495-502. 
5.Bettendorff, L., Hennuy, B., De Chrek, A., Wins P., 1994. Chloride permeability of rat brain vesicles correlates with thiamine triphosphate content. Brain. Res.652,157-160.
6.Bettendorff, L., Sluse, F., Goessens, G., Wins, P., Grisar, T. 1995. Thiamine deficiency-induced partial necrosis and mitochondrial uncoupling in neuroblastoma cells are rapidly reversed by addition of thiamine. J. Neurochem. 65(5), 2178-2184.
7.Blechert, J., Wilhelm, F. H., Meuret, A. E., Wilhelm, E. M., Roth, W. T. 2010. Respiratory, autonomic, and experiential responses to repeated inhalations of 20% CO(2) enriched air in panic disorder, social phobia, and healthy controls. Biol. Psychol.  Jan 11. [Epub ahead of print].
8.Bourcier, M. E., Vinik, A. L., 2008. A 41-year old man with polyarthritis and severe autonomic neuropathy. Ther. Clin. Risk. Manag. 4(4),837-842.
9.Cooper, J. R., Pincus, J. H., 1979. The role of thiamine in nervous tissue. Neurochem. Res. 4, 223-239.
10.Critchley, H. D., Taggart, P., Sutoon, P. M., Holdright, D. R., Batchvarov, V., Hnatkova K., Malik, M., Dolan, R. J., 2005. Mental stress and sudden cardiac death: asymmetric midbrain activity as a linking mechanism. Brain. 128(Pt1), 75-86.
11.Dror, V., Eliash, S., Rehavi, M., Assaf, Y., Biton, I. E., Fattai-Valevski, A., 2009. Neurodegeneration in thiamine deficient rats- A longitudinal  MRI study. Brain. Res. Oct 24 [Epub ahead of print].
12.Eccles, R., Eccles, K. S., 1981. Asymmetry in the autonomic nervous system with reference to the nasal cycle, migraine, anisocoria and Meniere’s syndrome. Rhinology. 19(3),121-125.
13.Eder, L., Hirt, L., Dunant Y., 1976 Possible involvement of thiamine in acetylcholine release. Nature. 264,186-188.
14.Elmadfa, I., Majehrzak, D., Rust, P., Genser, D., 2001. The thiamine status of adult humans depends on carbohydrate intake.  Int. J. Viam. Nutrr. Res. 71(4), 217-221.
15.Fedorowski, A., Burri, P., Melander, O., 2009. Orthostatic hypotension in genetically related hypertension and normotensive individuals. Hypertens. 27(5), 976-982.
16.Foster, P. S., Harrison, D. W., 2006 Magnitude of cerebral asymmetry at rest: covariation with baseline cardiovascular activity. Brain. Cogn. 61(3),286-297.
17.Gangolf, M., Wins, P., Thiry, M., El Moualij, B., Bettendorff, L., 2010 Thiamine triphosphate synthesis occurs in mitochondria and is coupled to the respiratory chain. J. Biol. Chem. Jan 1;285(1):583-94. Epub 2009 Nov 11.
18.Gangolf, M., Czerniecki, J., Radermecker, M., Detry, O., Nisolle, M., Jouan, C., et al. 2010 Thiamine status in humans and content of phosphorylated thiamine derivatives in biopsies and cultured cells. PLoS One. 5(10), e132616 doi:10.1371/journal.pone.00113616.
19.Gibson, G. E., Blass, J. P., 2007. Thiamine-dependent processes and treatment strategies in neurodegeneration. Antioxid. Redox. Signal. 9(10):\,1605-1619.
20.Hazell, A. S., Butterworth, R. F., 2009. Update of cell damage mechanisms in thiamine deficiency: a focus on oxidative stress, excitotoxicity and inflammation. Alcohol. Alcohol. 44(2),141-147.
21.Hoffman, C. F., Palmer, D. M., Papadopoulos, D., 2003. Vitamin B 12 deficiency: a case report of ongoing cutaneous hyperpigmentation. Cutis. 71(2),127-130; quiz 138-140. Erratum in Cutis. 71(4),322.
22.Inouye, K., Katsura, E., 1965. Etiology and pathology of beriberi. In: Thiamine and Beriberi. Igaku Shoin Ltd.. Tokyo, pp1-28.
23.Johnson, T. S., Young, J. B., Landsberg, L., Dana, C. A., 1983. Sympathoadrenal responses to acute and chronic hypoxia in the rat. J. Clin. Invest. 71,1263-1272.
24.Kawai, C,, Wakabayashi, A., Matsumura, T., Yui, Y., 1980. Reappearance of beriberi heart disease in Japan. A study of 23 cases. Am. J. Med. 669(3),383-386.
25.Khakh, B. S., Burnstock, G., December 2009. The double life of ATP. Scientific. American. :84-92.
26.Köllensperger, M., Stampfer-Kountchev, M., Seppi K., Geser, F., Frick, C., Del Sorbo, F., et al. 2007 Progression of dysautonomia in multiple system atrophy: a prospective study of self-perceived impairment. European. Journal. of Neurology. 14 (1), 66–72.
27.Kril, J. J., 1996. Neuropathology of thiamine deficiency disorders. Metab. Brain. Dis. 11(1), 9-17.
28.Lee, T., Donegan, C., Moore, A.. 2005 Combined hypertension and orthostatic hypotension in older patients: a treatment dilemma for clinicians. Expert. Rev. Cardiovasc. Ther. 3(3), 433-44.
29.Lonsdale, D., Nodar, R. H., Orlowski, J. P., 1979 The effects of thiamine on abnormal brainstem auditory evoked potentials. Cleve. Clin. Quart. 46,83-88.    
30.Lonsdale, D.. 1978. Wernicke’s encephalopathy and hyperalimentation. JAMA. 239:1133,  (Letter to the editor).
31.Lonsdale, D., 1987. A Nutritionist’s Guide to the Clinical Use of Vitamin B1. Life Sciences Press, Tacoma, Washington (on line, Soil and Health Library).
32.Lonsdale, D., Shamberger, R. J., 1980. Red cell transketolase as an indicator of nutritional deficiency. Am. J. Clin. Nutr.  33, 205-211.
33.Lonsdale, D., 1990. Asymmetric Functional Dysautonomia. J. Nutr. Med. 1,59-66.
34.Lonsdale, D., Shamberger, R. J., Audhya, T., 2002. Treatment of autistic spectrum children with thiamin tetra hydrofurfuryl disulfide: a pilot study. Neuroendocrinol. Lett. 23,303-308.
35.Lonsdale, D.. 2006. A review of the biochemistry, metabolism and clinical benefits of thiamin(e) and its derivatives. eCAM.3(1),49-59.
36.Lonsdale, D., 2009. Dysautonomia, a heuristic approach to a revised etiology for disease.  eCAM. 6(1),3-10.
37.Lychkova, A. E., 2005 Functional asymmetry in the innervation of smooth muscle organs. Bull. Exp. Biol. Med. 139(2),163-167.
38.Massod, M. F., McGuire, S. L., Werner, W. R., 1971 Analysis of blood transketolase activity Am. J. Clin. Path. 55, 465-70.
39.McKeon, A., Lennon, V. A., Lachance, D. H.., Fealey, A. D., Pittock, S. J., 2009 Ganglionic acetylcholine receptor autoantibody: oncological, neurological and serological accompaniments. Arch. Neurol. 66(6), 735-741.
40.Ming, X., Julu, P. O. O., Brimacombe, M., Connor, S., Daniels, M. L.,2005 Reduced cardiac parasympathetic Activity in children with autism. Brain. Dev. Jpn. 27, 509-516.
41.Mimori, Y., Katsuoka, H., Nakamura, S., 1996 Thiamine therapy in Alzheimer’s disease. Metab. Brain.  Dis. 11(1), 89- 94.
Montagna, P.,  2006. May 27, Suppl 2. Hypothalamus, sleep and headaches. Neurol. Sci. S138-143.
42.Mori, K., Ando, I., Kukita A., 2001. Generalized hyperpigmentation of the skin due to vitamin B12 deficiency. J. Dermatol. 28(5),282-285.
43.O’Keeffe, S. T., Tormey, W. P., Glasgow, R., Lavan, J. N., 1994. Thiamine deficiency in hospitalized elderly patients. Gerontology. 40(1),18-24.
44.Oliveira, G., Diego, L., Grazina, M., Garcia, P., Ataide, A., Marques, C., Miguel, T., et al. 2005. Mitochondrial dysfunction in autism spectrum disorders:a population based study. Developmental. Medicine. Child. Neurol. 47(3), 185-189.

45.Peters, R. A., 1936. May 23. The biochemical lesion in vitamin B1 deficiency.  Lancet. i. 1162-1165.    

46. Pincus, J. H., Cooper, J. R., Murphy, J. V., Rabe, E. F., Lonsdale, D., Dunn, G., 1973. Thiamine derivatives in subacute necrotizing encephalomyelopathy. Pediat. 51(4),716-721.
47.Quinn, N., 1989. January, Special Supplement. Multiple system atrophy- the nature of the beast. J. Neurol. Neurosurg. Psychiat.. :78-89.
48.Read, D. J. C., 1978. The aetiology of the sudden infant death syndrome: current ideas on breathing and sleep and possible links to deranged thiamine neurochemistry. Aust. NZ J. Med. 8, 322-336.
49.Rindi, G., Patrini, C., Cominicioli, C., Reggiani, C., 1980. Thiamine content and turnover rates of some rat nervous regions using labeled thiamine as a tracer. Brain. Res. 181, 369-380.
50.Rosas-Ballina, M., Tracey, K. J., 2009. The neurology of the immune system: neural reflexes regulate immunity. Neuron. 64(1),28-32.
51.Rubin, L. S.. 1961 Patterns of pupillary dilatation and constriction in psychotic adults and autistic children. J.Nerv.Ment. Dis.135,130-142.
52.Shannahof-Kalsa, D. S., 2007. Selective unilateral autonomic activation: implications for psychiatry. CNS. Spectr. 12(8), 625-634.
53.Stricker, R. B., Winger, E. E.,  2001, Mar 10.Holmes-Adie syndrome and Lyme disease. Lancet. 2001,  357:805.
54.Ueno, Y., Asano, M., Nushida, H., Nakagawa, K., Adachi, J., Nagaski, Y., 2003. Sexual asphyxia by hanging: a case report and a review of the literature. Legal. Medicine. 5(3),175-180.
55.Voltmeyer, H. O., Hagel, C., Laas, R. 1993. Hypoxia-ischemia and thiamine deficiency. Clin. Neuropath. 12(4),184-190
56.Wali, C. M., 2004. Asymnmetric awake bruxism associated with multiple system atrophy. Mov. Disord. 19(3), 352-355.
57.Zhao, Y., Pan, X., Zhao, J., Wang, Y., Peng, Y., Zhong, C., 2009. Decreased transketolase activity contributes to impaired hippocampal neurogenesis induced by thiamine deficiency. J. Neurochem. 111(2), 537-546.

Source(s) of Funding


Competing Interests



This article has been downloaded from WebmedCentral. With our unique author driven post publication peer review, contents posted on this web portal do not undergo any prepublication peer or editorial review. It is completely the responsibility of the authors to ensure not only scientific and ethical standards of the manuscript but also its grammatical accuracy. Authors must ensure that they obtain all the necessary permissions before submitting any information that requires obtaining a consent or approval from a third party. Authors should also ensure not to submit any information which they do not have the copyright of or of which they have transferred the copyrights to a third party.
Contents on WebmedCentral are purely for biomedical researchers and scientists. They are not meant to cater to the needs of an individual patient. The web portal or any content(s) therein is neither designed to support, nor replace, the relationship that exists between a patient/site visitor and his/her physician. Your use of the WebmedCentral site and its contents is entirely at your own risk. We do not take any responsibility for any harm that you may suffer or inflict on a third person by following the contents of this website.

2 reviews posted so far

I agree that the numbers are not good enough for good statistical significance. My main object as a physician in private practice was to draw attention to the asymmetry of blood pressures because I ha... View more
Responded by Dr. Derrick Lonsdale on 05 May 2011 11:36:37 AM GMT

0 comments posted so far

Please use this functionality to flag objectionable, inappropriate, inaccurate, and offensive content to WebmedCentral Team and the authors.


Author Comments
0 comments posted so far


What is article Popularity?

Article popularity is calculated by considering the scores: age of the article
Popularity = (P - 1) / (T + 2)^1.5
P : points is the sum of individual scores, which includes article Views, Downloads, Reviews, Comments and their weightage

Scores   Weightage
Views Points X 1
Download Points X 2
Comment Points X 5
Review Points X 10
Points= sum(Views Points + Download Points + Comment Points + Review Points)
T : time since submission in hours.
P is subtracted by 1 to negate submitter's vote.
Age factor is (time since submission in hours plus two) to the power of 1.5.factor.

How Article Quality Works?

For each article Authors/Readers, Reviewers and WMC Editors can review/rate the articles. These ratings are used to determine Feedback Scores.

In most cases, article receive ratings in the range of 0 to 10. We calculate average of all the ratings and consider it as article quality.

Quality=Average(Authors/Readers Ratings + Reviewers Ratings + WMC Editor Ratings)