brintellex
ValprolBanner
Annals of Indian Academy of Neurology
  Users Online: 1569 Home | About the Journal | InstructionsCurrent Issue | Back IssuesLogin      Print this page Email this page  Small font size Default font size Increase font size

Table of Contents
LETTER TO THE EDITOR
Year : 2020  |  Volume : 23  |  Issue : 3  |  Page : 372-374
 

Vitamin E deficiency: An under-recognized cause of dystonia and ataxia syndrome


1 Department of Neurology, Kansas University Medical Center, Kansas City, KS, USA
2 Clinical Pharmacist, The University of Kansas Health System, Kansas City, KS, USA

Date of Submission16-Jan-2020
Date of Acceptance10-Feb-2020
Date of Web Publication30-Mar-2020

Correspondence Address:
Dr. Harsh V Gupta
10777 Nall Avenue, Overland Park, KS
USA
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aian.AIAN_29_20

Rights and Permissions

 



How to cite this article:
Gupta HV, Swank S, Sharma VD. Vitamin E deficiency: An under-recognized cause of dystonia and ataxia syndrome. Ann Indian Acad Neurol 2020;23:372-4

How to cite this URL:
Gupta HV, Swank S, Sharma VD. Vitamin E deficiency: An under-recognized cause of dystonia and ataxia syndrome. Ann Indian Acad Neurol [serial online] 2020 [cited 2020 Jul 4];23:372-4. Available from: http://www.annalsofian.org/text.asp?2020/23/3/372/281600




A 43-year-old right-handed man was seen in the clinic for an evaluation of progressive gait difficulty. He initially developed tingling in his hands and feet at the age of 30 years. After 3 years of initial symptoms, he developed weakness in his lower distal extremities. His symptoms progressed over the years and he developed unsteady gait, double vision, speech changes, and tremor in his right hand and head. He also complained of diarrhea (five to six loose watery bowel movements a day) and required frequent emergency evaluations for the management of the same. He was found to have colonic dilatation (11.4 cm). His past medical history was significant for jejunal resection at the time of birth. There was no family history of similar neurological problems.

His general examination was significant for generalized muscle bulk loss with a cachectic appearance. On neurological examination, his cognitive function was intact. His cranial nerves examination revealed an impairment in up gaze and visual acuity was reduced in the left eye (20/150). The impairment in vertical eye movement could not be overcome by the oculocephalic maneuver. On fundoscopic examination, he was found to have bilateral retinal thinning and optic neuropathy. His speech was dysarthric. The motor exam showed reduced strength in all four extremities distally (4/5) with reduced muscle bulk. Reflexes were absent throughout without Hoffman's or ankle clonus. Toes showed flexor response to plantar stimulation. The sensation was impaired to pinprick, temperature, vibration, and proprioception in all four extremities distally. The coordination exam showed dysmetria on finger-nose-finger testing, finger chase, and impaired heel-knee-shin (right more than the left). His gait was wide-based with an inability to stand or walk tandem. There was a rest, postural, and kinetic tremor in the right hand which was position-dependent and a low-frequency tremor in the head. Romberg's sign was positive [Video 1].




His MRI brain was normal without evidence of cerebellar atrophy. An MRI T-spine showed a signal abnormality in the dorsal column and SSEP showed impaired conduction in the central proprioceptive pathways. His EMG and nerve conduction study results were consistent with an asymmetric polyradiculoneuropathy. Further laboratory workup was either normal or negative: genetic testing for SCA, FRDA, serum protein electrophoresis, thyroid-stimulating hormone, vitamin B12, ANA, RPR, ceruloplasmin, creatine kinase, celiac screen, HIV, fecal pancreatic elastase, and lipid profile. His vitamin E level was undetectable in the serum which was tested on two separate occasions. There was a mild elevation in ALT (128 U/L) and AST (95 U/L) and liver biopsy showed steatohepatitis (NASH). Biopsies were also taken from stomach and duodenum (two separate occasions) which ruled out celiac disease or Whipple's procedure. His serum copper was mildly decreased at 59 mcg/dL (range: 70–155 mcg/dL), vitamin A level was mildly decreased, and INR was mildly elevated at 1.4.

The patient was started on a high dose of vitamin E supplementation (3000 U/day) for 3 months which did not lead to any significant improvement in serum alpha-tocopherol level. The patient has now been started on a transdermal multivitamin patch containing 200 IU of vitamin E and 2 mg of copper gluconate.


   Discussion Top


Vitamin E (alpha-tocopherol) is an antioxidant, which is important for neurological function.[1] It can lead to neurological, retinal, and hematological features because these cells work in an oxygen-rich environment and are susceptible to damage. The neuropathological findings described in patients with vitamin E deficiency include dystrophic axons and astrocytosis in spinal cord posterior column nuclei, degeneration of spinocerebellar tracts, loss of nerve cell nuclei in the brainstem, and patchy demyelination in peripheral nerves.[2]

In our patient, neurological symptoms and signs suggested a combination of central as well as a peripheral process. There was a sensory component of ataxia based on abnormal sensory findings such as loss of DTRs, impaired proprioception, and vibration. However, the presence of dysarthria, oculomotor abnormalities, dystonia, vertical eye movement impairment (not overcome by oculocephalic maneuver), and head tremor suggested cerebellar and brainstem pathology. The involvement of the peripheral component can be explained by a combination of copper and vitamin E deficiency but the central component is most likely due to vitamin E deficiency alone. Further, his ataxia did not get worse with closing his eyes supporting central ataxia as the predominant etiology.[3] It is important to recognize the predominant component of ataxia because cerebellar and peripheral pathology can exist together in the same patient such as SCA or alcoholic cerebellar degeneration.[4]

Different etiologies of vitamin E deficiency have been described [Table 1].[2],[5],[6] The clinical features of ataxia secondary to vitamin E deficiency can be difficult to differentiate from other forms of ataxia particularly Friedreich Ataxia (FRDA) and Niemann-Pick disease (NPC) [Table 2].[7],[8],[9]
Table 1: Causes of vitamin E deficiency

Click here to view
Table 2: Comparison of clinical features

Click here to view


Supplementation of vitamin E can sometimes be challenging since intramuscular, subcutaneous, or intravenous forms are not available. Published reports of FIVED have shown benefit with a high dose of oral vitamin E supplementation (2500–4000 IU/day).[7],[10],[11] However, the response was variable as some patients continued to get worse despite high dose vitamin E supplementation.[7] Water-soluble vitamin E can be a good option for patients with abetalipoproteinemia which is typically used in a dose of 15–25 IU/kg/day.[12] In patients with fat malabsorption syndrome, higher doses of oral alpha-tocopherol (100–200 IU/kg/day) may be needed.[13] There are a few other options such as a transdermal patch containing vitamin E (contains other vitamins as well) or a topical cream containing vitamin E and vitamin C.

Vitamin E d-α-tocopheryl polyethylene glycol succinate (Vitamin E TPGS or TPGS), an FDA approved pharmaceutical excipient, is a water-soluble derivative of vitamin E that can be delivered intravenously. TPGS is widely used as an adjuvant in drug delivery, especially chemotherapy.[14],[15] TPGS can be conjugated with drugs such as doxorubicin.[16] Long-term oral delivery of TPGS for vitamin E deficiency (20–25 units/kg/day) has been studied in pediatric patients with chronic cholestasis. All children (n = 60) tolerated the therapy and responded with normalization of vitamin E status. Neurological function improved or stabilized in most patients with two patients having worsening neurologic function.[17] To the author's knowledge to date, unmodified TPGS for intravenous administration has not been studied for vitamin E deficiency and maybe a novel therapy for patients with concomitant challenges to oral absorption and extrahepatic transport (i.e. abetalipoproteinemia, FIVED, etc.).[18]

In summary, this case highlights the varied etiology of vitamin E deficiency, heterogeneous neurological presentation secondary to it, and the challenges for vitamin E supplementation. Timely identification and supplementation may help in preventing the progression and improvement of symptoms. Future strategies are needed to develop subcutaneous or intravenous forms of vitamin E supplementation.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

[22]



 
   References Top

1.
Ulatowski L, Parker R, Warrier G, Sultana R, Butterfield DA, Manor D. Vitamin E is essential for Purkinje neuron integrity. Neuroscience 2014;260:120-9.  Back to cited text no. 1
    
2.
Rosenblum JL, Keating JP, Prensky AL, Nelson JS. A progressive neurologic syndrome in children with chronic liver disease. N Engl J Med 1981;304:503-8.  Back to cited text no. 2
    
3.
Kuo SH. Ataxia. Continuum (Minneap Minn) 2019;25:1036-54.  Back to cited text no. 3
    
4.
Chhetri SK, Gow D, Shaunak S, Varma A. Clinical assessment of the sensory ataxias; diagnostic algorithm with illustrative cases. Pract Neurol 2014;14:242-51.  Back to cited text no. 4
    
5.
Rader DJ, Brewer HB Jr. Abetalipoproteinemia. New insights into lipoprotein assembly and vitamin E metabolism from a rare genetic disease. JAMA 1993;270:865-9.  Back to cited text no. 5
    
6.
Arita M, Sato Y, Miyata A, Tanabe T, Takahashi E, Kayden HJ, et al. Human alpha-tocopherol transfer protein: cDNA cloning, expression and chromosomal localization. Biochem J 1995;306:437-43.  Back to cited text no. 6
    
7.
El Euch-Fayache G, Bouhlal Y, Amouri R, Feki M, Hentati F. Molecular, clinical and peripheral neuropathy study of Tunisian patients with ataxia with vitamin E deficiency. Brain 2014;137:402-10.  Back to cited text no. 7
    
8.
Parkinson MH, Boesch S, Nachbauer W, Mariotti C, Giunti P. Clinical features of Friedreich's ataxia: Classical and atypical phenotypes. J Neurochem 2013;126(Suppl 1):103-17.  Back to cited text no. 8
    
9.
Patterson MC, Nordli DR, Dashe JF. Overview of Niemann-Pick disease. Literature Review 2019. Available from: https://www.uptodate.com/contents/overview-of-niemann-pick-disease?search=niemann%20pick&source=search_result&selectedTitle=1~33&usage_type=default &display_rank=1.  Back to cited text no. 9
    
10.
Mariotti C, Gellera C, Rimoldi M, Mineri R, Uziel G, Zorzi G, et al. Ataxia with isolated vitamin E deficiency: Neurological phenotype, clinical follow-up and novel mutations in TTPA gene in Italian families. Neurol Sci 2004;25:130-7.  Back to cited text no. 10
    
11.
Marzouki N, Benomar A, Yahyaoui M, Birouk N, Elouazzani M, Chkili T, et al. Vitamin E deficiency ataxia with (744 del A) mutation on alpha-TTP gene: Genetic and clinical peculiarities in Moroccan patients. Eur J Med Genet 2005;48:21-8.  Back to cited text no. 11
    
12.
Feranchak AP, Sokol RJ. Medical and nutritional management of cholestasis in infants and children. In: Liver Disease in Children. 3rd ed. New York: Cambridge University Press; 2007. p. 190-231.  Back to cited text no. 12
    
13.
Thébaut A, Nemeth A, Le Mouhaër J, Scheenstra R, Baumann U, Koot B, et al. Oral Tocofersolan corrects or prevents vitamin E deficiency in children with chronic cholestasis. J Pediatr Gastroenterol Nutr 2016;63:610-5.  Back to cited text no. 13
    
14.
Yang C, Wu T, Qi Y, Zhang Z. Recent advances in the application of vitamin E TPGS for drug delivery. Theranostics 2018;8:464-85.  Back to cited text no. 14
    
15.
Tan S, Zou C, Zhang W, Yin M, Gao X, Tang Q. Recent developments in d-alpha-tocopheryl polyethylene glycol-succinate-based nanomedicine for cancer therapy. Drug Deliv 2017;24:1831-42.  Back to cited text no. 15
    
16.
Metin E, Mutlu P, Gunduz U. Co-delivery of doxorubicin and D-alpha-tocopherol polyethylene glycol 1000 succinate by magnetic nanoparticles. Anticancer Agents Med Chem 2018;18:1138-47.  Back to cited text no. 16
    
17.
Sokol RJ, Butler-Simon N, Conner C, Heubi JE, Sinatra FR, Suchy FJ, et al. Multicenter trial of d-alpha-tocopheryl polyethylene glycol 1000 succinate for treatment of vitamin E deficiency in children with chronic cholestasis. Gastroenterology 1993;104:1727-35.  Back to cited text no. 17
    
18.
Schmölz L, Birringer M, Lorkowski S, Wallert M. Complexity of vitamin E metabolism. World J Biol Chem 2016;7:14-43.  Back to cited text no. 18
    
19.
Isselbacher KJ, Scheig R, Plotkin GR, Caulfield JB. Congenital beta-lipoprotein deficiency: An hereditary disorder involving a defect in the absorption and transport of lipids. Medicine (Baltimore) 1964;43:347-61.  Back to cited text no. 19
    
20.
Bassen FA, Kornzweig AL. Malformation of the erythrocytes in a case of atypical retinitis pigmentosa. Blood 1950;5:381-7.  Back to cited text no. 20
    
21.
Ben Hamida C, Doerflinger N, Belal S, Linder C, Reutenauer L, Dib C, et al. Localization of Friedreich ataxia phenotype with selective vitamin E deficiency to chromosome 8q by homozygosity mapping. Nat Genet 1993;5:195-200.  Back to cited text no. 21
    
22.
Muller DP, Lloyd JK. Effect of large oral doses of vitamin E on the neurological sequelae of patients with abetalipoproteinemia. Ann N Y Acad Sci 1982;393:133-44.  Back to cited text no. 22
    



 
 
    Tables

  [Table 1], [Table 2]



 

Top
Print this article  Email this article

    

 
   Search
 
  
    Similar in PUBMED
    Article in PDF (312 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  


     Discussion
    References
    Article Tables

 Article Access Statistics
    Viewed69    
    Printed0    
    Emailed0    
    PDF Downloaded4    
    Comments [Add]    

Recommend this journal