Vitamin E deficiency: An under-recognized cause of dystonia and ataxia syndrome
Harsh V Gupta1, Steven Swank2, Vibhash D Sharma1 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
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Correspondence Address: Dr. Harsh V Gupta 10777 Nall Avenue, Overland Park, KS USA
Source of Support: None, Conflict of Interest: None
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
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.
Vitamin E (alpha-tocopherol) is an antioxidant, which is important for neurological function. 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.
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. 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.
Different etiologies of vitamin E deficiency have been described [Table 1].,, 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].,,
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).,, However, the response was variable as some patients continued to get worse despite high dose vitamin E supplementation. 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. In patients with fat malabsorption syndrome, higher doses of oral alpha-tocopherol (100–200 IU/kg/day) may be needed. 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., TPGS can be conjugated with drugs such as doxorubicin. 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. 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.).
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.
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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.
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