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NI FEATURE: FACING ADVERSITY…TOMORROW IS ANOTHER DAY! - LETTERS TO EDITOR
Year : 2019  |  Volume : 67  |  Issue : 3  |  Page : 866-869

Aluminum intoxication: A rare cause of myelopathy


Department of Neurology, King George's Medical University, Lucknow, Uttar Pradesh, India

Date of Web Publication23-Jul-2019

Correspondence Address:
Dr. Rajesh Verma
Department of Neurology, King George's Medical University, Lucknow - 226 003, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.263248

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How to cite this article:
Verma R, Sarkar S. Aluminum intoxication: A rare cause of myelopathy. Neurol India 2019;67:866-9

How to cite this URL:
Verma R, Sarkar S. Aluminum intoxication: A rare cause of myelopathy. Neurol India [serial online] 2019 [cited 2019 Dec 13];67:866-9. Available from: http://www.neurologyindia.com/text.asp?2019/67/3/866/263248




Sir,

Spinal cord disorders are caused by certain toxins apart from inflammatory, demyelinating, vascular, infective, and hereditary disorders. The important toxic causes of myelopathy include nitrous oxide exposure, heroin, radiation, various chemotherapeutic agents, liver disease, konzo, lathyrism, copper deficiency, and zinc excess.[1]

Aluminum intoxication is known to cause proximal muscle weakness, bone pain, multiple nonhealing fractures, acute or subacute alteration in mental status, and premature osteoporosis.[2],[3],[4] The causal link of aluminum has been reported with various neurodegenerative disorders, including Alzheimer disease.

We report the case of a 28-year old male patient who presented with progressive spastic quadriparesis for the last 4 years with clinical evidence of myelopathy and without radiological evidence of compression. In view of exposure to aluminum in his workplace in the railways, serum aluminum levels were sent for examination and exceedingly high levels of the same were observed. This is perhaps the first case of aluminum intoxication-related chronic myelopathy in humans. Physicians should suspect aluminum toxicity as a cause of toxic myelopathy, particularly in patients with a history of exposure.

A 28-year old, right-handed male patient, working in the railways, as a track maintainer, complained of insidious onset weakness in his lower limbs for the last 4 years, that started symmetrically and was associated with progressive stiffness. He had difficulty in walking. Later in the course of the disease, he developed difficulty in getting up from squatting posture. Two years later, he started to have problems in buttoning his shirt and gripping the instruments in his workplace. The symptoms in his limbs had been slowly progressing to the extent that he could now walk with support only and was dependent on his family members for most of the activities of daily living. There was no history of fasciculations, radicular neck pain, tingling or numbness in the limbs or trunk. There was absence of bladder and bowel symptoms. There was no history of difficulty in speech or deglutition. There was no past history of any significant illness or trauma. He took a mixed diet and had no addictive habituation. The history was negative for high-risk sexual behavior. There was no past history of blood transfusion or any surgery. His father suffered from dementia for the last 10 years. The occupational history disclosed his involvement as a railway worker on tracks, where he was exposed to aluminum fumes in track maintenance. He was employed for the last 7 years, and throughout his carrier, he was involved in the same type of work. The track workers are involved in bonding and earthing of railway tracks, where they used aluminum, steel and other metallic tools.

The family history was noncontributory. All the family members were examined and no clinical finding was revealed. All these individuals were subjected to screening for metals, including aluminum, but the blood levels were found to be within the normal limits.

On examination, he had normal higher mental functions. Cranial nerve examination did not reveal any abnormality. Motor examination revealed spasticity in all four limbs with mild atrophy in his lower limbs, especially the quadriceps musculature. The motor power was 4/5 in his upper limbs on both sides and 4-/5 in his lower limbs in a symmetrical distribution. No fasciculations were seen. Sensory examination was within the normal limits. General systemic examination was also unremarkable.

Routine blood investigations revealed a hemoblobin level of 16.7 g/dl; total leukocyte count 8200 cells/mm 3; and, platelet 1.7 lakh cells/mm 3. Serum urea (25.1 mg/dl) and creatinine (1.06 mg/dl) were within the normal limits. Serum sodium (141.9 mmol/l), potassium (4.02 mmol/l), ionic calcium (5.25 mg/l) were all within the normal limits. Fasting plasma glucose was 70.6 mg/dl. Liver function tests were also unremarkable. The serum creatinine phosphokinase, serum aldolase, and low-density lipoprotein levels were within the normal limits.

Serum vitamin B 12 levels were within the normal limits (418 pg/ml). Viral markers (HIV, HBsAg, anti HCV) and venereal disease research laboratory test were negative. Serum human T-cell lymphotropic virus antibodies were not detected. Routine cerebrospinal fluid examination was noncontributory (cells: <5/cumm, protein: 30.6 mg%, sugar 65.2 mg%).

Magnetic resonance imaging (MRI) of the cervical spine showed no abnormality in the cervical cord [Figure 1] and [Figure 2]. MRI brain did not show any abnormality. The nerve conduction study (NCS) and electromyographic (EMG) studies were unremarkable.
Figure 1: MRI cervical spine: (a) T1-weighted and (b) T2-weighted images showing normal cervical cord without any evidence of compression

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Figure 2: Postcontrast T1-weighted image not revealing a contrast enhancing lesion

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On reviewing his occupational history, it was learnt that his job in the railways as a trackman entailed handling of steel and aluminum and that he has been exposed to it for the last 6 years. Accordingly, metal screening was sent. To our utter surprise, his blood aluminum levels were staggeringly high (61.8 μg/dl; reference range <0.54 μg/dl). The 24-h urinary excretion level was 4.8 μmol.

Zinc and copper levels were within the normal limits, while lead, arsenic, and mercury were not detectable. The clinical assessment and investigations did not suggest infective, inflammatory, vascular, demyelinating, or degenerative cause of myelopathy. Due to the remarkably elevated levels of aluminum and exclusion of other conditions related to chronic myelopathies, the diagnosis of myelopathy due to aluminum intoxication was entertained. In view of the toxic levels of aluminum, the chelating agent, deferoxamine (2.5 mg/kg/week), was administered. He showed partial improvement in his motor deficits at follow-up after 1 month.

This patient presented with chronic progressive, pure motor spastic quadriparesis without sensory or bladder involvement. There was clinical and radiologic evidence of noncompressive myelopathy.

Although all common causes were ruled out by laboratory investigations, an exceedingly high serum aluminum level (raised more than 100 times of normal) pointed toward a toxic etiology for this myelopathy.

Aluminum is a trivalent cation found in its ionic form in most kinds of animal and plant tissues and in the natural water everywhere.[5] It is absorbed from the gastrointestinal tract in the form of oral phosphate-binding agents (aluminum hydroxide); parenterally via immunizations; as a dialysate in patients on dialysis or as a contaminant in patients on total parenteral nutrition. It may also be absorbed through the urinary mucosa during bladder irrigation, and transdermally during administration of antiperspirants. It is also absorbed through aerosols via the olfactory epithelium and the pulmonary route. If a significant aluminum load exceeds the body's excretory capacity, the excess is deposited in various tissues, including bone, brain, liver, heart, spleen, lung, and muscle. This accumulation causes morbidity and mortality through various mechanisms.[6] The toxic effects of aluminum depend on the amount of metal ingested, its entry rate, tissue distribution, concentration achieved, and excretion rate.[7],[8],[9],[10] Mechanisms of aluminum toxicity include inhibition of enzyme activity and protein synthesis, alterations in nucleic acid function, and changes in cell membrane permeability. Aluminum causes an oxidative stress and free radical formation within brain tissue.[11] As the elimination half-life of aluminum from the human brain is 7 years, this can result in cumulative damage via the element's interference with neurofilament axonal transport and neurofilament assembly.

Proximal muscle weakness, bone pain, multiple nonhealing fractures, acute or subacute alteration in mental status, and premature osteoporosis have been reported with aluminum intoxication. These patients almost always have had some degree of renal disease. Most patients are on hemodialysis or peritoneal dialysis.

A possible etiologic link between aluminum exposure and Alzheimer disease emerged from several studies, some showing that aluminum causes neurofibrillary tangles in the brains of rabbits.[12],[13],[14],[15] The direct damage to motor neurons has been reported due to aluminum toxicity, ascertained by published observations of amyotrophic lateral sclerosis-like syndrome due to aluminum exposure. Some studies highlighted increased serum/cerebrospinal fluid prostaglandin (PG)E2 levels in individuals with amyotrophic lateral sclerosis. They explained the degenerative process through neuronal destruction due to oxidation and glutamate-induced excitotoxicity.[16]

No case of aluminum intoxication-associated myelopathy in humans has been reported in the literature. However, aluminum-induced chronic myelopathy has been reported in rabbits. Strong et al.,[17] observed that young adult New Zealand white rabbits, inoculated intra-cisternally once monthly with 100 mcg AlCl3 developed progressive hyperreflexia, hypertonia, gait impairment, weight loss, muscle wasting, and abnormal righting reflexes over the course of 8 months. No overt encephalopathic features were present. In the spinal motor neuron perikarya, dendrites, and axonal processes, argentophilic globular inclusions were extensively present.

The pathogenesis of myelopathy due to aluminum intoxication remains to be determined. The combination of factors which can be hypothesized to cause myelopathy are reduced enzymatic activity, impaired protein synthesis, nucleic acid functional abnormalities, alterations in cell membrane permeability, oxidative stress, interference in axonal transport system, dysregulation of glutamatergic neurotransmission, and glutamate-mediated excitotoxicity related to proinflammatory cytokines.[8],[9],[18]

The long-term implications depend on the timely detection of aluminum intoxication, administration of chelating agents, withdrawal from aluminum exposure, and long-term strategy to monitor aluminum-related laboratory parameters. As aluminum intoxication is a multisystemic disorder and not detectable early, it leads to a substantial morbidity and mortality.

This case is probably the first case of aluminum-induced myelopathy in humans. Physicians should be aware of this entity and it should be suspected in persons with chronic myelopathy with a positive exposure history, especially in whom other causes have been ruled out. This is important because the disease progression can be averted if exposure is stopped at an appropriate time. This is just the opening chapter of aluminum-related toxic myelopathy. A large, high-powered original study is required to establish the cause–effect relationship of aluminum excess myelopathy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

1.
Goodman BP. Metabolic and toxic causes of myelopathy. Continuum (MinneapMinn) 2015;21:84-99.  Back to cited text no. 1
    
2.
Cannata-Andía JB, Fernández-Martín JL. The clinical impact of aluminium overload in renal failure. Nephrol Dial Transplant 2002;17(Suppl 2):9-12.  Back to cited text no. 2
    
3.
Alfrey AC, LeGendre GR, Kaehny WD. The dialysis encephalopathy syndrome. Possible aluminum intoxication. N Engl J Med 1976;294:184.  Back to cited text no. 3
    
4.
Dunea G, Mahurkar SD, Mamdani B, Smith EC. Role of aluminum in dialysis dementia. Ann Intern Med 1978;88:502-4.  Back to cited text no. 4
    
5.
Jiang HX, Chen LS, Zheng JG, Han S, Tang N, Smith BR. Aluminum-induced effects on Photosystem II photochemistry in citrus leaves assessed by the chlorophyll a fluorescence transient. Tree Physiol 2008;28:1863-71.  Back to cited text no. 5
    
6.
Verstraeten SV, Aimo L, Oteiza PI. Aluminium and lead: Molecular mechanisms of brain toxicity. Arch Toxicol 2008;82:789-802.  Back to cited text no. 6
    
7.
Riihimaki V, Valkonen S, Engstrom B, Tossavainen A, Mutanen P, Aitio A. Behavior of aluminum in aluminum welders and manufacturers of aluminum sulfate--Impact on biological monitoring. Scand J Work Environ Health 2008;34:451-62.  Back to cited text no. 7
    
8.
Vasudevaraju P, Govindaraju M, Palanisamy AP, Sambamurti K, Rao KS. Molecular toxicity of aluminium in relation to neurodegeneration. Indian J Med Res 2008;128:545-56.  Back to cited text no. 8
[PUBMED]  [Full text]  
9.
Lemire J, Mailloux R, Puiseux-Dao S, Appanna VD. Aluminum-induced defective mitochondrial metabolism perturbs cytoskeletal dynamics in human astrocytoma cells. J Neurosci Res 2009;87:1474-83.  Back to cited text no. 9
    
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Hernández G1, Bollini A, Huarte M, Bazzoni G, Piehl L, Chiarotto M, et al. In vitro effect of aluminium upon erythrocyte membrane properties. Clin Hemorheol Microcirc 2008;40:191-205.  Back to cited text no. 10
    
11.
Drago D, Cavaliere A, Mascetra N, Ciavardelli D, di Ilio C, Zatta P, et al. Aluminum modulates effects of beta amyloid (1-42) on neuronal calcium homeostasis and mitochondria functioning and is altered in a triple transgenic mouse model of Alzheimer's disease. Rejuvenation Res 2008;11:861-71.  Back to cited text no. 11
    
12.
Klatzo I, Wisniewski HM, Streicher E. Experimental production of neurofibrillary degeneration. J Neuropath Exp Neurol 1965;24:187-99.  Back to cited text no. 12
    
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Wisniewski HM, Terry RD, Peña C, Streicher E, Klatzo I. Experimental production of neurofibrillary degeneration. J Neuropath Exp Neurol 1965;24:139.  Back to cited text no. 13
    
14.
Terry RD, Peña C. Experimental production of neurofibrillary degeneration. J Neuropath Exp Neurol 1965;24:200-10.  Back to cited text no. 14
    
15.
Crapper DR, Krishnan SS, Dalton AJ. Brain aluminium distribution in Alzheimer's disease and experimental neurofibrillary degeneration. Science 1973;180:511-3.  Back to cited text no. 15
    
16.
Iłzecka Prostaglandin E2 is increased in amyotrophic lateral sclerosis patients. Acta Neurol Scand 2003;108:125-9.  Back to cited text no. 16
    
17.
Strong MJ, Wolff AV, Wakayama I, Garruto RM. Aluminum-induced chronic myelopathy in rabbits. Neurotoxicology 1991;12:9-21.  Back to cited text no. 17
    
18.
Blaylock RL, Strunecka A. Immune-glutamatergic dysfunction as a central mechanism of the autism spectrum disorders. Curr Med Chem 2009;16:157-70.  Back to cited text no. 18
    


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