Lead toxicity is a multisystemic disorder affecting hematopoietic, gastrointestinal, cardiovascular, renal, reproductive, and the nervous system. 1 , 2 Occupational exposure is often the cause in adults apart from exposure through food or water contamination, paint, gasoline, and traditional medicines. Lead neurotoxicity can present with varied presentations and can often be challenging to diagnose if a relevant exposure history is not taken. We report a case of myoclonus‐ataxic presentation of chronic lead toxicity because of occupational exposure.
Case Report
A 36‐year‐old male born to consanguineous parents, with normal perinatal and developmental history presented with action‐predominant jerky tremulousness of bilateral upper‐limbs for the past 2 years and of bilateral lower‐limbs for the past 1 year. In addition, he had slurring of speech. These symptoms were preceded approximately for 2 months by leg cramps, fatigue, and difficulty focusing during tasks. On evaluation, he had anemia and received blood transfusions. There was no history of any other relevant past, family, or treatment history. However, the patient was working in a battery factory for the past 10 years and continued to work even when he had anemia. On examination (Video 1), the patient had dysarthria, left‐side and distal predominant jerky postural, and action tremor of all four limbs suggestive of myoclonic jerks, and had a cautious gait with impaired tandem gait and tremulousness of legs and trunk. The rest of the neurological and systemic examinations were normal.
VIDEO 1.
Video of the patient at presentation and follow‐up. The video demonstrates jerky postural and action predominant tremulousness of left > right upper limbs and bilateral lower limbs suggestive of myoclonus, mildly impaired finger nose test, dysdiadokokinesia, impaired knee–heel–shin test, ataxic gait, and impaired tandem walking with truncal and lower limb tremulousness. Even though the left arm swing appears reduced, there was no bradykinesia or rigidity on examination. At follow‐up, there was improvement in upper limb myoclonus and tandem gait. The video was taken after written informed consent for online publication and dissemination.
Blood investigations revealed mild hypochromic anemia (11.2 g/dL) with normal ferritin and elevated serum creatinine (1.7 mg/dL), but with a normal ultrasound abdomen and urine biochemistry. Magnetic resonance imaging (MRI) of the brain was abnormal as described in Figure 1. Surface electromyography was consistent with cortical myoclonus. However, nerve conduction studies (NCS) were normal with no giant somatosensory evoked potentials. Blood lead level was elevated (53.9 μg/dL). Other blood investigations including Wilson's disease workup and screening for abnormal metabolites, ammonia, and lactate were normal. Whole exome sequencing was negative, which ruled out an underlying genetic etiology. The patient was advised for alternative occupation and started on symptomatic medications along with d‐penicillamine (750 mg/day). At 1‐year follow‐up the patient had mild symptomatic improvement with normal lead level.
FIG. 1.
MRI of the brain of the patient. T1 (A), T2 (B,F), and FLAIR sequences (C–E) of MRI showing bilaterally symmetrical T2 and FLAIR hyperintensities of caudate, putamen, claustrum, and posterior‐medial thalamus (B,C), medial temporal and midbrain tegmentum, (D) and posterior pontine (E,F) regions. MRI, magnetic resonance imaging; FLAIR, fluid attenuated inversion recovery.
Discussion
Commonly recognized symptoms with lead toxicity are colicky abdominal pain, unexplained anemia, cramps, and wrist and/or foot drop. 3 Lead poisoning can affect both central and peripheral nervous systems. Adults are less susceptible than children owing to the ability of the mature adult brain to sequester lead away from the mitochondrial site of action in the neurons. Acute lead neurotoxicity results in encephalopathic presentation with headache, vomiting, convulsions, irritability, stupor, and coma. Chronic lead neurotoxicity may cause cognitive‐behavioral impairment, concentration disturbances, insomnia, tremor, and ataxia. Myoclonus is rarely reported and usually occurs in acute encephalopathic presentations. 4
In a patient with myoclonus‐ataxia, post‐infectious, inflammatory, autoimmune, and paraneoplastic causes predominate in acute to subacute presentations, and it can be part of opsoclonus‐myoclonus‐ataxia syndrome. 5 In chronic presentations, genetic causes are frequent. In association with seizures, various progressing myoclonic epilepsy syndromes form an important differential diagnosis. 5 In addition, some of the autosomal‐recessive and dominant causes of ataxia such as ataxia telangiectasia, POLG‐related neurological disorders, COQ8A deficiency, spinocerebellar ataxia type‐2, dentatorubral‐pallidoluysian atrophy etc. can have myoclonus‐ataxia presentation. 5 Hence, exome sequencing and triplet‐primed polymerase chain reaction tests are important when evaluating chronic presentations of myoclonus‐ataxia. Acquired causes such as celiac disease, Creutzfeldt–Jacob disease, and multiple system atrophy should also be kept in the differentials of myoclonus‐ataxia. 5
To the best of our knowledge, the myoclonus‐ataxic presentation of chronic lead toxicity has not been previously reported. There were prior symptoms suggestive of lead toxicity such as leg cramps, fatigue, and unexplained anemia. In addition, our patient also had renal involvement in the form of elevated serum creatinine. The blue line along the gum, bluish‐black edging to the teeth, known as a Burton line, transverse white line across the nail known as the Mees line and pallor or lividity of the skin called lead hue are other clinical clues. In addition, patients can have reproductive abnormalities (loss of libido, infertility, and miscarriage) and gastrointestinal symptoms (constipation, colicky abdominal pain, decreased appetite, and weight loss). 1 , 2 , 6 , 7
On investigation, microcytic hypochromic anemia with basophilic stippling can occur because of impaired heme synthesis. Blood lead level is normally less than 10 μg/dL in children and less than 25 μg/dL in adults. Values greater than 40 μg/dL result in toxicity and is often greater than 100 μg/dL in acute encephalopathy. MRI brain shows cerebral and cerebellar edema, hyperintensities of periventricular white matter, basal ganglia, posterior thalamus, insula, claustrum, and brainstem. 8 , 9 NCS may show motor and upper‐limb predominant axonal neuropathy. Oxidative stress, mitochondrial dysfunction, ionic mechanism by interfering with divalent cations, vascular mechanism and disruption of blood–brain barrier have been implicated in the pathogenesis. 1 , 2
Treatment involves decontamination, cessation of exposure, precautions and chelation. Blood lead level of greater than 50 μg/dL if symptomatic and greater than 80 μg/dL if asymptomatic warrants chelation with intravenous edetate calcium disodium, intramuscular British anti‐lewisite, oral dimercaptosuccinic acid, or d‐penicillamine. Chelation needs to be continued till the level drops to less than 50 μg/dL. 1 Adults tend to have favorable responses compared to children and early treatment is more likely to result in a better recovery. Improvement may take months to years and can have residual deficits. 1
Author Roles
(1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique.
V.V.H.: 1A, 1B, 1C, 2A, 2B, 3A.
P.S.: 1B, 2B, 3B
N.K.: 1B, 2C, 3B.
R.Y.: 1B, 2C, 3B.
P.K.P.: 1A, 1C, 2C, 3B.
Disclosures
Ethical Compliance Statement: Institute Ethics Committee waiver was obtained for the publication and informed consent was obtained from the patients for video recording and publishing. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.
Funding Sources and Conflicts of Interest: No specific funding was received for this work and there are no conflicts of interest relevant to this work.
Financial Disclosures for the Previous 12 Months: There are no financial disclosures to report.
Acknowledgments
None.
Relevant disclosures and conflict of interest are listed at the end of this article.
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