Acute Lead Encephalopathy Secondary to Ayurvedic Medication Use: Two Cases with Review of Literature
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.329591
Source of Support: None, Conflict of Interest: None
Keywords: Ayurvedic, encephalopathy, lead
Ayurvedic medicine (also known as Ayurveda) is India's primary and traditional system native to Indian healthcare system. Ayurvedic formulations are based on herbal products which are safe but often include toxic metals and other elements based on Rasa Shastra practice. These elements are believed to restore good health and normal function to the human body. A 2015 published survey of people who use Ayurvedic preparations showed that 40 percent had elevated blood levels of lead and some had elevated blood levels of mercury and other heavy metals. Lead poisoning affects multiple organs like skeletal system, hematological, neurological, gingiva and kidneys. In the central nervous system, the lesions are thought to be the result of vascular injury. Lead encephalopathy in adults is uncommon and due to ayurvedic medications is even more rare. According to a survey by State Adult Blood Lead Epidemiology and Surveillance (ABLES), the national prevalence rate of BLLs ≥10 μg/dL declined from 26.6 adults per 100,000 employed in 2010 (among 37 states) to 20.4 in 2013 (among 29 reporting states).
Lead acts as a cellular toxin by inhibiting mitochondrial respiration. The increased resistance of the adult to encephalopathy and ataxia is believed to be caused by the capacity of the mature brain to sequestrate lead away from its mitochondrial site of action within the cerebral and cerebellar neurons. Here authors would like to describe two cases of Lead poisoning due to long-term ayurvedic medication intake presenting as acute encephalopathy of varying severity.
A 54-year-old female known case of diabetes mellitus and systemic hypertension on medications came to emergency department with 2 weeks history of acute confusional state, disorientation, forgetfulness and irrelevant talking. There was history of abdominal pain colicky in nature since 2 months. CT Abdomen pelvis was normal and endoscopy suggestive of mild antral gastritis for which she was initiated on proton pump inhibitors. There was history of long-term multiple ayurvedic medication consumption for her diabetes and hypertension. Patient procured it from ayurved practioner and were dispensed as tablets.
Clinical examination revealed hypertension. Pallor was present. Patient was confused, disoriented and restless with difficulty in understanding complex commands. Plantar response was extensor. Gait was ataxic. Complete hemogram revealed hemoglobin of 8.4 gram% with microcytic hypochromic picture. Biochemical tests including renal and liver function tests were normal. MRI Brain study suggestive of multiple T2 FLAIR hyperintensities in putamen, thalami and subcortical white matter with gyral edema [Figure 1]. DWI revealed subtle diffusion restriction in left occipital lobe [Figure 2]. CSF study revealed 5 cells (mononuclear) with proteins of 15 mg% and normal sugars. CSF cultures were negative. EEG electroencephalogram revealed mild slowing of background. Blood toxin anaylsis revealed elevated lead levels in blood (105 μg/dL). All her ayurvedic medications were stopped and patient was given symptomatic treatment. Oral chelation therapy started which included oral D penicillamine 250 mg twice a day. Gradually abdominal pain and confusional state resolved. Patient was given oral chelation therapy for 3 months with periodic monitoring of lead levels. Repeat MRI Brain at 3 months showed complete resolution of signal changes previously seen [Figure 1] and [Figure 2]. Clinically patient had a normal neurological examination at follow-up.
A 45-year-old female known case of hypertension was taking medications for her blood pressure from ayurvedic practioner since 6 months. Patient developed headaches since 3 weeks followed by multiple episodes of vomiting and drowsiness. She presented to emergency with extreme stupor. Vitals examination revealed hypertension and bradycardia. Glasgow coma scale (GCS) was E2M3V2 (7/15). Fundus examination revealed papilledema. Plantar response was extensor. CBC revealed Hb of 9.5 gram % with microcytic picture. Renal and liver profile was normal. MRI Brain suggestive of diffuse cerebral edema, gyral swelling with basal ganglia signal changes [Figure 3]. CSF Study revealed cell count of 4 cells with normal protein and sugar. Meningitis biofire and aerobic cultures were negative. Patient initiated on injection mannitol, antiepileptics and hydration. Lead levels were 140 μg/dL. Patient became comatose and succumbed to the illness.
Ayurvedic preparations contain lead and/or mercury at 100 to 10,000 times greater than acceptable limits. Excess levels of lead leads to production of free radicals which subsequently causes oxidative damage of cellular components including DNA and cell membranes. It interferes with DNA transcription, enzymatic synthesis of vitamin D, and enzymes that maintain the integrity of the cell membranes. Lead results in denaturation of enzymes such as deltaaminolevulinic acid dehydratase (ALA-D) and ferrochelatase which are important for heme synthesis. Inhibition of pyrimidine 5'-nucleotidase can prevent the degradation of ribosomal RNA in red blood cells leading to basophilic stippling on a peripheral smear, a classic finding which can be apparent at BLLs of ~50 μg/Dl. Basophilic stippling of erythrocytes is reported in 91% of patients by Whitfield et al. but was seen in only 40% of cases reported by Greengard et al. Basophilic stippling couldn't be demonstrated in either of our cases.
Symptoms of adult lead poisoning are variable depending on duration of exposure. The usual manifestations of lead poisoning in adults are colic, anemia, and peripheral motor neuropathy. The adult form of lead encephalopathy is rarer than the pediatric form and can present with serious neurodeterioration and even death. Lead encephalopathy can present in acute and chronic forms. Acute lead encephalopathy presents pathologically as cerebral edema whereas in chronic lead encephalopathy, extensive tissue destruction with cavity formation and thickening of the veins with cellular disorganization of their walls is seen. All this can lead to edema, gliosis, hemorrhage, neuronal loss, and perivascular proteinaceous exudate. Patients present with headache, vomiting, ataxia, convulsions, paralysis, stupor, and coma in acute forms whereas in chronic encephalopathy, patients present with memory and concentration disturbances, headache, psychiatric symptoms, diminished libido, syncope, tremor, seizure and ataxia. In severe conditions, cerebral or cerebellar edema may develop; such patients may present with vomiting, apathy, stupor, coma, paralysis, and death.
The symptoms of lead toxicity usually appear at BLLs of 40-60 μg/dL in adults. Over the last 25 years, numerous cases of lead toxicity associated with Ayurvedic medicine have been reported in the literature. Whitfield et al. (1972) reported the largest series of 23 adults with lead encephalopathy. Ten of these patients had altered sensorium; 18 of them had seizures. Bhaskara rao et al. reported 2 cases with lead encephalopathy presenting as seizures and abdominal complaints with good response to chelation treatment. Atre et al. reported a case of lead encephalopathy due to ayurvedic medication presenting as acute onset short-term memory loss, loss of appetite, apathy and imbalance with hyperreflexia and spasticity. Our first case presented with acute onset confusional state, disorientation, memory disturbances and lead colic. Second case presented with rapid worsening of sensorium leading to coma and ultimately death.
Neuroimaging especially magnetic resonance imaging MRI can give some clue of toxin-induced encephalopathy. Schroter et al. reported high signal intensities in the periventricular white matter, basal ganglia, insula, posterior thalamus, and pons. Perelman et al. reported MR imaging findings such as cerebellar edema, suggested by an enlarged cerebellum with the disappearance of the cerebellar fissure and protrusion. Mani et al. reported high signal intensities in both thalami on T2 weighted MR images. Tuzun et al. reported low signal intensities on T1-weighted images and high signal intensities on T2-weighted images located bilaterally and symmetrically in thalami, lateral putamen, claustrum, and insula. Bhaskara rao et al. reported 2 cases with MRI showing bilateral symmetric involvement of the thalamus and lentiform nucleus, subcortical white matter and external capsule. Both our cases showed cortical and basal ganglionic signal changes except the edema was serious in the second case. In the first case we could demonstrate reversal of signal changes post-treatment.
Management varies widely and includes oral chelation with D-penicillamine or DMSA (Dimercapto succinic acid) or intravenous infusions of Calcium EDTA, Na-EDTA (Ethylene diamine tetraacetic acid) or dimercaprol. In some instances combination therapy is administered. The current reference range for acceptable BLLs in healthy individuals without excessive exposure to environmental sources of lead is <10 μg/dL for children and <25 μg/dL for adults. To date, there are no clinical trials that define the optimal management although it is generally accepted that the first step is to identify and remove the source of the exposure. Chelation therapy should be initiated when the BLL is >80 μg/dL in asymptomatic and >50 μg/dL in symptomatic adults and should be continued until the BLL is <50 μg/dL. We used oral D penicillamine in our case with normalization of lead levels post-treatment. Timely diagnosis and identification of source of exposure are critical in preventing the long-term consequences of lead poisoning. Detailed medication history is essential in cases with unknown cause of encephalopathy.
In a case of rapidly progressive encephalopathy with no identifiable cause, toxin-induced encephalopathy should be suspected especially with MRI findings showing symmetric basal ganglia, cortical and subcortical white matter signal change. Prompt elimination of toxin and initation of chelation treatment may prevent neurological worsening and result in complete clinical recovery.
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[Figure 1], [Figure 2], [Figure 3]