Arsenic‐Induced Polyneuropathy Mimicking Guillain‐Barré Syndrome: A Conundrum

ABSTRACT

We present a patient with flaccid paralysis caused by chronic arsenic exposure, most likely due to illicit drug use. Arsenic is known to cause polyneuropathy, but is not often considered in the differential diagnosis of a patient presenting with flaccid paralysis.

Summary.

• When a patient presents with flaccid paralysis, obtaining a thorough history, including a history of exposure to all possible illicit and over‐the‐counter drugs, and a thorough physical examination is crucial to investigate the possibility of chronic arsenic poisoning.

1. Introduction

Patients often are referred to the neurology department with symptoms of Guillain‐Barré syndrome (GBS). With this case report, we aimed to emphasize the importance of a thorough history and clinical examination. The Health Sciences Research Ethics Committee (HSREC) of the University of the Free State approved the publication of this case report (reference number UFS‐HSD2023/1899/2805) and written informed consent was obtained from the patient.

2. Case History/Examination

A 37‐year‐old male patient residing in Bloemfontein, Free State province, South Africa, was referred with a diagnosis of suspected Guillain‐Barré syndrome (GBS) and was being treated with intravenous immunoglobulins. The patient reported that 3 weeks before presenting, he had noticed lower limb weakness that progressed throughout the day until the evening, when he was unable to stand. He did not complain of upper limb weakness. He had urinary and fecal incontinence. On clinical examination, he had non‐painful white lines traversing the width of his nails and obvious alopeci. On further inquiry, he reported experiencing episodes of intense abdominal cramps over the past 4 months, each lasting approximately a week and resolving spontaneously.

The patient had a strong smoking history, which could not be quantified, and was using illicit drugs, dagga (cannabis) and Rodger. According to him, Rodger is a mixture of cannabis, antiretroviral drugs, and other unknown components that are crushed and consumed as tea. He had used this “herbal” tea for the past few years. He denied exposure to heavy metals. He had not painted with lead‐containing paint and had no exposure to well water or pesticides. He worked as a motor vehicle mechanic. He was newly diagnosed with human immunodeficiency virus (HIV) and had a viral load of 232 copies/mL. He was also diagnosed with hypertension a year before but was not taking any treatment.

On clinical examination, the patient had severe alopecia, also of his eyebrows (Figure 1). He had asymptomatic horizontal white lines on his finger‐ (Figure 2) and toenails (Figure 3) suggestive of Mees' lines.

FIGURE 1.

Severe alopecia, including the eyebrows.

FIGURE 2.

Mees' lines on the fingernails. Mees' lines are commonly seen in patients with arsenic exposure.

FIGURE 3.

Mees' lines less clearly visible on the toenails.

His blood pressure was 168/100 mmHg and he had left ventricular hypertrophy without signs of cardiac failure. On neurological examination, he had normal cognition. He had mild facial weakness. Diffuse atrophy of all limb muscles was seen, with flaccid weakness more pronounced in his legs (1/5 power) than in his arms (4/5 power) and areflexia. Sensory examination showed a symmetrical glove‐and‐stocking sensory loss for both spinothalamic (pinprick) and dorsal column (joint position sense and vibration sense) sensation. These signs were in keeping with peripheral sensory‐motor neuropathy. A sensory level consistent with spinal cord pathology was not found, but he did complain of urinary and fecal incontinence.

3. Methods (Investigations)

Nerve conduction studies showed demyelinating neuropathy with secondary axonal changes. Results of cerebrospinal fluid (CSF) cytochemical investigations showed a lymphocytic pleocytosis of 15 cells/μL, with no polymorphs. Protein was present in the CSF at a level of 3.03 g/L (reference range 0.1–0.4 g/dL) and the glucose level was 3.2 mmol/L. His blood glucose level was 5.7 mmol/L. No organism was cultured from the CFS. Type 3 oligoclonal bands were found in the CSF.

Magnetic resonance imaging (MRI) of the brain (Figure 4) and cervical spine (Figure 5) was performed to exclude cerebral and spinal cord lesions. No mass lesion or infective process was observed, but the MRI showed white matter hyperintensities suggestive of demyelination.

FIGURE 4.

Axial fluid‐attenuated inversion recovery (FLAIR) image of the brain showing multiple bilateral asymmetrical hyperintensities with no obvious restricted diffusion and no post‐contrast enhancement. These are features of possible demyelination/vasculitis with a vast differential as described below.

FIGURE 5.

Sagittal T1 with contrast of the cervical spine demonstrated contrast enhancement of the meninges ventral to the medulla and posterior to the spinal cord, but no compression or inflammatory response in the spinal cord.

With Mees' lines on the nails and the history of abdominal cramps 4 months before, the possibility of heavy metal poisoning was considered, in addition to GBS. Chronic, sub‐acute exposure was suspected due to the illicit substances he had been using over a number of years. Urine samples were sent to the National Health Laboratory Service (NHLS) in Braamfontein, South Africa, to test for heavy metals. The corrected arsenic level in his urine was 49.87 μg/g creatinine (reference range 0.0–26.5 μg/g creatinine). Other heavy metals (lead and thallium) were within normal limits. He was counseled about the diagnosis and the possibility that illicit drug use could have been the cause of his symptoms.

4. Conclusion and Results (Outcome and Follow‐Up)

Prior to referral to our tertiary hospital, the patient completed intravenous immunoglobulin therapy for the working diagnosis of GBS. With the demyelinating features on the nerve conductions and the history of ascending weakness, the initial management by the primary physician was justifiable. Given his extensive alopecia and young‐onset hypertension with left ventricular hypertrophy kept in mind, we considered the diagnosis of arsenic exposure.

The patient was advised to stop taking drugs and adhere to the newly started antiretroviral therapy. He was managed supportively. Chelation therapy was not given as he had not been using any drugs in the 3 weeks preceding his presentation to the neurology department and the 3 weeks he spent in our ward awaiting laboratory findings. The arsenic test results had a prolonged turnaround time. During this time, his condition did not deteriorate, and therefore, in addition to avoiding the potential side effects of chelating agents, this therapeutic approach was not considered. On referral to a primary care facility, he was able to mobilize from bed to wheelchair.

He was followed up regularly in 3‐monthly intervals and continued to improve clinically. At 1‐year follow‐up, he walked with crutches and had 5/5 power in his lower limbs, which were now spastic. These signs were in keeping with myelopathy rather than peripheral neuropathy, which was included in the differential diagnosis of his initial presentation. The clinical myelopathy was attributed to the HIV infection and possibly also to arsenic poisoning.

5. Discussion

Arsenic is toxic to humans. The four common ways of exposure are medicinal (melarsoprol), dietary, including drinking water, and industrial. Environmental arsenic may also be found in soil, especially in areas more prone to volcanic eruptions [1, 2].

It can be absorbed via different routes, most often via the gut, specifically the small intestine. Arsenic is absorbed in the bloodstream and may be taken up into both red and white blood cells. Arsenate (inorganic arsenic) is reduced to arsenite and then to monomethyl arsonate (MMA) and dimethyl arsenate (DMA) [3, 4]. The metabolite usually found in urine is DMA, which is excreted via the kidneys by the fifth day after exposure [3]. In chronic exposure, arsenic accumulates in multiple organs, including the lungs, liver, kidneys, heart, and nervous system. It may also accumulate in the hair and nails, which may be identified up to 14 days after exposure [1]. Diagnosing arsenic poisoning is difficult since serum levels have a rapid clearance rate. Therefore, analyzing urine, hair, and nail samples for elevated arsenic levels is the preferred diagnostic approach [5]. On review of chronic exposure to heavy metals, Koszewics et al. reported that four of their patients with peripheral neuropathy had urine levels of arsenic (As‐U) exceeding 35 μg/g creatinine, whereas four others had levels below that value [6]. Arsenic exposure may cause neurotoxicity via several mechanisms in both the peripheral nervous system and the central nervous system after crossing the blood–brain barrier. Neurotoxicity occurs due to abnormal lipid peroxidation, decreased acetylcholinesterase activity, increased oxidative stress causing mitochondrial dysfunction, thiamine deficiencies, and apoptosis. This in turn may cause cellular DNA damage and chromosomal aberrations. Arsenic exposure in the extracellular space may alter the glutamate and cystine balance, leading to microglia deterioration and death. The white matter changes on the MRI brain (Figure 4) itself have a vast differential diagnosis, but taking into account our patient's hypertension, HIV‐related vasculopathy as well as arsenic exposure may be considered [1, 3, 4, 7, 8].

Neurological complications of chronic arsenic exposure include a vast array of symptoms and signs ranging from headaches and sleep disturbances to severe peripheral neuropathy, memory loss, and dementia [1, 2, 9]. Other complications include diabetes mellitus, malignancies, cardiovascular disease, and hypertension [1, 10].

Peripheral neuropathy is common, and heavy metal poisoning is one of the possible etiologies, then called toxic neuropathy (TN). Arsenic exposure is known to mimic GBS in both chronic low‐dose exposure and higher‐dose poisoning [11]. Occupational and environmental factors may cause TN. It may be from oral intake due to poisoning or illicit drug use [6, 12]. Furthermore, it can be prescribed by a physician; for example, arsenic trioxide (ATO; As₂O₃) is a chemotherapeutic agent used in clinical practice in the treatment of acute promyelocytic leukemia and several other malignancies [13, 14].

The TN that develops due to chronic exposure is often not preceded by the typical multiorgan failure, and usually presents as distal, symmetrical axonal neuropathy with a slow onset and progression. An acute or sub‐acute demyelinating polyneuropathy may also develop 1 to 3 weeks after exposure [5]. One study described the sensory involvement as more consistent with axonopathy, and the motor involvement as a demyelinating neuropathy [6].

Heavy metal toxic neuropathies more commonly affect the motor nerves. In lead poisoning, the radial and peroneal nerves are predominantly involved [6, 12]. Koszewicz et al. found that patients with high levels of arsenic in the urine had more significant changes in vibration sense, and 48% of their patients also had symptoms indicative of autonomic nervous system involvement [6].

Arsenic is commonly found as an ingredient of ethnic Indian remedies, and reports describing diseases due to arsenic poisoning have been published. A case report described a 9‐year‐old patient who presented with progressive weakness after preceding diarrhea. She also had Mees' lines on her nails [5], which are commonly found in heavy metal poisoning such as arsenic [15].

The patient presented in this case report had no known industrial exposure to arsenic and drank tap water. His only possible exposure was the Rodger “herbal tea” he was taking. He infrequently ate fish and did not take fish oil supplements. The hyperintensities on the MRI brain of the patient might have been explained by the chronic hypertension that he had, possibly due to arsenic exposure, or from the HIV infection. This case highlights the importance of a thorough history, including a history of exposure to all possible illicit and over‐the‐counter drugs, and a thorough physical examination.

A thorough history and clinical examination are critical regardless of the presumed diagnosis. It should be kept in mind to check for Mees's lines in a patient presenting with peripheral neuropathy. Patients may have more than one reason for neuropathy; in our case, HIV could also have been a contributing factor.

Author Contributions

Carin Behrens‐van Tonder: conceptualization, data curation, methodology, writing – original draft, writing – review and editing. Liesl Smit: data curation, methodology, writing – review and editing.

Ethics Statement

All investigations were performed in accordance with the relevant guidelines and regulations. The Health Sciences Research Ethics Committee (HSREC) of the University of the Free State approved the publication of this case report (reference number UFS‐HSD2023/1899/2805).

Consent

Written informed consent was obtained from the patient for the publication of this case report and any accompanying images.

Conflicts of Interest

The authors declare no conflicts of interest.

Behrens‐van Tonder C. and Smit L., “Arsenic‐Induced Polyneuropathy Mimicking Guillain‐Barré Syndrome: A Conundrum,” Clinical Case Reports 13, no. 9 (2025): e70853, 10.1002/ccr3.70853.

Data Availability Statement

Anonymised data and findings of the investigations performed are available from the corresponding author upon reasonable request.