Annals of Neurosciences, Vol 14, No 4 (2007)

Annals of Neurosciences, Volume 14, Issue 4 (October), 2007

Case Report


Singh MP*, Agrawal V*, Shukla R** Verma S***

*Senior Residents, **Professor, ***Research Associate Department of Neurology, CSMMU.

Corresponding author:
Dr. Rakesh Shukla
Professor of Neurology
CSM Medical University, Lucknow 226003
(Recieved on 10.10.2007)


Polyneuropathies due to toxins continue to pose a challenge to the medical profession. Early suspicion of the condition, correct identification of the toxin and timely institution of therapy is not only life saving but can also greatly reduce the morbidity burden of the condition. We report six cases (2 females, 4 males) belonging to the same family and presenting with similar features of an acute to subacute onset, symmetrical, predominantly distal, graded, painful, sensori-motor polyneuropathy. All these patients complained of recurrent episodes of vomiting which started within 30 minutes to two hours of ingestion of home cooked vegetarian meal. After a variable period of 2–7 days the symptoms of polyneuropathy appeared. Electrophysiological studies demonstrated an axonal type of sensori-motor polyneuropathy. The temporal onset of symptoms, involvement of several individuals at the same time and a consistent and similar pattern of clinical findings were features highly suggestive of a toxin etiology. Using a structured and a logical approach in the background of the characteristic clinical picture the diagnostic possibilities were significantly narrowed down. Since the patients presented late and due to financial and technical constraints all tests could not be performed the toxin could not be confirmed.

Key Words: Arsenic, Chelating agents, Polyneuropathy, Toxin.


There are four well recognized sources of neurotoxic disorders-pharmaceutical agents, biological agents (animal, botanical or bacterial products), occupational or environmental chemical exposure, and self administration of a toxin as suicide, abuse or homicide (1). Toxin is the likely etiology of a neurological disorder when there is temporal onset of symptoms, clustering of a similar type of illness, clinical features which display a consistent pattern and correspond to previous known cases and when the presence of a suspected agent is confirmed by environmental or clinical chemical analysis (1).

Polyneuropathy is one of the most common reaction of the nervous system to toxins. Neurotoxic agents may produce peripheral neuropathy by distal axonal degeneration (axonopathy), nerve cell body degeneration (neuronopathy), or primary demyelination (myelinopathy). Till date 49 agents have been identified which are capable of producing polyneuropathy (2). Most of the toxic neuropathies present clinically with length-dependent sensorimotor or purely sensory deficits. Presence of a large number of toxins and an almost similar clinical presentation in the majority necessitates knowledge about the prevalent toxins and their clinical spectrum, which should then be coupled with a structured approach to significantly narrow down the diagnostic possibilities.

Case Reports

A twenty one year old housewife, was admitted in the department of neurology with complaints of recurrent episodes of vomiting starting within 1–2 hours of food intake and lasting for 5 days, six weeks prior to her admission. Six to eight days after the onset of vomiting she developed tingling and numbness in all four limbs which started distally from the lower limbs was symmetrical and gradually progressed upwards over the next week to reach the level of knees in the lower limbs and wrists in the upper limbs. This was associated with dull poorly localized pain in all four limbs. Eight to ten days after the onset of vomiting she developed weakness in all four limbs which progressed over next two weeks to cause both distal and proximal weakness in lower limbs and only distal weakness in the upper limbs. There was also history of development of dry scaly skin over both lower limbs. There was no history of diarrhea, constipation, hematemesis, malena, excessive lacrimation or salivation, autonomic dysfunction, cranial nerve, bladder bowel involvement, presence of hypo or hyper pigmented skin patches, alteration or loss of consciousness or seizures.

General examination revealed normal vitals, presence of pallor and hyperkeratosis over the lower limbs. Nervous system examination showed normal higher mental functions and cranial nerves. Hypotonic weakness in all four limbs with absence of distal deep tendon reflexes was present. A pansensory, circumferential, graded sensory loss in glove and stocking distribution was evident on sensory examination. Cerebellar and extra-pyramidal system were within normal limits. There were no signs of meningeal irritation and systemic examination did not reveal any abnormality. Investigations revealed anemia with hemoglobin of 10.3 gm%. Blood sugar levels, serum electrolytes, liver and renal function tests were within normal limits. ELISA for HIV 1 & 2 was non-reactive. Hectrophysiological findings were suggestive of a sensori-motor (predominantly sensory) axonal degenerative type of polyneuropathy.

Further questioning revealed that all other family members were similarly affected but to a variable degree. (Table 1 & 2) Investigations of these patients revealed anemia in patient 1 (Hb 10.3 gm%) and 3 (Hb 9.3gm%) and hyperkeratosis in patients 1, 2 & 3. Rest of the findings were similar to that in patient 1 (index case). All of them were engaged in different occupations and there was no history of any drug intake (allopathic, ayurvedic or folk remedies), occupational or environmental exposure to solvents, toxic dust or fumes or similar disorder in the co-workers or neighbours.

Since all patients presented with a (variable degree) similar type of illness ie acute-subacute onset, symmetrical, graded predominantly distal lower motor neuron type of sensori-motorquadriparesis without bulbar or bladder bowel involvement and since the basic tenets of a neurotoxic illness were being fulfilled viz- clustering of a similar type of illness, temporal onset of symptoms and a consistent pattern of clinical features a diagnosis of probable toxin induced polyneuropathy was considered.

Urine arsenic estimation was done at ITRC, Lucknow. The levels of arsenic ranged between 20–35 micrograms/Lt (normal levels < 50 micrograms/Lt).


Till date 49 toxic agents are known to cause peripheral neuropathy (2). Out of these 22 agents are pharmacological drugs and 19 agents require chronic low level long term exposure in an environmental or occupational setting to produce the characteristic illness. Since none of these patients were taking any pharmacological drugs, were engaged in different occupations, and were not working or residing in or near a industrial area these 41 agents could be excluded and the list was narrowed down to 8 agents. In view of patients histories, clinical features and investigations which revealed a acute-subacute, painful, sensorimotor axonal degenerative type of peripheral neuropathy the list was further narrowed down to a list of 3 likely etiologies which included arsenic, thallium and triorthocresyl phosphate (TOCP).

Though all three of them present with the above mentioned features, intoxication with thallium was unlikely because with thallium there is relative preservation of deep tendon reflexes, alopecia is a predominant feature and cranial nerve involvement is common which were not seen in any of our patients. Poisoning with TOCP was less likely as it is well known to produce characteristic preceding cholinergic symptoms, usually occurs in epidemic form, does not cause hyperkeratosis and neuropathy due to it improves over 1–2 months and is replaced by spasticity. Points in favour of arsenic were that apart from producing a similar type of illness, it is easily available, is colorless, odorless and tasteless, can be easily mixed with food and is well known to produce hyperkeratosis. Also there was no symptom or sign which could not be explained with arsenic toxicity or which required an alternative diagnosis.

Their 24 hour urine samples were sent for arsenic estimation.

Levels ranged between 20–35 microgramsAt. (Normal levels < 50 micrograms/lt). This could be explained by the fact that arsenic is excreted in urine in three different phases with half times of 2 hours, 8 hours and 8 days (3) and urine levels remain high for 4–5 weeks after a single massive dose. Due to financial and technical constraints a complete toxicological screening examination could not be performed and arsenic levels in nail and hair could not be determined. As definite diagnosis of arsenic toxicity could not be made, and as arsenic levels in the urine were already less than 200 micrograms/litre, chelating agents were not given (as per American Medical Association guidelines). The inherent toxicity of the chelating agents was another reason not to use them. Follow up of the patients after one month showed no significant improvement.

Though the etiological agent could not be confirmed with investigations, probable toxin induced polyneuropathy due to arsenic still remains the most likely diagnosis.

Though there is abundance of literature from the Indian subcontinent regarding chronic low level long term exposure to arsenic in epidemiological studies due to ground water contamination or environmental pollution (4,5,6,7) and acute or chronic poisoning in the form of accidental or deliberate poisoning in single individual, data regarding acute toxicity affecting all members of the family is sparse. (8). In contrast to these studies all members of the family were affected in our series, none of the patients developed Mee's lines and none of them improved on subsequent follow up.

These cases merit attention because they emphasize that in case of temporal onset of symptoms and clustering together of a similar illness one should strongly suspect toxin as the likely etiology. They also show that a single neurotoxic agent can produce variable degree of dysfunction in different individuals which may depend upon age, weight, renal and liver integrity etc. It shows that Mees lines are not universally associated with arsenic toxicity. It also reveals that knowledge about prevailing toxins, their clinical spectrum coupled with a structured and logical approach significantly narrows down the diagnostic possibilities which is especially valuable in a country like India where due to financial or technical constraints not all tests can be performed.

Table-1. Demographic data and temporal profile of symptom evolution.

Features Patient-1 Patient-2 Patient-3 Patient-4 Patient-5 Patient-6
Age/sex 21 F 60 M 56 F 28 M 22 M 18 M
Relation index father mother brother brother brother
Occupation Housewife Farmer Housewife Taxi-driver Manual labourer Helper cook
First symptom Vomiting- started within 15 min to 2 hrs of food intake and persisted from 2–12 days
Probable source Food/vegetarian/home-cooked/prepared by mother/No tinned, preserved food items were used No new oil or food grains were used.
Tingling & numbness Started within 5–8 days of onset of vomiting Progressed over next 2–15 days
Weakness Started within 8–14 days of onset of vomiting Progressed over next 8–20 days

Table-2. Summary of the main clinical features and investigations in all family members.

Clinical Features/Investigation Patient-1 Patient-2 Patient-3 Patient-4 Patient-5 Patient-6
Pallor + +
Hyperkeratosis + + +
Higher Mental Functions WNL WNL WNL WNL WNL WNL
Motor Hypotonie weakness with absence of distal deep tendon reflexes in all. Pt 3 most severely affected, Pt 4 least severely affected
Sensory Pansensory, circumferential and graded sensory loss in glove and stocking distribution. Pt 3 most severely affected, Pt 4 least severely affected
Cerebellar and extrapyramidal were within normal limits. No signs of meningeal irritation. Systemic examination within normal limits. No evidence of Mees line, hair loss, autonomic dysfunction or other cutaneous markers.
Routine inv. Anemia in pt1 (Hb 10.3 gm%) and 3(Hb 9.3 gm%). Blood sugar levels, serum electrolytes, liver and renal function tests within normal limits in all. ELISA for HIV 1 & 2 was non reactive. ECG did not reveal any significant abnormality.
Electrophysiology Findings suggestive of sensori-motor (predominantly sensory) axonal degenerative type of polyneuropathy.
Toxicology Level of arsenic in urine (24 hr urine samples) ranged between 20–35 micrograms/lt. (Normal levels < 50 micrograms/lt)


1. Schaumburg HN. Human Neurotoxic Disease in Experimental & Clinical Neurotoxicity. Spencer PS, Schaumburg HN eds. Oxford University Press, MA, New York . 2000: 55–82.

2. Schaumburg HH. Classification of peripheral nervous systems disorders. In: Disorders of Peripheral Nerves. Schaumburg HN, Berger A, Thomas PK eds. FA Davis, Philadelphia. 1994: 11–2.

3. Mealey J Jr, Bronwell GL, Sweet WN. Radioarsenic in plasma, urine normal tissue & in cranial neoplasms, distribution & turnover after intravenous injection in man. Arch Neurol Psychiat 1989; 81: 30.

4. A study of ground water contamination by arsenic in the residential areas of Calcutta due to industrial pollution. Environ Pollut 1993; 80: 57–65.

5. Dutta DV, Kaul MK. Arsenic content of drinking water in villages in Northern India. A concept of arsenicosis. J Assoc Physicians India 1976; 24: 599–605.

6. Chatterjee A, Mukherjee A. Hydrogeological investigations of ground water contamination in South Calcutta. Sci Total Environ 1999; 225: 249–62.

7. Environmental pollution and chronic arsenicosis in South Calcutta. Bull World Health Organisation 1992; 670: 481–85.

8. Jha S, Dhanuka AK, Singh MN. Arsenic poisoning in family. Neurology India 2002; 50: 364–5.