Letter to the Editor: A Case of Horner's Syndrome and Delayed Polyneuropathy Due to Dichlorvos Intoxication

To the Editor:

The delayed polyneuropathy after organophosphate (OP) intoxication is reported following exposure to some OPs, including dichlorvos (1,2). OP-induced delayed polyneuropathy (OPIDP) is usually subacute and occurs within 1–3 weeks after the initial symptoms (3), with signs including foot drop, weakness of the intrinsic hand muscles, absent tendon jerks and weakness of flexors. Paralysis is usually limited to the distal muscles of the limbs and the condition affects predominantly motor neurons (4), with electrophysiological findings of axonal neuropathy.

Horner's syndrome can be caused by injury to sympathetic nervous system or may be a complication of contraceptive pills (5,6), but we have not found Horner's syndrome associated with OP intoxication in the literature. We report the case of a 45-year-old man who developed OPIDP accompanied by miosis and ptosis of right eye after ingestion of dichlorvos.

A 45-year-old man drank approximately 30 millilitres of a commercial emulsion comprising 55% 2,2-dichlorovinyl dimethyl phosphate (dichlorvos). He was treated with atropine and pralidoxime and transferred to our emergency department following 2 days in another facility. On admission to our department, the patient was drowsy, exhibited bilateral miosis and was only slightly responsive to deep pain. He could not breathe spontaneously, so artificial ventilation was established via an endotracheal tube. Atropine and pralidoxime chloride were administered and ventilator support was carried out. Venous access was achieved via a right subclavian catheter. The patient's serum cholinesterase was 47 IU/L (normal = 4250–7250 IU/L). His mental status improved progressively over the ensuing 6 days, and the patient was weaned from the ventilator after 21 days. However, 30 days after intoxication, he began to complain of weakness of his legs and difficulty standing. He exhibited severe bilateral weakness of the lower extremities and moderate bilateral weakness of the forearms. Right-sided unilateral ptosis was noted. Direct and indirect light reflexes were intact in both eyes. Pain, temperature, tactile, vibration and pressure senses were normal. Electrophysiological studies (on day 40 after ingestion) revealed a symmetrical pure motor neuropathy. Mixed polyneuropathy was detected in both legs and symmetrical axonal polyneuropathy was detected in both arms. The sensory nerve conduction test was normal.

Ptosis of the right eye was noted; pupil size in the right and left eyes was about 2–3 mm and 3 mm, respectively. A repetitive nerve stimulation test and serum acetylcholinesterase receptor antibody levels performed to rule out myasthenia gravis were normal. A darkroom test was performed to evaluate the equivocal anisocoria. In the dark room, the right pupil was fixed, but the left dilated to 4 mm (Fig. 1). The patient was followed for 6 months and during that time experienced a slight improvement of his motor neuropathy and ptosis.

FIG. 1. Pupil size: showing anisocoria aggregation in dark-room conditions. A) Right pupil size 2–3 mm, left pupil size 3 mm in bright-room conditions. B) Left pupil size 4 mm in dark-room conditions.

Organophosphate esters are used as insecticides, petroleum additives, modifiers of plastics, lubricants, antioxidants and flame-retardants. They may be absorbed via the skin or the respiratory and gastrointestinal tracts (7). The lipid solubility of OPs allows them to penetrate the central and peripheral nervous systems.

The characteristic manifestations of organophosphate intoxication can be divided into three phases: cholinergic crisis, intermediate syndrome and organophosphate-induced delayed polyneuropathy (OPIDP) (8). Intermediate syndrome occurs in up 20–50% of cases depending on the severity of poisoning, its duration and the type of organophosphate compound ingested. The symptoms occur usually 24–96 h after the poisoning, on recovery from the cholinergic crisis. Intermediate syndrome predominately affects muscles innervated by the cranial nerves, neck flexors, proximal muscles of the limbs and the respiratory muscles (4). OPIDP is usually subacute and occurs within 1–3 weeks after the initial symptoms (5). OPIDP-associated signs include foot drop, weakness of the intrinsic hand muscles, absent jerks and weakness of the knee flexors. Paralysis is usually limited to the distal muscles of the limbs and a predominantly motor neuropathy (4). Dichlorvos induces such a delayed polyneuropathy (2).

Electrophysiological changes are usually detected concurrently with the onset of the clinical symptoms and signs of OPIDP. When performed during the symptom-free period between the disappearance of cholinergic toxicity and the clinical onset of OPIDP, the electrophysiological examination yields normal results (9). Electrodiagnostic studies of OPIDP demonstrate axonal neuropathy with acute and chronic denervation in the distal, and occasionally proximal, limb muscles. Our patient complained of flaccid paralysis of both lower limbs at 4 weeks after recovery from the cholinergic symptoms. In our case, both the upper and lower limbs were affected symmetrically. We observed axonal changes in the upper limbs, and predominantly distal motor polyneuropathy in the legs. We believed that dichlorvos-induced delayed polyneuropathy had occurred. However, unusually, right ptosis and anisocoric pupils were also observed in the OPIDP phase.

Horner's syndrome occurs following lesions of the brain, cervical cord, spinal root at T1, and the sympathetic chain, which include the carotid artery and cranial nerves IX, X, and XI. Horner's syndrome has been reported after central vein catheterization, complication contraceptive pills, and infection (5,6). Horner's syndrome developed shortly after central catheterization, but our patient developed ptosis 4 weeks following right subclavian catheterization. We suggest that the cause of Horner's syndrome in this case may be the organophosphate, because the symptoms developed only during OPIDP phase. Cranial nerves are spared in OPIDP and in most toxic neuropathy. We feel that lesions of the sympathetic chain caused our patient's symptoms. The vulnerability of nerve fibres is directly related to axonal length and diameter, long and large-diameter fibres being more susceptible than short and small-diameter ones (10). We are unsure why the right side was involved, but suggest that in this case the right sympathetic chain was more vulnerable due to the size of its axons, or to other pre-existing asymmetry. There is no evidence, however, to show that the diameter or length of right sympathetic chain axons is larger, nor is there evidence of subclinical damage to the unaffected side.

The patient was followed for 6 months. At 2 months, he could walk by himself but occasionally needed assistance, and his ptosis and anisocoria had not improved. At 6 months, his ptosis was slightly improved, and we hope to extend follow-up to 1 year so that results can be compared directly with those of previous studies.

In conclusion, Horner's syndrome may be induced by organophosphate intoxication accompanied with OPIDP.