Agency for Toxic Substances and Disease Registry 
Case Studies in Environmental Medicine (CSEM) 

Cholinesterase Inhibitors
Including Insecticides and Chemical Warfare Nerve Agents
Part 7: Organophosphorus Ester-Induced Chronic Neurotoxicity (OPICN)

Learning Objectives

Upon completion of this section, you should be able to describe:

• Our current level of understanding about the association of OPICN and asymptomatic exposures to cholinesterase inhibitors.
• Currently recommended treatment options.

Introduction

Organophosphorus ester-induced chronic neurotoxicity (OPICN) --- also called chronic organophosphate-induced neuropsychiatric disorder (COPIND) --- is a set of long-term, persistent, chronic neuropsychiatric findings that some have attributed to cholinesterase inhibitor toxicity.

Signs and Symptoms

Some of the signs and symptoms that have been ascribed to this condition include (Jamal 1997; Abou-Donia 2003)

• Apathy
• Decreased visual memory
• Impaired vigilance
• Reduced abstract reasoning
• Anxiety
• Depression
• Increased social isolation
• Reduced fine motor coordination
• Confusion
• Dizziness
• Insomnia
• Reduced vibrotactile sensitivity
• Decreased academic skills
• Emotional lability
• Irritability
• Short-term memory deficits
• Decreased verbal attention
• Fatigue
• Problems with concentration
• Slowing of reaction time

Controversy

There is a great deal of debate surrounding the subject of Organophosphorus ester-induced chronic neurotoxicity (OPICN).  (Jamal 1997; Bateman 1999; Vale 1999; Colosio, Tiramani et al. 2003) It has been argued that the condition can follow either an acute, symptomatic exposure or repeated, asymptomatic exposures. (Abou-Donia 2003)

A number of the key studies supporting this argument, particularly those relating to asymptomatic exposures, have been criticized on methodological grounds.  (Bateman 1999; Vale 1999; Colosio, Tiramani et al. 2003) In particular, determination of exposure in most studies has been based on recall rather than on objective measurements. This method of assessing exposure has not been shown to be very reliable. (Boyer, Templin et al. 1995) In addition, a number of the studies have been based on recall of exposures to pesticides in general, rather than specifically to cholinesterase inhibitors.

Some have pointed out that neuropsychiatric findings following severe acute exposures are consistent with damage from seizures and hypoxia, and may not represent a specific toxic effect. (Vale 1999) However, current evidence cannot rule out such a toxic effect, and better-designed studies are needed to resolve the debate. (Colosio, Tiramani et al. 2003)

Treatment

No specific treatment has been identified.

Key Points

• Studies suggesting that OPICN result from asymptomatic, chronic exposure to cholinesterase inhibitors have suffered from methodological problems.
• Clinical findings attributed to OPICN are consistent with brain damage due to hypoxia and seizures and my not represent a specific toxic effect.
• No specific treatment for OPICN has yet been identified.

Progress Check