Toxic oil timeline: diagnosing effects decades later.

Two decades after contaminated cooking oil caused widespread sickness in Spain, patients with so-called toxic oil syndrome (TOS) continue to report neurologic symptoms. Accurately assessing these symptoms--which include headache, insomnia, and muscle weakness--has been challenging, because the symptoms are numerous and tend to be vague. Standard clinical examinations have detected few or no problems, and patients have sometimes been accused of exaggerating or malingering. This month, a team led by Manuel Posada de la Paz of the Instituto de Salud Carlos III in Madrid provides the first quantitative evidence that TOS patients do indeed experience neurologic abnormalities [EHP 111:1326-1334].

In May 1981, Spanish health officials were puzzled and alarmed by the emergence of a severe, possibly novel respiratory illness. The outbreak, which occurred in Madrid and the northwestern Spanish provinces, affected 10,000 people and claimed at least 80 lives in the first month. Initial symptoms included fluid in the lungs, shortness of breath, fever, headache, rash, muscle pain, and a proliferation of eosinophils (a type of white blood cell). An infectious agent seemed implicated, but by mid-June epidemiologic studies revealed the cause to be cooking oil derived from aniline-denatured rapeseed oil. This oil had been produced for industrial uses but was illegally refined to remove the aniline and sold as pure olive oil. The Spanish government acted quickly to remove all suspect oil from the market, but TOS eventually affected at least 20,000 people and caused more than 300 deaths.

Even after the cause was identified, the crisis continued. TOS comprises three phases: the early acute phase, an intermediate phase involving neurologic complaints and intense muscle pain, and, for approximately 60% of victims, a chronic phase marked by motor and sensory nerve disorders and muscle pain and cramping. Researchers strongly suspect that unknown toxic compounds created during refining triggered autoimmune disease.

In general, the difficulty in assessing TOS-related neurologic symptoms arises from the vagueness and subtlety of those symptoms. A possible solution rests with quantitative neurologic testing methods that have been developed since the late 1980s and used to detect subtle nerve damage associated with other diseases. These neurobehavioral tests include computerized examination of the central, peripheral, and autonomic nervous systems and use of a "vibrotactile threshold" as a measure of large myelinated nerve fiber function. This study was the first time such tests have been used with TOS patients.

The researchers recruited a random sample of TOS patients who lived in the Alcorcon locality of Madrid province in 1981 and assembled an age- and sex-matched referent group from the same area. All participants completed a questionnaire covering neurologic symptoms, environmental exposures, demographics, and other factors. Participants also underwent clinical examination and completed neurobehavioral testing.

Analysis of the neurobehavioral data revealed significant differences between the groups. The TOS group had higher incidences of muscle cramps and spasms; abnormal sensations such as numbness, burning, and paresthesias; loss of strength; diminished sensitivity to stimulus (hypoesthesias); poor coordination; headache; sleep disturbances; and memory loss. Female TOS patients over 35 were most affected, and some group differences (such as hypoesthesias) were significant only for women. The standard clinical neurologic examination did not reveal any differences aside from increased upper-limb pain and diminished lower-limb sensation in the TOS group. Questionnaire data uncovered no significant differences in neurologic history between the groups.

The researchers suggest that quantitative neurologic testing could help track symptom development over time, not only with TOS but in other hard-to-document neurologic diseases as well.