Table 1.

Case definitions of encephalopathy following treatment with ivermectin*

Definite Case of Loa Encephalopathy
•	Encephalopathy in which brain tissue obtained by autopsy or by needle sampling has microscopic findings consistent with L. loa encephalopathy (vasculopathy with evidence of L. loa microfilariae as a likely etiology), and
•	Onset of Central Nervous System (CNS) symptoms and signs within 7 days of treatment with ivermectin; illness progressing to coma without remission.
Probable Case of Loa Encephalopathy
•	Encephalopathy (without seizures, usually with fever) in a person previously healthy and has no other underlying cause for encephalopathy, and
•	Onset of progressive CNS symptoms and signs within 7 days of treatment with ivermectin; illness progressing to coma without remission, and
•	Peripheral blood L. loa > 10,000 mf/ml pre-treatment or > 1,000 mf/ml within 1 month post-treatment or > 2700 mf/ml within 6 months of treatment; and/or L. loa microfilariae present in cerebrospinal fluid (CSF) within 1 month post-treatment.
Possible Case of Loa Encephalopathy
•	Encephalopathy (without seizures, usually with fever) in a person previously healthy and has no other underlying cause for encepahalopathy, and
•	Onset of progressive CNS symptoms and signs within 7 days of treatment with ivermectin; illness progressing to coma without remission, and
•	Semi-quantitative or non-quantitative positive (i.e. +, ++, +++) L. loa microfilariae in peripheral blood within 1 month post-treatment.
Encephalopathy of other known etiology
•	Encephalopathy with sufficient clinical information to determine an etiology other than L. loa (e.g. cerebral malaria)
Encephalopathy of unknown etiology
•	Encephalopathy (without seizures, usually with fever) in a person previously healthy and has no other underlying cause for encephalopathy, and
•	Onset of progressive CNS symptoms and signs within 7 days of treatment with ivermectin, and
•	Clinical and/or laboratory findings are inadequate to determine probable etiology.

*These definitions were adapted from those originally put forth, by a group of independent experts that consulted for the MDP in 1995 in the following ways: 1 the timeframe within which a case would be considered was extended from 5 to 7 days because a prospective study published in 1997 showed that the onset of symptoms may be as late as 7 days post treatment [12]; 2 the interval between ivermectin treatment and initial L. loa laboratory studies was shortened to 1 month since a later study had shown that L. loa microfilarial loads decrease by 96% of pre-treatment levels 1 month after a single standard dose of ivermectin [15]; 3 the thresholds for the quantitative L. loa laboratory studies were broadened to include samples taken 5 or 6 months post-treatment since several cases in Cameroon who were treated in peripheral health centers and had no laboratory studies performed initially, were subsequently evaluated in their villages by a team of clinicians sponsored by the national-level Ministry of Health; the figure of 2700 mf/ml at 6 months was derived from a calculation based on the finding that on average L. loa microfilarial loads are reduced by at least 73% 6 months after a single standard dose of ivermectin [19]; 4 the category of 'possible' L. loa encephalopathy was added to the list of presumptive diagnoses to better capture the reality of the field situation where most of the encephalopathic cases were treated in peripheral hospitals which were not equipped to perform lumbar punctures or quantitative L. loa microfilaremia studies until very recently.