What are reported human CSF concentrations of ivermectin in cases of neurotoxicity, and which studies measured them?

1. What the clinical case literature actually measured: detection, not a concentration series

A systematic review of post‑marketing and case‑report literature identified a small series of serious neurological adverse events temporally related to ivermectin and specifically notes that in one human case investigators found the drug present in brain tissue, supporting CNS exposure in that individual, but the publication does not provide an array of numeric CSF concentration values across cases ^[1].

2. Surveillance reports: clinical signal without quantitative CSF data

Pharmacovigilance reviews and descriptive studies from mass‑drug‑administration programs and national reporting systems document encephalopathy, coma, and other central and peripheral neurologic disorders after ivermectin use and often examine co‑factors such as Loa loa microfilarial density, yet these surveillance datasets focus on clinical and parasitological metrics rather than reporting serial human CSF ivermectin concentrations ^{[5] [6]}.

3. Genetic and drug‑interaction explanations measured by sequencing and pharmacology, not CSF assays

Investigators have linked rare fatal or severe human cases to potential ABCB1 (mdr‑1/P‑gp) dysfunction and in at least one pediatric encephalopathy case performed ABCB1 sequencing, implicating transporter defects that would theoretically permit CNS accumulation of ivermectin, but that report centers on genetic and clinical findings rather than providing CSF drug levels ^[7].

4. What animal and drug‑interaction experiments measured about CNS levels

Controlled animal and interaction studies give the clearest quantitative picture: P‑glycoprotein inhibition or genetic knockout increases brain concentrations of ivermectin in preclinical models, and coadministration of P‑gp inhibitors such as verapamil produced roughly threefold increases in brain ivermectin concentration at 2 hours postdose in experimental settings — findings used to infer human risk though they are not human CSF measurements ^{[4] [3]}.

5. Mechanistic consensus and why CSF measures are scarce

The dominant mechanistic explanation across reviews is that human blood–brain barrier P‑glycoprotein function normally excludes ivermectin from the CNS, and altered function (due to ABCB1 mutations or interacting drugs) or extremely high dosing can permit CNS penetration and neurotoxicity; most human reports therefore document clinical effect, co‑medications, Loa loa burden, or genetic sequencing rather than systematic CSF drug quantitation ^{[2] [5] [8]}.

6. Balanced interpretation and limits of the available reporting

Taken together, the literature provided establishes that ivermectin has been detected in at least one human CNS specimen in the context of neurotoxicity and that preclinical models quantify brain accumulation when transport is impaired, but the reviewed sources do not present a series of numeric CSF ivermectin concentrations from multiple human neurotoxicity cases — a gap that prevents establishing typical CSF concentration ranges associated with toxicity in humans from these reports alone ^{[1] [4] [3]}.

7. Implications for clinicians and researchers

The available evidence indicates clinicians should consider transporter interactions, ABCB1 dysfunction, and high Loa loa microfilarial loads when evaluating post‑ivermectin neurologic syndromes and that focused studies measuring human CSF and brain ivermectin concentrations in confirmed neurotoxicity cases would be required to define toxic CSF thresholds — a need implicit in the case literature but unmet in the cited reports ^{[5] [6] [7]}.