| domain | key finding/statistic | evidence type and population | source/date/URL | caveat |
|---|---|---|---|---|
| Acquired etiology | In 633 patients with isolated oculomotor nerve palsy, etiologies were microvascular 26.5%, vascular anomalies 17.4%, neoplastic 13.6%, inflammatory 12.5%, idiopathic 9.5%, traumatic 8.4%; congenital 4.1%; infectious 1.9%. MRI was performed in 96.1%; incidence showed peaks before age 10 and in the 60s; men:women 1.3:1. (pqac-00000004, pqac-00000022, pqac-00000023, pqac-00000024) | Retrospective referral-hospital cohort; human clinical; n=633 isolated CN III palsy cases | Kim et al., *Eur J Neurol* (Feb 2024), doi:10.1111/ene.16261, https://doi.org/10.1111/ene.16261 | Referral bias likely; single-center retrospective study; incidence estimate cited in paper but not population-based within this cohort. |
| Recovery/prognosis | In 65 CN III palsy cases, ischemic and compressive etiologies were most common (24.6% each). Complete recovery rates: ischemic 9/16, compressive 1/16, trauma 5/13, inflammation 6/10, idiopathic 2/10. Better long-term outcome associated with symptom onset <7 days and isolated nerve involvement. (pqac-00000001, pqac-00000002) | Retrospective tertiary-hospital cohort; human clinical; n=65 CN III palsy cases within larger ocular motor palsy study | Srimanan & Panyakorn, *Clin Ophthalmol* (Feb 2024), doi:10.2147/OPTH.S449127, https://doi.org/10.2147/OPTH.S449127 | Single-center; mixed referral population; prognostic modeling includes all third/fourth/sixth nerve palsies, though CN III data are reported separately. |
| Congenital genetics / MRI | In 122 CCDD patients from 96 families, all had restrictive eye movements; 47.9% had multiple congenital malformations. MRI in 94 patients showed cranial-nerve hypoplasia in essentially all except HGPPS cases; 17.0% had additional craniocerebral malformations. WES found 10 pathogenic variants in KIF21A, TUBB3, and CHN1 across 43 families; novel variants included KIF21A p.F355S, TUBB3 p.S78T, CHN1 p.H217R. In CFEOM, mutation detection was 63.6% (42/66), with KIF21A 73.8% and TUBB3 26.2% among solved CFEOM probands. (pqac-00000005, pqac-00000006, pqac-00000007, pqac-00000008) | Cohort with MRI + whole-exome sequencing; human congenital cranial dysinnervation disorders; n=122 | Jia et al., *Orphanet J Rare Dis* (Dec 2022), doi:10.1186/s13023-022-02582-5, https://doi.org/10.1186/s13023-022-02582-5 | CCDD cohort, not isolated acquired CN III palsy; data most directly inform congenital oculomotor dysinnervation/CFEOM. |
| Developmental mechanism | Pathogenic TUBB3 missense variants alter microtubule dynamics and cranial axon guidance; pathogenic KIF21A missense variants alter kinesin function and can phenocopy TUBB3 variants. CFEOM reflects hypoplasia of the oculomotor nerve with failed superior-division innervation of levator palpebrae superioris and superior rectus. (pqac-00000025, pqac-00000026, pqac-00000027) | Review synthesizing human genetics, MRI, in vitro and mouse studies | Puri, Barry & Engle, *Front Neurosci* (4 Aug 2023), doi:10.3389/fnins.2023.1226181, https://doi.org/10.3389/fnins.2023.1226181 | Mechanistic synthesis, not a treatment or epidemiology study; focuses on congenital disease biology rather than common acquired palsy. |
| Additional causal gene | Three unrelated probands with CFEOM had novel heterozygous TUBA1A missense variants: c.1216C>G p.His406Asp, c.467G>A p.Arg156His, c.1193T>G p.Met398Arg. MRI showed small oculomotor-innervated muscles and asymmetric caudate/lateral ventricular abnormalities; 2/3 also had malformations of cortical development. (pqac-00000028, pqac-00000029) | Primary sequencing study; human congenital CFEOM/tubulinopathy; n=3 probands | Jurgens et al., *Eur J Hum Genet* (1 Mar 2021 online), doi:10.1038/s41431-020-00804-7, https://doi.org/10.1038/s41431-020-00804-7 | Very small case series; supports rare congenital etiology only. |
| Clinical trial / acupuncture | Randomized parallel triple-masked interventional trial in ONP; estimated enrollment 177. Compared ocular electroacupuncture vs ocular acupuncture vs sham acupuncture over 6 weeks; primary outcome was change in ocular motor nerve function subscale at 6 weeks. Last known status: RECRUITING; overall registry status listed as UNKNOWN. (pqac-00000015, pqac-00000016) | ClinicalTrials.gov registry entry; interventional; adults with complete ONP | NCT03099447, first posted 4 Apr 2017, https://clinicaltrials.gov/study/NCT03099447 | Registry record only; no posted results in provided context; efficacy remains unproven here. |
| Clinical trial / retrospective acupuncture cohort | Observational retrospective cohort of ocular motor nerve palsy treated by ocular acupuncture; estimated enrollment 900; includes oculomotor, trochlear, and abducens palsy. Primary outcome: investigator-assessed clinical efficacy rate; last known status NOT_YET_RECRUITING, overall status UNKNOWN. (pqac-00000017) | ClinicalTrials.gov registry entry; observational retrospective cohort | NCT03461809, first posted 12 Mar 2018, https://clinicaltrials.gov/study/NCT03461809 | Mixed ocular motor palsies; registry-only description; no posted outcomes in context. |
| Clinical trial / genetics registry | Large observational genetics study of strabismus/CCDDs and related anomalies; estimated enrollment 20,000; recruiting. Includes Third Nerve Palsy, Fourth Nerve Palsy, Sixth Nerve Palsy, CFEOM, DRS, Möbius, HGPPS, and related phenotypes; biospecimens include DNA. Primary outcome is gene discovery/characterization. (pqac-00000018, pqac-00000019) | ClinicalTrials.gov registry entry; observational genetics cohort | NCT03059420, recruiting; first posted 23 Feb 2017; updated 11 Feb 2026, https://clinicaltrials.gov/study/NCT03059420 | Broad congenital cranial dysinnervation/strabismus study, not specific to isolated acquired CN III palsy; observational, not therapeutic. |


*Table: This table compacts the highest-yield evidence identified for oculomotor nerve palsy, separating common acquired clinical data from rarer congenital genetic mechanisms and ongoing registry studies. It is useful as a source map for etiology, prognosis, molecular biology, and current trial activity.*