The causes of acquired 3rd nerve palsy

April 15, 2017

Among all cases of ocular misalignment from cranial nerve palsies, third nerve palsies are the most worrisome, because a subset of these cases is caused by life-threatening aneurysms. There is significant disagreement, however, regarding the true incidence of third nerve palsies and the relative incidence of the various etiologies. Studies conducted in the U.S. have not been population-based, and therefore may suffer from referral bias toward more severe disease.

John J. Chen, M.D., Ph.D., Chengbo Fang, M.D., David O. Hodge, Jonathan M. Holmes, M.D., Jacqueline A. Leavitt, M.D., and Brian G. Mohney, M.D., at Mayo Clinic's campuses in Rochester, Minnesota, and Jacksonville, Florida, turned to the Rochester Epidemiology Project (REP) database to help determine the population-based incidence and etiologies of acquired third nerve palsies. Their study was published in JAMA Ophthalmology in 2017.

The researchers searched the REP records for a diagnosis of third nerve palsy and reviewed those records to confirm the diagnosis. In confirmed cases, the cause of the third nerve palsy was determined. The researchers also documented details of the acquired third nerve palsy at presentation, including age, imaging that was performed, pupil involvement, ptosis, degree of ophthalmoplegia, presence of eye pain or headache, other neurological symptoms, recovery, and aberrant regeneration.

In all, the researchers identified 145 newly diagnosed cases of acquired third nerve palsy that occurred over a 37-year period in Olmsted County, Minnesota. The age- and sex-adjusted annual incidence of acquired third nerve palsy was 4 cases per 100,000. The annual incidence in patients older than 60 was greater than patients younger than 60, predominantly due to a large increase in microvascular third nerve palsies in older adults.

The most common causes of acquired third nerve palsy were:

  • Presumed microvascular (42 percent)
  • Trauma (12 percent)
  • Compression from neoplasm (11 percent)
  • Post-neurosurgery (10 percent)
  • Compression from aneurysm (6 percent)

Pupil involvement

Ten patients (17 percent) with microvascular third nerve palsies had pupil involvement, while pupil involvement was seen in 16 patients (64 percent) with compressive third nerve palsies. "Our primary goal was to confirm incidence and etiologies of third nerve palsies," says Dr. Chen. "A secondary outcome was confirmation of the incidence of pupil involvement in acquired third nerve palsies."

Overall, 62 of 145 patients (43 percent) with acquired third nerve palsies had pupil involvement at the time of presentation. Pupil involvement was seen in:

  • 71 percent of traumatic third nerve palsies
  • 71 percent of post-neurosurgical third nerve palsies
  • 64 percent of compressive third nerve palsies
  • 16 percent of microvascular third nerve palsies

Among compressive third nerve palsies, 33 percent of aneurysms had pupil involvement at presentation, while 81 percent of nonaneurysmal compressive third nerve palsies had pupil involvement. All three patients with posterior communicating artery aneurysm presented with pupil involvement, while all five patients with intracavernous sinus aneurysm initially presented with pupil-sparing third nerve palsies but then developed pupil involvement over time.

"The study provides a population-based incidence and etiologies of acquired third nerve palsy, which have demonstrated a higher incidence of microvascular and a lower incidence of aneurysmal third nerve palsies than previously reported. This likely reflects the true etiologic incidences because it was a population-based study and therefore does not suffer from inherent referral bias," says Dr. Chen.

"The incidence upsurges in the sixth decade of life associated with an increase in microvascular third nerve palsies. And while pupil involvement was more common in compressive lesions, pupil involvement was seen in some cases of microvascular third nerve palsies, and pupil sparing was seen in some cases of compressive lesions, including aneurysm."

For more information

Fang C, et al. Incidence and etiologies of acquired third nerve palsy using a population-based method. JAMA Ophthalmology. 2017;135:23.