Pupil-Involving Third Cranial Nerve Paresis at High Altitude

Neurological conditions can occur at altitude that fall outside the usual definition of altitude sickness (Basnyat et al., 2004). Sixth cranial nerve palsy is a well-recognized entity occurring at high altitude (Virmani and Seamy, 1993; Shlim et al., 1995) in both association and independent of the syndrome of high-altitude cerebral edema (HACE). The palsy usually resolves in several weeks to months when unrelated to HACE (Murdoch, 1994).

Isolated 7th and 12th cranial nerve palsies have also been reported to occur at high altitude that improve with descent (Basnyat, 2001). These cranial nerve palsies are hypothesized to occur due to altitude-induced increased intracranial pressure and/or brain swelling with injury to the sixth nerve as it enters the cavernous sinus through the canal of Dorello or compression of the other cranial nerves as they course through the foramina of the skull base. This report describes a case of pupil-involving third nerve paresis occurring at altitude.

A 55-year-old woman flew from Dallas, Texas (elevation 176 m) to Breckenridge, Colorado (elevation 2900 m). She then went hiking at 3600 m. She felt light-headed with mild nausea, but did not have headache. The next afternoon in Breckenridge she began experiencing binocular vertical diplopia worse on left gaze and mild headache. There was no neck pain, loss of vision, weakness, numbness, or facial droop. She descended the next day to 1650 m and was seen by a neurologist. Blood pressure was 134/80 with pulse of 87 bpm and oxygen saturation of 92%. Visual acuity was 20/20 in each eye. She was noted to have 4 mm of right ptosis, anisocoria worse in bright illumination with a dilated right pupil with some reactivity, and decreased infraduction, supraduction, and adduction of the right eye. The rest of her neurological examination was unremarkable.

A basic metabolic panel and complete blood count were normal, with white blood count of 8.7 10⁹/L, hemoglobin 13.5 g/dL, hematocrit 41.0%, platelets 367 10⁹/L, and the erythrocyte sedimentation rate was 16 mm/h. Computed tomography (CT) of the brain without contrast, CT angiogram of the head and neck (with 0% carotid stenosis noted bilaterally), magnetic resonance imaging with and without contrast, and electrocardiogram were all normal. She opted to forego lumbar puncture.

She returned to Dallas 2 days later and was seen again by a neurologist. The examination was unchanged. I saw her 1 week later. Notably I had seen her 3 months earlier when she had a completely normal examination. At this visit, however, although vision remained 20/20 without correction, her right ptosis had improved slightly, her pupils were only mildly anisocoric with 0.5 mm difference in both bright and dim illumination (although the larger right pupil was slightly sluggish in response to light compared with the left), and her diplopia had improved such that she only was diplopic when looking down and left. The rest of her complete ophthalmological examination, including dilated ophthalmoscopy, was normal.

Additional laboratory work included angiotensin converting enzyme, C-reactive protein, folate, vitamins B1 and B12, hemoglobin A_1c, p-ANCA, c-ANCA, and West Nile virus antibodies IgG and IgM, all of which were negative. An autoimmune panel did show a 1:320 antinuclear antibody (ANA) titer with a homogeneous staining pattern and elevated ribonucleoprotein antibody, but after examination, a consulting rheumatologist deemed that she was one of the 10%–15% of people with a positive ANA of no clinical significance. A lipid panel showed normal triglycerides, but elevated total cholesterol (224 mg/dL), low-density lipoprotein (149 mg/dL), and high-density lipoprotein (HDL) (64 mg/dL) such that cholesterol/HDL ratio was normal (3.5).

A hypercoagulable workup was normal. The hypercoagulable workup included testing of fasting serum homocysteine; factor VIII activity; antithrombin acitivity; protein C activity; protein S antigen; activated protein C resistance; prothrombin mutation G20210A; antiprothrombin antibodies; anticardiolipin IgG, IgM, and IgA; antibeta 2 glycoprotein-1 IgG, IgM, and IgA; antiphosphatidylserine IgG, IgM, and IgA; and lupus anticoagulant. By 3 months after the initial onset, her symptoms had resolved and her ophthalmological examination had returned to normal. She returned at that time to ski in Colorado at an elevation of 3350 m, but she took a day to acclimate at 2400 m and took acetazolamide 125 mg twice daily with plenty of water to avoid acute mountain sickness. She experienced no return of symptoms on this trip.

It is likely that altitude played a part in the occurrence of this third cranial nerve paresis in a woman who has never smoked, is active, and whose only vasculopathic risk factor is mild hypercholesterolemia. Unlike the mechanism of increased intracranial pressure and/or brain swelling invoked to account for other cranial nerve palsies at altitude, it is unlikely to be the case for third cranial nerve paresis in a conscious individual. Although previously silent brain tumors (Shlim et al., 1991) and subarachnoid cysts (Hackett, 2000) can become symptomatic at high altitude, her negative neuroimaging excludes those possibilities. Hypoxia, dehydration, and, perhaps, vascular spasms or a hypercoagulable state are more likely. It is unclear whether a prothrombotic state can develop from hypobaric hypoxia alone (Baumgartner et al., 2007).

In any event, it is reassuring that this highly unusual pupil-involving third nerve paresis occurring at altitude in an otherwise healthy woman resolved completely in 3 months.