Intra-axial (fascicular) ocular motor nerve palsies are due to lesions of the nerve distal to its nucleus but within the confines of the brainstem. Brainstem lesions tend to impact many structures and therefore produce multiple deficits, which allows accurate topographic localization of the lesion. At the level of the midbrain, intra-axial lesions can damage either the third or fourth nerve. Intra-axial involvement of the fascicle of the third nerve can produce 1 of 4 syndromes, each of which causes an ipsilateral third nerve palsy. Damage to the ventral midbrain can damage the cerebral peduncle and cause a contralateral hemiparesis (Weber syndrome). Involvement of the red nucleus and substantia nigra may produce contralateral ataxia and/or tremor (Benedikt syndrome). Damage to the dorsal midbrain may involve the superior cerebellar peduncle and produce contralateral ataxia (Claude syndrome). A dorsal lesion with a slightly different configuration can produce the same type of ataxia plus a third nerve nuclear lesion and features of supranuclear eye movement dysfunction (Nothnagel syndrome). The localization and direct anatomical correlation of these lesions is more important than the eponym, especially because use and definitions of these eponyms have varied in the literature.
, CrennerCW, LogigianEL, CharnessME, SamuelsMA. Midbrain syndromes of Benedikt, Claude, and Nothnagel: setting the record straight.. 1992;42(9):1820–1822.
As mentioned earlier, involvement of the fourth cranial nerve within the brainstem is uncommon. Pineal tumors may compromise the proximal course of both fourth nerves by compressing the tectum of the midbrain. Such lesions may also obstruct the Sylvian aqueduct, leading to elevated intracranial pressure and hydrocephalus (often producing the dorsal midbrain syndrome).
Intra-axial lesions of the sixth cranial nerve that involve its nucleus may also injure the seventh cranial nerve, whose fibers swing around the sixth nerve nucleus at the facial genu. Intra-axial lesions that involve the fascicle of the sixth nerve may also damage the fascicle of the seventh nerve, the tractus solitarius, and the descending tract of the trigeminal nerve, which produces an ipsilateral abduction palsy, facial weakness, loss of taste over the anterior two thirds of the tongue, and facial hypoesthesia, respectively (Foville syndrome). Lesions of the ventral pons can damage the sixth and seventh nerves along with the corticospinal tract, which produces contralateral hemiplegia and ipsilateral facial nerve palsy and abduction deficit (Millard-Gubler syndrome).
. The rule of 4 of the brainstem: a simplified method for understanding brainstem anatomy and brainstem vascular syndromes for the non-neurologist.2005;35(4):263–266.
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The subarachnoid segment of the ocular motor nerves extends from the brainstem to the cavernous sinus, where the nerves exit the dura, and it is within this section that most ischemic cranial nerve palsies are thought to occur. The diagnosis of ischemic (microvascular or diabetic) ocular motor nerve palsies is one of exclusion. Ischemic cranial mononeuropathies typically occur in isolation and with maximal deficit at presentation; however, occasionally the loss of function progresses over 7–10 days. Pain may or may not be present and, if present, may be quite severe in some patients; pain does not distinguish benign from more serious causes.
The oculomotor nerve is a special case of isolated cranial mononeuropathy due to its close anatomical proximity to the cerebral vasculature (especially the posterior communicating artery) and potential for aneurysmal compression (see later in the chapter). Ocular misalignment due to ischemic ocular motor palsy always improves, and diplopia usually resolves within 3 months.
Progression of ocular misalignment beyond 2 weeks or failure to improve within 3 months is inconsistent with this cause of cranial neuropathy and should prompt a thorough evaluation for another etiology. Risk factors include diabetes mellitus, hypertensive vascular disease, and elevated serum lipids. Hence, these patients require a medical evaluation for vasculopathic risk factors.
Myasthenia gravis may mimic any pattern of painless, pupil-sparing extraocular motor dysfunction and should be kept in the differential diagnosis of such cases.
, AldredgeH, HershbergR, et al. Oculomotor palsy in diabetes mellitus: a clinico-pathological study.. 1970;93(3):555–566.
, McCannaTD, LaydePM. Risk factors for ischemic ocular motor palsies.1994;112(7):961–966.
, JonesFRJr, YoungeBR. Causes and prognosis in 4,278 cases of paralysis of the oculomotor, trochlear, and abducens cranial nerves.. 1992;113(5):489–496.