Fourth cranial nerve palsy (4NP) from intra-axial lesions usually is associated with other neurological deficits (1). Since the trochlear nucleus and fascicles are adjacent to the inferior colliculus (IC) (2,3), auditory symptoms including tinnitus may accompany an intra-axial 4NP (4). However, tinnitus has not been described as the only accompaniment of 4NP from a midbrain lesion. We describe a patient with sudden aggravation of mild tinnitus and contralesional 4NP from midbrain infarction.
A 53-year-old man with hypertension and diabetes for 12 years was referred for evaluation of binocular vertical diplopia of 1-month duration. The diplopia developed while driving a car and worsened in leftward and downward gazes. He also reported sudden aggravation of bilateral tinnitus, which had been intermittent and mild as “chirrups of a cicada” for several years, becoming louder than “airplane sounds” and persistent with the onset of diplopia. He denied headache, hearing impairment, or history of head trauma. His medications included amlodipine and metformin.
Examination revealed a right hypertropia of 5 prism-diopters (PD) in primary position, which increased in leftward (7 PD) and downward (8 PD) gazes and in right head tilt (10 PD). Abnormal torsion of the right eye was not noted on fundus photography. Pure tone audiometry showed a mild high tone sloping in both ears, consistent with presbycusis, and brain stem auditory evoked potentials (BAEP) were normal bilaterally.
Four days after onset of symptoms, brain MRI revealed an acute infarction circumscribed to the area of left fourth cranial nerve fascicle and IC (Fig. 1). MRA was normal. Antiplatelet therapy (75 mg/day clopidogrel) was begun, and the tinnitus and diplopia gradually improved over several weeks.
Our patient developed contralesional 4NP from infarction involving the midbrain tectum and aggravation of tinnitus was the only accompanying neurologic deficit. The trochlear nucleus lies dorsal to the medial longitudinal fasciculus (MLF) and just ventrolateral to the cerebral aqueduct at the level of the IC (2,3). The nerve fascicles course posteroinferiorly around the aqueduct to decussate in the anterior medullary velum (2,3). Damage to the trochlear nucleus or the proximal fascicles before their decussations gives rise to contralateral palsy (1,5,6).
Since the trochlear nucleus and fascicles are adjacent to various structures in the lower midbrain, accompanying neurological symptoms or signs are diagnostic hallmarks of an intra-axial lesion. Internuclear ophthalmoplegia, Horner syndrome, upbeat nystagmus, and sensory disturbances are frequently associated since the trochlear nucleus and fascicles are in close proximity with the ascending trigeminothalamic tract, spinothalamic tract, MLF, descending sympathetic tract, decussating fibers of the superior cerebellar peduncle, and lateral lemniscus (Fig. 2) (1,3-7). However, to the best of our knowledge, tinnitus has not been described as the only accompaniment in 4NP from an intra-axial lesion.
Our patient reported sudden worsening of preexisting tinnitus without hearing loss. Even though the mechanism of tinnitus is only partially understood (8-10), cochlear impairment is a frequent cause of tinnitus at the peripheral level (e.g., senile hearing loss) (8,10,11). Accordingly, the preexisting mild tinnitus in our patient may be ascribed to the high tone hearing loss consistent with presbycusis.
Tinnitus is also associated with dysfunction of the central auditory pathways (8,10,11). Central auditory neurons are subject to glutaminergic and GABAergic modulation, and inhibitory GABAergic synapses are affected more than excitatory glutaminergic ones in generating tinnitus (9,11). In particular, the IC is a relay nucleus for all ascending auditory information. Accordingly, impaired inhibitory processing in the IC could give rise to tinnitus or aggravate preexisting tinnitus. The IC is consisted of 3 parts: central nucleus, external nucleus, and dorsal cortex (Fig. 2) (9,12). The central nucleus of IC is connected to the ventral medial geniculate body (MGB) and the primary auditory cortex (9,12). These structures constitute the classical auditory pathway. In contrast, the nonclassical pathway consists of the dorsal cortex and external nucleus of IC, dorsal MGB, and secondary auditory cortex (9,12). This pathway has diffuse and bilateral interconnections with other neural structures and integrates other sensory information (8,9). Both the classical and nonclassical pathways may be responsible for tinnitus (8,9). However, in view of the bilateral tinnitus, and normal hearing and BAEP, our patient most likely had tinnitus from isolated damage to the nonclassical pathway.
Differentiation of 4NP from skew deviation is important in lesions involving the brain stem (1,14). Skew deviation is usually contraversive in the upper brain stem lesions, that is, the eye on the involved side is hypertropic (15), while ipsilesional eye was hypotropic in our patient. Skew deviation is also more likely to accompany contraversive ocular torsion (ocular tilt reaction) (16,17). Furthermore, results of the Parks-Bielschowsky 3-step test in our patient were consistent with a 4NP.
In conclusion, tinnitus may accompany 4NP due to an intra-axial lesion. The clinician should inquire about auditory symptoms in the evaluation of patients with vertical diplopia.
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