The presentation of adult-onset Alexander disease in our patient was characterized by a predominance of ocular motility disturbances, which correlated well with the distribution of MRI signal abnormalities within the medulla. Poor tracking of moving objects, gaze-evoked nystagmus, and rebound nystagmus indicate impairment of ocular motor control circuits involving the flocculus and medullary structures, such as the medial vestibular nuclei and nuclei prepositus hypoglossi (7,8). The primary position nystagmus could indicate dysfunction in central vestibular pathways. His recurrent unprovoked episodes of right-beating nystagmus a year later are highly unusual. Although the patient attributed his several-week episode of oscillopsia and nystagmus to the use of steroids and antibiotics to treat his cellulitis, this may have been coincidental. Regardless, this period of episodic nystagmus also likely indicates a time of unstable central vestibular function. Saccadic dysmetria implicates circuits within the dorsal vermis and fastigial nuclei, some of which project to pontine structures (9) and others to the lateral medullary region (10,11). Abnormal auditory-evoked responses also support pontine involvement. Gait ataxia, sensory symptoms, and abnormal somatosensory potentials are consistent with structural changes in the medullary tegmentum or cervical cord.
Our patient presented with cerebellar findings and a family history of parkinsonism. This raises the diagnostic possibility of a spinocerebellar atrophy (SCA), such as SCA-2 or SCA-3 (12,13). Genetic testing ruled out the common forms of SCA and the neuroimaging findings proved diagnostic. Our patient had medullary and cervical cord atrophy consistent with adult-onset Alexander disease. Brain MRI showed no cerebellar abnormalities that would be seen in SCA (14).
In summary, ocular motor signs are common in adult-onset Alexander disease due to involvement of the medulla and upper cervical cord. This results in damage to vestibular pathways, structures important for gaze-holding, and olivary pathways required for gaze stabilization. In our case, there was also evidence of damage to circuits involving the cerebellar vermis that determines saccadic accuracy.
The authors thank Drs M. Wong, J. Beckman, and A. J. Stoessl for kindly providing them with previous records and K. Mohaseb for referring the patient.
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