Niemann-Pick Type C: Typical Ocular Motor Findings and Red Flags

Niemann-Pick Type C (NPC) is a rare, autosomal-recessive lysosomal storage disorder. 95% of all patients develop a vertical supranuclear saccadic palsy (VSSP). First, downward saccades deteriorate. The underlying mechanism is probably a unilateral innervation of the eye depressors by the neurons of the rostral interstitial nucleus of the medial longitudinal fascicle (riMLF) in the mesencephalon. In contrast, the eye elevators are bilaterally innervated by the riMLF and thus they are not functionally impaired until a later stage. During the course of the disease, a complete vertical supranuclear gaze palsy (VSGP) with an eye movement restriction can develop. This is caused by an additional functional impairment of the interstitial nucleus of Cajal.

In the routine clinical examination, often only smooth pursuit and not saccades is examined, so that a VSSP often remains undetected. Detection of a VSSP is made even more difficult due to compensation strategies developed by the patients: blinks and head movements during the saccades. These strategies help patients to initiate and accelerate the saccades and they can be found even in small children with a VSSP and/or VSGP. Because the toddlers and small children do not tolerate the eyelids and head being held, these compensation strategies are an important diagnostic red flag for this and other neurodegenerative disorders. The diagnosis of NPC is especially important because it has direct therapeutic consequences: the disease can be treated with miglustat (substrate reduction therapy).