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Clinical Case

CLINICAL CASE | Horizontal Gaze Palsy With Progressive Scoliosis

Horizontal gaze palsy with progressive scoliosis (HGPPS) is an extremely rare genetic syndrome. It is the result of mutation in the ROBO3 gene, essential for normal axon guidance in many developing neurons, including those of the corticospinal tract and the medial lemniscus. Mutations in this gene are associated with a failure of axonal crossing in certain regions of the brain. Because it is so rare, this syndrome is not likely to be encountered in routine medical practice. Nevertheless, by examining brain images from patients with HGPPS, we have the opportunity to see how brain structure changes when decussation does not occur. Further, by assessing their neurological signs and the results of electrophysiological testing, we have the opportunity to see how mutation can affect the way sensory and motor information is processed by the brain.

A 12-year-old boy with a genetically determined mutation of the ROBO3 gene was examined for somatic sensory, limb motor, and ocular motor functions. Sensory testing did not reveal impairment. He has mild gait instability and a tremor during reaching (intention tremor). He is able to follow a visual stimulus moving vertically with his eyes. He is unable to follow a horizontal moving stimulus. His eyes remain fixated in the forward direction, bilaterally.

Figure 2–1A1 is a midsagittal magnetic resonance imaging (MRI) from a person with HGPPS. Brain tissue is shades of gray (gray matter darker than white matter) and cerebrospinal fluid, black. The bracket is located dorsal to the pons and medulla. Cerebrospinal fluid penetrates into this region on the midline because there is a shallow groove (sulcus). Note that this is not present in the control MRI (Figure 2–1B1). The transverse MRI through the upper medulla (A2) reveals an abnormally flattened appearance in the patient with HGPPS compared with the control brain (B2). A section through the caudal medulla reveals an aberrant deep midline groove (A3, arrow; B3).

Neurophysiological testing was conducted to assess the integrity of the touch and corticospinal motor pathways (see Figure 2–2). To determine the function of the sensory pathway, the skin is electrically stimulated and the overall change in on-going neuronal activity of parietal lobe (ie, EEG) is recorded. Recording the EEG in the region of the somatic sensory cortex in response to electrical stimulation of skin revealed ipsilateral activation, not the customary contralateral activation. To determine the function of the corticospinal tract, transcranial magnetic stimulation (TMS) is used to activate the motor cortex, and the evoked change in muscle activity is recorded. TMS of the motor cortex activated muscles on the ipsilateral side, not the typical contralateral side.

Finally, diffusion tensor imaging (DTI; this is discussed in Box 2–2) was performed on the patient's MRIs in order to follow the corticospinal tract. This method permits imaging of neural pathways in the brain. Figure 2–1A4 shows the DTI image from a HGPPS patient. There are ...

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