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Ipsilateral hemiparesis caused by putaminal hemorrhage in a patient with horizontal gaze palsy with progressive scoliosis: a case report
© Yamada et al.; licensee BioMed Central. 2015
Received: 10 December 2014
Accepted: 25 February 2015
Published: 10 March 2015
Horizontal gaze palsy with progressive scoliosis (HGPPS) is an autosomal recessive disorder caused by mutations in the ROBO3 gene, resulting in a critical absence of crossing fibers in the brainstem.
We present a patient with ipsilateral hemiparesis caused by putaminal hemorrhage who had a history of horizontal gaze paralysis and scoliosis since childhood. Diffusion tensor imaging (DTI) tractography confirmed the presence of uncrossed corticospinal tracts. Sequence analysis of the entire ROBO3 coding regions revealed a novel nonsense mutation.
We report the first known HGPPS case with intracranial hemorrhage and ROBO3 mutation showing an absence of major crossing pathways by DTI.
Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare congenital disorder with autosomal recessive inheritance that is associated with mutations in the ROBO3 gene located at chromosome 11q23-25 . HGPPS is characterized by the absence of conjugate horizontal eye movements, preservation of the vertical gaze and convergence, and progressive scoliosis during childhood and adolescence. The syndrome also includes a distinctive brain stem malformation and defective crossing of certain brain stem neuronal pathways. A few reports have used diffusion tensor imaging (DTI) to identify specific fiber tracts and their directionality in HGPPS and have shown the absence of major crossing pathways within the pons and midbrain [2-5].
There are a few reports of ipsilateral hemiplegia or hemiparesis following a supratentorial cerebral stroke [6-8]. Two case reports have described patients with ipsilateral hemiplegia or hemiparesis caused by intracranial hemorrhage [6,8], but mutations in the ROBO3 gene were not examined in these cases. Only one report showed that HGPPS patients with ROBO3 mutations displayed ischemic stroke symptoms on the ipsilateral side of the infarct .
We report the first known HGPPS case with intracerebral hemorrhage and mutation in the ROBO3 gene showing the absence of major crossing pathways by DTI.
She was treated and showed significant clinical improvement, and she was subsequently discharged to home.
ROBO3 aids in the regulation of hindbrain axonal midline crossing, helps direct cell migration, and specifies the lateral position of longitudinal pathways . ROBO3 mutations result in abnormal horizontal eye movement, progressive scoliosis, distinctive brain stem malformation, and defective crossing of select brain stem neuronal pathways. The ROBO3 gene does not appear to have a region at high risk of mutation, and 32 different ROBO3 mutations have been reported [1,7,9-15]. In our case, we found a novel homozygous nonsense mutation c.2392C > T in exon 15.
DTI is a unique tool able to map the white matter fiber tracts non-invasively and advances our understanding of abnormal brain anatomy [16,17]. In previous reports, DTI revealed the absence of major crossing pathways in the pons and midbrain in HGPPS [2-5]. Our case also showed uncrossed corticospinal tract on DTI.
Previously, only two reports described patients with ipsilateral hemiplegia or hemiparesis caused by intracranial hemorrhage [6,8]. Terakawa et al. described a patient with putaminal hemorrhage who had marked congenital scoliosis in the thoracolumbar spine and horizontal eye movement that was mildly restricted bilaterally . Similarly, Hosokawa et al. described a patient with internal capsule and thalamic hemorrhage who had marked congenital scoliosis . An MRI showed medulla hypoplasia in both cases. Mutations in the ROBO3 gene were not examined in either case; however, these two cases suggested the clinical features of HGPPS. Only one report has identified ROBO3 mutation in HGPPS patients presenting with ischemic stroke symptoms on the ipsilateral side of the infarct . The present case is the first known report of hemorrhagic stroke with a confirmed ROBO3 mutation and uncrossed corticospinal tracts resulting in ipsilateral putaminal hemorrhage and hemiparesis.
We report the first HGPPS case with putaminal hemorrhage and ROBO3 gene mutation showing an absence of major crossing pathways by DTI. Clinicians who encounter a patient with ipsilateral hemiparesis and intracerebral hemorrhage should suspect HGPPS and examine the patient for clinical and radiological features of HGPPS.
We obtained written informed consent from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
This work was supported by Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (No. 24791520 to Y.O.) and the Research on Applying Health Technology, Health and Labour Sciences Research Grants (to Y.K.) from the Ministry of Health, Labor, and Welfare of Japan. The funding agencies had no role in the study design; in the collection, analysis or interpretation of the data; in the preparation of the manuscript; or in the decision to submit the manuscript for publication.
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