Multimodal imaging in urea cycle-related neurological disease – What can imaging after hyperammonemia teach us?

Abstract

BACKGROUND: Urea cycle-related brain disease may take on variable neuroimaging manifestations, ranging from normal to abnormal with or without a signature appearance. In the past, we have described the usefulness of multimodal imaging in identifying biomarkers of neuronal injury in UCD patients. In this study, we report unique findings in an adolescent male with neonatal-onset OTC deficiency after an episode of hyperammonemia. MATERIALS AND METHODS: Multiplanar, multisequence MR imaging (T1WI, T2WI, T2 FLAIR, diffusion weighted images and gradient echo) of the brain was performed on seven separate occasions over the course following the acute illness; first five exams were performed within 28 days of admission and the final two exams were performed approximately 3 and 5 months later. RESULTS: 1.The initial MR revealed increased signal on T2WI in the basal ganglia, claustrum and frontoparietal white matter; which remained stable over time. By the 5th exam, signal changes had developed in frontal cortex; reflecting permanent injury. 2. DTI tractography of the corticospinal tracts displayed revealed diminution of the number of projectional and commissural fibers over time. 3. Blood flow measurements demonstrated hypoperfusion on the fifth exams followed by hyperperfusion on the final two studies. 4. MR spectroscopy demonstrated that glutamine was elevated during hyperammonemia with myoinositol reduction, reflecting osmotic buffering. CONCLUSION: This particular multimodal magnetic resonance neuroimaging showed novel, temporally specific manifestations over the disease course in OTC deficiency. This prospective imaging study expands our understanding of the effect of hyperammonemia on the structure and biochemistry of the nervous system.

Physical, cognitive, and social status of patients with urea cycle disorders in Japan

“…Brain disorders related to UCDs may be evidenced by neuroimaging with manifestations ranging from normal to abnormal with or without a signature appearance. In recent years, it has been demonstrated that multimodal brain MRI using T1 weighted image, T2 weighted image, T2 fluid-attenuated inversion recovery, diffusion-weighted image, functional MRI, or/and 1 H/ 13 C magnetic resonance spectroscopy (MRS) is effective for the identification and evaluation of pathogenic neurologic conditions in patients with UCDs [ 37 ]. In patients with OTCD, even a partial or asymptomatic OTCD, 1 H MRS could detect increased glutamine levels, reduced myoinositol and choline levels in the brain, including frontal and parietal white matter, frontal gray matter, posterior cingulate gray matter, and thalamus [ 38 ].…”

Review of Multi-Modal Imaging in Urea Cycle Disorders: The Old, the New, the Borrowed, and the Blue

“…Other MRI findings may include signal intensity increase in the regions of frontal lobes, cingulate gyri, temporal lobes, as well as the insular regions ( 60 ). Many patients may have a normal MRI with changes that appear after an acute hyperammonemic episode ( 61 ).…”

“…Early in the course of HA, the MRI may be normal, and the only abnormal finding may be an elevated glutamine peak (gln) on MRS. MRS can detect elevated brain gln levels that is helpful in detection of subtle variations in OTCD females ( 59 ). Early diagnosis is critical to instituting ammonia lowering therapies, thus where available, 1HMRS adds typically 5–10 extra min to conventional MRI and can help in expediting diagnosis for partial or atypical OTCD when biochemical and molecular confirmation can take up to several days and weeks, respectively, and provides complementary information that can lead to early diagnosis ( 61 ) ( Figure 2 ). At our institution, modern neuroimaging techniques play a role in clinical monitoring and clinical decision making.…”

“…Although there are several reports of multimodal MRI at baseline or during acute HA, less is known about the recovery of HA with regard to changes in time and space. A prospective multimodal sequence of an OTCD patient with MRI/MRS exams performed during (5 over 1 month) and after (3 and 5 months) a hyperammonemic episode demonstrated abnormal signal changes in the posterolateral putamen, and supplemental motor strip (SMA), pre-motor cortex, and post-central gyrus ( 61 ). This occurred with cerebral hypoperfusion evolving to hyperperfusion.…”

Hemodynamics of Prefrontal Cortex in Ornithine Transcarbamylase Deficiency: A Twin Case Study

“…Ornithine transcarbamylase deficiency (OTCD) is an X-linked inborn error of metabolism and the most common of the urea cycle disorders ( 1 ). Deficient protein metabolism in OTCD results in hyperammonemia (HA) that, in turn, disrupts the neurocognitive function in domains of working memory and executive function in several brain regions, including prefrontal cortex (PFC) ( 2 – 4 ). Investigation of neurocognitive function in working memory domain can become critical to understand the underlying effects of hyperammonemia in patients with OTCD.…”