Background & Aims
Acute intermittent porphyria (AIP) is a rare metabolic syndrome caused by deficiencies in enzyme activity in the heme-biosynthesis pathway. Misdiagnosis and mistreatment of abdominal pain in AIP are highly prevalent. As high concentrations of porphyrins could cause damage in organs including the brain, there is an urgent need to understand the pain mechanism and its related psychiatric/physiological syndromes as well as for accurate management of abdominal pain. As gene-based diagnosis takes weeks, using other techniques to perform accurate differential diagnosis of AIP is also important. In this study, we tried to use functional magnetic resonance imaging (fMRI), to unravel the neural mechanisms and pharmacotherapeutics of AIP.
Methods
Abdominal pain in a female (36 years old) patient with AIP due to hydroxymethylbilane synthase (HMBS) gene mutation was diagnosed. She has been with recurrent paroxysmal abdominal pain occurs for 7 to 10 days every 3 months. Clinical routine brain structural MRI revealed no abnormalities. Three resting-state brain functional MRI datasets were acquired at different stage of the disease: the remission stage after her previous pain onset (Time-point 1), the peak period of the subsequent episodic stage (Time-point 2), and one week later with duloxetine taken orally at 60mg per night for 7 consecutive days (Time-point 3), by a 3T scanner (TR, 700ms, voxel size, 2.5mm isotropic, 8min22s). Whole brain functional connectivity (FC) was calculated and compared with the imaging from 47 females at the age of 32-40 years old out of a brain imaging database of healthy population by using a 1-vs-group abnormality detection method (z-test, p<0.05, corrected for multiple comparisons with NBS in FSL).
Results
At the peak period in the episodic phase, the patient suffered very severe abdominal pain with depression/anxiety (SDS=65, SAS=54). A total of 20 FC links were found to decrease from the normal status, with the 7 most changed brain regions at the frontoparietal, somatomotor, and cerebellar areas. Alterations in the connectivity associated with the supplementary motor area may imply impaired physical movement ability, while the findings at the cerebellar crus probably indicate general aversive emotions associated with pain. At remission stage, fewer FC links involving the cingulate and orbitofrontal cortex showed reduction as no pain was manifested. After 7 days of continuous Duloxetine taken, the patient felt moderate pain, where 3 FC links with the somatomotor area and cerebellum were found to still decrease, possibly indicating lingering pain and depressive mood.
Conclusions
Our findings demonstrate that resting-state brain functional connectivity analysis helped reveal brain disorders during the progression of AIP. The fMRI scan shed light on the porphyria pain mechanism, where decreased brain functional connectivity involved the most affected brain regions including those in the frontoparietal, somatomotor, default mode, and cerebellar networks. These findings extend our knowledge of porphyria pain that, accumulated porphyrins could also affect the brain functional organization, cause depression, anxiety, hallucination, and claudication gait while the structural MRI was normal. Our study could help future studies on accurate diagnosis of this rare disease as well as the development of better pain management and supportive treatment strategies for psychiatric/physiological problems.
References
Reference
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Presenting Author
Yinghui Fan
Poster Authors
Ying Hui Fan
MD, PhD
Renji Hospital, School of Medicine, Shanghai Jiatong Univ.
Lead Author
Topics
- Pain Imaging