Quantitative Diagnosis And Pathogenesis Of Congenital Idiopathic Nystagmus

Background:Congenital idiopathic nystagmus (ICN) is an unique form of congenital nystagmus inwhich no visual or neurological impairment can be found. A common clinical characteristic ofICN is involuntary eye movement which is often associated with abnormal visual functionand irregular head posture.It is a common clinical problem to record the eye movement quantitatively andobjectively in nystagmus. Video-oculography is the best choice for recording the eyemovement, but we do not have the similar domestic digital video eye tracker. We havesuccessfully developed the prototype of infrared video eye tracker and the preliminary trial ineye movement detection have been done, which needs more improvements and extensiveclinical applications.The etiology and pathophysiology of ICN are poorly understood. With the advance oftechnologies of imaging brain function, researchers now have some novel approaches tounderstand the structure and function of the brain. We used a recently developed fMRImethod known as resting-state fMRI and task-related fMRI to assess brain function in acohort of ICN patients. We also used regional homogeneity (ReHo) to analyze resting-statedata. Through these methods, we would like to know whether there are abnormal activities inthe brain of the ICN and also want to explore the neural mechanism of ICN.Surgery is a common choice to treat ICN. As the visual cortex activation can be analysedobjectively and quantitatively through fMRI, we would like to explore that whether surgerycan influence the brain activities and whether fMRI can be used as a new method to assess theeffect of surgery.Part â… : Design and development of digital eye tracker and its clinical applications incongenital idiopathic nystagmus Purpose:To develope current digital eye tracker and assess its clinical application in ICN.Materials and Methods:1. Updated software of user interface, waveform and data analysis in low-frequency eyetracker.2. Designed and developed one kind of high-frequency eye tracker: using camera ofhigher sampling frequency, improved data collection methods, new visual stimulation mode,the lighting of the infrared light source and special software for nystagmus detection.3. Tested all kinds of congenital nystagmus using the new eye tracker and analyzed theresults.Results:1. The low-frequency eye tracker is easier to operate and has automatic or semi-automatic detection process and real-time data processing. High-frequency eye tracker hashigher sampling frequency, higher accuracy and related software for nystagmus.2. Improved digital eye tracker can record various types of congenital nystagmus quicklyand accurately.Conclusions:Improved digital eye tracker can be used as an objective and quantitative examination forpatients with idiopathic nystagmus nystagmus.Part â…¡: Observation of surgical treatment for congenital idiopathic nystagmus:quantitative detection by digital eye trackerPurpose:To evaluate the feasibility and practicality of self-developed digital eye tracker in surgeryof ICN.Materials and Methods:Recorded the data of ICN and other kinds of nystagmus with improved eye trackerbefore and after the operations.Results:Digital eye tracker can judge the speed of nystagmus and the null zone quickly andquantitatively. Head position can be corrected effectively by surgery based on the quantitative results, and the results can quantitatively reflect the overall changes of the nystagmusintensity after the surgery.Conclusions:Our self-developed digital eye tracker can assist to determine the way and quantity ofsurgery and it also can quantitatively analyze the effects of surgery for various types ofnystagmus.Part â…¢: Study of functional magnetic resonance imaging in congenital idiopathicnystagmusPurpose:1. To explore the regional homogeneity alterations in patients with ICN and thecorrelation between these changes and clinical index.2. To explore the abnormal activation of brain regions in patients with ICN bytask-related fMRI and the correlation between these changes and clinical index.3. To explore the changes of visual cortical activation after operation of nystagmus andto observe the feasibility of functional magnetic resonance imaging in evaluating the effect ofsurgery.Materials and Methods:1. A regional homogeneity (ReHo) method was used to investigate the neural activity ofcongenital idiopathic nystagmus patients in resting state. Data were acquired from14patientswith ICN and matched normal controls. We used nystagmus intensity as an indicator of theseverity of disease and explored the relationship between ReHo and nystamus intensity.2. Patients with ICN (n=14) and matched normal controls were scanned by fMRI withcheckerboard visual stimulation and the groups of ICN were also scanned in different gazedirection (In front, the fast phase and the slow phase). We analyzed the different activationcharacteristics comparing with normal control and itself in each side. The activation indifferent levels of visual cortex was observed as well.3. Used fMRI to detect the changes in visual cortex of two cases with congenitalnystagmus before and after the operation, and compared the results with eye movementrecordings.Results: 1. We found the decreased ReHo in ICN patients, which distributed in the cerebellum,brain stem, frontal lobe and superior frontal gyrus and increased ReHo in the parietal andoccipital lobes. ReHo had a negative correlation with nystagmus intensity in the occipital lobeand a positive correlation with nystagmus intensity in the frontal lobe and supplementarymotor area.2. In the study of task-related fMRI we found:1) Abnormal activation of brain areas can be observed in each direction. The mainabnormal activation of brain regions in front side distributed in the left anterior cingulatecortex and left cuneus; abnormal activation in slow phase side distributed in the left anteriorcingulate and left precuneus and abnormal activation in fast side mainly distributed in thebrain stem, cerebellum, frontal lobe, temporal lobe.2) There was statistical difference of the total voxels in Brodmann17area between thegroups of fast side of ICN and normal control, and there was statistical difference of the totalvoxels in Brodmann18area between the groups of the fast or slow phase sides of ICN andnormal control. The total voxels in Brodmann19area have statistical difference between thegroups of each side of ICN and normal control. There were statistically significant differencesof average activation intensity in Brodmann17,18and19areas between the groups of ICNand normal control.3) The brain activations were different in different gaze directions. The main abnormalactivation of brain regions in fast phase side compared to slow phase side were distributed incerebellum, frontal and occipital lobe in left cerebrum. There was statistically significantdifference of total voxels in Brodmann17,18areas of the comparison of front and fast phaseside.4) ReHo had a negative correlation in the occipital lobe and a positive correlation withnystagmus intensity in the frontal lobe and supplementary motor area. The nystagmusintensity had not obvious correlation with total voxel and average intensity.3. The results of fMRI showed that the cortical activation increased in the patients ofICN on Brodmann17,18,19areas after operation, while another patient decreased. And theresults are consistent with that recorded by eye tracker.Conclusions:1. Our study demonstrates that resting-state neural activity has altered in patients with ICN. And these abnormal brain regions mainly located in the neural pathways of the smoothpursuit system, suggesting that the smooth pursuit system abnormalities maybe one reason ofnystagmus.2. The results of task-related fMRI demonstrate that there is abnormal activation in ICN.And the activation areas are different in different direction.3. Significant dysfunction was found in Brodman17,18,19.in the patients with ICN.4. The activation of visual cortex changes of fMRI can be effectively and quantitativelyobserved in the patient of nystagmus before and after surgery.