Spectral analysis of dual jerk waveforms in congenital nystagmus

Congenital nystagmus (CN) is a disorder of the ocular motility characterized by oscillatory eye movements preventing the correct fixation of a target. Many typical waveforms of eye position recordings have been recognized and classified in the literature: in jerk CN a slow phase eye movement is followed by a fast phase, giving rise to a typical saw-tooth waveform, while in pendular CN the eyes exhibit a periodic motion, giving rise to an approximately sinusoidal waveform. Dual jerk waveforms seemed to show small, rapid oscillations superimposed on a jerk-like waveform, thus being originary classified as a mixture of jerk and pendular CN. On the contrary, a theoretical model of CN has appeared recently, which suggests a possible interpretation of the small amplitude oscillations in dual jerk waveforms as consecutive pieces of growing and decaying exponentials.By spectral analysis of dual jerk waveforms in a number of patients with CN, we show that the oscillations are truly sinusoidal in nature, thus suggesting the possibility of a different explanation of dual jerk waveforms in CN.Preliminary results of this work were presented at XIV ICMP —International Congress of Medical Physics, Espoo, Finland, 11–16 August 1985     

A hypothetical explanation of congenital nystagmus

Congenital nystagmus (CN) is a conjugate, rhythmic, eye movement disorder characterized by a wide variety of waveforms ranging from jerk to pendular types. No detailed mechanisms have been proposed to explain the generation of the CN wave-form This paper proposes a hypothetical mechanism for CN, and shows with computer simulations that a model based on this hypothesis can account for a variety of disparate waveforms. The basis of this model is a gaze-holding network, or neural integrator, that has both position and velocity feedback loops. The signals carried in these loops could arise from either afference or efference. In normal subjects, the position feedback would be positive and the velocity feedback would be negative. Both would help to increase the time constant of an imperfect neural integrator in the brain stem. We propose that in patients with CN the sign of the velocity pathway is reversed, making the neural integrator unstable. This instability could manifest as many different CN waveforms, depending on the direction and velocity of post-saccadic ocular drift and actions of nonlinearities within the position and velocity feedback loops. Thus a single underlying abnormality may be responsible for a variety of CN waveforms.     

Nonlinear time series analysis of jerk congenital nystagmus

Nonlinear dynamics provides a complementary framework to control theory for the quantitative analysis of the oculomotor control system. This paper presents a number of findings relating to the aetiology and mechanics of the pathological ocular oscillation jerk congenital nystagmus (jerk CN). A range of time series analysis techniques were applied to recorded jerk CN waveforms, and also to simulated jerk waveforms produced by an established model in which the oscillations are a consequence of an unstable neural integrator. The results of the analysis were then interpreted within the framework of a generalised model of the unforced oculomotor system. This work suggests that for jerk oscillations, the origin of the instability lies in one of the five oculomotor subsystems, rather than in the final common pathway (the neural integrator and muscle plant). Additionally, experimental estimates of the linearised foveation dynamics imply that a refixating fast phase induced by a near-homoclinic trajectory will result in periodic oscillations. Local dimension calculations show that the dimension of the experimental jerk CN data increases during the fast phase, indicating that the oscillations are not periodic, and hence that the refixation mechanism is of greater complexity than a homoclinic reinjection. The dimension increase is hypothesised to result either from a signal-dependent noise process in the saccadic system, or the activation of additional oculomotor components at the beginning of the fast phase. The modification of a recent saccadic system model to incorporate biologically realistic signal-dependent noise is suggested, in order to test the first of these hypotheses. Action Editor: Peter Latham     

Deriving heart period variability from blood pressure waveforms.

International standards for calculating heart period variability (HPV) from a series of R-wave intervals (R-R) in an electrocardiographic (ECG) recording have been widely accepted. It is possible, and potentially useful in various settings, to use systolic blood pressure waveform intervals to estimate HPV, but the validity of HPV derived from blood pressure (BP) waveforms has not been established. To test the reliability between BP- and ECG-derived HPV indexes, we evaluated data from 234 healthy adults in four studies of HPV reactivity to stress. Study conditions included resting baseline, arithmetic, Stroop test, speech presentation, and orthostatic tilt. Continuous ECG and BP recordings were sampled at a rate of 500 Hz, scored by the same methods, and used to calculate heart rate and time- and frequency-domain measures of HPV. Overall, reliability between the two methods was very high for computing heart rate and HPV indexes. High-frequency HPV indexes were somewhat less reliably computed. In conclusion, in healthy adults, with the use of appropriate methods, BP waveforms can produce reliable indexes of HPV.     

Murine neonatal infection provides an efficient model for congenital ocular toxoplasmosis

Congenital infection is one of the most serious settings of infection with the apicomplexan parasite Toxoplasma gondii. Ocular diseases, such as retinochoroiditis, are the most common sequels of such infection in utero. However, while numerous studies have investigated the physiopathology of acquired toxoplasmosis, congenital infection has been largely neglected so far. Here, we establish a mouse model of congenital ocular toxoplasmosis. Parasite load and ocular pathology have been followed for the first 4 weeks of life. Ocular infection developed slowly compared to cerebral infection. Even after 4 weeks, not all eyes were infected and ocular parasite load was low. Therefore, we evaluated a scheme of neonatal infection to overcome problems associated with congenital infection. Development of infection and physiopathology was similar, but at a higher, more reliable rate. In summary, we have established a valuable model of neonatal ocular toxoplasmosis, which facilitates the research of the underlying physiopathological mechanisms and new diagnostic approaches of this pathology.     

Role of NMDA receptors in the compensation of ocular nystagmus induced by hemilabyrinthectomy in the guinea pig.

The possibility that N-methyl-D-aspartate (NMDA) receptor activation plays a role in inducing the vestibular compensation following hemilabyrinthectomy (HL) in guinea pigs, was verified by means of continuous intraventricular osmotic pumping of DL-2-Amino-5-phosphono-valeric acid (APV). Our results show that high doses (40 and 20 mM) of APV decrease both the combined OKR and VOR and the nystagmus following HL. Low doses of APV (2.5 mM), affect the time course of the ocular compensation by maintaining a higher level of nystagmus beat frequency and by delaying the nystagmus disappearance. On the contrary, the compensation time course is not affected by administering APV later on in the compensation period. Therefore, it appears that NMDA receptors are activated during the precocious phase of vestibular compensation, when a large vestibular imbalance is present. This finding is explained by the development of NMDA receptor hypersensitivity, in the functionally inactivated commissural system or by the occurrence of NMDA-mediated long-term potentiation.     

A normal ocular motor system model that simulates the dual-mode fast phases of latent/manifest latent nystagmus

 The fast phases of latent/manifest latent nystagmus (LMLN) may either cause the target image to fall within (foveating) or outside (defoveating) the foveal area. We previously verified that both types are generated by the same mechanism as voluntary saccades and propose a hypothetical, dual-mode mechanism (computer model) for LMLN that utilizes normal ocular-motor control functions. Fixation data recorded during the past 30 years from 97 subjects with LMLN using both infrared and magnetic search coil oculography were used as a basis for our simulations. The MATLAB/Simulink software was used to construct a robust, modular, ocular motor system model, capable of simulating LMLN. Fast-phase amplitude versus both peak velocity and duration of simulated saccades were equivalent to those of saccades in normal subjects. Based on our LMLN studies, we constructed a hypothetical model in which the slow-phase velocity acted to trigger the change between foveating and defoveating LMLN fast phases. Foveating fast phases were generated during lower slow-phase velocities whereas defoveating fast phases occurred during higher slow-phase velocities. The bidirectional model simulated Alexander's law behavior under all viewing and fixation conditions. Our ocular-motor model accurately simulates LMLN patient ocular motility data and provides a hypothetical explanation for the conditions that result in both foveating and defoveating fast phases. As is the case for normal physiological saccades, the position error determined the saccadic amplitudes for foveating fast phases. However, the final slow-phase velocity determined the amplitudes of defoveating fast phases. In addition, we suggest that individuals with LMLN use their fixation subsystem to further decrease the slow-phase velocity as the target image approaches the foveal center. Received: 16 June 2000 / Accepted in revised form: 20 May 2001     

Confirmation and refinement of a genetic locus of congenital motor nystagmus in Xq26.3-q27.1 in a Chinese family

Congenital motor nystagmus (CMN), a subtype of nystagmus, may reduce vision or be associated with other, more serious, conditions that limit vision. The genetic basis for CMN is still unknown. To identify a locus for CMN, genotyping and linkage analysis were performed in 22 individuals from a Chinese family with X-linked CMN using markers from X chromosome. The maximum LOD score obtained for microsatellite maker DXS1192 linked the CMN locus in this family to Xq. By haplotype construction the locus for CMN was finally localized to an approximately 4.4-cM region at chromosome Xq26.3-q27.1. The SLC9A6 and FGF13 genes in this region, were selected and screened for mutation in this family, but no mutation was detected.B. Zhang and K. Xia contribute to this work equally     

Acquired and congenital ocular toxoplasmosis experimentally induced in Calomys callosus (Rodentia, Cricetidae)

An experimental model for acquired and congenital ocular toxoplasmosis as well as a model to induce experimental autoimmune uveitis (EAU) was investigated in Calomys callosus. Toxoplasma gondii, ME-49 strain, was used to infect males and pregnant- and not pregnant-females while S-antigen, a major glycoprotein of the retinal photoreceptor cell, was used to induce EAU. The ocular lesions elicited by T. gondii were characterized by the presence of cysts, free tachyzoites and inflammatory cells in the retina or related tissues. In the congenital form, 40% of the fetus presented ocular lesions, i.e., presence of cysts in the retina, vitreous, and extra-retinal tissues. In the acquired form, 75% of the females and 50% of the males presented unilateral ocular cysts both at 21 and 47 days post-infection. It was also demonstrated that S-antigen was not uveitogenic in the C. callosus model. No lesion was observed in the animals exclusively immunized with this retinal component, even when jacalin was used as additional adjuvant for polyclonal response to the retinal antigen. It can be concluded that C. callosus may constitute in a promising model for study both acquired and congenital ocular toxoplasmosis, particularly when it is important to make sure that a non autoimmune process is involved in the genesis of the ocular infection.     

A case of congenital syphilis during the colonial period in Mexico City

Congenital syphilis has been diagnosed very seldom in ancient populations. The case that we examined comes from San Jeronimo's Church (17th and 18th centuries AD; Mexico City). Coffin 43 contained an incomplete skeleton of an approximately 2-year-old infant. The pathological lesions of this skeleton include bilateral osteochondritis, diaphyseal osteomyelitis, and osteitis and/or periostitis on the long bones. The radiographic appearance depicts symmetrical osteomyelitic foci, particularly at the proximal extremity of both tibiae (Wimberger's sign). The skull exhibits hydroceph-aly and periosteal changes on the vault, and the unerupted upper incisors evince dental hypoplasia and other pathological alterations reminiscent of Hutchinson's incisors. All these features strongly suggest a case of early Congenital syphilis. © 1995 Wiley-Liss, Inc.     

A gene for X-linked idiopathic congenital nystagmus (NYS1) maps to chromosome Xp11.4-p11.3

Congenital nystagmus (CN) is a common oculomotor disorder (frequency of 1/1,500 live births) characterized by bilateral uncontrollable ocular oscillations, with onset typically at birth or within the first few months of life. This condition is regarded as idiopathic, after exclusion of nervous and ocular diseases. X-linked, autosomal dominant, and autosomal recessive modes of inheritance have been reported, but X-linked inheritance is probably the most common. In this article, we report the mapping of a gene for X-linked dominant CN (NYS1) to the short arm of chromosome X, by showing close linkage of NYS1 to polymorphic markers on chromosome Xp11.4-p11.3 (maximum LOD score of 3.20, over locus DXS993). Because no candidate gene, by virtue of its function, has been found in this region of chromosome Xp, further studies are required, to reduce the genetic interval encompassing the NYS1 gene. It is hoped that the complete gene characterization will address the complex pathophysiology of CN.