Modeling the effect of gravity on periodic alternating nystagmus.

Periodic alternating nystagmus (PAN) is a rare oscillatory ocular motor disorder. The effects of gravity on the dynamic behavior of PAN can be studied by monitoring the nystagmus while changing head orientation. Previous studies of patients with PAN reached different conclusions about the effect of changing the orientation of the head relative to gravity on the ongoing PAN, either no effect or a damping of the nystagmus within several minutes. What neuronal circuits could account for the difference in the effects of gravity among PAN patients? We modeled how the brain resolves the tilt-translation ambiguity in normal individuals and added an unstable, oscillatory vestibular system generating PAN. PAN was suppressed in our patient in ear-down positions, in a similar pattern to that of a previously reported patient. This effect was simulated by reducing the gain of the projection of the "rotation feedback" loop to the velocity-storage integrator to approximately 5% of its normal value. With normal "rotation feedback" PAN is expected to dissipate quickly as soon as the head is rotated away from upright position. Moreover, by disconnecting the rotation feedback completely (gain = zero) the model simulated PAN that was reported to be unaffected by gravity. Thus, understanding the effect of this single parameter, the gain of the rotation feedback, can explain the observed variability among our own and previous studies.

Modeling the interaction among three cerebellar disorders of eye movements: periodic alternating, gaze-evoked and rebound nystagmus.

A woman, age 44, with a positive anti-YO paraneoplastic cerebellar syndrome and normal imaging developed an ocular motor disorder including periodic alternating nystagmus (PAN), gaze-evoked nystagmus (GEN) and rebound nystagmus (RN). During fixation there was typical PAN but changes in gaze position evoked complex, time-varying oscillations of GEN and RN. To unravel the pathophysiology of this unusual pattern of nystagmus, we developed a mathematical model of normal function of the circuits mediating the vestibular-ocular reflex and gaze-holding including their adaptive mechanisms. Simulations showed that all the findings of our patient could be explained by two, small, isolated changes in cerebellar circuits: reducing the time constant of the gaze-holding integrator, producing GEN and RN, and increasing the gain of the vestibular velocity-storage positive feedback loop, producing PAN. We conclude that the gaze- and time-varying pattern of nystagmus in our patient can be accounted for by superposition of one model that produces typical PAN and another model that produces typical GEN and RN, without requiring a new oscillator in the gaze-holding system or a more complex, nonlinear interaction between the two models. This analysis suggest a strategy for uncovering gaze-evoked and rebound nystagmus in the setting of a time-varying nystagmus such as PAN. Our results are also consistent with current ideas of compartmentalization of cerebellar functions for the control of the vestibular velocity-storage mechanism (nodulus and ventral uvula) and for holding horizontal gaze steady (the flocculus and tonsil).

Dizziness and Vertigo: The Skillful Examination.

BACKGROUND: The visual, ocular motor and vestibular systems have intimate neural and close anatomical relationship that dictates their assessment in a patient with dizziness and vertigo. RESULTS: Recognition of the pearls and pitfalls of a targeted clinical examination HINTS/HINTS "Plus" allows the clinician to probe at the bedside the most crucial hypothesis in a patient with acute isolated vestibular syndrome, "Is this a stroke?" CONCLUSION: By applying a methodical approach to examination of patients with dizziness and vertigo, localization of the offending lesion, management, and even elucidation of the underlying diagnosis is feasible.

Eye Movement Disorders and the Cerebellum.

The cerebellum works as a network hub for optimizing eye movements through its mutual connections with the brainstem and beyond. Here, we review three key areas in the cerebellum that are related to the control of eye movements: (1) the flocculus/paraflocculus (tonsil) complex, primarily for high-frequency, transient vestibular responses, and also for smooth pursuit maintenance and steady gaze holding; (2) the nodulus/ventral uvula, primarily for low-frequency, sustained vestibular responses; and (3) the dorsal vermis/posterior fastigial nucleus, primarily for the accuracy of saccades. Although there is no absolute compartmentalization of function within the three major ocular motor areas in the cerebellum, the structural-functional approach provides a framework for assessing ocular motor performance in patients with disease that involves the cerebellum or the brainstem.

Limitations of the standard agglutination test for detecting patients with Brucella melitensis bacteremia.

The sensitivity of the standard agglutination test (SAT) for detecting brucellosis was determined in 264 Israeli patients from whom a positive blood culture for Brucella melitensis and serology were obtained within ± 1 week. A SAT titer ≥1:160 had a diagnostic sensitivity of 91.7%, whereas raising the cutoff to ≥1:320, as recommended to decrease false-positive rates in endemic areas, reduced the sensitivity to 82.6%. Physicians working in regions endemic for brucellosis should be aware of the limitations of the SAT for detecting patients with the disease.