Vestibular-Podokinetic interaction without vestibular perception.

After prolonged stepping in place relative to space over the center of a rotating turntable, blindfolded subjects cannot step on the stationary platform without unknowingly turning themselves relative to space, a phenomenon termed podokinetic after rotation (PKAR). We asked what role the resulting vestibular stimulation might play in the expression of this form of PKAR. A method of servo-stabilizing the body relative to space during PKAR was devised to compare PKAR expression with and without significant vestibular stimulation. Simulated estimates of average central vestibular response profiles were obtained by passing the averaged unidirectional body angular velocity profiles relative to space through a first-order model of the canal system (tau=15 s). Such simulation results suggested that during normal PKAR performed on a stationary platform, the average central vestibular response would likely rise to peak levels equivalent to that induced by about 9 degrees /s within the frequency range of natural head movement. In the servo-stabilized condition, the simulated response was reduced to insignificant levels. Experimental results demonstrated that in the unstabilized condition the rate of rise of PKAR angular velocity was roughly four times slower than in the stabilized condition. We conclude that the normal expression of PKAR conducted on a stationary platform tends to be substantially slowed by interaction with an unperceived vestibular response.

Podokinetic after-rotation in patients with compensated unilateral vestibular ablation.

Previous studies showed that after stepping-in-place on a rotating turntable, blindfolded subjects cannot step-in-place on firm ground. Instead they involuntarily turn themselves relative to space in the same direction as they were turning relative to the rotating turntable. This phenomenon has been termed podokinetic after-rotation (PKAR). PKAR comprises a brief exponentially rising phase of response during the first 2 min followed by a prolonged second phase of slow exponential decline during the next 28 min. Here we ask whether PKAR is modified in patients with compensated unilateral vestibular loss. Eleven patients who had previous vestibular ablation underwent (1) a Fukuda-like control stepping test, (2) podokinetic adaptation to 30 min of stepping in place on the centre of a turntable rotating at 45 deg/s and (3) PKAR. Control tests showed that the blindfolded patients had no significant rotational bias while stepping-in-place on the ground for 1 min. After 30 min of adaptation, the 2-min rising phase of PKAR was indistinguishable from normal. In contrast, the subsequent 28-min phase of exponential decline showed a lesion-dependent asymmetry. PKAR had significantly higher mean velocities toward the side of the lesion than away from the lesion. The observed PKAR asymmetry may signify occult residual static vestibular imbalance.

Podokinetic after-rotation following unilateral and bilateral podokinetic stimulation.

Previous studies demonstrated an aftereffect of walking on a rotating treadmill, involving inadvertent circular navigation with eyes closed [podokinetic after-rotation (PKAR)]. We compared PKAR following unilateral and bilateral podokinetic (PK) stimulation to determine whether the left and right legs could be independently adapted. Each subject performed two sessions of PK stimulation, stepping in place with one foot on either side of the axis of a rotating disk. Subjects experienced bilateral stimulation (i.e., both left and right feet stepped on the rotating disk) in one session and unilateral stimulation (i.e., the left foot stepped on the rotating disk and the right foot stepped on a stationary surface) in the other. Following stimulation, we recorded foot lift-off and touchdown times and pelvic angular velocity while subjects stepped in place on a stationary surface. PKAR velocity following unilateral stimulation was lower than that following bilateral stimulation. Following bilateral stimulation, pelvic rotation was in the counterclockwise (CCW) direction during single-limb support on both the left and right sides. Immediately following left unilateral stimulation, subjects demonstrated CCW pelvic rotation during left single-limb support but not during right single-limb support. Across the first 13 strides, the difference between left and right sides diminished; pelvic angular velocity was then CCW during single-limb support on both sides. This suggests that both the adapted left and the unadapted right limb influenced the final PKAR response with information from the two limbs being integrated over the first few strides.

Transfer of podokinetic adaptation from stepping to hopping.

Following stepping in-place on the surface of a rotating circular treadmill, a subject attempting to step in-place or walk in a straight line across the floor without vision will rotate relative to space. This adaptation, termed podokinetic after-rotation (PKAR), transfers to backward walking following forward walking on the rotating disk. We asked whether adaptation obtained during stepping in-place on the rotating disk would transfer to hopping on both feet. We hypothesized that subjects would demonstrate PKAR during both hopping and stepping, adding support to the hypothesis that PKAR is a centrally mediated adaptation of general locomotor trajectory that is not specific to the form of locomotion used while on the rotating disk. Subjects demonstrated PKAR during both hopping and stepping after stepping in-place on the rotating disk. The time courses of PKAR during hopping and stepping were similar, although the angular velocity amplitude of PKAR was lower in hopping than in stepping. This difference in amplitude suggests an incomplete transfer of PKAR.

Forward versus backward walking: transfer of podokinetic adaptation.

We asked whether podokinetic adaptation to walking on a circular treadmill transfers to different forms of locomotion. Subjects were blindfolded and asked to walk straight across the floor, in the forward and backward directions, following podokinetic (PK) stimulation that consisted of 30 min of forward walking-in-place on the perimeter of a disk rotating in the clockwise direction. During both forward and backward walking following forward-walking PK stimulation, subjects involuntarily walked along curved trajectories at angular velocities well above vestibular threshold, although they perceived that they were walking along straight paths. The curved paths of forward and backward walking were indistinguishable from one another. Transfer of PK adaptations acquired during forward walking on the turntable to backward walking trials suggests that the PK system controls general locomotor trajectory. Adaptation of the system thus influences forms of locomotion other than that used during acquisition of the adaptation. This transfer also supports the concept that forward and backward walking are controlled by neural networks that share common elements. An interesting feature of the transfer of PK adaptation is that for both forward and backward walking, subjects turned in a counterclockwise direction. As such, the direction of relative rotation between the trunk and feet was maintained for both forward and backward walking. However, the relationship of the lower extremities to the center of rotation was not preserved. The left limb was the inner leg during PK stimulation and forward walking after adaptation, but the left leg was the outer leg during backward walking. These results suggest that PK adaptation affects general locomotor trajectory via a remodeling of the rotational relationship between the trunk and the feet.

Spontaneous regression of optic gliomas: thirteen cases documented by serial neuroimaging.

OBJECTIVE: To demonstrate spontaneous regression of large, clinically symptomatic optic pathway gliomas in patients with and without neurofibromatosis type 1 (NF-1). METHODS: Patient cases were collected through surveys at 2 consecutive annual meetings of the North American Neuro-Ophthalmology Society (NANOS) and through requests on the NANOSNET Internet listserv. Serial documentation of tumor signal and size, using magnetic resonance imaging in 11 patients and computed tomography in 2 patients, was used to evaluate clinically symptomatic optic pathway gliomas. All tumors met radiologic criteria for the diagnosis of glioma and 4 patients had biopsy confirmation of their tumors. In 3 patients, some attempt at therapy had been made many years before regression occurred. In one of these, radiation treatment had been given 19 years before tumor regression, while in another, chemotherapy had been administered 5 years before signal changes in the tumor. In the third patient, minimal surgical debulking was performed 1 year before the tumor began to shrink. RESULTS: Spontaneous tumor shrinkage was noted in 12 patients. Eight patients did not have NF-1. In an additional patient without NF-1, a signal change within the tumor without associated shrinkage was detected. Tumor regression was associated with improvement in visual function in 10 of 13 patients, stability of function in 1, and deterioration in 2. CONCLUSIONS: Large, clinically symptomatic optic gliomas may undergo spontaneous regression. Regression was seen in patients with and without NF-1. Regression may manifest either as an overall shrinkage in tumor size, or as a signal change on magnetic resonance imaging. A variable degree of improvement in visual function may accompany regression. The possibility of spontaneous regression of an optic glioma should be considered in the planning of treatment of patients with these tumors.

Photodynamic endometrial ablation in the nonhuman primate.

OBJECTIVE: To test the effectiveness of 5-aminolevulinic acid (ALA)-induced photodynamic endometrial ablation in the rhesus monkey under varying conditions of light delivery (fractionated versus continuous) and steroid priming. METHODS: Photodynamic endometrial ablation was carried out in 17 rhesus monkeys that were either postmenopausal or in the early proliferative phase. Four hours after intralumenal injection of ALA (250 mg in 1 mL hyskon), a quartz fiber with a diffusing tip was inserted. A KTP tunable dye laser delivered 300 mW of light (635 nm) for 60 minutes in either continuous or fractionated fashion (20 minutes on, 5 minutes off, and 40 minutes on). In some experiments, thermistors were used to monitor temperature in the lumen and myometrium during light treatment. Hysterectomy was performed 3 or 4 days after treatment, and endometrial damage was assessed histologically. Two additional monkeys (one rhesus and one cynomolgus monkey) were exposed to the same protocol, except hyskon was substituted for ALA to control for potential ablative effects due to light treatment alone. RESULTS: Endometrial ablation was evident in all ALA-photosensitized specimens. The degree of ablation around the light fiber ranged from moderate to complete. The depth of ablation ranged from 1.14 +/- 0.54 to 2.15 +/- 1.62 mm (mean +/- standard deviation). Ablation was most complete in uteri of menopausal monkeys. Light treatment after ALA increased lumenal temperature from 36 C to 50 C, whereas temperature was not significantly increased by light treatment in the controls. CONCLUSION: This is the first report of endometrial destruction in the primate using a photodynamic approach. Whereas clinical application of photodynamic therapy (PDT) requires complete endometrial ablation to produce long-lasting amenorrhea, our results suggest that PDT may offer a simple office-based approach to endometrial ablation.

Oculomotor responses to on-axis rotational stepping in normal and adaptively altered podokinetic states.

Previous studies investigated adaptive properties of a podokinetic (PK) system that senses and controls angular movement of the trunk relative to the stance foot when walking around a curved trajectory or during rotational stepping on the spot. In particular, after adaptively modifying the PK system by prolonged stepping-in-place over the axis of a horizontally rotating platform, blind-folded subjects could no longer step in place on firm ground. When trying to do so they invariably rotated themselves relative to space without perceiving their rotation, a phenomenon termed podokinetic after-rotation (PKAR). It is well known that normal rotational stepping generates a specifically podokinetic component of compensatory nystagmus which is independent of the VOR. The present study investigated whether during PKAR this podokinetic component of oculomotor activity follows the somatosensory correlate of actually stepping around, or the cognitive intent or percept of 'no rotation'. Experiments were conducted in two phases on five normal human subjects. In the first phase, the normal passively induced VOR was compared with the combined VOR and PK oculomotor response induced by intentional rotational stepping on the spot. In both cases the angular stimulus was a 2-min rotation at 15 degrees/s. Subtraction of the decaying VOR from the actively induced combined response revealed a constant podokinetic nystagmus with slow-phase velocity gain of about 0.4 maintained throughout this period. The PK and VOR response components appeared to sum linearly. In the second phase, we measured oculomotor activity during PKAR, when the blindfolded subjects involuntarily rotated themselves at around 15 degrees/s while attempting to step-in-place after the podokinetic adaptation procedure noted above. The striking result of the second phase of experiments was that, although an apparently normal decaying VOR was present, the maintained PK component of response was consistently absent, despite an essentially normal physical pattern of rotational stepping. Thus, in the adapted state, non-vestibular oculomotor activity followed the cognitive intent or percept of 'no rotation', rather than the prevailing somatosensory-motor activity of the lower limbs. The finding points to an important cognitive element in this form of oculomotor control.

Complex podokinetic (PK) response to post-rotational vestibular stimulation.

Recent studies identified an adaptive "Podokinetic" (PK) sensory motor system involved in sensing and controlling spatial orientation during locomotion, by referencing body orientation to the space-stable stance foot. This paper investigates the interaction of vestibular and PK systems by asking blindfolded subjects to 'step-in-place' (i.e. without turning) after exposing them to a unidirectional post-rotational vestibular stimulus. Six of the nine subjects consistently began by vigorously propelling themselves round in the direction of preceding turntable rotation, but notably without any sensation of turning. In all these subjects the speed of this PK-induced rotation progressively declined to zero over about the next 30 sec and then reversed direction with increasing speed for about 50 sec. Thereafter the speed of rotation declined slowly to zero over the next 4 to 5 minutes. Since the PK-generated body rotation presumably feeds back into the vestibular-PK drive, we formulated a closed loop model of the combined system to investigate the complex nature of the behavioral response. The simulated response of this model closely resembled the experimental data, suggesting that there is indeed a functionally closed loop operating between the vestibular and podokinetic systems in natural life.

Relative afferent pupillary defects in patients with Leber hereditary optic neuropathy and unilateral visual loss.

PURPOSE: It has been suggested that the pupillary light reaction is relatively preserved in the affected eyes of patients with Leber hereditary optic neuropathy (LHON). To test the hypothesis that visual-pupillomotor dissociation exists in LHON, we performed a retrospective study to evaluate the magnitude of the relative afferent pupillary defect (RAPD) in patients who had experienced monocular visual loss. We also compared the size of the measured RAPD with the size of the RAPD that would be expected on the basis of documented visual field loss. METHODS: We identified a cohort of patients with LHON and monocular visual loss, whose pupillary reactions had been quantified using neutral density filters. From a review of the case records, we determined whether an RAPD was present, as well as the magnitude of the documented RAPDs. We also calculated the expected size of the RAPD for each patient, using previously established templates that correlated the size of the RAPD with the degree of visual field loss. RESULTS: An RAPD was identified in all 10 patients in this study. There was no significant difference between the size of the measured and predicted RAPD, nor did the size of the RAPD correlate with visual acuity or the time interval between the onset of visual loss and evaluation. CONCLUSION: The results of this study do not support the hypothesis that visual-pupillomotor dissociation is a common feature of LHON.

Motor learning in the "podokinetic" system and its role in spatial orientation during locomotion.

The present study characterizes a previously reported adaptive phenomenon in a somatosensory-motor system involved in directional control of locomotor trajectory through foot contact with the floor. We call this the "podokinetic" (PK) system. Podokinetic adaptation was induced in six subjects by stepping in-place over the axis of a horizontally rotating disc over a range of disc angular velocities (11.25-90 degrees/s) and durations (7.5-60 min). After adaptation, subjects were blindfolded and attempted to step in-place on the floor without turning. Instead they all rotated relative to space. The rate of the "podokinetic afterrotation" (PKAR) was linearly related to stimulus amplitude up to 45 degrees/s, and the ratio of initial PKAR velocity to that of the adaptive stimulus was approximately 1:3. PKAR exhibited exponential decay, which was composed of "short-" and "long-term" components with "discharging" time constants on the order of 6-12 min and 1-2 h, respectively. The effect of stimulus duration on PKAR revealed a "charging" time constant that approximated that of the short-term component. A significant suppression of PKAR occurred during the 1 st min of the postadaptive response, suggesting functional interaction between the PK and vestibular systems during the period of vestibular stimulation. During PKAR subjects perceived no self-rotation, indicating that perception as well as locomotor control of spatial orientation were remodeled by adaptation of the PK system.

Neonatal tracheal obstruction caused by aspiration of decidual tissue.

We report a newborn female born at 29 weeks' gestation who was unable to be resuscitated following a vaginal breech delivery. At autopsy the larynx and trachea contained a 1.2 x 0.2 cm fragment of tissue. Microscopic sections of this tissue revealed it to consist of decidua. This is the first report in the literature of tracheal obstruction secondary to aspiration of decidua. The mechanism by which this tissue may have resulted in completed obstruction of the trachea is discussed.

Congenital erythroleukemia in a neonate with severe hypoxic ischemic encephalopathy.

We report a case of a neonate who presented with hypoxic ischemic encephalopathy, persistent hypoglycemia and hypotension, intractable metabolic acidosis, renal failure and a coagulopathy but who, at autopsy, was found to have massive infiltration of nonhematopoietic tissues with blasts. The diagnosis of congenital erythroleukemia was confirmed by the detection of glycophorin A, a major erythrocyte membrane protein, on the surface of the blasts. The clinical presentation and course of the case described here have not previously been reported for this extremely rare condition.

Chiasmal glioma in neurofibromatosis type 1 with severe visual loss regained with radiation.

Children with neurofibromatosis type 1 (NFI) and chiasmal gliomas are often considered unlikely to experience progressive visual loss. However, this may not be true. We report a 5-year, 6-month-old boy, with recently diagnosed NF1, who had a chiasmal glioma diagnosed after neuroimaging. He subsequently experienced rapid visual acuity loss. His vision improved significantly after irradiation. The controversy surrounding radiotherapy for chiasmal glioma is discussed.

Is the stepping test a specific indicator of vestibulospinal function?

We studied the effect of walking on a horizontally rotating disk (circular treadmill) on the stepping test in seven normal subjects. Subjects walked for 2 hours on the perimeter of the treadmill with eyes open while remaining stationary in space. Then, off the treadmill, they attempted to step in place with eyes closed for 50 paces without turning. All subjects exhibited post-treadmill turning in the same direction as that of the previous walking relative to the treadmill. Post-treadmill average angular velocities were 207 to 880 deg/min greater than pretreadmill values. No subject experienced any sensation of motion relative to ground or space. The stepping test may no longer be considered a specific indicator of vestibulospinal function.

Adaptive plasticity in the control of locomotor trajectory.

Eight human subjects were exposed to 2 h of walking on the perimeter of a horizontally rotating disc with the body remaining still in space. After adaptation to this experience subjects were blindfolded and asked to walk straight ahead on firm ground. When doing so all subjects generated curved walking trajectories of radii ranging from 65 to 200 inches and angular velocities from 7 to 20 deg/s. Subsequent trials over the next half hour revealed retained, but decreasing, trajectory curvature. Angular velocities associated with these trajectories were well above vestibular sensory threshold, yet all subjects consistently perceived themselves as walking straight ahead. The blindfolded subjects were also asked to propel themselves in a straight line in a wheel chair. Post-adaptation wheel chair trajectories showed no change from those before adaptation. Hence we infer that it was the relation between somatosensory/motor elements of gait and the perception of trunk rotation that had been remodelled during walking on the turning disc. This novel form of adaptive plasticity presumably serves to maintain optimal values of central neural parameters that control the trajectory of locomotion. The findings may have significant implications for the diagnosis and rehabilitation of locomotor and vestibular disorders.

Magnetic resonance features in carbon monoxide poisoning.

The authors describe unusual magnetic resonance findings due to carbon monoxide poisoning in a 34-year-old woman. With T2-weighted imaging, increased signal intensity was observed bilaterally in the putamen and the caudate nucleus. Lesions of high signal intensity in the globus pallidus, which have been previously reported, were also observed.

Ophthalmological aspects of Alzheimer's disease.

Patients with Alzheimer's disease may present to the ophthalmologist with visual symptoms that precede or overshadow the features of dementia. This visual variant of Alzheimer's disease has been recognized only recently and typically appears in late middle age as progressive visuospatial and reading dysfunction, with normal visual acuity and fields. Common features include simultanagnosia and the other features of Balint's syndrome, and variable hemispatial neglect and hemianopia. The neuroimaging and neuropathological findings in this Alzheimer's variant are distinct and suggest disruption of occipitoparietal visual projections. The identification of the visually symptomatic patient who is destined to develop other signs of Alzheimer's disease depends on the use of appropriate screening tests, including text reading, figure-ground discrimination, and other bedside tests of visuospatial attention and perception.