Safety and feasibility of long-term temozolomide treatment in patients with high-grade glioma.

We surveyed neuro-oncologists regarding patients treated with temozolomide for at least 12 cycles or 12 months. Patients receiving first-line temozolomide for a median 13 cycles had a median progression-free survival (PFS) of 14 months. Patients with recurrent disease receiving a median 14 cycles had a median PFS of 15.5 months. A small percentage of patients experienced grade III to IV toxicity. These results suggest that long-term treatment with temozolomide is feasible and well tolerated.

Positron-emission tomographic study of human amblyopia with use of defined visual stimuli.

PURPOSE: The purpose of this study was to use positron emission tomography (PET) to evaluate effects of amblyopia on cerebral blood flow and glucose metabolism in humans viewing defined visual stimuli and to correlate these effects with specific behavioral and electrophysiologic measures of visual function. METHODS: One subject with normal vision and five patients with amblyopia were prospectively studied. During monocular viewing of a checkerboard reversal stimulus by each subject, we performed PET imaging of relative cerebral glucose metabolism with use of [18F]fluorodeoxyglucose, PET imaging of relative cerebral blood flow with use of H2(15)O, and visual evoked potentials. Control studies were also performed with use of binocular occlusion and during presentation of stationary and horizontally drifting checkerboards. These data were correlated with letter acuities and contrast sensitivity functions for each eye. RESULTS: Although spatial resolution was superior for glucose metabolic imaging, PET readily demonstrated activation of calcarine cortex with use of both metabolic and blood flow tracers. Even in patients with mild amblyopia, functional activation of calcarine cortex was reduced in amblyopic eyes compared with sound eyes to a degree more closely correlated with visual acuity than were visual evoked potential amplitudes to the same stimulus. When responses to drifting versus stationary stimuli were compared, a putative motion processing center was identified in the right temporoparietal region. Activity in this motion center was relatively preserved during viewing of drifting stimuli by the affected eye of an anisometropic amblyopic subject, but was attenuated during viewing of the same stimulus by the affected eye of a strabismic amblyopic subject. CONCLUSIONS: PET imaging of blood flow and metabolism can quantitatively evaluate functional deficits resulting from amblyopia in striate as well as extrastriate visual areas. Calcarine cortical function correlates closely with severity of amblyopia, but function in a putative motion processing area may vary according to the type of amblyopia present.

Finding the depth of magnetic brain stimulation: a re-evaluation.

The depth of threshold magnetic nerve stimulation can be estimated by using thresholds from two different-sized stimulus coils and plotting their induced electric field vs. depth profiles. Stimulation is presumed to take place where the two field profiles are equal. If the two coils have unequal inductances, however, there is a relative shift in threshold between coils that alters the intersection point and the apparent stimulus depth. This systematic error arises from two sources: (1) there is a difference in the fraction of stimulator energy reaching each coil, and (2) pulse durations are different, causing threshold shifts governed by the nerve strength-duration curve. Both sources of error are additive. If the larger coil has the lesser inductance, stimulus depth is underestimated; if it has the greater inductance, it is overestimated. This can lead to large disparities in the measured depth, depending on the sets of coils used. In this paper, we show how to correct for errors introduced by unequal inductance and how this resolves discrepancies in depth measurement. Our own depth measurements in the motor area for threshold finger movements, and recalculated depths from Epstein et al., indicate that stimulation is slightly deeper (18-21 mm, average 19+ mm) than previously thought. This suggests that threshold magnetic stimulation in the motor area may arise from large, tangentially oriented fibers in the superficial white matter, or in the gray matter at the upper sulcus or lip of the gyrus.

Phosphenes induced by magnetic stimulation over the occipital brain: description and probable site of stimulation.

Phosphenes were elicited by brief, intense magnetic pulses directed to the occipital area of the brain with two different magnetic stimulators and various coils. The observed phosphenes were described or sketched by the subject. Phosphenes were usually wedge-shaped flashes of light in the midperiphery, although occasionally structured phosphenes were reported (stripes or grids). The depth of effective stimulation was measured by determining the phosphene threshold for two different size coils. Additional depth measurements were made at the cortical motor strip for threshold finger twitches. The visual stimulation site was clearly deeper (approximately 4 cm) than the site for motor stimulation (approximately 2 cm), and lay near the midline. Both foveal and peripheral phosphenes had identical stimulation depths, implying a subcortical stimulation site, possibly in the optic radiation fibers adjacent to the posterior tip of the lateral ventricles. Fibers closest to the ventricle, representing the horizontal meridian of the visual field, would be preferentially stimulated, in agreement with experimental results.

Magnetostimulation of vision: direct noninvasive stimulation of the retina and the visual brain.

The history of magnetophosphenes and their closely related predecessor, electrophosphenes, is described from the mid-18th century to the present time. The current era of magnetic stimulation started in 1985 with the development of a practical capacitor-discharge electromagnetic stimulator by Barker and his colleagues at the University of Sheffield, and their application of it to the brain with Merton and Morton at the National Hospital, London. The safety of magnetostimulation of the brain is discussed as well as the advantages of magnetostimulation over electrostimulation. Principles of magnetostimulation of nerves and magnetic measurement are considered. Effects on motor and sensory systems of the brain are described including magnetic perceptual suppression in the visual cortex and other pioneering work of Amassian, Cracco and Maccabee at SUNY Health, Brooklyn. Magnetophosphenes from retinal and cortical magnetostimulation are distinguished. Now that visual cortical stimulation is possible with the strong magnetic pulses generated by capacitor-discharge instruments, the functional viability of the visual cortex may be tested directly and noninvasively.

Imaging visual function of the human brain.

Imaging of human brain structure and activity with particular reference to visual function is reviewed along with methods of obtaining the data including computed tomographic (CT) scan, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and positron emission tomography (PET). The literature is reviewed and the potential for a new understanding of brain visual function is discussed. PET is reviewed from basic physical principles to the most recent visual brain findings with oxygen-15. It is shown that there is a potential for submillimeter localization of visual functions with sequentially different visual stimuli designed for the temporal separation of the responses. Single photon emission computed tomography (SPECT), a less expensive substitute for PET, is also discussed. MRS is covered from basic physical principles to the current state of the art of in vivo biochemical analysis. Future possible clinical applications are discussed. Improved understanding of the functional neural organization of vision and brain will open a window to maps and circuits of human brain function.

[HIV infection: neuropsychiatric symptoms]. / Die HIV-Infektion: Neuropsychiatrische Symptome.

Basing on the actual publications, the most important neurological and psychopathological symptoms of HIV-infection are systematically reported. Opportunistic infections are producing important neurological symptoms. A case of Cryptococcus neoformans-Infection of the brain is described.

Stimulus deprivation amblyopia in children. Sensitivity, plasticity, and elasticity (SPE).

In the SPE model we propose, sensitivity (S) to deprivation results in changes that may be either plastic (P) (permanent) or elastic (E) (temporary). The effects of various levels (hours per day) of monocular occlusion in amblyopic children are measured as the change in visual acuity in each eye. At the patching level extremes (12 or more hours per day, zero hours per day) the effects on visual acuity in the two eyes are reciprocal, but nearly equal (symmetrical). At intermediate levels of occlusion, the asymmetries in effects necessary for successful occlusion can be demonstrated. Additional measurements of SPE parameters in children may allow for the determination of occlusion dose response whereby the risks of occlusion amblyopia and interference with binocularity may be avoided.

Amblyopia and congenital esotropia. Visually evoked potential measurements.

Amblyopia in patients with congenital esotropia was studied using visually evoked cortical potentials. In only four of 31 patients with esotropia and no abducting nystagmus was amblyopia detected before surgery. Postoperatively, 19 of these patients had amblyopia. In contrast, nine of the 11 patients with esotropia and nystagmus exhibited amblyopia before surgery. We conclude that amblyopia occurs infrequently in patients with congenital esotropia and no nystagmus until surgery reduces the angle of deviation and breaks down the cross-fixation reflex.

Eye patching and visual evoked potential acuity in children four months to eight years old.

The monocular visual acuities of six children aged 4 months to 8 years were measured using visual evoked potentials (VEP's) before and during patching therapy. A seventh child had both Snellen and VEP monocular acuities determined before patching. In a cooperative child, it was estimated that VEP acuity was within 0.25 octaves (one line on an eye chart) of Snellen acuity. In the four children less than 3 years of age, patching resulted in a 1.8-octave decrease in acuity of the patched eye and a 2.0-octave improvement in the unpatched eye. After cessation of patching therapy, acuity of the previously patched eye improved 2.0 octaves and that of the abnormal eye declined 1.75 octaves. In the two children older than 4 years, patching resulted in 1.25-octave acuity decrease in the patched eye. Cessation of patching resulted in a 1.25-octave improvement in acuity of the patched eye. No permanent deleterious effects of patching on acuity were observed.

Prentice-Memorial Lecture: Is the animal model for stimulus deprivation amblyopia in children valid or useful?

The animal models are not, strictly speaking, valid for clinical application to children, primarily because of the large differences in the duration of the critical or sensitive period. However, they do provide a useful conceptual framework to follow, especially while determining the waxing and waning of the amblyopia in each eye by preferential looking or visual evoked potential acuity methods. These methods allow us to detect or determine the degree of amblyopia and guide the treatment or prevention of stimulus deprivation amblyopia in each child by direct measurement. The reciprocal effect of amblyopia found by Thomas, Mohindra and Held in infants by the preferential looking method and confirmed and extended in age by our group with the visual evoked potential acuity method could have been predicted by the animal modelers from the cross-suturing experiments. It appears that more harm than good may be done by patching infants for the treatment of amblyopia without measuring the acuity of each eye to avoid the significant loss of connections to the patched eye and to both eyes (binocular units).

Long-term visual results in bilateral congenital cataracts.

In 24 infants who underwent surgery for bilateral congenital cataracts, 29 eyes (60%) achieved visual acuities of 6/18 (20/60) or better and 13 (27%) had visual acuities of 6/60 (20/200) or worse. The best results occurred in patients who underwent surgery before they were 8 weeks old. Only one patient of the seven operated on after the age of 8 weeks achieved a visual acuity of better than 6/60 (20/200). These favorable visual outcomes were the result of early surgery, short intervals between operations on fellow eyes (48 hours or less), total bilateral occlusion between operations, careful postoperative monitoring with retinoscopy and visual-evoked potentials, and early correction of aphakia.

Effect of natural deprivation and unilateral eye patching on visual acuity of infants and children. Evoked potential measurements.

Evoked potential measurements of visual acuity were made on four children aged from 5 months to 8 years. They were deprived of normal visual stimulation by various disorders: unilateral aphakia from a congenital cataract, vitreous hemorrhage, polar cataract, and esotropia. In the two younger children, aged 5 and 15 months, respectively, the visual acuity improved when the eye had good optical imagery and declined with poor or no imagery. Reversal of the imagery to the contralateral eyes again brought large changes in opposite directions. In the two older children, aged 4 and 8 years, respectively, there were marked decreases in acuity in the patched eye, but little or no change in the unpatched eye. It is not know whether these differences are due to age or to the original kind of visual disorder, such as deprivation, occlusion, or strabismus, or are merely individual differences. It is clear, however, that some children exhibit large changes in acuity in response to visual deprivation or patching, or to its removal, in a readily reversible manner. Also, we have demonstrated that visually evoked potential acuities may be obtained from pediatric, clinical patients without regard to age, which may be useful in management of the conditions.

Good visual function after neonatal surgery for congenital monocular cataracts.

We treated eight neonates who had total, monocular, congenital cataracts with surgery, occlusion, and contact lenses. Visual results in all eight patients were good. In five patients visual acuities improved to 6/9 (20/30) or better in the aphakic eye. In three patients visual acuities improved to 6/24 (20/80) or better. Problems with contact lenses probably accounted for the poorer results in two of these three patients. Binocularity was not demonstrated in any of our patients.

[The clinical picture of essential myoclonus]. / Zum Krankheitsbild der essentiellen Myoklonie.

Familial essential myoclonus, a rare hereditary disease, is characterized by spontaneous myocloni without any other neurological and psychic symptoms. The report deals with two sisters who suffered from the disease and in whose family the syndrome occurred in two more generations. The outlook for a favourable therapeutic effect is limited. The prognosis is good.

[Lymphadenopathy in phenytoin treatment]. / Lymphadenopathie unter Phenytoinbehandlung.

The authors report on a 20-year-old patient who developed hydantoin lymphadenopathy during treatment with diphenylhydantoin. The problems associated with clinical and histological delimination from malignant lymphomata are described by reference to the literature. Hydantoin lymphadenopathy is regarded as a drug-induced allergic and toxic process.

Computer-assisted eye examination. VII. Final evaluation of the refractor. III system for subjective examination after reducing software and hardware errors.

Eighty patient-volunteers were refracted by the computer-assisted Refractor III system and the results were compared with those obtained by the usual manual method. For the distance prescription 95% of the results were satisfactory. For the near add all were satisfactory. Relative validity of the system was also measured objectively by repeatability data. System test differences and test-retest manual-examination data were found comparable, indicating that the validity of the system is similar to that of the manual method. Further developments are expected to improve reliability, simplify maintenance, and extend testing so that the system will be an economical and useful instrument in eye clinics.