Deep gray matter and fatigue in MS: a T1 relaxation time study.

UNLABELLED: Fatigue in multiple sclerosis (MS) occurs commonly, sometimes as the earliest symptom. Some MS patients consider fatigue to be their most troublesome complaint, and it has been shown to be an independent predictor of impaired quality of life. Several reports have demonstrated that subcortical gray matter pathology is related to fatigue. We hypothesized that MRI detectable changes in the deep gray matter of MS patients may correlate with fatigue severity. Our objective was: to assess the relationship between fatigue severity and detectable changes on magnetic resonance imaging (MRI), quantified using the mean T1 relaxation time (T1), in deep gray matter structures in relapsing remitting multiple sclerosis (RRMS). Using region of interest analysis, T1 values were measured for the thalamus, putamen and caudate nucleus in 52 RRMS patients and 19 healthy volunteers. Fatigue was assessed using the Fatigue Severity Scale. RESULTS: The median T1 in the thalamus and the putamen were significantly higher in the patient cohort than in the healthy controls; the median T1 in the caudate was also higher in the MS patients but did not reach statistical significance. There was a significant correlation between fatigue severity and the T1 of the thalamus (rho = 0.418; p = 0.014). Furthermore, the median T1 in the thalamus was significantly higher in patients with fatigue compared with those without (p = 0.018). Our results provide further evidence for the role of subcortical gray matter structures in the pathogenesis of multiple sclerosis (MS)-related fatigue. This study also demonstrates that T1 relaxation time measurement is a suitable technique for detecting abnormalities of the deep gray matter in RRMS and presents further support of gray matter involvement in MS.

[An automated and spectral differentiating dark adaptometer--initial results of a clinical study]. / Ein automatisiertes und spektral differenzierendes Dunkeladaptometer--erste Ergebnisse einer klinischen Studie.

BACKGROUND: Routine measurement of dark adaptation is a lengthy process and the presence of a qualified operator is required. MATERIALS AND METHODS: Our dark adaptometer uses either a red or a green light-emitting diode to produce the threshold stimulus. Through an electronic circuit arrangement the dark adaptation curve is automatically measured. A computer stores the resulting data and renders the statistical analysis possible. To obtain the normal adaptation curve, 33 healthy volunteers were tested. We subsequently examined 32 patients in the clinical assay. RESULTS: The adaptation for the green test light results in an overlapping photopic/scotopic graph and is used as an analogy for the curve resulting from a white test light. The red LED produces the scotopic graph later on with a more elevated threshold. Of the patients examined, 14 with night blindness show the expected pathological results. Correlating to the type of disease, the other 18 patients without night blindness show normal dark adaptation. CONCLUSIONS: In 150 examinations the dark adaptometer proved to be easy to handle, yielding valid and reliable results. The automatic recording allows operator-independent measurements. The dark adaptation rate for red and green and the final cone and rod threshold can be evaluated. The computer control provides statistical analysis and the possibility to delegate the examination.

Cone interaction and color substitution as revealed by pattern ERG.

Transient electroretinograms to a reversing color-contrast checkerboard pattern (P-ERG) were recorded in a protanomalous, a deuteranomalous, and a normal observer. Alternate monochromatic checks were of constant wavelength (630 nm red-531 nm green), while the relative energies were varied systematically. When changing the radiance ratio 630 nm-531 nm of the stimulus, the normal subject exhibited a P-ERG to all stimuli with only a relative amplitude minimum at a distinct radiance ratio, whereas the color-deficient observers failed to show a P-ERG at some color contrast 630 nm-531 nm, the radiance ratio of which was different in the protan and deutan. From the radiance ratio of color contrast for the smallest potential in the normal observer, we conclude that the green- and red-sensitive cone mechanism provides a difference signal which generates the response. The data from the color-deficient observer support the view that color discrimination in protans and deutans is reduced because the input of one type of photoreceptor is missing.

Pattern electroretinogram of the blue cones.

In man the electroretinogram to pattern reversal stimuli (P-ERG) represents a cone response of the proximal retina, dominated by the cone mechanisms sensitive to red (R) and green (G). Additionally there is a cone mechanism sensitive to blue (B) which can be studied with and without steady exposure to yellow light. During exposure to a superimposed uniform yellow background (576 nm) the transient P-ERG of the B cones is represented by potentials of small amplitude (less than 1 microV). The latency (peak time) of the response is about 30 ms longer than that of the midspectral (R and G) cones. Furthermore, the P-ERG of the B cones saturates at low luminances and exhibits a maximum amplitude at about 460 nm. Without yellow adaptation, the P-ERG of the B cones can be studied only with low-intensity stimuli of short wavelengths. Near threshold, both the long-latency response of the B cones and the short-latency response of the R and G cones are recorded simultaneously, forming a double-peaked wave shape. At suprathreshold luminances, even of short wavelength (435 nm) the P-ERG of the B cones is concealed by the larger short latency response of the midspectral cone mechanism.

Effect of pre-adaptation on pattern electroretinogram (P-ERG).

Up to now light and dark adaptation are considered as of minor importance when recording the pattern electroretionogram (P-ERG) which in man reflects cone vision. In order to test this supposition transient P-ERGs were recorded in six healthy subjects to a reversing checkerboard pattern produced by a pivoted mirror system after two minutes of pre-exposure to darkness (1), to the pattern reversal stimulus (2), and to uniform illumination of 3.3 log cd/m2 (3). Field size was 18 x 20 degrees, check size 69 min of arc, reversal frequency 3.5/s, contrast 0.95. When recording the P-ERG within the first 30 s after pre-exposure, the amplitude/luminance function of the p-q and the q-r component was shifted along the luminance axis without changing the maximum amplitude. For a criterion response of 1.5 microV there was a sensitivity difference of 1.3 log units between measurements after pre-exposure to darkness and after strong illumination. Furthermore, the P-ERG latencies of the q and the r component displayed significantly shorter values after pre-exposure to strong light than after darkness, whereas no change of p-latency was recorded. We conclude that pre-exposure to darkness and strong illumination has no effect on the P-ERG elicited at high luminance levels. However, pre-adaptation should be considered when recording the P-ERG at luminance levels near threshold.