The association of CAG repeat length with clinical progression in Huntington disease.

OBJECTIVE: To determine whether the rate of clinical progression in Huntington disease (HD) is influenced by the size of the CAG expansion. METHODS: The dataset consisted of 3,402 examinations of 512 subjects seen through the Baltimore Huntington's Disease Center. Subjects were seen for a mean of 6.64 visits, with mean follow-up of 6.74 years. Subjects were administered the Quantified Neurological Examination, with its subsets the Motor Impairment and Chorea Scores, the Mini-Mental State Examination, and the HD Activities of Daily Living (ADL) Scale. RESULTS: In an analysis based on the Random Effects Model, CAG length was significantly associated with the rate of progression of all measures except chorea and ADL. There was a significant interaction term between CAG length and disease duration for all measures except chorea. Further graphical exploration of the data supported these linear models and suggested that subjects at the low end of the expanded CAG repeat range may experience a more benign late course. CONCLUSIONS: CAG repeat length has a small effect on rate of progression that may be clinically important over time. Individuals with the shortest expansions appear to have the best prognosis. These effects of the CAG length may be relevant in the analysis of clinical trials.

Onset and rate of striatal atrophy in preclinical Huntington disease.

BACKGROUND: Huntington disease (HD) is characterized by striatal atrophy that begins long before the onset of motor symptoms. OBJECTIVE: To determine when striatal atrophy begins, the extent and rate of atrophy before diagnosis of motor symptoms, and whether striatal atrophy can predict when symptom onset will occur. METHODS: Caudate and putamen volumes were measured on MRI scans of 19 preclinical subjects with the HD gene expansion who were very far (9 to 20 years) from estimated onset, and on serial scans from 17 preclinical subjects, six of whom were diagnosed with HD within 5 years after the initial scan. RESULTS: Striatal volumes were significantly smaller for the subjects who were very far from estimated onset than for age-matched control subjects. Statistical models fit to the longitudinal data suggest that rate of caudate atrophy becomes significant when subjects are approximately 11 years from estimated onset and rate of putamen atrophy becomes significant approximately 9 years prior to onset. In the six incident cases, caudate and putamen were approximately one-third to one-half of normal volume at diagnosis, and caudate volume alone was able to predict with 100% accuracy those subjects who would be diagnosed within 2 years of imaging. CONCLUSIONS: Striatal atrophy begins many years prior to diagnosable HD, and assessment of atrophy on MRI may be very useful in both predicting HD onset and in tracking progression in future therapeutic trials in preclinical subjects.

Occurrence of Ergot (Sugary Disease) Incited by a Sphacelia sp. on Sorghum in Mississippi in 1997.

Ergot (sugary disease) incited by a Sphacelia sp. was observed on Sorghum bicolor (L.) Moench var. Sweet Leaf II at Leland and Pop-larville, MS, in October 1997. The disease was characterized by droplets of a thick, sticky, semi-transparent secretion similar to aphid honeydew. The caryopsis of infected florets was converted to relatively soft, chalky pink, tumescent, immature sclerotia (1.5 to 1.7 × 4 mm) with blunt ends. Abundant conidia (11 to 17 × 5 to 7 µm) were produced on stromatic tissue and in large numbers in the sugary secretion. This fungus is similar to that described by Zummo in West Africa (2). Velazquez-Valle et al. (1) recently reported the distribution of Claviceps africana Frederiksen, Mantle & de Milliano in the United States in 1997. The Sphacelia stage of the fungus found in Mississippi is similar to that reported from other areas of the U.S. Our report extends the range for this fungus, which is contiguous to those areas reported by Velazquez-Valle et al. (1). References: (1) R. Velazquez-Valle et al. 37th Annu. Mtg. Carib. Div., Am. Phytopa-thol. Soc., San Jose, Costa Rica, No. 77, 1997. (2) N. Zummo. 1984. Sorghum Diseases in West Africa. An Illustrated Text. USDA/USAID, Zaria, Nigeria.

A double-blind provocative study of chocolate as a trigger of headache.

A provocative double-blind study of headache was performed using chocolate as the active agent and carob as the placebo. The chocolate and carob samples were formulated to duplicate products used in an earlier study (1) in which strong differential effects between the ability of chocolate and carob to trigger headache in migraine were shown. Sixty-three women with chronic headache (50% migraine, 37.5% tension-type, 12.5% combined migraine and tension-type) participated in the study. After 2 weeks of following a diet that restricted vasoactive amine-rich foods, each subject underwent double-blinded provocative trials with two samples of chocolate and two of carob presented in random order. Diaries were maintained by the subjects throughout the study, monitoring diet and headache. The results demonstrated that chocolate was not more likely to provoke headache than was carob in any of the headache diagnostic groups (chi2(2)=0.36, p=0.83). Interestingly, these results were independent of subjects' beliefs regarding the role of chocolate in the instigation of headache (chi2(1)=0.73, p=0.39). Headache diagnosis and the concomitant use of additional vasoactive amine-containing foods were also not associated with chocolate acting as a headache trigger. Thus, contrary to the commonly held belief of patients and physicians, chocolate does not appear to play a significant role in triggering headaches in typical migraine, tension-type, or combined headache sufferers.