We have prospectively followed 16 Finnish xeroderma pigmentosum (XP) patients for up to 23 years. Seven patients were assigned by complementation analysis to the group XP-A, two patients to the XP-C group and one patient to the XP-G group. Six of the seven XP-A patients had the identical mutation (Arg228Ter) and the seventh patient had a different mutation (G283A). Further patients were assigned to complementation groups on the basis of their consanguinity to an XP patient with a known complementation group. The first sign of the disease in all the cases was severe sunburn with minimal sun exposure in early infancy. However, at the time the diagnosis was made in only two cases. The XP-A patients developed neurological and cognitive dysfunction in childhood. The neurological disease advanced in an orderly fashion through its successive stages, finally affecting the whole nervous system and leading to death before the age of 40 years. Dermatological and ocular damage of the XP-A patients tended to be limited. The two XP-C patients were neurologically and cognitively intact despite mild brain atrophy as seen by neuroimaging. The XP-G patients had sensorineural hearing loss, laryngeal dystonia and peripheral neuropathy. The XP-C patients had severe skin and ocular malignancies that first presented at pre-school age. They also showed immunosuppression in cell-mediated immunity. Neurological disease appears to be associated with the complementation group and the failure of fibroblasts to recover RNA synthesis following UV irradiation, but not necessarily to the severity of the dermatological symptoms, the hypersensitivity of fibroblasts to UVB killing or the susceptibility of keratinocytes to UVB-induced apoptosis.

SUMMARYObjective: To study the impact of childhood-onset epilepsy on a variety of outcomes across the life span. Methods: A population-based cohort of 245 subjects with childhood-onset epilepsy was assessed for outcomes at 45 years. In addition, 51 of 78 surviving subjects with uncomplicated epilepsy and 52 of 99 originally matched controls participated in a detailed evaluation including electroencephalography (EEG), imaging, and laboratory studies at 50 years. Results: Of 179 surviving subjects, 61% were in terminal 10-year remission and 43% in remission off medications. At 45 years, 95% of the idiopathic group, 72% of the cryptogenic group, and 47% of the remote symptomatic group were in terminal remission (p < 0.001). Abnormal neurologic signs were significantly more common in subjects with uncomplicated epilepsy than in controls. Mortality during period 1992-2012 was higher in subjects than in controls (9% vs. 1%, p = 0.02). The rate of 3T MRI abnormalities was higher in subjects than in controls (risk ratio [RR] 2.0; 1.3-3.1) specifically including findings considered markers of cerebrovascular disease (RR 2.5; 1.04-5.9). Even subjects with idiopathic epilepsy had higher rates of imaging abnormalities than controls (73% vs. 34%, p = 0.002). Significance: Long-term seizure outcomes are excellent and a function of etiology. The presence of imaging abnormalities suggestive of vascular disease may put these subjects at higher risk for clinically evident stroke and cognitive changes as they age.

Abstract. Laaksonen S, Voipio-Pulkki L-M, Erkinjuntti M, Asola M, Falck B (University Hospital, Turku, Finland). Does dialysis therapy improve autonomic and peripheral nervous system abnormalities in chronic uraemia? J Intern Med 2000; 248: 21±26.Objectives. Autonomic nervous system (ANS) dysfunction and peripheral neuropathy occur in patients with chronic renal insufficiency. Adequate renal replacement therapy should prevent development or correct these abnormalities. Design and subjects. We studied retrospectively ANS and peripheral neuropathy in 32 patients with chronic uraemia who received either haemodialysis (16) or peritoneal dialysis (16) therapy, and compared the observed dialysis efficiency with changes in neurological function. Methods. Heart rate variability (HRV) time domain indices and peripheral sensory nerve conduction studies were followed for a mean of 2.9 years. The adequacy of haemodialysis (HD) efficiency was estimated by Kt/V, an index of fractional urea clearance. Adequacy of continuous ambulatory peritoneal dialysis (CAPD) was estimated on the basis of the patient's wellbeing and nutritional status as excellent, satisfactory or poor. Based on observed changes in HRV time domain measures, the observations were divided in three subgroups: improved, unchanged or deteriorated. Results. The peripheral sensory nerve conduction studies were abnormal in 38% of the patients and did not change significantly during the study. Improvement in HRV time domain measures occurred in HD patients with mean Kt/V . 1.20 or in CAPD patients with satisfactory or excellent response to dialysis treatment. Values of Kt/V , 0.85 in HD patients were associated with progressive deterioration of autonomic neuropathy. Diabetic patients (n = 4) differed from others as their HRV was grossly abnormal and did not improve. Conclusions. The adequacy of haemodialysis is a predictor of improvement of cardiac autonomic nervous function in chronic uraemia. The same trend of improvement was seen also in CAPD patients.

Insulin and exercise have been shown to activate glucose transport at least in part via different signaling pathways. However, it is unknown whether insulin resistance is associated with a defect in the ability of an acute bout of exercise to enhance muscle glucose uptake in vivo. We compared the abilities of insulin and isometric exercise to stimulate muscle blood flow and glucose uptake in 12 men with type 1 diabetes (age 24 ؎ ; normal subjects versus patients with type 1 diabetes, NS), and exercise increased oxygen consumption similarly in both groups (25.3 ؎ 4.3 vs. 20.1 ؎ 3.0 ml ⅐ kg ؊1 muscle ⅐ min ؊1 , respectively, NS). Rates of insulin-stimulated muscle blood flow and the increments in muscle blood flow induced by exercise were also similar in normal subjects (129 ؎ 14 ml ⅐ kg ؊1 ⅐ min ؊1) and in patients with type 1 diabetes (115 ؎ 12 ml ⅐ kg ؊1 ⅐ min ؊1). The patients with type 1 diabetes exhibited resistance to both insulin stimulation of glucose uptake (34 ؎ 6 vs. 76 ؎ 9 mol ⅐ kg ؊1 muscle ⅐ min ؊1 , P < 0.001) and also to the exercise-induced increment in glucose uptake (82 ؎ 15 vs. 162 ؎ 29 mol ⅐ kg ؊1 muscle ⅐ min ؊1 , P < 0.05). We conclude that the ability of exercise to increase insulin-stimulated glucose uptake in vivo is blunted in patients with insulin-resistant type 1 diabetes compared with normal subjects. This could be caused by either separate or common defects in exercise-and insulinstimulated pathways.

Infantile spasms are often associated with transient cortical, especially occipital, hypometabolic foci that are not necessarily associated with structural lesions and do not indicate a poor prognosis.