Segmental demyelination induced by cerebrospinal fluid of progressive spastic paraparesis: correlation with altered proteolytic parameters.

Progressive spastic paraparesis (PSP) is a demyelinating disease of the central nervous system. We studied the ability of the cerebrospinal fluid (CSF) of patients to induce alterations in rat peroneal nerves, and to modify the proteolytic activity of trypsin in vitro. Subperineurial injection of native or heated CSF of patients induced segmental demyelination and other cytological alterations 5-7 days later, in the infiltrated zone, while proximal and distal regions were normal. The CSF of normal subjects did not induce demyelination, but upon heating, it did so. Trypsin was strongly inhibited by the normal CSF but upon heating, its inhibitory activity was replaced by a strong potentiation. In contrast, native and heated CSF of patients potentiated trypsin. Our findings indicate that (1) the normal CSF contains a thermostable factor that potentiates trypsin whose function is overruled by thermolabile protease inhibitors; (2) the CSF of PSP patients has a reduced inhibitory activity and a conserved ability to potentiate trypsin; and (3) the CSF is endowed with a pathogenic power that correlates with an unchecked potentiating activity. We propose that the imbalance of a protease system may play a role in the pathogenesis of PSP lesions.

Ultrashort sleep-walking schedule. I. Evidence of ultradian rhythmicity in "sleepability'.

After a 7-8 h sleep at home, 9 young adults were placed on an ultrashort 15 min waking-5 min sleeping schedule for 12 consecutive hours, followed by a monitored recovery night in the laboratory. Six of 4 of the 9 subjects were also investigated in the same way after one night of selective REM deprivation and after one night of total sleep deprivation, respectively. In the first experiment, the amount of stage 1 in each of the sleep attempts varied rhythmically with a frequency of about 14.4 c/day. The average variance at the peak spectral frequency significantly exceeded the mean variance at the rest of the spectral frequencies and the mean variance at the adjacent frequencies. Stage 2 occurred more often around 15-16 h, with no evidence of ultradian rhythmicity. Both REM deprivation and total sleep deprivation disrupted the 100 min periodicity in stage 1 and modified the distribution of stage 2 toward a bimodal rather than a unimodal distribution. The result of the first experiment were interpreted in the light of Kleitman's BRAC model. The ultradian rhythmicity in sleepiness is suggested to play a role in the adaptability and flexibility of the circadian sleep-waking cycle.