Auditory event-related potentials (ERP) elicited in a target detection stimulus paradigm and pattern-shift visual ERPs were studied in 20 male patients with idiopathic Parkinson disease (PD) and 20 age-matched normal controls. Patients showed significantly increased latencies for both the P200 and P300 components of the auditory ERP. Patients and controls showed no significant differences in latency of the visual ERP but patients showed significantly decreased amplitude. Only one of five neuropsychological measures, the Symbol Digit Modalities test (SDMT), showed a significant negative correlation with P300 latency. The significant association between the two measures that showed impairments in the PD patients (P300 latency and SDMT scores) suggested that these measures reflect a common, disrupted aspect of cognitive function in PD.

Sixty-one normal men whose ages ranged from 20 to 80 years were evaluated on two occasions by means of a comprehensive series of 128 instrumented tests of neurologic function. The tests measured cognition, vision, strength, steadiness, reactions, speed, coordination, fatigue, gait, station, sensations, and tasks of daily living. The reliability of each test measured was determined, and any measure found unreliable (r less than or equal to 0.41) was not further analyzed. Significant age-related linear decreases were found for almost all neurologic functions. The declines over the age span varied from less than 10 percent to more than 90 percent for different functions. For the upper extremities, the largest declines (greater than 50 percent) were in hand-force steadiness, speed of hand-arm movements, and vibration sense; for the lower extremities, the largest declines were in one-legged balance with eyes closed and in vibration sense. For 13 of 14 tests in which significant dominant body-side effects were found, larger re-testing 7-10 days later, the subjects improved their scores by more than 5 percent on only 17 tests, 9 of which concerned the activities of daily living. No significant differential learning effects were found across age groups. The results point to the importance of developing a data bank on age-based neurologic function so that therapeutic effects can be evaluated in terms of age- and sex-matched normal functioning.

An empirical formula has been developed to calculate the de novo rate of synthesis of IgG in the central nervous system (CNS), based on physiologic principles that govern the passage of albumin and IgG across the blood-brain barrier (BBB). To validate the formula, radiolabeled IgG and albumin from pooled normal sera were followed from the blood to the cerebrospinal fluid (CSF) over 21 days in nine patients with definite multiple sclerosis (MS). IgG synthesis rates were calculated by the isotope exchange method and compared to values obtained with the empirical formula. There was excellent concordance, from a low rate of synthesis of 5 mg per day to a high rate of 120 mg per day. A double radiolabeled IgG experiment in two patients showed that the MS BBB processed normal serum IgG in the same way as IgG derived from autologous MS serum. Accordingly, the empirical formula, which requires only one sample of CSF and matched serum, can reliably and validly estimate the de novo rate of IgG synthesis in CNS of patients with MS.

We hold that the intra-blood-brain-barrier (BBB) IgG synthesis (SYN) rate can be quantitated reliably and validly. Although several formulas distinguish patients with multiple sclerosis from normal controls equally well, only the SYN rate formula has been validated in humans using isotopic tracer techniques. Our formula for the IgG SYN rate is reducible to Reiber's formula; therefore, both can be used to quantify the IgG SYN rate in a manner not possible using the IgG index. Although our SYN rate formula has been validated for a modest range of BBB abnormalities (cerebrospinal fluid/serum albumin ratios), there is evidence to suggest that it may be used even in patients having severe BBB damage. We question the acceptance of unique cerebrospinal fluid IgG bands as indisputable evidence of intra-BBB IgG SYN in the presence of a modest to severely damaged BBB. Finally, the utility of quantitation and detection of intra-BBB IgG SYN by standardized methods in a group of asymptomatic, normal individuals compared with a group of patients with clinical definite multiple sclerosis is presented.