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Background: It was noticed in the mid-1950s that the incidence of ALS and parkinsonism–dementia complex (PDC) were much higher on Guam than anywhere else in the world. In 1958, a registry of patients and controls was established to ascertain the familial and genetic aspects of these diseases. Patients and individually matched controls and their relatives were registered from 1958 to 1963. The registry was updated and analyzed in 1998 through 1999. Objective: To ascertain whether first-degree relatives of patients had a higher risk for developing ALS or PDC than relatives of controls. Methods: During the period of 1958 to 1963, 126 new patients and 126 individually matched controls and their respective first-degree relatives and spouses were evaluated neurologically and registered. Forty years later, the number of new cases among the patient and control relatives were compared to an expected number of new cases based on the age- and sex-specific incidence of ALS and PDC in the population at large. Results: From 1958 to 1999, there were 102 new ALS or PDC cases among relatives of patients and 33 among relatives of controls. These values were compared with the derived expected values. There were more observed than expected new cases among patients’ relatives, and less observed cases than expected among the controls’ relatives. Conclusions: Relatives of patients with ALS or PDC have significantly higher risks for developing the disease than the Guamanian population, whereas relatives of controls have significantly lower risks.

OBJECTIVE: In this study, we examined the association of non-insulin-dependent diabetes mellitus (NIDDM) and impaired glucose tolerance (IGT) with cognitive function in a population-based sample of older individuals. RESEARCH DESIGN AND METHODS: Subjects were 1509 healthy, community-dwelling men and women aged 55 years and older who were participants in the Rancho Bernardo Study and attended clinic visits in 1984–87 and in 1988–91. An oral glucose tolerance test was administered during the 1984–87 visits. Based on World Health Organization criteria, participants were classified into those with NIDDM, IGT, or normal glucose tolerance. During the 1988–91 clinic visits, 12 tests of cognitive function were administered. RESULTS: Of the participants, 14.3% of the men and 9.9% of the women had NIDDM, and 21.0% of the men and 28.0% of the women had IGT. Multiple regression analysis was used to compare the cognitive function of individuals with NIDDM and IGT with individuals with normal glucose tolerance after adjustment for age, education, obesity, depression, blood pressure, and current estrogen use. In men, there were no statistically significant differences in any of the 12 cognitive function tests by glucose tolerance category. Compared with those with normal glucose tolerance, women with IGT had lower scores on almost every cognitive function test, whereas women with NIDDM had higher scores, but none of these differences were statistically significant after adjustment for multiple comparisons. Futhermore, observed differences by NIDDM or IGT status were small and accounted for

Frontotemporal dementia with parkinsonism, chromosome 17 type (FTDP-17), a recently defined disease entity, is clinically characterized by personality changes sometimes associated with psychosis, hyperorality, and diminished speech output, disturbed executive function and nonfluent aphasia, bradykinesia, and rigidity. Neuropathological changes include frontotemporal atrophy often associated with atrophy of the basal ganglia, substantia nigra, and amygdala. Neurofibrillary tangles (NFTs) are seen in some but not all families. Inheritance is autosomal dominant and the gene has been regionally localized to 17q21-22 in a 2- to 4-centimorgan (cM) region flanked by markers D17S800 and D17S791. The gene for tau, the primary component of NFTs, is located in the same region of chromosome 17. Tau was evaluated as a candidate gene. Physical mapping studies place tau within 2 megabases or less of D17S791, but it is probably outside the D17S800-D17S791 FTDP-17 interval. DNA sequence analysis of tau coding regions in affected subjects from two FTDP-17 families revealed nine DNA sequence variants, eight of which were also identified in controls and are thus polymorphisms. A ninth variant (Val279Met) was found in one FTDP-17 family but not in the second FTDP-17 family. Three lines of evidence indicate that the Val279Met change is an FTDP-17 causative mutation. First, the mutation site is highly conserved, and a normal valine is found at this position in all three tau interrepeat sequences and in other microtubule associated protein tau homologues. Second, the mutation co-segregates with the disease in family A. Third, the mutation is not found in normal controls.

Qualitative features of the neuropsychological test performance of individuals with dementia of the Alzheimer type (DAT) were examined in a population-based study. Qualitative error scores were derived from measures of verbal and figural memory, verbal fluency and confrontation naming for 38 patients with clinically diagnosed DAT, 236 normal elderly (NE) individuals, and 72 others who were questionably demented and at risk (AR) for DAT. Persons with DAT made a greater proportion of intrusion and perseverative errors, and more lexical and semantic naming errors, than the NE participants. These measures provided fair specificity but poor sensitivity for the diagnosis of DAT, and a logistic model based on these measures correctly classified 98% of the NE participants, but only 29% of the DAT participants. The AR participants demonstrated a pattern of errors that was highly similar to that of the DAT patients, and when their scores were subjected to the logistic model, 90% were classified as NE and 10% as DAT. These results indicate that specific error types that have been associated with DAT in self-referred or clinic-based samples also occur in the general population to a greater degree in individuals with DAT or questionable dementia than in NE individuals. Furthermore, these qualitative features may have some diagnostic usefulness in that their presence provides reasonable specificity for DAT or questionable dementia. (JINS, 1997, 3, 387–393.)

A dinucleotide repeat polymorphism in a tau intron was identified and used in a case-control study to analyze the genetic association of tau with several neurodegenerative diseases with tau pathology. Subjects with the homozygous tau AO alleles were excessively represented in the progressive supranuclear palsy (PSP) group, compared with the age-matched healthy control group. Consequently, this allele is more frequently found in PSP than in a group of healthy subjects. This trend was not found in Alzheimer's disease or parkinsonism-dementia complex of Guam, both of which are accompanied by major tau pathology. The result suggests a possible involvement of tau in the pathogenesis of PSP.

OBJECTIVE: To determine whether the weight loss associated with Alzheimer's disease precedes or follows the dementia. DESIGN: Older community-dwelling men (n = 134) and women (n = 165) were followed for 20 years before they were diagnosed as cognitively intact or demented. A repeated measures analysis was used to compare weight change in those who developed Alzheimer's Disease (AD) with those who remained cognitively intact. MEASUREMENTS: Weight was measured at three clinic visits between 1972-74, 1984-87, and 1990-93. Participants were classified as having probable or possible AD or being cognitively intact at the 1990-93 evaluation. Diagnoses were made by two neurologists and a neuropsychometrist, based on neuropsychological tests and physical examination, using NINCDS-ADRDA criteria. RESULTS: There were 36 men and 24 women diagnosed with probable or possible AD; they were considered to have mild to moderate dementia based on their test scores and community-dwelling status. Those who developed dementia were older than those diagnosed as cognitively intact. In age-adjusted analyses, both men and women who were later diagnosed with AD had a significant decrease in weight after the baseline visit (P < .001 and P < .003, respectively), but there was no significant weight loss in the men and women who remained cognitively intact. These differences were not explained by lifestyle, depression, or other illness. CONCLUSION: Weight loss precedes mild to moderate dementia; early weight loss is, therefore, unlikely to be a consequence of AD patients being unable or unwilling to eat.

This study reports the sensitivity and specificity of the Clock Drawing Test (CDT) for detecting dementia of the Alzheimer type in a community-dwelling sample of elderly subjects. Forty-two patients with clinically diagnosed Alzheimer's disease and 237 cognitively intact subjects were administered the CDT as part of an epidemiological study of aging and dementia. Three individual measures of clock drawing performance (quantitative score, qualitative score, and combined quantitative and qualitative score) were determined for each participant. When qualitative elements such as errors and strategies were incorporated into the CDT score, the sensitivity was 84% and the specificity was 72%. The findings suggest that a CDT score which evaluates qualitative and quantitative features provides reasonably good discrimination between normal elderly individuals and DAT patients. However, the CDT appears to have limited utility as a single screening instrument in the community. Instruments such as the Dementia Rating Scale (Mattis, 1976) provide better discrimination of DAT, indicating that functions such as memory and verbal fluency need to be assessed during screening.

The ability to detect dementia of the Alzheimer type (DAT) in a community-dwelling sample of elderly individuals on the basis of neuropsychological test performance was examined. Three hundred sixty community-dwelling individuals were identified by neurological examination as having probable or possible Alzheimer’s disease, being at risk for Alzheimer’s disease, or having no cognitive impairment. A logistic model comprised of tests of verbal and nonverbal memory, mental flexibility, and confrontation naming correctly classified 82% of DAT subjects and 98% of normal elderly subjects. The logistic model classified 77% of subjects who were diagnosed as at risk for Alzheimer's disease as being cognitively normal. A cross-validation with a clinically based sample of subjects correctly classified 89% of DAT patients and 100% of normal control subjects. The results suggest that psychometric discrimination of dementia may be less accurate in community-dwelling populations than in clinically based samples. (JINS, 1995, I, 252–260.)

Objective: To compare neurologists' initial clinical diagnoses made according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition guidelines with neuropathological diagnoses of Alzheimer's disease (AD) and related dementias. Design: Consecutive autopsies in a prospective cohort study. Setting: Community-dwelling patients with dementia referred to neurologists at an Alzheimer's Disease Research Center and satellite clinics (n=151) and patients initially evaluated when institutionalized (n=19). Patients: Of 204 elderly patients who had an autopsy performed, 170 had received a complete dementia evaluation according to NINCDS-ADRDA guidelines. Main Outcome Measures: Percentage agreement between neurologists' initial clinical diagnoses and pathological findings. Results: Of 137 patients clinically diagnosed as having probable or possible AD, 123 (90%) had AD neuropathological findings; this included 29 with AD accompanied by Lewy bodies, and 14 with AD and one or more infarcts. Cases of vascular and mixed dementia (AD and infarct [s]) had lower rates of agreement with pathological findings. Possible AD cases were more likely than probable AD cases to show pathological features other than AD. Clinicians predicted the presence or absence of AD pathological findings significantly better than chance. In patients with AD pathological lesions, older age of onset and male gender were significantly associated with shorter duration from disease onset to death. Conclusions: Clinicians accurately predicted AD pathological findings or their absence in most cases. Attributing other degenerative dementias to AD, misdiagnosing patients with combined AD and Lewy bodies and misjudging the vascular contribution to dementia were the major areas of inaccuracy. Formal criteria for dementia associated with non-AD lesions, Lewy bodies, and infarcts need to be developed and tested.

Objective: To establish population-based data, with special emphasis on the effects of age, gender, and education, for eight, widely used neuropsychological tests in a community-dwelling cohort of normal and cognitively impaired older adults. Design: A population-based observational study. Setting: Examinations were performed in a research clinic by specially trained staff during a 1988–1992 evaluation for osteoporosis. Participants: 1,692 community-dwelling subjects, aged 55 to 94 years, who were members of the Rancho Bernardo Heart and Chronic Disease Study initiated in 1972. The mean age for men was 73.9 years (SD 9.3) and for women, 73.5 (SD 9.1). Outcome measures: Eight neuropsychological tests were used to measure cognitive functions. Analysis of variance and post hoc contrasts were performed to determine the effects of age, gender, education, and their interactions on performance on these tests. Results: Performance on all tests decreased progressively, without leveling off, from the youngest, age 55, to the oldest, age 94. Women performed better on verbal tasks and men on tests of visuospatial, visuoconceptual, and mental control functions. Performances of men on several tests declined more rapidly with advancing age than those of women. Both men and women with some college education performed better on most tests than men and women with high school educations, and the rate of decline with age was sometimes slower in the college-educated group. Only the savings score from the Visual Reproduction Test, which is a measure of rate of forgetting, and the scores of short-term recall derived from the Selective Reminding Test (Buschke-Fuld) were unaffected by educational attainment. Conclusions: In a community-dwelling cohort, including normal and cognitively impaired elderly men and women, advancing age is accompanied by decline in cognitive functions as measured by neuropsychological tests. This decline is slower in women and in college-educated subjects. Two cognitive indices were unaffected by education, and these may be especially useful in cross-cultural studies.

Although the original Centers for Disease Control study of the relation between A/New Jersey/8/76 (swine flu) vaccine and Guillain-Barre syndrome (polyradiculoneuritis) demonstrated a statistical association and suggested a causal relation between the two events, controversy has persisted. To reassess this association, the authors obtained medical records of all previously reported adult patients with Guillain-Barre syndrome in Michigan and Minnesota from October 1, 1976 through January 31, 1977. To identify previously unreported hospitalized cases with onset of symptoms during this period, the authors surveyed medical care facilities. A group of expert neurologists formulated diagnostic criteria for Guillain-Barre syndrome and then reviewed the clinical records in a blinded fashion. Of the 98 adult patients from the original Centers for Disease Control study eligible for consideration, three were found to have been misclassified by date of onset and were excluded. Of the remaining 95, the 28 (29%) who did not meet the diagnostic criteria were equally distributed between the vaccinated group (18 of 60, 30%) and the unvaccinated group (10 of 35, 29%). In addition to the 67 remaining cases who met the diagnostic criteria, six previously unreported cases (three of whom had been vaccinated) were found and included in this analysis. The relative risk of developing Guillain-Barre syndrome in the vaccinated population of these two states during the 6 weeks following vaccination was 7.10, comparable to the relative risk of 7.60 found in the original study. These findings suggest that there was an increased risk of developing Guillain-Barre syndrome during the 6 weeks following vaccination in adults. The excess cases of Guillain-Barre syndrome during the first 6 weeks attributed to the vaccine was 8.6 per million vaccinees in Michigan and 9.7 per million vaccinees in Minnesota. No increase in relative risk for Guillain-Barre syndrome was noted beyond 6 weeks after vaccination.

In the 1950s, the incidence of amyotrophic lateral sclerosis (ALS, or Lytico) and parkinsonism-dementia complex (PDC, or Bodig) on the island of Guam was much higher than anywhere else in the world. From the late 1960s to the early 1980s, the incidence of both disorders has decreased. The objective of the present study was to ascertain whether the decreasing incidence continued until the end of the century (1999). The average annual incidence of ALS and PDC was calculated for each 5-year period from 1940 to 1999, utilizing registration records of all ALS and PDC cases on Guam during that period. The results of this study confirmed that the incidence of ALS declined steadily during the past 40 years. The incidence of PDC also declined until the late 1980s but, unlike ALS, showed a slight increase from 1980 to 1999. The rapid decrease in incidence is not likely to be due to genetic factors. Instead, it is most likely to be the results of radical socioeconomic, ethnographic, and ecologic changes brought about by the rapid westernization of Guam.

Qualitative features of the neuropsychological test performance of individuals with dementia of the Alzheimer type (DAT) were examined in a population-based study. Qualitative error scores were derived from measures of verbal and figural memory, verbal fluency and confrontation naming for 38 patients with clinically diagnosed DAT, 236 normal elderly (NE) individuals, and 72 others who were questionably demented and at risk (AR) for DAT. Persons with DAT made a greater proportion of intrusion and perseverative errors, and more lexical and semantic naming errors, than the NE participants. These measures provided fair specificity but poor sensitivity for the diagnosis of DAT, and a logistic model based on these measures correctly classified 98% of the NE participants, but only 29% of the DAT participants. The AR participants demonstrated a pattern of errors that was highly similar to that of the DAT patients, and when their scores were subjected to the logistic model, 90% were classified as NE and 10% as DAT. These results indicate that specific error types that have been associated with DAT in self-referred or clinic-based samples also occur in the general population to a greater degree in individuals with DAT or questionable dementia than in NE individuals. Furthermore, these qualitative features may have some diagnostic usefulness in that their presence provides reasonable specificity for DAT or questionable dementia.

Parkinsonism-dementia complex (PDC), a neurodegenerative disorder in the Chamorro, Guam population, has been epidemiologically ascribed to the ingestion of the neurotoxin cycasin. This disease is characterized neuropathologically by the presence of abundant neurofibrillary tangles (NFTs). We analyzed a genetic risk factor of Alzheimer's disease (AD), apolipoprotein E, hypothesized to be linked to NFT formation, and a genetic risk factor of Parkinson's disease (PD), CYP2D6 mutation, linked to slower metabolism of exogenous toxins, in Chamorro, Guam individuals with and without PDC. The representation of the G-to-C mutation in exon 9 of the CYP2D6 gene was higher in Chamorro and Filipino than in Caucasian individuals, but this mutant allele had similar high frequencies in both PDC patients and healthy Chamorro individuals. We found no alleles of these genes associated with AD or PD to be overrepresented among those with PDC.NEUROLOGY 1996;47: 779-784

OBJECTIVE: To compare the cognitive performance and functional status of the normal oldest old (85+ years) with that of normal older persons aged 65 to 84 years to identify age-associated changes in cognition in individuals considered clinically normal. BACKGROUND: Advancing age appears to be a risk factor for dementia. DESIGN/METHODS: Analysis of performance on an extensive neuropsychological battery and the Pfeffer Outpatient Disability Scale in 243 normal individuals age 65 to 99 years. RESULTS: Fifty-two normal subjects who were 85 years of age and older (mean age 88.2 ± 3.1) and 191 normal subjects aged 65–84 years (mean age 75.8 ± 5.0) were compared. Mean education for both groups was not statistically different. No significant differences in functional disability were found between the two groups. Normal subjects aged 85 years and older performed significantly less well than their younger counterparts on verbal and nonverbal memory, psychomotor/executive tasks, and category verbal fluency. CONCLUSIONS: Advancing age in normal subjects is accompanied by a decrease in cognitive function, measured by various neuropsychological tests, but is not accompanied by functional impairment.

This study reports the sensitivity and specificity of the Clock Drawing Test (CDT) for detecting dementia of the Alzheimer type in a community-dwelling sample of elderly subjects. Forty-two patients with clinically diagnosed Alzheimer's disease and 237 cognitively intact subjects were administered the CDT as part of an epidemiological study of aging and dementia. Three individual measures of clock drawing performance (quantitative score, qualitative score, and combined quantitative and qualitative score) were determined for each participant. When qualitative elements such as errors and strategies were incorporated into the CDT score, the sensitivity was 84% and the specificity was 72%. The findings suggest that a CDT score which evaluates qualitative and quantitative features provides reasonably good discrimination between normal elderly individuals and DAT patients. However, the CDT appears to have limited utility as a single screening instrument in the community. Instruments such as the Dementia Rating Scale (Mattis, 1976) provide better discrimination of DAT, indicating that functions such as memory and verbal fluency need to be assessed during screening.

The magnitude and importance of changes in scores of neuropsychological tests on retest in the elderly, especially over long time periods, is not well established. Three neuropsychological tests and one mental status test were initially administered to screen for potential dementia and were readministered to 380 of the surviving individuals 2.4 years later who either failed the screening examination or were an age matched control. Of the 380 women and men aged 65 and older, 56 were diagnosed as having Alzheimer disease (AD), 82 as at risk for developing AD, and 242 as having normal cognition. The present report focuses on changes in test scores between the two visits. In the normal and at risk groups, significant improvements were seen on retest of the Visual Reproduction Test (VRT), the Trails B test, and the Mini-Mental Status examination; verbal fluency decreased, and savings score of the VRT showed small variations. On most tests, scores of the AD group decreased. Practice effects, biases, and other variables may have played a role in the improvements seen in those labeled normal and at risk. If these results are confirmed, savings score of the VRT (which remained stable over time in normals and individuals at risk and decreased in patients with dementia) and verbal fluency (which decreased in all groups) may be better measures of true cognitive performance than the other tests that we evaluated.

Stroke databanks may provide important information regarding regional and temporal variations in the causes of stroke.Five hundred consecutive patients presenting to the University of California, San Diego, stroke services with acute ischemic stroke were evaluated prospectively. A specific cause of stroke was assigned in each case according to predetermined diagnostic criteria.Relative incidences of ischemic stroke causes were as follows: lacunar, 27%; unknown cause, 23%; cardioembolic, 22%; large-vessel atherothrombotic/embolic, 18%; and miscellaneous, 10%.These relatively high rates of lacunar stroke and stroke of unknown cause are similar to those from other recent surveys and may reflect an important shift in the pathophysiologic mechanisms that underlie ischemic stroke.

Although the original Centers for Disease Control study of the relation between A/New Jersey/8/76 (swine flu) vaccine and Guillain-Barré syndrome (polyradiculoneuritis) demonstrated a statistical association and suggested a causal relation between the two events, controversy has persisted. To reassess this association, the authors obtained medical records of all previously reported adult patients with Guillain-Barré syndrome in Michigan and Minnesota from October 1, 1976 through January 31, 1977. To identify previously unreported hospitalized cases with onset of symptoms during this period, the authors surveyed medical care facilities. A group of expert neurologists formulated diagnostic criteria for Guillain-Barré syndrome and then reviewed the clinical records in a blinded fashion. Of the 98 adult patients from the original Centers for Disease Control study eligible for consideration, three were found to have been misclassified by date of onset and were excluded. Of the remaining 95, the 28 (29%) who did not meet the diagnostic criteria were equally distributed between the vaccinated group (18 of 60, 30%) and the unvaccinated group (10 of 35, 29%). In addition to the 67 remaining cases who met the diagnostic criteria, six previously unreported cases (three of whom had been vaccinated) were found and included in this analysis. The relative risk of developing Guillain-Barré syndrome in the vaccinated population of these two states during the 6 weeks following vaccination was 7.10, comparable to the relative risk of 7.60 found in the original study. These findings suggest that there was an increased risk of developing Guillain-Barré syndrome during the 6 weeks following vaccination in adults. The excess cases of Guillain-Barré syndrome during the first 6 weeks attributed to the vaccine was 8.6 per million vaccinees in Michigan and 9.7 per million vaccinees in Minnesota. No increase in relative risk for Guillain-Barré syndrome was noted beyond 6 weeks after vaccination.

Objective: To assess the clinical validity of the Dementia Rating Scale (DRS) in detecting patients with dementia of the Alzheimer type (DAT). Background: The DRS is widely used to evaluate cognitive functioning in older adults. Adequate normative data are unavailable; studies addressing the clinical validity of the DRS are limited by small sample sizes. Design and Methods: Administered the DRS to 254 outpatients with DAT and 105 healthy elderly subjects. Performed (1) multiple regressions of demographic factors on the DRS and its subscales; (2) derivation of optimal DRS cutoff scores using receiver operating characteristic curves; (3) double cross-validation with stepwise logistic regressions; and (4) application of results to a community-dwelling sample. Results: Age- and education-adjusted DRS scores were computed. The optimal DRS cutoff score for DAT of 129 or less revealed a sensitivity of 98% and a specificity of 97%. The logistic regressions resulted in a combination of the Memory and Initiation/Perseveration subscales that correctly classified 98% of all subjects, 92% of a subsample of 76 patients with mild DAT, and 100% of the 51 patients with autopsyconfirmed DAT. The resultant equation was then applied to a community-dwelling sample (238 healthy elderly subjects and 44 patients with DAT): 91% of patients and 93% of normal subjects were correctly classified. Of an additional 77 individuals with questionable DAT, 43 were classified as demented and 34 were classified as nondemented. Conclusions: The DRS is a clinically valid psychometric test for the detection of DAT. The Memory and Initiation/Perseveration subscales are its best discriminative indexes for an abbreviated version.

Background: Stroke databanks may provide important information regarding regional and temporal variations in the causes of stroke. Methods: Five hundred consecutive patients presenting to the University of California, San Diego, stroke services with acute ischemic stroke were evaluated prospectively. A specific cause of stroke was assigned in each case according to predetermined diagnostic criteria. Results: Relative incidences of ischemic stroke causes were as follows: lacunar, 27%; unknown cause, 23%; cardioembolic, 22%; large-vessel atherothrombotic/embolic, 18%; and miscellaneous, 10%. Conclusions: These relatively high rates of lacunar stroke and stroke of unknown cause are similar to those from other recent surveys and may reflect an important shift in the pathophysiologic mechanisms that underlie ischemic stroke. (Arch Intern Med. 1993;153:619-624)

In rats with unilateral carotid artery ligation pyramidal tract responses were studied during hypoxia and during trimethaphan-induced hypotension. Observations on EEG activity during hypoxia suggest that unilateral carotid artery ligation produces a more severe perfusion defect in lateral portions of the hemisphere. During hypoxia and during trimethaphan-induced hypotension indirect PTRs disappeared first from the hemisphere on the side of carotid artery ligation and next from the opposite hemisphere. This was followed by loss of direct PTRs in the same order. Animals could not be resuscitated once the direct PTR from the non-ligated hemisphere had disappeared. Hypotension appears to be a late contributing factor in impairing electrocerebral activity during hypoxia in this study.

• Short-latency somatosensory evoked potentials were studied in 14 normal human subjects with the technique of paired stimuli with different interstimulus intervals. Interstimulus intervals were 5, 10, 15, 25, 50, 100, 150, and 200 ms. To obtain the response to the second stimulus of the pair, amplitudes of the second responses (R2) were subtracted from those of the first responses (R1) and recovery curves constructed. Results of this study support previous conclusions that P10 is generated in peripheral nerves (brachial plexus), P14 in medial lemniscus, N19 in sensory radiation, and P23 in sensory cortex.

• Short-latency components of the somatosensory evoked potential (SEP) were studied in 20 subjects who had median nerve stimulation using knee, forehead, and ear reference recordings. Six potentials were identified (P10, P12, P14, N19, P20, P23). Potential P10 seems to originate in the brachial plexus, P12 most likely is generated in dorsal column nuclei and medial lemniscus, P14 is probably thalamic in origin but is frequently bilobed and may have a second generator source, and N19 may originate in sensory radiation or cortex. The origin of P20 is unclear, and P23 appears to be generated in the contralateral somatosensory cortex. Clinically, we recommend using right, left, and bilateral median nerve stimulation at 4 Hz. Intensity of stimulus should produce at least a small thumb twitch. It was only with knee reference recording that all early potentials were seen.

Longitudinal studies of subjects with autopsy-proven Alzheimer's disease in one skilled nursing home and of clinically diagnosed cases (NINCDS/ADRDA criteria) in three community cohorts are compared with regard to the annual rate of change in the error score of the Blessed information-memory-concentration test (IMC) in which the maximum number of errors possible is 33. The four cohorts differed significantly from each other in regard to age, education, sex, and the degree of dementia as measured by the initial IMC score. Subjects spanned the age range of 52 to 96 years and had 2 to 20 years of education. The rate of change in error score per year was similar whether the initial error score was 0 to 7, 8 to 15, or 16 to 23; however, the rate was reduced when the initial error score was 24 or above, due to a ceiling effect of the test. Among subjects with initial IMC scores less than 24, the annual rate of change varied considerably. However, the mean annual rate of change, 4.4 errors (SD 3.6, SEM 0.3) per year, was independent of residence in a nursing home, location of the study site, and of the patient's sex or education. Of particular importance was the finding that the rate of change in mental test score was independent of age. It can be concluded that the rate of cognitive deterioration in patients with Alzheimer's disease is quite variable among individuals and is independent of the patient's age and whether the patient resides in the community or in a nursing home. More importantly, the rate of change of the IMC test provides no evidence for a difference between early-onset and late-onset Alzheimer's disease. The average rate of change on the IMC and its variance can be used as the basis for designing studies of drugs or procedures that might alter the course of Alzheimer's disease.

Electroencephalograms were performed on 58 of 100 patients treated withl-dopa for Parkinsonism. Half the electroencephalograms were abnormal and, with few exceptions, showed slowing of normal background activity and increased generalized theta activity. The degree of electroencephalographic abnormality paralleled the degree of clinical disability. In twelve patients mean energy content of the electroencephalogram, coefficient of variation and reaction time were studied before and during treatment withl-dopa. Mean energy content of the electroencephalogram did not change during therapy. Coefficient of variation was markedly reduced before and during treatment. Reaction time shortened withl-dopa therapy in patients who improved clinically. It is suggested that reaction time can be used as an objective measure to assess efficacy of treatment in Parkinsonism.

Forty-five consecutive patients with unstable carotid artery syndrome were evaluated and treated, 23 surgically and 22 medically. Early cerebral angiogra phy and carotid endarterectomy yielded permanent neurologic morbidity/mor tality incidences of 0% and 8.7%, respectively. Despite a fairly high incidence of stroke acutely and during the follow-up period (24% and 8%, respectively), 80% of the total group continued at their baseline, prepresentation level of daily function at an average follow-up of 22.3 months. Aggressive clinical manage ment of this patient group is generally safe, but the efficacy of such manage ment remains unproven.

An electroencephalographic analysis of personality-dependent psychomotor performance was investigated in 11 volunteers under 160 μg/kg psilocybin-induced ergotropic arousal. Significant psilocybin-induced changes in mean energy content of EEG, reaction time, and latency and duration of alpha attenuation to photic stimuli were noted in all subjects, as well as significant correlations between EEG parameters, personality types and psychomotor (handwriting) test results. Moreover, a ‘clustering’ of certain EEG, personality, and handwriting characteristics in specific subjects seems to justify their classification into two general groups.

Median nerve sensory fibres were stimulated with minimal and supramaximal stimuli at the base of the third digit in 30 normal subjects. Evoked nerve action potentials were simultaneously recorded from two points on the median nerve just above the wrist. As stimulus voltage was increased from minimal to supramaximal, amplitudes of nerve action potentials increased, latencies decreased, but conduction velocities remained unchanged. The shortening of latencies was interpreted as movement of the effective point of nerve excitation away from the stimulating cathode towards the recording electrodes. Therefore, the effective point of nerve excitation cannot be assumed to be underneath the cathode, but at some distance from it depending on stimulus intensity. Furthermore, the fastest conducting sensory fibres in the human median nerve do have a lower threshold than slower conducting fibres.

• Central pontine myelinolysis was suspected in two chronic alcoholics who developed and recovered from a progressive spastic paresis of all muscles, that derived innervation at and below the level of the pons. In both cases, short-latency auditory-evoked responses aided in the diagnosis by indicating a slowing of conduction in the pontine auditory pathway, which varied in degree with the severity of the clinical manifestations of pontine demyelination.

In Reply. —Since we initiated the studies that have now led to a reevaluation of the alleged association of the swine influenza vaccine and Guillain-Barre syndrome (GBS) as reported by the Centers for Disease Control (CDC), 1 Atlanta, we shall reply on behalf of our coauthors of the publications cited by Alvord. 2-4 He has criticized two relatively minor points and has ignored the major arguments in this series of articles, the principal one being that the CDC accepted as GBS the reported cases obtained by nonclinical health officers and their paramedical assistants, without a systematic review of the medical records by clinical neurologists and frequently without any follow-up information. There is now reason to suspect that many of the CDC cases would not meet reasonable diagnostic criteria for GBS; but whether and how the relative risks as reported by the CDC will be affected awaits the reevaluation in which the CDC

For many years acute experimental allergic encephalomyelitis (EAE) has been studied as a presumptive model for multiple sclerosis (MS) [1, 2, 13]; more recently, a chronic form of EAE has been described [14, 15]. However, a comparison of MS with either form of EAE has revealed both similarities and differences [9, 10, 13, 15, 20]. Since EAE in animals can be suppressed by the administration of myelin basic protein (MBP) and its derivatives [3, 6, 7, 11, 12, 16, 18], or by synthetic polypeptides [19], an investigation was undertaken to determine the relationship between EAE and MS in this respect by studying the effect of MBP administration in patients with MS.

The incidence of tuberous sclerosis in Rochester, MN, was 0.56 per 100,000 person-years in 1950 through 1982, and point prevalence on December 31, 1980, was 10.6 per 100,000 persons. The true incidence and prevalence may be even higher, because cases with hypomelanotic macules and no other clinical manifestations are often unrecognized. Pertinent clinical observations in the eight cases identified included familial occurrence in two; hypomelanotic macules in all eight; seizures with onset before age 2 in four, of whom two were mentally retarded; and no neurologic abnormalities in those free of seizures.

• A study of the epidemiologic and clinical features of Guillain-Barre syndrome in the population of Olmsted County, Minnesota, over the 46-year period 1935 through 1980 was conducted through the centralized diagnostic index maintained at Mayo Clinic, Rochester, Minn. A total of 48 cases were identified, giving an age- and sex-adjusted incidence of 1.8 per 100,000 person-years. The rate increased over time from 1.2 in the interval 1935 through 1956 to 2.4 in the interval 1970 through 1980. Males were affected more than females (age-adjusted rates of 2.3 and 1.2, respectively). The rate increased with age from 0.8 in those under 18 years old to 3.2 for those 60 years and older. Antecedent infectious diseases were reported in 65% of the cases. Implications with regard to the incidence of Guillain-Barre syndrome associated with the A/New Jersey/76 (swine flu) vaccine are discussed.

Forty-seven consecutive patients presenting acutely with repetitive symptoms indicative of anterior circulation ischemia (“crescendo” transient ischemic attacks) were evaluated to identify clinical features that might reliably predict the presence of significant stenosis, ulceration, or both in the presumably symptomatic internal carotid artery. Angiographic or intraoperative correlation was obtained in all patients, and 26 (55%) were found to have anatomically significant disease. Of 20 patients with signs or symptoms suggestive of cortical ischemia, amaurosis fugax, or both, 17 (85%) had "positive" angiograms; of 18 with numbness/weakness only, 9 (50%) had positive angiograms; of 9 whose symptoms suggested lacunar ischemia, none had positive angiograms.

We have previously identified, with surface-recording techniques, four potentials (I, II, III, IV) preceding the cortical component of the somatosensory evoked potential (SEP) in the cat. In the present study, we correlated surface and depth activity in the cat by recording SEPs simultaneously from skull electrodes and from depth electrodes placed in the cervical posterior columns, cuneate nucleus, medial lemniscus, inferior cerebellar peduncle, ventral posterior thalamus, and sensory radiation. Latencies and amplitudes of surface- and depth-recorded potentials and their responses to repetitive stimulation were analyzed. Our findings indicate that: (1) component I originates in cervical posterior columns and nucleus cuneatus; (2) component II reflects postsynaptic activity in nucleus cuneatus, medial lemniscus, and inferior cerebellar peduncle; (3) component III-A probably originates in the cerebellar hemispheres; (4) component III-B consists of component III-A and superimposed activity in the ventral posterior thalamus and sensory radiation; and (5) component IV originates in the sensory radiation.

Physicians in the United States have generally accepted as fact that the (A/New Jersey/76) swine flu vaccine administered to nearly 45 million people from October through December 1976 was responsible for an increase in Guillain-Barre syndrome (GBS). However, the only substantive evidence for that association is a single study based on data collected by health officers during the highly publicized swine flu program and the moratorium on the immunizations which was declared on 16 December 1976.

Worldwide, cysticercosis is the most common CNS parasite. Because of immigration from endemic areas, cysticercosis has become more common in the United States. Seventeen cases have been seen at the University of California Medical Center, San Diego (La Jolla) over the last ten years. Eight patients had intracranial hypertension; three, seizures; three, intracranial hypertension; and seizures; two, strokes; and one, retinal involvement. Diagnosis was by surgical biopsy in five cases and by clinical setting plus positive serologic findings in 12. Twelve patients underwent surgical procedures during their illness, one patient died, and five improved with steroid therapy. Clinical, serologic, and pathologic criteria permit definitive diagnosis. Therapy is currently directed toward complications of the primary infection, which usually is inactive at the time of presentation.

Anoxic ischemia with resultant unilateral cerebral infarction was produced in the rat by unilateral ligation of the external and common carotid arteries and exposure of the animal to nitrogen. EEG and behavior were studied for one month after the anoxic insult. Infarcted animals showed prominent circling, contralateral flexion postures, and absent visual and tactile placing. At the end of one month the only persistent clinical abnormality was absent contralateral tactile placing. Acutely the EEG showed loss of normal background activity and high voltage slow waves over the infarcted hemisphere. EEG improvement paralleled clinical improvement. At the end of one month only minor asymmetries were observed in the EEG but sleep spindles remained absent on the infarcted side. Present address: VA Hospital, San Diego, California 92161