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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.

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.)

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.

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.

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.

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.

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.

Excerpt To the editor: Spontaneous spinal epidural hemorrhage causing acute spinal cord compression is a relatively rare occurrence, with slightly more than 100 cases reported (1). We report here a...

Epileptic beagle dogs were studied with surface and depth electrodes. Recording during the resting state showed rare independent spike discharges, usually arising bilaterally from temporal pole, amygdala and hippocampus and, less often, from central and anterior cortical areas. Intravenous administration of pentylenetetrazol, methohexital and thiopental, activated spike discharges primarily in the same areas. During pentylenetetrazol infusion, 300 to 500 Hz activity was observed in tegmental and pontine reticular formation preceding generalized seizure discharges. The findings suggest that in the epileptic beagle a diffuse cerebral irritability exists, manifesting itself primarily in those areas prone to develop epileptiform activity regardless of the underlying etiology. No evidence was found to implicate a primary abnormality in the reticular formation or thalamus.