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The recently described conditions of primary progressive aphasia and frontal lobe dementia overlap clinically and pathologically to a considerable extent with each other and with clinical and pathological descriptions of Pick’s disease. Our clinical and neuropathological experience is summarized, leading us to the conclusion that the degree of overlap justifies the concept of “Pick complex” to include, in addition to the above, corticobasal ganglionic degeneration and some instances motor neuron disease with dementia.

The evolution of cerebral asymmetries and their relationship to functional lateralization in the brain are important topics in anthropology, anatomy, biology, and neuropsychology. A brief review of the phylogeny of cerebral asymmetry is appropriate in this context. Evolutionary theory has assumed that functional lateralization in the higher levels of the phylogenetic scale leads to asymmetry in structure. It was believed that the more complex an organism, the more asymmetry in brain structure. In particular, cerebral asymmetries have been assumed to be related to language development in man, since Broca (1865) proposed his notion of cerebral dominance for language. Anthropological considerations led Broca (1861), among others, to believe that the frontal lobes were important for language because of the dramatic increase in their size in humans. When he produced lesion evidence in support of this he also observed that language loss usually occurred with left-sided lesions, establishing the most consistent functional asymmetry in the human brain.

Objective: To detect neuropsychological differences between Alzheimer's disease (AD) and vascular dementia (VAD). Design: Neuropsychological measures were compared in clinically defined AD and VAD patient groups. Setting: Ambulatory and hospitalized patients were referred to a behavioral neurology clinic and to the neuropsychology department of a teaching hospital. Patients: Consecutive, referred patients who fulfilled National Institute of Neurological Disorders and Stroke/Alzheimer's Disease and Related Disorders Association and Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition , criteria for AD and VAD were selected to participate in the study based on the history and clinical findings. A modified ischemie score of 3 or less was an independent selection criterion for AD (n=103) and a score of 4 or more for VAD (n=25). Computed tomography or magnetic resonance imaging was used to exclude other structural causes. Patients with cognitive changes related directly to a stroke were excluded. Patients were matched for age, education, age at onset, and severity of dementia. Measures: The variable measures were the subtests of the Wechsler Adult Intelligence Scale-Revised (WAISR), Wechsler Memory Scale-Revised, Mattis Dementia Rating Scale (MDRS), and Western Aphasia Battery (WAB). Patients were further stratified into mild and severe dementia categories, based on their performance on the MDRS. Results: Variables that were significantly different were selected for discriminant function analysis. The Writing subtest of the WAB, the Picture Arrangement subtest of the WAIS-R, and the Motor Performance subtest of the MDRS were the best discriminators of AD and VAD in the overall and severely affected populations. Patients with VAD performed significantly worse on the MDRS Motor Performance subtest, the WAIS-R Picture Arrangement subtest, the WAB Writing subtest, the WAIS-R Object Assembly subtest, and the WAB Block Design subtest. The AD group performed significantly worse on the WAB Repetition subtest, and patients with severe AD performed significantly worse on the Story Recall test. Conclusions: Patients with VAD performed worse on tests that are influenced by frontal and subcortical mechanisms. Patients with AD performed worse on memory and some language subtests.

We present three cases of primary progressive aphasia (PPA) with Pick-variant pathology to support a hypothesis of an underlying nosologic relatedness. Neuropathologic examination demonstrated focal brain atrophy with corresponding neuronal loss and gliosis, accompanied by superficial spongiosis. Specific histologic findings were ballooned neurons (Pick cells) in the atrophic areas, and in two of the cases, Pick bodies. They were immunoreactive for tau. In contrast to classic Pick's disease, there were no Pick bodies in the hippocampus. The intense neurofilament immunoreactivity of the perikarya of the ballooned neurons greatly facilitated their recognition. Based on our cases and a critical review of the literature, we hypothesize that the common underlying pathology of PPA is a variant of Pick's disease. Furthermore, we propose the concept of “Pick complex” to include other neurodegenerative diseases characterized by focal cortical degeneration, such as PPA, frontal lobe dementia, ALS with PPA, and corticonigral and corticobasal ganglionic degenerations.

We trained a series of simulated neural networks with the raw scores on the Western Aphasia Battery from 91 aphasic patients. Patients were tested at 3 and at 12 months post onset. The most successful network we trained is able to predict AQ for an individual in 12 months from the raw scores at 3 months post-onset to a tolerance of + or −4.5. We then compared the relative success of a small range of trained networks to predict recovery with linear multiple regression. With the small groups of subjects involved in this preliminary study, the networks appeared to be more successful at predicting recovery.

The functional utility of regional parameters of the corpus callosum (CC) derived from factor analysis has been demonstrated in the rat and the human. In this study, we have utilized factor analysis to compare CC structure between two independent groups of human subjects. Tracings of the CC were taken from the midsagittal MRIs of two human samples consisting of 103 healthy volunteers and 146 neurological patients. CCs were digitized and factor analyses were performed on 99 widths, area, axis length, and perimeter. The factor structures of these two data sets were highly congruent except that one factor analysis yielded a seven-factor solution, whereas the factor analysis of the other subject population gave six factors. Further study determined that the six-factor structure could be attributed to the presence of non-consistent right-handed males whose wider CCs in the isthmus region biased the correlations. When CC parameters of consistent and non-consistent right-handed subjects were standardized, a seven-factor structure resulted. Reproducibility of the factor structure indicates that there are shared neuroanatomical characteristics of CC morphology among two disparate populations of humans in spite of variability in CC size due to sex, age, hand preference, and hand consistency.

A computer-assisted mapping program was developed to determine changes of cerebral perfusion in normal and pathological aging using single photon emission computer tomography (SPECT) and 99mTc-hexamethylpropyleneamine oxime (HMPAO). The software program outlined the cortex on 14 adjacent brain slices, and superimposed a ring of 12 regions of interest on each slice. Regional/global and regional/cerebellar relative flow values were calculated in 27 patients with clinically diagnosed Alzheimer's disease (AD) (mean age 71 years, SD 7.6) and in 10 normal controls (mean age 73.7 years, SD 7.3). The Dementia Rating Scale (DRS) was used to assess mental status in all subjects. Multiple regression analysis demonstrated a significant correlation between relative flow values and the DRS score. Regional/cerebellar (R = 0.88, p0.0001) relative flow values were a better indicator of cortical impairment than regional/global relative flow values (R = 0.68, p = 0.003). Of the brain regions of interest, the left parietal flow values correlated best with the DRS score (r = 0.83, p0.0001), a cutoff value of 77 accurately classifying 80% of the normals and 100% of the patients diagnosed as having Alzheimer's disease. The data show that computer-assisted mapping of SPECT can provide semiquantitative flow values with high diagnostic accuracy.

Introduction: Vascular dementia (VaD) is considered an important entity, despite the difficulties in defining it or the widely variable estimates of its incidence. It is often repeated (without supporting evidence) that VaD is the second most common form of dementia, but it is probably more accurate to say that mixed dementia combining Alzheimer's disease (AD) with cerebrovascular disease is more common. In fact, this study targets such a mixed population, although it attempts to study the efficacy of galantamine in "probable vascular dementia" as well. Until recently, the treatment of cognitive impairment, secondary to vascular disease, has been stroke prevention and management of the vascular risk factors. So far, there has not been any medication to show efficacy for symptomatic treatment. Galantamine with a dual action of inhibiting acetyl cholinesterase and modulating nicotinic receptors has been shown to have efficacy to improve cognition, behavior, and activities of daily living in AD patients. It seems logical to extend these efficacy studies to mixed dementia and VaD. Furthermore, the difficulty differentiating VaD from AD is notorious, and showing efficacy of a drug in the management of both would ease the impact of this diagnostic dilemma.

Music and language functions were studied in two musicians with degenerative disease. Both patients were tested on a standardized language battery and a series of music tasks. In the first case with left cortical atrophy and primary progressive aphasia, expressive music functions were spared with impaired reception of rhythm. The second case with posterior cortical atrophy, greater on the right, was nonaphasic, had spatial agraphia, a visuopractic deficit, and severe expressive music deficits, but intact rhythm repetition. The aphasic patient showed dissociations between music and language in fluency and content; continuous, organized, although reiterative music production was contrasted with nonfluent language. The nonaphasic patient showed the opposite pattern of deficits; unmusical production with impaired melody and rhythm organization that was contrasted with fluent, intelligible language. The double dissociation between language and music functions supports the existence of independent cognitive systems, one consistent with conventional left lateralization models of language, temporal sequence, and analytic music processing and another with a right lateralization model of implicit music cognition.

• Objective. —The profile of language impairment in patients with primary progressive aphasia in comparison with the language impairment in patients with Alzheimer's disease and after stroke. Design. —The Western Aphasia Battery and the Mattis Dementia Rating Scale evaluated the language and cognitive impairment. Follow-up studies were done 1 to 5 years after the initial testing in seven of 10 patients with primary progressive aphasia, and a postmortem examination of the brain was done in two patients. Setting. —All 10 patients with primary progressive aphasia were previously healthy, community-dwelling persons when first tested. Patients and Other Participants. —All patients with primary progressive aphasia reported at least a 2-year history of slowly progressive aphasia without other signs of global dementia. The initial Western Aphasia Battery results of the 10 patients with primary progressive aphasia were compared with those of a sample of 10 patients with probable Alzheimer's disease and with those of a sample of 10 patients with aphasia due to a left hemispheric stroke. Both reference samples were matched for age and sex; the sample with stroke-caused aphasia was additionally matched for the aphasia type. Results. —Expressive language disability with reduced speech fluency and anomia but preserved language comprehension and nonverbal cognition were typical features in early stages of primary progressive aphasia. Spontaneous speech was significantly more impaired in patients with primary progressive aphasia in comparison with those with aphasia after left hemisphere stroke and with language impairment in patients with Alzheimer's disease. Follow-up examinations revealed continuous, often rapid deterioration of language impairment. The neuropathological examination showed Alzheimer's disease in one patient and Pick's disease in the other. Conclusion. —The profile of aphasia suggests that primary progressive aphasia tends to affect anterior parts of the language-dominant cortex first.

P163 Background: Although, elderly patients (≥80 years) are not excluded from receiving tPA for acute ischemic stroke (AIS), uncertainty still exists regarding the effectiveness and safety of tPA in this age group. Objective: To compare baseline characteristics, outcomes, and complications of AIS patients treated with iv tPA aged ≥80 with their younger counterparts (Methods: Patients ≥80 were compared to the younger group aged 1/3 middle cerebral artery territory was involved. Findings: To date 62 patients have been treated. Median ages of the young group (n=46) are 68 years (range of 37–79) and of the older group (n=16) are 85 years (range of 80–93). Thirty-one of 46 younger patients and eleven of 16 older patients have reached the 3 month follow-up mark. The elderly group had a statistically significant higher mean pre-stroke Modified Rankin Score (mRS) of 1.5 compared to 0.6 for the younger group (p=0.01). The mean initial National Institutes of Health Stroke Scale Scores (NIHSSS), and mean time to tPA from stroke onset do not differ significantly: 14 (young) and 17 (old) (p=0.07), and 151 minutes (young) and 155 minutes (old) (p=0.67). Percent of patients achieving ≥4 point improvement in NIHSS 24 hours post tPA, a 3 month NIHSS of 0–1, and a 3 month MRS of 0–1 are 63 V.S. 44 (p=0.29), 35 V.S. 36 (p=0.80)and 41 V.S. 9 (p=0.12) for the young and old groups respectively. Only one patient (age 81) had a fatal intracranial hemorrhage (ICH). No other patients in the registry suffered a symptomatic ICH. Of the younger group, 11% and of the elderly group, 19% had an asymptomatic ICH (p=0.71). Conclusions: Despite the elderly patients having greater pre-stroke disability, iv tPA for AIS in this group does not significantly differ in effectiveness and complications compared to the same treatment in patients under age 80. TPA should not be withheld from AIS patients on the basis of age alone.

Neurologic manifestations, afflicting up to 70% of SLE patients, include psychosis, seizures, chorea, neuropathies, and stroke. MRI is useful in evaluation of lupus patients and several reports have documented cerebral atrophy or focal hyperintensities. We report an unusual MRI appearance in a 56-year-old woman with SLE, diagnosed on the basis of pleuritis, lymphopenia, anti-DNA antibodies, and neurologic involvement. She reported recent onset of Raynaud's phenomenon and generalized macular rash. She presented after two months of gradual deterioration with memory loss, flattened affect, dysphagia, dysarthria, anomia, and somnolence, without focal neurologic signs. Investigations included elevated ESR, reduced complement, normal CSF without oligoclonal bands, negative viral serology, normal hormone and vitamin levels, normal renal and hepatic function. Neuropsychologic testing showed widespread impairment (WAIS-R: FSIQ-63; WMS-69; DRS-98; RCPM-14; WAB AQ-78.8). CT was normal but MRI showed strikingly symmetric, confluent hyperintensities extensively involving cerebral and cerebellar white matter on Tl and T2 weighted scans. Basal ganglia and subependymal and subcortical white matter were spared. Treated with prednisone, the patient made a gradual, but incomplete, recovery. These MRI findings may reflect widespread vasculopathy or direct immunologic brain insult with or without imunologic blood-brain barrier disruption.

We have recently developed a computer program for measuring midsagittal sections of the human corpus callosum, similar to one used for the rat. Callosal area, perimeter, axis length, and 99 widths for 104 subjects were entered into a factor analysis in order to define regional clusters. Seven width factors were obtained. Regional widths were found to be sensitive to Sex × Handedness interactions in the anterior body, with right-handed females and left-handed males being larger. In the posterior body males had wider callosa than females. A further analysis within the ‘isthmus’ region compared consistent and non-consistent right-handed males and females. Consistent right-handed males and both female groups had smaller callosa than non-consistent right-handed males. These findings confirmed the use of consistency of handedness as an important independent variable with respect to human callosal morphology.

Spontaneous drawings of 38 patients, diagnosed by the National Institute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria as "probable Alzheimer's disease," and of 39 normal control subjects were analyzed by two independent observers using a standardized scoring system. Drawings of patients with Alzheimer's disease displayed fewer angles, impaired perspective and spatial relations, simplification, and overall impairment compared with those of the control subjects. This represents a combination of the deficits seen following right- and left-hemisphere lesions. Neglect, tremor, and perseveration were not prominent. Drawing impairment was relatively independent of language or memory impairment, but drawing performance was related to perceptual and executive dysfunction in the visuospatial domain. Deterioration was followed up for up to 3 years.

This study investigated the relationship between intrahemispheric location of lesion and disturbances of emotional expression and comprehension. Twenty-eight right hemisphere strokes, 18 left hemisphere strokes, and 20 controls were examined on a standardized test of the expression, repetition, and comprehension of emotional prosody as well as the visual recognition of emotional situations and faces. The patients were classified into aprosodic syndromes according to the test scores. The lesions were independently traced, and overlapped for each aprosodic syndrome. The results, for lesions in either hemisphere, indicated involvement of the basal ganglia most frequently in aprosodic syndromes followed by anterior temporal lobe and insula lesions. Basal ganglia damage was also seen most frequently in patients with impaired comprehension of emotional facial expressions and situations. The anterior temporal lobe was also frequently involved in patients with such deficits. The basal ganglia emerged as a structure of particular importance in the mediation of emotional expression and comprehension.

• In a prospective magnetic resonance imaging and cognitive study of 38 demented patients and 15 control subjects, 11 of 27 patients with Alzheimer's disease and 8 of 11 patients with vascular dementia had significant periventricular hyperintensities. Memory and language testing in the early investigation of dementia is useful to distinguish patients with or without periventricular hyperintensities on magnetic resonance imaging. Patients without periventricular hyperintensities are worse on memory and conceptualization tests than patients with periventricular hyperintensities, who tend to be worse on comprehension and attention tests. These differences in cognitive pattern are present between patients with different pathogenesis who are otherwise matched for dementia severity. Language and some nonverbal cognitive deficits correlate with the extent of cortical and ventricular atrophy in Alzheimer's disease.

To the editor: Litvan et al.1 correctly state that Pick's disease (PiD) is underdiagnosed. They document the low sensitivity of a small group of movement disorder neurologists to the diagnosis. However, their study actually perpetuates the myth of rarity of PiD, as they only had seven cases in an otherwise highly selected population dominated by progressive supranuclear palsy (PSP) and Parkinson's disease. The real obstacle to accurate clinical diagnosis of PiD is the dichotomy between clinically and pathologically diagnosed PiD, if the pathology is restricted to the presence of typical Pick bodies. In fact, the majority of cases of clinical PiD …

A 69-year-old woman was referred with a progressive 2-year history of problems reading, locating items in front of her, and knocking over things she reached for. Examination revealed normal acuity and visual fields, slowness directing voluntary saccades (oculomotor apraxia), and mis-reaching toward visual …

Reply from the Authors: Dr. Bianchetti and his colleagues point out that cases of PPA frequently exhibit clinical characteristics of frontotemporal dementia. We agree with this, and, in fact, two of our three cases clearly showed personality changes that could be considered a sign of frontal lobe involvement. [1] Patient 2 became depressed, irritable, and began to drink …

P196 Background: Many rural community hospitals (RCH) in Southwestern Ontario lack a CT scanner. The stroke team (ST) in London provides tertiary care to these RCH. Advance notification of transfer of non-London patients (NLP) from RCH allows the ST to manage them from arrival at the LER. In contrast, the ST is notified of London patients (LP) after their arrival and registration in the London ER (LER). Objective: Assess feasibility of tPA administration to rural patients transferred to a tertiary care center. Methods: Mean symptom to LER, door to imaging, imaging to tPA, and door to tPA (DtPA) for LP and NLP times were compared. In-patients were excluded from the analysis. Results: Between Dec 1, 98 and Jun 30, 00, 61 patients were treated with tPA in London: 16 (26%) were NLP, 45 (74%) were local (37 LP, 8 in-patients). For NLP the mean symptom to RCH time was 37 mins, the mean RCH to LER distance was 41 miles (range 11–80) and the mean transfer time was 90 mins. (range 46–138). Symptom onset to LER time was significantly longer for NLP, but door to imaging, imaging to tPA, and DtPA were significantly lower (p< 0.001, see table). Conclusions: 1. The establishment of a network of RCH and a tertiary center can extend the benefits of tPA to a rural population. 2. DtPA can be shortened if the ST manages the patients from arrival to the ER. This strategy could be applied to local patients if EMS notifies the ST of potential candidates for tPA.

P237 Background: In the setting of acute myocardial infarction, aspirin has a significant benefit on mortality when combined with a thrombolytic. The NINDS guidelines recommend witholding antiplatelet agents (APA) for 24 hours after tPA administration for acute stroke. Post hoc analysis of the NINDS tPA study did not show worse outcomes in patients using APA prior to treatment, even though APA have a long platelet-inhibitory effect (the life of the platelet). Objective: To determine whether concomitant APA and tPA use was associated with worse outcomes. Method: We compared demographics, vascular risk factors, hemorrhagic complications, and 3 month outcomes of patients on APA at the time of their stroke with those patients not taking APA, in our prospective registry of tPA-treated patients. Results: Between 1 December 1998 and 24 July 2000, 64 patients were treated with tPA; 3 month follow-up data are available on 47 (73%). At the time of their stroke, 24 (38%) were taking APA, 40 (62%) were not. Patients taking APA were more likely to have a history of coronary heart disease, previous stroke and previous TIA, and they had higher baseline modified Rankin Scores (mRS). There was a trend for them to be older (75.3 years [APA] vs. 70.2 years [no APA], p =0.06). There was no increase in major intracranial or systemic hemorrhages at 36 hours (0% [APA] vs. 5% [no APA], p =0.54), or in mortality at 3 months (13% [APA] vs. 15% [no APA], p =1.00). More patients taking an APA had a NIH Stroke Scale score (NIHSSS) of 0–1, but this did not reach statistical significance (40% [APA] vs. 29% [no APA], p =0.42). There was a non-significant trend for fewer patients on an APA to have a 3 month mRS of 0–1 (20% [APA] vs. 41% [no APA], p =0.17). However, given their higher baseline mRS, we also looked at the percentage who returned to their baseline mRS, this favored the APA group but again it did not reach statistically significance (40% [APA] vs. 28% [no APA], p =0.38). Conclusion: Concomitant APA and tPA use appears safe and may be associated with an improved outcome. The potential beneficial effect of the combination merits further study.

Language can be remarkably preserved, even in face of relatively severe mental retardation, a fact that has been known to pediatricians, child neurologists, psychologists, and many others who have had contact with such individuals. Yamada's book Laura , a case study of a woman, illustrates this dissociation. The introduction touches on the duality of cognition and language and reviews some evidence for their dissociation in cases of Turner's syndrome, hydrocephalics, William's syndrome, and other reports. Somewhat related cases are the descriptions of hyperlexia and the relatively large literature on "savants" with selectively superior abilities in memory, music, calendar calculation, and mental arithmetic. The case report begins with anecdotal descriptions of her early development. Mention is made of Laura's hypothyroidism (cretinism), precocious puberty, abnormal electroencephalogram, and dysmorphic features. The assessment included language and nonlanguage measures, using a rather widely ranging battery of tests. In the linguistic analysis of Laura's speech, Yamada em

Pick disease(PiD), or circumscribed atrophy, as Pick called it, is like the proverbial elephant. When blind men are asked to define it, one feeling a leg calls it a tree, another touching the trunk declares it a snake, and a third encountering the body calls it a wall. The term means different things to different people. Pick disease is used either to designate clinically defined cases of progressive frontal and temporal degeneration, as was described by Pick, 1 or a pathologic entity defined histologically by the presence of argyrophilic globular inclusions (Pick bodies) and swollen achromatic neurons (Pick cells). Pick's initial patient with progressive aphasia and behavioral disturbance, and his subsequent patients with frontal lobe dementia and aphasia, underwent anatomical examination only. The histological description came later. 2 It also became apparent that cases of clinical PiD with frontal and temporal lobe atrophy may not show the typical histological

David Caplan was not content to sit on his laurels after his book on psycholinguistics but produced another volume on language with emphasis on aphasic disturbances, this time with an intent to introduce the subject to a more general audience. The book manages to be a fairly sophisticated and critical account of recent advances as well as providing definitions and introductory explanations to those outside the field. The emphasis is on linguistic structure and processing. It deals with the central issue of auditory word recognition, semantics, production of words, and reading and writing. It then proceedes to complex morphology and syntax with both sentence comprehension and sentence production. It also has an excellent chapter on discourse and touches on issues relating to the diagnosis and treatment of language disorders. It is in this last chapter that Caplan criticizes existing aphasia batteries and describes his own test of psycholinguistic assessment of

Consistency of right-hand preference correlates with callosal isthmus size. Anterior corpus callosum (CC) regions vary as a function of sex and right- versus left-hand preference. We analyzed regional CC anatomy in a sample of right- and left-handed men and women on the basis of both degree (“Consistency”) and direction (“Hand”) of hand preference scores. Significant Hand × Consistency effects indicated that both are important factors in CC organization. These data also suggested that a single continuum of hand preference and regional CC size may not be applicable across all subjects.

The introduction introduces a new term (at least new to me),neuropsycholinguistics. Actually, I have been waiting for this to appear to see who will breach the English restraint of piling up components of words. I suppose the next one will beneuropsychocognitolinguistics. The first chapter is a good example of the style and the approach. It contains the by-now familiar model of the lexical system and summarizes the various single case reports of Caramazza and Miceli. These case reports typically take linguistic tasks, such as naming and reading words and analyze the errors to draw conclusions about the nature of various stages of lexical production. Some of these observations have been well known for almost a century, such as the patient who cannot name objects or produces semantic errors but who can, in fact, circumlocute or circumscribe, or patients who cannot respond orally but who can write. The authors