Transatlantic Crossings: Early neurological exchanges between USA and France.

Transnational exchanges have existed for centuries, with both economic and cultural effects. At the end of the 18th century, in the aftermath of the French Revolution, medical education in France underwent radical innovations, prefiguring the training system now almost universally accepted. This paper presents 19th and early 20th century neurology-related exchanges between the United States (US) and Europe, particularly, Paris, which had become a major medical center and where many US neurologists were trained. We discuss some of the intense neurology-related exchanges between the USA and Europe, notably the role of US neurology founders William Alexander Hammond, Silas Weir Mitchell, Edward Seguin as well as Mauritius-born Charles Edouard Brown-Séquard and a few others. We emphasize the mutual benefits that resulted from such exchanges. In later years, the trend reversed with many foreigners, particularly Europeans coming to improve their knowledge in the US. More recently, a shared pattern of travel and enrichment is occurring despite current threats caused by isolationism and undue stress on local identity.

Family study of platelet membrane fluidity in Alzheimer's disease.

The fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene in labeled platelet membranes, an index of membrane fluidity, identifies a prominent subgroup of patients with Alzheimer's disease who manifest distinct clinical features. In a family study, the prevalence of this platelet membrane abnormality was 3.2 to 11.5 times higher in asymptomatic, first-degree relatives of probands with Alzheimer's disease than in neurologically healthy control subjects chosen without regard to family history of dementia. The pattern of the platelet membrane abnormality within families was consistent with that of a fully penetrant autosomal dominant trait. Thus, this abnormality of platelet membranes may be an inherited factor that is related to the development of Alzheimer's disease.

[Neuropsychological impairment in the early Alzheimer's disease]. / Le déficit neuropsychologique dans la maladie d'Alzheimer débutante.

This analysis is centered on the study of cognitive disorders in Alzheimer's disease (AD), mainly for major neuro-psychological functions. We insist on the heterogeneity of the clinical picture peculiarly in the early stages of the illness, even if the deficits of episodic memory and of attentional/executive capacities are the first to deteriorate, preceding impairment in perceptual and language function and potentially having a substantial impact on the patient's capacity to cope independently. An episodic memory deficit is the hallmark of AD, but it must be stressed that this deficit may take different forms and its origin may be traced back to different cognitive mechanisms. One of the most striking aspects of episodic memory impairment in AD is the rapidity of forgetfulness on which screening and diagnostic tests of AD are based. There is some evidence that the episodic memory deficit in AD is one of learning (encoding and storage) of information rather than to a deficit of retrieval. Furthermore, episodic memory performance in AD depends on the integrity of semantic memory abilities, so giving support to a hierarchical model of organization of human memory. Finally, recent results show that an impairment of conscious recollection is responsible for the poor performance of AD patients in recognition memory. Executive deficits appear predominantly in tasks requiring cognitive flexibility and self-monitoring. With the progression of the disease, additional deficits are observed in the verbal concept formation abilities. These findings might be also very useful in the differential diagnosis between AD and the other cortical and subcortical dementias, as well as in the differentiation between AD and fronto-temporal dementia. We consider that studying early stages of the illness is necessary to delineate the diagnostic signs, to validate the new therapeutic experiments, to predict stages of decline. Recent research suggested that onset of AD is commonly preceded by an interim phase known as mild cognitive impairment (MCI). MCI refers to the clinical condition in which persons experience memory loss to a greater extent than one would expect for age, yet they do not meet currently accepted criteria for clinically probable AD. Persons who experience this condition are at increased risk for the development of AD. In MCI, despite the comparable global cognitive functioning, the findings show more impaired retrieval from long-term storage than in NC. The cued recall improves slightly the total recall but the recognition is significantly impaired. Moreover, the data indicate that MCI patients had additional problems with response inhibition, switching and cognitive flexibility. This suggests, that MCI may be identified by using a more detailed procedure for the assessment of cognitive decline than the evaluation of memory alone. As preventive strategies are developed and new cognitive enhancing therapies emerge, these results may also help us to define which domains are expected to improve in MCI populations.

Clinical prediction rules for computed tomographic scanning in senile dementia.

The role of computed tomography (CT) of the head in evaluating patients with dementing illnesses remains a controversial issue. Several prediction rules to guide the selective application of CT in the evaluation of dementia have recently been proposed in the medical literature. The present authors examine the value of four such rules through a validation study performed in an outpatient geriatric assessment unit. The rules were assessed in terms of their diagnostic sensitivities, specificities, misclassification rates, and information contents. Prediction rule sensitivities ranged from 12.5% to 87.5%, specificities from 37.2% to 77.9%, and misclassification rates from 23.5% to 60.8%. Of the four prediction rules examined, one emerged as significantly more sensitive than the others, and also served to reduce diagnostic uncertainty a full order of magnitude more than the others, as determined by an information content analysis. Disadvantages to this rule, however, were found in its more complex nature and the assessment of a very high rate of misclassification. Through a critique of existing strategies, this study purports to determine the potential for establishing a useful clinical prediction rule to guide selective CT scanning in the diagnostic evaluation of dementia.

T2-weighted MRI studies of mouse lemurs: a primate model of brain aging.

Previous histological and behavioral studies of aging mouse lemurs have demonstrated changes similar to those observed in elderly humans and in patients with Alzheimer's disease. We explored 18 animals of ages 6 months to 9 years. Axial T2-weighted images of the brain were performed on a 4.7 Tesla Bruker Biospec 47/30 system. We estimated cerebral atrophy by adding measures of high signal areas characteristic of cerebrospinal fluid (interlobular and sylvian fissures, lateral and third ventricles) of four contiguous cortical slices. We observed a significant increase of cerebral atrophy with aging and one case of an apathetic 8-year-old animal presenting a considerably higher cerebral atrophy. We also observed high correlations between decreased signal intensities and age for the pallidum, the substantia nigra, and the putamen. These results suggest that aging mouse lemurs present similar magnetic resonance images of cerebral alterations to those encountered in aging humans and that high-field T2-weighted magnetic resonance images can help in the early detection, in vivo, of animals suspected of pathological aging.

MRI description of cerebral atrophy in mouse lemur primates.

We assessed cerebral atrophy in mouse lemur primates (Microcebus murinus) by estimating CSF volume in their brains from 4.7 Tesla T2-weighted magnetic resonance images. Thirty animals aged from 1 to 10.3 years were imaged, 14 of them were followed for up to 2 years. Seven of these animals were examined for neuropathology. In 12 out of 17 animals older than 3.5 years, CSF volumes were increased. A subgroup of six animals had severe atrophy of the temporal lobe. Another subgroup of five animals displayed diffuse atrophy in addition to the temporal atrophy. One animal had a dilation of the external part of the temporal horn of the lateral ventricle in addition to the temporal atrophy. The three animals with diffuse atrophy that could be studied for neuropathology had diffuse cerebral amyloid deposits detected by immunocytochemistry. The other animals did not display amyloid deposits. Relations between the different types of atrophy as well as their causes will have to be assessed in future studies.

Cerebral T2-weighted signal decrease during aging in the mouse lemur primate reflects iron accumulation.

4.7 Tesla T2-weighted magnetic resonance images showed a highly significant signal decrease in the pallidum, substantia nigra, putamen, and a less significant decrease in the thalamus and the caudate of aging mouse lemurs (Microcebus murinus). We evaluated the contribution of iron deposits to the signal decrease comparing Perls' stained histological sections of six mouse lemurs brains aged 1 to 10 years to magnetic resonance images. In young animals, none of the brain structures was stained. A large number of iron deposits were visible in the pallidum and substantia nigra of aged animals and a moderate number in the middle aged ones. In the putamen, few iron deposits were visible in aged and middle-aged animals. The thalamus and the caudate appeared unstained with Perls' technique; iron was too low to be detected. The intensification of the reaction by diaminobenzidine revealed iron deposits in the thalamus of aging animals. This study suggests that in mouse lemurs, iron deposits are responsible for T2-weighted signal decrease in the central gray nuclei.

Platelet membrane fluidity in Alzheimer's disease and major depression.

Double-blind fluorescence studies of platelet membrane fluidity were conducted at 37 degrees C for 51 patients with Alzheimer-type dementia, 24 nondemented depressed patients, and 50 neurologically healthy subjects. The fluidity of the hydrocarbon region of platelet membranes from the demented group, as reflected by the steady-state anisotropy of the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH), was significantly greater than that for the depressed and normal control subjects. Within the demented group, platelet membrane fluidity was significantly correlated with severity of dementia but not with duration of illness or age at onset. Demented patients with "increased" platelet membrane fluidity had an earlier onset, were more severely demented, and deteriorated more rapidly.

Alzheimer's disease and depression: neuropsychological impairment and progression of the illness.

The authors longitudinally evaluated the cognitive functions of patients with probable Alzheimer's disease who also met criteria for major depression and compared them with matched patients with Alzheimer's disease who were not depressed. They found no significant difference in the pattern of neuropsychological deficits between the two groups; composite scores on attention, language, memory, learning, and visuospatial functions did not differentiate the two groups at baseline or at 1-year follow-up. The results of this preliminary report suggest that depression does not modify the neuropsychological features and the rate of progression of Alzheimer's disease.

Johann Baptist Schmidt. A pioneer in the history of aphasia.

Wernicke is usually credited with the first significant description of comprehension disorders in aphasia. Before Wernicke, however, others had reported patients with impaired comprehension. This communication deals with one of those pioneer papers, that written by Schmidt, an obstetrician, in 1871. It concerns a 25-year-old woman who developed sudden language difficulty ten days after delivery. She had trouble understanding oral or written language. Through careful examination, Schmidt showed that she was neither deaf nor psychotic. He concludes his paper with a prediction of the area of the brain he suspected to be involved. Schmidt's paper represents an early, noteworthy effort to clarify the relations between brain and behavior.

1914 to 1917: the Great War years.

In 1914, American and international neurology were already very well developed, but like the other scientific and societal forces of the time, they underwent numerous changes as a result of World War I. This article reviews the state of neurology between 1914 and 1917 as it can be inferred from the journals of the time, the main topics they covered, the meetings, and the neurological societies, as well as some of the actors on the neurology scene during these years. It concludes with a brief survey of the ways in which neurology was changed by the Great War. During these years, neurology was there.

Unilateral gunshot wound of the pons: clinical, electrophysiologic, and neuroradiologic correlates.

Following a gunshot wound to the face, a 17-year-old male patient experienced a right trigeminal and abducens paralysis, dysarthria, right-sided ataxia, left-sided weakness of the lower part of the face and limbs, and left-sided sensory loss from his neck down. Brainstem auditory evoked potentials showed a decreased P5/P1 amplitude ratio for left ear presentation, and inconsistent replication of P2 and P3 on the right and, to a lesser extent, on left ear click presentations. A computerized tomography scan showed right pontine atrophy. These findings point to a unilateral lesion of the right pons.

Severe impairment battery. A neuropsychological test for severely demented patients.

OBJECTIVE: Patients with progressive dementia invariably evolve to a stage where they can no longer be tested by standard neuropsychological tests. We studied the use of the Severe Impairment Battery (SIB) in such patients. DESIGN: Case series. SETTING: Geriatric long-term facility. PATIENTS: Sixty-nine patients who met the criteria of the Diagnostic and Statistical Manual for Mental Disorders, Revised Third Edition, for dementia were selected. The diagnosis of probable Alzheimer's disease was established according to the guidelines suggested by the National Institute of Neurologic and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association. There were 18 men and 51 women. The mean age of the population was 82.99 +/- 5.66 years. The mean Mini-Mental State Examination (MMSE) score was 10.71 +/- 6.14. MAIN OUTCOME MEASURE: To characterize the cognitive profile and evolution of severely demented patients by means of the SIB. RESULTS: The mean score on the SIB was 92.52 +/- 31.92, with a possible maximum of 133 points. Subgroups of patients with the most severe degree of dementia (MMSE scores of 0 to 5 and 6 to 11) showed significant differences in their scores on the SIB. In contrast, no differences were found between subgroups with MMSE scores of 6 to 11, 12 to 17, and greater than 17. Fifteen patients who had MMSE scores of less than 6 had SIB scores ranging from 7 to 81. All cognitive domains showed a deterioration across the four severity groups as determined by the MMSE scores and also during a longitudinal study performed on 26 patients. CONCLUSION: Our study indicates that the SIB is useful for the neuropsychological evaluation of severely demented patients and for their follow-up.

Neuropsychological correlates of hypertension.

Twenty newly diagnosed, untreated hypertensive men (diastolic blood pressure greater than 105 mm Hg) and 20 normotensive controls were given a neuropsychological battery, including tests of generalized, more global functions (eg, reaction time and full-scale IQ) and of specific functions (eg, language and visual-spatial abilities) sensitive to focal damage. Tests of specific abilities yielded no differences between the two groups. In contrast, tests of general neuropsychological functioning revealed a deficit among hypertensives, who were significantly slower on the reaction time test and had a shorter span for digits in forward order. Results suggest that arterial hypertension is associated with impairment of vigilance and attention span. Future research will determine whether this impairment is associated with the diffuse pathological changes seen in the brain of hypertensive subjects, or with a more "functional" change (eg, reduced cerebral blood flow).

Learning deficit in Parkinson's disease. Comparison with Alzheimer's disease and normal aging.

The learning ability of 12 patients with Parkinson's disease (PD) was studied using a verbal paired-associate learning task, and was compared with that of ten patients with Alzheimer's Disease (AD) and 12 controls (NC). Overall, the PD patients performed significantly better than the AD patients but significantly worse than the NC subjects. Their performance was not related to their overall level of cognitive functioning as measured by the Mattis' Dementia Rating Scale, but was unequally distributed suggesting that the PD population actually consisted of more than one subgroup. A low error group performed like controls, while a high error group had a learning impairment comparable to that of AD patients. It is concluded that PD patients may have three patterns of neuropsychologic performance: some are unimpaired, some have "focal" abnormalities, and some have a generalized impairment of cognitive function.

The neurologic examination in patients with probable Alzheimer's disease.

Abnormal findings on a standardized neurologic examination were compared between patients with a clinical diagnosis of probable Alzheimer's disease (AD) and healthy control subjects. Aside from mental status findings, the most useful examination findings for differentiating AD from control subjects were the presence of release signs, olfactory deficit, impaired stereognosis or graphesthesia, gait disorder, tremor, and abnormalities on cerebellar testing. These abnormalities probably reflect the different areas of the central nervous system that are affected pathologically in AD. In the clinical diagnosis of AD, particular attention should be given to these aspects of the neurologic examination.

Correlation of phosphorus-31 magnetic resonance spectroscopy and morphologic findings in Alzheimer's disease.

Senile plaques (SPs), especially, and neurofibrillary tangles are important pathologic markers for the diagnosis of Alzheimer's disease (AD), but neither is pathognomonic for AD. We hypothesize that elevations in levels of phosphomonoesters, precursors of membrane phospholipids, occur early in the pathogenesis of AD and precede the appearance of SPs. In contrast, elevations in levels of phosphodiesters, breakdown products of phospholipids, reflect degeneration of neural membranes and will correlate with the appearance of SPs. Correlative phosphorus-31 magnetic resonance spectroscopy and morphologic studies conducted to test this hypothesis disclosed that elevations in levels of phosphomonoesters had a negative correlation with the numbers of SPs, and elevations in levels of phosphodiesters had a positive correlation with the numbers of SPs. No correlations were observed for either membrane parameter and neurofibrillary tangles. These findings support our hypothesis and suggest that aberrations in the synthesis of membrane phospholipids are early metabolic events in the pathogenesis of AD.

Thalamic and subcortical gliosis with dementia.

We describe two cases of patients with "primary dementia" in whom autopsy showed marked astrocytosis in several subcortical nuclei, but chiefly in those of the thalamus. One patient had the onset of symptoms at 31 years of age and a subacute course. The second patient was an elderly man with a strong familial history of dementia. These cases offer further evidence that subcortical lesions, especially in the thalamus, may produce a dementia that is not always clinically distinguishable from Alzheimer's disease and other "cortical" dementias.

Neuropsychological function in Alzheimer's disease. Pattern of impairment and rates of progression.

Although patients with Alzheimer's disease (AD) generally have impairments in multiple areas of cognitive function, there are those patients who appear to have neuropsychological deficits more prominent in one domain than in other domains. We examined the neuropsychological status of 86 patients with probable AD and 92 elderly control subjects and identified the patterns of impairments in the patients with AD. Independent deficits of visuoconstructional and lexical/semantic abilities were identified in a subset of patients by a principal components analysis. Individual patients were identified who were predominantly impaired in one, but not the other, neuropsychological domain. There were no striking relationships between the demographic characteristics of the patients and their pattern of deficits at the initial evaluation. There were no significant differences in age at onset or rate of progression of dementia among patients with different patterns of cognitive dysfunction. A review of the results of this and other studies suggests that the language impairment in AD may be associated with two distinct neuropsychological abnormalities: a lexical/semantic impairment that is unrelated to onset or progression of symptoms, and a syntactic impairment that may be associated with earlier onset and more rapid progression of dementia.

Visuospatial impairment in Parkinson's disease. Role of perceptual and motor factors.

We investigated the role of perceptual and motor factors in visuospatial impairment in 30 patients with Parkinson's disease (PD) and 30 matched controls. All subjects were administered visuospatial tests, which included "visuoperceptual" tasks, requiring minimal motor responses, and "visuomotor" tasks. The performance of patients with PD was considerably impaired on several tasks from both groups, and this impairment was not related to depression or intellectual impairment. Patients in stage 3 of the disease tended to show the greatest impairment. Those in stage 1 (unilateral symptoms), however, tended to show more impairment than those in stage 2.