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.

[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.

Genetic heterogeneity in familial idiopathic basal ganglia calcification (Fahr disease).

Familial idiopathic basal ganglia calcification (IBGC, Fahr disease) is an inherited neurologic condition characterized by basal ganglia and extra-basal ganglia brain calcifications, parkinsonism, and neuropsychiatric symptoms. The authors examined six families for linkage to the previously identified genetic locus (IBGC1) located on chromosome 14q. The authors found evidence against linkage to IBGC1 in five of the six families supporting previous preliminary studies demonstrating genetic heterogeneity in familial IBGC.

Factorial validation of the Severe Impairment Battery for patients with Alzheimer's disease. A pilot study.

The Severe Impairment Battery (SIB) estimates the cognitive aptitudes and other skills of severely impaired dementia patients. The main objective of this pilot study was to clearly identify the number of factors present in the SIB and to analyze the relationships between the different cognitive domains explored by the SIB and loss of autonomy. We administered the SIB, the Mini Mental State Examination (MMSE) and two scales of dependency to 48 patients with Alzheimer's disease in its late stages. A factorial analysis (Principal Components Analysis) showed a 4-factor solution for the SIB: a cognitive factor, a praxis and visuospatial functions factor, the reactivity to external stimuli factor and the social aptitudes factor. A factorial analysis involving the dependency scales showed a cognitive factor, a dependency and constructional praxis factor, the reactivity to external stimuli factor and the social aptitudes factor. Reactivity to external stimuli and social aptitudes were not significantly correlated to cognitive aspects nor to dependency. The finding of dependency as a factor different from cognitive deterioration suggests that, in setting a treatment strategy for demented patients, attempts should be made to treat dependency in its own right. In addition, since reactivity to external stimuli and social aptitudes are not related to cognitive aspects nor to dependency, these functions should also be encouraged and stimulated.

Maurice Ravel and right-hemisphere musical creativity: influence of disease on his last musical works?

The problem of finding correspondence between a particular neuronal organization and a specific function of the human brain remains a central question of neuroscience. It is sometimes thought that language and music are two sides of the same intellectual coin, but research on brain-damaged patients has shown that the loss of verbal functions (aphasia) is not necessarily accompanied by a loss of musical abilities (amusia). Amusia without aphasia has also been described. This double dissociation indicates functional autonomy in these mental processes. Yet verbal and musical impairments often occur together. The global picture that emerges from studies of music and its neural substrate is by no means clear and much depends on which subjects and which aspect of musical abilities are investigated. An illustration of these concepts is provided by the case of the French composer Maurice Ravel, who suffered from a progressive cerebral disease of uncertain aetiology, with prominent involvement of the left hemisphere. As a result, Ravel experienced aphasia and apraxia and became unable to compose. The available facts favour a clinical diagnosis of primary progressive aphasia (PPA), with the possibility of an overlap with corticobasal degeneration (CBD). In view of Ravel's clinical history, we propose that two of his final compositions, the Bolero and the Concerto for the Left Hand, include certain patterns characteristic of right-hemisphere musical abilities and may show the influence of disease on the creative process.

Association of the apolipoprotein E epsilon4 allele with late-onset depression.

Apolipoprotein E (ApoE) phenotyping was determined in 42 subjects with Alzheimer's disease (AD), 49 with depression, including 26 with early-onset depression (EOD) and 23 with late-onset depression (LOD), and 49 controls. In the EOD group, the frequency of the ApoE epsilon4 allele was not different from the control frequency (p = 0.532) but was significantly lower than in AD (p < 0.001). In the LOD group, the ApoE epsilon4 frequency was significantly higher than in the controls (p = 0.034) but was not different from that in the AD group (p = 0.229). Individuals with ApoE epsilon4 were at greater risk of getting AD (odds ratio, OR = 5.5, 95% confidence interval, CI, 2.0-14.0) or LOD (OR = 6.1, 95% CI, 1.9-19.0) than of EOD (OR = 0.7, 95% CI, 0.2-2.5). These results suggest an association between the ApoE epsilon4 allele frequency and LOD. Patients with LOD could be at risk of developing AD by an epsilon4-dependent pathway.

Neuropsychological tests in Alzheimer's disease.

The recent development of symptomatic pharmacological treatment for Alzheimer's disease (AD) and the probable introduction of new therapies in a near future make the assessment of dementia at its different stages an even greater scientific and public health challenge. Neuropsychological tests, together with clinical data, are at present the only in vivo non-invasive screening and diagnostic tools for AD and related disorders. This chapter reviews the application to AD of standard batteries and short screening tests. It also analyzes the tests to be applied to detect and assess the specific deficits of the disease, and discusses the advantages and flaws of current screening and diagnostic tests of dementia. Emphasis is placed on the need to devise and use tests developed in a rational manner, with high sensitivity and specificity, not only in the moderate stages of the disease, but also in the very early and even "preclinical" stages, as well as during the late stages (severe dementia). It is known that neuropsychological tests allow one to determine various patients' profiles. Future research should determine the possible predictive value of these profiles. This has important implications for therapeutic trials. The current implicit assumption that all patients with AD tend to evolve and decline in a similar fashion needs to be critically re-examined.

The apolipoprotein E epsilon4 allele and the response to tacrine therapy in Alzheimer's disease.

The objective of our study was to evaluate the effects of the apolipoprotein E (ApoE) phenotype and gender on the response to tacrine treatment in Alzheimer's disease (AD). ApoE phenotyping was performed on 76 patients treated with tacrine for AD. This group comprised 33 ApoE epsilon4 allele carriers (epsilon4+) and 43 non-epsilon4 carriers (epsilon4-). Patients were treated blindly in relation to the ApoE phenotype, with incremental tacrine dosages ranging from 40 mg/day up to the highest dosage (160 mg) tolerated without side-effects. At least 6 weeks elapsed between each increase. Changes in the scores for the Alzheimer Disease Assessment Scale-Cognitive Component (ADAS-Cog) between baseline and each increment in dosage were assessed in the epsilon4- and epsilon4+ groups. The cut-off point for being considered as responsive to tacrine treatment was a 4-point decrease in the ADAS-Cog score. There was no tendency for the epsilon4- carriers to respond better than the epsilon4+ carriers. When patients were stratified by gender, no differences were found between the effects of the treatment on men and women. Consequently, these results do not support the hypothesis that the ApoE phenotype and gender are predictors of the response to tacrine in AD patients.

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.

Absence of amusia and preserved naming of musical instruments in an aphasic composer.

M.M., a right-handed, 74 year old professional musician and composer, presented with a progressive aphasia with a severe anomia. His musical competence was apparently totally preserved, and he continued his activity as a composer. There was a striking discrepancy between his impaired naming of nonmusical stimuli and his normal naming of musical instruments' sounds. We suggest that the preservation of skills in the musical domain results from an expanded cortical representation of this function in the left hemisphere, secondary to his lifelong formal training, and to the high level of his professional competence. As for his preserved naming of musical instruments, we argue that the early age-of-acquisition and higher than "normal" frequency/familiarity for names of musical instruments facilitate the access to their lexical representation and/or their retrieval within the lexicon.

Remote memory in Alzheimer's disease.

The authors examined the severity and type of deficits in remote memory in patients with probable Alzheimer's disease (AD). In the first study, 40 AD patients showed significantly more severe deficits on both the free-recall and the recognition sections of the Remote Memory Scale (which measures memory for famous people and well-known events) compared with normal control subjects. In the second study, 25 AD patients showed significantly more deficits on the free-recall section of the Autobiographical Memory Scale compared with normal control subjects. Remote memory deficits in AD may be related to both retrieval deficits and damage to memory traces.

Psychiatric medication and abnormal behavior as predictors of progression in probable Alzheimer disease.

OBJECTIVE: To examine whether the use of psychiatric medication and the presence of abnormal behaviors affects the progression of Alzheimer disease. DESIGN: Cross-sectional with longitudinal follow-up and the likelihood of arriving at 4 end points: (1) Mini-Mental State Examination score of 9 or lower; (2) Blessed Dementia Rating Scale score of 15 or higher for activities of daily living; (3) nursing home admission; and (4) death, evaluated using a proportional hazard model with 9 variables: psychosis, insomnia, wandering, aggression, psychomotor agitation, depression, and use of antidepressants, antipsychotic agents, or sedatives/hypnotics. SETTING: Multidisciplinary dementia research clinic. PATIENTS: We examined baseline and follow-up behavioral symptoms and the use of psychiatric medication in 179 mildly to moderately impaired patients with probable Alzheimer disease participating in a longitudinal study of dementia. Patients were observed from 2.4 to 172 months (mean duration +/- SD, 49.5+/-27.4 months). RESULTS: Nine patients (5%) were taking sedatives/ hypnotics; 16 (9%), antipsychotic agents; and 22 (12%), antidepressants at study entry. Patients taking antipsychotic agents had lower Mini-Mental State Examination scores and higher Blessed Dementia Rating Scale scores for activities of daily living than patients not taking any medication. Using proportional hazard analysis with time-dependent covariates for individual psychiatric symptoms and medications, we found that the development of psychosis was associated with functional decline (time to Blessed Dementia Rating Scale score of > or =15), institutionalization, aggression, and agitation with functional decline after adjusting for age at study entry, education, Mini-Mental State Examination scores, and Blessed Dementia Rating Scale scores. Use of antipsychotic medication was associated with functional decline, and sedatives/hypnotics with death. Neither the presence of psychiatric symptoms nor use of medication was associated with rate of cognitive decline (time to Mini-Mental State Examination score of < or =9). CONCLUSIONS: These findings indicate that the use of antipsychotic agents and sedatives can affect the natural course of Alzheimer disease. Psychosis, agitation, and aggression are important predictors of outcome, even when the effects of medication to treat them is taken into account.

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.