Penetrance of marked cognitive impairment in older male carriers of the FMR1 gene premutation.

BACKGROUND: Male carriers of the FMR1 premutation are at risk of developing the fragile X-associated tremor/ataxia syndrome (FXTAS), a newly recognised and largely under-diagnosed late onset neurodegenerative disorder. Patients affected with FXTAS primarily present with cerebellar ataxia and intention tremor. Cognitive decline has also been associated with the premutation, but the lack of data on its penetrance is a growing concern for clinicians who provide genetic counselling. METHODS: The Mattis Dementia Rating Scale (MDRS) was administered in a double blind fashion to 74 men aged 50 years or more recruited from fragile X families (35 premutation carriers and 39 intrafamilial controls) regardless of their clinical manifestation. Based on previous publications, marked cognitive impairment was defined by a score

Ulnar neuropathy at the elbow: Reappraisal of the wrist-upper arm latency difference between ulnar and median nerves.

OBJECTIVES: To evaluate the sensitivity and specificity of the latency difference (DLat) between ulnar and median nerves of the arm after stimulation at the wrist; one of the easiest techniques proposed for recognizing ulnar neuropathy at the elbow (UNE). As latency difference is not a standardized technique, we set up a multicenter study to recruit large numbers of normal subjects and patients with UNE or generalized neuropathy. METHODS: Six centers participated in the study with data obtained from three groups of participants, controls (CTRLs), patients with UNE and patients with generalized neuropathy (GNP). We first verified the anatomical superposition of the ulnar and median nerves in cadaver examination. The optimal recording site for these two nerves was found to be 10 cm above the medial epicondyle. We then standardized the position of the arm with full extension of the elbow and stimulated first the median and then the ulnar nerves at the wrist. CTRLs were examined on both arms at two consecutive visits. RESULTS: We recorded 32 idiopathic UNE cases, 44 GNP patients and 62 controls. We demonstrated that a DLat cut-off value of 0.69 ms brings a sensitivity of 0.86 and specificity of 0.89 to discriminate CTRLs from UNE. We also validated that intra-examiner reproducibility was good. CONCLUSION: We report a lower normal value for DLat than reported in several non-standardized studies and CTRL and UNE groups have clearly separated DLat values. SIGNIFICANCE: Due to its high sensitivity, our standardized technique could be used as a first-line diagnostic tool when UNE is suspected.

Direct interhemispheric visual input to human speech areas.

Very little is known about the connectivity of the human cerebral cortex. Nonhuman primates often serve as a model, but they are very unsatisfactory when it comes to specifically human functions. Evidence from (human) lesion and activation studies indicates that Broca's and Wernicke's areas play a critical role in language functions, whereas the inferior temporal cortex of the right hemisphere tends to be associated with high-level visual recognition. We describe here monosynaptic interhemispheric input from the right inferior temporal cortex to Wernicke's and Broca's areas. The connections were traced in a brain with a right inferior temporal infarction by means of the Nauta method for anterogradely degenerating axons. Afferents were found both in Broca's and Wernicke's areas, with a higher density in the latter. Three organizational principles emerge from this study. First, the presence of direct connections from the right inferior temporal cortex to the speech areas indicates that human interhemispheric connections can be widely heterotopic. Second, the fact that connections from the inferior temporal cortex terminate in both Wernicke's and Broca's areas speaks in favor of parallel pathways in visuo-verbal processing. And third, the patchy distribution of visual interhemispheric afferents in Wernicke's area hints at a possible functional compartmentalization within this area.

Cortical regions contributing to the anterior commissure in man.

The human anterior commissure is believed, by extrapolation from data obtained in macaque monkeys, to convey axons from the temporal and orbitofrontal cortex. Reports of interhemispheric transfer and sexual dimorphism related to the anterior commissure, however, make more precise data on the human anterior commissure desirable. We investigated the connectivity of the human anterior commissure in six adults (male and female) that had circumscribed hemispheric lesions in temporal, frontal, parietal or occipital cortices or in infrapallidal white matter using the Nauta for anterogradely degenerating axons. Axons originating in the inferior part of temporal or occipital lobes, occipital convexity and possibly central fissure and prefrontal convexity were found to cross the midsagittal plane in the anterior commissure. The largest contingent of commissural axons originated in the inferior part of the temporal lobe; it displayed a roughly topographic organization, preferentially running through the inferior part of the commissure. The inferior temporal contingent seemed to reach homotopic and heterotopic targets in the opposite hemisphere. Among the latter were the amygdala and possibly the orbitofrontal cortex. The present data suggest that the human anterior commissure conveys axons from much larger territories than expected from work on non-human primates. Similarly to the human and non-human primate corpus callosum, the anterior commissure is roughly topographically organized and participates in heterotopic connectivity.