Jean-Denis Degos

Motor and cognitive improvements in patients with Huntington's disease after neural transplantation.

BACKGROUND Huntingtons disease is a neurodegenerative disease of genetic origin that mainly affects the striatum. It has severe motor and cognitive consequences and, up to now, no treatment. Motor and cognitive functions can be restored in experimental animal models by means of intrastriatal transplantation of fetal striatal neuroblasts. We explored whether grafts of human fetal striatal tissue could survive and have detectable effects in five patients with mild to moderate Huntingtons disease. METHODS After 2 years of preoperative assessment, patients were grafted with human fetal neuroblasts into the right striatum then, after a year, the left striatum. Final results were assessed 1 year later on the basis of neurological, neuropsychological, neurophysiological, and psychiatric tests. The results obtained were compared with those of a cohort of 22 untreated patients at similar stages of the disease who were followed up in parallel. Repeated magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning with fluorine-18-labelled fluorodeoxyglucose was also done to assess metabolic activity. FINDINGS The final PET-scan assessment showed increased metabolic activity in various subnuclei of the striatum in three of five patients, contrasting with the progressive decline recorded in the two other patients in the series, as seen in patients with untreated Huntingtons disease. Small areas of even higher metabolic activity, coregistering with spherical hyposignals on MRI were also present in the same three patients, suggesting that grafts were functional. Accordingly, motor and cognitive functions were improved or maintained within the normal range, and functional benefits were seen in daily-life activities in these three patients, but not in the other two. INTERPRETATION Fetal neural allografts could be associated with functional, motor, and cognitive improvements in patients with Huntingtons disease.

DEFICIT OF SUPPRESSOR T CELLS IN ACTIVE MULTIPLE SCLEROSIS

Suppressor T cells in forty-seven patients with multiple sclerosis (MS) were studied by indirect immunofluorescence by means of monoclonal antibodies directed at T-cell subsets. Suppressor cell numbers were depressed in patients with acute exacerbation of MS and in patients with continuous progressive deterioration. In one case the T-cell anomaly was observed one week before the onset of the acute phase; it had been absent 4 months before exacerbation.

A CONTROLLED STUDY OF THERAPEUTIC PORTACAVAL SHUNT IN ALCOHOLIC CIRRHOSIS

A controlled study of therapeutic end-to-side portacaval shunt was carried out from 1968 to 1971 in 89 patients with alcoholic cirrhosis. Recurrent gastrointestinal bleeding was less common and chronic hepatic encephalopathy was more common in patients with shunts than in patients without shunts. The survival-rate was lower, but not significantly, in patients with shunts. No overall benefit of the operation could be demonstrated in cirrhotic patients with the selection criteria and the type of surgical shunt used in this study.

Detection of genomic viral RNA in nerve and muscle of patients with HCV neuropathy

Background: Hepatitis C virus (HCV)–associated neuropathy is usually associated with mixed cryoglobulinemia (MC) and vasculitis. MC may contain viral RNA, and tissues showing vasculitis may contain intracellular HCV. Local HCV replication remains to be evidenced. Objective: To delineate the spectrum of HCV-associated neuropathy and to assess the presence of HCV in nerve and muscle tissues. Methods: Thirty consecutive HCV-infected patients with peripheral neuropathy were included. Genomic and replicative strands of HCV RNA were detected in both nerve and muscle biopsy samples using distinctive reverse transcription nested PCR. Results: Neuropathy was consistent with distal axonal polyneuropathy (DPN) in 25 of 30 patients, mononeuropathy multiplex (MM) in 3 of 30, and demyelinating polyneuropathy in 2 of 30. Pain was present in 18 of 30 patients and MC in 16 of 30. Biopsy showed inflammatory vascular lesions in 26 of 30 patients (87%), including necrotizing arteritis (6/30), small-vessel vasculitis (12/30) of either the lymphocytic (9/12) or the leukocytoclastic (3/12) type, and perivascular inflammatory infiltrates (8/30). All patients with necrotizing arteritis had DPN and positive MC detection. Both pain (p < 0.03) and positive MC detection (p < 0.01) were associated with the presence of vasculitis. Positive-strand genomic HCV RNA was detected in tissues of 10 of 30 patients (muscle 9, nerve 3). In contrast, negative-strand replicative RNA was never detected. Genomic RNA was found in nerve tissue samples showing vasculitis (necrotizing arteritis 2, small-vessel lymphocytic vasculitis 1). Conclusion: Painful DPN associated with MC and neuromuscular vasculitis is the most frequent type of HCV neuropathy. The usual detection of MC and the lack of local HCV replication indicate that HCV neuropathy results from virus-triggered immune-mediated mechanisms rather than direct nerve infection and in situ replication.

Multiple-domain dissociation between impaired visual perception and preserved mental imagery in a patient with bilateral extrastriate lesions.

A brain-damaged patient is described whose pattern of performance provides insight into both the functional mechanisms and the neural structures involved in visual mental imagery. The patient became severely agnosic, alexic, achromatopsic and prosopagnosic following bilateral brain lesions in the temporo-occipital cortex. However, her mental imagery for the same visual entities that she could not perceive was perfectly preserved. This clear-cut dissociation held across all the major domains of high-level vision: object recognition, reading, colour and face processing. Our findings, together with other reports on domain-specific dissociations and functional brain imaging studies, provide evidence to support the view that visual perception and visual mental imagery are subserved by independent functional mechanisms, which do not share the same cortical implementation. In particular, our results suggest that mental imagery abilities need not be mediated by early visual cortices.

Retest effects and cognitive decline in longitudinal follow-up of patients with early HD

Objective: To assess the natural progression of cognitive impairment in Huntington’s disease (HD) and to reveal factors that may mask this progression. Background: Although numerous cross-sectional studies reported cognitive deterioration at different stages of the disease, progressive cognitive deterioration has been, up to now, difficult to demonstrate in neuropsychological longitudinal studies. Methods: The authors assessed 22 patients in early stages of HD at yearly intervals for 2 to 4 years (average, 31.2 ± 10 months), using a comprehensive neuropsychological battery based on the Core Assessment Program for Intracerebral Transplantation in Huntington’s Disease (CAPIT-HD). Results: The authors observed a significant decline in different cognitive functions over time: these involved primarily attention and executive functions but also involved language comprehension, and visuospatial immediate memory. Episodic memory impairment that was already present at the time of enrollment did not show significant decline. The authors found a significant retest effect at the second assessment in many tasks. Conclusion: Many attention and executive tasks adequately assess the progression of the disease at an early stage. For other functions, the overlapping of retest effects and disease progression may confuse the results. High interindividual and intraindividual variability seem to be hallmarks of the disease.

Inversion superiority in visual agnosia may be common to a variety of orientation polarised objects besides faces

Selective impairment in recognition of faces (prosopagnosia) resulting from certain localized cortical lesions has been advanced as an argument for a face specific brain module. The argument is claimed to be strengthened by the discovery of an inversion superiority effect in the recognition of faces by a prosopagnosic patient (Farah et al., Vis Res 1995b;35:2089-2093). The present paper reports an inversion superiority effect in the recognition of faces and shoes in a visual agnosic patient. The finding raises the possibility that several classes of orientationally polarized objects, of which shoes and faces are examples, will exhibit inversion superiority.

Selective deficit of visual size perception: two cases of hemimicropsia.

Hemimicropsia is a rare disorder of visual perception characterized by an apparent reduction of the size of objects when presented in one hemifield. We report two cases of hemimicropsia resulting from focal brain lesions. The first patient was an art teacher and could accurately depict his abnormal visual perception. He subsequently died and his brain was examined post mortem. In the second patient, micropsia was assessed by a quantified size comparison task. The size of a given object is normally perceived as constant across any spatial position. Hemimicropsia may thus be considered a limited violation of the size constancy principle. Behavioural and anatomical data are discussed in relation to the neural basis of visual object perception in humans.

All-trans retinoic acid in relapsing malignant gliomas: clinical and radiological stabilization associated with the appearance of intratumoral calcifications

Abstract(1) Purpose: To evaluate the therapeutic effect ofall-trans retinoic acid (ATRA) with and without cytosinearabinoside in relapsing malignant gliomas.(2) Patients and methods: 9 patients (8 male,1 female, age 53.9 ± 11.2) with relapsingmalignant gliomas (grade IV:6; grade III:3) were treatedby ATRA 1 to 21 months after theend of their initial treatment. ATRA was givenunceasingly during 2 to 17 months at 90mg/d. In 6 patients it was associated tocytosine arabinoside (4 g/course, 1 to 9 coursesevery 4 weeks).(3) Results: 4 non-responder patients died 2.5 to4 months after starting therapy. One patient whohad been reoperated before receiving ATRA and cytosinearabinoside (5 courses) had no sign of tumorrecurrence after 17 months of treatment. In 4responder patients (2 glioblastoma and 2 anaplastic astrocytoma)a clinical and radiological stabilization (time to progression)during 9 ± 2.5 months was observed. Thisstabilization was associated in 3 of them withthe appearance of intra tumoral calcifications visualized onrepeated CT scans and confirmed in one patientby post-mortem examination. All of them had receivedcytosine arabinoside (1 to 9 courses) with ATRA;however small calcifications were also observed in onenon-responder patient who did not receive aracytine.(4) Conclusion: These results suggest: a) a therapeuticeffect of ATRA in combination with cytosine arabinosidein patients with relapsing malignant gliomas b) thatintratumoral calcifications are related to the effects ofATRA on differentiation and/or on endothelial t-PA productionand that these effects explain the tumor progressionarrest in responder patients. The transient efficiency isprobably related to the pharmacokinetics of ATRA orto changes of cellular mechanisms that modulate thecell response to the drug and is acritical issue for this therapy.

Visually- and motor-based knowledge of letters: evidence from a pure alexic patient

We describe a patient, VSB, whose reading was impaired as a consequence of a left temporal-parietal lesion, whereas writing was relatively preserved. At variance with other pure alexic patients described in the literature, VSB claimed to have become unable to mentally visualise letters and words. Indeed, his performance on a series of tests tapping visual mental imagery for orthographic material was severely impaired. However, performance on the same tests was dramatically ameliorated by allowing VSB to trace each item with his finger. Visual mental imagery for non-orthographic items was comparatively spared. The pattern of dissociation shown by VSB between impaired visual mental imagery and relatively preserved motor-based knowledge for orthographic material lends support to the view that separate codes, respectively based on visual appearance and on motor engrams, may be used to access knowledge of the visual form of letters and words.