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Huntington's disease is a rare, severe, and inherited neurodegenerative disorder that affects young adults. To date, there is no treatment to stop its progression. The primary atrophy of the striatum in HD, is limited in space and centrally focalised in the brain and thus constitutes a good candidate for graft. Therefore, transplantation of foetal cells from the ganglionic eminence, the germinal zone of the striatum, has the potential to restore disrupted fronto-cortical circuits and corresponding clinical functions. The international Multicentric intracerebral Grafting in Huntington's disease trial was not as successful as two pilot trials (Créteil and London) which showed promising results in the 2000s, displaying stabilisation/recovery of symptoms in some patients. A point-by-point comparison of the differences between MIG-HD and the pilot trial from Créteil in which similar data are available provides lessons on the grafting procedure and allows for strategic thinking before embarking on future trials. MIG-HD demonstrated the existence of intracerebral alloimmunisation leading to acute or chronic graft rejection into the brain and showed the limitations of surgical standardisation and immunosuppression. It has also improved the safety of the procedure and provided guidance for the follow-up of future patients. Indeed, even if disease modifiers treatments are currently the focus of intense research, they may not stop or slow the progression of the disease sufficiently, or even be administered in all patients, to prevent brain atrophy in all cases. Although disease-modifying therapies are currently the subject of intense research, they may not stop or slow disease progression sufficiently, or may not be given to all patients to prevent brain atrophy. A combination with intracerebral transplantation to repair the damaged structures may thus prove beneficial. Altogether, pursuing research in intracerebral transplantation remains necessary.

Neurological disorders associated with SARS-CoV-2 infection represent a clinical challenge because they encompass a broad neurological spectrum and may occur before the diagnosis of COVID-19.

La malattia di Huntington è una malattia neurologica evolutiva, autosomica dominante e a insorgenza tardiva, caratterizzata clinicamente dalla comparsa di disturbi motori, psichiatrici e cognitivi. Essa è legata a un’espansione di trinucleotidi CAG nel gene HTT, situato sul cromosoma 4 e codificante la proteina huntingtina. Sul piano anatomopatologico, si constata una degenerazione neuronale che colpisce, in primo luogo, lo striato. La malattia, di cui non si può prevedere l’età di insorgenza, evolve verso una perdita di autonomia motoria e cognitiva e l’aumento del rischio di complicanze letali, dopo un progressivo aggravamento dei sintomi per 10-30 anni. I capisaldi della gestione dei pazienti comportano una consulenza genetica alle famiglie, delle misure efficaci di sostegno sociale e psicologico e l’avvio di trattamenti sintomatici farmacologici e rieducativi volti a migliorare la qualità della vita. Non esiste, attualmente, alcun trattamento curativo della malattia, ma la ricerca è attiva e, ormai, particolarmente focalizzata sulla terapia genica, non trascurando gli altri assi derivanti dalla conoscenza accumulata sulle disfunzioni indotte dalla huntingtina mutata, sulle funzioni della huntingtina selvatica nonché sulle terapie cellulari.

Evidence-based medicine is a difficult goal to achieve in rare diseases where randomized controlled trials are lacking. This report provides guidelines that capitalize on both the literature and expertise of the French National Huntington Disease Reference Centre to optimalize pharmacological therapeutic interventions for Huntington's disease (HD).

Huntington's disease is currently incurable, but cell therapy is seen as a promising alternative treatment. We analyze the safety and efficacy of the intrastriatal transplantation of human fetal neuroblasts from ganglionic eminences in patients with Huntington's disease. A few rare surgical incidents were reported, but the main difficulty associated with this therapeutic approach is the occurrence of recipient alloimmunization against the graft and the lack of availability, standardization and quality control for the fetus-derived products required for cell therapy. Some patients showed sustained cognitive improvement over periods of more than six years, and motor improvements for more than four years. Grafting outcomes are variable even within individual transplantation centers. The reasons for this variability are poorly understood, highlighting the need for further research in this specific area. With the perspective of additional trials in the future, we review here the development of human pluripotent stem cell-derived cell therapy products for HD, and their advantages and disadvantages with respect to fetal cells.

The somatotropic axis (growth hormone GH and insulinlike growth factor I IGFI) play a role in the cognitive deficits seen with aging, GH deficiency, and neurodegenerative disorders such as Alzheimer disease. We recently reported elevations in basal plasma GH and IGFI levels in patients with Huntington disease (HD). Here, our objective was to determine whether somatotropic axis abnormalities predicted cognitive dysfunction in HD.

To assess the natural progression of cognitive impairment in Huntington’s disease (HD) and to reveal factors that may mask this progression.

Huntington's disease (HD) is an autosomal dominant genetic disease with devastating clinical effects on cognitive, psychological, and motor functions. These clinical symptoms primarily relate to the progressive loss of medium-spiny GABA-ergic neurons of the striatum. There is no known treatment to date. Several neurotrophic factors have, however, demonstrated the capacity to protect striatal neurons in various experimental models of HD. This includes the ciliary neurotrophic factor (CNTF), the substance examined in this protocol. An ex vivo gene therapy approach based on encapsulated genetically modified BHK cells will be used for the continuous and long-term intracerebral delivery of CNTF. A device, containing up to 106 human CNTF-producing BHK cells surrounded by a semipermeable membrane, will be implanted into the right lateral ventricle of 6 patients. Capsules releasing 0.15-0.5 μg CNTF/day will be used. In this phase I study, the principal goal will be the evaluation of the safety and tolerability of the procedure. As a secondary goal, HD symptoms will be analyzed using a large battery of neuropsychological, motor, neurological, and neurophysiological tests and the striatal pathology monitored using MRI and PET-scan imaging. It is expected that the gene therapy approach described in this protocol will mitigate the side effects associated with the peripheral administration of recombinant hCNTF and allow a well-tolerated, continuous intracerebroventricular delivery of the neuroprotective factor.

A few neuropsychological studies have suggested the existence of bilateral hemispheric representations for the proximal parts of the limbs in humans. We report the case of a patient who presented with a callosal disconnection syndrome, which at a later stage of disease became restricted to left agraphia, left agraphesthesia and left auditory extinction. The anomic character of the agraphesthesia was demonstrated. Tactile naming was normal, which allows us to conclude that separate callosal pathways related to the left language areas transmit information for graphesthesia and tactile naming. Agraphia and agraphesthesia were not observed when the proximal part of the left upper limb was utilized. These observations support the conclusion that writing and graphesthesia with the proximal part of the limb can be mediated by the ipsilateral cortex.

This study describes issues related to the safety and tolerability of fetal striatal neural allografts as assessed in five patients with Huntington's disease. Huntington's disease (HD) is characterized by motor, cognitive, and behavioral disturbances. The latter include psychological disturbances and, as a consequence, we took particular care to analyze behavioral changes, in addition to the usual “safety” follow-up. We conducted multidisciplinary follow-up at least 2 years before and 1 year after grafting. Psychological care extended to close relatives. The grafting procedure itself was altogether safe and uneventful, and there were no apparent clinical deleterious effects for 1 year. The immunosuppressive treatment, however, was complicated by various problems (irregular compliance, errors of handling, side effects). Direct psychological consequences of the transplantation procedure were rare and not worrisome, although mood alteration requiring treatment was observed in one patient. Indirectly, however, the procedure required patients and relatives to accept constraints that tended to complicate familial situations already marred by aggressivity and depression. All patients and close relatives expressed major expectations, in spite of our strong and repeated cautioning. It is clearly important to be aware of these particular conditions since they may eventually translate into psychological difficulties in coping with the long-term clinical outcome of the procedure, if not beneficial. Despite an overall good tolerance, therefore, this follow-up calls for caution regarding the involvement of HD patients in experimental surgical protocols.

To investigate whether tactile extinction alters the cortical somatosensory activations induced by hand vibration.

Unilateral neglect-the inability to pay attention to events occurring on one side of space-usually occurs for left-side events after focal right-hemisphere damage. We report a 73-year-old woman with probable AD and no evidence of focal brain lesions who showed signs of right-side neglect and extinction. Neglect was more severe after 1 year. Neuroimaging techniques demonstrated an asymmetry of cortical involvement, with cortical atrophy and hypoperfusion predominant in the left posterior regions. Unilateral neglect should be assessed systematically in AD.