Aurélia Poujois

Brain plasticity in the motor network is correlated with disease progression in amyotrophic lateral sclerosis

Objective: To test the influence of functional cerebral reorganization in amyotrophic lateral sclerosis (ALS) on disease progression. Methods: Nineteen predominantly right‐handed ALS patients and 21 controls underwent clinical evaluation, functional Magnetic Resonance Imaging (fMRI), and diffusion tensor imaging. Patients were clinically re‐evaluated 1 year later and followed until death. For fMRI, subjects executed and imagined a simple hand‐motor task. Between‐group comparisons were performed, and correlations were searched with motor deficit arm Medical Research Council (MRC) score, disease progression ALS Functional Rating Scale (ALSFRS), and survival time. Results: By the MRC score, the hand strength was lowered by 12% in the ALS group predominating on the right side in accordance with an abnormal fractional anisotropy (FA) limited to the left corticospinal tract (37.3% reduction vs. controls P < 0.01). Compared to controls, patients displayed overactivations in the controlateral parietal (P < 0.004) and somatosensory (P < 0.004) cortex and in the ipsilateral parietal (P < 0.01) and somatosensory (P < 0.01) cortex to right‐hand movement. Movement imagination gave similar results while no difference occurred with left‐hand tasks. Stepwise regression analysis corrected for multiple comparisons showed that controlateral parietal activity was inversely correlated with disease progression (R2 = 0.43, P = 0.001) and ipsilateral somatosensory activations with the severity of the right‐arm deficit (R2 = 0.48, P = 0.001). Conclusions: Cortical Blood Oxygen Level Dependent (BOLD) signal changes occur in the brain of ALS patients during a simple hand‐motor task when the motor deficit is still moderate. It is correlated with the rate of disease progression suggesting that brain functional rearrangement in ALS may have prognostic implications. Hum Brain Mapp 34:2391–2401, 2013.

Bioavailable Trace Metals in Neurological Diseases

Opinion statementMedical treatment in Wilson’s disease includes chelators (d-penicillamine and trientine) or zinc salts that have to be maintain all the lifelong. This pharmacological treatment is categorised into two phases; the first being a de-coppering phase and the second a maintenance one. The best therapeutic approach remains controversial, as only a few non-controlled trials have compared these treatments. During the initial phase, progressive increase of chelators’ doses adjusted to exchangeable copper and urinary copper might help to avoid neurological deterioration. Liver transplantation is indicated in acute fulminant liver failure and decompensated cirrhosis; in cases of neurologic deterioration, it must be individually discussed. During the maintenance phase, the most important challenge is to obtain a good adherence to lifelong medical therapy. Neurodegenerative diseases that lead to a mislocalisation of iron can be caused by a culmination of localised overload (pro-oxidant siderosis) and localised deficiency (metabolic distress). A new therapeutic concept with conservative iron chelation rescues iron-overloaded neurons by scavenging labile iron and, by delivering this chelated metal to endogenous apo-transferrin, allows iron redistribution to avoid systemic loss of iron.

Implicit and explicit emotional processing in Parkinson's disease

Introduction: Our study investigated the ability of nondemented Parkinsons disease (PD) patients to explicitly identify emotional words and to show implicit sensitivity to these emotions in a task that did not require emotional processing. Methods: Twelve PD patients and 12 healthy controls, matched for age and education, performed lexical decision (LD) and emotional categorisation tasks (fear, disgust, and happiness) on the same words. Results: PD patients were specifically impaired in the explicit identification of disgust with a decreased accuracy in LD. However, a slowdown in LD latency in both PD patients and the control group suggested the persistence of emotional sensitivity to disgust. Conclusion: Despite the persistence of an automatic capture by the emotional content of disgust, PD patients may suffer from emotional deficits in recognising both the emotional and semantic components of words, resulting in blunted emotional responses.

Liver Transplantation in Wilson's Disease with Neurological Impairment: Evaluation in 4 Patients.

Background: The aim of this work is to report our early experiences about the benefits of liver transplantation (LT) in the treatment of persistent neurological symptoms in Wilsons disease (WD) patients. Methods: We describe our findings in 4 WD patients with neurological impairment or symptoms treated by LT: 2 patients had transplants due to worsening of neurological symptoms despite long-term appropriate medical treatment. The other 2 required LT because of symptoms associated with liver failure. Patients were evaluated using the modified Rankin scale and the Unified Wilsons Disease Rating Scale (UWDRS). Results: The 4 patients experienced neurological improvement after LT. The pre-LT Rankin score of the 2 patients transplanted due to neurological impairment was 4 compared to 3 and 2, respectively, post LT. The pre-LT Rankin scores of the 2 WD cases transplanted because of hepatic failure were 1 and 2, respectively, compared to 0 in both cases post LT. UWDRS score improved in 2 cases and remained stable in 1 less severely impaired case. Brain MRI abnormalities proved partially reversible in 3 patients and remained stable for 1 patient. Conclusions: These results suggest that LT could be envisaged for neurologically impaired WD patients.

Characteristics and prevalence of Wilson's disease: A 2013 observational population-based study in France

BACKGROUND AND AIMS Only a few epidemiological studies on the incidence and prevalence of Wilsons disease (WD) have been performed to date, and the results vary widely according to the reports. The aim of the study was to investigate the prevalence, ambulatory care and treatments of patients with WD in France. METHODS Among the 58 million general health scheme beneficiaries (86% of the French population), people managed for WD in 2013 were identified using hospitalisation diagnosis in 2011-2013 or specific long-term disease status with a 100% reimbursement for specific healthcare in 2013. Data were derived from the Sniiram (National Health Insurance Information System database). Prevalence by age and sex were calculated. RESULTS In 2013, 906 prevalent cases were identified, yielding a crude prevalence of 1.5 cases per 100,000; 1.65 per 100,000 in males and 1.44 per 100,000 in females. This prevalence is comparable to that reported in other population-based studies in European countries and to a study using a similar method. Almost 40% of patients were treated by D-penicillamine and 14.3% were treated by zinc acetate. Trientine, delivered on a compassionate basis, was not available in the reimbursement database. In 2013, 1.3% of patients underwent liver transplantation and 4% had already undergone liver transplantation in previous years. Fifteen per cent of patients received antidepressants, a higher rate than in general population. CONCLUSIONS This is the first French population-based epidemiological study of WD in a comprehensive population based on administrative data and constitutes an important step to understand the impact of WD and to study quality of care.

Public events and flashbulb memories in Parkinson's disease.

Public events and Flashbulb memories were investigated in 12 non-demented patients with Parkinson’s disease (PD) and 12 controls. Knowledge of public events and flashbulbs memories were assessed using a Famous Events Test (EVE 30). Contributions of semantic, episodic, as well as executive functioning and anterograde memory were examined. Results primarily showed that the performances of patients with PD were lower than these of controls in 4 tasks: free recall, specific questions, dating events and date recognition. They also had difficulties in finding the temporal order of 8 events. In contrast, the PD group benefited from events recognition themselves to the same extent as the controls. Secondly, the recall of flashbulb memories (FBM) was lower in the PD group than in the controls. Finally, correlations appeared in PD between the detailed recall of the events with the “recall” abilities of the MATTIS scale, possibly reflect an impairment in rebuilding memories. A positive correlation is also observed with the initiation score of the MATTIS (executive component), suggesting that the difficulties of rebuilding can be related to a dysfunction in accessing information because of a certain degree of frontal amnesia.

Manifestations neurologiques multiples associées à une insuffisance anté-hypophysaire

Resume Les manifestations neurologiques des insuffisances endocriniennes sont classiques mais leur association chez un meme patient est rare. Nous rapportons l’observation d’une patiente qui installa insidieusement, en relation avec une insuffisance ante-hypophysaire, un trouble neurologique associant une deterioration intellectuelle, un delire, une atteinte cerebelleuse, une myopathie et une neuropathie demyelinisante.

Wilson’s Disease

Wilson’s disease (WD) is an autosomal recessive disorder characterized by copper accumulation in many organs. WD is caused by mutations in the ATP7B gene located on chromosome 13. Copper cellular metabolism is regulated by two copper-transporting ATPases (ATP7A and ATP7B). In WD, defective ATP7B function impaired both copper incorporation to ceruloplasmin and copper release into the bile, resulting in copper accumulation in the liver. In the absence of diagnosis and treatment at this stage, WD evolves towards a systemic disease, with copper accumulation in other organs including the brain, eyes, kidneys, etc. First symptoms are usually hepatic in children and neurological in adults. WD is characterized by low serum ceruloplasmin and total copper concentrations and increased urinary copper excretion. A new tool, the relative exchangeable copper is very useful for diagnosis and family screening. Differential diagnosis of copper abnormalities are reviewed. Molecular biology confirms the diagnosis in 95% of cases. Treatment is based on diet, copper chelators or zinc salts. Liver transplantation is the treatment of acute fulminant liver failure and of decompensated cirrhosis. It remains controversial in severe neurological forms. WD has a good prognosis if treatment is initiated early and continued all the lifetime. So, follow up of these patients is very important to make sure of the observance, the efficiency and the tolerance of the treatment and to search for hepatocellular carcinoma that is a late complication of the liver disease.

Neurological presentations revealing acquired copper deficiency: diagnosis features, etiologies and evolution in seven patients

Acquired copper deficiency (ACD) is a rare condition usually diagnosed from haematological changes.

Sleep Abnormalities in Wilson’s Disease

Purpose of reviewThe aim of this article was to review the different sleep disorders associated with Wilson’s disease (WD), their mechanisms and their treatments.Recent findingsSome of these disorders such as REM sleep behavior disorder or sleepiness can appear as a prodromal phase phenomenon in WD allowing an early treatment of the disease and sometimes a resolution of the sleep disorder.SummarySleep disorders in WD are frequent combining insomnia, daytime sleepiness, restless legs syndrome (RLS), cataplexy-like episodes, and REM sleep behavior disorder (RBD). Sleep recordings confirm these disorders. Mechanisms involved in these disorders are complex associating (a) lesions of the pathways regulating sleep and wake or mood but also controlling movement, (b) iatrogenic effects of the treatments, and (3) consequences of the motor or dysautonomic or metabolic disorders.