The cognitive spectrum in neurodegenerative Langerhans cell histiocytosis.

Clinical spectrum of cognitive troubles complicating neurodegenerative Langerhans cell histiocytosis (ND-LCH) is poorly known. The aim of this study is to evaluate cognitive functions in ND-LCH. The cognitive functions of a series of eight adult patients (7 males and 1 female; mean age 26 years IQ 25-75; range 20-33) suffering from clinical and/or radiological ND-LCH were evaluated using the following tests: (1) forward/backward digit and spatial span tasks of the WAIS-R scale and the Corsi block task, (2) the French version of the free and cued selective reminding test, (3) verbal fluency tests, (4) the Frontal Assessment Battery (FAB), (5) backward measurement of the verbal and visuospatial memories of the WAIS-R scale, (6) the Rey complex figure test, (7) the trail making tests A and B, (8) digit symbol and symbol search of the WAIS-IV scale, and (9) the Stroop test. Episodic (i.e. autobiographical or personal) memory free recall, categorical verbal fluency, phonological verbal fluency, visuospatial processing skills, attention, speed of processing, and sensitivity to interference were impaired in ND-LCH patients. In contrast, verbal and visuospatial short-term memories (i.e. immediate memories or forward span tasks) were preserved in all patients. Adult ND-LCH patients suffer from a severe but dissociated dysexecutive syndrome, mostly affecting executive strategies and relatively sparing short-term memory. Our study supports the need of assessing executive functions using comprehensive cognitive evaluation in ND-LCH patients for early diagnosis.

"Habit" gambling behaviour caused by ischemic lesions affecting the cognitive territories of the basal ganglia.

We report the case of a patient suffering from sudden apathy and pathological gambling-like behaviour after bilateral ischemic lesions involving the dorsal portion of the head of the caudate nuclei and adjacent anterior limb of the internal capsules. This is the first report of the association of an apathy and abnormal gambling behaviour following a stroke affecting sub-cortical structures. Although the location of the lesions, affecting the dorsal striatum, may explain the emergence of an apathetic state, it is, however, at first sight, not easy to explain the gambling behaviour because the patient was normal in tests evaluating sensitivity to reward, and no radiological abnormality was found in the cortical-sub-cortical system of reward. It is proposed that, for this patient, the mechanism of maladaptive gambling behaviour was the development of a routine behaviour related to the patient's cognitive inertia, a mechanism different from the changes in reward sensitivity observed after damage to the orbital ventral prefrontal-ventral striatum system or in dopamine dysregulation syndrome in Parkinson's disease.

Sleep and rhythm consequences of a genetically induced loss of serotonin.

BACKGROUND: A genetic deficiency in sepiapterin reductase leads to a combined deficit of serotonin and dopamine. The motor phenotype is characterized by a dopa-responsive fluctuating generalized dystonia-parkinsonism. The non-motor symptoms are poorly recognized. In particular, the effects of brain serotonin deficiency on sleep have not been thoroughly studied. OBJECTIVE: We examine the sleep, sleep-wake rhythms, CSF neurotransmitters, and melatonin profile in a patient with sepiapterin reductase deficiency. PATIENT: The patient was a 28-year-old man with fluctuating generalized dystonia-parkinsonism caused by sepiapterin reductase deficiency. METHODS: A sleep interview, wrist actigraphy, sleep log over 14 days, 48-h continuous sleep and core temperature monitoring, and measurement of CSF neurotransmitters and circadian serum melatonin and cortisol levels before and after treatment with 5-hydroxytryptophan (the precursor of serotonin) and levodopa were performed. RESULTS: Before treatment, the patient had mild hypersomnia with long sleep time (704 min), ultradian sleep-wake rhythm (sleep occurred every 11.8 +/- 5.3 h), organic hyperphagia, attentionlexecutive dysfunction, and no depression. The serotonin metabolism in the CSF was reduced, and the serum melatonin profile was flat, while cortisol and core temperature profiles were normal. Supplementation with 5-hydroxytryptophan, but not with levodopa, normalized serotonin metabolism in the CSF, reduced sleep time to 540 min, normalized the eating disorder and the melatonin profile, restored a circadian sleep-wake rhythm (sleep occurred every 24 +/- 1.7 h, P < 0.0001), and improved cognition. CONCLUSION: In this unique genetic paradigm, the melatonin deficiency (caused by a lack of its substrate, serotonin) may cause the ultradian sleep-wake rhythm.

"Do you remember what you did on March 13, 1985?" A case study of confabulatory hypermnesia.

We report on a patient, LM, with a Korsakoff's syndrome who showed the unusual tendency to consistently provide a confabulatory answer to episodic memory questions for which the predicted and most frequently observed response in normal subjects and in confabulators is "I don't know". LM's pattern of confabulation, which we refer to as confabulatory hypermnesia, cannot be traced back to any more basic and specific cognitive deficit and is not associated with any particularly unusual pattern of brain damage. Making reference to the Memory, Consciousness and Temporality Theory - MCTT (Dalla Barba, 2002), we propose that LM shows an expanded Temporal Consciousness - TC, which overflows the limits of time ("Do you remember what you did on March 13, 1985?") and of details ("Do you remember what you were wearing on the first day of summer in 1979?") that are usually respected in normal subjects and in confabulating patients.

Impaired orienting of attention in left unilateral neglect: a componential analysis.

Twenty-six patients suffering from damage to the right side of the brain, 19 of whom exhibited signs of left neglect, as well as 32 matched controls, ran 3 spatial cuing tasks. Patients were also tested with 2 cancellation tests, a line-bisection test, the copy of a complex drawing, and a visual extinction procedure. Results first showed correlations between extinction and cancellation tests performance on one hand, and between line bisection and copy on the other hand. Second, results demonstrated that an engagement deficit toward contralesional targets appeared to be the most striking feature of neglect, and the engagement score was correlated with the cancellation score and extinction. Most patients with neglect also presented a deficit in disengagement, a deficit of inhibition of return, and probably a deficit of alertness. Deficits in engagement and in disengagement, as well as poor scores in cancellation tests, seemed to be related with posterior cortical and subcortical lesions. Most important, even if an endogenous deficit (frequently related with a thalamic lesion) could aggravate the neglect behavior, neglect syndrome was mainly explained by a deficit of exogenous attention.

The phenomenology of endogenous orienting.

Can we build endogenous expectations about the locus of occurrence of a target without being able to describe them? Participants performed cue-target detection tasks with different proportions of valid and invalid trials, without being informed of these proportions, and demonstrated typical endogenous effects. About half were subsequently able to correctly describe the cue-target relationships ('verbalizers'). However, even non-verbalizer participants showed endogenous orienting with peripheral cues (Experiments 1 and 3), not depending solely on practice (Experiment 2). Explicit instructions did not bring about dramatic advantages in performance (Experiment 4). With central symbolic cues, only verbalizers showed reliable endogenous effects (Experiment 5). We concluded that endogenous orienting with peripheral cues can occur independently of participants developing explicit hypotheses about the cue-target relationships.

Independent effects of endogenous and exogenous spatial cueing: inhibition of return at endogenously attended target locations.

Inhibition of return (IOR) is thought to reflect a bias against returning attention to previously attended locations. According to this view, IOR should occur only if attention is withdrawn from the target location prior to target appearance. In the present study, endogenous attention and exogenous cueing were manipulated orthogonally. IOR was observed both when a target appeared at an unexpected location, and when a target appeared at the expected location. A similar pattern of results was obtained in a reanalysis of data from a study with Neglect patients. These results suggest that IOR is independent of endogenous orienting.