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CADASIL with NOTCH3 S180C presenting anticipation of onset age and hallucinations.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited disease leading to strokes and vascular dementia. The average age of onset for stroke is 45 years with a range of about 30 to 70 years. We describe a Japanese CADASIL family showing S180C in the exon 4 of NOTCH3, presenting an anticipation of the onset age for stroke. MRI demonstrated a similar extent of white matter involvement in younger and older individuals, supporting the presence of anticipation. In addition, hallucinations in 71% of affected patients, and delusions in 57% were also described. Our findings in this family suggest that a specific NOTCH3 mutation was related to unique clinical features, although such correlations have seldom been encountered in CADASIL.

Adult↗

Visual hallucinations in Parkinson's disease: clues to separate origins.

Our paper discusses two experimental studies suggesting that Visual Hallucinations (VH) in Parkinson's Disease (PD) may have separate origins. The first is a prospective 8years study evaluating the appearance of VH, visual abnormalities assessed by Visual Evoked Potentials (VEPs) and REM sleep Behaviour Disorder (RBD), in 80 PD patients treated with l-Dopa and Dopaminoagonists (DA). In chronically treated, cognitively unimpaired, PD patients VH were statistically related (p=0.001) to RBD occurrence and high DA doses. Visual abnormalities were significantly reduced by l-Dopa or DA intake, and were statistically unrelated to VH. The second study involved PD patients placed in a Virtual Reality Environment, to decontextualize visual input. When motor symptoms worsened and VEP abnormalities developed patients consistently described hallucinatory dysperceptions of the virtual environment. The two studies therefore show that VH can occur in two seemingly distinct conditions, one is related to chronic treatment and to a sleep disorder frequently observed in PD, the other is probably related to a hypodopaminergic state. Our studies support a recently proposed integrative model of VH, and show that the neural circuits purported to explain VH must include the retinal dopaminergic system and the REM sleep regulatory system.

Antiparkinson Agents↗

Hallucinations after hypospadias repair.

The authors report a case of a 4-year-old child who developed hallucinations after hypospadias repair. He was brought to the emergency department the morning after outpatient surgery where the diagnosis of central anticholinergic syndrome was made. We review oxybutynin overdose and the importance of providing clear instruction to parents and caregivers about the administration of medications.

Child, Preschool↗

The A9 allele of the dopamine transporter gene increases the risk of visual hallucinations during alcohol withdrawal in alcohol-dependent women.

Previous studies have found an association between the A9 allele (nine-copy repeat) of the dopamine transporter (DAT) gene and two complications of alcohol withdrawal, namely delirium tremens (DT) and alcohol withdrawal seizures (AWS). Most of these studies only included male alcohol-dependent patients. Even those that included a small proportion of women did not look at the effect of gender. We compared the frequency of the A9 allele in 64 French Caucasian alcohol-dependent women with a history of alcohol withdrawal complications. Women carrying the A9 allele had more visual hallucinations during withdrawal than those without this allele (P = 0.03). However, women with the A9 allele were not more susceptible to DT or AWS than those without (P = 0.48 and P = 1.00, respectively). Our results suggest that the A9 allele of the DAT gene is involved in vulnerability to alcohol withdrawal complications in women, but that these complications differ from those associated with this polymorphism in alcohol-dependent men.

Adult↗

Elman topology with sigma-pi units: an application to the modeling of verbal hallucinations in schizophrenia.

The development of neural network models has greatly enhanced the comprehension of cognitive phenomena. Here, we show that models using multiplicative processing of inputs are both powerful and simple to train and understand. We believe they are valuable tools for cognitive explorations. Our model can be viewed as a subclass of networks built on sigma-pi units and we show how to derive the Kronecker product representation from the classical sigma-pi unit. We also show how the connectivity requirements of the Kronecker product can be relaxed considering statistical arguments. We use the multiplicative network to implement what we call an Elman topology, that is, a simple recurrent network (SRN) that supports aspects of language processing. As an application, we model the appearance of hallucinated voices after network damage, and show that we can reproduce results previously obtained with SRNs concerning the pathology of schizophrenia.

Brain↗

Cortical and amygdalar Lewy body burden in Parkinson's disease patients with visual hallucinations.

Visual hallucinations (VH) are among the most common non-motor complications of Parkinson's disease (PD). A few studies on their etiopathogenesis have suggested involvement of cortical and amygdalar areas. In order to investigate the possible association between extranigral Lewy Body (LB) distribution across cortical and amygdalar regions and the presence of VH in PD brain donors, we conducted a clinico-pathological comparison of 10 PD patients with VH vs 10 closely matched PD patients without VH. The LB burden was significantly higher across the amygdala and the frontal, temporal and parietal cortical areas in patients with VH. Although our results suggest significant extranigral involvement, the precise etiopathologic mechanisms responsible for the development of VH need further clarification.

Aged↗

Dichotic listening in schizophrenic patients: effects of previous vs. ongoing auditory hallucinations.

Auditory hallucinations (AH) in schizophrenia have been found to be related to both functional and structural brain abnormalities of left temporal lobe language areas. We do not know if these rain abnormalities are state or trait markers for AH. This study tested these alternatives by contrasting schizophrenic patients with ongoing AH and with a previous history of AH. A heterogeneous group of 26 schizophrenic patients was compared with a healthy control group matched for education and age. We used a verbal dichotic listening (DL) test with consonant-vowel syllables to study hemispheric asymmetry and the functional integrity of the left temporal lobe language areas. All subjects were tested during a divided and two focused attention conditions. Our data suggest that abnormal DL asymmetry for language stimuli is a state marker for AH, seen during the perception of AH. In contrast, problems of modulating DL performance by means of attentional control are a trait marker, seen both in patients with ongoing AH and only a history of AH.

Adult↗

Are auditory-verbal hallucinations associated with auditory affective processing deficits?

We investigated whether the presence of auditory-verbal hallucinations (AVH) was associated with impaired auditory affect perception. Controls, schizophrenia patients with a history of AVH (AVH) or with no history of AVH (NAVH) completed four perceptual auditory affect tasks. The tasks used either non-verbal/non-semantic or verbal/semantic stimuli. AVH patients showed significant impairments on a non-verbal task requiring the recognition of environmental sounds, this was particularly so for the affective stimuli and not the neutral valance stimuli. Thus, confirming auditory affect deficits in AVH patients. AVH patients also showed reduced right ear performance on a dichotic listening task. Conversely, both patient groups showed impairments on auditory affect tasks that used verbal/semantic stimuli; as these tasks require proficient semantic processing we speculated that significant semantic impairments in schizophrenia masked the additional auditory affect deficits present in the AVH group. The overall results support the notion that patients with AVH have increased liability for auditory affect perception deficits.

Adult↗

Quantitative EEG and low resolution electromagnetic tomography (LORETA) imaging of patients with persistent auditory hallucinations.

Electrophysiological studies have demonstrated gamma and beta frequency oscillations in response to auditory stimuli. The purpose of this study was to test whether auditory hallucinations (AH) in schizophrenia patients reflect abnormalities in gamma and beta frequency oscillations and to investigate source generators of these abnormalities. This theory was tested using quantitative electroencephalography (qEEG) and low-resolution electromagnetic tomography (LORETA) source imaging. Twenty-five schizophrenia patients with treatment refractory AH, lasting for at least 2 years, and 23 schizophrenia patients with non-AH (N-AH) in the past 2 years were recruited for the study. Spectral analysis of the qEEG and source imaging of frequency bands of artifact-free 30 s epochs were examined during rest. AH patients showed significantly increased beta 1 and beta 2 frequency amplitude compared with N-AH patients. Gamma and beta (2 and 3) frequencies were significantly correlated in AH but not in N-AH patients. Source imaging revealed significantly increased beta (1 and 2) activity in the left inferior parietal lobule and the left medial frontal gyrus in AH versus N-AH patients. These results imply that AH is reflecting increased beta frequency oscillations with neural generators localized in speech-related areas.

Adult↗

The management of other psychiatric states. Hallucinations, delusions, and other disturbances.

The behavioral disturbances that are most common in Alzheimer's disease are not those directly associated with the core characteristics of the disease; however, they often cause the most difficult problems of management. These disturbances include agitation, hallucinations, and delusions. This article reviews their prevalence, etiology, differential diagnosis, and management.

Aged↗

Contralateral induction by frequency spectrum in hallucinating schizophrenics.

Seventeen schizophrenic patients who had all experienced auditory hallucinations were compared with 14 subjects of a reference group on a test of contralateral induction. Contralateral induction means that a sound is illusively heard as coming from a location where it belongs according to its spectral content. The phenomenon is connected with a simultaneous relative elimination of masking. The schizophrenic subjects deviated from the reference group in several aspects. Some of them did not hear the sound being induced to the contralateral side, which it was for all reference subjects. Another subgroup of the schizophrenics noticed the induction unusually early with a prolonged experience of it, and finally some of them experienced the induction now and then. The aberrations were interpreted as rigidity of adaptation on the one hand and as effects of an enhanced sensitivity on the other. Discontinuity, meaning that the fluency in mental processing is broken, was interpreted to cause the ratings of the third group of schizophrenics in this sample, who heard the contralateral induction now and then. These phenomena are clearly reminiscent of descriptions in research reports, and witnessed by clinical experience of the schizophrenic disturbance. The results represent another example of discontinuous neurophysiological functions between neural systems and between individuals suffering from schizophrenia.

Adult↗

Case study: trauma-related hallucinations.

Proper differential diagnosis of psychiatric disorders with psychotic symptoms is imperative, as the treatment implications of the various conditions are quite different. A case study of a 5-year-old abused child with posttraumatic stress disorder is presented to illustrate some of the characteristic features of psychotic symptoms in traumatized children. Literature reviewed suggests that trauma-related hallucinations frequently contain content which is related to children's life experiences, are exacerbated by "triggers" and safety concerns, resolve with psychotherapy or psychosocial interventions, and are resistant to standard neuroleptic treatments. They are also associated with unique clinical, familial, developmental, and psychobiological correlates, and they require multifaceted treatment interventions.

Child↗

Inhibition in schizophrenia: association with auditory hallucinations.

The study investigated whether auditory hallucinations (AH) in schizophrenia are linked to a deficit in inhibition. Two tasks assessing the intentional suppression of cognitive events-the Hayling Sentence Completion Test (HSCT) [Neuropsychologia 34 (1996) 263] and the Inhibition of Currently Irrelevant Memories Task (ICIM) [Nature Neuroscience 2 (1999) 677]-were administered to 42 patients with schizophrenia and 24 normal controls. Presence and severity of symptoms in the patient group were examined using the Positive and Negative Syndrome Scale (PANSS). Patients performed significantly worse on the measures of inhibition compared to controls. More importantly, among patients, significant positive correlations were obtained between an index of AH severity (defined as an increase in frequency of AH on PANSS) and the number of type A errors on the HSCT and errors in the last three runs of the ICIM. An increase in AH severity was, therefore, associated with increasingly impaired control of intentional inhibition. Furthermore, no significant correlations were found between these indices of inhibition and either negative, general or positive symptoms (excluding AH scores).

Adult↗

On the non-significance of internal versus external auditory hallucinations.

Traditionally, auditory hallucinations (AHs) heard outside the head have been regarded as more pathological than those heard inside, partly on the basis that internal AHs are conceptually closer to normal thinking than external AHs. Our data show that many patients hear AHs both internally and externally, and there were very few associations between location and demographic and clinical characteristics of the patients or with other characteristics of the AHs themselves. There was evidence that AHs heard internally were associated with better insight than those heard externally. Of those patients whose AHs included commands, greater proportions of those who heard them externally said they could resist than those who heard them internally or in both locations. There appears to be no consistent differential impact and effect of internal and external AHs, and there was no support for the historical view that internal AHs are more benign.

Adolescent↗

Inverse correlation between hallucinations and serum prolactin in patients with non-affective psychoses.

Serum prolactin (PRL) was correlated with clinical symptomatology in 17 drug-free patients suffering from non-affective psychoses. A clear-cut negative correlation was found between the Comprehensive Psychiatric Rating Scale (CPRS) items assessing hallucinations and serum PRL levels (r=-6.14, P=0.009). No correlation was observed between clinical measures (total CPRS score, schizophrenia subscale score or depression and anxiety subscale score) and serum PRL.

Adolescent↗

Hallucinations: synchronisation of thalamocortical gamma oscillations underconstrained by sensory input.

What we perceive is the product of an intrinsic process and not part of external physical reality. This notion is consistent with the philosophical position of transcendental idealism but also agrees with physiological findings on the thalamocortical system. gamma-Frequency rhythms of discharge activity from thalamic and cortical neurons are facilitated by cholinergic arousal and resonate in thalamocortical networks, thereby transiently forming assemblies of coherent gamma oscillations under constraints of sensory input and prefrontal attentional mechanisms. Perception and conscious experience may be based on such assemblies and sensory input to thalamic nuclei plays merely a constraining role in their formation. In schizophrenia, the ability of sensory input to modulate self-organisation of thalamocortical gamma activity may be generally reduced. If during arousal thalamocortical self-organisation is underconstrained by sensory input, then attentional mechanisms alone may determine the content of perception and hallucinations may arise.

Cerebral Cortex↗

Episodic nocturnal wandering and complex visual hallucination. A case with long-term follow-up.

Episodic nocturnal wandering is rare and thought to be an atypical form of nocturnal epilepsy which is responsive to anticonvulsant therapy. We report a case of adult-onset episodic sleep-walking and daytime complex visual hallucination. Ambulatory EEG recordings suggested that both events were ictal phenomenon. Interictal sphenoidal EEG and SPECT studies revealed an epileptogenic focus in the left anterior temporal lobe. During the nocturnal wanderings, the patient had bizarre but non-violent behaviour, and was at risk of minor or severe injury to himself. Both events were completely controlled by carbamazepine for a follow-up period of 8 years. The present case further supports the notion that episodic nocturnal wandering represents an unusual type of nocturnal complex partial seizures.

Adult↗