Pulvinar quantitative susceptibility mapping predicts visual hallucinations post-deep brain stimulation in Parkinson's disease.

PURPOSE: We have reported the relationship between low pulvinar nuclei (PN) intensity in susceptibility-weighted imaging and the appearance of visual hallucinations and cognitive function. The aim of the study was to examine the changes in the quantitative susceptibility mapping (QSM) in patients with Parkinson's disease (PD) who underwent deep brain stimulation (DBS) and verify whether the PN susceptibility value (SV) on QSM can predict visual hallucination and cognitive changes after DBS. METHODS: This study examined 24 patients with PD who underwent DBS along with QSM imaging on magnetic resonance imaging (MRI). All MRIs were performed within 3 months before surgery. The PN SV was further assessed based on the QSM. Then, associations were examined among cognitive changes, hallucination, and PN SV. The cognitive function of the patient was compared immediately before surgery and at 1 year postoperatively. RESULTS: Visual hallucinations were observed in seven patients during the follow-up period. The PN SV was ≥0.045 ppm in nine patients with PD, and six of them had visual hallucinations, whereas only one of 15 patients with PD with SV of <0.045 ppm had visual hallucinations (Fisher's exact test, p = .0037). CONCLUSIONS: The SV of >0.045 ppm at the PN in QSM in patients with PD may provide useful information suggesting visual hallucination and cognitive deterioration after DBS treatment.

Optic radiation atrophy in Lewy body disease with visual hallucination on phase difference enhanced magnetic resonance images.

Visual hallucinations (VH) occur commonly in Lewy body disease (LBD), including Parkinson's disease (PD), PD with dementia, and dementia with Lewy bodies. We aimed to use phase difference enhanced imaging (PADRE) to assess structural abnormalities of optic radiation (OR) in patients with Lewy body disease (LBD) concomitant with VH. Firstly, two radiologists reviewed the OR appearances in healthy subjects (HS) on PADRE. Next, based on the OR abnormalities, two reviewers assessed the PADRE images from 18 HS and 38 and 110 patients with LBD, with and without VH, respectively, in a blinded manner. Finally, all patients with LBD without VH were eventually followed up for at least 5 years after magnetic resonance imaging to determine the appearance of VH. The radiologists identified three layers, namely external sagittal stratum, internal sagittal stratum, and tapetum, in OR on the PADRE in HS. Moreover, they were able to consensually define the OR as abnormal when the layers were obscured and the disappearance of the cranial side. The sensitivity/specificity of abnormal OR for each case was 68%/81% (LBD with VH vs. LBD without VH). Furthermore, VH appeared in 12 of the 21 (57%) patients with LBD and abnormal OR during the follow-up period. However, no patients without abnormal OR reported VH. Patients with LBD and VH demonstrated the abnormal OR. This, in turn, might be a useful marker to distinguish the patients with VH from those without VH and HS. Moreover, abnormal OR on PADRE may precede the appearance of VH in LBD.

Neurological Soft Signs Predict Auditory Verbal Hallucinations in Patients With Schizophrenia.

Neurological soft signs (NSS) are well documented in individuals with schizophrenia (SZ), yet so far, the relationship between NSS and specific symptom expression is unclear. We studied 76 SZ patients using magnetic resonance imaging (MRI) to determine associations between NSS, positive symptoms, gray matter volume (GMV), and neural activity at rest. SZ patients were hypothesis-driven stratified according to the presence or absence of auditory verbal hallucinations (AVH; n = 34 without vs 42 with AVH) according to the Brief Psychiatric Rating Scale. Structural MRI data were analyzed using voxel-based morphometry, whereas intrinsic neural activity was investigated using regional homogeneity (ReHo) measures. Using ANCOVA, AVH patients showed significantly higher NSS in motor and integrative functions (IF) compared with non-hallucinating (nAVH) patients. Partial correlation revealed that NSS IF were positively associated with AVH symptom severity in AVH patients. Such associations were not confirmed for delusions. In region-of-interest ANCOVAs comprising the left middle and superior temporal gyri, right paracentral lobule, and right inferior parietal lobule (IPL) structure and function, significant differences between AVH and nAVH subgroups were not detected. In a binary logistic regression model, IF scores and right IPL ReHo were significant predictors of AVH. These data suggest significant interrelationships between sensorimotor integration abilities, brain structure and function, and AVH symptom expression.

Alice in Wonderland syndrome: "Who in the world am I?" / Síndrome de Alice no País das Maravilhas: "Quem sou eu no mundo?"

ABSTRACT Alice in Wonderland syndrome (AIWS) is a paroxysmal, perceptual, visual and somesthetic disorder that can be found in patients with migraine, epilepsy, cerebrovascular disease or infections. The condition is relatively rare and unique in its hallucinatory characteristics. Objective: To discuss the potential pathways involved in AIWS. Interest in this subject arose from a patient seen at our service, in which dysmetropsia of body image was reported by the patient, when she saw it in her son. Methods: We reviewed and discussed the medical literature on reported patients with AIWS, possible anatomical pathways involved and functional imaging studies. Results: A complex neural network including the right temporoparietal junction, secondary somatosensory cortex, premotor cortex, right posterior insula, and primary and extrastriate visual cortical regions seem to be involved in AIWS to varying degrees. Conclusions: AIWS is a very complex condition that typically has been described as isolated cases or series of cases.

RESUMO Síndrome de Alice no País das Maravilhas (SAPM) é uma condição paroxística visual perceptiva e somestésica que pode ser encontrada em pacientes com enxaqueca, epilepsia, doença cerebrovascular ou infecções. A condição é relativamente rara e tem características alucinatórias peculiares. Objetivo: Discutir as potenciais vias envolvidas na SAPM. O interesse pelo assunto surgiu com um caso de nosso serviço, onde a distropsia da imagem corporal foi relatada pela paciente, que via isto em seu filho. Métodos: Os autores revisaram e discutiram a literatura médica de casos relatados de SAPM, possíveis vias anatômicas envolvidas e estudos de imagem funcional. Resultados: Uma complexa rede neural incluindo junção temporoparietal direita, córtex somatossensitivo secundário, córtex pré-motor, região posterior da ínsula direita, e regiões do córtex visual primário e extra-estriatal têm diferentes graus de envolvimento na SAPM. Conclusão: SAPM é uma condição complexa que tipicamente foi descrita apenas com casos isolados ou séries de casos.

Functional imaging localization of complex organic hallucinations.

Background: fMRI of mental phenomena is quite difficult to perform because lack of patient's cooperation or because the symptoms are stable. In some exceptional cases, however, fMRI and DTI are capable to provide insights on the anatomy of organic hallucinations. Methods: In this report we describe a 14-year-old boy with a left fronto-dorsal tumor who experienced chronic complex brief, frequent and repetitive complex visual and auditory hallucinations. His clinical picture included multiple and severe social and mood problems. During a presurgical fMRI mapping the patient complained of having the visual and auditory hallucinations. A block-design FMRI paradigm was obtained from the event timecourse. Deterministic DTI of the brain was obtained seeding the lesion as ROI. The patient underwent surgery and electrocorticography of the lesional area. Results: The fMRI of the hallucinations showed activation in the left inferior frontal gyrus (IFG) and the peri-lesional area. The tractography of the tumor revealed structural aberrant connectivity to occipital and temporal areas in addition to the expected connectivity with the IFG via the aslant fasciculus and homotopic contralateral areas. Intraoperative EEG demonstrated epileptic discharges in the tumor and neighboring areas. After resection, the patient's hallucinations stopped completely. He regained his normal social life and recover his normal mood. He remained asymptomatic for 90 days. Afterwards, hallucinations reappeared but with less intensity. Conclusions: To our knowledge, this is the first reported case of combined functional and structural connectivity imaging demonstrating brain regions participating in a network involved in the generation of complex auditory and visual hallucinations.

VEGFA GENE variation influences hallucinations and frontotemporal morphology in psychotic disorders: a B-SNIP study.

Vascular endothelial growth factor A (VEGFA) dysfunction may contribute to a number of pathological processes that characterize psychotic disorders. However, the influence of VEGFA gene variants on clinical and neuroimaging phenotypes in psychotic disorders has yet to be shown. In the present study, we examined whether different VEGFA gene variants influence psychosis risk, symptom severity, cognition, and brain volume. The study group included 480 probands (Bipolar I disorder with psychosis, n = 205; Schizoaffective disorder, n = 112; Schizophrenia, n = 163) and 126 healthy controls that were recruited across six sites in the B-SNIP consortium. VEGFA variants identified for analysis (rs699947, rs833070, and rs2146323) were quantified via SNP chip array. We assessed symptoms and cognition using standardized clinical and neuropsychological batteries. The dorsolateral prefrontal cortex (DLPFC), medial temporal lobe, and hippocampal volumes were quantified using FreeSurfer. In our sample, VEGFA rs2146323 A- carriers showed reduced odds of being a proband (p = 0.037, OR = 0.65, 95% CI = 0.43-0.98) compared to noncarriers, but not for rs699947 or rs833070. In probands, rs2146323 A- carriers demonstrated fewer hallucinations (p = 0.035, Cohen's d = 0.194), as well as significantly greater DLPFC (p < 0.05, Cohen's d = -0.21) and parahippocampal volumes (p < 0.01, Cohen's d = -0.27). No clinical or neuroimaging associations were identified for rs699947 or rs833070. In general, we found that the three SNPs exhibited several significant negative relationships between psychosis symptoms and brain structure. In the probands and control groups, positive relationships were identified between several cognitive and brain volume measures. The findings suggest VEGFA effects in the DLPFC and hippocampus found in animals may also extend to humans. VEGFA variations may have important implications in identifying dimensional moderators of function that could be targeted through VEGFA-mediated interventions.

Superior temporal metabolic changes related to auditory hallucinations: a (31)P-MR spectroscopy study in antipsychotic-free schizophrenia patients.

Structural deficits in the superior temporal cortex and transverse temporal gyri appear to be related to auditory hallucinations in schizophrenia, which are a key symptom of this disorder. However, the cellular and neurochemical underpinnings are poorly understood and hardly studied in vivo. We used (31)P-MRS (magnetic resonance spectroscopy) with chemical shift imaging to assess the association between left superior temporal cortex metabolism and severity of auditory hallucinations in 29 schizophrenia patients off antipsychotics. Hallucinations scores derived from the Scale for the Assessment of Positive Symptoms showed significant positive correlations with both measures of phospholipids (phosphomonoesters and phosphodiesters), and energy (inorganic phosphate and phosphocreatine, but not adenosine tri-phosphate) metabolism in left superior temporal gyrus/Heschl gyrus voxels. There was no correlation of metabolites in these regions with formal thought disorder, a symptom also linked to superior temporal pathology, thus suggesting symptom specificity. Our findings provide a link between established structural deficits and neurochemical pathology related to membrane pathology and markers of general metabolic turnover.

Psychosis revealing familial idiopathic basal ganglia calcification.

We describe the case of a 39-year-old woman presenting with auditory hallucinations and delusions responsive to antipsychotic drugs. Computerized tomography scans revealed basal ganglia calcifications in the proband and in her two asymptomatic parents. Extensive etiological clinicobiological assessment allowed us to exclude known causes of brain calcifications and diagnose familial idiopathic basal ganglia calcification (IBGC). Neurological symptoms associated with psychiatric symptoms are common in IBGC. Nevertheless, purely psychiatric presentations, as demonstrated by the present case, are possible. However, a fortuitous association between asymptomatic IBGC and schizophrenia cannot be ruled out. Only brain imaging, followed by an extensive etiological assessment, allows for diagnosis of this rare disorder.

Transient and spontaneously-remitting complex hallucinations in a patient with melanoma and brain metastases.

BACKGROUND: Neuropsychiatric sequelae are common in primary and secondary brain tumors, with symptoms varying as a function of tumor type, location, and size. OBJECTIVE: The author presents a case of a 49-year-old woman with melanoma metastatic to the brain, in an effort to link lesions and complex olfactory and visual hallucinations. METHOD: The patient's history and clinical diagnostic procedures are presented. RESULTS: A computerized tomographic scan showed lesions in the right parietal lobe, bilateral ring enhancing lesions, an enhancing lesion in the frontal lobes, and another lesion in the left temporal lobe. DISCUSSION: The author discusses possible causal connections among lesions found and various complex symptoms.

Value of (99m)Tc-ECD SPET for the diagnosis of dementia with Lewy bodies.

Despite improved diagnostic accuracy, differentiation of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) on the basis of clinical findings remains problematic. The purpose of this retrospective study was to evaluate the utility of technetium-99m ethyl cysteinate dimer (ECD) single-photon emission tomography (SPET) as a potential tool for the diagnosis of DLB and discrimination from AD. Cerebral perfusion patterns detected by (99m)Tc-ECD SPET were compared in patients presenting with a probable diagnosis of DLB ( n=34) or AD ( n=28). Tracer distribution was quantified using the region of interest technique in eight symmetrical paired zones and expressed as a perfusion index (ratio of mean uptake in a brain region to that in the cerebellum). Comparison of findings in the DLB and AD groups demonstrated significant differences in mean perfusion indexes in the right occipital region ( P=0.004), left occipital region ( P=0.005) and left medial temporal region ( P=0.013). Mean perfusion indexes in the right and left occipital regions were lower in DLB than in AD patients. Conversely, the mean perfusion index in the left medial temporal region was lower in AD than in DLB patients. DLB was correctly identified in 22 patients (sensitivity, 65%) while AD was correctly identified in 20 patients (specificity, 71%). In the DLB group, right and left occipital perfusion indexes were 0.95 or more in all eight non-hallucinating patients, and bilateral occipital hypoperfusion was observed in 15 of the 26 patients with visual hallucinations (57.7%). To our knowledge, this is the first study in which (99m)Tc-ECD SPET has been used exclusively for the diagnosis of DLB. The results suggest that brain perfusion scintigraphy could be helpful in distinguishing DLB from AD if diagnosis based on clinical criteria alone is difficult. The findings also support a link between visual hallucinations and structural/functional changes in the occipital region in DLB patients.

Tc-99m ethylcysteinate dimer brain SPECT perfusion imaging in ictal nonepileptic visual hallucinations.

PURPOSE: Visual hallucinations can occur within the central nervous system and may be associated with a lesion anywhere in the visual pathway. The purpose of this study was to assess "ictal" regional cerebral blood flow with Tc-99m ethylcysteinate dimer (ECD) SPECT in patients having acute hallucinations, and to compare the findings to the "interictal" state. METHODS: A prospective study was performed to evaluate patients admitted to the neurology department with nonpsychiatric and nonepileptic visual hallucinations. The nine patients included in the study underwent thorough neurologic and psychiatric evaluations. A computed tomographic (CT) scan was performed when each patient was admitted, and electroencephalographic (EEG) recordings were made during their hallucinations. All patients underwent a brain SPECT while having acute hallucinations (ictal SPECT), and a follow-up scan was obtained 2 to 3 weeks later. RESULTS: All patients had normal ictal EEG findings during the hallucinations. Seven of nine patients had increased perfusion on the SPECT studies in one or more regions, with a mean lesion-to-contralateral ratio of 2.1 (range, 1.5 to 2.7). Three of the seven patients had findings consistent with a cerebrovascular accident. After treatment, the hallucinations disappeared in two patients and the motor deficit improved dramatically. The follow-up SPECT study showed significant improvement in all patients 1 week later. Charles Bonnet syndrome, frontal lobe dementia, and Anton syndrome were diagnosed in three other patients, and the last one had no identifiable background disease, all with normal findings of EEG, CT, and magnetic resonance examinations. They all responded readily to carbamazepine therapy, and the follow-up SPECT study showed resolution of the findings. Two of nine patients showed posterior cortical hypoperfusion, and eventually Lewy body disease was diagnosed. The SPECT showed no evidence of regional hyperperfusion. CONCLUSIONS: This prospective preliminary study suggests that brain imaging using SPECT may be useful in identifying the mechanisms and evolution of blood flow abnormalities in certain subgroups of patients who have visual hallucinations and may assist in the selection of specific therapy.