Casting shadows of perception: An exploration of visual hallucinations.

ABSTRACT: Hallucinations can be caused by biological, psychological, neurological, ophthalmological, and environmental factors. This article discusses a selection of the various conditions that can present with visual disturbances and hallucinations including schizophrenia, HIV, neurosyphilis, hyperammonemia, migraine, substance use, brain tumors, sleep disturbances, thyroid disorders, delirium, ophthalmologic conditions, and Lewy body dementia, providing an overview of the differential diagnosis of visual hallucinations. The mechanisms by which these conditions can lead to hallucinations are also discussed, and insight into the recommended medical workup for each is provided.

Peduncular hallucinosis associated with pontine hemorrhage in an adult patient.

Peduncular hallucinosis refers to a rare neurophychiatric disorder presenting with vivid visual hallucinations, disturbances of sleep, and oculomotor dysfunction. It is typically caused by mesencephalic lesions. Nonetheless, a few cases have also been reported, in which the same syndrome was associated with thalamic and pontine lesions. We report the case of a 63-year-old male patient presenting to the Emergency Department of our hospital with irritability, gait difficulty, and diplopia of sudden onset two hours ago. Neurological examination revealed dysarthria, right facial palsy, bilateral gaze palsy, dysmetria of his left extremities, left-sided hemihypaethesia and extensory plantar response on the left. Brain computerized tomography (CT) showed a hemorrhagic lesion on the right lateral side of the pons. During his hospitalization at the Department of Neurology, he developed visual hallucinations, confusion, disorientation, insomnia, and strong emotional response. An extensive laboratory screening was performed and showed no abnormal findings. Suspecting peduncular hallucinosis due to the brainstem lesion, treatment with quetiapine and melatonin was administered to the patient and symptoms resolved completely within days. Subsequently, gradual neurological clinical improvement was also noted and two weeks after his admission, a repeated brain CT and a brain magnetic resonance imaging (MRI) showed partial absorption of the brainstem hemorrhage. The patient underwent rehabilitation for two months, showing further clinical improvement, and treatment with quetiapine and melatonin was discontinued without any further episodes being noted. A repeated brain MRI was performed two months after his admission to our hospital and showed no hemorrhage, but a mixed signal intensity core and a hypointense hemosiderin rim at the location of the absorbed hemorrhagic lesion, compatible with pontine carvenoma. Peduncular hallucinosis is most commonly associated with ischemic lesions of the posterior brain blood circulation, but different lesions have been reported, like vasospasm, brain tumors, encephalitis, hemorrhage associated with vascular malformations, such as a carvenoma, as seen in our case, representing a very rare form of peduncular hallucinosis.

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.

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.

Risk Factors and Pathological Substrates Associated with Agitation/Aggression in Alzheimer's Disease: A Preliminary Study using NACC Data.

BACKGROUND: Neuropsychiatric symptoms are common manifestations of Alzheimer's disease (AD). A number of studies have targeted psychosis, i.e., hallucinations and delusions in AD, but few have assessed agitation/aggression in AD. OBJECTIVE: To investigate the risk factors and pathological substrates associated with presence [A(+)] and absence [A(-)] of agitation/aggression (A) in autopsy-confirmed AD. METHODS: Data was collected from the UDS data as of 2015 on the NACC database. Patients were stratified as intermediate (IAD) or high (HAD) pathological load of AD. Clinical diagnoses were not considered; additional pathological diagnoses were treated as variables. Analysis of data did not include a control group or corrections for multiple comparisons. RESULTS: 1,716 patients met the eligibility criteria; 31.2% of the IAD and 47.8% of the HAD patients were A(+), indicating an association with severity of pathology (p = 0.001). Risk factors for A(+) included: age at initial visit, age at death, years of education, smoking (in females), recent cardiac events (in males), and clinical history of traumatic brain injury (TBI) (in males). A history of hypertension was not related to A(+). In terms of comorbidity, clinical diagnosis of Lewy body dementia syndrome was associated with A(+) but the association was not confirmed when pathological diagnosis based on demonstration of Lewy bodies was used as the criterion. The additional presence of phosphorylated TDP-43, but not tau pathologies, was associated with A(+)HAD. Vascular lesions, including lacunes, large arterial infarcts, and severity of atherosclerosis were negatively associated with A(+). Associated symptoms included delusions, hallucinations, and depression, but not irritability, aberrant motor behavior, sleep and night time behavioral changes, or changes in appetite and eating habits. CONCLUSIONS: Smoking, TBI, and phosphorylated TDP-43 are associated with A(+)AD in specific groups, respectively. A(+) is directly associated with AD pathology load and inversely with vascular lesions.

Visual hallucinations of autobiographic memory and asomatognosia: a case of epilepsy due to brain cysticercosis.

The current study describes the case of a woman with symptomatic epilepsy due to brain cysticercosis acquired during childhood. During her adolescence, she developed seizures characterized by metamorphopsia, hallucinations of autobiographic memory and, finally, asomatognosia. Magnetic brain imaging showed a calcified lesion in the right occipitotemporal cortex, and positron emission tomography imaging confirmed the presence of interictal hypometabolism in two regions: the right parietal cortex and the right lateral and posterior temporal cortex. We discuss the link between these brain areas and the symptoms described under the concepts of epileptogenic lesion, epileptogenic zone, functional deficit zone, and symptomatogenic zone.

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.

Neuropsychiatric manifestations and treatment of disseminated neurocysticercosis: a compilation of three cases.

BACKGROUND: Neurocysticercosis (NCC) is the most serious form of cysticercal infection and is a major public health problem in the developing world. NCC presents with a range of psychiatric symptoms besides neurological symptoms. There have been few reports from the Asian continent describing the neuropsychiatric manifestations. Our aim was to report manifestations and treatment issues in three cases with disseminated NCC. METHODS AND RESULTS: Informed consent was obtained from all the three patients for the purpose of reporting. All three had multiple cysticerci in the brain and presented with several neuropsychiatric manifestations. All the patients had epilepsy and in addition they had varying psychiatric symptoms of delusions, hallucinations and catatonia, and cognitive symptoms. Also, interestingly in one patient, worsening of psychiatric and neurological symptoms correlated with anti-helminthic treatment. The psychotic symptoms responded to anti-psychotic treatment in one case. Anti-epileptics and steroid courses when given improved the clinical status. CONCLUSION: NCC presents with a myriad of manifestations. Epilepsy, psychotic and cognitive symptoms respond to symptomatic treatment. Use of anti-parasitic agents might worsen the symptoms as has been reported in a few cases earlier.

Nicotine and the hallucinating brain: effects on mismatch negativity (MMN) in schizophrenia.

Elevated smoking rates have been noted in schizophrenia, and it has been hypothetically attributed to nicotine's ameliorating abnormal brain processes in this illness. There is some preliminary evidence that nicotine may alter pre-attentive auditory change detection, as indexed by the EEG-derived mismatch negativity (MMN), but no previous study has examined what role auditory verbal hallucinations (AVH) may have on these effects. The objective of this study was to examine MMN-indexed acoustic change detection in schizophrenia (SZ) following nicotine administration and elucidate its association with AVH. Using a modified multi-feature paradigm, MMNs to duration, frequency and intensity deviants were recorded in 12 schizophrenia outpatients (SZ) with persistent AVHs following nicotine (6mg) and placebo administration. Electrical activity was recorded from 32 scalp electrodes; MMN amplitudes and latencies for each deviant were compared between treatments and were correlated with trait (PSYRATS) and state measures of AVH severity and Positive and Negative Syndrome Scale (PANSS) ratings. Nicotine administration resulted in a shortened latency for intensity MMN. Additionally, nicotine-related change in MMN amplitude was correlated with nicotine-related change in subjective measures of hallucinatory state. In summary, nicotine did not affect MMN amplitudes in schizophrenia patients with persistent AVHs, however this study reports accelerated auditory change detection to intensity deviants with nicotine in this group. Additionally, nicotine appeared to induce a generalized activation of the auditory cortex in schizophrenia, resulting in a concurrent increase in intensity MMN amplitude and subjective clarity of AVHs.

Auditory hallucinations and migraine of possible brainstem origin.

BACKGROUND: Concurrence of migraine and hallucinations is extremely rare and the underlying mechanism is poorly understood. METHODS: We report a 22-year-old man with migraine associated with auditory hallucinations. Concurrent psychotic illness has been excluded. RESULTS: Brain MR scans showed a stable, patchy FLAIR hyperintensity over the posterolateral aspect of the left cerebral peduncle, just below the level of the red nucleus. This was felt to represent an area of gliosis based on the interval stability over 19 months. There was absence of features for aggressive neoplasms, such as lesional high cellular turnover (choline/NAA ratio >1.0) or high cerebral blood volume on advanced MR imaging with MR spectroscopy and dynamic perfusion MR. EEG and brainstem auditory evoked potentials were unremarkable. CONCLUSIONS: To our knowledge, there are no reports to date on similar auditory hallucinations in adult migraine patients, as well as with associated MRI brainstem lesions. The peduncular lesion could represent a previous migrainous infarct, and a possible analogy can be drawn from the descriptions of peduncular hallucinosis. Brainstem lesions, particularly in the midbrain and pons, have rarely been associated with this condition. It has been postulated that the damage to ascending reticular systems or thalamocortical circuitry may contribute to its pathogenesis.

Spatial perspective and coordinate systems in autoscopy: a case report of a "fantome de profil" in occipital brain damage.

Autoscopic phenomena refer to complex experiences involving the illusory reduplication of one's own body. Here we report the third long-lasting case of autoscopy in a patient with right occipital lesion. Instead of the commonly reported frontal mirror view (fantôme spéculaire), the patient saw her head and upper trunk laterally in side view (fantôme de profil). We found that the visual appearance and completeness of the autoscopic image could be selectively modulated by active and passive movements, without being influenced by imagining the same movements or by tactile and auditory stimulation. Eyes closure did not disrupt either the perception of the autoscopic body or the effects of the motor stimulation. Moreover, the visual body reduplication was coded neither in purely eye-centered nor in head-centered frames of reference, suggesting the involvement of egocentric coordinate systems (eyes and head centered). A follow-up examination highlighted the stability of the visual characteristics of the body reduplication and its shift induced by displacement of both head and eyes. These findings support the view that autoscopic phenomena have a multisensory motor origin and proprioceptive signals may play an important role in modulating the illusory visual reduplication of the patient's own body, most likely via cross-modal modulation of extrastriate areas involved in body and face perception.

Alucinaciones auditivas / Auditory allucinations

The author studies the psychotic disorder auditory allucinations giving some considerations related to the pathologic mechanisms of this extremely complex syndrome.

Visual epilepsy in glioblastoma multiforme.

We report a 33-year-old Chinese gentleman who presented with visual epilepsy and symptoms of raised intracranial pressure in which clinical examination revealed normal visual fields and acuity despite Magnetic Resonance Imaging (MRI) brain showing large contrast enhancing mass at the right occipital lobe. Craniotomy and excision of tumour was done and the histology confirmed glioblastoma multiforme (GBM). He completed radiotherapy and recovered well except developing left inferior homonymous quadrantropia post operatively which improved with time.

[Charles-Bonnet Syndrome: a report of two cases]. / Charles Bonnet sendromu: iki olgu sunumu.

Charles-Bonnet syndrome (CBS) occurs after the loss of vision or a decrease in visual ability and is characterized by visual hallucinations with insight and preserved cognitive status. In this paper, 2 cases in which vision was lost (in one patient due to hypophyseal macroadenoma and in the other due to diabetic retinopathy) are presented. The first case is a 35-year-old male referred to the psychiatry department for depressive complaints. He lost his vision due to optic atrophy following multiple surgeries for hypophyseal macroadenoma and visual hallucinations developed afterwards. Ziprasidone 80 mg/day was started and the hallucinations disappeared on the fifth day, but the medication had to be withdrawn because of severe vascular type headaches. Olanzapine 5 mg/day was subsequently used without benefit. He refused further medication and the visions gradually changed into sparkling lights and simple figures at the 7-month follow-up. The second case was a 54-year-old woman with a 20-year history of type-II diabetes mellitus. Visual hallucinations developed after bilateral visual loss due to diabetic retinopathy 4 years earlier. She responded well to treatment with quetiapine 100 mg/day and paroxetine 20 mg/day. Neither of the cases had reported their visual symptoms to their physicians; the second case was diagnosed after 4 years by active screening. Both of the cases had neuroanatomic lesions. CBS symptoms should be screened actively in patients with visual loss and physicians should be educated about diagnosing CBS. Novel antipsychotics, such as ziprasidone and quetiapine, seem to be effective alternatives for the treatment of CBS.

Síndrome de Charles Bonnet: alucinações visuais em pacientes com doenças oculares - Relato de caso / Charles Bonnet syndrome: visual hallucinations in patients with ocular diseases - Case report

Neste artigo, os autores descrevem dois casos de síndrome de Charles Bonnet, definida como a percepção de alucinações visuais complexas em pacientes com déficit visual, tendo os pacientes a consciência da natureza irreal do fenômeno. Grande número de casos não é diagnosticado pela ausência do questionamento direto do médico. Em vista do transtorno emocional causado por esta doença, o reconhecimento dos seus sintomas é essencial no manejo destes pacientes.