Psychosis in Parkinson's Disease: Looking Beyond Dopaminergic Treatments.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. The symptoms of PD are characterized not only by motor alterations but also by a spectrum of nonmotor symptoms. Some of these are psychiatric manifestations such as sleep disorders; depression; cognitive difficulties that can evolve into dementia; and symptoms of psychosis, which include hallucinations, illusions, and delusions. Parkinson's disease psychosis (PDP) occurs in 18-50% of patients with PD. Treating PDP is challenging because antipsychotic drugs tend to be inefficient or may even worsen the disease's motor symptoms. OBJECTIVE: This review aims to summarize the current understanding of the molecular mechanisms involved in PDP and recent innovative alternatives for its treatment. METHODS: This is a narrative review in which an extensive literature search was performed on the Scopus, EMBASE, PubMed, ISI Web of Science, and Google Scholar databases from inception to August 2021. The terms "Parkinson's disease psychosis", "Parkinson psychosis," "neurodegenerative psychosis", and "dopamine psychosis" were among the keywords used in the search. RESULTS: Recently, views on the etiology of hallucinations and illusions have evolved remarkably. PDP has been cemented as a multifactorial entity dependent on extrinsic and novel intrinsic mechanisms, including genetic factors, neurostructural alterations, functional disruptions, visual processing disturbances, and sleep disorders. Consequently, innovative pharmacological and biological treatments have been proposed. Pimavanserin, a selective 5-HT2A inverse agonist, stands out after its approval to treat PDP-associated hallucinations and illusions. CONCLUSION: Future results from upcoming clinical trials should further characterize the role of this drug in the management of PDP as well as other treatment options with novel mechanisms of action, such as saracatinib, SEP-363856, cannabidiol, electroconvulsive therapy, and transcranial magnetic stimulation.

Musical hallucination associated with hearing loss.

In spite of the fact that musical hallucination have a significant impact on patients' lives, they have received very little attention of experts. Some researchers agree on a combination of peripheral and central dysfunctions as the mechanism that causes hallucination. The most accepted physiopathology of musical hallucination associated to hearing loss (caused by cochlear lesion, cochlear nerve lesion or by interruption of mesencephalon or pontine auditory information) is the disinhibition of auditory memory circuits due to sensory deprivation. Concerning the cortical area involved in musical hallucination, there is evidence that the excitatory mechanism of the superior temporal gyrus, as in epilepsies, is responsible for musical hallucination. In musical release hallucination there is also activation of the auditory association cortex. Finally, considering the laterality, functional studies with musical perception and imagery in normal individuals showed that songs with words cause bilateral temporal activation and melodies activate only the right lobe. The effect of hearing aids on the improvement of musical hallucination as a result of the hearing loss improvement is well documented. It happens because auditory hallucination may be influenced by the external acoustical environment. Neuroleptics, antidepressants and anticonvulsants have been used in the treatment of musical hallucination. Cases of improvement with the administration of carbamazepine, meclobemide and donepezil were reported, but the results obtained were not consistent.

Musical hallucination associated with hearing loss / Alucinações musicais associadas a perda auditiva

In spite of the fact that musical hallucination have a significant impact on patients' lives, they have received very little attention of experts. Some researchers agree on a combination of peripheral and central dysfunctions as the mechanism that causes hallucination. The most accepted physiopathology of musical hallucination associated to hearing loss (caused by cochlear lesion, cochlear nerve lesion or by interruption of mesencephalon or pontine auditory information) is the disinhibition of auditory memory circuits due to sensory deprivation. Concerning the cortical area involved in musical hallucination, there is evidence that the excitatory mechanism of the superior temporal gyrus, as in epilepsies, is responsible for musical hallucination. In musical release hallucination there is also activation of the auditory association cortex. Finally, considering the laterality, functional studies with musical perception and imagery in normal individuals showed that songs with words cause bilateral temporal activation and melodies activate only the right lobe. The effect of hearing aids on the improvement of musical hallucination as a result of the hearing loss improvement is well documented. It happens because auditory hallucination may be influenced by the external acoustical environment. Neuroleptics, antidepressants and anticonvulsants have been used in the treatment of musical hallucination. Cases of improvement with the administration of carbamazepine, meclobemide and donepezil were reported, but the results obtained were not consistent.

Apesar das alucinações musicais causarem grandes repercussões na vida dos pacientes, sempre foram pouco valorizadas e estudadas pelos profissionais. Alguns investigadores sugerem uma combinação de disfunções periféricas e centrais como o mecanismo causador das alucinações. A fisiopatologia mais aceita entre os pesquisadores de alucinação musical associada à hipoacusia ou anacusia (causada por lesão coclear, de nervo coclear ou interrupção de informação na ponte ou mesencéfalo) é a desibinição de circuitos de memória auditiva devido à deprivação sensorial. Em relação às áreas corticais envolvidas na alucinação musical, há evidência de que um mecanismo excitatório no córtex temporal superior, como nas epilepsias, seja responsável pela alucinação musical. Finalmente, considerando a lateralidade, estudos funcionais de percepção e imagética em indivíduos normais mostraram que canções com letras levam a ativação temporal bilateral e melodias ativam apenas o lobo temporal direito. É bem documentado o efeito de aparelhos auditivos na alucinação musical através de uma melhora da perda auditiva. Neurolépticos, antidepressivos e anticonvulsivantes têm sido usados no tratamento de alucinação musical na experiência clínica, mas não há eficácia comprovada na maioria dos casos. Há casos descritos na literatura com melhora das alucinações musicais com uso de carbamazepina, meclobemide e donepezil, entretanto sem resultados consistentes.

[Charles Bonnet syndrome: report of one case managed with haloperidol]. / Síndrome de Charles Bonnet: Manejo con haloperidol en paciente nonagenaria. Caso clínico.

Charles Bonnet syndrome is an underrecognized condition characterized by complex visual hallucinations, ocular problems causing visual deterioration and preserved cognitive status. Its prevalence is 5/1000 in ambulatory ophthalmologic patients. Generally occurs in elderly people in whom it may be confused with delirium or dementia. The first management step is to improve vision, if possible. Hallucinations may be managed pharmacologically. We report a 94 year-old woman with the characteristic clinical picture of the syndrome that improved with haloperidol.

Síndrome de Charles Bonnet: Manejo con haloperidol en paciente nonagenaria. Caso clínico / Charle Bonnet syndrome: Report of one case managed with haloperidol

Charles Bonnet syndrome is an underrecognized condition characterized by complex visual hallucinations, ocular problems causing visual deterioration and preserved cognitive status. Its prevalence is 5/1000 in ambulatory ophthalmologic patients. Generally occurs in elderly people in whom it may be confused with delirium or dementia. The first management step is to improve vision, if possible. Hallucinations may be managed pharmacologically. We report a 94 year-old woman with the characteristic clinical picture of the syndrome that improved with haloperidol.

Effects of repetitive transcranial magnetic stimulation on auditory hallucinations refractory to clozapine.

OBJECTIVE: To study the therapeutic effects on auditory hallucinations refractory to clozapine with 1-Hz repetitive transcranial magnetic stimulation (rTMS) applied on the left temporoparietal cortex. METHOD: Eleven patients with schizophrenia (DSM-IV) experiencing auditory hallucinations (unresponsive to clozapine) were randomly assigned to receive either active of rTMS (N = 6) or sham stimulation (N = 5) (with concomitant use of clozapine) using a double-masked, sham-controlled, parallel design. A total of 160 minutes of rTMS (9600 pulses) was administered over 10 days at 90% motor threshold. The study was conducted from January 2003 to December 2005. RESULTS: There was a reduction in hallucination scores in both groups, which persisted during follow-up in the active group for the items reality (p = .0493) and attentional salience (p = .0360). Both groups showed similar patterns of symptomatic changes on subscales (negative symptoms, general psychopathology) and total scores of the Positive and Negative Syndrome Scale, Clinical Global Impressions scale, and Visual Analog Scale. CONCLUSION: Active rTMS in association with clozapine can be administered safely to treat auditory hallucinations, although its clinical utility is still questionable. No significant clinical effects were observed in the sample studied, possibly because it was too small and/or due to its high refractoriness.

[Dementia with Lewy bodies. A description of a case with a genetic variant]. / Demencia con cuerpos de Lewy. Presentación de un caso con variante genética.

INTRODUCTION: Dementia with Lewy bodies represents the third cause of dementia in the clinicopathological series reported to date. CASE REPORT: A 79-year-old white female with a 3-year history of symptoms of dementia, Parkinsonism and visual hallucinations; the symptoms were difficult to control with medication and there was a family history of similar clinical pictures of dementia in the paternal grandfather, an aunt on the father's side and six siblings. A genetic study was not possible. The study thus involves a patient with relatives that may have had the pure or mixed variant of these dementias, without the DNA study for determining the e4 allele of the gene for apolipoprotein E that has been found most frequently in dementia due to Alzheimer.

Diabetic ketoacidosis associated with olanzapine in an adolescent patient.

Olanzapine (Zyprexa) is an atypical neuroleptic used in adult and pediatric patients for the management of schizophrenia. Common side effects include increased appetite and weight gain. An uncommon but severe adverse effect is the development of diabetic ketoacidosis, reported until now only in adults. We report a case of acute onset diabetic ketoacidosis presenting in a 16-year-old girl during olanzapine therapy.

Alzheimer's disease with delusions and hallucinations: neuropsychological and electroencephalographic correlates.

We longitudinally evaluated the neuropsychological functions, rate of progression, and waking EEG findings in 17 patients with probable Alzheimer's disease (AD) with delusions and hallucinations, and compared them with those of matched AD patients without delusions and hallucinations. AD patients with delusions and hallucinations had a more rapid rate of decline, as measured by the Mini-Mental State Examination, a specific defect in receptive language, and a greater frequency of aggression and hostility. Visual EEG analysis showed that these patients had a significantly greater proportion of moderately abnormal EEGs, and spectral analysis confirmed the increased amount of delta and theta activity. These data demonstrate that AD patients with delusions and hallucinations have a greater degree of cerebral dysfunction and a relatively focal neuropsychological defect, which may indicate a localized pathologic abnormality.