Mario Meloni

Capgras syndrome in Parkinson’s disease: two new cases and literature review

The Capgras syndrome (CS) is a rare psychiatric disorder. CS is classified as a delusional misidentification syndrome. Initially, CS was described in paranoid schizophrenia and schizoaffective disorders. CS has also been reported in neurodegenerative diseases such as Alzheimer’s disease and Lewy body dementia. To date, there are very few descriptions of the occurrence of CS in idiopathic Parkinson’s disease (PD), with or without dementia. Considering the recent observation of two new cases in PD patients, a systematic overview of the literature published between 1976 and 2016 reporting CS in PD was conducted. The purpose of this article is to examine the phenomenon in people with PD with and without dementia, the psychopathologic context in which it happened, the role played by the dopaminergic medications and to define useful therapeutic strategies. Our CS cases occurred in two elderly patients with advanced PD and cognitive impairment, respectively, after an acute stressor event and after an increase of the total daily dose of levodopa. In light of our observations and the cases reported in the literature, we argue that CS is an acute or subacute psychotic disorder occurring mostly in PD with dementia. Besides, the increase in brain dopamine levels induced by acute stressful events and/or dopamine-enhancing medications should be considered as a possible causal mechanism of CS in patients with advanced stages of PD and cognitive decline.

The 5-alpha reductase inhibitor finasteride reduces dyskinesia in a rat model of Parkinson's disease

Abstract Levodopa‐induced dyskinesia (LID) is a disabling motor complication occurring in Parkinsons disease patients (PD) after long‐term l‐DOPA treatment. Although its etiology remains unclear, there is accumulating evidence that LID relies on an excessive dopamine receptor transmission, particularly at the downstream signaling of D1 receptors. We previously reported that the pharmacological blockade of 5‐alpha reductase (5AR), the rate limiting enzyme in neurosteroids synthesis, rescued a number of behavioral aberrations induced by D1 receptor‐selective and non‐selective agonists, without inducing extrapyramidal symptoms. Thus, the present study was designed to verify whether the 5AR inhibitor finasteride (FIN) may counteract the dyskinesias induced by dopaminergic agonists in 6‐hydroxydopamine (6‐OHDA)‐lesioned rats. First, we assessed the acute and chronic effect of different doses of FIN (30–60 mg/kg) on LID, in male 6‐OHDA‐lesioned dyskinetic rats. Thereafter, to fully characterize the therapeutic potential of FIN on LID and its impact on l‐DOPA efficacy, we assessed abnormal involuntary movements and forelimb use in hemiparkinsonian male rats chronically injected with FIN (30–60 mg/kg/24 days) either prior to‐ or concomitant with l‐DOPA administration. In addition, to investigate whether the impact of FIN on LID may be ascribed to a modulation of the D1‐ or D2/D3‐receptor function, dyskinesias were assessed in l‐DOPA‐primed 6‐OHDA‐lesioned rats that received FIN in combination with selective direct dopaminergic agonists. Finally, we set to investigate whether FIN may produce similar effect in female hemiparkinsonian rats, as seen in males. The results indicated that FIN administrations significantly dampened LID in all tested treatment regimens, without interfering with the ability of l‐DOPA to ameliorate forelimb use in the stepping test. The antidyskinetic effect appears to be due to modulation of both D1‐ and D2/D3‐receptor function, as FIN also reduced abnormal involuntary movements induced by the selective D1 receptor agonist SKF‐82958 and the D2/D3 receptor agonist ropinirole. Significant dampening of LID was also observed in female rats, although only at the higher tested dose. Clinical investigations are warranted to assess whether similar protection from dyskinesia is seen in PD patients. HighlightsFinasteride reduces already established LID in a rat model of PD.Finasteride dampens development of LID.Finasteride 30 mg/kg does not reduce the therapeutic effect of l‐DOPA on forelimb use.

Priapism and Hypersexuality Associated With Rotigotine in an Elderly Parkinsonian Patient: A Case Report.

To the Editor: P riapism is an uncommon condition defined as prolonged (greater than 4 hours) penile erection not initiated by sexual stimulation. There are many different causes of priapism including hematologic disorders, trauma, metabolic conditions, and medications. Several classes of medication are involved: antihypertensives, anticoagulants, α-blockers, antidepressants, psychoactive substances. In particular, about 50% of drug-induced priapism is due to typical and atypical antipsychotics, such as chlorpromazine, zuclopenthixol, clozapine, risperidone, olanzapine, quetiapine, ziprasidone,21 aripiprazole, and iloperidone. To date, there is only 1 case report on the association between priapism and cabergoline. Cabergoline is an ergotderived dopamine agonist with high affinity for the dopamine D2 receptor, but also possesses low affinity for dopamine D1, α1and α2-adrenergic, and 5-HT1and 5-HT2serotonin receptors. Herein we present the first detailed case of rotigotine-induced priapism and hypersexuality in a patient with Parkinson disease (PD). P.P. is a 79-year-old man, with a 10-year history of an idiopathic PD with resting tremor and rigidity more marked on the left side, bradykinesia, and camptocormia. Neuropsychological testing revealed subtle executive dysfunction and mild cognitive impairment. At the beginning, tremor, rigidity, and bradykinesia were well controlled under a treatment of a combination of levodopa/ carbidopa (400 mg/daily) and pramipexole extended release (1.05 mg/daily). Six years later, he experienced significant and unpredictable levodopa-induced motor fluctuations. At the time of our first observation, the patient showed the symptoms of an advanced and complicated PD with signs of fluctuating mood, sleep disturbances, such as excessive daytime sleepiness and falling asleep suddenly for short periods of time, similar to narcolepsy. Considering that the major cause of sleepiness was drug induced, we decided to reduce and then

Pisa-Like Syndrome Under Baclofen in a Patient With Spastic Hemiparesis due to Ischemic Stroke

In its original description, Pisa syndrome was reported as an iatrogenic dystonia of the trunk caused by neuroleptic drugs. However, sometimes, not dystonic lateral flexion of the trunk is described as Pisa syndrome. These observations support the possibility of a drug-induced lateral flexion of the trunk with clinical presentation similar to Pisa syndrome, although with a different etiology and pathophysiology. Here, we describe the case of a male patient, with a previous ischemic stroke and residual spastic hemiparesis to the right side, who subacutely developed a dramatic lateral flexion of trunk (approximately 45° to the right) a few days after the introduction of Baclofen (5 mg 3 times per day). After the discontinuation of baclofen, a full recovery of the correct posture was obtained. In this respect, our case is paradigmatic: it is drug-induced but not clearly dystonic in its manifestation. Baclofen reduces the spasticity depressing the monosinaptic and polisinaptic reflex in the spinal cord by stimulating Gamma-aminobutyric acid B (GABA-B) receptors, which inhibit the release of excitatory amino acids, glutamate and aspartate. We believe that the definition of Pisa syndrome for these forms, not clearly dystonic, might be not completely appropriate, but they should be defined more correctly as Pisa-like syndromes.

C9ORF72 Intermediate Repeat Expansion in a Patient With Psychiatric Disorders and Progressive Cerebellar Ataxia

Introduction: Large expansions of the noncoding GGGGCC repeat (more than 30) in the first intron of the C9ORF72 gene have been demonstrated to cause amyotrophic lateral sclerosis and frontotemporal dementia. Recent papers have investigated the possible pathogenic role and associated clinical phenotypes of hexanucleotide expansions with intermediate repeat lengths ranging between 20 and 29 repeats. Case Report: We report a case of a 71-year-old Sardinian female patient with a long history of psychiatric disorders such as mixed anxiety-depressive disorder associated with somatization disorder and histrionic personality who developed a slowly progressive cerebellar syndrome, mild cognitive impairment, pyramidal signs, and rapid eye movement sleep behavior disorder with imaging abnormalities on the DaTSCAN single-photon emission computed tomography indicating an alteration in the presynaptic dopaminergic system. The patient was found to have intermediate C9ORF72 repeat expansions. Conclusions: Early psychiatric presentations are a recurrent phenotypic manifestation of C9ORF72 expansions. In our patient, the intermediate C9ORF72 repeat expansion may have a pathogenic role in the cooccurrence of psychiatric and sleep disorders, cognitive dysfunctions, pyramidal system involvement, and late-onset cerebellar ataxia. This observation widens the spectrum of neurodegenerative conditions linked to C9ORF72 mutations.

Dopamine dysregulation syndrome and psychosis in 24-h intestinal levodopa infusion for Parkinson's disease.

We read with interest the paper of Ricciardi et al. [1] describing a male patient affected by advanced Parkinson’s disease (PD) who developed a dopamine dysregulation syndrome (DDS) associated with Othello and Capgras Syndromes in the context of a severe psychosis while on 24-h levodopa/carbidopa intestinal gel (LCIG). While Othello syndrome is a paranoid delusion supported by the absolute certainty of the infidelity of the partner, Capgras syndrome is a delusional misidentification syndrome (DMS) in which the patients are convinced that a familiar person has been replaced by an impostor or a double who is physically very similar to the original. We previously described the presence of Othello Syndrome in PD patients as a dopaminergic-induced psychosis not necessarily associated with cognitive impairment [2], while Capgras syndrome has been scarcely explored. The merits of the paper of Ricciardi et al. lie precisely in the demonstration of a DDS associated with the appearance of these delusional syndromes, triggered by unnecessary dosages of LCIG, with a review of several cases of Capgras syndrome in PD patients, suggesting a dopaminergic-induced psychosis in the setting of cognitive impairment. However, several fundamental issues, especially on dopaminergic treatment, remain not discussed. First of all, it is not clear why the patient, with a previous history of levodopa/entacapone visual hallucinations triggered at a dosage of 400/600 mg/day, was started on a levodopa dose of 48 mg/h for 16 h (768 mg/day) which appears excessive in comparison with his previous treatment (even considering the possible use of extra doses self-administered by the patient), although the authors described a virtual elimination of OFF time and no side effects. Secondly, we were relatively surprised that the same patient on overnight LCIG, may have self-administered a levodopa dosage of 2030 mg/day within six months, and maintained for other two (which means more of one cassette per day) without any of dyskinesias at follow-up visits. In our clinical practice, the choice of an overnight administration of LCIG requires a more frequent and stricter control of motor and non motor complications. As described by the same authors, we were the first to describe two patients who developed DDS on LCIG and both developed delusional disorders, mainly of paranoid type [3]. These patients did not respect follow-up schedule, preferring telephonic contacts to visits, with an inappropriate monitoring of the treatment and insufficient therapeutical adjustment [3]. According to author’s opinion, although the use of LCIG in PD patients is generally a safe and efficacious treatment option in advanced PD patients, this case emphasizes that a correct management of this anti-parkinsonian infusional treatment is needed. Moreover, we think that the authors reported erroneously as “two cases of DDS have been reported recently after LCIG initiation” [3,4] citing both our first description of two patients who developed DDS on LCIG and the case of a patient with a previous history of DDS who subsequently relapsed on LCIG. Indeed, the cases previously described are four, because these authors have missed the more recent paper of Salomone et al. [5], who described another patient with DDS and punding on LCIG. Finally it seems worth noting that the review of previous cases of PD patients with Capgras syndrome reported in the literature (seven cases reported plus the case of the paper) is largely incomplete, as at least four cases were not included [6e8]. These cases not only confirm the key role of the cognitive impairment in the development of Capgras syndrome, but also add new elements, given that neurosurgical procedures as pallidotomy intervention [6] and deep brain stimulation [7] may be associated with Capgras syndrome. Aside these criticisms on the incomplete review of the literature, we are in strong agreement with the general view of the authors on the crucial need of treatment monitoring for the prevention and management of behavioural disorders such as DDS in PD patients on LCIG, particularly in patients with previous dopaminergicrelated abnormal behaviours, and high total daily dosage of dopaminergic drugs. We retain that PD patients on 24-h administration of LCIG should be more carefully monitorized with a more frequent and tighter control of motor and non motor complications.

Suicide in Parkinsons Disease: An Open Question and a Complex andPoorly Explored Phenomenon

Susceptibility to suicide and suicidal ideation is a very serious issue in patients with Parkinson’s disease (PD). There is much that is still unknown about the relationship between suicide, age, medical treatment and disease in the PD patient population. Depression is the most common psychiatric disturbance that affects people with PD. On multivariate analysis, severity of depression and psychosis were the only predictors of suicide or death ideation for PD patients.