Victor Parant (1848-1924) and the first report of psychosis in the course of Parkinson's disease with dementia.

Until the beginning of the twentieth century, neurologists considered that mental disorders in the course of Parkinson's disease (PD) occurred in the terminal phases of the disease or were due to coincidental pathologies. Benjamin Ball (1834-1893), in 1881 and 1882, drew attention to the frequency of cognitive and depressive disorders in PD. In 1883, Victor Parant (1848-1924), referring to Ball's work, published the first detailed observation of a PD patient with dementia and psychotic symptoms. Parant was an alienist running a private clinic for mental diseases in Toulouse, France. One of his main interests was the question of the responsibility of the insane, and he was called upon as a forensic expert in several cases. In this context, Parant examined a man who had been suffering from PD for several years, and later developed concurrently severe cognitive impairment and psychotic disorders. The patient would meet modern criteria for PD-associated psychosis: he had multimodal hallucinations (visual, auditory and somatic), visual illusions, and paranoid delusions. He also reported unusual symptoms: supernumerary limbs and Alice in Wonderland syndrome. Parant forwarded the far-sighted hypothesis that cognitive and psychotic disorders were due to the extension of PD lesions within the brain. The unheralded work of Victor Parant should be recognized in the history of neuropsychiatry.

The landmark contributions of Paul Blocq, Georges Marinesco, and Édouard Brissaud in Parkinson's disease.

Two students of Jean-Martin Charcot, Paul Blocq and Georges Marinesco, presented a case of hemi-parkinsonism to the Société de Biologie on 27 May 1893. A tuberculoma was found at post-mortem in the cerebral peduncle contralateral to the side of the body affected by Parkinson's disease. A year later, in one of his lessons, Édouard Brissaud suggested that damage to the substantia nigra caused by the granuloma might have been responsible for the physical signs. This article provides brief biographical accounts of both Blocq and Marinesco and a detailed review of their seminal paper before going on to discuss how the substantia nigra was eventually established as the most consistent pathological substrate for Parkinson's disease and its role in the dopamine miracle which led to striatal dopamine replacement therapy in 1967.

Clinical description of the broad range of neurological presentations of COVID-19: A retrospective case series.

BACKGROUND: Neurological disorders associated with SARS-CoV-2 infection represent a clinical challenge because they encompass a broad neurological spectrum and may occur before the diagnosis of COVID-19. METHODS: In this monocentric retrospective case series, medical records from patients with acute neurological disorders associated with SARS-CoV-2 infection from medicine departments of an academic center in Paris area were collected between March 15th and May 15th 2020. Diagnosis of SARS-CoV-2 was ascertained through specific RT-PCR in nasopharyngeal swabs or based on circulating serum IgG antibodies. RESULTS: Twenty-six patients diagnosed with SARS-CoV-2 infection presented with neurological disorders: encephalitis (N=8), encephalopathy (N=6), cerebrovascular events (ischemic strokes N=4 and vein thromboses N=2), other central nervous system (CNS) disorders (N=4), and Guillain-Barré syndrome (N=2). The diagnosis of SARS-CoV-2 was delayed on average 1.6 days after the onset of neurological disorder, especially in case of encephalitis 3.9 days, encephalopathy 1.0 day, and cerebrovascular event 2.7 days. CONCLUSIONS: Our study confirms that COVID-19 can yield a broad spectrum of neurological disorders. Because neurological presentations of COVID-19 often occur a few days before the diagnosis of SARS-COV-2 infection, clinicians should take preventive measures such as patient isolation and masks for any new admission to avoid nosocomial infections. Anti-SARS-CoV2 antibody detection in RT-PCR SARS CoV-2 negative suspected cases is useful to confirm a posteriori the diagnosis of atypical COVID-19 presentations.

High-dose transdermal nicotine in Parkinson's disease patients: a randomized, open-label, blinded-endpoint evaluation phase 2 study.

BACKGROUND AND PURPOSE: Studies of the effects of nicotine on motor symptoms in Parkinson's disease (PD) brought out discordant results. The aim of the present study was to evaluate the efficacy and safety of high doses of transdermal nicotine on motor symptoms in PD. METHODS: Forty PD patients were randomly assigned to a treated and untreated arm in an open-label study. Treated patients received increasing doses of nicotine to reach 90 mg/day by 11 weeks. This dosage was maintained for 28 weeks (W39) and then reduced over 6 weeks. Final evaluation was performed 6 weeks after washout. The main outcome measure was the OFF-DOPA Unified Parkinson's Disease Rating Scale (UPDRS) motor score measured on video recordings by raters blinded to the medication status of the patients. RESULTS: There was no significant difference in OFF-DOPA UPDRS motor scores between the nicotine-treated and non-treated groups, neither at W39 (19.4 ± 9.3 vs. 21.5 ± 14.2) nor considering W39 differences from baseline (-1.5 ± 12.1 vs. +0.9 ± 12.1). The 39-item Parkinson's disease questionnaire scores decreased in nicotine-treated patients and increased in non-treated patients, but the difference was not significant. Overall tolerability was acceptable, and 12/20 treated patients reached the maximal dosage. CONCLUSIONS: High doses of transdermal nicotine were tolerated, but our study failed to demonstrate significant improvement in UPDRS motor scores. Improvement in unblinded secondary outcomes (UPDRS-II, UPDRS-IV, doses of l-DOPA equivalents) suggest a possible benefit for patients treated with nicotine, which should be confirmed in larger double blind, placebo-controlled studies.

Hallucinations in schizophrenia and Parkinson's disease: an analysis of sensory modalities involved and the repercussion on patients.

Hallucinations have been described in various clinical populations, but they are neither disorder nor disease specific. In schizophrenia patients, hallucinations are hallmark symptoms and auditory ones are described as the more frequent. In Parkinson's disease, the descriptions of hallucination modalities are sparse, but the hallucinations do tend to have less negative consequences. Our study aims to explore the phenomenology of hallucinations in both hallucinating schizophrenia patients and Parkinson's disease patients using the Psycho-Sensory hAllucinations Scale (PSAS). The main objective is to describe the phenomena of these clinical symptoms in those two specific populations. Each hallucinatory sensory modality significantly differed between Parkinson's disease and schizophrenia patients. Auditory, olfactory/gustatory and cœnesthetic hallucinations were more frequent in schizophrenia than visual hallucinations. The guardian angel item, usually not explored in schizophrenia, was described by 46% of these patients. The combination of auditory and visual hallucinations was the most frequent for both Parkinson's disease and schizophrenia. The repercussion index summing characteristics of each hallucination (frequency, duration, negative aspects, conviction, impact, control and sound intensity) was always higher for schizophrenia. A broader view including widespread characteristics and interdisciplinary works must be encouraged to better understand the complexity of the process involved in hallucinations.

Assessing health-related quality of life with the SCOPA-PS in French individuals with Parkinson's disease having undergone DBS-STN: A validation study.

INTRODUCTION: The aims of this study were to validate the French version of the SCales for Outcomes in Parkinson's Disease-PsychoSocial (SCOPA-PS) in individuals with Parkinson's disease (PD) who underwent deep brain stimulation of the subthalamic nucleus (DBS-STN), to confirm the unifactorial structure of this questionnaire, and to establish its psychometric properties. METHODS: Routinely used psychological questionnaires (BDI-II, STAI-Y, PDQ-39, UPDRS III) and the SCOPA-PS were used for a cross-sectional observational study of 154 PD patients. SCOPA-PS acceptability, scaling assumption, reliability, ordinal confirmatory factor analysis and validity were assessed. RESULTS: The ICC for two-week test-retest reliability was 0.88. SEM was 8.42. In confirmatory factor analysis, the one-factor model showed an acceptable fit to the data (Chi(2)/df=2.130; CFI=0.976; RMSEA=0.086). No floor or ceiling effects were observed. Skewness was 0.33. Item-total correlation coefficients ranged from 0.47 to 0.71. Cronbach's alpha was 0.86. SCOPA-PS SI correlated with PDQ-39 SI (rs=0.83) and with state-anxiety and depression (rs=0.56 and 0.69 respectively). The SCOPA-PS SI was higher in more depressed patients and in those with the most severe PD motor symptoms. CONCLUSION AND DISCUSSION: SCOPA-PS French version is a one-factor scale with satisfactory psychometric properties consistent with other language versions. This short scale can be used to evaluate the psychosocial component of QoL in PD patients treated with DBS-STN.

Validation of a Psycho-Sensory hAllucinations Scale (PSAS) in schizophrenia and Parkinson's disease.

OBJECTIVE: If hallucinations are the most common of schizophrenic symptoms, they have been described in other pathologies such as Parkinson's disease (PD) but may differ considerably in their phenomenology. However, no multi-modal clinical scale with a transnosographic approach has been developed today. The purpose of this study was to create and validate a new tool for the hetero-assessment of all sensory modalities of hallucinations schizophrenia (SCZ) and in PD. METHOD: Scale items were generated by literature review and validated by medical board. A study was then made to evaluate psychometric properties of the Psycho-Sensory hAllucinations Scale (PSAS) that include four domains (auditory, visual, olfactory and gustatory, cenesthetic modalities) and one specific item 'guardian angel'. RESULTS: It was then validated in 137 patients: 86 PD (53.5% male; mean age=53.3years) and 51 SCZ (64.7% male; mean age=38.5years). Factorial analysis of the PSAS found four factors. The PSAS showed good internal consistency [Kuder-Richardson alpha coefficient 0.49 to 0.77] and good test-retest reliability [Agreement %=0.75 to 0.97] and inter-rater reliability [Agreement %=0.78 to 1.0]. The convergent validity illustrates the concomitant evaluation of the concept between PSAS and PANSS P3 and UPDRS1 I2. CONCLUSION: The PSAS can be useful to describe the whole hallucination and its evolution during the course of the disease and treatment in schizophrenia and PD. Moreover, it can allow us to undertake a clinic-pathological comparison of hallucination modalities between these two diseases, to enhance our understanding of their precise neurological mechanisms.

[The Alice in Wonderland syndrome: an unusual aura in migraine]. / Le syndrome d'Alice au pays des merveilles: une aura migraineuse inhabituelle.

INTRODUCTION: The Alice in Wonderland syndrome consists in a perceptual distortion of one's body size and shape. It is rarely encountered in adults, where it is mainly associated with migraine with aura and epilepsy. CASE REPORT: A 37-year-old woman had had a migraine without aura since puberty. In the months following a parturition, she experienced several epidodes of unusual auras preceding typical migrainous headache. The aura lasted about 30min and consisted in the feeling of lengthening of the trunk and of the four limbs, associated with a sensation of well-being. DISCUSSION AND CONCLUSION: Epileptologic and experimental data suggest that the Alice in Wonderland syndrome is associated with a transient dysfunction of associative somatosensory areas in the parietal cortex.

Changes in quality of life, burden and mood among spouses of Parkinson's disease patients receiving neurostimulation.

BACKGROUND: Deep brain stimulation improves motor function and quality of life in patients with Parkinson's disease. The impact of these changes on patients' spouses is largely unknown. METHODS: Twenty-six spouses of patients undergoing surgery were evaluated before and 12 months after surgery, using the 36-Item Short Form Health Survey for quality of life, the Beck Depression Inventory, and the Zarit Burden Inventory. RESULTS: The spouses' mean mood and quality of life scores changed little, while burden improved in younger spouses. There was no significant change in the spouses' overall status. However, at the individual level the effect of surgery was more frequently negative than positive. Changes in psychological status and quality of life in the spouses did not correlate with changes in the patients' motor status or quality of life. CONCLUSIONS: Spouses' experience of neurostimulation for Parkinson's disease is variable and complex. The improvement in burden experienced by younger spouses may reflect a greater capacity to cope with new situations.

[Biotherapies and Parkinson's disease]. / Biothérapies et maladie de Parkinson.

In the last years, several experimental biotherapies have been developed to treat Parkinson's disease. Initially, fetal dopaminergic transplants were proposed. Although a proof of concept and encouraging results have been provided, limitations of this treatment emerged over the years and the failure of controlled trials have conducted to a pause in the development of strategies based on fetal cells. Alternative approaches such as the use of retinal pigmented cells recently provided disappointing results in patients and much hope has now been reported on other sources of dopaminergic neurons such as those originating from stem cells. This strategy is however not yet ready for clinical trials in patients. Eventually, gene therapy is a new original experimental technique which has elicited several trials in the last few years some of them being promising.

Attempted and completed suicides after subthalamic nucleus stimulation for Parkinson's disease.

A higher than expected frequency of suicide has been reported among patients undergoing subthalamic nucleus deep brain stimulation (STN DBS) for advanced Parkinson's disease (PD). We conducted a retrospective survey of 200 patients with PD who underwent STN DBS. Two patients (1%) committed suicide and four (2%) attempted suicide, despite clear motor improvements. Suicidal patients did not differ from non-suicidal patients with respect to age, disease duration or preoperative depressive and cognitive status. Suicidal behaviour was associated with postoperative depression and/or altered impulse regulation. Suicidal behaviour is a potential hazard of STN DBS, calling for careful preoperative assessment and close postoperative psychiatric and behavioural follow-up.

[Multi-infarct disorder presenting as corticobasal degeneration (DCB): vascular pseudo-corticobasal degeneration?]. / Infarctus cérébraux multiples se présentant comme une dégénérescence cortico-basale: pseudo dégénérescence cortico-basale vasculaire?

We report on five patients with a clinical presentation of corticobasal degeneration (CBD), including gradually progressive, asymmetric, L-DOPA-resistant parkinsonism associated variously with apraxia, focal action myoclonus, focal dystonia, cortical sensory loss and alien limb phenomenon. Some patients also presented an atypical CBD clinical history or signs - notably sudden onset. The disease was however not suggestive of another diagnosis. Magnetic resonance imaging of the brain revealed extensive vascular lesions. Only five similar cases have been published to our knowledge. Although we cannot exclude underlying CBD pathology, our cases illustrate the fact that multi-infarct pathology can masquerade as CBD or alter the clinical phenotype of the disease.

[Primary central nervous system lymphoma presenting with central neurogenic hyperventilation. A case report and review of the literature]. / Hyperventilation neurogène centrale révélant un lymphome cérébral primitif. Une observation et revue de la littérature.

INTRODUCTION: Central neurogenic hyperventilation (CNH) in an awake patient is a rare entity. OBSERVATION: We report here a 54-year-old patient who developed central neurogenic hyperventilation as the initial presentation of a primary central nervous system lymphoma located in the brainstem. CONCLUSION: The patient's hyperventilation resolved completely with chemotherapy for primary CNS lymphoma. Most of the cases reported in the literature are related to a diffuse tumor of the brainstem with an intriguing overrepresentation of primary CNS lymphoma. The pathogenesis of CNH is discussed.

[Convergence nystagmus and vertical gaze palsy of vascular origin]. / Nystagmus de convergence et paralysie de la verticalité du regard d'origine vasculaire.

A case of convergence-retraction nystagmus with upward vertical gaze paralysis and skew deviation (right hypotropia), without any other neurological signs, is reported. The probably vascular lesion was located at the mesodiencephalic junction, lying between the right border of the posterior commissure, the right interstitial nucleus of Cajal and the periaqueductal grey matter, accounting for the three ocular motor signs. The particular interest of this case is due to the relative smallness of the lesion.