Marian apparitions: A multidisciplinary approach. The case of Île Bouchard.

Discussing Marian apparitions in the light of current knowledge in neuroscience is a challenge: the testimonies are often old and indirect, and the "visionaries" could not be questioned or even examined according to current neurological or psychiatric standards. In doing so, we are not unaware of the heterogeneity of seers and the facts they reported: there is not necessarily a single hypothesis. It is the appearances of Île Bouchard that will be discussed here. Our interpretation calls on two non-exclusive "mechanisms": on the one hand, mental imagery, which we know can be unconscious and is modulated or generated by frontal "top-down" mechanisms; on the other hand, the sociological consideration of events, using the concept of enchantment.

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.

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.

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.

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.

[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.

[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.

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.

[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.

[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.

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.

Central complex of the primate thalamus: a quantitative analysis of neuronal morphology.

Neuronal morphology was analyzed in the central complex (centre median-parafascicular complex) of macaques and humans. Cell bodies were described from Nissl material. Golgi-impregnated dendritic arborizations were reconstructed from serial sections and digitized in three dimensions by computer-assisted microscopy. The central complex was subdivided into three parts on the basis of cytoarchitectonic and hodological criteria: pars parafascicularis (medial), pars media (intermediate), and pars paralateralis (lateral). The mean cross-sectional areas of cell bodies were identical (181 microns2) in the three parts in macaques. In humans they were larger in the pars parafascicularis (304 microns2) than in the other parts (248 and 240 microns2). Small local circuit neurons were found throughout the complex. Large projection neurons differed statistically in the three parts. In macaques, pars parafascicularis neurons had few dendritic stems and tips (3-11) and a short total dendritic length (2,000 microns). Pars paralateralis neurons had more ramified (5-60) and longer (5,800 microns) dendrites. They bore numerous axonlike processes. Pars media neurons had intermediate characteristics (5-19; 2,400 microns). In humans, pars parafascicular neurons had similar topological characteristics (3-12) but longer dendrites (3,000 microns) than in the monkey. Pars paralateralis neurons had more branched (6-71) and longer (9,000 microns) dendrites, with more numerous axonlike processes. Pars media neurons also had intermediate characteristics (4-25; 3,800 microns). The present study supports a tripartite subdivision of the primate central complex and demonstrates significant interspecies differences.

Topography of the projection from the central complex of the thalamus to the sensorimotor striatal territory in monkeys.

The distribution of axons arising from the central complex (or centre médian-parafascicular complex) and terminating in the striatum was studied in seven macaques and one squirrel monkey. Deposits of anterograde tracers were made in the two lateral-most subdivisions of the central complex, i.e., the middle part (or pars media) and the lateral part (or pars paralateralis). All injections avoided the pars parafascicularis. The intrastriatal distribution of labeled axonal endings was mapped in relation to the standard ventricular (CA-CP) system of coordinates. Labeled endings were observed in the major posterior and dorsal parts of the putamen (excluding its anteromedial and ventral parts) and also in a restricted ventrolateral part of the caudate nucleus. The topography of the central territory of the striatum, defined as the striatal space receiving axons from the central complex, was found to correspond exactly to that of the cortical sensorimotor territory delineated after cortical injections. The termination pattern of the central axons within the striatum was patchy. Viewed as a whole, the irregular and hazy patches formed oblique streaks, parallel one with the other. The three-dimensional reconstructions of data from transverse sections revealed that the streaks were bi-dimensional pictures of three-dimensional parasagittal layers covering the whole anteroposterior extent of the cortical sensorimotor territory of the striatum. Our work shows that the pars media of the central complex, which receives selectively pallidal afferent axons (François et al., '88: Brain Res. 473:181-186), is the main source of the centroputaminal projection. The probable implication of this in a closed sensorimotor loop of the basal ganglia is discussed.

AIDS-associated progressive multifocal leukoencephalopathy revealed by new-onset seizures.

PURPOSE: To describe the clinical features of new-onset seizures in HIV-1-infected persons with progressive multifocal leukoencephalopathy (PML), and to discuss potential mechanisms. PATIENTS AND METHODS: Forty-nine consecutive HIV-1-infected patients with PML attended our institutions between January 1988 and September 1993. We retrospectively analyzed cases with seizures as the presenting symptom of PML. RESULTS: Twenty percent of the HIV-1-infected patients with PML presented with new-onset seizures of various types, generalized or partial. None of them met the criteria of the AIDS dementia complex or had a concomitant opportunistic infection. Their mean CD4 cell count was < 60/mm3. Brain magnetic resonance imaging showed areas of increased signal intensity on T2-weighted images in 9 cases, and atrophy in only 1 case. Lesions most often involved subcortical white matter in parieto-occipital or frontal lobes, but 2 patients had posterior fossa lesions. Image-guided stereotactic brain biopsies in 8 cases and postmortem examination in 2 confirmed the diagnosis of PML. Typical histological lesions were observed in all cases, and positive immunolabelling of oligodendroglial nuclei was obtained in all cases with the polyclonal antibody directed against late SV40 antigens. Putative causative factors for the seizures include demyelinated lesions adjacent to the cerebral cortex acting as irritative foci, axonal conduction abnormalities, or disturbances of the neuron-glia balance. CONCLUSION: These cases illustrate that PML should be considered as a possible cause of new-onset seizures in patients with HIV-1 infection.

Topographic distribution of the neurons of the central complex (centre médian-parafascicular complex) and of other thalamic neurons projecting to the striatum in macaques.

The distribution of the neurons of the central complex (or "centre médian-parafascicular complex") and of other thalamic regions projecting to the striatum was studied using a cartographic technique based on ventricular landmarks. The brain of a macaque was used as a reference for the cytoarchitectonic study of the complex. Three parts were isolated: the pars parafascicularis (or medial part), the pars media (or middle part) and the pars paralateralis (or lateral part). Wheat germ agglutinin conjugated to horseradish peroxidase was stereotaxically injected into either the sensorimotor or the associative territory of the striatum (i.e. the striatal space occupied by the axonal endings coming from either the sensorimotor or the associative cortex) of four macaques. Neurons projecting to the sensorimotor territory of the striatum were found to be located within the pars media (middle part) of the central complex while neurons projecting to the associative territory of the striatum were located within the pars parafascicularis. In all experimental cases, labelled neurons were scarce or absent in the pars paralateralis (or lateral part). Outside the central complex, neurons projecting to the sensorimotor territory of the striatum were scattered within the lateral part of the lateral mass, in the intralaminar nuclei and in the posterior part of the internal lamina. Neurons projecting to the associative territory of the striatum were observed mainly in the paraventricular region, dorsal to the rostral part of the lateral mass, and in the dorsolateral part of the nucleus oralis medialis. Our three-dimensional analysis of the clusters of the central complex cells projecting to the two striatal territories justifies the partitioning of the central complex into three parts. The pars media (or middle part), which projects to the sensorimotor territory of the striatum, receives selectively pallidal afferent axons. It belongs to the Nauta-Mehler loop, a closed loop linking the central complex to the basal ganglia. The pars parafascicularis, which projects to the associative territory of the striatum, seems more related to oculomotor neuronal systems. The pars paralateralis (or lateral part) appears to have very little, if any, relation with the striatum.

Prognostic significance of transient complete atrioventricular block during radiofrequency ablation of atrioventricular node reentrant tachycardia.

One hundred eighty-six consecutive patients underwent radiofrequency ablation and were divided into 2 groups: group 1 included 19 patients (13 women, mean age 50 +/- 15 years) with transient atrioventricular (AV) block during the procedure. The duration of AV block ranged from 4 seconds to 30 minutes (mean 2.8 +/- 7.0 minutes); and group 2 included 167 patients (142 women, mean age 40 +/- 17 years) without transient AV block. Follow-up was 8.6 +/- 8.3 months in group 1 and 10.1 +/- 9.4 months in group 2. No significant differences were observed between the 2 groups concerning the ablation approach (fast or slow pathway), the number of radiofrequency applications, and recurrences of tachycardia. Four patients from group 1 who underwent fast pathway ablation developed late complete AV block, whereas no patient in group 2 had such a complication (p = 0.0001). Late complete AV block occurred 20 hours, 6 days, 1 month, and 25 days after ablation, respectively, and was not related to the duration of transient AV block. Another patient from group 1 developed an asymptomatic 2:1 AV block during exercise, 3 months after slow pathway ablation. Transient AV block, a common finding occurring as often during fast as during slow pathway ablation, did not preclude recurrences of tachycardia but was associated with late complete AV block.