Microglia Density and Its Association With Disease Duration, Severity, and Orexin Levels in Patients With Narcolepsy Type 1.

BACKGROUND AND OBJECTIVES: Narcolepsy type 1 (NT1) is due to the loss of hypothalamic neurons that produce orexin (ORX), by a suspected immune-mediated process. Rare postmortem studies are available and failed to detect any inflammation in the hypothalamic region, but these brains were collected years after the first symptoms. In vivo studies close to disease onset are lacking. We aimed to explore microglia density in the hypothalamus and thalamus in NT1 compared with controls using [18F]DPA-714 PET and to study in NT1 the relationships between microglia density in the hypothalamus and in other regions of interest (ROIs) with disease duration, severity, and ORX levels. METHODS: Patients with NT1 and controls underwent a standardized clinical evaluation and [18F]DPA-714 PET imaging using a radiolabeled ligand specific to the 18 kDa translocator protein (TSPO). TSPO genotyping determined receptor affinity. Images were processed on peripheral module interface using standard uptake value (SUV) on ROIs: hypothalamus, thalamus, frontal area, cerebellum, and the whole brain. SUV ratios (SUVr) were calculated by normalizing SUV with cerebellum uptake. RESULTS: A total of 41 patients with NT1 (21 adults, 20 children, 10 with recent disease onset <1 year) and 35 controls were included, with no significant difference between groups for [18F]DPA-714 binding (SUV/SUVr) in the hypothalamus and thalamus. Unexpectedly, significantly lower SUVr in the whole brain was found in NT1 compared with controls (0.97 ± 0.06 vs 1.08 ± 0.22, p = 0.04). The same finding between NT1 and controls in the whole brain was observed in those with high or mixed TSPO affinity (p = 0.03 and p = 0.04). Similar trend was observed in the frontal area in NT1 (0.96 ± 0.09 vs 1.09 ± 0.25, p = 0.05). In NT1, no association was found between SUVr in different ROIs and age, disease duration, severity, or ORX levels. DISCUSSION: We found no evidence of in vivo increased microglia density in NT1 compared with controls, even close to disease onset, and even unexpectedly a decrease in the whole brain of these patients. These findings do not support the presence of neuroinflammation in the destruction process of ORX neurons. TRIAL REGISTRATION INFORMATION: ClinicalTrials.org NCT03754348.

Evolution in the management of vestibular schwannoma: a single-center 15-year experience.

PURPOSE: To highlight the changes in the management of vestibular schwannoma (VS) since 2004 with a focus on small- to middle-size VS. METHODS: Retrospective analysis of the decisions made in skull base tumor board between 2004 and 2021. RESULTS: 1819 decisions were analyzed (average age 59.25, 54% females). Overall, 850 (47%) cases were allocated to a Wait and Scan (WS) approach, 416 (23%) received radiotherapy and 553 (30%) were treated surgically (MS). All stages considered WS increased from 39% before 2010 to 50% after 2010. Similarly, Stereotactic Radio Therapy (SRT) increased from 5 to 18%. MS decreased from 46 to 25%. It was more commonly proposed to younger patients and larger tumors, p < 0.001. For Koos stages 1, 2, and 3 there was a statistically significant increase in SRT, and a decrease in MS, p < 0.001. WS also increased for stages 1 and 2. However, such a trend was not observed for stage 3. MS remained the primary treatment modality for stage 4 tumors throughout the study period, p = 0.057. The significance of advanced age as a factor favoring SRT decreased over time. The opposite is true for serviceable hearing. There was also a decrease in the percentage of the justification "young age" in the MS category. CONCLUSION: The is a continuing trend towards non-surgical treatment. Small- to medium-sized VS witnessed an increase in both WS and SRT. There is only an increase in SRT for moderately large VS. Physicians are less and less considering young age as a factor favoring MS over SRT. There is a tendency towards favoring SRT when hearing is serviceable.

Specific profiles of new-onset vs. non-inaugural status epilepticus: From diagnosis to 1-year outcome.

While new-onset status epilepticus (NOSE) is a harbinger of chronic epilepsy, prospective medical data are sparse in terms of specifying whether the evolution of status epilepticus (SE) and seizure expression in NOSE resembles what occurs in patients who have already been diagnosed with epilepsy [non-inaugural SE (NISE)] in all aspects apart from its inaugural nature. The aim of this study was to compare the clinical, MRI, and EEG features that could distinguish NOSE from NISE. We conducted a prospective monocentric study in which all patients ≥18 years admitted for SE over a 6-month period were included. A total of 109 patients (63 NISE and 46 NOSE cases) were included. Despite similar modified Rankin scores before SE, several aspects of the clinical history distinguished NOSE from NISE patients. NOSE patients were older and frequently had neurological comorbidity and preexisting cognitive decline, but they had a similar prevalence of alcohol consumption to NISE patients. NOSE and NISE evolve in the same proportions as refractory SE (62.5% NOSE, 61% NISE) and share common features such as the same incidence (33% NOSE, 42% NISE, and p = 0.53) and volumes of peri-ictal abnormalities on MRI. However, in NOSE patients, we observed greater non-convulsive semiology (21.7% NOSE, 6% NISE, and p = 0.02), more periodic lateral discharges on EEG (p = 0.004), later diagnosis, and higher severity according to the STESS and EMSE scales (p < 0.0001). Mortality occurred in 32.6% of NOSE patients and 21% of NISE patients at 1 year (p = 0.19), but with different causes of death occurring at different time points: more early deaths directly linked to SE at 1 month occurred in the NOSE group, while there were more remote deaths linked to causal brain lesions in the NISE group at final follow-up. In survivors, 43.6% of the NOSE cases developed into epilepsy. Despite acute causal brain lesions, the novelty related to its inaugural nature is still too often associated with a delay in diagnosing SE and a poorer outcome, which justifies the need to more clearly specify the various types of SE to constantly raise awareness among clinicians. These results highlight the relevance of including novelty-related criteria, clinical history, and temporality of occurrence in the nosology of SE.

Erdheim-Chester Disease Revealed by Central Positional Nystagmus: A Case Report.

Erdheim-Chester disease (ECD) is a rare histiocytic disorder, recently recognized to be neoplastic. The clinical phenotype of the disease is extremely heterogeneous, and depends on the affected organs, with the most frequently reported manifestations being bone pain, diabetes insipidus and neurological disorders including ataxia. In this article, we report on a case of a 48-year-old woman, whose initial symptom of gait instability was isolated. This was associated with positional nystagmus with central features: nystagmus occurring without latency, clinically present with only mild symptoms, and resistant to repositioning maneuvers. The cerebral MRI showed bilateral intra-orbital retro-ocular mass lesions surrounding the optic nerves and T2 hyperintensities in the pons and middle cerebellar peduncles. A subsequent CT scan of the chest abdomen and pelvis found a left "hairy kidney", while 18 F-FDG PET-CT imaging disclosed symmetric 18F-FDG avidity predominant at the diametaphyseal half of both femurs. Percutaneous US-guided biopsy of perinephric infiltrates and the kidney showed infiltration by CD68(+), CD1a(-), Langerin(-), PS100(-) foamy histiocytes with BRAF V600E mutation. The combination of the different radiological abnormalities and the result of the biopsy confirmed the diagnosis of ECD. Many clinical and radiological descriptions are available in the literature, but few authors describe vestibulo-ocular abnormalities in patients with ECD. Here, we report on a case of ECD and provide a precise description of the instability related to central positional nystagmus, which led to the diagnosis of ECD.

Assessment of quality of life with the multiple system atrophy health-related quality of life scale.

BACKGROUND: Multiple system atrophy (MSA) has considerable effect on health-related quality of life (Hr-QoL). The aim of this study was to prospectively evaluate Hr-QoL by using the MSA health-related Quality of Life (MSA-QoL) scale. METHODS: Evaluation of 100 patients at baseline and after a mean follow-up of 11.5 months was performed. Assessment was made of potential associations with established markers of disease progression. Calculation was performed of sample-size estimates for various effect sizes. RESULTS: MSA-QoL scale scores were less responsive to change than Unified MSA Rating Scale (UMSARS) scores. Responsiveness was largely improved and reasonable sample-size estimates were obtained when limiting the analysis to items with significant change over time. CONCLUSIONS: The UMSARS remains the "gold standard" for disease-modifying/neuroprotection trials. An MSA-QoL Change Scale, based on the most responsive items, may become a valuable tool.

Assessment of the Scopa-Aut questionnaire in multiple system atrophy: relation to UMSARS scores and progression over time.

Autonomic failure is a key feature of multiple system atrophy (MSA). Moreover, early autonomic failure is an independent predictive factor for rapid disease progression and shorter survival. The assessment of autonomic failure is therefore important for both, the diagnosis and prognosis of MSA. Here, we evaluate autonomic dysfunction in MSA patients by the Scopa-Aut questionnaire. Potential associations between the Scopa-Aut questionnaire and established markers of disease progression - that is the Unified MSA Rating Scale (UMSARS) - were further assessed. The results confirm early and prominent autonomic failure in MSA patients. Relative scores were highest for the sexual and urinary subdomains. Surprisingly, relative scores in the cardiovascular subdomain were lowest suggesting that the Scopa-Aut questionnaire is suboptimal for the screening and evaluation of cardiovascular symptoms in MSA. A multivariate regression showed an association between total Scopa-Aut and UMSARS I scores. No significant changes in Scopa-Aut scores were observed during follow-up except for the urinary subdomain, while UMSARS I, II and IV scores significantly increased over time. In conclusion, Scopa-Aut can be used as a simple auto-questionnaire for the screening of autonomic symptoms in multiple system atrophy. It seems not useful as endpoint for disease-modification or neuroprotection trials.

Hallucinations in narcolepsy with and without cataplexy: contrasts with Parkinson's disease.

BACKGROUND: Narcolepsy and Parkinson's disease (PD) are associated with hallucinations, excessive daytime sleepiness, REM sleep behavior disorder (RBD), as well as complete (narcolepsy with cataplexy) vs. partial (PD, narcolepsy without cataplexy) hypocretin-1 deficiency. OBJECTIVE: To compare the hallucinations associated with narcolepsy to those of PD. METHODS: One hundred patients with narcolepsy (with and without cataplexy) and 100 patients with PD were consecutively interviewed about their hallucinations (frequency, phenomenology, insight into unreality and association with sleep) as well as their risk factors. RESULTS: Hallucinations occurred more frequently and with more motor and multimodal aspects in narcolepsy with cataplexy (59%) than in narcolepsy without cataplexy (28%) and PD (26%). Compared to PD, the hallucinations in narcolepsy were less frequently of the passage/presence type (passage: brief visions of a person or animal passing sideways; presence: perception that a living character or an animal is behind or near the subject, without the subject actually seeing, hearing or touching it), more frequently auditory and more often associated with sleep. However, in 40% of the patients with narcolepsy and 54% of the patients with PD, the hallucinations occurred while the patients were wide awake. Patients with cataplexy had reduced immediate insight into the unreality of their hallucinations compared to patients with PD, but the delusions were exceptional (2%), transient and based on hallucinations in both groups. The risk factors for hallucinations were sleep paralysis and RBD in narcolepsy and motor disability and sleepiness in PD. CONCLUSIONS: The multimodal, dreamlike aspect of hallucinations in narcolepsy with cataplexy could transiently impair the patients' insight. The high frequency of these hallucinations (compared to those in narcolepsy without cataplexy or PD) suggests that complete (more than partial) hypocretin-1 deficiency promotes hallucinations.

The improvement of movement and speech during rapid eye movement sleep behaviour disorder in multiple system atrophy.

Multiple system atrophy is an atypical parkinsonism characterized by severe motor disabilities that are poorly levodopa responsive. Most patients develop rapid eye movement sleep behaviour disorder. Because parkinsonism is absent during rapid eye movement sleep behaviour disorder in patients with Parkinson's disease, we studied the movements of patients with multiple system atrophy during rapid eye movement sleep. Forty-nine non-demented patients with multiple system atrophy and 49 patients with idiopathic Parkinson's disease were interviewed along with their 98 bed partners using a structured questionnaire. They rated the quality of movements, vocal and facial expressions during rapid eye movement sleep behaviour disorder as better than, equal to or worse than the same activities in an awake state. Sleep and movements were monitored using video-polysomnography in 22/49 patients with multiple system atrophy and in 19/49 patients with Parkinson's disease. These recordings were analysed for the presence of parkinsonism and cerebellar syndrome during rapid eye movement sleep movements. Clinical rapid eye movement sleep behaviour disorder was observed in 43/49 (88%) patients with multiple system atrophy. Reports from the 31/43 bed partners who were able to evaluate movements during sleep indicate that 81% of the patients showed some form of improvement during rapid eye movement sleep behaviour disorder. These included improved movement (73% of patients: faster, 67%; stronger, 52%; and smoother, 26%), improved speech (59% of patients: louder, 55%; more intelligible, 17%; and better articulated, 36%) and normalized facial expression (50% of patients). The rate of improvement was higher in Parkinson's disease than in multiple system atrophy, but no further difference was observed between the two forms of multiple system atrophy (predominant parkinsonism versus cerebellar syndrome). Video-monitored movements during rapid eye movement sleep in patients with multiple system atrophy revealed more expressive faces, and movements that were faster and more ample in comparison with facial expression and movements during wakefulness. These movements were still somewhat jerky but lacked any visible parkinsonism. Cerebellar signs were not assessable. We conclude that parkinsonism also disappears during rapid eye movement sleep behaviour disorder in patients with multiple system atrophy, but this improvement is not due to enhanced dopamine transmission because these patients are not levodopa-sensitive. These data suggest that these movements are not influenced by extrapyramidal regions; however, the influence of abnormal cerebellar control remains unclear. The transient disappearance of parkinsonism here is all the more surprising since no treatment (even dopaminergic) provides a real benefit in this disabling disease.

Thought disorders among non-demented outpatients with Parkinson's disease: prevalence and associated factors.

The objectives of the study are to evaluate the prevalence and the associated factors of thought disorders in a large cross-sectional population of non-demented out patients with Parkinson's disease (PD). Four-hundred and nineteen consecutive non-demented PD patients were studied through the DoPaMiP cross-sectional study. Demographic and clinical variables were recorded, including motor and cognitive status, dependency, depressive and anxious symptoms, dysautonomia and sleep disorders. The presence of thought disorders over the past 15 days was assessed by the Unified Parkinson's Disease Rating Scale part I. Patients with and without thought disorders were compared using parametric tests. Logistic regression was applied to significant data. Thought disorders were present in 105 patients (25%) including vivid dreams in 83 (19.8%), benign hallucinations in 17 (4.1%), and hallucinations without insight in 5 (1.2%). No patient had delusion. Patients with thought disorders were more dependent than the others. Thought disorders were associated with longer PD duration, greater UPDRS scores and the presence of motor complications. Conversely, UPDRS tremor sub-score was lower in patients without thought disorders. Thought disorders were also associated with dysautonomia, lower MMSE score, depression and sleep disorders. Logistic regression identified PD duration, lower MMSE score, depressive and dysautonomic signs as independent risk factors. In conclusion, mild thought disorders were present in 25% of non-demented outpatients with PD, but hallucinations were present in 5% only. Thought disorders were associated with PD duration, depressive and dysautonomic symptoms and lower MMSE score.