A Novel Approach to Screen for Somatosensory Evoked Potentials in Critical Care.

BACKGROUND: Somatosensory evoked potentials (SSEPs) help prognostication, particularly in patients with diffuse brain injury. However, use of SSEP is limited in critical care. We propose a novel, low-cost approach allowing acquisition of screening SSEP using widely available intensive care unit (ICU) equipment, specifically a peripheral "train-of-four" stimulator and standard electroencephalograph. METHODS: The median nerve was stimulated using a train-of-four stimulator, and a standard 21-channel electroencephalograph was recorded to generate the screening SSEP. Generation of the SSEP was supported by visual inspection, univariate event-related potentials statistics, and a multivariate support vector machine (SVM) decoding algorithm. This approach was validated in 15 healthy volunteers and validated against standard SSEPs in 10 ICU patients. The ability of this approach to predict poor neurological outcome, defined as death, vegetative state, or severe disability at 6 months, was tested in an additional set of 39 ICU patients. RESULTS: In each of the healthy volunteers, both the univariate and the SVM methods reliably detected SSEP responses. In patients, when compared against the standard SSEP method, the univariate event-related potentials method matched in nine of ten patients (sensitivity = 94%, specificity = 100%), and the SVM had 100% sensitivity and specificity when compared with the standard method. For the 49 ICU patients, we performed both the univariate and the SVM methods: a bilateral absence of short latency responses (n = 8) predicted poor neurological outcome with 0% FPR (sensitivity = 21%, specificity = 100%). CONCLUSIONS: Somatosensory evoked potentials can reliably be recorded using the proposed approach. Given the very good but slightly lower sensitivity of absent SSEPs in the proposed screening approach, confirmation of absent SSEP responses using standard SSEP recordings is advised.

Description and Outcome of Severe Hypoglycemic Encephalopathy in the Intensive Care Unit.

BACKGROUND: Disorders of consciousness due to severe hypoglycemia are rare but challenging to treat. The aim of this retrospective cohort study was to describe our multimodal neurological assessment of patients with hypoglycemic encephalopathy hospitalized in the intensive care unit and their neurological outcomes. METHODS: Consecutive patients with disorders of consciousness related to hypoglycemia admitted for neuroprognostication from 2010 to 2020 were included. Multimodal neurological assessment included electroencephalography, somatosensory and cognitive event-related potentials, and morphological and quantitative magnetic resonance imaging (MRI) with quantification of fractional anisotropy. Neurological outcomes at 28 days, 3 months, 6 months, 1 year, and 2 years after hypoglycemia were retrieved. RESULTS: Twenty patients were included. After 2 years, 75% of patients had died, 5% remained in a permanent vegetative state, 10% were in a minimally conscious state, and 10% were conscious but with severe disabilities (Glasgow Outcome Scale-Extended scores 3 and 4). All patients showed pathologic electroencephalography findings with heterogenous patterns. Morphological brain MRI revealed abnormalities in 95% of patients, with various localizations including cortical atrophy in 65% of patients. When performed, quantitative MRI showed decreased fractional anisotropy affecting widespread white matter tracts in all patients. CONCLUSIONS: The overall prognosis of patients with severe hypoglycemic encephalopathy was poor, with only a small fraction of patients who slowly improved after intensive care unit discharge. Of note, patients who did not improve during the first 6 months did not recover consciousness. This study suggests that a multimodal approach capitalizing on advanced brain imaging and bedside electrophysiology techniques could improve diagnostic and prognostic performance in severe hypoglycemic encephalopathy.

Guillain-Barré Syndrome During Platinum-Based Chemotherapy: A Case Series and Review of the Literature.

Platinum-based chemotherapy is commonly associated with toxic sensory neuropathies, but also, although rarely, with Guillain-Barré syndrome (GBS). We describe five patients who developed GBS while receiving platinum-based chemotherapy for a solid tumor and report the five cases published so far. Most patients had received cumulative platinum doses below known neurotoxic levels, and all of them had an optimal outcome after platinum discontinuation, associated in most cases with administration of intravenous immunoglobulin. Clinical presentation, electroneuromyography, and cerebrospinal fluid analysis help clinicians to differentiate GBS from toxic neuropathy. Platinum compounds are the only chemotherapeutic agents used for solid tumors that have been associated to GBS. Thus, we propose that GBS may constitute a non-dose-dependent side effect of platinum drugs and that awareness needs to be raised among oncologists on this rare but potentially life-threatening complication of platinum chemotherapy. IMPLICATIONS FOR PRACTICE: Many patients on platinum-based chemotherapy for solid tumors develop sensory neuropathy, a common dose-dependent side effect. The authors propose that Guillain-Barré syndrome may constitute an immune-mediated, non-dose-related side effect of platinum-based chemotherapy. Prompt diagnosis of Guillain-Barré syndrome and distinction from classical toxic neuropathy are crucial for optimal treatment. Platinum discontinuation, associated if needed to intravenous immunoglobulin administration, radically changes the course of the disease and minimizes neurological sequelae.

Increased blood-brain barrier permeability on perfusion computed tomography predicts hemorrhagic transformation in acute ischemic stroke.

BACKGROUND/PURPOSE: Perfusion computed tomography (CT) is capable of measuring the permeability surface product (PS). PS reflects the permeability of the blood-brain barrier, involved in the pathophysiology of hemorrhagic transformation (HT) of ischemic stroke. The aim of our study was to determine if an increased PS can predict HT. METHODS: A total of 86 patients with ischemic stroke were included. They underwent multimodality CT, including the measurement of PS. We compared the clinical and radiological characteristics of patients who developed HT to those who did not, using univariate analysis. Multivariate regression analyses were then used to determine HT predictors. RESULTS: HT was observed in 27 patients (31%). Infarct PS was significantly associated with HT (p = 0.047), as were atrial fibrillation (p = 0.03), admission National Institute of Health Stroke Scale score (p = 0.02), infarct volume (p = 0.0004), presence of large-vessel occlusion (p = 0.0005) and a poorer collateral status (p = 0.003). Using logistic regression modeling, an infarct PS >0.84 ml/100 g/min was an independent predictor of HT (OR 28, 95% CI 1.75-452.98; p = 0.02). Other independent predictors of HT were infarct volume and a history of atrial fibrillation. CONCLUSIONS: Our findings suggest that infarct PS can be a predictor of HT and may help clinicians to improve patient care around thrombolysis decisions in the acute phase of ischemic stroke.

Older patients with COVID-19 and neuropsychiatric conditions: A study of risk factors for mortality.

BACKGROUND: Little is known about risk factors for mortality in older patients with COVID-19 and neuropsychiatric conditions. METHODS: We conducted a multicentric retrospective observational study at Assistance Publique-Hôpitaux de Paris. We selected inpatients aged 70 years or older, with COVID-19 and preexisting neuropsychiatric comorbidities and/or new neuropsychiatric manifestations. We examined demographics, comorbidities, functional status, and presentation including neuropsychiatric symptoms and disorders, as well as paraclinical data. Cox survival analysis was conducted to determine risk factors for mortality at 40 days after the first symptoms of COVID-19. RESULTS: Out of 191 patients included (median age 80 [interquartile range 74-87]), 135 (71%) had neuropsychiatric comorbidities including cognitive impairment (39%), cerebrovascular disease (22%), Parkinsonism (6%), and brain tumors (6%). A total of 152 (79%) patients presented new-onset neuropsychiatric manifestations including sensory symptoms (6%), motor deficit (11%), behavioral (18%) and cognitive (23%) disturbances, gait impairment (11%), and impaired consciousness (18%). The mortality rate at 40 days was 19.4%. A history of brain tumor or Parkinsonism or the occurrence of impaired consciousness were neurological factors associated with a higher risk of mortality. A lower Activities of Daily Living score (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.58-0.82), a neutrophil-to-lymphocyte ratio ≥ 9.9 (HR 5.69, 95% CI 2.69-12.0), and thrombocytopenia (HR 5.70, 95% CI 2.75-11.8) independently increased the risk of mortality (all p < .001). CONCLUSION: Understanding mortality risk factors in older inpatients with COVID-19 and neuropsychiatric conditions may be helpful to neurologists and geriatricians who manage these patients in clinical practice.

Association of Clinical, Biological, and Brain Magnetic Resonance Imaging Findings With Electroencephalographic Findings for Patients With COVID-19.

Importance: There is evidence of central nervous system impairments associated with coronavirus disease 2019 (COVID-19) infection, including encephalopathy. Multimodal monitoring of patients with COVID-19 may delineate the specific features of COVID-19-related encephalopathy and guide clinical management. Objectives: To investigate clinical, biological, and brain magnetic resonance imaging (MRI) findings in association with electroencephalographic (EEG) features for patients with COVID-19, and to better refine the features of COVID-19-related encephalopathy. Design, Setting, and Participants: This retrospective cohort study conducted in Pitié-Salpêtrière Hospital, Paris, France, enrolled 78 hospitalized adults who received a diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) and underwent EEG between March 30 and June 11, 2020. Exposures: Detection of SARS-CoV-2 from a nasopharyngeal specimen using a reverse transcription-polymerase chain reaction assay or, in the case of associated pneumonia, on a computed tomography scan of the chest. Main Outcomes and Measures: Data on the clinical and paraclinical features of the 78 patients with COVID-19 were retrieved from electronic patient records. Results: Of 644 patients who were hospitalized for COVID-19, 78 (57 men [73%]; mean [SD] age, 61 [12] years) underwent EEG. The main indications for EEG were delirium, seizure-like events, and delayed awakening in the intensive care unit after stopping treatment with sedatives. Sixty-nine patients showed pathologic EEG findings, including metabolic-toxic encephalopathy features, frontal abnormalities, periodic discharges, and epileptic activities. Of 57 patients who underwent brain MRI, 41 showed abnormalities, including perfusion abnormalities, acute ischemic lesions, multiple microhemorrhages, and white matter-enhancing lesions. Fifty-five patients showed biological abnormalities, including dysnatremia, kidney failure, and liver dysfunction, the same day as the EEG. The results of cerebrospinal fluid analysis were negative for SARS-Cov-2 for all tested patients. Nine patients who had no identifiable cause of brain injury outside COVID-19 were further isolated; their brain injury was defined as COVID-19-related encephalopathy. They represented 1% (9 of 644) of patients with COVID-19 requiring hospitalization. Six of these 9 patients had movement disorders, 7 had frontal syndrome, 4 had brainstem impairment, 4 had periodic EEG discharges, and 3 had MRI white matter-enhancing lesions. Conclusions and Relevance: The results from this cohort of patients hospitalized with COVID-19 suggest there are clinical, EEG, and MRI patterns that could delineate specific COVID-19-related encephalopathy and guide treatment strategy.

[Organic and psychiatric intricacy: The complex psychiatric disorder concept, paraclinical investigations]. / Intrications organo-psychiatriques : le concept de troubles psychiatriques complexes, quels examens complémentaires ?

The purpose of this article is to describe complex psychiatric disorders, to recall "minimal classical" explorations in psychiatry, to describe the concept of "complex psychiatric disorders" and to propose a systematized method of exploration. Some organic diseases are well known for their links with psychiatric disorders (manic syndrome and hyperthyroidism, depressive syndrome and corticotropic insufficiency, anxiety disorder and heart disease, etc.). Many other neurological, autoimmune, metabolic, paraneoplastic or endocrine pathologies can have essentially psycho-behavioral manifestations before being neurological or systemic. A large number of factors (nutritional, toxic, immunological, etc.), often ignored, influence the links between organicity and psychiatric pathologies. It is necessary to optimize the medical management of these patients in whom the psychiatric diagnosis masks a curable organo-psychiatric cause.

Subthalamic stimulation: toward a simplification of the electrophysiological procedure.

BACKGROUND: The aim of the present study was to assess the consequences of a simplification of the electrophysiological procedure on the post-operative clinical outcome after subthalamic nucleus implantation in Parkinson disease. METHODS: Microelectrode recordings were performed on 5 parallel trajectories in group 1 and less than 5 trajectories in group 2. Clinical evaluations were performed 1 month before and 6 months after surgery. RESULTS: After surgery, the UPDRS III score in the off-drug/on-stimulation and on-drug/on-stimulation conditions significantly improved by 66,9% and 82%, respectively in group 1, and by 65.8% and 82.3% in group 2 (P<0.05). Meanwhile, the total number of words (P<0.05) significantly decreased for fluency tasks in both groups. Motor disability improvement and medication reduction were similar in both groups. CONCLUSIONS: Our results suggest that the electrophysiological procedure should be simplified as the team's experience increases.

Seizures in dominantly inherited Alzheimer disease.

OBJECTIVE: To assess seizure frequency in a large French cohort of autosomal dominant early-onset Alzheimer disease (ADEOAD) and to determine possible correlations with causative mutations. METHODS: A national multicentric study was performed in patients with ADEOAD harboring a pathogenic mutation within PSEN1, PSEN2, APP, or a duplication of APP, and a minimal follow-up of 5 years. Clinical, EEG, and imaging data were systematically recorded. RESULTS: We included 132 patients from 77 families: 94 PSEN1 mutation carriers (MCs), 16 APP duplication carriers, 15 APP MCs, and 7 PSEN2 MCs. Seizure frequency was 47.7% after a mean follow-up of 8.4 years (range 5-25). After 5-year follow-up and using a Cox model analysis, the percentages of patients with seizures were respectively 19.1% (10.8%-26.7%) for PSEN1, 28.6% (0%-55.3%) for PSEN2, 31.2% (4.3%-50.6%) for APP duplications, and no patient for APP mutation. APP duplication carriers showed a significantly increased seizure risk compared to both APP MCs (hazard ratio [HR] = 5.55 [95% confidence interval 1.87-16.44]) and PSEN1 MCs (HR = 4.46 [2.11-9.44]). Among all PSEN1 mutations, those within the domains of protein hydrophilic I, transmembrane II (TM-II), TM-III, TM-IV, and TM-VII were associated with a significant increase in seizure frequency compared to other domains (HR = 4.53 [1.93-10.65], p = 0.0005). CONCLUSIONS: Seizures are a common feature of ADEOAD. In this population, risk was significantly higher in the APP duplication group than in all other groups. Within PSEN1, 5 specific domains were associated with a higher seizure risk indicating specific correlations between causative mutation and seizures.

Pre-operative obesity may influence subthalamic stimulation outcome in Parkinson's disease.

BACKGROUND: Pre-operative predictive factors for optimal post-operative effect of subthalamic nucleus (STN) stimulation in Parkinson's disease (PD) have been previously reported. No study has explicitly assessed the link between excess pre-operative body weight and STN stimulation outcome. METHODS: We retrospectively compared STN stimulation outcomes of 36 PD patients with excess pre-operative body weight (group 1) and 36 matched normal-weight pre-operative (group 2) PD patients. We focused on the post-operative outcomes in the sub-group of 12 obese (group 3) PD patients. RESULTS: The post-operative motor improvement and the reduction of severity of levodopa-related complications were not statistically different between groups 1 and 2 (P>0.05). In the obese group (group 3), the axial sub-score significantly improved by 29.8% in the on-drug/on-stimulation conditions whereas the improvement was not significant in the off-drug/on-stimulation condition (22.4%, P=0.20). The post-operative Mattis Dementia Rating Score was significantly reduced in group 1 and group 3. DISCUSSION: We considered that the post-operative axial impairment observed in the obese PD patients might be essentially consecutive to disease progression and/or post-operative DBS consequences, i.e. surgical procedure or electrical stimulation itself. Moreover, it could be argued that musculoskeletal disorders associated with obesity were responsible for the incomplete efficacy of STN stimulation on axial sub-scores, by increasing gait and balance impairment. CONCLUSION: Pre-operative obesity may be regarded as a predictive clinical factor of axial and cognitive impairment after STN-DBS.

Decline in verbal fluency after subthalamic nucleus deep brain stimulation in Parkinson's disease: a microlesion effect of the electrode trajectory?

BACKGROUND: Decline in verbal fluency (VF) is frequently reported after chronic deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson disease (PD). OBJECTIVE: We investigated whether the trajectory of the implanted electrode correlate with the VF decline 6 months after surgery. METHODS: We retrospectively analysed 59 PD patients (mean age, 61.9 ± 7; mean disease duration, 13 ± 4.6) who underwent bilateral STN-DBS. The percentage of VF decline 6 months after STN-DBS in the on-drug/on-stimulation condition was determined in respect of the preoperative on-drug condition. The patients were categorised into two groups (decline and stable) for each VF. Cortical entry angles, intersection with deep grey nuclei (caudate, thalamic or pallidum), and anatomical extent of the STN affected by the electrode pathway, were compared between groups. RESULTS: A significant decline of both semantic and phonemic VF was found after surgery, respectively 14.9% ± 22.1 (P < 0.05) and 14.2% ± 30.3 (P < 0.05). Patients who declined in semantic VF (n = 44) had a left trajectory with a more anterior cortical entry point (56 ± 53 versus 60 ± 55 degree, P = 0.01) passing less frequently trough the thalamus (P = 0.03). CONCLUSIONS: Microlesion of left brain regions may contribute to subtle cognitive impairment following STN-DBS in PD.

Tendon rupture as an adverse effect of rasagiline.

A 66-year-old woman with advanced Parkinson disease (PD) was referred to our center for an adjustment of her antiparkinsonian medication. To reduce daily off-time, we introduced rasagiline 1 mg/d. Three days after starting this new treatment, she presented with intense arthralgia that symmetrically affected the shoulders, hands, and hips without myalgia. Ten days later, while walking, she experienced acute pain on the inner side of her right thigh, with the absence of any trauma. Findings of ultrasonography confirming the diagnosis of partial avulsion of the right harmstrings. Rasagiline was stopped immediately, and the arthralgia disappeared within 48 hours and did not recur. To our knowledge, this is the first reported case of a spontaneous tendon rupture possibly caused by rasagiline. Our observation emphasizes that, although often well tolerated, rasagiline may cause muscle and joint complications that could increase disability in patients with PD.

Does early verbal fluency decline after STN implantation predict long-term cognitive outcome after STN-DBS in Parkinson's disease?

BACKGROUNDS: An early and transient verbal fluency (VF) decline and impairment in frontal executive function, suggesting a cognitive microlesion effect may influence the cognitive repercussions related to subthalamic nucleus deep brain stimulation (STN-DBS). METHODS: Neuropsychological tests including semantic and phonemic verbal fluency were administered both before surgery (baseline), the third day after surgery (T3), at six months (T180), and at an endpoint multiple years after surgery (Tyears). RESULTS: Twenty-four patients (mean age, 63.5 ± 9.5 years; mean disease duration, 12 ± 5.8 years) were included. Both semantic and phonemic VF decreased significantly in the acute post-operative period (44.4 ± 28.2% and 34.3 ± 33.4%, respectively) and remained low at 6 months compared to pre-operative levels (decrease of 3.4 ± 47.8% and 10.8 ± 32.1%) (P < 0.05). Regression analysis showed phonemic VF to be an independent factor of decreased phonemic VF at six months. Age was the only independent predictive factor for incident Parkinson's disease dementia (PDD) (F (4,19)=3.4, P<0.03). CONCLUSION: An acute post-operative decline in phonemic VF can be predictive of a long-term phonemic VF deficit. The severity of this cognitive lesion effect does not predict the development of dementia which appears to be disease-related.

Non-motor fluctuations in Parkinson's disease: prevalence, characteristics and management in a large cohort of parkinsonian outpatients.

OBJECTIVE: To describe demographic and clinical characteristics in a group of Parkinson's disease (PD) patients with non-motor fluctuations (NMF) and to evaluate the management of medications proposed to treat NMF. METHODS: Three hundred and three PD patients (mean age, 66 ± 10.3 years; mean disease duration, 10.1 ± 6.5 years) were enrolled. Each patient was interviewed in a non-directed fashion about the main NMF manifestations, i.e. dysautonomic, mental, and sensory symptoms. Both groups of patients with and without NMF were compared. Dysautonomia, motor fluctuations, age, disease duration, and LEDD were included in a multiple regression to determine which were predictive of NMF. RESULTS: NMF were found in 57 (19%) patients, mean age 65 ± 10.1 years, mean age at onset of PD 53.7 ± 10.9 years, mean disease duration 12.5 ± 6.9 years. NMF occurred on average 9.8 ± 7.7 years after the onset of PD. Fifty patients (86%) with NMF had also MF and 10 (21%) had PDD. Twenty-five (44%) patients suffered from sensory, 28 (49%) from autonomic and 25 (44%) from neuropsychiatric symptoms. Both disease and L-Dopa treatment durations, and LEDD were significantly higher in NMF patient's group. Motor fluctuations (p = 0.0016) and presence of dysautonomia (p = 0.007) were found to be two independent predictors of NMF. CONCLUSION: The development of new instruments to assess NMF is crucial for optimized management of advanced PD.

Psychosis revealing familial idiopathic basal ganglia calcification.

We describe the case of a 39-year-old woman presenting with auditory hallucinations and delusions responsive to antipsychotic drugs. Computerized tomography scans revealed basal ganglia calcifications in the proband and in her two asymptomatic parents. Extensive etiological clinicobiological assessment allowed us to exclude known causes of brain calcifications and diagnose familial idiopathic basal ganglia calcification (IBGC). Neurological symptoms associated with psychiatric symptoms are common in IBGC. Nevertheless, purely psychiatric presentations, as demonstrated by the present case, are possible. However, a fortuitous association between asymptomatic IBGC and schizophrenia cannot be ruled out. Only brain imaging, followed by an extensive etiological assessment, allows for diagnosis of this rare disorder.