Stratifying sudden death risk in adults with drug-resistant focal epilepsy: The SUDEP-CARE score.

BACKGROUND AND PURPOSE: A clinical risk score for sudden unexpected death in epilepsy (SUDEP) in patients with drug-resistant focal epilepsy could help improve prevention. METHODS: A case-control study was conducted including (i) definite or probable SUDEP cases collected by the French National Sentinel Mortality Epilepsy Network and (ii) control patients from the French national research database of epilepsy monitoring units. Patients with drug-resistant focal epilepsy were eligible. Multiple logistic regressions were performed. After sensitivity analysis and internal validation, a simplified risk score was developed from the selected variables. RESULTS: Sixty-two SUDEP cases and 620 controls were included. Of 21 potential predictors explored, seven were ultimately selected, including generalized seizure frequency (>1/month vs. <1/year: adjusted odds ratio [AOR] 2.6, 95% confidence interval [CI] 1.25-5.41), nocturnal or sleep-related seizures (AOR 4.49, 95% CI 2.68-7.53), current or past depression (AOR 2.0, 95% CI 1.19-3.34) or the ability to alert someone of an oncoming seizure (AOR 0.57, 95% CI 0.33-0.98). After internal validation, a clinically usable score ranging from -1 to 8 was developed, with high discrimination capabilities (area under the receiver operating curve 0.85, 95% CI 0.80-0.90). The threshold of 3 has good sensitivity (82.3%, 95% CI 72.7-91.8), whilst keeping a good specificity (82.7%, 95% CI 79.8-85.7). CONCLUSIONS: These results outline the importance of generalized and nocturnal seizures on the occurrence of SUDEP, and show a protective role in the ability to alert someone of an oncoming seizure. The SUDEP-CARE score is promising and will need external validation. Further work, including paraclinical explorations, could improve this risk score.

Adult phenotype of KCNQ2 encephalopathy.

BACKGROUND: Pathogenic KCNQ2 variants are a frequent cause of developmental and epileptic encephalopathy. METHODS: We recruited 13 adults (between 18 years and 45 years of age) with KCNQ2 encephalopathy and reviewed their clinical, EEG, neuroimaging and treatment history. RESULTS: While most patients had daily seizures at seizure onset, seizure frequency declined or remitted during childhood and adulthood. The most common seizure type was tonic seizures (early) infancy, and tonic-clonic and focal impaired awareness seizures later in life. Ten individuals (77%) were seizure-free at last follow-up. In 38% of the individuals, earlier periods of seizure freedom lasting a minimum of 2 years followed by seizure recurrence had occurred. Of the 10 seizure-free patients, 4 were receiving a single antiseizure medication (ASM, carbamazepine, lamotrigine or levetiracetam), and 2 had stopped taking ASM. Intellectual disability (ID) ranged from mild to profound, with the majority (54%) of individuals in the severe category. At last contact, six individuals (46%) remained unable to walk independently, six (46%) had limb spasticity and four (31%) tetraparesis/tetraplegia. Six (46%) remained non-verbal, 10 (77%) had autistic features/autism, 4 (31%) exhibited aggressive behaviour and 4 (31%) destructive behaviour with self-injury. Four patients had visual problems, thought to be related to prematurity in one. Sleep problems were seen in six (46%) individuals. CONCLUSION: Seizure frequency declines over the years and most patients are seizure-free in adulthood. Longer seizure-free periods followed by seizure recurrence are common during childhood and adolescence. Most adult patients have severe ID. Motor, language and behavioural problems are an issue of continuous concern.

Emergency room diagnoses of psychogenic nonepileptic seizures with psychogenic status and functional (psychogenic) symptoms: Whopping.

Collecting 130 electronic medical records and diagnoses from emergency room stays of eleven patients with confirmed psychogenic nonepileptic seizure (PNES) over a 17-year period (2001-2018), 48 different diagnostic terms were retrieved. This emphasized the need for a consensual terminology encompassing not only PNES but also all functional transient (paroxysmal) events, including episodes of motor or sensory deficits, and cognitive symptoms. Rather than defining what it is not (PNES, stroke mimicks…), it would be more accurate to define what it is: a paroxysmal functional event.

PNESSE 1: Psychogenic status and status epilepticus: Could they be distinguished retrospectively? A survey among neurologists.

OBJECTIVE: The aim of this study was to evaluate neurologists' reliability in recognizing retrospectively a diagnosis of psychogenic status and status epilepticus (SE) based solely on clinical semiology, as reported in medical charts. METHODS: This is a retrospective analysis of medical records of patients with suspected SE, diagnosed with psychogenic status and SE, proven by video-electroencephalography (EEG) monitoring, over a two-year period, from January 1st 2012 to December 31st 2013. Eight additional patients outside this time frame were included in this series because they had video-EEG proven psychogenic status, and they met all the inclusion criteria. The group with SE was divided into symptomatic SE (SSE) if a precipitating factor was identified, and undetermined SE (USE) if none were identified. Twenty-two neurologists from the CHU de Grenoble-Alpes were asked to fill out a survey where they were asked to score, for each patient, their agreement, using Likert scales, for the respective diagnoses of psychogenic status and SE. Their opinions were based on a provided written sheet summarizing the clinical description of the event and patients' clinical context. Neurologists were blinded to video-EEG monitoring results and final diagnosis. The level of agreement, disagreement, and the homogeneity of neurologist's responses according to the final diagnosis were then calculated. Finally, clinical data, as provided in the event's clinical description and context, considered as highly relevant by neurologists to establish an accurate diagnosis were gathered. RESULTS: Eighteen neurologists completed the survey for 48 patients, including 11 diagnosed with psychogenic status and 37 with SE (30 with SSE and 7 with USE). For patients diagnosed with SE, the presence of a precipitating factor increased the likelihood and the homogeneity among neurologists of a diagnosis of SE (77%), with a specificity (Sp) of 96% and a positive predictive value of 95%. The lack of a precipitating factor significantly decreased the diagnosis likelihood of SE (55%) with a predictive value of 82%. For patients diagnosed with psychogenic status, most of neurologists agreed with the diagnosis of psychogenic status (69%) with a predictive value of 82%, although heterogeneity in the diagnosis was found. According to neurologists participating in this study, most significant terms, found in the medical charts, helping to distinguish SE from psychogenic status were "stereotypical movements", "limb myoclonus", "epilepsy", and "vigilance alteration". To differentiate psychogenic status from SE, most relevant terms used by neurologists were "resistance to eyes opening", "anarchic movements", "prolonged motor manifestations", "limb tremor" and "opisthotonus". However, analysis of the distribution of the terms among the different groups (SSE, USE, and psychogenic status) showed no significant difference. SIGNIFICANCE: This study is in line with previous literature highlighting the difficulty in retrospectively differentiating SE from psychogenic status based on clinical events description recorded in the medical chart.

Long-term negative impact of an inappropriate first antiepileptic medication on the efficacy of a second antiepileptic medication in mice.

Childhood absence epilepsy (CAE) is one of the most frequent epilepsies in infancy. The first-line recommended therapy for CAE is based on the prescription of the narrow-spectrum ethosuximide and the broad-spectrum valproic acid, which have similar efficacy in the first 12 months. Nevertheless, some antiepileptic drugs (AEDs) may worsen seizure duration and type in this syndrome. In line with this, we have encountered a case of identical twins with CAE and early exposure to different antiseizure drugs leading to divergent outcomes. From this, we hypothesized that the first AED to treat CAE may determine the long-term prognosis, especially in the developing brain, and that some situations leading to drug resistance may be explained by use of an inappropriate first AED. Therefore, we investigated this hypothesis by using a genetic mouse model of absence epilepsy (BS/Orl). Mice received a first appropriate or inappropriate AED followed by the same appropriate AED. Our data demonstrate that an inappropriate first AED has a negative impact on the long-term efficacy of a second appropriate AED. This work supports the necessity to effectively diagnose epileptic syndromes prior to medication use, particularly in children, in order to prevent the deleterious effects of an inappropriate initial AED.

An Eye Fixation-Related Potential Study in Two Reading Tasks: Reading to Memorize and Reading to Make a Decision.

We investigated how two different reading tasks, namely reading to memorize [Read & Memorize (RM)] and reading to decide whether a text was relevant to a given topic [Read & Decide (RD)], modulated both eye movements (EM) and brain activity. To this end, we set up an ecological paradigm using the eye fixation-related potentials (EFRP) technique, in which participants freely moved their eyes to process short paragraphs, while their electroencephalography (EEG) activity was recorded in synchronization with their EM. A general linear model was used to estimate at best EFRP, taking account of the overlap between adjacent potentials, and more precisely with the potential elicited at text onset, as well as saccadic potentials. Our results showed that EM patterns were top-down modulated by different task demands. More interestingly, in both tasks, we observed slow-wave potentials that gradually increased across the first eye fixations. These slow waves were larger in the RD task than in the RM task, specifically over the left hemisphere. These results suggest that the decision-making process during reading in the RD task engendered a greater memory load in working memory than that generated in a classic reading task. The significance of these findings is discussed in the light of recent theories and models of working memory processing.

Pallidal deep brain stimulation for dystonia: a long term study.

BACKGROUND: Pallidal deep brain stimulation (globus pallidus internus (GPi) DBS) is the best therapeutic option for disabling isolated idiopathic (IID) and inherited (INH) dystonia. Acquired dystonia (AD) may also benefit from GPi DBS. Efficacy and safety in the long-term remained to be established. OBJECTIVE: To retrospectively assess long-term clinical outcomes and safety in dystonic patients who underwent GPi DBS. METHODS: Patients were videotaped and assessed preoperatively and postoperatively (1-year and at last available follow-up) using the Burke-Fahn-Marsden Dystonia Rating Scale (motor score (BFMDRS-M); disability score (BFMDRS-D)). RESULTS: Sixty-one patients were included (follow-up 7.9±5.9 years; range 1-20.7). In IID and INH (n=37), the BFMDRS-M improved at first (20.4±24.5; p<0.00001) and last (22.2±18.2; p<0.001) follow-ups compared with preoperatively (50.5±28.0). In AD (n=19), the BFMDRS-M ameliorated at 1-year (40.8±26.5; p<0.02) and late follow-ups (44.3±24.3; p<0.04) compared with preoperatively (52.8±24.2). In INH dystonia with other neurological features (n=4) there was no motor benefit. In IID and INH, the BFMDRS-D improved at 1-year (9.5±7.5; p<0.0002) and late follow-ups (10.4±7.8; p<0.016) compared with preoperatively (13.3±6.9). In AD, the BFMDRS-D reduced at 1-year (12.0±8.1; p<0.01) and late follow-ups (12.7 ±6.1; p=0.2) compared with preoperatively (14.35±5.7). Most adverse events were hardware related. CONCLUSIONS: GPi DBS is an effective and safe treatment in most patients with dystonia.

Epilepsy diagnostic and treatment needs identified with a collaborative database involving tertiary centers in France.

OBJECTIVE: To obtain perspective on epilepsy in patients referred to tertiary centers in France, and describe etiology, epilepsy syndromes, and identify factors of drug resistance and comorbidities. METHODS: We performed a cross-sectional analysis of the characteristics of 5,794 pediatric and adult patients with epilepsy included in a collaborative database in France between 2007 and 2013. Comparisons between groups used Student's t-test or Fisher's exact test for binary or categorical variables. Factors associated with drug resistance and intellectual disability were evaluated in multi-adjusted logistic regression models. RESULTS: Mean age at inclusion was 17.9 years; children accounted for 67%. Epilepsy was unclassified in 20% of patients, and etiology was unknown in 65%, including those with idiopathic epilepsies. Etiologies differed significantly in adult- when compared to pediatric-onset epilepsy; however, among focal structural epilepsies, mesial temporal lobe epilepsy with hippocampal sclerosis began as often in the pediatric as in adult age range. Drug resistance concerned 53% of 4,210 patients evaluable for seizure control and was highest in progressive myoclonic epilepsy (89%), metabolic diseases (84%), focal cortical dysplasia (70%), other cortical malformations (69%), and mesial temporal lobe epilepsy with hippocampal sclerosis (67%). Fifty-nine percent of patients with focal structural epilepsy and 69% with epileptic encephalopathies were drug resistant; however, 40-50% of patients with West syndrome and epileptic encephalopathy with continuous spike-and-waves during sleep were seizure-free. Ages at onset in infancy and in young adults shared the highest risk of drug resistance. Epilepsy onset in infancy comprised the highest risk of intellectual disability, whereas specific cognitive impairment affected 36% of children with idiopathic focal epilepsy. SIGNIFICANCE: Our study provides a snapshot on epilepsy in patients referred to tertiary centers and discloses needs for diagnosis and treatment. Large databases help identify patients with rare conditions that could benefit from specific prospective studies.

[Psychogenic NonEpileptic Seizures: Current Knowledge and Contributions of the Study of Emotions]. / Crises psychogènes non épileptiques : état des connaissances et apports de l'évaluation des traitements émotionnels.

Psychogenic nonepileptic seizures (PNES) are paroxysmal attacks that can imitate epileptic seizures but do not have a neurological origin. There has been mounting interest these last few years to unravel psychological and neuronal factors that contribute to the development of PNES. The objective of this review is twofold. First, we examine recent contributions of clinical and researches studies to define the main features of PNES. Then, we focus on the possible link between changes in processing of emotional information and the onset of PNES. In this article, we identify promising directions for future research and argue that affective neuroscience may provide original findings to better understand this disease.

Voltage-gated potassium channels autoantibodies in a child with rasmussen encephalitis.

Rasmussen encephalitis (RE) is a severe epileptic and inflammatory encephalopathy of unknown etiology, responsible for focal neurological signs and cognitive decline. The current leading hypothesis suggests a sequence of immune reactions induced by an indeterminate factor. This sequence is thought to be responsible for the production of autoantibody-mediated central nervous system degeneration. However, these autoantibodies are not specific to the disease and not all patients present with them. We report the case of a 4-year-old girl suffering from RE displaying some atypical features such as fast evolution and seizures of left parietal onset refractory to several antiepileptics, intravenous immunoglobulins, and corticosteroids. Serum autoantibodies directed against voltage-gated potassium channels (VGKC) were evidenced at 739 pM, a finding never previously reported in children. This screening was performed because of an increased signal in the temporolimbic areas on brain magnetic resonance imaging, which was similar to what is observed during limbic encephalitis. The patient experienced epilepsia partialis continua with progressive right hemiplegia and aphasia. She underwent left hemispherotomy at the age of 5.5 years after which she became seizure free with great cognitive improvement. First described in adults, VGKC autoantibodies have been recently described in children with various neurological manifestations. The implication of VGKC autoantibodies in RE is a new observation and opens up new physiopathological and therapeutic avenues of investigation.

A simple febrile seizure with focal onset.

Simple febrile seizures last for less than 10 minutes and resolve spontaneously, in the context of a febrile illness, without focal features or recurrence during the subsequent 24 hours. We report the case of fortuitous video-EEG recording of a FS, clinically classified as "simple", which demonstrated a focal, temporal onset. This clinical finding is in agreement with animal model studies demonstrating focal onset.

The epileptic blip syndrome.

We report on the case of an adolescent with juvenile myoclonic epilepsy exhibiting compulsory sporadic voluntary movement. These movements entailed the deliberate act of touching her forehead with her hand and were triggered by a short and indefinable cephalic sensation. Upon inquiry regarding the nature of this movement, the patient reported a sudden perception of a peculiar event localized "inside her head". In the course of a prolonged video-electroencephalographic recording, it appeared that the movements consistently followed the occurrence of diffuse Generalized Spike-and-Wave Bursts (GSWBs), lasting one to three seconds. This observation suggests that the impact of the GSWBs on the patient's stream of consciousness could be detected by the patient herself, who attributed it to an internal sensation, like a "blip on a screen". This clinical observation echoes the "blip syndrome", as described by the neurologist James W. Lance thirty years ago. These findings give some support that "blips" could be of an epileptic origin and lend weight to the notion that some patients could perceive their own EEG discharges. Moreover, this observation should be added to the perennial debate on the cognitive impact of intercritical discharges.

Sex modulation of faces prediction error in the autistic brain.

Recent research suggests that autistic females may have superior socio-cognitive abilities compared to autistic males, potentially contributing to underdiagnosis in females. However, it remains unclear whether these differences arise from distinct neurophysiological functioning in autistic males and females. This study addresses this question by presenting 41 autistic and 48 non-autistic adults with a spatially filtered faces oddball paradigm. Analysis of event-related potentials from scalp electroencephalography reveal a neurophysiological profile in autistic females that fell between those of autistic males and non-autistic females, highlighting sex differences in autism from the initial stages of face processing. This finding underscores the urgent need to explore neurophysiological sex differences in autism and encourages efforts toward a better comprehension of compensation mechanism and a clearer definition of what is meant by camouflaging.

Reduced spatial frequency differentiation and sex-related specificities in fearful face detection in autism: Insights from EEG and the predictive brain model.

Face processing relies on predictive processes driven by low spatial frequencies (LSF) that convey coarse information prior to fine information conveyed by high spatial frequencies. However, autistic individuals might have atypical predictive processes, contributing to facial processing difficulties. This may be more normalized in autistic females, who often exhibit better socio-communicational abilities than males. We hypothesized that autistic females would display a more typical coarse-to-fine processing for socio-emotional stimuli compared to autistic males. To test this hypothesis, we asked adult participants (44 autistic, 51 non-autistic) to detect fearful faces among neutral faces, filtered in two orders: from coarse-to-fine (CtF) and from fine-to-coarse (FtC). Results show lower d' values and longer reaction times for fearful detection in autism compared to non-autistic (NA) individuals, regardless of the filtering order. Both groups presented shorter P100 latency after CtF compared to FtC, and larger amplitude for N170 after FtC compared to CtF. However, autistic participants presented a reduced difference in source activity between CtF and FtC in the fusiform. There was also a more spatially spread activation pattern in autistic females compared to NA females. Finally, females had faster P100 and N170 latencies, as well as larger occipital activation for FtC sequences than males, irrespective of the group. Overall, the results do not suggest impaired predictive processes from LSF in autism despite behavioral differences in fear detection. However, they do indicate reduced brain modulation by spatial frequency in autism. In addition, the findings highlight sex differences that warrant consideration in understanding autistic females.

From one to many: Hypertonia in schizophrenia spectrum psychosis an integrative review and adversarial collaboration report.

Different types of resistance to passive movement, i.e. hypertonia, were described in schizophrenia spectrum disorders (SSD) long before the introduction of antipsychotics. While these have been rediscovered in antipsychotic-naïve patients and their non-affected relatives, the existence of intrinsic hypertonia vs drug-induced parkinsonism (DIP) in treated SSD remains controversial. This integrative review seeks to develop a commonly accepted framework to specify the putative clinical phenomena, highlight conflicting issues and discuss ways to challenge each hypothesis and model through adversarial collaboration. The authors agreed on a common framework inspired from systems neuroscience. Specification of DIP, locomotor paratonia (LMP) and psychomotor paratonia (PMP) identified points of disagreement. Some viewed parkinsonian rigidity to be sufficient for diagnosing DIP, while others viewed DIP as a syndrome that should include bradykinesia. Sensitivity of DIP to anticholinergic drugs and the nature of LPM and PMP were the most debated issues. It was agreed that treated SSD should be investigated first. Clinical features of the phenomena at issue could be confirmed by torque, EMG and joint angle measures that could help in challenging the selectivity of DIP to anticholinergics. LMP was modeled as the release of the reticular formation from the control of the supplementary motor area (SMA), which could be challenged by the tonic vibration reflex or acoustic startle. PMP was modeled as the release of primary motor cortex from the control of the SMA and may be informed by subclinical echopraxia. If these challenges are not met, this would put new constraints on the models and have clinical and therapeutic implications.

Ictal inner speech jargon.

We report on the case of a woman with jargon aphasic seizures who provided a careful written report of inner speech jargon occurring during her seizures. This inner speech jargon description is an unusual finding since in most aphasic disorders, patients also suffer from anosognosia. This case report may suggest that jargon could also involve inner speech and could be innerly detected as such. It provides an argument supporting the idea that common mechanisms may underlie both "overt" and "covert" production of jargon during aphasia.

The natural history of terms describing functional (neurological) disorders in the medical literature of the last 60 years.

BACKGROUND: Functional neurological disorders (FND), a subtype of functional disorders (FD), are a frequent motive for neurology referrals. The various presentations and the unknown physiopathology of FD have led to the multiplication of terms describing these disorders over the years. METHODS: We examined the FD-related articles published from 1960 to 2020 in PubMed and PsycINFO databases. We searched for: psychogenic, somatization, somatoform, medically unexplained symptoms, hysteria, conversion disorder, dissociative, functional neurological disorder, and functional disorder. Use rates in the title, abstract, keyword, or MeSH fields were collected over successive 5-year periods. After correcting for off-topic results, we examined proportional distribution over time, term associations, and disciplinary fields (neurology and psychiatry). Term impact was estimated via H-index and number of citations. RESULTS: We found that none of the terms is prevailing in the recent medical literature. We observed three trends in the use rates: stability, increase, and decrease of use over time. While most of the terms were present in a stable proportion of the publications, hysteria and psychogenic lost popularity over time. We found a differential preference for terminology between disciplines. Functional neurological disorder showed the highest citation impact, yielding 10% of highly cited publications. CONCLUSION: We found a dynamic and evolving use of the different terms describing FD in the last 60 years. Despite the tendency to use the term functional in the recent highly cited publications, its low prevalence and coexistence with several other terms suggest that a precise, explanatory and non-offensive term remains yet to be found.

Long-term analgesic effect of trans-spinal direct current stimulation compared to non-invasive motor cortex stimulation in complex regional pain syndrome.

The aim of the present study was to compare the analgesic effect of motor cortex stimulation using high-frequency repetitive transcranial magnetic stimulation or transcranial direct current stimulation and transcutaneous spinal direct current stimulation in patients with complex regional pain syndrome. Thirty-three patients with complex regional pain syndrome were randomized to one of the three treatment groups (repetitive transcranial magnetic stimulation, n = 11; transcranial direct current stimulation, n = 10; transcutaneous spinal direct current stimulation, n = 12) and received a series of 12 sessions of stimulation for 3 weeks (induction phase) and 11 sessions for 4 months (maintenance therapy). The primary end-point was the mean pain intensity assessed weekly with a visual numerical scale during the month prior to treatment (baseline), the 5-month stimulation period and 1 month after the treatment. The weekly visual numerical scale pain score was significantly reduced at all time points compared to baseline in the transcutaneous spinal direct current stimulation group, at the last two time points in the repetitive transcranial magnetic stimulation group (end of the 5-month stimulation period and 1 month later), but at no time point in the transcranial direct current stimulation group. A significant pain relief was observed at the end of induction phase using transcutaneous spinal direct current stimulation compared to repetitive transcranial magnetic stimulation (P = 0.008) and to transcranial direct current stimulation (P = 0.003). In this trial, transcutaneous spinal direct current stimulation was more efficient to relieve pain in patients with complex regional pain syndrome compared to motor cortex stimulation techniques (repetitive transcranial magnetic stimulation, transcranial direct current stimulation). This efficacy was found during the induction phase and was maintained thereafter. This study warrants further investigation to confirm the potentiality of transcutaneous spinal direct current stimulation as a therapeutic option in complex regional pain syndrome.

How valid are proxy assessment of mental health and sleep comorbidities of patients with epilepsy using standardized questionnaires?

BACKGROUND: The study aimed to determine the level of agreement between patients with epilepsy and their proxies when assessing psychiatric comorbidities, sleep disorders, and medication adherence using standardized questionnaires. METHODS: This agreement study is an ancillary analysis of the PRERIES study, a matched case-control study exploring SUDEP risk factors. Controls aged 15 years and older, with active epilepsy or in remission for less than 5 years were recruited between 01/01/2011 and 03/31/2019. An interview was carried out by a trained psychologist on both the patient and a proxy-respondent. During these independent interviews, the following comorbidities were explored: psychiatric comorbidities using the MINI, the STAI- Y2 and NDDI-E scales, sleep disorders with the SDQ-SA and Epworth scales and medication adherence. Level of agreement between patient and their proxy was estimated using Gwet's AC1&2. RESULTS: Among the 107 patient-proxy dyads recruited, proxy respondents were mainly family members (65.4%) or spouses (30.8%). Exploration of present major depression showed excellent agreement at 0.81 [0.65;0.97], as well as exploration of dysthymia at 0.96 [0.61;1]. Suicidal risk evaluation had a lesser agreement at 0.77 [0.60;0.94]. Agreement on anxiety was moderate 0.5 [0.38;0.62]. For sleep disorder, SDQ-SA presented a better agreement than the Epworth questionnaire with respectively 0.73 [0.51;0.95] and 0.45 [0.26;0.63]. For medication adherence, the overall agreement rate was excellent (0.90 [0.78;1]). CONCLUSION: Exploration of potential risk factors through families can give valuable and relatively robust information, especially if the respondent lives with the patient, and should be retrieved, when possible, in usual clinical setting.