Association between free thyroxine levels and clinical phenotype in first-episode psychosis: a prospective observational study.

Aim: To determine whether thyroid hormone levels are associated with a specific clinical phenotype in patients with first-episode psychosis (FEP). Methods: Ninety-eight inpatients experiencing FEP and with less than 6 weeks of antipsychotic treatment were included in the study and were followed up for one year. Baseline psychiatric evaluation included assessment of prodromal symptoms, positive and negative symptoms, depressive symptoms, stressful life events and cycloid psychosis criteria. Thyroid function (thyroid-stimulating hormone (TSH) and free thyroxin (FT4)) was determined at admission. Partial correlation analysis was conducted to analyse the correlation between levels of TSH/FT4 and symptoms. Logistic regression was performed to explore the association between psychopathological symptoms, 12-month diagnoses and thyroid hormones while adjusting for covariates. Results: Patients with prodromal symptomatology showed lower baseline FT4 levels (OR = 0.06; p = 0.018). The duration of untreated psychosis (DUP) was inversely associated with FT4 concentrations (r =  - 0.243; p = 0.039). FEP patients with sudden onset of psychotic symptoms (criteria B, cycloid psychosis) showed higher FT4 levels at admission (OR = 10.49; p = 0.040). Patients diagnosed with affective psychotic disorders (BD or MDD) at the 12-month follow-up showed higher FT4 levels at admission than patients diagnosed with nonaffective psychosis (schizophrenia, schizoaffective) (OR = 8.57; p = 0.042). Conclusions: Our study suggests that higher free-thyroxine levels are associated with a specific clinical phenotype of FEP patients (fewer prodromal symptoms, shorter DUP duration and sudden onset of psychosis) and with affective psychosis diagnoses at the 12-month follow-up.

Routine cerebrospinal fluid parameters as biomarkers in first-episode psychosis: A prospective observational study.

In recent years, multiple studies have investigated the role of biomarkers in first-episode psychosis (FEP) to facilitate early diagnosis, disease stratification, therapeutic choice and outcome prediction. Few studies have focused on cerebrospinal fluid (CSF) investigations. In this prospective observational study, 95 FEP inpatients were followed up for one year. A lumbar puncture was performed at index admission (baseline) to study the CSF parameters (glucose, total proteins, lactate dehydrogenase [LDH], and pleocytosis). At the baseline visit, the clinical assessment included prodromal (psychotic and non-psychotic) symptoms before the psychotic outbreak and psychopathology at admission. The SCID-I was administered to obtain a clinical diagnosis at baseline and at 12 months. The relationship between prodromal and psychopathology symptoms at the baseline visit was tested with multiple linear regression. Multinomial logistic regression was also used to explore the association between CSF biomarkers and longitudinal diagnoses at follow-up (schizophrenia/schizoaffective disorder vs unipolar/bipolar depression vs other psychoses). Higher CSF glucose was associated with depressive (Standardized beta = 0.27, p = 0.041) and disorganized/concrete symptoms (Standardized beta = 0.33, p = 0.023) and lower CSF LDH was associated with prodromal symptoms (Standardized beta = -0.25, p = 0.042). Lower LDH concentrations were also associated with social withdrawal (r = -0.342, p = 0.001). CSF glucose was a predictor of the long-term diagnosis (lower CSF concentrations were associated with schizophrenia or schizoaffective disorder diagnoses [OR = 0.88, CI95%: 0.77-0.99). Our study suggests that CSF biomarkers that involve bioenergetic systems are associated with prodromal symptoms and the phenotype of psychotic disorders during the early stages of the disease.

Anti-NMDA receptor encephalitis in older adults: A systematic review of case reports.

OBJECTIVE: To ascertain the clinical characteristics of anti-NMDA receptor encephalitis (NMDARE) in older patients. METHOD: A systematic literature review using PubMed and Scopus of all published case reports of NMDARE was undertaken, from database inception to June 2020. From this, cases reporting on patients older than 65 years of age and whose diagnosis was confirmed by the presence of anti-NMDAR antibodies in CSF were selected. RESULTS: 23 case reports fulfilling the study's criteria were found. Median age was 70.1 years (range 65-84), fourteen were female (60.9%), and mostly presented with acute behavioral and cognitive changes (95.7%). Atypical psychosis occurred in eleven patients (47.8%) with a sudden onset and fluctuating clinical pattern of delusions (39.1%), hallucinations (30.4%), and motility disturbances (34.8%) including catatonia (17.4%). Nine patients presented with seizures (39.1%). Pleocytosis in CSF (>5 WBC) was described in twelve cases (52.2%). Eleven cases (47.8%) had abnormal brain magnetic resonance imaging (MRI) scans with limbic inflammatory lesions. Thirteen patients had an abnormal EEG (56.5%). CONCLUSION: NMDARE should be included in the differential diagnosis of older patients who present with new psychiatric episodes, especially when characterized by sudden onset psychotic polymorphic symptomatology, fluctuating course with marked cognitive decline, and with catatonic features.

Effect of Transcutaneous Electrical Stimulation in Chronic Poststroke Patients with Oropharyngeal Dysphagia: 1-Year Results of a Randomized Controlled Trial.

Background. Chronic poststroke oropharyngeal dysphagia (CPSOD) is associated with impaired oropharyngeal sensory/motor function. We aimed to assess effect of sensory (SES) and motor (NMES) transcutaneous electrical stimulation (TES) on safety of swallow and clinical outcomes in patients with CPSOD in a one-year follow-up randomized controlled trial. Methods. Ninety patients (74.1 ± 11.5 y, modified Rankin score 2.6 ± 1.7) with CPSOD and impaired safety of swallow were randomized to (a) compensatory treatment (CT), (b) CT + SES, and (c) CT + NMES. Patients were treated with up to two cycles (6 months apart) of 15 × 1 hour TES sessions over two weeks and followed up with 4-5 clinical and videofluoroscopic assessments during one year. Key results. Baseline penetration-aspiration scale (PAS) was 4.61 ± 1.75, delayed time to laryngeal vestibule closure (LVC) 396.4 ± 108.7 ms, and impaired efficacy signs 94.25%. Swallowing parameters significantly improved between baseline and 1-year follow-up in SES and NMES groups for prevalence of patients with a safe swallow (P < .001), mean PAS (P < .001), time to LVC (P < .01), and need for thickening agents (P < .001). Patients in the CT presented a less intense improvement of signs of impaired safety of swallow without significant changes in time to LVC. No differences between groups were observed for 1-year mortality (6.1%), respiratory infections (9.6%), nutritional and functional status, QoL, and hospital readmission rates (27.6%). No significant adverse events related to TES were observed. Conclusions and inferences. Transcutaneous electrical stimulation is a safe and effective therapy for older patients with CPSOD. After 1-year follow-up, TES greatly improved the safety of swallow and reduced the need for fluid thickening in these patients.

Clinical, Neuroimmunologic, and CSF Investigations in First Episode Psychosis.

OBJECTIVES: To report the neuropsychiatric features and frequency of NMDA receptor (NMDAR) and other neuronal immunoglobulin G antibodies in patients with first episode psychosis (FEP) and to assess the performance of reported warning signs and criteria for autoimmune psychosis (AP). METHODS: This was a prospective observational study of patients with FEP assessed for neuropsychiatric symptoms, serum and CSF neuronal antibodies (brain immunohistochemistry, cell-based assays, live neurons), and warning signs and criteria of AP. Previous autoimmune FEP series were reviewed. RESULTS: One hundred five patients were included; their median age was 30 (range 14-75) years, and 44 (42%) were female. None had neuronal antibodies. Two of 105 (2%) had CSF pleocytosis, 4 of 100 (4%) had brain MRI abnormalities, and 3 of 73 (4%) EEG alterations. Thirty-four (32%) and 39 (37%) patients fulfilled 2 sets of warning signs of AP, and 21 (20%) fulfilled criteria of possible or probable AP, yet none developed AP. The cause of FEP was psychiatric in 101 (96%) and nonpsychiatric in 4 (4%). During this study, 3 patients with psychosis caused by anti-NMDAR encephalitis were transferred to our center; 2 did not meet criteria for possible AP. Of 1,159 reported patients with FEP, only 7 (1%) had CSF studies; 36 (3%) had serum NMDAR antibodies (without definite diagnosis of AP), and 4 had CSF NMDAR antibodies (3 classic anti-NMDAR encephalitis and 1 with isolated psychiatric features). CONCLUSIONS: NMDAR antibodies were not found in patients with FEP unless they had anti-NMDAR encephalitis. Warning signs and criteria for AP have limited utility when neurologic symptoms are absent or paraclinical tests are normal. A diagnostic algorithm for autoimmune FEP is provided.

Emergency implementation of telemedicine for epilepsy in Spain: Results of a survey during SARS-CoV-2 pandemic.

Teleneurology in Spain had not been implemented so far in clinical practice, except in urgent patients with stroke. Telemedicine was hardly used in epilepsy, and patients and neurologists usually preferred onsite visits. Our goal was to study impressions of adult and pediatric epileptologists about the use of telemedicine after emergent implementation during the new coronavirus 2019 (COVID-19) pandemic. METHODS: An online survey was sent to the members of the Spanish Epilepsy Society and the members of the Epilepsy Study Group of the Catalan Neurological Society, inquiring about different aspects of telemedicine in epilepsy during the pandemic lockdown. RESULTS: A total of 66 neurologists responded, mostly adult neurologists (80.3%), the majority with a monographic epilepsy clinic (4 out of 5). Of all respondents, 59.1% reported to attend more than 20 patients with epilepsy (PWE) a week. During the pandemic, respondents handled their epilepsy clinics mainly with telephone calls (88%); only 4.5% used videoconference. Changes in antiseizure medications were performed less frequently than during onsite visits by 66.6% of the epileptologists. Scales were not administered during these visits, and certain types of information such as sudden expected unrelated death in epilepsy (SUDEP) were felt to be more appropriate to discuss in person. More than 4 out of 5 of the neurologists (84.8%) stated that they would be open to perform some telematic visits in the future. CONCLUSIONS: In Spain, emergent implantation of teleneurology has shown to be appropriate for the care of many PWE. Technical improvements, extended use of videoconference and patient selection may improve results and patient and physician satisfaction.

Neurophysiological and Biomechanical Evaluation of the Mechanisms Which Impair Safety of Swallow in Chronic Post-stroke Patients.

Oropharyngeal dysphagia (OD) is a common post-stroke complication and is associated with respiratory infections. The aim was to assess the biomechanical impairments in swallow function and the afferent and efferent swallowing pathways impairing swallow safety in chronic post-stroke patients. We studied 30 patients with unilateral stroke and chronic OD (> 3 months from stroke onset) with impaired safety of swallow (Penetration-Aspiration Scale [PAS] ≥ 2). We evaluated the efficacy, safety, and kinematics of the swallow response (residue, PAS, laryngeal vestibule closure time [LVCT]) with videofluoroscopy, sensory evoked potentials to pharyngeal electrical stimulation (pSEP), and pharyngeal motor evoked potentials (pMEP) to transcranial magnetic stimulation of both hemispheres. Mean age of patients was 70.1 ± 10.9 years (7 women). Stroke severity at onset was moderate (NIHSS median 10 [IQ range 3-11.5]), and modified Rankin Scale 2.8 ± 1.3. Mean PAS was 5.1 ± 1.9; prevalence of delayed LVCT was 86.7% and 30% presented aspirations. Pharyngeal hypoesthesia was present in 46.7% of patients and 92.3% showed abnormally asymmetrical pSEPs when comparing the ipsilesional with the contralesional hemisphere. Increased duration of swallow was associated with lower pSEP amplitude (P1-N2) in the contralesional hemisphere (p = 0.033). Patients with right hemispheric strokes showed greater reduction of pSEPs amplitude (N1-P1, p = 0.049). In contrast, pharyngeal resting motor threshold and pMEPs were symmetric in 73.3% patients without the physiologic hemispheric dominance. Mild-to-moderate disabled chronic post-stroke patients with OD presented severe impaired biomechanics of swallow response and high prevalence of aspirations. Initial results from the neurophysiological evaluation demonstrated prevalent impairments with disrupted integration of pharyngeal sensory inputs and reduced cortical excitability of efferent pathways. Patients with right hemispheric strokes showed poorer neurophysiological responses.

Natural History of Swallow Function during the Three-Month Period after Stroke.

Oropharyngeal dysphagia is a prevalent complication following stroke (PS-OD), and one that is sometimes spontaneously recovered. This study describes the natural history of PS-OD between admission and three months post-stroke, and the factors associated with its prevalence and development. PS-OD was assessed with the volume-viscosity swallow test (V-VST) in all stroke patients on admission and at the three-month follow-up. We analyzed clinical, demographic, and neuroanatomical factors of 247 older post-stroke patients (National Institute of Health Stroke Scale (NIHSS) = 3.5 ± 3.8), comparing among those with PS-OD the ones with and without spontaneous recovery. PS-OD prevalence on admission was 39.7% (34.0% impaired safety; 30.8%, efficacy) and 41.7% (19.4% impaired safety; 39.3%, efficacy) at three months. Spontaneous swallow recovery occurred in 42.4% of patients with unsafe and in 29.9% with ineffective swallow, associated with younger age and optimal functional status. However, 26% of post-stroke patients developed new signs/symptoms of ineffective swallow related to poor functional, nutritional and health status, and institutionalization. PS-OD prevalence on admission and at the three-month follow-up was very high in the study population. PS-OD is a dynamic condition with some spontaneous recovery in patients with optimal functional status, but also new signs/symptoms can appear due to poor functionality. Regular PS-OD monitoring is needed to identify patients at risk of nutritional and respiratory complications.

Encefalitis antirreceptor de NMDA. Diagnóstico y tratamiento precoz en pacientes con sintomatología psicótica aguda-subaguda / Anti-NMDA receptor encephalitis. Early diagnosis and treatment in patients with acute-subacute psychotic symptoms

Introducción. La encefalitis por anticuerpos antirreceptor de NMDA es una entidad aguda y grave, cuya rápida identificación y tratamiento puede comportar recuperaciones sin secuelas. Es más prevalente en mujeres jóvenes y a menudo está asociada a un tumor subyacente. Los síntomas iniciales son habitualmente psiquiátricos y en días o semanas adquieren el perfil neurológico característico. Casos clínicos. Tres mujeres, de 17, 23 y 35 años, que ingresaron en el Servicio de Psiquiatría con clínica psicótica aguda. La mala respuesta a los antipsicóticos, las fluctuaciones del nivel de conciencia, la disautonomía y las crisis epilépticas fueron los síntomas que despertaron la sospecha clínica. El líquido cefalorraquídeo mostró leve pleocitosis y positividad para los anticuerpos antirreceptor de NMDA en todas las pacientes. Sólo una mostró alteraciones en la resonancia magnética cerebral, y dos, el patrón electroencefalográfico extreme delta brush. En todas se diagnosticó un teratoma ovárico, que fue resecado antes del mes. Dos se recuperaron sin secuelas y la tercera, a los seis meses del alta, presenta secuelas cognitivas. Conclusiones. Los casos descritos comenzaron con clínica psicótica aguda. La evolución psiquiátrica atípica y la clínica neurológica alertaron de la posibilidad de una encefalitis. El reconocimiento de la enfermedad y la coordinación entre servicios es fundamental para un diagnóstico y tratamiento precoz. El análisis sistemático de líquido cefalorraquídeo en pacientes con un primer episodio psicótico agudo-subagudo contribuiría a adelantar el diagnóstico. En mujeres jóvenes hay que buscar siempre un teratoma ovárico u otro tumor asociado

Introduction. Encephalitis due to anti-NMDA receptor antibodies is an acute and severe condition, which, if identified and treated quickly, can entail recovery without any sequelae. It is more prevalent in young females and is often associated with an underlying tumour. The initial symptoms are usually of a psychiatric nature, and in a matter of days or weeks take on a characteristic neurological profile. Case reports. We report the cases of three women, 17, 23 and 35 years of age, who were admitted to Psychiatry with acute psychotic clinical features. The poor response to antipsychotics, the fluctuations in the level of consciousness, dysautonomia and epileptic seizures were the symptoms that led to the clinical suspicion. The cerebrospinal fluid revealed slight pleocytosis and gave positive for anti-NMDA receptor antibodies in all cases. Only one patient displayed alterations in the magnetic resonance brain scan, and in two cases there was an extreme delta brush electroencephalographic pattern. All three women were diagnosed with an ovarian teratoma which was resectioned within a month. Two of the patients recovered without any sequelae, and the third presents cognitive sequelae six months after being discharged. Conclusions. The cases described began with an acute psychotic clinical picture. The atypical psychiatric progression and the neurological symptoms indicated the possible presence of encephalitis. Recognition of the disease and coordination among the different services is essential for early diagnosis and treatment. The systematic analysis of cerebrospinal fluid in patients with a first acute-subacute psychotic episode would help to reach a diagnosis sooner. In young women, a search must always be carried out for an ovarian teratoma or other associated tumour

Neurorehabilitation strategies for poststroke oropharyngeal dysphagia: from compensation to the recovery of swallowing function.

Oropharyngeal dysphagia (OD) is very prevalent among poststroke patients, causing severe complications but lacking specific neurorehabilitation treatment. This review covers advances in the pathophysiology, diagnosis, and physiologically based neurorehabilitation strategies for poststroke OD. The pathophysiology of oropharyngeal biomechanics can be assessed by videofluoroscopy, as delayed laryngeal vestibule closure is closely associated with aspiration. Stroke may affect afferent or efferent neuronal circuits participating in deglutition. The integrity of oropharyngeal-cortical afferent pathways can be assessed by electroencephalography through sensory-evoked potentials by pharyngeal electrical stimulation, while corticopharyngeal efferent pathways can be characterized by electromyography through motor-evoked potentials by transcranial magnetic stimulation. Dysfunction in both cortico-mediated evoked responses is associated with delayed swallow response and aspiration. Studies have reported hemispherical asymmetry on motor control of swallowing and the relevance of impaired oropharyngeal sensitivity on aspiration. Advances in treatment include improvements in compensatory strategies but are mainly focused on (1) peripheral stimulation strategies and (2) central, noninvasive stimulation strategies with evidence of their clinical benefits. Characterization of poststroke OD is evolving from the assessment of impaired biomechanics to the sensorimotor integration processes involved in deglutition. Treatment is also changing from compensatory strategies to promoting brain plasticity, both to recover swallow function and to improve brain-related swallowing dysfunction.