Neuropsychiatric phenotypes of anti-NMDAR encephalitis: a prospective study.

BACKGROUND: Patients with anti-N-methyl-d-aspartate (NMDA) receptor encephalitis (ANMDARE) show a wide range of behavioral abnormalities and are often mistaken for primary psychiatric presentations. We aimed to determine the behavioral hallmarks of ANMDARE with the use of systematic neuropsychiatric and cognitive assessments. METHODS: A prospective study was conducted, with 160 patients admitted to the National Institute of Neurology and Neurosurgery of Mexico, who fulfilled criteria for possible autoimmune encephalitis and/or red flags along a time window of seven years. Cerebrospinal fluid (CSF) antibodies against the NR1 subunit of the NMDAR were processed with rat brain immunohistochemistry and cell-based assays with NMDA expressing cells. Systematic cognitive, neuropsychiatric, and functional assessments were conducted before knowing NMDAR antibodies results. A multivariate analysis was used to compare patients with and without definite ANMDARE according to antibodies in CSF. RESULTS: After obtaining the CSF antibodies results in 160 consecutive cases, 100 patients were positive and classified as having definite ANMDARE. The most frequent neuropsychiatric patterns were psychosis (81%), delirium (75%), catatonia (69%), anxiety-depression (65%), and mania (27%). Cognition was significantly impaired. A total of 34% of the patients had a predominantly neuropsychiatric presentation without seizures. After multivariate analysis, the clinical hallmarks of ANMDARE consisted of a catatonia-delirium comorbidity, tonic-clonic seizures, and orolingual dyskinesia. CONCLUSIONS: Our study supports the notion of a neurobehavioral phenotype of ANMDARE characterized by a fluctuating course with psychotic and affective symptoms, catatonic signs, and global cognitive dysfunction, often accompanied by seizures and dyskinesia. The catatonia-delirium comorbidity could be a distinctive neurobehavioral phenotype of ANMDARE.

Cotard syndrome in anti-NMDAR encephalitis: two patients and insights from molecular imaging.

Cotard syndrome is a clinical condition defined by the presence of nihilistic delusions. We report two patients with Cotard syndrome in whom anti-NMDAR encephalitis (ANMDARE) was confirmed. Both cases showed features of affective psychosis, developed catatonic syndrome, and worsened after the use of antipsychotics. 18F-FDG PET brain studies showed a bilateral hemispheric pattern of hypometabolism in posterior regions, mainly in the cingulate cortex and in the medial aspects of parietal and occipital lobes. A more severe hypometabolism was observed in the right hemisphere of both patients. Both cases remitted with the use of specific immunotherapy for ANMDARE.

Las concentraciones de glutamina y citrulina reflejan la síntesis del óxido nítrico en el sistema nervioso humano / Glutamine and citrulline concentrations reflect nitric oxide synthesis in the human nervous system

INTRODUCCIÓN: Aunque la citrulina es producida por la sintasa del óxido nítrico (NO) al activarse el receptor glutamatérgico NMDA, nitritos y nitratos (NOx) son considerados los mejores marcadores de síntesis del NO pues citrulina es también metabolizada por otras enzimas. En este estudio se realizó un análisis de correlaciones de concentraciones de citrulina y NOx en líquido cefalorraquídeo humano para evaluar la proporción en que la citrulina refleja la síntesis del NO y la neurotransmisión glutamatérgica. MÉTODOS: Se incluyeron pacientes con trastornos neurológicos agudos a los que se realizó punción lumbar (n = 240). Se determinó la concentración de NOx y aminoácidos por HPLC. RESULTADOS: NOx no fue diferente por la presencia de infección (p = 0,110) o inflamación (p = 0,349). La regresión múltiple mostró que NOx correlacionó con glutamina (r = -0,319, p < 0,001) y citrulina (r = 0,293, p = 0,005) pero no con el cociente citrulina/arginina (r = -0,160, p = 0,173). El ANCOVA confirmó que NOx está asociado con citrulina (F = 7,6, p = 0,007) pero no con el cociente citrulina/arginina (F = 2,2; p = 0,136), ni con la infección (F = 1,8; p = 0,173) o la inflamación (F = 1,4; p = 0,227). NOx no correlacionó con arginina ni con glutamato. CONCLUSIONES: Esto sugiere que citrulina refleja parte de la síntesis del NO a pesar de la contribución de otras vías metabólicas. Además, este estudio muestra que la glutamina es un modulador importante de la actividad de la NOS, y que arginina y glutamato no correlacionan con la concentración de NOx

INTRODUCTION: Although citrulline is produced by nitric oxide (NO) synthase upon activation of the NMDA glutamate receptor, nitrite and nitrate (NOx) concentration is considered the best marker of NO synthesis, as citrulline is also metabolised by other enzymes. This study analyses the correlation between human cerebrospinal fluid NOx and citrulline concentrations in order to determine the extent to which citrulline reflects NO synthesis and glutamatergic neurotransmission. METHODS: Participants were patients with acute neurological diseases undergoing lumbar puncture (n = 240). NOx and amino acid concentrations were determined by HPLC. RESULTS: NOx concentrations did not vary significantly where infection (p = 0,110) or inflammation (p = 0,349) were present. Multiple regression analysis showed that NOx concentration was correlated with glutamine (r = -0,319, p < 0,001) and citrulline concentrations (r = 0,293, p = 0,005) but not with the citrulline/arginine ratio (r = -0,160, p = 0,173). ANCOVA confirmed that NOx concentration was correlated with citrulline concentration (F = 7,6, p = 0,007) but not with the citrulline/arginine ratio (F = 2,2, p = 0,136), or presence of infection (F=1,8, p = 0,173) or inflammation (F = 1,4, p = 0,227). No association was found between NOx and arginine or glutamate concentrations. CONCLUSION: The results suggest that CSF citrulline concentration reflects NOx synthesis to some extent, despite the contribution of other metabolic pathways. In addition, this study shows that glutamine is an important modulator of NO synthase activity, and that arginine and glutamate are not correlated with NOx

Glutamine and citrulline concentrations reflect nitric oxide synthesis in the human nervous system. / Las concentraciones de glutamina y citrulina reflejan la síntesis del óxido nítrico en el sistema nervioso humano.

INTRODUCTION: Although citrulline is produced by nitric oxide (NO) synthase upon activation of the NMDA glutamate receptor, nitrite and nitrate (NOx) concentration is considered the best marker of NO synthesis, as citrulline is also metabolised by other enzymes. This study analyses the correlation between human cerebrospinal fluid NOx and citrulline concentrations in order to determine the extent to which citrulline reflects NO synthesis and glutamatergic neurotransmission. METHODS: Participants were patients with acute neurological diseases undergoing lumbar puncture (n=240). NOx and amino acid concentrations were determined by HPLC. RESULTS: NOx concentrations did not vary significantly where infection (p=0,110) or inflammation (p=0,349) were present. Multiple regression analysis showed that NOx concentration was correlated with glutamine (r=-0,319, p<0,001) and citrulline concentrations (r=0,293, p=0,005) but not with the citrulline/arginine ratio (r=-0,160, p=0,173). ANCOVA confirmed that NOx concentration was correlated with citrulline concentration (F=7,6, p=0,007) but not with the citrulline/arginine ratio (F=2,2, p=0,136), or presence of infection (F=1,8, p=0,173) or inflammation (F=1,4, p=0,227). No association was found between NOx and arginine or glutamate concentrations. CONCLUSION: The results suggest that CSF citrulline concentration reflects NOx synthesis to some extent, despite the contribution of other metabolic pathways. In addition, this study shows that glutamine is an important modulator of NO synthase activity, and that arginine and glutamate are not correlated with NOx.

Schizophrenia-like psychosis associated with right lacunar thalamic infarct.

Thalamic dysfunction has been associated with schizophrenia and other psychotic disorders. We describe an adult patient with a lacunar infarct in the posterior region of the right thalamus exhibiting a paranoid schizophrenia-like psychosis as the only clinical manifestation. Neuropsychological assessment showed alterations in visuospatial memory and executive functions at follow up. This case highlights the role of information processing by the thalamus in the development of delusions. We suggest that dysfunction of the right mediodorsal and pulvinar thalamic nuclei disrupts both thalamic sensory processing and thalamo-prefrontal circuits mediating belief evaluation, leading to delusional beliefs.

Cognitive-behavioral therapy for depression in patients with temporal lobe epilepsy: a pilot study.

Depression has a high prevalence among patients with temporal lobe epilepsy (TLE). A pilot study was carried out to evaluate group cognitive-behavioral therapy (CBT) as a treatment for depression in patients with TLE. Twenty-three outpatients with TLE and major depressive disorder, according to DSM-IV criteria, were enrolled and divided into two groups to receive 16 weekly sessions of CBT. The primary outcome measures were depression severity (assessed with the Beck Depression Inventory) and quality of life (measured with the Quality of Life in Epilepsy-31). Sixteen patients (70%) completed at least 80% of the sessions. From week 8, CBT had a significant positive effect on severity of depression that lasted until the end of treatment. A significant improvement in quality of life was also observed. CBT seems to be a useful intervention for treating depression and improving quality of life in patients with TLE.

Imbalance between nitric oxide and dopamine may underly aggression in acute neurological patients.

The neurochemical basis of aggressive behavior in humans is not fully understood. In this study we explored the relationship between aggressiveness (as measured by the Overt Aggression Scale), cognitive performance (as measured by the Mini Mental State Examination), and biochemical markers of dopamine neurotransmission (homovanillic acid, HVA) and nitric oxide synthesis (nitrite plus nitrate, NO(x)) in cerebrospinal fluid from 70 patients with acute brain disorders, mainly brain infections. Aggressive behavior and cognitive performance showed an inverse correlation. NO(x)/HVA ratio was inversely correlated to aggressive behavior, and positively correlated to cognitive performance. A subanalysis with antipsychotic-naïve patients confirmed those results. The balance between nitric oxide and dopamine could be related to the cognitive control of aggressive impulse.

Clinical presentation of anxiety among patients with epilepsy.

Different factors have been related with interictal anxiety, reported in 10%-25% of patients with epilepsy. We determined the frequency of interictal anxiety in 196 patients with active epilepsy in a cross-sectional survey to know which symptoms of anxiety were most frequently reported in patients with epilepsy and to analyze the factors associated with their presence. Patients were assessed with the Beck Depression Inventory (BDI), Montgomery-Asberg Depression Rating Scale (MADRS), and the Hamilton Anxiety Scale (HAMA). Data were analyzed with a logistic regression model. The HAMA ratings revealed that 38.8% experienced significant anxiety symptoms, as defined by a rating above 18 points. Use of primidone, depression, cryptogenic, and posttraumatic etiologies significantly predicted anxiety after logistic regression. Symptoms related to higher scores on HAMA were anxious mood, tension, insomnia, intellectual function, depressed mood, cardiovascular and genitourinary symptoms. Further studies should be performed to define the role of psychosocial factors in the development and evolution of anxiety among these patients.

[The value of quantitative electroencephalogram analysis in the study of dementias]. / Utilidad del análisis cuantitativo del electroencefalograma en el estudio de las demencias.

INTRODUCTION: The question as to whether an electroencephalogram (EEG) needs to be carried out as a preliminary study in patients with dementia is currently the subject of some controversy. AIMS: Our aim was to determine the value of conventional and quantitative analysis of EEG recordings in the treatment of dementia. PATIENTS AND METHODS: The EEG recordings of patients diagnosed with a syndrome of dementia were analysed both visually and quantitatively (comparing them with patients with major depressive disorder). RESULTS: A total of 45 EEG traces were analysed -25 from patients with dementia and 20 with major depressive disorder-. The most significant finding was the number of abnormal recordings in each group, which was higher in the dementia group, with 19 abnormal recordings (76%) versus five in the depression group (25%). The difference was statistically significant (p = 0.001). The slow base rhythm and low voltage also differed notably between the two groups. The two groups displayed significant differences in both the frontal d and the temporal q rhythms (relative power), although the percentage was higher in patients with dementia. The posterior a rhythm was the variable with the greatest difference, and the percentage was higher in patients with depression. In absolute power, only the posterior a rhythm displayed a significant difference between the two groups, and was greater in the patients with depression. CONCLUSIONS: Performing an EEG in the initial treatment of patients with dementia is useful to distinguish it from other pathological conditions, and its quantitative analysis helps in the search for the focus.

[Frequency of neuropsychiatric signs and symptoms in patients with viral encephalitis]. / Frecuencia de signos y síntomas neuropsiquiátricos en pacientes con encefalitis viral.

INTRODUCTION: Acute viral encephalitis (AVE) is a frequent condition that usually courses with psychiatric alterations but few systematic studies have been conducted to investigate it. AIMS: To determine the frequency and the progression of the neuropsychiatric symptoms in patients with AVE. PATIENTS AND METHODS: A retrospective study was carried out. AVE was defined as an acute and progressively coursing condition in previously healthy subjects, with clinical signs of diffuse alteration of the central nervous system, abnormal electroencephalogram and/or inflammatory cerebrospinal fluid (CSF). We excluded patients who previously had epilepsy, a positive serodiagnosis for human immunodeficiency virus (HIV), and cases compatible with herpes simplex encephalitis from electroencephalographic or imaging data with focalisation towards temporal, frontal, regions or a positive DNA test for herpes in CSF. Finally, 83 patients were included. The psychiatric signs and symptoms that were produced were recorded during the acute phase and one year after discharge from hospital (sequelae). RESULTS: The psychiatric disorders in the acute phase were psychomotor agitation (67%), drowsiness (55%), disorientation (47%), visual hallucinations (43%) and aggressiveness (34%). One year after hospitalisation, in a sample of 70 patients in a clinical control, we found memory disorders (16%), aggressiveness (9%), aphasia (8%), visual hallucinations (8%), and auditory hallucinations (7%). The mortality rate was 6%. CONCLUSIONS: Neuropsychiatric disorders are very frequent during the acute phase of viral encephalitis, which is relevant for the differential diagnosis in patients who visit emergency departments with behavioural disorders. One year after hospital discharge, the main sequelae are of a neuropsychiatric nature and cognitive impairment is predominant.

Is dementia reversible in patients with neurocysticercosis?

OBJECTIVE: To determine the correlates and outcome of dementia in patients with neurocysticercosis (NCC). METHODS: Ninety consecutive patients with untreated NCC underwent a cognitive assessment (Mini-mental State Examination, Neurobehavioral Cognitive Status Examination, and IQCODE) and were classified as having or not having dementia according to DSM-IV criteria. Imaging and cerebrospinal fluid examination data were recorded. The cognitive measures were repeated six months after treatment with albendazole and steroids. RESULTS: At the initial evaluation 15.5% (n = 14) of the patients were classified as having dementia. Dementia was associated with older age, lower education level, increased number of parasitic lesions in the brain (mostly in the frontal, temporal, and parietal lobes). After six months, 21.5% of the patients from the dementia group continued to have a full dementia disorder and 78.5% no longer fulfilled the DSM-IV criteria for dementia, although some of these patients still showed mild cognitive decline. CONCLUSIONS: The results of this study suggest that dementia occurs frequently in patients with untreated NCC, and it is reversible in most cases.

Utilidad del análisis cuantitativo del electroencefalograma en el estudio de las demencias / The value of quantitative electroencephalogram analysis in the study of dementias

Introducción. Actualmente existe controversia acerca dela necesidad de realizar o no, como estudio inicial, un electroencefalograma(EEG) en el paciente con demencia. Objetivo. Establecer lautilidad del análisis convencional y cuantitativo del EEG en el abordajede la demencia. Pacientes y métodos. Se realizó el análisisvisual y cuantitativo de los EEG de pacientes con diagnóstico de síndromedemencial (en comparación con pacientes con trastorno depresivomayor). Resultados. Se analizaron en total 45 EEG, 25 a pacientescon demencia y 20 con trastorno depresivo mayor. Los hallazgosmás relevantes fueron el número de registros anormales encada grupo, y fue superior en el grupo de demencia, con 19 registrosanormales (76%), contra cinco en el grupo de depresión (25%), conuna diferencia estadísticamente significativa (p = 0,001). El ritmode base lento y el bajo voltaje también constituyeron diferencias significativasentre ambos grupos. Tanto el ritmo ä frontal, como el ètemporal (poder relativo) mostraron diferencias significativas entreambos grupos, y existió en mayor porcentaje en los pacientes condemencia. El ritmo áposterior fue la variable con mayor diferencia,y fue mayor el porcentaje en pacientes con depresión. En el poderabsoluto, sólo el ritmo áposterior mostró una diferencia significativaentre los dos grupos, y fue mayor en los pacientes con depresión.Conclusiones. La realización de un EEG en el abordaje inicial delos pacientes con demencia resulta de utilidad discriminativa frentea otras patologías, y el análisis cuantitativo del mismo ayuda en labúsqueda de focalización

Introduction. The question as to whether an electroencephalogram (EEG) needs to be carried out as a preliminarystudy in patients with dementia is currently the subject of some controversy. Aims. Our aim was to determine the value ofconventional and quantitative analysis of EEG recordings in the treatment of dementia. Patients and methods. The EEGrecordings of patients diagnosed with a syndrome of dementia were analysed both visually and quantitatively (comparingthem with patients with major depressive disorder). Results. A total of 45 EEG traces were analysed –25 from patients withdementia and 20 with major depressive disorder–. The most significant finding was the number of abnormal recordings ineach group, which was higher in the dementia group, with 19 abnormal recordings (76%) versus five in the depression group(25%). The difference was statistically significant (p = 0.001). The slow base rhythm and low voltage also differed notablybetween the two groups. The two groups displayed significant differences in both the frontal äand the temporal èrhythms(relative power), although the percentage was higher in patients with dementia. The posterior árhythm was the variable withthe greatest difference, and the percentage was higher in patients with depression. In absolute power, only the posterior árhythm displayed a significant difference between the two groups, and was greater in the patients with depression.Conclusions. Performing an EEG in the initial treatment of patients with dementia is useful to distinguish it from otherpathological conditions, and its quantitative analysis helps in the search for the focus

Primidone is associated with interictal depression in patients with epilepsy.

Depressive symptoms are common in epilepsy. To determine associations between depression and demographic, clinical, and pharmacological factors among epileptic patients, we conducted a cross-sectional survey. We evaluated 241 epileptic outpatients at a neurological center in a 6-month period. Depressive syndrome was diagnosed when both the Montgomery-Asberg Scale and the Beck Depression Inventory were rated above the standard cutoff points. Bivariate and multivariate analyses were performed to assess the differences between depressed and nondepressed patients with respect to demographic, clinical, and pharmacological features. Depressive syndrome was diagnosed in 42.7% of patients (n=103). Factors associated in the bivariate analysis were: cryptogenic etiology, posttraumatic epilepsy, use of primidone, and inadequate seizure control. After logistic regression, inadequate seizure control (OR 3.08, 95% CI 1.40-6.77, P=0.005) and use of primidone (OR 4.08, 95% CI 2.09-7.98; P<0.001) remained significantly associated. Depression was common and associated with inadequate seizure control and use of primidone.

Frecuencia de signos y síntomas neuropsiquiátricos en pacientes con encefalitis viral / Frequency of neuropsychiatric signs and symptoms in patients with viral encephalitis

Introducción. La encefalitis viral aguda (EVA) es un padecimiento frecuente que suele cursar con alteraciones psiquiátricas, que han sido estudiadas de forma sistemática. Objetivo. Conocer la frecuencia y la evolución de las manifestaciones neuropsiquiátricas en pacientes con EVA. Pacientes y métodos. Se ha realizado un estudio retrospectivo. Se definió la EVA como un padecimiento agudo y de curso progresivo en sujetos previamente sanos, con signos clínicos de alteración difusa del sistema nervioso central, electroencefalograma anormal y/o líquido cefalorraquídeo (LCR) inflamatorio. Excluimos a los pacientes con epilepsia previa o serología positiva para el virus de la inmunodeficiencia humana (VIH), y los casos compatibles con encefalitis herpética por datos electroencefalográficos o de imagen con focalización hacia las regiones temporales o frontales, o con prueba de ADN positiva para herpes en el LCR. Se incluyeron 83 pacientes. Se registraron los signos y síntomas psiquiátricos manifestados durante la fase aguda y un año después del alta hospitalaria (secuelas). Resultados. Las alteraciones psiquiátricas en la fase aguda fueron: agitación psicomotora (67%), somnolencia (55%), desorientación (47%), alucinaciones visuales (43%) y agresividad (34%). Un año después de la hospitalización, en 70 pacientes en control clínico, encontramos: alteraciones de la memoria (16%), agresividad (9%), afasia (8%), alucinaciones visuales (8%) y alucinaciones auditivas (7%). La mortalidad fue del 6%. Conclusiones. Las alteraciones neuropsiquiátricas son muy frecuentes durante la fase aguda de la encefalitis viral, lo que es relevante para el diagnóstico diferencial de los pacientes que acuden a los servicios de urgencias con alteraciones conductuales. A un año del alta, las principales secuelas son neuropsiquiátricas, y predomina el déficit cognitivo (AU)

Introduction. Acute viral encephalitis (AVE) is a frequent condition that usually courses with psychiatric alterations but few systematic studies have been conducted to investigate it. Aims. To determine the frequency and the progression of the neuropsychiatric symptoms in patients with AVE. Patients and methods. A retrospective study was carried out. AVE was defined as an acute and progressively coursing condition in previously healthy subjects, with clinical signs of diffuse alteration of the central nervous system, abnormal electroencephalogram and/or inflammatory cerebrospinal fluid (CSF). We excluded patients who previously had epilepsy, a positive serodiagnosis for human immunodeficiency virus (HIV), and cases compatible with herpes simplex encephalitis from electroencephalographic or imaging data with focalisation towards temporal, frontal, regions or a positive DNA test for herpes in CSF. Finally, 83 patients were included. The psychiatric signs and symptoms that were produced were recorded during the acute phase and one year after discharge from hospital (sequelae). Results. The psychiatric disorders in the acute phase were psychomotor agitation (67%), drowsiness (55%), disorientation (47%), visual hallucinations (43%) and aggressiveness (34%). One year after hospitalisation, in a sample of 70 patients in a clinical control, we found memory disorders (16%), aggressiveness (9%), aphasia (8%), visual hallucinations (8%), and auditory hallucinations (7%). The mortality rate was 6%. Conclusions. Neuropsychiatric disorders are very frequent during the acute phase of viral encephalitis, which is relevant for the differential diagnosis in patients who visit emergency departments with behavioural disorders. One year after hospital discharge, the main sequelae are of a neuropsychiatric nature and cognitive impairment is predominant (AU)