Persistent psychosis associated with extreme delta brush in anti-NMDA receptor encephalitis: a case report.

BACKGROUND: Anti-NMDAR encephalitis is an emerging differential diagnosis of first episode and persistent psychosis in the psychiatric community, as clinical manifestations include psychiatric symptoms, cognitive dysfunction, seizures, decreased consciousness, and dyskinesias. This disease is associated with extreme delta brush (EDB), but the significance and temporal course of this EEG pattern still needs to be determined. Herein, we report a case of anti-NMDAR encephalitis with persistent psychosis associated with EDB occurrence on multiple occasions during a 5-year disease course. CASE PRESENTATION: A 15-year-old girl was diagnosed with anti-NMDAR encephalitis and treated with progressive improvement. Four years after initial manifestations, an EDB pattern was seen on electroencephalogram (EEG) without new neurological symptoms. She had residual symptoms of episodic auditory hallucinations and impulsivity. One year later, the patient had a recurrence of neurological symptoms (seizures, dyskinesias and impaired attention), persisting with EDB on EEG. Clinical symptoms and EDB resolved after second-line treatment with rituximab. CONCLUSION: We describe the first case of persistent psychosis in anti-NMDAR encephalitis associated with extreme delta brush on multiple EEGs on prolonged follow-up. Electroencephalographic patterns such as EDB may serve as markers of residual disease activity, including psychiatric symptoms. Further studies with prolonged EEG monitoring are needed to better understand these findings.

Parinaud syndrome due to cofirmed neurotuberculosis in a lupus eritematosis systemic patient.

INTRODUCTION: This article aims to describe a patient with Parinaud syndrome due to neurotuberculosis confirmed by cerebrospinal fluid analysis. CASE REPORT: Initially, patient sought medical care, performed a chest x-ray and later a chest CT scan, with a probable diagnosis of miliary tuberculosis. In addition, she presented binocular diplopia worse at right lateral gaze, paresis of vertical gaze, light near-dissociation and convergent retraction nystagmus and presence of mycobacterium tuberculosis on PCR Xpert MTB/RIF. The treatment of miliary tuberculosis was interrupted due to pharmacodermia, but after diagnosis of neurotuberculosis, it was restarted with isoniazid, pyrazinamide and ethambutol with partial visual symptoms improvement. DISCUSSION: This case demonstrates the importance of pursuing diagnosis through more accurate techniques, especially in a patient with previous treatment pharmacoderma, whose absence of proper diagnosis and treatment would be extremely deleterious.

Electrical status epilepticus during sleep in patients with congenital Zika virus syndrome: An unprecedented clinical finding.

BACKGROUND: Brazil experienced a disproportionately higher rate of microcephaly cases in November 2015 with evidence of a causal link with Zika virus (ZIKV) infections during pregnancy. Epilepsy is a major neurological feature seen as part of congenital Zika virus syndrome (CZVS). Different seizure types and electroencephalographic (EEG) abnormalities have been described in association with this syndrome. However, clinical and neurophysiological features of epilepsy seen in children with CZVS are not fully understood. METHODS: We evaluated children with CZVS showing an EEG pattern of electrical status epilepticus during slow-wave sleep (ESES). Information on gender, age of onset of seizures, head circumference at birth, gross motor function at the time of diagnosis, of clinical and EEG aspects of seizures, EEG features and response to drug treatment was assessed. RESULTS: Our case series included four patients. They were diagnosed with epilepsy between one month to 18 months of age and showed an ESES pattern at the age of three. They presented with a wide range of epileptic symptoms, but all experienced tonic seizures. Multiple drug treatment was the management approach for three patients; however, they showed poor response to treatment with conventional drugs used in the treatment of ESES. CONCLUSIONS: Children with CZVS may develop an EEG pattern of ESES. Clinicians and neurologists should be aware of this neurological presentation to improve the management of these patients.

Sensorimotor white matter projections and disease severity in primary Restless Legs Syndrome/Willis-Ekbom disease: a multimodal DTI analysis.

BACKGROUND: Restless Legs Syndrome, a potentially disabling sleep disorder, also known as Willis-Ekbom disease (RLS/WED), may be caused by loss of inhibitory modulation of descending central motor pathways, structural changes in the somatosensory cortex, abnormal connectivity between motor and sensory areas, as well as by subtle abnormalities in white matter micro-organization. OBJECTIVE: To compare diffusion-tensor imaging (DTI) metrics in areas associated with sensory or motor function, as well as sensorimotor integration, between subjects with primary mild-to-severe RLS/WED and controls. METHODS: DTI metrics were assessed in 38 subjects with RLS/WED (14 mild to moderate, 24 severe to very severe) and 24 healthy age-matched controls with whole-brain Tract Based Spatial Statistics (TBSS), Region-of-interest (ROI) and probabilistic tractography based analyses. The ROIs corresponded to the corticospinal tract (CST) at the level of the cerebral peduncle; the superior, middle and inferior cerebellar peduncles. Subgroup analyses were made according to the severity of RLS/WED symptoms. The corticospinal tract was evaluated with probabilistic tractography. We also explored associations between significant findings and severity of symptoms with the Spearman's correlation coefficient. RESULTS: TBSS analysis revealed decreased axial diffusivity (AD) in the left posterior thalamic radiation in RLS/WED. In subjects with severe RLS/WED, AD was reduced in the left posterior corona radiata and this reduction was negatively correlated with severity of symptoms. ROI-based analysis showed that radial diffusivity (RD) was increased in the superior cerebellar peduncles of individuals with severe RLS/WED. Tractography did not show between-group or subgroup differences. CONCLUSIONS: Our results are consistent with subtle white matter changes, prominently in RLS/WED subjects with more severe symptoms, in areas related to sensory or motor function, as well as to sensorimotor integration, compared to controls. These findings support the hypothesis, raised by prior pathophysiological studies, of defective integration within these networks.

Short-interval intracortical inhibition is decreased in restless legs syndrome across a range of severity.

BACKGROUND: Decreased short-interval intracortical inhibition (SICI) to transcranial magnetic stimulation (TMS) of the primary motor cortex was described in subjects with restless legs syndrome/Willis-Ekbom disease (RLS/WED). It remained to be determined whether the magnitude of SICI decrease would be similar across levels of RLS/WED severity. Moreover, it was unknown whether, in addition to decreases in SICI, changes in cortical thickness or area could be detected in subjects with RLS/WED compared to controls. The objective of this study was to compare SICI, cortical thickness, and cortical area in subjects with idiopathic mild to moderate RLS/WED, severe to very severe RLS/WED, and controls. METHODS: The severity of RLS/WED was assessed by the International Restless Legs Syndrome Severity Scale (IRLSS). SICI and 3T magnetic resonance imaging (MRI) data of subjects with RLS/WED and controls were compared. A receiver operating characteristic curve for SICI was designed for discrimination of participants with RLS/WED from controls. Cortical thickness and area were assessed by automated surface-based analysis. RESULTS: SICI was significantly reduced in patients with mild to moderate and severe to very severe RLS/WED, compared to controls (one-way analysis of variance: F = 9.62, p < 0.001). Receiver operating characteristic curve analysis predicted RLS/WED when SICI was above 35% (area under the curve = 0.79, 95% CI 0.67-0.91, p < 0.001). Analyses of the whole brain and of regions of interest did not reveal differences in gray matter thickness or area between controls and subjects with RLS/WED. CONCLUSION: SICI is an accurate cortical biomarker that can support the diagnosis of RLS/WED even in subjects with mild symptoms, but cortical thickness and area were not useful for discriminating subjects with this condition from controls.

The duration of the cortical silent period is not abnormal in Restless Legs Syndrome/Willis-Ekbom Disease.

OBJECTIVE: To compare the duration of the cortical silent period (CSP) measured in a hand muscle in subjects with primary Restless Legs Syndrome (RLS/WED) and controls, using four different methods of analysis. METHODS: The CSP to transcranial magnetic stimulation of the dominant motor cortex was assessed in the abductor digiti minimi of 33 subjects with RLS/WED and 24 controls. CSP duration was measured by an automated and three visually-guided methods. RESULTS: There were significant differences between absolute values of CSP duration according to the method of analysis. However, irrespectively of the method used for CSP assessment, no differences were found between measurements performed in subjects with RLS/WED and subjects from the control group. CONCLUSIONS: Absolute values of CSP durations analyzed by different methods should not be directly compared, because significantly different results can be obtained from the same data set. SIGNIFICANCE: The CSP assessed from a hand muscle is unlikely to be a biomarker of primary RLS/WED. Our results highlight the importance of standardizing the definition of CSP onset and offset, as well as of describing in detail the methodology chosen to record and measure CSP duration, in order to enable comparisons between studies.

Transcranial magnetic stimulation for evaluation of motor cortical excitability in restless legs syndrome/Willis-Ekbom disease.

There is no consensus about mechanisms underlying restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED). Cortical excitability may be abnormal in RLS. Transcranial magnetic stimulation (TMS) can provide insight about cortical excitability. We reviewed studies about measures of excitability to TMS in RLS. Original studies published between January 1999 and January 2015 were searched in PubMed, Scopus, and Web of Science databases. Inclusion criteria were as follows: original studies involving primary RLS in patients from both sexes and ages between 18 and 85 years; TMS protocols clearly described; and they were written in English, in peer-reviewed journals. Fifteen manuscripts were identified. TMS protocols were heterogeneous across studies. Resting motor threshold, active motor threshold, and amplitudes of motor-evoked potentials were typically reported to be normal in RLS. A reduction in short-interval intracortical inhibition (SICI) was the most consistent finding, whereas conflicting results were described in regard to short-interval intracortical facilitation and the contralateral silent period. Decreased SICI can be reversed by treatment with dopaminergic agonists. Plasticity in the motor cortex and sensorimotor integration may be disrupted. TMS may become a useful biomarker of responsiveness to drug treatment in RLS. The field can benefit from increases in homogeneity and sizes of samples, as well as from decrease in methodological variability across studies.