An Elusive Seizure

We present a case of a healthy 62-year-old woman who developed recurrent seizures preceded by subacute cognitive slowing, ataxia, night sweats, and weight loss. She was found to have cytopenias, multifocal T2/FLAIR hyperintensities on magnetic resonance imaging (MRI), and magnetic susceptibility artifact lesions on susceptibility weighted imaging (SWI). Her symptoms, imaging and laboratory abnormalities all improved with high-doses of steroids and intravenous immunoglobulin (IVIG). But recurred several weeks after completing treatment. Despite extensive work-up, she required multiple hospitalizations and repeat diagnostic studies to arrive at a diagnosis. With an expert discussant in hematology and oncology, we review the differential diagnosis and stepwise approach of unexplained neuro-inflammatory syndromes with cytopenias and systemic symptoms. Our case highlights how time, empiric treatment response, and repeated diagnostic studies refine differential diagnoses and subsequent evaluation. After revealing the diagnosis, we discuss the heterogenous clinical manifestations of this disease process.

New insights into the cognitive effects of sleep deprivation by decomposition of a cognitive throughput task

Study Objectives A cognitive throughput task known as the Digit Symbol Substitution Test (DSST) (or Symbol Digit Modalities Test) has been used as an assay of general cognitive slowing during sleep deprivation. Here, the effects of total sleep deprivation (TSD) on specific cognitive processes involved in DSST performance, including visual search, spatial memory, paired-associate learning, and motor response, were investigated through targeted task manipulations. Methods A total of 12 DSST variants, designed to manipulate the use of specific cognitive processes, were implemented in two laboratory-based TSD studies with N = 59 and N = 26 subjects, respectively. In each study, the Psychomotor Vigilance Test (PVT) was administered alongside the DSST variants. Results TSD reduced cognitive throughput on all DSST variants, with response time distributions exhibiting rightward skewing. All DSST variants showed practice effects, which were however minimized by inclusion of a pause between trials. Importantly, TSD-induced impairment on the DSST variants was not uniform, with a principal component analysis revealing three factors. Diffusion model decomposition of cognitive processes revealed that inter-individual differences during TSD on a two-alternative forced choice DSST variant were different from those on the PVT. Conclusions While reduced cognitive throughput has been interpreted to reflect general cognitive slowing, such TSD-induced impairment appears to reflect cognitive instability, like on the PVT, rather than general slowing. Further, comparisons between task variants revealed not one, but three distinct underlying processes impacted by sleep deprivation. Moreover, the practice effect on the task was found to be independent of the TSD effect and minimized by a task pacing manipulation.

Mal de Debarquement Syndrome

Mal de debarquement syndrome (MdDS) is a disorder of persistent vertigo characterized by a feeling of oscillation such as rocking, bobbing, or swaying. It is triggered by passive motion, typically by exposure to water, air, or land transportation. This syndrome affects middle-aged individuals who are predominantly women. MdDS presents as a balance disorder that carries significant risk of morbidity due to both the direct effects of balance impairment and associated symptoms of fatigue, cognitive slowing, and visual motion intolerance. The Barany Society will be publishing criteria for diagnosing persistent MdDS. In addition, more insight has been gained into the pathophysiology of MdDS, with current hypotheses pointing to a cerebral and cerebellar basis. Treatments have expanded beyond medication trials, and now include the use of noninvasive brain stimulation and readaptation of the vestibulo-ocular reflex.

Experiences of taking neuroleptic medication and impacts on symptoms, sense of self and agency: a systematic review and thematic synthesis of qualitative data

Purpose Neuroleptic (antipsychotic) drugs reduce psychotic symptoms, but how they achieve these effects and how the drugs’ effects are experienced by people who take them are less well understood. The present study describes a synthesis of qualitative data about mental and behavioural alterations associated with taking neuroleptics and how these interact with symptoms of psychosis and people’s sense of self and agency. Methods Nine databases were searched to identify qualitative literature concerning experiences of taking neuroleptic medication. A thematic synthesis was conducted. Results Neuroleptics were commonly experienced as producing a distinctive state of lethargy, cognitive slowing, emotional blunting and reduced motivation, which impaired functioning but also had beneficial effects on symptoms of psychosis and some other symptoms (e.g. insomnia). For some people, symptom reduction helped restore a sense of normality and autonomy, but others experienced a loss of important aspects of their personality. Across studies, many people adopted a passive stance towards long-term medication, expressing a sense of resignation, endurance or loss of autonomy. Conclusions Neuroleptic drugs modify cognition, emotions and motivation. These effects may be associated with reducing the intensity and impact of symptoms, but also affect people’s sense of self and agency. Understanding how the effects of neuroleptics are experienced by those who take them is important in developing a more collaborative approach to drug treatment in psychosis and schizophrenia.

Reduced arterial compliance along the cerebrovascular tree predicts cognitive slowing in multiple sclerosis: Evidence for a neurovascular uncoupling hypothesis

Background: Cognitive slowing occurs in ~70% of multiple sclerosis (MS) patients. The pathophysiology of this slowing is unknown. Neurovascular coupling, acute localized blood flow increases following neural activity, is essential for efficient cognition. Loss of vascular compliance along the cerebrovascular tree would result in suboptimal vasodilation, neurovascular uncoupling, and cognitive slowing. Objective: To assess vascular compliance along the cerebrovascular tree and its relationship to MS-related cognition. Methods: We tested vascular compliance along the cerebrovascular tree by dividing cerebral cortex into nested layers. MS patients and healthy controls were scanned using a dual-echo functional magnetic resonance imaging (fMRI) sequence while they periodically inhaled room air and hypercapnic gas mixture. Cerebrovascular reactivity was calculated from both cerebral blood flow (arterial) and blood-oxygen-level-dependent signal (venous) increases per unit increase in end-tidal CO2. Results: Arterial cerebrovascular reactivity changes along the cerebrovascular tree were reduced in cognitively slow MS compared to cognitively normal MS and healthy controls. These changes were fit to exponential functions, the decay constant (arterial compliance index; ACI) of which was associated with individual subjects’ reaction time and predicted reaction time after controlling for disease processes. Conclusion: Such associations suggest prospects for utility of ACI in predicting future cognitive disturbances, monitoring cognitive deficiencies and therapeutic responses, and implicates neurovascular uncoupling as a mechanism of cognitive slowing in MS.