Medically refractory epilepsy remains an area of intense clinical and scientific interest since a significant porportion of patients continue to suffer from debilitating seizures despite available therapies. In this setting, recent studies have focused on assessing the benefits of cannabidiol (CBD)-enriched cannabis, a plant based product without psychoactive properties which has been shown to decrease seizure frequency in animal models. More recently, several randomized controlled and open label trials have studied the effects of Epidiolex, a 99% pure oral CBD extract, on patients with refractory epilepsy. This in turn has led to the FDA approval of and more recently, to the Drug Enforcement Administration’s placement of Epidiolex into schedule V of the Controlled Substances Act (CSA). In this review, we summarize the major findings of several recent large-scale studies using this product with a focus on its adverse effects.

At perceptual threshold, some stimuli are available for conscious access whereas others are not. Such threshold inputs are useful tools for investigating the events that separate conscious awareness from unconscious stimulus processing. Here, viewing unmasked, threshold-duration images was combined with recording magnetoencephalography to quantify differences among perceptual states, ranging from no awareness to ambiguity to robust perception. A four-choice scale was used to assess awareness: "didn't see" (no awareness), "couldn't identify" (awareness without identification), "unsure" (awareness with low certainty identification), and "sure" (awareness with high certainty identification). Stimulus-evoked neuromagnetic signals were grouped according to behavioral response choices. Three main cortical responses were elicited. The earliest response, peaking at ∼100 ms after stimulus presentation, showed no significant correlation with stimulus perception. A late response (∼290 ms) showed moderate correlation with stimulus awareness but could not adequately differentiate conscious access from its absence. By contrast, an intermediate response peaking at ∼240 ms was observed only for trials in which stimuli were consciously detected. That this signal was similar for all conditions in which awareness was reported is consistent with the hypothesis that conscious visual access is relatively sharply demarcated.cognition | vision C onscious visual representations must be generated rapidly enough to affect behavior advantageously. Thus, vision must be fast. However, the network activation that supports visual perception is complex and involves many spatially segregated brain areas (1). As a result, certain integration delays must ensue for successful perceptual analysis to be achieved. An experimental paradigm was thus designed to address the temporal and neuronal conditions required for a rapid, high-level visual response.Several previous studies suggest that visual perception relies primarily on the early activation of occipital cortices (2-4). Others show that it results from the late activation (5, 6) of temporal (7), parietal, and frontal areas (8). Finally, others indicate that perception is associated with a midlatency evoked response (9), the timing of which can be delayed when stimulus energy is decreased to near-threshold levels (10,11).These conflicting findings demonstrate the unresolved nature of the timing underlying visual perception. Moreover, varied interpretations of the term "perception" may contribute to varied interpretations of the neuronal processes being studied, making it more difficult to understand the timing of cognitive events generated by the brain. To avoid such errors in communication, we define the term perception to mean the conscious awareness or detection of a presented visual stimulus: a phenomenon not to be confused with related processes such as visual identification and recognition. Although our definition is limited to the event in which a visual stimulus achieves conscious access, ...

Purpose: To assess the potential biological significance of variations in burst-suppression patterns (BSP) after cardiac arrest in relation to recovery of consciousness. In the context of recent theoretical models of BSP, bursting frequency may be representative of underlying network dynamics; discontinuous activation of membrane potential during impaired cellular energetics may promote neuronal rescue. Methods: We reviewed a database of 73 comatose post-cardiac arrest patients who underwent therapeutic hypothermia (TH) to assess for the presence of BSP and clinical outcomes. In a subsample of patients with BSP (n=14) spectral content of burst and suppression periods were quantified using multi-taper method. Results: BSP was seen in 45/73 (61%) patients. Comparable numbers of patients with (31.1%) and without (35.7%) BSP regained consciousness by the time of hospital discharge. In addition, in two unique cases, BSP initially resolved then spontaneously re-emerged after completion of TH and cessation of sedative medications. Both patients recovered consciousness. Spectral analysis of bursts in all patients regaining consciousness (n=6) showed a prominent theta frequency (5-7Hz) feature, but not in age-matched patients with induced BSP who did not recover consciousness (n=8). Conclusions: The prognostic implications of BSP after hypoxic brain injury may vary based on the intrinsic properties of the underlying brain state itself. The presence of theta activity within bursts may index potential viability of neuronal networks underlying recovery of consciousness;

Whether consciousness is an all-or-none or graded phenomenon is an area of inquiry that has received considerable interest in neuroscience and is as of yet, still debated. In this magnetoencephalography (MEG) study we used a single stimulus paradigm with sub-threshold, threshold and supra-threshold duration inputs to assess whether stimulus perception is continuous with or abruptly differentiated from unconscious stimulus processing in the brain. By grouping epochs according to stimulus identification accuracy and exposure duration, we were able to investigate whether a high-amplitude perception-related cortical event was (1) only evoked for conditions where perception was most probable (2) had invariant amplitude once evoked and (3) was largely absent for conditions where perception was least probable (criteria satisfying an all-on-none hypothesis). We found that averaged evoked responses showed a gradual increase in amplitude with increasing perceptual strength. However, single trial analyses demonstrated that stimulus perception was correlated with an all-or-none response, the temporal precision of which increased systematically as perception transitioned from ambiguous to robust states. Due to poor signal-to-noise resolution of single trial data, whether perception-related responses, whenever present, were invariant in amplitude could not be unambiguously demonstrated. However, our findings strongly suggest that visual perception of simple stimuli is associated with an all-or-none cortical evoked response the temporal precision of which varies as a function of perceptual strength.

A 48-year-old left-handed man presented to our emergency department (ED) with a 2-year history of auditory hallucinations that had become louder over several days. The hallucinations were the voices of the patient's mother and brother. They blamed him for his mother's death and sometimes gave him commands to shoplift, but never to harm himself or others. He denied visual hallucinations and paranoia. He had no significant medical or psychiatric history but did have a brother with schizophrenia. He had a history of cocaine and alcohol abuse but had been sober for over 200 days. Urine toxicology screen was negative. He was started on risperidone and observed overnight in the psychiatric ED. Because the patient's age was atypical for onset of a primary psychotic disorder, a CT scan of his head was obtained and neurology was consulted. On further interview, the patient demonstrated insight into the hallucinatory nature of the voices, remarking that whenever he carried out their commands, his actions felt unreal. He denied any episodes of shaking, loss of awareness, tongue-biting, or urinary incontinence. He reported having had 2 headaches in the prior 6 weeks, the worst of his life, described as severe, bifrontal, and without accompanying focal neurologic symptoms. The patient's neurologic examination was notable only for mildly impaired short-term recall, diminished sensation of light touch over the right forehead, and reduced amplitude and rate of finger taps on the right (his nondominant hand). Questions for consideration: 1. What is the differential diagnosis for auditory hallucinations? 2. What elements of the patient's presentation raise the possibility of a neurologic diagnosis? GO TO SECTION 2

We read with interest the recent report concerning the use of magnetic resonance imaging (MRI) to identify intestinal packets of illicit drug in suspected body packers [1]. We feel that several clarifications are required, however, before the authors' conclusions can be accepted.While it is not surprising that MRI can detect such packets, this study does not address how MRI performs in comparison to other diagnostic modalities. Computed tomography (CT) and abdominal ultrasound are more routinely available, though neither have exceptional negative predictive values [2][3][4]. It is also understood that in some localities the practice is to detain suspicious travelers and simply await the passage of several bowel movements. There was no mention of whether MRI was the only diagnostic procedure used in the population studied. It is stated that one subject underwent CT, but it is unclear whether that was the only case. If other diagnostics were also used in these patients an assessment of the positive and negative predictive values could have occurred.Additionally, it is unclear who interpreted the MRI images and whether they were blinded to the objectives of the study. Assuming it was considered unethical to expose subjects to multiple tests, the study conclusions would have been strengthened if the interpreters were asked to analyze a group of MRI images which included the study population and a negative control population without being told that some were suspected body packers.We wondered how the ethical concerns regarding the evaluation of subjects in custody of legal authorities were addressed. For example, the authors state that all subjects signed informed consent, but it is unclear what options were presented and if there was the potential for coercion.Finally, the authors state that body packers use ''parasympathomimetic drugs'' to prevent defecation while in transit. These medications are cholinergic and stimulate gastrointestinal motility, a potentially undesirable situation for a body packer. Antimuscarinic (anticholinergic; parasympatholytic) medications, which result in decreased peristalsis, are likely what the authors intended to write.In conclusion, we agree that MRI has the potential to be a useful test in the evaluation of travelers who are suspected of being body packers due to the lack of radiation exposure. Considering the cost and lack of availability of MRI and the lack of comparison with plain radiographs or CT, or simply awaiting defection, broad implementation cannot be recommended at this time.