Dermatological patients with itch report more stress, stigmatization experience, anxiety and depression compared to patients without itch: Results from a European multi-centre study.

BACKGROUND: Itch as the most common symptom in dermatology has been shown to be related to psychological factors such as stress, anxiety and depression. Moreover, associations were found between perceived stigmatization and itch. However, studies investigating the differences between patients with dermatoses with and without itch regarding perceived stress, stigmatization, anxiety and depression are missing. Therefore, one of the aims of the second study of the European Society for Dermatology and Psychiatry (ESDaP study II) was to investigate these relationships in a large cohort of patients with different itchy dermatoses. RESULTS: 3399 patients with 14 different itchy dermatoses were recruited at 22 centres in 17 European countries. They filled in questionnaires to assess perceived stigmatization, stress, signs of clinically relevant anxiety or depression, itch-related quality of life, the overall health status, itch duration, frequency and intensity. The most significant association between the severity of itching and the perception of stress was observed among individuals with rosacea (correlation coefficient r = 0.314). Similarly, the strongest links between itch intensity and experiences of stigmatization, anxiety, and depression were found in patients with seborrheic dermatitis (correlation coefficients r = 0.317, r = 0.356, and r = 0.400, respectively). Utilizing a stepwise linear regression analysis, it was determined that within the entire patient cohort, 9.3% of the variation in itch intensity could be accounted for by factors including gender, levels of anxiety, depression, and perceived stigmatization. Females and individuals with elevated anxiety, depression, and perceived stigmatization scores reported more pronounced itch intensities compared to those with contrary attributes. CONCLUSION: This study underscores the connection between experiencing itch and its intensity and the psychological strain it places on individuals. Consequently, psychological interventions should encompass both addressing the itch itself and the interconnected psychological factors. In specific cases, it becomes imperative for dermatologists to direct individuals towards suitable healthcare resources to undergo further psychological assessment.

Neuroimaging in the Epileptic Baboon.

Characterization of baboon model of genetic generalized epilepsy (GGE) is driven both electroclinically and by successful adoption of neuroimaging platforms, such as magnetic resonance imaging (MRI) and positron emission tomography (PET). Based upon its phylogenetic proximity and similar brain anatomy to humans, the epileptic baboon provides an excellent translational model. Its relatively large brain size compared to smaller nonhuman primates or rodents, a gyrencephalic structure compared to lissencephalic organization of rodent brains, and the availability of a large pedigreed colony allows exploration of neuroimaging markers of diseases. Similar to human idiopathic generalized epilepsy (IGE), structural imaging in the baboon is usually normal in individual subjects, but gray matter volume/concentration (GMV/GMC) changes are reported by statistical parametric mapping (SPM) analyses. Functional neuroimaging has been effective for mapping the photoepileptic responses, the epileptic network, altered functional connectivity of physiological networks, and the effects of anti-seizure therapies. This review will provide insights into our current understanding the baboon model of GGE through functional and structural imaging.

Non-convulsive status epilepticus in the setting of cannabidiol adjunctive therapy

Anti-seizure medications (ASMs) can cause non-convulsive status epilepticus (NCSE), but account for less than 5% of all NCSE cases. We present a 63-year-old, right-handed male with a history of intractable focal epilepsy since age seven years old, whose bouts of NCSE were triggered by cannabidiol (CBD) adjunctive therapy. His most common seizure types included focal myoclonic or tonic seizures with vocalization, usually with awakening, which occurred on a monthly basis despite the combination of tiagabine, perampanel, levetiracetam, lacosamide and clonazepam. After CBD was initiated, he began to exhibit episodes of prolonged confusion, at times with myoclonic or tonic seizures. Increasing CBD doses led to more frequent and prolonged episodes. The confusional episodes occurred predominantly in the morning, with spontaneous resolution by the afternoon. During one of these episodes, he was hospitalized, and NCSE was confirmed by video-EEG monitoring. CBD was withdrawn and the patient had no further episodes of NCSE. While CBD can cause NCSE, the medication interaction between CBD and tiagabine also needs to be considered.

Cerebral blood flow differences between high- vs low-frequency VNS therapy in the epileptic baboon.

PURPOSE: Cerebral blood flow (CBF) tracks physiological effects of ictal or interictal epileptic discharges (IEDs) and neurostimulation. This study compared CBF changes between high-frequency (HF; 300 Hz) microburst, and standard, low-frequency (LF; 30 Hz) vagal nerve stimulation (VNS) Therapy in 2 baboons with genetic generalized epilepsy (GGE), including one with photosensitivity. METHODS: The baboons were selected based on video recordings and scalp EEG studies. They were both implanted with Sentiva™ 1000 devices capable of stimulating at standard and microburst frequencies. Nine H215O (10-20 mCi) positron emission tomographic (PET) scans were performed each session (two PET sessions acquired for each animal). The baboons were sedated with ketamine, paralyzed, and monitored with scalp EEG. CBF changes were compared between the two modes of stimulation and resting scans in the first study, while in the second, VNS Therapy trials were combined with intermittent light stimulation (ILS) at 25 Hz and compared to CBF changes induced by ILS alone. RESULTS: ILS-associated IED rates were slightly reduced by HF- and LF-VNS Therapies in B1, while spontaneous IEDs were completely suppressed by HF-VNS Therapy in B2. Regional CBF changes were consistent between the two modes of therapy in each baboon, in particular with respect to the activation of the superior colliculus and cerebellum. Neither VNS mode suppressed the photoepileptic response in B1. In B2, IED suppression was associated with bilateral deactivations of the frontal and temporal cortices, cingulate and anterior striatum, as well as bilateral cerebellar activations. CONCLUSIONS: This pilot study reveals similar activation/deactivation patterns between LF- and HF-VNS Therapies, but the most pronounced CBF differences between the two baboons and the two modes of stimulation may have been driven by the suppression of the epileptic network by HF-VNS Therapy in B2. Some therapeutic targets appear to be subcortical, including the putamen, superior colliculus, brainstem nuclei, as well as the cerebellum, all of which modulate corticothalamic networks, which is particularly reflected by CBF changes associated with HF-VNS Therapy. These findings need to be replicated in larger samples and correlated with long-term clinical outcomes.

Absolute energies and emission line shapes of the L x-ray transitions of lanthanide metals.

We use an array of transition-edge sensors, cryogenic microcalorimeters with 4 eV energy resolution, to measure L x-ray emission-line profiles of four elements of the lanthanide series: praseodymium, neodymium, terbium, and holmium. The spectrometer also surveys numerous x-ray standards in order to establish an absolute-energy calibration traceable to the international system of units for the energy range 4 keV to 10 keV. The new results include emission line profiles for 97 lines, each expressed as a sum of one or more Voigt functions; improved absolute energy uncertainty on 71 of these lines relative to existing reference data; a median uncertainty on the peak energy of 0.24 eV, four to ten times better than the median of prior work; and six lines that lack any measured values in existing reference tables. The 97 lines comprise nearly all of the most intense L lines from these elements under broad-band x-ray excitation. The work improves on previous measurements made with a similar cryogenic spectrometer by the use of sensors with better linearity in the absorbed energy and a gold x-ray absorbing layer that has a Gaussian energy-response function. It also employs a novel sample holder that enables rapid switching between science targets and calibration targets with excellent gain balancing. Most of the results for peak energy values shown here should be considered as replacements for the currently tabulated standard reference values, while the line shapes given here represent a significant expansion of the scope of available reference data.

Cortical responsive neurostimulation in a baboon with genetic generalized epilepsy.

OBJECTIVE: To evaluate the efficacy of cortical responsive neurostimulation (CRN) in a male baboon with epilepsy and with genetic generalized epilepsy (GGE), as well as the alteration of seizure patterns and their circadian rhythms due to treatment. METHODS: The baboon was implanted with two subdural frontoparietal strips, bridging the medial central sulci bilaterally. Electrocorticography (ECoG) data were downloaded daily during a three-month baseline, then every 2-3 days over a five-month treatment period. Long episodes, reflecting ictal or interictal epileptic discharges, were also quantified. RESULTS: Twenty-three generalized tonic-clonic seizures (GTCS) and 2 episodes of nonconvulsive status epilepticus (NCSE) were recorded at baseline (median 8 events/month), whereas 26 GTCS were recorded under treatment (median 5/month). Similarly, daily indices of long episodes decreased from 0.46 at baseline to 0.29 with treatment. Ictal ECoG patterns and the circadian distribution of GTCS were also altered by RNS therapy. SIGNIFICANCE: This case study provides the proof-of-concept for RNS therapy in the baboon model of GGE. Cortical responsive neurostimulation (CRN) demonstrated a 38% median reduction in GTCS. Distinct ictal patterns were identified, which changed over the treatment period; the circadian pattern of his GTCS also shifted gradually from night to daytime with treatment. Future studies targeting the thalamic nuclei, or combining cortical and subcortical sites, may further improve detection and control of GTCS as well as other generalized seizure types. More broadly, this study demonstrates opportunities for evaluating seizure detection as well as chronic therapeutic interventions over long term in the baboon.

The baboon in epilepsy research: Revelations and challenges.

The baboon offers a natural model for genetic generalized epilepsy with photosensitivity. In this review, we will summarize some of the more important clinical, neuroimaging, and elctrophysiological findings form recent work performed at the Southwest National Primate Research Center (SNPRC, Texas Biomedical Research Institute, San Antonio, Texas), which houses the world's largest captive baboon pedigree. Due to the phylogenetic proximity of the baboon to humans, many of the findings are readily translatable, but there may be some important differences, such as the mutlifocality of the ictal and interictal epileptic discharges (IEDs) on intracranial electroencephalography (EEG) and greater parieto-occipital connectivity of baboon brain networks compared to juvenile myoclonic epilepsy in humans. Furthermore, there is still limited knowledge of the natural history of the epilepsy, which could be transformative for research into epileptogenesis in genetic generalized epilepsy (GGE) and sudden unexpected death in epilepsy (SUDEP).

Resolution of cryptogenic new onset refractory status epilepticus with tocilizumab.

New onset refractory status epilepticus (NORSE) was defined by the International League Against Epilepsy as occurring in patients presenting without a prior diagnosis of epilepsy or other neurological disease, with seizures that persist beyond 24 h. There is still a need to develop new treatment strategies for NORSE, particularly for those patients who are least responsive to conventional medical therapies. We present a case of a young female patient without any medical history presenting with status epilepticus, which was refractory not only to anti-seizure medications and anesthetics, but also to conventional immunomodulatory therapies. After nine weeks of electroclinical seizure activity, the patient responded to two doses of tocilizumab.

Contemporary x-ray wavelength metrology and traceability.

We report recent advances in absolute x-ray wavelength metrology in the context of producing modern standard reference data. Primary x-ray wavelength standards are produced today using diffraction spectrometers using crystal optics arranged to be operated in dispersive and non-dispersive geometries, giving natural-line-width limited profiles with high resolution and accuracy. With current developments, measurement results can be made traceable to the Système internationale definition of the meter by using diffraction crystals that have absolute lattice-spacing provenance through x-ray-optical interferometry. Recent advances in goniometry, innovation of electronic x-ray area detectors, and new in situ alignment and measurement methods now permit robust measurement and quantification of previously-elusive systematic uncertainties. This capability supports infrastructures like the NIST Standard Reference Data programs and the International Initiative on X-ray Fundamental Parameters and their contributions to science and industry. Such data projects are further served by employing complementary wavelength-and energy-dispersive spectroscopic techniques. This combination can provide, among other things, new tabulations of less-intense x-ray lines that need to be identified in x-ray fluorescence investigation of uncharacterized analytes. After delineating the traceability chain for primary x-ray wavelength standards, and NIST efforts to produce standard reference data and materials in particular, this paper posits the new opportunities for x-ray reference data tabulation that modern methods now afford.

'The psychosocial burden of alopecia areata and androgenetica': a cross-sectional multicentre study among dermatological out-patients in 13 European countries.

BACKGROUND: Hair diseases play an important burden on patients' lives, causing significant emotional and psychosocial distress. However, the impairment due to different hair conditions, such as alopecia areata (AA) and androgenetic alopecia (AGA), has rarely been compared. OBJECTIVE: The aim of this study was to assess the psychological burden of subgroups of patients with different hair diseases and to compare them to a healthy population. METHODS: In this study, we analysed a subgroup of patients with hair diseases from patients of a large multicentre study including 3635 dermatological patients and 1359 controls from 13 European countries. In the subgroup of patients with hair diseases, we analysed the socio-demographic characteristics, the stress level, and the impact of hair diseases on quality of life (QoL), anxiety, and depression and we compared them among patients with AA, AGA and healthy controls. RESULTS: The study population included 115 patients (77% women, 23% men) with hair diseases, 37 of whom with AA and 20 with AGA. Patients with hair diseases had a lower education level than healthy controls (medium educational level: 43% vs. 28%). Overall, 41% of the patients reported stressful life events during the last 6 months compared with 31% of the controls. Patients with the same age, sex, depression level and comorbidities had a worse QoL when suffering from AA than from AGA (Mean Dermatology Life Quality Index score: 5.8 vs. 2.5). CONCLUSION: Patients with hair diseases are more anxious, depressed and have a lower QoL than controls.

Cardiac changes in epileptic baboons with high-frequency microburst VNS therapy: A pilot study.

The epileptic baboon provides a natural model of idiopathic generalized epilepsy and sudden unexpected death in epilepsy (SUDEP). We sought to evaluate autonomic differences, including heart rate (HR), heart rate variability (HRV) and corrected QT-duration (QTc) between two epileptic (EB1, EB2) and one control (CB) baboon, and the autonomic effects of high-frequency (HF) microburst Vagal Nerve Stimulation (VNS) Therapy in the epileptic baboons. At baseline, EB2's HR was increased over both EB1 and CB, and EB1's HRV was decreased compared to the others. QTc-intervals were significantly prolonged in both epileptic baboons. EB1 became free of generalized tonic-clonic seizures (GTCS) with VNS therapy, whereas EB2's GTCS were reduced by a third. HR decreased in both epileptic baboons, but while HRV improved in EB1, it decreased in EB2. EB2 succumbed to SUDEP after 9 months. This pilot study demonstrates abnormalities in HR, HRV and QTc-intervals in epileptic baboons. HF VNS Therapy demonstrated different effects on HRV in the two epileptic baboons, which, in addition to persistent GTCS and elevated HR, may have contributed to SUDEP risk in EB2. Future studies are needed to establish normative values for HRV and determine variability of HR, HRV and QTc-intervals in epileptic baboons.

Effects of ketamine on EEG in baboons with genetic generalized epilepsy.

Ketamine, a noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist, used as an anesthetic has been reported to induce seizures both in humans and baboons predisposed to epilepsy. In this study, we aimed to characterize the acute effects of ketamine on scalp (sc-EEG) and intracranial EEG (ic-EEG) in the baboon, which offers a natural model of genetic generalized epilepsy (GGE). We evaluated the electroclinical response to ketamine in three epileptic baboons. The raw EEG data were analyzed within 10 min of intramuscular ketamine (5-6 mg/kg) administration. Earliest EEG changes occurred after 30 s in sc-EEG and after 15 s in ic-EEG of ketamine administration. These initial changes involved increased paroxysmal fast activity (PFA) followed by slowing, the latter emerging first occipitally, and then spreading more anteriorly. Generalized spike-and-wave discharges (GSWDs) were evident on both sc-EEG and ic-EEG within two minutes, but focal occipital discharges were already increased on ic-EEG after 15 s. Occipital slowing emerged on ic-EEG after 30 s, before spreading fronto-centrally and orbito-frontally. By 60-120 seconds post-injection, ic-EEG demonstrated a parieto-occipital burst suppression (BS), which was not noted on sc-EEG. Ketamine waves and seizures, especially if the latter were subclinical, also appeared earlier on ic-EEG. This study highlights the anesthetic and proconvulsant effects of ketamine originate in the occipital lobes before fronto-central regions. We speculate that NMDAR concentration difference in cortical regions, such as the occipital and frontal cortices, are mainly involved in the expression of ketamine's EEG effects, both physiological and epileptic.

Adult-onset Rasmussen's Syndrome with associated cortical dysplasia.

We describe a 23-year-old woman with previous right temporal lobe surgeries for underlying cortical dysplasia, presenting with drug-resistant right hemispheric seizures and epilepsia partialis continua (EPC). After anti-seizure medication adjustments, she developed focal status epilepticus with progressive EEG and neuroimaging changes. Cerebrospinal fluid and serum autoimmune panels were negative except for an elevated serum acetylcholine-receptor antibody titer, but she underwent immunosuppressive therapy. Stereotactic-EEG evaluation demonstrated multifocal independent ictal patterns in the right hemisphere. Rasmussen's Syndrome was confirmed by brain biopsy, and a hemispherectomy was performed. This patient demonstrates the rare association of adult-onset EPC with cortical dysplasia, precipitously evolving into Rasmussen's Syndrome.

The self-assessed psychological comorbidities of prurigo in European patients: a multicentre study in 13 countries.

BACKGROUND: Prurigo is defined by the presence of chronic pruritus and multiple localized or generalized pruriginous lesions. OBJECTIVE: The aim of this study was to assess the psychological burden of prurigo in patients of European countries. METHODS: In this multicentre European study, 3635 general dermatology outpatients and 1359 controls were included. Socio-demographic data and answers to questionnaires (regarding quality of life, general health, anxiety and depression and suicidal ideation) were collected. RESULTS: There were 27 patients with prurigo; of these, 63% were men, and the mean age was 58.6 years. Among patients with prurigo, 10 of 27 (37%) suffered from anxiety and 8 of 27 (29%) from depression. Suicidal ideation was reported in 5 of 27 (19%) patients, and for four of these five patients, suicidal ideation was related to their skin disease. These frequencies were higher in the 10 commonest dermatological diseases (including psoriasis, atopic dermatitis and leg ulcers). The impact on quality of life was severe, with a mean Dermatologic Life Quality Index (DLQI) of 12.4, with an extreme impact on quality of life for 23% of patients and a very large impact for 27% of patients. CONCLUSION: The psychological comorbidities of prurigo are common, greater than those of other skin diseases, and their impact on quality of life is significant. Thus, it is important to study this condition and to find new treatments.

Dermatologists across Europe underestimate depression and anxiety: results from 3635 dermatological consultations.

BACKGROUND: It was recently demonstrated that a significant number of patients with common skin diseases across Europe are clinically depressed and anxious. Studies have shown that physicians not trained as psychiatrists underdiagnose depression. This has not been explored among dermatologists. OBJECTIVES: To estimate the concordance between clinical assessment of depression and anxiety by a dermatologist and assessment with the Hospital Anxiety and Depression Scale (HADS). METHODS: The study was an observational cross-sectional multicentre study of prevalent cases of skin diseases in 13 countries in Europe. Consecutive patients were recruited in outpatient clinics and filled in questionnaires prior to clinical examination by a dermatologist who reported any diagnosis of skin disease and signs of mood disorders. RESULTS: Analysis of the 3635 consultations showed that the agreement between dermatologist and HADS was poor to fair (lower than 0·4) for all diagnosis categories. The true-positive rate (represented by the percentage of dermatologists recognizing signs of depression or anxiety in patients with depression or anxiety as defined by a HADS value ≥ 11) was 44·0% for depression and 35·6% for anxiety. The true negative rate (represented by the percentage of dermatologists not detecting signs of depression or anxiety in non-depressed or non-anxious patients defined by HADS-value < 11) was 88.8% for depression and 85.7% for anxiety. CONCLUSIONS: Dermatologists in Europe tend to underestimate mood disorders. The results suggest that further training for dermatologists to improve their skills in diagnosing depression and anxiety might be appropriate. When present, the psychological suffering of patients with dermatological conditions needs to be addressed.

High-frequency burst vagal nerve simulation therapy in a natural primate model of genetic generalized epilepsy.

PURPOSE: Since the approval of Vagal Nerve Stimulation (VNS) Therapy for medically refractory focal epilepsies in 1997, it has been also reported to be effective for a wide range of generalized seizures types and epilepsy syndromes. Instead of conventional VNS Therapy delivered at 20-30Hz signal frequencies, this study evaluates efficacy and tolerability of high-frequency burst VNS in a natural animal model for genetic generalized epilepsy (GGE), the epileptic baboon. METHODS: Two female baboons (B1 P.h. Hamadryas and B2 P.h. Anubis x Cynocephalus) were selected because of frequently witnessed generalized tonic-clonic seizures (GTCS) for VNS implantation. High-frequency burst VNS Therapy was initiated after a 4-5 week baseline; different VNS settings (0.25, 2 or 2.5mA, 300Hz, 4 vs 7 pulses, 0.5-2.5s interburst interval, and intermittent stimulation for 1-2 vs for 24h per day) were tested over the subsequent 19 weeks, which included a 4-6 week wash-out period. GTCS frequencies were quantified for each setting, while seizure duration and postictal recovery times were compared to baseline. Scalp EEG studies were performed at almost every setting, including intermittent light stimulation (ILS) to evaluate photosensitivity. Pre-ILS ictal and interictal discharge rates, as well as ILS responses were compared between trials. The Novel Object test was used to assess potential treatment effects on behavior. RESULTS: High-frequency burst VNS Therapy reduced GTCS frequencies at all treatment settings in both baboons, except when output currents were reduced (0.25mA) or intermittent stimulation was restricted (to 1-2h/day). Seizure duration and postictal recovery times were unchanged. Scalp EEG studies did not demonstrate treatment-related decrease of ictal or interictal epileptic discharges or photosensitivity, but continuous treatment for 120-180s during ILS appeared to reduce photoparoxysmal responses. High-frequency burst VNS Therapy was well-tolerated by both baboons, without cardiac or behavioral changes. Repetitive muscle contractions involving the neck and left shoulder girdle were observed intermittently, most commonly at 0.5 interburst intervals, but these were transient, resolving with a few cycles of stimulation and not noted in wakefulness. CONCLUSIONS: This preclinical pilot study demonstrates efficacy and tolerability of high-frequency burst VNS Therapy in the baboon model of GGE. The muscle contractions may be due to aberrant propagation of the stimulus along the vagal nerve or to the ansa cervicalis, but can be reduced by minimal adjustment of current output or stimulus duration.

Ictal laughter and crying: Should they be classified as automatisms?

Gelastic seizures (GS) describe ictal laughter and are associated with hypothalamic lesions, as well as other cortical areas. Dacrystic seizures (DS), characterized by ictal crying, also have been reported in hypothalamic lesions and focal epilepsy. We describe a young girl with drug resistant focal dyscognitive seizures associated with gelastic and dacrystic features. However, neither laughter nor crying was correlated with a stereotyped electroencephalographic (EEG) pattern or involvement of a particular brain region. Additionally, based on the variety of epileptogenic foci associated with GS and DS in the literature, laughter and crying appear to represent ictal or peri-ictal automatisms.