[Temporary and persistent visual phenomena in neurology]. / Passagere und anhaltende visuelle Phänomene in der Neurologie.

Temporary and persistent visual phenomena are a frequent reason for a neurological presentation. The diagnosis can usually be made with the help of a structured anamnesis with determination of the time of onset, the course and symptoms as well as the monocular vs. binocular manifestation. The visual aura in migraine is certainly the most frequent entity to be differentiated. In particular, persistent visual phenomena such as visual snow syndrome, hallucinogen persisting perception disorder and the Charles Bonnet syndrome (CBS) seem to be underdiagnosed in clinical practice for various reasons and are probably not that rare. Instrumental diagnostics are mostly used for exclusion diagnostics and are a component of a complete patient education, but can be indicative for certain questions (CBS, epilepsy). This article presents the most frequent visual phenomena from the neurological practice and their differential diagnoses, guided by a case history.

White matter volume loss drives cortical reshaping after thalamic infarcts.

OBJECTIVE: The integration of somatosensory, ocular motor and vestibular signals is necessary for self-location in space and goal-directed action. We aimed to detect remote changes in the cerebral cortex after thalamic infarcts to reveal the thalamo-cortical connections necessary for multisensory processing and ocular motor control. METHODS: Thirteen patients with unilateral ischemic thalamic infarcts presenting with vestibular, somatosensory, and ocular motor symptoms were examined longitudinally in the acute phase and after six months. Voxel- and surface-based morphometry were used to detect changes in vestibular and multisensory cortical areas and known hubs of central ocular motor processing. The results were compared with functional connectivity data in 50 healthy volunteers. RESULTS: Patients with paramedian infarcts showed impaired saccades and vestibular perception, i.e., tilts of the subjective visual vertical (SVV). The most common complaint in these patients was double vision or vertigo / dizziness. Posterolateral thalamic infarcts led to tilts of the SVV and somatosensory deficits without vertigo. Tilts of the SVV were higher in paramedian compared to posterolateral infarcts (median 11.2° vs 3.8°). Vestibular and ocular motor symptoms recovered within six months. Somatosensory deficits persisted. Structural longitudinal imaging showed significant volume reduction in subcortical structures connected to the infarcted thalamic nuclei (vestibular nuclei region, dentate nucleus region, trigeminal root entry zone, medial lemniscus, superior colliculi). Volume loss was evident in connections to the frontal, parietal and cingulate lobes. Changes were larger in the ipsilesional hemisphere but were also detected in homotopical regions contralesionally. The white matter volume reduction led to deformation of the cortical projection zones of the infarcted nuclei. CONCLUSIONS: White matter volume loss after thalamic infarcts reflects sensory input from the brainstem as well the cortical projections of the main affected nuclei for sensory and ocular motor processing. Changes in the cortical geometry seem not to reflect gray matter atrophy but rather reshaping of the cortical surface due to the underlying white matter atrophy.

Age- and frequency-dependent changes in dynamic contrast perception in visual snow syndrome.

OBJECTIVE: Patients with visual snow syndrome (VSS) suffer from a debilitating continuous ("TV noise-like") visual disturbance. They report problems with vision at night and palinopsia despite normal visual acuity. The underlying pathophysiology of VSS is largely unknown. Currently, it is a clinical diagnosis based on the patient's history, an objective test is not available. Here, we tested the hypothesis that patients with VSS have an increased threshold for detecting visual contrasts at particular temporal frequencies by measuring dynamic contrast detection-thresholds. METHODS: Twenty patients with VSS were compared to age-, gender-, migraine- and aura-matched controls in this case-control study. Subjects were shown bars randomly tilted to the left or right, flickering at six different frequencies (15 Hz, 20 Hz, 25 Hz, 30 Hz, 35 Hz, 40 Hz). The contrast threshold (CT) for detection of left or right tilt was measured in a two-alternative adaptive forced-choice procedure (QUEST). The threshold was defined as the Michelson contrast necessary to achieve the correct response in 75% of the cases. RESULTS: The CT increased for higher flicker frequencies (ANOVA: main effect frequency: F (5,180) = 942; p < 0.001), with an additional significant frequency*diagnosis interaction (ANOVA: F (5,180) = 5.00; p < 0.001). This interaction effect was due to an increased CT at a flicker frequency of 15 Hz in the VSS cohort (VSS: MC = 1.17%; controls: MC = 0.77%). At the other frequencies, group comparisons revealed no differences. Furthermore, in the VSS cohort we observed an increase of CT with higher age (r = 0.69; p < 0.001), which was not seen in controls (r = 0.30; p = 0.20). CONCLUSIONS: This study demonstrates a lower visual contrast sensitivity exclusively at 15 Hz in VSS patients and demonstrates frequency-dependent differences in dynamic contrast vision. The peak sensitivities of both parvo- and magnocellular visual pathways are close to a frequency of about 10 Hz. Therefore, this frequency seems to be of crucial importance in everyday life. Thus, it seems plausible that the impairment of contrast sensitivity at 15 Hz might be an important pathophysiological correlate of VSS. Furthermore, the overall age-related decrease in contrast sensitivity only in VSS patients underscores the vulnerability of dynamic contrast detection in VSS patients. Dynamic CT detection seems to be a promising neurophysiological test that may contribute to the diagnosis of VSS.

Visual Phenomena Associated With Migraine and Their Differential Diagnosis.

BACKGROUND: Visual phenomena are of many different kinds; their differential diagnosis is usually possible with directed history-taking. In this review, we describe common visual phenomena that must be distinguished from a migraine aura. METHODS: This review is based on publications retrieved by a selective search in PubMed and the Web of Knowledge/Science, with special attention to the current classification of the International Headache Society and the recommendations of the German Migraine and Headache Society. The following search terms were used: "visual phenomena/phenomenon," "migraine aura," and "persistent/complication/ long-lasting/ongoing." RESULTS: The most helpful questions for differential diagnosis are whether the symptoms are present in one eye only or in both, whether their onset was sudden or over minutes or days, and whether the phenomenon has occurred only once or repeatedly, or is persistently present. A visual aura associated with migraine must be distinguished, in rare cases, from an isolated epileptic aura, from cerebral/retinal ischemia, or from visual snow. Further differential diagnoses include a persisting perceptual disturbance after hallucinogen use (HPPD, "hallucinogen persisting perception disorder") and the Charles Bonnet syndrome (CBS); the latter arises as a consequence of severely impaired vision. Posterior reversible encephalopathy syndrome (PRES) is rare and generally reveals itself over its further course through the appearance of additional clinical manifestations. Primary ophthalmological causes can usually be readily identified and classified by ophthalmological examination. CONCLUSION: Patients with visual phenomena typically consult physicians from various medical specialties. A correct differential diagnosis can be made based on the history if the physician views the symptoms in their overall context to determine the particular disease entity that is responsible.

Stalling chromophore synthesis of the fluorescent protein Venus reveals the molecular basis of the final oxidation step.

Fluorescent proteins (FPs) have revolutionised the life sciences, but the mechanism of chromophore maturation is still not fully understood. Here we show that incorporation of a photo-responsive non-canonical amino acid within the chromophore stalls maturation of Venus, a yellow FP, at an intermediate stage; a crystal structure indicates the presence of O2 located above a dehydrated enolate form of the imidazolone ring, close to the strictly conserved Gly67 that occupies a twisted conformation. His148 adopts an "open" conformation so forming a channel that allows O2 access to the immature chromophore. Absorbance spectroscopy supported by QM/MM simulations suggests that the first oxidation step involves formation of a hydroperoxyl intermediate in conjunction with dehydrogenation of the methylene bridge. A fully conjugated mature chromophore is formed through release of H2O2, both in vitro and in vivo. The possibility of interrupting and photochemically restarting chromophore maturation and the mechanistic insights open up new approaches for engineering optically controlled fluorescent proteins.

Coincidental SARS-CoV-2 infection and mRNA vaccination: a case report addressing the most important clinical questions.

The case describes the coincidental mRNA vaccination and SARS-CoV-2 infection of a 31-year-old physician addressing the theoretical considerations and recommendations for further actions in such a particular constellation that we will expect more often in the near future.

Magnetic Suppression of Perceptual Accuracy Is Not Reduced in Visual Snow Syndrome.

Objective: Patients with visual snow syndrome (VSS) suffer from continuous ("TV snow-like") visual disturbance of unknown pathoetiology. In VSS, changes in cortical excitability in the primary visual cortex and the visual association cortex are discussed, with recent imaging studies tending to point to higher-order visual areas. Migraine, especially migraine with aura, is a common comorbidity. In chronic migraine and episodic migraine with aura but not in episodic migraine without aura, a reduced magnetic suppression of perceptual accuracy (MSPA) reflects a probably reduced inhibition of the primary visual cortex. Here we investigated the inhibition of the primary visual cortex using MSPA in patients with VSS, comparing that with MSPA in controls matched for episodic migraine. Methods: Seventeen patients with VSS were compared to 17 age- and migraine-matched controls. Visual accuracy was assessed by letter recognition and modulated by transcranial magnetic stimulation delivered to the occipital cortex at different intervals with respect to the letter presentation (40, 100, and 190 ms). Results: Suppression of visual accuracy at the 100-ms interval was present without significant differences between VSS patients and age- and migraine-matched controls (percentage of correctly recognized trigrams, control: 46.4 ± 34.3; VSS: 52.5 ± 25.4, p = 0.56). Conclusions: In contrast to migraine with aura, occipital cortex inhibition, as assessed with MSPA, may not be affected in VSS.

Reflexive and Intentional Saccadic Eye Movements in Migraineurs.

Background: Migraine has been postulated to lead to structural and functional changes of different cortical and subcortical areas, including the frontal lobe, the brainstem, and cerebellum. The (sub-)clinical impact of these changes is a matter of debate. The spectrum of possible clinical differences include domains such as cognition but also coordination. The present study investigated the oculomotor performance of patients with migraine with and without aura compared to control subjects without migraine in reflexive saccades, but also in intentional saccades, which involve cerebellar as well as cortical networks. Methods: In 18 patients with migraine with aura and 21 patients with migraine without aura saccadic eye movements were recorded in two reflexive (gap, overlap) and two intentional (anti, memory) paradigms and compared to 25 controls without migraine. Results: The main finding of the study was an increase of saccade latency in patients with and without aura compared to the control group solely in the anti-task. No deficits were found in the execution of reflexive saccades. Conclusions: Our results suggest a specific deficit in the generation of correct anti-saccades, such as vector inversion. Such processes are considered to need cortical networks to be executed correctly. The parietal cortex has been suggested to be involved in vector inversion processes but is not commonly described to be altered in migraine patients. It could be discussed that the cerebellum, which is recently thought to be involved in the pathophysiology of migraine, might be involved in distinct processes such as spatial re-mapping through known interconnections with parietal and frontal cortical areas.

Triptan efficacy does not predict onabotulinumtoxinA efficacy but improves with onabotulinumtoxinA response in chronic migraine patients.

Chronic migraine (CM) is a highly disabling primary headache. Botulinum toxin (onabotulinumtoxinA) is effective for treatment of CM, with ~ 50% of patients responding after 24 weeks. A response predictor would prevent unnecessary treatments. Inhibiting calcitonin gene related peptide (CGRP) release from trigeminal nociceptive fibres is one of the modes of acting discussed for onabotulinumtoxinA in CM. Therefore, we hypothesized that the response to triptans might predict response to onabotulinumtoxinA. Contrariwise, onabotulinumtoxinA treatment might affect triptan efficacy. 49 CM patients scheduled for their first onabotulinumtoxinA treatment were included. Before (T0) and three months after (T1) onabotulinumtoxinA treatment, patients rated triptan efficacy and indicated number of headache days/month. At T1, patients additionally rated onabotulinumtoxinA efficacy. Headache days/month were on average reduced by 7.1 ± 7.0 days from T0 to T1 (p < 0.001). Triptan efficacy ratings at T0 did not predict onabotulinumtoxinA efficacy ratings at T1 (p = 0.19) or reduction of headache days (p = 0.37). However, triptan efficacy significantly improved from T0 to T1 in onabotulinumtoxinA responders (p < 0.001) but not in non-responders (p = 1.00). Triptan efficacy did not predict response to onabotulinumtoxinA in CM. However, triptan efficacy increased after successful onabotulinumtoxinA treatment. This supports the hypothesis that efficacy of acute migraine treatment with triptans improves with effective migraine prophylaxis.

An investigation of the seroprevalence of CrimeanCongo Hemorrhagic Fever and Lumpy Skin Disease in domesticated water buffaloes in northern Turkey.

This study was conducted in Samsun Province of Turkey to investigate the serological status of domesticated water buffaloes for both Crimean-Congo Hemorrhagic Fever (CCHF) and Lumpy Skin Disease (LSD). Serum was collected from a total of 272 water buffaloes from different age groups and both genders; of the total, 48.1% had been vaccinated against LSD with heterologous sheep-goat pox vaccine. The serum samples were individually assessed by using a commercial ID screen enzyme-linked immune-sorbent assay (ELISA) to detect neutralizing antibodies against both CCHF virus and LSD virus. All 272 buffaloes were negative for antibodies against the CCHF virus. All the unvaccinated buffaloes (141) were seronegative for LSD virus but of the 131 vaccinated buffaloes, 10 (7.6%) were seropositive for the LSD virus. In addition, 8.6% of vaccinated animals age >1 year old were seropositive for LSD, whereas the seropositivity was 5.1% for the animals age <= 1 year old. There was no significant difference for seropositivity between male and female animals in the >1 year old or <= 1 year old age groups. When seroprevalances for LSD in the tested water buffaloes are evaluated by gender, there was a significant difference between females (8.6%) and males (0%) in the <1 year old water buffaloes (X2=20.24; P<0.001). Separately, the results of this study indicate that Bafra district water buffaloes are not infected by CCHFV and LSDV and some of the buffaloes that vaccinated with LSDV did not develop sufficient antibodies to protect them after they were vaccinated for the LSD virus. Furthermore, the authors of this study conclude that both the commercially produced vaccine that is currently administered and the vaccination strategy have to be urgently evaluated by the veterinary authorities in Turkey. This is essential in order to combat the spread of LSD virus infection with an effective vaccine and a comprehensive management strategy across Turkey.

Quantification of photophobia in visual snow syndrome: A case-control study.

OBJECTIVE: To quantify photophobia in visual snow syndrome (VSS), a debilitating migraine-associated visual disturbance manifesting with continuous "TV snow-like" flickering dots in the entire visual field and additional visual symptoms, such as photophobia. METHODS: Photophobia was compared between 19 patients with VSS and 19 controls matched for age, sex, migraine and aura using the Leiden Visual Sensitivity Scale (L-VISS). RESULTS: Patients with VSS had an increased L-VISS-score compared to matched controls [(22.2 ± 5.9 vs. 4.4 ± 4.8; ANOVA, factors VSS and comorbid migraine: Main effect for VSS (F = 100.70; p < 0.001), but not for migraine (F < 0.01; p = 1.00) or the interaction (F = 1.93; p = 0.16)]. An L-VISS-score of 14 identified VSS with a sensitivity and specificity of 95% (Receiver Operating Characteristic analysis, 0.986 ± 0.014, p ≤ 0.001). CONCLUSION: Patients with VSS suffer continuously from photophobia at a level similar to chronic migraineurs during attacks. Although migraine and VSS share dysfunctional visual processing, patients with VSS might be more severely affected.

An investigation of the seroprevalence of Crimean-Congo Hemorrhagic Fever and Lumpy Skin Disease in domesticated water buffaloes in northern Turkey

@# This study was conducted in Samsun Province of Turkey to investigate the serological status of domesticated water buffaloes for both Crimean-Congo Hemorrhagic Fever (CCHF) and Lumpy Skin Disease (LSD). Serum was collected from a total of 272 water buffaloes from different age groups and both genders; of the total, 48.1% had been vaccinated against LSD with heterologous sheep-goat pox vaccine. The serum samples were individually assessed by using a commercial ID screen enzyme-linked immune-sorbent assay (ELISA) to detect neutralizing antibodies against both CCHF virus and LSD virus. All 272 buffaloes were negative for antibodies against the CCHF virus. All the unvaccinated buffaloes (141) were seronegative for LSD virus but of the 131 vaccinated buffaloes, 10 (7.6%) were seropositive for the LSD virus. In addition, 8.6% of vaccinated animals age >1 year old were seropositive for LSD, whereas the seropositivity was 5.1% for the animals age < 1 year old. There was no significant difference for seropositivity between male and female animals in the >1 year old or < 1 year old age groups. When seroprevalances for LSD in the tested water buffaloes are evaluated by gender, there was a significant difference between females (8.6%) and males (0%) in the >1 year old water buffaloes (X2=20.24; P<0.001). Separately, the results of this study indicate that Bafra district water buffaloes are not infected by CCHFV and LSDV and some of the buffaloes that vaccinated with LSDV did not develop sufficient antibodies to protect them after they were vaccinated for the LSD virus. Furthermore, the authors of this study conclude that both the commercially produced vaccine that is currently administered and the vaccination strategy have to be urgently evaluated by the veterinary authorities in Turkey. This is essential in order to combat the spread of LSD virus infection with an effective vaccine and a comprehensive management strategy across Turkey.

A complex pattern of autonomic dysfunction in familial Mediterranean fever. Results from a controlled cross-sectional study.

OBJECTIVES: Autonomic dysfunction (AD) has been described in various chronic inflammatory diseases. Studies of AD in patients with familial Mediterranean fever (FMF) are inconclusive. We aimed to assess AD in a cohort of FMF patients. METHODS: Signs and symptoms of AD were investigated in patients with FMF and compared to age and gender matched healthy controls. Symptoms of AD were assessed by COMPASS-31, a validated questionnaire to evaluate orthostatic, vasomotor, secretomotor, gastrointestinal, pupillomotor and bladder function domains. Assessment of objective AD comprised heart rate variability during deep breathing, skin conductance changes during mental arithmetic, blood pressure response to pain and dynamic infrared pupillometry. RESULTS: 25 patients and 25 healthy controls were included and evaluated by COMPASS-31 and objective testing of AD. FMF patients had higher median COMPASS-31 total scores than controls (23.7 vs. 1.6, p=0.024). Significant differences were also found in the secretomotor and gastrointestinal sub-domains (4.2 vs. 0.0; p<0.001 and 8.0 vs. 0.0; p=0.004, respectively). Symptoms of autonomic dysfunction were correlated with patient reported global disease activity (r=0.71; p<0.001) and pain level (r=0.68; p<0.001). There were no differences in heart rate variability (HRV), skin conductance, blood pressure response to pain or sympathetic pupillomotor function between patients and controls. FMF patients revealed impaired parasympathetic pupillomotor function that was not associated with clinical parameters. However, patients that were on IL-1-blocking therapy had better parasympathetic pupillary function than patients on conventional treatment. CONCLUSIONS: FMF patients have AD in terms of symptoms and parasympathetic pupillomotor function. Dynamic pupillometry can provide additional information on autonomic regulation in patients with FMF.

The first serological report for genotype C bovine parainfluenza 3 virus in ruminant species of mid-northen Turkey: Traces from the past.

Bovine parainfluenza 3 virus (BPI3V)is one of the most important respiratory pathogens and a leading cause of serious respiratory illnesses in cattle, both independent of and in connection with other pathogens involved in the bovine respiratory disease complex (BRDC). In this study, we aimed to identify the historical circulation of genotype C bovine BPI3V (BPI3Vc) in Turkey using the archival serum samples of domestic ruminants that had been collected from six provinces of northern Anatolia in Turkey between 2009-2010. A total of 896 sera from cattle (n=442), sheep (n=330), and goats (n=124) were randomly selected and screened with a virus neutralization test in order to detect antibodies for BPI3Vc. The overall seropositivity rate was 21.09%, with seropositivity rates for cattle, sheep, and goats of 21.04%, 20.00%, and 24.19%, respectively. Neutralizing antibody titers for selected samples ranged between 1/4 to 1/512. This study represents the first serological study conducted using the first BPI3V isolate of Turkey.

The first serological report for genotype C bovine parainfluenza 3 virus in ruminant species of mid-northen Turkey: Traces from the past

@#Bovine parainfluenza 3 virus (BPI3V)is one of the most important respiratory pathogens and a leading cause of serious respiratory illnesses in cattle, both independent of and in connection with other pathogens involved in the bovine respiratory disease complex (BRDC). In this study, we aimed to identify the historical circulation of genotype C bovine BPI3V (BPI3Vc) in Turkey using the archival serum samples of domestic ruminants that had been collected from six provinces of northern Anatolia in Turkey between 2009-2010. A total of 896 sera from cattle (n=442), sheep (n=330), and goats (n=124) were randomly selected and screened with a virus neutralization test in order to detect antibodies for BPI3Vc. The overall seropositivity rate was 21.09%, with seropositivity rates for cattle, sheep, and goats of 21.04%, 20.00%, and 24.19%, respectively. Neutralizing antibody titers for selected samples ranged between 1/4 to 1/512. This study represents the first serological study conducted using the first BPI3V isolate of Turkey.

Non-invasive vagus nerve stimulation significantly improves quality of life in patients with persistent postural-perceptual dizziness.

Persistent postural-perceptual dizziness (PPPD) is one of the most common causes of chronic vestibular disorders, with a substantial portion of the affected patients showing no significant improvement to standard therapies (i.e., pharmacotherapy, behavioral psychotherapy). Patients with PPPD have been shown to have a significant comorbidity with anxiety disorders and depression. Further, these patients show an activation of the autonomic nervous system resulting in symptoms such as nausea, increase of heart rate, and sweating. Based on the comorbidities and the activation of the autonomic nervous system, we addressed the question whether non-invasive vagus nerve stimulation (nVNS) might be a treatment option for these patients. In this prospective study we, therefore, applied nVNS to patients with treatment-refractory (to the standard therapy) PPPD. The stimulation protocol was similar to previous studies in patients with cluster headache and consisted of stimulations during exacerbations or acute attacks of vertigo, but also with regular stimulations in the morning and evening as prophylactic treatment. Results showed that non-invasive vagus nerve stimulation significantly improved quality of life, as measured by the EQ-5D-3L (p = 0.04), and depression, as measured by the HADS-D (p = 0.002), in the nVNS group, but not in the age- and sex-matched group with standard of care (SOC) treatment. Moreover, in the pooled analysis (additional 4 weeks of stimulation also in the SOC-group), less severe vertigo attacks/exacerbations (p = 0.04), a decrease in total postural sway path as measured by posturography (p = 0.02), as well as tendentious less anxiety (p = 0.08), occurred after stimulation. These data imply that short term nVNS is a safe and promising treatment option in patients with otherwise refractory PPPD.

The cold pressor test in interictal migraine patients - different parasympathetic pupillary response indicates dysbalance of the cranial autonomic nervous system.

BACKGROUND: Data on autonomic nervous system (ANS) activations in migraine patients are quite controversial, with previous studies reporting over- and underactivation of the sympathetic as well as parasympathetic nervous system. In the present study, we explicitly aimed to assess the cranial ANS in migraine patients compared to healthy controls by applying the cold pressor test to a cohort of migraine patients in the interictal phase and measuring the pupillary response. METHODS: In this prospective observational study, a strong sympathetic stimulus was applied to 20 patients with episodic migraine in the interictal phase and 20 matched controls without migraine, whereby each participant dipped the left hand into ice-cold (4 °C) water for a maximum of 5 min (cold pressor test). At baseline, 2, and 5 min during the cold pressor test, infrared monocular pupillometry was applied to quantify pupil diameter and light reflex parameters. Simultaneously, heart rate and blood pressure were measured by the external brachial RR-method at distinct time intervals to look for at least clinically relevant changes of the cardiovascular ANS. RESULTS: There were no significant differences between the migraine patients and controls at baseline and after 2 min of sympathetic stimulation in all the measured pupillary and cardio-vascular parameters. However, at 5 min, pupillary light reflex (PLR) constriction velocity was significantly higher in migraineurs than in controls (5.59 ± 0.73 mm/s vs. 5.16 ± 0.53 mm/s; unpaired t-test p < 0.05), while both cardiovascular parameters and PLR dilatation velocity were similar in both groups at this time point. CONCLUSIONS: Our findings of an increased PLR constriction velocity after sustained sympathetic stimulation in interictal migraine patients suggest an exaggerated parasympathetic response of the cranial ANS. This indicates that brainstem parasympathetic dysregulation might play a significant role in migraine pathophysiology. More dedicated examination of the ANS in migraine patients might be of value for a deeper understanding of its pathophysiology.