[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.

Predictors of coronary tortuosity in patients with chronic coronary syndrome.

Aim    Coronary artery tortuosity is a common coronary angiographic finding. This tortuosity can cause myocardial ischemia even in the absence of significant coronary artery stenosis. Our aim was to compare the demographic, clinical and echocardiographic features of patients with chronic coronary syndrome (CCS) and with and without coronary artery tortuosity.Material and methods    361 patients who underwent elective coronary angiography (CAG) due to CCS were included in the study. These patients divided into two groups, those with coronary tortuosity (Group 1) and those without (Group 2). Univariable and multivariable logistic regression analysis was performed to identify predictors associated with coronary artery tortuosity.Results    The mean age of the 361 CCS patients (44 % female; 56 % male) was 56.7±11.5 years. In the univariable regression analysis, age, female sex, hypertension (HT), PR interval, QTc interval, ST / T segment changes, left ventricle diastolic dysfunction (LVDD), left ventricle hypertrophia (LVH) were identified as predictors of coronary tortuosity. In the multivariable regression analysis, age (OR: 1.059; 95 %CI: 1.032-1.087, p<0.001) and hypertension (OR: 0.484; 95 %CI: 0.278-0.843, p=0.01) were identified as independent predictors of coronary tortuosity.Conclusion    Coronary artery tortuosity is an angiographic finding that develops as a result of adaptive mechanisms in the heart and can cause myocardial ischemia. Predictors of coronary artery tortuosity in patients with CCS were long PR and QTc intervals, ST / T segment changes, LVH, LVDD, advanced age, and female gender. Evaluation of these demographic, electrocardiographic, and echocardiographic data may help clinicans to anticipate coronary artery tortuosity in patients with CCS and to be precautious for PCI.

Patients with chronic pain exhibit individually unique cortical signatures of pain encoding.

Chronic pain is characterised by an ongoing and fluctuating intensity over time. Here, we investigated how the trajectory of the patients' endogenous pain is encoded in the brain. In repeated functional MRI (fMRI) sessions, 20 patients with chronic back pain and 20 patients with chronic migraine were asked to continuously rate the intensity of their endogenous pain. Linear mixed effects models were used to disentangle cortical processes related to pain intensity and to pain intensity changes. At group level, we found that the intensity of pain in patients with chronic back pain is encoded in the anterior insular cortex, the frontal operculum, and the pons; the change of pain in chronic back pain and chronic migraine patients is mainly encoded in the anterior insular cortex. At the individual level, we identified a more complex picture where each patient exhibited their own signature of endogenous pain encoding. The diversity of the individual cortical signatures of chronic pain encoding results bridge between clinical observations and neuroimaging; they add to the understanding of chronic pain as a complex and multifaceted disease.

Reorganization of sensory networks after subcortical vestibular infarcts: A longitudinal symptom-related voxel-based morphometry study.

BACKGROUND AND PURPOSE: We aimed to delineate common principles of reorganization after infarcts of the subcortical vestibular circuitry related to the clinical symptomatology. Our hypothesis was that the recovery of specific symptoms is associated with changes in distinct regions within the core vestibular, somatosensory, and visual cortical and subcortical networks. METHODS: We used voxel- and surface-based morphometry to investigate structural reorganization of subcortical and cortical brain areas in 42 patients with a unilateral, subcortical infarct with vestibular and ocular motor deficits in the acute phase. The patients received structural neuroimaging and clinical monitoring twice (acute phase and after 6 months) to detect within-subject changes over time. RESULTS: In patients with vestibular signs such as tilts of the subjective visual vertical (SVV) and ocular torsion in the acute phase, significant volumetric increases in the superficial white matter around the parieto-opercular (retro-)insular vestibular cortex (PIVC) were found at follow-up. In patients with SVV tilts, spontaneous nystagmus, and rotatory vertigo in the acute phase, gray matter volume decreases were located in the cerebellum and the visual cortex bilaterally at follow-up. Patients with saccade pathology demonstrated volumetric decreases in cerebellar, thalamic, and cortical centers for ocular motor control. CONCLUSIONS: The findings support the role of the PIVC as the key hub for vestibular processing and reorganization. The volumetric decreases represent the reciprocal interaction of the vestibular, visual, and ocular motor systems during self-location and egomotion detection. A modulation in vestibular and ocular motor as well as visual networks was induced independently of the vestibular lesion site.

Frontal QRS/T angle can predict mortality in COVID-19 patients.

AIMS: The frontal QRS-T (fQRS) angle has been investigated in the general population, including healthy people and patients with heart failure. The fQRS angle can predict mortality due to myocarditis, ischaemic and non-ischaemic cardiomyopathies, idiopathic dilated cardiomyopathy, and chronic heart failure in the general population. Moreover, no studies to date have investigated fQRS angle in coronavirus disease 2019 (COVID-19) patients. Thus, the purpose of this retrospective multicentre study was to evaluate the fQRS angle of COVID-19 patients to predict in-hospital mortality and the need for mechanical ventilation. METHODS AND RESULTS: An electrocardiogram was performed for 327 COVID-19 patients during admission, and the fQRS angle was calculated. Mechanical ventilation was needed in 119 patients; of them, 110 died in the hospital. The patients were divided into two groups according to an fQRs angle >90° versus an fQRS angle ≤90°. The percentages of mortality and the need for mechanical ventilation according to fQRS angle were 67.8% and 66.1%, respectively, in the fQRs >90° group and 26.1% and 29.9% in the fQRS ≤90°group. Heart rate, oxygen saturation, fQRS angle, estimated glomerular filtration rate, and C-reactive protein level were predictors of mortality on the multivariable analysis. The mortality risk increased 2.9-fold on the univariate analysis and 1.6-fold on the multivariate analysis for the fQRS >90° patient group versus the fQRS ≤90° group. CONCLUSION: In conclusion, a wide fQRS angle >90° was a predictor of in-hospital mortality and associated with the need for mechanical ventilation among COVID-19 patients.

Localised increase in regional cerebral perfusion in patients with visual snow syndrome: a pseudo-continuous arterial spin labelling study.

OBJECTIVES: We aimed to investigate changes in regional cerebral blood flow (rCBF) using arterial spin labelling (ASL) in patients with visual snow syndrome (VSS), in order to understand more about the underlying neurobiology of the condition, which remains mostly unknown. METHODS: We performed an MRI study in which whole-brain maps of rCBF were obtained using pseudo-continuous ASL. Twenty-four patients with VSS and an equal number of gender and age-matched healthy volunteers took part in the study. All subjects were examined with both a visual paradigm consisting of a visual-snow like stimulus, simulating key features of the snow, and a blank screen at rest, randomly presented. RESULTS: Patients with VSS had higher rCBF than controls over an extensive brain network, including the bilateral cuneus, precuneus, supplementary motor cortex, premotor cortex and posterior cingulate cortex, as well as the left primary auditory cortex, fusiform gyrus and cerebellum. These areas were largely analogous comparing patients either at rest, or when looking at a 'snow-like' visual stimulus. This widespread, similar pattern of perfusion differences in either condition suggests a neurophysiological signature of visual snow. Furthermore, right insula rCBF was increased in VSS subjects compared with controls during visual stimulation, reflecting a greater task-related change and suggesting a difference in interoceptive processing with constant perception of altered visual input. CONCLUSION: The data suggest VSS patients have marked differences in brain processing of visual stimuli, validating its neurobiological basis.

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.

CHA2DS2-VASc score and modified CHA2DS2-VASc score can predict mortality and intensive care unit hospitalization in COVID-19 patients.

In this study, we investigated whether the CHA2DS2-VASc score could be used to estimate the need for hospitalization in the intensive care unit (ICU), the length of stay in the ICU, and mortality in patients with COVID-19. Patients admitted to Merkezefendi State Hospital because of COVID-19 diagnosis confirmed by RNA detection of virus by using polymerase chain reaction between March 24, 2020 and July 6, 2020, were screened retrospectively. The CHA2DS2-VASc and modified CHA2DS2-VASc score of all patients was calculated. Also, we received all patients' complete biochemical markers including D-dimer, Troponin I, and c-reactive protein on admission. We enrolled 1000 patients; 791 were admitted to the general medical service and 209 to the ICU; 82 of these 209 patients died. The ROC curves of the CHA2DS2-VASc and M-CHA2DS2-VASc scores were analyzed. The cut-off values of these scores for predicting mortality were ≥ 3 (2 or under and 3). The CHA2DS2-VASc and M-CHA2DS2-VASc scores had an area under the curve value of 0.89 on the ROC. The sensitivity and specificity of the CHA2DS2-VASc scores were 81.7% and 83.8%, respectively; the sensitivity and specificity of the M-CHA2DS2-VASc scores were 85.3% and 84.1%, respectively. Multivariate logistic regression analysis showed that CHA2DS2-VASc, Troponin I, D-Dimer, and CRP were independent predictors of mortality in COVID-19 patients. Using a simple and easily available scoring system, CHA2DS2-VASc and M-CHA2DS2-VASc scores can be assessed in patients diagnosed with COVID-19. These scores can predict mortality and the need for ICU hospitalization in these patients.

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.

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.

[Tension type headaches : Quo vadis?] / Kopfschmerz vom Spannungstyp : Quo vadis?

Episodic tension type headache is considered to be the most prevalent primary headache. If tension type headache occurs on more than 15 days per month for at least 3 consecutive months, it is classified as chronic tension type headache. In recent years, it has become obvious that it is difficult to distinguish between episodic tension type headache and a moderate migraine attack and also between chronic tension type headache and chronic migraine. In the paper, we discuss how the differential diagnosis can be more specific and which therapy is supported by the literature. In addition, we discuss differences and similarities of tension type headache and migraine and a possible similar pathophysiology of both (convergence hypothesis).

Evidence of dysfunction in the visual association cortex in visual snow syndrome.

Patients with visual snow syndrome (VS) suffer from a debilitating continuous visual disturbance of unknown mechanism. The present study tested the hypothesis of dysfunctional visual processing using visual evoked potentials. Eighteen patients were compared to age-matched migraineurs (M) and healthy controls (C) using 2-way analysis of variance with group (VS, M, C) and gender as factors. Visual evoked potentials from patients with VS demonstrated increased N145 latency (in milliseconds, VS: 152.7 ± 7.9 vs M: 145.3 ± 9.8 vs C: 145.5 ± 9.4; F = 3.28; p = 0.046) and reduced N75-P100 amplitudes (in microvolts, VS: 7.4 ± 3.5 vs M: 12.5 ± 4.7 vs C: 10.8 ± 3.4; F = 3.16; p = 0.051). Dunnett post hoc analysis was significant for all comparisons between VS and controls. These findings are in agreement with the idea that the primary disturbance in VS is a dysfunction of the visual association cortex. Ann Neurol 2018;84:946-949.

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 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.

Hemicrania Continua: Beneficial Effect of Non-Invasive Vagus Nerve Stimulation in a Patient With a Contraindication for Indomethacin.

Hemicrania continua (HC) is a primary chronic headache disorder, characterized by a continuous and strictly unilateral headache, with possible cranial autonomic symptoms during episodes of pain exacerbation. The unilateral headache generally responds well to indomethacin; however, continuous indomethacin intake is often not tolerated due to severe adverse effects, like hypertension, gastrointestinal discomfort (especially if combined with aspirin), slightly increased risk of vascular events, and bronchial spasms. Therefore, alternative treatment options are desperately needed. Non-invasive vagus nerve stimulation (nVNS) has been shown to be effective in patients with cluster headache, another trigeminal autonomic cephalalgia (TAC), with cranial parasympathetic autonomic activation during the attacks.

Headache service quality: evaluation of quality indicators in 14 specialist-care centres.

BACKGROUND: The study was a collaboration between Lifting The Burden (LTB) and the European Headache Federation (EHF). Its aim was to evaluate the implementation of quality indicators for headache care Europe-wide in specialist headache centres (level-3 according to the EHF/LTB standard). METHODS: Employing previously-developed instruments in 14 such centres, we made enquiries, in each, of health-care providers (doctors, nurses, psychologists, physiotherapists) and 50 patients, and analysed the medical records of 50 other patients. Enquiries were in 9 domains: diagnostic accuracy, individualized management, referral pathways, patient's education and reassurance, convenience and comfort, patient's satisfaction, equity and efficiency of the headache care, outcome assessment and safety. RESULTS: Our study showed that highly experienced headache centres treated their patients in general very well. The centres were content with their work and their patients were content with their treatment. Including disability and quality-of-life evaluations in clinical assessments, and protocols regarding safety, proved problematic: better standards for these are needed. Some centres had problems with follow-up: many specialised centres operated in one-touch systems, without possibility of controlling long-term management or the success of treatments dependent on this. CONCLUSIONS: This first Europe-wide quality study showed that the quality indicators were workable in specialist care. They demonstrated common trends, producing evidence of what is majority practice. They also uncovered deficits that might be remedied in order to improve quality. They offer the means of setting benchmarks against which service quality may be judged. The next step is to take the evaluation process into non-specialist care (EHF/LTB levels 1 and 2).

Evaluation of the correlation of neutrophil/lymphocyte ratio with prognostic classification systems in papillary thyroid carcinoma patients.

We aimed to evaluate the use of cost-effective NLR (Neutrophil Lymphocyte Ratio) in determining the prognosis and recurrence risk of thyroid papillary carcinoma patients. This retrospective, cross-sectional and single-center study was carried out in the Department of General Surgery, Istanbul Gaziosmanpasa Training and Research Hospital. Between 2018 and 2021, who were diagnosed with papillary thyroid cancer and underwent total thyroidectomy, and patients who underwent total thyroidectomy due to multinodular goiter were analyzed. For patients in the malignancy group, the NLR cutoff value was determined as 1.73, the sensitivity was calculated as 51.77% and the specificity as 86.15%. NLR in the malignant group was found to be 9.5 times higher than the NLR in the control group (Odds Ratio: 9.5). A statistically significant difference was found between NLR and papillary thyroid carcinoma prognostic classification systems (AJCC/TNM, AMES, and MACIS). NLR medians differ according to ATA recurrence risk classification (P = .020). According to the results we obtained in our study, we believe that cost-effective NLR can be a useful indicator in terms of predicting malignancy in a patient with thyroid nodule and in determining the prognosis and risk of recurrence in patients with thyroid papillary carcinoma.

Correlation between breast and axillary pathologic complete response after neoadjuvant chemotherapy in breast cancer.

AIM: The aim of this study was to evaluate the correlation of the pathological response in breast tissue and the axilla of patients with breast cancer who underwent surgery following neoadjuvant chemotherapy. METHOD: This retrospective cohort study included patients with T1-4, N1-3, M0 breast cancer who underwent surgery following neoadjuvant chemotherapy at Gaziosmanpasa Training and Research Hospital between 2013 and 2022. The response of the breast tissue to chemotherapy was evaluated with the Miller-Payne grading system, and the response of the axillary lymph nodes to chemotherapy was evaluated with the Pinder grading system. The patients were grouped histopathologically as luminal A, luminal B, Her-2 enriched, or triple negative breast cancer (TNBC). RESULTS: The study was completed with 140 patients. Pathological complete response (pCR) was seen in the breast in 40 patients and in the axilla in 34. Of the patients with pCR in the breast, pCR was also determined in the axilla in 45%. In the patients with pCR in both the breast and axilla, Her-2 enriched subtype, estrogen receptor negativity, progesterone receptor negativity, Her-2 neu positivity, and Ki-67 level >25% were determined to be effective (p<0.05). Her-2 neu positivity was evaluated as statistically significant in the development of pCR in both the breast and axilla (OR: 4.06, 95% CI:1.2-13.6, p=0.023). CONCLUSION: The development of pCR in the breast, especially in the Her-2 enriched subgroup, can be accepted as a predictive factor for the evaluation of axillary response in patients with breast cancer. The least compatibility was seen in the luminal A subgroup. KEY WORDS: Breast cancer, Miller-Payne, Neoadjuvant chemotherapy Pathological complete response, Pinder.