[Susac Syndrome: A Diagnostic Chameleon]. / Susac-Syndrom: ein diagnostisches Chamäleon.

Susac's syndrome (SuS) is a rare, probably autoimmune endotheliopathy of the central nervous system, retina and inner ear. It is characterized by a clinical triad of encephalopathy, branch retinal artery occlusions (BRAOs) and sensorineural hearing loss. To date, more than 300 cases of SuS have been reported in the literature. However, SuS remains an under- and misdiagnosed entity in the clinical setting. This report presents an exemplary case of a patient, who was initially misdiagnosed with relapsing-remitting multiple sclerosis. At initial presentation, the patient did not demonstrate the complete clinical triad, and the interval between symptom onset and diagnosis was 4 months. Typical diagnostic features, which enabled the diagnosis of SuS were: a) MRI findings with T2-hyperintense snowball-like lesions of the corpus callosum and subcortical white matter and hyperintense lesions in diffusionweighted imaging with reduced apparent diffusion coefficient; b) BRAOs and vessel wall hyperfluorescence in fluorescein angiography and a significant thickness reduction of the inner retinal layers in optical coherence tomography; c) bilateral sensorineural hearing loss. The patient was aggressively treated with cyclophosphamide, rituximab, glucocorticoids and acetylsalicylic acid with a good response to therapy. This report draws attention to the need to take SuS into consideration in the differential diagnosis at the interface of neurological, psychiatric, ophthalmological and otorhinolaryngological disorders. As SuS may result in severe and persistent neurological deficits, an interdisciplinary collaboration is fundamental for the prompt diagnosis and initiation of adequate immunosuppressive treatment.

The impact of the COMT genotype and cognitive demands on facets of intra-subject variability.

Intra-Subject Variability (ISV), a potential index of catecholaminergic regulation, is elevated in several disorders linked with altered dopamine function. ISV has typically been defined as reaction time standard deviation. However, the ex-Gaussian and spectral measures capture different aspects and may delineate different underlying sources of ISV; thus reflecting different facets of the construct. We examined the impact of factors associated with dopamine metabolism, namely, Catechol-O-Methyltransferase Val158Met (COMT) genotype and Working Memory (WM) and response-switching on ISV facets in young healthy adults. The Met allele was associated with overall increased variability. The rather exclusive sensitivity of ex-Gaussian tau to frequencies below 0.025 Hz and the quasi-periodic structure of particularly slow responses support the interpretation of tau as low frequency fluctuations of neuronal networks. Sigma, by contrast, may reflect neural noise. Regarding cognitive demands, a WM load-related increase in variability was present for all genotypes and all ISV facets. Contrastingly, ISV facets reacted differently to variations in response-switching as, across genotypes, sigma was elevated for rare target trials whereas tau was elevated for frequent standard trials, particularly for Met homozygotes. Our findings support the significant role of COMT in regulating behavioural ISV with its facetted structure and presumed underlying neural processes.

Electro-cortical correlates of multisensory integration using ecologically valid emotional stimuli: Differential effects for fear and disgust.

Multisensory integration (MSI) is crucial for human communication and social interaction and has been investigated in healthy populations and neurodevelopmental disorders. However, the use of stimuli with high ecological validity is sparse, especially in event-related potential (ERP) studies. The present study examined the ERP correlates of MSI in healthy adults using short (500 ms) ecologically valid professional actor-produced emotions of fear or disgust as vocal exclamation or facial expression (unimodal conditions) or both (bimodal condition). Behaviourally, our results show a general visual dominance effect (similarly fast responses following bimodal and visual stimuli) and an MSI-related speedup of responses only for fear. Electrophysiologically, both P100 and N170 showed MSI-related amplitude increases only following fear, but not disgust stimuli. Our results show for the first time that the known differential neural processing of fear and disgust also holds for the integration of dynamic auditory and visual information.

Recurrent ischaemic cerebrovascular events as presenting manifestations of myeloproliferative neoplasms.

BACKGROUND AND PURPOSE: Myeloproliferative neoplasms (MPNs) - polycythemia vera, essential thrombocythemia and primary myelofibrosis - are associated with increased risk for ischaemic cerebrovascular events (ICVEs). Due to their low prevalence, MPNs often remain undiagnosed as the cause of ICVEs. METHODS: Case records at the University of Tübingen between 2014 and 2017 were screened to identify patients with MPN-related ICVEs. Clinical features, brain imaging, laboratory findings, applied treatments and neurological outcomes were assessed. RESULTS: In all, 3318 patients with ICVEs were identified, and amongst them 17 patients with MPN-related ICVEs were included in a retrospective study. In 58% of these patients, ICVEs were the first manifestation of the underlying MPN; 24% presented with transient ischaemic attack and 76% with ischaemic stroke. Potentially concurrent ICVE etiologies were noted in 70% of the patients. The majority (94%) of patients were positive for the JAK2 V617F mutation, whilst in 29% recurrent ICVEs (range two to three) were noted prior to MPN diagnosis. Early MPN diagnosis and management was the only significant prognostic factor for ICVE recurrence (P < 0.001). DISCUSSION: Evidence is provided that, although rare, MPNs represent an underdiagnosed cause of recurrent ICVEs. High clinical awareness is warranted to identify an underlying MPN in patients presenting with sustained, abnormal blood count findings. Clinical algorithms for prompt MPN diagnosis and initiation of MPN treatment (e.g. cytoreductive therapy, phlebotomy) are required. As MPN management comprises a significant protective factor against ICVE recurrence, induction of MPN treatment should be regarded as an integral component of secondary stroke prevention in MPN-associated ICVEs.

Early onset slipped capital femoral epiphysis in children under 10 years old. Surgical treatment with two different methods and results.

BACKGROUND: Slipped capital femoral epiphysis (SCFE) is a condition commonly affecting adolescents. It is scarcely reported in children under ten years of age, but it can be debilitating when misdiagnosed. Our purpose was to report the incidence and treatment methods of SCFE that were applied in our institution in children under the age of ten. CASE SERIES: We retrospectively reviewed the records of patients with SCFE treated between 2007-2018 and excluded those older than ten years old. During the study period, 46 patients (49 hips) were diagnosed with SCFE, of whom nine patients (11 hips) were children younger than ten years old. The mean age at presentation was 8.25 years. The classification was made according to the Southwick slip angle and stability of the slip. Comorbidities and body mass index (BMI) were registered. There were nine milds, one moderate, and one severe slip. All but one case were stable. All the children were above the 97th percentile BMI for age. Three patients suffered from metabolic disease. In situ Kirschner wire (K-wire) fixation was used in five hips and in situ fixation with a single partially threaded cannulated screw (CS) in six. Only two complications that required intervention were recorded, one K-wire loosening, and one K-wire mechanical failure. The mean follow-up time was 40.1 (range: 10-74) months and included eight of the nine patients. They were monitored for pain, range of motion, avascular necrosis of the femoral head, and slip progression. CONCLUSION: The diagnosis of SCFE should be considered in overweight children under the age of ten, with hip-related clinical manifestations. Treatment in this young group of patients can be demanding. K-wire and partially threaded CS fixation both provide stability and accommodate the femoral head's future growth. The use of K-wire fixation is recommended at a very young age (6-8 years of age). Orthopedic surgeons have to be aware of the increased risk of hardware-related complications when using K-wires that may have to be addressed surgically. HIPPOKRATIA 2019, 23(4): 165-168.

Angle-resolved photoelectron spectroscopy and scanning tunnelling spectroscopy studies of the endohedral fullerene Li@C60.

Gas phase photoelectron spectroscopy (Rydberg Fingerprint Spectroscopy), TDDFT calculations and low temperature STM studies are combined to provide detailed information on the properties of the diffuse, low-lying Rydberg-like SAMO states of isolated Li@C60 endohedral fullerenes. The presence of the encapsulated Li is shown by the calculations to produce a significant distortion of the lowest-lying S- and P-SAMOs that is dependent on the position of the Li inside the fullerene cage. Under the high temperature conditions of the gas phase experiments, the Li is mobile and able to access different positions within the cage. This is accounted for in the comparison with theory that shows a very good agreement of the photoelectron angular distributions, allowing the symmetry of the observed SAMO states to be identified. When adsorbed on a metal substrate at low temperature, a strong interaction between the low-lying SAMOs and the metal substrate moves these states to energies much closer to the Fermi energy compared to the situation for empty C60 while the Li remains frozen in an off-centre position.

Central and peripheral nervous system immune-mediated demyelinating disease after allogeneic hematopoietic stem cell transplantation.

OBJECTIVE: We aimed to evaluate clinical and diagnostic features of central and peripheral immune-mediated demyelinating disease (CPID) in allogeneic hematopoietic stem cell transplantation (aHSCT) recipients. BACKGROUND: CPID refers to the late-onset, immune-mediated neurological complications following aHSCT, when other frequent differential diagnoses have been ruled out, and when symptoms and signs of systemic GvHD manifestations are absent. METHODS: Case records at the University of Tuebingen, between 2001 and 2015, were screened to identify patients with CPID after aHSCT. RESULTS: Seven patients who developed CPID after aHSCT were identified. The average time interval from aHSCT until onset of CPID was 2.6 (±2.8) years (mean±SD). The most prevalent manifestations of CPID were optic neuritis and/or myelitis and polyneuropathy. Cerebrospinal fluid analyses involved elevated protein concentration and lymphocytic pleocytosis, while oligoclonal bands in CSF, but not in serum, were detected in 28% of cases. Aquaporin-4-antibodies were consistently absent. MRI studies showed features suggestive of demyelination processes, with cerebral and/or spinal cord white-matter involvement, and features compatible with cerebral vasculitis. Corticosteroids, Immunoglobulins, Cyclophosphamide, Rituximab and Interferon beta-1a showed marginal treatment responses, whereas plasma exchange resulted in marked clinical improvement in two treated patients. A chronic disease-course with persisting neurological deficits was prevalent. CONCLUSIONS: CPID may comprise a rare complication of aHSCT, which manifests as optic neuritis and/or myelitis and is accompanied by sensorimotor polyneuropathy. A concomitant systemic manifestation of GvHD is not mandatory for CPID diagnosis. Usually, CPID exhibits a chronic, persisting disease course. Thus, clinical awareness is required, as early diagnosis and aggressive treatment may be prognostically advantageous.

A case of late-onset, thymoma-associated myasthenia gravis with ryanodine receptor and titin antibodies and concomitant granulomatous myositis.

BACKGROUND: Myasthenia gravis is an autoimmune neuromuscular disorder, which has only rarely been reported to co-manifest with myositis. The diagnosis of concomitant myositis in patients with myasthenia gravis is clinically challenging, and requires targeted investigations for the differential diagnosis, including EMG, autoantibody assays, muscle biopsy and, importantly, imaging of the mediastinum for thymoma screening. CASE PRESENTATION: This report presents a case-vignette of a 72-year-old woman with progressive proximal muscle weakness and myalgias, diagnosed with thymoma-associated myasthenia and bioptically verified granulomatous myositis, with positive autoantibody status for ryanodine receptor and titin antibodies. CONCLUSIONS: The diagnosis of concurrent myositis and myasthenia gravis, especially in the presence of ryanodine receptor and titin antibodies, should lead neurologists to adopt different treatment strategies compared to those applied in myasthenia or myositis alone. Moreover, further evidence is warranted that titin and, particularly, ryanodine receptor antibodies may co-occur or be pathophysiologically involved in myasthenia-myositis cases.

COMT Val158Met genotype is associated with fluctuations in working memory performance: converging evidence from behavioural and single-trial P3b measures.

Intra-subject variability in reaction times (ISV) is a promising endophenotype for several psychiatric conditions, but its neural underpinnings are not yet established. Converging evidence from neuroimaging, molecular genetics, and psychopharmacology suggests that ISV could index catecholaminergically-mediated neural noise. The fine-grained temporal resolution of electroencephalography is ideal for investigating ISV, but only if potential neural correlates of ISV can be assessed in single trials. Based on evidence that ISV is associated with dopaminergic functioning, we apply a recently developed method of single-trial P3b analysis to investigate the association of COMT Val(158)Met genotype with measures of ISV on the behavioural and neural levels at different working memory loads. Greater number of Met alleles was associated with poorer and more intra-individually variable performance on the tasks, and greater latency jitter in single-trial P3bs. These converging results at the behavioural and neurophysiological levels confirm previous observations that prefrontal dopamine availability is associated with stability and accuracy of cognitive performance. Together with previous studies, these data imply pleiotropic cognitive effects of COMT genotype.