Retrospective analysis of COVID-19 patients with Guillain-Barre, Miller-Fisher, and opsoclonus-myoclonus-ataxia syndromes-a case series.

BACKGROUND: In accordance with the rising number of SARS-CoV­2 infections, reports of neurological complications have also increased. They include cerebrovascular diseases but also immunological diseases such as Guillain-Barre syndrome (GBS), Miller-Fisher syndrome (MFS), and opsoclonus-myoclonus-ataxia syndrome (OMAS). While GBS and MFS are typical postinfectious complications, OMAS has only recently been described in the context of COVID-19. GBS, MFS, and OMAS can occur as para- and postinfectious, with different underlying pathomechanisms depending on the time of neurological symptom onset. The study aimed to describe clinical features, time between infection and onset of neurological symptoms, and outcome for these diseases. METHODS: All COVID-19 patients treated in the neurological ward between January 2020 and December 2022 were screened for GBS, MFS, and OMAS. The clinical features of all patients, with a particular focus on the time of onset of neurological symptoms, were analyzed. RESULTS: This case series included 12 patients (7 GBS, 2 MFS, 3 OMAS). All GBS and one MFS patient received immunomodulatory treatment. Three patients (2 GBS, 1 OMAS) had a severe COVID-19 infection and received mechanical ventilation. In patients with OMAS, only one patient received treatment with intravenous immunoglobulin and cortisone. The remaining two patients, both with disease onset concurrent with SARS-COV­2 infection, recovered swiftly without treatment. In all subgroups, patients with concurrent onset of neurological symptoms and COVID-19 infection showed a trend toward shorter disease duration. CONCLUSION: All patient groups displayed a shorter disease duration if the onset of neurological symptoms occurred shortly after the COVID-19 diagnosis. In particular, both the OMAS patients with symptom onset concurrent with COVID-19 showed only abortive symptoms followed by a swift recovery. This observation would suggest different pathomechanisms for immune-mediated diseases depending on the time of onset after an infection.

Clinical presentation and management strategies of cardiovascular autonomic dysfunction following a COVID-19 infection - A systematic review.

BACKGROUND: Cardiovascular autonomic dysfunction may reportedly occur after a coronavirus-disease-2019 (COVID-19) infection, but the available evidence is scattered. Here we sought to understand the acute and mid-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on cardiovascular autonomic function. METHODS: We performed a systematic PubMed, Embase, Web of Science, medRxiv, and bioRxiv search for cases of cardiovascular autonomic dysfunction during an acute SARS-CoV-2 infection or post-COVID-19 condition. The clinical-demographic characteristics of individuals in the acute versus post-COVID-19 phase were compared. RESULTS: We screened 6470 titles and abstracts. Fifty-four full-length articles were included in the data synthesis. One-hundred and thirty-four cases were identified: 81 during the acute SARS-CoV-2 infection (24 thereof diagnosed by history) and 53 in the post-COVID-19 phase. Post-COVID-19 cases were younger than those with cardiovascular autonomic disturbances in the acute SARS-CoV-2 phase (42 vs. 51 years old, p = 0.002) and were more frequently women (68% vs. 49%, p = 0.034). Reflex syncope was the most common cardiovascular autonomic disorder in the acute phase (p = 0.008) and postural orthostatic tachycardia syndrome (POTS) the most frequent diagnosis in individuals with post-COVID-19 orthostatic complaints (p < 0.001). Full recovery was more frequent in individuals with acute versus post-COVID-19 onset of cardiovascular autonomic disturbances (43% vs. 15%, p = 0.002). CONCLUSIONS: There is evidence from the scientific literature about different types of cardiovascular autonomic dysfunction developing during and after COVID-19. More data about the prevalence of autonomic disorders associated with a SARS-CoV-2 infection are needed to quantify its impact on human health.

Impact of the COVID-19 pandemic on clinical autonomic practice in Europe A survey of the European Academy of Neurology (EAN) and the European Federation of Autonomic Societies (EFAS).

OBJECTIVE: To investigate the impact of the coronavirus-disease-2019 (COVID-19) pandemic on European clinical autonomic practice. METHODS: Eighty-four neurology-driven or interdisciplinary autonomic centers in 22 European countries were invited to fill in a web-based survey between September and November 2021. RESULTS: Forty-six centers completed the survey (55%). During the first pandemic year, the number of performed tilt-table tests, autonomic outpatient and inpatient visits decreased respectively by 50%, 45% and 53%, and every-third center reported major adverse events due to postponed examinations or visits. The most frequent newly-diagnosed or worsened cardiovascular autonomic disorders after COVID-19 infection included postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension, and recurrent vasovagal syncope, deemed likely related to the infection by ≥50% of the responders. Forty-seven percent of the responders also reported about people with new-onset of orthostatic intolerance, but negative tilt-table findings, and 16% about people with psychogenic pseudosyncope after COVID-19. Most patients were treated non-pharmacologically and symptomatic recovery at follow-up was observed in ≥45% of cases. By contrast, low frequencies of newly-diagnosed cardiovascular autonomic disorders following COVID-19 vaccination were reported, most frequently POTS and recurrent vasovagal syncope, and most of the responders judged a causal association unlikely. Non-pharmacological measures were the preferred treatment choice, with 50-100% recovery rates at follow-up. CONCLUSIONS: Cardiovascular autonomic disorders may develop or worsen following a COVID-19 infection, while the association with COVID-19 vaccines remains controversial. Despite the severe pandemic impact on European clinical autonomic practice, a specialized diagnostic work-up was pivotal to identify non-autonomic disorders in people with post-COVID-19 orthostatic complaints.

EFAS/EAN survey on the influence of the COVID-19 pandemic on European clinical autonomic education and research.

PURPOSE: To understand the influence of the coronavirus disease 2019 (COVID-19) pandemic on clinical autonomic education and research in Europe. METHODS: We invited 84 European autonomic centers to complete an online survey, recorded the pre-pandemic-to-pandemic percentage of junior participants in the annual congresses of the European Federation of Autonomic Societies (EFAS) and European Academy of Neurology (EAN) and the pre-pandemic-to-pandemic number of PubMed publications on neurological disorders. RESULTS: Forty-six centers answered the survey (55%). Twenty-nine centers were involved in clinical autonomic education and experienced pandemic-related didactic interruptions for 9 (5; 9) months. Ninety percent (n = 26/29) of autonomic educational centers reported a negative impact of the COVID-19 pandemic on education quality, and 93% (n = 27/29) established e-learning models. Both the 2020 joint EAN-EFAS virtual congress and the 2021 (virtual) and 2022 (hybrid) EFAS and EAN congresses marked higher percentages of junior participants than in 2019. Forty-one respondents (89%) were autonomic researchers, and 29 of them reported pandemic-related trial interruptions for 5 (2; 9) months. Since the pandemic begin, almost half of the respondents had less time for scientific writing. Likewise, the number of PubMed publications on autonomic topics showed the smallest increase compared with other neurological fields in 2020-2021 and the highest drop in 2022. Autonomic research centers that amended their trial protocols for telemedicine (38%, n = 16/41) maintained higher clinical caseloads during the first pandemic year. CONCLUSIONS: The COVID-19 pandemic had a substantial negative impact on European clinical autonomic education and research. At the same time, it promoted digitalization, favoring more equitable access to autonomic education and improved trial design.

[Myalgic encephalomyelitis/chronic fatigue syndrome: an overview of current evidence]. / Myalgische Enzephalomyelitis/chronisches Fatigue-Syndrom: eine Übersicht zur aktuellen Evidenz.

Over the past 5 years both media and scientific interest has surged regarding the disorder myalgic encephalomyelitis and chronic fatigue syndrome (ME/CFS), not least because of the clinically similar manifestation in long COVID or post-COVID. In this review we discuss the process of clinical diagnosis and randomized controlled therapeutic studies on ME/CFS, and the similarities or differences to long COVID and post-COVID. So far, neither clear pathophysiologically causal nor therapeutic evidence-based results on ME/CFS have been identified in the many years of scientific research. Given the evident psychiatric comorbidity rates in patients with a diagnosis of ME/CFS, a psychosomatic etiology of this syndrome should be considered. Furthermore, a precise and reliable diagnostic classification based on stricter criteria would benefit both pathophysiological and therapeutic research.

Clinical autonomic nervous system laboratories in Europe: A joint survey of the European Academy of Neurology and the European Federation of Autonomic Societies: A joint survey of the European Academy of Neurology and the European Federation of Autonomic Societies.

BACKGROUND AND PURPOSE: Disorders of the autonomic nervous system (ANS) are common conditions, but it is unclear whether access to ANS healthcare provision is homogeneous across European countries. The aim of this study was to identify neurology-driven or interdisciplinary clinical ANS laboratories in Europe, describe their characteristics and explore regional differences. METHODS: We contacted the European national ANS and neurological societies, as well as members of our professional network, to identify clinical ANS laboratories in each country and invite them to answer a web-based survey. RESULTS: We identified 84 laboratories in 22 countries and 46 (55%) answered the survey. All laboratories perform cardiovascular autonomic function tests, and 83% also perform sweat tests. Testing for catecholamines and autoantibodies are performed in 63% and 56% of laboratories, and epidermal nerve fiber density analysis in 63%. Each laboratory is staffed by a median of two consultants, one resident, one technician and one nurse. The median (interquartile range [IQR]) number of head-up tilt tests/laboratory/year is 105 (49-251). Reflex syncope and neurogenic orthostatic hypotension are the most frequently diagnosed cardiovascular ANS disorders. Thirty-five centers (76%) have an ANS outpatient clinic, with a median (IQR) of 200 (100-360) outpatient visits/year; 42 centers (91%) also offer inpatient care (median 20 [IQR 4-110] inpatient stays/year). Forty-one laboratories (89%) are involved in research activities. We observed a significant difference in the geographical distribution of ANS services among European regions: 11 out of 12 countries from North/West Europe have at least one ANS laboratory versus 11 out of 21 from South/East/Greater Europe (p = 0.021). CONCLUSIONS: This survey highlights disparities in the availability of healthcare services for people with ANS disorders across European countries, stressing the need for improved access to specialized care in South, East and Greater Europe.

Retinal imaging with optical coherence tomography in multiple sclerosis: novel aspects.

Optical coherence tomography (OCT) is of increasing interest in the clinical assessment of multiple sclerosis (MS) patients beyond the scope of clinical studies. In this narrative review, we discuss novel changes of OCT parameters during acute optic neuritis and the disease course of MS patients. OCT images document the changes of retinal layers during an episode of acute optic neuritis and can therefore provide valuable insights into the pathophysiology. Moreover, MS patients show progredient thinning of retinal layers throughout the disease. The thinning is accelerated through relapses as well as disease progression without relapse. The OCT parameters are also associated with clinical outcome parameters, including disability, cognitive function, and brain atrophy. The impact of disease-modifying therapies on OCT parameters is the subject of ongoing research and depends on the agent used. Additional data are still necessary before OCT parameters can be implemented in the clinical standard of care of MS patients.

Evaluation of the 2020 European Academy of Neurology virtual congress: transition from a face-to-face to a virtual meeting.

BACKGROUND AND PURPOSE: Due to the COVID-19 pandemic, scientific congresses are increasingly being organized as virtual congresses (VCs). In May 2020, the European Academy of Neurology (EAN) held a VC, free of charge. In the absence of systematic studies on this topic, the aim of this study is to evaluate the attendance and perceived quality of the 2020 EAN VC compared to the 2019 EAN face-to-face congress (FFC). METHODS: An analysis of the demographic data of participants obtained from the online registration was done. A comparison of the two congresses based on a survey with questions on the perception of speakers' performance, quality of networking and other aspects was made. RESULTS: Of 43,596 registered participants, 20,694 active participants attended the VC. Compared to 2019, the number of participants tripled (6916 in 2019) and the cumulated number of participants attending the sessions was five times higher (169,334 in 2020 vs. 33,024 in 2019). Out of active participants 55% were from outside Europe, 42% were board-certified neurologists (FFC 80%) and 21% were students (FFC 0.6%). The content of the congress was evaluated as 'above expectation' by 56% of the attendees (FFC 41%). Of the respondents who had been exposed to earlier EAN congresses 73% preferred the FFC compared to the VC (17%). CONCLUSION: The VC fulfilled the main mission of organizing high quality EAN congresses despite the restrictions of the impersonal format. The geographical distribution of the participants proves the expected higher inclusivity of a VC. The large participation of students and neurologists in training opens new educational potentials for the EAN.

Recommendations for tilt table testing and other provocative cardiovascular autonomic tests in conditions that may cause transient loss of consciousness : Consensus statement of the European Federation of Autonomic Societies (EFAS) endorsed by the American Autonomic Society (AAS) and the European Academy of Neurology (EAN).

An expert committee was formed to reach consensus on the use of tilt table testing (TTT) in the diagnosis of disorders that may cause transient loss of consciousness (TLOC) and to outline when other provocative cardiovascular autonomic tests are needed. While TTT adds to history taking, it cannot be a substitute for it. An abnormal TTT result is most meaningful if the provoked event is recognised by patients or eyewitnesses as similar to spontaneous events. The minimum requirements to perform TTT are a tilt table, a continuous beat-to-beat blood pressure monitor, at least one ECG lead, protocols for the indications stated below and trained staff. This basic equipment lends itself to the performance of (1) additional provocation tests, such as the active standing test, carotid sinus massage and autonomic function tests; (2) additional measurements, such as video, EEG, transcranial Doppler, NIRS, end-tidal CO2 or neuro-endocrine tests; and (3) tailor-made provocation procedures in those with a specific and consistent trigger of TLOC. TTT and other provocative cardiovascular autonomic tests are indicated if the initial evaluation does not yield a definite or highly likely diagnosis, but raises a suspicion of (1) reflex syncope, (2) the three forms of orthostatic hypotension (OH), i.e. initial, classic and delayed OH, as well as delayed orthostatic blood pressure recovery, (3) postural orthostatic tachycardia syndrome or (4) psychogenic pseudosyncope. A therapeutic indication for TTT is to teach patients with reflex syncope and OH to recognise hypotensive symptoms and to perform physical counter manoeuvres.

Ultrasound Examination of the Pupil - A New Tool for the Neuro-Ophthalmological Assessment.

BACKGROUND: Pupil examination represents a diagnostic and prognostic test in the management of several neurological diseases. Infrared video pupillometry (IVP) is the gold standard, since it is not routinely available, a noninvasive bedside ultrasound assessment has been proposed as an alternative. The aim of this study was to assess the feasibility and reproducibility of ultrasound pupillometry (UP) in comparison with IVP. MATERIALS AND METHODS: 81 subjects (43 men and 38 women, mean age: 52 ±â€Š20 years and 49 ±â€Š19 years, respectively) with no history of neurophthalmologic disease were enrolled. UP was performed with a 12-MHz linear probe according to current guidelines for orbital insonation. Light and painful stimuli were applied to test pupillary light reflex (PLR) and ciliospinal reflex (CR). In 30 of these subjects IVP examination was performed additionally to obtain intra-observer and inter-observer agreement. RESULTS: Increasing age was associated with a decreased pupillary diameter (PD) at rest, after PLR and CR (R -0.728, p < 0.01, R -0.643, p < 0.01, R 0.674, p < 0.001 respectively), while no association was noticed with time to constriction/dilation. UP measurements were reproducible (rate of inter- and intra-observer agreement: R 0.979, p < 0.01, R 0.946, p < 0.01 respectively) and concordant with IVP (PLR R 0.831, p < 0.01; CR R 0.879, p < 0.01). CONCLUSION: According to our study, ultrasound pupillometry is a feasible and reliable technique for bedside pupillary function assessment, and is a good alternative to infrared video pupillometry. Moreover, it represents the only way for functional pupillary assessment in patients with periorbital hematoma.

Cardiovascular autonomic function testing in multiple system atrophy and Parkinson's disease: an expert-based blinded evaluation.

PURPOSE: Multiple system atrophy (MSA) and Parkinson's disease (PD) are sporadic neurodegenerative diseases characterized by an accumulation of misfolded α-synuclein. Cardiovascular autonomic failure develops in both MSA and PD, although studies indicate different sites of autonomic nervous system lesion. However, it is unclear whether this could potentially aid the differential diagnosis of these diseases. Here we determined whether cardiovascular autonomic function testing (CAFT) can discriminate between the parkinsonian variant of MSA (MSA-P) and PD based on either an expert-based blinded evaluation or a systematic comparison of cardiovascular autonomic function indices. METHODS: We included 22 patients aged 55-80 with neurogenic orthostatic hypotension (nOH) who had been diagnosed with either clinically probable MSA-P (n = 11) according to current consensus criteria or clinically definite PD (n = 11) according to the Queen Square criteria. Three physicians with expertise in CAFT were blinded to the neurological diagnosis and were asked to identify the correct neurological diagnosis by applying a self-created evaluation scheme to the CAFT recordings. Afterwards, a systematic comparison of clinical-demographic characteristics and CAFT parameters was carried out. RESULTS: Neither the raters (overall diagnostic accuracy: 58.46%) nor the evaluation scheme created post hoc (72.73%) showed reliable discriminatory capacity. The inter-rater reliability was slight (κ = 0.01). We observed no statistically significant differences in cardiovascular autonomic indices between PD and MSA-P patients. CONCLUSION: CAFT is the gold standard for assessing the presence and severity of cardiovascular autonomic failure, but the results of our pilot study suggest that CAFT might be of limited value in the differential diagnosis between MSA-P and PD once nOH is present.

Consensus statement on the definition of neurogenic supine hypertension in cardiovascular autonomic failure by the American Autonomic Society (AAS) and the European Federation of Autonomic Societies (EFAS) : Endorsed by the European Academy of Neurology (EAN) and the European Society of Hypertension (ESH).

PURPOSE: Patients suffering from cardiovascular autonomic failure often develop neurogenic supine hypertension (nSH), i.e., high blood pressure (BP) in the supine position, which falls in the upright position owing to impaired autonomic regulation. A committee was formed to reach consensus among experts on the definition and diagnosis of nSH in the context of cardiovascular autonomic failure. METHODS: As a first and preparatory step, a systematic search of PubMed-indexed literature on nSH up to January 2017 was performed. Available evidence derived from this search was discussed in a consensus expert round table meeting in Innsbruck on February 16, 2017. Statements originating from this meeting were further discussed by representatives of the American Autonomic Society and the European Federation of Autonomic Societies and are summarized in the document presented here. The final version received the endorsement of the European Academy of Neurology and the European Society of Hypertension. RESULTS: In patients with neurogenic orthostatic hypotension, nSH is defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, measured after at least 5 min of rest in the supine position. Three severity degrees are recommended: mild, moderate and severe. nSH may also be present during nocturnal sleep, with reduced-dipping, non-dipping or rising nocturnal BP profiles with respect to mean daytime BP values. Home BP monitoring and 24-h-ambulatory BP monitoring provide relevant information for a customized clinical management. CONCLUSIONS: The establishment of expert-based criteria to define nSH should standardize diagnosis and allow a better understanding of its epidemiology, prognosis and, ultimately, treatment.

A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset Parkinson disease.

To identify rare causal variants in late-onset Parkinson disease (PD), we investigated an Austrian family with 16 affected individuals by exome sequencing. We found a missense mutation, c.1858G>A (p.Asp620Asn), in the VPS35 gene in all seven affected family members who are alive. By screening additional PD cases, we saw the same variant cosegregating with the disease in an autosomal-dominant mode with high but incomplete penetrance in two further families with five and ten affected members, respectively. The mean age of onset in the affected individuals was 53 years. Genotyping showed that the shared haplotype extends across 65 kilobases around VPS35. Screening the entire VPS35 coding sequence in an additional 860 cases and 1014 controls revealed six further nonsynonymous missense variants. Three were only present in cases, two were only present in controls, and one was present in cases and controls. The familial mutation p.Asp620Asn and a further variant, c.1570C>T (p.Arg524Trp), detected in a sporadic PD case were predicted to be damaging by sequence-based and molecular-dynamics analyses. VPS35 is a component of the retromer complex and mediates retrograde transport between endosomes and the trans-Golgi network, and it has recently been found to be involved in Alzheimer disease.

VPS35 Parkinson's disease phenotype resembles the sporadic disease.

Recently a new autosomal dominant Parkinson's disease mutation (p.Asp620Asn) in the VPS35 gene was discovered. The clinical features of 14 PD patients with this mutation from three Austrian families were evaluated. Age at disease-onset appears lower and depression was more common in Austrian patients compared to sporadic PD patients. However, we were unable to identify a specific clinical maker of VPS35 patients, who otherwise resemble sporadic PD patients.

CXCL13 as a biomarker in the diagnostics of European lyme Neuroborreliosis - A prospective multicentre study in Austria.

Background: 'Definite Neuroborreliosis (NB)' is diagnosed with the presence of NB-specific symptoms, cerebrospinal fluid (CSF) pleocytosis and an elevated Borrelia Burgdorferi antibody index. However, some diagnostic uncertainties exist. The B-cell chemokine CXCL13 represents an emerging biomarker for the diagnosis and treatment of NB because its intrathecal concentration rises prior to the Borrelia antibody index and drops rapidly after antibiotic therapy. Nevertheless, due to lacking prospective data, a definite CXCL13 cut-off for the diagnosis of NB is still pending. Objective: Definition of a CSF CXCL13 cut-off for the diagnosis of acute and untreated NB in a prospective study setting. Design and methods: This multicentre prospective study involved 6 neurological departments treating patients in the Lower Austria district (1.7 million inhabitants). The controls were patients scheduled for a spinal tap but not clinically diagnosed with NB. Demographic data, clinical characteristics and blood counts, as well as inflammatory CSF values and CSF CXCL13-concentration were analysed. Results: We recruited 440 adult patients, of whom 42 have been diagnosed as having an acute and untreated 'definite NB'. Three hundred ninety-eight patients were assigned to the control group. The median intrathecal CXCL13 concentration was 2384 pg/ml for patients with NB and 0 pg/ml for controls. The difference was highly statistically significant (P ≤ .001). A CSF CXCL13 cut-off of 271 pg/ml resulted in a sensitivity of 95.2% and a specificity of 97.2% for the confirmation or exclusion of NB. Conclusion: Based on our results, we propose a CSF CXCL13 cut-off of 271 pg/ml with Euroimmun-Elisa for the diagnosis of acute and untreated NB. Due to its high sensitivity and specificity, CXCL13 is a strong candidate biomarker for routine NB assessment, especially in clinically unclear cases.

[S1 guidelines for the management of postviral conditions using the example of post-COVID-19]. / Leitlinie S1 für das Management postviraler Zustände am Beispiel Post-COVID-19.

These S1 guidelines are an updated and expanded version of the S1 guidelines on long COVID differential diagnostic and management strategies. They summarize the state of knowledge on postviral conditions like long/post COVID at the time of writing. Due to the dynamic nature of knowledge development, they are intended to be "living guidelines". The focus is on practical applicability at the level of primary care, which is understood to be the appropriate place for initial access and for primary care and treatment. The guidelines provide recommendations on the course of treatment, differential diagnostics of the most common symptoms that can result from infections like with SARS-CoV-2, treatment options, patient management and care, reintegration and rehabilitation. The guidelines have been developed through an interdisciplinary and interprofessional process and provide recommendations on interfaces and possibilities for collaboration.

MOG antibody associated disease (MOGAD) presenting with extensive brain stem encephalitis: A case report.

Background: Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is a relatively new entity of demyelinating diseases, clinically presenting with optic neuritis, transverse myelitis, or encephalic symptoms. Typical radiological features include demyelinating cerebral and spinal lesions, cortical involvement, leptomeningeal enhancement, or tumefactive lesions. Here we present a rare case of a young patient with extensive brain stem lesion on the MRI while exhibiting nystagmus, singultus and somnolence. Case presentation: A 30-year-old male patient presented initially with fever and impaired consciousness, but furthermore developed nystagmus, singultus and tetraparesis during the following week. Repeated MRI examinations revealed extensive brain stem edema with notable bilateral affection of the cerebellar peduncles and the pons. Antiviral and antibiotic treatment was changed to intravenous corticosteroids and immunoglobulins as soon as the diagnosis of MOGAD was established by testing serum and cerebrospinal fluid positive for MOG specific antibodies. MRI alterations vanished completely over time with a delayed, nearly complete clinical recovery of our patient. Conclusion: Brain stem affection in MOGAD is rare. However, in patients presenting with an unclear brain stem encephalitis the possibility of MOGAD should be considered and tested using MOG antibodies. In case of a positive testing treatment with steroids and immunoglobulins seems recommendable.