Global uncertainty in the diagnosis of neurological complications of SARS-CoV-2 infection by both neurologists and non-neurologists: An international inter-observer variability study.

INTRODUCTION: Uniform case definitions are required to ensure harmonised reporting of neurological syndromes associated with SARS-CoV-2. Moreover, it is unclear how clinicians perceive the relative importance of SARS-CoV-2 in neurological syndromes, which risks under- or over-reporting. METHODS: We invited clinicians through global networks, including the World Federation of Neurology, to assess ten anonymised vignettes of SARS-CoV-2 neurological syndromes. Using standardised case definitions, clinicians assigned a diagnosis and ranked association with SARS-CoV-2. We compared diagnostic accuracy and assigned association ranks between different settings and specialties and calculated inter-rater agreement for case definitions as "poor" (κ ≤ 0.4), "moderate" or "good" (κ > 0.6). RESULTS: 1265 diagnoses were assigned by 146 participants from 45 countries on six continents. The highest correct proportion were cerebral venous sinus thrombosis (CVST, 95.8%), Guillain-Barré syndrome (GBS, 92.4%) and headache (91.6%) and the lowest encephalitis (72.8%), psychosis (53.8%) and encephalopathy (43.2%). Diagnostic accuracy was similar between neurologists and non-neurologists (median score 8 vs. 7/10, p = 0.1). Good inter-rater agreement was observed for five diagnoses: cranial neuropathy, headache, myelitis, CVST, and GBS and poor agreement for encephalopathy. In 13% of vignettes, clinicians incorrectly assigned lowest association ranks, regardless of setting and specialty. CONCLUSION: The case definitions can help with reporting of neurological complications of SARS-CoV-2, also in settings with few neurologists. However, encephalopathy, encephalitis, and psychosis were often misdiagnosed, and clinicians underestimated the association with SARS-CoV-2. Future work should refine the case definitions and provide training if global reporting of neurological syndromes associated with SARS-CoV-2 is to be robust.

[Rabies and Bornavirus encephalitis : Fatal emerging viral encephalitis-a potential problem for organ recipients]. / Tollwut und Bornavirus-Enzephalitis : Fatale "emerging" virale Enzephalitis ­ ein potenzielles Problem bei Organempfängern.

A severe, often fatal encephalitis needs to be extensively and carefully clarified, especially when it occurs in a patient weeks or months after an organ transplantation. If the donor was viremic at the time of the organ removal or living viruses were present in the organ tissue, many viruses can be transferred to the organ recipient. This has been repeatedly reported in recent years and decades. In this overview rabies is discussed as a particularly important form of viral encephalitis, which is transferred via organs and always has a fatal outcome, because patients carry a high risk of infection for all caregivers. Bornavirus has been known in veterinary medicine for many decades and in human medicine has been discussed as possibly being associated with psychiatric diseases. Very recently Bornavirus has been identified as the causative pathogen of fatal encephalitis in organ recipients. The aim of this article is to raise awareness for rabies and Bornavirus disease in intensive care medicine and neurology for organ donors and those taking care of organ recipients. Prevention by knowledge can be lifesaving.

EAN consensus review on prevention, diagnosis and management of tick-borne encephalitis.

BACKGROUND AND PURPOSE: Tick-borne encephalitis (TBE) is an infection of the central nervous system (CNS) caused by tick-borne encephalitis virus (TBEV) and transmitted by ticks, with a variety of clinical manifestations. The incidence of TBE in Europe is increasing due to an extended season of the infection and the enlargement of endemic areas. Our objectives are to provide recommendations on the prevention, diagnosis and management of TBE, based on evidence or consensus decisions. METHODS: For systematic evaluation, the literature was searched from 1970 to 2015 (including early online publications of 2016), and recommendations were based on evidence or consensus decisions of the Task Force when evidence-based data were not available. RECOMMENDATIONS: Vaccination against TBE is recommended for all age groups above 1 year in highly endemic areas (≥5 cases/100 000/year), but also for individuals at risk in areas with a lower incidence. Travellers to endemic areas should be vaccinated if their visits will include extensive outdoor activities. Post-exposure prophylaxis after a tick bite is not recommended. A case of TBE is defined by the presence of clinical signs of meningitis, meningoencephalitis or meningoencephalomyelitis with cerebrospinal fluid (CSF) pleocytosis (>5 × 106 cells/l) and the presence of specific TBEV serum immunoglobulin M (IgM) and IgG antibodies, CSF IgM antibodies or TBEV IgG seroconversion. TBEV-specific polymerase chain reaction in blood is diagnostic in the first viremic phase but it is not sensitive in the second phase of TBE with clinical manifestations of CNS inflammation. Lumbar puncture should be performed in all patients with suspected CNS infection unless there are contraindications. Imaging of the brain and spinal cord has a low sensitivity and a low specificity, but it is useful for differential diagnosis. No effective antiviral or immunomodulating therapy is available for TBE; therefore the treatment is symptomatic. Patients with a potentially life threatening meningoencephalitis or meningoencephalomyelitis should be admitted to an intensive care unit. In the case of brain oedema, analgosedation should be deepened; osmotherapy and corticosteroids are not routinely recommended. If intracranial pressure is increased, therapeutic hypothermia or decompressive craniectomy might be considered. Seizures should be treated as any other symptomatic epileptic seizures. CONCLUSIONS: Tick-borne encephalitis is a viral CNS infection that may result in long-term neurological sequelae. Since its incidence in Europe is increasing due to broadening of endemic areas and prolongation of the tick activity season, the health burden of TBE is enlarging. There is no effective antiviral treatment for TBE, but the disease may be effectively prevented by vaccination.

Neurologic complications of sepsis.

Over the past decades, the incidence of sepsis and resultant neurologic sequelae has increased, both in industrialized and low- or middle-income countries, by approximately 5% per year. Up to 300 patients per 100 000 population per year are reported to suffer from sepsis, severe sepsis, and septic shock. Mortality is up to 30%, depending on the precision of diagnostic criteria. The increasing incidence of sepsis is partially explained by demographic changes in society, with aging, increasing numbers of immunocompromised patients, dissemination of multiresistant pathogens, and greater availability of supportive medical care in both industrialized and middle-income countries. This results in more septic patients being admitted to intensive care units. Septic encephalopathy is a manifestation especially of severe sepsis and septic shock where the neurologist plays a crucial role in diagnosis and management. It is well known that timely treatment of sepsis improves outcome and that septic encephalopathy may precede other signs and symptoms. Particularly in the elderly and immunocompromised patient, the brain may be the first organ to show signs of failure. The neurologist diagnosing early septic encephalopathy may therefore contribute to the optimal management of septic patients. The brain is not only an organ failing in sepsis (a "sepsis victim" - as with other organs), but it also overwhelmingly influences all inflammatory processes on a variety of pathophysiologic levels, thus contributing to the initiation and propagation of septic processes. Therefore, the best possible pathophysiologic understanding of septic encephalopathy is essential for its management, and the earliest possible therapy is crucial to prevent the evolution of septic encephalopathy, brain failure, and poor prognosis.

Behavioral characterization of the anterior injection model of subarachnoid hemorrhage.

BACKGROUND: The applicability of various neurological scores has not been sufficiently characterized in the anterior injection model of subarachnoid hemorrhage (SAH). Therefore this study was performed to evaluate different behavioral tests for quantifying disease severity. METHODS: Different volumes of autologous blood were injected stereotaxically into the prechiasmatic cistern of mice. Sham controls underwent the same procedure without blood injection. The following seven days after surgery, mice were evaluated for behavioral deficits by the SHIRPA score, beam balance and flex field analyses. Brains were further processed for histological analyses. RESULTS: Flex field analysis of SAH animals showed a significant reduction of locomotor activity compared to controls in the first two days after SAH. This reduction was more intense in animals with a higher amount of injected blood. The SHIRPA score revealed a significant reduction in motor behavior in SAH animals two days after surgery. A significant increase of GFAP expression, Fluoro Jade C and TUNEL positive cells as well as microthrombi was observed in SAH animals compared to sham controls in the early phase of SAH. There was a significant negative correlation between flex field righting and the number of degenerative neurons or microthrombi in the first two days after SAH. CONCLUSION: The results of flex field analysis and SHIRPA single test show behavioral and functional deficits in the first two days after SAH in parallel to histological alterations indicating neuronal damage. In summary these tests can be used as functional outcome parameters in the anterior injection model of SAH.

Acyclovir resistance in herpes simplex virus type I encephalitis: a case report.

Acyclovir resistance is rarely seen in herpes simplex virus (HSV) type I encephalitis. Prevalence rates vary between 0.5 % in immunocompetent patients (Christophers et al. 1998; Fife et al. 1994) and 3.5-10 % in immunocompromised patients (Stranska et al. 2005). We report a 45-year-old, immunocompetent (negative HIV antigen/antibody testing), female patient, without previous illness who developed-after a febrile prodromal stage-aphasia and psychomotor slowing. Cerebral magnetic resonance imaging (cMRI) showed right temporal and insular T2-hyperintense lesions with spreading to the contralateral temporal lobe. Cerebrospinal fluid (CSF) analysis yielded lymphocytic pleocytosis and elevated protein level. Polymerase chain reaction testing for HSV type I showed a positive result in repeat lumbar puncture. HSV type I encephalitis was diagnosed and intravenous acyclovir treatment was initiated (750 mg t.i.d.). Acyclovir treatment was intensified to 1000 mg t.i.d., due to clinical deterioration, ongoing pleocytosis and progression on cMRI 5 days after initiation of antiviral therapy. In parallel, acyclovir resistance testing showed mutation of thymidine kinase gene at position A156V prompting foscarnet therapy (60 mg t.i.d.). Patient's condition improved dramatically over 2 weeks. Acyclovir resistance is rare but should be considered in case of clinical worsening of patient's condition. To our knowledge, this is the first report of acyclovir resistance in HSV type I encephalitis of an immunocompetent and previously healthy patient in Austria.

[Posterior reversible encephalopathy syndrome]. / Das posteriore reversible Enzephalopathiesyndrom.

Posterior reversible encephalopathy syndrome refers to a neurological disorder characterized by headache, disorders of consciousness, visual disturbances, epileptic seizures, and subcortical vasogenic edema. About two thirds of patients develop neurological symptoms, which are associated with blood pressure fluctuations. One hypothesis is that hypertensive episodes cause autoregulatory failure, and values above the upper limit of cerebral autoregulation result in a breakthrough followed by hyperperfusion and blood-brain barrier dysfunction. In another hypothesis, endothelial dysfunction triggered by numerous factors including preeclampsia, immunosuppressive agents, chemotherapeutics, sepsis, or autoimmune disorders is thought to be the key pathomechanism. Endo- or exogenic toxic agents including pharmacological substances, cytokines, or bacterial toxins are supposed to trigger endothelial activation and dysfunction resulting in the release of vasoconstrictors, pro-inflammatory mediators, and vascular leakage. Diagnosis is usually based on clinical and neuroimaging findings that frequently show a bilateral, symmetric, and parietooccipital pattern. However, the diagnosis can often only be confirmed during the course of disease after excluding important differential diagnoses. Currently, there is no specific treatment available. Lowering of arterial blood pressure and eliminating the underlying cause usually leads to an improvement of clinical and neuroradiological findings. Admission to a critical care unit is required in about 40 % of patients due to complicating conditions including status epilepticus, cerebral vasoconstriction, ischemia, or intracerebral hemorrhage. Prognosis is favorable; in the majority of patients neurological deficits and imaging findings resolve completely.

Human seroprevalence against Borrelia burgdorferi sensu lato in two comparable regions of the eastern Alps is not correlated to vector infection rates.

Seroprevalences were determined by testing sera of 1607 blood donors from North, East, and South Tyrol. In the Tyrols, the continental divide delimitates areas with high seroprevalences of IgG antibodies against Borrelia burgdorferi sensu lato in the North (7.2%) from areas with low seroprevalences in the South (1.5%). To determine Borrelia prevalences in unfed Ixodes ricinus ticks, 755 questing ticks were tested by PCR. Prevalences in nymphal and adult ticks were found to be 19.7% (n=132) and 21.5% (n=205) in North Tyrol and 23% (n=43) and 23.7% (n=376) in South Tyrol, respectively. Sequencing of 46 Borrelia-positive ticks yielded 74% Borrelia (B.) afzelii, 11% B. garinii, 7% B. lusitaniae, 7% B. burgdorferi sensu stricto, and 2% B. valaisiana infections. Distinct genetic clusters could not be delimitated on either side of the continental divide. This study describes occurrence and geographic dispersion of Borrelia spp. in the Tyrols, discusses possible reasons for significant differences in human seroprevalence, and indicates that prevalence of Borrelia in vector ticks is not a direct predictive factor for the local seroprevalence in humans.

Clusters of cortical spreading depolarizations in a patient with intracerebral hemorrhage: a multimodal neuromonitoring study.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is associated with high morbidity and mortality. Cortical spreading depolarizations (CSDs) increase brain matrix metalloproteinase (MMP)-9 activity leading to perihematomal edema expansion in experimental ICH. METHODS: The purpose of this report is to describe cerebral metabolic changes and brain extracellular MMP-9 levels in a patient with CSDs and perihematomal edema expansion after ICH. RESULTS: We present a 66-year-old male patient with ICH who underwent craniotomy for hematoma evacuation. Multimodal neuromonitoring data of the perihematomal region revealed metabolic distress and increased MMP-9 levels in the brain extracellular fluid during perihematomal edema progression. At the same time, subdural electrocorticography showed clusters of CSDs, which disappeared after ketamine anesthesia on day six. Perihematomal edema regression was associated with decreasing cerebral MMP-9 levels. CONCLUSIONS: This novel association between clusters of CSDs, brain metabolic distress, and increased MMP-9 levels expands our knowledge about secondary brain injury after ICH. The role of ketamine after this devastating disorder needs further studies.

MRI findings in people with epilepsy and nodding syndrome in an area endemic for onchocerciasis: an observational study.

BACKGROUND: Onchocerciasis has been implicated in the pathogenesis of epilepsy. The debate on a potential causal relationship between Onchocerca volvulus and epilepsy has taken a new direction in the light of the most recent epidemic of nodding syndrome. OBJECTIVE: To document MRI changes in people with different types of epilepsy and investigate whether there is an association with O. volvulus infection. METHODS: In a prospective study in southern Tanzania, an area endemic for O. volvulus with a high prevalence of epilepsy and nodding syndrome, we performed MRI on 32 people with epilepsy, 12 of which suffered from nodding syndrome. Polymerase chain reaction (PCR) of O. volvulus was performed in skin and CSF. RESULTS: The most frequent abnormalities seen on MRI was atrophy (twelve patients (37.5%)) followed by intraparenchymal pathologies such as changes in the hippocampus (nine patients (28.1%)), gliotic lesions (six patients (18.8%)) and subcortical signal abnormalities (three patients (9.4%)). There was an overall trend towards an association of intraparenchymal cerebral pathologies and infection with O. volvulus based on skin PCR (Fisher's Exact Test p=0.067) which was most pronounced in children and adolescents with nodding syndrome compared to those with other types of epilepsy (Fisher's Exact Test, p=0.083). Contrary to skin PCR results, PCR of CSF was negative in all patients. CONCLUSION: The observed trend towards an association of intraparenchymal cerebral pathological results on MRI and a positive skin PCR for O. volvulus despite negative PCR of CSF is intriguing and deserves further attention.

EFNS-ENS guidelines for the use of PCR technology for the diagnosis of infections of the nervous system.

BACKGROUND: Polymerase chain reaction (PCR) as a means to amplify nucleic acids has become an essential element in diagnosis of infections. It has evolved into a simple and rapid, easy- to- use approach. At present there are no published guidelines for the usage of PCR technology for the diagnosis of infections of the nervous system. METHODS: We reviewed the advantages and pitfalls of PCR in order to guide neurologists and infectious diseases experts in its application for the diagnosis of infections of the nervous system. Medical reference systems were searched, and original papers, meta-analyses, review papers, book chapters and guidelines recommendations were reviewed. The final literature search was performed in May 2012. Recommendations were reached by consensus. RECOMMENDATIONS: The reliability of PCR technology for the diagnosis of neurological infections is currently based on the pathogens. The main contribution of PCR is to the diagnosis of viral infections followed by bacterial CNS infections with the notable exception of tuberculous meningitis. Efficacy for the diagnosis of protozoal infections and helminthic infestations has also been established in many instances. Unfortunately, current molecular PCR technology is far from becoming routine in resource-poor countries where such infections are prevalent. Despite the importance of fungal infections in the context of the immune-compromised host, there is not enough data to recommend the routine use of PCR. CONCLUSIONS: PCR technology is currently a reliable method for the diagnosis of viral and bacterial (except tuberculosis) infections, and only for some protozoal infections and helminthic infestations.

Cerebral vasospasm following temporal lobe epilepsy surgery.

OBJECTIVE: Selective amygdalohippocampectomy (AHE) has been associated with postoperative cerebral vasospasm (CVS) in patients with medically intractable temporal lobe epilepsy. The incidence in temporal lobe resection (TLR) is unknown. This retrospective cohort study evaluates the incidence of and risk factors for the development of CVS in patients with TLR and AHE. METHODS: A total of 119 patients were included between 1998 and 2009. All patients were evaluated by standardized preoperative and postoperative transcranial Doppler sonography (TCD) evaluations and neurologic examinations. Postoperative CT scans were evaluated by an independent radiologist and the volume of bleeding within the resection cavity was quantified. RESULTS: Of 107 patients with longitudinal TCD data, 35 (32.7%) developed postoperative CVS. The incidence of CVS did not differ between patients with TLR and AHE. CVS was associated with female gender and a higher bleeding volume in the postoperative CT scan (p = 0.035 and 0.046). Patients with CVS showed a significantly higher incidence of postoperative neurologic signs and symptoms (48.6%) compared to patients without CVS (25%, p = 0.015). The mean length of stay was significantly prolonged in patients with diffuse CVS compared to patients with localized CVS or no CVS (28.8 ± 10.9, 24.2 ± 6.6, and 18.2 ± 6.1 days, p < 0.001). CONCLUSION: CVS is a frequent complication of surgery for temporal lobe epilepsy irrespective of the resection method. Important risk factors for the development of postoperative CVS are female gender and a higher amount of bleeding in the postoperative CT. Patients with CVS more frequently have neurologic signs and symptoms resulting in prolonged hospital stay.

Absence of indigenous specific West Nile virus antibodies in Tyrolean blood donors.

In the last several years, West Nile virus (WNV) was proven to be present especially in the neighboring countries of Austria, such as Italy, Hungary, and the Czech Republic, as well as in eastern parts of Austria, where it was detected in migratory and domestic birds. In summer 2010, infections with WNV were reported from Romania and northern Greece with about 150 diseased and increasingly fatal cases. We tested the sera of 1,607 blood donors from North Tyrol (Austria) and South Tyrol (Italy) for antibodies against WNV by using IgG enzyme-linked immunosorbent assay (ELISA). Initial results of the ELISA tests showed seroprevalence rates of 46.2% in North Tyrol and 0.5% in South Tyrol, which turned out to be false-positive cross-reactions with antibodies against tick-borne encephalitis virus (TBEV) by adjacent neutralization assays. These results indicate that seropositivity against WNV requires confirmation by neutralization assays, as cross-reactivity with TBEV is frequent and because, currently, WNV is not endemic in the study area.

Basilar artery dissection: series of 12 consecutive cases and review of the literature.

BACKGROUND: Current knowledge on primary or isolated basilar artery dissection (IBAD) is limited to case vignettes and small patient series. OBJECTIVE: To delineate the frequency and clinical presentations of IBAD along with short-term outcome, specific prognosis and targeted management. METHODS: Data were derived from a series of 12 consecutive patients and a review of 88 cases reported in the literature. In all the cases, the dissection was confined to the basilar artery. RESULTS: Disease incidence was estimated at 0.25 per 100,000 person-years. IBAD accounted for roughly 1.0% of all subarachnoid hemorrhage events and for no less than 10.5 and 4.5% of posterior circulation and brain-supplying artery dissections, respectively. The main clinical presentations were subarachnoid hemorrhage (46%) and posterior circulation brain ischemia (42%). Subarachnoid hemorrhage typically manifested at a higher age than brain ischemia (mean age, 48.9 vs. 41.4 years) and was more prevalent among women. Rebleedings related to pseudoaneurysm formation in patients with subarachnoid hemorrhage and recurrent ischemia in stroke patients were common in the acute phase (26.1 and 33.3%, respectively) but were rare in the long term. The outcome was generally favorable in stroke patients but variable in subarachnoid hemorrhage (case fatality rate, 21.7%). The mainstay of therapy for subarachnoid hemorrhage related to IBAD was endovascular occlusion of the aneurysm pouch whereas stroke patients were usually put on anticoagulants. CONCLUSIONS: IBAD is probably an underrecognized disease with heterogeneous clinical presentation and prognosis. It should be considered as a differential diagnosis in peritruncal subarachnoid hemorrhage, classic subarachnoid hemorrhage and posterior circulation stroke, especially in young individuals. Case management is challenging and has to be tailored to each patient.

[Parasitic diseases of the central nervous system]. / Parasitäre Erkrankungen des Nervensystems.

Central nervous system infections and infestations by protozoa and helminths constitute a problem of increasing importance throughout all of central European and northern/western countries. This is partially due to the globalisation of our society, tourists and business people being more frequently exposed to parasitic infection/infestation in tropical countries than in moderate climate countries. On top of that, migrants may import chronic infestations and infections with parasitic pathogens, eventually also--sometimes exclusively--involving the nervous system. Knowledge of epidemiology, initial clinical signs and symptoms, diagnostic procedures as well as specific chemotherapeutic therapies and adjunctive therapeutic strategies is of utmost important in all of these infections and infestations of the nervous systems, be it by protozoa or helminths. This review lists, mainly in the form of tables, all possible infections and infestations of the nervous systems by protozoa and by helminths. Besides differentiating parasitic diseases of the nervous system seen in migrants, tourists etc., it is very important to have in mind that disease-related (e.g. HIV) or iatrogenic immunosuppression has led to the increased occurrence of a wide variety of parasitic infections and infestations of the nervous system (e. g. babesiosis, Chagas disease, Strongyloides stercoralis infestation, toxoplasmosis, etc.).