Multifocal motor neuropathy as a mimic of amyotrophic lateral sclerosis: Serum neurofilament light chain as a reliable diagnostic biomarker.

INTRODUCTION/AIMS: The clinical presentation of multifocal motor neuropathy (MMN) may mimic early amyotrophic lateral sclerosis (ALS) with predominant lower motor neuron (LMN) involvement, posing a diagnostic challenge. Both diseases have specific treatments and prognoses, highlighting the importance of early diagnosis. The aim of this study was to assess the diagnostic value of serum neurofilament light chain (NfL) in differentiating MMN from LMN dominant ALS. METHODS: NfL was measured in serum in n = 37 patients with MMN and n = 37 age- and sex-matched patients with LMN dominant ALS, to determine the diagnostic accuracy. Clinical and demographic data were obtained at the time of NfL sampling. RESULTS: Serum NfL concentration was significantly lower in MMN patients compared to ALS patients (mean 20.7 pg/mL vs. 59.4 pg/mL, p < .01). NfL demonstrated good diagnostic value in discriminating the two groups (AUC 0.985 [95% CI 0.963-1.000], sensitivity 94.6%, specificity 100%, cut-off 44.00 pg/mL). DISCUSSION: NfL could be a helpful tool in differentiating MMN from LMN dominant ALS in those patients in whom electrophysiological and clinical examinations remain inconclusive early in the diagnostic process.

Multiple sclerosis in the elderly: a retrospective cohort study.

BACKGROUND: There is a lack of knowledge of disease course, prognosis, comorbidities and potential treatments of elderly MS patients. OBJECTIVE: To characterize the disease course including disability progression and relapses, to quantify the use of DMTs and to identify comorbidities and risk factors for progression in elderly multiple sclerosis (MS) patients. METHODS: This is a retrospective study of 1200 Austrian MS patients older than 55 years as of May 1st, 2017 representing roughly one-third of all the MS patients of this age in Austria. Data were collected from 15 MS centers including demographics, first symptom at onset, number of relapses, evolvement of disability, medication, and comorbidities. RESULTS: Median observation time was 17.1 years with 957 (80%) relapsing and 243 (20%) progressive onsets. Average age at diagnosis was 45 years with a female predominance of 71%. Three-hundred and twenty-six (27%) patients were never treated with a DMT, while most treated patients received interferons (496; 41%) at some point. At last follow-up, 420 (35%) patients were still treated with a DMT. No difference was found between treated and never-treated patients in terms of clinical outcome; however, patients with worse disability progression had significantly more DMT switches. Pyramidal onset, number of comorbidities, dementia, epilepsy, and psychiatric conditions as well as a higher number of relapses were associated with worse outcome. The risk of reaching EDSS 6 rose with every additional comorbidity by 22%. In late and very-late-onset MS (LOMS, VLOMS) time to diagnosis took nearly twice the time compared to adult and early onset (AEOMS). The overall annualized relapse rate (ARR) decreased over time and patients with AEOMS had significantly higher ARR compared to LOMS and VLOMS. Four percent of MS patients had five medications or more fulfilling criteria of polypharmacy and 20% of psychiatric drugs were administered without a matching diagnosis. CONCLUSIONS: In this study, we identified number of comorbidities, pyramidal and cerebellar signs, and a higher number of relapses as unfavorable prognostic factors in elderly MS patients filling gaps of knowledge in patients usually underrepresented in clinical trials and may guide future therapeutic studies.

Lyme neuroborreliosis: Progressive cerebral vasculitis responsive to cyclophosphamide. A case report and review of the literature.

OBJECTIVES: Less than 1 % of patients with Lyme Neuroborreliosis (LNB) present with a cerebrovascular event. Ischaemic strokes occur more commonly than parenchymal or subarachnoid haemorrhages. If cerebral vasculitis due to LNB is suspected, antibiotic treatment should be started immediately, which will normally lead to remission. Very rarely progression and recurrent strokes are observed despite sufficient antibiotic therapy, even if steroids are added. Currently there are no guidelines on the adequate treatment of cerebral vasculitis due to LNB which is not responsive to antibiotics and steroids, but in very few reported cases cyclophosphamide led to disease stabilisation. We reviewed the literature regarding cyclophosphamide treatment in these patients and want to share our experience of cyclophosphamide therapy in progressive cerebral vasculitis due to LNB. RESULTS: We report a 71-year-old female patient with cerebral vasculitis and multiple strokes as a complication of LNB. Progression could only be halted by additional immunosuppressive treatment using cyclophosphamide. However, at that point the patient had already suffered severe ischaemic brain damage. Similarly, in existing case reports cyclophosphamide had been administered only at a time when patients already showed serious neurological deficits. CONCLUSION: Cerebral vasculitis in patients with LNB is very rare and normally responds to antibiotic treatment. A minority of patients show disease progression despite antibiotics and steroids. Our case report strengthens the recommendation that in those patients - even if signs of progressive vasculitis are only detectable on imaging and not clinically - cyclophosphamide should be considered without delay to prevent further cerebrovascular events.

Rituximab versus mitoxantrone: comparing effectiveness and safety in advanced relapsing multiple sclerosis.

BACKGROUND: Rituximab (RTX), a CD20 depleting agent, is a frequently used off-label treatment for multiple sclerosis (MS), while mitoxantrone (MTX) is approved, albeit rarely used for active relapsing MS (RMS). However, observational data comparing RTX and MTX effectiveness and safety are scarce. OBJECTIVE: We aimed to compare effectiveness and safety of MTX and RTX in patients with active RMS. METHODS: From combined retrospective clinical data of three MS centers, we selected patients who had received at least one infusion of RTX or MTX and had at least a 6-month clinical follow-up available. Treatment groups were compared by propensity score (PS)-adjusted regression and inverse PS-weighted generalized estimated equation models regarding disability progression, relapse activity, and adverse events (AEs). RESULTS: We included 292 RMS patients (mean age 41.8 years, 71.6% female) who received RTX (119 patients, mean age 36.8 years, 74.8% female) or MTX (173 patients mean age 45.3 years, 69.4% female). Using both PS methods, we did not find a significant effect favoring RTX or MTX treatment regarding the probability of disability worsening or relapse occurrence. However, RTX treatment was associated with a significantly lower probability of severe AEs and AEs. CONCLUSIONS: RTX shows comparable effectiveness but a favorable safety profile compared with MTX in active RMS.

Functional Recovery in Autoimmune Encephalitis: A Prospective Observational Study.

Background: Prospective observations of functional recovery are lacking in patients with autoimmune encephalitis defined by antibodies against synaptic proteins and neuronal cell surface receptors. Methods: Adult patients with a diagnosis of autoimmune encephalitis were included into a prospective registry. At 3, 6 and 12 months of follow-up, the patients' modified Rankin Scale (mRS) was obtained. Results: Patients were stratified into three groups according to their antibody (Ab) status: anti-NMDAR-Ab (n=12; group I), anti-LGI1/CASPR2-Ab (n=35; group II), and other antibodies (n=24; group III). A comparably higher proportion of patients in group I received plasma exchange/immunoadsorption and second line immunosuppressive treatments at baseline. A higher proportion of patients in group II presented with seizures. Group III mainly included patients with anti-GABABR-, anti-GAD65- and anti-GlyR-Ab. At baseline, one third of them had cancer. Patients in groups I and III had much higher median mRS scores at 3 months compared to patients in group II. A median mRS of 1 was found at all follow-up time points in group II. Conclusions: The different dynamics in the recovery of patients with certain autoimmune encephalitides have important implications for clinical trials. The high proportion of patients with significant disability at 3 months after diagnosis in groups I and III points to the need for improving treatment options. More distinct scores rather than the mRS are necessary to differentiate potential neurological improvements in patients with anti-LGI1-/CASPR2-encephalitis.

Hereditary ATTR Amyloidosis in Austria: Prevalence and Epidemiological Hot Spots.

BACKGROUND: Hereditary transthyretin amyloidosis (hATTR) is an autosomal dominantly inherited disorder caused by an accumulation of amyloid fibrils in tissues due to mutations in the transthyretin (TTR) gene. The prevalence of hATTR is still unclear and likely underestimated in many countries. In order to apply new therapies in a targeted manner, early diagnosis and knowledge of phenotype-genotype correlations are mandatory. This study aimed to assess the prevalence and phenotypic spectrum of hATTR in Austria. METHODS: Within the period of 2014-2019, patients with ATTR-associated cardiomyopathy and/or unexplained progressive polyneuropathies were screened for mutations in the TTR gene. RESULTS: We identified 43 cases from 22 families carrying 10 different TTR missense mutations and confirmed two mutational hot spots at c.323A>G (p.His108Arg) and c.337G>C (p.Val113Leu). Two further patients with late onset ATTR carried TTR variants of unknown significance. The majority of patients initially presented with heart failure symptoms that were subsequently accompanied by progressive polyneuropathy in most cases. A total of 55% had a history of carpal tunnel syndrome before the onset of other organ manifestations. CONCLUSIONS: Our study underlined the relevance of hATTR in the pathogenesis of amyloid-driven cardiomyopathy and axonal polyneuropathy and indicated considerable genetic heterogeneity of this disease in the Austrian population. The estimated prevalence of hATTR in Austria based on this study is 1:200,000 but a potentially higher number of unknown cases must be taken into account. With respect to new therapeutic approaches, we strongly propose genetic testing of the TTR gene in an extended cohort of patients with unexplained heart failure and progressive polyneuropathy.

Correction to: Routine diagnostics for neural antibodies, clinical correlates, treatment and functional outcome.

The original version of this article unfortunately contained a mistake.

Routine diagnostics for neural antibodies, clinical correlates, treatment and functional outcome.

OBJECTIVE: To determine frequencies, interlaboratory reproducibility, clinical ratings, and prognostic implications of neural antibodies in a routine laboratory setting in patients with suspected neuropsychiatric autoimmune conditions. METHODS: Earliest available samples from 10,919 patients were tested for a broad panel of neural antibodies. Sera that reacted with leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-2 (CASPR2), or the voltage-gated potassium channel (VGKC) complex were retested for LGI1 and CASPR2 antibodies by another laboratory. Physicians in charge of patients with positive antibody results retrospectively reported on clinical, treatment, and outcome parameters. RESULTS: Positive results were obtained for 576 patients (5.3%). Median disease duration was 6 months (interquartile range 0.6-46 months). In most patients, antibodies were detected both in CSF and serum. However, in 16 (28%) patients with N-methyl-D-aspartate receptor (NMDAR) antibodies, this diagnosis could be made only in cerebrospinal fluid (CSF). The two laboratories agreed largely on LGI1 and CASPR2 antibody diagnoses (κ = 0.95). The clinicians (413 responses, 71.7%) rated two-thirds of the antibody-positive patients as autoimmune. Antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), NMDAR (CSF or high serum titer), γ-aminobutyric acid-B receptor (GABABR), and LGI1 had ≥ 90% positive ratings, whereas antibodies against the glycine receptor, VGKC complex, or otherwise unspecified neuropil had ≤ 40% positive ratings. Of the patients with surface antibodies, 64% improved after ≥ 3 months, mostly with ≥ 1 immunotherapy intervention. CONCLUSIONS: This novel approach starting from routine diagnostics in a dedicated laboratory provides reliable and useful results with therapeutic implications. Counseling should consider clinical presentation, demographic features, and antibody titers of the individual patient.

Month-of-birth-effect in multiple sclerosis in Austria.

BACKGROUND: The month-of-birth-effect (MoBE) describes the finding that multiple sclerosis (MS) patients seem to have been born significantly more frequently in spring, with a rise in May, and significantly less often in autumn and winter with the fewest births in November. OBJECTIVES: To analyse if the MoBE can also be found in the Austrian MS population, and if so, whether the pattern is similar to the reported pattern in Canada, United Kingdom, and some Scandinavian countries. METHODS: The data of 7886 MS patients in Austria were compared to all live births in Austria from 1940 to 2010, that is, 7.256545 data entries of the Austrian birth registry and analysed in detail. RESULTS: Patterns observed in our MS cohort were not different from patterns in the general population, even when stratifying for gender. However, the noticeable and partly significant ups and downs over the examined years did not follow the distinct specific pattern with highest birth rates in spring and lowest birth rates in autumn that has been described previously for countries above the 49th latitude. CONCLUSION: After correcting for month-of-birth patterns in the general Austrian population, there is no evidence for the previously described MoBE in Austrian MS patients.

Secondary dementia due to Lyme neuroborreliosis.

Dementia-like syndromes are rare manifestations of Lyme neuroborreliosis. The clinical patterns are summarized using our own cases and case reports from the literature, which were diagnosed as definite Lyme neuroborreliosis according to the European guidelines. The cases disclose signs of subcortical dementia that occur more rapidly than in patients suffering from primary dementia. Gait disturbances early in the disease course is another frequently observed characteristic feature. The response to 2-4 weeks of antibiotic treatment with ceftriaxone was excellent. There were no indications for a prolonged antibiotic treatment. It is essential to be aware of this manifestation of Lyme neuroborreliosis, because early antibiotic treatment will prevent permanent sequelae that may occur throughout the further course of the untreated disease.

Coronary ectasia in amyloid cardiomyopathy and neuropathy due to the transthyretin mutation c.323A>G.

BACKGROUND: atrial fibrillation(AF) is a frequent manifestation of cardiac involvement in genetic and wild-type transthyretin-related familial amyloidosis(TTR-FA). However, ectasia of coronary arteries and ablation for AF have not been reported in TTR-FA. METHODS AND RESULTS: A 65yo male developed progressive sensori-motor polyneuropathy since age 59y. At age 60y bifascicular block and myocardial thickening were recognised. At age 62y heart failure developed and work-up with cardiac MRI suggested amyloidosis but biopsy was non-informative. Coronary angiography revealed ectasias of the coronary arteries. At age 65y AF developed, neither responding to electrical cardioversion nor ablation. Work-up for polyneuropathy revealed the point mutation c.323A>G (p.His108Arg) in the TTR-gene. Tafamidis was started but did not exhibit a beneficial effect after 7 months. CONCLUSIONS: TTR-FA may manifest in the coronary arteries with ectasia. Ablation for AF in TTR-FA may be unsuccessful. Tafamidis has been unsuccessful for cardiac or nerve involvement after the first seven months.

Affection of the Respiratory Muscles in Combined Complex I and IV Deficiency.

OBJECTIVES: Combined complex I+IV deficiency has rarely been reported to manifest with the involvement of the respiratory muscles. CASE REPORT: A 45y male was admitted for hypercapnia due to muscular respiratory insufficiency. He required intubation and mechanical ventilation. He had a previous history of ophthalmoparesis since age 6y, ptosis since age 23y, and anterocollis since at least age 40y. Muscle biopsy from the right deltoid muscle at age 41y was indicative of mitochondrial myopathy. Biochemical investigations revealed a combined complex I+IV defect. Respiratory insufficiency was attributed to mitochondrial myopathy affecting not only the extra-ocular and the axial muscles but also the shoulder girdle and respiratory muscles. In addition to myopathy, he had mitochondrial neuropathy, abnormal EEG, and elevated CSF-protein. Possibly, this is why a single cycle of immunoglobulins was somehow beneficial. For muscular respiratory insufficiency he required tracheostomy and was scheduled for long-term intermittent positive pressure ventilation. CONCLUSION: Mitochondrial myopathy due to a combined complex I+IV defect with predominant affection of the extra-ocular muscles may progress to involvement of the limb-girdle, axial and respiratory muscles resulting in muscular respiratory insufficiency. In patients with mitochondrial myopathy, neuropathy and elevated cerebrospinal fluid protein, immunoglobulins may be beneficial even for respiratory functions.

Differences in T cell cytotoxicity and cell death mechanisms between progressive multifocal leukoencephalopathy, herpes simplex virus encephalitis and cytomegalovirus encephalitis.

During the appearance of human immunodeficiency virus infection in the 1980 and the 1990s, progressive multifocal leukoencephalopathy (PML), a viral encephalitis induced by the JC virus, was the leading opportunistic brain infection. As a result of the use of modern immunomodulatory compounds such as Natalizumab and Rituximab, the number of patients with PML is once again increasing. Despite the presence of PML over decades, little is known regarding the mechanisms leading to death of infected cells and the role the immune system plays in this process. Here we compared the presence of inflammatory T cells and the targeting of infected cells by cytotoxic T cells in PML, herpes simplex virus encephalitis (HSVE) and cytomegalovirus encephalitis (CMVE). In addition, we analyzed cell death mechanisms in infected cells in these encephalitides. Our results show that large numbers of inflammatory cytotoxic T cells are present in PML lesions. Whereas in HSVE and CMVE, single or multiple appositions of CD8+ or granzyme-B+ T cells to infected cells are found, in PML such appositions are significantly less apparent. Analysis of apoptotic pathways by markers such as activated caspase-3, caspase-6, poly(ADP-ribose) polymerase-1 (PARP-1) and apoptosis-inducing factor (AIF) showed upregulation of caspase-3 and loss of caspase-6 from mitochondria in CMVE and HSVE infected cells. Infected oligodendrocytes in PML did not upregulate activated caspase-3 but instead showed translocation of PARP-1 from nucleus to cytoplasm and AIF from mitochondria to nucleus. These findings suggest that in HSVE and CMVE, cells die by caspase-mediated apoptosis induced by cytotoxic T cells. In PML, on the other hand, infected cells are not eliminated by the immune system but seem to die by virus-induced PARP and AIF translocation in a type of cell death defined as parthanatos.

Susac's syndrome: clinical course and epidemiology in a Central European population.

OBJECTIVE: Susac's syndrome is characterized by inflammation and occlusion of pre-capillary arterioles with the clinical triad of branch retinal artery occlusion (BRAO), encephalopathy and hearing loss. No epidemiological data are available for the disease. METHODS: All neurology departments in Austria were addressed to report adult patients who were on immunosuppressive treatment for a diagnosis of Susac's syndrome between 1 August 2010 and 1 August 2015. Clinical course, treatment regimens, period and point prevalence rates, and annual incidence of Susac's syndrome in Austria in people over 19 years of age are reported. RESULTS: Ten patients with Susac's syndrome were identified, and eight of them were newly diagnosed within the five-year timeframe. Minimum five-year period prevalence of the disease is 0.148/100,000 (95% confidence interval (CI) 0.071-0.272), annual incidence is 0.024/100,000 (95% CI 0.010-0.047). Minimum point prevalence rates varied from 0.030/100,000 (95% CI 0.004-0.108) to 0.088/100,000 (95% CI 0.032-0.192). Of all 10 patients, 8 showed typical callosal or internal capsule magnetic resonance imaging lesions at first presentation, 7 presented with BRAO and 5 had hearing loss or tinnitus at the beginning of the disease. Four patients developed the complete clinical triad of Susac's syndrome during the observation period. CONCLUSIONS: We provide for the first time population-based data about the clinical course, prevalence and incidence of Susac's syndrome.

CROP - The Clinico-Radiologico-Ophthalmological Paradox in Multiple Sclerosis: Are Patterns of Retinal and MRI Changes Heterogeneous and Thus Not Predictable?

BACKGROUND: To date, no direct scientific evidence has been found linking tissue changes in multiple sclerosis (MS) patients, such as demyelination, axonal destruction or gliosis, with either steady progression and/or stepwise accumulation of focal CNS lesions. Tissue changes such as reduction of the retinal nerve fiber layer (RNFL) and the total macular volume (TMV), or brain- and spinal cord atrophy indicates an irreversible stage of tissue destruction. Whether these changes are found in all MS patients, and if there is a correlation with clinical disease state, remains controversial. The objective of our study was to determine, whether there was any correlation between the RNFL or TMV of patients with MS, and: (1) the lesion load along the visual pathways, (2) the ratios and absolute concentrations of metabolites in the normal-appearing white matter (NAWM), (3) standard brain atrophy indices, (4) disease activity or (5) disease duration. METHODS: 28 MS patients (RRMS, n = 23; secondary progressive MS (SPMS), n = 5) with moderately-high disease activity or long disease course were included in the study. We utilised: (1) magnetic resonance imaging (MRI) and (2) -spectroscopy (MRS), both operating at 3 Tesla, and (3) high-resolution spectral domain-OCT with locked reference images and eye tracking mode) to undertake the study. RESULTS: There was no consistency in the pattern of CNS metabolites, brain atrophy indices and the RNFL/TMV between individuals, which ranged from normal to markedly-reduced levels. Furthermore, there was no strict correlation between CNS metabolites, lesions along the visual pathways, atrophy indices, RNFL, TMV, disease duration or disability. CONCLUSIONS: Based on the findings of this study, we recommend that the concept of 'clinico-radiologico paradox' in multiple sclerosis be extended to CROP-'clinico-radiologico-ophthalmological paradox'. Furthermore, OCT data of MS patients should be interpreted with caution.

Adult, isolated respiratory chain complex IV deficiency with minimal manifestations.

OBJECTIVES: Isolated complex IV (cytochrome c oxidase) deficiency is one of the most frequent respiratory chain defects in mitochondrial disorders (MIDs) and usually occurs together with severe pediatric or rarely adult multisystem disease. Here we report an adult with isolated complex IV deficiency with unusually mild clinical manifestations. CASE REPORT: A 50-year-old man had developed generalized muscle aches and occasional twitching and stiffness of the musculature since age 48 years. He had a previous history of diabetes, acute hearing loss, hyperlipidemia, hyperuricemia, arterial hypertension, polyarthrosis, hypogonadism, and hypothyroidism. The family history was positive for diabetes (mother), CK elevation (brother), myalgias (brother), and proximal weakness of the upper limbs (mother). Work-up revealed hypoacusis, postural tremor and reduced tendon reflexes, recurrent mild hyper-CK-emia, neurogenic needle electromyography, and a muscle biopsy with mild non-specific changes. Biochemical investigations of the muscle homogenate revealed an isolated complex IV defect and reduced amounts of coenzyme Q (CoQ). He profited from CoQ supplementation, low-carbohydrate diet, and gluten-free diet. CONCLUSIONS: Isolated complex IV deficiency may present with only mild muscular, endocrine, or cardiac manifestations in adults. Coenzyme Q supplementation, low-carbohydrate diet, and gluten-free diet may have a beneficial effect at least on some of the manifestations.

Conjoint occurrence of GABAB receptor antibodies in Lambert-Eaton myasthenic syndrome with antibodies to the voltage gated calcium channel.

Antibodies (abs) to the GABAB receptor have been recently found to be responsible for immune-mediated encephalitis with dominant seizures. They are in approximately 50% of cases associated with small-cell lung cancer (SCLC). GABAB receptors are mainly located in the hippocampus, thalamus and cerebellum in the presynaptic and postsynaptic regions of synapses. The main function of these receptors is to reduce activity states of neurons. In some instances, GABAB receptor abs in these patients were accompanied by other antibodies, among them VGCC abs (Lancaster et al., 2010, Boronat et al., 2011). VGCC abs cause paraneoplastic Lambert Eaton myasthenic syndrome (LEMS) by reduction of presynaptic VGCCs (Titulaer et al., 2011). In the domain of CNS disease, VGCC abs have been found in association with paraneoplastic cerebellar ataxia (Mason et al., 1997) and rarely and at low titres also in other paraneoplastic encephalopathies together with Hu abs (Lennon et al., 1995). It has been a long-standing debate if abs in paraneoplastic conditions associate rather with the neurological syndrome or the tumour. Here, we describe the conjoint occurrence of abs to the GABAB receptor and to the VGCC in a patient with SCLC presenting only symptoms of the peripheral nervous system giving another example of the latter hypothesis.

An optimized immunohistochemistry technique improves NMO-IgG detection: study comparison with cell-based assays.

Cell-based assays (CBA) have increased the sensitivity of the neuromyelitis optica (NMO)-IgG/aquaporin-4-antibody detection compared to classical tissue-based indirect assays. We describe the sensitivity of an optimized immunohistochemistry (IHC-o) to detect NMO-IgG/aquaporin-4-antibody in comparison with that of two CBA: an in-house (CBA-ih) and a commercial (CBA-c) assay (Euroimmun, Germany). Coded serum from 103 patients with definite NMO and 122 inflammatory controls were studied by IHC-o, CBA-ih, and CBA-c. IHC-o used the same protocol described to detect antibodies against cell surface antigens. CBA-ih used live cells transfected with the aquaporin-4-M23-isoform. The sensitivity of the IHC-o was 74.8% (95% confidence interval [CI] 65-83) and was similar to that of the CBA-ih 75.7% (95% CI 66-84) and the CBA-c 73.8% (95% CI 64-82). The specificity of the three assays was 100% (95% CI 97-100). Interassay concordance was high, 100 of 103 samples were coincident in all techniques. The optimized immunohistochemistry proves to be as sensitive and specific as the cell-based assays. This assay extends the available tools for NMO-IgG/aquaporin-4-antibody detection.

Neuromyelitis optica in Austria in 2011: to bridge the gap between neuroepidemiological research and practice in a study population of 8.4 million people.

BACKGROUND: In 2008 the Austrian Task Force for Neuromyelitis Optica (NMO) started a nation-wide network for information exchange and multi-centre collaboration. Their aim was to detect all patients with NMO or NMO spectrum disorders (NMO-SD) in Austria and to analyse their disease courses and response to treatment. METHODS: (1) As of March 2008, 1957 serum samples (of 1557 patients) have been tested with an established cell based immunofluorescence aquaporin-4 antibody (AQP4-ab) assay with a high sensitivity and specificity (both >95%). All tests were performed in a single reference laboratory (Clinical Dept. of Neurology of the Innsbruck Medical University). (2) A nation-wide survey with several calls for participation (via email newsletters, articles in the official journal of the Austrian Society of Neurology, and workshops) was initiated in 2008. All collected data will be presented in a way that allows that every individual patient can be traced back in order to ensure transparency and to avoid any data distortion in future meta-analyses. The careful and detailed presentation allows the visualization and comparison of the different disease courses in real time span. Failure and response to treatment are made visible at one glance. Database closure was 31 December 2011. All co-operators were offered co-authorship. RESULTS: All 71 NMO- or NMO-SD patients with AQP4-ab positivity (age range 12.3 to 79.6 years) were analysed in detail. Sex ratio (m:f = 1:7) and the proportion of patients without oligoclonal bands in cerebrospinal fluid (86.6%) were in line with previously published results. All identified patients were Caucasians. CONCLUSIONS: A nationwide collaboration amongst Austrian neurologists with good network communications made it possible to establish a database of 71 AQP4-ab positive patients with NMO/NMO-SD. This database is presented in detail and provides the basis for further studies and international cooperation in order to investigate this rare disease.