Preferences and perceptions of 617 migraine patients on acute and preventive migraine treatment attributes and clinical trial endpoints.

BACKGROUND: To identify the preferences and perceptions of migraine patients for acute and preventive treatment options and to investigate which treatment outcomes are the most important. DESIGN AND METHODS: The authors performed a choice-format survey in a cohort of migraine patients from Greece and Cyprus. A self-administered questionnaire developed in collaboration with the Greek Society of Migraine Patients was used. RESULTS: Questionnaires were collected from 617 migraine patients. Efficacy was preferred over safety as the single most important parameter, both in acute and preventive treatment. When analyzing single outcomes, patients prioritized a complete pain remission at 1-hour post-dose for acute therapies. Regarding migraine prevention, a 75% reduction in frequency, intensity of pain, accompanying symptoms and acute medication intake were considered as most important. Conversely, outcomes routinely used in clinical trials, namely complete or partial pain remission at 2-hours post-dose for acute treatment and 50% or 30% reduction in migraine frequency for prevention, were not deemed particularly relevant. Tablet formulation was mostly preferred, both in acute and preventive treatment. Conclusion: Listening to patients' needs may add a piece of the puzzle that is generally missing in clinical practice and often explains the lack of adherence in both acute and preventative anti-migraine therapies.

Biomarkers of therapeutic efficacy in adolescents and adults with 5q spinal muscular atrophy: a systematic review.

BACKGROUND: The therapeutic landscape of spinal muscular atrophy (SMA) was dramatically transformed with the introduction of three disease-modifying therapies (DMTs). A systematic review was performed to assess available evidence regarding quantitative therapeutic biomarkers used in SMA patients older than 11 years under treatment with DMTs. METHODS: Latest literature search in MEDLINE, EMBASE, Cochrane databases and gray literature resources was performed in June 2021. Studies reporting only motor function or muscle strength scales or pulmonary function tests were excluded. Primary outcome was the change from baseline score of any serum, cerebrospinal fluid (CSF) or neurophysiologic biomarker examined. RESULTS: Database and gray literature search yielded a total of 8050 records. We identified 14 records published from 2019 until 2021 examining 18 putative serum, CSF or neurophysiologic biomarkers along with routine CSF parameters in 295 SMA nusinersen-treated type 2-4 patients older than 11 years of age. There is evidence based on real-world observational studies suggesting that serum creatinine, creatine kinase activity levels along with CSF Αß42, glial fibrillary acidic protein concentration as well as ulnar compound motor action potential amplitude and single motor unit potential amplitude changes may depict therapeutic response in this population. CONCLUSION: This systematic review explored for the first-time biomarkers used to monitor therapeutic efficacy in SMA adolescents and adults treated with DMTs. Research in this area is in its early stages, and our systematic review can facilitate selection of quantitative therapeutic biomarkers that may be used as surrogate measures of treatment efficacy in future trials. PROTOCOL REGISTRATION: PROSPERO CRD42021245516.

COVID-19 pandemic impact on neurologic emergencies: a single-center retrospective cohort study.

Introduction: COVID-19 pandemic caused a major disruption to healthcare system. A year after COVID-19 outbreak, the question remains to what extent the lockdowns changed the volume of non-infected patients who were admitted to the Neurologic Department (ND). To determine the impact of the pandemic´s first year on a tertiary ND. Methods: non-infected patients admitted to ND between March 2020 and February 2021 were examined. A control group was generated for the same time interval starting from March 2019. Primary outcomes were the number of patients presenting with neurologic complaint who were admitted to the hospital and the diagnosis type. Secondary outcomes were hospitalization length and patients´ outcome. Results: overall, 816 patients (49.4% females) were admitted during the predetermined periods. Median age was 55 years. Median length of hospitalization was six days. We observed a 47.2% reduction in our department´s admissions during pandemic (n=282). None of the examined variables (type of neurologic diagnosis, age, gender, hospitalization length and outcome) changed significantly during pandemic. However, the number of patients admitted during the pandemic with a diagnosis categorized as "other" was statistically significant lower compared to the year before COVID-19 (p=0.007). Hospitalization length was associated only with patients´ age. Conclusion: our study examined for the first-time the consequences of the first year of COVID-19 pandemic on ND admissions. COVID-19 outbreak resulted in decreased admissions. Delays in seeking medical consultation for urgent or undiagnosed neurologic conditions require rigorous long-term monitoring to fully understand the impact of COVID-19 pandemic on patients with neurologic diseases.

Primary Sjögren's Syndrome Presenting with Rapidly Progressive Dementia: A Case Report.

BACKGROUND: Rapidly progressive dementias (RPDs) are dementias that progress subacutely over a time period of weeks to months. Primary Sjögren's syndrome (pSS) is an autoimmune disease that can affect any organ system and may present with a wide range of clinical features that may mimic a plethora of medical conditions and, in rare cases, may manifest as RPD. We describe a unique case of pSS, in which rapidly progressive dementia (RPD) was the first disease manifestation, and the patient's radiological and electroencephalogram findings were compatible with Creutzfeldt- Jakob disease (CJD). CASE PRESENTATION: Here, we report a 58-year-old woman who presented with cognitive impairment rapidly deteriorating over the last 6 months prior to admission. Brain MRI and EEG were indicative of CJD. However, CSF 14-3-3 and tau/phospho tau ratio were within normal limits and therefore alternative diagnoses were considered. Blood tests were significant for positive antinuclear antibodies, anti-ENA, and anti-SSA and a lip biopsy was consistent with pSS. The patient was started on intravenous steroids followed by oral prednisone taper, which prevented further deterioration. CONCLUSION: This rare case expands the spectrum of neurological manifestations in pSS and highlights the importance of considering pSS in the differential diagnosis of RPDs in order to avoid misdiagnosis and provide appropriate treatment in a timely fashion.

Nusinersen in Adults with 5q Spinal Muscular Atrophy: a Systematic Review and Meta-analysis.

Evidence for nusinersen administration in adult 5q spinal muscular atrophy (5q-SMA) patients is scarce and based on real-world observational data. The present systematic review and meta-analysis aimed to explore the efficacy and safety of nusinersen in patients older than 12 years of age with 5q-SMA. We searched MEDLINE, EMBASE, the Cochrane Library, and grey literature through April 2021. Cross-sectional studies, case reports, review articles, and studies with follow-up less than 6 months were excluded. We included 12 records (seven case-series, five cohorts) representing 11 population cohorts and enrolling 428 SMA patients. We observed statistically significant improvements on motor function Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM) scores at the longest follow-up assessments [SMD = 0.17(95% CI 0.01-0.33), SMD = 0.22(95% CI 0.06-0.38), respectively]. HFMSE and RULM significant improvements were also detected at the subgroup analysis during 10 and 14 months. HFMSE and RULM amelioration occurred earlier in patients with SMA type 3 or 4 during short-term analysis (≤ 6 months). 6-min walk tests (6MWT) and pulmonary function tests did not change. Minimal clinically important differences in HFMSE and RULM were observed in 43.3% (95% CI 34.5-52.3) and 38.9% (95% CI 27.7-50.7), respectively. Severe adverse events were reported in 2% (95% CI 0-5.8). Treatment withdrawal rate was 3% (95% CI 0.5-6.6). Despite the low quality of evidence and the unmet need for randomized data to establish the safety and efficacy of nusinersen in adults, our meta-analysis confirms that nusinersen is a valuable treatment option for older patients with longer-disease duration.Trial registration: PROSPERO database CRD42020223109.

Biomarkers of disease progression in adolescents and adults with 5q spinal muscular atrophy: a systematic review and meta-analysis.

Since the introduction of disease modifying treatments there is an unmet need to identify biomarkers of spinal muscular atrophy (SMA) natural history. We performed a systematic review and meta-analysis to summarize available evidence. We searched MEDLINE, Embase, Cochrane Library and gray literature until February 2021. The primary outcome was biomarkers longitudinal course in adolescents and adults. The secondary outcome was the discrimination of patients from controls. We included 42 records examining 606 patients from 19 population cohorts over a maximum follow-up of 17-years. Lung function and serum biomarkers could not depict disease progression. We identified potential biomarkers of disease activity [SMA functional rating scale, MoviPlate, pinch strength, compound muscle action potential (CMAP), motor unit number estimation (MUNE)] that require further investigation. Data regarding Hammersmith functional motor scale expanded, Revised upper limb module, 6-minute walk test were contradictory impeding any pooled estimate. The pooled analysis regarding our secondary outcome revealed that upper limb CMAP amplitudes and MUNE mean values differed significantly between SMA patients and controls [mean difference -3.63(-6.2, -1.06), -119.74(-153.93, -85.56) respectively]. Given the lack of natural history data on this population, our qualitative synthesis and meta-analysis could provide valuable evidence and identify promising predictive biomarkers requiring further longitudinal examination. PROSPERO Registration: CRD42021235605.

Atrial High-Rate Episodes in Patients with Devices Without a History of Atrial Fibrillation: a Systematic Review and Meta-analysis.

PURPOSE: Atrial high-rate episodes (AHREs) recorded with cardiac implantable electronic devices (CIEDs) have been associated with the development of clinical atrial fibrillation (AF) and increase in stroke and death risk. We sought to perform a systematic review with a meta-analysis to evaluate the prevalence of AHREs detected by CIEDs, their association with stroke risk, development of clinical AF, and mortality among patients without a documented history of AF. METHODS: We searched several databases, ClinicalTrials.gov, references of reviews, and meeting abstract books without any language restrictions up to 9 September 2020. We studied patients with CIEDs in whom AHREs were detected. Exclusion criterion was AF history. Our primary outcome was the risk of ischemic stroke in patients with AHREs. RESULTS: We deemed eligible eight studies for the meta-analysis enrolling a total of 4322 patients with CIED and without a documented AF history. The overall AHRE incidence ratio was estimated to be 17.56 (95% CI, 8.61 to 35.79) cases per 100 person-years. Evidence of moderate certainty suggests that patients with documented AHREs were 4.45 times (95% CI 2.87-6.91) more likely to develop clinical AF. Evidence of low confidence suggests that AHREs were associated with a 1.90-fold increased stroke risk (95% CI 1.19-3.05). AHREs were not associated with a statistically significant increased mortality risk. CONCLUSION: The present systematic review and meta-analysis demonstrated that among patients without a documented history of AF, the detection of AHREs by CIEDs was associated with significant increased risk of clinical AF and stroke. REGISTRATION NUMBER (DOI): Available in https://doi.org/10.17605/OSF.IO/ZRF6M .

Intrathecal Administration of Nusinersen Using the Ommaya Reservoir in an Adult with 5q-Related Spinal Muscular Atrophy Type 1 and Severe Spinal Deformity.

Spinal muscular atrophy (SMA) is a hereditary neuromuscular disorder, typically caused by survival motor neuron 1 (SMN1) gene deletion in chromosome 5q resulting in loss of SMN protein. SMA type 1 progresses rapidly leading to increased mortality usually before the age of 2 years. Nusinersen, the first approved disease-modifying treatment for all 5q-SMA types and ages, is an antisense oligonucleotide administered intrathecally via repeated lumbar punctures. However, adult SMA patients typically present with severe scoliosis and spinal deformity. We present a 28-year-old patient with SMA type 1 and severe spinal deformity, who received nusinersen via a subcutaneously implanted Ommaya reservoir connected with an intrathecal catheter at the thoracic level. The repetitive administrations were completed uneventfully, obviating the need for repeated laborious lumbar punctures and eliminating radiation exposure. In adult SMA patients, performing recurrent lumbar punctures can be technically challenging raising the need for an alternative route of administration. The use of Ommaya reservoirs is a viable, practical for repeated infusions, and safe option for the intrathecal delivery of nusinersen for select cases such as an adult SMA type 1 survivor with severe spinal deformity.

Genetic cause of heterogeneous inherited myopathies in a cohort of Greek patients.

Inherited muscle disorders are caused by pathogenic changes in numerous genes. Herein, we aimed to investigate the etiology of muscle disease in 24 consecutive Greek patients with myopathy suspected to be genetic in origin, based on clinical presentation and laboratory and electrophysiological findings and absence of known acquired causes of myopathy. Of these, 16 patients (8 females, median 24 years-old, range 7 to 67 years-old) were diagnosed by Whole Exome Sequencing as suffering from a specific type of inherited muscle disorder. Specifically, we have identified causative variants in 6 limb-girdle muscular dystrophy genes (6 patients; ANO5, CAPN3, DYSF, ISPD, LAMA2, SGCA), 3 metabolic myopathy genes (4 patients; CPT2, ETFDH, GAA), 1 congenital myotonia gene (1 patient; CLCN1), 1 mitochondrial myopathy gene (1 patient; MT-TE) and 3 other myopathy-associated genes (4 patients; CAV3, LMNA, MYOT). In 6 additional family members affected by myopathy, we reached genetic diagnosis following identification of a causative variant in an index patient. In our patients, genetic diagnosis ended a lengthy diagnostic process and, in the case of Multiple acyl-CoA dehydrogenase deficiency and Pompe's disease, it enabled specific treatment to be initiated. These results further expand the genotypic and phenotypic spectrum of inherited myopathies.

West Nile neuroinvasive disease. Report of four cases in Northern Greece, 2018.

West Nile virus (WNV) is a mosquito-borne RNA flavivirus which caused several epidemics worldwide. The year 2018 was a WNV record year for Europe, including Greece, with earlier and longer transmission season with higher than the previous number of cases. It has been proposed that some simple biochemical markers may be helpful for the recognition of WNV neuroinvasive disease, its differential from other neurological infectious diseases and prognosis. We describe four cases that suffered from WNV meningitis and/or encephalitis hospitalized in 2018 in a tertiary hospital in Thessaloniki, Greece, and investigate the importance of simple biomarkers for the recognition of WNV etiology.

Deciphering anti-MOG IgG antibodies: Clinical and radiological spectrum, and comparison of antibody detection assays.

IgG antibodies to myelin oligodendrocyte glycoprotein (MOG) detected by cell based assays (CBA) have been identified in a constantly expanding spectrum of CNS demyelinating disorders. However, a universally accepted CBA has not been adopted yet. We aimed to analyze the clinical and radiological features of patients with anti-MOG IgG1-antibodies detected with a live-cell CBA and to compare the three most popular MOG-CBAs. We screened sera from 1300 Greek patients (including 426 patients referred by our 8 clinics) suspected for anti-MOG syndrome, and 120 controls with the live-cell MOG-CBA for IgG1-antibodies. 41 patients, versus 0 controls were seropositive. Clinical, serological and radiological data were available and analyzed for the 21 seropositive patients out of the 426 patients of our clinics. Their phenotypes were: 8 optic neuritis, 3 myelitis, 3 neuromyelitis optica, 2 encephalomyelitis, 2 autoimmune encephalitis and 3 atypical MS. We then retested all sera of our 426 patients with the other two most popular MOG-CBAs for total IgG (a live-cell and a commercial fixed-cell CBAs). Seven IgG1-seropositive patients were seronegative for one or both IgG-CBAs. Yet, all 21 patients had clinical and radiological findings previously described in MOG-antibody associated demyelination disease supporting the high specificity of the IgG1-CBA. In addition, all IgG1-CBA-negative sera were also negative by the IgG-CBAs. Also, all controls were negative by all three assays, except one serum found positive by the live IgG-CBA. Overall, our findings support the wide spectrum of anti-MOG associated demyelinating disorders and the superiority of the MOG-IgG1 CBA over other MOG-CBAs.

Switching from fingolimod to alemtuzumab in patients with highly active relapsing-remitting multiple sclerosis: Α case series.

BACKGROUND: The management of "aggressive" and "highly-active" relapsing-remitting multiple sclerosis remains problematic. Although a number of highly efficacious agents are currently available, the optimal timing of their use and the balancing between efficacy and immediate and long-term consequences are still a matter of conjecture. METHODS: We describe the clinical, radiological and immunological profile of three multiple sclerosis patients with persistent clinical and radiological disease activity under fingolimod treatment. After fingolimod cessation patients demonstrated severe disease exacerbation and were successfully treated with alemtuzumab. RESULTS: All patients experienced significant improvement after the administration of alemtuzumab and achieved no evidence of disease activity status that persisted after a median of 19 months of follow-up (range: 17-25 months). Confirmed disability improvement was achieved in all cases. Quantitative MRI data demonstrated a reduction of the T2 lesion load in 2 out of 3 patients and complete abrogation of inflammatory activity in all patients after the administration of alemtuzumab. Α patient presented a previously unreported, persistent lymphocytosis after alemtuzumab administration, that was not associated with infectious, lymphoproliferative or autoimmune diseases and had no apparent clinical implications. CONCLUSIONS: Alemtuzumab appears to be an effective and safe short-term therapeutic option both as a rescue therapy for the disease flare-up associated with fingolimod withdrawal, as well as for the reversal of the deteriorating course observed in patients who fail treatment with fingolimod.

Extracranial internal carotid artery occlusive dissection - multimodality presentation in a case series.

Background: Carotid dissection is a rare disease, mainly affecting young and middle-aged patients potentially ending up in stroke. Multimodality imaging plays an essential role, both in terms of prompt and accurate diagnosis and follow-up of this entity. Patients and methods: We herein present a case series of patients with internal carotid artery dissection and compare the various imaging findings of ultrasonography, multidetector computed tomography angiography and magnetic resonance angiography, with a purpose to illustrate the value of multimodality imaging in the diagnosis of carotid dissection. Results: Ultrasound represents the first-line imaging modality for the evaluation of a suspected carotid pathology. Digital subtraction angiography is considered the gold standard method for evaluation of carotid luminal abnormalities and is currently reserved for those patients selected for endovascular surgery. Nevertheless, the widespread availability of modern cross-sectional techniques such as multi-detector computed tomography angiography and magnetic resonance angiography has made angiography marginalised. Computed tomography and magnetic resonance angiography offered accurate delineation of vascular lumen and providing valuable information for the vascular wall composition. Conclusions: Careful interpretation of imaging findings on various imaging modalities can lead to early and accurate diagnosis of carotid dissection.

Headache Linked to Intracranial Hypertension and Hypertrophic Pachymeningitis as the Initial and Dominant Presentation of Granulomatosis With Polyangiitis. Case Report and Review of the Recent Literature.

OBJECTIVE: The objective of this article is to report a rare case of headache as the initial symptom of granulomatosis with polyangiitis (GPA) and to review the recent literature. BACKGROUND: Granulomatosis with polyangiitis is a rare, systemic, autoimmune disease of unknown etiology. GPA has a wide spectrum of clinical symptomatology, including involvement of the nervous system, even as the initial manifestation. Symptoms of the peripheral nervous system used to dominate the clinical symptomatology. However, recent reports are focusing increasingly in granulomatous lesions of the central nervous system, and especially on the increased frequency of patients with hypertrophic pachymeningitis (HP). We report the case of a patient with headache linked to intracranial hypertension and hypertrophic pachymeningitis as the initial and dominant presentation of GPA and we review the recent literature. METHODS: A 54-year-old male, without any related medical history developed a severe headache. In the following 2 months, he gradually developed hoarseness and diplopia at the left and lower fields of vision. A brain MRI revealed wide-spread fattening and meningeal enhancement over the left hemisphere and the left cerebellar hemisphere. An endoscopy of the pharynx revealed the presence of a tumor-like mass in the left half of the nasopharynx. A biopsy showed inflammation with presence of polykaryocyte Langhans giant cells. The laboratory testing revealed important albuminuria and microhematuria, positive c-ANCA and negative p-ANCA. A diagnosis of GPA was established. RESULTS: A steroid treatment was administered initially, which improved the headache drastically, followed by the administration of a combination of cyclophosphamide and corticosteroid, which led to a gradual resolve of the remaining symptomatology. A follow-up brain MRI showed a decrease in meningeal enhancement, whereas a second one, 2 years later, was completely normal. CONCLUSIONS: HP was considered an extremely rare manifestation of GPA. However, recent studies are reporting an increased frequency of HP and are distinguishing a granulomatous and a vasculitic phenotype, with different localization and relapse rates, that may eventually constitute a different clinical spectrum of GPA.