Idiopathic intracranial hypertension secondary to Superior Sagittal Sinus Stenosis: a case report.

INTRODUCTION: Idiopathic intracranial hypertension (IIH) is a disease characterized by elevated intracranial pressure (ICP) without established etiology. Venous sinus stenosis contributes to IIH; however, it is still uncertain whether the stenosis is a primary cause of IIH or a secondary result in response to elevated ICP. Transverse sinus stenosis is frequently identified in patients with IIH and it is suggestive of raised ICP. Here, we report a case of IIH caused by intrinsic superior sagittal sinus stenosis (SSS). CASE PRESENTATION: A 43-year-old man suffered from IIH with headache, papilledema, and visual impairment. Angiography demonstrated isolated SSS stenosis with a pressure gradient of 30 mmHg. SSS stenosis was resistant to revascularization by stenting alone and intrastent balloon angioplasty was then performed to overcome such resistance. The rigidity of the vein wall suggests that the vein is not collapsed and the stenosis is intrinsic, secondary to idiopathic anatomical local changes. Post-procedure headache disappeared and visual acuity improved. CONCLUSION: An isolated SSS stenosis could lead to intracranial hypertension and this condition should be taken into account in the diagnostic workup of IIH. By now, SSS stenosis is not mentioned in any current consensus guidelines or paper on the diagnostic workflow of intracranial hypertension.

Analysis of a European general wildlife health surveillance program: Chances, challenges and recommendations.

In a One Health perspective general wildlife health surveillance (GWHS) gains importance worldwide, as pathogen transmission among wildlife, domestic animals and humans raises health, conservation and economic concerns. However, GWHS programs operate in the face of legal, geographical, financial, or administrative challenges. The present study uses a multi-tiered approach to understand the current characteristics, strengths and gaps of a European GWHS that operates in a fragmented legislative and multi-stakeholder environment. The aim is to support the implementation or improvement of other GWHS systems by managers, surveillance experts, and administrations. To assess the current state of wildlife health investigations and trends within the GWHS, we retrospectively analyzed 20 years of wildlife diagnostic data to explore alterations in annual case numbers, diagnosed diseases, and submitter types, conducted an online survey and phone interviews with official field partners (hunting administrators, game wardens and hunters) to assess their case submission criteria as well as their needs for post-mortem investigations, and performed in-house time estimations of post-mortem investigations to conduct a time-per-task analysis. Firstly, we found that infectious disease dynamics, the level of public awareness for specific diseases, research activities and increasing population sizes of in depth-monitored protected species, together with biogeographical and political boundaries all impacted case numbers and can present unexpected challenges to a GWHS. Secondly, we found that even a seemingly comprehensive GWHS can feature pronounced information gaps, with underrepresentation of common or easily recognizable diseases, blind spots in non-hunted species and only a fraction of discovered carcasses being submitted. Thirdly, we found that substantial amounts of wildlife health data may be available at local hunting administrations or disease specialist centers, but outside the reach of the GWHS and its processes. In conclusion, we recommend that fragmented and federalist GWHS programs like the one addressed require a central, consistent and accessible collection of wildlife health data. Also, considering the growing role of citizen observers in environmental research, we recommend using online reporting systems to harness decentrally available information and fill wildlife health information gaps.

Are anti-calcitonin gene-related peptide monoclonal antibodies effective in treating migraine aura? A pilot prospective observational cohort study.

BACKGROUND: About 15% to one third of migraineurs experience aura symptoms. Aura is a reversible focal neurological phenomenon involving visual, sensory, speech, and motor symptoms that usually precede migraine pain. Monoclonal antibodies against calcitonin-related peptide (anti- CGRP mAbs) are effective in preventing chronic and episodic migraine, but little is known about their effectiveness on specifically preventing migraine with aura. METHODS: This is a pilot prospective observational cohort study, aiming at evaluating the effectiveness and safety of Erenumab, Fremanezumab or Galcanezumab for the treatment of migraine aura. We enrolled 14 patients at the Headache Centre of University Federico II of Naples. Duration of follow-up was 12 months. We assessed mean monthly days with aura symptoms, with or without subsequent headache, as well as mean monthly days with headache and mean monthly MIDAS score, by reviewing standardized paper patient headache diaries every three months. RESULTS: A significant decrease in mean monthly aura days was observed throughout the observation period (median baseline: 13, interquartile range: 4-16; after 12 months: 1, interquartile range: 0-3, p < 0.001). We observed a statistically significant decrease in mean monthly headache days as well (median baseline 21, interquartile range: 16-30; after 12 months: 5, interquartile range: 4-7, p < 0.001). During the 12-month treatment period, none of the 14 patients reported mild or serious adverse events. CONCLUSION: Our findings suggest that anti-CGRP mAbs are highly effective in migraine with aura, both in reducing mean monthly aura days and mean monthly days with headache.

Recurrent reflex syncope in idiopathic intracranial hypertension patient resolved after lumbar puncture: pathogenetic implications.

BACKGROUND: Idiopathic intracranial hypertension is a disease characterized by increased intracranial cerebrospinal fluid volume and pressure without evidence of other intracranial pathology. Dural sinuses are rigid structures representing a privileged low-pressure intracranial compartment. Rigidity of dural sinus ensures that the large physiologic fluctuations of cerebrospinal fluid pressure associated with postural changes or to Valsalva effect cannot be transmitted to the sinus. An abnormal dural sinus collapsibility, especially when associated with various anatomical sinus narrowing, has been proposed as a key factor in the pathogenesis of idiopathic intracranial hypertension. This pathogenetic model is based on an excessive collapsibility of the dural sinuses that leads to the triggering of a self-limiting venous collapse positive feedback-loop between the cerebrospinal fluid pressure, that compresses the sinus, and the increased dural sinus pressure upstream, that reduces the cerebrospinal fluid reabsorption rate, increasing cerebrospinal fluid volume and pressure at the expense of intracranial compliance and promoting further sinus compression. Intracranial compliance is the ability of the craniospinal space to accept small volumetric increases of one of its compartments without appreciable intracranial pressure rise. In idiopathic intracranial hypertension, a condition associated with a reduced rate of CSF reabsorption leading to its volumetric expansion, a pathologically reduced IC precedes and accompanies the rise of ICP. Syncope is defined as a transient loss of consciousness due to a transient cerebral hypoperfusion characterized by rapid onset, short duration, and spontaneous complete recovery. A transient global cerebral hypoperfusion represents the final mechanism of syncope determined by cardiac output and/or total peripheral resistance decrease. There are many causes determining low cardiac output including reflex bradycardia, arrhythmias, cardiac structural disease, inadequate venous return, and chronotropic and inotropic incompetence. Typically, syncopal transient loss of consciousness is mainly referred to an extracranial mechanism triggering a decrease in cardiac output and/or total peripheral resistance. Conversely, the association of syncope with a deranged control of intracranial compliance related to cerebral venous outflow disorders has been only anecdotally reported. CASE PRESENTATION: We report on a 57-year-old woman with daily recurrent orthostatic hypotension syncope and idiopathic intracranial hypertension-related headaches, which resolved after lumbar puncture with cerebrospinal fluid subtraction. CONCLUSIONS: A novel mechanism underlying the triggering of orthostatic syncope in the presence of intracranial hypertension-dependent reduced intracranial compliance is discussed.

Detection of novel RNA viruses in wild noble crayfish (Astacus astacus): A virome analysis in Swiss water bodies.

European native crayfish populations are undergoing a strong decline due to environmental factors and the introduction of highly competitive non-native species. Pathogens are an additional threat to native crayfish. However, aside from the crayfish plague, other infectious diseases are still widely unknown. This study aimed to investigate viruses present in seven populations of wild noble crayfish (Astacus astacus) in Switzerland, through high-throughput sequencing. Sequence analysis revealed the presence of 11 novel RNA viruses (one bunya-like, four hepe-like, two dicistro-like, three picorna-like, and one permutotetra-like) in the samples. The discovery of a novel bunya-like virus in noble crayfish without associated mortality or macroscopical alterations is of particular interest since it is closely related to the bunya-like brown spot virus, a virus described in 2019 from diseased native white-clawed crayfish (Austropotamobius pallipes) during a mass mortality event in France. It seems that these two closely related viruses have very different impacts on their respective hosts, raising the need for further investigations on virulence factors and host susceptibility towards these viruses. This study provides a basis for future investigations, permitting to gradually fill the knowledge gap in crayfish viral diseases.

Non-convulsive status epilepticus versus periodic EEG pattern in sporadic Creutzfeldt-Jakob disease: two sides of the same coin?

Sporadic Creutzfeldt-Jakob disease is characterized by rapid cognitive and neuropsychiatric impairment. The Heidenhain variant of Creutzfeldt-Jakob disease is known for isolated visual disturbance that precedes other features. Periodic sharp wave complexes on EEG are typical of sporadic Creutzfeldt-Jakob disease, but at the onset, the electroclinical pattern may be unclear and suggest the hypothesis of a non-convulsive status epilepticus. Furthermore, non-convulsive status epilepticus and sporadic Creutzfeldt-Jakob disease could coexist simultaneously. We report the case of a patient admitted to our hospital for progressive psychiatric and cognitive disorders. In the initial phase, based on clinical, EEG, and neuroradiological features, a diagnosis of possible non-convulsive status epilepticus was made. Subsequently, the rapid neurological degeneration led to the diagnosis of Creutzfeldt-Jakob disease confirmed by cerebrospinal fluid real-time quaking-induced conversion. Non-convulsive status epilepticus could mimic Creutzfeldt-Jakob disease or be present in overlap. Antiseizure drugs may be started when the etiology is unclear, but overtreatment should be avoided when invasive treatment protocols fail, and the neurological progression suggests an encephalopathy.

A head-to-head observational cohort study on the efficacy and safety of monoclonal antibodies against calcitonin gene-related peptide for chronic and episodic migraine.

OBJECTIVE: To compare the effectiveness and safety of galcanezumab, fremanezumab, and erenumab for the treatment of chronic and episodic migraine, through real-world data. BACKGROUND: Monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway have been tested extensively in several clinical trials for both episodic and chronic migraine, showing high effectiveness, safety, and tolerability; however, there are no prospective real-world studies intending to compare their efficacy and safety. METHODS: This is a prospective observational cohort study comparing the effectiveness and safety profiles of galcanezumab, fremanezumab, and erenumab for the treatment of chronic and episodic migraine. We enrolled 140 patients at the Headache Centre of University Federico II of Naples, with a history of multiple failed treatments with validated migraine preventatives. Framenezumab, erenumab, or galcanezumab were administered for 12 months. The mean monthly days with headache, Migraine Disability Assessment (MIDAS) score, and adverse events were evaluated during the run-in period and every 3 months by reviewing standardized paper patient headache diaries. RESULTS: We found a mean reduction of migraine monthly days from baseline of -12.0 (-9.8, -14.1) in the galcanezumab group, -12.3 (-10.2, -14.3) in the fremanezumab group, and -10.8 (-8.5, -13.1) in the erenumab group (for all, p < 0.001). We found a mean reduction of MIDAS score of -32.6 (-26.6, -38.5) in the galcanezumab group, -33.4 (-28.0, -38.9) in the fremanezumab group, and -29.2 (-23.0, -35.4) in the erenumab group (for all, p < 0.001). We found no significant differences between mAbs in the reduction of mean monthly days with headache and MIDAS score. We found a more rapid effect of galcanezumab and erenumab compared to fremanezumab in medication overuse headache patients after 3 months of treatment (-10.8 and -11.1 vs. -4.0 days; p = 0.029). CONCLUSION: Our results confirm the therapeutic benefits of anti-CGRP mAbs. There is no evidence that suggests that one antibody may be superior to the others in terms of effectiveness, both in chronic and episodic patients.

Multiple cranial neuropathy due to varicella zoster virus reactivation without vesicular rash: a challenging diagnosis.

Ramsay Hunt syndrome is due to reactivation of varicella zoster virus (VZV) dormant in the geniculate ganglion of the facial nerve. The diagnosis is typically based on clinical triad of ipsilateral facial paralysis, otalgia, and vesicles in the auditory canal or the auricle. However, Ramsay Hunt syndrome may occur without skin eruption in up to one third of patients. Moreover, the involvement of other cranial nerves in addition to the facial nerve has been also reported. Herein, we reported a case report of a man who developed a multiple cranial neuropathy caused by VZV reactivation without skin vesicular eruption. The present case underlines a possible diagnostic challenge that clinicians may hit when facing a common disorder such as peripheral facial palsy. Indeed, clinicians must be aware that Ramsay Hunt syndrome may develop without skin vesicular eruption as well it may be complicated by multiple cranial nerve involvement. Antiviral therapy is effective in VZV reactivation for recovery of nerve function.

Sarcoptic mange in Felidae: does Sarcoptes scabiei var. felis exist? A first molecular study.

Domestic and wild felids are considered suitable hosts for the parasitic mite Sarcoptes scabiei, and sarcoptic mange is reported in several felid species in the scientific literature. However, the historic classification of Sarcoptes mites into host-specific varieties does not include S. scabiei var. felis. It is unclear whether sarcoptic mange transmission in felids involves canids, other sympatric species, or exclusively felids. This study aimed to characterize the genetic structure of S. scabiei mites from domestic cats (Felis catus) and Eurasian lynx (Lynx lynx carpathicus), comparing them with Sarcoptes mites from sympatric domestic and wild carnivores. Ten Sarcoptes microsatellite markers were used to genotype 81 mites obtained from skin scrapings of 36 carnivores: 4 domestic cats, one dog (Canis lupus familiaris), 4 Eurasian lynx, 23 red foxes (Vulpes vulpes), and 4 grey wolves (Canis lupus lupus) from either Italy, Switzerland or France. Two genetic clusters of S. scabiei with a geographical distribution pattern were detected: mites from cats originating from Central Italy clustered with those from sympatric wolves. In contrast, all the other mites from Switzerland, France and Northern Italy clustered together. These results strengthen the previously advanced hypothesis that genetic variants of S. scabiei have a predominant geographic-related distribution with cryptic transmission patterns. These patterns may rely on the interactions between different hosts living in the same ecological niche rather than a simple infection among hosts belonging to the same taxon, reinforcing the idea that the S. scabiei historic classification into "var" might have little ongoing relevance.

Title: La gale sarcoptique chez les félidés : Sarcoptes scabiei var. felis existe-t-il ? Première étude moléculaire. Abstract: Les félidés domestiques et sauvages sont considérés comme des hôtes appropriés pour l'acarien parasite Sarcoptes scabiei, et la gale sarcoptique est signalée chez plusieurs espèces de félidés dans la littérature scientifique. Cependant, la classification traditionnelle des acariens du genre Sarcoptes en variétés spécifiques à l'hôte n'inclut pas S. scabiei var. felis. On ne sait pas si la transmission de la gale sarcoptique chez les félidés implique des canidés, d'autres espèces sympatriques ou exclusivement des félidés. Cette étude visait à caractériser la structure génétique des acariens S. scabiei des chats domestiques (Felis catus) et du lynx eurasien (Lynx lynx carpathicus), en les comparant aux Sarcoptes des carnivores domestiques et sauvages sympatriques. Dix marqueurs microsatellites de Sarcoptes ont été utilisés pour génotyper 81 acariens issus de grattages cutanés de 36 carnivores : 4 chats domestiques, un chien (Canis lupus familiaris), 4 lynx eurasiens, 23 renards roux (Vulpes vulpes) et 4 loups gris (Canis lupus lupus) d'Italie, de Suisse ou de France. Deux groupes génétiques de S. scabiei, qui suivent un modèle de distribution géographique, ont été détectés. Les acariens des chats originaires du centre de l'Italie se regroupent avec ceux des loups sympatriques. En revanche, tous les autres acariens de Suisse, de France et d'Italie du Nord sont groupés ensemble. Ces résultats renforcent l'hypothèse précédemment avancée selon laquelle les variants génétiques de S. scabiei ont une distribution géographique prédominante avec des schémas de transmission cryptiques. Ces modèles peuvent reposer sur les interactions entre différents hôtes vivant dans la même niche écologique plutôt que sur une simple transmission parmi des hôtes appartenant au même taxon, renforçant l'idée que la classification historique de S. scabiei en "var" a peu de pertinence.

Anti-calcitonin gene-related peptide monoclonal antibodies for the treatment of vestibular migraine: A prospective observational cohort study.

BACKGROUND: Vestibular migraine is considered the most common cause of recurrent vertigo for which specific treatments are missing. Monoclonal antibodies against calcitonin gene-related peptide,, are effective in preventing migraine. Since CGRP is also detected in human cochlear and vestibular organs it may also play a role in vestibular physiology. METHODS: This is a prospective observational cohort study, aiming at evaluating the efficacy of erenumab, fremanezumab or galcanezumab for the treatment of fifty vestibular migraine patients. We assessed mean monthly days with headache and dizziness/vestibular symptoms, pain intensity and migraine-related clinical burden occurring for 18 months. RESULTS: Response to treatment was excellent as 45 (90%) patients had at least a 50% reduction in vertigo frequency, 43 (86%) had at least a 50% reduction in headache frequency, and 40 (80%) a MIDAS reduction of at least 50%. Overall, 39 (78%) patients had a concomitant reduction of all three parameters. Mean monthly days with dizziness/vestibular symptoms showed an overall significant decrease from a mean of 10.3 ± 1.9 at baseline to 0.8 ± 0.3 days, difference 9.5 (CI 95% 3.6, 15.4; p < 0.001) after twelve months. CONCLUSION: We show that anti-CGRP mAbs may be effective in the treatment of Vestibular Migraine. Their use should be encouraged early in the disease course to allow for a better symptom control and quality of life improvement.

Detection and Characterization of a De Novo Alu Retrotransposition Event Causing NKX2-1-Related Disorder.

BACKGROUND: Heterozygous NKX2-1 loss-of-function variants cause combinations of hyperkinetic movement disorders (MDs, particularly childhood-onset chorea), pulmonary dysfunction, and hypothyroidism. Mobile element insertions (MEIs) are potential disease-causing structural variants whose detection in routine diagnostics remains challenging. OBJECTIVE: To establish the molecular diagnosis of two first-degree relatives with clinically suspected NKX2-1-related disorder who had negative NKX2-1 Sanger (SS), whole-exome (WES), and whole-genome (WGS) sequencing. METHODS: The proband's WES was analyzed for MEIs. A candidate MEI in NKX2-1 underwent optimized SS after plasmid cloning. Functional studies exploring NKX2-1 haploinsufficiency at RNA and protein levels were performed. RESULTS: A 347-bp AluYa5 insertion with a 65-bp poly-A tail followed by a 16-bp duplication of the pre-insertion wild-type sequence in exon 3 of NKX2-1 (ENST00000354822.7:c.556_557insAlu541_556dup) segregated with the disease phenotype. CONCLUSIONS: We identified a de novo exonic AluYa5 insertion causing NKX2-1-related disorder in SS/WES/WGS-negative cases, suggesting that MEI analysis of short-read sequencing data or targeted long-read sequencing could unmask the molecular diagnosis of unsolved MD cases. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Truncating Variants in RFC1 in Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia Syndrome.

BACKGROUND AND OBJECTIVE: Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is an autosomal recessive neurodegenerative disease characterized by adult-onset and slowly progressive sensory neuropathy, cerebellar dysfunction, and vestibular impairment. In most cases, the disease is caused by biallelic (AAGGG)n repeat expansions in the second intron of the replication factor complex subunit 1 (RFC1). However, a small number of cases with typical CANVAS do not carry the common biallelic repeat expansion. The objective of this study was to expand the genotypic spectrum of CANVAS by identifying sequence variants in RFC1-coding region associated with this condition. METHODS: Fifteen individuals diagnosed with CANVAS and carrying only 1 heterozygous (AAGGG)n expansion in RFC1 underwent whole-genome sequencing or whole-exome sequencing to test for the presence of a second variant in RFC1 or other unrelated gene. To assess the effect of truncating variants on RFC1 expression, we tested the level of RFC1 transcript and protein on patients' derived cell lines. RESULTS: We identified 7 patients from 5 unrelated families with clinically defined CANVAS carrying a heterozygous (AAGGG)n expansion together with a second truncating variant in trans in RFC1, which included the following: c.1267C>T (p.Arg423Ter), c.1739_1740del (p.Lys580SerfsTer9), c.2191del (p.Gly731GlufsTer6), and c.2876del (p.Pro959GlnfsTer24). Patient fibroblasts containing the c.1267C>T (p.Arg423Ter) or c.2876del (p.Pro959GlnfsTer24) variants demonstrated nonsense-mediated mRNA decay and reduced RFC1 transcript and protein. DISCUSSION: Our report expands the genotype spectrum of RFC1 disease. Full RFC1 sequencing is recommended in cases affected by typical CANVAS and carrying monoallelic (AAGGG)n expansions. In addition, it sheds further light on the pathogenesis of RFC1 CANVAS because it supports the existence of a loss-of-function mechanism underlying this complex neurodegenerative condition.

Description of a Sarcoptic Mange Outbreak in Alpine Chamois Using an Enhanced Surveillance Approach.

Since 1995, the Alpine chamois (Rupicapra r. rupicapra) population of the Dolomites has been affected by sarcoptic mange with considerable management concerns. In this study, 15 years (2006-2020) of passive surveillance and demographic data were analyzed in order to describe a mange outbreak. Furthermore, an enhanced passive surveillance protocol was implemented in order to evaluate the efficiency of ordinary vs. enhanced surveillance protocol in identifying dead chamois in the field and in reaching a correct diagnosis. Our results confirm the role of mange as a determining factor for chamois mortality, while stressing the importance of a wider view on the factors affecting population dynamics. The enhanced passive surveillance protocol increased the probability of carcass retrieval and identification of the cause of death; however, its adoption may be too costly if applied for long periods on a wide scale. Passive surveillance, in both ordinary and enhanced surveillance protocol, should encompass the use of other strategies in the future to study the eco-epidemiology of the disease in wild Caprinae.

The putative role of trigemino-vascular system in brain perfusion homeostasis and the significance of the migraine attack.

Besides representing the place where a migraine attack generates, what is the physiological role of peptidergic control of arteriolar caliber within the trigemino-vascular system? Considering that the shared goal of most human CGRP-based neurosensory systems is the protection from an acute threat, especially if hypoxic, what is the end meaning of a migraine attack? In this paper, we have reviewed available evidence on the possible role of the trigemino-vascular system in maintaining cerebral perfusion pressure homeostasis, despite the large physiological fluctuations in intracranial pressure occurring in daily life activities. In this perspective, the migraine attack is presented as the response to a cerebral hypoxic threat consequent to a deranged intracranial pressure control aimed at generating a temporary withdrawal from the environment with limitation of physical activity, a condition required to promote the restoration of cerebral fluids dynamic balance.

Phylogeography and population genetic structure of the European roe deer in Switzerland following recent recolonization.

In the early 1800s, the European roe deer (Capreolus capreolus) was probably extirpated from Switzerland, due to overhunting and deforestation. After a federal law was enacted in 1875 to protect lactating females and young, and limiting the hunting season, the roe deer successfully recovered and recolonized Switzerland. In this study, we use mitochondrial DNA and nuclear DNA markers to investigate the recolonization and assess contemporary genetic structure in relation to broad topographic features, in order to understand underlying ecological processes, inform future roe deer management strategies, and explore the opportunity for development of forensic traceability tools. The results concerning the recolonization origin support natural, multidirectional immigration from neighboring countries. We further demonstrate that there is evidence of weak genetic differentiation within Switzerland among topographic regions. Finally, we conclude that the genetic data support the recognition of a single roe deer management unit within Switzerland, within which there is a potential for broad-scale geographic origin assignment using nuclear markers to support law enforcement.

Monocular Diplopia in Idiopathic Intracranial Hypertension: A Case Report and Literature Review.

BACKGROUND: Diplopia is the double vision of a single object, and can be binocular or monocular. Binocular diplopia is caused by the misalignment of the visual axes, with images falling on the fovea of the fixating eye and on the extra-foveal retina of the non-fixating eye, as a consequence of both neurological (i.e., oculomotor nerve palsies, ocular myopathies, neuromuscular junction disorders) and ophthalmic disorders (i.e., decompensation of a pre-existing strabismus). In contrast, monocular diplopia is generally explained by intraocular pathology (i.e., refractive errors, ocular media abnormalities, dry eyes), causing the image of a single object to fall, at the same time, on the fovea and on the extra-foveal retina of the same eye. METHODS: We report the case of a 22-year-old woman presenting with acute-onset monocular diplopia. RESULTS: The diagnosis of idiopathic intracranial hypertension (IIH) was based on the presence of papilloedema and elevated cerebrospinal fluid (CSF) pressure. Monocular diplopia resolved after CSF subtraction. CONCLUSIONS: We describe a case of monocular diplopia as a presenting symptom of IIH, and discuss diagnostic issues of this possibly underestimated symptom in neurology clinical practice. Careful ophthalmic and neuro-ophthalmic examination can identify clinical features of diplopia, and drive diagnosis and treatment. LEARNING POINTS: Monocular diplopia is mostly an ophthalmological condition but can occur in a number of neurological diseases.Idiopathic intracranial hypertension can present with monocular diplopia.Differential diagnoses of diplopia in neurology and ophthalmology settings need to account for headache disorders.

Clinical features, disease progression, and use of healthcare resources in a large sample of 866 patients from 24 headache centers: A real-life perspective from the Italian chROnic migraiNe (IRON) project.

OBJECTIVE: To develop a dedicated Italian chronic migraine (CM) database (IRON project) to overcome disease misconceptions, improve clinical administration, reduce patients' burden, and rationalize economic resource allotment. BACKGROUND: Proper CM management requires a comprehensive appraisal of its full clinical, social, and economic complexity. METHODS: In this cross-sectional study, CM patients were screened in 24 certified headache centers with face-to-face interviews. Information on sociodemographic factors, medical history, characteristics of CM, and of prior episodic migraine (EM), and healthcare resource use was gathered using a semistructured web-based questionnaire. RESULTS: A total of 866 CM patients were enrolled. CM started ~20 years after EM onset (age at EM onset 17.4 ± 9.1 vs. age at CM onset 35.3 ± 12.5 [mean ± SD]). CM prophylaxis, used by 430/866 (49.6%) of the patients, was often ineffective, not tolerated, and prematurely discontinued. Medications and diagnostic workup, frequently inappropriate, were mostly subsidized by the Italian national health service. CM patients with ≥25 headache days/month revealed substantial clinical differences and heavier disability and economic burden compared with those with <25 headache days/month. CONCLUSIONS: CM is a heterogeneous headache disorder deserving more in-depth clinical characterization, sharper diagnostic criteria, and tailored treatments. CM registries are expected to improve clinical management, resulting in increased disease awareness, better healthcare resource allocation, and reduced economic burden.

MIR-NATs repress MAPT translation and aid proteostasis in neurodegeneration.

The human genome expresses thousands of natural antisense transcripts (NAT) that can regulate epigenetic state, transcription, RNA stability or translation of their overlapping genes1,2. Here we describe MAPT-AS1, a brain-enriched NAT that is conserved in primates and contains an embedded mammalian-wide interspersed repeat (MIR), which represses tau translation by competing for ribosomal RNA pairing with the MAPT mRNA internal ribosome entry site3. MAPT encodes tau, a neuronal intrinsically disordered protein (IDP) that stabilizes axonal microtubules. Hyperphosphorylated, aggregation-prone tau forms the hallmark inclusions of tauopathies4. Mutations in MAPT cause familial frontotemporal dementia, and common variations forming the MAPT H1 haplotype are a significant risk factor in many tauopathies5 and Parkinson's disease. Notably, expression of MAPT-AS1 or minimal essential sequences from MAPT-AS1 (including MIR) reduces-whereas silencing MAPT-AS1 expression increases-neuronal tau levels, and correlate with tau pathology in human brain. Moreover, we identified many additional NATs with embedded MIRs (MIR-NATs), which are overrepresented at coding genes linked to neurodegeneration and/or encoding IDPs, and confirmed MIR-NAT-mediated translational control of one such gene, PLCG1. These results demonstrate a key role for MAPT-AS1 in tauopathies and reveal a potentially broad contribution of MIR-NATs to the tightly controlled translation of IDPs6, with particular relevance for proteostasis in neurodegeneration.