BMC Neurology

Changes to spatiotemporal gait metrics in gait-altering conditions are characteristic of the pathology. This data can be interpreted by machine learning (ML) models which have recently emerged as an adjunct to clinical medicine. However, the literature is undecided regarding its utility in diagnosing pathological gait and is heterogeneous in its approach to applying ML techniques. This study aims to address these gaps in knowledge. This was a prospective observational study involving 32 patients with Parkinsons disease and 88 normative subjects. Spatiotemporal gait metrics were gathered from all subjects using the MetaMotionC inertial measurement unit and data obtained were used to train and evaluate the performance of 10 machine learning models. Principal component analysis and Genetic Algorithm were amongst the feature selection techniques used. Classification models included Logistic Regression, Support Vector Machine, Naive - Bayes, Random Forest, and Artificial Neural Networks. ML algorithms can accurately distinguish pathological gait in Parkinsons disease from that of normative controls. Two models which used the Random Forest classifier with Principal Component analysis and Genetic Algorithm feature selection techniques separately, were 100% accurate in its predictions and had an F1 score of 1. A third model using principal component analysis and Artificial neural networks was equally as successful (100% accuracy, F1 = 1). We conclude that ML algorithms can accurately distinguish pathological gait from normative controls in Parkinsons Disease. Random Forest classifiers, with Genetic Algorithm feature selection are the preferred ML techniques for this purpose as they produce the highest performing model. Author summaryThe way humans walk, are emblematic of their overall health status. These walking patterns, otherwise, can be captured as gait metrics from small and portable wearable sensors. Data gathered from these sensors can be interpreted by machine learning algorithms which can then be used to accurately distinguish healthy and non-healthy patients based on their gait or walking pattern. The applications of this technology are many and varied. Firstly, it can be used to simply aid in diagnosis as explored in this paper. In future, researchers may use their understanding of normal and pathological gait, and their differences to quantify how severely ones gait is affected in a disease state. This data can be used to track, and quantify, improvements or further deteriorations post treatment, whether these be medication-based or interventions like surgery. Retrospective analyses on data such as this can be used to judge the value of an intervention in reducing a patients disability, and advise health related expenditure.

Over 400,000 U.S. military personnel have been diagnosed with a mild or moderate traumatic brain injury (TBI) since the year 2000. Posttraumatic headache (PTH) is one of the most common and bothersome sequela after a mild or moderate head injury. Persistent posttraumatic headache are headaches due to the head injury lasting longer than 3 months. About 40% of military personnel who develop PTH after a TBI have persistent PTH and about 20% have PTH lasting longer than a year after the original injury. Persistent PTH has a negative impact on daily activities, including work and social functioning. There are no available guidelines for treating posttraumatic headache, and there is extraordinary variability in treatment practices as a result. The present study aims to identify predictive factors that account for heterogeneity in response to behavioral intervention for posttraumatic headache attributable to mild to moderate TBI. We intend to create a predictive model of PTH through the adoption of the Predictive Approaches to Treatment effect Heterogeneity Statement (PATH Statement). This rigorous, guided approach will be used to develop and validate a predictive model of psychosocial factors related to PTH treatment outcomes, thereby improving individualized treatment of PTH. This protocol provides an overview of the research design and methods for this study.

We tested a low-dose naltrexone and acetaminophen combination for episodic migraine prevention. We randomly assigned patients to naltrexone and acetaminophen combination (n=6) or placebo (n=6) for a 12-week double-blind treatment. Non-responders continued into open-label treatment with naltrexone and acetaminophen combination (n=5) for additional 12 weeks. Patients were adults who experienced 5 to 17 (average 9.7) migraine days at baseline. The primary endpoint was the mean change in the monthly migraine days during the last 4 weeks of the double-blind treatment period. The key secondary endpoint was the mean change in the monthly migraine days from the 4-week double-blind follow-up (2nd baseline) to the last 4 weeks of the open-label treatment period. The magnitude of the treatment effect for the naltrexone and acetaminophen combination observed in the double-blind period was 2.2 fewer monthly migraine days than placebo (p=0.43). Four out of 6 (66.7%) naltrexone and acetaminophen-treated patients experienced 75% reduction in migraine days compared to 1 out of 6 (16.7%) placebo-treated patients (p=0.09). In the open-label phase, treatment with the naltrexone and acetaminophen combination (n=5) led to 8.2 fewer mean monthly migraine days (from 11.8 to 3.6), representing 69.5% improvement (p=0.03), and 100% of the patients experienced a 50% reduction in monthly migraine days. Adverse events were mild to moderate and transient, included dry mouth, fatigue, sedation, nausea, and feeling jittery. We postulate that naltrexones toll-like receptor (TLR4) antagonism properties prevent pro-inflammatory cytokines production in the trigeminal ganglion averting "overactive nerves" (laymans term) and migraine. Although this trial used low-dose naltrexone (defined as 1 - 5 mg/day), in future phase 3 studies we will test a range of naltrexone and acetaminophen combination doses.

State of the ArtApathy and impulsivity are common in syndromes associated with frontotemporal lobar degeneration (FTLD). They are associated with high carer distress and poor patient outcomes. There are limited treatment options and progress has been hindered by a lack of appropriate outcome measures. This study aimed to develop a carer-rated questionnaire oriented to people with syndromes associated with FTLD. MethodologyPrincipal component and Rasch analysis were conducted on carer-, clinician- and patient-reported questionnaires and performance-based tests of behavioural change in the "Picks Disease and Progressive Supranuclear Palsy Prevalence and Incidence" (PiPPIN) study. We identified two key components which informed subsequent item development for a novel scale which we call the Cambridge Questionnaire for Apathy and Impulsivity Traits (CamQUAIT). The resulting scale comprised two subscales assessing "motivation and support" (CamQUAIT-M) and "impulsivity and challenging behaviours" (CamQUAIT-C). An independent sample of 132 carers for people with FTLD-associated syndromes completed the CamQUAIT, along with a battery of existing measures. The CamQUAIT was reduced to 15 items following Rasch analysis. ResultsBoth subscales showed good construct validity as assessed by high Person separation index (CamQUAIT-M=0.9; CamQUAIT-C=0.7) and Cronbachs alpha (CamQUAIT-M=0.9; CamQUAIT-C=0.8). The subscales correlated moderately with each other (r=0.376, p<0.001), and with existing measures of behavioural change. ConclusionThe CamQUAIT is a targeted measurement tool to assess apathy, impulsivity, and related behavioural change in the context of FTLD-related syndromes. The scale demonstrates good measurement properties and is sensitive to group differences, providing a suitable outcome measure to evaluate novel symptomatic treatments.

ObjectiveTo analyze and compare the magnitudes of nonmotor symptoms in depressed individuals with and without Parkinsons Disease. MethodsDownloaded in January 2023, symptoms and characteristics of depressed individuals with and without Parkinsons Disease were extracted from the longitudinal study Fox Insight. The directed acyclic graph theory was used to represent causal relationships and to determine the associations between nonmotor symptoms, depression, and Parkinsons Disease. The 2-PL and the Rasch models were used to better fit the data and identify the items consistent with the assumptions. ResultsDropped interests and activities was the item that was of greatest impact and most characteristic for depressed individuals both with and without PD. Double vision was the item of least difficulty while an additional item of significant impact was Preferred to stay at home. Education attainment had little to no impact on depression severity in individuals with and without PD. ConclusionsDropped interests and activities was most severe within both populations. Relatedly, an increased average number of leisure hours was associated with greater depression severity. Overall, as an individuals depression worsens, there is an overall upward trend in the severity of their nonmotor symptoms. We recommend additional analyses on the strength of relationships between these neurologic disorders and nonmotor symptoms.

Structured AbstractO_ST_ABSObjectiveC_ST_ABSWe represent primary headaches of the ICHD3 in matrix form and show that this representation allows for automated diagnosis as well as additional insights into headache classification. MethodsEach diagnosis in the ICHD3 is defined by a list of characteristics; combinations of characteristics form phenotypes. Multiple phenotypes may fit a given diagnosis. We first translated all characteristics for primary headache diagnoses in the ICHD3 into true/false statements. We generated a matrix of valid ICHD3 diagnosis as follows: O_LIEach row of the matrix represents a phenotype. C_LIO_LIEach column of the matrix represents a characteristic. C_LIO_LIIf any phenotype contains a characteristic, then that element is encoded as 1. Otherwise, it is encoded as 0. C_LI From this matrix, we calculated its bipartite projection and Markov cluster. We also row reduced to derive the basis vectors that span the space of all headache phenotypes. ResultsChronic migraine diagnoses as well as the characteristics "greater than 15 days per month" and "more than 3 months" have the strongest associations based on bipartite projection. Markov clustering yields 64 clusters. These clusters can be organized by ICHD3 diagnoses and demonstrates the level of fragmentation of individual diagnosis in the classification: Migraine is composed of 1 cluster, for example, whereas paroxysmal hemicrania can be broken down into 9 clusters. Finally, row reduction of our matrix yields 63 basis vectors, implying that all headache diagnoses in the ICHD3 can be represented as linear combinations of 63 characteristics. These 63 characteristics corresponds to the following: duration, frequency, aura characteristics, size/location, laterality, clearly remembered onset, TAC features, total number of episodes, severity, nausea/vomiting, photophobia, pulsating, alleviation by triptans, and association with awakening, sexual activity, physical activity, temperature, compression or traction, coughing. ConclusionOur result demonstrates that ICHD3 is a mathematical entity and that headache diagnoses exist in a 63-dimensional vector space. This mathematical embodiment of classification allows us to conduct 1) large scale systematic investigations of relationships between headache and phenotypes, 2) generate a graphical representation of characteristics and phenotypes and 3) improves diagnostic accuracy and efficiency.

Structured AbstractO_ST_ABSBackgroundC_ST_ABSEmbolization of the middle meningeal artery (MMA) for the treatment of chronic subdural hematoma (cSDH) has gained increasing acceptance since the publication of several nonrandomized studies that appear to demonstrate a high level of efficacy for the procedure both when performed as an adjunct to patients undergoing surgical drainage and when performed in minimally symptomatic patients treated without surgical drainage. MethodsWe conducted a single-center, randomized controlled trial (RCT) of MMA embolization in consecutive patients presenting to our hospital with cSDH from April 2020 to July 2023. Enrolled patients were randomized to standard of care (observation vs. surgical drainage per the treating neurosurgeon) or standard of care plus MMA embolization. The primary endpoint was the combined criteria of cSDH resolution (defined as < 5mm), resolution of clinical symptoms, no further intervention, and no major treatment-related complications. ResultsIn total, 190 patients were screened, 46 were enrolled/randomized, and 1 withdrew immediately after randomization but before treatment. Accrual was ended early due to diminished enrollment; 79% of the accrual goal was achieved. Of the 45 study patients, 40 had sufficient follow up for primary outcome analysis. The primary endpoint was met by 14/20 (70%) in the control group and 15/20 (75%) in the MMA embolization group, respectively, p=0.5. ConclusionsIn this RCT, no significant difference was observed between standard of care and standard of care plus MMA embolization for cSDH. While the effect size appears to be smaller than that suggested by early case series, ongoing trials with greater statistical power may show benefit for the procedure. Previously presented in abstract form atNew England Neurosurgical Society (NENS) 2024 Meeting Key MessagesWhat is already known on this topic - Middle meningeal artery (MMA) embolization appears to be a safe and effective treatment for chronic subdural hematoma (cSDH), based on large case series. Randomized controlled trials of MMA embolization are just now being completed. What this study adds - This study found no significant difference in the primary endpoint within 1 year (resolution of cSDH defined as < 5mm, no return of clinical symptoms, no need for further intervention, and no major treatment-related complications). How this study might affect research, practice or policy - Further research, specifically RCTs with greater statistical power, are needed to better elucidate whether MMA embolization adds a statistically significant benefit to standard of care in cSDH.

BackgroundTraumatic brain injury (TBI) is a critical problem which portends an intensive burden with increased mortality and disability affecting more the young population worldwide. The primary goal of TBI treatment is to control intracranial pressure (ICP) and to prevent he devastating effect of secondary brain insult. For over a hundred years decompressive craniectomy has been a standard surgical intervention for treatment of TBI, however it is not without harm since it causes serious complications including meningitis, subdural hygroma, hydrocephalous and increased reoperation rate. Cisternostomy is the most recently introduced intervention for management of cerebral edema Cisternostomy has proven its efficiency a standalone treatment as an adjunctive to decompressive craniectomy in treatment of severe traumatic brain injury. This review aims at investigating the therapeutic effects of cisternostomy when used independently or as an adjunctive to decompressive craniectomy (DC) across the available randomized clinical trials (RCTs) and non randomized studies of effect intervention (NRSI) sectional studies to optimize the strength of evidence for underpinning the strategy for treatment of traumatic brain injury. Methods and AnalysisWe will conduct the systematic review and meta-analysis by employing the provisions of Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) 2020 guideline and the review protocol has been submitted to International Prospective Register of Systematic Reviews (PROSPERO) for registration before commencement of the study. We will construct the search strategy using the all field terms, medical subheading terms [MeSH Terms] with all permutations combined with Boolean operators such as AND and OR. PubMed, EMBASE, Scopus, COCHRAINE, Web Of Science, Global Index Medicus, Semantic Scholar and Google Scholar electronic databases will be searched. Ethical Consideration and DisseminationThis review will not include any human participant such that the ethical clearance approval is not applicable. The protocol of this review has been registered at PROSPERO ID CRD42023400894. We will disseminate the final report of this review to local and international scientific conferences and The results of this review will be submitted for publication in the Journal of Neurotrauma.

BackgroundIn normal pressure hydrocephalus (NPH) there is blood brain barrier (BBB) disruption, which should increase the CSF formation rate (CSFfr) and therefore the intracranial pressure (ICP). However, the ICP is normal in NPH. A lumped parameter study suggested that the CSFfr could be reduced in this condition if the BBB disruption was moderated by a reduction in the capillary transmural pressure (TMP) secondary to arteriolar constriction. In early Alzheimers disease (AD), there is BBB disruption, reduced ICP and global ischemia. This raises the possibility that the same physiology may be occurring in AD as occurs in NPH. ObjectiveThis hypothesis can be analyzed further using a lumped parameter hydrodynamic model we have developed. MethodsA lumped parameter model previously used to describe the hydrodynamics of NPH was modified to investigate the effects of changes in CSF pressure and blood flow in patients with mild cognitive impairment (MCI) and AD. ResultsThe model indicates the capillary TMP is normal in MCI but decreases as AD progresses. Removing CSF in AD patients during a tap test initially increases the capillary TMP. The brain in AD responds to a tap test by increasing its level of ischemia and this reduces the capillary TMP. ConclusionsA hypothesis is put forward that the BBB disruption in AD is partially mitigated by the brain making itself ischemic. Modelling gives support to this hypothesis. The model can explain the development of ischemic neuronal loss and amyloid accumulation secondary to glymphatic flow disruption as AD progresses.

BackgroundMiddle meningeal artery embolization is an emerging neuroendovascular therapy for chronic subdural hematoma. Recently, a number of randomized control trials have been conducted to assess the efficacy of middle meningeal artery embolization to reduce the recurrence or progression of chronic subdural hematoma. MethodsA systematic review will be conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The authors will systematically search MEDLINE, EMBASE, Cochrane, and ClinicalTrials.gov (National Library of Medicine) for randomized control trials evaluating middle meningeal artery embolization for chronic subdural hematoma. A meta-analysis will be undertaken to compare patients undergoing middle meningeal artery embolization and standard care compared to standard care alone; primary effectiveness endpoints will be symptomatic recurrence, radiographic re-accumulation, or reoperation; secondary safety endpoints will be new disabling stroke, myocardial infarction, or death within 30 days. DiscussionThis proposed systematic review and meta-analysis will synthesize and appraise available data regarding middle meningeal artery embolization, a novel neurointerventional therapy. Findings will help clinicians, patients, administrators, policy makers to determine the role of this new treatment and its potential benefits. Systematic review registrationPROSPERO #CRD42024512049

IntroductionIn clinical practice, headache presentations may fit more than one ICHD3 diagnoses. This project seeks to exhaustively list all these logically consistent "codiagnoses" according to ICHD3 criteria. We limit our project to cases where only two diagnoses are involved. MethodsWe included the ICHD3 criterias for "Migraine" (1.1, 1.2, 1.3), "Tension-type headache" (2.1, 2.2, 2.3, 2.4), "Trigeminal autonomic cephalalgias" (3.1, 3.2, 3.3, 3.4, 3.5), as well as all "Other primary headache disorders". We excluded "Complications of migraine"(1.5) and "Episodic syndrome that may be associated with migraine" (1.6) since these diagnoses require codiagnoses of migraine as first assumption. We also excluded "probable" diagnosis criteria. Each phenotype in the above criteria is assigned an unique prime number. We then encoded each ICHD3 criteria into integers, call "criteria representations", through multiplication in a list format. "Codiagnoses representations" are generated by multiplying all possible pairings of criteria representations. To eliminate logical inconsistent codiagnses, we manually encode a list of logically inconsistent phenotypes through multiplication: For example, headache lasting "seconds" would be logically inconsistent with "headache lasting hours"; the prime representation for both are multiplied together. We called this list the "inconsistency representations". All codiagnoses representation divisible by any inconsistency representations are filtered out, generating a list of codiagnoses represenation that are logically consistent. This list is then translated back into ICHD3 diagnoses. ResultsA total of 103 prime numbers were used to encode phenotypes from the included ICHD3 criteria diagnosis with 578 encodings generated. We generated 99 pairs of illogical phenotypes. Once illogical phenotypes were excluded, a total of 253,842 composite numbers representing unique dual-diagnosis clinical profiles were obtained. The number of profiles, although unique, yields duplicate dual diagnoses; once these duplicates are removed, we obtained 145 possible logical dual diagnoses. Of the dual diagnoses, 2 contains with intersecting phenotypes due to subset relationships, 14 dual diagnoses with intersecting phenotype without subset relationships, 129 contains dual diagnoses as a result of non-intersecting phenotypes. ConclusionPrime number representations of primary headache disorders not only offer clinicians with an automated way of diagnosing headaches but also provides a powerful method of investigating co-diagnosis in headache classifications. Applications of this method to the investigations of dual diagnosis and headaches may offer insight into "loopholes" in the ICHD3 as well as potential explanation for sources of a number of controversies in headache disorders. Futures applications of the method includes extending the methodology to all of ICHD3.

Structured AbstractO_ST_ABSObjectiveC_ST_ABSDifferential diagnosis is fundamental to medicine. Using DiffNet, a differential diagnosis generator, as a model we studied the structure and organization of how collections of diagnose (i.e. sets of diagnoses) are related in the ICHD3. Specifically, we asked: Which sets of differential diagnoses are subsets of each other? What is the minimum number of sets of differential diagnoses that encompass all ICHD3 codes? Furthermore, we explored the clinical and theoretical implication of these answers. MethodsDiffNet is a freely distributed differential diagnosis generator for headaches using graph theoretical properties of ICHD3. For each ICHD3 diagnosis, we generated a set of differential diagnoses using DiffNet. We then determined algorithmically the set/subset relationship between these sets. We also determined the smallest list of ICHD3 diagnosis whose differential diagnoses would encompass the totality of ICHD3 diagnoses. ResultsAll ICHD3 diagnoses can be represented by a minimum of 92 differential diagnosis sets. Differential diagnosis sets for 10 of the 14 first digit subcategories of ICHD3 are represented by more than one differential diagnosis sets. Fifty-one of the 93 differential diagnosis sets contain multiple subset relationships; the remaining 42 do not enter into any set/subset relationship with other differential diagnosis sets. Finally, we included a hierarchical presentation of differential diagnosis sets in ICHD3 according to DiffNet. ConclusionWe propose a way of interpreting headache differential diagnoses as partial ordered sets (i.e. poset). For clinicians, fluency with the 93 diagnoses and their differential put forth here implies a complete description of ICHD3. On a theoretical level, interpreting ICHD3 differential diagnosis as poset, allows researchers to translate differential diagnoses sets topologically, algebraically, and categorically.

Subanesthetic ketamine infusion has been used for managing refractory headache in inpatient or outpatient infusion settings. Intranasal (IN) ketamine may be an alternative option for outpatient care. We performed a retrospective study at a single tertiary headache center to assess the clinical effectiveness and tolerability of IN ketamine in patients with refractory chronic migraine (rCM). Candidates who received IN ketamine between January 2019 and February 2020 were screened through an electronic medical record query. Manual chart reviews and structured phone interviews were conducted upon obtaining informed consent. Among 242 subjects screened, 169 (age 44.3{+/-}13.8; female 79.9%) were interviewed. They reported 25.0{+/-}8.7 monthly headache days and tried 6.9{+/-}3.1 preventive medications. Overall, they used roughly 7.8{+/-}7.0 sprays (ie., 78 mg) per day and 11.6{+/-}8.9 days per month. Intranasal ketamine was reported as "very effective" in 49.1% and quality of life (QOL) was considered "much better" in 35.5%. However, 74.0% reported at least one adverse event (AE). In this retrospective study, IN ketamine can serve as an acute treatment for rCM by reducing headache intensity and improving QOL with relatively tolerable AEs. Most patients found IN ketamine effective and continued to use it despite these AEs. The study is limited by its single-center design and selection/recall biases. Well-designed prospective placebo-controlled trials are necessary to demonstrate the efficacy and safety of IN ketamine in patients with migraine. O_LIWhat is already known on this topic - Intravenous ketamine, although has been used for chronic pain and refractory headache, is limited to infusion settings. Intranasal ketamine, a more convenient alternative, has not been well-studied for refractory headache. C_LIO_LIWhat this study adds - This real-world study describes the usage pattern, effectiveness, and adverse event profiles of intranasal ketamine in patients with refractory chronic migraine. C_LIO_LIHow this study might affect research, practice or policy - Intranasal ketamine is probably effective with minimal adverse events for refractory chronic migraine, but more well-designed studies are needed. C_LI

IntroductionHeadaches significantly impair quality of life, and primary headaches are among the most common neurological complaints. Stimulating carotid baroreceptors via carotid sinus massage (CSM) combined with modified Trendelenburg positioning may modulate autonomic activity and alleviate acute headache symptoms. Thus, this study evaluated the effectiveness and safety of this combined approach (CSM+T). MethodsSeventeen patients (14 females; ages 16-64) with tension-type headaches (6), chronic migraines (10), or mixed-headaches (1) and various comorbidities received up to three 15-second CSM+T applications at one-minute intervals. Pain was assessed using a 10-point visual analog scale (VAS), while heart rate (HR), blood pressure (BP), and oxygen saturation (SpO2) were recorded before and after the intervention. A 24-hour follow-up evaluated headache recurrence and adverse effects. ResultsSixteen patients experienced significant pain reduction (median decrease: 9 VAS points; p < 0.0001) without complications. Pain relief persisted 24 hours without the need for additional medication or adverse effects. HR, BP, and SpO2 decreased following CSM+T. A negative correlation was observed between HR reduction and pain relief. Among responders, migraine patients had a smaller mean HR decrease than tension-type headache patients, yet both groups achieved similar median pain relief. These results suggest that a more pronounced cardiovagal response does not necessarily confer greater analgesia, implying additional central or multifactorial mechanisms. ConclusionCSM+T appears to be a safe and effective non-pharmacological intervention for rapid headache relief in a heterogeneous patient population. Larger, controlled trials are warranted to confirm these findings and refine clinical protocols.

BackgroundIn clinical circumstances with more than one headache disorders, misrecognition can occur if each headache disorder is not separately and individually evaluated. For example, consider the case of a patient with baseline tension type headaches lasting hours who now develops cluster headaches with nausea. Merging the characteristics of both disorders may yield the illusion of migraine. Do these types of misrecognitions occur necessarily because of ICHD3 criteria? Are there combinations of ICHD3 criteria, if any, which necessarily yield this type of misrecognition? ObjectiveThis work seeks to determine whether new, unintended diagnosis, can be arrived when one merges two ICHD3 diagnoses. MethodsWe translated ICHD3 primary headache disorders, as well as headache phenotypes closely mimicking ICHD3 criteria, as numerical data using prime encoding method. We then model the encoding of two concurrent diagnoses in an individual by multiplying all pairing of ICHD3 encoding. We then diagnose the result algorithmically to see which pairings, if any, generate "new"/" illusionary" diagnoses. ResultsA total of 117,526 phenotypes were generated. After duplicate pairing of diagnoses were removed, we derived a total of 72 pairings of unique ICHD3 diagnoses that yield a "new" diagnosis. Thirty-seven (51%) of these pairings were not judged to be "illusionary": they simply arise from our models idiosyncrasy of encoding chronic migraine without encoding migraine with or without aura explicitly. Of the rest, 23 pairings involve combining paroxysmal hemicrania with either a longer or shorter duration headache. We further generalize the condition under which the above "illusionary" diagnosis occurs as a mathematical observation. ConclusionMisrecognition arises naturally if diagnostic criteria consist solely of characteristics from another headache disorder or a combination of two headache disorders. Specifically, combining headaches with different duration and/or frequency are most likely to yield these "illusionary" diagnoses.

IntroductionHeadache disorders are one of the most common health problems worldwide, they can be classified into primary and secondary disorders. In the primary group, migraine - the second most common type of headache - is the most disabling one and one of the most important reasons why its treatment is mandatory. Migraine treatment involves different steps and kinds of medical therapy and patient education, and in these past years studies have been exploring the effect music therapy can have in reducing the severity and duration of an acute migraine attack. It has been reported that adding music to the pharmacological treatment can help decrease the pain severity, thus, reducing the disability migraine can cause. ObjectiveEvaluate the effectiveness of music therapy as a treatment or coadjuvant of migraine attacks in people who suffer this condition. Methods and analysisThis protocol is consistent with the methodology recommended by the PRISMA-P and the Cochrane handbook for systematic reviews of interventions. This study will be carried out as a systematic review and meta-analysis. In order to do so, electronic searches will be performed in PubMed, Medline and Cochrane (through Ovid) and Embase. The data range parameters used in searching all databases are from the last 20 years. Randomized controlled trials (RCTs) published in English, Spanish, French and Portuguese; with the primary outcomes being reduction of headache intensity, resolution of the migraine and decreased frequency of migraine attacks. Three investigators will screen all retrieved studies titles and abstracts, making a first preliminary list. A second screen will be done by the same three investigators similarly to the first one, but reviewing the full texts and building the final list. Then, the evaluation of the risk of bias and extraction of all data will be performed. The risk of bias of the included RCTs will be evaluated by the Cochrane Collaborations tool. A qualitative synthesis will be provided in text and tables, to summarize the main results of the selected publications. The heterogeneity between studies will be assessed through the I2 statistic. If there is sufficient homogeneity across outcomes, a meta-analysis will be conducted. ConclusionsThis systematic review will provide evidence regarding the effectiveness of music therapy as a single or coadjuvant treatment in patients with migraine attacks. Based on this analysis, it will be feasible to know whether this intervention is effective in the reduction of the intensity of the migraine attack, if it can help resolve the migraine attack, or reduce the frequency of migraine attacks.

IntroductionThe current literature suggests hyperglycemia can predict poor outcomes in patients with primary intracerebral hemorrhage (ICH). Chronic hyperglycemia is seen in patients with pre-existing diabetes (DM), however, acute hyperglycemia in non-diabetic patients is defined as stress-induced hyperglycemia (SIH). This study explored the influence of hyperglycemia on outcomes of primary ICH patients both in the presence and absence of pre-existing DM. MethodsData regarding admission glucose, pre-existing DM, inpatient mortality, and modified Rankin scale (mRS) scores at discharge were available for 636 patients admitted to Stony Brook Hospital from January 2011 to December 2022 with a primary diagnosis of ICH. Regression models were used to compare outcomes between patients with admission hyperglycemia and/or pre-existing DM to a control group of normoglycemic and non-diabetic ICH patients. ResultsPatients with SIH had higher inpatient mortality rates and worse mRS scores at discharge (p<0.001). An association with higher mortality and worse mRS scores at discharge was also seen in patients with hyperglycemia secondary to DM, although the strength of this association was weaker when compared to patients with SIH. ConclusionIn conclusion, our studys findings suggest that SIH may play a greater role in predicting poor outcomes at discharge rather than a history of poorly controlled DM with chronic hyperglycemia. To develop a more thorough understanding of this topic, prospective studies evaluating the effect of changes in serum glucose during hospital stay on short and long-term outcomes is needed.

IntroductionThe assessment of vestibular schwannoma (VS) requires a standardized measurement approach as growth is a key element in defining treatment strategy for VS. Volumetric measurements offer higher sensitivity and precision, but existing methods of segmentation, are labour-intensive, lack standardisation and are prone to variability and subjectivity. A new core set of measurement indicators reported consistently, will support clinical decision-making and facilitate evidence synthesis. This systematic review aimed to identify indicators used in 1) magnetic resonance imaging (MRI) acquisition and 2) measurement or 3) growth of VS. This work is expected to inform a Delphi consensus. MethodsSystematic searches of Medline, Embase and Cochrane Central were undertaken on 4th October 2024. Studies that assessed the evaluation of VS with MRI, between 2014 and 2024 were included. ResultsThe final dataset consisted of 102 studies and 19001 patients. Eighty-six (84.3%) studies employed post contrast T1 as the MRI acquisition of choice for evaluating VS. Nine (8.8%) studies additionally employed heavily weighted T2 sequences such as constructive interference in steady state (CISS) and FIESTA-C. Only 45 (44.1%) studies reported the slice thickness with the majority 38 (84.4%) choosing <3mm in thickness. Fifty-eight (56.8%) studies measured volume whilst 49 (48.0%) measured the largest linear dimension; 14 (13.7%) studies used both measurements. Four studies employed semi-automated or automated segmentation processes to measure the volumes of VS. Of 68 studies investigating growth, 54 (79.4%) provided a threshold. Significant variation in volumetric growth was observed but the threshold for significant percentage change reported by most studies was 20% (n = 18). ConclusionSubstantial variation in MRI acquisition, and methods for evaluating measurement and growth of VS, exists across the literature. This lack of standardization is likely attributed to resource constraints and the fact that currently available volumetric segmentation methods are very labour-intensive. Following the identification of the indicators employed in the literature, this study aims to develop a Delphi consensus for the standardized measurement of VS and uptake in employing a data-driven artificial intelligence-based measuring tools.

IntroductionDespite limited scientific evidence, trigeminal nerve blocks are alternative therapies for refractory trigeminal neuralgia (RTN). The duration of analgesia far exceeds the length of the conduction block. This study evaluated the quality of life 15 days after performing this block to treat RTN. MethodsThis retrospective study included all patients who, after informed consent, received iterative trigeminal blocks to treat a RTN between 2014 and 2018 in a university hospital. Patients received 0.5% levobupivacaine in combination with clonidine and a corticosteroid (cortivazol or betamethasone according their availability). Data were obtained from patients medical data files and a telephone questionnaire for the SF-12 score. The main criteria of evaluation was the change in quality of life according SF-12 performed at day 15. ResultsTwenty-one patients aged 62 {+/-}14 years were included. All patients exhibited RTN after many different clinical treatments according ICHD-3 criteria. Seventy-one per cent of RTN occurred after trauma or surgery. Before receiving blocks, SF-12 physical (SF12-PS) and mental (SF-12 MS) scores reached respectively 35 {+/-} 14 and 29 {+/-} 11. A mean time of 4 {+/-} 5 years elapsed between the occurrence of RTN and nerve blockade. At day 15, SF-12 PS increased by a 3 point mean value and SF-12 MS by 5 points. Approximately half of the patients (55%) were considered as non-responders with a cut-off value of less than 10% variation of their initial SF-12 score. When excluding these patients, SF-12 PS and SF-12 MS were increased by 17 and 9 points respectively. The mean duration of blocks lasted 15 {+/-} 59 days and no severe adverse effects were observed. Patient satisfaction was correlated with increased SF-12 PS (r2 = 0.3 p = 0.01) and with the length of analgesia (r2 = 0.51 p = 0.001) but not to SF-12 MS variation (p = 0.12). ConclusionTrigeminal nerve blocks are temporarily effective on pain that may increase the quality of life in responder patients. The reason why some patients are unresponsive to this treatment and why durations in efficacy are so variable remain unsolved. However, in responders, trigeminal nerve blocks seem simple, harmless, not excessively cumbersome and without severe adverse effects.

BackgroundMigraine is one of the most disabling diseases that continues to pose a significant societal burden. Although there are now treatment options for people with migraine, it remains challenging to identify them as clinical features are diverse and complex, and there are no validated diagnostic or treatment prediction biomarkers. Identification is based on either diagnostic coding or the use of certain acute headache abortive treatments. However, socioeconomic disparities can contribute to under-diagnosis and under-treatment of migraine. Thus, efforts to find biomarkers to identify individuals with migraine and which variables could explain migraine-related chronification and disability are warranted. We aimed to investigate the levels of migraine inducing neuropeptides; calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) in peripheral blood samples as potential biomarkers of migraine. MethodsWe developed highly sensitive assays for CGRP and PACAP on the MSD S-PLEX assay platform and used them for bioanalysis of preclinical and clinical samples. Wildtype and neuropeptide challenged mice and rats were profiled using the developed assay. To follow-up, commercially obtained plasma samples from healthy controls and migraineurs were initially profiled. Subsequently, we profiled plasma samples from people with migraine (during and after a headache attack and healthy controls. Both MSD S-PLEX assays were transferred to Celerion where they were validated for analysis of clinical samples. ResultsUsing the highly sensitive PACAP assay, we were able to reliably measure circulating levels of endogenous and administrated PACAP38in mouse and rat plasma. Additionally, using the highly sensitive CGRP assay, we were able to reliably measure circulating levels of endogenous and administrated CGRP in mouse and rat plasma. Furthermore, in the initial human samples, circulating CGRP and PACAP levels were not significantly different in healthy controls compared to people with migraine patients. However, [&ge;]50% people with migraine showed increased circulating CGRP and PACAP levels during their attack period compared to post attack. Overall, people with migraine showed a 3 - 396% increase in one or both neuropeptides during their attack period compared to post attack. Circulating plasma CGRP and PACAP levels in healthy control subjects were consistent with previously measured levels. ConclusionOur highly sensitive PACAP and CGRP assays were successful in measuring circulating levels of endogenous PACAP38 and CGRP in mouse and rat plasma. Our highly sensitive PACAP and CGRP assays were qualified for measurement of human CGRP and PACAP in healthy control and migraine samples. Plasma CGRP and PACAP levels are elevated in migraineurs during an attack period, and the increased plasma neuropeptide levels during an attack may help the differentiation of migraineurs from non-Migraineurs, or amongst people with migraines to help identify the best treatment for each patient.