A Retrospective Comparison of Onabotulinum Toxin A and Incobotulinum Toxin A in Terms of Efficacy, Tolerability, Duration of Effect, and Pain on Injection Administration Site for the Treatment of Chronic Migraine.

Background Onabotulinum toxin A (OnA) is a well-tolerated and effective treatment for chronic migraine (CM). However, based on research indications that incobotulinum toxin A (InA) would be equally effective, a Veterans Health Administration medical center mandated a two-year trial of InA as a more cost-effective alternative to OnA. Although InA is used for many similar indications as OnA, it is not Food and Drug Administration-approved for treating CM, and complications occurred in several patients with CM following this treatment change. We conducted this retrospective analysis to evaluate differences in the efficacy of OnA and InA and identify the reasons for the adverse effects of InA in some of these patients. Methods We performed a retrospective review of 42 patients who had been effectively treated with OnA and were then switched to InA. The differences between treatment responses to OnA and InA were assessed through the evaluation of pain on injection, number of headache days, and duration of action. Patients received injections at 10- to 13-week intervals. Those who reported severe pain on injection of InA were switched back to OnA. Results Severe burning pain on InA injection was reported by 38% of patients (nine males and seven females, i.e., a total of 16 patients out of 42 patients). One male patient reported the same degree of pain from both InA and OnA injections. A total of 66.7% of women with obesity and 83.3% of men with obesity or diabetes experienced severe pain on injection. Neither migraine suppression nor the duration of effect was significantly different between OnA and InA. Conclusions OnA is better tolerated than InA in the treatment of CM. InA appears to effectively suppress migraines, but some patients complain of a severe localized burning sensation during the injections. Some of these patients, all of whom were previously treated with OnA, requested to switch back to OnA. This suggested that InA is not equivalent to OnA in terms of tolerability and effectiveness. The present study found 2.38% of patients experienced an insufficient duration of effect with InA, and none with OnA. However, these lower rates may, in part, be due to variability in injection intervals in this sample, which could be because of scheduling considerations at the Harry S. Truman Veterans Health Administration Medical Center. In cases where OnA fails because of the development of antibodies, it might be reasonable to switch to InA treatment. Reformulation of InA with a pH-buffered solution may eliminate the difference in pain on injection. InA would then be a good alternative to OnA for treating CM.

Onabotulinum toxin A vs. incobotulinum toxin A for the treatment of chronic migraine: a retrospective review.

Background: Onabotulinum toxin A (OnA) is a well-tolerated and effective treatment for chronic migraine (CM). However, based on research indications that incobotulinum toxin A (InA) would be equally effective, a Veterans' Health Administration Medical Center mandated a 2-year trial of InA as more cost-effective alternative to OnA. Although InA is used for many similar indications as OnA, it is not Food and Drug Administration approved for treating CM, and complications occurred in several patients with CM following this treatment change. We conducted this retrospective analysis to evaluate differences in the efficacy of OnA and InA and identify the reasons for the adverse effects of InA in some of these patients. Methods: We performed a retrospective review of 42 patients who had been effectively treated with OnA and were then switched to InA. The differences between treatment responses to OnA and InA were assessed through the evaluation of pain on injection, number of headache days, and duration of action. Patients received injections at 10- to 13-week intervals. Those who reported excessive pain on injection of InA were switched back to OnA. Findings: Severe burning pain on injection was reported by 16 (38%) patients for InA only and by 1 (2%) patient for both InA and OnA. Neither migraine suppression nor the duration of effect was significantly different between OnA and InA. Conclusions: Reformulation of InA with a pH-buffered solution may eliminate the difference in pain on injection. InA would then be a good alternative to OnA for treating CM.

Unusual Presentation of COVID-19 Headache and Its Possible Pathomechanism.

Headache was the most common neurological symptom during the H1N1 pandemic in 2009 and the most recrudescing symptom of human coronavirus (hCoV) in 2016. Even in this prevailing global coronavirus disease 2019 (COVID-19) pandemic, the main neurological symptom is found to be a headache. Headache phenotypes identified with COVID-19 are largely migraine, tension-type headache, or cough headache located in the frontotemporal or occipital region with wavering intensity and essentially of acute onset. We present two cases of unusual headache phenotypes with COVID-19 infection and attempt to shed light on their pathomechanism. Trigeminal autonomic cephalgia may be a possibility in our case, triggered by the virus itself, either directly or through an indirect path elaborated well in the pathomechanism segment. Severe acute respiratory syndrome coronavirus 2 (SARs-CoV-2) binds to angiotensin-converting enzyme 2 (ACE2) located in the peripheral nerve and intracranial vascular endothelium, sensitizing the trigeminovascular system by further interacting with higher cortical pain centers via the thalamic and hypothalamic nuclei, producing pain. CSF analysis along with opening pressure measurement in Case 2 may portray a comprehensive understanding of our patient's headache. Coupling with the dorsal pons and trigeminal nucleus caudalis (TNC), the hypothalamus could be the supreme generator for an attack. Hypothalamic perturbance could be a possible phenomenon for abnormal headache experiences and requires further validation. The possible COVID-19 pain pathway pathomechanism engaging interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF) alpha aided with a cortical spreading depression disturbing the hypothalamus is also described in this study. Undoubtedly, this pandemic could prove to be a guiding tool for mankind, for a comprehensive understanding of the enigmatic concepts of headaches.

Artificial Intelligence-Aided Headache Classification Based on a Set of Questionnaires: A Short Review.

Wielding modern technology in the form of artificial intelligence (AI) or deep learning (DL) can utilize the best possible latest computer application in intricate decision-making and enigmatic problem-solving. It has been recommended in many fields. However, it is a long way from achieving an ambitious genuine intention when it comes to understanding and identifying any headache condition or classification, and using it error-free. No studies hitherto formalized any headache AI models to accurately classify headaches.  A machine's job can be arduous when incorporating an emotional dimension in decision making, re-challenging its own diagnosis by keeping a differential at all times, where even experienced neurologists or headache experts sometimes find it demanding to make a precise analysis and formulate a methodical plan. This could be because of spanning clinical presentation at a given moment of time or a change in clinical pattern over time which apparently could be due to intercrossing multiple pathophysiologies. We did a short literature review on the role of artificial intelligence and machine learning in headache classification. This brings forth a minuscule insight into the vastness of headaches and the perpetual effort and exploration headache may demand from AI when trying to scrutinize its classification. Undoubtedly, AI or DL could better be utilized in identifying the red flags of headache, as it might help our patients at home or the primary care physicians/practicing doctors/non- neurologists in their clinic to triage the headache patients if they need an imperative higher center referral to a neurologist for advanced evaluation. This outlook can limit the burden on a handful of headache specialists by minimizing the referrals to a tertiary care setting.

T2-Sampling Perfection With Application-Optimized Contrasts by Using Flip Angle Evolution (SPACE) Protocol MRI: A Safe, Minimally Invasive Screening Tool for Spinal CSF Leak Causing Spontaneous Intracranial Hypotension.

Spontaneous intracranial hypotension (SIH) due to a spinal cerebrospinal fluid (CSF) leak is secondary cause of headache with potentially devastating consequences. Its diagnosis is complicated owing to the lack of a reasonable, minimally invasive screening test. This results in many patients remaining undiagnosed for years after the headache onset. Current testing approaches are either overly invasive, namely the CSF infusion protocol or both invasive and insensitive viz. lumbar puncture (LP) with an opening pressure (OP) or computed tomography myelogram (CTM). These diagnostic methods are frequently employed in a clinical setting since they require access to the thecal space; they unfortunately have a dearth of sensitivity. CTM will not document a leak if it is intermittent or very slow and in the setting of a spinal CSF leak, the OP on LP may be high, low, or normal. A potential remedy for this state is the T2-sampling perfection with application-optimized contrasts by using flip angle evolution (SPACE) protocol spinal magnetic resonance imaging (MRI). We present two cases that demonstrate its potential value as a screening tool. It is well known for its high sensitivity for identifying spinal pathology and is minimally invasive, making it a good choice for a screening modality when diagnosing possible SIH cases.

Novel Case Presentation of Abulia After Lone Star Tick Bite As Evidenced by Raised Titers of Alpha-Gal Specific IgM Immunoglobulin and a Possibility of Alpha-Gal Driven Hypothalamic Dysfunction As the Pathomechanism.

Galactose-α-1,3-galactose, an oligosaccharide epitope better acknowledged as α-Gal, is present in non-primate mammal meat, tick bites, microorganisms, and vaccines as a glycoprotein or glycolipid moiety. This can manifest hyperimmune reactions as it enters the human body, known as α-Gal syndrome (AGS). AGS and Guillain-Barré syndrome share cognate immunogenic pathomechanism via conquering immune tolerance further speculating galactose navigated neurological sequel. Unusual symptomatic presentation of abulia in our case, with incidental finding of high titers of α-Gal specific IgE immunoglobulin further supported by temporal resolution of symptoms on abstinence of meat products, raises a high degree of suspicion of neuro-psychiatric manifestation in sensitized α-Gal patients. The pathomechanism is blurry, and an absence of an objective diagnostic tool makes the neurological diagnosis challenging. α-Gal driven immune-related hypothalamic dysfunction could be a possibility that needs further exploration and is a topic of research.

A Rare Case of Domperidone-Induced Acute Dystonia in a Young Adult Due to Consumption of Combination Drug (Proton Pump Inhibitors With Domperidone) and Its Possible Pathomechanism.

Globally, a substantial number of people are tormented by dystonia. Domperidone, a D-2 receptor antagonist acts outside the blood-brain barrier in the brain stem as well as on the gastrointestinal tract. In India, domperidone is conveniently obtainable over the counter as a combination drug with proton pump inhibitors (PPIs) for dyspepsia and gastro-esophageal reflux disease. We present a rare case of domperidone-induced acute dystonia in a young adult presented within 72 hours after consuming two oral doses of this combination drug (PPIs with domperidone) for dyspepsia. Drug-induced extra pyramidal symptoms (EPS) are often misdiagnosed as some psychiatric condition and undoubtedly its expeditious diagnosis staves off unnecessary investigations and ameliorates prognosis. Our case ignites alertness amongst practitioners in India over the judicious use of PPIs with domperidone as the latter may trigger EPS. Such combination drugs can be prescribed if absolutely mandatory by the treating physician. The possible pathomechanism of this hyperkinetic motor phenomenon, perturbing the equilibrium of the cortical-subcortical circuit and resulting in an overflow of muscular activity, is attempted to be explained here, although the explicit mechanism is still blurry.

Varicella-Zoster Reactivation in a Non-immunized Elderly Multiple Sclerosis Patient While on Delayed-Release Dimethyl Fumarate With Grade 2 Lymphopenia and Profoundly Low CD4+ and CD8+ Cell Counts: A Case Report.

Increased susceptibility to opportunistic infections (OI) in multiple sclerosis (MS) patients is a real concern amongst neurologists when using disease-modifying therapies (DMTs). DMTs used in modulating or suppressing the immune system for MS management may risk the patient with lymphocytopenia, raising the possibility of OI; however, this lymphopenia may contemplate as a biomarker for drug response, degree of immunomodulation, and drug compliance. The OI could be reactivation of varicella-zoster, progressive multifocal leukoencephalopathy (PML) induced by John Cunningham virus (JC virus), Pneumocystis jirovecii infection, cryptococcal meningitis, atypical mycobacteria, and many more. We present a non-immunized case of varicella-zoster reactivation with dimethyl fumarate (DMF) therapy. Surprisingly, the patient's lymphocyte count trend during her previous follow-up visits remained in the range of normal to grade 1 lymphopenia but with her current flared-up rash presentation, she had a profoundly low CD8+ and CD4+ cell counts (CD8+ cell count << CD4+ cell counts) despite an absolute lymphocyte (ALC) level far above 500 cells/µl; in fact, it was 13.6% higher when compared to her last quarterly levels. Controlled trials with DMF claimed no serious infection even with a lymphopenia range of 500-800 cells/µl, which is untrue in real clinics and it would be wise and reasonable to follow the lymphocyte subsets along with ALC to prevent potential opportunistic infections. Recently, comprehensive strategies were evolved to mitigate OI risk for MS patients while on DMTs. These were not only limited to lymphocyte threshold monitoring but extended to address features in terms of screening recommendation, vaccination advice, the need for antibiotic prophylaxis, neuroimaging, laboratory checkups, medication dosing, and behavioral modifications. Our patient was not immunized with zoster vaccine and, unfortunately, DMF has no proper structured guidelines regarding vaccination against OI prevention as other few DMTs have. Our case could suggest that MS patients need proper vaccination guidelines from the Centers for Disease Control and Prevention (CDC) before starting DMF.

Laugh Headache, Not a Joke! A Case Report.

Well delineated precipitating factors of migraine or incapacitating headaches are well known in the literature. Few peculiar and under-recognized precipitants are crying, shouting, straining in stools, urination, orgasm, childbirth, powerlifting. We present a case of a young student whose laughing aloud is a potent headache precipitant and is consistently reproducible despite normal brain imaging. It is worth mentioning here that laugh-induced headache has recently been assigned a place in the International Classification of Headache Disorders (ICHD-III) in 2018. The proposed pathophysiology in our case could be loud laugh induced Valsalva maneuver raising intra-abdominal and intra-thoracic pressure momentarily causing venous congestion of head presenting as episodic headache. Another plausible explanation related to craniospinal pressure dissociation and the concept of dural elasticity and compliance needs to be explored if the symptoms persist and repeat scans show no pathology. Momentarily rise of intracranial pressure due to vigorous laugh could press the tonsils or distal cerebellar portion to herniate down transiently, causing symptoms and may be back to normal position once the laugh ceases. Social laughter releases enormous endogenous opioids, which is supported using positron emission tomography (PET) and u-opioid-receptor (MOR)-specific ligand carfentanil. A mirthful laugh could trigger a primary laugh headache. The role of modulated opioidergic activity and social mirthful laugh, if connected with such rare headaches requires further study.

The Role of Onabotulinum Toxin Type A in the Management of Chronic Non-migraine Headaches.

Objectives: FDA has approved Onabotulinum toxin type A (BoNTA) for prophylactic treatment of chronic migraines. Recent studies have explored its potential new indications, like treating post-traumatic headaches. Patients and Methods: This is a retrospective chart review of 717 patients, who had failed at least two prophylactic treatments and received BoNTA injections at University of Missouri Hospital from July 2014 to June 2017. Patient demographics, headache type, associated symptoms, prophylaxes tried were reported. Patient's pain severity (numeric pain scale) and frequency (number of headache days/month) pretreatment, at 6 months, and at 12 months were collected. Results: For a single headache type, post-traumatic headaches showed reduction in headache pain severity at 6 months (2.9 ± 0.7) compared to pre-treatment (7 ± 0.7). Headache frequency for post-traumatic headaches was also reduced at 6 months (10.6 ± 2.3) and 12 months (5.1 ± 1.2) compared to pre-treatment (25 ± 1.8). For pseudotumor cerebri headaches, pain severity at pretreatment was 6.4 ± 0.6 compared to 2 ± 0.8 at 6 months, and headache days reduced at 6 months (9.8 ± 2.5) and 12 months (6 ± 4) compared to pretreatment (26 ± 2.9). Opioid use reduced by 67 ± 55.4 at 6 months and 133.3 ± 106.6 at 12 months in morphine equivalent units. Conclusions: Onabotulinum toxin type A is effective in treating multiple types of chronic non-migraine headaches.

A Case of Recurrent Lobar Intracerebral Hemorrhage in the Setting of Phosphodiesterase-5 Inhibitor Use.

Intracerebral hemorrhage occurs when a diseased blood vessel within the brain bursts. We present a case of 69-year-old patient with two sequential episodes of lobar intracerebral hemorrhage occurring during sexual intercourse. Both episodes were associated with the use of phosphodiesterase-5 inhibitors. This is the first case reported which is temporally associated with isolated bilateral lobar bleeds with appropriate use of phosphodiesterase-5 inhibitor on two different occasions associated with sexual intercourse.