Narrative review of migraine management in patients with renal or hepatic disease.

OBJECTIVES/BACKGROUND: Treatment of migraine in the setting of either renal or hepatic disease can be daunting for clinicians. Not only does the method of metabolism have to be considered, but also the method of elimination/excretion of the parent drug and any active or toxic metabolites. Furthermore, it is difficult to think about liver or kidney disease in isolation, as liver disease can sometimes contribute to impaired renal function and renal disease can sometimes impair hepatic metabolism, through the cytochrome P450 system. METHODS: A detailed search for terms related to liver disease, renal disease, and migraine management was performed in PubMed, Ovid Medline, Embase, and the Cochrane Library.For each medication, product labels were retrieved and reviewed using the US FDA website, with additional review of IBM Micromedex, LiverTox, and the Renal Drug Handbook. RESULTS: This manuscript provides an overview of migraine drug metabolism and how it can be affected by liver and renal impairment. It reviews the standard terminology recommended by the US Food and Drug Administration for the different stages of hepatic and renal failure. The available evidence regarding the use of abortive and preventative medicines in the setting of organ failure is discussed in detail, including more recent therapies such as lasmiditan, gepants, and calcitonin gene-related peptide antibodies. CONCLUSIONS: For acute therapy, the use of NSAIDS should be limited, as these carry risk for both severe hepatic and renal disease. Triptans can be selectively used, often with dose guideline adjustments. Ubrogepant may be used in severe hepatic disease with dose adjustment and lasmiditan can be used in end stage renal disease. Though non-medicine strategies may be the most reasonable initial approach, many preventative medications can be used in the setting of hepatic and renal disease, often with dose adjustment. This review provides tables of guidelines, including reduced dosing recommendations, for the use of abortive and preventative migraine medications in hepatic and renal failure.

Functional neurological seizures and migraine: A systematic review and case series.

BACKGROUND: The seizure subtype of functional neurological disorder (FND-seizures) is a common neuropsychiatric condition manifesting with episodic epilepsy-like events. Despite the common belief that FND-seizures are precipitated by psychological stressors, neurological disorders may also be triggers. In 1890, Babinski described four cases of FND symptoms associated with migraine attacks. Despite the passing of more than 130 years since this first clinical observation, the relationship between FND-seizures and migraine is not fully elucidated. OBJECTIVES: (1) To complete a systematic review of the literature that investigated potential associations between FND-seizures and migraine and the response of FND seizures to treatment with migraine prophylactic medications (2). To undertake a retrospective study of patients with FND-seizures and migraine, including response to migraine prophylaxis. METHODS: (1) Using PRISMA methods, we completed a systematic review of EMBASE and Scopus databases from inception to March 31, 2021, for literature on FND-seizures and migraine. (2) Our multi-disciplinary team, including subspecialists in psychosomatic medicine, epilepsy, and headache disorders, reviewed consecutive patients diagnosed with FND-seizures and migraine to assess potential causal associations and responses to standard migraine prophylactic medications. RESULTS: (1) The search yielded seven studies from 126 screened manuscripts (N = 1,186 patients with FND-seizures; mean age 38.7 years; 72.6% female). They varied substantially in design, population, diagnostic measures, and outcomes. Nevertheless, all studies found associations between FND-seizures and migraine, which were stronger than those between epileptic seizures and migraine in comparative investigations, but provided limited information on treatment response. (2) In our case series, investigators reached unanimous consensus that migraine attacks triggered FND-seizures in 28/43 (65.1%) patients reviewed (mean age, 38.8 years; 74% female). In 19/26 (73%) patients with adequate follow-up data, treatment with migraine prophylactic medications alone (no behavioral interventions) concomitantly reduced FND-seizure and headache frequency by >50%. CONCLUSION: Our systematic review and case series indicate that migraine attacks may trigger FND-seizures, perhaps more often that currently understood, and suggest that migraine prophylaxis may reduce FND-seizure frequency in such cases. To validate these observations, fully powered prospective investigations are required.

Two hundred and forty-eight cases of visual snow: A review of potential inciting events and contributing comorbidities.

OBJECTIVE: To review characteristics and outcomes of all cases of visual snow seen at our institution, with attention to possible triggering events or comorbidities. METHODS: This is a retrospective case series of patients seen at our tertiary care center from January 1994 to January 2020. Charts were reviewed if they contained the term "visual snow". RESULTS: Of the 449 charts reviewed, 248 patients described seeing visual snow in part or all of their vision. Thirty-eight reported transient visual snow as their typical migraine aura. Of the remaining 210 patients, 89 were reported to have either an inciting event or contributing comorbidity for their visual snow symptoms, including: Post-concussion (n = 15), dramatic change in migraine or aura (n = 14), post-infection (n = 13), hallucinogen persisting perception disorder (n = 10), ocular abnormalities (n = 7), idiopathic intracranial hypertension (n = 4), neoplastic (n = 1), and posterior cortical atrophy (n = 1). Some patients had partial improvement with benzodiazepines (n = 6), lamotrigine (n = 5), topiramate (n = 3) and acetazolamide (n = 3). Presenting characteristics were similar, but patients with visual snow attributed to an inciting event or contributing comorbidity were more likely to have some improvement in their symptoms by last follow-up compared to spontaneous visual snow (p < .001). CONCLUSIONS: Though most cases of visual snow are spontaneous, potential secondary causes should be recognized by clinicians. Patients who develop visual snow after an inciting event or related to an underlying comorbidity may have a better prognosis than those in whom it develops spontaneously. In select cases, treatment of the suspected underlying cause may significantly alleviate the otherwise typical intractable visual disturbances associated with visual snow.

Great Auricular Neuralgia: Case Series.

BACKGROUND/OBJECTIVE: The great auricular nerve (GAN) arises from C2-C3 and provides innervation over the skin in the pre-auricular region, jaw angle, posteroinferior pinna, and mastoid. Although damage to the GAN has been reported following trauma or procedures nearby this nerve course, neuralgia of this nerve is uncommon with knowledge based on a handful of case reports in literature. The objective of this study is to describe the presentation, treatment, and outcome of 13 cases of GAN neuralgia. METHODS: Case series. Retrospecive review of charts from 1994 to 2018 with diagnoses: "auricular neuralgia," "auricular neuritis," or "auricular neuropathy." We included subjects with neuralgic pain within the distribution of the GAN, and excluded patients with atypical facial pain, GAN neuropathy, or unclear etiology. RESULTS: Of 79 charts, 13 patients met criteria (age at onset 11-59; 11 women, 2 men). Pain was most often described as paroxysmal stabbing provoked by: turning the head (n = 7), touching the neck (n = 5), neck position during sleep (n = 2), jaw movement (n = 2), and other (n = 2). Seven patients received GAN blocks: all noted dramatic improvement in pain, including 3 who continued to receive serial blocks at our institution successfully for the next 2 to 5 years. Two patients successfully transitioned from GAN blocks to GAN stimulators. One patient with GAN lymphoma had resolution of pain following GAN resection. CONCLUSION: GAN neuralgia should be considered in the differential for periauricular pain. GAN blocks or stimulators may be helpful for pain management.

COVID-19 and Headache Medicine: A Narrative Review of Non-Steroidal Anti-Inflammatory Drug (NSAID) and Corticosteroid Use.

OBJECTIVE: To summarize the current literature on non-steroidal anti-inflammatory drug and corticosteroid use during the coronavirus disease 2019 (COVID-19) pandemic, recognizing that these are commonly used treatments in the field of headache medicine. BACKGROUND: The use of non-steroidal anti-inflammatory drugs and corticosteroids in patients during the COVID-19 pandemic has been a controversial topic within the medical community and international and national health organizations. Lay press and social media outlets have circulated opinions on this topic despite the fact that the evidence for or against the use of these medications is sparse. In the field of headache medicine, these medications are used commonly and both patients and clinicians may have questions or hesitations pertaining to their use during the COVID-19 pandemic. METHODS: A detailed search of the scientific and popular literature was performed. RESULTS: There is limited literature pertaining to the safety of non-steroidal anti-inflammatory drugs and corticosteroids during the COVID-19 pandemic. To date, there are no clear scientific data that preclude the use of non-steroidal anti-inflammatory drugs in the general population who may acquire COVID-19 or in those acutely infected with the virus. Several health organizations have concluded that treatment with corticosteroids during active infection should be avoided due to concerns of prolonged viral shedding in the respiratory tract and the lack of survival benefit based on the data from past coronaviruses and influenza virus; specific exceptions exist including treatment for underlying asthma or chronic obstructive pulmonary disease, septic shock, and acute respiratory distress syndrome. CONCLUSION: Scientific information regarding the COVID-19 pandemic is constantly evolving, and limited or contradictory information can lead to confusion for both patients and clinicians. It is recommended that prior to prescribing non-steroidal anti-inflammatory drugs and steroids for the treatment of headache, clinicians have open discussions with their patients about the potential risks and benefits of using these medications during the COVID-19 pandemic. This manuscript summarizes the currently available evidence and understanding about these risks and benefits to help clinicians navigate such discussions.

Headache due to spontaneous spinal cerebrospinal fluid leak secondary to cerebrospinal fluid-venous fistula: Case series.

OBJECTIVE: Cerebrospinal fluid-venous fistula is an uncommon cause of spontaneous spinal cerebrospinal fluid leak (SSCSFL). We aim to describe the clinical presentation, imaging evaluation, treatment and outcome of SSCSFL secondary to cerebrospinal fluid-venous fistula. METHODS: A retrospective review was undertaken of SSCSFL cases secondary to cerebrospinal fluid-venous fistula confirmed radiologically or intraoperatively, seen at our institution from January 1994 to March 2019. Cases with undetermined SSCSFL etiology, alternative etiology or unconfirmed fistula were excluded. RESULTS: Forty-four of 156 patients met the inclusion criteria (31 women, 13 men). Mean age of symptom onset was 52.6 years (SD 8.7, range 33-71 years). Headache was the presenting symptom in almost all, typically daily (69%), and most often in occipital/suboccipital regions. Headache character was most commonly pressure (38%), followed by throbbing/pulsing (21.4%). Orthostatic headache worsening occurred in 69% and an even greater percentage of patients (88%) reported Valsalva-induced headache exacerbation or precipitation. Headache occurred in isolation to Valsalva maneuvers in 12%. Of 37 patients with documented cerebrospinal fluid opening pressure, 13% were <6 cmH2O; 84%, 7-20 cmH2O; and one, 25 cmH2O. Fistulas were almost exclusively thoracic (95.5%). Only one patient responded definitively to epidural blood patch (EBP). Forty-two patients underwent surgery. Most improved following surgery; 48.7% were completely headache free and 26.8% had at least 50% improvement. CONCLUSION: In our series, cerebrospinal fluid-venous fistula was associated with a greater occurrence of Valsalva-induced headache exacerbation or precipitation than orthostatic headache and did not respond to EBP. Surgery provided significant improvement. Cerebrospinal fluid-venous fistula should be considered early in the differential diagnosis of Valsalva-induced ("cough") headache.

The Effect of OnabotulinumtoxinA on Aura Frequency and Severity in Patients With Hemiplegic Migraine: Case Series of 11 Patients.

BACKGROUND: OnabotulinumtoxinA has been demonstrated to be effective for the preventive treatment of headache in individuals with chronic migraine and has been approved and recommended for this patient population. While the therapeutic effect of onabotulinumtoxinA on migraine headache is well documented, there is limited information on the effect of onabotulinumtoxinA on migraine aura. OBJECTIVE: Given the prolonged and often debilitating nature of aura in patients with hemiplegic migraine, our group sought to examine the effect of onabotulinumtoxinA on aura frequency and severity in this specific subset of migraine patients. METHODS: All clinical notes from July 1, 1994 to December 1, 2017 at our institution were retrospectively reviewed to identify patients diagnosed with hemiplegic migraine who received at least one set of onabotulinumtoxinA injections. Thirty-four patients were identified; and of those, 23 were excluded due to incomplete documentation regarding aura symptoms at follow-up visits. The clinical notes of the remaining 11 patients (4 with familial hemiplegic migraine [FHM] and 7 with sporadic hemiplegic migraine [SHM]) were reviewed, and the frequency and description of their headaches and aura before and after receiving onabotulinumtoxinA were recorded. RESULTS: Nine of the 11 patients in our series noted a decrease in the frequency, severity, and/or duration of their aura after receiving onabotulinumtoxinA. Of the 2 non-responders, one was FHM and one was SHM. Of the 9 that noticed improved aura symptoms, 6 described a "wearing off" effect of onabotulinumtoxinA around week 9 or 10 of the 12-week cycle, with subsequent improvement after the next round. CONCLUSION: For 9 of 11 patients with hemiplegic migraine, onabotulinumtoxinA was helpful not only in reducing the frequency and severity of headaches but also in reducing the frequency and severity of the aura. In this manuscript, we speculate on potential pathophysiologic mechanisms that could have contributed to this effect.

Chronic Daily Headache: Ten Steps for Primary Care Providers to Regain Control.

BACKGROUND: Chronic daily headache (CDH) affects 2% to 4% of the North American and European population. Various pathways lead to this condition, although chronification of migraine and the occurrence of central sensitization in tension headache are the 2 most common. Medication overuse headaches complicate a substantial portion of other primary headaches that have become chronic and often make their treatment more complex and less successful. METHODS/RESULTS: A 10-step process to help primary care providers evaluate and treat CDH patients begins with excluding secondary headache disorders, then moves on to classification of the primary underlying headache disorder. Next, the exacerbating factors, as well as relevant comorbid conditions, are identified. The patient's current acute therapy is examined, and attempts are made to identify and resolve medication overuse if present. Past preventive therapies are reviewed, allowing for thoughtful design of a headache action plan with preventive, acute, and lifestyle components. Patients are asked to keep a headache diary, used to initiate a cycle of continuous improvement in a patient's response to acute and preventive therapeutic approaches. CONCLUSIONS: A systematic approach and partnership with patients often make it possible to convert CDH to episodic headache that is responsive to both acute and preventive therapies.

A tale of two systems: cardiac cephalalgia vs migrainous thoracalgia.

The practice of headache medicine is challenging, and excluding secondary causes of headaches is essential for proper diagnosis and treatment. The evaluation of secondary headaches often leads to investigations involving organ systems other than the nervous system. As such, headache, which is typically thought to be neurologic in origin, can be a manifestation of cardiac pathology in the form of cardiac cephalalgia. Conversely, chest pain, which is typically thought to be cardiac in origin, could be a manifestation of a neurologic disease process in the form of atypical migraine aura. In the presented cases, we demonstrate headaches that involve cardiac and neurologic pathology with atypical presentations.

Triggerless neuralgic otalgia: a case series and systematic literature review.

BACKGROUND: Isolated neuralgic pain in the deep ear may arise from either nervus intermedius (NIN) or glossopharyngeal (GPN) neuralgias. Current International Headache Society (IHS) International Classification of Headache Disorders, second edition (ICHD-2) criteria for these cranial neuralgias require the presence of a characteristic trigger. AIM: The aim of this article is to report cases of triggerless neuralgic otalgia to better understand a subset of patients for whom there may be diagnostic uncertainty. METHODS: Methods included an observational cohort series and systematic literature review. RESULTS: We identified five female patients with a median age at symptom onset of 58 (range: 47 to 73). Our patients generally experienced an excellent clinical response to carbamazepine. Patients were contacted by telephone at a median follow-up duration of seven years (range: four to 32) from symptom onset, at which time carbamazepine-free remissions were reported by five of five (100%) of the patients. A systematic review of the literature on neuralgic otalgia led us to conclude that NIN was most common among young women (age < 50), and GPN across a wider range of ages of either gender. Among surgically validated cases reported in the literature, triggers were frequently absent in NIN, and variably noted in GPN. CONCLUSIONS: We conclude that the presence of a trigger is not fundamental, and may be impractical, to the diagnosis of neuralgic otalgia, but remains important for specificity between NIN and GPN.

Auriculotemporal neuralgia secondary to TMJ synovial cyst: a rare presentation of a rare entity.

Synovial cysts of the temporomandibular joint are rare, and to our knowledge, only 14 cases have been reported. The most common presentation is local pain and swelling. We present a case of a synovial cyst presenting with neuralgia in the distribution of the auriculotemporal nerve, initially misdiagnosed as trigeminal neuralgia.

Clinical and imaging outcomes of 100 patients with cerebrospinal fluid-venous fistulas treated by transvenous embolization.

BACKGROUND: Cerebrospinal fluid-venous fistulas (CSFVF) are a common cause of spontaneous intracranial hypotension (SIH). Transvenous embolization has emerged as a reliable treatment option. We review the clinical presentation, imaging, and clinical outcomes of 100 consecutive CSFVF patients who underwent embolization over 2 years. METHODS: Baseline clinical characteristics, imaging findings (including Bern SIH score), technical outcomes, and long-term imaging and clinical outcomes were collected. All patients had at least 3 months of clinical follow-up and had baseline MRI. 99/100 patients underwent follow-up imaging at ≥3 months post-treatment. RESULTS: 100 patients were included. Mean imaging and clinical follow-up duration was 8.3±7.7 months and 15.0±6.8 months, respectively. The mean duration of symptoms before embolization was 40.9±52 months. Mean baseline Bern SIH score was 5.9±3.3. The most common baseline symptoms were headache (96 patients), tinnitus (55 patients), and cognitive dysfunction (44 patients). Technical success rate was 100%. Mean post-treatment Bern SIH score was 0.9±1.6 (P<0.0001). Following treatment, 95% of patients reported significant improvement or resolution in symptoms (58 patients reporting resolution and 37 reporting improvement). 5 patients reported no improvement. There were no major procedural or periprocedural complications. 10 patients had minor procedural complications that did not result in any change in management (Onyx emboli, venous perforation). 19 patients had rebound intracranial hypertension requiring acetazolamide therapy. 7 patients had recurrent fistula at the initially treated level. CONCLUSIONS: Transvenous embolization of CSFVF in SIH patients is safe and effective with a 95% treatment response, significant improvement in imaging outcomes, and a very low rate of complications.

Clinical and Imaging Outcomes of Surgically Repaired Cerebrospinal Fluid-Venous Fistulas Identified by Lateral Decubitus Digital Subtraction Myelography.

OBJECTIVE: To describe clinical and radiographic outcomes of surgical repair of cerebrospinal fluid-venous fistula (CVF), an increasingly recognized cause of spontaneous intracranial hypotension that is poorly responsive to epidural blood patch (EBP). METHODS: Retrospective review identified adult patients who had lateral decubitus digital subtraction myelography indicative of cerebrospinal fluid leak at Mayo Clinic between November 2018 and February 2020, with clearly localized CVF, followed by surgical treatment. Patients without available imaging before or after surgery were excluded. History of EBP and clinical response to EBP were evaluated along with surgical outcomes. RESULTS: Of 25 patients with CVF who met protocol criteria and were included in the data analysis, 22 (88%) received EBP, but clinical benefit lasting ≥4 weeks occurred in only 2 of 22 (9%). Headache was the most prominent preoperative feature among patients (24/25; 96%). Following surgery, 18 of 24 (75%) patients had complete headache improvement, 4 (17%) had partial improvement, and 2 (8%) had no improvement. Ten of 25 (40%) patients reported cognitive disturbance at baseline; at follow-up, 5 of 10 (50%) had complete improvement, 3 (30%) had partial improvement, and 2 (20%) had no improvement. On postoperative brain magnetic resonance imaging, 6 of 25 (24%) patients had complete resolution of findings by Bern score criteria, 18 (72%) showed partial improvement, and 1 (4%) patient showed no improvement. Adverse events were minor and included surgical site pain and paresthesias. CONCLUSIONS: Surgical repair of CVF resulted in improvements in headache and other symptoms, with few side effects.

Clinical and imaging outcomes of cerebrospinal fluid-venous fistula embolization.

BACKGROUND: We report outcomes of spontaneous intracranial hypotension (SIH) patients who underwent transvenous embolization of cerebrospinal fluid-venous fistulas (CSFVFs) confirmed on digital subtraction myelography (DSM) performed at our institution. METHODS: This is a retrospective evaluation of a prospectively collected database of SIH patients who underwent transvenous embolization of CSFVFs. Only patients who had fistulas confirmed on DSM performed at our institution were included. All patients had a baseline MRI and an MRI performed at least 90 days post-embolization, as well as clinical evaluation using the six item Headache Impact Test (HIT-6) and the Patient Global Impression of Change (PGIC) scales. Paired t-test was used to report changes in Bern MRI scores and HIT-6 scores at follow-up. RESULTS: 40 patients were included (29 female, 11 male). Mean age was 57.4±10.3 years. Mean Bern score improved from 5.7±3.0 at baseline to 1.3±2.0 at follow-up (p<0.0001). Mean HIT-6 score at baseline was 67.2±11.1 and at follow-up was 41.5±10.1 (p<0.0001). Median PGIC was 1, with 36 patients (90.0%) reporting at least minimal improvement and 32 patients (82.5%) reporting much or very much improvement. Complications included persistent local site pain in 12 patients (30%), suspected rebound intracranial hypertension requiring medical intervention in 7 patients (17.5%), and asymptomatic tiny Onyx emboli to the lungs in 3 patients (7.5%). CONCLUSIONS: Transvenous embolization of CSFVFs using Onyx is safe and effective, resulting in significant improvement in headache and overall clinical outcomes in nearly 90% of patients, and substantial improvements in brain MRI abnormalities.

Headache.

Headache is one of the most common complaints among patients presenting to an outpatient neurology practice. The evaluation, diagnosis, and treatment of headache can be rather cumbersome and at times quite challenging for even the most seasoned neurologist. Many complex issues that although not causative, can play an exacerbating role in the genesis of headaches. In this article, the authors review some of the essential elements that are part of headache evaluation including headache-specific history, physical examination, warning signs of secondary headache disorders, and when to consider further studies. They then provide a brief review on the diagnosis of primary headache disorders according to the International Headache Society's International Classification of Headache Disorders, 2nd Edition (ICHD-2), and treatment strategies of the more common primary headache disorders with a focus on migraine, trigeminal autonomic cephalalgias, tension-type headache, and chronic daily headache.

Genetic variants related to successful migraine prophylaxis with verapamil.

BACKGROUND: Currently, there is no biologically based rationale for drug selection in migraine prophylactic treatment. METHODS: To investigate the genetic variation underlying treatment response to verapamil prophylaxis, we selected 225 patients from a longitudinally established, deeply phenotyped migraine database (N = 5983), and collected uninterrupted quantitated verapamil treatment response data and DNA for these 225 cases. We recorded the number of headache days in the four weeks preceding treatment with verapamil and for four weeks, following completion of a treatment period with verapamil lasting at least five weeks. Whole-exome sequencing (WES) was applied to a discovery cohort consisting of 21 definitive responders and 14 definitive non-responders, and the identified single nucleotide polymorphisms (SNPs) showing significant association were genotyped in a separate confirmation cohort (185 verapamil treated patients). Statistical analysis of the WES data from the discovery cohort identified 524 SNPs associated with verapamil responsiveness (p < 0.01); among them, 39 SNPs were validated in the confirmatory cohort (n = 185) which included the full range of response to verapamil from highly responsive to not responsive. RESULTS: Fourteen SNPs were confirmed by both percentage and arithmetic statistical approaches. Pathway and protein network analysis implicated myo-inositol biosynthetic and phospholipase-C second messenger pathways in verapamil responsiveness, emphasizing the earlier pathogenic understanding of migraine. No association was found between genetic variation in verapamil metabolic enzymes and treatment response. CONCLUSION: Our findings demonstrate that genetic analysis in well-characterized subpopulations can yield important pharmacogenetic information pertaining to the mechanism of anti-migraine prophylactic medications.

Case series of sixteen patients with nummular headache.

INTRODUCTION: Nummular headache is a rare primary headache disorder described by a focal circumscribed area of pain (2-6 cm in diameter). Literature on this disorder is sparse. PATIENTS AND METHODS: Here, we describe a case series of 16 patients (6 men, 10 women) seen at the Mayo Clinic. RESULTS: Mean age of onset was 50 years (range, 19-79 years) and mean duration of headache was 7.9 years (range, 0.33-40 years). Location of headache varied and was found to be an average of 3.9 cm in diameter (range, 2-10 cm). Headache was episodic (< 15 days/month) in four patients and chronic (>15 days/month) in 12 patients. Attention was paid to therapeutic interventions. Resolution was seen in 38% of patients. Migraine was present in the history of 56% of patients and medication overuse headache was found in 25%. CONCLUSIONS: Our series results support previous findings. In our population, no specific therapy was identified to be effective in more than one patient.