Isolated intracranial hypertension following COVID-19 vaccination: A case report

Increased intracranial pressure in cerebral venous sinus thrombosis or metabolic disease has been reported. We present a case of new-onset chronic headache and bilateral papilledema in the setting of elevated intracranial pressure in strong temporal association to vaccination against COVID-19 with AstraZeneca. After repeated drainage of cerebrospinal fluid and conservative drug therapy, pathological findings were regredient. Even in absence of typical risk factors, increased intracranial pressure should be considered in case of clinical suspicion after COVID-19 vaccination.

Efficacy of galcanezumab in patients with episodic cluster headaches and a history of preventive treatment failure

Objective: The efficacy of galcanezumab was evaluated in patients with episodic cluster headache and history of preventive treatment failure. Methods: In the randomized, 8-week, double-blind study (CGAL), patients with episodic cluster headache received once-monthly subcutaneous injections of galcanezumab 300 mg or placebo. Patients who completed CGAL and enrolled in an open-label study were queried for preventive treatment history. In a subset of patients with a known history of failure of verapamil or any other prior preventive treatment, a post hoc analysis of least square mean change from baseline in weekly cluster headache attack frequency across Weeks 1 to 3 was assessed. Results: Fifteen patients provided data for known history of prior preventive treatment failure (6 placebo, 9 galcanezumab), of whom 11 failed verapamil. The mean reduction in the weekly frequency of cluster headache attacks was greater with galcanezumab compared to placebo among patients with prior preventive treatment failure (8.2 versus 2.4); mean difference 5.8 (95% confidence interval [CI] 2.0, 13.6) and among patients with verapamil failure (10.1 versus 1.6); mean difference 8.5 (95% CI 0.4, 16.7). Conclusion: In this exploratory analysis of patients with a known history of prior preventive treatment failures, treatment with galcanezumab resulted in greater mean reductions in weekly cluster headache attacks compared with placebo. ClinicalTrials.gov: NCT02397473 (I5Q-MC-CGAL) NCT02797951 (I5Q-MC-CGAR)

Safety of select headache medications in patients with cerebral and spinal cavernous malformations

Background: Patients with cerebral or spinal cavernous malformations (CM) and a primary headache disorder are often limited in medication options due to concern for bleeding risk. Methods: From a prospective cohort of CM patients (2015–2020), demographics, mode of clinical presentation, and radiographic data were collected. Follow up of patients was performed with electronic medical record review, in person visits and/or written surveys. Select medication use was ascertained from the time of the CM diagnosis to a censor date of first prospective symptomatic hemorrhage, complete surgical excision of sporadic form CM, or death. The influence of non-aspirin NSAID (NA-NSAID), triptan, or OnabotulinumtoxinA on prospective hemorrhage risk was assessed. Results: As of August 20, 2020, 329 patients with spinal or cerebral CM (58% female; 20.1% familial; 42.2% initial presentation due to hemorrhage; 27.4% brainstem) were included. During a follow-up of 1799.9 patient years, 92 prospective hemorrhages occurred. Use of NA-NSAIDs, triptans, and OnabotulinumtoxinA after the diagnosis of CM was unassociated with an increased risk of prospective hemorrhage. Conclusions: Use of triptans and NA-NSAIDs, does not precipitate CM hemorrhage. Similarly, we did not find that OnabotulinumtoxinA precipitated CM hemorrhage in a limited number of patients at doses <200 units per session.

Effects of CYP3A4 and P-glycoprotein inhibition or induction on the pharmacokinetics of ubrogepant in healthy adults: Two phase 1, open-label, fixed-sequence, single-center, crossover trials

Background: Ubrogepant is metabolized by cytochrome P450 3A4 (CYP3A4) and is a P-glycoprotein (P-gp) substrate. Objective: To assess effects of multiple-dose moderate-strong CYP3A4 and strong P-gp inhibitors and inducers on ubrogepant pharmacokinetic (PK) parameters. Methods: Two phase 1, open-label, fixed-sequence, single-center, crossover trials enrolled healthy adults to receive ubrogepant 20 mg with/without verapamil 240 mg (a moderate CYP3A4 inhibitor) or ketoconazole 400 mg (a strong CYP3A4 and P-gp transporter inhibitor) (Study A), or ubrogepant 100 mg with/without rifampin 600 mg (a strong CYP3A4 inducer and P-gp inducer) (Study B). Outcomes included ubrogepant PK parameters (area under plasma concentration-time curve, time 0 through infinity [AUC0-∞], peak plasma concentration [Cmax]), and safety (treatment-emergent adverse events [TEAEs]). PK parameters were compared between ubrogepant with/without coadministered medications using linear mixed-effects models. Cmax and AUC0-∞ least-squares geometric mean ratios (GMR) of ubrogepant with/without coadministration were constructed. Results: Twelve participants enrolled in Study A and 30 in Study B. AUC0-∞ and Cmax GMR (90% CI) were 3.53 (3.32–3.75) and 2.80 (2.48–3.15), respectively, for ubrogepant with verapamil; 9.65 (7.27–12.81) and 5.32 (4.19–6.76) with ketoconazole; and 0.22 (0.20–0.24) and 0.31 (0.27–0.36) with rifampin. TEAEs were predominantly mild; no treatment-related serious TEAEs or TEAE-related discontinuations occurred. Conclusion: The PK of ubrogepant were significantly affected by the concomitant use of CYP3A4 moderate-strong inhibitors and strong inducers.

Identification of predictors of response to Erenumab in a cohort of patients with migraine

Background: The migraine-specific monoclonal antibody Erenumab targeting the calcitonin gene related peptide receptor is an effective and well tolerated preventive treatment of episodic and chronic migraine. However, its price limits its use as a first line therapy against migraine. Therefore, identifying patients who will adequately respond to such treatment is paramount. Methods: In this retrospective, real-life cohort study, 172 adult patients with refractory episodic or chronic migraine treated with Erenumab were included. To identify the predictors of response to Erenumab, bivariate subgroup analysis of several potential factors was performed, and multivariate logistic regression modeling was done to obtain Odds Ratio (OR). Results: Of the 172 patients, 57.0% achieved a successful treatment response (reduction of monthly migraine days by ≥50%). Statistically significant predictors of a treatment response were the presence of chronic migraine, tension-type headache, and a positive response to triptan with an odd ratio of 0.473 (95% CI, 0.235–0.952), 0.485 (95% CI, 0.245–0.962) and 3.985 (95% CI, 1.811–8.770), respectively (P < 0.05). Conclusions: Successful Erenumab treatment response rate was 57.0% in this retrospective cohort. As chronic migraine and tension-type headache were negative predictors of Erenumab response while triptan response was a positive predictor, this data suggests the potential for Erenumab monotherapy without the need for traditional preventive treatment in refractory migraine sufferers improving side effect profile and treatment adherence for a cohort of patients difficult to treat.

The quest for a headache pattern in giant cell arteritis: A cohort study

Aim: To help clinicians in the diagnostic approach of giant cell arteritis (GCA) by providing a better knowledge on headache patterns in GCA. Methods: Cross-sectional data of a cohort of 30 known GCA patients regarding symptoms, clinical signs, laboratory and pathology data were collected retrospectively. Results: Headache was experienced by the majority of our cohort (26/30; 87%) and the most common pattern reported was a continuous, unilateral pain centered in or around the temporal area (13/26; 50% of all headaches). Pain confined to the occiput or frontal areas of the head was rarely reported as well as migrainous or cluster-like headaches. Conclusion: This data suggests that the headache pattern in GCA is heterogeneous, but that the most common pattern is a continuous, unilateral, temporal headache. Several other patterns were infrequently reported and these should question the clinical diagnosis of GCA. A large prospective study will be necessary to further elaborate these findings.

Long term outcome for onabotulinumtoxinA (Botox) therapy in chronic migraine: A 2-year prospective follow-up audit of patients attending the Hull (UK) migraine clinic

Objective: The objective of this prospective audit was to determine the long term outcome of patients diagnosed with chronic migraine who were treated with onabotulinumtoxinA for the prevention of chronic migraine. Background: While long term and real-world studies have confirmed the safety and efficacy of onabotulinumtoxinA in CM, there remains limited information from large patient numbers on the number of cycles and duration of onabotulinumtoxinA needed to successfully convert chronic migraine to episodic migraine, development of resistance to treatment and sustainability of response after stopping treatment. Methods: A total of 655 adult patients diagnosed with chronic migraine who received onabotulinumtoxinA at the Hull Migraine Clinic were followed up prospectively for a minimum of 2 years. OnabotulinumtoxinA was delivered as per the PREEMPT study protocol and patients were asked to keep a headache diary for at least 30 days prior to and continuously after receiving onabotulinumtoxinA. The primary outcome assessed in this prospective real-world audit was either the number of patients who achieved a ≥50% reduction in headache days or migraine days or an increment in crystal clear days twice that of baseline in a 30-day period. Patients were also assessed for analgesic medication overuse. Results: Treatment data were available for 655 patients who commenced treatment between July 2010 and October 2016 and followed for at least 2 years (24–70 months), with the last follow-up taking place in September 2018. Of the 655 patients, 380 patients responded to treatment after two cycles and went on to receive the third cycle. Of these, 152 patients were still on active treatment at 2 years. A further 61 patients had relapsed and were on treatment at 2 years. Of the 228 patients who stopped treatment, 112 were successfully converted to episodic migraine and showed a sustained response, 28 reverted to chronic migraine after the initial response despite continuing treatment (developed resistance), 14 were lost to follow up and 61 patients after achieving remission relapsed after a mean of 9 months (range 4–24 months) and recommenced treatment with onabotulinumtoxinA. Conclusion: After a minimum of 2 years, 29.4% of patients with chronic migraine who initially responded to treatment were successfully converted to episodic migraine and maintained a sustained response. Forty percent of the initial cohort of responders continued therapy with onabotulinumtoxinA to manage their chronic migraine.

The impact of the disease burden on the quality of life of cluster headache patients

Background: Cluster headache cannot be cured, and not all attacks can be aborted or prevented. Nevertheless, therapeutic guidelines focus solely on the attacks and ignore reverberations of the disorder on patients’ lives. However, it is likely that not only pain reduces patients’ quality of life (QoL). Objective: To investigate whether the interictal burden independently influence the QoL of subjects suffering from cluster headache. Methods: In this cross-sectional study, we asked patients with a self-reported cluster headache diagnosis to answer a modified EUROLIGHT questionnaire that included the EURO-HIS QoL scale. We built a generalised linear model and included the QoL as the dependent variable. Independent variables comprised both the ictal and the interictal burden. Results: The data of 625 participants entered the analysis. Several aspects of the interictal burden independently reduced the QoL. Among them were fear of pain, self-concealment, and private life difficulties due to the disorder. Conclusion: Both the ictal and the interictal burden of cluster headache independently reduce patients’ QoL. We advocate adopting a more holistic approach to cluster headache management extending the focus towards the afflicted person and their QoL, which would generate novel therapeutic goals and strategies, complementary to treating and preventing cluster headache attacks.

Levetiracetam in management of bilateral trigeminal neuralgia due to large glomus tumor case report

Background: Trigeminal neuralgia can be classical or idiopathic. While trigeminal neuralgia (TN) due to space-occupying lesions is atypical, such lesions rarely cause severe TN secondary to trigeminal nerve irritation. Mass effect from these lesions has been shown to correlate with symptom burden, due to direct or indirect compressive effects. A tethering effect, provoked by an abnormal root-stretching force, theoretically plays a role in trigeminal nerve hyperexcitability. Case: The likely etiology in this case presentation is a large glomus tumor invading the middle and posterior cranial fossa. Glomus tumors are uncommon benign tumors of the head and neck derived from neural crest cells. Even more strikingly, a large glomus tumor causes bilateral TN due to direct compression on one side and indirect compression on the contralateral side. Conclusion: Although the gold standard in TN management is carbamazepine, other anti-epileptic drugs (AEDs) have been used in the treatment of patients unable to take carbamazepine. A few studies suggest levetiracetam alleviates central and neuropathic pain, supporting the hypothesis that it may be effective in management of TN.

Cranial suture headache: An extracranial head pain syndrome originating in the cranial sutures of the skull

Objective: To define a new type of head pain syndrome termed “cranial suture headache” which is a localized headache originating along the cranial suture lines of the skull. Background: Well localized headaches maybe extracranial in origin. As trigeminal nociceptors are localized within the cranial sutures of the skull, these fibrous joints maybe the source of head pain for some patients. Methods: Case series. To diagnose cranial suture headache, the patient’s pain had to be localized to the skull and elicited/mimicked by mild to moderate palpation over one or more distinct cranial suture lines. Results: Ten cases are presented. Most of the patients were women (9/10). The headache started daily from onset in all cases. Range of age of headache onset was 32–64 years. Headache was one sided, unless confined to the midline and typically lacked any migrainous and/or cranial autonomic symptoms. Most cranial suture headaches localized to either the sagittal, coronal or squamosal suture lines. Headache duration prior to diagnosis was on average 8.5 years. Triggering events: three began immediately after head trauma, two had very remote head trauma, one was post infectious, one was post craniotomy, while three patients had no known triggering event. All patients were treatment refractory failing at least three preventive medications. All improved with localized anesthetic injection to the suture line(s) and/or onabotulinum toxin A injection only to the cranial sutures. Discussion: Without the recognition of cranial suture-based pain, patients may have unremitting headaches that can last years to decades. The observation that “cranial suture” headache improves with localized treatment only to the cranial sutures would seem to suggest the extracranial origin of the pain.