Treatment of SUNCT/SUNA, Paroxysmal Hemicrania, and Hemicrania Continua: An Update Including Single-Arm Meta-analyses

Purpose of Review: This review presents a critical appraisal of the treatment strategies for short-lasting unilateral neuralgiform headache attacks (SUNHA), paroxysmal hemicrania (PH), and hemicrania continua (HC). We assess the available, though sparse, evidence on both medical and surgical treatments. In addition, we present estimated pooled analyses of the most common treatments and emphasize recent promising findings. / Recent Findings: The majority of literature available on the treatment of these rare trigeminal autonomic cephalalgias are small open-label observational studies and case reports. Pooled analyses reveal that lamotrigine for SUNHA and indomethacin for PH and HC are the preventative treatments of choice. Second-line choices include topiramate, gabapentin, and carbamazepine for SUNHA; verapamil for PH; and cyclooxygenase-2 inhibitors and gabapentin for HC. Parenteral lidocaine is highly effective as a transitional treatment for SUNHA. Novel therapeutic strategies such as non-invasive neurostimulation, targeted nerve and ganglion blockades, and invasive neurostimulation, including implanted occipital nerve stimulators and deep brain stimulation, appears to be promising options. / Summary: At present, lamotrigine as a prophylactic and parenteral lidocaine as transitional treatment remain the therapies of choice for SUNHA. While, by definition, both PH and CH respond exquisitely to indomethacin, evidence for other prophylactics is less convincing. Evidence for the novel emerging therapies is limited, though promising

Treatment of SUNCT/SUNA, Paroxysmal Hemicrania, and Hemicrania Continua: An Update Including Single-Arm Meta-analyses

Purpose of Review: This review presents a critical appraisal of the treatment strategies for short-lasting unilateral neuralgiform headache attacks (SUNHA), paroxysmal hemicrania (PH), and hemicrania continua (HC). We assess the available, though sparse, evidence on both medical and surgical treatments. In addition, we present estimated pooled analyses of the most common treatments and emphasize recent promising findings. / Recent Findings: The majority of literature available on the treatment of these rare trigeminal autonomic cephalalgias are small open-label observational studies and case reports. Pooled analyses reveal that lamotrigine for SUNHA and indomethacin for PH and HC are the preventative treatments of choice. Second-line choices include topiramate, gabapentin, and carbamazepine for SUNHA; verapamil for PH; and cyclooxygenase-2 inhibitors and gabapentin for HC. Parenteral lidocaine is highly effective as a transitional treatment for SUNHA. Novel therapeutic strategies such as non-invasive neurostimulation, targeted nerve and ganglion blockades, and invasive neurostimulation, including implanted occipital nerve stimulators and deep brain stimulation, appears to be promising options. / Summary: At present, lamotrigine as a prophylactic and parenteral lidocaine as transitional treatment remain the therapies of choice for SUNHA. While, by definition, both PH and CH respond exquisitely to indomethacin, evidence for other prophylactics is less convincing. Evidence for the novel emerging therapies is limited, though promising

R1352Q CACNA1A Variant in a Patient with Sporadic Hemiplegic Migraine, Ataxia, Seizures and Cerebral Oedema: A Case Report

Mutations in the CACNA1A gene show a wide range of neurological phenotypes including hemiplegic migraine, ataxia, mental retardation and epilepsy. In some cases, hemiplegic migraine attacks can be triggered by minor head trauma and culminate in encephalopathy and cerebral oedema. A 37-year-old male without a family history of complex migraine experienced hemiplegic migraine attacks from childhood. The attacks were usually triggered by minor head trauma, and on several occasions complicated with encephalopathy and cerebral oedema. Genetic testing of the proband and unaffected parents revealed a de novo heterozygous nucleotide missense mutation in exon 25 of the CACNA1A gene (c.4055G>A, p.R1352Q). The R1352Q CACNA1A variant shares the phenotype with other described CACNA1A mutations and highlights the interesting association of trauma as a precipitant for hemiplegic migraine. Subjects with early-onset sporadic hemiplegic migraine triggered by minor head injury or associated with seizures, ataxia or episodes of encephalopathy should be screened for mutations. These patients should also be advised to avoid activities that may result in head trauma, and anticonvulsants should be considered as prophylactic migraine therapy

Medical treatment of SUNCT and SUNA: a prospective open-label study including single-arm meta-analysis

Introduction: The management of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and shortlasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) remains challenging in view of the paucity of data and evidence-based treatment recommendations are missing. Methods: In this single-centre, non-randomised, prospective open-label study, we evaluated and compared the efficacy of oral and parenteral treatments for SUNCT and SUNA in a real-world setting. Additionally, single-arm meta-analyses of the available reports of SUNCT and SUNA treatments were conducted. Results: The study cohort comprised 161 patients. Most patients responded to lamotrigine (56%), followed by oxcarbazepine (46%), duloxetine (30%), carbamazepine (26%), topiramate (25%), pregabalin and gabapentin (10%). Mexiletine and lacosamide were effective in a meaningful proportion of patients but poorly tolerated. Intravenous lidocaine given for 7–10 days led to improvement in 90% of patients, whereas only 27% of patients responded to a greater occipital nerve block. No statistically significant differences in responders were observed between SUNCT and SUNA. In the meta-analysis of the pooled data, topiramate was found to be significantly more effective in SUNCT than SUNA patients. However, a higher proportion of SUNA than SUNCT was considered refractory to medications at the time of the topiramate trial, possibly explaining this isolated difference. Conclusions: We propose a treatment algorithm for SUNCT and SUNA for clinical practice. The response to sodium channel blockers indicates a therapeutic overlap with trigeminal neuralgia, suggesting that sodium channels dysfunction may be a key pathophysiological hallmark in these disorders. Furthermore, the therapeutic similarities between SUNCT and SUNA further support the hypothesis that these conditions are variants of the same disorder

Open-Label, Multi-Dose, Pilot Safety Study of Injection of OnabotulinumtoxinA Toward the Otic Ganglion for the Treatment of Intractable Chronic Cluster Headache

BACKGROUND: The otic ganglion (OG) provides parasympathetic innervation to the cerebral circulation and cranial structures and may be involved in the pathophysiology of trigeminal autonomic headaches. This structure has never been targeted in any headache disorder. OBJECTIVE: To investigate the safety of injecting onabotulinumtoxin A (BTA) toward the OG in 10 patients with intractable chronic cluster headache and to collect efficacy data. METHODS: A total of 10 patients with chronic cluster headache were enrolled in this open-label, multi-dose pilot safety study. All patients were recruited and treated on an out-patient basis at St Olav's University Hospital (Norway). In 5 patients each, the OG was the injection target with 12.5 IU of BTA or 25 IU, respectively. The primary outcome measure was adverse events (AEs) and the main secondary outcome was the number of attacks per week measured at baseline and in the second month following injection. RESULTS: For the primary endpoint, we analyzed data for all 10 patients. There were a total of 17 AEs in 6 of the 10 patients. All AEs were considered mild and disappeared by the end of follow-up. The median number of attacks per week at baseline was 17.0 [7.8 to 25.8] vs 14.0 [7.3 to 20.0] in the second month following injection; difference: 3 (95%CI: -0.3 to 7.9), P = .063. CONCLUSIONS: Injection with BTA toward the OG appears to be safe. We did not find a statistically significant reduction in the number of attacks per week at month 2 after injection compared to the baseline. This study suggests that the OG is not an important target for the treatment of chronic cluster headache. A future study employing more precise targeting of the OG may be indicated

Angiotensin-converting enzyme gene insertion/deletion polymorphism in migraine patients

<p>Abstract</p> <p>Background</p> <p>The main objective of this study was to investigate the angiotensin converting enzyme (<it>ACE</it>) genotype as a possible risk factor for migraine (both with and without aura) compared to controls. We also wanted to examine whether a clinical response to an ACE inhibitor, lisinopril, or an angiotensin II receptor blocker, candesartan, in migraine prophylaxis was related to <it>ACE </it>genotype.</p> <p>Methods</p> <p>347 migraine patients aged 18–68 (155 migraine without aura (MoA), 187 migraine with aura (MwA) and 5 missing aura subgroup data) and 403 healthy non-migrainous controls > 40 years of age were included in the study. A polymerase chain reaction (PCR) was performed on the genomic DNA samples to obtain the <it>ACE </it>insertion (I)/deletion(D) polymorphisms.</p> <p>Results</p> <p>No significant differences between migraine patients and controls were found with regard to <it>ACE </it>genotype and allele distributions. Furthermore, there was no significant difference between the controls and the MwA or MoA subgroups.</p> <p>Conclusion</p> <p>In our sample there is no association between <it>ACE </it>genotype or allele frequency and migraine. In addition, <it>ACE </it>genotype in our experience did not predict the clinical response to lisinopril or candesartan used as migraine prophylactics.</p

Pilot Study of Injection of OnabotulinumtoxinA Toward the Sphenopalatine Ganglion for the Treatment of Classical Trigeminal Neuralgia

BACKGROUND: The sphenopalatine ganglion (SPG) has previously been targeted in trigeminal neuralgia (TN), but its role in this condition has not been established. OBJECTIVE: To investigate the safety of injecting onabotulinumtoxinA (BTA) toward the SPG using the MultiGuide® in 10 patients with refractory classical TN, and collect preliminary efficacy data. METHODS: Twenty-five international units (IU) of BTA were injected toward the SPG in a prospective, open-label study in 10 patients with refractory classical TN. All patients were recruited and treated on an out-patient basis at St. Olav's University Hospital in Trondheim (Norway). PRIMARY OUTCOME: adverse events (AEs). Primary efficacy outcome: number of TN attacks at weeks 5-8 after injection compared to baseline. A treatment responder was predefined as at least 50% reduction in the median number of attacks per day between baseline and weeks 5-8. Other efficacy outcomes were intensity of attacks (numeric rating scale, 0 to 10) and functional level (1 to 4; 1 best and 4 worst) at weeks 5-8 after injection compared to baseline. Percentage of the day with concomitant persistent pain was registered at baseline and at weeks 1-4, 6, 8, and 12 after injection. Patient global impression of change (PGIC) was ascertained at month 3. RESULTS: For the primary endpoint, we analyzed data for all 10 patients. For efficacy outcomes we analyzed data for 9 patients (1 patient violated protocol). We registered 13 AEs, none of which were serious. The median number of TN attacks during the 4-week baseline and weeks 5-8 after injection was 5.5 (range: 1.0-51.5) and 5 (range: 0-225.0), respectively (P = .401). Four patients were treatment responders. The median intensity of attacks at baseline and weeks 5-8 after injection was 6 (range: 3.0-8.5) and 3 (range: 0.0-9.0) respectively (P = .024). The median functional level at baseline was 2 (range: 1.0-3.3) and at month 2, 1 (range 1.0-4.0; P = .750). Median percentage of the day with concomitant persistent pain was 75% (minimum 37.5%, maximum 100%) at baseline and 18.75% (minimum 0%, maximum 100%) at week 8 (P = .023). CONCLUSIONS: Injection of BTA toward the SPG using the MultiGuide® in patients with TN appears to be safe and well tolerated. This study was negative for the main efficacy endpoint (reduction in the number of attacks from baseline to weeks 5-8). Further studies examining the role of the SPG in TN are necessary

Depicting the pterygopalatine ganglion on 3 Tesla magnetic resonance images

PURPOSE: The pterygopalatine ganglion has yet not been identified on medical images in living humans. The primary aim of this study was to evaluate whether the pterygopalatine ganglion could be identified on 3 T MR imaging. METHODS: This study was performed on medical images of 20 Caucasian subjects on both sides (n = 40 ganglia) with an exploratory design. 3 T MR images were assessed by two physicians for the presence and size of the pterygopalatine ganglion. The distance from the pterygopalatine ganglion to four bony landmarks was registered from fused MR and CT images. In an equivalence analysis, the distances were compared to those obtained in an anatomical cadaveric study serving as historical controls (n = 50). RESULTS: A structure assumed to be the pterygopalatine ganglion was identified on MR images in all patients on both sides by both physicians. The mean size was depth 2.1 ± 0.5 mm, width 4.2 ± 1.1 mm and height 5.1 ± 1.4 mm, which is in accordance with formerly published data. Equivalence of the measurements on MR images and the historical controls was established, suggesting that the structure identified on the MR images is the pterygopalatine ganglion. CONCLUSION: Our findings suggest that the pterygopalatine ganglion can be detected on 3 T MR images. Identification of the pterygopalatine ganglion may be important for image-guided interventions targeting the pterygopalatine ganglion, and has the potential to increase the efficacy, safety and reliability for these treatments

Association between blood pressure measures and recurrent headache in adolescents: cross-sectional data from the HUNT-Youth study

The relationship between blood pressure and headache in youth has not been explored and the objective of the present study was to provide data on this association in an adolescent population. Cross-sectional data from a large population-based survey, the Young-HUNT study, on 5,847 adolescents were used to evaluate the association between blood pressure (systolic, diastolic, mean arterial and pulse pressure) and recurrent headache, including migraine and tension-type headache. Increasing pulse pressure was inversely related to recurrent headache prevalence, and both tension-type headache and migraine. For systolic blood pressure such an inverse relationship was present for recurrent headache and tension-type headache prevalence. For migraine, the results were not significant, although there was a tendency in the same direction (p = 0.05). High-pulse pressure has previously been found to be inversely related to the prevalence of migraine and tension-type headache in an adult population. This inverse relationship has now been demonstrated to be present among adolescents also, supporting the results from a previous study in adults, that blood pressure regulation may be linked to the pathophysiology of headache