Marcella Curone

Vagus nerve stimulation in drug-resistant daily chronic migraine with depression: preliminary data

Drug refractory chronic daily headache (CDH) is a highly disabling condition. CDH is usually regarded as the negative evolution of chronic migraine (CM) and is characterized by high prevalence of psychiatric disorders, especially mood disorders. Vagal nerve stimulation (VNS) is an established treatment option for selected patients with medically refractory epilepsy and depression. Neurobiological similarities suggest that VNS could be useful in the treatment of drug-refractory CM associated with depression. The aim of the study was to evaluate the efficacy of VNS in patients suffering from drug-refractory CM and depressive disorder. We selected four female patients, mean age 53 (range 43–65 years), suffering from daily headache and drug-refractory CM. Neurological examination and neuroradiological investigations were unremarkable. Exclusion criteria were psychosis, heart and lung diseases. The preliminary results in our small case series support a beneficial effect of chronic VNS on both drug-refractory CM and depression, and suggest this novel treatment as a valid alternative for this otherwise intractable and highly disabling condition.

Sphenopalatine Endoscopic Ganglion Block: A Revision of a Traditional Technique for Cluster Headache

The diagnosis of chronic cluster headache (CH), the most painful form of headache, is based on typical clinical features characterized by strictly unilateral pain with no side shift and ipsilateral oculofacial autonomic phenomena. The attacks occur several times a day for periods of 1 to 2 months in the episodic form of the disease or less frequently on a daily basis in the chronic form. The pathogenesis of CH involves the activation of parasympathetic nerve structures located within the sphenopalatine ganglion (SPG), which explains many of the associated symptoms, whereas the activation of the ipsilateral hypothalamic gray matter may explain its typical circadian and circannual periodicity. A number of surgical approaches have been tried in cases of chronic CH resistant to pharmacologic therapy, of which SPG blockade has been shown to have certain efficacy. We have adopted a new technique based on endoscopic ganglion blockade that approaches the pterigo‐palatine fossa by way of the lateral nasal wall and consists of the injection of a mixture of local anesthetics and corticosteroids, which was performed in 20 selected patients with chronic CH, according to the International Headache Society criteria (18 male, 2 female; mean age 40 yr), who were selected for SPG blockade because they were totally drug resistant. The symptoms improved significantly, but always only temporarily, in 11 cases. These results should be considered rather good because, unlike other frequently used techniques, SPG blockade is not invasive and should therefore always be attempted before submitting patients to more invasive surgical approaches.

Deep brain stimulation and cluster headache.

In recent years, neuroimaging data have greatly improved the knowledge on trigeminal autonomic cephalalgias’ (TACs) central mechanisms. Positron emission tomography studies have shown that the posterior inferior hypothalamic grey matter is activated during cluster headache attacks as well as in short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT). Voxel-based morphometric MRI has also documented alteration in the same area in cluster headache patients. These data suggest that the cluster headache generator is located in this region and leads us to hypothesise that stimulation of this brain area could relieve intractable cluster headache just as deep brain stimulation improves intractable movements disorders. This view received support by the observation that high frequency stimulation of the ipsilateral hypothalamus prevented attacks in an otherwise intractable chronic cluster headache patient previously treated unsuccessfully by surgical procedures to the trigeminal nerve. So far, 16 patients with intractable cronic cluster headache (CCH) and one intractable SUNCT patient have been successfully treated by hypothalamic stimulation. The procedures were well tolerated with no significant adverse events. Hypothalamic DBS is an efficacious and safe procedure to relieve otherwise intractable CCH and SUNCT.

Disability Pattern in Chronic Migraine With Medication Overuse: A Comparison With Migraine Without Aura

Objectives.—To assess headache‐related disability in chronic migraine with medication overuse (CMO), as defined by Silberstein and Lipton (1996, 2001) in comparison to that caused by migraine without aura, investigating similarities and differences in disability patterns in these two conditions.

Neuroimaging and pain: a window on the autonomic nervous system.

Pain is one of the most common experiences of humans. Neuroimaging techniques can visualize the main brain areas involved in pain modulation, the pain matrix. It is noteworthy that many of the brain areas forming the pain matrix are also involved in modulating autonomic nervous system (ANS) activity that in turn plays a major role in determining the best adaptive response to the pain experience. The tight connection between the pain system and ANS is also evident from neuroanatomical studies indicating that the lamina 1 neurons receive both painful and visceral stimuli from all visceral organs giving rise to the spinothalamocortical pathway concerned with conveying interoceptive information to central structures. The resulting interoceptive stream projects to the viscerosensory cortex in the mid-insula and onto the right anterior insula and orbitofrontal cortices. Right anterior insula activation is involved in the sympathetic arousal associated with mental tasks. This brain region receives numerous other inputs including pain and painful stimuli are conveyed somatotopically to both insulae. A similar somatotopic organization of painful stimuli has also been shown in the basal ganglia involved in cognitive, affective, motor and autonomic states. This highly specialized organization of nociceptive information in these brain areas may subserve a number of functions, particularly of coupling pain with the most appropriate autonomic states and affective/emotional states. The anterior cingulated cortex, another brain area playing a crucial role in nociception, is also directly involved in the control of autonomic functions such as arousal during volitional behaviour, including effortful cognitive processing. It is evident that the nociceptive system and ANS closely interact in many processes involved in maintaining internal homeostatis and in order to give the most appropriate biological substrate for cognitive, affective and emotional states.

Psychopathological profile of patients with chronic migraine and medication overuse: Study and findings in 50 cases

Patients with chronic migraine (CM) have high frequence of psychiatric comorbidity or psychological distress. The presence of depression, anxiety, panic or obsessive disorders in these patients contributes to poor quality of life and can influence prognosis and treatment. A systematic investigation of psychiatric comorbidity is needed in patients with CM especially in those with medication overuse (MO), in order to reach a more comprehensive clinical management. We assessed the psychological profile of 50 patients, 40 women and 10 men suffering from CM with MO. The Spectrum Project, a complementary way of describing and assessing psychopathology with structured clinical interviews, was used for the psychological evaluation of the patients to explore personality traits. Spectrum instruments mood disorders (MOODS), panic agoraphobic disorders (PAS) and obsessive–compulsive disorder (OBS) were applied to study patients. OBS-questionnaire was positive in 28% of the patients, MOODS-questionnaire in 44%, PAS-questionnaire in 46%. 19 on 50 patients (38%) presented positivity to 2 or to all questionnaires in variable associations. None of the patients of the studied group had complete normal findings in the questionnaires. Clinical records of patients with OBS-questionnaire positivity showed a worse clinical course and tendency to relapse. These results suggest that psychological assessment is an essential step in the evaluation and treatment of patients with CM and MO. The remarkable percentage of OBS-questionnaire positivity in this group indicates that obsessive–compulsive trait represents besides depression and anxiety, a major risk of chronification and overusing.

Frovatriptan for the prevention of postdural puncture headache

Efficacy of 5–day treatment with oral frovatriptan 2.5 mg/die for the prophylaxis of post-dural puncture headache (PDPH) was tested in 50 in-patients. A mild headache occurred in 7 (14%) patients for a total of 9 days (p < 0.01 vs. no-PDPH). Most episodes of PDPH occurred in the first days of treatment (only 1 patient had headache at dismissal): 5 patients had only 1 episode, while 2 had headache for 2 consecutive days. No other symptoms were recorded. Occurrence of PDPH in a subgroup of 6 (12%) patients previously submitted to a diagnostic lumbar puncture was also examined: 4 of them reported a PDPH on the previous lumbar puncture in absence of triptans. In only 1 of these 4 patients PDPH recurred under treatment with frovatriptan. In conclusion, our non-randomized open-label study suggests efficacy of oral frovatriptan for PDPH prevention. These results need to be confirmed in a randomized, controlled, double-blind study.

Functional neuroimaging and headache pathophysiology: new findings and new prospects

In the last ten years pathophysiology of primary headaches has received new insights from neuroimaging studies. Positron emission tomography (PET) showed activation of specific brain structures, brainstem in migraine and hypothalamic grey in trigeminal autonomic cephalalgias. This brain activation suggests it may intervene both in a permissive or triggering manner and as a response to pain driven by the first division of the trigeminal nerve. Voxel-based morphometry has suggested that there is a correlation between the brain area activated specifically in acute cluster headache – the posterior hypothalamic grey matter – and an increase in grey matter in the same region. New insights into mechanisms of head pain have emerged thanks to neuroimaging obtained in experimentally induced headaches, and during peripheral and central neurostimulation.

Chronic migraine with medication overuse: Association between disability and quality of life measures, and impact of disease on patients' lives

Patients with chronic migraine with medication overuse (CM-MO) have decreased quality of life (QoL) and increased disability: the degree to which these outcomes are connected to disease severity and the pattern of MO towards disease severity are unclear. Patients under withdrawal were administered the Migraine Disability Assessment (MIDAS), the WHO Disability Assessment Schedule (WHODAS), and the Migraine-Specific Quality of Life Questionnaire (MSQ). They overused NSAIDs, triptans, NSAIDs and triptans, and other drugs (ergotamine, caffeine, opioids/barbiturates). We calculated the correlations between MIDAS, WHODAS, and MSQ; compared WHODAS to normative scores; compared MIDAS, WHODAS, and MSQ in patients with different CM-MO severity; and run a logistic regression to predict CM-MO severity based on overused drugs. One hundred ninety-four patients were enrolled: correlations between WHODAS, MSQ, and MIDAS were moderate; wide differences on WHODAS against normative were found; and no trend was found across severity groups. Compared to triptans overusers, patients overusing NSAID and other drugs had higher odds of severe CM-MO. Coupling different disability measures with QoL assessment offered different insights on the lived experience of CM-MO. Future studies are needed to clarify the relationship between overused drugs and CM-MO severity: we added evidence that NSAIDs do not have protective effect in high-frequency CM-MO.

Disability and mood state in patients with episodic and chronic migraine associated to medication overuse

This study aims to compare disability and mood state in patients with episodic (EM) and chronic migraine associated to medication overuse (CM-MO), and to assess the relationships between the two outcomes. Patients, matched for age and gender, were administered the MIDAS, the WHO-DAS-2 and BDI-2. Difference between EM and CM-MO was assessed with the Kolmogorov–Smirnov Test; difference in distribution of patients with severe disability and low mood was tested with contingency coefficient; the correlation between MIDAS, WHO-DAS-2 and BDI-2 was tested with Spearman’s index. Seventy patients were enrolled: CM-MO patients reported higher BDI-2 scores and higher MIDAS and WHO-DAS-2 scores, and were more likely to have severe disability and low mood state than those with EM; BDI-2 scores were correlated with disability scores, particularly with WHO-DAS-2. The study shows that disability and mood state are negatively impacted by the presence of more frequent headaches and by the overuse of acute medications.