Roberto De Simone

Headache, anxiety and depressive disorders: the HADAS study

The objective of this paper was to assess prevalence and characteristics of anxiety and depression in migraine without aura and tension-type headache, either isolated or in combination. Although the association between headache and psychiatric disorders is undisputed, patients with migraine and/or tension-type headache have been frequently investigated in different settings and using different tests, which prevents meaningful comparisons. Psychiatric comorbidity was tested through structured interview and the MINI inventory in 158 adults with migraine without aura and in 216 persons with tension-type headache or migraine plus tension-type headache. 49 patients reported psychiatric disorders: migraine 10.9%, tension-type headache 12.8%, and migraine plus tension-type headache 21.4%. The MINI detected a depressive episode in 59.9, 67.0, and 69.6% of cases. Values were 18.4, 19.3, and 18.4% for anxiety, 12.7, 5.5, and 14.2%, for panic disorder and 2.3, 1.1 and 9.4% (pxa0=xa00.009) for obsessive–compulsive disorder. Multivariate analysis showed panic disorder prevailing in migraine compared with the other groups (OR 2.9; 95% CI 1.2–7.0). The association was higher (OR 6.3; 95% CI 1.4–28.5) when migraine (with or without tension-type headache) was compared to pure tension-type headache. This also applied to obsessive–compulsive disorder (OR 4.8; 95% CI 1.1–20.9) in migraine plus tension-type headache. Psychopathology of primary headache can reflect shared risk factors, pathophysiologic mechanisms, and disease burden.

Chronic migraine classification: Current knowledge and future perspectives

In the field of so-called chronic daily headache, it is not easy for migraine that worsens progressively until it becomes daily or almost daily to find a precise and universally recognized place within the current international headache classification systems. In line with the 2006 revision of the second edition of the International Classification of Headache Disorders (ICHD-2R), the current prevailing opinion is that this headache type should be named chronic migraine (CM) and be characterized by the presence of at least 15xa0days of headache per month for at least 3 consecutive months, with headache having the same clinical features of migraine without aura for at least 8 of those 15xa0days. Based on much evidence, though, a CM with the above characteristics appears to be a heterogeneous entity and the obvious risk is that its definition may be extended to include a variety of different clinical entities. A proposal is advanced to consider CM a subtype of migraine without aura that is characterized by a high frequency of attacks (10–20xa0days of headache per month for at least 3xa0months) and is distinct from transformed migraine (TM), which in turn should be included in the classification as a complication of migraine. Therefore, CM should be removed from its current coding position in the ICHD-2 and be replaced by TM, which has more restrictive diagnostic criteria (at least 20xa0days of headache per month for at least 1xa0year, with no more than 5 consecutive days free of symptoms; same clinical features of migraine without aura for at least 10 of those 20xa0days).

Changes in cerebral blood flow velocities during childhood absence seizures

A simultaneous recording of mean flow velocity in the right middle cerebral artery by transcranial Doppler ultrasonography and electroencephalographic activity was performed in 5 children with multiple daily typical absence seizures. Twenty-eight absence episodes were recorded. Mean flow velocity increased gradually a few seconds before the clinical and electroencephalographic manifestations of each seizure and reached the maximum values (range of increase: 25.5-42.8% with respect to baseline) within 2-3 seconds from their onset. This increase was then followed by a fast reduction in flow velocity, with the lowest levels (range of decrease: 30.8-44.0% with respect to baseline) recorded within 4-6 seconds from the end of each absence seizure. These findings suggest that changes in cerebral blood flow and activity are quite complex during absence seizures and that they do not fully correlate with clinical and electroencephalographic manifestations.

Intracranial pressure in unresponsive chronic migraine

To assess the prevalence and possible pathogenetic involvement of raised intracranial pressure in patients presenting with unresponsive chronic migraine (CM), we evaluated the intracranial opening pressure (OP) and clinical outcome of a single cerebrospinal fluid withdrawal by lumbar puncture in 44 consecutive patients diagnosed with unresponsive chronic/transformed migraine and evidence of sinus stenosis at magnetic resonance venography. The large majority of patients complained of daily or near-daily headache. Thirty-eight (86.4xa0%) had an OP >200xa0mmH2O. Lumbar puncture-induced normalization of intracranial pressure resulted in prompt remission of chronic pain in 34/44 patients (77.3xa0%); and an episodic pattern of headache was maintained for 2, 3 and 4xa0months in 24 (54.6xa0%), 20 (45.4xa0%) and 17 (38.6xa0%) patients, respectively. The medians of overall headache days/month and of disabling headache days/month significantly decreased (pxa0<xa00.0001) at each follow-up versus baseline. Despite the absence of papilledema, 31/44 (70.5xa0%) patients fulfilled the ICHD-II criteria for “Headache attributed to Intracranial Hypertension”. Our findings indicate that most patients diagnosed with unresponsive CM in specialized headache clinics may present an increased intracranial pressure involved in the progression and refractoriness of pain. Moreover, a single lumbar puncture with cerebrospinal fluid withdrawal results in sustained remission of chronic pain in many cases. Prospective controlled studies are needed before this procedure can be translated into clinical practice. Nonetheless, we suggest that intracranial hypertension without papilledema should be considered in all patients with almost daily migraine pain, with evidence of sinus stenosis, and unresponsive to medical treatment referred to specialized headache clinics.

Panic disorder or epilepsy? A case report

Psychiatric and neurological disturbances can show up with panic attack symptoms. This report illustrates the difficulty in distinguishing between panic disorder and epilepsy in a subgroup of epileptic patients that suffer panic attacks as symptoms of seizures. This is the first report of panic attacks due to a focal lesion involving the left temporal lobe and the second case of panic attacks related to a meningioma.

Sinus Venous Stenosis–Associated Idiopathic Intracranial Hypertension Without Papilledema as a Powerful Risk Factor for Progression and Refractoriness of Headache

Data from two recent studies strongly support the hypothesis that idiopathic intracranial hypertension without papilledema (IIHWOP) could represent a powerful risk factor for the progression of pain in primary headache individuals. The first study highlights that an asymptomatic IIHWOP is much more prevalent than believed in the general population and occurs only in central venous stenosis carriers. In the second study, about one half of a large consecutive series of unresponsive primary chronic headache patients shows significant sinus venous stenosis. A continuous or intermittent IIHWOP was detectable in 91% of this subgroup and in no patient with normal venography. Moreover, after the lumbar puncture, a 2- to 4-week improvement in headache frequency was observed in most of the intracranial hypertensive patients. These findings strongly suggest that patients prone to primary headache who carry central venous outflow abnormalities are at high risk of developing a comorbid IIHWOP, which in turn is responsible for the progression and the unresponsiveness of the pain. Based on the available literature data, we propose that central sinus stenosis–related IIHWOP, although highly prevalent among otherwise healthy people, represents an important modifiable risk factor for the progression and refractoriness of pain in patients predisposed to primary headache. The mechanism could refer to up to one half of the primary chronic headache patients with minimal response to treatments referring to specialized headache clinics. Due to the clinical and taxonomic relevance of this hypothesis further studies are urgently needed.

Is chronic migraine a primary or a secondary condition

In the light of the pathophysiologic knowledge acquired in recent years, a tentative redefinition of some types of headache, until now defined as primary, is now possible. Chronic migraine is proposed here as the consequence of “processes” to be ascribed to mechanisms activated by comorbid conditions. The observations supporting the possibility that allodynia represents the process leading to pain progression, which occurs in some migraineurs, are discussed.

Sinus venous stenosis-associated IIHWOP is a powerful risk factor for progression and refractoriness of pain in primary headache patients: a review of supporting evidences.

Reported prevalence of idiopathic intracranial hypertension without papilledema (IIHWOP) in series of patients with chronic or transformed migraine is significantly higher than expected; yet, IIHWOP is not included among the risk factors for migraine progression. However, several studies provided evidences suggesting that IIHWOP could represent a possible, largely underestimated, risk factor for progression of pain in migraine and, possibly, in other primary headaches. Data from two recent studies, albeit aimed to different end-points, strongly support this hypothesis. In the first study, conducted on a large series of neurological patients without any sign or symptom of raised intracranial pressure (ICP), including chronic headache, the prevalence of bilateral central venous stenosis at magnetic resonance venography (MRV) was 23% and an IIHWOP at opening pressure was found in 48% of this subgroup (11% of the whole sample) while it was not detected in any of the subjects with normal MRV. This indicates that IIHWOP may be much more prevalent than believed in general population and that it can run without any symptom or sign of raised ICP in most of affected subjects. In the second paper, sinus venous stenosis-associated IIHWOP has been found in about one half of a large chronic primary headache patients series with poor response to treatments and in none of those with normal MRV. Moreover, after the diagnostic lumbar puncture, a transient improvement of headache frequency has been observed in the majority of intracranial hypertensive chronic headache subjects. Taken together, the data of these two recent papers rise the following hypothesis: (1) asymptomatic IIHWOP is much more prevalent than expected in general population; (2) IIHWOP is a powerful and largely unrecognized risk factor for progression of pain in primary headache patients; (3) sinus venous stenosis at MRV is a reliable predictor of raised intracranial hypertension also in asymptomatic patients; (4) sinus venous stenosis has a causative role in IIH pathophysiology. These assumptions share a potential high clinical impact and need to be urgently tested in adequately designed controlled studies.

Inter-hemispheric asymmetry of cerebral flow velocities during generalized spike-wave discharges

The aim of this study was to verify the symmetry of cerebral blood flow changes during the generalized spike-wave discharges of typical absence seizures. A recording of mean flow velocity in the left and right middle cerebral arteries and of electroencephalographic activity was performed simultaneously in two subjects with multiple daily absence seizures. A total of 12 generalized spike-wave discharges were recorded. Mean flow velocities showed a significant increase during the discharges with respect to baseline. The increase of flow velocity started simultaneously or a few seconds before the discharges. In 91.6 % of all recordings, the percentage increase of mean flow velocity was significantly higher in the left than in the right side (7.03 % ± 3.3 vs 5.14 % ± 3.3; p < 0.1). The extent of the following decrease of flow velocity was also significantly greater in the left than in the right side (-16.91 % ± 8.1 vs -14.07 % ± 8.3; p < 0.01). These findings show an inter-hemispheric asymmetry in cerebral blood flow during generalized spike-wave discharges in two patients with absence seizures. Transcranial Doppler ultrasonography promises to be an interesting approach to detect rapid changes in cerebral hemispheric activity not otherwise recognizable.

Patterns of care of brain tumor-related epilepsy. A cohort study done in Italian Epilepsy Center

Epilepsy is the most common comorbidity in patients with brain tumors. Study Aims: To define characteristics of brain tumor-related epilepsy (BTRE) patients and identify patterns of care. Nationwide, multicenter retrospective cohort study. Medical records of BTRE patients seen from 1/1/2010 to 12/31/2011, followed for at least one month were examined. Information included age, sex, tumor type/treatments, epilepsy characteristics, antiepileptic drugs (AEDs). Time to modify first AED due to inefficacy and/or toxicity was assessed with the Kaplan-Meier method and Cox proportional hazard models were used to identify predictors of treatment outcome. Enrolled were 808 patients (447 men, 361 women) from 26 epilepsy centers. Follow-up ranged 1 to 423 months (median 18 months). 732 patients underwent surgery, 483 chemotherapy (CT), 508 radiotherapy. All patients were treated with AEDs. Levetiracetam was the most common drug. 377 patients (46.7%) were still on first drug at end of follow-up, 338 (41.8%) needed treatment modifications (uncontrolled seizures, 229; side effects, 101; poor compliance, 22). Treatment discontinuation for lack of efficacy was associated with younger age, chemotherapy, and center with <20 cases. Treatment discontinuation for side effects was associated with female sex, enzyme-inducing drugs and center with > 20 cases. About one-half of patients with BTRE were on first AED at end of follow-up. Levetiracetam was the most common drug. A non enzyme-inducing AED was followed by a lower risk of drug discontinuation for SE.