The rare primary headache short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is characterized by 3 to 200 attacks per day of severe unilateral orbital pain. Functional magnetic resonance imaging shows increased blood flow in the ipsilateral posterior inferior hypothalamus during attacks, indicating activation. We report the first patient with SUNCT in whom severe intractable pain (70 per day) was well controlled by electrode implant to and continuous stimulation of the posterior inferior hypothalamus. Ann Neurol 2005;57:925-927.

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) commonly complicates with coagulopathy. A syndrome called Long-COVID-19 is emerging recently in COVID-19 survivors, characterized, in addition to the persistence of symptoms typical of the acute phase, by alterations in inflammatory and coagulation parameters due to endothelial damage. The related disseminated intravascular coagulation (DIC) can be associated with high death rates in COVID-19 patients. It is possible to find a prothrombotic state also in Long-COVID-19. Early administration of anticoagulants in COVID-19 was suggested in order to improve patient outcomes, although exact criteria for their application were not well-established. Low-molecular-weight heparin (LMWH) was commonly adopted for counteracting DIC and venous thromboembolism (VTE), due to its pharmacodynamics and anti-inflammatory properties. However, the efficacy of anticoagulant therapy for COVID-19-associated DIC is still a matter of debate. Thrombin and Factor Xa (FXa) are well-known components of the coagulation cascade. The FXa is known to strongly promote inflammation as the consequence of increased cytokine expression. Endothelial cells and mononuclear leucocytes release cytokines, growth factors, and adhesion molecules due to thrombin activation. On the other hand, cytokines can activate coagulation. The cross-talk between coagulation and inflammation is mediated via protease-activated receptors (PARs). These receptors might become potential targets to be considered for counteracting the clinical expressions of COVID-19. SARS-CoV-2 is effectively able to activate local and circulating coagulation factors, thus inducing the generation of disseminated coagula. LMWH may be considered as the new frontier in the treatment of COVID-19 and Long-COVID-19. Indeed, direct oral anticoagulants (DOACs) may be an alternative option for both early and later treatment of COVID-19 patients due to their ability to inhibit PARs. The aim of this report was to evaluate the role of anticoagulants—and DOACs in particular in COVID-19 and Long-COVID-19 patients. We report the case of a COVID-19 patient who, after administration of enoxaparin developed DIC secondary to virosis and positivity for platelet factor 4 (PF4) and a case of Long-COVID with high residual cardiovascular risk and persistence of blood chemistry of inflammation and procoagulative state.

BackgroundPrognostic stratification of elderly patients with chronic obstructive pulmonary disease (COPD) is difficult due to the wide inter-individual variability in the course of the disease. No marker can exactly stratify the evolution and natural history of COPD patients. Studies have shown that leukocyte count is associated with increased risk of mortality in COPD patients. The aim of this study was to evaluate the possible role of relative lymphocyte count as a risk marker for mortality in elderly patients with COPD.Methods and resultsThis is a3-year prospective study. A total of 218patients, mean age 75.2±7 years, with moderate to severe COPD and free from conditions affecting lymphocyte count were enrolled. The population was divided into two groups according to the relative lymphocyte count, with a cut-off of 20%. Eighty-five patients (39%) had a relative lymphocyte count ≤20%. Three-year mortality rates from any cause in patients with relative lymphocyte count ≤ or > 20% were 68 and 51%, respectively (p = 0.0012). Survival curve analysis showed higher mortality in patients with relative lymphocyte count ≤20% (p = 0.0005). After adjustment for age and sex, the hazard ratio for mortality risk according to lymphocyte count was 1.79 (95% confidence interval [CI]: 1.26–2.57, p = 0.0013), even in the analysis limited to the 171 patients without congestive heart failure (1.63; 95% CI: 1.03–2.58, p = 0.038).ConclusionsLow relative lymphocyte count was associated with higher mortality in elderly patients with severe COPD.Electronic supplementary materialThe online version of this article (10.1186/s12890-018-0685-6) contains supplementary material, which is available to authorized users.

Post-traumatic headache (PTH) is the most common secondary headache disorder, corresponding to approximately 4 % of all symptomatic headaches. PTH, a cardinal feature of the post-concussive syndrome, usually shows a phenotype similar to migraine or tension-type headache. However, rare cases of PTH similar to trigeminal autonomic cephalalgias have been described. Many studies have investigated PTH prevalence and potential risk factors for its development and maintenance. In general population, the majority of PTH patients is female and has been involved in vehicle-related accidents. Generally, headache gradually disappears over few weeks or months; however, PTH could become persistent and very disabling in a minority of patients. This brief review will focus on PTH epidemiological aspects.

The use of opioids for migraine is still controversial. Evidence-based guidelines do not recommend opioids as first-line treatment of migraine attacks, while clinical and epidemiological surveys demonstrate that the use of opioids is associated with more severe headacherelated disability, symptomology and comorbidities, and greater health-care resource utilization. There are concerns that opioids may be misused or abused, leading to opioid abuse or dependence and migraineurs are particularly prone and at risk for the development of chronic daily headache from opioids overuse. Since clinical and preclinical studies evidence a pathophysiological role of opioids in migraine progression, opioids should be avoided in migraine patients.The role of opioids in clinical practice for migraine: the state-of-the-art Migraine is a common disabling neurologic disorder, characterized by recurrent headache attacks manifesting with unilateral location, pulsating quality, moderate or severe intensity, aggravation by routine physical activity, and association with nausea and/or photophobia and phonophobia [1]. The goals of acute migraine treatments are to treat attacks rapidly and consistently without recurrence, restore the patient's ability to function, minimize the use of back-up and rescue medications, optimize self-care and reduce subsequent use of resources, be cost-effective for overall management, and have minimal or no adverse events [2]. Acute treatments used for migraine include nonspecific agents such as aspirin, acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and barbiturates among others, as well as migraine-specific medications, including ergot alkaloids and triptans [2]. International guidelines recommend triptans and NSAIDs as first-line treatment of migraine attacks [2][3][4]. Use of opioids for treatment of migraine is controversial. Despite evidence-based guidelines do not recommend opioids as first-line treatment of migraine attacks [2][3][4], and no randomized controlled trial has shown any significant effect of opioids on migraine attacks when pain-free was the primary end-point of the study [5], their use in clinical practice [6][7][8] and, even more, in emergency departments (EDs) is very large, especially in USA and Canada [9,10]. Moreover, among studies about the efficacy of opioids as rescue medication for acute migraine in EDs recently revised, only one evidenced a superiority of meperidina 75 mg i.m. versus ketorolac 30 mg i.m., three reported superiority of competitors and eight reported similar results for opioids versus competitors such as DHE, metoclopramide, chlorpromazine, droperidol, and ketorolac [5]. In any case, opioids did not adequately restore the patient's ability to function. The negative impact of opioids on migrainous population is reported in several clinical and epidemiological studies. In fact, opioids use for migraine resulted associated with more severe headache-related disability, symptomology, and comorbidities (primarily, psychiatric, and cardi...

Long-COVID-19 refers to the signs and symptoms that continue or develop after the “acute COVID-19” phase. These patients have an increased risk of multiorgan dysfunction, readmission, and mortality. In Long-COVID-19 patients, it is possible to detect a persistent increase in D-Dimer, NT-ProBNP, and autonomic nervous system dysfunction. To verify the dysautonomia hypothesis in Long-COVID-19 patients, we studied heart rate variability using 12-lead 24-h ECG monitoring in 30 Long-COVID-19 patients and 20 No-COVID patients. Power spectral analysis of heart rate variability was lower in Long-COVID-19 patients both for total power (7.46 ± 0.5 vs. 8.08 ± 0.6; p < 0.0001; Cohens-d = 1.12) and for the VLF (6.84 ± 0.8 vs. 7.66 ± 0.6; p < 0.0001; Cohens-d = 1.16) and HF (4.65 ± 0.9 vs. 5.33 ± 0.9; p = 0.015; Cohens-d = 0.76) components. The LF/HF ratio was significantly higher in Long-COVID-19 patients (1.46 ± 0.27 vs. 1.23 ± 0.13; p = 0.001; Cohens-d = 1.09). On multivariable analysis, Long-COVID-19 is significantly correlated with D-dimer (standardized β-coefficient = 0.259), NT-ProBNP (standardized β-coefficient = 0.281), HF component of spectral analysis (standardized β-coefficient = 0.696), and LF/HF ratio (standardized β-coefficient = 0.820). Dysautonomia may explain the persistent symptoms in Long COVID-19 patients. The persistence of a procoagulative state and an elevated myocardial strain could explain vagal impairment in these patients. In Long-COVID-19 patients, impaired vagal activity, persistent increases of NT-ProBNP, and a prothrombotic state require careful monitoring and appropriate intervention.

Mood and anxiety disorders are comorbid with migraine. The coexistence of a psychiatric disorder alters the quality of life, the total disability, the course of migraine and the final prognosis; it increases the probability of central sensitization, other chronic pain conditions and the evolution to chronic migraine. All patients presenting with frequent episodic and chronic migraine should be screened for depression and anxiety. When these conditions are present, drugs for migraine prevention that may worsen the psychiatric comorbid disorder have to be avoided. When it is possible, both conditions should be treated with a single agent. Amitriptiline can be used both in mood disorders and migraine prevention. Flunarizine and beta-blockers may help if anxiety is present. Pregabalin has demonstrated efficacy in anxiety disorders and fibromyalgia. Divalproex sodium, topiramate and lamotrigine that have demonstrated efficacy in mood stabilization are also indicated in migraine without aura (divalproex sodium and topiramate) and with aura (lamotrigine). When a specific treatment for the comorbid psychiatric disorder is needed, the selective serotonin reuptake inhibitors or the serotonin norepinephrine reuptake inhibitors are the drugs of choice both in depression and anxiety, and the cognitive behavioural therapy has good evidence of efficacy in anxiety disorders. Vagal nerve stimulation may be an option in patients with refractory chronic migraine and depression.