Unusual presentation of COVID-19 Headache. its Possible Pathomechanism

S. no. Study detail N Where is the source of the headache Type of headache and percent Associate symptoms or triggers Progression of symptoms Investigations, trends in the laboratory and other related conclusions Key elements/Outcomes inference and drawbacks Reference 1 Edoardo Caronna et al., Spain. Sept . 2020. Prospective study. N = 130 The number of respondents was 74.6 7.6% (97/130) Female = 57.7 percent, mean age is 50.6+-15.3 B/L frontal 47.4 percent, Holocranial 38.1 percent Cervical fronto-cervical 6.2 percent, Hemicranial 5.2%, Cervical 4.1 percentage Pressing 70.1%, Throbbing 19.6%, Drilling 5.2%, Shooting 4.1%, Burning 1.0%. Nausea vomiting, nausea, photophobia daily pain, phonophobia getting worse with movement Anosmia, ageusia vertigo, dizziness and neck stiffness After six weeks 37.8 percent (28 of 74 patients who were followed-up) suffered from a persistent and persistent headache A stable or low level of LDH and IL-6. LDH was observed with headache Low or stable levels of the IL-6 and LDH was observed with headache. However, D-dimer ferritin and CRP exhibit the same pattern with as well as without the headache. Headache that is not connected to fever. Reacted to treatment for acute symptoms. Efficacy: (Yes = 58.6%, No = 41.4%) [3] 17.7% out of 60.7 77% of them had a continuous headache that lasted for a full day. D-dimer and ferritin as well as CRP all show the same pattern with or without headaches The time span of COVID-19-related disease for patients with headaches is 23.9+-11.6 days (compared to 31.2+-12 days for non-headache COVID-19 sufferers) No difference in mortality was observed in the group with headache. They believed that different mechanisms could be at work in the brain, which could explain the various characteristics of headaches under different conditions. 2 Pedro Augusto et al. Brazil. September 2020. Cross-sectional study. N = 73 N = 64.4 6.4% (47/73). Median age : 56. Male = 59.6 percent (28/47) Frontal 80%, Temporal 55%, Parietal 49%, Occipital 36%, Bilateral 94%. B/l migraine phenotype (51%), TTH like 40% Hyposmia or Anosmia = 38.4 percent No No No scans were performed or cerebrospinal liquid (CSF) evaluation was conducted. 80percent of patients reported that the present headache was distinct from the previous headaches. [5] Anxiety history prior to headache; Migraine or TTH Total 64 percent Cough-related headache (16.4 percent total) The cough trigger TTH = 4, cough trigger migraine is 4, and cough trigger TTH = 4. Ageusia or hypogeusia = 39.7 percent Anosmia/hyposmia was present for the median time of 10 weeks (6-17.5 day). Ageusia, or hypogeusia (39.7 percent) was present for a median of five weeks (4.5-8.5 Days). No difference in gender. Certain subjects’ anosmia remained for more than 3 months. Daily, new headaches were reported by 11 people. 3 Rehab et al. Egypt. 2020. Cross-sectional study. N = 172 Headache headache, n = 172/172 Diffuse = 52.9%, temporal = 18%, Frontal = 23.3%, occipital = 5.8% Pressing = 40.7%, exploding = 26.2%, Dull = 16.9%, Throbbing = 16.3% If a/w fever was present the intensity of headaches, as well as frequency were more intense No CRP is a procedure that can be done. A higher level of CRP typically reduces the threshold for pain to 6(37) however, during this research, CRP showed no correlation with headache frequency or intensity Scans: not completed [1] Median Age = 33 Intensity of the test: mild = 67.4 percent moderate = 24.4 percent severe = 8.1 percent If dehydration was present, only the frequency of headaches was higher A high neutrophil/lymphocyte ratio is seen in migraine attacks 6(40) but no relation found with lymphocytes level Male = 37.2%, Female = 62.8% There is no correlation between Ferritin level or levels in D-dimer (although D-dimer levels are often high in migraine) Migraine = 26.2 percent TTH = 26.7 percent 4 Ozge Uygun et al. Turkey, Istanbul. 2020. A Survey study that is based on a questionnaire online with two groups: Group 1) COVID-positive headache group, and Group 2) COVID patients who are not diagnosed who have developed new headaches in the context of the pandemic. It’s a cross-sectional design. N = 3458 Headache, not 1886. Bilateral: 85percent of the COVID group, and 64 percent in the non-COVID group. In the COVID group, new onset headaches have been identified In COVID group new onset headache: Pulsating = 32.5 percent Pressing = 43.7 percentage Stabbing = 16.1 percent Fiery = 2.3 percent In the COVID group and non-COVID group Anosmia/ageusia: 60.4 percent, gastrointestinal disturbance = 57.7 percent (diarrhea nausea, stomachache) Phonophobia, photophobia and allodynia. Osmophobia is the most common (reported only in the COVID group) General course of headache in severity = 23.3% Among 1886 patients. the severity of headache = 23.3% Reduced the severity of headache = 72.4% Duration increase = 28.7% Duration decreased = 66.4% Frequency increases = 28.7% Reduced frequency = 12.3 The percentage of patients with associated symptoms increased to 14% No The chance to research headaches of patients with COVID and those without here. In comparison to previous headaches 50% of patients experienced an entirely different kind of headache the first headache [6] Age = 43.21+-11.2 In headaches that are not COVID In non-COVID headaches: Pulsating = 42.5 percent and pressing = 38.6 percentage Stabbing = 11.2 percent and Fiery = 5 Triggers (In the trend of decreasing percentage) in the COVID group: stress, infection itself, drug use masks and social isolation If a previous experience of headache is found in both groups, then the pulsating quality headache occurs in 50.9 percent and 55.5 percent, respectively. One drawback to the study is the report bias that the patient was not screened; individuals with education could have participated as a result of the web-based survey. Male in COVID Group = 40%. males in the non-COVID group = 25 percent Intensity of COVID headache Mild = 26.6 percent moderate = 47.7 percent Severe = 23.4 percent Triggers in the COVID non-COVID group The triggers are stress social isolation, stress, and wearing masks Males are at a higher risk It could be due to one of the following: 1)) hormones that protect females are anti-inflammatory properties. 2) the ACE-2 site might be linked to the X chromosomes that have a high level of immune function for females and the expression of ACE-2 various The intensity is nearly like a headache that is not COVID. Gastrointestinal disorders: Relative to the gut-brain-axis, and inflammation mediators such as IL-1 TNF-alpha, IL-6 and gut microbiota. CGRP 22.5 percent of patients who had COVID-19 who had a prior experience of headaches and headaches, didn’t experience any headaches when they were infected. There was no clear cause however, it could be due to lower viral burden or individual variations 5 Tugce Toptan et al. Turkey. 2020. A case collection of thirteen patients. N = 13 Patients suffering from headaches Headache patients, n = 13 Holocranial, bilateral frontal and temporal zones A rapid onset, Throbbing quality which is superimposed by press and stabbing character Phonophobia, Photophobia, Nausea Osmophobia, weight loss No No scans were made. Previous migraine sufferers reported that the symptoms as severe compared to previous experiences of headaches prior to the viral infection [7] Female = 9/13 The severity of the headache ranged from moderate to severe. Affected by movements and bent forward All headaches were distinct from prior history of headaches. Partially responsive to NSAIDs and paracetamol was observed. 9/13 patient’s headache was cured within 72 hours. Of that, 5/13 was a migraine victim. 1/1 was diagnosed with TTH. 2/1 (case 4 and 7) was a case with an background of DM A significant decrease in body weight (5 kg over three days) was observed, but it was without any connection to eating disorders or diarrhea and lasting for one day. This could be due to catabolism that is attributed to cortisol levels or cytokines 6 Pedro Augusto et al. Brazil. 2020. Case report. N = 1. Female The headache first appeared at the 5 ^day-day of the illness. Frontotemporal Pulsating characteristic. Duration = 7 days, constant and intense intensity 4 ^{day. 4} day, I had anosmia and facial pain that persisted for 48 hours Pt states that her intra-covid headache was very different and disturbing in comparison to her COVID headaches even though the character was like migraine. No scans done The cause of headache is not the intake of painkillers. Despite the use of painkillers, headaches improved gradually , and so the medication overuse headache (MOH) is not ruled out in this case, but it could be classified as a possible new daily permanent headache (NDPH) due to the fact that the COVID headache was present for approximately 3 months [8] 40 years old 5 ⁵-day headache with Phonophobia and photophobia. It also gets worse by slight movements Following follow-up after the 85th day of COVID disease and in the this follow-up, persistent headache and anosmia can be seen. The headache lasts for 6 hours and can be severe or moderate in intensity, frequency not specified. Previous history of migraine that included or without aura There was no lumber puncture. MRI, MRA, and MRV were all normal, with no enhancement of contrast (this scan was performed within 23 days of the onset of the first symptoms) 7 Robert Belvis. Barcelona, Spain. 2020. Case report. N = 1. Male. Professionally trained as a Neurologist, specialist in headaches Posterior to disperse Headache phenotypes within the three days prior to the onset 1 ^1st Day: Synodic fulfilled the criteria of ICHD3 (code9.2.2.1) moderate pain moderate intensity associated with fever, and was well-responded to Acetaminophen Anosmia dysgeusia, dysgeusia during the initial three days On 7 ⁷ morning: recurrence of a headache. A diffuse location, constant with moderate intensity and mild cervical stiffness, and photophobia Acute phase reactant: D’dimer ferritin, procalcitonin and CRP were elevated, but lymphopenia was low with a low platelet count. Potential triggers for TTH may be a cervicogenic cause caused by the phone use in the bed, stress from fear of a negative prognosis for the disease in the future or insomnia caused by anxiety [9] Age = 51 years old 2 ^2nd Day: Primary headache of cough (code 9.2.2.1) A abrupt onset, lasted for 2 minutes in the posterior and b/l locations and b/l location. It was well-responded to the above medication On the 7th day: It is associated with stiff neck and photophobia 7 ⁷-day headache: More severe with changes in posture and physical activity due to hypercapnia and hypoxia (code 10.1) 7 ⁷-day headaches could be the result of a cytokine surge more of an aseptic activity in the meningeal and may be included in ICHD3-Headache as a result of other non-infect intracranial inflammation (code 7.3.3) as well as due as a result of exposure to different substances (code 8.1.11) such as cytokines 3 ^3rd Day 3rd Day: pressing migraine (code2) of a tension-type headache, mild intensity gradual, tenderness in the splenius, sternocleidomastoid and trapezius 8 Javier Trigo et al. Spain. 2020. Cohort design. Retrospective study. The number of participants was 580. Headache No headache, n = 137/580. No headache Headache, 170/580 = There were no detailed descriptions given regarding the exact location or nature of the headache. Headache is the 1 ^1st sign of headache is seen in 26 percent of patients Anosmia-related headache = 46.7 percent and syncope = 6.6 percent No Significantly significant mean values for lab parameters in both groups, and the “No-headache” group had higher values, as follows The worst lymphocyte, leucocyte, LDH count, CRP, Procalcitonin, ferritin, D-Dimer, IL-6, and the worst INR values The headache is interpreted as an atypical sign of COVID-19, and has a lower risk of death, as an independent factor. Similar results with no less prognosis for COVID-19 patients in the meta-analysis of 19 studies conducted in the first quarter of 2020. [4] Mean Age is 59.25 years Female = 58.4 percent Headache is felt: Within 1 day = 38.5 percent, In two days = 62.5%, and within three days, 74 percent Non-headache group: associated with anosmia 18.7 percent and syncope = 7.7 percent No brain scans done Lower inflammatory markers might not trigger a surge of cytokines, which results in lower mortality Co-morbidities HTN = 38 percent and DM = 14.6 percent, smoking = 14.6 percent CVS = 13.9 Percentage Pulmonary = 24.1 percent Cancer = 13.1%, Previous headache = 10.9 percent, ACEi and ARBs equal 30.7 percent The drawbacks are the absence of imaging studies and CSF studies. A single center study. The study sample consisted of just hospitalized patients. A retrospective study that included relatives who were also contacted in lieu of patients. Details about the character of headaches were was not provided. In a different prospective cohort study of COVID-19 patients in 179 hospitals and a mortality rate of 3% recorded for headache was higher (23.8%)) when compared with those who had not headache. 9 David et al. Spain. 2020. Study cross-sectional, with hospitalized patients. N = 576 Headache 22.6 percent (130/576) however, 104 of them were that were part of the study Quality and location were mentioned within the red flags for headache part 1 ^1st COVID symptom: headache is reported in 26.0 percent of patients Anosmia= 64.4%, AMS = 9.6 percent, Weakness= 1.9 percent Vertigo = 2.9 percent, loss of consciousness = 5.8 percent Headache-related red flags were observed in 95.2 percent of patients. the most common was changes in the nature of headache that was preexistent, which was observed in 49.0 percent. Blood tests Lymphopenia = 21.1 percent, higher LDH = 48 percent INR = 8.7 percent D-Dimer is 54% CRP = 84%. Procalcitonin = 3.8 percent The most frequent atypical manifestation of headaches that take the form of warning signs is a pattern change in headache. This is 49%, new start in headaches = 42.3 percent, and the most severe headache = 37.5 percentage. (Could be a false high due to a history of headache) [10] Mean age is 67.6 years+ 12.2 The headache symptoms were questioned about Prior Medical history Onset >50 years = 72.1 percentage, h/o tumor = 12.5 percent, and Immune-compromised condition = 4.8 percent. No scans done Other conditions are associated with systemic issues like fever= 89.4 percent and cough= 84.6%, elevated CRP= 84 percent Female = 74.1 percent The headache red flags were questioned about recent symptoms of headache Precepting factors = 37.5 percent, thunderclap beginning = 4.8 percent, changes of pattern is 49 percent, progressive worsening = 17.3%, ocular discomfort equals 30.8 percent or any other autonomic feature of the cranium are 5.8%, pattern of posture equals 6.7 percent, disrupting sleep = 16.3 percent, the most severe headache to date = 37.5 percentage unilaterality equals 15.4 percent Treatment resistance is 14.4 percentage The study was limited to patients admitted to hospital with severe symptoms. Here in this study, 95 percent of patients had pneumonia Co-morbidities HTN = 34.6 percent The DM is 11.5 percent, smoking 11.5 percent CVS = 8.7%, Pulmonary = 23.1 percent, Cancer= 12.5 percent, Previous headache = 57.7 percent Migraine= 16.3%, TTH = 28.8 percent Family headache = 37.5 percent, on the other hand, ACEi or AT-II= 28.8 percent CSF research and scanning were not carried out because of a shortage of equipment Focused on phenotypes, but not focusing on it. 10 Omer Karadas et al. Turkey. October, 2020. A cross-sectional prospective study. N=287 Headache, n= 28.9% (83/287). From the 83 subjects, 85.5% had no complaints of headache. Frontal= 54%, Occipital= 15.6%, Frontotemporal= 3.6%, Unilateral= 7.2%, Bilateral= 92.8% Throbbing= 56.6%, Pressing= 25.3%, Stabbing= 8.4%. Hyposmia= 8.4%, agneusia= 7.2%, Photophobia= 30.1%, Phonophobia= 27.7%. Others included the loss of appetite as well as weight loss and diarrhea No D-dimer was prevalent in the headache group. B/L headache was prevalent in frontal areas and also had higher IL-6 levels and D-dimer concentrations. The quality of the throbbing had a higher response to medication. The loss of appetite, weight reduction, and diarrhea were prominent in the group with headaches (could be due to CGRP neuro-peptides released by both the digestive and nervous system) [11] Male (58 percent of patients suffering from headaches were male) Injecting paracetamol intravenously 1000mg, and greater orccipital nerve block (GON) with lidocaine at 2% were employed. The high levels of IL-6 and pneumonic patients were more likely to have greater VAS scores. Patients who were not responsive to medical treatments were young, with an average age of 40 years and had high levels of IL-6. Co-morbid states in headache group: HTN= 39.8%, DM= 14%, CAD= 9.6% Patients that responded to the GON block younger and, as a result, unresponsive patients had a high level of IL-6. This study revealed hyposmia rate of 5% and a very high recovery rate were found suggesting that hyposmia does not serve as an outcome predictor. 11 Javier et al. Madrid, Spain. 2020. Study of cross-sectional areas in an emergency room. N = 145. Possible COVID-19 patients as the study was conducted in an emergency department. Headache 68.3% (99/145) Bilateral = 86.9 Percent, Holocranial = 34.3%, Bifrontal = 34.3% Pressing = 73.7%, Throbbing = 14.1%, Stabbing = 11.1%, Burning = 1% Anosmia = 49.5%, light aversion = 29.3%, phonophobia = 27.3%, osmophobia= 9.1% No No Noted diverse headache semiology. Migraineurs presented with more intense symptoms earlier, and also had a longer headache. [12] Average Age 42.7+-11.5 (Range 21- 70 yrs.) Moderate to extreme intensity Triggers included afternoon fever, physical exercise and coughing No CSF studies were done. It was impossible to determine if SARS-CoV-2 meningitis was present. The patient had a different headache quality when compared with the previous patients. Female = 36.4 percent One patient presented with trigeminal autonomic symptoms of edema in the eyelids and the otics were full with an the ipsilateral headache. One patient was diagnosed with visual aura History of headache = 33.3 percent, hypertension = 15.2 percent, DM = 3%, Dyslipidemia = 11.1%