Headache Patterns in Cerebral Venous Sinus Thrombosis

Inclusion criteria

Patients of CVT who were present in neurology casualty or were admitted to Neurology wards and those who were conscious, cooperative, and were able to give a reliable history.

The diagnosis of CVT was based on clinical presentation and confirmation by imaging (computed tomography [CT] with CT venogram/magnetic resonance [MR] brain with MR venography)

Anemia was considered mild when hemoglobin levels are 11–11.9 g/dl in women and 11.0–12.9 g/dl in men; moderate when hemoglobin levels are 8–10.9 g/dl (both men and women); and severe when hemoglobin levels are lower than 8 g/dl.

Exclusion criteria

The patients with the following features: (1) arterial stroke, (2) unconscious or uncooperative patient who was unable to provide a reliable history, (3) head trauma, (4) neuro infection, (5) nonavailability of reliable history (at the time of recruitment if the history is given by a person/relative who was not with the patient at the onset of symptoms and may provide inaccurate history), and (6) patients in whom the diagnosis was not confirmed by imaging studies (CT with CT venogram or magnetic resonance imaging brain with MR venogram).

The patients were interviewed by investigators in the preformed format, and details of history with particular reference to headache and CVT were recorded. Details of headache included mode of onset, location, severity, pattern, and evolution, associated symptoms, aggravating factors, relieving factors, and other comorbidities. A visual analog scale (VAS) was used to record pain severity (severe headache = VAS >70).[13] Headache severity was assessed by visual analog scale where numerical pain rating scale 0–100 was used. The absence of pain was given a score of 0 and worst pain was given a score of 100 in numerical pain rating score. The headache severity was recorded at the time of recruitment and at the time of discharge. Three modes of onset of headache were defined depending on the time between the initial pain sensation and the most severe headache.

Sudden/thunderclap like was the headache that began with catastrophic sudden onset with a VAS more than (80/100) reaching maximum intensity in <1 min, and lasting more than 1 h. Acute headache was defined by the duration from onset of <24 h. Subacute was defined as duration of more than 24 h and <14 days. Chronic headache was defined by duration of more than 14 days

The patients were treated with anticoagulation in the form of unfractionated heparin 5000–10,000 units intravenous (IV) initially, followed by 50–70 units/kg (5000–10,000 units) q4–q6 h for 10–14 days followed by oral anticoagulation. The patients were given standard antiepileptics for seizures (phenytoin; valproate; levetiracetam), antiedema measures (mannitol - 1.5–2 g/kg IV infused over 30–60 min; oral glycerol; acetazolamide), and general nursing care as per the decision of the treating physician. The patients were given inpatient care in ward or intensive care unit depending on the clinical condition. In case of worsening due to raised intracranial pressure (ICP) and midline shift, the patients were taken up for decompressive craniectomy.

The outcome was measured in terms of VAS, Barthel's index and modified Rankin Scale (mRS). The degree of independence in activities of daily living was assessed by Barthel's index. The degree of disability was assessed by mRS. Barthel's index and mRS were assessed both at admission and at discharge.

Statistical analysis

The data were collected systematically and analyzed by SPSS Version 16 (IBM SPSS, IBM Corporation Armonk, New York, USA) software using descriptive statistics, t-tests, Pearson's correlation for parametric data and Spearman's correlation for nonparametric data. We had calculated two-tailed P value and our significant cutoff value was set at 95% confidence interval and P ≤ 0.05.

Mode of presentation

Acute headache was the most common presentation in our series followed by subacute type. The acute presentation was also the most common type in International Study on Cerebral Vein Thrombosis (ISCVT) study although in the series by Damak et al. study the mode of onset was predominantly subacute (72%). Another study reported similar findings as our series.[14] One reason for these differences could be the criteria used to define the acute, subacute and chronic type of a headache during recruitment in these studies. The criteria used by Damak et al. was acute <2 days, subacute 2 days to 1 month and chronic was more than 1 month.[15] Wasay et al. used 1–3 days as acute, 4–14 days as subacute and more than 14 days as chronic. A study by Cumurciuc et al. defined only acute and thunderclap headache in their series of 17 cases and found headache of progressive type as the most common type (>24 h).

We found the first symptom as headache in 95% of the patients. However, the patient presenting only with headache were 6.38%, and the most common sinus involved was transversal sinus (TS) and superior sagittal sinus (SSS) in our cohort. We could not demonstrate laterality of headache in our cohort due to coexisting involvement of other sinuses. The commonest type of headache observed in our study was holocranial or bifrontal probably due to this reason. In our cohort, 11 (23.4%) patients had headache as the sole presentation. A French study on 123 patients of CVT, found that headache was the only clinical symptom at presentation in 23% (17) of the patients. The lateral sinus was the most common sinus that was involved in these patients. Once established a headache was continuous in 15 patients and was usually ipsilateral to the occluded sinus.[11] Sparaco et al. reported headache as a sole manifestation of CVT in nearly one-third of the patients.[16] Timóteo et al. reported headache as the only presenting symptom in 40% of their patients.[17] Wasay et al. found no association between localization of headache and site of sinus thrombosis, however, they found association between the involvement of sigmoid sinus alone or in combination with transverse sinus and localization of pain to occipital area and neck. Other studies have not published any such association.[17]

In our study, prothrombotic state was seen in 68.1% cases. 5 (10.6%) cases had mild anemia, 13 (27.7%) had moderate anemia, 8 (17%) had severe anemia, and 9 (19.1%) had polycythemia.[18] The mean hemoglobin level was 11.52 ± 3.54 g/dl. Phlebotomy was opted for these patients with polycythemia. Previous studies had mentioned anemia and polycythemia as a risk factor for CVT.[19202122] Secondary causes of anemia and polycythemia were evaluated. One patient with polycythemia had dehydration. One patient with anemia had rheumatoid arthritis. There were no underlying malignancies in any of these patients. None of the cases were detected to be myeloproliferative neoplasms in hospital. The other causes of thrombotic states were puerperal in 40.4%, and oral contraceptive pill (OCP) pill usage in 10.6% in women. In ISCVT study, the most common prothrombotic state was OCP's in 54.3%, genetic in 22%, acquired in 15.7%, and puerperal in 13.8%.[1] In the series by Damak et al. the most common prothrombotic causes were OCP's and other etiologies.[15] Martinelli et al. have reported a strong association between OCP's usage and risk of CVT.[23] OCPs cause a decrease in protein S levels and hypercoagulability.[24]

Headache characteristics

In our study, holocranial headache was the predominant type of headache followed by frontal and most of the patients presented with bilateral headache [Table 2]. Although one previous study has reported unilateral headache as the most common type which was either localized to frontal, temporal, occipital and neck. They reported unilateral headache in 37%, localized headache (frontal, temporal, occipital, and neck) in 19% and diffuse in 20% of the patients. They also found the quality of headache as band like in 27 (20%), other (pounding, exploding, stabbing, etc.) types in 26 (20%), throbbing in 12 (9%), and thunderclap in 7 (5%). Another study also has reported headache as the most frequent symptom of CVT.[25]

In the series by Cumurciuc et al. (n = 17) throbbing headache was seen in 13 (76%) and severe in 13 (76%) of the patients (VAS ≥7). It was diffuse in 4, unilateral in 13 and associated with ipsilateral neck pain in three patients. This study also found association between the laterality of headache and the side of sinus involved.[11] We found that throbbing type of pain was the most commonly described pain in our cohort followed by aching type and pressure type.

In our study, headache mimicking migraine was present in 12 (25.5%) patients, although history of migraine was present in one of them. Tension-type headache was present in 4 (8.5%) patients In Cumurciuc et al. series four patients had a history of migraine before CVT, but they reported change in nature of headache at the time of presentation. One of their patients had headache similar to migraine.[11] This character of headache has been reported before in case reports and small studies.[8] The causative mechanism in patients with migraine like headache could be aseptic inflammatory changes in the region of trigeminal nerve innervation leading to dilatation of vessels and mimicking the migraine etiology.

The unilateral headache found in other studies ipsilateral to the sinus involved could be due to the stretching of dura which is innervated by branches of trigeminal nerve and thus is referred over the same side. On the contrary, when multiple sinuses are involved, the predominant feature is raised ICP thus leading to diffuse stretching of dura and thus resulting in holocranial headache. Similar pathogenesis is seen in cases of SSS thrombosis where the midline location of the sinus gives rise to poor localization and holocranial headache. The inability to find direct correlation between the site of sinus thrombosis and lateralization of headache was due to multiple sinus involvement in most of the patients.

In our study, there was a significant improvement in headache severity, GCS scores, Barthel's index and mRS at the time discharge after standard treatment. In Damak et al. study, death was seen in 1%, 9% were dependent with mRS scores of 3–5 at discharge, 17.4% showed partial recovery and 73% showed complete recovery. The low mortality of CVT in our group points toward the selection bias as only stable patients were recruited. This is at par with declining trends of mortality in CVT patients over time due to improvement in diagnostic and treatment modalities.[26]

The strengths of the study are prospective design, detailed characterization of headache, strict recruitment criteria of conscious patients for a description of headache and confirmation by imaging. This study further adds to the information about the headache patterns commonly seen in patients with CVT as a whole.

The weakness of the study was small sample size and cases with significant multiple venous sinus involvement. There was also probable selection and referral bias as the study was done at a tertiary neurocarecenter. Only conscious CVT patients were included as per the design of the study. Therefore, the results can only be generalized to conscious patients with CVT and not all patients with CVT.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.