Acta Neurol Belg DOI 10.1007/s13760-014-0305-z
ORIGINAL ARTICLE
Dural puncture: an overlooked cause of cerebral venous thrombosis Derya Guner • Bedile Irem Tiftikcioglu • Irem Fatma Uludag • Dilek Oncel • Yasar Zorlu
Received: 28 February 2014 / Accepted: 30 April 2014 Ó Belgian Neurological Society 2014
Abstract Cerebral venous thrombosis (CVT) accounts for 0.5–1 % of all strokes. Although dural puncture is proposed as one of the rare risk factors, this association has only been mentioned in anecdotal reports. Headache, i.e., usually the first and the most frequent clinical symptom on admission, is often attributed to the dural puncture itself. We investigated the frequency of CVT following a recent dural puncture in our stroke database, together with the other risk factors. The computerized medical records of patients (n = 10,740) registered in our tertiary-care neurology clinic stroke database were reviewed retrospectively. Patients diagnosed with CVT were reanalyzed. Patients who had a dural puncture in the preceding 7 days were included in the study. A total of 46 patients were diagnosed with CVT. Nine patients (19.6 %) had a recent dural puncture before the onset of the symptoms. Patients were younger than 45 years and had at least one more predisposing condition for thromboembolism other than the dural puncture. All patients have received either spinal anesthesia or intrathecal chemotherapy. Dural puncture seems to trigger CVT particularly in patients with predisposing disorders. Although reported as an extremely rare complication, our data indicate a much higher association. This case series emphasize the importance of reevaluation of patients with persistent/progressive headache following dural puncture. The effect of change in the biochemical D. Guner B. I. Tiftikcioglu (&) I. F. Uludag Y. Zorlu Department of Neurology, Neurology Clinic, TCSB Izmir Tepecik Education and Research Hospital, Gaziler Cad. No:468, Yenisehir, Izmir, Turkey e-mail: [email protected] D. Oncel Department of Radiology, Izmir Tepecik Education and Research Hospital, Izmir, Turkey
composition of CSF due to intrathecal drug administration in pathogenesis is not known. Larger controlled trials are warranted to clarify the causal relationship between lumbar puncture and/or intrathecal drug administration and CVT. Keywords Dural puncture Lumbar puncture Cerebral venous thrombosis Complication Headache
Introduction Cerebral venous thrombosis (CVT) is a type of cerebrovascular disease that affects approximately 3–4 people per million and accounts for 0.5–1 % of all strokes [1, 2]. The blockade of cerebral veins and dural sinuses by a thrombus may result in a wide spectrum of neurological conditions, including isolated headache, focal neurological deficits, seizures and coma. The diversity of clinical symptoms may cause a delay in diagnosis and initiation of treatment. The etiology seems to be multifactorial and several disorders and conditions including diagnostic and therapeutic procedures have been proposed to be the risk factors [1, 3]. Dural puncture, the term which refers to all lumbar puncture procedures including both diagnostic and therapeutic interventions, has been described as one of the rare risk factors for CVT [4]. However, this association has been reported only in several case reports [5–11]. The aim of our study was to investigate the temporal relationship between CVT and dural puncture in our stroke database, which includes all patients diagnosed with cerebrovascular diseases in our hospital registry. We described the clinical and laboratory features of patients with CVT following a recent dural puncture and discuss the frequency, risk factors and proposed underlying disease mechanisms.
123
Acta Neurol Belg
Patients and methods In this retrospective study, we screened 10,740 patients treated with the diagnosis of cerebrovascular diseases at our tertiary-care neurology clinic, between August 2007 and November 2013. From the computerized patient database of Tepecik Education and Research Hospital, we recruited all the patients with definite CVT diagnosis, confirmed by neuroimaging. Medical records of 46 consecutive patients diagnosed with CVT in a 6-year period were reviewed and their information of demographical data (age and sex), clinical presentation, disease course, precursor factors, laboratory data (routine complete blood count, serum biochemical analysis including homocysteine, folic acid, antiphospholipid antibodies, protein C, protein S, and antithrombin III screening, urinalysis, etc.) and neuroimaging data were noted. All patients were imaged with a 1.5 T MR scanner (Philips Achieva, The Netherlands). On conventional cranial MR examination, the included pulse sequences were: T1-weighted (T1WI) (TR 450 ms; TE 15 ms) images on axial and sagittal planes, fast spin-echo T2-weighted (T2WI) (TR 3,800 ms; TE 100 ms; echo-train length 19) images on axial and coronal planes and fluid-attenuated inversion recovery (FLAIR) (TR, 6,000 ms; TI, 2,000 ms; TE, 120 ms) sequence on axial plane. Section thickness was 5.0 mm on all sequences, contiguously acquired. The venous MR angiography was obtained with 3D phase contrast technique (TR 17 ms, TE 7 ms, Flip angle 10). VENC factor was chosen as 15 cm/s. Scanning included the whole brain starting from C2 level till vertex. The evaluation was done using the reconstructed MIP images along with the axial source data. The absence of a flow void and the presence of altered signal intensity in the sinus were considered as the primary findings of sinus thrombosis on conventional MR images (hyperintense signal both on T1- and T2-weighted images). Venous MR angiography demonstrated absent flow as a lack of flow signal intensity in the sinus in case of thrombosis. The interval between dural puncture and CVT was considered as \7 days, as the inclusion criteria for a possible causal and temporal relationship. Only descriptive statistical analysis could be performed due to the small number of cases. The study was approved by The Regional Committee for Research Ethics.
puerperal state. The symptoms have either begun or changed feature 2–4 days following the dural puncture. Besides, all patients had at least one additional predisposing factor for thrombosis other than dural puncture. Demographical, clinical, laboratory and neuroimaging data of each patient are summarized in Table 1. The common symptom was headache. Eight out of nine patients described their headache as worsening with a significant change in quality in days. After the dural puncture all eight patients had slight headache with postural component, which worsened later on and changed character; became non-positional, mainly frontal and occipital, dull, but sometimes throbbing and severely disabling. One patient described acute onset of headache without any postural component on the second day following the dural puncture. Papilledema (grade-I) was present in 6 patients (66.6 %) only. Three patients had epileptic seizures. One had episodic left motor seizures accompanied by dizziness, confusion and vomiting. The other two patients were admitted with the first episode of generalized tonic–clonic convulsions and loss of consciousness. Both had a second seizure in ER. Antiepileptic treatment was initiated immediately. Two patients with generalized seizures became seizure free. However, focal motor seizures continued in the first patient for another week. According to the neuroimaging findings, the majority of patients displayed only venous sinus thrombosis; one patient had bilateral subdural hematoma and one had cerebral cortical venous infarcts, additionally. All were treated with intravenous heparin, followed by warfarin. Antiepileptic treatment was given for seizures, where necessary. All patients fully recovered and had no neurological deficit in follow-up. Neither of the patients was given prophylaxis for thrombosis before the onset of CVT after the dural puncture. Thirty-five patients with CVT had no history of a recent dural puncture. Mean age was 39 years (range 15–77 years). Nineteen were women (54.3 %). Headache was the major complaint in 25 patients (71.4 %), followed by blurred vision (28.6 %), seizure (17.1 %), hemiparesis (11.4 %), vomiting (5.7 %). Papilledema was present in 24 patients (68.6 %). Clinical and laboratory workup for predisposing factors revealed a relevant etiology only in 27 patients (77.1 %). The most frequent predisposing condition was hematological factor deficiencies (42.9 %), followed by peripartum state (14.3 %), oral contraceptive use (11.4 %), malignancy (5.7 %) and meningitis (2.9 %).
Results We found that 9 patients out of 46 (19.6 %) had a dural puncture within the 7 days preceding the symptoms of CVT. All were under 45 years of age (mean 25 years, range 15–41 years). Five patients (55.6 %) were women in
123
Discussion Venous thrombosis is often multifactorial and several factors may have additive effects [3]. Ferro et al. [12]
Acta Neurol Belg Table 1 Clinical summary of patients with a recent dural puncture prior to CVT Patient # Gender
Age
L/P indication
Duration for symptom onset/change
Symptom(s)
CVT site/MRI lesion
Predisposing factor(s)
1
M
15
Intrathecal MTX therapy
2 days
Headache, dizziness, confusion, nausea, vomiting, seizure
Bilateral subdural effusion thrombosis in superior sagittal and L transverse sinuses
Malignancy
2
M
41
SA for surgery
3 days
Headache, seizure
Thrombosis in superior sagittal sinus
Antithrombin deficiency
3
M
28
SA for surgery
3 days
Headache
Thrombosis in superior sagittal, L transverse and sigmoid sinuses
Prot S deficiency, antithrombin deficiency
4
F
22
SA for C/S
2–3 days
Headache, dizziness, double vision, nausea, vomiting
Thrombosis in confluence of sinuses, L transverse and sigmoid sinuses
Pregnancy, prot S deficiency
5
F
18
SA for C/S
3 days
Headache, nausea, blurred vision, L-sided weakness
R cerebral cortical venous infarct thrombosis in superior sagittal, L transverse sinuses
Pregnancy, antithrombin deficiency, hyperhomocysteinemia
6
F
19
SA for C/S
4 days
Headache
Thrombosis in straight sinus
Pregnancy, protein S deficiency
7
F
21
SA for C/S
3 days
Seizure, headache
Thrombosis in L transverse and sigmoid sinuses
Pregnancy, protein S deficiency
8
F
28
SA for C/S
4 days
Headache, dizziness, double vision
Thrombosis in R transverse sinus
Pregnancy, antithrombin deficiency
9
M
36
SA for arthroscopy
2 days
Headache
Thrombosis in superior sagittal, L transverse and sigmoid sinuses
Protein C deficiency, hyperhomocysteinemia
SA spinal anesthesia, LP lumbar puncture, CVT cerebral venous thrombosis C/S cesarian section, MTX methotrexate
reported more than one predisposing factor in 44 % of CVT patients. Thus, it is recommended to investigate for congenital thrombophilia even when acquired risk factors are present. On the other hand, when no cause is found (approximately 15 %) repeated investigations in a longterm follow-up are also suggested [2]. In this retrospective study, all patients had at least one additional predisposing condition for CVT other than the dural puncture. No family history and no previous history of a thromboembolic event were present, except the second patient. All patients either had spinal anesthesia with bupivacaine or received intrathecal chemotherapy. Lumbar puncture (LP) is generally recognized as a safe procedure. Serious complications of LP are reported in \0.5 % of cases, but too high to be ignored even so [6]. Increasing number of anecdotal reports suggest LP as a risk factor for CVT [4–11]. In 2004, International Study of CVT (ISCVT) identified LP as a risk factor in 12 out of 624 cases (1.9 %) [12]. Wilder-Smith et al. [6] reported a preceding dural puncture in 8 % of 66 CVT patients. However, we found a much higher percentage (19.6 %) in our group. Five out of nine patients were women in puerperium. This might suggest a potential inclusion bias and could be explained by being the major referral center
for many specialties including obstetrics and gynecology of our hospital in western Turkey. Higher frequencies might be expected in referral centers, particularly for rare causes. Two mechanisms for pathogenesis have been described for CVT [1]. First one is the thrombosis of cerebral veins which results in local effects, venous infarction and local edema. The second is the thrombosis of the major venous sinuses which results in increased intracranial pressure. The latter usually leads the first. The theory of how a dural puncture induces CVT is much complicated [6]. First, the loss of cerebrospinal fluid (CSF) lowers intracranial pressure which causes cerebral venous and arterial dilatation. Venous endothelium becomes fragile due to stretching of the cerebral vessels by a negative spinal–cranial pressure gradient. This might explain the subdural hematoma and effusion seen in CVT. Secondly, the venous blood flow velocities decrease in dural sinuses following LP, as has been demonstrated with transcranial Doppler ultrasound [13]. Thirdly, CSF leakage reduces the absorption of CSF into the sinuses; thereby, blood viscosity increases in the venous sinuses [14]. Hereby, we believe that dural puncture has triggered the thrombotic cascade in our patients through the mechanisms discussed above.
123
Acta Neurol Belg
The proposed disease mechanism induced by dural puncture seems more likely to trigger the thrombosis of major dural sinuses, primarily. The reported frequencies of affected sinuses and veins in the central nervous system support this hypothesis. ISCVT reported that the transverse sinuses are most frequently occluded (86 %), which is followed by superior sagittal (62 %), straight sinus (18 %), cortical veins (17 %), jugular veins (12 %) and vein of Galen and internal cerebral veins (11 %) in order [1, 12]. In our group, eight patients had occlusion in either one or both the superior sagittal and transverse venous sinuses, and one patient had occlusion in the straight sinus. We did not notice any MR signal abnormalities in deep cerebral veins, and this could be explained by their relatively rare involvement. There are several anecdotal reports pointing out CVT as a complication of dural puncture; a few following intrathecal drug injections and others following a diagnostic LP [5–11, 15–18]. Two patient reports suggest a causative relationship between myelography and CVT [16, 17]. Milhaud et al. reported a case of a young woman on oral contraception. She was diagnosed with CVT shortly after epidural injection of methylprednisolone for L5 radiculalgia, which actually resulted in a dural puncture [8]. In their report, they mentioned the 11 previously reported cases in the literature; three of them were observed after intrathecal corticosteroid injection, three after intrathecal injections of anesthetic drugs, two cases after myelography, one after a diagnostic LP for multiple sclerosis and in two cases no details were available. Bienfait et al. [10] described another patient, who developed CVT after intrathecal injection of methotrexate and dexamethasone for the treatment of his malignant hematological disease. There are a few other reports suggesting diagnostic LP and administration of high-dose intravenous methylprednisolone as an etiological factor for CVT [18]. Intrathecal corticosteroid injection was suggested to induce prothrombotic state in venous sinuses, but no hypothesis was asserted for an association with bupivacaine or methotrexate. In our group, patients had received intrathecal injections of either bupivacaine or MTX. Thus, the procedure was not merely a simple LP. It is not known whether injection of corticosteroids, or methotrexate, or anesthetic drugs intrathecally has a role in the pathogenesis of CVT, or this is only a co-incidence. Nevertheless, it is a remarkable finding. One explanation to this might be the effect of the change in the biochemical composition of CSF. The changed vascular content might have irritated the venous sinuses chemically and provoked local thrombosis, together with the other predisposing factors. Also, one could speculate the possibility of chemical or infectious meningitis after the intrathecal drug injection. However, the
123
clinical features, neuroimaging findings and quick response to the anticoagulant therapy were not in accordance with these complications. Headache is usually the first, most frequent and sometimes the only presenting symptom in CVT, which was also the main clinical presentation in all our patients. Papilledema was present only in six patients. Thus, recognizing those patients without papilledema is extremely important. In our group of patients, headache started or changed feature 2–4 days after the dural puncture. The characteristics of headache due to CVT complicating LP, often mimics post-dural puncture headache (PDPH), particularly leading to missed or delayed diagnosis [4]. In PDPH, headache starts shortly after the LP with a predominant postural component. However, the headache in CVT tends to be more diffuse in location, usually does not vary with changes in body position and accompanies dizziness, confusion or other neurological signs in most cases. There are several limitations to this study. First, the data were retrieved retrospectively. Second, our data present the proportion of patients who had a recent dural puncture among all the patients diagnosed with CVT in our stroke database. The actual prevalence of CVT following a dural puncture is not known. Hence, this study emphasizes the possible consequential relationship between CVT and dural puncture, but not represent the incidence or prevalence of CVT complicating dural puncture. Third, the effect of intrathecal drug administration in pathogenesis of CVT is not known. Finally, no information regarding the opening pressure at dural puncture was available for the patients. None had any prior complaint which could be related to a pre-existing CVT. Since the need for the dural puncture was not related with a neurological disease in either case, no information of opening pressure was noted in their medical records. However, information of both the fundus examination before the procedure and opening pressure of CSF would aid the understanding of temporal and/or causative relationship between dural puncture and CVT. In conclusion, it is important to reassess the patient with persistent PDPH and remember the CVT in differential diagnosis. Although it is reported as an extremely rare complication, our data indicate a much higher association. Early diagnosis is extremely important in CVT which is one of the main factors affecting the outcome. Immediate and appropriate treatment could prevent further morbidity and mortality. Patients who underwent a spinal tap should be informed about the symptoms of CVT. Persistence or any change in the features of headache should be a sign for the patient to consult a physician. Larger controlled trials are warranted to clarify the causal relationship between LP and/or intrathecal drugs and CVT.
Acta Neurol Belg Conflict of interest The authors declare that they have no conflict of interest to declare and nothing to disclose.
References 1. Stam J (2005) Thrombosis of the cerebral veins and sinuses. N Engl J Med 352:1791–1798 2. Bousser MG, Ferro JM (2007) Cerebral venous thrombosis: an update. Lancet Neurol 6:162–170 3. De Freitas GR, Bogousslavsky J (2008) Risk factors of cerebral vein and sinus thrombosis. Front Neurol Neurosci 23:23–54 4. Lockhart EM, Baysinger CL (2007) Intracranial venous thrombosis in the parturient. Anesthesiology 107:652–658 5. Gunal DI, Afsar N, Tuncer N, Aktan S (2002) A case of multiple sclerosis with cerebral venous thrombosis: the role of lumbar puncture and high-dose steroids. Eur Neurol 47:57–58 6. Wilder-Smith E, Kothbauer-Margreiter I, Lammle B, Sturzenegger M, Ozdoba C, Hauser SP (1997) Dural puncture and activated protein C resistance: risk factors for cerebral venous sinus thrombosis. J Neurol Neurosurg Psychiatry 63:351–356 7. Ravindran RS, Zandstra GC (1989) Cerebral venous thrombosis versus postlumbar puncture headache. Anesthesiology 71:478–479 8. Milhaud D, Heroum C, Charif M, Saulnier P, Pages M, Blard JM (2000) Dural puncture and corticotherapy as risks factors for cerebral venous sinus thrombosis. Eur J Neurol 7:123–124 9. Ferrante E, Spreafico C, Regna-Gladin C, Protti A (2009) Images from headache. Cerebral venous thrombosis complicating lumbar puncture. Headache 49:276–277
10. Bienfait HP, Gijtenbeek JM, van den Bent MJ, de Bruin HG, Voogt PJ, Pillay M (2002) Cerebral venous and sinus thrombosis with cerebrospinal fluid circulation block after the first methotrexate administration by lumbar puncture. Neuroradiology 44:929–932 11. Ucler S, Ocal R, Coskun O, Inan LE (2011) Cerebral venous thrombosis after lumbar puncture: case report (article in turkish). Turkiye Klinikleri J Neur 6:52–56 12. Ferro JM, Canhao P, Stam J, Bousser MG, Barinagarrementeria F (2004) Prognosis of cerebral vein and dural sinus thrombosis: results of the international study on cerebral vein and dural sinus thrombosis (ISCVT). Stroke 35:664–670 13. Canhao P, Batista P, Falcao F (2005) Lumbar puncture and dural sinus thrombosis—a causal or casual association? Cerebrovasc Dis 19:53–56 14. Schievink WI, Maya MM (2008) Cerebral venous thrombosis in spontaneous intracranial hypotension. Headache 48:1511–1519 15. Mouraux A, Gille M, Dorban S, Peeters A (2002) Cortical venous thrombosis after lumbar puncture. J Neurol 249:1313–1315 16. Tuite P, Ahmad F, Grant I, Stewart JD, Carpenter S, Ethier R (1993) Cerebral vein thrombosis due to hereditary antithrombin III deficiency. Can J Neurol Sci 20:158–161 17. Brugeilles H, Penisson-Besnier I, Pasco A, Oillic P, Lejeune P, Mercier P (1996) Cerebral venous thrombosis after myelography with iopamidol. Neuroradiology 38:534–536 18. Vandenberghe N, Debouverie M, Anxionnat R, Clavelou P, Bouly S, Weber M (2003) Cerebral venous thrombosis in four patients with multiple sclerosis. Eur J Neurol 10:63–66
123
ORIGINAL ARTICLE
Dural puncture: an overlooked cause of cerebral venous thrombosis Derya Guner • Bedile Irem Tiftikcioglu • Irem Fatma Uludag • Dilek Oncel • Yasar Zorlu
Received: 28 February 2014 / Accepted: 30 April 2014 Ó Belgian Neurological Society 2014
Abstract Cerebral venous thrombosis (CVT) accounts for 0.5–1 % of all strokes. Although dural puncture is proposed as one of the rare risk factors, this association has only been mentioned in anecdotal reports. Headache, i.e., usually the first and the most frequent clinical symptom on admission, is often attributed to the dural puncture itself. We investigated the frequency of CVT following a recent dural puncture in our stroke database, together with the other risk factors. The computerized medical records of patients (n = 10,740) registered in our tertiary-care neurology clinic stroke database were reviewed retrospectively. Patients diagnosed with CVT were reanalyzed. Patients who had a dural puncture in the preceding 7 days were included in the study. A total of 46 patients were diagnosed with CVT. Nine patients (19.6 %) had a recent dural puncture before the onset of the symptoms. Patients were younger than 45 years and had at least one more predisposing condition for thromboembolism other than the dural puncture. All patients have received either spinal anesthesia or intrathecal chemotherapy. Dural puncture seems to trigger CVT particularly in patients with predisposing disorders. Although reported as an extremely rare complication, our data indicate a much higher association. This case series emphasize the importance of reevaluation of patients with persistent/progressive headache following dural puncture. The effect of change in the biochemical D. Guner B. I. Tiftikcioglu (&) I. F. Uludag Y. Zorlu Department of Neurology, Neurology Clinic, TCSB Izmir Tepecik Education and Research Hospital, Gaziler Cad. No:468, Yenisehir, Izmir, Turkey e-mail: [email protected] D. Oncel Department of Radiology, Izmir Tepecik Education and Research Hospital, Izmir, Turkey
composition of CSF due to intrathecal drug administration in pathogenesis is not known. Larger controlled trials are warranted to clarify the causal relationship between lumbar puncture and/or intrathecal drug administration and CVT. Keywords Dural puncture Lumbar puncture Cerebral venous thrombosis Complication Headache
Introduction Cerebral venous thrombosis (CVT) is a type of cerebrovascular disease that affects approximately 3–4 people per million and accounts for 0.5–1 % of all strokes [1, 2]. The blockade of cerebral veins and dural sinuses by a thrombus may result in a wide spectrum of neurological conditions, including isolated headache, focal neurological deficits, seizures and coma. The diversity of clinical symptoms may cause a delay in diagnosis and initiation of treatment. The etiology seems to be multifactorial and several disorders and conditions including diagnostic and therapeutic procedures have been proposed to be the risk factors [1, 3]. Dural puncture, the term which refers to all lumbar puncture procedures including both diagnostic and therapeutic interventions, has been described as one of the rare risk factors for CVT [4]. However, this association has been reported only in several case reports [5–11]. The aim of our study was to investigate the temporal relationship between CVT and dural puncture in our stroke database, which includes all patients diagnosed with cerebrovascular diseases in our hospital registry. We described the clinical and laboratory features of patients with CVT following a recent dural puncture and discuss the frequency, risk factors and proposed underlying disease mechanisms.
123
Acta Neurol Belg
Patients and methods In this retrospective study, we screened 10,740 patients treated with the diagnosis of cerebrovascular diseases at our tertiary-care neurology clinic, between August 2007 and November 2013. From the computerized patient database of Tepecik Education and Research Hospital, we recruited all the patients with definite CVT diagnosis, confirmed by neuroimaging. Medical records of 46 consecutive patients diagnosed with CVT in a 6-year period were reviewed and their information of demographical data (age and sex), clinical presentation, disease course, precursor factors, laboratory data (routine complete blood count, serum biochemical analysis including homocysteine, folic acid, antiphospholipid antibodies, protein C, protein S, and antithrombin III screening, urinalysis, etc.) and neuroimaging data were noted. All patients were imaged with a 1.5 T MR scanner (Philips Achieva, The Netherlands). On conventional cranial MR examination, the included pulse sequences were: T1-weighted (T1WI) (TR 450 ms; TE 15 ms) images on axial and sagittal planes, fast spin-echo T2-weighted (T2WI) (TR 3,800 ms; TE 100 ms; echo-train length 19) images on axial and coronal planes and fluid-attenuated inversion recovery (FLAIR) (TR, 6,000 ms; TI, 2,000 ms; TE, 120 ms) sequence on axial plane. Section thickness was 5.0 mm on all sequences, contiguously acquired. The venous MR angiography was obtained with 3D phase contrast technique (TR 17 ms, TE 7 ms, Flip angle 10). VENC factor was chosen as 15 cm/s. Scanning included the whole brain starting from C2 level till vertex. The evaluation was done using the reconstructed MIP images along with the axial source data. The absence of a flow void and the presence of altered signal intensity in the sinus were considered as the primary findings of sinus thrombosis on conventional MR images (hyperintense signal both on T1- and T2-weighted images). Venous MR angiography demonstrated absent flow as a lack of flow signal intensity in the sinus in case of thrombosis. The interval between dural puncture and CVT was considered as \7 days, as the inclusion criteria for a possible causal and temporal relationship. Only descriptive statistical analysis could be performed due to the small number of cases. The study was approved by The Regional Committee for Research Ethics.
puerperal state. The symptoms have either begun or changed feature 2–4 days following the dural puncture. Besides, all patients had at least one additional predisposing factor for thrombosis other than dural puncture. Demographical, clinical, laboratory and neuroimaging data of each patient are summarized in Table 1. The common symptom was headache. Eight out of nine patients described their headache as worsening with a significant change in quality in days. After the dural puncture all eight patients had slight headache with postural component, which worsened later on and changed character; became non-positional, mainly frontal and occipital, dull, but sometimes throbbing and severely disabling. One patient described acute onset of headache without any postural component on the second day following the dural puncture. Papilledema (grade-I) was present in 6 patients (66.6 %) only. Three patients had epileptic seizures. One had episodic left motor seizures accompanied by dizziness, confusion and vomiting. The other two patients were admitted with the first episode of generalized tonic–clonic convulsions and loss of consciousness. Both had a second seizure in ER. Antiepileptic treatment was initiated immediately. Two patients with generalized seizures became seizure free. However, focal motor seizures continued in the first patient for another week. According to the neuroimaging findings, the majority of patients displayed only venous sinus thrombosis; one patient had bilateral subdural hematoma and one had cerebral cortical venous infarcts, additionally. All were treated with intravenous heparin, followed by warfarin. Antiepileptic treatment was given for seizures, where necessary. All patients fully recovered and had no neurological deficit in follow-up. Neither of the patients was given prophylaxis for thrombosis before the onset of CVT after the dural puncture. Thirty-five patients with CVT had no history of a recent dural puncture. Mean age was 39 years (range 15–77 years). Nineteen were women (54.3 %). Headache was the major complaint in 25 patients (71.4 %), followed by blurred vision (28.6 %), seizure (17.1 %), hemiparesis (11.4 %), vomiting (5.7 %). Papilledema was present in 24 patients (68.6 %). Clinical and laboratory workup for predisposing factors revealed a relevant etiology only in 27 patients (77.1 %). The most frequent predisposing condition was hematological factor deficiencies (42.9 %), followed by peripartum state (14.3 %), oral contraceptive use (11.4 %), malignancy (5.7 %) and meningitis (2.9 %).
Results We found that 9 patients out of 46 (19.6 %) had a dural puncture within the 7 days preceding the symptoms of CVT. All were under 45 years of age (mean 25 years, range 15–41 years). Five patients (55.6 %) were women in
123
Discussion Venous thrombosis is often multifactorial and several factors may have additive effects [3]. Ferro et al. [12]
Acta Neurol Belg Table 1 Clinical summary of patients with a recent dural puncture prior to CVT Patient # Gender
Age
L/P indication
Duration for symptom onset/change
Symptom(s)
CVT site/MRI lesion
Predisposing factor(s)
1
M
15
Intrathecal MTX therapy
2 days
Headache, dizziness, confusion, nausea, vomiting, seizure
Bilateral subdural effusion thrombosis in superior sagittal and L transverse sinuses
Malignancy
2
M
41
SA for surgery
3 days
Headache, seizure
Thrombosis in superior sagittal sinus
Antithrombin deficiency
3
M
28
SA for surgery
3 days
Headache
Thrombosis in superior sagittal, L transverse and sigmoid sinuses
Prot S deficiency, antithrombin deficiency
4
F
22
SA for C/S
2–3 days
Headache, dizziness, double vision, nausea, vomiting
Thrombosis in confluence of sinuses, L transverse and sigmoid sinuses
Pregnancy, prot S deficiency
5
F
18
SA for C/S
3 days
Headache, nausea, blurred vision, L-sided weakness
R cerebral cortical venous infarct thrombosis in superior sagittal, L transverse sinuses
Pregnancy, antithrombin deficiency, hyperhomocysteinemia
6
F
19
SA for C/S
4 days
Headache
Thrombosis in straight sinus
Pregnancy, protein S deficiency
7
F
21
SA for C/S
3 days
Seizure, headache
Thrombosis in L transverse and sigmoid sinuses
Pregnancy, protein S deficiency
8
F
28
SA for C/S
4 days
Headache, dizziness, double vision
Thrombosis in R transverse sinus
Pregnancy, antithrombin deficiency
9
M
36
SA for arthroscopy
2 days
Headache
Thrombosis in superior sagittal, L transverse and sigmoid sinuses
Protein C deficiency, hyperhomocysteinemia
SA spinal anesthesia, LP lumbar puncture, CVT cerebral venous thrombosis C/S cesarian section, MTX methotrexate
reported more than one predisposing factor in 44 % of CVT patients. Thus, it is recommended to investigate for congenital thrombophilia even when acquired risk factors are present. On the other hand, when no cause is found (approximately 15 %) repeated investigations in a longterm follow-up are also suggested [2]. In this retrospective study, all patients had at least one additional predisposing condition for CVT other than the dural puncture. No family history and no previous history of a thromboembolic event were present, except the second patient. All patients either had spinal anesthesia with bupivacaine or received intrathecal chemotherapy. Lumbar puncture (LP) is generally recognized as a safe procedure. Serious complications of LP are reported in \0.5 % of cases, but too high to be ignored even so [6]. Increasing number of anecdotal reports suggest LP as a risk factor for CVT [4–11]. In 2004, International Study of CVT (ISCVT) identified LP as a risk factor in 12 out of 624 cases (1.9 %) [12]. Wilder-Smith et al. [6] reported a preceding dural puncture in 8 % of 66 CVT patients. However, we found a much higher percentage (19.6 %) in our group. Five out of nine patients were women in puerperium. This might suggest a potential inclusion bias and could be explained by being the major referral center
for many specialties including obstetrics and gynecology of our hospital in western Turkey. Higher frequencies might be expected in referral centers, particularly for rare causes. Two mechanisms for pathogenesis have been described for CVT [1]. First one is the thrombosis of cerebral veins which results in local effects, venous infarction and local edema. The second is the thrombosis of the major venous sinuses which results in increased intracranial pressure. The latter usually leads the first. The theory of how a dural puncture induces CVT is much complicated [6]. First, the loss of cerebrospinal fluid (CSF) lowers intracranial pressure which causes cerebral venous and arterial dilatation. Venous endothelium becomes fragile due to stretching of the cerebral vessels by a negative spinal–cranial pressure gradient. This might explain the subdural hematoma and effusion seen in CVT. Secondly, the venous blood flow velocities decrease in dural sinuses following LP, as has been demonstrated with transcranial Doppler ultrasound [13]. Thirdly, CSF leakage reduces the absorption of CSF into the sinuses; thereby, blood viscosity increases in the venous sinuses [14]. Hereby, we believe that dural puncture has triggered the thrombotic cascade in our patients through the mechanisms discussed above.
123
Acta Neurol Belg
The proposed disease mechanism induced by dural puncture seems more likely to trigger the thrombosis of major dural sinuses, primarily. The reported frequencies of affected sinuses and veins in the central nervous system support this hypothesis. ISCVT reported that the transverse sinuses are most frequently occluded (86 %), which is followed by superior sagittal (62 %), straight sinus (18 %), cortical veins (17 %), jugular veins (12 %) and vein of Galen and internal cerebral veins (11 %) in order [1, 12]. In our group, eight patients had occlusion in either one or both the superior sagittal and transverse venous sinuses, and one patient had occlusion in the straight sinus. We did not notice any MR signal abnormalities in deep cerebral veins, and this could be explained by their relatively rare involvement. There are several anecdotal reports pointing out CVT as a complication of dural puncture; a few following intrathecal drug injections and others following a diagnostic LP [5–11, 15–18]. Two patient reports suggest a causative relationship between myelography and CVT [16, 17]. Milhaud et al. reported a case of a young woman on oral contraception. She was diagnosed with CVT shortly after epidural injection of methylprednisolone for L5 radiculalgia, which actually resulted in a dural puncture [8]. In their report, they mentioned the 11 previously reported cases in the literature; three of them were observed after intrathecal corticosteroid injection, three after intrathecal injections of anesthetic drugs, two cases after myelography, one after a diagnostic LP for multiple sclerosis and in two cases no details were available. Bienfait et al. [10] described another patient, who developed CVT after intrathecal injection of methotrexate and dexamethasone for the treatment of his malignant hematological disease. There are a few other reports suggesting diagnostic LP and administration of high-dose intravenous methylprednisolone as an etiological factor for CVT [18]. Intrathecal corticosteroid injection was suggested to induce prothrombotic state in venous sinuses, but no hypothesis was asserted for an association with bupivacaine or methotrexate. In our group, patients had received intrathecal injections of either bupivacaine or MTX. Thus, the procedure was not merely a simple LP. It is not known whether injection of corticosteroids, or methotrexate, or anesthetic drugs intrathecally has a role in the pathogenesis of CVT, or this is only a co-incidence. Nevertheless, it is a remarkable finding. One explanation to this might be the effect of the change in the biochemical composition of CSF. The changed vascular content might have irritated the venous sinuses chemically and provoked local thrombosis, together with the other predisposing factors. Also, one could speculate the possibility of chemical or infectious meningitis after the intrathecal drug injection. However, the
123
clinical features, neuroimaging findings and quick response to the anticoagulant therapy were not in accordance with these complications. Headache is usually the first, most frequent and sometimes the only presenting symptom in CVT, which was also the main clinical presentation in all our patients. Papilledema was present only in six patients. Thus, recognizing those patients without papilledema is extremely important. In our group of patients, headache started or changed feature 2–4 days after the dural puncture. The characteristics of headache due to CVT complicating LP, often mimics post-dural puncture headache (PDPH), particularly leading to missed or delayed diagnosis [4]. In PDPH, headache starts shortly after the LP with a predominant postural component. However, the headache in CVT tends to be more diffuse in location, usually does not vary with changes in body position and accompanies dizziness, confusion or other neurological signs in most cases. There are several limitations to this study. First, the data were retrieved retrospectively. Second, our data present the proportion of patients who had a recent dural puncture among all the patients diagnosed with CVT in our stroke database. The actual prevalence of CVT following a dural puncture is not known. Hence, this study emphasizes the possible consequential relationship between CVT and dural puncture, but not represent the incidence or prevalence of CVT complicating dural puncture. Third, the effect of intrathecal drug administration in pathogenesis of CVT is not known. Finally, no information regarding the opening pressure at dural puncture was available for the patients. None had any prior complaint which could be related to a pre-existing CVT. Since the need for the dural puncture was not related with a neurological disease in either case, no information of opening pressure was noted in their medical records. However, information of both the fundus examination before the procedure and opening pressure of CSF would aid the understanding of temporal and/or causative relationship between dural puncture and CVT. In conclusion, it is important to reassess the patient with persistent PDPH and remember the CVT in differential diagnosis. Although it is reported as an extremely rare complication, our data indicate a much higher association. Early diagnosis is extremely important in CVT which is one of the main factors affecting the outcome. Immediate and appropriate treatment could prevent further morbidity and mortality. Patients who underwent a spinal tap should be informed about the symptoms of CVT. Persistence or any change in the features of headache should be a sign for the patient to consult a physician. Larger controlled trials are warranted to clarify the causal relationship between LP and/or intrathecal drugs and CVT.
Acta Neurol Belg Conflict of interest The authors declare that they have no conflict of interest to declare and nothing to disclose.
References 1. Stam J (2005) Thrombosis of the cerebral veins and sinuses. N Engl J Med 352:1791–1798 2. Bousser MG, Ferro JM (2007) Cerebral venous thrombosis: an update. Lancet Neurol 6:162–170 3. De Freitas GR, Bogousslavsky J (2008) Risk factors of cerebral vein and sinus thrombosis. Front Neurol Neurosci 23:23–54 4. Lockhart EM, Baysinger CL (2007) Intracranial venous thrombosis in the parturient. Anesthesiology 107:652–658 5. Gunal DI, Afsar N, Tuncer N, Aktan S (2002) A case of multiple sclerosis with cerebral venous thrombosis: the role of lumbar puncture and high-dose steroids. Eur Neurol 47:57–58 6. Wilder-Smith E, Kothbauer-Margreiter I, Lammle B, Sturzenegger M, Ozdoba C, Hauser SP (1997) Dural puncture and activated protein C resistance: risk factors for cerebral venous sinus thrombosis. J Neurol Neurosurg Psychiatry 63:351–356 7. Ravindran RS, Zandstra GC (1989) Cerebral venous thrombosis versus postlumbar puncture headache. Anesthesiology 71:478–479 8. Milhaud D, Heroum C, Charif M, Saulnier P, Pages M, Blard JM (2000) Dural puncture and corticotherapy as risks factors for cerebral venous sinus thrombosis. Eur J Neurol 7:123–124 9. Ferrante E, Spreafico C, Regna-Gladin C, Protti A (2009) Images from headache. Cerebral venous thrombosis complicating lumbar puncture. Headache 49:276–277
10. Bienfait HP, Gijtenbeek JM, van den Bent MJ, de Bruin HG, Voogt PJ, Pillay M (2002) Cerebral venous and sinus thrombosis with cerebrospinal fluid circulation block after the first methotrexate administration by lumbar puncture. Neuroradiology 44:929–932 11. Ucler S, Ocal R, Coskun O, Inan LE (2011) Cerebral venous thrombosis after lumbar puncture: case report (article in turkish). Turkiye Klinikleri J Neur 6:52–56 12. Ferro JM, Canhao P, Stam J, Bousser MG, Barinagarrementeria F (2004) Prognosis of cerebral vein and dural sinus thrombosis: results of the international study on cerebral vein and dural sinus thrombosis (ISCVT). Stroke 35:664–670 13. Canhao P, Batista P, Falcao F (2005) Lumbar puncture and dural sinus thrombosis—a causal or casual association? Cerebrovasc Dis 19:53–56 14. Schievink WI, Maya MM (2008) Cerebral venous thrombosis in spontaneous intracranial hypotension. Headache 48:1511–1519 15. Mouraux A, Gille M, Dorban S, Peeters A (2002) Cortical venous thrombosis after lumbar puncture. J Neurol 249:1313–1315 16. Tuite P, Ahmad F, Grant I, Stewart JD, Carpenter S, Ethier R (1993) Cerebral vein thrombosis due to hereditary antithrombin III deficiency. Can J Neurol Sci 20:158–161 17. Brugeilles H, Penisson-Besnier I, Pasco A, Oillic P, Lejeune P, Mercier P (1996) Cerebral venous thrombosis after myelography with iopamidol. Neuroradiology 38:534–536 18. Vandenberghe N, Debouverie M, Anxionnat R, Clavelou P, Bouly S, Weber M (2003) Cerebral venous thrombosis in four patients with multiple sclerosis. Eur J Neurol 10:63–66
123
