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prospective observational study. PLoS ONE. 2013;8: e71007. Alpers BJ, Berry RG, Paddison RM. Anatomical studies of the circle of Willis in normal brain. AMA Arch Neurol Psychiatry. 1959;81:409-418. Marshall RS, Lazar RM, Pile-Spellman J, et al. Recovery of brain function during induced cerebral hypoperfusion. Brain. 2001;124:1208-1217. Urbanski PP, Lenos A, Blume JC, et al. Does anatomical completeness of the circle of Willis correlate with sufficient cross-perfusion during unilateral cerebral perfusion? Eur J Cardiothorac Surg. 2008;33:402-408. Lee JH, Choi CG, Kim DK, et al. Relationship between circle of Willis morphology on 3D time-of-flight MR angiograms and transient ischemia during vascular clamping of the internal carotid artery during carotid endarterectomy. AJNR Am J Neuroradiol. 2004;25:558-564. van Laar PJ, van der Grond J, Bremmer JP, et al. Assessment of the contribution of the external carotid artery to brain perfusion in patients with internal carotid artery occlusion. Stroke. 2008;39:3003-3008. Hoksbergen AW, Majoie CB, Hulsmans FJ, et al. Assessment of the collateral function of the circle of Willis: Three-dimensional time-of-flight MR angiography compared with transcranial color-coded duplex sonography. AJNR Am J Neuroradiol. 2003;24:456-462. Alnaes MS, Isaksen J, Mardal KA, et al. Computation of hemodynamics in the circle of Willis. Stroke. 2007;38:25002505. Lebedeva ER, Gurary NM, Sakovich VP, et al. Migraine before rupture of intracranial aneurysms. J Headache Pain. 2013;14:15. Ujiie H, Liepsch DW, Goetz M, et al. Hemodynamic study of the anterior communicating artery. Stroke. 1996;27:20862093. Barstad RM, Orvim U, Hamers MJ, et al. Reduced effect of aspirin on thrombus formation at high shear and disturbed laminar blood flow. Thromb Haemost. 1996;75:827832. Holme PA, Orvim U, Hamers MJ, et al. Shear-induced platelet activation and platelet microparticle formation at blood flow conditions as in arteries with a severe stenosis. Arterioscler Thromb Vasc Biol. 1997;17:646-653. Stam AH, Haan J, van den Maagdenberg AM, et al. Migraine and genetic and acquired vasculopathies. Cephalalgia. 2009;29:1006-1017. Perko D, Pretnar-Oblak J, Sabovic M, et al. Associations between cerebral and systemic endothelial function in migraine patients: A post-hoc study. BMC Neurol. 2011; 11:146. Borgdorff P, Tangelder GJ. Migraine: Possible role of shear-induced platelet aggregation with serotonin release. Headache. 2012;52:1298-1318.
June 2014 18. Jenxoxo. Sticky blood platelets cause migraines. http://
www.migraineconnect.com/discussions/5-sticky-bloodplatelets-cause-migraines. 2013. 19. Kruit MC, Launer LJ, Ferrari MD, et al. Infarcts in the posterior circulation territory in migraine. The populationbased MRI CAMERA study. Brain. 2005;128:2068-2077. 20. Glor FP, Ariff B, Hughes AD, et al. Influence of head position on carotid hemodynamics in young adults. Am J Physiol Heart Circ Physiol. 2004;287:H1670-H1681.
Orthostatic Headache Without Intracranial Hypotension: A Headache Due to Psychiatric Disorder? Orthostatic headache with or without associated symptoms (neck or intrascapular pain, nausea and vomiting, change in hearing, diplopia, visual blurring, bitemporal hemianopsia, upper limb paresthesias, parkinsonism,1 stupor, and coma2) is indicative of intracranial hypotension that can occur either after active cerebrospinal fluid (CSF) removal (eg, after a lumbar puncture) or spontaneously (spontaneous intracranial hypotension [SIH]) as a result of a spinal meningeal CSF leak.3,4 Spontaneous CSF leaks are attributed to the underlying fragility of the spinal meninges (sometimes associated with connective-tissue disorders) that easily tear when exposed to a mechanical factor, such as a minor trauma.3 A trivial trauma such as coughing, pulling, pushing, and lifting is reported in a minority of the patients.3 Diagnosis is based on clinical presentation and typical brain magnetic resonance imaging (MRI): thickening of the dura with diffuse pachymeningeal enhancement,sometimes brain sagging, subdural fluid collections, dilatation of the venous compartment with dural sinuses,and pituitary gland enlargement. When these aspects are present, it is not necessary to measure the CSF opening pressure.4 The first-line treatment of this disorder is conservative, including bed rest, oral hydration, analgesics, nonsteroidal anti-inflammatory drugs, and caffeine or theophylline intake.3 Spinal MRI, computed tomography or MRI myelography and radionuclide cisternography should be used to identify the site of the CSF leak3 if conservative treatment fails. Treatment is usually conservative, but autologous epidural blood patch (EBP) has emerged as the most important nonsurgical management.5 Some resistant cases underwent percutaneous injection of fibrin glue6 and surgical repair of the dural tear is reserved for refractory cases when the site of the CSF leak is located.3 Conflict of Interest: None.
Headache From among 214 patients referred to one of us (E.F.) over a 21-year period between April 1992 and May 2013, for evaluation of orthostatic headache (OH) and suspected SIH, 10 patients with negative head and spinal MRI and normal CSF opening pressure (CSF-OP) were identified. Nine patients were women. Mean age at the time of evaluation was 37 years (range 16-65). All patients also had anxiety-depressive disorder (mild grade in 7 patients and moderate grade in 3 patients), one of them was also suffering from conversion disorder, another from pseudoseizures, and one from mild hyperlaxity joints. Median duration of orthostatic headache prior to evaluation at our institution was 9.5 months (range 3-36). Cochleovestibular symptoms were present in 4 patients. Eight patients performed the lumbar puncture in sideways (mean CSF-OP was 140.2 mmH2O [range 80-240]), while 2 in a sitting position (mean CSF-OP was 490 mmH2O [range 440-540]). On the top of best psychiatric treatment, 9 patients performed EBP in Trendelenburg position2 ex juvantibus criterium. One patient was treated with bed rest and overhydration for a short time. After mean follow-up of 21.6 months (range 6-74), 3 patient experienced a complete recovery, and 3 patients improved after EBP; the one treated with only conservative therapy improved with a low dose of aripiprazole (1 mg/day). Three patients with moderate psychiatric disorder had persistent OH. A small series of 6 similar patients has been published,7 in which 5 patients remained severely symptomatic and work disabled at an average follow-up of 4 years. The most likely explanation for these cases is the existence of an intermittent or very slow flow leak that would evade identification by existing imagining techniques. Alternative etiological hypotheses are of increased compliance of the lower spinal CSF space shifting the hydrostatic indifferent point downward in the orthostatic position (inducing compensatory dilation of painsensitive intracranial venous structures without changing CSF pressure at the lumbar level8 or of orthostatic CSF leakage to the epidural venous network.9 In this small series, it is not described whether or not the patients had psychiatric disorders in their medical history. A similar case has been described10 in which a progressive improvement occurred simultaneously to the introduction of vitamin A supplementation. A beneficial effect of vitamin A supplementation was speculated from this report. This patient was also suffering from chronic fatigue treated with bupropion 150 mg qd, amitriptyline 35 mg qd. Orthostatic headache can occur without evidence of intracranial hypotension or detectable CSF leak despite extensive diagnostic testing. Clinical features alone are unlikely to differentiate between
1057 orthostatic headache with and without identifiable CSF leak. We think that in our series, as also in the case report (the patient was taking antidepressant drugs), the underlying psychiatric disorder was the major cause of orthostatic headache that might be considered as a new type of headache attributed to psychiatric disorder. Further studies are needed to confirm these data.
Acknowledgments: We acknowledge Dr. Daria Roccatagliata for having kindly reviewed the manuscript.
Enrico Ferrante, MD; Fabio Rubino, MD Headache Centre, Neurosciences, Ospedale Niguarda Cà Granda, Milano, Italy (E. Ferrante); Anesthesiology Department, Ospedale Niguarda Cà Granda, Milano, Italy (F. Rubino)
REFERENCES 1. Pakiam A, Lee C, Lang A. Intracranial hypotension with Parkinsonism, ataxia, and bulbar weakness. Arch Neurol. 1999;56:869-872. 2. Ferrante E, Arpino I, Citterio A, et al. Coma resulting from spontaneous intracranial hypotension treated with the epidural blood patch in the Trendelenburg position premedicated with acetazolamide. Clin Neurol Neurosurg. 2009;111:699-702. 3. Mokri B. Spontaneous low cerebrospinal pressure, low volume headaches: Spontaneous CSF leaks. Headache. 2013;53:1034-1053. 4. International Headache Society. The International Classification of Headache Disorders: 2nd ed. Cephalalgia. 2004;24(Suppl. 1):9-160. 5. Ferrante E, Arpino I, Citterio A, et al. Epidural blood patch in Trendelenburg position pre-medicated with acetazolamide to treat spontaneous intracranial hypotension. Eur J Neurol. 2010;17:715-719. 6. Schievink WI, Moser FG, Pikul BK. Reversal of coma with an injection of glue. Lancet. 2007;369:1402. 7. Leep Hunderfund AN, Mokri B. Orthostatic headache without CSF leak. Neurology. 2008;71:1902-1906. 8. Levine DN, Rapalino O. The pathophysiology of lumbar puncture headache. J Neurol Sci. 2001;192:1-8. 9. Franzini A, Messina G, Nazzi V, et al. Spontaneous intracranial hypotension syndrome: A novel speculative physiopathological hypothesis and a novel patch method in a series of 28 consecutive patients. J Neurosurg. 2010;112: 300-306. 10. Gil-Gouveia R. Treatment of orthostatic headache without intracranial hypotension: A case report. Cephalalgia. 2013; 33:948-950.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
prospective observational study. PLoS ONE. 2013;8: e71007. Alpers BJ, Berry RG, Paddison RM. Anatomical studies of the circle of Willis in normal brain. AMA Arch Neurol Psychiatry. 1959;81:409-418. Marshall RS, Lazar RM, Pile-Spellman J, et al. Recovery of brain function during induced cerebral hypoperfusion. Brain. 2001;124:1208-1217. Urbanski PP, Lenos A, Blume JC, et al. Does anatomical completeness of the circle of Willis correlate with sufficient cross-perfusion during unilateral cerebral perfusion? Eur J Cardiothorac Surg. 2008;33:402-408. Lee JH, Choi CG, Kim DK, et al. Relationship between circle of Willis morphology on 3D time-of-flight MR angiograms and transient ischemia during vascular clamping of the internal carotid artery during carotid endarterectomy. AJNR Am J Neuroradiol. 2004;25:558-564. van Laar PJ, van der Grond J, Bremmer JP, et al. Assessment of the contribution of the external carotid artery to brain perfusion in patients with internal carotid artery occlusion. Stroke. 2008;39:3003-3008. Hoksbergen AW, Majoie CB, Hulsmans FJ, et al. Assessment of the collateral function of the circle of Willis: Three-dimensional time-of-flight MR angiography compared with transcranial color-coded duplex sonography. AJNR Am J Neuroradiol. 2003;24:456-462. Alnaes MS, Isaksen J, Mardal KA, et al. Computation of hemodynamics in the circle of Willis. Stroke. 2007;38:25002505. Lebedeva ER, Gurary NM, Sakovich VP, et al. Migraine before rupture of intracranial aneurysms. J Headache Pain. 2013;14:15. Ujiie H, Liepsch DW, Goetz M, et al. Hemodynamic study of the anterior communicating artery. Stroke. 1996;27:20862093. Barstad RM, Orvim U, Hamers MJ, et al. Reduced effect of aspirin on thrombus formation at high shear and disturbed laminar blood flow. Thromb Haemost. 1996;75:827832. Holme PA, Orvim U, Hamers MJ, et al. Shear-induced platelet activation and platelet microparticle formation at blood flow conditions as in arteries with a severe stenosis. Arterioscler Thromb Vasc Biol. 1997;17:646-653. Stam AH, Haan J, van den Maagdenberg AM, et al. Migraine and genetic and acquired vasculopathies. Cephalalgia. 2009;29:1006-1017. Perko D, Pretnar-Oblak J, Sabovic M, et al. Associations between cerebral and systemic endothelial function in migraine patients: A post-hoc study. BMC Neurol. 2011; 11:146. Borgdorff P, Tangelder GJ. Migraine: Possible role of shear-induced platelet aggregation with serotonin release. Headache. 2012;52:1298-1318.
June 2014 18. Jenxoxo. Sticky blood platelets cause migraines. http://
www.migraineconnect.com/discussions/5-sticky-bloodplatelets-cause-migraines. 2013. 19. Kruit MC, Launer LJ, Ferrari MD, et al. Infarcts in the posterior circulation territory in migraine. The populationbased MRI CAMERA study. Brain. 2005;128:2068-2077. 20. Glor FP, Ariff B, Hughes AD, et al. Influence of head position on carotid hemodynamics in young adults. Am J Physiol Heart Circ Physiol. 2004;287:H1670-H1681.
Orthostatic Headache Without Intracranial Hypotension: A Headache Due to Psychiatric Disorder? Orthostatic headache with or without associated symptoms (neck or intrascapular pain, nausea and vomiting, change in hearing, diplopia, visual blurring, bitemporal hemianopsia, upper limb paresthesias, parkinsonism,1 stupor, and coma2) is indicative of intracranial hypotension that can occur either after active cerebrospinal fluid (CSF) removal (eg, after a lumbar puncture) or spontaneously (spontaneous intracranial hypotension [SIH]) as a result of a spinal meningeal CSF leak.3,4 Spontaneous CSF leaks are attributed to the underlying fragility of the spinal meninges (sometimes associated with connective-tissue disorders) that easily tear when exposed to a mechanical factor, such as a minor trauma.3 A trivial trauma such as coughing, pulling, pushing, and lifting is reported in a minority of the patients.3 Diagnosis is based on clinical presentation and typical brain magnetic resonance imaging (MRI): thickening of the dura with diffuse pachymeningeal enhancement,sometimes brain sagging, subdural fluid collections, dilatation of the venous compartment with dural sinuses,and pituitary gland enlargement. When these aspects are present, it is not necessary to measure the CSF opening pressure.4 The first-line treatment of this disorder is conservative, including bed rest, oral hydration, analgesics, nonsteroidal anti-inflammatory drugs, and caffeine or theophylline intake.3 Spinal MRI, computed tomography or MRI myelography and radionuclide cisternography should be used to identify the site of the CSF leak3 if conservative treatment fails. Treatment is usually conservative, but autologous epidural blood patch (EBP) has emerged as the most important nonsurgical management.5 Some resistant cases underwent percutaneous injection of fibrin glue6 and surgical repair of the dural tear is reserved for refractory cases when the site of the CSF leak is located.3 Conflict of Interest: None.
Headache From among 214 patients referred to one of us (E.F.) over a 21-year period between April 1992 and May 2013, for evaluation of orthostatic headache (OH) and suspected SIH, 10 patients with negative head and spinal MRI and normal CSF opening pressure (CSF-OP) were identified. Nine patients were women. Mean age at the time of evaluation was 37 years (range 16-65). All patients also had anxiety-depressive disorder (mild grade in 7 patients and moderate grade in 3 patients), one of them was also suffering from conversion disorder, another from pseudoseizures, and one from mild hyperlaxity joints. Median duration of orthostatic headache prior to evaluation at our institution was 9.5 months (range 3-36). Cochleovestibular symptoms were present in 4 patients. Eight patients performed the lumbar puncture in sideways (mean CSF-OP was 140.2 mmH2O [range 80-240]), while 2 in a sitting position (mean CSF-OP was 490 mmH2O [range 440-540]). On the top of best psychiatric treatment, 9 patients performed EBP in Trendelenburg position2 ex juvantibus criterium. One patient was treated with bed rest and overhydration for a short time. After mean follow-up of 21.6 months (range 6-74), 3 patient experienced a complete recovery, and 3 patients improved after EBP; the one treated with only conservative therapy improved with a low dose of aripiprazole (1 mg/day). Three patients with moderate psychiatric disorder had persistent OH. A small series of 6 similar patients has been published,7 in which 5 patients remained severely symptomatic and work disabled at an average follow-up of 4 years. The most likely explanation for these cases is the existence of an intermittent or very slow flow leak that would evade identification by existing imagining techniques. Alternative etiological hypotheses are of increased compliance of the lower spinal CSF space shifting the hydrostatic indifferent point downward in the orthostatic position (inducing compensatory dilation of painsensitive intracranial venous structures without changing CSF pressure at the lumbar level8 or of orthostatic CSF leakage to the epidural venous network.9 In this small series, it is not described whether or not the patients had psychiatric disorders in their medical history. A similar case has been described10 in which a progressive improvement occurred simultaneously to the introduction of vitamin A supplementation. A beneficial effect of vitamin A supplementation was speculated from this report. This patient was also suffering from chronic fatigue treated with bupropion 150 mg qd, amitriptyline 35 mg qd. Orthostatic headache can occur without evidence of intracranial hypotension or detectable CSF leak despite extensive diagnostic testing. Clinical features alone are unlikely to differentiate between
1057 orthostatic headache with and without identifiable CSF leak. We think that in our series, as also in the case report (the patient was taking antidepressant drugs), the underlying psychiatric disorder was the major cause of orthostatic headache that might be considered as a new type of headache attributed to psychiatric disorder. Further studies are needed to confirm these data.
Acknowledgments: We acknowledge Dr. Daria Roccatagliata for having kindly reviewed the manuscript.
Enrico Ferrante, MD; Fabio Rubino, MD Headache Centre, Neurosciences, Ospedale Niguarda Cà Granda, Milano, Italy (E. Ferrante); Anesthesiology Department, Ospedale Niguarda Cà Granda, Milano, Italy (F. Rubino)
REFERENCES 1. Pakiam A, Lee C, Lang A. Intracranial hypotension with Parkinsonism, ataxia, and bulbar weakness. Arch Neurol. 1999;56:869-872. 2. Ferrante E, Arpino I, Citterio A, et al. Coma resulting from spontaneous intracranial hypotension treated with the epidural blood patch in the Trendelenburg position premedicated with acetazolamide. Clin Neurol Neurosurg. 2009;111:699-702. 3. Mokri B. Spontaneous low cerebrospinal pressure, low volume headaches: Spontaneous CSF leaks. Headache. 2013;53:1034-1053. 4. International Headache Society. The International Classification of Headache Disorders: 2nd ed. Cephalalgia. 2004;24(Suppl. 1):9-160. 5. Ferrante E, Arpino I, Citterio A, et al. Epidural blood patch in Trendelenburg position pre-medicated with acetazolamide to treat spontaneous intracranial hypotension. Eur J Neurol. 2010;17:715-719. 6. Schievink WI, Moser FG, Pikul BK. Reversal of coma with an injection of glue. Lancet. 2007;369:1402. 7. Leep Hunderfund AN, Mokri B. Orthostatic headache without CSF leak. Neurology. 2008;71:1902-1906. 8. Levine DN, Rapalino O. The pathophysiology of lumbar puncture headache. J Neurol Sci. 2001;192:1-8. 9. Franzini A, Messina G, Nazzi V, et al. Spontaneous intracranial hypotension syndrome: A novel speculative physiopathological hypothesis and a novel patch method in a series of 28 consecutive patients. J Neurosurg. 2010;112: 300-306. 10. Gil-Gouveia R. Treatment of orthostatic headache without intracranial hypotension: A case report. Cephalalgia. 2013; 33:948-950.
