Case Report Central Nervous System Superficial Siderosis, Headache, and Epilepsy S. Iannacconc, MD; V. Golzi, MD; B. Sferrazza, MD; FE de Rino, MD; S. Smirne, MD; L. Ferini-Strambi, MD Almost 95 cases of superficial siderosis of the central nervous system have been reported in the literature. These patients showed a clinical syndrome characterized by ataxia, deafness, pyramidal system involvement, and mental deterioration with xanthochromic cerebrospinal fluid and neuroradiological findings of hemosiderin deposits. About 30% of the patients had headache as an accompanying symptom. In the present case report, we describe a 33-year-old man with the typical clinical features of superficial siderosis, who complained, since aged 8, of a severe recurrent frontal headache often associated with loss of consciousness occurring after at least 2 hours of pain. The MRI and CSF findings were consistent with subarachnoid bleeding. In our patient, headache due to meningeal irritation by subarachnoid blood induced seizures as a probable reflex of extreme pain. Carbamazepine and nimodipine praphylaxis dramatically reduced the frequency of headaches and seizures. Key words: siderosis, central nervous system, epilepsy, headache Abbreviations: SS superficial siderosis (Headache 1999;39:666-669) Superficial siderosis (SS) of the central nervous sys- tem (CNS) is a rare disorder characterized by hemosiderin deposits in the leptomeninges, subpial tissues, spinal cord, and cranial nerves in contact with cerebrospinal fluid (CSF).!2 Experimentally, similar deposits have been pro- duced in animals following intrathecal, but not intra- venous, injections of blood: this could be explained by the inability of a high blood iron concentration to break down the intact blood-brain barrier.3 The etiology of SS is attrib- uted to chronic bleeding into the subarachnoid spaces by well-identified causes in about 55% of cases (dural pathology, ependymomas, aneurysms, arteriovenous mal- formations). In patients without detectable brain or spinal cord lesions, a microscopic venous or capillary origin of From the Department of Neurology, IRCCS H. S. Raffaele, University of Milan, Italy. Address all correspondence to Dr. S. lannaccone, Department of Neurology, via Prinetti, 29, 20127 Milan, Italy. Accepted for publication January 22, 1999. 666 blood extravasation is suspected.!45 The clinical picture is severe and is quite variable. The cardinal features are sensorineural deafness (95%), cerebellar ataxia (88%), and pyramidal signs (76%), but other features include headache (30%), dementia (24%), bladder disturbances (24%), anosmia (17%), anisocoria (10%), and sensory symptoms (13%).6 In both human and experimental SS, the CSF is typi- cally xanthochromic and rich in protein.'5 T2-weighted MRI images are specific and show marginal hypointensi- ty involving several parts of the CNS.7-° We report a patient with SS, headache, and related epileptic seizures, an association not previously described. CASE HISTORY A 33-year-old man was admitted to our neurological department in order to investigate a severe, recurrent, frontal headache of which he had been complaining since aged 8. The headache was described as stabbing, frontal, sudden in onset, gradually increasing in severity, lasting 8 to 12 hours, and generally occurring twice a week. At the beginning, the headache attacks occurred everyday. The October, 1999 headache was often associated with nausea, vomiting, and photophobia. During the painful attacks, several episodes (usually two or three) of loss of consciousness and rigidi- ty of the limbs were described, with recovery to full con- sciousness after a few minutes each time. At 3 years of age, the patient had suffered a head injury with coma of 40 days’ duration. The neurological examination at that time revealed a left-sided hemiparesis. At aged 18, a diagnosis of neurosensory hearing loss was made. Neurological examination on admission revealed deafness, a mild left-sided hemiparesis, generalized brisk reflexes, and gait ataxia. Routine blood chemistry tests were normal, including serum iron and ferritin levels. A routine EEG revealed slow background activity with spo- radic sharp discharges over the left temporal lobe. An EEG performed during a headache attack, followed 40 minutes later by a seizure, showed diffuse theta activity and, at the onset of the seizure, a brief and sudden burst suppression followed by diffuse generalized slow waves (Figure 1). The seizure was clinically characterized by torsion of the head to the left, rigidity of the right limbs, vocalization, and loss of consciousness. The seizure lasted 80 seconds and return to full consciousness was 10 minutes later, but headache continued for about 3 hours. Lumbar puncture performed 2 days after this headache attack revealed xanthochromic CSF with a red cell count of 9000/mm? and a ferritin level of 72 ng/mL (reference values 17 to 20 ng/mL). T2-weighted cerebral and spinal MRIs, before and after intravenous administration of gadolinium, showed deposi- tion of hemosiderin all along the spinal cord and around the cerebellum, brain stem, and bilateral eighth cranial nerves (Figures 2 and 3). Cerebral and spinal angiography showed no arteriovenous malformation or other source of bleeding. Treatment with carbamazepine 400 mg twice a day and nimodipine 90 mg per day was started. Over the next 3 years, he complained of only one cephalalgic crisis. Epileptic seizures had not recurred. COMMENTS Fearnley et al, who reviewed 69 cases, and Arnaud et al!° described headache as a common symptom in SS; a sudden severe headache occurred in at least 30% of patients. The headache was related to subarachnoid bleed- ing even if the CSF sometimes failed to show evidence of Headache Fig 1.-Electroencephalogram performed during one headache attack. Arrow shows the onset of the seizure. hemorrhage or the examination was not performed imme- diately.6'0 On the contrary, seizures have not frequently been reported. Only three patients affected by SS showed convulsions unrelated to headache attacks.!! The clinical course of the case presented here is not typical of previously published descriptions. The sympto- matology, which began with the onset of headache attacks and seizures in childhood, persisted into adult life. Hypoacusis and ataxic gait were diagnostic symptoms, but they did not progressively worsen during the years, as is typical of primary SS. However, the neuroradiological and CSF findings were consistent with the diagnosis. The strict association of headache with epileptic seizures in SS has never been previously described. Our patient always had seizures following a severe and pro- tracted (at least 2 hours) headache; treatment with carba- mazepine and nimodipine drastically reduced the symptoms. In our patient, the casual relationship between the two disorders, headache and epilepsy, is evident on clinical grounds. It has been reported that classical (migraine with aura), basilar, and confusional migraine attacks may all lead to epileptic events.'? The triggering of epileptic events by migraine without aura remains a matter of speculation. Our hypothesis is that the association of a cerebral pathology, siderosis, with prolonged headache, induced seizures in our patient. By history, all of the epileptic attacks were preceded by headache, showing that the cere- bral pathology alone did not induce seizures. Our observation suggests that the prophylactic treat- ment with nimodipine reduced the frequency of headache 667 Fig 2A Fig 2B Fig 2D Fig 2A-E.-Axial spin echo T2-weighted images. There is a marked hypointensity of the surface of the pons, mid brain, ver- mis, cerebellar dentati nuclei, and bilateral eighth cranial nerves. Fig 2E 668 October, 1999 Fig 3A Fig 3B Fig 3A-B.-Sagittal spin echo T2-weighted images. Marked hypointensity of the surface of brain stem and spinal cord. and treatment with carbamazepine prevented the related epileptic seizures. The efficacy of nimodipine prophylaxis in our patient suggests a vasomotor or vasospastic patho- genesis for headache symptoms. Conversely, a possible prophylactic effect of the associated carbamazepine therapy can not be excluded. Headache REFERENCES 1. Hughes JT, Oppenheimer DR. Superficial siderosis of the central nervous system. A report on nine cases with autopsy. Acta Neuropathol (Berl). 1969;13:56-74. Koeppen AH, Dentinger MP. Brain hemosiderin and superficial siderosis of the central nervous system. J Neuropathol Exp Neurol. 1988;47:249-270. Noetzel H, Ohlmeier R. Zur frage der randzonesiderose des zentralnervensystems. Tierexperimentelle untersuchung. Acta Neuropathol (Berl). 1963;3:164-183. Koeppen AH, Dickson AC, Chu RC, Thach RE. The pathogenesis of superficial siderosis of the central nervous system. Ann Neurol. 1993;34:646-653. McGee DA, Van Patter HJ, Morotta J, Olszewski J. Subpial cerebral siderosis. Neurology. 1962;12:108- 113. Fearnley JM, Stevens JM, Rudge P. Superficial siderosis of the central nervous system. Brain. 1995;118:1051-1066. Offenbacher H, Fazekas F, Reisecker F, Schmidt R, Payer F, Lechner H. Superficial siderosis of the spinal cord: a rare cause of myelopathy diagnosed by MRI. Neurology. 1991;41:1987-1989. Offenbacher H, Fazekas F, Schmidt R, Kapeller P, Fazekas G. Superficial siderosis of the central ner- vous system: MRI findings and clinical significance. Neuroradiology. 1996;38(suppl [):S51-S56. Pyhtinen J, Paakk6 E, IIkko E. Superficial siderosis in the central nervous system. Neuroradiology. 1995;37:127-128. . Arnaud A, Hermosilla E, Ferrer X, Devoize JL, Rajabally Y, Lagueny A. Case of superficial hemo- siderosis of the central nervous system treated with trientine [in French]. Rev Neurol. 1998;154:243-245. . Willeit J, Aichner F, Felber S, et al. Superficial sidero- sis of the central nervous system: report of three cases and review of the literature. J Neurol Sci. 1992;111:20-25. . Andermann F. Migraine and epilepsy. An overview. In: Andermann F, Lugaresi F, eds. Migraine and Epilepsy. Boston: Butterworths; 1987;27:405-422. 669