With Vasospasm and Delayed

Andrew J. Cole, MD, Michel Aub\l=e'\,MD

\s=b\Three women with well-documented -stem have each been de¬ difficult to arouse, and was again brought to migraine associated with intracerebral scribed. In the majority, neurological the emergency department. She was hyper- hemorrhage are described. In each case, dysfunction is attributed to ischemie tesive, bradycardic, and stuporous, but, af¬ ter was able to follow migraine began during adult- , presumably secondary to vas¬ stimulation, simple commands. She had a dense left hemiplegia hood. Unusually severe and protracted cular spasm. Intracerebral hemor¬ associated with a left-sided homonymous heralded the onset of fixed neu- in has rhage migrainous patients only hemianopia and right gaze preference. rological deficits associated with lobar in- rarely been reported,7 and has some¬ Brain computed tomographic scanning tracerebral carotid hemorrhage. Striking times been associated with preexisting demonstrated a right frontoparietal intra¬ artery tenderness was characteristic. Ex- arteriovenous malformations.8·9 This cerebral hemorrhage (Fig 1, center). A ca¬ cept for a history of migraine, no cause for article describes a group of patients, rotid arteriogram showed narrowing of the intracerebral hemorrhage could be estab- all of whom are female, affected with Ml segment of the right middle cerebral lished. In each case arteriography showed migraine who presented with lobar in¬ artery (Fig 1, right). There was mass effect related to the but no evidence of extensive spasm of the appropriate ex- tracerebral hemorrhage either during , arteriovenous or tracranial or intracranial artery. Surgical or mi¬ malformation, , immediately following typical tumor. A pathology following evacuation of two attacks. All were in¬ right frontoparietal craniotomy graine patients was performed with evacuation of the hem¬ hematomata demonstrated signs of ves- in no evidence of un¬ vestigated detail; atoma. Pathologic examination of the sur¬ sel wall necrosis associated with subacute derlying vascular malformation or tu¬ gical material showed areas of cerebral inflammatory changes. Vasospasm asso- mor was discovered. Radiologie studies necrosis surrounding partially necrotic ciated with severe migraine attacks may suggested that early and severe vaso¬ ruptured small arteries without evidence of result in ischemia of intracranial vessel spasm of either the intracranial or ex¬ vascular malformation, tumor, or amyloid walls, leading to necrosis and subsequent tracranial vessels was important in angiopathy. She made a slow recovery and vessel rupture when perfusion pressure is the of was discharged with a persistent neurolog¬ development hemorrhage. ical deficit. restored. REPORT OF CASES woman suffered (Arch Neurol. 1990;47:53-56) Case 2.—A 45-year-old Case 1.—A 61-year-old woman had a from common migraine headaches associ¬ 4-year history of migraine headaches pre¬ ated with photophobia and nausea for sev¬ eral She took no medications and in that ceded by an aura of left-sided paresthesias. years. 1881, suggested any to the used no illicit drugs. One day prior to Charcot,the transient neural She presented emergency depart¬ of dysfunc¬ ment complaining of severe bitemporal admission she had an attack similar to her tions of migraine could become headache, similar to previous attacks. A usual headaches, but somewhat more se¬ permanent.1 Since then, migraine has neurological consultant found the patient vere. Twenty-four hours later, she suddenly been associated with residual neuro¬ to be normotensive, and the examination developed a left , associated logical deficits in a large number of results to be entirely normal. A lumbar with left hemihypesthesia. On admission, her blood and heart rate were cases, and the concept of compli¬ puncture was performed and the results re¬ pressure cated has become vealed normal cerebrospinal fluid. She was normal. She was alert and cooperative. migraine widely was tenderness over the Retinal, cortical, and discharged on analgesics and propranolol. There striking accepted.26 Two days later she returned complaining right carotid artery, but the pulse was nor¬ of severe headache, and, on this occasion, mal and there were no bruits. She had a Accepted for publication April 24,1989. had a mild left hemiparesis with a left dense left hemiplegia. From the Montreal (Canada) Neurological Hos- Babinski's sign. was again Brain computed tomographic scanning now the pital and Institute. Dr Cole is with normal. Computed tomographic scans of showed a homogeneous, well-defined, round Departments of Neurology and Neuroscience, The the brain, with and without contrast infu¬ hyperdensity in the right frontoparietal Johns University School of Medicine, Hopkins were normal 1, and she was consistent with an intracerebral he¬ Baltimore, Md. sion, (Fig left), region on in an ef¬ matoma 2, A internal Reprint requests to Department of Neuro- discharged prednisone therapy (Fig left). right-sided science, The Johns Hopkins University School of fort to abort a severe migraine attack. carotid arteriogram demonstrated an avas- Medicine, 725 N Wolfe St, Baltimore, MD 21205 Twenty-four hours later her headache cular mass in the right . There (Dr Cole). worsened. The following morning she was was beadlike narrowing of the extracranial

Downloaded From: http://jamanetwork.com/ by a Harvard University User on 12/29/2016 Fig 1.—Case 1. Left, Normal brain computed tomographic scan with intravenous contrast infusion 2 days prior to intrace¬ rebral hemorrhage. Center, Brain computed tomographic scan without contrast at time of admission showing large right-sided frontoparietal hematoma. Right, Right-sided internal carotid arteriogram showing focal spasm of initial segment of right middle cerebral artery.

portion of the right internal carotid artery (Fig 2, right), which was unchanged on two separate injections. Two days later, because of the suspicion of underlying tumor, a right-sided frontal craniotomy with evacuation of the hem¬ atoma was performed. There was no patho¬ logic evidence of tumor or of underlying vascular abnormality. A subacute inflam¬ matory infiltrate composed mainly of mac¬ rophages was seen in the neuropil (Fig 3). There was some thickening of vessel walls with increased cellularity and a mild lym- phocytic perivascular infiltrate. Case 3.—A 46-year-old woman with a 20- year history of common migraine developed a right frontal throbbing headache associ¬ ated with nausea and photophobia, which was similar to her usual attacks, but in¬ creased progressively over several days. She was treated with analgesics that pro¬ vided partial relief. Four days later, after continued headache, she noted left face and arm weakness and numbness, and came to the emergency department. Blood pressure Fig 2.—Case 2. Left, Brain computed tomographic scan without contrast, showing large left-sided and heart rate were normal. Carotid pulses frontoparietal intracerebral hemorrhage. Right, Left internal carotid arteriogram showing spasm of were full, but there was tenderness over the extracranial portion of internal carotid artery. Intracranial vessels are displaced by large avascu- right carotid artery. She had right-gaze lar mass. preference associated with a left hemipare¬ sis involving the face and arm more than the leg and a left Babinski's sign. Computed that had been present on the first study (Fig rhage in each of these patients can tomographic scan showed a right-sided 4, right). be inferred. Intracerebral hemor¬ frontoparietal hematoma (Fig 4, left). A only is selective digital right-sided carotid arterio¬ COMMENT rhage most commonly associated gram demonstrated severe narrowing of with , aneurysmal bleed¬ the extracranial portion of the internal ca¬ These patients all manifested a rel¬ ing, rupture of macroscopic or cryptic rotid artery (Fig 4, center). There was no atively stereotyped pattern of head¬ vascular malformations, tumor necro¬ evidence of arteriovenous malformation. ache associated with intracerebral sis, primary vasculopathy, or, in popu¬ Over the next 24 severe hours, right-sided hemorrhage (Table). Two had common lations at risk, or co¬ headache and was associated with persisted migraine and one suffered from classic caine abuse. None of these conditions tenderness over the on the side. scalp right was demonstrated either the clin¬ She was discharged with residual left-sided migraine. Suddenly, following typical by each suffered lobar in¬ or weakness, and continued to make a slow re¬ attacks, major ical, artériographie, pathologic covery. Three months later she underwent tracerebral . studies. a repeated right-sided carotid arteriogram A relationship between preexisting The finding of tenderness over the that showed resolution of the narrowing migraine and intracerebral hemor- appropriate carotid artery was strik-

Downloaded From: http://jamanetwork.com/ by a Harvard University User on 12/29/2016 ing in two of the patients, and sug¬ gested by the artériographie findings performed 2 days before the hemor¬ gested that carotid vessel pathologic in case 3, remains a possibility in that rhage occurred, was entirely normal. findings were important in the devel¬ case, but has typically been associated There was no evidence of ischemia or opment of intracerebral hemorrhage. with ischemie stroke.12 of vascular malformation. Carotidynia has been associated with Brain computed tomographic scan¬ All patients underwent artério¬ carotid artery dissection, carotid ar¬ ning was highly suggestive of sponta¬ graphie studies of appropriate vessels. tery occlusion, carotid artery aneu¬ neous hemorrhage in two patients, and In each case there was evidence of sig¬ rysm, giant cell arteritis, and mi¬ in one case (case 2) suggested the pos¬ nificant spasm of a major vessel sup¬ graine.10" None of our patients had a sibility of underlying tumor. The im¬ plying the area in which hemorrhage vessel biopsy performed to rule out ages were not consistent with the di¬ occurred. In the two patients with ca¬ giant cell arteritis, but normal sedi¬ agnosis of hemorrhagic in rotidynia, spasm was apparent in the mentation rates argued against this that the hematomata were dense, well extracranial portion of the internal diagnosis. There was no evidence of circumscribed, and did not show the carotid artery. In those patients the occlusion or aneurysm in any of these patchy hyperdensity usually associ¬ possibility of -induced spasm cases. Spontaneous carotid artery dis¬ ated with that condition. In one case seemed unlikely in view of both its section, a diagnosis that might be sug- (case 1), a computed tomographic scan, persistence on repeated injections and the existence of carotidynia prior to the arteriogram. In the third patient, spasm was seen in the proximal seg¬ ment of the middle cerebral artery. , cerebral trauma, central nervous system infec¬ tion, drug abuse, toxemia, fibromuscu- lar dysplasia, carotid artery dissec¬ tion, and cerebral vasculitis have all been associated with the radiographie appearance of spasm of the cerebral arteries. In the present cases, only the latter three possibilities could be rea¬ sonably entertained. One patient (case 3) in whom the di¬ agnoses of fibromuscular dysplasia or carotid artery dissection were consid¬ ered underwent follow-up study 3 months after intracerebral hemor¬ rhage. At that time, spasm had com¬ pletely resolved, and the vascular ap¬ pearance was normal. Follow-up an¬ giographie studies in fibromuscular dysplasia have demonstrated either stable or progressive pathologic find¬ Fig 3.—Case 2. Brain specimen from area adjacent to intracerebral hemorrhage showing suba¬ ings, but resolution of that process has cute inflammatory infiltrate. Arrows point to macrophages. Note perivascular lymphocytic infiltra¬ not been described1317 Carotid artery tion (hematoxylin-eosin, X115). narrowing due to dissection may dis-

Fig 4.—Case 3. Left, Brain computed tomographic scan without contrast showing right-sided frontoparietal intracerebral hemorrhage. Center, Digital angiogram showing extensive narrowing of extracranial portion of right internal carotid artery. Right, Right common carotid arteriogram 3 months later, showing resolution of spasm.

Downloaded From: http://jamanetwork.com/ by a Harvard University User on 12/29/2016 scribed represents one extreme of the Summary of Clinical Features spectrum of "benign" cerebral vaso¬ Cases spasm. A migrainous cause for the arterio- Characteristic graphically demonstrated spasm of Age, y/sex 61/F 45/F 46/F vessels, either extracranial or intra¬ Type of migraine Classic Common Common cranial, in each of the patients can only Duration of 24 h 4 d be suspected because of the similarity headache prior of each patient's prodromal symptoms to intracerebral those hemorrhage to associated with her typical attacks. It is Carotidynia Not noted ++++ possible that intracere¬ bral was the Angiographie Spasm of middle Spasm of internal Spasm of internal hemorrhage result of findings cerebral artery carotid artery carotid artery temporary ischemia of vessel walls Pathologic findings Vessel wall necrosis Subacute Not available followed by sudden reperfusion with perivascular rupture of ischemie ves¬ inflammation subsequent sels. An analogous process, as recently suggested by Caplan,23 may explain in¬ tracerebral hemorrhage associated appear over time, thus the diagnosis tracranial and extracranial cerebral with and has been remains in the which when toxemia,24 suggested possible present case, arteries, largely improved to explain intracerebral hemorrhage although spontaneous hemorrhage re¬ repeated examinations were done associated with sympathomimetic from as to weeks or months later. Serdaru et al22 sulting dissection, opposed abuse,25 nerve stimu¬ has have a in whom a bi¬ drug trigeminal hemorrhagic infarction, not previ¬ described patient lation with resultant been our knowl¬ the of a abrupt hyper¬ ously reported (to opsy of narrowing portion tension,26 cold exposure,27 and carotid edge).12 temporal artery, as documented by with was Based on endarterectomy subsequent None of these patients had clinical angiography, performed. reperfusion.28 or serologie evidence of systemic vas- the absence of inflammation, those au¬ several have thors that cerebral culitis. Recently, reports suggested "benign We wish to thank Dr D. Melancon for interpre¬ described a condition known as acute vasculitis" may represent a vasospas- tation of neuroradiological studies, Dr Y. Ro- benign cerebral vasculitis character¬ tic phenomenon related to an underly¬ bitaille for interpretation of pathologic material, ized by the occurrence of transient fo¬ ing migrainous diathesis. Two such Drs A. Hakim and G. Francis for caring for two cal often associ¬ with intracerebral of the patients, Drs A. Olivier and R. Leblanc for neurological deficits, patients presented neurosurgical consultations, Dr F. Andermann ated with severe headache and mild hemorrhage. While not described in for reviewing the manuscript, and Dr L. Caplan abnormalities of the cerebrospinal detail in their article,18 those patients for helpful discussions and advice. fluid.1822 Angiography in those patients resemble ours in their outline, and it is disclosed narrowing of multiple in- likely that the condition we have de-

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