Progressive facial hemiatrophy: Abnormality of intracranial vasculature Article abstract-Progressive facial hemiatrophy (PFH) or Parry-Romberg syndrome is associated with ipsilateral brain lesions and neurologic symptoms. We describe a 35-year-old man with PFH and frequent hemiplegic migraine. On cerebral angiography, reversible vessel caliber changes were seen within the symptomatic hemisphere. An abnormality of the intracranial vasculature may be present in some patients with PFH and neurologic manifestations. NEUROLOGY 1998;50:1915-1917 Andrew R. Woolfenden, MD; David C. Tong, MD; Alexander M. Norbash, MD; and Gregory W. Albers, MD At age 34 years, the patient developed an atrophic hyProgressive facial hemiatrophy (PFH; also known as perpigmented patch of skin on his left forehead diagnosed Parry-Romberg syndrome) is characterized by slowly as PFH. His history was otherwise unremarkable. There progressive but self-limited atrophy of facial subcuwas no family history of neurologic illness. taneous fat, which can be followed by wasting of associated skin, cartilage, connective or ocular tissue, muscle, and bone.lS2 PFH is most often unilateral and usually affects one or more of the trigeminal dermatomes, although body parts outside this distribution may be involved.lX2 Its relation t o linear scleroderma is unclear, although some authors consider these to be overlapping c0nditions.l Symptoms usually begin in the first or second decades of life, but onset has occurred in patients older than 60 years.2 Many patients are neurologically normal, although symptoms attributable to ipsilateral cerebral hemispheric dysfunction are not uncommon. Seizures are the most frequent neurologic sympt0rn.l Others include cranial nerve deficits, masticatory spasms, cognitive abnormalities, and fixed focal deficits.lX2 Hemiplegic migraine has been the focus of only two previous report^.^,^ CT and MRI findings in PFH patients with neurologic disease are usually ipsilateral and may include hemispheric calcifications, leptomeningeal enhancement, loss of cortical gyration, hyperintensities in deep white and gray matter structures, and atrophy (manifested by dilatation of the lateral ~ e n t r i c l e ) . ~ . ~ , ~ The underlying pathophysiology of these changes is unknown. Results of cerebral angiography have frequently been normal in those s t ~ d i e d . ~ We describe a patient with PFH and frequent hemiplegic migraine observed over 5 years. On cerebral angiography, reversible vessel caliber changes were seen within the symptomatic hemisphere. Case report. The patient, a 35-year-old right-handed man, began having neurologic symptoms in early 1991. At that time, he developed hesitant initiation of speech when reading aloud. In late 1991, he had an episode of numbness and paresthesias in his right arm. The spell started in the fingertips and migrated, over several minutes, to the shoulder. His arm became weak and he developed an expressive dysphasia. His leg was unaffected. These symptoms lasted about 1hour and as they resolved, the patient developed a generalized throbbing headache with nausea, vomiting, photophobia, and phonophobia. He had two similar episodes over the next 2 months, although the transient symptoms before the headache lasted 2 hours rather than 1. Figure 1. Image A is a T2-weighted axial MRI (time to repeat [TR] = 2400, time to echo [TE] = 80) which demonstrates abnormalities within the left hemisphere including increased signal in the subcortical and deep white matter and effacement of the normal gyral pattern. Abnormal leptomeningeal enhancement and dilation of the lateral ventricle are seen on the TI-weighted (TR = 800, TE = 20) gadolinium-enhanced scan in image B. Image C is a follow-up T2-weighted MRI (TR = 2500, T E = 100) at a similar level to image A which shows slightly more prominent white matter T2 hyperintensity with otherwise similar abnormalities. Image D is a follow-up TI-weighted (TR = 616, T E = 14) gadolinium-enhanced MRI that shows less prominent leptomeningeal enhancement. Copyright 0 1998 by the American Academy of Neurology 1915 In early 1992, he had another neurologic episode, which began in an identical fashion; however, the hemiparesis, aphasia, and headache persisted, prompting transfer to Stanford University Medical Center. On admission, general examination was remarkable only for atrophy of the subcutaneous tissue of his left forehead and nares. On neurologic examination, he was alert and combative with a global aphasia. Meningismus was absent. He had a mild left gaze preference with a right homonymous hemianopsia. Right upper motor neuron facial weakness was present with ipsilateral increased limb tone, unsustained ankle clonus, hemisensory loss, and significant hemiparesis. Reflexes were brisk on the right with a positive Babinski response. Results of a complete blood count, hepatic and renal function, erythrocyte sedimentation rate, and CSF analysis were normal. Results of a complete hypercoagulable screen were negative. Syphilis, lyme, and HIV serology were negative. Antinuclear antibodies were present at a low titre (1:40). There was diffuse monomorphic delta activity over the left hemisphere on EEG. MRI demonstrated unilateral leptomeningeal enhancement, marked increase of T2 signal in the white matter, loss of the normal cortical gyral pattern, and enlargement of the lateral ventricle of the left hemisphere (figure 1, A and B). Several irregular intracranial vessels were seen on a left carotid angiogram (figure 2, A and C). A left frontal leptomeningeal and brain biopsy revealed minimal mononuclear inflammatory infiltrate and moderate fibrosis of the leptomeninges with mild astrocytosis in the white matter. The patient was treated with prednisone and cyclophosphamide for possible CNS vasculitis. His neurologic deficits completely resolved over 1 week. In the next 2 months, the patient had three more transient 1 to 2 hour episodes of right hemiparesis with aphasia followed by headache, prompting readmission to the medical center. Results of bloodwork and CSF examinations were again normal. The MRI was unchanged. Repeat left carotid angiography was normal (see figure 2, B and D). The neurologic diagnosis remained uncertain; however, he was continued on immunosuppressive therapy for 1 year. In 1997, he was referred to the Stanford Stroke Service for evaluation of continued intermittent right hemiplegia, hemisensory loss, and aphasia followed by headache and one separate generalized seizure. The headache episodes had continued a t a frequency of one every 2 to 4 weeks since 1992. He had one isolated unprovoked generalized seizure in the weeks preceding this visit. On neurologic examination, the only abnormal finding was a reduced right arm swing while walking. There was no progression of the hemifacial atrophy. A repeat MRI revealed more substantial white matter disease without other worsening (figure 1, C and D). A diagnosis of PFH complicated by hemiplegic migraine and seizures was made and the patient was started on valproic acid to use one medication for both migraine and seizure prophylaxis. There were no recurrent seizures and the migrainous episodes were substantially improved a t follow-up 4 months later. Figure 2. (A) Cerebral angiography shows subtle irregularities in proximal (open arrow) and distal (closed arrow) cerebral artery branches; (B) improvement in these abnormalities 2 months later; (C) magnified view of the area denoted by the closed arrow in A; (D) and magnified view of the area denoted by the closed arrow in B. 1916 NEUROLOGY 50 June 1998 Discussion. The pathophysiology of PFH is uncergraine is uncertain. However, stellate ganglion block tain. Four proposed theories include cortical dysgenhas precipitated migraine with aura, which demonesis,I sympathetic nervous system d y s f ~ n c t i o n , ~ strates the potential for vascular alterations to prechronic localized meningoencephalitis,z,6and autoimcipitate an aura.lo m ~ n i t y . Fry ~ , ~ et al. have suggested that PFH is a The presence of reversible angiographic changes regional disorder of the face and underlying neural in our patient lends further credence to a vascular structures of undetermined pathophysiology.8 These abnormality in PFH. There are many reports of norhypotheses attempt to explain the presence of conmal angiography in patients with PFH.5 Therefore, comitant involvement of the ipsilateral face and we conclude with caution that the reversible vessel brain in the context of known clinical, radiologic, changes observed in our patient are due to PFH. experimental, and limited pathologic data. The abAlternatively, the findings may represent vasospasm sence of definitive supportive pathology, the observaattributable to the patient’s migraine. tion of disease onset as late as the 6th decade,2 and cases (including our own) documenting new or worsening lesions on serial MR13x5argues against dysgenFrom the Departments of Neurology (Drs. Woolfenden, Tong, and Albers) and Radiology (Dr. Norbash), the Stanford Stroke Center, esis in all patients. Contradictory experimental Stanford University, Palo Alto, CA. evidence5and the frequent lack of clinically apparent Received December 3, 1997. Accepted in final form January 9, autonomic dysfunction in PFH cast doubt on the 1998. sympathetic theory’s relevance t o most patients. Address correspondence and reprint requests to Dr. David C. Pathologic data have shown evidence of perivascular Tong, Stanford Stroke Center, 701 Welch Road, Building B, Suite 325, Palo Alto, CA 94304-1705. inflammation within brain tissue, leptomeningeal or cortical blood vessel irregularities with meningeal fibrosis, and lymphocytic infiltration of neurovascular bundles with abnormalities of vascular endoReferences thelium in the skin.2,6The development of linear 1. Dupont S, Catala M, Hasboun D, Semah F, Baulac M. Proscleroderma following local trauma and the presence gressive facial hemiatrophy and epilepsy: a common underlying dysgenetic mechanism. Neurology 1997;48:1013-1018. of autoantibodies in some patients further supports 2. Terstegge K, Kunath B, Felber S, Speciali JG, Henkes H, an inflammatory etiology6 but does not account for Hosten N. MR of brain involvement in progressive facial hemithe focal nature of the disorder. Prior pathology and atrophy (Romberg disease): reconsideration of a syndrome. our biopsy results may not be contradictory but may Am J Neuroradiol 1994;15:145-150. 3. Sagild JC, Alving J. Hemiplegic migraine and progressive represent different stages of a self-limiting vascular hemifacial atrophy. Ann Neurol 1985;17:620. Letter. inflammatory process. Alternatively, the pathologic 4. Ong B, Chong PN, Ye0 PPB. Progressive hemifacial atrodata may support a heterogeneous pathophysiology phy-a report of two cases. Singapore Med J 1990;31:497499. (inflammation, dysgenesis, or sympathetic dysfunc5. Cory RC, Clayman DA, Faillace WJ, McKee SW, Gama CH. tion) related to abnormalities of intracranial and exClinical and radiologic findings in progressive facial hemiatrotracranial vasculature. phy (Parry-Romberg syndrome). Am J Neuroradiol 1997;18: Our patient satisfies clinical criteria for migraine 751-757. 6. Pupillo G, Andermann F, Dubeau F. Linear scleroderma and with prolonged aura (hemiplegic migraine). Only two intractable epilepsy: neuropathologic evidence for a chronic prior reports have specifically addressed the associainflammatory process. Ann Neurol 1996;39277-278. Letter. tion of PFH and hemiplegic mig~-aine.~.~ Neverthe7. Peterson LS, Nelson AM, Su WPD. Subspecialty clinics: rheumatology and dermatology. Classification of morphea (localless, this association is additionally seen within the case descriptions of numerous other s e r i e ~ ,sug~ ~ ~ , ~ ~ized ~ scleroderma). Mayo Clin Proc 1995;70:1068-1076. 8. Fry, JA, Alvarellos A, Fink CW, Blaw ME, Roach ES. Intragesting that the association is more than coincidencranial findings in progressive facial hemiatrophy. J Rheumatal. Although controversial, a migrainous aura is to1 1992;19:956-958. 9, Wartenberg R. Progressive facial hemiatrophy. Arch Neurol likely a primary neuronal event rather than a priPsychiatr 1945;54:75-96. mary vascular event. Why some patients with PFH, 10. Lehmann LJ, Warfield CA, Bajwa ZH. Migraine headache whom we suspect have an abnormality of intracrafollowing stellate ganglion block for reflex sympathetic dystronial vasculature, are predisposed to hemiplegic miphy. Headache 1996;36:335-337. ~ ~ ~ ~~ ~ ~~~~~~ June 1998 NEUROLOGY 50 1917 Progressive facial hemiatrophy: Abnormality of intracranial vasculature Andrew R. Woolfenden, David C. Tong, Alexander M. Norbash, et al. Neurology 1998;50;1915-1917 DOI 10.1212/WNL.50.6.1915 This information is current as of June 1, 1998 Updated Information & Services including high resolution figures, can be found at: http://www.neurology.org/content/50/6/1915.full.html Citations This article has been cited by 3 HighWire-hosted articles: http://www.neurology.org/content/50/6/1915.full.html##otherarticles Permissions & Licensing Information about reproducing this article in parts (figures,tables) or in its entirety can be found online at: http://www.neurology.org/misc/about.xhtml#permissions Reprints Information about ordering reprints can be found online: http://www.neurology.org/misc/addir.xhtml#reprintsus Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 1998 by the American Academy of Neurology.. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.