Parry Romberg Syndrome: 7 Cases and Literature Review

Discussion

Parry Romberg syndrome is a sporadic and rare condition that has been reported to be more common in females,^{2⇓⇓⇓–6,10,15⇓–17,20} without apparent geographic or ethnic predilection.¹⁵ Onset typically occurs during the first and second decades of life, resulting in an initially insidious but progressive hemiatrophy of the face during a span of 2–20 years, with a slight propensity for the left side.^{3⇓⇓–6,8⇓–10,13⇓⇓⇓–17,20,25} Seemingly without cause, the progression abruptly arrests and stabilizes, reaching a “burned-out” phase.^{2,3,8⇓–10,14⇓⇓–17,25} Diagnosis of PRS mainly relies on the clinical history and examination and exclusion of other possibilities, supported by histopathologic and imaging studies.¹⁶

Patients characteristically experience atrophy of the skin and subcutaneous tissues and may develop atrophy of the underlying muscular, cartilaginous, osseous, and glandular structures as the disease progresses.^{1⇓⇓⇓⇓⇓⇓⇓–9,13⇓⇓⇓–17,20} The affected area typically begins in the maxillary or periorbital region and may expand to involve the forehead, perioral region, teeth, jaw, and neck to varying degrees.^{5⇓–7,12,14⇓⇓–17} Involvement of the teeth may help in determining the age of onset in unclear cases,¹⁷ because the presence of relatively smaller teeth with short roots has been reported in PRS.²¹ Earlier onset and longer duration of PRS have been reported to relate to increased severity of the disease.^3,17 Superficial changes such as skin discoloration and cicatricial alopecia may occur as well.^{5,7,15⇓–17} PRS is typically limited to 1 side of the head and neck, but bilateral disease has been reported. Similar manifestations involving the trunk and extremities are even rarer.^{14⇓⇓–17}

Neurologic symptoms occur in 15%–20% of patients, with the most common being ipsilateral headaches, facial pain, and seizures, which may be refractory to treatment.^{5,6,8,9,12⇓⇓⇓–16} Other reported neurologic symptoms include trigeminal neuritis, facial paresthesia, cranial nerve dysfunction, fixed focal neurologic defects, hemiparesis, and cognitive impairment.^{1⇓–3,5,8,9,11⇓⇓⇓⇓–16} Ophthalmologic symptoms occur in 10%–35% of patients and usually involve the ipsilateral orbit. Enophthalmos is common due to atrophy of the retrobulbar fat^{2,6,15⇓–17}; other potential orbital abnormalities include uveitis and retinal or optic nerve alterations.^{1,2,12,15⇓–17}

Many theories have developed during the years in an attempt to explain this peculiar disease. However, no single theory has been satisfactory in fully characterizing and predicting PRS, and our understanding of the underlying pathophysiology remains limited.³ Proposed etiologies have included trauma, genetic predisposition, infection, radiation exposure, embryonic developmental dysfunction, sympathetic cervical ganglion dysfunction, and metabolic and endocrinologic disturbances.^{1⇓–3,5⇓⇓–8,13⇓⇓⇓–17} Currently, the strongest laboratory and histologic evidence supports an inflammatory autoimmune disorder with or without associated vasculopathy.^{1⇓⇓⇓⇓–6,12,14,15,17} Clinical improvement with immunosuppressive therapy during active disease further supports an underlying immunologic-mediated process.^8,25

On radiologic assessment, common facial imaging findings include varying degrees of hemiatrophy accompanied by obliteration of fat planes, ipsilateral deviation of the aerodigestive tract, and enophthalmos due to loss of retrobulbar fat.^15,17 No abnormal CT attenuation or MR signal has been reported within the affected facial structures.¹⁵ Intracranially, the most common findings are the following: 1) ipsilateral linear or discrete subcortical calcifications in the frontal lobe, 2) white matter hypoattentuation on CT corresponding to hyperintense T2 signal on MR imaging,^{1⇓–3,7⇓⇓–10,13⇓⇓⇓⇓–18} and 3) ipsilateral focal or hemispheric brain atrophy.^16⇓–18 These findings typically occur ipsilateral to the affected side of the face¹⁵ and may worsen with disease progression.¹ Less frequently described imaging findings include the loss of cortical gyration, cortical thickening, ventricular dilation, focal corpus callosum infarcts, leptomeningeal thickening and contrast enhancement, attenuated mineral deposits, hamartomas, and MR signal abnormality involving the thalamus or gray matter.^{2,3,7,13,15⇓–17} Vascular abnormalities such as microhemorrhages, malformations, stenoses, and aneurysms have also been reported in association with PRS.^{3,13,15⇓–17,25}

In our case series, we demonstrated a variety of imaging findings in 7 patients with PRS. All patients had varying degrees of facial atrophy, and the affected extracranial structures retained normal signal patterns on MR imaging. Our first 4 patients underwent scanning for evaluation of facial findings. In 1 of the 4 patients, additional brain imaging was performed but revealed no abnormality. The remaining 3 patients with known diagnoses of PRS underwent dedicated brain imaging to evaluate neurologic symptoms; all had substantial intracranial manifestations with white matter signal abnormality ipsilateral to the side of facial atrophy being a consistent finding. One patient demonstrated a striking pattern of innumerable foci of susceptibility in the ipsilateral brain—these may represent microhemorrhages or foci of mineralization. In another patient, unexplained ventriculomegaly and associated small sulci could represent underlying hydrocephalus or may reflect an as-yet-undocumented intracranial manifestation of PRS.

PRS shares many clinical features, such as age of onset, associated neurologic symptoms, and cutaneous presentations with en coup de sabre, a rare variant of linear scleroderma that occurs along the anterior aspect of the scalp.^10,25,26 These 2 entities are commonly discussed in conjunction due to their overlapping presentations and lack of distinguishing clinical features.^{3,5,8,10,17,25} To make differentiation even more complicated, conversion of en coup de sabre to PRS has been reported,^7,17,21 and 30%–40% of patients with PRS have changes typical of scleroderma localized outside the face.^5,8,12 This has led many authors to consider these 2 entities variants that share a common underlying pathogenesis related to linear scleroderma.^{17⇓–19,21,22,25} Other authors, however, argue against this claim^10,26 because deeper head and neck structures, such as the oral or pharyngeal musculature, are not commonly involved in en coup de sabre, and there are typically elevated titers of autoantibodies in en coup de sabre but not in PRS.^21,22 On the other hand, PRS demonstrates little-to-no sclerosis of the cutaneous and subcutaneous structures, variable perivascular chronic inflammation, and preservation of dermal elastic tissue on histopathologic examinations, differentiating it from the spectrum of scleroderma diseases.^{3,16,17,25,26}

PRS also shares features with Rasmussen encephalitis, an autoimmune/inflammatory disorder affecting 1 side of the brain, resulting in refractory epilepsy and progressive hemiplegia and typically affecting children in the first decade of life.^14,27,28 On imaging, Rasmussen encephalitis is characterized by predominately unilateral hemispheric areas of hyperintense T2 signal with eventual development of unilateral cerebral atrophy,^27,28 findings that may be indistinguishable from intracranial imaging features of PRS. There have been reported cases of coexisting Rasmussen encephalitis and PRS in pediatric patients,^4,8,14,15,17 supporting a possible pathophysiologic correlation between these 2 entities. In younger patients, differentiating these 2 entities may be difficult, but clinical signs and symptoms, such as the presence of epilepsia partialis continua, a hallmark symptom of Rasmussen encephalitis, and involvement of cutaneous structures should guide the clinician and radiologist to the correct diagnosis.^{1,4,7,8,27,28}

Other diseases in which facial asymmetry is a prominent clinical feature include hemifacial microsomia (first and second brachial arch syndrome) and Goldenhar syndrome, but unlike PRS, these conditions are typically congenital and nonprogressive.^19,21,22 Hemifacial hyperplasia causes asymmetry of the face as well, but rather than atrophy, this entity is characterized by overgrowth and hyperplasia.^21,29 Partial lipodystrophy (Barraque-Simons syndrome) may have manifestations similar to those of PRS, but typically these are bilateral.^19,22 Silent sinus syndrome may also be considered, but these patients present later in life with characteristic imaging findings of opacification and atelectasis of the maxillary sinus and evidence of ipsilateral ostiomeatal unit obstruction.³⁰

No standard treatment algorithm currently exists for PRS,^12,17 especially given that response to treatment is difficult to assess.¹⁵ In general, treatment goals are to obtain seizure control if seizures are present, provide symptomatic relief, and halt disease progression.^17,18 PRS-related seizures are usually treated with anticonvulsive therapy despite their commonly refractory nature.^1,4,14 At times, lobectomy may be warranted for seizure control.^4,8 Additionally, similar to treatments for scleroderma, immunosuppressive therapies, ranging from topical corticosteroids to systemic corticosteroids, immunomodulators, and plasmapheresis, have been used with varying degrees of success. Antimalarials, antibiotics, vitamin D₃ analogues, and penicillamine are also treatment options that have demonstrated variable responses.^{5,8,10,14⇓⇓⇓–18} Once the disease stabilizes, cosmetic therapies, including pulse dye lasers, dermal fat grafts, autologous fat grafts, muscle flap grafts, free silicone injections, and bone augmentations, are available for aesthetic management.^10,23,24 Recently, autologous fat grafting with adipose-derived stem cells has been shown to provide the most favorable cosmetic results.^23,24 In these incidences, objective serial volumetric analysis of both hemifaces is important to monitor fat reabsorption, an indicator of successful grafting. Volumetric calculations can be easily achieved with 3D reconstructions of CT data acquired periprocedurally and on serial follow-up examinations, but alternative methods are being investigated as well due to concerns for cost and patient radiation exposure.^23,24

In summary, PRS is a rare, self-limiting, and slowly progressive hemiatrophy of the face that typically affects the skin and subcutaneous tissues and may affect deeper tissues such as the musculature, cartilage, and osseous structures. Neurologic and ophthalmologic symptoms are common, but underlying pathophysiology remains uncertain. Intracranial involvement is best evaluated with MR imaging and can range widely, with the most common findings being parenchymal calcifications, white matter abnormalities, and brain atrophy. In addition to evaluating the extent of disease, radiologic assessments may also facilitate the exclusion of other differential considerations, help monitor disease progression, and evaluate posttreatment responses.