progressive hemifacial atrophy ( pha ) is a rare disorder characterized by unilateral facial atrophy affecting the skin , subcutaneous tissue , and fat , muscle , and osteocartilagenous structures creating a sunken hemiface appearance .
we report a 41-year - old woman with pha who showed an uncharacteristic  relapsing  remitting  evolution of brain lesions and was seropositive for hepatitis b virus ( hbv ) .
magnetic resonance imaging ( mri ) showed progressive atrophy and multiple white matter lesions in the left side of the brain .
interestingly , the serial mri examination ( 4 mri scans over a period of 9 years ) showed a  relapsing  remitting  pattern of brain lesions akin to that observed in a subtype of multiple sclerosis .
autoimmune - related investigations revealed increased serum levels of immunoglobulin ( ig ) g , anti - nuclear antibody ( ana ) , and -igg .
however , the association of peripheral infection such as hbv infection with pha has not been reported .
our experience with this case suggests that pha may have a relapsing  remitting disease course . autoimmune inflammatory response to chronic hbv infection
progressive hemifacial atrophy ( pha ) ( also referred to as the parry  romberg syndrome ) was first reported by parry in 1825 , and , later , described in more detail by moritz heinrich romberg ( 1846 ) . it is a rare disorder that usually presents in the first or second decade of life and is characterized by unilateral atrophy of the face and subcutaneous tissues . sometimes , the condition may affect the underlying bony structures . in the majority of patients ,
the disease stabilizes over a period of 2 to 10 years after its first presentation ; a small proportion of patients ( 26% ) , however , may experience sustained progression .
neurological complications such as epilepsy , migraine , hemiplegia , and trigeminal neuralgia may develop in 15% of all pha patients .
the etiology of pha remains poorly understood ; defects of vascular supply , trauma , sympathetic over - excitation , and infection have all been postulated as possible causes . in this report
, we describe a case of pha who manifested serial changes in brain lesions on magnetic resonance imaging ( mri ) .
the case suggests that pha may have a  relapsing  remitting  disease course and that periphery hepatitis b virus ( hbv ) infection associated auto - immune inflammatory process may be one of the triggers for relapse of pha .
a 41-year - old woman was referred to our department because of recurrent tonic - clonic seizures .
her left side of the face was of smaller size ; the deformity was noticed since she was a teenager , and which progressed with increase in age . the first episode of seizures occurred when she was 32 years old .
the patient was diagnosed as a case of encephalitis and received acyclovir treatment . the second episode of tonic - clonic seizures occurred at the age of 40 years . a diagnosis of encephalitis - related seizure was made and antiepileptic therapy prescribed .
eight months after the second seizure attack she sustained a third attack and was therefore referred to our department .
besides , she also had a history of paroxysmal electric discharge like abnormal sensations on the left half of face and memory decline .
neurological examination showed facial asymmetry with marked hypoplasia of the left side of the face , left enophthalmos , left eyelid , tongue , gingival and periodontal tissue atrophy , and left teeth crowdedness ( fig .
her lower left lips were thinner than that at the right side and a big linear dark scar ( coup de sabre ) was observed .
the muscle strength of the right lower extremity was 4/5 on muscle strength grading scale .
on electroencephalography ( eeg ) , spike and slow waves were observed over the left temporal area .
she tested positive for antibodies against hepatitis b virus ( hbv ) surface antigen ( hbsag ) and envelope antigen ( hbeag ) .
immunoglobulin g ( igg ) levels were increased both in csf ( 51.7  mg / l , normal range : 034.0  mg / l ) and in the serum ( 16.4 
laboratory tests related to autoimmune function showed higher values of -igg levels ( 23.1% , normal range : 9.018.0% ) and lower levels of complement c3 ( 0.86 
( a  g ) mri axial t2-flair performed in december 2014 showed enlarged left ventricle and multiple hyperintensities in the left frontal , temporal , occipital and parietal lobes and the periventricular area ( a and b ) ; some lesions presented heterogeneous enhancement on t1 postcontrast images ( c and d ) .
the left ventricle was bigger on mri axial t2-flair in january 2015 ; lesions in the left orbitofrontal cortex and the basal ganglia were more widespread , whereas the lesions in the periventricular area were smaller ( e and f ) . in august 2015 ,
the left ventricle enlarged more on mri , mri axial t2-flair also showed attenuation of lesions in the left orbitofrontal cortex ( h and i ) and new lesions in the left superior frontal gyrus ( i ) , some lesions are partially enhanced ( j and k ) . photograph of the patient ( g ) .
flair = fluid - attenuation inversion recovery , mri = magnetic resonance imaging . the first mri scan performed at the time of the first seizure episode showed multiple white matter lesions in the left frontal lobe and the parieto - occipital area ; some lesions were enhanced after the gadolinium contrast injection ( the mri was lost ) .
the second mri examination was performed in december 2014 , immediately after the second seizure episode .
it showed enlargement of the left lateral ventricle and multiple lesions in the left frontal and parietal lobes and the periventricular area ( fig .
1a and b ) ; heterogeneous gadolinium enhancement was observed in the left frontal and parietal lobes ( fig .
mri performed 1 month after the second seizure episode ( i.e. , in january , 2015 ) showed that the lesions in the left orbitofrontal cortex and basal ganglia were more widely diffused , whereas the lesions at the periventricular space and the posterior horn of the lateral ventricle had attenuated ( fig .
the most recent mri ( august , 2015 ) showed increase in the size of left ventricle , when compared with previous mri study performed 7 months ago . moreover , the lesions in the left orbitofrontal cortex had attenuated and new lesions appeared in the left superior frontal gyrus , some of which are partially enhanced ( fig .
no intracranial vascular abnormalities were identified on magnetic resonance angiography ( mra ) or digital subtraction angiography ( dsa ) ( data not shown ) .
pha is characterized by unilateral atrophy of the face , including that of skin and the subcutaneous tissue .
our patient experienced slow progressive atrophy of her left face since her teenage , as evidenced by changes on mri .
neurological complications such as seizures are known to occur in up to 15% of all pha patients .
the eeg showed spikes and slow waves predominantly in the left temporal lobe , which is indicative of seizure activity .
besides , the patient also had a history of migraine , which is a common accompaniment in pha patients .
serial changes in imaging findings with progression of the disease have rarely been reported . in the present patient , 4 mri examinations performed over a period of 9 years showed progressive left brain atrophy and multiple lesions affecting both white and gray matter in the left hemisphere .
interestingly , brain lesions in this patient appeared and resolved , a pattern similar to that associated with a subtype of multiple sclerosis ( ms ) , the relapsing  remitting ms . to date , no disease - modifying drugs are available for pha .
the relapsing  remitting lesions in this patient indicate that identification of triggers for relapse may help prevent the progression of the disease . in ms , relapses are believed to represent recurrent episodes of inflammation and demyelination that are often accompanied by axonal injury .
immune cell - infiltration in the central nervous system ( cns ) and microbial infections have been considered as immunological triggers for relapse in ms , all of which can elicit an inflammatory response .
typical histological findings in patients with pha include epidermal atrophy , inflammatory infiltrate , gliosis , and neuronal loss .
therefore , it is plausible that the  relapsing  remitting  lesions in this patient may have similar inflammatory background . some brain lesions of this patient showed gadolinium enhancement , which indicates disruption of the bbb and inflammation . after excluding the possibility of brain tumor and vascular malformations by mr spectroscopy and dsa analysis , we think the enhancement of lesions might be related to vasculitis .
indeed , perivascular inflammation and microglial activation have been reported in a pha patient with epilepsy at brain biopsy , which suggests that inflammation can be one of the factors that drive the acceleration of pha .
various infections such as borrelia burgdorferi , poliomyelitis , and herpes zoster have been reported in patients with pha .
however , neurologic complications of hbv such as acute disseminated encephalomyelitis ( adem ) and guillain barr syndrome have also been noticed , which suggests that periphery disease can affect the brain .
in addition , hbsag has been identified in the csf of patients without active liver disease but with positive hbsag in serum . for a long period of time , the blood brain barrier ( bb ) was thought to protect brain from infections in the periphery .
it has been controversial whether hbsag crosses bbb from the periphery or if it is locally generated within the cns .
on the other hand , recent studies suggest that there are intensive communications between the periphery and cns
. the molecular mimicry between hbv dna and myelin proteins and the subsequent activation of autoimmune inflammatory cells could constitute the other possible underlying mechanisms of neurological injury in this patient .
concomitant occurrence of autoimmune diseases such as systematic lupus erythematosus ( sle ) and pha has been reported .
autoimmunity - related antibodies are often found positive in pha patients . in line with previous reports ,
increased serum levels of ana and  igg were observed in this patient , which suggests a common autoimmune - related background .
therefore , it is highly likely that the inflammatory microenvironment induced by infection or dysregulated autoimmunity may render the patient more susceptible to pha .
surgical aesthetic treatments of hemifacial atrophy such as augmentation of the atrophic region and restoration of the symmetry of the face have been used in clinics . however , these treatments do not have a long - lasting effect .
beneficial effect of immunosuppressive drugs on a pha patient with cerebral involvement have been reported .
the present case showed inflammatory relapsing and remission lesions on mri . whether anti - inflammatory and immune suppressive drugs can halt or slow down disease progression is worth further investigation . in summary
the autoimmune inflammatory process due to chronic hbv infection may be one of the triggers for relapse . to date
 abstractintroduction : progressive hemifacial atrophy ( pha ) is a rare disorder characterized by unilateral facial atrophy affecting the skin , subcutaneous tissue , and fat , muscle , and osteocartilagenous structures creating a sunken hemiface appearance.etiopathogenesis of pha is poorly understood ; no definitive treatment is currently available.clinical findings : we report a 41-year - old woman with pha who showed an uncharacteristic  relapsing  remitting  evolution of brain lesions and was seropositive for hepatitis b virus ( hbv ) . 
 she presented with a history of recurrent tonic - clonic seizures . magnetic resonance imaging ( mri ) showed progressive atrophy and multiple white matter lesions in the left side of the brain . 
 interestingly , the serial mri examination ( 4 mri scans over a period of 9 years ) showed a  relapsing  remitting  pattern of brain lesions akin to that observed in a subtype of multiple sclerosis . 
 autoimmune - related investigations revealed increased serum levels of immunoglobulin ( ig ) g , anti - nuclear antibody ( ana ) , and -igg . 
 infection is considered as one of the possible causes of pha . 
 however , the association of peripheral infection such as hbv infection with pha has not been reported.conclusion:our experience with this case suggests that pha may have a relapsing  remitting disease course . 
 autoimmune inflammatory response to chronic hbv infection may have triggered the relapse in this case . 
 this case underlines a novel etiopathogenetic mechanism of pha . 
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Introduction
Case report
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