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acute haemorrhagic leukoencephalitis ( ahle ) is a rare , usually fulminant demyelinating disease occurring predominantly in young adults .
it is considered by some to be a severe form of the more common acute disseminated encephalomyelitis .
first described by hurst in 1941 , and also known as hurst disease , it is characterised by progressive multifocal white matter inflammation , haemorrhage , and necrosis , often diagnosed at autopsy [ 1 , 2 ] .
it typically presents as a monophasic illness with headache , followed by rapid progression to confusion , somnolence and eventually coma and death , frequently preceded by a nonspecific viral illness .
the mortality reported in the literature is as high as 70% [ 4 , 5 , 6 ] .
herein , we describe a young female with unilateral disease and a more indolent course with a good functional outcome .
we postulate that this atypical presentation and clinical course may represent a milder spectrum of the disease .
a previously healthy 33-year - old female presented with headache and left - sided apraxia .
she had no significant comorbidities , and her only regular medication was the oral contraceptive pill .
her children were aged 2 and 4 years , and both were well with no recent illnesses .
she was a lifelong nonsmoker , did not drink alcohol regularly , and had no history of recreational drug use .
the patient presented with acute onset of right retro - orbital headache following a shower , with associated nausea and photophobia . the day following onset , she developed left - hand clumsiness and presented to her general practitioner , who referred her to the emergency department .
she reported no recent infective symptoms , no new medications or recent immunisation , and no unwell contacts or recent travels .
initial examination findings were left - sided apraxia , a subtle left pronator drift , and mild facial droop .
brain magnetic resonance imaging ( mri ) showed a right frontoparietal lesion with extensive white matter oedema and mass effect .
it was hypointense on t1 , t2 , and fluid attenuation inversion recovery sequences , and demonstrated restricted diffusion and blooming artefact .
ct of the chest , abdomen , and pelvis did not show any evidence of malignancy .
it showed scattered reactive astrocytes outnumbered by sheets of foamy macrophages associated with small areas of perivascular necrosis .
there were perivascular foci of haemorrhage , oedema , and necrosis with fibrin deposition associated with a mild - to - moderate inflammatory infiltrate .
reactive gemistocytic astrocytes , including frequent forms with fragmented nuclei typical of creutzfeldt - peters cells , were seen in viable areas of the biopsy .
special and immunohistochemical stains demonstrated perivascular loss of myelin and phagocytosed fragments of myelin within the foamy macrophages .
based on the perivascular haemorrhage , the necrosis with fibrin deposition and the limited nature of the demyelination with progression to cystic necrosis , a diagnosis of acute haemorrhagic encephalomyelitis was favoured . a progress mri 2 weeks following
her original presentation revealed extensive white matter cystic necrosis , with an increased t2 signal .
the rapid development of cystic necrosis was thought to be highly atypical of a glial tumour and supported a diagnosis of ahle .
an mri of the whole spine was also performed at this stage to exclude other central nervous system involvement .
cerebrospinal fluid ( csf ) analysis performed 26 days after commencement of corticosteroids showed an elevated igg index but no oligoclonal bands .
there was no pleocytosis , and protein , glucose , and flow cytometry were all normal .
markers of autoimmunity and vasculitis were negative , including negative ana , ena , dsdna , anca , and anti - nmo antibodies .
she continued to improve with home - based occupational therapy exercises and oral dexamethasone at a dose of 8 mg twice daily maintained for 4 weeks , followed by a slow wean over 2 months .
3 ) . at day 90 , she remains clinically well with no evidence of progression and resolving neurological deficit .
recent case reports show improved outcomes with a variety of immunomodulatory treatments [ 4 , 7 ] . however , there are no established prognostic features to determine the severity of the disease .
the above case highlights an unusual presentation of ahle , with a successful outcome following a prolonged course of high - dose corticosteroids .
we propose the disease may have a spectrum of severity , and a consideration to possible prognostic factors should be further evaluated .
cross reactivity between human myelin antigens and viral or bacterial antigens is postulated , with a preceding respiratory illness evident in approximately half of the cases [ 3 , 4 , 7 , 8 ] .
there are reported cases of presumed cross reactivity with mycoplasmapneumoniae , epstein - barr virus , herpes simplex virus , and influenza a [ 9 , 10 ] .
there was no evidence of recent infection on history or examination in our case ; however , serological markers were not tested .
histopathologically , the disease is characterised by perivascular microhaemorrhages and necrosis , demyelination accompanied by axonal injury and fibrin exudate .
a variable degree of perivascular inflammation is present , typically neutrophilic with some macrophage and lymphocyte infiltration [ 3 , 9 ] .
csf typically shows pleocytosis with predominant polymorphonuclear cells , in contrast to the lymphocytic predominance in acute disseminated encephalomyelitis [ 9 , 11 ] .
we postulate that the absence of pleocytosis in the csf of our patient may reflect a milder degree of inflammation , or prior treatment with steroids .
mri has a critical role in the early diagnosis of ahle , which typically involves white matter tracts with relative sparing of grey matter , accompanied by haemorrhage on susceptibility - weighted imaging [ 12 , 13 , 14 ] .
classically , the changes are multifocal with predominant involvement of the frontal and parietal lobes , although it may also affect the basal ganglia , brainstem , and spinal cord . in our case ,
the frontoparietal white matter lesion with multifocal petechial haemorrhages was consistent with previously described cases of this disease .
the degree of gadolinium uptake reported in the literature is variable , and homogenous enhancement was clearly present in our patient .
diffusion restriction , which was noted on our patient 's mri , is likely due to cytotoxic oedema .
the initial diagnosis was thought to be a primary brain neoplasm ; however , the rapid progression to cystic necrosis was strongly suggestive of demyelination with haemorrhage .
less likely differential diagnoses that were considered based on the imaging findings included ( a ) steroid - treated lymphoma , although the normal flow cytometry and biopsy results made this unlikely , and ( b ) haemorrhagic encephalitis due to parasite infection ; however , she had no peripheral eosinophilia and a more diffuse picture would be expected .
progress imaging was consistent with cystic necrosis , consistent with the available literature . in our case ,
serial mri scans provided vital evidence of the oedema , demyelination , necrosis , and haemorrhages that characterise this disease and helped facilitate a timely diagnosis .
there are no published large case series or controlled trials to help guide management of this rare and frequently fatal condition .
management is based largely on the understanding of the underlying pathology , expert opinion , and data from isolated case reports .
there are several case reports published reporting favourable outcomes with different modes of immunosuppression , including high - dose corticosteroids , intravenous immunoglobulin , plasmapheresis , and cyclophosphamide [ 2 , 11 , 13 ] . in the case described by seales and greer ,
aggressive management of raised intracranial pressure with mannitol , hyperventilation , and phenobarbital was undertaken . in that case
surgical management of raised intracranial pressure has also been described [ 6 , 7 ] .
our patient was initially commenced on high - dose dexamethasone when the presumed aetiology was a neoplasm .
prior to definitive diagnosis , she had undergone open excisional biopsy 2 weeks after symptom onset , with resultant debulking of the lesion .
our case differs from most previous reports by her comparatively mild symptoms , which , unlike most described cases , were not followed by rapidly progressive neurological deficit and coma .
consequently , it is not clear whether early immunosuppression or debulking contributed to her improvement or altered her clinical course , or if her disease would have remained indolent without progressive deficit in the absence of treatment .
previous reports have described a monophasic illness with good prognosis if an individual survives the initial insult [ 2 , 11 , 13 ] .
there is a paucity of data regarding whether or not immunosuppression has a role in preventing relapse .
in our case , the presentation and progression were inconsistent with previous descriptions of ahle . however , her biopsy results , progression of imaging findings , and response to immunosuppression were strongly supportive .
possible diagnoses raised by the clinical , radiological , and histological findings in isolation were less likely when these differing modalities were considered in combination .
one of the questions raised by this unusual case is whether or not unifocal disease or lack of csf pleocytosis is predictive of a more indolent clinical course . given that the patient remained clinically well throughout the course of the illness , the natural history of this patient 's disease had she not undergone surgical debulking and immunosuppression is unclear . whether the presence or absence of a preceding respiratory illness has any prognostic value is also uncertain .
further study is required to better characterise this rare disease and provide further guidance regarding prognosis and treatment .
backgroundacute haemorrhagic leukoencephalitis ( ahle ) is a rare and rapidly fatal disease of unknown aetiology . 
 there is a paucity of literature on the presentation and management of this rare disease.case descriptionwe report the case of a 33-year - old female presenting with headache and left - sided apraxia . 
 imaging revealed a right - sided white matter lesion with extensive cytotoxic oedema . 
 pathology was suggestive of ahle . 
 she underwent an open excisional biopsy and was treated with high - dose corticosteroids . 
 three months since symptom onset she remains clinically well with resolving apraxia and radiological appearance.conclusionthis case may represent a milder spectrum of ahle , which responded favourably to corticosteroids .