Table 1 Adult-onset cases of leukoencephalopathy with calcifications and cysts published until end of 2014

18

F

–

Bilateral foci of calcification in white matter, both thalami and left basal ganglia, cysts in right frontal and left temporal lobes.

Right frontal and left temporal lobes cysts with thin uniformly enhancing walls. Increased T2 signal bilaterally in the white matter with sparing of the gray matter. No cerebral atrophy.

Extensive gliosis with Rosenthal fibers, rarefied microcystic foci, and a larger cyst with abundant hemosiderin along the wall. Extensive calcifications and absence of any abnormal blood vessels.

Seizures, learning disability

Y

–

Ogles et al. 2014 [4]

19

M

–

Low-density cysts with high-density ring and bilateral calcifications.

Extensive leukoencephalopathy.

Numerous bilateral cysts with hyperintense boundaries (T1 + T2) of various sizes including thalamus, basal ganglia and left ventricle. Cyst wall enhancement. Heterointense cystic content in T1 and FLAIR.

Pronounced reactive gliosis with Rosenthal-fibers. In addition, focal hemosiderin deposits, which indicate previous hemorrhage, and microcalcifications. Many ectatic vessels and angiomatous changes with cellulose-like degeneration.

Analysis of the cyst fluid did not suggest malignancy or infection.

Weakness of right limbs; vision loss

N

Excision of left frontal cyst

Wang et al. 2013 [13]

19

M

–

Calcifications in pons, basal ganglia, and all lobes mostly in white matter. Some with cysts. Diameters from a few to 15 mm. Ring enhancement of the cyst wall.

Many cysts associated with calcifications, increased signal intensity in the bulbous, pons, bilateral cerebellar, and cerebral peduncles, basal ganglia, white matter, not in cortical gray matter. Vasogenic edema.

Contrast-enhanced scans showed ring enhancement in all cysts.

Angiomatous changes, numerous small, tortuous blood vessels, either contiguous or separated by nervous tissue, hyaline vascular thickening with fragmented rough reticulin fibers and associated irregular calcifications. Microhemorrhagia, ferric iron deposits Rosenthal fibers surrounding the abnormal vascular configurations.

Seizures

Yes

Diagnostic right temporal lesionectomy; after 2 years removal of a pontine cyst

Sener et al. 2006 [14]

24

M

–

Dense calcifications in left corona radiata and bilateral thalamus; pontine cyst; Ventriculo-megaly.

Additionally to CCT, peri-ventricular and pericyst fluid-attenuated inversion recovery (FLAIR) signal abnormalities.

Analysis of the green cystic fluid and the thickened cystic wall: no evidence of neoplastic processes. No angiomatous rearrangement of microvasculature or Rosenthal fibers.

Several weeks of progressive headache, imbalance and diplopia

Exam: right internuclear ophthalmoplegia (INO), hypesthesia in left arm.

–

1. bilateral suboccipital craniectomy and cyst drainage 2. cyst draining shunt

Berry-Candelario et al. 2011 [10]

25

F

–

Bifrontal cysts and dense calcification in both thalami and left basal ganglia; left frontal cyst with a hemorrhage.

Bifrontal cysts with thin uniformly enhancing walls and also extensive bilateral white matter increased T2 signal with sparing of the gray matter. No cerebral atrophy.

Extensive gliosis with Rosenthal fibers, abnormal thick-walled congo-red negative and acid-Schiff positive blood vessels, rarefied microcystic foci, and a larger cyst with abundant hemosiderin along the wall.

Left hemiparesis postpartum and 1 week of headache

N

Resection of a cyst

Ogles et al. 2014 [4]

26

M

Normal protein + glucose, slightly increased pyruvate

Bilateral symmetric calcifications at basal ganglia, thalamus, cerebellum, triventricular hydrocephalus,

cerebral edema.

Additionally, cystic peripherally enhancing cerebellar and thalamic masses on the left side; hypointense on T1 and hyperintense on T2; calcified focus near cyst.

Calcification of the vasculature, areas of demyelination, and gliosis. No signs of malignancy.

Vertigo, vomiting, imbalance.

Exam: Severe disorientation, bilateral nystagmus, papilledema, right-sided clonus, gait ataxia, Babinski positive.

–

–

Daglioglu et al. 2009 [15]

27

F

–

Nodules in the basal ganglia, thalami and centrum semiovale, densely calcified at CT

Large left thalamic cyst compressing aqueduct and third ventricle with triventricular hydrocephalus cerebellar cyst; cerebral and left cerebellar white matter hyperintensities on T2; post contrast enhancing nodules in the basal ganglia, thalami and centrum semiovale.

Angiomatous-like microangiopathy, calcifications in brain tissue and vessel walls, and abundant Rosenthal-fibres with predominant perivascular arrangement.

Initially: Symptoms of increased brain pressure. 6 months after surgery: slight dysarthria, mild left IVth nerve palsy, right mydriasis, lower limb incoordination, left pyramidal signs. Mild dysexecutive impairment.

-

3^rd ventri-culostomy and removal of cerebellar lesion

Marelli et al. 2008 [16]

30

F

Normal

Calcifications in right thalamus, left basal ganglia, right cerebellum, with cystic formation on right parietal lobe. Asymmetric diffuse leucopathy.

Acute ischemic lesion in posterior left internal capsule. Asymmetric white-matter hypersignals, always surrounding cysts and calcification foci on T2. Gradient echo imaging revealed extent of calcifications, which were not seen on CT or conventional MRI. Ring-contrast enhancement of cysts walls and adjacent to calcifications. MRI-angiography was normal.

–

Right-sided hemiparesis

N

–

Wargon et al. 2008 [17]

30

M

–

–

Expansive solid/cystic interhemispheric lesion with hemosiderin deposition and high capillary density (MR perfusion) in its walls. Multiple enhancing nodular lesions in supra- and infratentorial brain parenchyma some with hemorrhagic component on T2. Symmetric calcifications in periventricular white matter, basal ganglia, brainstem, dentate nucleus.

Inconclusive

Headache for 7 days

N

Surgery

Bertotti et al. 2011 [18]

31

M

–

Bilateral calcification in the basal ganglia.

Extensive bilateral leukodystrophy and cysts with marginal enhancement after intravenous contrast; progression in repeat MRI.

Foci of dystrophic calcifications and focal accumulations of macrophages xanthomized. No signs of malignancy.

Tonic-clonic seizures for 7 years

Y

5 surgeries for removal of brain cysts

Pessoa et al. 2012 [19]

36

M

–

Extensive calcification in basal ganglia, deep cerebellar nuclei, right thalamus.

Diffuse symmetric white matter hyperintensity; large rounded cystic lesion in the left occipito-temporal region.

–

Mild right hemiparesis, Tremor, seizures for 5 years;

Exam: strength 4/5 right; mild spasticity

Yes

Anti-epileptic with Valproate

Gulati et al. 2011 [20]

42

M

–

Left parietal ring -enhancing lesion with calcification.

Multiple, irregular, and heterogeneously enhancing

lesions scattered throughout the brain.

Multifocal vascular proliferation associated with necrosis, gliosis, and macrophage infiltration.

Right footdrop for 2 weeks

No

Corticosteroids

Kleinschmidt-Demasters et al.2009 [21]

44

F

–

Calcifications in the basal ganglia.

Diffuse cerebral and cerebellar leukoencephalopathy, mass effect with right-to-left shift, with cysts and enhancing lesions in the cerebral white matter. Type I Chiari malformation, cervical syrinx.

3 brain biopsies between 1999–2003.

Generalized daily headaches; Ataxia, seizures, mild cognitive dysfunction over last 6 years

Yes

Cortico-steroids ➜ responsive-ness

Kleinschmidt-Demasters et al. 2009; Corboy et al. 2006 and [8, 21]

45

M

Normal

Asymmetric basal ganglia calcifications. Small right calcification on skull X-ray at age 12 years.

Diffuse leucoencephalopathy and multiple cysts with a rim of post contrast enhancement. Normal spinal MRI.

Dilated blood vessels with a thickened wall, arranged in an angiomatous-like fashion, associated with abundant microcalcifications and Rosenthal fibers.

Progressive gait impairment for 3 years

Exam: atactic-spastic gait

Y (2 GTC at age 12 + 18)

Resection of the right frontal cyst

Marelli et al. 2008 [16]

50

M

Slightly xantho-chromic; 26 leuko-cytes, protein 1060 mg/l

Multiple calcifications in basal ganglia and white matter.

Multiple bilateral cerebral cystic lesions and large right cerebellar cyst with mass effect; diffuse T2 hyperintensity.

Pilocytic gliosis with Rosenthal fibers, prominent angiomatous changes, microcalcifications, microhemorrhages and hemosiderin pigment deposits. Small blood-filled vessels, many showing hyalinized walls. Extensive Microcalcifications + concentric fine calcification around blood vessel walls.

Headache for 4 months, progressive unsteadiness of gait for 1 month, recurrent vomiting for 1 week

Exam: papilledema, finger-nose and heel-knee dyscoordination, dysdiadochokinesia; spastic-atactic gait

Dur-ing child-hood as-soci-ated with fever

Posterior fossa- crani-ectomy with resection of a cyst

Ummer et al. 2010 [22]

55

F

Normal

Abnormalities

Widespread leukoencephalopathy more prominent anteriorly with multifocal cysts up to 1 cm in diameter. Numerous punctate-enhancing lesions distributed throughout the cerebrum. Little mass effect and edema.

Angiomatous small blood vessels with relatively thin walls and minimal hyalinization but with focal fibrinoid vascular necrosis and microhemorrhages; numerous Rosenthal fibers.

None (incidental finding after car accident)

No

Corticosteroids

Kleinschmidt-Demasters et al.2009 [21]

59

F

Protein: 890 mg/l No cells No OCBs

–

Diffuse infra- and supratentorial leukencephalopathy, extensive calcifications in basal ganglia, thalamus, cerebellum (dentate nuclei), multiple voluminous cysts.

Pronounced reactive gliosis with numerous Rosenthal fibers, mild myelin pallor without signs of active demyelination. Focal hemosiderin deposits and microcalcifications.

Increasing urinary urgency for 5 years, change in behavior with increasing apathy for 1 year; left homonymous hemianopia

–

Resection of a cyst

Kaffenberger et al. 2009 [9]

65

F

–

Calcifications in the cerebellum and basal ganglia, frontoparietal ICH with 1-cm midline shift + extensive white matter hypodensities.

On admission as well as 6 years prior.

Increased FLAIR around hemorrhage and in the bilateral periventricular white matter. T2 hyper-intensity, consistent with cysts, posterior to the left frontal horn and in the left cerebellum. Follow up MRI after operation demonstrated resolution of the hemorrhage and surrounding edema.

Gliosis and thickened blood vessels, but no amyloid deposition or malignancy.

Worsening of residual hemiparesis on the left and headache for 3 weeks

Exam: left hemineglect, spastic left hemiparesis, confusion

N

Right hemi-craniectomy and resection for the hemor-rhagic mass

Banks et al. 2013 [6]

69

F

–

Calcifications of thalamus, basal ganglia, deep white matter, brain stem and dentate gyrus.

Extensive white matter hyperintensities in T2 and FLAIR.

Organizing hemorrhagic tissue with gliosis, no angiomatous or hyalinized blood vessels, myelin loss, calicifications, Rosenthal fibers.

Confusion, ataxia, gait unsteadiness, repetitive falls, left homonymous anopia over several months

N

–

Coeytaux et al. 2011 [7]

71

F

total protein (721 mg/l), no cells, normal lactate

Some intraparenchymal calcification, but none in the basal ganglia, thalamus or cerebellum.

Extended brain edema of the left hemisphere including left parietal cystic lesions.

Blood vessels with hyaline degeneration, signs of micro-bleedings and perivascular loss of myelin.

Incomplete right-sided hemianopia, discrete right-sided hemiparesis,. Coordination mildly impaired. Word-finding difficulties and signs of apraxia

Y

Surgery + Corticosteroids

Stephani et al. [this report]