Table 3 Review of the literature on neuroimaging data in cystinosis patients.

Cochat, 1985

repeated seizures, tremor, mental retardation, pseudobulbar or pyramidal syndrome

10

TDM

-

brain atrophy

10 control patients with another primary renal disease (mean age=11,8 years, SD=3,7)

Jonas, 1987

impairment in visual perception, moderate bilateral sensorineural hearing loss, mild peripheral neuropathy,

depression, lack of motivation, inability to function independently. One year later: confusion with impaired short-term memory

1

TDM

-

cerebral atrophy

no

Nichols, 1990

NA

10

1.5T MRI

T1, T2, DP

subjective cerebral atrophy in 10 of the 11 patients (7: moderate to severe, 3: mild)

no

1

TDM

Broyer, 1996

neurological complications in 7 patients with 2 forms: - encephalopathie (cerebellar and pyramidal signs, mental deterioration and pseudo-bulbar palsy): 4/7 - stroke-like episode with coma and hemiplegia or milder symptoms

2

1.5T MRI

T2

moderate brain atrophy, spontaneously regressive T2 hyperintensities in the 2 lenticular nuclei and in the caudate nucleus, a right temporo-occipital area of demyelinization

no

6

TDM

-

brain atrophy (6/6); multiple areas of mineralization (4/6) including basal ganglia and frontal WM; frontotemporal ischemic stroke (1/6)

Dogulu, 2004

Documented ICHT (papilledema, CSF opening pressure greater than 200mm of H2O)

7

1.5T MRI

NA

mild diffuse atrophy in 1 patient

no

1

TDM

none

Muller, 2008

progressive distal myopathy; cerebellar syndrome regressive under cysteamin

recurrent depressive episodes

2

1,5T MRI

NA

cerebral atrophy (the second MRI performed 11 years later did not reveal any progression of the atrophy)

no

1

FDG PET

none

Ulmer, 2009

none

9

1.5T MRI

T1, T2, DTI, ¹H MR spectroscopy

- 4 mildly or moderately enlarged ventricles,

- a mesial slerosis of the hippocampus,

- a developmental venous anomaly

no

Berger, 2009

increasing neck pain and left hand and finger numbness; impaired coordination in both upper extremities; dysmetria (L>R), spasticity in both legs, strength deficit (4/5), unable to walk without assistance, pyramidal syndrome, diminished position sense in left , fingers and in left lower extremity, diminished vibratory sense in both lower extremities, impaired in pinprick and temperature sensation on the right side, and focal seizures

1

1,5T MRI

T2, FLAIR

T2 and FLAIR hyperintensities extended throught the brainstem into both internal capsules; small subcortical lesions in both parietal lobes

no

1

Spinal chord MRI

edematous cord along the entire extent of the cervical cord with contrast-enhancing lesions^a

Trauner, 2010

NA

46

1,5T MRI

T1

- 25 N,

- 11 mild volume loss,

- 5 moderate to severe volume loss,

- 5 isolated Chiari I malformation;

- No difference in motor coordination between different MRI groups (but very small number of patients per group); No age-related MRI findings

49 controls [2-17] years

Bava, 2010

none

21^b

1,5T MRI

3DT1, DTI 6 directions

8/24 cortical or central atrophy; significantly decreased FA in the following manually defined ROI: bilateral superior parietal lobule and right inferior parietal lobule, but not in temporal ROI, in cystinosis versus controls; in children older than 5: positive relationship between FA in the RIPL and performance on the Beery VMI test (visuospatial performance); positive correlation between age and FA in the RIPL, LIPL and LSPL in cystinosis patients but not in controls

24 TD age-matched controls

Rogers, 2010

3/6 had intracranial hypertension (age range [19-22]), all were post-renal transplant, 1 marked optic nerve atrophy, 1 papilledema, 2 wide optic nerve sheath diameter measured with a B-scan ultrasound; 3/3 optic nerve sheath fenestration, 1/3 VPD

3

1,5T MRI

NA

N

no

Marquardt, 2013

Posterior Reversible Encephalopathy Syndrome (PRES): generalized seizures, headache, hypertension, vigilance deterioration

1

1,5T MRI

FLAIR, ADC, contrast enhanced MR angiogram

parieto-occipital and fronto-parietal mild oedematous swelling

no

Cazals, 2013

encephalopathy: stroke, then gradually walkind difficulties, cerebellar and frontal pyramidal syndrome

1

1,5T (and 3T 3 years later)

Diffusion, FLAIR, T2*

diffuse atrophy, multiple ischemic lesions in the semi-oval centre, T2 hyperintensity in the periventricular areas, a few frontal sub-cortical T2* hypointensity and slight uptake of contrast in the pervascular spaces in the fronto-parietal WM and central grey nuclei

no

CT angiography

N

Neutel, 2013

sudden onset of speech and gait disturbance

1

1,5T MRI

DWI, angioMRI

recurrent strokes caused by intracranial arterial stenosis (right internal carotid artery stenosis and right middle cerebral artery stenosis)

no

Ballantyne, 2013

NA

16

1,5T MRI

NA

12: N; 1: Chiari I malformation; 3: moderate cortical volume loss for age

MRI results from an earlier study

Aly, 2014

NA

13

1,5T MRI

NA

7/13 cortical brain atrophy, dysmyelination

13 age- and sex-matched healthy controls

Rao, 2015

10/53 had Chiari I malformation, 2 of the 10 were symptomatic

53

1,5T MRI

3DT1

10/53 (18,9%) Chiari I malformation (>5mm) or tonsillar ectopia (3-5mm), 1 syrinx, 1 syringohydromyelia

120 healthy controls: 2 (1,6%) Chiari I or tonsillar ectopia

Martin-Begué, 2016

Intracranial Hypertension in 4/8 with papilledema and confirmed high CSF pressure (at the age of 6-10 years); 1/4 symptomatic (had a Arnold-Chiari anomaly and enlarged ventricules); 2/4 VPD

4

1,5T MRI

NA

1 Arnold-Chiari and enlarged ventricules; 1 great distension of the perioptic subarachnoid space; 2N