Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia: An MRI Study of 16 French Cases

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Fig 1.
Characteristic MR imaging abnormalities in patients with ALSP on FLAIR (A–H, K, L), T2WI (I), and T1WI (J) images. MR imaging usually discloses subtle (A) or marked (B) white mater hyperintensities with frontal predilection (B). WMH can be confluent (B) or patchy (C) and are usually asymmetric (D). Corticospinal tract involvement (A and E) and corpus callosum involvement (F and G) are frequent. At the posterior fossa level, WMH can be of a vascular-like type (H). Some patients can present with enlarged perivascular spaces on T2WI (I). T1WI frequently reveals atrophy, usually marked, with frontal predominance (J). During a 32-month follow-up (case 8), a clear increase of WMH and atrophy is seen (K and L). A cavum septum pellucidum is frequently observed (A and B).
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Fig 2.
Typical DWI in ALSP. Persistent deep white matter diffusion-restricted lesions (A–C) with corresponding low ADC values (D–F) are found.
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Fig 3.
Small calcifications in ALSP. CT images reveal punctate calcifications located in the subcortical parietal WM and the periventricular frontal WM (A–C). Sagittal reconstruction shows the typical stepping stone distribution (D).

Table 1:

Clinical and genetic findings

Case	Sex	Age at Onset (yr)	Family History	Initial Symptoms	First Suspected Diagnosis	CSF1R Mutation	MRI Delay (yr)
1	M	57	Yes	Cognitive/psychiatric	FTLD (genetic form)	c.2330G>A(p.Arg777Gln)	1
2	M	44	Yes	Cognitive	FTLD (genetic form)	c.2330G>A(p.Arg777Gln)	4
3	F	42	Yes	Parkinsonism	Corticobasal degeneration	c.2566T>C(p.Tyr856His)	3
4	M	28	Yes	Gait	CNS lesions related to celiac disease	c.2381T>C(p.Ile794Thr)	4
5	M	57	Yes	Speech	Undetermined leukoencephalopathy	c.2381T>C(p.Ile794Thr)	5
6	F	28	No	Gait/apraxia	Undetermined leukoencephalopathy	c.2381T>C(p.Ile794Thr)	0.5
7	F	31	No	Motor	PPMS	c.2342C>T(p.Ala781Val)	1.5
8	M	60	Yes	Cognitive/apraxia	Corticobasal degeneration	c.2525G>T(p.Gly842Val)^{^a}	1
9	F	47	Yes	Parkinsonism	Vascular leukoencephalopathy (inherited)	c.2522A>G(p.Tyr841Cys)^{^a}	1
10	F	60	Yes	Cognitive/parkinsonism	Vascular leukoencephalopathy (inherited)	c.2522A>G(p.Tyr841Cys)^{^a}	1
11	M	36	Yes	Cognitive	LCC	c.2534T>C(p.Leu845Pro)^{^a}	2
12	F	55	Yes	Psychiatric/speech	LCC	c.2534T>C(p.Leu845Pro)^{^a}	2
13	F	–	Yes	Asymptomatic	NA	c.2498C>A(p.Thr833Lys)^{^a}	49^{^b}
14	F	57	Yes	Cognitive	FTLD (genetic form)	c.2498C>A(p.Thr833Lys)^{^a}	1
15	F	33	Yes	Gait	NA	c.2498C>A(p.Thr833Lys)^{^a}	0.5
16	M	52	No	Cognitive/psychiatric	Vascular leukoencephalopathy (inherited)	c.2308G>C(p.Ala770Pro)	2

Note:—NA indicates not applicable (diagnosis already known in family member); PPMS, primary-progressive MS; LCC, leukoencephalopathy with calcifications and cysts.
↵a Mutation not previously described.
↵b Patient asymptomatic at the time of MRI. Each family is separated by dashed lines.

Table 2:

Neuroimaging findings

Imaging Findings	No.	%	Imaging Findings	No.	%
White matter abnormalities	16/16	100	Atrophy	15/16	94
Symmetry			Atrophy predominance
Symmetric	10/16	63	Frontal	6/15	40
Asymmetric	6/16	37	Frontoparietal	8/15	53
Confluence of lesions			Parietal	1/15	7
Confluent	10/16	63	Corpus callosum involvement
Patchy	6/16	37	Hyperintensities	13/16	81
White matter abnormalities predominance			Atrophy	14/16	88
Frontal	13/16	81	Corticospinal tract Deep gray matter nuclei	10/16 2/16	63 13
Frontoparietal	3/16	19	External capsule	7/16	44
Lobar distribution			Posterior fossa	6/16	37
Frontal	16/16	100	Enlarged perivascular spaces	4/16	25
Parietal	16/16	100	Diffusion-weighted imaging
Temporal	11/16	69	Hyperintensities	6/8	75
Occipital	8/16	50	Restricted ADC	4/6	67
U-fiber involvement	8/16	50	Calcifications
White matter rarefaction	0/16	0	T2*	0/8	0
			CT	4/6	67
			Gadolinium enhancement	0/6	0
			Cavum septum pellucidum	8/16	50