Radiological imaging plays an important role in diagnosing and monitoring Leigh disease. Leigh disease is a rare, progressive neurodegenerative disorder that typically presents in infants and leads to death in childhood. MRI is commonly used and shows characteristic symmetrical lesions in areas like the brainstem, basal ganglia, and thalamus. Over time, the lesions enlarge and involve more areas of the brain. Spectroscopy may reveal elevated lactate levels. The patterns of involvement on imaging can help confirm a diagnosis of Leigh disease.

1. Radiological imaging of Leigh disease.
Dr/ ABD ALLAH NAZEER. MD.

2. Leigh disease, also known as subacute necrotizing
encephalomyelopathy (SNEM), is a progressive
neurodegenerative disorder and invariably leads to death in
childhood.
Clinical presentation
Typically, symptoms become evident before the age of 2, with
the presentation in later childhood (juvenile form) or
adulthood (adult form) being uncommon. Symptoms include:
psychomotor delay/regression
superimposed signs of basal
ganglia and brainstem dysfunction
ataxia
opthalmoplegia
dystonia
respiratory rhythm disturbance
cranial nerve palsies

3. Pathology
Leigh disease is one of many mitochondrial disorders, due to a broad
range of genetic mutations in mitochondrial DNA (mt DNA). As such it
is only inherited from the mother, as is the case with other
mitochondrial disorders. Some mutations (e.g. SURF 1) are particularly
devastating.
Chronic energy deprivation leads to histological features such as:
spongiform degeneration
capillary proliferation
demyelination
neuronal loss
gliosis
These findings are similar to those seen in infarction 4.
Genetics
The inheritance pattern may be either autosomal recessive or X-linked.
Markers
CSF lactate may be elevated.

4. Radiographic features
CT: CT demonstrates regions of low-density matching areas of the abnormal T2 signal on
MRI. Occasionally some of these areas can show contrast enhancement.
MRI: The distribution tends to be symmetrical.
T2: characterized by high signal typically in:
brainstem
periaqueductal gray matter
medulla
midbrain
putamen: characteristic but not always present
other sites of T2 signal change include:
the remainder of the corpus striatum [globus pallidus and caudate
nucleus (heads)
subthalamic nuclei
substantia nigra
thalami
involvement of cerebral or cerebellar white matter is unusual
T1: usually demonstrates reduced signal in T2 abnormal areas, although some areas of
hyperintensity can be seen, as can some enhancement
DWI: in the acute setting some restricted diffusion may be evident
MR spectroscopy:
elevated choline
occasionally elevated lactate
reduced NAA

5. Symmetric low attenuation in lentiform nuclei in keeping with Leigh Syndrome.

6. Symmetric low attenuation in lentiform nuclei in keeping with Leigh Syndrome.

7. Computed tomography (CT) and magnetic resonance imaging (MRI) of patients IV7 and IV11. respectively. (A) CT
scan of patients IV7 brain at the age of 5 years. The CT scan shows a hypodensity and slight atrophy of the caudate
nuclei and the putamen (arrows) and a widening of the frontal horns of the cerebral ventricles. (B-1) Cranial MRI
of patient IV11 at the age of 23 years. Prolongation of T2 weighted signals in the residual part of the nucleus
caudatus and putamen and (B-2) at the level of the midbrain of the substantia nigra (arrow).

8. Axial T1 weighted MR image showing symmetrical hypointense lesions in the putamina.

9. A–C, Axial T2-weighted images (3000/120/1
[TR/TE/NEX]) show hyperintense lesions
involving the region of the inferior olivary
nuclei (arrow in A) and the dorsolateral
medulla at the base of the restiform bodies
(arrowhead in A), punctuate lesions in the
pontine tegmentum (arrowhead in B) and
more extensive abnormalities in the
cerebellar white matter, and lesions in the
periaqueductal area and subthalamic nuclei
(arrowhead in C).
D and E, Coronal T2-weighted sections
(3000/120/1) confirm the presence of
lesions in the subthalamic nuclei
(arrowhead in D) and show extensive white
matter involvement of the cerebellum
centered on the dentate nuclei (in E).

10. A and B, Axial T2-weighted MR images (3000/120/1) obtained at first examination show hyperintense lesions in the
substantia nigra (arrow in A) and medial thalamic nuclei (arrowhead in B). The globi pallidi and white matter, still
unmyelinated, are slightly hyperintense, with a tiny, focal hyperintensity in the left pallidum.
C, Follow-up MR image (2028/120/2), obtained 2 years and 2 months later, shows lesions in the basal ganglia that
involve both the putamina and the head of the left caudate nucleus. A minimal residual right thalamic lesions is
visible (arrowhead). Moderate diffuse brain atrophy is present.

11. 4 months old child with encephalopathy (Leigh disease): Axial T2-weighted images reveal
symmetrical hyperintense lesions involving the substantia nigra(yellow arrow), central
tegmental tracts in the pons (red arrow) as well as the cervical cord (Dotted arrow).

12. 6 months old child with altered sensorium: A) Coronal T2-weighted image reveals symmetrical
hyperintense lesions involving the thalamus(dotted arrow), subthalamic nuclei(black long
arrows) and substantia nigra(arrow).B and C) Diffusion-weighted images reveal restricted
diffusion in substantia nigra(black small arrow), tegmentum and periaqueductal location(red
arrow), basal ganglia (Dotted yellow arrow) and thalamus (Dotted white arrow).

13. 6 months old with altered sensorium: A) Axial T2-weighted image
reveals symmetrical hyperintense lesions involving the substantia
nigra. B-C) Axial T2 and Diffusion-weighted images reveal swollen
basal ganglia with hyperintense signal and restricted diffusion.

14. Leigh’s Syndrome: MRI Brain Diffusion and Axial T2- weighted images: Bilateral symmetric T2
hyper intensity with faint high signal on diffusion involving putamen and caudate nuclei.

15. Leigh's disease: Areas of high signal intensity in putamen bilaterally as well as in the
head of the caudate nucleus on T2-weighted images, with sparing of globus pallidus.

16. 2 year old with developmental delay shows bilateral, symmetric regions of
signal abnormality (yellow arrow) and diffusion restriction (blue) in the basal
ganglia concerning for a metabolic disorder such as Leigh Syndrome (LS).

17. Leigh Syndrome.

18. Leigh disease.
Axial T1 W1 images
show homogenous
hypointensity in bilateral
caudate nuclei and
anteromedial thalami.
Axial T2 WI images show
homogenous hyperintensity in
bilateral caudate nuclei,
lentiform nuclei, antero medial
thalami, cerebral peduncles and
periaqueductal gray matter.
All the above mentioned areas
show restricted diffusion.

19. Leigh's Disease. Symmetric T2 hyperintensities involving the basal ganglia and brain stem.

21. Axial T2-weighted MRI showing progression of the striatal lesions at the ages
of nine (A), ten (B), fourteen (C), seventeen (D1&D2) and eighteen (E) years.

22. Bilateral symmetric T2 hyper intensity with faint high signal on diffusion involving putamen and caudate nuclei.
An upright Doublet of lactate at 1.3ppm on short TE of 35 ms with inversion at long TE of 144 ms on MRS.

24. Bilateral symmetrical T2 hyper intensity with restricted diffusion involving Putamen, Paramedian Thalami,
Substantia nigra of mid brain, Dentate nuclei of cerebellum and periventricular white matter. An upright
Doublets of lactate at 1.3 ppm on short TE of 35 ms and inversion at long TE of 144 ms on MR Spectroscopy.

25. Pedigree chart of the family with the Leigh syndrome (LS) and neuroimaging of the proband. (A) Pedigree chart. I and II denote generation
number, and 1–2 individual number; the black circle denotes the proband. (B–E) T2-weighted images (T2WI) from magnetic resonance
imaging (MRI) of the proband show prolonged signals (arrows) in the (B) basal ganglia and thalamus, (C) midbrain, (D) pons, and (E) medulla
oblongata. (F and G) As shown in the magnetic resonance spectra, there is a markedly increased lactate doublet (arrows) in the prolonged
signal region in the bilateral basal ganglia. Following one-year treatment, the lesions disappeared in the (H) thalamus, (I) bilateral cerebral
peduncle, (J) pons and (K) medulla oblongata, and partially reduced in the (H) basal ganglia and (I) the dorsal midbrain, as shown by T2WI.

26. Axial MRI scan (A) and MRS spectrum (B) of a 9-year old boy with Leigh syndrome due to a mutation in the mtDNA

27. Layout of the ROIs and the brain MRI (T2WI) in patient 1. ROIs were placed manually in the pons (1), mid brain (2), and
bilateral cerebellar hemisphere (3) (at the slice level with the maximum cerebellar hemisphere), thalami (4), basal ganglia (5),
and lower temporal (6), lower frontal (7), mid temporal (8), mid frontal (9), occipital (10), upper frontal (11), and parietal
cortices (12). The MRI showed nodular high intensity lesions in the bilateral caudate, putamina and thalami on T2WI.

28. Results of FDG-PET study in patients with Leigh syndrome. The images of FDG-PET (a–b, e–f, i–j, m–n) and MRI (T2WI) (c–d, g–
h, k–l) of patient 1 (a–d), patient 4 (e–h) and patient 2 (i–l) and disease control (m–n) were shown. The glucose up take was
reduced in the cerebellum in patients 1 and 4, bilateral basal ganglia in patient 1, 2 and 4, and temporal lobes in patients 1
and 4. The cerebellar hypometabolism was observed even in a patient whose MRI showed no abnormalities (a–d).

29. FDG-PET (left), axial T2 MRI (middle) and superimposed PET-MRI images of the brain
showing frontal hypermetabolism (A), no detectable uptake in the putamina and
reduced uptake in the left caudate (B) and hypometabolism in the cerebellum (C).

30. Thank You.