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CT and MRI appearance of mitochondrial encephalopathy

July 2007
JBR-BTR: organe de la Société royale belge de radiologie (SRBR) = orgaan van de Koninklijke Belgische Vereniging voor Radiologie (KBVR) 90(4):288-9

July 2007
90(4):288-9

Source
PubMed

Authors:

AZ Sint-Lucas Brugge

A case is reported of a 20-year-old female presenting with confusion and progressive sensory aphasia. CT and MRI showed bilateral and symmetric acute necrosis of the basal ganglia and of the left temporal and occipital lobe, besides chronic spinocerebellar degeneration. The imaging findings suggested a mitochrondrial encephalopathy. Genetic examination confirmed a MELAS syndrome (mitochondrial myopathy, encephalopathy, lactate acidosis and stroke like episodes).

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JBR–BTR, 2007, 90: 288-289.

Mitochondrial encephalomyo-

pathy can manifest in multiple

syndromes with considerable radio-

logical, anatomopathological and

biochemical overlapping. These are

chronic disorders with acute necrot-

ic and, therefore, diffusion-hyperin-

tense episodes. Necrosis takes place

in different vascular territories and

both grey and white matters are

affected. There is typical bilateral

and symmetrical infestation of the

basal ganglia. All these features

were present in this case of a 20-

year-old female, who presented at

the neurology department with con-

fusion and progressive sensory

aphasia.

Case report

A 20-year-old Caucasian female

presented at the neurology depart-

ment with confusion and progres-

sive sensory aphasia. Anamnesis

revealed occipital headache of a few

days duration, radiating to the left

cranial hemisphere. For two years,

she was known at the department of

pediatrics with progressive external

ophtalmoplegy, impairment of gait

and ataxia. EMG showed signs of

myopathy. Laboratory examination

revealed lactate acidosis and

increased alanine and organic acid

levels. This suggested a secondary

mitochondrial dysfunction, but at

that time, MRI of the brain showed

no anomalies. There were no

contributive antecedents in family

history.

Because of the acute deteriora-

tion of the patient, a new CT scan

(Fig. 1) was performed. The left tem-

poral lobe was hypodense with

mass-effect on the lateral ventricle

(Fig. 1A,B). There was bilateral and

symmetrical hypodensity of the

basal ganglia (Fig. 1C). The cerebel-

lum and the brainstem were atroph-

ic (Fig. 1A,B). Further MRI examina-

tion (Fig. 2) showed on FLAIR

images a diffuse hyperintense left

temporal lobe with cortical thicken-

ing and compression of the lateral

ventricle (Fig. 2A), hyperintensity

and thickening of the cortex around

the left calcarine fissure and bilater-

al and symmetrical hyperintensity of

the striatal corpora and innominate

substance (Fig. 2A). All these lesions

were hyperintense on the diffusion

sequences (Fig. 2C,D) and hypo-

intense on the T1-weighted images

without contrast. No enhancement

was seen after contrast administra-

tion. The coronal T1 inversion recov-

ery images displayed the perfect

symmetry of the infestated striatal

corpora and innominate substance

(Fig. 2E).

Lateralisation to the left was seen

on EEG. Color-Doppler examination

of the carotid arteries and ECG were

normal.

In summary, imaging showed

acute lesions of the basal ganglia

and innominate substance bilateral-

ly, acute white and grey matter

lesions of the left temporal and

occipital lobe, which are different

vascular territories, and chronic

spinocerebellar degeneration. A

chronic disorder with acute

episodes was suspected. A key fea-

ture to the differential diagnosis is

the bilateral basal ganglia infesta-

tion, which had to be integrated with

the acute white and grey matter

lesions in different vascular territo-

ries, the chronic spinocerebellar

degeneration and the clinical pre-

sentation and history. The diagnosis

of mitochondrial encephalopathy

was proposed.

Genetic screening of the blood

revealed a 3243 A to G mutation in

the lymfocytes, which is found in

MELAS syndrome (mitochondrial

myopathy, encephalopathy, lactate

acidosis and stroke like episodes).

Discussion

Mitochondrial encephalopathy

has to be considered as one entity,

consistent with multiple variants or

syndromes as there are MELAS,

Leigh’s disease (subacute necrotic

CT AND MRI APPEARANCE OF MITOCHONDRIAL ENCEPHALOPATHY

K. Geldof

, K. Ramboer

, J.-M. Goethals

, L. Verhaeghe

A case is reported of a 20-year-old female presenting with confusion and progressive sensory aphasia. CT and MRI

showed bilateral and symmetric acute necrosis of the basal ganglia and of the left temporal and occipital lobe,

besides chronic spinocerebellar degeneration. The imaging findings suggested a mitochrondrial encephalopathy.

Genetic examination confirmed a MELAS syndrome (mitochondrial myopathy, encephalopathy, lactate acidosis and

stroke like episodes).

Key-words: Brain, diseases — Brain, MR.

From:

1. Department of Radiology, AZ St.- Lucas, Assebroek, Belgium, 2. Department

of Psychiatry-Neurology, AZ OLV Ter Linden, Knokke-Heist, Belgium.

Address for correspondence:

Dr K. Geldof, Wilselsesteenweg 10, B-3010 Kessel-Lo,

Belgium. E-mail: Koen.Geldof@telenet.be or koen.geldof@uz.kuleuven.ac.be.

Fig. 1.

— CT shows on axial scan through the posterior fossa and temporal lobes (A)

atrophy of the cerebellum with dilatated fourth ventricle (open arrow) and a hypo-

dense left temporal lobe (arrows). Axial scan more cranial through the posterior fossa

and temporal lobes (B) shows atrophy of the brainstem (open arrow) and a hypodense

left temporal lobe with compression of the lateral ventricle due to oedema (arrows).

Axial scan through the basal ganglia (C) shows bilateral and symmetrical hypodensi-

ty of the basal ganglia (arrows).

ABC

CT AND MRI APPEARANCE OF MITOCHONDRIAL ENCEPHALOPATHY — GELDOF et al 289

encephalitis), MERRF (myoclonus,

epilepsy and ragged red fibers),

Kearnes-Sayre (chronic external

ophtalmoplegia with retinal pig-

mentary abnormalities) and Alper’s

disease (progressive infantile

poliodystrophy). Pathogenesis in

these syndromes are similar (1) and,

therefore, radiological, anato-

mopathological and biochemical

overlapping is the rule. Encoding for

(co)enzymes in the Krebs-cycle is

disturbed due to mitochondrial DNA

mutations with impaired ATP pro-

duction as result. This energy deple-

tion leads to cellular death. The most

affected tissues are brain, muscle

and eye, leading respectively to

necrotic encephalopathy, myopathy

and ophtalmo- or retinopathy. Two

main hypotheses have been put for-

ward in the physiopathology of

MELAS (2, 3). The vascular hypothe-

sis holds that metabolic damage to

the endothelium leads to small-ves-

sel occlusion and secundary neu-

ronal death. The defect in neuronal

metabolism hypothesis states that

mitochondrial dyfunction results in

anaerobic metabolism and neuronal

death from acidosis.

These acute necrotic episodes

present on diffusion weighted imag-

ing (DWI) as hyperintense lesions.

DWI displays regional mobility of

protons and it is claimed that it can

help distinguish between cellular

and extracellular oedema. In gener-

al, the apparent diffusion coefficient

(ADC), presenting intercellular diffu-

sion of protons, is restricted or

reduced in ischaemic infarcts, giving

dark areas on ADC mapping.

Decreased ADC values correspond

to cellular oedema, whereas

increased ADC values correspond to

an increase in the extracellular space

or extracellular oedema (2). More

recent studies (2-5) support the

metabolic rather than the ischemic

hypothesis by showing no signifi-

cant ADC restriction in acute lesions

caused by mitochondrial dysfunc-

tion, which has been attributed to

smooth muscle and endothelial cell

damage of small arteries and pial

arterioles, causing increased perme-

ability of the blood-brain barrier, and

therefore vasogenic or extracellular

oedema. This phenomenon can help

us to differentiate these stroke-like

episodes from real stroke. Normal or

increased ADC values within

48 hours of a neurological deficit of

abrupt onset should raise the possi-

bility of MELAS, especially if conven-

tional MR images show infarct-like

lesions (2). Unfortunately, ADC map-

ping was not done in our patient,

nevertheless, there are other key

imaging features besides this typical

DWI characteristics, which lead to

diagnosis and they can be detected

by CT as well. Necrosis in the brain

takes place in different vascular terri-

tories and both grey and white mat-

ter are affected (1, 4, 6). The combi-

nation of deep grey matter involve-

ment and peripheral white matter

involvement in young adults or

children should suggest the diagno-

sis (7, 8). Bilateral and symmetrical

infestation of the basal ganglia is

very common (4, 6-8) and chronic

spinocerebellar degeneration is

often a predominant neuroradiolog-

ic finding in patients with respiratory

chain defects (8).

Inheritance is non-Mendelian (1)

because mitochondria contain

unique mitochondrial DNA that the

ovum has exclusively contributed to

the zygote. The trait can, therefore,

only be inherited from the mother.

Characteristic variability in the

expression of the trait is due to the

proportion of normal and abnormal

mitochondrial DNA in each cell.

Prognosis is poor and often leads to

death, as was the case in this young

woman.

References

1. Zeviani M., Di Donato S.:

Mitochondrial disorders.

Brain

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127: 2153-2172.

2. Oppenheim C., Galanaud D.,

SamsonY., et al.: Can diffusion weight

ed magnetic resonance imaging help

differentiate stroke from stroke-like

events in MELAS?

J Neurol Neuro-

surg Psychiatry

, 2000, 69: 248-250.

3. Abe K., Yoshimura H., Tanaka H.,

Fujita N., Hikita T., Sakoda S.:

Comparison of conventional and dif-

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Fig. 2.

— MRI – Axial FLAIR

image through the temporal

lobe shows (A) a diffuse hyper-

intense left temporal lobe with

cortical thickening (open arrow)

and compression of the lateral

ventricle (arrow). Axial FLAIR

image through the basal gan-

glia (B) shows hyperintensity

and thickening of the cortex

around the left calcarine fissure

(open arrow) and bilateral and

symmetrical hyperintensity of

the striatal corpora (arrows).

ABE

Diffusion-weighted sequence at the same level as fig. 2A (C) shows hyperintensity of

all focal lesions.Diffusion-weighted sequence at the same level as fig. 2B (D) shows

hyperintensity of all focal lesions. Coronal T1-weighted inversion recovery sequence

(E) shows perfect symmetry of the striatal corpora and innominate substance lesions

(arrows).

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In a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS), both T2- and diffusion-weighted MR imaging revealed lesions as hyperintense areas in the occipital lobes early after strokelike episodes. In these lesions, no significant reduction in apparent diffusion coefficient was noted. Apparent diffusion coefficient mapping may help to differentiate strokelike episodes in MELAS from acute ischemic stroke. The strokelike episodes may be related to vasogenic edema and hyperperfusion, which were suggested by our single-photon emission CT and MR imaging studies.

Comparison of conventional and diffusion-weighted MRI and proton MR spectroscopy in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like events

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The mechanism of neurological disturbances in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is controversial. We studied 12 patients with MELAS using conventional and diffusion weighted MRI (DWI) and MR spectroscopy (MRS), to look at the physiopathology of the stroke-like events. Although conventional MRI showed lesions in all patients, DWI was more sensitive. One patient did not show high signal on DWI 48 h after a from stroke-like episode, but MRS demonstrated a lactate peak in left occipital lobe; 2 weeks after the attack, high signal was demonstrated on the right frontal lobe where MRS had shown a lactate peak. Our findings suggest a possible predictive ability of (1)H-MRS, in showing early MELAS lesions and supports the hypothesis that mitochondrial metabolic dysfunction may precedes abnormalities on DWI.

Mitochondrial disorders

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Nov 2004
BRAIN

In the medical literature the term 'mitochondrial disorders' is to a large extent applied to the clinical syndromes associated with abnormalities of the common final pathway of mitochondrial energy metabolism, i.e. oxidative phosphorylation (OXPHOS). Faulty oxidative phosphorylation may be due to overall dysfunction of the respiratory chain, a heteromultimeric structure embedded in the inner mitochondrial membrane, or can be associated with single or multiple defects of the five complexes forming the respiratory chain itself. From the genetic standpoint, the respiratory chain is a unique structure of the inner mitochondrial membrane formed by means of the complementation of two separate genetic systems: the nuclear genome and the mitochondrial genome. The nuclear genome encodes the large majority of the protein subunits of the respiratory complexes and most of the mitochondrial DNA (mtDNA) replication and expression systems, whereas the mitochondrial genome encodes only 13 respiratory complex subunits, and some RNA components of the mitochondrial translational apparatus. Accordingly, mitochondrial disorders due to defects in OXPHOS include both mendelian-inherited and cytoplasmic-inherited diseases. This review describes human genetic diseases associated with mtDNA and nuclear DNA mutations leading to impaired OXPHOS.

Jan 2004
BRAIN
2153-2172

M Zeviani
Di Donato

Zeviani M., Di Donato S.: Mitochondrial disorders. Brain, 2004, 127: 2153-2172.

CT and MRI appearance of mitochondrial encephalopathy

Abstract

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