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Proton (1H) MRS in extratemporal epilepsies

A multivoxel 1H MRS imaging (MRSI) study reported reduced NAA in frontal lobes
ipsilateral to frontal lobe epileptic seizures and the decrease in NAA was inversely related to
seizure frequency, suggesting that a higher seizure frequency is associated with more
neuronal dysfunction or loss104.

Malformations of cortical development

Reduced NAA/choline and NAA/creatine have been shown in focal cortical dysplasia105 and
other malformations of cortical development106. Quantitative short echo time MRSI, with
correction for partial volume effects, has shown that metabolic abnormalities were
heterogeneous and more extensive than the structural lesions evident on MRI107. A post-ictal
rise in lactate has been shown using MRSI in the ipsilateral temporal lobe in patients with
unilateral TLE108. An elevation of cerebral lactate has been noted during and for a few hours
after complex partial seizures, with no change in NAA109. MRS has shown elevated lactate,
decreased NAA and elevated choline during status epilepticus. Subsequently, lactate and
choline returned to normal, whereas the NAA level remained reduced, implying neuronal loss
or dysfunction110,111.

GABA

GABA is the principal inhibitory neurotransmitter in the brain, acting at up to 40% of
synapses, with a resting concentration of 12 mmol/L and a major role in regulation of seizure
activity. Proton MRS, using spectral editing, can identify cerebral GABA in vivo and estimate
the rise in cerebral GABA concentrations that occurs after administration of vigabatrin112,
gabapentin113 and topiramate114. Low GABA concentrations have been associated with
continued seizure activity115. Low GABA levels were associated with poor seizure control in
patients with complex partial seizures, but not in juvenile myoclonic epilepsy. Higher
homocarnosine concentrations were associated with better seizure control in both types of
epilepsy116.

Glutamate and glutamine

Glutamate is the principal excitatory neurotransmitter in the brain and responsible for
mediating excitotoxicity and initiating epileptic activity117. Glutamate is also an intermediary
metabolite, and present at a concentration of 812 mmol/L. Aspartate, also an excitatory
transmitter, is present at a concentration of 13 mmol/L. Discrimination between glutamate
and glutamine in vivo on clinical scanners requires spectral modelling, because of the large
number of coupled overlapping peaks and the limited achievable spectral resolution118.

MRS using short echo times (30 msec), voxels tailored to individual hippocampi and
quantitative assessment has shown reduced NAA and increased myoinositol (reflecting
gliosis) in epileptogenic sclerotic hippocampi, and similar but less severe abnormalities
contralaterally96. In patients with TLE and normal MRI, the MRS profile was characterised
by elevation of glutamate and glutamine. An increased concentration of combined glutamate
+ glutamine was noted following focal status epilepticus, with resolution at three months, but
persistence of low levels of NAA119. Malformations of cortical development, such as
heteroptopia and polymicrogyria, have also shown changes in glutamate, glutamine and
GABA concentrations consistent with abnormal metabolism of both inhibitory and excitatory

neurotransmitters106.