Neuroimaging In Epilepsy

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					                                  Neuroimaging In Epilepsy

                                                                                                  Shahina Bano and Sachchida Nand Yadav

                                A seizure is defined as a paroxysmal alteration
                                in   neurologic        function        due    to     excessive    The major utility of computed tomography (CT)
                                electrical discharge from the central nervous                     scanning is in the initial evaluation of seizures,
                                system. Epilepsy is defined as a condition of                     particularly in trauma, hemorrhage, infarction,
                                recurrent seizures, and medical intractability                    tumors, calcified lesions and major structural
                                as recurrent seizures despite optimal treatment                   changes. In perioperative patients, it is the
                                under       the     direction     of     an       experienced     imaging technique of choice as it can detect
                                neurologist over a two to three year period.                      the bleed, hydrocephalus and asses electrode
                                Determining the underlying cause of a patient’s                   placement. However, the overall sensitivity of
                                seizure is the fundamental goal in the workup of                  CT in patients with epilepsy is low (~ 30%),
                                epilepsy. Imaging of the brain provides valuable                  and because of poor resolution in the temporal
                                information in this regard. The main purposes                     fossa CT is of no use in detecting mesial
                                of neuroimaging in epilepsy patients are to                       temporal sclerosis, the most common pathology
                                identify underlying structural or metabolic                       in intractable temporal lobe epilepsy.1
                                abnormalities that require specific treatment
                                and to aid in formulating a syndromic or                          Magnetic resonance imaging (MRI), with its
                                etiologic diagnosis. Neuroimaging is even more                    excellent spatial resolution, soft tissue contrast,
                                important for those patients who have medically                   and multiplanar capabilities, is the imaging
                                intractable seizures. Advances in technology to                   modality of choice in investigating patients
                                localize epileptogenic focus, especially with                     with seizure disorder. The sensitivity of MRI
                                                                                                  in identifying epileptogenic foci in patients
                                high resolution magnetic resonance imaging
                                                                                                  with medically refractory patients has been
                                (MRI), have substantially improved the success
                                                                                                  reported to be more than 80%. However, in
                                of surgical treatment.
                                                                                                  patients with idiopathic generalized epilepsy,
                                                                                                  MRI has not been shown to be useful. The
                                Common            structural    disorders           associated
                                                                                                  correlation of the MRI finding with clinical
                                with seizure and detected on imaging can
                                                                                                  and electroencephalography (EEG) findings are
                                be categorized into the following groups:
                                                                                                  essential to avoid false positive localization of
                                hippocampal or mesial temporal sclerosis,
                                                                                                  epileptogenic focus.2
                                cortical          developmental               malformations
                                or   neuronal        migration     disorders          (cortical
                                                                                                  Routine scanning protocol for a patient with
                                dysplasias, heterotopias, hemimegalencephaly,
                                                                                                  refractory epilepsy may include axial or coronal
                                lissencephaly,        schizencephaly,              pachygyria,
                                                                                                  T1 and T2-weighted imaging, Fluid-attenuated
                                polymicrogyria,          Rasmussen            encephalitis),
                                                                                                  inversion recovery (FLAIR) imaging, and 3D
                                phakomatoses          (Tuberous         sclerosis,     Sturge
                                                                                                  volume acquisition sequences. Common 3D
                                Weber syndrome, neurofibromatosis), vascular
                                                                                                  acquisition sequences include high resolution
                                abnormalities         (arteriovenous          malformation,
                                                                                                  T1-weighted magnetization prepared rapid
                                cavernous             hemangiomas),                 infections    acquisition gradient echo (MPRAGE) and fast
                                (Tuberculoma, neurocysticercosis), neoplasms                      spoiled GRASS(3D-FSPGR), where GRASS is
                                (ganglioglima, dysembryoplastic neuroepithelial                   gradient recalled echo acquisition at steady
                                tumor,      low      grade     gliomas        and     cerebral    state. T1-weighted sequences are used to
                                metastasis in adults), stroke, posttraumatic                      define the brain anatomy, and T2-weighted
 Shahina Bano                   epilepsy, and miscellaneous conditions (gliosis,                  or FLAIR sequences are used to detect the
 Consultant Radiologist
 RML Hospital                   encephalocele).                                                   brain pathologies. High-resolution 3D volume
 Delhi                                                                                            acquisition provides good T1-weighted contrast
                                This article highlights the specific role of                      between gray and white matter and helps to
 Sachchida Nand Yadav
 Consultant Radiologist         various imaging modalities in patients with                       detect subtle cortical dysplasias and internal
 RML Hospital                   epilepsy, and their practical applications in the                 structure of hippocampus in case of mesial
                                management of epileptic patients.                                 temporal sclerosis.3,4,5 For optimal assessment

Vol. 9, Issue 3 & 4, April-September 2010
of hippocampus the imaging should be in hippocampal axis                     noted in these lesions, as well as in the normal appearing
(oblique coronal plane) with thin slices and good signal-to-                 brain contralateral to the lesion, when compared with gray and
noise ratio. The application of contrast agent is indicated if               white matter of neurologic controls.10,11 MRS is of particular
there is suspicious of primary or metastatic tumor, infection, or            importance in patients with brain tumors. The characteristic
inflammatory lesion.                                                         elevation of choline makes MRS a valuable tool for the diagnosis
                                                                             of tumors and their differentiation from other lesions. There is
The specialized protocol includes Quantitative volumetry and T2              also evidence that MRS can differentiate between tumor types.12
relaxometry, MR spectroscopy, Functional MRI (fMRI), Diffusion               Neurotransmitter MRS studies have potential therapeutic impact
weighted imaging (DWI) & Diffusion tensor imaging (DTI), and                 in seizure patients. Glutamate and γ amino-butyric-acid(GABA)
Magnetic source imaging (MSI).                                               can be measured using MRS editing techniques. Intracellular
                                                                             glutamate concentrations remain elevated in the epileptogenic
High resolution T1-weighted 3D volume gradient echo sequences                hippocampus and neocortex, and contribute to the epileptic
are also used for quantitative measurement of volume of any                  state by increasing cellular excitability. 13
particular region of interest. In the case of epilepsy this is usually
the hippocampus. Volumetric analysis of the hippocampus                      Surgical treatment of refractory focal seizure has been an important
can be performed both in adults and children with epilepsy,                  and effective means for seizure control. However, the surgical
to detect more subtle volume deficits (atrophy) that may be                  outcome is dependant on precise localization of epiletogenic
missed by visual assessment alone. Volumetric measurements                   focus and functional areas of the brain. The functional MRI
can be performed manually or with half-or fully-automated                    (fMRI), plays a very important role in preoperative localization
software, however, needs good knowledge of anatomical                        of epileptogenic focus and assessment of cognitive function in
details. Longitudinal studies done to asses the progression                  patients with refractory epilepsy. During focal seizure, cerebral
of volumetric changes correlate with the seizure associated                  blood flow and metabolism is considerably increased. fMRI using
damage.6 T2 relaxometry is the quantitative determinant of the               blood oxygen level dependent (BOLD) technique can detect
T2 relaxation time. To achieve this, several T2-weighted images              these cerebral hemodynamic changes. The excellent spatial
are acquired at different echo times, and with these values an               resolution of fMRI helps to study cortical activation during
exponential decay curve is obtained to estimates the T2 decay                epileptic activity and define epiletogenic focus in originally
rate of the imaged tissue. The tissues that have prolonged T2 are            activated area. The recent development of EEG-triggered fMRI
considered abnormal. In epileptic patients with hippocampal                  which allows interpretable electroencephalographic data to be
sclerosis, signal increase on T2-weighted images is typically                recorded during MRI scanning, has advantage of combining the
observed in the hippocampus. The measured values of the                      spatial resolution of imaging with the temporal resolution of
hippocampal volume and the T2 times are correlated with each                 electrophysiology in precise localization of seizure foci, thus
other, indicating that a marked volume loss is associated with               increasing the rate of successful resection of the epileptogenic
a significant increase in T2 relaxation, reflecting the complex              focus. The EEG-triggered fMRI is highly reliable, repeatable and
pathology of hippocampal sclerosis. 7                                        noninvasive tool in localization of the seizure foci of patients
                                                                             with intractable focal seizure. Combined video-EEG and fMRI in
Proton MR spectroscopy (MRS) has proven to be a sensitive                    localization of seizure foci has also shown good results.14,15 Long
measure to detect metabolic dysfunction in patients with                     term epileptic activity in patients with epilepsy results in atypical
temporal lobe epilepsy (TLE), particularly mesial temporal                   distribution of cognitive function areas because of reorganization
sclerosis (MTS) involving hippocampus. 20% of patients with                  of cortical language and memory areas. Accurate localization of
TLE have normal structural MRI scan and the findings in                      cognitive functional areas is necessary, to avoid their resection
children generally tend to be more subtle than those in adults.              at the time of surgery, to modify surgical approaches for those
MRS metabolite abnormalities may be found even in the absence                patients at risk of language and memory deficit and to predict
of detectable structural abnormalities. NAA, NAA/Cho, NAA/Cr,                postoperative cognitive deficit after resection of seizure foci.16
and NAA/(Cho+Cr) all are decreased in atrophic hippocampi, as
well as in nonatrophic hippocampi with abnormal EEG findings.                The diffusion-weighted signal reflects the molecular motion of
Reduced N-acetylaspartate concentration suggests neuronal loss               water in the intra-and extra-cellular environments. In tissue
or dysfunction. TLE patients may also show increased choline                 components such as CSF, molecular motion is not restricted
and myoinositol signals, suggestive of gliosis. Studies of patients          in any direction and is known as isotropic diffusion, detected
during or immediately after seizures (within 6 hours) may also               by diffusion weighted imaging (DWI). In tissues with linear
show lactate increase in the epiletogenic focus. MRS also has                arrangement of myelinated fibers such as white matter tracts, the
promising role in the evaluation of patients with extratemporal              molecular motion is restricted to the axis along the white tracts
epilepsy (frontal lobe epilepsy).8,9 In patients with structural             and is known as anisotropic diffusion, detected by diffusion
MR evidence of malformations of cortical development (MCD)                   tensor imaging (DTI) or tractography. In epilepsy, DWI is used
or neuronal migration disorders (NMD), MRS provides insight                  to asses acute cerebral ischemia, tumors or infections, while
into both the pathology and true extent of the disease processes.            DTI has been used to assess the degree of distortion of white
Abnormally decreased NAA/Cr and Cho/Cr ratios have been                      matter tracts in case of developmental abnormalities and other

Vol. 9, Issue 3 & 4, April-September 2010
lesions responsible for seizure. Anisotropy is reduced in areas of
                                                                                  Hippocampal volumetric and morphometric studies in
structural abnormalities suggesting structural disorganization of
                                                                                  frontal and temporal lobe epilepsy. Brain 1992; 115:
white matter.17,18
                                                                            7.    Van paesschen W, Connelly A, King MD, Jackson GD,
Magnetoencephalography (MEG), also known as MSI when
                                                                                  Duncan JS. The spectrum of hippocampal sclerosis. A
combined with structural imaging, has proved to be new
                                                                                  quantitative magnetic resonance imaging study. Ann
noninvasive tool for localization of epileptic focus. MSI is similar
                                                                                  Neurol 1997;41:41-51.
to EEG, but unlike EEG it detects magnetic rather than electric
                                                                            8.    Danielsen ER, Ross B. The clinical significance of
signal and is more accurate for localizing abnormal focus. It is
                                                                                  metabolites. In: Danielsen ER, Ross B, eds. Magnetic
increasingly useful for presurgical localization of epileptogenic
                                                                                  resonance spectroscopy of Neurological Disease. New
lesions and stimulus induced normal neuronal function to
                                                                                  York: Marcel Dekker inc, 1999:23-42.
minimize postoperative neurological deficits.19
                                                                            9.    Kuzniecky R, Palmer C, Hugg J, et al. Magnetic resonance
Besides      purely structural imaging techniques like MRI,                       spectroscopic Imaging in temporal lobe epilepsy:
functional imaging studies like interictal positron emission                      neuronal dysfunction or cell loss? Arch Neurol 2001;
tomography (PET), and ictal and interictal single photon                          58:2048-53.
emission computed tomography (SPECT) may provide additional                 10.   Li LM, Cendes F, Bastos AC, et al: Neuronal metabolic
information in some patients and thus aid in clinical decision                    dysfunction in patients with cortical developmental
making. PET and SPECT are usually not indicated for the majority                  malformations:     A    proton     magnetic    resonance
of patients with epilepsy but has important role in the surgical                  spectroscopic imaging study. Neurology 50:755-759,
candidates. The detection of cryptogenic lesions is the main goals                1998.
of functional epilepsy imaging with PET or SPECT. PET utilizes              11.   Simone IL, Federico F, Tortorella C, et al: Metabolic
an injection of tracer 18F- labeled deoxyglucose (18 FDG) to                      changes in neuronal migration disorders: Evaluation by
measure brain metabolism. Interictal PET shows hypometabolism                     combined MRI and proton MR spectroscopy. Epilepsa
in the seizure focus, especially in TLE. Ictal PET is not practical               40:872-879,1999.
due to extremely short half life of the radiotracers used. PET              12.   Burtscher IM, Holtas S. Proton magnetic resonance
remains a diagnostic modality for presurgical localization of                     spectroscopy in brain tumors: clinical applications.
the focus in temporal lobe and extratemporal epilepsy when                        Neuroradiology 2001;43:345-352.
MRI is normal.20 SPECT utilizes injection of radio-labeled                  13.   Petroff O. GABA and glutamate in the human brain.
tracer Technetium99m hexamethyl-propyleneamineoxime (Tc-                          Neuroscientist 2002;8:562-573.
HMPAO) or ethyl cysteinate dimmer(Tc ECD), which has very                   14.   YU AH, Piao CK, Li KC. Progress of functional MRI in
slow distribution once in the brain. The tracer is stable for several             epilepsy. Clin Radiol(Chin) 2005;24:270-272.
hours, allowing delayed imaging. The most useful study for                  15.   Al asmi A, Benar CG, Gross DW, et al. fMRI activation
presurgical evaluation is an ictal SPECT, which usually reveals                   in continous and spike triggered EEG-fMRIstudies of
increased blood flow at site of seizure onset. Interictal studies                 epileptic spikes. Epilepsia 2003;44:1328-1330.
often show relative hypoperfusion at the site of seizure onset.             16.   Zhang L, Jin Z, Zeng YW, et al. Preoperative
The substraction of the interictal from the ictal SPECT, and then                 brain functional mapping using fMRI in patients
coregistration of the resulting images onto MRI (substraction                     with intractable epilepsy. Chin J sterotact Funct
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the accuracy of this method.                                                17.   Romero JM, Schaefer PW, Grant PE, Becerra L, Gonzalez
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Vol. 9, Issue 3 & 4, April-September 2010