Quantitative analysis of the morphometric analysis program MAP in patients with truly MRI-negative focal epilepsy.

OBJECTIVE: In the presurgical evaluation of epilepsy, identifying the epileptogenic zone is challenging if magnetic resonance imaging (MRI) is negative. Several studies have shown the benefit of using a morphometric analysis program (MAP) on T1-weighted MRI scans to detect subtle lesions. MAP can guide a focused re-evaluation of MRI to ultimately identify structural lesions that were previously overlooked. Data on patients where this additional review after MAP analysis did not reveal any lesions is limited. Here we evaluate the diagnostic yield of MAP in a large group of truly MRI-negative patients. METHODS: We identified 68 patients with MRI-negative focal epilepsy and clear localization of the epileptogenic zone by intracranial EEG or postoperative seizure freedom. High resolution 3D T1 data of patients and 73 healthy controls were acquired on a 3 T scanner. Morphometric analysis was performed with MAP software, creating five z-score maps, reflecting different structural properties of the brain and a patient's deviation from the control population, and a neural network-based focal cortical dysplasia probability map. Ten brain regions were specified to quantify whether MAP findings were located in the correct region. Receiver operating characteristic (ROC) analyses were performed to identify the optimal thresholds for each map. RESULTS: MAP-guided visual re-evaluation of the original MRI revealed overlooked lesions in three patients. The remaining 65 truly MRI-negative patients were included in the statistical analysis. At the optimal thresholds, maximum sensitivity was 84 %, with 35 % specificity. Balanced accuracy (arithmetic mean of sensitivity and specificity) of the respective maps ranged from 51 % to 60 %, creating three to six times more false positive than true positive findings. CONCLUSION: This study confirms that MAP is useful in detecting previously overlooked subtle structural lesions. However, in truly MRI-negative patients, the additional diagnostic yield is very limited.

Brain diffusion tensor imaging changes in cerebrotendinous xanthomatosis reversed with treatment.

Cerebrotendinous xanthomatosis (CTX, MIM 213700) is a rare autosomal recessive lipid storage disorder caused by CYP27A1 mutations. Treatment with chenodeoxycholic acid (CDCA) may slow the progression of the disease and reverse some symptoms in a proportion of patients. In a non-consanguineous Caucasian family, two siblings with CTX were evaluated before treatment and prospectively followed-up every 6 months after starting CDCA therapy, using systematic clinical examination, neuropsychological tests, laboratory tests, electroencephalography (EEG) and brain MRI, diffusion tensor imaging (DTI) and tractography. A 30-year-old patient and her 27-year-old brother were referred for progressive spastic paraparesis. Both had epilepsy, learning difficulties, chronic diarrhoea and juvenile-onset cataracts. CTX was diagnosed by increased cholestanol levels and compound heterozygosity for CYP27A1 mutations. Therapy with CDCA led to resolution of chronic diarrhoea, normalisation of serum cholestanol and EEG, and a progressive improvement in gait, cognition and seizure control. Before treatment, conventional brain MRI showed no CTX-related abnormalities for the proband and no cerebellar abnormalities for the brother, while DTI showed reduced fractional anisotropy (FA) and tract-density in the cerebellum and widespread cerebral reductions of FA in both patients, compared to a group of 35 healthy controls. Repeated DTI after starting therapy showed progressive increases of cerebellar tract density and of cerebral FA. In patients with CTX, therapy with CDCA may lead to significant clinical improvement, with normalisation of biochemical and electrophysiological biomarkers. DTI and tractography may detect changes when the conventional MRI is unremarkable and may provide potential neuroimaging biomarkers for monitoring treatment response in CTX, while the conventional MRI remains unchanged.