A low symptomatic form of neurodegeneration in younger carriers of the FMR1 premutation, manifesting typical radiological changes.

Fragile X-associated tremor/ataxia (FXTAS) is a late onset disorder caused by a premutation in the FMR1 gene, in which neurological symptoms are associated with white matter (wm) changes, especially within the middle cerebellar peduncles (MCP sign), seen on magnetic resonance images (MRIs). We report a discrepancy between obvious radiological presentations and minimal clinical involvement in two younger male premutation carriers. These carriers, aged 52 and 39 years, showed distinct MCP sign, but reported no neurological symptoms. If this discrepancy represents the initial stage of FXTAS, our findings suggest the possibility of early diagnosis from MRI scans.

Clinical utility of current-generation dipole modelling of scalp EEG.

OBJECTIVE: To investigate the clinical utility of current-generation dipole modelling of scalp EEG in focal epilepsies seen commonly in clinical practice. METHODS: Scalp EEG recordings from 10 patients with focal epilepsy, five with Benign Focal Epilepsy of Childhood (BFEC) and five with Mesial Temporal Lobe Epilepsy (MTLE), were used for interictal spike dipole modelling using Scan 4.3 and CURRY 5.0. Optimum modelling parameters for EEG source localisation (ESL) were sought by the step-wise application of various volume conductor (forward) and dipole (inverse) models. Best-fit ESL solutions (highest explained forward-fit to measured data variance) were used to characterise best-fit forward and inverse models, regularisation effect, additional electrode effect, single-to-single spike and single-to-averaged spike variability, and intra- and inter-operator concordance. Inter-parameter relationships were examined. Computation times and interface problems were recorded. RESULTS: For both BFEC and MTLE, the best-fit forward model was the finite element method interpolated (FEMi) model, while the best-fit single dipole models were the rotating non-regularised and the moving regularised models. When combined, these forward-inverse models appeared to offer clinically meaningful ESL results when referenced to an averaged cortex overlay, best-fit dipoles localising to the central fissure region in BFEC and to the basolateral temporal region in MTLE. Single-to-single spike and single-to-averaged spike measures of concordance for dipole location and orientation were stronger for BFEC versus MTLE. The use of an additional pair of inferior temporal electrodes in MTLE directed best-fit dipoles towards the basomesial temporal region. Inverse correlations were noted between unexplained variance (RD) and dipole strength (Amp), RD and signal to noise ratio (SNR), and SNR and confidence ellipsoid (CE) volume. Intra- and inter-operator levels of agreement were relatively robust for dipole location and orientation. Technical problems were infrequent and modelling operations were performed within 5min. CONCLUSIONS: The optimal forward-inverse single dipole modelling set-up for BFEC and MTLE interictal spike analysis is the FEMi model using the combination of rotating non-regularised and moving regularised dipoles. Dipole modelling of single spikes characterises best-fit dipole location and orientation more reliably in BFEC than in MTLE for which spike averaging is recommended. SIGNIFICANCE: The clinical utility of dipole modelling in two common forms of focal epilepsy strengthens the case for its place in the routine clinical work-up of patients with localisation-related epilepsy syndromes.

Tremor/ataxia syndrome and fragile X premutation: diagnostic caveats.

The fragile X-associated tremor/ataxia syndrome (FXTAS) is a newly discovered late-onset neurodegenerative disorder caused by a premutation in the FMR1 X-linked gene. We present examples of a discrepancy between obvious brain changes observed on MRI, and minimal clinical neurological manifestations in three older carriers of this premutation. This discrepancy occurred in three of nine carriers ascertained in an unbiased manner. If the systematic follow-up studies of adult carriers confirm this trend, this will have an impact on early diagnosis of neurological involvement and possible prevention. If MRI changes precede clinical manifestation of FXTAS this may explain the low detection rate of fragile X carriers among patients with neurological syndromes associated with tremor/ataxia.

Short-term effects of methylprednisolone on cerebral volume in multiple sclerosis relapses.

We prospectively investigated the short-term effects of intravenous methyl-prednisolone (IVMP) on cerebral volume in patients suffering a multiple sclerosis (MS) relapse. Ten patients underwent MRI brain studies immediately before and after IVMP treatment, and 4 and 8 weeks later. Whole brain volumes decreased significantly over the 8-week period. The greatest change occurred during IVMP administration. This has implications for MS treatment trials using cerebral atrophy as an endpoint.

Clinical, EEG, and quantitative MRI differences in pediatric frontal and temporal lobe epilepsy.

OBJECTIVE: To examine the clinical, electrographic, and quantitative MRI differences between frontal lobe (FLE) and mesial temporal lobe epilepsy (MTLE) in children. METHODS: The population included children who underwent video-EEG monitoring between 1995 and 2000 who were classified as either FLE (n = 39) or MTLE (n = 17) according to the criteria of the International League Against Epilepsy. Clinical, EEG, and quantitative MRI data (including frontal cortical volumes) were compared between the two syndromes and a control group (n = 42). RESULTS: In FLE, seizures were significantly briefer, more frequent, and predominantly from sleep, and had differing motor characteristics. The rates of bilateral epileptiform interictal and ictal EEG abnormalities were significantly higher in FLE. A nonlesional MRI was significantly more common in FLE. Mean frontal cortical volume in FLE was significantly lower than MTLE and controls. Seizure freedom after surgery was lower in FLE. CONCLUSIONS: The clinical syndrome of FLE is clearly distinct from MTLE. The etiology of this disorder is unknown in the majority of cases despite extensive investigation. Because of a lack of a clearly defined etiology and frequent nonlateralizing EEG changes, few of these children are considered optimal surgical candidates. The demonstration of bilateral frontal cortical volume loss and bilateral EEG abnormalities suggests that FLE is a bilateral disease in a high proportion of patients. The outcome in those patients who were deemed surgical candidates was significantly worse than the MTLE cases.

Serial MRI in multiple sclerosis: a prospective pilot study of lesion load, whole brain volume and thalamic atrophy.

Using serial magnetic resonance imaging (MRI), we investigated the relationship between diffuse cerebral atrophy, T1 and T2 lesion volumes, mean thalamic volumes and clinical progression in patients with established multiple sclerosis (MS). Eleven patients were included in this prospective serial study. Cerebral volumes, T1 hypointense lesion volumes, and T2 hyperintense lesion volumes at baseline and at up to 3 years follow-up were assessed on MRI brain scans. As a putative measure of cerebral atrophy mean thalamic volumes were also obtained. The outcome measures were the MRI parameters and disability on Kurtzke's expanded disability status scale (EDSS). Of the 11 patients 6 worsened clinically as measured by an increase of 0.5 or more on the EDSS. Cerebral atrophy occurred in 91% of patients and was independent of changes in lesion volumes and was not associated with disease progression as determined by the EDSS.

Clinical utility of distributed source modelling of interictal scalp EEG in focal epilepsy.

OBJECTIVE: Assess the clinical utility of non-invasive distributed EEG source modelling in focal epilepsy. METHODS: Interictal epileptiform discharges were recorded from eight patients - benign focal epilepsy of childhood (BFEC), four; mesial temporal lobe epilepsy (MTLE), four. EEG source localization (ESL) applied 48 forward-inverse-subspace set-ups: forward - standardized, leadfield-interpolated boundary element methods (BEMs, BEMi), finite element method (FEMi); inverse - minimum norm (MNLS), L1 norm (L1), low resolution electromagnetic tomography (LORETA), standardized LORETA (sLORETA); subspace- whole volume (3D), cortex with rotating sources (CxR), cortex with fixed sources (CxN), cortex with fixed extended sources (patch). Current density reconstruction (CDR) maxima defined 'best-fit'. RESULTS: From 19,200 CDR parameter results and 2304 CDR maps, the dominant variables on best-fit were inverse model and subspace constraint. The most clinically meaningful and statistically robust results came with sLORETA-CxR/patch (lower Rolandic in BFEC, basal temporal lobe in MTLE). Computation time was inverse model dependent: sub-second (MNLS, sLORETA), seconds (L1), minutes (LORETA). CONCLUSIONS: From the largest number of distributed ESL approaches compared in a clinical setting, an optimum modelling set-up for BFEC and MTLE incorporated sLORETA (inverse), CxR or patch (subspace), and either BEM or FEMi (forward). Computation is efficient and CDR results are reproducible. SIGNIFICANCE: Distributed source modelling demonstrates clinical utility for the routine work-up of unilateral BFEC of the typical Rolandic variety, and unilateral MTLE secondary to hippocampal sclerosis.

Visual disturbances representing occipital lobe epilepsy in patients with cerebral calcifications and coeliac disease: a case series.

Paroxysmal visual manifestations may represent epileptic seizures arising from the occipital lobe. In coeliac disease (CD) bilateral occipital calcifications and seizure semiology consistent with an occipital origin have been described, primarily in Mediterranean countries. By reporting three adult patients from an Australian outpatient clinic with visual disturbances, occipital cerebral calcifications, and CD, this study seeks to emphasise that CD should be considered even when patients of non-Mediterranean origin present with these symptoms. Seizure types included simple partial, complex-partial, and secondarily generalised seizures. The seizure semiology consisted of visual disturbances such as: blurred vision, loss of focus, seeing coloured dots, and brief stereotyped complex visual hallucinations like seeing unfamiliar faces or scenes. Symptoms of malabsorption were not always present. Neurological examination was unremarkable in two patients, impaired dexterity and mild hemiatrophy on the left was noted in one. Routine electroencephalography was unremarkable. In all cases, computed tomography demonstrated bilateral cortical calcification of the occipital-parietal regions. Magnetic resonance imaging showed no additional lesion. All patients had biopsy confirmed CD. Seizure control improved after treatment with gluten free diet and anticonvulsants. This report illustrates the association between seizures of occipital origin, cerebral calcifications, and CD even in patients not of Mediterranean origin.