Hippocampal deformation mapping in MRI negative PET positive temporal lobe epilepsy.

OBJECTIVES: To compare hippocampal surface structure, using large deformation high dimensional mapping (HDM-LD), in subjects with temporal lobe epilepsy (TLE) with (HS+ve) and without (HS-ve) hippocampal sclerosis. METHODS: The study included 30 HS-ve subjects matched with 30 HS+ve subjects from the previously reported epilepsy patient cohort. To control for normal right-left asymmetries of hippocampal surface structure, subjects were regrouped based on laterality of onset of epileptic seizures and presence of HS. Gender ratio, age, duration of epilepsy and seizure frequency were calculated for each of the four groups. Final HDM-LD surface maps of the right and left TLE groups were compared to define differences in subregional hippocampal involvement within the groups. RESULTS: There were no significant differences in comparisons of the left TLE (left HS-ve compared with HS+ve) or right TLE (right HS-ve compared with HS+ve) groups with respect to age, duration of epilepsy or seizure severity scores. HDM-LD maps showed accentuated surface changes over the lateral hippocampal surface, in the region of the Sommer sector, in the hippocampi affected by HS. However, HS-ve hippocampi showed maximal surface changes in a different pattern, and did not involve the region of Sommer sector. CONCLUSION: We conclude that differences in segmental volume loss between the HS-ve and HS+ve groups are suggestive that the underlying pathophysiology of hippocampal changes in the two groups is different, and not related to chronic seizure duration or severity.

Predictive value of hippocampal MR imaging-based high-dimensional mapping in mesial temporal epilepsy: preliminary findings.

BACKGROUND AND PURPOSE: We objectively assessed surface structural changes of the hippocampus in mesial temporal sclerosis (MTS) and assessed the ability of large-deformation high-dimensional mapping (HDM-LD) to demonstrate hippocampal surface symmetry and predict group classification of MTS in right and left MTS groups compared with control subjects. METHODS: Using eigenvector field analysis of HDM-LD segmentations of the hippocampus, we compared the symmetry of changes in the right and left MTS groups with a group of 15 matched controls. To assess the ability of HDM-LD to predict group classification, eigenvectors were selected by a logistic regression procedure when comparing the MTS group with control subjects. RESULTS: Multivariate analysis of variance on the coefficients from the first 9 eigenvectors accounted for 75% of the total variance between groups. The first 3 eigenvectors showed the largest differences between the control group and each of the MTS groups, but with eigenvector 2 showing the greatest difference in the MTS groups. Reconstruction of the hippocampal deformation vector fields due solely to eigenvector 2 shows symmetrical patterns in the right and left MTS groups. A "leave-one-out" (jackknife) procedure correctly predicted group classification in 14 of 15 (93.3%) left MTS subjects and all 15 right MTS subjects. CONCLUSION: Analysis of principal dimensions of hippocampal shape change suggests that MTS, after accounting for normal right-left asymmetries, affects the right and left hippocampal surface structure very symmetrically. Preliminary analysis using HDM-LD shows it can predict group classification of MTS and control hippocampi in this well-defined population of patients with MTS and mesial temporal lobe epilepsy (MTLE).

Epilepsy in the nevoid basal-cell carcinoma syndrome (Gorlin syndrome): report of a case due to a focal neuronal heterotopia.

We present a case of uncontrolled temporal lobe epilepsy due to a focal left temporal neuronal heterotopia associated with the nevoid-basal-cell carcinoma syndrome. This is the first pathologically described lesion associated with temporal lobe epilepsy in this syndrome. Because the patient's seizures resolved after a modified left anterior temporal lobectomy, this case illustrates that epilepsy in patients with the nevoid basal-cell carcinoma syndrome is potentially curable and should be investigated appropriately.

The relationship between tonic accommodation and ciliary muscle innervation.

Previous studies have used Badal laser optometry to demonstrate significant variance in the distribution of tonic (or "dark-focus") resting positions of accommodation (TA) for groups of observers. This study investigates whether individual differences in TA are due to individual differences in autonomic tone of the ciliary muscle by comparing separately the effects of a muscarinic receptor antagonist (Tropicamide 0.5%) and a beta receptor agonist (Isoprenaline 3%) on the distribution of TA. Ten subjects were used for each study with mean ages of 23.2 and 23.0 yr, respectively. The distribution of TA within each subject group was equivalent to the large sample distributions published in previous literature. Darkroom measurements of TA and pupil diameter were determined with a Badal laser optometer and infrared photography. Distance correction and amplitude of accommodation were determined by standard optometric techniques. Isoprenaline produced a significant hyperopic shift in TA of 0.47 D over 22 min but this was not accompanied by a significant change in standard deviation of the TA distribution. This finding was in accord with the authors' previously reported investigation using the beta receptor antagonist Timolol Maleate. Tropicamide also produced a significant hyperopic shift in TA of 1.24 D over 24 min, and this was accompanied by a significant change in standard deviation of the distribution from 0.87 to 0.17. The results indicate that the parasympathetic system plays a significant role in determining the TA position and that the variations in TA between individuals is a consequence of parasympathetic rather than sympathetic ciliary muscle tone.

The effect of Timolol Maleate on tonic accommodation, tonic vergence, and pupil diameter.

The beta-adrenoceptor antagonist Timolol Maleate (0.5%) was employed topically to determine whether the resting (or "tonic") position of accommodation is a consequence of steady-state equilibrium between parasympathetic and sympathetic innervation of the ciliary muscle. Ten subjects were used, eight men and two women, with an age range of 19-37 (mean = 23.2). All subjects wore an optimum refractive correction giving visual acuities of 20/20 or better. Darkroom measurements of tonic accommodation (TA), tonic vergence (TV), and pupil diameter were determined with a Badal laser optometer , a nonius alignment device and infra-red photography, respectively. Far and near points of accommodation and oculo-motor balance tests were determined by standard optometric techniques and intraocular pressure (IOP) was measured by applanation tonometry. Both TA (mean = 1.66 D) and TV (mean = 2.10 deg) assumed intermediate resting positions in the absence of visual stimulation. A double-blind protocol between Timolol and Saline demonstrated a mean myopic shift in TA of +0.85 D over 40 min with Timolol. All other experimental parameters, apart from IOP, were unaffected by Timolol. It is concluded that sympathetic innervation to the ciliary muscle plays a significant role in determining the TA position and that this innervation is mediated by inhibitory beta adrenoceptors.

Triple-technique (MR imaging, single-photon emission CT, and CT) coregistration for image-guided surgical evaluation of patients with intractable epilepsy.

Ictal and interictal single-photon emission CT (SPECT) play an increasingly important role in the surgical evaluation of patients with epilepsy. We present a method of coregistration of MR, SPECT, and CT images to correlate structural data (MR imaging), blood flow changes (SPECT), and location of subdural electrodes (CT) for patients undergoing image-guided surgical treatment of epilepsy. MR-SPECT root mean square (rms) mismatch distances were 2.1 to 2.5 mm, and MR-CT rms mismatch distances were 1.0 to 4.5 mm. Coregistration assisted in image-guided placement of subdural electrodes and in surgical resection of the suspected epileptogenic focus.

Accuracy of coregistration of single-photon emission CT with MR via a brain surface matching technique.

We describe a technique of brain surface matching of single-photon emission CT and MR images in human subjects and document the accuracy of this technique with the use of fiduciary markers. This mismatch averaged 4.3 mm as measured by the fiduciary markers and 2.1 mm as measured by the root mean square distance.

Total percentage body weight changes during add-on therapy with tiagabine, carbamazepine and phenytoin.

Changes in body weight were evaluated in 349 patients from a study comparing efficacy of add-on therapy with tiagabine (TGB), carbamazepine (CBZ) or phenytoin (PHT). TGB add-on therapy showed no significant weight changes when added to either PHT or CBZ. CBZ add-on therapy showed a significant percentage weight gain of a mean body increase of 1.5% (P = 0.002). Adjunctive TGB therapy had no significant effect on total body weight, while adjunctive CBZ therapy was associated with weight gain.

The magnitude of longitudinal chromatic aberration of the human eye between 458 and 633 nm.

The longitudinal chromatic aberration (LCA) of the human eye was determined between wavelengths 458 and 633 nm for ten observers by incorporating Argon and Helium-Neon Lasers into a Badal optometer system such that tonic (or "dark focus") resting positions of accommodation could be measured under darkroom conditions. A mean chromatic range of 1.87 D was found between 488 and 633 nm. The range increased slightly to 1.91 D when the experiment was repeated under cycloplegia on a subset of three subjects. Additional wavelengths (458 and 476 nm) for a further subset (four subjects) increased the range to 2.65 D. This magnitude of LCA would support recent predictions based on Abbe and Pulfrich refractometry analyses of the dispersion of the human crystalline lens and ocular media.

Magnetic resonance and positron emission tomography changes during the clinical progression of Rasmussen encephalitis.

The authors describe serial positron emission tomography (PET) and magnetic resonance imaging (MRI) studies in a patient with pathologically confirmed Rasmussen Encephalitis (RE). Results of initial PET and MRI studies were normal. Subsequent studies showed involvement of the percentral and postcentral gyri and the putamen on PET, and the precentral and postcentral gyri on MRI. Coregistration of PET and MR images showed good correlation between the precentral and postcentral gyri involvement. However, subcortical involvement occurred earlier on PET than on MRI. The authors demonstrate the evolution of changes on PET and MR images in a patient with RE. Despite early pathologic confirmation of RE, there were no definite structural or functional imaging changes on PET or MRI until 3 years after symptom onset. These findings demonstrate the variability of imaging changes in RE, and the need to carefully correlate electro-physiologic and clinical findings to confirm the diagnosis of RE.

Neuro-ophthalmological signs during rapid intravenous administration of phenytoin.

We prospectively studied eye movement after rapid intravenous administration of phenytoin. Nineteen healthy young adults participated in a study of i.v. phenytoin pharmacokinetics. Subjects received a standard dose of 15 mg/kg at a rate of 25 mg/min, and were examined neuro-ophthalmologically before and at the end of the infusion. All patients had horizontal gaze-evoked nystagmus (HGN), and impairment of horizontal smooth pursuit (SP). Other signs were present in the following percentages: vertical gaze-evoked nystagmus (16 19 ,84%), and impairment of vertical SP (15 19 , 79%). Total and free phenytoin levels did not directly correlate with the degree of any of the neurological signs tested. By review of the past studies of nystagmus during phenytoin therapy, we propose that nystagmus is present consistently during toxicity with initial phenytoin therapy, but occurs less consistently during ongoing phenytoin use or chronic toxicity.

Fluctuating and constant valproate administration gives equivalent seizure control in rats with genetic and acquired epilepsy.

PURPOSE: Controlled-release formulations of Valproate (VPA) reduce side effects by minimizing peak plasma VPA concentrations in patients with epilepsy. However, the impact of this on anti-seizure efficacy has not been thoroughly explored. Here the pharmacokinetics and pharmacodynamics of chronic intermittent (consequently, peak VPA concentrations) and continuous VPA administration were directly compared in two rat models of epilepsy. METHODS: Genetic Absence Epilepsy Rats from Strasbourg (GAERS) received a single acute bolus of VPA (100 mg/kg intravenously) combined with electroencephalography (EEG) and/or blood sampling for 180 min post-injection. GAERS and epileptic rats post-kainic acid-induced status epilepticus were chronically infused intravenously (3-5 days, respectively) with (i) saline followed by in random order (ii) intermittent and (iii) continuous VPA (42 mg/kg/h), separated by two days of wash-out. Seizures were quantified using video-EEG monitoring and VPA levels measured in brain, cerebrospinal fluid and plasma. RESULTS: Following acute VPA administration seizure suppression in GAERS persisted after plasma VPA levels became very low. Chronic intermittent and continuous VPA significantly suppressed seizures in both models (p<0.01) with no difference between administration regimens. In GAERS, the pattern of seizure suppression during intermittent treatment was constant, in contrast to the fluctuating VPA plasma and brain levels. There was discordance between the temporal pattern of plasma, brain VPA levels and seizure suppression efficacy in GAERS. CONCLUSION: Administration regimes that result in fluctuating VPA blood levels achieve equivalent sustained seizure suppression as those that maintain steady mid-range concentrations.

Hemifacial motor and crying seizures of temporal lobe onset: case report and review of electro-clinical localisation.

OBJECTIVE: To report a case of temporal lobe epilepsy with clinical presentation of paroxysmal episodes of "tightness" over the right hemiface, and ictal crying, and review electroclinical localisation of this phenomenon. METHODS: Clinical semiology, neurophysiological localising tests, and epilepsy surgery outcome are reported in a subject presenting with paroxysmal right hemifacial movements and ictal crying. Pertinent past reports of somato-motor signs and ictal crying in temporal lobe epilepsy are reviewed and the findings correlated with proposed human facial cortical representation. RESULTS: Simple partial seizures caused by temporal lobe epilepsy presented with right sided tonic facial movements and ictal crying. Intracranial EEG monitoring documented a left medial temporal onset of seizures that remained asymptomatic until they propagated to the left cingulate region. Anterior temporal lobectomy with resection of the amygdala and anterior hippocampus resulted in cessation of seizures. CONCLUSIONS: This is a rare example of epileptic seizures of medial temporal onset presenting with isolated somato-motor manifestations and ictal crying. Anatomical-electrical-clinical correlations with cortical regions controlling facial movements were highly suggestive that this case represents secondary activation of "emotional" motor cortex M3 and M4 (rostral and caudal cingulate motor cortex), giving rise to focal hemifacial movements and ictal crying.

The effects of moderate doses of ethanol on heterophoria and other aspects of binocular vision.

It has been known for many years that ethanol has an impairing effect on binocular vision and the co-ordination of the ocular motor balance. Various parameters were compared before and after imbibition of a moderate dosage of ethanol. The results show an increase in esophoria (or decrease in exophoria) at 6 m, with a reduction in the negative fusional ability. They also show an increase in exophoria (or decrease in esophoria) at near, with a decrease in both the AC/A ratio and near point of convergence. There was no significant effect on the amplitude of accommodation. This study raises the possibility of an ophthalmic practitioner attempting to correct a transient, ethanol-induced ocular motor imbalance.

The relationship between tonic vergence and oculomotor stress induced by ethanol.

Previous investigations have demonstrated an ethanol-induced increase in distance esophoria and an increase in near exophoria, together with a decrease in negative fusional ability, the AC/A ratio and near point of convergence. The present study (N = 10) was designed to test the hypothesis that these effects are due to a biasing of vergence towards its tonic resting state when under conditions of oculomotor stress. Measurements of the parameters before and 1 hr after imbibition of a moderate dose of ethanol supported the previous findings. Darkroom measures of tonic vergence (vernier alignment) and tonic accommodation (laser optometry) were unaffected by ethanol. The study indicates that the changes in oculomotor function induced by the central inhibitory action of ethanol represent a shift towards the tonic vergence position.

Objective and subjective measurement of tonic accommodation.

Measurements of tonic accommodation (TA) were made on 25 subjects using He-Ne laser optometry (HNL), infra-red optometry (IR) and near retinoscopy (NR) under darkroom conditions. All three techniques were shown to produce comparable mean estimates of TA (HNL: 1.10 D; IR: 1.15 D; NR: 1.07 D). Significant correlations were found between HNL and IR (r = 0.88, p less than 0.001) and between HNL and NR (r = 0.81. p less than 0.001). Control studies under cycloplegia indicate that the estimates are not seriously affected by fluctuations in accommodative state. These findings indicate that ophthalmic practitioners can gain access to refractive data that aids the clinical management of the "anomalous myopias" and asthenopia associated with VDU work.

Tooth-brushing epilepsy: a report of a case with structural and functional imaging and electrophysiology demonstrating a right frontal focus.

Patients with reflex epilepsies may provide insights into cerebral pathophysiology. We report a patient with an unusual form of reflex epilepsy in whom seizures are induced by tooth brushing. Magnetic resonance imaging (MRI) demonstrated a right posterior frontal low-grade tumor predominantly involving the precentral gyrus. Video-telemetry demonstrated right-sided epileptiform activity during a typical induced complex partial seizure. An ictal single photon emission computed tomography (SPECT) scan showed an area of hyperfusion that corresponded to the MRI lesion on coregistration with a surface-matching technique. A subsequent coregistered interictal SPECT scan demonstrated hypoperfusion in the same region. Ours is the first report to demonstrate a structural focus in this unusual form of reflex epilepsy. Possible mechanisms to explain the induction of the seizures are discussed.