Impact of severe epilepsy on development: recovery potential after successful early epilepsy surgery.

PURPOSE: Epilepsy surgery in young children with focal lesions offers a unique opportunity to study the impact of severe seizures on cognitive development during a period of maximal brain plasticity, if immediate control can be obtained. We studied 11 children with early refractory epilepsy (median onset, 7.5 months) due to focal lesion who were rendered seizure-free after surgery performed before the age of 6 years. METHODS: The children were followed prospectively for a median of 5 years with serial neuropsychological assessments correlated with electroencephalography (EEG) and surgery-related variables. RESULTS: Short-term follow-up revealed rapid cognitive gains corresponding to cessation of intense and propagated epileptic activity [two with early catastrophic epilepsy; two with regression and continuous spike-waves during sleep (CSWS) or frontal seizures]; unchanged or slowed velocity of progress in six children (five with complex partial seizures and frontal or temporal cortical malformations). Longer-term follow-up showed stabilization of cognitive levels in the impaired range in most children and slow progress up to borderline level in two with initial gains. DISCUSSION: Cessation of epileptic activity after early surgery can be followed by substantial cognitive gains, but not in all children. In the short term, lack of catch-up may be explained by loss of retained function in the removed epileptogenic area; in the longer term, by decreased intellectual potential of genetic origin, irreversible epileptic damage to neural networks supporting cognitive functions, or reorganization plasticity after early focal lesions. Cognitive recovery has to be considered as a "bonus," which can be predicted in some specific circumstances.

Localization of electrodes in the subthalamic nucleus on magnetic resonance imaging.

OBJECT: The authors describe a new method of localizing electrodes on magnetic resonance (MR) images and focus on the positions of both the most efficient contact and the electrode related to the MR imaging target. METHODS: Thirty-one patients who had undergone bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) were included in this study. Target coordinates were calculated in the anterior commissure-posterior commissure referential. A study of the correlation between the artifact and the related contact allowed one to deduce the contact position from the identification of the distal artifact on MR imaging. The best stimulation point corresponded with the contact resulting in the best Unified Parkinson's Disease Rating Scale (UPDRS) motor score improvement. It was compared (Student t-test) with the dorsal margin of the STN (DM STN), which was determined electrophysiologically. The distance between the target and the electrode was calculated individually in each axis. The best stimulation point was located at anteroposterior -2.34 +/- 1.63 mm, lateral 12.04 +/- 1.62 mm, and vertical -2.57 +/- 1.68 mm. This point was not significantly different from the DM STN (p < 0.05). The postoperative UPDRS motor score was 28.07 +/- 12.16, as opposed to the preoperative score of 46.27 +/- 13.89. The distance between the expected and actual target in the x- and y-axes was 1.34 +/- 1.02 and 1.03 +/- 0.76 mm, respectively. In the z-axis, 39.7% of the distal contacts were located proximal to the target. CONCLUSIONS: This approach proposed for the localization of the electrodes on MR imaging shows that DBS is most effective in the dorsal and lateral part of the STN and indicates that the DBS electrode can be located more proximally than originally expected because of the caudal brain shift that may occur during the implantation procedure.

Radiosurgery for trigeminal neuralgia using a linear accelerator with BrainLab system: report on initial experience in Lausanne, Switzerland.

BACKGROUND/AIMS: Radiosurgery is an effective treatment for trigeminal neuralgia (TN) with minimal complications. Most experience is based on gamma knife radiosurgery (GKRS) and to a lesser extent on linear accelerators. METHODS: We report our initial experience in 17 patients with TN treated by an adapted linear accelerator using the BrainLab system. The trigeminal root entry zone immediately adjacent to the pons (target volume: 0.01-0.09 cm3, mean: 0.02 cm3) was targeted by use of a multileaf collimator to deliver 40-45 Gy to the 80% isodose (dose max 50-56 Gy). Median follow-up was 12 months (range: 1-60). RESULTS: All patients reported some initial improvement in level of pain after treatment (mean time: 1 month). Initial pain responses were as follows: 6 patients (35%) had complete pain relief and required no medication, 6 (35%) had occasional pain but were off medication, and 5 (30%) experienced partial relief of pain but still required medication, usually in lower doses. Five patients (29%) who experienced initial pain relief had recurrences ranging from 4-13 months after procedure. There were no major or minor complications of radiosurgery except one case of mild facial itching. CONCLUSION: Stereotactic radiosurgery using a linear accelerator appears to be effective and can be a favourable alternative to other procedures, including GKRS. The procedure is very safe and side effects are rare and minor. However, a randomised trial with a longer follow-up comparing radiosurgery to other surgical procedures is needed to assess the long term effectiveness of this treatment.

Long-duration response to levodopa in patients with advanced Parkinson disease treated with subthalamic deep brain stimulation.

BACKGROUND: Long-duration response (LDR) to levodopa is supposed to decrease with Parkinson disease (PD) progression, but direct observation of this response in advanced PD has never been performed. OBJECTIVE: To study the LDR to levodopa in patients with advanced PD treated with subthalamic deep brain stimulation (DBS). DESIGN AND SETTING: We studied 30 consecutive patients with PD who underwent subthalamic DBS. One group had no antiparkinsonian treatment since surgery (no-levodopa group), whereas medical treatment had to be reinitiated in the other group (levodopa group). MAIN OUTCOME MEASURE: Motor subscale score of the Unified Parkinson's Disease Rating Scale. RESULTS: Compared with preoperative assessment, evaluation 6 months postoperatively with DBS turned off for 3 hours found a worsening of the motor subscale score of the Unified Parkinson's Disease Rating Scale in the no-levodopa group. This worsening being absent in the levodopa group, it probably reflected the loss of the LDR to levodopa in the no-levodopa group. When DBS was turned on, postoperative motor subscale scores of the Unifid Parkinson's Disease Rating Scale in both groups were similar to preoperative scores while receiving medication, suggesting that subthalamic DBS compensated for the short-duration response and LDR to levodopa. CONCLUSIONS: Our results suggest that the LDR to levodopa remains significant even in advanced PD, and that subthalamic DBS compensates for the short-duration response and LDR to levodopa.

A cross validation study of deep brain stimulation targeting: from experts to atlas-based, segmentation-based and automatic registration algorithms.

Validation of image registration algorithms is a difficult task and open-ended problem, usually application-dependent. In this paper, we focus on deep brain stimulation (DBS) targeting for the treatment of movement disorders like Parkinson's disease and essential tremor. DBS involves implantation of an electrode deep inside the brain to electrically stimulate specific areas shutting down the disease's symptoms. The subthalamic nucleus (STN) has turned out to be the optimal target for this kind of surgery. Unfortunately, the STN is in general not clearly distinguishable in common medical imaging modalities. Usual techniques to infer its location are the use of anatomical atlases and visible surrounding landmarks. Surgeons have to adjust the electrode intraoperatively using electrophysiological recordings and macrostimulation tests. We constructed a ground truth derived from specific patients whose STNs are clearly visible on magnetic resonance (MR) T2-weighted images. A patient is chosen as atlas both for the right and left sides. Then, by registering each patient with the atlas using different methods, several estimations of the STN location are obtained. Two studies are driven using our proposed validation scheme. First, a comparison between different atlas-based and nonrigid registration algorithms with a evaluation of their performance and usability to locate the STN automatically. Second, a study of which visible surrounding structures influence the STN location. The two studies are cross validated between them and against expert's variability. Using this scheme, we evaluated the expert's ability against the estimation error provided by the tested algorithms and we demonstrated that automatic STN targeting is possible and as accurate as the expert-driven techniques currently used. We also show which structures have to be taken into account to accurately estimate the STN location.

Conjugate eye deviation due to traumatic striatal-subthalamic lesion.

We report the case of a 22-year-old man after severe cranial trauma, who was noted to have conjugate eye deviation (CED) to the left. A magnetic resonance imaging (MRI) scan demonstrated a lesion in the left (ipsilateral) striatal-subthalamic region. The involvement of supranuclear fibres from the left frontal eye field (FEF) traveling to the right parapontine reticular formation (PPRF) could explain this clinical finding. Alternatively, involvement of deep brain nuclei, such as the striatum and the subthalamic nucleus, could be responsible for this phenomenon. This neurological presentation is unusual after severe cranial trauma.

Prognostic factors for low-grade gliomas.

Low-grade gliomas are a heterogenous group of diseases characterized by relatively slow-growing primary brain tumors of astrocytic and/or oligodendroglial origin. Many patients present with easily controlled seizures and remain stable for years, whereas others progress rapidly to higher-grade tumors. Several studies have retrospectively investigated tumor-, patient-, and treatment-related prognostic factors in this patient population. Tumor histology, grade, location, contrast enhancement, and molecular markers have been identified as prognostic factors for survival. Likewise, patient age, performance status, and seizure history are patient-dependent prognostic factors. However, although patients who undergo surgical resection and receive adjuvant radiotherapy tend to have improved survival, treatment-dependent prognostic factors have yet to be definitively identified. Recursive partitioning and multivariant analyses have identified a class of patients with good prognosis. Younger patients with good performance status, non-contrast-enhancing tumors (<5 cm), and tumors of oligodendroglial or mixed-oligoastrocytic subtype have improved survival. The European Organisation for Research and Treatment of Cancer has recently developed a prognostic score based on identified prognostic factors to assist in the management of low-grade gliomas. For patients with a favorable (low-risk) score, treatment with radiotherapy or chemotherapy treatment should be withheld until tumor progression. For patients with a high-risk score, treatment at diagnosis may be indicated. However, other than surgery, the optimal types and sequence of therapies are not yet established. Improvements in defining prognostic factors will assist in low-grade glioma management.

Electrophysiological localization of the subthalamic nucleus in parkinsonian patients.

Deep brain stimulation of the subthalamic nucleus (STN) is becoming the procedure of choice to reduce symptoms of Parkinson's disease such as rigidity, akinesia and tremor. We present here a series of electrophysiological recordings performed in 34 patients along a standardized electrode trajectory. Neuronal activity along the trajectory consists of a first heterogeneous population of thalamic cells with a mean frequency of 24.8+/-1.4 Hz followed by a silent zone and a second population of STN neurones with a significantly higher spiking frequency (P<0.001) of 42.3+/-1.8 Hz. This study confirms previous findings and suggests that rapid measurement of neuronal spiking frequency and burst index is sufficient to determine precisely the vertical position of the STN.

Recording of ventral posterior lateral thalamus neuron response to contact heat evoked potential in patient with neurogenic pain.

Microrecording of single unit response to contact heat-evoked potential (CHEP) were performed in right ventral posterior lateral (VPL) thalamus during deep brain stimulation (DBS) surgery in a patient with chronic neurogenic pain. In our patient, neurons (n = 10) recorded in the ventral thalamus fired at a higher rate of 40 Hz compared to neurons recorded in Parkinsonian patients (24 Hz). Contact heat was applied by a fast heating and cooling probe of 5 cm2 area on the dermatome C6 territory of the left hand. One out of four thalamic cells located in the VPL responded repetitively 325 ms after the peak temperature was reached with a burst of action potential, suggesting A-delta fibre activation. This observation supports the use of CHEP for mapping nociceptive neurons location during DBS surgery for intractable pain.

Relationship between severity of lumbar disc disease and disability scores in sciatica patients.

OBJECTIVE: To study the association between the clinical examination and the radiological assessment of lumbar disc disease in patients with sciatica. METHODS: The study included 394 consecutive sciatica patients. The patients' disabilities were evaluated by a visual analog pain scale, the Prolo functional-economic rating scale, the modified Roland-Morris disability questionnaire, and the health-related quality of life short form (SF-36) questionnaire. Radiological imaging findings were independently classified according to the Modic criteria into five groups of increasing severity of disc disease. Stepwise multivariate logistic regression was used to determine which scores were significant independent predictors of a severe disc disease (extrusion or sequestration). RESULTS: Of these patients, 9.6% had no disc disease, 3.3% had a bulging, 11.4% had a protrusion, 68.5% had an extrusion, and 7.1% had a disc sequestration. Statistically significant positive linear associations with the severity of disc disease were found for the leg pain scale, the Roland-Morris and Prolo disability scales, and the SF-36 scores related to physical functioning, physical role, and bodily pain (all P < 0.005). A poor (<5) Prolo score (odds ratio, 2.91; 95% confidence interval, 1.74-4.87), a higher leg pain score (odds ratio, 1.16 per centimeter increase; 95% confidence interval, 1.07-1.27), and a lower low back pain score (odds ratio, 0.90 per centimeter decrease; 95% confidence interval, 0.82-0.98) were retained in the multivariate logistic model as independent predictors of severe disc disease. CONCLUSION: The positive correlation between disability status and imaging findings validates both assessment methods. Routine use of disability scores brings a useful contribution to the assessment of sciatica patients.

Proton magnetic resonance spectroscopic imaging can predict length of survival in patients with supratentorial gliomas.

OBJECTIVE: We compared the ability of proton magnetic resonance spectroscopic imaging ((1)H-MRSI) measures with that of standard clinicopathological measures to predict length of survival in patients with supratentorial gliomas. METHODS: We developed two sets of leave-one-out logistic regression models based on either 1) intratumoral (1)H-MRSI features, including maximum values of a) choline and b) lactate-lipid, c) number of (1)H-MRSI voxels with low N-acetyl group values, and d) number of (1)H-MRSI voxels with high lactate-lipid values, all (a-d) of which were normalized to creatine in normal-appearing brain, or 2) standard clinicopathological features, including a) tumor histopathological grade, b) patient age, c) performance of surgical debulking, and d) tumor diagnosis (i.e., oligodendroglioma, astrocytoma). We assessed the accuracy of these two models in predicting patient survival for 6, 12, 24, and 48 months by performing receiver operating characteristic curve analysis. Cox proportional hazards analysis was performed to assess the extent to which patient survival could be explained by the above predictors. We then performed a series of leave-one-out linear multiple regression analyses to determine how well patient survival could be predicted in a continuous fashion. RESULTS: The results of using the models based on (1)H-MRSI and clinicopathological features were equally good, accounting for 81 and 64% of the variability (r(2)) in patients' actual survival durations. All features except number of (1)H-MRSI voxels with lactate-lipid/creatine values of at least 1 were significant predictors of survival in the (1)H-MRSI model. Two features (tumor grade and debulking) were found to be significant predictors in the clinicopathological model. Survival as a continuous variable was predicted accurately on the basis of the (1)H-MRSI data (r = 0.77, P < 0.001; median prediction error, 1.7 mo). CONCLUSION: Our results suggest that appropriate analysis of (1)H-MRSI data can predict survival in patients with supratentorial gliomas at least as accurately as data derived from more invasive clinicopathological features.

Atlas-based segmentation of pathological MR brain images using a model of lesion growth.

We propose a method for brain atlas deformation in the presence of large space-occupying tumors, based on an a priori model of lesion growth that assumes radial expansion of the lesion from its starting point. Our approach involves three steps. First, an affine registration brings the atlas and the patient into global correspondence. Then, the seeding of a synthetic tumor into the brain atlas provides a template for the lesion. The last step is the deformation of the seeded atlas, combining a method derived from optical flow principles and a model of lesion growth. Results show that a good registration is performed and that the method can be applied to automatic segmentation of structures and substructures in brains with gross deformation, with important medical applications in neurosurgery, radiosurgery, and radiotherapy.

Effect of deep brain stimulation of GPI on neuronal activity of the thalamic nucleus ventralis oralis in a dystonic patient.

OBJECTIVE: To record the possible effect of acute deep brain stimulation (DBS) of the globus pallidus internus (GPI) on the neuronal activity of the ventralis oralis anterior (VOA) nucleus of the thalamus. METHODS: Under general propofol anaesthesia, extracelullar single unit recordings were performed in VOA of a post-anoxic dystonic patient previously implanted with GPI located electrodes for chronic DBS. RESULTS: Neurons recorded in the VOA could be classified in two cell subpopulations: a high firing rate (16.5 Hz) and low burst index (BI; 15.6) type and a low firing rate (5.5 Hz) and high BI (35.6) type. GPI electrical stimulation reduced the frequency and increased the BI of the high firing rate cells while leaving the other cell type unchanged. CONCLUSION: These results demonstrate that pallidal DBS is able to inhibit a subpopulation of motor thalamic cells and question the pathophysiological model of dystonia based on a low firing rate of GPI cells.

Quality index for the quantification of the information recorded along standard microelectrode tracks to the subthalamic nucleus in parkinsonian patients.

OBJECTIVE: To quantify the usefulness of the neuronal activity recorded on a standard microelectrode track to the subthalamic nucleus (STN) for the determination of the transition between the thalamus and the STN. METHODS: The study is based on analysis of 689 extracelullar single units recorded on 70 tracks passing through the thalamus and the STN. Using four neuron parameters that were correlated with electrode depth, a quality index (QI) for each track was computed and compared with the subjective assessment by the electrophysiologist of the track quality. RESULTS: Subjectively, the transition between the thalamus and the STN was detected in 49 tracks (usual track) and not detected on 21 tracks (unusual tracks). Objectively, spike frequency, cell burst index (BI), signal relative root mean square (RMS) and spike relative amplitude were correlated with electrode depth and used to compute track QI. The average QI index of usual and unusual tracks was 0.25 +/- 0.9 and 0.85 +/- 0.15 (mean +/- confidence interval at P < 0.001), respectively. In 20 patients, QI correlates with post-operative measurement of electrode length in the STN. CONCLUSION: These results demonstrate that simple statistical analysis taking into account the variation of single-unit characteristics with electrode depth can discriminate between useful and useless tracks for the determination of the STN localisation.

Intractable reflex audiogenic epilepsy successfully treated by peri-insular hemispherotomy.

We report a case of an infantile hemiplegia seizure syndrome (IHSS) that presented with intractable reflex audiogenic startle epilepsy which in itself is an uncommon form of seizure disorder. Peri-insular hemispherotomy provided complete seizure control. Also of particular interest was that this syndrome resulted from an iatrogenic brain injury sustained during the course of a caesarian section. We review the different mechanisms of birth injury reported in the literature and, discuss the physiopathogenesis of the hemispheric damage in this patient. We also review the literature on "reflex epilepsy" as it applies to this case. Intractable reflex audiogenic (startle) epilepsy in IHSS submitted to hemispherotomy has not previously been reported.

Disconnective hemispherectomy for hemispheric dysplasia.

Twelve patients suffering from intractable epilepsy and presenting with radiological evidence of diffuse hemispheric involvement of a dysplastic process, were treated by disconnective hemispherectomy, either functional hemispherectomy or peri-insular hemispherotomy. The median age at surgery was 4.5 years old and the interval between seizure onset and surgery, 3 years. All patients underwent a presurgical evaluation that led to the suggestion of disconnective hemispherectomy. Over 70% of patients have remained in Engel's seizure outcome class I since surgery and another 18% have had a satisfactory seizure outcome. There was one unexplained death and one case of early hydrocephalus. Hemispherectomy offers the possibility to improve seizure control in the majority of patients undergoing surgery for extensive dysplastic pathology of the hemisphere. Disconnective techniques reduce the rate of complications in this specific pathology.

Adjuvant or radical fractionated stereotactic radiotherapy for patients with pituitary functional and nonfunctional macroadenoma.

PURPOSE: To evaluate the efficacy and toxicity of stereotactic fractionated radiotherapy (SFRT) for patients with pituitary macroadenoma (PMA). METHODS AND MATERIALS: Between March 2000 and March 2009, 27 patients (male to female ratio, 1.25) with PMA underwent SFRT (median dose, 50.4 Gy). Mean age of the patients was 56.5 years (range, 20.3 - 77.4). In all but one patient, SFRT was administered for salvage treatment after surgical resection (transphenoidal resection in 23, transphenoidal resection followed by craniotomy in 2 and multiple transphenoidal resections in another patient). In 10 (37%) patients, the PMAs were functional (3 ACTH-secreting, 3 prolactinomas, 2 growth hormone-secreting and 2 multiple hormone-secretion). Three (11.1%) and 9 (33.3%) patients had PMA abutting and compressing the optic chiasm, respectively. Mean tumor volume was 2.9 ± 4.6 cm3. Eighteen (66.7%) patients had hypopituitarism prior to SFRT. The mean follow-up period after SFRT was 72.4 ± 37.2 months. RESULTS: Tumor size decreased for 6 (22.2%) patients and remained unchanged for 19 (70.4%) other patients. Two (7.4%) patients had tumor growth inside the prescribed treatment volume. The estimated 5-year tumor growth control was 95.5% after SFRT. Biochemical remission occurred in 3 (30%) patients with functional PMA. Two patients with normal anterior pituitary function before SFRT developed new deficits 25 and 65 months after treatment. The 5-year survival without new anterior pituitary deficit was thus 95.8%. Five patients with visual field defect had improved visual function and 1 patient with no visual defect prior to SFRT, but an optic chiasm abutting tumor, had a decline in visual function. The estimated 5-year vision and pituitary function preservation rates were 93.2% and 95.8%, respectively. CONCLUSIONS: SFRT is a safe and effective treatment for patients with PMA, although longer follow-up is needed to evaluate long-term outcomes. In this study, approximately 1 patient with visual field defect out of two had an improved visual function.

Chronic deep brain stimulation in mesial temporal lobe epilepsy.

The objective of this study was to evaluate the efficiency and the effects of changes in parameters of chronic amygdala-hippocampal deep brain stimulation (AH-DBS) in mesial temporal lobe epilepsy (TLE). Eight pharmacoresistant patients, not candidates for ablative surgery, received chronic AH-DBS (130 Hz, follow-up 12-24 months): two patients with hippocampal sclerosis (HS) and six patients with non-lesional mesial TLE (NLES). The effects of stepwise increases in intensity (0-Off to 2 V) and stimulation configuration (quadripolar and bipolar), on seizure frequency and neuropsychological performance were studied. The two HS patients obtained a significant decrease (65-75%) in seizure frequency with high voltage bipolar DBS (≥1 V) or with quadripolar stimulation. Two out of six NLES patients became seizure-free, one of them without stimulation, suggesting a microlesional effect. Two NLES patients experienced reductions of seizure frequency (65-70%), whereas the remaining two showed no significant seizure reduction. Neuropsychological evaluations showed reversible memory impairments in two patients under strong stimulation only. AH-DBS showed long-term efficiency in most of the TLE patients. It is a valuable treatment option for patients who suffer from drug resistant epilepsy and who are not candidates for resective surgery. The effects of changes in the stimulation parameters suggest that a large zone of stimulation would be required in HS patients, while a limited zone of stimulation or even a microlesional effect could be sufficient in NLES patients, for whom the importance of the proximity of the electrode to the epileptogenic zone remains to be studied. Further studies are required to ascertain these latter observations.

Hippocampal atrophy predicts conversion to dementia after STN-DBS in Parkinson's disease.

BACKGROUND: Hippocampal atrophy (HA) is a known predictor of dementia in Alzheimer's disease. HA has been found in advanced Parkinson's disease (PD), but no predicting value has been demonstrated yet. The identification of such a predictor in candidates for subthalamic deep brain stimulation (STN-DBS) would be of value. Our objective was to compare preoperative hippocampal volumes (HV) between PD patients who subsequently converted to dementia (PDD) after STN-DBS and those who did not (PDnD). METHODS: From a cohort of 70 consecutive STN-DBS treated PD patients, 14 converted to dementia over 25.6+/-20.2 months (PDD). They were compared to 14 matched controls (PDnD) who did not convert to dementia after 43.9+/-11.7 months. On the preoperative 3D MPRAGE MRI images, HV and total brain volumes (TBV) were measured by a blinded investigator using manual and automatic segmentation respectively. RESULTS: PDD had smaller preoperative HV than PDnD (1.95+/-0.29 ml; 2.28+/-0.33 ml; p<0.01). This difference reinforced after normalization for TBV (3.28+/-0.48, 3.93+/-0.60; p<0.01). Every 0.1 ml decrease of HV increased the likelihood to develop dementia by 24.6%. A large overlap was found between PD and PDnD HVs, precluding the identification of a cut-off score. CONCLUSIONS: As in Alzheimer's disease, HA may be a predictor of the conversion to dementia in PD. This preoperative predictor suggests that the development of dementia after STN-DBS is related to the disease progression, rather then the procedure. Further studies are needed to define a cut-off score for HA, in order to affine its predictive value for an individual patient.