Impact of Mesial Temporal Lobe Resection on Brain Structure in Medically Refractory Epilepsy.

OBJECTIVE: Surgical resection can decrease seizure frequency in medically intractable temporal lobe epilepsy. However, the functional and structural consequences of this intervention on brain circuitry are poorly understood. We investigated structural changes that occur in brain circuits after mesial temporal lobe resection for refractory epilepsy. Specifically, we used neuroimaging techniques to evaluate changes in 1) contralesional hippocampal and bilateral mammillary body volume and 2) brain-wide cortical thickness. METHODS: Serial T1-weighted brain magnetic resonance images were acquired before and after surgery (1.6 ± 0.5 year interval) in 21 patients with temporal lobe epilepsy (9 women, 12 men; mean age, 39.4 ± 11.5 years) who had undergone unilateral temporal lobe resection (14 anterior temporal lobectomy; 7 selective amygdalohippocampectomy). Blinded manual segmentation of the unresected hippocampal formation and bilateral mammillary bodies was performed using the Pruessner and Copenhaver protocols, respectively. Brain-wide cortical thickness estimates were computed using the CIVET pipeline. RESULTS: Surgical resection was associated with a 5% reduction in contralesional hippocampal volume (P < 0.01) and a 9.5% reduction in mammillary body volume (P = 0.03). In addition, significant changes in cortical thickness were observed in contralesional anterior and middle cingulate gyrus and insula (Pfalse discovery rate < 0.01) as well as in other temporal, frontal, and occipital regions (Pfalse discovery rate < 0.05). Postoperative verbal memory function was significantly associated with cortical thickness change in contralesional inferior temporal gyrus (R2 = 0.39; P = 0.03). CONCLUSIONS: These results indicate that mesial temporal lobe resection is associated with both volume loss in spared Papez circuitry and changes in cortical thickness across the brain.

Anterior thalamic nucleus deep brain stimulation for refractory epilepsy: Preliminary results in our first 5 patients.

OBJECTIVES: Deep brain stimulation (DBS) of the anterior thalamic nucleus (ATN) has been recognized to be an efficient treatment of refractory epilepsy (RE). However, ATN targeting is difficult and up to 8% of lead misplacement is reported. Our objective is to report our surgical procedure based on MRI targeting and our clinical results. PATIENTS AND METHODS: Our first five consecutive patients (4M, 1F, mean age: 42.8 years) treated by DBS of ATN between March and October 2016 were included. The mean duration of their epilepsy was 29 years. Four patients had already vagal nerve stimulation and 2 mammillary body stimulation. Stereotactic coordinates were calculated using distal segment of mammillothalamic tract as landmark. All procedures were performed under general anesthesia with intraoperative control of lead position using a robotic 3D fluoroscopy and image fusion with the preoperative MRI. RESULTS: No complications or lead misplacement was observed. The mean 3D distance between the planned target and location of the lead was 1.8 mm. Each patient was followed up at least one year (15+3months). The stimulation parameters were: 140Hz, 90m/s and 5 Volts with one minute ON/five minutes OFF cycle. The mean reduction of seizure frequency reached -52.5% (+32.2) at 6-months but decreased to -24.5% (+65.7) at the last follow-up due to some adverse events not related to stimulation. CONCLUSION: No complication, no lead misplacement and the improvement in our first patients, previously not help by multiple medications or surgeries, are encouraging.

Korsakoff syndrome from retrochiasmatic suprasellar lesions: rapid reversal after relief of cerebral compression in 4 cases.

Korsakoff syndrome is a chronic memory disorder caused by a severe deficiency of thiamine that is most commonly observed in alcoholics. However, some have proposed that focal structural lesions disrupting memory circuits-in particular, the mammillary bodies, the mammillothalamic tract, and the anterior thalamus-can give rise to this amnestic syndrome. Here, the authors present 4 patients with reversible Korsakoff syndromes caused by suprasellar retrochiasmatic lesions compressing the mammillary bodies and adjacent caudal hypothalamic structures. Three of the patients were found to have large pituitary macroadenomas in their workup for memory deficiency and cognitive decline with minimal visual symptoms. These tumors extended superiorly into the suprasellar region in a retrochiasmatic position and caused significant mass effect in the bilateral mammillary bodies in the base of the brain. These 3 patients had complete and rapid resolution of amnestic problems shortly after initiation of treatment, consisting of resection in 1 case of nonfunctioning pituitary adenoma or cabergoline therapy in 2 cases of prolactinoma. The fourth patient presented with bizarre and hostile behavior along with significant memory deficits and was found to have a large cystic craniopharyngioma filling the third ventricle and compressing the midline diencephalic structures. This patient underwent cyst fenestration and tumor debulking, with a rapid improvement in his mental status. The rapid and dramatic memory improvement observed in all of these cases is probably due to a reduction in the pressure imposed by the lesions on structures contiguous to the third ventricle, rather than a direct destructive effect of the tumor, and highlights the essential role of the caudal diencephalic structures-mainly the mammillary bodies-in memory function. In summary, large pituitary lesions with suprasellar retrochiasmatic extension and third ventricular craniopharyngiomas can cause severe Korsakoff-like amnestic syndromes, probably because of bilateral pressure on or damage to mammillary bodies, anterior thalamic nuclei, or their major connections. Neuropsychiatric symptoms may rapidly and completely reverse shortly after initiation of therapy via surgical decompression of tumors or pharmacological treatment of prolactinomas. Early identification of these lesions with timely treatment can lead to a favorable prognosis for this severe neuropsychiatric disorder.

Neurosurgical relevance of the dissection of the diencephalic white matter tracts using the Klingler technique.

OBJECTIVE: The Klingler fiber dissection technique is a relevant and reliable method for neurosurgery to identify with accuracy the fine structure of the brain anatomy highlighting white matter tracts. In order to demonstrate the significance of the application of this technique, we aimed to observe the course and relations of the mammillothalamic and habenulo-interpeduncular tracts as there are very few papers showing these important diencephalic tracts. MATERIAL AND METHODS: Twelve formalin-fixed brains were dissected using the Klingler technique in order to expose the medial diencephalic surface. Diencephalic white matter tracts, particularly the mammillothalamic and habenulo-interpeduncular tracts, were dissected using wooden spatulas and metallic dissectors with different sizes and tips. Several measurements were performed in both dissected hemispheres relative to the mammillothalamic and habenulo-interpeduncular tracts. RESULTS: The course and length of these two tracts were visualized and the relations with other fiber systems and with the neighboring gray matter structures quantified and registered. The mammillothalamic tract approximately marks the anteroposterior coordinate of the anterior pole of the subthalamic nucleus in the anterior commissure - posterior commissure plane. CONCLUSION: The present study helps to understand the three-dimensional architecture of the white matter systems of tracts when the Klingler technique is used. The numerical data obtained may be helpful to neurosurgeons while approaching brain paraventricular and ventricular lesions and deep brain stimulation. Finally, the anatomical knowledge can lower surgical complications and improve patient care particularly in the field of neurosurgery.

Behavioral effects of deep brain stimulation of different areas of the Papez circuit on memory- and anxiety-related functions.

Deep brain stimulation (DBS) has gained interest as a potential therapy for advanced treatment-resistant dementia. However, possible targets for DBS and the optimal stimulation parameters are not yet clear. Here, we compared the effects of DBS of the CA1 sub-region of the hippocampus, mammillothalamic tract, anterior thalamic nucleus, and entorhinal cortex in an experimental rat model of dementia. Rats with scopolamine-induced amnesia were assessed in the object location task with different DBS parameters. Moreover, anxiety-related side effects were evaluated in the elevated zero maze and open field. After sacrifice, we applied c-Fos immunohistochemistry to assess which memory-related regions were affected by DBS. When comparing all structures, DBS of the entorhinal cortex and CA1 sub-region was able to restore memory loss when a specific set of stimulation parameters was used. No anxiety-related side effects were found following DBS. The beneficial behavioral performance of CA1 DBS rats was accompanied with an activation of cells in the anterior cingulate gyrus. Therefore, we conclude that acute CA1 DBS restores memory loss possibly through improved attentional and cognitive processes in the limbic cortex.

Displacement of mammillary bodies by craniopharyngiomas involving the third ventricle: surgical-MRI correlation and use in topographical diagnosis.

OBJECT: Accurate diagnosis of the topographical relationships of craniopharyngiomas (CPs) involving the third ventricle and/or hypothalamus remains a challenging issue that critically influences the prediction of risks associated with their radical surgical removal. This study evaluates the diagnostic accuracy of MRI to define the precise topographical relationships between intraventricular CPs, the third ventricle, and the hypothalamus. METHODS: An extensive retrospective review of well-described CPs reported in the MRI era between 1990 and 2009 yielded 875 lesions largely or wholly involving the third ventricle. Craniopharyngiomas with midsagittal and coronal preoperative and postoperative MRI studies, in addition to detailed descriptions of clinical and surgical findings, were selected from this database (n = 130). The position of the CP and the morphological distortions caused by the tumor on the sella turcica, suprasellar cistern, optic chiasm, pituitary stalk, and third ventricle floor, including the infundibulum, tuber cinereum, and mammillary bodies (MBs), were analyzed on both preoperative and postoperative MRI studies. These changes were correlated with the definitive CP topography and type of third ventricle involvement by the lesion, as confirmed surgically. RESULTS: The mammillary body angle (MBA) is the angle formed by the intersection of a plane tangential to the base of the MBs and a plane parallel to the floor of the fourth ventricle in midsagittal MRI studies. Measurement of the MBA represented a reliable neuroradiological sign that could be used to discriminate the type of intraventricular involvement by the CP in 83% of cases in this series (n = 109). An acute MBA (< 60°) was indicative of a primary tuberal-intraventricular topography, whereas an obtuse MBA (> 90°) denoted a primary suprasellar CP position, causing either an invagination of the third ventricle (pseudointraventricular lesion) or its invasion (secondarily intraventricular lesion; p < 0.01). A multivariate model including a combination of 5 variables (the MBA, position of the hypothalamus, presence of hydrocephalus, psychiatric symptoms, and patient age) allowed an accurate definition of the CP topography preoperatively in 74%-90% of lesions, depending on the specific type of relationship between the tumor and third ventricle. CONCLUSIONS: The type of mammillary body displacement caused by CPs represents a valuable clue for ascertaining the topographical relationships between these lesions and the third ventricle on preoperative MRI studies. The MBA provides a useful sign to preoperatively differentiate a primary intraventricular CP originating at the infundibulotuberal area from a primary suprasellar CP, which either invaginated or secondarily invaded the third ventricle.

Factores relacionados con el pronóstico de la ventriculostomía premamilar endoscópica en pacientes pediátricos / No disponible

La ventriculostomía premamilar endoscópica (VPME) en edad pediátrica tiene tasas de éxito publicadas variables, que hacen controvertida su recomendación. Factores como la falta de consenso en la definición de éxito de la VPME, la etiología de la hidrocefalia o la edad del paciente podrían influir en el resultado del procedimiento. El objetivo del trabajo consiste en el análisis de una serie propia y el estudio de los factores relacionados con el éxito de la VPME. Estudio retrospectivo de 45 pacientes tratados entre 2003 y 2009 mediante VPME en nuestro hospital infantil. Se definió éxito de VPME como mejoría o estabilidad clínica acompañada de al menos un parámetro radiológico indicativo de buen pronóstico y se analizó la relación de la edad, la etiología de la hidrocefalia, la existencia o no de shunt previo y el tipo de procedimiento endoscópico con el pronóstico de la VPME. Un 29% de los pacientes eran menores de un año. Las causas más frecuentes de hidrocefalia fueron: tumores, estenosis de acueducto y mielomeningocele. El éxito de la VPME se obtuvo en un 69% de casos, con un seguimiento medio de 26 meses y una supervivencia media de la VPME de 14 meses. Se obtuvieron diferencias significativas en el éxito de la VPME según la edad del paciente fuera superior o inferior a 6 meses. La tasa de éxito de la VPME en nuestro medio la hacen recomendable para el tratamiento de la hidrocefalia en edad pediátrica. La VPME es más efectiva en pacientes de edad mayor o igual a 6 meses (AU)

Suprapineal recess: an alternate site for third ventriculostomy? Case report.

This 30-year-old woman presented with clinical symptoms and signs of intracranial hypertension and Parinaud syndrome secondary to ventriculoperitoneal shunt dysfunction. Magnetic resonance (MR) imaging revealed gross triventricular hydrocephalus with a large suprapineal recess due to aqueductal stenosis. Using an endoscopic approach, a ventriculostomy was performed within the floor of the dilated suprapineal recess. Following this procedure the patient experienced alleviation of all her neurological symptoms and signs. Postoperative MR imaging and cerebrospinal fluid flow studies demonstrated a functioning ventriculostomy. The anatomy of the suprapineal recess and its suitability for endoscopic ventriculostomy are discussed.

MR imaging and spectroscopic study of epileptogenic hypothalamic hamartomas: analysis of 72 cases.

BACKGROUND AND PURPOSE: Reports of MR imaging in hypothalamic hamartomas associated with epilepsy are few, and the number of patients studied is small. We aimed to detail the relationship of hypothalamic hamartomas to surrounding structures, to determine the frequency and nature of associated abnormalities, and to gain insight into mechanisms of epileptogenesis. METHODS: We systematically examined MR imaging studies of 72 patients with hypothalamic hamartoma and refractory epilepsy (patient age, 22 months to 31 years). A dedicated imaging protocol was used in 38 cases. Proton MR spectroscopy of the hypothalamic hamartoma was performed for 19 patients and compared with the metabolite profile of the thalamus in 10 normal children and the frontal lobe in 10 normal adults. RESULTS: Compared with normal gray matter, hypothalamic hamartomas were hyperintense on T2-weighted images (93%), hypointense on T1-weighted images (74%), and had reduced N-acetylaspartate and increased myoinositol content shown by MR spectroscopy. Hypothalamic hamartomas always involved the mammillary region of the hypothalamus, with attachment to one or both mammillary bodies. Intrahypothalamic extension (noted in 97%) tended to displace the postcommissural fornix and hypothalamic gray matter anterolaterally, such that the hypothalamic hamartomas nestled between the fornix, the mammillary body, and the mammillothalamic tract. Larger hamartoma size was associated with central precocious puberty. Associated findings of questionable epileptic significance included anterior temporal white matter signal intensity abnormalities (16%) and arachnoid cysts (6%). Malformations of cortical development were observed in only two patients, and hippocampal sclerosis was not observed. CONCLUSIONS: Hypothalamic hamartomas can be readily distinguished from normal hypothalamic gray and adjacent myelinated fiber tracts, best appreciated on thin T2-weighted images. MR imaging and spectroscopy suggest reduced neuronal density and relative gliosis compared with normal gray matter. Associated epileptogenic lesions are rare, supporting the view that the hypothalamic hamartoma alone is responsible for the typical clinical features of the syndrome. The intimate relationship to the mammillary body, fornix, and mammillothalamic tract suggests a role for these structures in epileptogenesis associated with hypothalamic hamartomas.

Hypothalamic hamartoma with refractory epilepsy: surgical procedures and results in 18 patients.

AIM: To study the surgical procedures and results on seizures, in 18 patients with refractory epilepsy due to hypothalamic hamartoma. PATIENTS AND METHODS: Eighteen patients aged from 9 months to 32 years underwent surgery between 1997 and 2002. The mean age at seizure onset was 15.5 months. Seventeen patients had gelastic seizures, 14 had partial seizures, two had infantile spasms, 10 had tonic or atonic seizures and three had generalized seizures. The mean seizure frequency was 21 per day. Four patients had borderline intellectual disability and the others were mentally retarded. Five patients had precocious puberty, one had acromegaly and four suffered from obesity. Brain MRI, performed at least twice in each patient showed the hamartoma as a stable, homogeneous interpeduncular mass implanted either on the mammillary tubercle or on the wall of the third ventricle, with variable extension to the bottom. Ictal SPECT, performed in four patients, showed hyperperfusion within the hamartoma in two. SURGICAL PROCEDURE: Twenty-six operations were performed in 18 patients. The first patient underwent a total removal of the hamartoma, whereas the following patients underwent a disconnection, either through open surgery (14 patients) or endoscopy (10 patients). RESULTS: Regarding the seizure outcome with a mean follow up of three years four months (one year to 4.5 years), nine patients are seizure-free, one patient has only brief gelastic seizures and eight are dramatically improved. Surgery was uncomplicated in all but two patients: one had transitory hemiplegia and paresis of the third cranial nerve, the other presented with hemiplegia due to ischemia of the middle cerebral artery territory. The quality of life, behavior and school performance were greatly improved in most of the patients. CONCLUSION: Our series illustrates the feasibility and relative safety of disconnecting surgery of hypothalamic hamartomas, with seizure relief in 50% and a dramatic improvement in the others. Endoscopic disconnection seems to be a very safe way to treat the intra-ventricular part of hamartomas.

Are some memory deficits unique to lesions of the mammillary bodies?

The role of the mammillary bodies in human memory is still in debate. A recent model of human amnesia proposes similar functions for the mammillary bodies and the hippocampus. But the main evidence for this model comes from animal studies using the delayed non-matching to sample paradigm. We describe a patient who developed a severe memory impairment after surgical removal of a germinoma. Postsurgical high resolution MRI revealed bilaterally shrunken mammillary bodies and an infarct of the left mammillary body. There were no other relevant lesions. Neuropsychological testing showed mildly impaired frontal lobe functions (executive functions, working memory and word fluency), almost intact learning and recognition, but severely impaired free and delayed recall. Experimental investigations revealed a reduced but preserved release of proactive interference and a pronounced impairment of recency and source judgments. We conclude that the mammillary bodies do play a prominent role in human memory, although the role differs slightly from that of the hippocampus.

Stereotactic radiofrequency ablation for the treatment of gelastic seizures associated with hypothalamic hamartoma. Case report.

The author presents the case of a patient with gelastic seizures associated with a hypothalamic hamartoma, in whom partial resection of the hamartoma followed by temporal lobectomy and orbitofrontal corticectomy failed to reduce the seizures. Subsequent stereotactic radiofrequency ablation of the hamartoma resulted in progressive improvement in the seizure disorder during a 28-month follow-up period. There is support in the literature for the concept that gelastic seizures originate directly from the hamartoma; however, direct surgical approaches to these lesions pose significant risks. It is proposed that the technique of radiofrequency ablation provides a minimally invasive, low-risk approach for the treatment of hypothalamic hamartomas.

Preoptic area grafts implanted in mammillary bodies of hypogonadal mice: patterns of GnRH neuronal projections.

Gonadotropin-releasing hormone (GnRH) axons project to the median eminence, where the peptide is released to stimulate pituitary gonadotrophs. Hypogonadal mice (hpg) do not synthesize GnRH due to a deletion in the gene. When neonatal preoptic area (POA) tissue from normal mice containing GnRH neurons is transplanted into the third ventricle of hpg mice, GnRH axons exit the graft and specifically project to the median eminence, where the release of GnRH in the portal circulation induces the stimulation of the pituitary-gonadal axis. To test the hypothesis that the median eminence region is critical to targeting, we placed POA grafts in the region of the mammillary bodies, which never contains GnRH cell bodies, but is nevertheless close to the median eminence. Control mice received bilateral grafts into the anterior hypothalamus. GnRH axons innervated the median eminence in animals with grafts in the mammillary bodies and posterior hypothalamus. Mice with such grafts for 4-5 months had gonadal development, while those with grafts for shorter periods did not. Anterior hypothalamic grafts merged into the third ventricle and, consistent with previous studies, this resulted in GnRH innervation of the median eminence and gonadal development. However, when grafts were located within dorsal regions such as the thalamus, no median eminence innervation was seen. In these cases, GnRH axons borrowed other bundles of fibers to travel within the host brain. The pattern of innervation from grafts within ventro-caudal regions of the hypothalamus vs. that from dorsal regions supported the hypothesis that the median eminence releases diffusible substances directing GnRH outgrowth.

MRI of the fornix and mamillary body in temporal lobe epilepsy.

We performed MRI on 27 patients with clinically proven temporal lobe epilepsy (TLE), all with prior EEG lateralisation, and 10 volunteers, studied to evaluate disparity in size arising from biological variation (group 1). Three-dimensional spoiled GRASS (3DSPGR) sequences provided 2-mm contiguous sections of the limbic system, enabling assessment of the hippocampus (HC), fornix (FN) and mamillary body (MB). Measurements of FN and MB width were made from a workstation. Any percentage difference in size was computed. In 19 cases there was unilateral abnormality in the HC (group 2); in 18 and 19 cases respectively there was a smaller FN and MB on the same side as the abnormal HC. This percentage difference in size was significantly greater than that in group 1 in the FN and MB in 17 and 17 cases respectively. Comparison of percentage difference computations for FN and MB between groups 1 and 2 showed high statistical significance (P < 0.0002). In 5 patients with clinical TLE the HC was normal on MRI (group 3). Unequal FN and MB sizes were found in 4, significant in 2. Comparison of percentage difference computations for FN and MB showed statistical significance (P < 0.0005 and P < 0.0003 respectively). There was no case of discordance between the sides of hippocampal abnormality and the smaller FN or MB or between the sides of smaller FN and MB. The strong concordance between the changes in the HC and those in the FN and MB suggests that this combination will play an important role in the assessment of TLE and limbic system abnormality.

Hypothalamic hamartomas: with special reference to gelastic epilepsy and surgery.

This study presents six patients with hypothalamic hamartomas diagnosed on the basis of magnetic resonance imaging. Histological confirmation was performed in three patients who underwent surgery. Immunohistological assays were used to determine the neurosecretory pattern. Four patients presented with epilepsy, including gelastic seizures. Other symptoms included behavioral abnormalities in four patients and precocious puberty and visual impairment in two patients. One patient presented associated developmental defects. Good results without morbidity were achieved with surgical resectioning in two patients with large hamartomas associated with behavioral abnormalities and gelastic epilepsy that was unresponsive to conventional medical treatment and in one patient with visual impairment. We propose a classification of the hypothalamic hamartomas based on topographical and clinical data obtained from 36 selected cases in the literature and six of our own cases. This classification should help to classify the various treatment methods and the surgical risks into four subgroups (Types la, lb, lla, and llb). We conclude that the surgical approach is a realistic alternative in certain cases, including large and broad-based Type llb hamartomas associated with gelastic epilepsy and behavioral disorders.

Adrenal response to acute stress in mammillary medial nuclei lesioned rats.

In view of the inhibitory influence of Mammillary Medial Nuclei, pars lateralis (MMN) on corticoadrenal activity, experiments were conducted in order to determine whether these nuclei are involved in the control of adrenal response to ether stress. In bilateral MMN lesioned rats, prestress plasma corticosterone concentration (C) is significantly higher than that in sham lesioned animals. Acute stress produced a significant C increase in both, sham and lesioned rats, being this increase lower in lesioned animals. After exposure to ether vapors. adrenal concentration of norepinephrine was similar in lesioned and control animals. Whereas, adrenal epinephrine concentration was significantly higher in lesioned rats than that found in the sham lesioned ones. This study demonstrates that the integrity of MMN is not essential for adrenal response to acute stress.

Ablations of the mammillary nuclei in monkeys: effects on postoperative memory.

A new procedure was developed for ablating the mammillary nuclei in nonhuman primates via direct visual exposure. Using this technique, monkeys receiving lesions of the mammillary nuclei were compared to control animals after surgery to assess the retention of preoperatively acquired visuospatial discriminations and subsequent postoperative ability to attain a demanding spatial memory task. Although the lesions proved to be accurate and complete, no changes in gross behavior or deficits in preoperatively acquired visual and spatial behaviors were noted. The monkeys with mammillary body lesions were, however, impaired in their ability to acquire postoperatively the demanding spatial memory task. These findings are consistent with previous investigations suggesting that the mammillary bodies are involved in the acquisition of spatial discriminations and skills.