Comment to the paper: palliative functional hemispherectomy for treatment of refractory status epilepticus associated with Alpers' disease.

INTRODUCTION: Performing epilepsy surgery in a child with a neurodegenerative illness is a relatively unexplored challenge. In this issue of CNS, Lupashko and coauthors report the use of epilepsy surgery to eliminate seizures without influencing the underlying progressive disorder. METHOD: Functional hemispherectomy was performed in a 4-year-old girl with seizures caused by Alpers' disease. RESULTS: Seizure freedom and an improved quality of life were achieved briefly despite deteriorating neurologic status. CONCLUSION: Further studies will be needed to confirm the positive benefits of palliative epilepsy surgery in children with progressive neurologic illnesses.

Palliative functional hemispherectomy for treatment of refractory status epilepticus associated with Alpers' disease.

PURPOSE: Palliative epilepsy surgery is considered for patients that would benefit from surgical therapy for intractable epilepsy but are not candidates for curative procedures. In many cases, the goals of therapy focus on improved quality of life more than seizure freedom. We discuss the use of epilepsy surgery for refractory status epilepticus, as well as the rationale and ethical considerations for employing a palliative procedure in otherwise fatal diseases. METHODS: We present a child with Alpers' disease presenting with refractory status epilepticus which was treated with functional hemispherectomy after failure of multiple typical therapies. Hemispherectomy allowed for the child to be extubated and ultimately discharged to home with her family. Unfortunately, the child died several months later after developing new-onset liver failure in the setting of a viral illness. CONCLUSION: Functional hemispherectomy was effective for the treatment of refractory status epilepticus in Alpers' disease. We believe that the procedure resulted in improved quality of life which was the primary outcome goal. Palliative procedures should be considered in diseases with ultimate fatal outcome when the short-term benefits outweigh the risks. The ethical aspects of treatment must be carefully considered to insure treatment is provided in the best interest of the patient.

Multiple extradural spinal arachnoid cysts causing diffuse myelomalacia of the spinal cord.

INTRODUCTION: Extradural spinal cyst is a rare cause of compression myelopathy. It is usually solitary and its typical location is posterior to the spinal cord. We present a case of multiple spinal arachnoid cysts causing diffuse myelomalacia secondary to a significant compression of the spinal cord with no symptom relief after surgical decompression. CASE REPORT: A 35-year-old female patient presented to our hospital complaining of progressive weakness and numbness of both lower extremities for the last 2 months, being more prominent on the right side. Her history was significant for back pain that started after a vaginal delivery 1 year ago. Spinal MRI revealed multiple extradural arachnoid cysts and diffuse myelomalacia. A T4-T6 level laminectomy was performed. The cyst was nearly totally resected. There was partial symptomatic relief after surgery, but 5 months later her symptoms worsened. MRI revealed nodular syringomyelia and atrophy of the thoracic spinal cord. CONCLUSIONS: Extradural spinal arachnoid cyst is to be considered in the differential diagnosis of spinal cord compression. Vaginal delivery may accelerate the process and symptoms by a sudden increase in the cyst size. In cases of myelomalacia secondary to cyst pressure postoperative results are quite poor.

Anestesia en enfermedades mitocondriales / No disponible

Las enfermedades mitocondriales son un raro grupo de enfermedades que se manifiestan a través de un defecto en la cadena de transporte de electrones o de la fosforilación oxidativa. Se trata de una alteración del ADN nuclear o del mitocondrial que provoca miopatía hipotónica, encefalopatía y aumento del ácido láctico. Para su correcto diagnóstico deben realizarse, entre otras pruebas, una biopsia muscular y una resonancia magnética. El anestesista debe realizar su trabajo en un paciente con miopatía sin diagnosticar y con riesgo de complicaciones cardiorrespiratorias y neurológicas, por ello es importante el conocimiento de las acciones sobre la cadena respiratoria de los agentes anestésicos. Presentamos el desarrollo esquemático de las enfermedades de la cadena respiratoria mitocondrial y su manejo anestésico

Diseases of the mitochondrial respiratory chain are a rare pathologic group that can be manifested through a defect in the transport chain of electrons or by oxidative phosphorylation alteration. It is a disturbance of the nuclear or mitochondrial DNA, causing hypotonic myopathy, encephalopathy and hyperlactacidemya. For its correct diagnosis must be performed muscle biopsy and magnetic resonance. The anaesthetist must do their work in a patient without a correct diagnostic of myopathy, and a high risk of cardiorrespiratory and neurologic complications. That’s why it’s important the knowledge of the actions of de anaesthetic agents by de respiratory chain. We present the schematic development of the mitochondrial respiratory chain diseases and its anaesthetic management

Neuropathological spectrum of lesions associated with intractable epilepsies: a 10-year experience with a series of 153 resections.

BACKGROUND: Surgical management of intractable epilepsies is currently an established mode of therapy in various clinical settings. AIMS: To retrospectively evaluate the neuropathological findings in both temporal and extratemporal lobe resections in such patients. MATERIALS AND METHODS: The study included resected specimens from patients with intractable epilepsy managed at a tertiary care hospital of India, during a 10-year period (1995-2004). RESULTS: A total of 153 patients, with mean age of 19.4 years and male predominance (73.2%) were included in the study. Overall, there was a predilection for the temporal lobe (73.2%), while 41cases were extratemporal in location. On histopathology, mesial temporal sclerosis (MTS) (24.8%) was the commonest lesion, followed by tumors (19.6%) and isolated focal cortical dysplasia (FCD - 15.11%). Other less common findings included Rasmussen encephalitis, non-specific gliosis and vascular malformations. In addition, 20.9% (32 cases) had dual lesions, majority of which included FCD with ganglioglioma (15 cases) or with dysembryoplastic neuroepithelial tumor (12 cases). In the temporal lobe, neoplasms and dual lesions formed the majority (apart from MTS), unlike dual lesions followed by neoplasms and FCD, in the extratemporal location. CONCLUSION: This series demonstrates that most patients with chronic intractable epilepsy have significant histopathological findings and highlights the neuropathological spectrum of such lesions, in the Indian context. This was similar to that reported from the West, but different from the single Indian series available in the literature. Further, the overall profile of temporal lobe lesions was not different from the extratemporal ones.

Decompressive aspiration in myelinoclastic diffuse sclerosis or Schilder disease. Case report.

This 9-year-old girl with rapidly progressive cerebral demyelinating disease presented with hemiplegia and intracranial hypertension. Brain images revealed four lesions with mass effect in the subcortical white matter of both hemispheres. Demyelination was found on pathological studies of these lesions. The patient experienced some recovery with corticosteroid treatment but improved completely with decompressive aspiration of the largest lesion.

Seizures in family members of patients with hippocampal sclerosis.

OBJECTIVE: To characterize seizures in family members of patients with refractory temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS). METHODS: The authors systematically investigated family history (FH) of seizures in 66 probands with histologically proven HS, and in 51 control subjects. A positive FH was defined as at least one first-to-third-degree relative being affected. The odds ratio (OR) to be affected with seizures was calculated for siblings, parents, and aunts/uncles. RESULTS: An FH of seizures was found in 58% of patients, and in 24% of control subjects (p = 0.02). A variety of seizure types were found. Siblings of patients were more likely to be affected than siblings of control subjects (OR 11.5; 95% CI = 1.5 to 86.9 p = 0.003), with febrile convulsions occurring in 5.8% of the siblings of patients. The OR of being affected was 5.7 for parents of patients, and 1.9 for aunts/uncles of patients (p = NS). CONCLUSION: FH of seizures, particularly febrile convulsions, are a risk factor for TLE with HS. These data suggest that a variety of genes contributing to epilepsy phenotypes in relatives may be involved in the pathogenesis of HS.

Baló's concentric sclerosis: clinical and radiologic features of five cases.

Baló's concentric sclerosis (BCS) is a rare demyelinating disease considered to be a variant of multiple sclerosis. Five BCS cases were diagnosed antemortem based on their typical concentric mass patterns on MR images and based on clinical and CSF findings. Histopathologic investigation was also performed in one case. Our case report supports the concept that BCS may be a self-limited disease that is not always fatal. Characteristic MR imaging findings may allow antemortem diagnosis of BCS when performed at the onset of the disease.

Large demyelinating brain lesion mimicking a herniating tumor.

We describe the case of a large brain lesion whose computed tomography appearance and clinical evolution mimicked a herniating tumor. The patient progressed to coma within 6 days of hospitalization despite high-dose steroid treatment. Emergency excision of the lesion was carried out. Histological analysis showed massive demyelination, axon preservation and no tumor cells. No lesion recurrence was seen during a 55-month follow-up. Recognition of such lesions through magnetic resonance imaging or spectroscopy may spare unnecessary surgery or biopsy. However, our case shows that such lesions may still require resection in the face of a rapid clinical progression and poor response to medical treatment.

Intraoperative hippocampal electrocorticography to predict the extent of hippocampal resection in temporal lobe epilepsy surgery.

OBJECT: Among the variety of surgical procedures that are performed for the treatment of medically refractory mesial temporal lobe epilepsy (TLE), no consensus exists as to how much of the hippocampus should be removed. Whether all patients require a maximal hippocampal resection has not yet been determined. METHODS: At the University of Washington, all TLE operations are performed in a tailored fashion, guided by electrocorticography (ECoG). The amount of hippocampal resection is determined intraoperatively by the extent of interictal epileptiform abnormalities on ECoG recorded from that structure, resulting in a hippocampal resection that is individualized for each patient. Using this approach, the authors prospectively observed 140 consecutive patients who underwent surgery for mesial TLE with pathological diagnoses of either mesial temporal sclerosis with neuronal loss (MTS group) or mild gliosis without neuronal loss (non-MTS group) to determine whether the extent of hippocampal resection correlates with outcome when a tailored approach is used. Additionally, the authors analyzed whether the presence of residual interictal epileptiform activity on ECoG following mesial temporal resection predicts poorer seizure control. With at least 18 months of clinical follow up, 67% of the 140 patients were seizure free or had only a single postoperative seizure. There was no correlation between the size of the hippocampal resection and seizure control in the group as a whole or when stratified by pathological subtype. Using an intraoperatively tailored strategy, individuals with a larger hippocampal resection (> 2.5 cm) were not more likely to have seizure-free outcomes than patients with smaller resections (p = 0.9). Additionally, both MTS and non-MTS patients, in whom postoperative ECoG detected residual epileptiform hippocampal (but not cortical or parahippocampal) interictal activity following surgical resection, had significantly worse seizure outcomes (p = 0.01 in the MTS group; p = 0.002 in the non-MTS group). CONCLUSIONS: Intraoperative hippocampal ECoG can predict how much hippocampus should be removed to maximize seizure-free outcome, allowing for sparing of possibly functionally important hippocampus.

Leukodystrophy and bone marrow transplantation: role of mixed hematopoietic chimerism.

Bone Marrow Transplantation (BMT) is currently the most physiologic treatment for some types of leukodystrophies. In enzyme deficiency states, replacement of defective genes with cells carrying "normal" copies of these genes offers a natural form of gene therapy. This review will cover the various disease states which may be treated using bone marrow transplantation as well as the obstacles and advantages offered by this treatment modality. The potential for mixed hematopoietic chimerism, with reference to the advantages and disadvantages of treating various leukodystrophies, is reviewed. Finally, certain approaches which would reduce the morbidity and mortality associated with conventional BMT are discussed. If these obstacles can be overcome, BMT may offer the hope of cure to a number, but certainly not all, leukodystrophies.

White matter lesions in patients with idiopathic normal pressure hydrocephalus and in an age-matched control group: a comparative study.

OBJECTIVE: To compare the occurrence of periventricular lesions (PVLs) and deep white matter lesions (DWMLs) in elderly patients with idiopathic normal pressure hydrocephalus (NPH) and in an age-matched control group. METHODS: PVLs and DWMLs were evaluated using T2-weighted magnetic resonance scans of 37 patients with idiopathic NPH and 35 participants from an age-matched control group. All patients with idiopathic NPH included in this study improved after shunting. The control group consisted of 16 healthy elderly persons and 19 patients with depression. To allow quantitative assessment and comparison, scores for PVLs and DWMLs were calculated. Furthermore, possible correlations between white matter lesion scores, ventricular width, and age were investigated. RESULTS: There was a significantly higher incidence of PVLs and DWMLs in patients with idiopathic NPH. The mean total PVL was 12.1 (range, 2-24) in the NPH group and 3.9 (range, 0-10) in the control group (P < 0.001). The mean total DWML score was 12.9 (range, 3-24) in the NPH group and 4.5 (range, 0-16) in the control group (P < 0.001). There were significant correlations between the severity of PVL and DWML scores in both groups. Only a weak positive correlation between the severity of DWMLs and age was found in the NPH group, whereas this correlation was significant in the control group. There was a significant negative correlation between the width of the anterior horns and the severity of both PVLs and DWMLs in patients with NPH; however, positive correlations were found in the control group. CONCLUSION: Elderly patients with idiopathic NPH have more frequent and more severe PVLs and DWMLs than people in age-matched control groups. Our data suggest a frequent co-occurrence of idiopathic NPH and vascular subcortical encephalopathy; however, they do not support a direct causal relationship.

The predictive value of intraoperative electrocorticography in resections for limbic epilepsy associated with mesial temporal sclerosis.

OBJECTIVE: Prior studies on the predictive value of intraoperative electrocorticography (ECoG) have been performed on heterogeneous groups of patients with both temporal and extratemporal interictal spikes, lesional and nonlesional pathological findings, and variably extensive resections by different surgeons. METHODS: We performed both pre- and postresection intraoperative ECoG on 29 consecutive patients with medial temporal lobe epilepsy (17 left-sided) who underwent standard nontailored resections by one surgeon (RRG). All patients had only temporal interictal spikes (six bitemporal) and mesial temporal sclerosis diagnosed by preoperative magnetic resonance imaging and confirmed by pathological examination of resected tissue. RESULTS: After a mean follow-up of 24.8 months, there were 15 (52%) patients who were seizure-free, 6 (21%) who were seizure-free except for auras, and 8 (28%) who had any seizure after the 1st postoperative month. Fourteen patients (48%) had active interictal discharges outside the area of planned resection revealed by preresection ECoG. Neither the presence of these spikes nor their mean frequency correlated with seizure outcome. Eleven patients (38%) had residual spike discharges after resection, and 18 patients (62%) had new spikes revealed by the postresection ECoG. Neither of these findings nor the mean spike frequency of residual or new spikes related to seizure outcome. Persistent spikes increased in frequency after resection in all outcome groups. CONCLUSIONS: Electrocorticographic monitoring of interictal epileptiform activity intraoperatively is not useful in the surgical treatment of patients undergoing standard resection for medial temporal lobe epilepsy with magnetic resonance imaging evidence of mesial temporal sclerosis.

Clinical significance of asymmetry of the fornix and mamillary body on MR in hippocampal sclerosis.

PURPOSE: To investigate the clinical significance of MR-defined asymmetry of the fornix and mamillary body for presurgical determination of the side of hippocampal sclerosis in patients with temporal lobe epilepsy. METHODS: Fast spin-echo MR images were evaluated for evidence of an asymmetrically small fornix and mamillary body in 33 patients with pathologically proved hippocampal sclerosis (presurgical hippocampal sclerosis group), 7 patients who had undergone anterior temporal lobectomy (mean, 3 years from surgery) because of hippocampal sclerosis (postsurgical hippocampal sclerosis group), and 34 healthy subjects (control group). Fast spin-echo hippocampal volumetry was performed in each patient. RESULTS: In the control group, 6% (2 of 34) of subjects had MR evidence of asymmetrically small fornix and none (0 of 34) of the subjects had asymmetrically small mamillary body. In the patient population, an asymmetrically small fornix was seen in 42% of presurgical hippocampal sclerosis group, 39% (13 of 33) ipsilateral, and 3% (1 of 33) contralateral, and in 71% of the postsurgical hippocampal sclerosis group (5 of 7), all ipsilateral. In the presurgical hippocampal sclerosis group, hippocampal atrophy measured with MR was more severe in patients with an ipsilaterally small fornix than in patients without. An asymmetrically small mamillary body was found ipsilaterally in 3% (1 of 33) of the presurgical hippocampal sclerosis group and in 57% (4 of 7) of the postsurgical hippocampal sclerosis group; all patients with an asymmetrically small mamillary body in the postsurgical hippocampal sclerosis group also had an asymmetrically small fornix on the same side. CONCLUSION: In presurgical hippocampal sclerosis patients, an asymmetrically small fornix can be seen ipsilaterally on the side of the hippocampal sclerosis; however, its low frequency, its association with severe hippocampal atrophy only, and the possibility of false-positive results limit its clinical usefulness in determining the side of the seizure focus. An asymmetrically small mamillary body is too rare to be used for presurgical location of hippocampal sclerosis. However, an asymmetrically small fornix and mamillary body are frequently seen on MR images after temporal lobectomy.

Myelinoclastic diffuse sclerosis (Schilder's disease): report of a case and review of the literature.

The clinical, neuroimaging, and neuropathologic features of Schilder's disease in a 17-year-old girl are presented and compared to 11 well-documented cases reported since 1912. The evolution of knowledge about Schilder's disease and the confusion in nomenclature are reviewed. Signs and symptoms in this case and others reported in the literature are nonspecific and may mimic mass lesions. Neuroimaging studies also may mimic brain tumor or abscess; however, the absence of significant edema, the irregular and incomplete ring enhancement, the discrepancy between size of the lesions and the associated mass effect, and the absence of other lesions elsewhere in the brain may help differentiate Schilder's disease from neoplasm, infection, and other demyelinating lesions. Although frozen sections of these lesions are often interpreted as astrocytoma, the inflammatory, primarily histiocytic, nature of Schilder's disease is more easily recognized in paraffin-embedded material. Unique features of this case include multiple unilateral lesions and the cyst-like degeneration present in both lesions. Multiple lesions in Schilder's disease are characteristically bilateral. The examination of aspirated fluid is the first such report in Schilder's disease. The limitation of multiple lesions in our case to one hemisphere calls for reexamination of the restrictive 1985 criteria of Poser for the diagnosis of Schilder's disease.

MR and positron emission tomography in the diagnosis of surgically correctable temporal lobe epilepsy.

PURPOSE: To determine the association of an MR abnormality and a positron emission tomography (PET) abnormality with a good outcome in patients with temporal lobe epilepsy after lobectomy, the association of combined PET and MR findings with good outcomes after lobectomy, and MR and PET pathologic correlation. METHODS: MR and PET were performed on 27 patients in a blinded study. Histologic studies were correlated with foci of increased T2 signal. RESULTS: Increased signal or decreased volume of the hippocampus was noted in 13 of 15 patients with mesial temporal sclerosis. Twelve of 15 had positive PET findings. MR identified 20 (83%) of the 24 patients with good outcomes. PET identified 71%. When MR and PET were combined, they detected 95% of the patients with good outcome. Region of interest measurements of the hippocampus in 11 study patients and 7 control subjects documented a significant increase in signal in the patients with seizures. Histologic correlative studies demonstrated that increased T2 signals related to astrocytosis in the hippocampus and adjacent white matter. CONCLUSIONS: MR (increased signal and decreased volume of the hippocampus) significantly improved the capability to identify those persons who would be helped by lobectomy. MR sensitivity exceeded that of PET.