Michal Tichy

Pediatric Intracranial Ependymomas: Prognostic Relevance of Histological, Immunohistochemical, and Flow Cytometric Factors

The correlation between the histological features and clinical outcome remains poor in pediatric intracranial ependymomas. We performed a retrospective study of a group of 31 patients (diagnosed from 1985 to 1995) to assess prognostic implications of the current grading system, of histological and immunohistochemical features, and of ploidy status estimated by flow cytometry. Immunoexpression of a broad spectrum of antigens was evaluated, including MIB-1, topoisomerase-IIα, cyclin D1, glial and epithelial proteins (GFAP, EMA, cytokeratins), molecules involved in controlling apoptosis (bcl-2, caspase-3/CPP32), and p53 oncoprotein. Univariate and multivariate statistical analyses were performed to evaluate the influence of each variable on both the progression free survival (PFS) and the overall survival (OS) with at least 7-year follow up. Although we showed a significant correlation between histological grade and prognosis, the current grading system failed in predicting outcome in nearly one third of individual cases. Problems with interpathologist reproducibility were also demonstrated. The extent of surgical resection was the only clinical factor that was associated with survival. Both the PFS and the OS were significantly decreased for the following pathological variables: increased cellularity (>300 nuclei per HPF), mitotic activity of >7 per 10 HPF, increased MIB-1 labeling index (LI), topoisomerase-IIα LI, S-phase fraction, and p53 and bcl-2 positivity. Increased cyclin D1 LI was demonstrated to have only a marginally significant impact on PFS. A flow chart modeling was further performed to formulate a scheme for discriminating of prognostic subgroups. Based on that, p53 immunopositivity and/or MIB-1 LI of >5% (after subtotal resection) or MIB-1 LI of >15% (after complete resection) were the strongest indicators of the tumors aggressive behavior and of a poor prognosis of the disease. Foci of hypercellularity should be specifically looked for in ependymomas for assessing the immunohistochemical studies.

SISCOM and FDG-PET in patients with non-lesional extratemporal epilepsy: correlation with intracranial EEG, histology, and seizure outcome

AimsTo assess the practical localising value of subtraction ictal single-photon emission computed tomography (SISCOM) coregistered with MRI and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with extratemporal epilepsy and normal MRI.MethodsWe retrospectively studied a group of 14 patients who received surgery due to intractable epilepsy and who were shown to have focal cortical dysplasia, undetected by MRI, based on histological investigation. We coregistered preoperative SISCOM and PET images with postoperative MRI and visually determined whether the SISCOM focus, PET hypometabolic area, and cerebral cortex, exhibiting prominent abnormalities on intracranial EEG, were removed completely, incompletely, or not at all. These results and histopathological findings were compared with postoperative seizure outcome.ResultsTwo patients underwent one-stage multimodal imageguided surgery and the remaining 12 underwent long-term invasive EEG. SISCOM findings were localised for all but 1 patient. FDG-PET was normal in 3 subjects, 2 of whom had favourable postsurgical outcome (Engel class I and II). Complete resection of the SISCOM focus (n=3), the area of PET hypometabolism (n=2), or the cortical regions with intracranial EEG abnormalities (n=7) were predictive of favourable postsurgical outcome. Favourable outcome was also encountered in: 4 of 8 patients with incomplete resection and 1 of 2 with no resection of the SISCOM focus; 4 of 7 patients with incomplete resection and 1 of 2 with no resection of the PET hypometabolic area; and 2 of 7 patients with incomplete resection of the area corresponding to intracranial EEG abnormality. Nocorrelation between histopathological FCD subtype and seizure outcome was observed.ConclusionComplete resection of the dysplastic cortex localised by SISCOM, FDG-PET or intracranial EEG is a reliable predictor of favourable postoperative seizure outcome in patients with non-lesional extratemporal epilepsy.

Peri-ictal headache due to epileptiform activity in a disconnected hemisphere

A 4-year-old girl with intractable epilepsy due to left-side hemispheric cortical dysplasia underwent a hemispherotomy. She was seizure-free after the surgery. EEG showed persistent abundant epileptiform activity over the left (disconnected) hemisphere, including ictal patterns that neither generalised nor had clinical correlates. Antiepileptic medication was completely withdrawn four years following the surgery. One week after the withdrawal, she developed episodes of intense left-sided hemicranias (ipsilateral to the surgery) with vomiting and photophobia that did not resemble her habitual seizures and were unresponsive to non-steroidal anti-inflammatory drugs. Video-EEG showed association of the headache attacks with ictal patterns over the disconnected hemisphere. Brain MRI revealed increased signal changes in the left hemisphere. Attacks responded promptly to i.v. midazolam and carbamazepine at a low dose. Mechanisms underlying peri-ictal headache originating in the disconnected hemisphere are discussed. [Published with video sequences].

Frontal lobe epilepsy with atypical seizure semiology resembling shuddering attacks or wet dog shake seizures.

We report a girl with a drug-resistant frontal lobe epilepsy caused by focal cortical dysplasia, who exhibited uncommon seizures. The seizures consisted of shoulder or whole body shuddering after a short psychic aura and face grimacing. Consciousness was fully preserved. The seizures resembled “wet dog shake” seizures described in rat models of epilepsy or shuddering attacks in infants. EEG findings were inconclusive, however, MRI showed a clear dysplastic lesion in the right frontal mesial and polar structures. The patient underwent an extended lesionectomy guided by neuronavigation and intraoperative electrocorticography. Focal cortical dysplasia type Ib was histologically confirmed and the patient has been seizure-free for the three years following resection.

Intraoperative thermography in safety control of the electrical stimulation mapping

The cortical Electric Stimulation Mapping (ESM) procedure is used as a standard approach to localize and continuously monitor function of the eloquent cortex and corticospinal tract during neurosurgical intervention. However, eliciting motor responses using standard ESM paradigm is frequently difficult to young children. We have thus developed and tested a novel EMS protocol, which uses intense, high frequency and short stimulation pulses. However, the intense stimulation peak-peak current (up to 100 mA) possess the potential risk of tissue damage.

Initial manifestation of type I diabetes mellitus as an unusual cause of early post-operative seizures

We present a case of an 18-year-old patient who underwent resective epilepsy surgery for intractable epilepsy caused by focal cortical dysplasia. In the early post-surgical period, the patient started experiencing atypical seizures refractory to antiepileptic treatment. In due course, abnormally low levels of blood sodium and extremely high levels of blood glucose were discovered. Significant hyperglycaemia was initially ascribed to steroid-induced diabetes, and antibodies specific to type I diabetes mellitus were subsequently detected, confirming the diagnosis. Following stabilization of glucose and electrolyte levels, the patient became seizure-free. To our knowledge, this is the first report of presentation of type I diabetes as the cause of early post-operative seizures. We discuss less common aetiologies of seizures in the early post-operative period, including metabolic disturbances. Based on our experience, we stress the importance of electrolyte and glucose monitoring in the setting of acute post-operative seizures.