Outcome after conservative or surgical treatment for new-onset epilepsy in children with cerebral cavernous malformation.

OBJECTIVE: This study aimed to investigate and compare the outcome of conservatively or surgically treated children with cerebral cavernous malformation (CCM) and new-onset CCM-related epilepsy (CRE) during a 5-year period. METHODS: In this observational monocentric cohort study, data were collected ambispectivley. Our database was screened for CCM patients treated between 2003 and 2020. Patients ≤18 years of age with complete magnetic resonance imaging dataset, clinical baseline characteristics, and diagnosis of new-onset CRE were included. Definite seizure control was classified as International League Against Epilepsy class <2. Functional outcome was assessed using the modified Rankin Scale score. CRE patients were separated into two groups according to their treatment modality. Seizure control, intake of antiseizure medication, and functional outcomes were assessed. Systematic literature research was performed to identify other cases of new-onset CRE in children and to compare the collected data with published data. RESULTS: Thirty-nine pediatric CRE patients were analyzed. A total of 18 (46.1%) patients were conservatively treated, while 21 (53.8%) underwent surgical CCM removal. While the functional outcome was similar in both groups at the last follow-up, definite seizure control was better in the surgical group (77.8%) than in the conservative group (25.0%) both after 5-years of follow-up (p = 0.038), and at last follow-up with 85.7% versus 50% respectively (p = 0.035). We found substantially higher rates of discontinuation of antiseizure medication at the last available follow-up in patients undergoing surgical resection (p = 0.009). The systematic literature review identified 4 studies with a total of 30 additional children with early onset CRE. CONCLUSION: Surgical treatment of pediatric patients with new-onset CRE had higher rates of complete seizure control and early discontinuation of antiseizure medication than conservative treatment. Neurological outcomes of patients managed surgically or conservatively were comparable. These results encourage early surgical management of children with CRE even in the absence of pharmacoresistant epilepsy, but randomized control trials are urgently needed for further decision-making.

Modifiable vascular risk factors in patients with cerebral and spinal cavernous malformations: a complete 10-year follow-up study.

BACKGROUND AND PURPOSE: The aim was to investigate the effect of modifiable vascular risk factors on the risk of first and recurrent bleeding for patients with a cavernous malformation (CM) of the central nervous system (CNS) over a 10-year period. METHODS: A retrospective review of our CM institutional database was performed spanning from 2003 to 2021. The inclusion criteria were non-missing serial magnetic resonance imaging studies and clinical baseline metrics such as vascular risk factors. The exclusion criteria were patients who underwent surgical CM removal and patients with less than a decade of follow-up. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative risk (10 years) of hemorrhage. RESULTS: Eighty-nine patients with a CM of the CNS were included. Our results showed a non-significant increased risk of hemorrhage during 10 years of follow-up in patients using nicotine (hazard ratio 2.11, 95% confidence interval 0.86-5.21) and in patients with diabetes (hazard ratio 3.25, 95% confidence interval 0.71-14.81). For the presence of modifiable vascular risk factors at study baseline different cumulative 10-year risks of bleeding were observed: arterial hypertension 42.9% (18.8%-70.4%); diabetes 66.7% (12.5%-98.2%); hyperlipidemia 30% (8.1%-64.6%); active nicotine abuse 50% (24.1%-76%); and obesity 22.2% (4%-59.8%). Overall cumulative (10-year) hemorrhage risk was 30.3% (21.3%-41.1%). CONCLUSIONS: The probability of hemorrhage in untreated CNS CM patients increases progressively within a decade of follow-up. None of the modifiable vascular risk factors showed strong indication for an influence on hemorrhage risk, but our findings may suggest a more aggressive course in patients with active nicotine abuse or suffering from diabetes.

The architecture of the chess player's brain.

The game of chess can be seen as a typical example for an expertise task requiring domain-specific training and experience. Despite intensive behavioural studies the neural underpinnings of chess performance and expertise are not entirely understood. A few functional neuroimaging studies have shown that expert chess players recruit different psychological functions and activate different brain areas while they are engaged in chess-related activities. Based on this functional literature, we predicted to find morphological differences in a network comprised by parietal and frontal areas and especially the occipito-temporal junction (OTJ), fusiform gyrus, and caudate nucleus. Twenty expert chess players and 20 control subjects were investigated using voxel-based and surface-based morphometry as well as diffusion tensor imaging. Grey matter volume and cortical thickness were reduced in chess players compared with those of control men in the OTJ and precunei. The volumes of both caudate nuclei were not different between groups, but correlated inversely with the years of chess playing experience. Mean diffusivity was increased in chess players compared with that of controls in the left superior longitudinal fasciculus and the Elo score (a chess tournament ranking) was inversely related to mean diffusivity within the right superior longitudinal fasciculus. To the best of our knowledge we showed for the first time that there are specific differences in grey and white matter morphology between chess players and control subjects in brain regions associated with cognitive functions important for playing chess. Whether these anatomical alterations are the cause or consequence of the intensive and long-term chess training and practice remains to be shown in future studies.

Effective surgical treatment of cerebral cavernous malformations: a multicenter study of 79 pediatric patients.

OBJECT: Cerebral cavernous malformations (CCMs) are common vascular lesions in the brain, affecting approximately 0.5% of the population and representing 10%-20% of all cerebral vascular lesions. One-quarter of all CCMs affect pediatric patients, and CCMs are reported as one of the main causes of brain hemorrhage in this age group. Symptoms include epileptic seizures, headache, and focal neurological deficits. Patients with symptomatic CCMs can be treated either conservatively or with resection if lesions cause medically refractory epilepsy or other persistent symptoms. METHODS: The authors retrospectively analyzed 79 pediatric patients (41 boys and 38 girls) from 3 different centers, who were surgically treated for their symptomatic CCMs between 1974 and 2004. The mean age of the children at first manifestation was 9.7 years, and the mean age at operation was 11.3 years. The main goal was to compare the clinical outcomes with respect to the location of the lesion of children who preoperatively suffered from epileptic seizures. RESULTS: Of these patients, 77.3% were seizure free (Engel Class I) after the resection of the CCM. Significant differences in the outcome between children who harbored CCMs at different locations were not found. CONCLUSIONS: Resection seems to be the favorable treatment of symptomatic CCMs not only in adults but also in children.

Serum cholesterol levels do not influence outcome or recovery in acute ischemic stroke.

OBJECTIVE: To examine the influence of admission serum cholesterol levels (SCL) on severity of initial neurological deficit, neurological outcome at month 3 and neurological recovery in patients with acute first-ever ischemic stroke. METHODS: Prospectively collected data from 889 consecutive patients with first-ever acute ischemic stroke were retrospectively analysed. Patients who suffered a recurrent ischemic stroke (n=22) or died (n=30) during the follow-up period were excluded from this study. Age, gender, arterial hypertension, diabetes mellitus, smoking, stroke etiology, SCL and severity of neurological deficit, using the National Institute of Health Stroke Scale (NIHSS), at presentation (NIHSS0) and after 3 months (NIHSS1), were assessed. Neurological recovery was defined as difference in NIHSS score (Delta(NIHSS)), according to Delta(NIHSS)=NIHSS0 - NIHSS1. RESULTS: Data from 837 patients (66% men, age: 62 +/- 14 years) were analysed. NIHSS1 was 2.3 +/- 1.8 and Delta(NIHSS) was 3.4 +/- 3. Clinically insignificant correlations between SCL and NIHSS0 (r=-0.13, p=0.0002), NIHSS1 (r=-0.09, p=0.001) and Delta(NIHSS) (r=-0.1, p=0.03) were evident. Multivariate binary logistic regression analysis revealed smoking (p=0.008), stroke etiology (p=0.023) and NIHSS0 (p<0.001) but not age, gender, arterial hypertension, diabetes mellitus or SCL as predictors for Delta(NIHSS). CONCLUSION: Our data suggest that SCL in patients with acute ischemic stroke are not associated with neurological deficit on admission, outcome or neurological recovery.

Gustav Flaubert's "nervous disease": an autobiographic and epileptological approach.

More than 20 years ago, complex partial epilepsy of occipital-temporal origin was suggested as having been the "nervous disease" of Gustave Flaubert, one of the most famous French novelists. The aim of the present work, therefore, was to reevaluate the diagnosis of Flaubert's "nervous disease" in the light of reemerged biographic information and letters, as well as the numerous scientific advances in epilepsy and its psychopathology in recent years. If the semiology of the reported attacks is considered, epilepsy ranks among the most probable diagnoses. In our opinion, psychopathological considerations suggest primary involvement of mesial temporal lobe structures with typical findings of ictal and interictal mood behavior.

Going high with preexisting neurological conditions.

This review presents the potential impact of high altitude exposure on preexisting neurological conditions in patients usually living at low altitude. The neurological conditions include permanent and transient ischemia of the brain, occlusive cerebral artery disease, cerebral venous thrombosis, intracranial hemorrhage and vascular malformations, multiple sclerosis, intracranial space-occupying lesions, dementia, extrapyramidal disorders, migraine and other headaches, and epileptic seizures. New developments in diagnostic work-up and treatment of preexisting neurological conditions are also mentioned where applicable. For each neurological disorder, the authors developed absolute and relative contraindications for a trip to high altitude. These recommendations are not based on the results of controlled randomized trials, but mainly on case reports, pathophysiological considerations, and extrapolations from the low altitude situation.

Seizure outcome after resection of supratentorial cavernous malformations: a study of 168 patients.

PURPOSE: The optimal management of cerebral cavernous malformations (CCMs) with epileptic seizures is still a matter of debate. The aim of our study was to examine seizure outcome in the largest published series of surgically treated patients with epilepsy due to a supratentorial CCM, and to define predictors for good surgical outcome. METHODS: We retrospectively studied 168 consecutive patients with a single supratentorial CCM and symptomatic epilepsy in a multicenter study. Pre- and postoperative clinical examinations, age at epilepsy onset, age at operation, type of symptoms due to the CCM (seizures, headache, hemorrhage, focal deficits), type and frequency of epileptic seizures, and the localization and size of the CCM were assessed. Seizure outcome was determined in the first, second, and third postoperative years. RESULTS: The CCM was completely resected in all patients. More than two thirds of the patients were classified as seizure free in the first 3 postoperative years. Predictors for good seizure outcome were age older than 30 years at the time of surgery, mesiotemporal CCM localization, CCM size <1.5 cm, and the absence of secondarily generalized seizures. No mortality occurred in our series, but only mild postoperative neurologic deficits in 12 (7%) patients. CONCLUSIONS: Considering the natural history of CCMs, the favorable neurologic and seizure outcome, surgical resection of CCMs should be considered in all patients with supratentorial CCMs and concomitant epilepsy, irrespective of the presence or absence of predictors for a favorable seizure outcome.

Lipoma on the corpus callosum in a patient with schizophrenia-like episode: is there a causal relationship?

Disturbed interhemispheric communication has been proposed as responsible for schizophrenia. We present a case of a schizophrenia-like episode with no neurologic or other psychiatric symptoms. However, magnetic resonance imaging revealed a lipoma on the splenium of the corpus callosum. Neuropsychologic examination revealed normal interhemispheric transfer, but a slight dysfunction associated with right-hemispheric anterior regions. Rather than supporting the hypothesis of a causal relationship between callosal abnormality and schizophrenia-like symptoms, our findings argue against a direct causal relationship between lesion site and psychotic episode. We conclude that cerebral abnormality per se may represent a risk factor for neuropsychiatric symptoms.

Good outcomes in ischemic stroke patients treated with intravenous thrombolysis despite regressing neurological symptoms.

BACKGROUND AND PURPOSE: We evaluated the clinical course of 19 acute stroke patients with rapid early improvement of neurological deficit within the 3-hour window, treated with intravenous thrombolytics. RESULTS: No patient demonstrated a neurological deterioration during hospitalization. National Institutes of Health Stroke Scale (NIHSS) scores at therapy decision and discharge were 5 (4 to 6) and 0.5 (0 to 1.5), respectively. At 3-month follow-up, 1 patient had died; in remaining patients, NIHSS was 0 (0 to 1) and modified Rankin Scale 0.5 (0 to 1; < or =1 in 15 patients). CONCLUSIONS: Withholding of intravenous thrombolysis because of spontaneous early regression of neurological symptoms may not be justified.

Seizure outcome after resection of cavernous malformations is better when surrounding hemosiderin-stained brain also is removed.

PURPOSE: Considering the epileptogenic effect of cavernoma-surrounding hemosiderin, assumptions are made that resection only of the cavernoma itself may not be sufficient as treatment of symptomatic epilepsy in patients with cavernous malformations. The purpose of this study was to test the hypothesis whether seizure outcome after removal of cavernous malformations may be related to the extent of resection of surrounding hemosiderin-stained brain tissue. METHODS: In this retrospective study, 31 consecutive patients with pharmacotherapy-refractory epilepsy due to a cavernous malformation were included. In all patients, cavernomas were resected, and all patients underwent pre- and postoperative magnetic resonance imaging (MRI). We grouped patients according to MRI findings (hemosiderin completely removed versus not/partially removed) and compared seizure outcome (as assessed by the Engel Outcome Classification score) between the two groups. RESULTS: Three years after resection of cavernomas, patients in whom hemosiderin-stained brain tissue had been removed completely had a better chance for a favorable long-term seizure outcome compared with those with detectable postoperative hemosiderin (p=0.037). CONCLUSIONS: Our study suggests that complete removal of cavernoma-surrounding hemosiderin-stained brain tissue may improve epileptic outcome after resection of cavernous malformations.

Biological activity of paediatric cerebral cavernomas: an immunohistochemical study of 28 patients.

OBJECTIVE: According to the hypothesis that paediatric cerebral cavernomas may have different biological activity compared to adult cavernomas, immunohistochemical analysis was used to elucidate the biological nature of paediatric cavernomas. PATIENTS AND METHODS: We examined the histological features and the proliferative and angiogenic capacity of the tissue specimens acquired from 28 paediatric patients. Normal paediatric brain tissues obtained from paediatric autopsy cases were used as a control group. The proliferative activity of the endothelium and the neoangiogenetic capacity were investigated by immunohistochemistry for proliferating cell nuclear antigen (PCNA), Ki-67 epitope (MIB-1), Flk-1 receptor, vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF)-1 alpha, and endoglin antibody, respectively. Afterwards, the results of the paediatric lesions were analysed and compared with the correspondent values of previously reported immunohistochemical analysis in adult cavernomas. RESULTS: Positive immunostaining of VEGF was detected significantly less in paediatric cavernomas compared to adult cases (p<0.05). In contrast, endoglin, a protein that is upregulated during an increased vascular shear stress, was expressed more often in paediatric cavernomas (p<0.05). Neither the expression of the PCNA nor the expression of the HIF-1alpha was found significantly different between paediatric and adult cavernomas. However, the positive immunoreaction for MIB-1 occurred more often in the paediatric cases (p<0.05). CONCLUSIONS: The immunohistochemical study indicates that paediatric cavernomas are dynamic lesions. The VEGF/Flk-1 associated neoangiogenesis may play a minor role for the biology of paediatric cavernomas, while endoglin seems to act more prominently than previously thought, particularly for the biology of paediatric cavernomas.

Did Fyodor Mikhailovich Dostoevsky suffer from mesial temporal lobe epilepsy?

Many scientific authors--among them famous names such as Henri Gastaut or Sigmund Freud--dealt with the question from what kind of epilepsy Fyodor Mikhailovitch Dostoevsky (1821-1881) might had suffered. Because of the tight interplay between Dostoevsky's literary work and his own disease we throw light on the author's epilepsy against the background of his epileptic fictional characters. Moreover, we attempt to classify Dostoevsky's epilepsy on the basis of his bibliography, language, and literary work.

Hypersomnia in an epilepsy patient treated with levetiracetam.

We report a patient with focal epilepsy in whom increased sleep needs (hypersomnia) developed in the absence of subjective excessive daytime sleepiness (EDS) during an add-on treatment with levetiracetam (LEV).

Biological activity of adult cavernous malformations: a study of 56 patients.

OBJECT: Cerebral cavernous malformations (CCMs) have previously been considered as congenital and biologically static malformations. On the other hand, the potential for growth and de novo generation of CCMs have also been reported. It is therefore important to study the proliferative and neoangiogenetic capacity of these lesions. METHODS: The authors studied the surgical specimens of 56 CCMs (23 deep and 33 superficial) obtained from adult patients. The proliferative activity of the endothelium and the neoangiogenetic capacity of these lesions were considered through immunohistochemical anaylsis of proliferating cell nuclear antigen (PCNA), MIB-1, Flk-1, vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF)-1alpha, and endoglin antibodies. Positive immunostaining of endothelial cells occurred in 86% of patients for PCNA and in 38% of the cases for MIB 1. The expression of Flk-1 was observed in the endothelium of 71% of the cases, for VEGF in 41%, for HIF-1 alpha in 48.1%, and for endoglin in 63.6% of the cases. The correlation of immunohistochemical and clinical data indicated that VEGF was expressed in significantly less deep-seated lesions when compared with superficial CCMs. Neither the expression of the proliferative markers nor the expression of the angiogenetic antibodies correlated with patient age at surgery, sex, or the number of recent prior hemorrhagic episodes in the patients. CONCLUSIONS: The CCMs from adult patients are active lesions exhibiting endothelial proliferation and neoangiogenesis. According to the data in this study, neoangiogenesis is more prominent in superficial CCMs than in deep-seated CCMs and is not associated with recent prior hemorrhages.

Presurgical evaluation and surgical treatment of medically refractory epilepsy.

Thanks to today's modern imaging examination techniques and especially to the common use of intracranial electrodes for localizing seizure foci, more and more patients with partial epilepsy can be treated microsurgically. The results of such neurosurgical therapies are very good, particularly in mesial temporal lobe epilepsy. In recent years, good results (60-70% seizure freedom) have also been achieved in extratemporal epilepsy surgery, so that such procedures can now be recommended for carefully selected patients. In this review, presurgical evaluations and the different surgical approaches are presented.

Validation of ictal single photon emission computed tomography with depth encephalography and epilepsy surgery.

Many centers have reported that ictal single photon emission computed tomography (SPECT) localizes regions of seizure onset with greater sensitivity and specificity than interictal SPECT. Here we report interictal and ictal SPECT scan results in both lesional and nonlesional cases. Using technetium hexamethyl propylamenamine oxide (HMPAO) or ethyl cysteinate dimer (ECD), these scans were done in 52 patients with partial and secondarily generalized seizures. Twenty-five had normal MRI and 27 showed structural lesions. None had mesial temporal sclerosis clearly identified on MRI. All 52 subsequently had interictal and ictal intracranial EEG studies that appeared to localize the seizure focus. Thirty-nine patients had surgery and have been followed for 2 or more years. Interictal SPECT scans showed focal hypoperfusion consistent with intracranial EEG localization of the seizure focus in 29% of patients. In another 13%, there was correct lateralization but not localization. Ictal SPECT scans showed focal hyperperfusion consistent with intracranial EEG localization of the seizure focus in 52% of patients. In another 25%, there was correct lateralization but not localization. The presence or absence of structural lesions on MRI did not affect ictal hyperperfusion or its correlation with intracranial EEG. Thirty-nine patients had resective surgery, of whom 62% had class I outcomes. There was a trend towards better outcome when ictal SPECT data were concordant with intracranial EEG data. The presence or absence of structural lesions on MRI did not affect the likelihood of class I outcome. Ictal SPECT is superior to interictal SPECT in localizing and lateralizing seizure foci. Its results correlate well with intracranial EEG, but in more than one third of cases, the latter shows focal seizure onset in areas that do not show focal hyperperfusion. Surgical outcome tends to be better when the two modalities give concordant results.

Mutations in a gene encoding a novel protein containing a phosphotyrosine-binding domain cause type 2 cerebral cavernous malformations.

Cerebral cavernous malformations (CCMs) are congenital vascular anomalies of the central nervous system that can result in hemorrhagic stroke, seizures, recurrent headaches, and focal neurologic deficits. Mutations in the gene KRIT1 are responsible for type 1 CCM (CCM1). We report that a novel gene, MGC4607, exhibits eight different mutations in nine families with type 2 CCM (CCM2). MGC4607, similar to the KRIT1 binding partner ICAP1alpha, encodes a protein with a phosphotyrosine-binding domain. This protein may be part of the complex pathway of integrin signaling that, when perturbed, causes abnormal vascular morphogenesis in the brain, leading to CCM formation.