Deciphering glycomics and neuroproteomic alterations in experimental traumatic brain injury: Comparative analysis of aspirin and clopidogrel treatment.

As populations age, the number of patients sustaining traumatic brain injury (TBI) and concomitantly receiving preinjury antiplatelet therapy such as aspirin (ASA) and clopidogrel (CLOP) is rising. These drugs have been linked with unfavorable clinical outcomes following TBI, where the exact mechanism(s) involved are still unknown. In this novel work, we aimed to identify and compare the altered proteome profile imposed by ASA and CLOP when administered alone or in combination, prior to experimental TBI. Furthermore, we assessed differential glycosylation PTM patterns following experimental controlled cortical impact model of TBI, ASA, CLOP, and ASA + CLOP. Ipsilateral cortical brain tissues were harvested 48 h postinjury and were analyzed using an advanced neuroproteomics LC-MS/MS platform to assess proteomic and glycoproteins alterations. Of interest, differential proteins pertaining to each group (22 in TBI, 41 in TBI + ASA, 44 in TBI + CLOP, and 34 in TBI + ASA + CLOP) were revealed. Advanced bioinformatics/systems biology and clustering analyses were performed to evaluate biological networks and protein interaction maps illustrating molecular pathways involved in the experimental conditions. Results have indicated that proteins involved in neuroprotective cellular pathways were upregulated in the ASA and CLOP groups when given separately. However, ASA + CLOP administration revealed enrichment in biological pathways relevant to inflammation and proinjury mechanisms. Moreover, results showed differential upregulation of glycoproteins levels in the sialylated N-glycans PTMs that can be implicated in pathological changes. Omics data obtained have provided molecular insights of the underlying mechanisms that can be translated into clinical bedside settings.

Awake Versus Asleep Craniotomy for Patients With Eloquent Glioma: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Awake vs asleep craniotomy for patients with eloquent glioma is debatable. This systematic review and meta-analysis sought to compare awake vs asleep craniotomy for the resection of gliomas in the eloquent regions. METHODS: MEDLINE and PubMed were searched from inception to December 13, 2022. Primary outcomes were the extent of resection (EOR), overall survival (month), progression-free survival (month), and rates of neurological deficit, Karnofsky performance score, and seizure freedom at the 3-month follow-up. Secondary outcomes were duration of operation (minute) and length of hospital stay (LOS) (day). RESULTS: Fifteen studies yielded 2032 patients, from which 800 (39.4%) and 1232 (60.6%) underwent awake and asleep craniotomy, respectively. The meta-analysis concluded that the awake group had greater EOR (mean difference [MD] = MD = 8.52 [4.28, 12.76], P < .00001), overall survival (MD = 2.86 months [1.35, 4.37], P = .0002), progression-free survival (MD = 5.69 months [0.75, 10.64], P = .02), 3-month postoperative Karnofsky performance score (MD = 13.59 [11.08, 16.09], P < .00001), and 3-month postoperative seizure freedom (odds ratio = 8.72 [3.39, 22.39], P < .00001). Furthermore, the awake group had lower 3-month postoperative neurological deficit (odds ratio = 0.47 [0.28, 0.78], P = .004) and shorter LOS (MD = -2.99 days [-5.09, -0.88], P = .005). In addition, the duration of operation was similar between the groups (MD = 37.88 minutes [-34.09, 109.86], P = .30). CONCLUSION: Awake craniotomy for gliomas in the eloquent regions benefits EOR, survival, postoperative neurofunctional outcomes, and LOS. When feasible, the authors recommend awake craniotomy for surgical resection of gliomas in the eloquent regions.

Craniocervical Rosai-Dorfman Disease presentation: Case report and review of literature.

Rosai Dorfman Disease (RDD) is a benign histiocytic lymphoproliferative disease that has variable presentations. The concurrent presentation of RDD in the spinal cord and brain parenchyma is an extremely rare entity. Here, we report another case of a 24-year-old gentleman who presented with a tuberculum sellae and bilateral cavernous extra-axial tumors extending to the subtemporal lobe and was found to have craniocervical lesions. Axillary lymph node biopsy was done showing markedly dilated sinuses filled with large histiocytes and emperipolesis of numerous lymphocytes and plasma cells confirming the diagnosis of RDD. Because the definitive diagnosis of RDD is always pathological, the clinical presentation plays a major role in widening the margin of differential diagnosis. Finally, surgical intervention is the first option to treat RDD with relatively satisfactory follow-up outcomes, and other adjuvant therapies optimize the prognosis.

Severe hyponatremia and bilateral sequential facial palsy: A case report.

Facial palsy (FP) is a known consequence of head trauma, manifesting either immediately at the time of injury or with delayed onset, typically occurring 2 days or more post-trauma. Unilateral FP is the more common presentation and is often attributed to partial or complete transection of facial nerves or delayed onset edema. Conversely, bilateral facial palsy is a rare occurrence, reported in only a small number of cases, accounting for approximately 3% of patients presenting with bilateral weakness. In this report, we present the case of a previously healthy 28-year-old female who suffered a closed head injury during the Beirut Port Blast. Four days following the incident, the patient exhibited right-sided peripheral FP, which was consistent with a right temporal bone fracture. Subsequently, on the fifth day, the right-sided FP worsened, accompanied by the development of new FP on the left side, characterized by sparing of the frontal region, indicating a central origin for the left-sided FP. Laboratory investigations revealed severe hypovolemic hyponatremia with a sodium level of 105 mmol/L. As isotonic saline fluid replacement was initiated, there was progressive improvement in the left-sided FP. The right-sided palsy also resolved gradually with the implementation of facial rehabilitation therapy. It is important to note that severe head trauma, particularly with a concussive injury, can lead to facial paralysis through various mechanisms. Furthermore, severe hyponatremia should be considered a potential cause of central facial palsy, particularly in the presence of bilateral facial involvement. A thorough evaluation is encompassing assessment of palsy patterns, comprehensive imaging studies, and metabolic investigations is crucial for accurate diagnosis and timely intervention, resulting in successful treatment.

Epilepsy surgery in a developing country (Lebanon): ten years experience and predictors of outcome.

We present our 10-year experience and preoperative predictors of outcome in 93 adults and children who underwent epilepsy surgery at the American University of Beirut. Presurgical evaluation included video-EEG monitoring, MRI, neuropsychological assessment with invasive monitoring, and other tests (PET, SPECT, Wada). Surgeries included temporal (54%), extratemporal (22%), and multilobar resections (13%), hemispherectomy (4%), vagal nerve stimulation (6%), and corpus callosotomy (1%). Mesial temporal sclerosis was the most common aetiology (37%). After resective surgery, 70% had Engel class I, 9% class II, 14% class III, and 7% class IV. The number of antiepileptic drugs before surgery was the only preoperative factor associated with Engel class I (p=0.005). Despite the presence of financial and philanthropic aid, many patients could not be operated on for financial reasons. We conclude that advanced epilepsy presurgical workups, surgical procedures, and favourable outcomes, comparable to those of developed countries, are achievable in developing countries, but that issues of financial coverage remain to be addressed.

Orofacial dyskinesia post resection of pineal gland tumor.

We reported a case of a 33-year-old lady who was diagnosed with a Pineal tumor and underwent craniotomy and gross total surgical resection of the mass through a right occipital transtentorial approach. Immediately upon extubation, the patient started to have persistent chewing-like movements typical of orofacial dyskinesia that resulted later in buccal mucosal injury and swelling of the lips. The movements spontaneously resolved after 3 days. The patient was not taking any medications that were known to induce such movements. Literature review showed that one of the possible mechanisms could be that the suddenly reduced melatonin level in the acute postoperative period leads to dysregulation of dopamine secretion in the nigrostriatal and limbic system causing these abnormal movements. To the best of our knowledge, this is the first such reported complication of orofacial dyskinesia post craniotomy for resection of the pineal tumor in humans.

Intracarotid propofol testing: a comparative study with amobarbital.

Twenty-five consecutive patients who underwent the Wada test using propofol as anesthetic were compared with 15 randomly selected patients who were tested using amobarbital. Time to verbal and nonverbal responses and time to motor power 3/5 did not differ between the two groups (P>0.05). The number of doses received by each patient and the percentage of patients needing more than one dose were significantly greater in the propofol group (P<0.005). Only one patient developed confusion, combativeness, and agitation. Despite the need for multiple doses, our patients had no residual drowsiness within 10 to 15 minutes of the propofol injection. This allowed us to perform the test on both sides on the same day separated only by 45 minutes. Propofol is an effective alternative to amobarbital in the Wada test, and may be used successfully in multiple repeated injections within the same test without significant residual sedation or significant adverse effects.

Quality of life after vagal nerve stimulator insertion.

AIM: Assess quality-of-life after vagal nerve stimulation and determine patient characteristics associated with improvement in quality-of-life. METHODS: Sixteen patients (11 children, 5 adults) who had vagal nerve stimulation at our center were studied. Quality-of-life was assessed pre- and post-vagal nerve stimulation using the Quality-of-Life in Childhood Epilepsy questionnaire for children and the Epilepsy Surgery Inventory-55 for adults. RESULTS: Sixteen patients who did not qualify for resective surgery were included; seven (43.75%) were males and 9 (56.25%) were females. Mean age at onset of seizures was 3.96 +/- 4.00 years and at surgery was 15.78 +/- 10.78. Follow-up time was 1.26 +/- 0.92 years. Fourteen patients (87.5%) were mentally retarded. Ten (62.5%) had cryptogenic etiology and 6 patients (37.5%) symptomatic etiology. Fifty percent had localization-related epilepsy. Six of 7 patients with generalized cryptogenic etiology (85.71%) had Lennox-Gastaut syndrome. Seizures dropped from 122.31 +/- 159.49 to 67.84 +/- 88.22 seizures/month. Seizure reduction (> 50%) correlated with improvement in total quality-of-life (p = 0.034). Post-vagal nerve stimulation, the total group scored significantly higher in the social domain (p = 0.039). In patients with localization-related epilepsy, significant improvements were detected in the social domain (p = 0.049) and in total quality-of-life (p = 0.042). CONCLUSION: Despite a diverse and small population size, we observed significant improvements in the social domain 1.26 years post-vagal nerve stimulation. In addition, there was an improvement in total quality-of-life amongst patients with partial seizures. Finally, seizure reduction was associated with quality-of-life improvement. Our results support previous studies from the West reporting improvement in quality-of-life following vagal nerve stimulation, contradict those studies that did not show such differences, and are the first coming from a developing country.

Prognostic significance of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation and isocitrate dehydrogenase-1 (IDH-1) mutation in glioblastoma multiforme patients: A single-center experience in the Middle East region.

OBJECTIVES: To determine the prevalence and prognostic value of MGMT promoter methylation and IDH1 mutation in glioblastoma multiforme (GBM) patients from the Middle East. PATIENTS AND METHODS: Records of patients diagnosed between 2003 and 2015 were reviewed. MGMT promoter methylation was measured using methylation-specific polymerase chain reaction and IDH-1 mutation was reported. The primary endpoint was overall survival (OS). RESULTS: A total of 110 patients were included. The median age was 51 years and 71 patients (64.5%) were males. The median diameter of GBM was 4.6 cm and 29 patients (26.4%) had multifocal disease. Gross total resection was achieved in 38 patients (24.9%). All patients received adjuvant radiation therapy, and 96 patients (91.4%) received concomitant temozolomide. At a median follow up of 13.6 months, the median OS was 17.2 months, and the OS at 1 and 2 years were 71.6% and 34.8%, respectively. On multivariate analysis, age at diagnosis (HR 1.019; P = 0.044) and multifocality (HR 2.373; P = 0.001) were the only independent prognostic variables. MGMT promoter methylation was found in 28.2% of patients but did not significantly correlate with survival (HR 1.160; P = 0.635). IDH-1 mutation was found in 10% of patients was associated with a non-significant trend for survival improvement (HR 0.502; P = 0.151). CONCLUSION: Patients with GBM from the Middle East have adequate survival outcomes when given the optimal treatment. In our patient population, MGMT promoter methylation did not seem to correlate with outcomes, but patients with IDH1 mutation had numerically higher survival outcomes.

Periosteal osteoblastoma of the calvaria mimicking a meningioma.

While osteoblastoma of the cranial vault is rare, the periosteal form of the tumor is highly unusual, with only one case reported in the English literature. We report on a 24-year-old woman presenting with headache and tinnitus. Magnetic resonance imaging of the brain showed an extra-axial temporal mass with findings that were suggestive of a meningioma. The mass was excised completely, and histological examination revealed a periosteal osteoblastoma arising from the inner surface of the temporal bone and adhering to the dura. The tumor was strongly positive for epithelial membrane antigen, a feature not previously described in osteoblastoma, and one that could lead to a mistaken diagnosis of metaplastic meningioma in a limited sample. A detailed literature review of 40 other reported cases of calvarial osteoblastoma is presented. Apart from being slightly more common in females, calvarial osteoblastoma is similar in all other respects to that arising at conventional skeletal sites. Accurate histological diagnosis of a calvarial osteoblastoma requires adequate sampling of the tumor, including its interface with adjacent structures. Correlation with the radiological findings is crucial for the diagnosis in most cases; however, it is not helpful in differentiating the rare intracranial periosteal variant from a meningioma.

Craniocervical Rosai-Dorfman Disease presentation: Case report and review of literature / Presentación de la enfermedad craneocervical de Rosai-Dorfman: reporte de caso y revisión de la literatura

Rosai Dorfman Disease (RDD) is a benign histiocytic lymphoproliferative disease that has variable presentations. The concurrent presentation of RDD in the spinal cord and brain parenchyma is an extremely rare entity. Here, we report another case of a 24-year-old gentleman who presented with a tuberculum sellae and bilateral cavernous extra-axial tumors extending to the subtemporal lobe and was found to have craniocervical lesions. Axillary lymph node biopsy was done showing markedly dilated sinuses filled with large histiocytes and emperipolesis of numerous lymphocytes and plasma cells confirming the diagnosis of RDD. Because the definitive diagnosis of RDD is always pathological, the clinical presentation plays a major role in widening the margin of differential diagnosis. Finally, surgical intervention is the first option to treat RDD with relatively satisfactory follow-up outcomes, and other adjuvant therapies optimize the prognosis (AU)

La enfermedad de Rosai-Dorfman (RDD) es una dolencia linfoproliferativa histiocítica benigna que tiene presentaciones variables. La presentación concurrente de RDD en la médula espinal y el parénquima cerebral es una entidad extremadamente rara. Aquí exponemos otro caso de un varón de 24 años que presentó un tuberculum sellae y tumores extraaxiales cavernosos bilaterales que se extendían al lóbulo subtemporal y en el que se encontraron lesiones craneocervicales. Se realizó biopsia del ganglio linfático axilar, que mostró senos marcadamente dilatados llenos de histiocitos de gran tamaño y emperipolesis de numerosos linfocitos y células plasmáticas, confirmando el diagnóstico de RDD. Dado que el diagnóstico definitivo de RDD siempre es patológico, la presentación clínica juega un papel importante en la ampliación del margen del diagnóstico diferencial. Finalmente, la intervención quirúrgica es la primera opción para tratar la RDD, con resultados de seguimiento relativamente satisfactorios, y otras terapias adyuvantes optimizan el pronóstico (AU)

Sub-second dopamine detection in human striatum.

Fast-scan cyclic voltammetry at carbon fiber microelectrodes allows rapid (sub-second) measurements of dopamine release in behaving animals. Herein, we report the modification of existing technology and demonstrate the feasibility of making sub-second measurements of dopamine release in the caudate nucleus of a human subject during brain surgery. First, we describe the modification of our electrodes that allow for measurements to be made in a human brain. Next, we demonstrate in vitro and in vivo, that our modified electrodes can measure stimulated dopamine release in a rat brain equivalently to previously determined rodent electrodes. Finally, we demonstrate acute measurements of dopamine release in the caudate of a human patient during DBS electrode implantation surgery. The data generated are highly amenable for future work investigating the relationship between dopamine levels and important decision variables in human decision-making tasks.

Quality of life after surgery for intractable partial epilepsy in children: a cohort study with controls.

PURPOSE: Investigate if quality of life (QOL) normalizes on long-term follow-up after surgery for partial epilepsy in children. METHODS: This is a cohort study with controls in which a consecutive cohort of nineteen 2-14-year-old children who underwent focal resections for intractable partial seizures between 1996 and 2006, were matched with 19 non-surgery intractable partial epilepsy patients, and with 19 healthy subjects. The two epilepsy groups were matched for age, sex, socio-economic status (SES), cognitive level, seizure type, and seizure frequency. The healthy group was matched with the two epilepsy groups for age, sex, SES, and cognitive level. QOL was assessed using the QOLCE (Quality of Life in Childhood Epilepsy Questionnaire). RESULTS: In the surgery group (follow-up 3.84+/-2.26 years), 78.9% had Engel class-I versus 21.1% in non-surgery (p=0.01) (follow-up 3.44+/-2.95 years). Surgery patients were similar to healthy subjects in the social, emotional, cognitive, behavioral, and overall QOL (p>0.05) but had lower scores in the total QOL, physical, and health domains (p<0.05). Surgery patients scored better than non-surgery in the behavioral domain and the HASES (Hague Side Effects Scale) score (p<0.05). Non-surgery patients scored worse than healthy in total QOL, physical, behavioral, health, and overall QOL (p<0.05). IQ, HASS (Hague Seizure Severity Scale), and HASES scores were positively associated with total QOL score (p<0.05). Subgroup analysis on seizure-free surgery patients showed that they did not differ from healthy subjects in any of QOL domains (p>0.05, power>0.8). CONCLUSION: Our data indicate that epilepsy surgery for partial seizures in children is associated with better QOL as compared to children with intractable epilepsy who are not operated on, and suggest that in those who achieve seizure freedom normal QOL may at least potentially be possible.

Surgical outcome for focal cortical dysplasia: an analysis of recent surgical series.

OBJECT: Focal cortical dysplasia (FCD) is an important cause of intractable epilepsy and is at times treatable by resection. The now widespread use of MR imaging and recent advancement of functional imaging have increased the number of patients undergoing surgical treatment for FCD. The objective of this review is to critically examine and to provide a summary of surgical series on FCD published since 2000. METHODS: Studies concerning surgery for FCD were identified from MEDLINE and references of selected articles and book chapters. Data from these included studies were summarized and analyzed to identify factors correlated with seizure outcome. RESULTS: Sixteen studies were identified, and 469 patients met our selection criteria. Seizure-free outcome at 1-year postoperatively was achieved in 59.7% of the patients. Children and adults were equally likely to benefit from the surgery. Complete resection (OR 13.7, 95% CI 6.68-28.1; p < 0.0001) and temporal location (OR 2.15, 95% CI 1.26-3.69; p = 0.0073) were two positive prognostic indicators of seizure-free outcome. Utilization of invasive monitoring did not affect the chance of seizure remission, but firm conclusions could not be drawn because patients were not randomized. CONCLUSIONS: The advancement of modern imaging has transformed the process of surgical candidate selection for partial epilepsy due to FCD. Patients from recent surgical series were more homogeneous in their clinical presentations and might represent FCD as an independent pathological entity. This likely explained the improved surgical outcome for this group of patients. These reports also documented the increased utilization of functional imaging, but their efficacy needs to be verified with further studies.

Deep brain stimulation as a mode of treatment of early onset pantothenate kinase-associated neurodegeneration.

We report a case of a young girl with early onset pantothenate kinase-kssociated neurodegeneration (PKAN) whose initial clinical manifestation was ataxia at the age of 2.5 years. Subsequently the patient presented to us with refractory severe dystonia resulting in essentially complete loss of motor control. She had a mutation in PANK2 gene consisting of an aminoacid change of Alanine to Valine in exon 5 (A382V). After Globus Pallidus deep brain stimulation (DBS) at the age of 11 years, the patient regained useful motor function and speech with a marked decrease in the severity of the dystonia. The patient's condition gradually returned to her pre-DBS status when the device had to be removed 3 months later due to infection. Our case is the sixth case with classical PKAN that was treated by Globus Pallidus stimulation, the fifth one to have a favorable response to it and the only one in whom response was proven by the inadvertent removal of the DBS device due to infection. In addition, our case had a novel mutation and novel clinical features (onset with ataxia, occurrence of early seizure activity) on top of her other symptoms that were otherwise typical of early onset disease.

Functional recovery following resection of an epileptogenic focus in the motor hand area.

Despite recent technical advances, the surgical management of epileptic foci in the primary motor area, especially the motor hand area, continues to represent a significant challenge because of the risk of permanent neurological deficit. We describe the case of a 19-year-old woman with intractable epilepsy secondary to cortical dysplasia of the motor hand area who was treated with surgical resection. The patient showed immediate complete motor deficit, started improving at around 1 month of follow-up, and had a substantial recovery at 6 months, with only mild limitations of fine hand movements. At the latest follow-up (3 years), she remained seizure-free. This case demonstrates that, in selected cases, resections in the primary motor cortex can be performed and that the immediately observed motor deficit is transient. We discuss the proposed mechanisms for recovery based on available data from experimental animal and clinical human studies.

Normalization of quality of life three years after temporal lobectomy: a controlled study.

PURPOSE: The goal of epilepsy surgery is not merely to control previously intractable seizures, but also to improve quality of life (QOL). Our goals were to assess, in our Middle Eastern population, the QOL of adults with temporal lobe epilepsy (TLE) 3 years after temporal lobectomy as compared with matched TLE patients who did not undergo surgery and with healthy individuals in the same community. METHODS: Twenty consecutive TLE patients who underwent temporal lobectomy 3 years previously were matched in the following variables: age, sex, seizure frequency, seizure duration, age at onset of epilepsy, duration of epilepsy, and number of medications, with 17 TLE patients who underwent the presurgical evaluation and subsequent optimization of medical therapy but did not undergo surgery. They were also matched for age, sex, educational level, income, and residence with 20 healthy individuals. All groups were interviewed by using the ESI-55 questionnaire. RESULTS: Compared with the nonsurgery group, QOL was significantly better in the surgery group (85% seizure free) in the well-being, functioning, and role-limitation domains. QOL was similar in the surgery and healthy control groups in all domains and scales. The nonsurgery group scored significantly lower than healthy controls in the functioning and role-limitation domains. CONCLUSIONS: Intractable TLE was associated with marked impairments in QOL despite continued attempts to optimize medical therapy. Three years after temporal lobectomy QOL in our patient population achieved levels similar to those of matched healthy individuals. To our knowledge, this is the first study to report normalization of QOL after temporal lobectomy, in any population.

Pattern-induced partial seizures with repetitive affectionate kissing: an unusual manifestation of right temporal lobe epilepsy.

We report a case of recurrent partial seizures that were often precipitated by looking up a flight of stairs and included spitting as well as repetitive affectionate kissing automatisms. These seizures were shown by long-term video/EEG monitoring to be of right temporal origin and completely subsided after right temporal lobectomy. This case is unique because: (1) The patient had partial rather than primarily generalized pattern-induced seizures. (2) Affectionate kissing automatisms were a part of his partial seizures and, to our knowledge, have not been reported in the literature before.

Effects of epilepsy surgery on quality of life: a controlled study in a Middle Eastern population.

The purpose of this study was to investigate which areas of quality of life (QOL) change after epilepsy surgery and generate QOL data specific to the Lebanese population. The QOL of 20 consecutive patients 1 year after surgery was compared (using the ESI-55 scale) with that of 20 matched patients who underwent the same presurgical evaluation, but no surgery. Overall QOL improved in both groups, but was greater in the surgery group (85% seizure free as compared to 0% in nonsurgery group). Significant differences were noted within the "well-being" domain including health perception (5/9 items), energy-fatigue (2/4), and emotional well-being (2/5). Differences were less common in the "functioning" domain including physical (1/10 items), social (1/2), and cognitive (0/5) functioning scales, and in the role limitation domain (1/17 items). Our patients experienced, 1 year after epilepsy surgery, improvements similar to those reported in Western populations after a similar period: they had marked improvements in overall QOL, health perception, well-being, and cognitive functioning areas. They had less remarkable improvements in social functioning and role limitation areas.