Damianos E. Sakas

Indomethacin and acetylsalicylic acid block neurogenic plasma protein extravasation in rat dura mater

Leakage of 125I-bovine serum albumin was measured in rat dura mater, conjunctiva, eyelid and lip, after unilateral electrical stimulation of the trigeminal ganglion. In one animal, 99Tc-human serum albumin leakage was imaged in ipsilateral facial tissues. Pretreatment with indomethacin 1 mg/kg i.p. decreased leakage in dura mater but not in extracranial tissues. When extravasation was expressed as a ratio of stimulated to unstimulated sides, indomethacin 1 mg/kg, or acetylsalicylic acid 50 mg/kg decreased this ratio from 1.80 to 1.27 (P less than 0.01) or from 1.84 to 1.21 (P less than 0.01), respectively. Dexamethasone (1 mg/kg i.p. tid X 1 day) caused only a very small decrease. Only large doses of indomethacin (10 mg/kg) or acetylsalicylic acid (50 mg/kg) reduced substance P (SP)-induced leakage in the dura. The latter results suggest that both drugs block plasma extravasation by acting on neuropeptides-induced changes in vascular permeability and/or smooth muscle contractility. However, inhibition of SP release from sensory axons cannot be excluded at concentrations which block neurogenic plasma extravasation but not SP-induced plasma leakage. Together, these results provide a possible mechanism for the therapeutic effects of indomethacin and acetylsalicylic acid in headache.

Surgical and hardware complications of deep brain stimulation. A seven-year experience and review of the literature

PurposeDeep brain stimulation (DBS) has been established as a safe and efficient method for the treatment of various movement disorders. As the emerging applications continue to expand and more centers become eligible for the procedure, complication rates and complication avoidance become increasingly important. Our aim was to report the DBS-related complication in our department over the last 7xa0years, compare our rates with those reported in the literature, and highlight those practices that will aid complications avoidance.Patients and methodsSince 2003, 106 patients underwent DBS for various pathologies in our department. There were 38 (36%) females and 68 (64%) males with a mean age of 57xa0years. Preoperative diagnoses included Parkinson’s disease (nu2009=u200988), dystonia (nu2009=u200912), tremor (nu2009=u20093), epilepsy (nu2009=u20091), obsessive-compulsive disorder (nu2009=u20091), and central pain syndrome (nu2009=u20091). Surgical and hardware-related complications, their treatment, and outcome were recorded and compared with those reported in the literature.ResultsThere were 12 procedure-related complications (11.3% of patients, 5.7% of the procedures). These included death (nu2009=u20091), aborted procedure (nu2009=u20091), postoperative respiratory distress (nu2009=u20093), intracranial hemorrhage (nu2009=u20092), epilepsy (nu2009=u20091), postoperative confusion or agitation (nu2009=u20093), and malignant neuroleptic syndrome (nu2009=u20091). Hardware-related complications presented in 4.3% of the procedures and included infection (five patients, 4.7%), electrode breakage (0.94%), lead migration or misplacement (0.94%), and stricture formation (two patients, 1.9%).ConclusionsComplication rates after DBS surgery remain low, proving that DBS is not only effective but also safe. Certain strategies do exist in order to minimize complications.

Outcome in 1,000 head injury hospital admissions: the Athens head trauma registry

BACKGROUNDnThe aim of this study was to establish a head trauma registry to (a) examine demographics, etiology, severity, clinical course, and outcome; (b) compare results with previous published series; (c) identify causes of bad outcomes; and (d) propose methods to improve therapy and prognosis.nnnMETHODSnThe following data were collected on 1,000 consecutive victims with head injury over 14 years of age admitted during a 4-year period: demographic characteristics, cause of injury, clinical variables, neuroimaging, therapy data, and outcome in 6 months.nnnRESULTSnSeventy-four percent were men, and mean age was 43 years. Seventy-one percent suffered injuries due to road crashes, 14% due to alcohol, and 2% due to substances. The secondary transfer rate was 49%. For severe injuries, the time intervals from incident to hospital and subsequently to neurosurgical unit were 35 minutes and 4 hours, respectively. In 65% and 72% of cases, there was no record of preresuscitation hypoxia or hypotension, respectively, whereas suspected or definite episodes of hypoxia and hypotension were 27% and 13%, respectively. Most cases were mild trauma (63%), the remaining were severe (26%) and moderate (11%) injuries. Severe systemic trauma coexisted in 18%. Cranial surgery rate was 19% and it increased to 39% in severe trauma. The 6-month overall good outcome was 71%, with lower rates in moderate (58%) and severe (24%) injuries.nnnCONCLUSIONSnThe organization of Greeces first head injury registry offered an important preliminary core data concerning brain trauma etiology, management, and long-term outcome.

Interobserver variability, and visual and quantitative parameters of 123 I-FP-CIT SPECT (DaTSCAN) studies

ObjectiveTo evaluate the degree of interobserver agreement in the visual interpretation of 123I-FP-CIT studies and to investigate for potential associations between visual and semi-quantitative parameters.MethodsEighty-nine 123I-FP-CIT studies were blindly reviewed by 3 independent observers: a consultant, a resident doctor and a radiographer. They classified every study as either “normal” or “abnormal” and assigned visual 123I-FP-CIT uptake scores (2: normal, 1: reduced and 0: no uptake) in basal ganglia nuclei (right and left putamina and caudate nuclei) on every scan. Striatal 123I-FP-CIT binding ratios were calculated using crescent-ROI software. The interobserver agreement for the interpretation of studies and for visual score assignment was evaluated by means of κ statistics. We investigated for associations of binding ratios with visual scores and clinical parameters; patients’ clinical diagnoses served as the reference standard.ResultsThere was excellent interobserver agreement (κ 0.89–0.93) in classifying studies as “normal” or “abnormal” and fine agreement in assignment of visual scores (κ 0.71–0.80 for putamina and 0.50–0.79 for caudate nuclei). Nuclei with scores of 1 and 0 showed significantly reduced binding ratios (about 30 and 50%, respectively) compared with the nuclei scored as 2. ROC analysis indicated the optimal cutoff point of striatal binding ratio at 3.8 (sensitivity 98.5%, specificity 95%) for the detection of parkinsonian syndromes. Striatal binding ratios were negatively associated with age in normal subjects and disease duration in Parkinson’s disease patients.ConclusionVisual interpretation of 123I-FP-CIT studies showed very good interobserver agreement. We found significant associations among visual, semi-quantitative and clinical parameters.

PlGF and sVEGFR-1 in chronic subdural hematoma: implications for hematoma development

OBJECTnA considerable body of evidence indicates that inflammation and angiogenesis play a significant role in the development and progression of chronic subdural hematoma (CSDH). While various experimental and clinical studies have implicated placental growth factor (PlGF) in the processes that underpin pathological angiogenesis, no study has thus far investigated its expression in CSDH. The actions of PlGF and its related proangiogenic vascular endothelial growth factor (VEGF) are antagonized by a high-affinity soluble receptor, namely soluble VEGF receptor-1 (sVEGFR-1), and thus the ratio between sVEGFR-1 and angiogenic factors provides an index of angiogenic capacity.nnnMETHODSnIn the present study, using an automated electrochemiluminescence assay, levels of PlGF and sVEGFR-1 were quantified in serum and hematoma fluid obtained in 16 patients with CSDH.nnnRESULTSnLevels of PlGF and sVEGFR-1 were significantly higher in hematoma fluid than in serum (p < 0.0001). In serum, levels of sVEGFR-1 were higher than those of PlGF (p < 0.0001), whereas in hematoma fluid this difference was not apparent. Furthermore, the ratio of sVEGFR-1 to PlGF was significantly lower in hematoma fluid than in serum (p < 0.0001).nnnCONCLUSIONSnGiven previous evidence indicating a role for PlGF in promoting angiogenesis, inflammatory cell chemotaxis, and stimulation, as well as its ability to amplify VEGF-driven signaling under conditions favoring pathological angiogenesis, enhanced expression of PlGF in hematoma fluid suggests the involvement of this factor in the mechanisms of inflammation and angiogenesis in CSDH. Furthermore, a reduced ratio of sVEGFR-1 to PlGF in hematoma fluid is consistent with the proangiogenic capacity of CSDH. Future studies are warranted to clarify the precise role of PlGF and sVEGFR-1 in CSDH.

Paroxysmal otalgia due to compression of the intermediate nerve: a distinct syndrome of neurovascular conflict confirmed by neuroimaging. Case report.

The authors present the case of a 52-year-old female patient with a 6-year history of intractable paroxysmal otalgia. Preoperative magnetic resonance (MR) angiography demonstrated an anterior inferior cerebellar artery loop compressing the intermediate nerve in the seventh/eighth cranial nerve complex inside the internal auditory canal. The pain resolved completely after a microvascular decompression via a retromastoid craniotomy. To the best of the authors knowledge, the combined neuroimaging and intraoperative findings of this case provide a unique demonstration that vascular compression of the intermediate nerve can be the exclusive cause of paroxysmal otalgia. Magnetic resonance imaging and MR angiography can establish the causative mechanism and distinguish this otalgia due to vascular compression of the intermediate nerve from other pain syndromes that are designated as geniculate neuralgia (GN). The present case indicates that intermediate nerve neuralgia is a distinct syndrome of neurovascular conflict and a variant of GN. The causative classification of GN should be reexamined with the use of advanced MR imaging.

The perfluorocarbon fluoromethyloadamantane offers cerebral protection in a model of isovolemic hemodilution in rabbits.

Background and Purpose Perfluorocarbons (PFCs) are considered promising cerebral protection agents because they could combine the beneficial effects of decreased blood viscosity with enhanced oxygen-carrying capacity and oxygen tissue delivery, but trials of PFCs as hemodilutants have been very limited. We evaluated fluoromethyloadamantane (FMA), a new perfluorocarbon compound, as an isovolemic hemodilutant and compared it with low-molecular-weight dextran 40 (D40) and a control group. Methods Through a transorbital craniectomy, the internal carotid, anterior, and middle cerebral arteries were coagulated to create a cerebral infarction in anesthetized, mechanically ventilated rabbits. No other experimental procedure was performed in control animals. In the two other groups, hemodilution was commenced 30 minutes after the arterial occlusion with either D40 or FMA. Hemodynamic parameters and brain and systemic temperature were monitored throughout the experiments. All animals were killed 6 hours after the arterial occlusion. Results Hemodynamic and metabolic parameters and blood oxygen content were not affected by the infusion of either FMA or D40. Brain and systemic temperature remained constant. The ratio of infarct volume to the hemispheric volume was 19.6±3.7% in the FMA group (n=17), 19.9±4.6% in the D40 group (n=16), and 40.3±5.7% in the control group (n=17). The difference in infarct volume of both FMA and D40 animals compared with controls was statistically significant (P < .01) when tested with Students t test. There was no significant difference between FMA and D40 groups. Conclusions These results suggest that FMA has cerebral protective properties and should be purified, optimized, and further tested experimentally to develop a stable, efficient, and safe oxygen carrier, potentially suitable for clinical trials.

Prognostic value of time-related Glasgow coma scale components in severe traumatic brain injury: a prospective evaluation with respect to 1-year survival and functional outcome.

The severity of traumatic brain injury (TBI) is determined by many variables, the complexity of which has made prediction of functional outcome an elusive target. To evaluate whether the three components of the Glasgow Coma Scale (GCS) and their alterations over time can serve as predictors of functional outcome after a severe TBI at 12 months after the TBI insult, we carried out a prospective study of patients with severe TBI. Seventy patients were initially enrolled. Data were retrieved from the emergency department records and the patients’ intensive care unit, neurosurgical, and rehabilitation unit records. All patients underwent follow-up at 3, 6, and 12 months after injury. GCS components were evaluated on the day of injury and 2 weeks after injury. Functional outcome was estimated using the Glasgow Outcome Scale and the Functional Independence Measure motor scale. It was evaluated during rehabilitation and at 12 months after injury. Fifty-one patients were alive and followed up until 12 months. Logistic regression and receiver–operator characteristic curve analyses were carried out. In terms of functional outcome at 12 months, only GCS on day 15 was found to be a prognostic factor, with all its subscales being related to outcome 12 months later, whereas a higher GCS score on day 15 was also related to survival. A higher motor and verbal response on day 15 was strongly associated with a patient’s functional independence, whereby the motor response was a better predictor. The GCS motor score 2 weeks after injury was statistically significantly associated with the 12-month functional outcome in TBI survivors. Motor response was the most useful predictor among the GCS components with respect to the long-term functional outcome in patients with severe TBI. Der Schweregrad von Schädel-Hirn-Traumata (SHT) hängt von verschiedenen Variablen ab, deren Komplexität die funktionelle Outcome-Vorhersage erschwert. Um zu evaluieren, ob die drei Komponenten der Glasgow-Komaskala (GCS) und ihre Änderungen im Laufe der Zeit als Prädiktoren des funktionellen Outcomes nach schwerem SHT nach 12 Monaten eingesetzt werden können, haben wir eine prospektive Studie mit Patienten mit schwerem SHT durchgeführt. In der Studie wurden eingangs 70 Patienten eingeschlossen. Hinzugezogen wurden Daten aus den Akten der Notfallambulanz sowie aus den Akten der Intensivstation, Neurochirurgie und der Rehazentren, in denen die Patienten behandelt wurden. Alle Patienten unterzogen sich nach jeweils 3, 6 und 12 Monaten nach der Verletzung einer Nachuntersuchung. GCS-Komponenten wurden am Tag der Verletzung sowie zwei Wochen danach evaluiert. Das funktionelle Outcome wurde mittels Glasgow-Outcome-Skala (GOS) und Motorik-Subskala des Maßes der funktionellen Unabhängigkeit geschätzt. Es wurde während der Rehabilitation und 12 Monate nach der Verletzung evaluiert. Die 51 überlebenden Patienten wurden bis 12 Monate nach der Verletzung nachuntersucht. Mittels logistischer Regression und Receiver-Operating Characteristic-Kurve wurden Analysen durchgeführt. Was das funktionelle Outcome nach 12 Monaten anbelangt, so erwies sich nur die GCS an Tag 15 als prognostischer Faktor. Alle ihre Subskalen bezogen sich auf das Outcome 12 Monate später, während ein höherer GCS-Score an Tag 15 sich auch auf das Überleben bezog. Ein stärkeres motorisches und verbales Ansprechen an Tag 15 wurde vor allem auf die funktionelle Unabhängigkeit von Patienten zurückgeführt. Das motorische Ansprechen hingegen war ein besserer Prädiktor. Der GCS Motorik-Score wurde zwei Wochen nach der Verletzung auf statistisch signifikante Weise mit dem funktionellen Outcome von SHT-Überlebenden nach 12 Monaten in Verbindung gebracht. Das motorische Ansprechen war der brauchbarste Prädiktor unter den GCS-Komponenten hinsichtlich des langfristigen funktionellen Outcomes bei Patienten mit schwerem SHT. La gravedad de una lesión cerebral traumática (LCT) se determina mediante una serie de variables, cuya complejidad ha hecho que la predicción de los resultados funcionales se haya convertido en un objetivo impreciso. Con el fin de evaluar si los tres componentes de la Escala de Coma de Glasgow (ECG) y sus alteraciones a lo largo del tiempo pueden funcionar como indicadores de los resultados funcionales tras una LCT severa 12 meses después de producirse la lesión, se llevó a cabo un estudio prospectivo sobre pacientes con LCT severa. En el estudio participaron setenta pacientes, cuyos datos fueron proporcionados por los historiales de la unidad de urgencias y de cuidados intensivos de los mismos, así como por los historiales de la unidad de rehabilitación y neurocirugía. Todos los pacientes se sometieron a una prueba de seguimiento 3, 6 y 12 meses tras haber sufrido la lesión. Los componentes de la ECG fueron evaluados el mismo día en que se produjo la lesión y 2 semanas más tarde. Los resultados funcionales se estimaron mediante la Escala de Coma de Glasgow y la escala motora de Medida de Independencia Funcional, y se evaluaron durante la rehabilitación y 12 meses después de producirse la lesión. Cincuenta y un pacientes sobrevivieron pasados los 12 meses. Se llevaron a cabo análisis de regresión logística y análisis de la curva característica receptor-operador. En términos de los resultados funcionales a los 12 meses, solamente el día 15 de la ECG presentó un factor pronóstico, cuyas subescalas mostraron una relación con los resultados 12 meses más tarde, mientras que la obtención de una puntuación más elevada en la ECG en el día 15 también estaba relacionada con la supervivencia. La mayor respuesta motora y verbal del día 15 estaba altamente asociada con la independencia funcional del paciente, por lo que se confirmó que la respuesta motora funcionaba mejor como indicador. La puntuación motora de la ECG dos semanas después de producirse la lesión se vio significativamente estadísticamente asociada con los resultados funcionales que presentaban los supervivientes de LCT tras 12 meses. La respuesta motora resultó ser el indicador más útil de entre los componentes de la ECG con respecto a los resultados funcionales a largo plazo en pacientes con LCT severa. La gravité de la lésion cérébrale traumatique (LCT) est déterminée par de nombreux facteurs, dont la complexité fait de la prédiction du résultat fonctionnel un objectif difficile à atteindre. Afin dévaluer si les trois composantes de léchelle de coma de Glasgow (Glasgow Coma Scale, GCS) et leurs modifications au fil du temps peuvent servir de prédicteurs du résultat fonctionnel 12 mois après une LCT sévère, nous avons réalisé une étude prospective de patients affectés par ce type de lésion. Soixante-dix patients ont été recrutés au départ. Les données ont été extraites des dossiers des services durgence et des dossiers des patients auprès des unités de soins intensifs, de neurochirurgie et de rééducation. Tous les patients ont été suivis à 3, 6 et 12 mois après la lésion. Les composantes GCS ont été évaluées le jour de laccident et 2 semaines après. Le résultat fonctionnel a été estimé en utilisant l’échelle Glasgow Outcome Scale et léchelle motrice de mesure de lindépendance fonctionnelle. Les patients ont été évalués lors de la rééducation et 12 mois après l’accident. Cinquante et un patients étaient encore vivants et suivis au bout de 12 mois. Des analyses par régression logistique et de courbe caractéristique récepteur-opérateur ont été effectuées. En termes de résultat fonctionnel à 12 mois, seule la GCS au jour 15 s’est avérée être un facteur pronostique, avec toutes ses sous-échelles liées au résultat 12 mois plus tard, tandis quun score GCS plus élevé au jour 15 a également été associé à la survie. Une réponse motrice et verbale plus importante au jour 15 a été fortement associée à lindépendance fonctionnelle dun patient, pour laquelle la réponse motrice constituait un meilleur prédicteur. Le score moteur GCS 2 semaines après la lésion présentait une association significative avec le résultat fonctionnel après 12 mois chez les survivants d’une LCT. La réponse motrice était le facteur prédictif le plus utile parmi les composantes GCS en ce qui concerne le résultat fonctionnel à long terme chez les patients victimes dune LCT sévère.

Predictors of long-term outcome in an elderly group after laminectomy for lumbar stenosis.

OBJECTnThis is a retrospective long-term outcome study of results after laminectomy for lumbar spinal stenosis in an elderly group of patients. The study was designed to evaluate possible demographic, comorbidity, and clinical prognosticators for pain reduction and functional improvement in this population. Because the assessment of functional outcome in the elderly is complicated by several specific factors, the use of outcome measurement parameters should be revised and refined. Moreover, despite numerous relevant studies, the results of various techniques remain equivocal, particularly among the elderly, which renders the implementation of focused studies necessary. New data could be used to refine patient selection and choice of technique to improve prognosis.nnnMETHODSnDuring a 5-year period, lumbar laminectomies were performed in 182 elderly patients. Of these 182, 125 patients (68.8%) were followed up for a mean period of 60.8 months. The outcome was assessed by means of pain visual analog scale (VAS) pain score, Oswestry Disability Index (ODI), and patient satisfaction questionnaire, and results were correlated to demographic (age, sex), comorbidity (Charlson Comorbidity Index, diabetes, depression, and history of lumbar spine surgery), and clinical (main preoperative complaint, preoperative VAS score, and ODI) factors.nnnRESULTSnIn terms of the VAS score, 106 patients (84.8%) exhibited improvement at follow-up. The corresponding ODI improvement rate was 69.6% (87 patients). The mean VAS and ODI differences were 5.1 and 29.1, respectively. One hundred two patients (81.6%) were satisfied with the results of the operation. Univariate analysis for possible prognostic factors revealed the significant influence of low-back pain on VAS score (p = 0.024) and ODI (p < 0.001) not improving, while the ODI was also affected by sex (females had a poorer outcome [p = 0.019]). In contrast, patient satisfaction was not related to any of the preoperative parameters recorded; nevertheless, it was strongly related to all functional measurements on follow-up.nnnCONCLUSIONSnConsidering the methodological issues of such studies, particularly in elderly patients, the authors conclude that the ODI is more sensitive than the VAS score in assessing prognostic value and that patient satisfaction is difficult to prognosticate, underscoring the particularities that this population presents regarding functionality assessment. Considering the prognostic value of preoperative factors, a negative influence of low-back pain and female sex is reported.

Restoration of erect posture in idiopathic camptocormia by electrical stimulation of the globus pallidus internus

The authors report on 2 young patients who developed drug-resistant idiopathic dystonic camptocormia (bent spine) and were treated successfully by deep brain stimulation (DBS) of the globus pallidus internus (GPi). The first patient, a 26-year-old woman, suffered for 3 years from such severe camptocormia that she became unable to walk and was confined to bed or a wheelchair. The second patient, a 21-year-old man, suffered for 6 months from less severe camptocormia; he was able to walk but only for short distances with a very bent spine, the arms in a parallel position to the legs, and the hands almost approaching the floor to potentially support him in case of a forward fall. Within a few days following DBS, both patients experienced marked clinical improvement. At most recent follow-up (44 months in one case and 42 in the other), the patients ability to walk upright remained normal. Similar findings have only been reported recently in a few cases of camptocormia secondary to Parkinson disease or tardive dyskinesia. On the basis of the experience of these 2 idiopathic cases and the previously reported cases of secondary camptocormia with a favorable response to GPi DBS, the authors postulate that specific patterns of oscillatory activity in the GPi are vital for the maintenance of erect posture and the adoption of bipedal walking by humans.