Exploring the Clinical and Genetic Landscape of Angelman Syndrome: Patient-Reported Insights from an Italian Registry.

Background: The Angelman Syndrome Registry (RISA) was developed as a retrospective study with the following objectives: to evaluate the clinical history of individuals with Angelman Syndrome (AS) in Italy and compare it with the existing literature; to investigate the feasibility of gathering data by directly involving participants in the data collection process; and to explore the relationship between different symptoms and genotypes. Methods: Established in 2018, RISA enrolled a total of 82 participants, with 62 (75.6%) providing complete data. Demographic, clinical, and genetic information was collected using electronic case report forms. Descriptive statistics characterized the sample, while associations between genotype and clinical characteristics were examined. Results: Descriptive analysis revealed a median participant age of 8.0 years, with males comprising 48.8% of the sample. Deletion (58.1%) was the most common genotype. The majority (82.2%) experienced epilepsy, with seizures typically onset before 3 years of age. Most patients (86.2%) required multiple anti-epileptic drugs for control, with generalized tonic-clonic seizures and atypical absence seizures being most prevalent. The deletion group exhibited more severe developmental delays and a trend towards higher seizure severity. Sleep problems affected 69.4% of participants, characterized by difficulties in sleep onset and maintenance. Conclusions: This study offers valuable insights into the clinical history and genetic characteristics of AS in Italy, consistent with the prior literature. Additionally, it underscores the efficacy of patient registries in capturing comprehensive data on rare diseases such as AS, highlighting their potential to advance research and enhance patient care.

Cerebral autoregulation in traumatic brain injury: ultra-low-frequency pressure reactivity index and intracranial pressure across age groups.

BACKGROUND: The ultra-low-frequency pressure reactivity index (UL-PRx) has been established as a surrogate method for bedside estimation of cerebral autoregulation (CA). Although this index has been shown to be a predictor of outcome in adult and pediatric patients with traumatic brain injury (TBI), a comprehensive evaluation of low sampling rate data collection (0.0033 Hz averaged over 5 min) on cerebrovascular reactivity has never been performed. OBJECTIVE: To evaluate the performance and predictive power of the UL-PRx for 12-month outcome measures, alongside all International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) models and in different age groups. To investigate the potential for optimal cerebral perfusion pressure (CPPopt). METHODS: Demographic data, IMPACT variables, in-hospital mortality, and Glasgow Outcome Scale Extended (GOSE) at 12 months were extracted. Filtering and processing of the time series and creation of the indices (cerebral intracranial pressure (ICP), cerebral perfusion pressure (CPP), UL-PRx, and deltaCPPopt (ΔCPPopt and CPPopt-CPP)) were performed using an in-house algorithm. Physiological parameters were assessed as follows: mean index value, % time above threshold, and mean hourly dose above threshold. RESULTS: A total of 263 TBI patients were included: pediatric (17.5% aged ≤ 16 y) and adult (60.5% aged > 16 and < 70 y and 22.0% ≥ 70 y, respectively) patients. In-hospital and 12-month mortality were 25.9% and 32.7%, respectively, and 60.0% of patients had an unfavorable outcome at 12 months (GOSE). On univariate analysis, ICP, CPP, UL-PRx, and ΔCPPopt were associated with 12-month outcomes. The cutoff of ~ 20-22 for mean ICP and of ~ 0.30 for mean UL-PRx were confirmed in all age groups, except in patients older than 70 years. Mean UL-PRx remained significantly associated with 12-month outcomes even after adjustment for IMPACT models. This association was confirmed in all age groups. UL-PRx resulted associate with CPPopt. CONCLUSIONS: The study highlights UL-PRx as a tool for assessing CA and valuable outcome predictor for TBI patients. The results emphasize the potential clinical utility of the UL-PRx and its adaptability across different age groups, even after adjustment for IMPACT models. Furthermore, the correlation between UL-PRx and CPPopt suggests the potential for more targeted treatment strategies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05043545, principal investigator Paolo Gritti, date of registration 2021.08.21.

Clinical frailty scale as a predictor of outcome in elderly patients affected by moderate or severe traumatic brain injury.

Background: Older age is a well-known risk factor for unfavorable outcome in traumatic brain injury (TBI). However, many older people with TBI respond well to aggressive treatments, suggesting that chronological age and TBI severity alone may be inadequate prognostic markers. Frailty is an age-related homeostatic imbalance of loss of physiologic and cognitive reserve resulting in both limitation in autonomy of activities of daily living and vulnerability to adverse events. We hypothesized that frailty would be associated with 6-month adverse functional outcome in older people affected by moderate or severe TBI. Methods: This was a single-center prospective observational study. We enrolled consecutive patients aged ≥65 years after TBI with Glasgow Coma Scale ≤13 and admitted to our Neurosurgical Intensive Care Unit. Frailty was evaluated by Clinical Frailty Scale (CFS). Relationships between TBI severity, frailty and extended Glasgow Outcome Scale (GOSE) at 6-month were evaluated. Results: Sixty patients were studied, 65% were males, their age was 76 years (IQR 70-80) and their admission GCS was 8 (IQR 6-11) with a GCS motor score of 5 (IQR 4-5). Twenty eight were vulnerable-frail (defined as CFS ≥ 4). Vulnerable-frail patients showed greater 6-month mortality and unfavorable outcome compared to non-frail [87% vs. 30% OR and 95% CI: 15.7 (3.9-55.2), p < 0.0001 and 92% vs. 51% OR and 95% CI: 9.9 (2.1-46.3), p = 0.002]. In univariate analysis patients with unfavorable outcome were more frequently male and vulnerable-frail, had a higher prevalence of pre-existing neurodegenerative disease, abnormal pupil, lower GCS and had worst CT scan characteristics. At multivariate analysis, only CFS ≥ 4 and traumatic subarachnoid hemorrhage remained associated to 6-month outcome. Conclusion: Frailty was associated with 6 month-outcome, suggesting that the pre-injury functional status could represent an additional indicator to stratify patient's severity and to predict outcome.

Evaluation and application of ultra-low-frequency pressure reactivity index in pediatric traumatic brain injury patients.

PURPOSE: While clinical practice suggests that knowing the cerebral autoregulation (CA) status of traumatic brain injury (TBI) patients is crucial in assessing the best treatment, evidence in pediatric TBI (pTBI) is limited. The pressure reactivity index (PRx) is a surrogate method for the continuous estimation of CA in adults; however, calculations require continuous, high-resolution monitoring data. We evaluate an ultra-low-frequency pressure reactivity index (UL-PRx), based on data sampled at ∼5-min periods, and test its association with 6-month mortality and unfavorable outcome in a cohort of pTBI patients. METHODS: Data derived from pTBI patients (0-18 years) requiring intracranial pressure (ICP) monitoring were retrospectively collected and processed in MATLAB using an in-house algorithm. RESULTS: Data on 47 pTBI patients were included. UL-PRx mean values, ICP, cerebral perfusion pressure (CPP), and derived indices showed significant association with 6-month mortality and unfavorable outcome. A value of UL-PRx of 0.30 was identified as the threshold to better discriminate both surviving vs deceased patients (AUC: 0.90), and favorable vs unfavorable outcomes (AUC: 0.70) at 6 months. At multivariate analysis, mean UL-PRx and % time with ICP > 20 mmHg, remained significantly associated with 6-month mortality and unfavorable outcome, even when adjusted for International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT)-Core variables. In six patients undergoing secondary decompressive craniectomy, no significant changes in UL-PRx were found after surgery. CONCLUSIONS: UL-PRx is associated with a 6-month outcome even if adjusted for IMPACT-Core. Its application in pediatric intensive care unit could be useful to evaluate CA and offer possible prognostic and therapeutic implications in pTBI patients. CLINICALTRIALS: GOV: NCT05043545, September 14, 2021, retrospectively registered.

Evaluation and Application of Ultra-Low-Resolution Pressure Reactivity Index in Moderate or Severe Traumatic Brain Injury.

BACKGROUND: The pressure reactivity index (PRx) has emerged as a surrogate method for the continuous bedside estimation of cerebral autoregulation and a predictor of unfavorable outcome after traumatic brain injury (TBI). However, calculation of PRx require continuous high-resolution monitoring currently limited to specialized intensive care units. The aim of this study was to evaluate a new index, the ultra-low-frequency PRx (UL-PRx) sampled at ∼0.0033 Hz at ∼5 minutes periods, and to investigate its association with outcome. METHODS: Demographic data, admission Glasgow coma scale, in-hospital mortality and Glasgow outcome scale extended at 12 months were extracted from electronic records. The filtering and preparation of time series of intracranial pressure (ICP), mean arterial pressure and cerebral perfusion pressure (CPP), and calculation of the indices (UL-PRx, Δ-optimal CPP), were performed in MATLAB using an in-house algorithm. RESULTS: A total of 164 TBI patients were included in the study; in-hospital and 12-month mortality was 29.3% and 38.4%, respectively, and 64% of patients had poor neurological outcome at 12 months. On univariate analysis, ICP, CPP, UL-PRx, and ΔCPPopt were associated with 12-month mortality. After adjusting for age, Glasgow coma scale, ICP and CPP, mean UL-PRx and UL-PRx thresholds of 0 and +0.25 remained associated with 12-month mortality. Similar findings were obtained for in-hospital mortality. For mean UL-PRx, the area under the receiver operating characteristic curves for in-hospital and 12-month mortality were 0.78 (95% confidence interval [CI]: 0.69-0.87; P <0.001) and 0.70 (95% CI: 0.61-0.79; P <0.001), respectively, and 0.65 (95% CI: 0.57-0.74; P =0.001) for 12-month neurological outcome. CONCLUSIONS: Our findings indicate that ultra-low-frequency sampling might provide sufficient resolution to derive information about the state of cerebrovascular autoregulation and prediction of 12-month outcome in TBI patients.

Markers of blood-brain barrier disruption increase early and persistently in COVID-19 patients with neurological manifestations.

Background: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is associated with disorders affecting the peripheral and the central nervous system. A high number of patients develop post-COVID-19 syndrome with the persistence of a large spectrum of symptoms, including neurological, beyond 4 weeks after infection. Several potential mechanisms in the acute phase have been hypothesized, including damage of the blood-brain-barrier (BBB). We tested weather markers of BBB damage in association with markers of brain injury and systemic inflammation may help in identifying a blood signature for disease severity and neurological complications. Methods: Blood biomarkers of BBB disruption (MMP-9, GFAP), neuronal damage (NFL) and systemic inflammation (PPIA, IL-10, TNFα) were measured in two COVID-19 patient cohorts with high disease severity (ICUCovid; n=79) and with neurological complications (NeuroCovid; n=78), and in two control groups free from COVID-19 history, healthy subjects (n=20) and patients with amyotrophic lateral sclerosis (ALS; n=51). Samples from COVID-19 patients were collected during the first and the second wave of COVID-19 pandemic in Lombardy, Italy. Evaluations were done at acute and chronic phases of the COVID-19 infection. Results: Blood biomarkers of BBB disruption and neuronal damage are high in COVID-19 patients with levels similar to or higher than ALS. NeuroCovid patients display lower levels of the cytokine storm inducer PPIA but higher levels of MMP-9 than ICUCovid patients. There was evidence of different temporal dynamics in ICUCovid compared to NeuroCovid patients with PPIA and IL-10 showing the highest levels in ICUCovid patients at acute phase. On the contrary, MMP-9 was higher at acute phase in NeuroCovid patients, with a severity dependency in the long-term. We also found a clear severity dependency of NFL and GFAP levels, with deceased patients showing the highest levels. Discussion: The overall picture points to an increased risk for neurological complications in association with high levels of biomarkers of BBB disruption. Our observations may provide hints for therapeutic approaches mitigating BBB disruption to reduce the neurological damage in the acute phase and potential dysfunction in the long-term.

Development and assessment of competency-based neurotrauma course curriculum for international neurosurgery residents and neurosurgeons.

OBJECTIVE: Traumatic brain injuries (TBIs) are a significant disease burden worldwide. It is imperative to improve neurosurgeons' training during and after their medical residency with appropriate neurotrauma competencies. Unfortunately, the development of these competencies during neurosurgeons' careers and in daily practice is very heterogeneous. This article aimed to describe the development and evaluation of a competency-based international course curriculum designed to address a broad spectrum of needs for taking care of patients with neurotrauma with basic and advanced interventions in different scenarios around the world. METHODS: A committee of 5 academic neurosurgeons was involved in the task of building this course curriculum. The process started with the identification of the problems to be addressed and the subsequent performance needed. After this, competencies were defined. In the final phase, educational activities were designed to achieve the intended learning outcomes. In the end, the entire process resulted in competency and outcomes-based education strategy, including a definition of all learning activities and learning outcomes (curriculum), that can be integrated with a faculty development process, including training. Further development was completed by 4 additional academic neurosurgeons supported by a curriculum developer specialist and a project manager. After the development of the course curriculum, template programs were developed with core and optional content defined for implementation and evaluation. RESULTS: The content of the course curriculum is divided into essentials and advanced concepts and interventions in neurotrauma care. A mixed sample of 1583 neurosurgeons and neurosurgery residents attending 36 continuing medical education activities in 30 different cities around the world evaluated the course. The average satisfaction was 97%. The average usefulness score was 4.2, according to the Likert scale. CONCLUSIONS: An international competency-based course curriculum is an option for creating a well-accepted neurotrauma educational process designed to address a broad spectrum of needs that a neurotrauma practitioner faces during the basic and advanced care of patients in different regions of the world. This process may also be applied to other areas of the neurosurgical knowledge spectrum. Moreover, this process allows worldwide standardization of knowledge requirements and competencies, such that training may be better benchmarked between countries regardless of their income level.

Addressing Key Clinical Care and Clinical Research Needs in Severe Pediatric Traumatic Brain Injury: Perspectives From a Focused International Conference.

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in children and adolescents. Survivors of severe TBI are more prone to functional deficits, resulting in poorer school performance, poor health-related quality of life (HRQoL), and increased risk of mental health problems. Critical gaps in knowledge of pathophysiological differences between children and adults concerning TBI outcomes, the paucity of pediatric trials and prognostic models and the uncertain extrapolation of adult data to pediatrics pose significant challenges and demand global efforts. Here, we explore the clinical and research unmet needs focusing on severe pediatric TBI to identify best practices in pathways of care and optimize both inpatient and outpatient management of children following TBI.

Acute and Subacute Outcome Predictors in Moderate and Severe Traumatic Brain Injury: A Retrospective Monocentric Study.

BACKGROUND: Prognostic factors affecting outcome of traumatic brain injury (TBI), despite their importance, are still under discussion. The purpose of this study was to describe risk factors of in-hospital mortality and outcome at 1 year in a homogeneously treated population of patients with moderate/severe TBI. METHODS: A total of 193 consecutive patients with moderate or severe TBI (Glasgow Coma Scale [GCS] score 13-3, including patients with initial GCS score of 13 at high risk for subsequent neurologic deterioration), admitted to the intensive care unit, were retrospectively analyzed. In-hospital mortality and unfavorable outcome at 1 year, based on a Glasgow Outcome Scale-Extended score ≤4, were considered as primary and secondary outcomes. RESULTS: At 1 year, unfavorable outcome occurred in 47.2%, including an in-hospital mortality of 19.7%. Increasing age, GCS motor score <3, coagulation disorders, and intracranial hypertension were acute risk factors of in-hospital mortality. In the 155 remaining survivors, Oxford Handicap Scale (OHS), posttraumatic cerebral infarction, cerebrospinal fluid disturbances, and length of intensive care unit stay were associated with unfavorable outcome at 1 year, in univariate analysis. A cutoff OHS score ≥3 discriminated the probability of an unfavorable outcome (area under the curve, 0.87; P < 0.001; specificity, 74%; sensitivity, 84%). Combining the effect of acute and subacute variables in a multivariate analysis, increasing age and OHS score were independent predictors of outcome. CONCLUSIONS: The results of this retrospective study confirmed age as the main acute risk factor and identified OHS as new potential subacute predictor of unfavorable outcome in moderate and severe TBI.

The cavernous sinus meningiomas' dilemma: Surgery or stereotactic radiosurgery?

Despite the advances in techniques and technologies, the management of cavernous sinus (CS) meningiomas still remains a challenge for both neurosurgeons and radiation oncologists. On the other hand, the improvement of the anatomical knowledge and the microsurgical techniques together with diffusion of radiosurgery are currently changing the treatment strategy, opening new perspectives to the patients which are suffering from such lesions. The authors reviewed here the literature data. A multidisciplinary treatment algorithm is also proposed.

Craniovertebral junction instability as an extension of cocaine-induced midline destructive lesions: case report.

With the increasingly widespread illicit use of cocaine, a broad spectrum of clinical pathologies related to this form of drug abuse is emerging. The most frequently used method of administration of powdered cocaine is intranasal inhalation, or "snorting." Consequently, adverse effects of cocaine on the nasal tract are common. Habitual nasal insufflations of cocaine can cause mucosal lesions. If cocaine use becomes chronic and compulsive, progressive damage of the mucosa and perichondrium leads to ischemic necrosis of the septal cartilage and perforation of the nasal septum. Occasionally, cocaine-induced lesions cause extensive destruction of the osteocartilaginous structures of the nose, sinuses, and palate and can mimic other diseases such as tumors, infections, and immunological diseases. In the literature currently available, involvement of the craniovertebral junction in the cocaine-induced midline destructive lesions (CIMDLs) has never been reported. The present case concerns a 44-year-old man who presented with long-standing symptoms including nasal obstruction, epistaxis, dysphagia, nasal reflux, and severe neck pain. A diagnosis of CIMDL was made in light of the patient's history and the findings on physical and endoscopic examinations, imaging studies, and laboratory testing. Involvement of the craniovertebral junction in the destructive process was evident. For neurosurgical treatment, the authors considered the high grade of atlantoaxial instability, the poorly understood cocaine-induced lesions of the spine and their potential evolution overtime, as well as cocaine abusers' poor compliance. The patient underwent posterior craniovertebral fixation. Understanding, classifying, and treating cocaine-induced lesions involving the craniovertebral junction are a challenge.

The use of a stand-alone interbody fusion cage in subaxial cervical spine trauma: a preliminary report.

BACKGROUND: Anterior spinal surgery has a predominant role in the treatment of traumatic lesions of the subaxial cervical spine. Plating is considered indispensable to achieve stability but may cause dysphagia, dysphonia, and adjacent-level ossification. Zero-P (Synthes GmbH, Oberdorf, Switzerland), an anchored interdisc spacer, can be used without an associated plate. The present study aimed to test if this new implant would be associated with a low rate of dysphagia and other short-term complications compared with the standard for anterior spinal fusion surgery and would be able to achieve a solid fusion and maintain correct metamere alignment. MATERIAL AND METHODS: This is a preliminary presentation of a clinical case series of patients with subaxial cervical injuries who underwent anterior interbody fusion. From July 2009 until September 2011, 12 patients were treated with a Zero-P cage. The data for analysis included operating time compared with the standard for spinal fusion surgery with a cage plus plate construct, intraoperative blood loss, clinical and radiographic results, and complications. RESULTS: In the postoperative period no patient had neurologic worsening. One patient experienced transient dysphonia and moderate dysphagia. All the patients were followed up for a minimum of 6 months (mean: 13 months; range: 6-27 months). Stability and fusion were obtained in all patients together with correct metamere alignment. CONCLUSION: We presented the preliminary results of a clinical case series. Our results support the initiation of prospective randomized trials with more patients and longer follow-up.

Spontaneous regression after extensive recurrence of a pediatric cervical spine aneurysmal bone cyst.

Aneurysmal bone cyst is a pseudotumoral lesion. Complete resection prior to selective arterial embolization seems to be the treatment of choice for the more extensive and destructive lesions. In these cases maintaining stability of the cervical spine is critical. This can be very challenging in children and adolescents in whom the axial skeleton is still growing. In this case a young girl presented with a voluminous cervical aneurysmal bone cyst encaging both vertebral arteries and spinal cord. The lesion was treated with aggressive surgical resection, followed by cervical vertebral fusion with instrumentation. After nine months the patient referred no pain and no neurological deficit. MRI scans showed an extensive local recurrence. The family of the young girl refused any other therapy and any other followup. The patients returned to our attention after five years with no pain and neurological deficit. Cervical spine radiographs and MRI scans showed a complete regression of the extensive local recurrence. In the literature, the possibility of spontaneous regression of residual part or local recurrence is reported. The case of this young girl provided the chance to attend a spontaneous regression in an extensive recurrence of aneurismal bone cyst.

Collagen-only biomatrix as dural substitute: What happened after a 5-year observational follow-up study.

OBJECTIVES: To assess long-term efficacy of the collagen-only biomatrix as a dural substitute in a large case series. PATIENTS AND METHODS: We reviewed a prospectively acquired database of patients who underwent neurosurgical surgeries in whom the dural substitute was used and who were the subject of two previous studied with shorter follow-ups. RESULTS: The present study was conducted on 111 subjects of the original 209 patients. No late complications, nor local or systemic toxicity were observed during the observational period. As a matter of facts, 5 patients (4.5%) underwent reoperation for different reasons and 2 out of 5 experienced subcutaneous fluid collections; another case (0.9%), already reported in our previous studies, developed a CSF leak after an endoscopic endonasal operation for an intra-suprasellar arachnoid cyst. CONCLUSIONS: Our data further confirm that the collagen-only biomatrix derived from horse equine tendon is a safe and effective dural substitute for routine neurosurgical procedures.

Hypocortisolism in noncomatose patients during the acute phase of subarachnoid hemorrhage.

BACKGROUND: Hypopituitarism represents a common long-term complication of subarachnoid hemorrhage (SAH). The incidence of hypocortisolism may be higher during the acute phase of SAH. Although hypocortisolism may be harmful in critically ill SAH patients, data are still lacking. The primary objective of this study was to investigate the incidence of hypocortisolism during the acute phase of SAH (15 days). Secondary objectives included an analysis of the relationship between hypocortisolism and outcome and the computation of the cortisol-time secretion curve. METHODS: Clinical data of a consecutive series of 26 noncomatose patients with aneurysmal SAH were collected prospectively. The sample size was calculated considering an expected proportion of hypocortisolism of 30%, a confidence level of 95%, and a total width of confidence interval of 0.35. The definition of hypocortisolism (as taken from a statement from the critical care medicine task forces) includes random total cortisol <10 µg/dL or a Δtotal serum cortisol <9 µg/dL after 1 µg of corticotrophin hormone. RESULTS: Hypocortisolism was diagnosed in 11 patients (42.3%). Cortisol increment after stimulation test was always >9 µg/dl, suggesting a hypothalamic-pituitary impairment. Hypocortisolism was independently associated with a higher risk of poor outcome (P = .046) even after adjusting for age and Hunt and Hess grade. The cortisol-time secretion curve showed a peak at day 5 and a minimum at day 8. The peak at day 5 correlated with the risk of delayed cerebral ischemia (P = .001), and the cortisol concentration slope between days 1 and 8 correlated with the risk of poor outcome (P = .033). CONCLUSIONS: Patients with SAH are at high risk of secondary hypocortisolism during the first 15 days after bleeding. Hypocortisolism independently increases the risk of poor outcome. The acute phase of hypothalamo-pituitary dysfunction, as reflected by an abnormal day-by-day cortisol secretion pattern, may affect the risk of delayed cerebral ischemia.

Cerebral watershed hypoperfusion in subarachnoid hemorrhage: computed tomography perfusion analysis.

OBJECT: A better understanding of the pathophysiology of vasospasm-induced delayed cerebral ischemia and earlier detection of hypoperfusion before ischemic injury are needed to guide therapy in subarachnoid hemorrhage (SAH). The cerebrovascular physiology of the major arterial territories differs from that of the watershed zones (WZs) in a way that would suggest a differential topographic sensitivity of the brain to vasospasm. The primary end point of the study was to investigate the vasospasm-induced hypoperfusion in relation to cerebrovascular topography and timing from the onset of SAH. METHODS: Forty-one patients were prospectively enrolled and scheduled for perfusion-weighted (PW) CT at 3 time points (≤ 3 days, Days 4-8, and Days 9-15 after SAH). Perfusion-weighted CT maps were visually assessed for side-to-side perfusion asymmetry. The PW CT topographic pattern was categorized into absence of asymmetry, WZ, and vascular territory hypoperfusion. Perfusion-weighted CT revision was performed by investigators blinded to clinical information. The null hypothesis for the primary end point was that there would be no difference in hypoperfusion space-time distribution among the different vascular territories. Multivariate logistic regression and Cox proportional hazards modeling were used for statistical analysis. RESULTS: Delayed cerebral ischemia occurred in 26 patients and its predicting variables were increasing age (p = 0.045), Fisher grade (p = 0.007), and hypoperfusion on the PW CT performed within the 1st 72 hours after SAH (p = 0.004). The timing of the PW CT with respect to the day of SAH affected the topographic pattern of hypoperfusion: watershed-zone hypoperfusion was more common within the first 3 days after SAH (p = 0.018), while the proportion of territorial hypoperfusion increased subsequently. Among the different covariates, a young age was independently associated with a higher risk of developing hypoperfusion in the WZs (p = 0.02). CONCLUSIONS: This study suggests the existence of a cerebral topographic heterogeneity to the hemodynamic effects of SAH and differential pathogenetic mechanisms of hypoperfusion according to timing, age, and brain topography. Hypoperfusion in the WZs may be an early precursor to more profound ischemic events. The PW CT detection of such brain-sensitive zones could offer a warning signal of the early hemodynamic effects of SAH and cerebral vasospasm.

Decompressive surgery in malignant dural sinus thrombosis: report of 3 cases and review of the literature.

Cerebral venous and dural sinus thrombosis (CVDST) is a rare cause of stroke in young and middle-aged adults. When the clinical course is complicated by uncontrollable intracranial hypertension and brainstem compression due to edema or cerebral hemorrhage, the prognosis is poor. The authors evaluated the therapeutic role of surgical decompression in patients with clinical signs of impending herniation. Cerebral venous and dural sinus thrombosis complicated by impending brain herniation a very rare, life-threatening but potentially treatable clinical condition. Three patients with pupillary signs of transtentorial herniation due to brain edema and hemorrhage caused by CVDST (superior sagittal sinus in 1 patient and transverse and sigmoid sinus in 2 patients) were treated surgically. The intervention consisted of clot removal, infarcted tissue resection, and frontotemporoparietooccipital craniectomy with duraplasty. According to the Glasgow Outcome Scale, 2 patients were classified as having good recovery and 1, moderate disability. The results of neuropsychological assessment were normal in 2 patients and demonstrated a partial neuropsychological deficit (neglect) in the other. Surgery may be indicated in selected patients with CVDST whose condition is deteriorating because of intractable intracranial hypertension and impending brain herniation.

Surgical management in spinal sarcoidosis: case report.

STUDY DESIGN: Case report of a patient with transient paraplegia and spine instability because of sarcoidosis of 2 vertebral bodies. OBJECTIVES: To report a rare case of vertebral sarcoidosis accompanied by transient neurologic symptoms and spine instability, and to discuss the diagnostic and therapeutic management. SUMMARY OF BACKGROUND DATA: Vertebral sarcoidosis is a rare condition, and only a few case reports exist in the literature. In most cases, treatment with steroids improves associated neurologic symptoms. Operative intervention is necessary in cases with spinal instability because of progressive vertebral destruction and impending or progressive neurologic deterioration. METHODS: After steroids therapy and subsequent neurologic improvement, operative treatment by a 2-stage posterior stabilization followed by anterior vertebrectomy and fusion was given to a patient with 2-level vertebral sarcoidosis and residual spine instability. RESULTS: After steroids therapy, the patient had a complete neurologic recovery; satisfactory spinal stability was achieved after surgery. CONCLUSION: In the absence of any spinal instability, neurologic symptoms associated with vertebral sarcoidosis respond satisfactorily to nonoperative treatment with steroids. Progressive neurologic deterioration or spinal instability caused by bone destruction requires operative intervention. Steroids therapy provided neurologic improvement, posterior stabilization combined with anterior vertebrectomy and fusion provided spine stability for the patient in this report.

Novel equine collagen-only dural substitute.

OBJECTIVE: A watertight and meticulous dural closure is an essential step after intradural neurosurgical procedures. When such a task cannot be performed, dural replacement materials and other adjunctive measures can provide an effective barrier between the subarachnoid compartment and the extradural space. METHODS: We present our experience with a novel collagen-derived dural substitute in a series of 114 patients undergoing a variety of neurosurgical procedures. The patients were clinically or neuroradiologically observed, for immediate and delayed local or systemic complications related to the implant. In three patients who underwent reoperation after decompressive duraplasty and craniectomy for bone flap repositioning, we performed biopsy of the dural implant for histopathological studies. RESULTS: None of the patients experienced local or systemic complications or toxicity related to the dural patch. None of the patients experienced a postoperative cerebrospinal fluid fistula, except one patient who underwent an endoscopic endonasal transsphenoidal marsupialization of a large intrasuprasellar arachnoid cyst; the fistula required reoperation for cerebrospinal fluid fistula repair and intravenous antibiotic therapy for bacterial meningitis. Postoperative magnetic resonance imaging scans showed signs of severe inflammatory response in only one patient who did not present any postoperative clinical symptom or neurological deficits. Three patients underwent reoperation for bone flap repositioning after decompressive craniectomy; in all patients, the dural substitute appeared to have promoted satisfactory dural regeneration, as confirmed by the histological studies. Furthermore, in such patients, no or minimal adherence with the other tissues and the brain cortex was observed. CONCLUSION: This study demonstrates that the new collagen-only biomatrix is a safe and effective dural substitute for routine neurosurgical procedures. The absence of local and systemic toxicity or complications and the scarce promotion of adherences and inflammation make this material appealing for its use as a dural substitute, even in cases in which the necessity of reoperation is foreseen.