Existing clinical evidence on the use of cellular bone matrix grafts in spinal fusion: updated systematic review of the literature.

OBJECTIVE: Spinal fusion surgery is increasingly common; however, pseudarthrosis remains a common complication affecting as much as 15% of some patient populations. Currently, no clear consensus on the best bone graft materials to use exists. Recent advances have led to the development of cell-infused cellular bone matrices (CBMs), which contain living components such as mesenchymal stem cells (MSCs). Relatively few clinical outcome studies on the use of these grafts exist, although the number of such studies has increased in the last 5 years. In this study, the authors aimed to summarize and critically evaluate the existing clinical evidence on commercially available CBMs in spinal fusion and reported clinical outcomes. METHODS: The authors performed a systematic search of the MEDLINE and PubMed electronic databases for peer-reviewed, English-language original articles (1970-2020) in which the articles' authors studied the clinical outcomes of CBMs in spinal fusion. The US National Library of Medicine electronic clinical trials database (www.ClinicalTrials.gov) was also searched for relevant ongoing clinical trials. RESULTS: Twelve published studies of 6 different CBM products met inclusion criteria: 5 studies of Osteocel Plus/Osteocel (n = 354 unique patients), 3 of Trinity Evolution (n = 114), 2 of ViviGen (n = 171), 1 of map3 (n = 41), and 1 of VIA Graft (n = 75). All studies reported high radiographic fusion success rates (range 87%-100%) using these CBMs. However, this literature was overwhelmingly limited to single-center, noncomparative studies. Seven studies disclosed industry funding or conflicts of interest (COIs). There are 4 known trials of ViviGen (3 trials) and Bio4 (1 trial) that are ongoing. CONCLUSIONS: CBMs are a promising technology with the potential of improving outcome after spinal fusion. However, while the number of studies conducted in humans has tripled since 2014, there is still insufficient evidence in the literature to recommend for or against CBMs relative to cheaper alternative materials. Comparative, multicenter trials and outcome registries free from industry COIs are indicated.

Seizure treatment in Angelman syndrome: A case series from the Angelman Syndrome Clinic at Massachusetts General Hospital.

Epilepsy is a common feature of Angelman syndrome (~80-90%), with the most common seizure types including myoclonic, atonic, atypical absence, focal, and generalized tonic-clonic. Seizure types are similar among the various genetic subtypes, but epilepsy in those with maternal deletions is more frequent and more refractory to medication. Treatment with older antiepileptic drugs such as valproic acid and clonazepam is effective, but these medications tend to have less favorable side effect profiles in Angelman syndrome compared with those in newer medications. This study aimed to assess the use of newer antiepileptic drug therapies in individuals with Angelman syndrome followed at the Angelman Syndrome Clinic at the Massachusetts General Hospital. Many of the subjects in this study were on valproic acid therapy prior to their initial evaluation and exhibited increased tremor, decreased balance, and/or regression of motor skills, which resolved after tapering off of this medication. Newer antiepileptic drugs such as levetiracetam, lamotrigine, and clobazam, and to a lesser extent topiramate, appeared to be as effective - if not more so - as valproic acid and clonazepam while offering more favorable side effect profiles. The low glycemic index treatment also provided effective seizure control with minimal side effects. The majority of subjects remained on combination therapy with levetiracetam, lamotrigine, and clobazam being the most commonly used medications, indicating a changing trend when compared with prior studies.

Angelman syndrome in adulthood.

Angelman syndrome (AS) is a neurogenetic disorder. The goal of this study was to investigate the primary health issues affecting adults with AS and to further characterize the natural history and genotype-phenotype correlations. Standardized phone interviews with caregivers for 110 adolescents and adults with AS were conducted. The impact of age, sex, and genotype on specific outcomes in neurology, orthopedics, internal medicine, and psychiatry were investigated. The mean age of individuals with AS was 24 years (range 16-50y). Active seizures were present in 41% of individuals, and 72% had sleep dysfunction. Significant constipation was present in 85%, and 32% were overweight or obese, with obesity disproportionately affecting women. Scoliosis affected 50% with a mean age at diagnosis of 12 years, and 24% of those diagnosed with scoliosis required surgery, an intervention disproportionately affecting men. Sixty-eight percent were able to walk independently, and 13% were able to speak 5 or more words. Self-injurious behavior was exhibited in 52% of individuals. The results of this study indicate that epilepsy severity may assume a bimodal age distribution: seizures are typically most severe in early childhood but may recur in adulthood. While late-adolescent and adult sleep patterns were improved when compared to the degree of sleep dysfunction present during infancy and childhood, the prevalence of poor sleep in adults remained quite high. Primary areas of clinical management identified include the following: seizures, sleep, aspiration risk, GERD, constipation, dental care, vision, obesity, scoliosis, bone density, mobility, communication, behavior, and anxiety.

Microbubble Contrast-Enhanced Transcutaneous Ultrasound Enables Real-Time Spinal Cord Perfusion Monitoring Following Posterior Cervical Decompression.

INTRODUCTION: Ultrasound imaging is inexpensive, portable, and widely available. The development of a real-time transcutaneous spinal cord perfusion monitoring system would allow more precise targeting of mean arterial pressure goals following acute spinal cord injury (SCI). There has been no prior demonstration of successful real-time cord perfusion monitoring in humans. METHODS: Four adult patients who had undergone posterior cervical decompression and instrumentation at a single center were enrolled into this prospective feasibility study. All participants had undergone cervical laminectomies spanning ≥2 contiguous levels ≥2 months prior to inclusion with no history of SCI. The first two underwent transcutaneous ultrasound without contrast and the second two underwent contrast-enhanced ultrasound (CEUS) with intravenously injected microbubble contrast. RESULTS: Using non-contrast ultrasound with or without Doppler (n=2), the dura, spinal cord, and vertebral bodies were apparent however ultrasonography was insufficient to discern intramedullary perfusion or clear white-gray matter differentiation. With application of microbubble contrast (n=2), it was possible to quantify differential spinal cord perfusion within and between cross-sectional regions of the cord. Further, it was possible to quantify spinal cord hemodynamic perfusion using CEUS by measuring peak signal intensity and the time to peak signal intensity after microbubble contrast injection. Time-intensity curves were generated and area under the curves were calculated as a marker of tissue perfusion. CONCLUSION: CEUS is a viable platform for monitoring real-time cord perfusion in patients who have undergone prior cervical laminectomies. Further development has the potential to change clinical management acute SCI by tailoring treatments to measured tissue perfusion parameters.

Cardiac fat-containing lesions are common in tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a highly variable, multisystem, genetic disorder that affects approximately 1:6,000 individuals. It has previously been thought that the cardiac manifestation of TSC is congenital rhabdomyomas, which occur during infancy and typically regress during childhood. Recently, there have been findings of cardiac fat-containing lesions in adult TSC patients that appear distinct from the presence of cardiac rhabdomyomas. We review the chest CT scans of 73 individuals with TSC to check for cardiac fat-containing lesions. Fat-containing lesions were found in the heart of approximately one-third of adolescents and adults with TSC. In this population with cardiac fat-containing lesions, no statistically significant difference was observed between the genders and between the different mutation types. Compared to those without cardiac fat findings, those with cardiac fat were more than twice as likely to have another abdominal manifestation of TSC. The results indicate that it may be appropriate to consider these cardiac fat foci as a clinical criterion for the diagnosis of TSC, given their frequency in our population. Our findings also suggest that a relation exists between the cardiac fat-containing lesions and other abdominal angiomyolipomas. More research regarding these cardiac fat-containing lesions is needed to better characterize their origin and clinical significance.

Utility of automated MRI perfusion (RAPID) with or without MR angiography for detection of angiographic vasospasm after aneurysmal subarachnoid hemorrhage.

Delayed cerebral ischemia (DCI) is a major etiology of poor neurologic outcomes after aneurysmal subarachnoid hemorrhage (aSAH). Although the development of DCI is certainly multifactorial, the presence of vasospasm is strongly correlated with it. Cerebral angiography remains the gold standard for evaluation of vasospasm, though it is not always practical or cost-effective. In this study, the authors assess the utility of automated MRI Perfusion imaging, with or without MR Angiography (MRA), as a confirmatory tool for suspected angiographic vasospasm. All patients admitted to a single institution with aneurysmal subarachnoid hemorrhage between January 2014 and February 2020 and who underwent MR Perfusion imaging with or without MRA for suspected vasospasm no >24 h prior to an angiogram were identified. 43 subjects were identified. 29 of these patients (67%) underwent simultaneous MRA. 25 patients (53%) received intra-arterial treatment for symptomatic vasospasm. The sensitivity, specificity, PPV, and NPV of MR Perfusion were 43%, 82%, 53%, and 75% for any angiographic vasospasm and 57%, 81%, 42%, and 89% for treated vasospasm. The sensitivity, specificity, PPV, and NPV of MR Perfusion in conjunction with MRA were 61%, 81%, 59%, and 82% for any angiographic vasospasm and 62%, 74%, 35%, and 89% for treated vasospasm. The sensitivity, specificity, PPV, and NPV of transcranial Dopplers (TCDs) in these patients were 35%, 93%, 71%, and 75% for angiographic vasospasm and 42%, 90%, 47%, and 88% for treated vasospasm. Automated MR Perfusion imaging demonstrated relatively low sensitivity and PPV for detection of angiographic and treated vasospasm in this subset of patients after aSAH.

Incidence, Characteristics, and Outcomes of Pseudomeningocele and Cerebrospinal Fluid Fistula after Posterior Fossa Surgery.

OBJECTIVE: Posterior fossa approaches are common neurosurgical procedures. Rates of postoperative infection, pseudomeningocele, and cerebrospinal fluid (CSF) fistula are high; however, evidence regarding predisposing risk factors and treatment outcomes remain sparse. METHODS: A retrospective cohort study was carried out of all posterior fossa surgeries conducted at a single institution between January 2015 and October 2019. Univariate statistical methods and stepwise logistic regression were used to assess which factors contributed most to risk of development of postoperative complications. RESULTS: A total of 269 patients were included; 18.6% experienced any postoperative complication, 13% developed either pseudomeningocele or CSF fistula, and 9.7% developed an infection. In multivariate analysis, development of a pseudomeningocele was significantly associated with previous cranial surgery (hazard ratio [HR], 3.15; 95% confidence interval [CI], 1.12-9.28; P = 0.0391). Development of a CSF fistula was significantly associated with index surgery for resection of neoplasm (HR, 7.65; 95% CI, 1.86-22.31; P = 0.0174). Development of an infection was significantly associated with concurrent CSF fistula (HR, 7.16; 95% CI, 1.91-23.19; P = 0.0041) and concurrent pseudomeningocele (HR, 3.41; 95% CI, 1.37-5.95; P = 0.0082) and nonsignificantly associated with diabetes requiring treatment (HR, 2.42; 95% CI, 0.69-8.50; P = 0.168). Other hypothesized risk factors for these complications, such as nonmidline approaches to the posterior fossa, watertight duraplasty, use of dural fibrin sealant, and cranioplasty were not associated with these complications on multivariate analysis. Although many patients with pseudomeningocele were successfully managed with observation, only 38% of patients in whom CSF diversion was attempted avoided surgery. CONCLUSIONS: History of diabetes, cranioplasty, revision surgery, and surgery for tumor resection are identified as risk factors for the development of infection, pseudomeningocele, and CSF fistula, respectively.

Influence of Time of Discharge and Length of Stay on 30-Day Outcomes After Elective Anterior Cervical Spine Surgery.

BACKGROUND: Encouraging early time of discharge (TOD) for medical inpatients is commonplace and may potentially improve patient throughput. It is unclear, however, whether early TOD after elective spine surgery achieves this goal without a consequent increase in re-presentations to the hospital. OBJECTIVE: To evaluate whether early TOD results in increased rates of hospital readmission or return to the emergency department after elective anterior cervical spine surgery. METHODS: We analyzed 686 patients who underwent elective uncomplicated anterior cervical spine surgery at a single institution. Logistic regression was used to evaluate the relationship between sociodemographic, procedural, and discharge characteristics, and the outcomes of readmission or return to the emergency department and TOD. RESULTS: In multiple logistic regression, TOD was not associated with increased risk of readmission or return to the emergency department within 30 days of surgery. Weekend discharge (odds ratio [OR] 0.33, 95% CI 0.21-0.53), physical therapy evaluation (OR 0.44, 95% CI 0.28-0.71), and occupational therapy evaluation (OR 0.32, 95% CI 0.17-0.63) were all significantly associated with decreased odds of discharge before noon. Disadvantaged status, as measured by area of deprivation index, was associated with increased odds of readmission or re-presentation (OR 1.86, 95% CI 0.95-3.66), although this result did not achieve statistical significance. CONCLUSION: There does not appear to be an association between readmission or return to the emergency department and early TOD after elective spine surgery. Overuse of inpatient physical and occupational therapy consultations may contribute to decreased patient throughput in surgical admissions.

Neighborhood-Level Socioeconomic Status Predicts Extended Length of Stay After Elective Anterior Cervical Spine Surgery.

BACKGROUND: A significant portion of health care spending is driven by a small percentage of the overall population. Understanding risk factors predisposing patients to disproportionate use of health care resources is critical. Our objective was to identify risk factors leading to a prolonged length of stay (LOS) after cervical spine surgery. METHODS: A single-center cohort analysis was performed on patients who underwent elective anterior spine surgery from 2015 to 2021. Multivariate logistic regression evaluated the effects of sociodemographic factors including Area of Deprivation Index (quantifies income, education, employment, and housing quality), procedural, and discharge characteristics on postoperative LOS. Extended LOS was defined as greater than the 90th percentile in midnights for the study population (≥3 midnights). RESULTS: A total of 686 patients were included in the study, with a mean age of 57 years (range, 26-92 years), median of 1 level (1-4) fused, and median LOS of 1 midnight (interquartile range, 1-2). After adjusting for confounders, patients had increased odds of extended LOS if they were highly disadvantaged on the Area of Deprivation Index (odds ratio [OR], 2.24; 95% confidence interval [CI], 1.04-4.82; P = 0.039); had surgery on Thursday or Friday (OR, 1.94; 95% CI, 1.01-3.72; P = 0.046); had a corpectomy performed (OR, 2.81; 95% CI, 1.26-6.28; P = 0.012); or discharged not to home (OR, 8.24; 95% CI, 2.88-23.56; P < 0.001). Patients with extended LOS were more likely to present to the emergency department or be readmitted within 30 days after discharge (P = 0.024). CONCLUSIONS: After adjusting for potential cofounders, patients most disadvantaged on Area of Deprivation Index were more likely to have an extended LOS.

Hippocampal abnormalities in magnetic resonance imaging (MRI) of 15q duplication syndromes.

Patients with 15q duplication syndromes, including isodicentric chromosome 15 and interstitial duplications, usually present with autism spectrum disorder, intellectual disability, and frequently epilepsy. Neuroimaging studies in these patients are typically reported as normal, but nonspecific findings such as thinning of the corpus callosum and increased pericerebral spaces have been reported. A review of brain magnetic resonance imaging (MRI) studies of 11 individuals seen at the Massachusetts General Hospital Dup15q Center was performed. Hippocampus morphology was specifically reviewed, as a recent neuropathologic study has found frequent hippocampal heterotopias and dysplasias in these disorders. Two subjects had unilateral hippocampal sclerosis and 6 had bilateral hippocampal malformations. Hypoplasia of the corpus callosum was present in 2 subjects.

Gastrointestinal problems in 15q duplication syndrome.

Chromosome 15q duplication syndrome (Dup15q syndrome) is a neurodevelopmental disorder involving copy number gains of the maternal chromosome 15q11.2-q13 region, characterized by intellectual disability, developmental delay, autism spectrum disorder (ASD), and epilepsy. Gastrointestinal (GI) problems in Dup15q syndrome have been reported only rarely, mostly focused on neonatal feeding difficulties. A retrospective review of the medical records of 46 patients with Dup15q syndrome was conducted to assess GI issues and their treatments in this population. GI symptoms were present in 76.7% of subjects with an isodicentric duplication and 87.5% with an interstitial duplication. There was no clear association between GI issues and ASD, with symptoms occurring in 78.9% of all subjects and 78.2% of ASD subjects. The most commonly reported symptoms were gastroesophageal reflux (56.7%) and constipation (60%), with 30% of subjects reporting both. The most common treatments were polyethylene glycol for constipation and proton pump inhibitors for reflux. Behaviors such as irritability and aggressiveness improved with treatment of GI symptoms in several subjects. The results indicate that GI symptoms are common in Dup15q syndrome and may have an atypical presentation. Diagnosis may be difficult, especially in individuals who are nonverbal or minimally verbal, so increased awareness is critical for early diagnosis and treatment.

Intracranial arteriopathy in tuberous sclerosis complex.

Arterial aneurysms, mostly aortic and intracranial, have been occasionally reported in patients with tuberous sclerosis complex. Brain magnetic resonance imaging reports of 404 patients with definite and 16 patients with either probable or possible tuberous sclerosis complex were revised for intracranial aneurysms. Among these patients, brain images of 220 patients with definite and 16 with probable or possible tuberous sclerosis complex were reviewed. Intracranial aneurysms were reported in 3 of 404 patients with a definite diagnosis (0.74%) (general population: 0.35%), including 2 children. A fourth intracranial aneurysm was found in a patient with probable tuberous sclerosis complex, who did not have tubers or subependymal nodules but had clinical manifestations related to neural crest derivatives, including lymphangioleiomyomatosis and extrarenal angiomyolipomas. The authors hypothesize that neural crest dysfunction can have a major role in intracranial arteriopathy in tuberous sclerosis complex, as smooth muscle cells in the forebrain vessels are of neural crest origin.