Month: June 2021

Michigan Spine Surgery Improvement Collaborative

Michigan Spine Surgery Improvement Collaborative

https://mssic.org/

The Michigan Spine Surgery Improvement Collaborative (MSSIC) is a statewide quality improvement collaborative involving orthopedic surgeons and neurosurgeons with the aim of improving the quality of care of spine surgery. The objective of this collaborative is to heighten patient care outcomes while consequently increasing the efficiency of treatment.

The Michigan Spine Surgery Improvement Collaborative (MSSIC) is a prospective, longitudinal, multicenter, quality-improvement collaborative.

Michigan Spine Surgery Improvement Collaborative (MSSIC) prospectively collects data on all patients undergoing operations for degenerative and/or deformity indications.

In 2013, Blue Cross Blue Shield of Michigan (BCBSM) and Blue Care Network (BCN) established the Michigan Spine Surgery Improvement Collaborative (MSSIC) as a Collaborative Quality Initiative (CQI). MSSIC is one of the newest of 21 other CQIs that have significantly improved and continue to improve the quality of patient care throughout the state of Michigan. METHODS MSSIC focuses on lumbar and cervical spine surgery, specifically indications such as stenosis, disk herniation, and degenerative disease. Surgery for tumors, traumatic fractures, deformity, scoliosis, and acute spinal cord injury are currently not within the scope of MSSIC. Starting in 2014, MSSIC consisted of 7 hospitals and in 2015 included another 15 hospitals, for a total of 22 hospitals statewide. A standardized data set is obtained by data abstractors, who are funded by BCBSM/BCN. Variables of interest include indications for surgery, baseline patient-reported outcome measures, and medical history. These are obtained within 30 days of surgery. Outcome instruments used include the EQ-5D general health state score (0 being worst and 100 being the best health one can imagine) and EQ-5D-3 L. For patients undergoing lumbar surgery, a 0 to 10 numeric rating scale for leg and back pain and the Oswestry Disability Index for back pain are collected. For patients undergoing cervical surgery, a 0 to 10 numeric rating scale for arm and neck pain, Neck Disability Index, and the modified Japanese Orthopaedic Association score are collected. Surgical details, postoperative hospital course, and patient-reported outcome measures are collected at 90-day, 1-year, and 2-year intervals. RESULTS As of July 1, 2015, a total of 6397 cases have been entered into the registry. This number reflects 4824 eligible cases with confirmed surgery dates. Of these 4824 eligible cases, 3338 cases went beyond the 120-day window and were considered eligible for the extraction of surgical details, 90-day outcomes, and adverse events. Among these 3338 patients, there are a total of 2469 lumbar cases, 862 cervical cases, and 7 combined procedures that were entered into the registry.

In addition to functioning as a registry, MSSIC is also meant to be a platform for quality improvement with the potential for future initiatives and best practices to be implemented statewide in order to improve quality and lower costs. With its current rate of recruitment and expansion, MSSIC will provide a robust platform as a regional prospective registry. Its unique funding model, which is supported by BCBSM/BCN, will help ensure its longevity and viability, as has been observed in other CQIs that have been active for several years 1).

Macki et al. aimed to identify which factors are significantly associated with return-to-work after lumbar surgery at long-term follow-up.

Summary of background data: Prior publications have created a clinically relevant predictive model for return-to-work, wherein education, gender, race, comorbidities, and preoperative symptoms increased the likelihood of return-to-work at 3 months after lumbar surgery. They sought to determine if these trends 1) persisted at 1 year and 2 years postoperatively, or 2) differed among preoperatively employed versus unemployed patients.

MSSIC was queried for all patients undergoing lumbar operations (2014-2019). All patients intended to return to work postoperatively. Patients were followed for up to 2 years postoperatively. Measures of association were calculated with multivariable generalized estimating equations (GEE).

Return-to-work increased from 63% (3542/5591) at 90 days postoperatively to 75% (3143/4147) at 1 year and 74% (2133/2866) at 2 years postoperatively. Following GEE, neither clinical nor surgical variables predicted return-to-work at all three-time intervals: 90 days, 1 year, and 2 years postoperatively. Only socioeconomic factors reached statistical significance at all follow-up points. Preoperative employment followed by insurance status had the greatest associations with return-to-work. In a sub-analysis of patients who were preoperatively employed, insurance was the only factor with significant associations with return-to-work at all three follow-up intervals. The return-to-work rates among unemployed patients at baseline increased from 29% (455/1100) at 90 days, 44% (495/608) at 1 year, and 46% (366/426) at 2 years postoperatively. The only two significant factors associated with return-to-work at all three follow-up intervals were Medicaid, as compared to private insurance, and male gender.

In patients inquiring about long-term return-to-work after lumbar surgery, health insurance status represents the important determinant of employment status.Level of Evidence: 2 2).

While a complex myriad of socio-economic factors interplay between race and surgical success, they identified modifiable risk factors, specifically depression, that may improve patient-reported outcomes (PROs) among African American patients after elective lumbar spine surgery 3).

Correction of sagittal balance is associated with greater odds of discharge to home. These findings, coupled with the recognized implications of admission to a rehabilitation facility, will emphasize the importance of spine surgeons accounting for the sagittal vertical axis (SVA) in their surgical planning of MIS lumbar interbody fusions 4)

Using MSSIC, Zakaria et al. sought to identify the relationship between a positive Patient Health Questionnaire-2 (PHQ-2) screening, which is predictive of depression, and patient satisfaction, return to work, and achieving Oswestry Disability Index (ODI) minimal clinically important difference (MCID) scores up to 2 years after lumbar fusion.

Data from a total of 8585 lumbar fusion patients were analyzed. Patient satisfaction was measured by the North American Spine Society patient satisfaction index. A positive PHQ-2 score is one that is ≥ 3, which has an 82.9% sensitivity and 90.0% specificity in detecting major depressive disorder. Generalized estimating equation models were constructed; variables tested include age, sex, race, past medical history, severity of surgery, and preoperative opioid usage.

Multivariate analysis was performed. Patients with a positive PHQ-2 score (i.e., ≥ 3) were less likely to be satisfied after lumbar fusion at 90 days (relative risk [RR] 0.93, p < 0.001), 1 year (RR 0.92, p = 0.001), and 2 years (RR 0.92, p = 0.028). A positive PHQ-2 score was also associated with decreased likelihood of returning to work at 90 days (RR 0.76, p < 0.001), 1 year (RR 0.85, p = 0.001), and 2 years (RR 0.82, p = 0.031). A positive PHQ-2 score was predictive of failure to achieve an ODI MCID at 90 days (RR 1.07, p = 0.005) but not at 1 year or 2 years after lumbar fusion.

A multivariate analysis based on information from a large, multicenter, prospective database on lumbar fusion patients was performed. The authors found that a positive score (≥ 3) on the PHQ-2, which is a simple and accurate screening tool for depression, predicts an inability to return to work and worse satisfaction up to 2 years after lumbar fusion. Depression is a treatable condition, and so in the same way that patients are medically optimized before surgery to decrease postoperative morbidity, perhaps patients should have preoperative psychiatric optimization to improve postoperative functional outcomes 5).

Ninety-day readmission occurred in 9.0% of patients, mainly for pain, wound infection, and radicular symptoms. Increased focus on postoperative pain may decrease readmissions. Among factors impacting the likelihood of 90-d readmission, early postoperative ambulation may be most easily modifiable. Optimization of preexisting medical conditions could also potentially decrease readmission risk 6).

Multivariate analysis identified the common adverse events after cervical spine surgery, along with their associated risk factors. They found that early mobilization after cervical spine surgery has the potential to significantly decrease adverse events 7).

1)

Chang V, Schwalb JM, Nerenz DR, Pietrantoni L, Jones S, Jankowski M, Oja-Tebbe N, Bartol S, Abdulhak M. The Michigan Spine Surgery Improvement Collaborative: a statewide Collaborative Quality Initiative. Neurosurg Focus. 2015 Dec;39(6):E7. doi: 10.3171/2015.10.FOCUS15370. PMID: 26621421.
2)

Macki M, Anand SK, Hamilton T, Lim S, Mansour T, Bazydlo M, Schultz L, Abdulhak MM, Khalil JG, Park P, Aleem I, Easton R, Schwalb JM, Nerenz D, Chang V. Analysis of Factors associated with Return to Work After Lumbar Surgery up to 2-years follow-up: A Michigan Spine Surgery Improvement Collaborative (MSSIC) Study. Spine (Phila Pa 1976). 2021 Jul 7. doi: 10.1097/BRS.0000000000004163. Epub ahead of print. PMID: 34265812.
3)

Macki M, Hamilton T, Lim S, Telemi E, Bazydlo M, Nerenz DR, Zakaria HM, Schultz L, Khalil JG, Perez-Cruet MJ, Aleem IS, Park P, Schwalb JM, Abdulhak MM, Chang V. Disparities in outcomes after spine surgery: a Michigan Spine Surgery Improvement Collaborative study. J Neurosurg Spine. 2021 May 7:1-9. doi: 10.3171/2020.10.SPINE20914. Epub ahead of print. PMID: 33962387.
4)

Macki M, Fadel HA, Hamilton T, Lim S, Massie LW, Zakaria HM, Pawloski J, Chang V. The influence of sagittal spinopelvic alignment on patient discharge disposition following minimally invasive lumbar interbody fusion. J Spine Surg. 2021 Mar;7(1):8-18. doi: 10.21037/jss-20-596. PMID: 33834123; PMCID: PMC8024762.
5)

Zakaria HM, Mansour TR, Telemi E, Asmaro K, Macki M, Bazydlo M, Schultz L, Nerenz DR, Abdulhak M, Schwalb JM, Park P, Chang V. Use of Patient Health Questionnaire-2 scoring to predict patient satisfaction and return to work up to 1 year after lumbar fusion: a 2-year analysis from the Michigan Spine Surgery Improvement Collaborative. J Neurosurg Spine. 2019 Aug 23:1-8. doi: 10.3171/2019.6.SPINE1963. [Epub ahead of print] PubMed PMID: 31443085.
6)

Park P, Nerenz DR, Aleem IS, Schultz LR, Bazydlo M, Xiao S, Zakaria HM, Schwalb JM, Abdulhak MM, Oppenlander ME, Chang VW. Risk Factors Associated With 90-Day Readmissions After Degenerative Lumbar Fusion: An Examination of the Michigan Spine Surgery Improvement Collaborative (MSSIC) Registry. Neurosurgery. 2019 Sep 1;85(3):402-408. doi: 10.1093/neuros/nyy358. PMID: 30113686.
7)

Zakaria HM, Bazydlo M, Schultz L, Pahuta MA, Schwalb JM, Park P, Aleem I, Nerenz DR, Chang V; MSSIC Investigators. Adverse events and their risk factors 90 days after cervical spine surgery: analysis from the Michigan Spine Surgery Improvement Collaborative. J Neurosurg Spine. 2019 Feb 15:1-13. doi: 10.3171/2018.10.SPINE18666. Epub ahead of print. PMID: 30771759.

Electrical stimulation for peripheral nerve injury treatment

Electrical stimulation for peripheral nerve injury treatment

Peripheral nerve injury afflicts individuals from all walks of life. Despite the peripheral nervous system’s intrinsic ability to regenerate, many patients experience incomplete functional recovery. Surgical repair aims to expedite this recovery process in the most thorough manner possible. However, full recovery is still rarely seen especially when nerve injury is compounded with polytrauma where surgical repair is delayed. Pharmaceutical strategies supplementary to nerve microsurgery have been investigated but surgery remains the only viable option 1).

Electrical stimulation is regarded pivotal to promote repair of nerve injury, however, failed to get extensive application in vivo due to the challenges in noninvasive electrical loading accompanying with construction of biomimetic cell niche.

Building on decades of experimental evidence in animal models, several recent, prospective, randomized clinical trials have affirmed electrical stimulation as a clinically translatable technique to enhance functional recovery in patients with peripheral nerve injuries requiring surgical treatment 2).

Implantable wireless stimulators can deliver therapeutic electrical stimulation to injured peripheral nerve tissue. Implantable wireless nerve stimulators might represent a novel means of facilitating therapeutic electrical stimulation in both intraoperative and postoperative settings 3).

Zhang et al. demonstrated a new concept of magneto responsive electric 3D matrix for remote and wireless electrical stimulation. By the preparation of magnetoelectric core/shell structured Fe3 O4 @BaTiO3 NPs-loaded hyaluronan/collagen hydrogels, which recapitulate considerable magneto-electricity and vital features of native neural extracellular matrix, the enhancement of neurogenesis both in cellular level and spinal cord injury in vivo with external pulsed magnetic field applied is proved. The findings pave the way for a novel class of remote controlling and delivering electricity through extracellular niches-mimicked hydrogel network, arising prospects not only in neurogenesis but also in human-computer interaction with higher resolution 4).

The frequency of stimulation is an important factor in the success of both quality and quantity of axon regeneration as well as growth of the surrounding myelin and blood vessels that support the axon. Histological analysis and measurement of regeneration showed that low frequency stimulation had a more successful outcome than high frequency stimulation on regeneration of damaged sciatic nerves.

The use of autologous nerve grafting procedures that involve redirection of regenerative donor nerve fibers into the graft conduit has been successful in restoring target muscle function. Localized delivery of soluble neurotrophic factors may help promote the rate of axon regeneration observed within these graft conduits.

An expanding area of nerve regeneration research deals with the development of scaffolding and bio-conduits. Scaffolding developed from biomaterial would be useful in nerve regeneration if they successfully exhibit essentially the same role as the endoneurial tubes and Schwann cell do in guiding regrowing axons.

The surgeon, who treats nerve injuries, should have knowledge about how peripheral nerves react to trauma, particularly an understanding about the extensive pathophysiological alterations that occur both in the peripheral and in the central nervous system. A large number of factors influence the functional outcome, where the surgeon only can affect a few of them. In view of the new knowledge about the delicate intracellular signaling pathways that are rapidly initiated in neurons and in nonneuronal cells with the purpose to induce nerve regeneration, the timing of nerve repair and reconstruction after injury has gained more interest. It is crucial to understand and to utilize the inborn mechanisms for survival and regeneration of neurons and for activation, survival, and proliferation of the Schwann cells and other cells that are acting after a nerve injury. Thus, experimental and clinical data clearly point toward the advantage of early nerve repair and reconstruction of injuries. Following an appropriate diagnosis of a nerve injury, the nerve should be promptly repaired or reconstructed, and new rehabilitation strategies should early be initiated. Considering nerve transfers in the treatment arsenal can shorten the time of nerve reinnervation of muscle targets. Timing of nerve repair and reconstruction is crucial after nerve injury 5).

1)

Willand MP, Nguyen MA, Borschel GH, Gordon T. Electrical Stimulation to Promote Peripheral Nerve Regeneration. Neurorehabil Neural Repair. 2016 Jun;30(5):490-6. doi: 10.1177/1545968315604399. Epub 2015 Sep 10. PMID: 26359343.
2)

Zuo KJ, Gordon T, Chan KM, Borschel GH. Electrical stimulation to enhance peripheral nerve regeneration: Update in molecular investigations and clinical translation. Exp Neurol. 2020 Oct;332:113397. doi: 10.1016/j.expneurol.2020.113397. Epub 2020 Jul 3. PMID: 32628968.
3)

MacEwan MR, Gamble P, Stephen M, Ray WZ. Therapeutic electrical stimulation of injured peripheral nerve tissue using implantable thin-film wireless nerve stimulators. J Neurosurg. 2018 Feb 9:1-10. doi: 10.3171/2017.8.JNS163020. Epub ahead of print. PMID: 29424647.
4)

Zhang Y, Chen S, Xiao Z, Liu X, Wu C, Wu K, Liu A, Wei D, Sun J, Zhou L, Fan H. Magnetoelectric Nanoparticles Incorporated Biomimetic Matrix for Wireless Electrical Stimulation and Nerve Regeneration. Adv Healthc Mater. 2021 Jun 27:e2100695. doi: 10.1002/adhm.202100695. Epub ahead of print. PMID: 34176235.
5)

Dahlin LB. The role of timing in nerve reconstruction. Int Rev Neurobiol. 2013;109:151-64. doi: 10.1016/B978-0-12-420045-6.00007-9. Review. PubMed PMID: 24093611.

Malignant middle cerebral artery territory infarction

Malignant middle cerebral artery territory infarction

General information

The malignant middle cerebral artery territory infarction is a distinct syndrome that occurs in up to 10% of stroke patients, 1) 2) which carries a mortality of up to 80% (mostly due to severe postischemic cerebral edema → increased ICP → herniation 3)

Patients usually present with findings of severe hemispheric stroke (hemiplegia, forced eye and head deviation) often with CT findings of major infarct within the first 12 hours. Most develop drowsiness shortly after admission. There is progressive deterioration during the first 2 days, and subsequent transtentorial herniation usually within 2–4 days of stroke. Fatalities are often associated with: severe drowsiness, dense hemiplegia, age > 45–50 yrs, 4) early parenchymal hypodensity involving > 50% of the MCA distribution on CT scan,23 midline shift > 8–10 mm, early sulci effacement, and hyperdense artery sign (p. 1354) 5) in MCA. Neurosurgeons may become involved in caring for these patients because aggressive therapies in these patients may reduce morbidity and mortality. Options include:

  1. conventional measures to control ICP (with or without ICP monitor): mortality is still high in this group and elevated ICP is not a common cause of initial neurologic deterioration in large hemispheric stroke

2. hemicraniectomy (decompressive craniectomy):

  1. ✖ to date, the following treatments have not improved outcome: agents to lyse clot, hyperventilation, mannitol, or barbiturate coma.

In patients with severe middle cerebral artery (MCA), intracranial atherosclerotic disease (ICAD), the mechanism of stroke is multifactorial, but hemodynamic insufficiency plays a significant role. This finding is important in selecting a subgroup of patients who may benefit from revascularization 6).

Clinical features

see Malignant middle cerebral artery syndrome.

Diagnosis

Malignant middle cerebral artery territory infarction diagnosis.

Treatment

Malignant middle cerebral artery territory infarction treatment.

Outcome

Malignant middle cerebral artery territory infarction outcome.

Case reports

A case of a child with serological evidence of SARS-CoV-2 infection whose onset was a massive right cerebral artery ischemia that led to a malignant cerebral infarction. The patient underwent a life-saving decompressive hemicraniectomy, with good functional recovery, except for residual hemiplegia. During rehabilitation, the patient also developed a lower extremity peripheral nerve neuropathy, likely related to a long-Covid syndrome 7).

A 39-year-old woman in the 24th week of pregnancy who suffered a right malignant MCA infarction that eventually required DC. The patient delivered a healthy baby and underwent a second surgery for cranioplasty 7 months later. 8).

References

1)

Moulin DE, Lo R, Chiang J, et al. Prognosis in Middle Cerebral Artery Occlusion. Stroke. 1985;16:282–284
2) , 3)

Hacke W, Schwab S, Horn M, et al. Malignant Middle Cerebral Artery Territory Infarction: Clinical Course and Prognostic Signs. Arch Neurol. 1996; 53:309–315
4) , 5)

Wijdicks EFM, Diringer MN. Middle Cerebral Artery Territory Infarction and Early Brain Swelling: Progression and Effect of Age on Outcome. Mayo Clin Proc. 1998; 73:829–836
6)

Dubow JS, Salamon E, Greenberg E, Patsalides A. Mechanism of Acute Ischemic Stroke in Patients with Severe Middle Cerebral Artery Atherosclerotic Disease. J Stroke Cerebrovasc Dis. 2014 Jan 11. pii: S1052-3057(13)00425-4. doi: 10.1016/j.jstrokecerebrovasdis.2013.10.015. [Epub ahead of print] PubMed PMID: 24424333.
7)

Scala MR, Spennato P, Cicala D, Piccolo V, Varone A, Cinalli G. Malignant cerebral infarction associated with COVID-19 in a child. Childs Nerv Syst. 2021 Jun 26. doi: 10.1007/s00381-021-05273-x. Epub ahead of print. PMID: 34175976.
8)

Fernández García A, Jiménez Zapata HD, de Lera Alfonso MC, Sánchez Fernández C, Jiménez Arribas P, Rodríguez Arias CA. Decompressive Craniectomy in Pregnant Women. J Neurol Surg A Cent Eur Neurosurg. 2021 Jun 2. doi: 10.1055/s-0041-1726108. Epub ahead of print. PMID: 34077979.

Helmet

Helmet

Construction helmets are considered essential personal protective equipment for reducing traumatic brain injury risks at work sites. In a study, we proposed a practical finite element modeling approach that would be suitable for engineers to optimize construction helmet design. The finite element model includes all essential anatomical structures of a human head (i.e. skin, scalp, skull, cerebrospinal fluid, brain, medulla, spinal cord, cervical vertebrae, and discs) and all major engineering components of a construction helmet (i.e. shell and suspension system). The head finite element model has been calibrated using the experimental data in the literature. It is technically difficult to precisely account for the effects of the neck and body mass on the dynamic responses, because the finite element model does not include the entire human body. An approximation approach has been developed to account for the effects of the neck and body mass on the dynamic responses of the head-brain. Using the proposed model, we have calculated the responses of the head-brain during a top impact when wearing a construction helmet. The proposed modeling approach would provide a tool to improve the helmet design on a biomechanical basis 1).

Snow Sport

Neurotrauma from snow-sports related injuries is infrequently documented in the literature. In Australia no collective data has ever been published. The aim of this study is to document the injury pattern of snow sports related neurotrauma admissions to The Canberra Hospital, the regional trauma centre for the Snowy Mountains. A computerised hospital record search conducted between January 1994 and July 2002 revealed 25 head and 66 spinal injury admissions. The incidence of severe injuries requiring referral to tertiary trauma hospital was estimated to be 7.4 per 100,000 skier-days and for head and spinal injury 1.8 per 1,000,000 skier-days and 5.6 per 1,000,000 skier-days, respectively. Collision with a stationary object was disproportionately associated with head injury and falling forward with spinal injury. Snowboarders tended to sustain cervical fractures more often than skiers. The importance of helmet usage in buffering the impact of head-on collision and the proposition of having both feet fastened to a snowboard in leading to cervical injury were highlighted 2).

Helmets may provide some protection from head injury among skiers and snowboarders involved in falls or collisions 3).

Similar to bicycle helmet promotion programs, ski and snowboard helmet campaigns should focus on delivering a positive image of helmet use and peer acceptance 4).

Parent’s helmet-wearing behavior was strongly associated with the child/adolescent’s helmet-wearing behavior. The results demonstrate the overwhelming influence parental helmet use has on their child/adolescent’s decision to wear a helmet 5).

Skiing

Snowboard

The incidence of possible concussion is high among snowboarding class participants. Emphasis should be given for instituting pre-participation balance training, especially for females to reduce falling in snowboarding. To verify the effects of pre-participation balance training and falling results in a concussion, more research is needed in the future.

Frequently involving occipital impact, could lead to more major head injuries. Measures should be taken to protect the head, especially the occiput, in snowboarding 6).

Not wearing a helmet and riding on icy slopes emerged as a combination of risk factors associated with injury.

Several risk factors and combinations exist, and different risk profiles were identified. Future research should be aimed at more precise identification of groups at risk and developing specific recommendations for each group-for example, a snow-weather conditions index at valley stations 7).

Alpine skiing

The association between helmet use during alpine skiing and incidence and severity of head injury was analyzed. All patients admitted to a Level I Trauma Center for traumatic brain injurys (TBI) sustained due to skiing accidents during the seasons 2000/01-2010/11 were eligible. Primary outcome was the association between helmet use and severity of TBI measured by Glasgow Coma Scale (GCS), CT-results, and necessity of neurosurgical intervention. Of 1362 patients injured during alpine skiing, 245 (18%) sustained TBI and were included. TBI was fatal in 3%. Head injury was minor (GCS 13-15) in 76%, 6% moderate and 14% severe. Number and percentage of TBI patients showed no significant trend over the investigated seasons. Forty-five percent of the 245 patients had pathological CT-findings and 26% of these required neurosurgical intervention. Helmet use increased from 0% in 2000/2001 to 71% in 2010/2011 (p<0.001). The main analysis, comparing TBI in patients with or without a helmet, showed an adjusted Odds Ratio (OR) of 1.44 (p=0.430) for suffering moderate head injury to severe head injury in helmet users. Analyses comparing off-piste to on-slope skiers revealed a significantly increased OR among off-piste skiers of 7.62 (p=0.004) for sustaining a TBI requiring surgical intervention. Despite increases in helmet use Baschera et al., found no decrease in severe TBI among alpine skiers. Logistic regression analysis showed no significant difference in TBI with regard to helmet use, but increased risk for off-piste skiers. The limited protection of helmets and dangers of skiing off-piste should be targeted by prevention programs 8).

Motorcycle

see Helmet for motorcycle.

Electrically Assisted Pedal Cycles

Electrically Assisted Pedal Cycles (EAPCs) are pedal bikes that are fitted with a motor that travel at higher speeds than conventional bicycles. Recent international data shows that there is an association with increased severity of injury, particularly in paediatric populations. Currently, EAPCs are subject to the same legislation regarding helmet use as pedal bikes in the UK and EU which does not mandate the use of a helmet.

Trichinopoly Krishna et al. examined safety concerns surrounding EAPCs in the context of existing EU and UK legislation to assess whether changes to these should be made by public health bodies to mitigate the increased risk of injury.

A retrospective international literature review looking at electric bicycle-related trauma and legislation was conducted using a systematic search of internet databases. Peer-reviewed articles and online resources were reviewed based on relevance to the above objective.

EAPCS can travel at up to 17.5 mph, resulting in higher speeds of travel and collision. The use of EAPCs has been associated with increased severity of head injury. Bicycle helmets have been shown to reduce the severity of head injury in accidents involving both EAPCs and pedal cycles. Healthcare providers should pay extra attention to the possibility of severe injuries when a patient had a bicycle accident with an EAPC, especially in paediatric populations.

Given that EAPCS have been associated internationally with increased severity of head injuries they propose that existing EU and UK legislation may not be fit for purpose with respects to increased EAPC usage and criteria for impact protection of existing helmets. Further research and audit with more accurate recording of data associated with EAPCs use and associated injuries would inform enhanced regulation regarding EAPC usage in the future 9).

1) 
Wu JZ, Pan CS, Wimer BM, Rosen CL. Finite element simulations of the head-brain responses to the top impacts of a construction helmet: Effects of the neck and body mass. Proc Inst Mech Eng H. 2017 Jan;231(1):58-68. doi: 10.1177/0954411916678017. PubMed PMID: 28097935.
2) 
Siu TL, Chandran KN, Newcombe RL, Fuller JW, Pik JH. Snow sports related head and spinal injuries: an eight-year survey from the neurotrauma centre for the Snowy Mountains, Australia. J Clin Neurosci. 2004 Apr;11(3):236-42. PubMed PMID: 14975409.
3) 
Mueller BA, Cummings P, Rivara FP, Brooks MA, Terasaki RD. Injuries of the head, face, and neck in relation to ski helmet use. Epidemiology. 2008 Mar;19(2):270-6. doi: 10.1097/EDE.0b013e318163567c. PubMed PMID: 18277163.
4) 
Peterson AR, Brooks MA. Pilot study of adolescent attitudes regarding ski or snowboard helmet use. WMJ. 2010 Feb;109(1):28-30. PubMed PMID: 20942297; PubMed Central PMCID: PMC2957671.
5) 
Provance AJ, Engelman GH, Carry PM. Implications of parental influence on child/adolescent helmet use in snow sports. Clin J Sport Med. 2012 May;22(3):240-3. doi: 10.1097/JSM.0b013e3182410335. PubMed PMID: 22270869
6) 
Nakaguchi H, Fujimaki T, Ueki K, Takahashi M, Yoshida H, Kirino T. Snowboard head injury: prospective study in Chino, Nagano, for two seasons from 1995 to 1997. J Trauma. 1999 Jun;46(6):1066-9. PubMed PMID: 10372627.
7) 
Hasler RM, Berov S, Benneker L, Dubler S, Spycher J, Heim D, Zimmermann H, Exadaktylos AK. Are there risk factors for snowboard injuries? A case-control multicentre study of 559 snowboarders. Br J Sports Med. 2010 Sep;44(11):816-21. doi: 10.1136/bjsm.2010.071357. PubMed PMID: 20820060.
8) 
Baschera D, Hasler RM, Taugwalder D, Exadaktylos A, Raabe A. Association between head injury and helmet use in alpine skiers: Cohort study from a Swiss level I trauma center. J Neurotrauma. 2014 Sep 22. [Epub ahead of print] PubMed PMID: 25244343.
9) 
Trichinopoly Krishna S, Roberts S, Dardis R. Electrically assisted pedal cycles: is new legislation required to mitigate increased head injury risk? Br J Neurosurg. 2021 Jun 26:1-4. doi: 10.1080/02688697.2021.1940846. Epub ahead of print. PMID: 34180330.

Pituitary adenoma classification

Pituitary adenoma classification

They are classified based on size or cell of origin. Pituitary adenoma can be described as microadenoma, macroadenoma, and giant tumors based on size. Microadenoma is tumors less than 10 mm, while macroadenoma includes tumors larger than 10mm. Giant pituitary adenomas are more than 40 mm. There are functional pituitary adenomas in which the cell type that composes them causes increased secretion of one or multiple hormones of the anterior pituitary. Alternatively, there are Non-Functioning Pituitary Adenomas that do not secrete hormones, but they can compress the surrounding areas of the anterior pituitary leading to hormonal deficiencies 1).

The 2017 World Health Organization classification of tumors of the pituitary gland

see The 2017 World Health Organization classification of tumors of the pituitary gland.

In the fourth edition of the World Health Organization classification of endocrine tumors, are two critical changes to the classification for pituitary adenomas.

One is that the term “atypical adenoma,” which was characterized based on highly proliferative properties to predict adenomas that carry a poor prognosis, was completely eliminated due to the lack of definitive evidence. The other change is the introduction of more precise cell lineage-based classification of pituitary adenoma that is defined based on lineage-specific transcription factors and hormones produced. Accordingly, null cell adenomas have been re-defined as those that show completely negative immunostaining either for hormones or for adenohypophyseal transcription factors 2).

Somatotroph adenoma.

Lactotroph adenoma.

Tyrotroph adenoma.

Corticotroph adenoma.

Gonadotroph adenoma.

Null cell adenoma

Plurihormonal pituitary adenoma and double adenomas.

The classification is based upon the size, invasion of adjacent structures, sporadic or familial cases, biochemical activity, clinical manifestations, morphological characteristics, response to treatment, and recurrence 3).

Current classification systems for PAs are based primarily on secretory characteristics of the tumor but are also classified on the basis of phenotypical characteristics, including tumor size, degree of invasiveness (e.g., Knosp grade), and immunohistological findings 4).

The anterior WHO classification system for PAs was refined to include designations for benign adenoma, atypical adenoma, and pituitary carcinoma on the basis of p53 immunoreactivity, MIB-1 index, mitotic activity, and the absence/presence of metastases 5) 6).

These tumor types can be microadenomas or macroadenomas and can either be functional or non-functional.

By Size

Pituitary microadenoma

Pituitary macroadenoma

Giant pituitary adenoma

Volume can be calculated using MRI-guided volumetrics and an ellipsoid approximation (TV × AP × CC/2) transverse (TV), antero-posterior (AP) and cranio-caudal (CC).

By Function

Functioning pituitary adenoma

Nonfunctioning pituitary adenoma

Pituitary adenomas with gangliocytic component are rare tumors of the sellar region that are composed of pituitary adenoma cells and a ganglion cell component. Their histogenesis and hence nosology is not yet resolved because of the small number of cases reported and lack of large series in the literature 7).

Invasive pituitary adenomas and pituitary carcinomas are clinically indistinguishable until the identification of metastases.

Consistency

Although most authors differentiate easily aspirated (soft) tumors from those that are not (fibrous, might require prior fragmentation), there is no universally accepted PA consistency classification. Fibrous PA tends to be hypointense on T2WI and has lower apparent diffusion coefficient (ADC) values. Fibrous tumors seemed to present higher invasion into neighboring structures, including the cavernous sinus. Several articles suggest that dopamine agonists could increase PA consistency and that prior surgery and radiotherapy also make PA more fibrous. The anatomopathological studies identify collagen as being mainly responsible for fibrous consistency of adenomas.

Conclusions: Preoperative knowledge of PA consistency affords the neurosurgeon substantial benefit, which clearly appears to be relevant to surgical planning, risks, and surgery outcomes. It could also encourage the centralization of these high complexity tumors in reference centers. Further studies may be enhanced by applying standard consistency classification of the PA and analyzing a more extensive and prospective series of fibrous PA. 8).

Knosp Grade

Knosp Grade.

Hardy’s Classification of Pituitary Adenomas

Hardy’s Classification of Pituitary Adenomas.

References

1)

Russ S, Shafiq I. Pituitary Adenoma. 2020 Feb 4. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK554451/ PubMed PMID: 32119338.
2)

Inoshita N, Nishioka H. The 2017 WHO classification of pituitary adenoma: overview and comments. Brain Tumor Pathol. 2018 Apr;35(2):51-56. doi: 10.1007/s10014-018-0314-3. Epub 2018 Apr 23. Review. PubMed PMID: 29687298.
3)

Syro LV, Rotondo F, Ramirez A, Di Ieva A, Sav MA, Restrepo LM, Serna CA, Kovacs K. Progress in the Diagnosis and Classification of Pituitary Adenomas. Front Endocrinol (Lausanne). 2015 Jun 12;6:97. doi: 10.3389/fendo.2015.00097. eCollection 2015. Review. PubMed PMID: 26124750; PubMed Central PMCID: PMC4464221.
4)

Knosp E, Steiner E, Kitz K, Matula C: Pituitary adenomas with invasion of the cavernous sinus space: a magnetic resonance imaging classification compared with surgical findings. Neurosurgery 33:610–618, 1993
5)

Barnes L, Eveson JW, Reichart P, David Sidransky: World Health Organization Classification of Tumours: Pathology and Genetics of Head and Neck Tumours Lyon, IARC Press, 2005
6)

Zada G, Woodmansee WW, Ramkissoon S, Amadio J, Nose V, Laws ER Jr: Atypical pituitary adenomas: incidence, clinical characteristics, and implications. J Neurosurg 114:336–344, 2011
7)

Balci S, Saglam A, Oruckaptan H, Erbas T, Soylemezoglu F. Pituitary adenoma with gangliocytic component: report of 5 cases with focus on immunoprofile of gangliocytic component. Pituitary. 2014 Jan 16. [Epub ahead of print] PubMed PMID: 24430434.
8)

Acitores Cancela A, Rodríguez Berrocal V, Pian H, Martínez San Millán JS, Díez JJ, Iglesias P. Clinical relevance of tumor consistency in pituitary adenoma. Hormones (Athens). 2021 Jun 19. doi: 10.1007/s42000-021-00302-5. Epub ahead of print. PMID: 34148222.

Brain death

Brain death

The published World Brain Death Project aims in alleviating inconsistencies in clinical guidelines and practice in the determination of death by neurologic criteria. However, critics have taken issue with a number of epistemic and metaphysical assertions that critics argue are either false, ad hoc, or confused.

Lazaridis disscussed the nature of a definition of death; the plausibility of neurologic criteria as a sensible social, medical, and legal policy; and within a Rawlsian liberal framework, reasons for personal choice or accommodation among neurologic and circulatory definitions. Declaration of human death cannot rest on contested metaphysics or unmeasurable standards, instead it should be regarded as a plausible and widely accepted social construct that conforms to best available and pragmatic medical science and practice. The definition(s) and criteria should be transparent, publicly justifiable, and potentially allow for the accommodation of reasonable choice. This is an approach that situates the definition of death as a political matter. The approach anticipates that no conceptualization of death can claim universal validity, since this is a question that cannot be settled solely on biologic or scientific grounds, rather it is a matter of normative preference, socially constructed and historically contingent 1).

The concept of brain death has periodically come under criticism 2).

Confirmatory tests for the diagnosis of brain death in addition to clinical findings may shorten observation time required in some countries and may add certainty to the diagnosis under specific circumstances.

The current U.S. approach to determining death was developed in response to the emergence of technologies that made the traditional standard of cardiopulmonary death problematic. In 1968, an ad hoc committee at Harvard Medical School published an influential article arguing for extending the concept of death to patients in an “irreversible coma.“ 3). The emerging neurologic criteria for death defined it in terms of loss of the functional activity of the brain stem and cerebral cortex. Although clinical criteria were developed in the 1960s, it took more than a decade for consensus over a rationale for the definition to emerge. In 1981, the President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research provided a philosophical definition of brain death in terms of the loss of the critical functions of the organism as a whole 4).

Shortly thereafter, the National Conference of Commissioners on Uniform State Laws produced the Uniform Determination of Death Act, which has been adopted in 45 states and recognized in the rest through judicial opinion 5).

Computed tomography angiography for brain death

see Computed tomography angiography for brain death.

S100B

Changes in S100B protein, especially the levels of this dimer 48 hours after trauma can be used as marker to predict brain death. Alongside other known prognostic factors such as age, GCS and diameters of the pupils, however, this factor individually can not conclusive predict the patient’s clinical course and incidence of brain death. However, it is suitable to use GCS, CT scan, clinical symptoms and biomarkers together for a perfect prediction of brain death 6).

Near-Infrared Spectroscopy

Near-Infrared Spectroscopy for Brain death

Gadolinium-enhanced magnetic resonance angiography

The practicability of Gadolinium-enhanced magnetic resonance angiography to confirm cerebral circulatory arrest was assessed after the diagnosis of brain death in 15 patients using a 1.5 Tesla MRI scanner. In all 15 patients extracranial blood flow distal to the external carotid arteries was undisturbed. In 14 patients no contrast medium was noted within intracerebral vessels above the proximal level of the intracerebral arteries. In one patient more distal segments of the anterior and middle cerebral arteries (A3 and M3) were filled with contrast medium. Gadolinium-enhanced MRA may be considered conclusive evidence of cerebral circulatory arrest, when major intracranial vessels fail to fill with contrast medium while extracranial vessels show normal blood flow 7).

The level of knowledge of medical students at Centro Universitário Lusíada – UNILUS- Santos (SP), Brazil, regarding brain death and transplantation is limited, which could be the result of inadequate education during medical school 8).

Criteria

Brain death criteria.

Case reports

In a editorial, Hibi et al., aimed to provide an outline of the world history of liver transplantation (LT), with a special focus on the innovation, development, and current controversies of living donor (LD) LT from East Asian and Western perspectives. In 1963, Starzl et al. (University of Colorado, U.S.) performed the world’s first human LT for a 3-year-old child with biliary atresia. The donor was a 3-year-old patient who had suffered from brain death following neurosurgery. 9).

1)

Lazaridis C. Defining Death: Reasonableness and Legitimacy. J Clin Ethics. 2021 Summer;32(2):109-113. PMID: 34129526.
2)

Truog RD, Miller FG, Halpern SD. The dead-donor rule and the future of organ donation. N Engl J Med 2013;369:1287-1289
3)

A definition of irreversible coma: report of the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death. JAMA 1968;205:337-340
4)

President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research. Defining death: a report on the medical, legal and ethical issues in the determination of death. Washington, DC: Government Printing Office, 1981.
5)

National Conference of Commissioners on Uniform State Laws. Uniform Determination of Death Act, 1981 (http://www.uniformlaws.org/shared/docs/determination%20of%20death/udda80.pdf).
6)

Shakeri M, Mahdkhah A, Panahi F. S100B Protein as a Post-traumatic Biomarker for Prediction of Brain Death in Association With Patient Outcomes. Arch Trauma Res. 2013 Aug;2(2):76-80. doi: 10.5812/atr.8549. Epub 2013 Aug 1. PubMed PMID:24396798.
7)

Luchtmann M, Beuing O, Skalej M, Kohl J, Serowy S, Bernarding J, Firsching R. Gadolinium-enhanced magnetic resonance angiography in brain death. Sci Rep. 2014 Jan 13;4:3659. doi: 10.1038/srep03659. PubMed PMID: 24413880.
8)

Reis FP, Gomes BH, Pimenta LL, Etzel A. Brain death and tissue and organ transplantation: the understanding of medical students. Rev Bras Ter Intensiva. 2013 Oct-Dec;25(4):279-283. Portuguese, English. PubMed PMID: 24553508.
9)

Hibi T, Eguchi S, Egawa H. Evolution of living donor liver transplantation: A global perspective. J Hepatobiliary Pancreat Sci. 2018 Jun 28. doi: 10.1002/jhbp.571. [Epub ahead of print] PubMed PMID: 29953731.

Anterior Thalamic Stimulation

Anterior Thalamic Stimulation

Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) is a novel and promising treatment method for patients with drug-resistant epilepsy.

Clinical efficacy

More than 70% of patients implanted with ANT-DBS benefit significantly from this method, i.e., they report seizure-reduction rates higher than 50%

The median percent seizure reduction from baseline at 1 year was 41%, and 69% at 5 years. The responder rate (≥50% reduction in seizure frequency) at 1 year was 43%, and 68% at 5 years. In the 5 years of follow-up, 16% of subjects were seizure-free for at least 6 months. There were no reported unanticipated adverse device effects or symptomatic intracranial hemorrhages. The Liverpool Seizure Severity Scale and 31-item Quality of Life in Epilepsy measure showed statistically significant improvement over baseline by 1 year and at 5 years (p < 0.001).

Long-term follow-up of ANT deep brain stimulation showed sustained efficacy and safety in a treatment-resistant population.

Classification of evidence: This long-term follow-up provides Class IV evidence that for patients with drug-resistant partial epilepsy, anterior thalamic stimulation is associated with a 69% reduction in seizure frequency and a 34% serious device-related adverse event rate at 5 years. 1).

Adverse events

When focusing on the adverse events reported in a study of stimulation of the anterior nuclei of thalamus (SANTE study), the patients reported paresthesia (18% patients), pain in the implant side (10.9% patients), and infection at the implant site (9.1% patients) 2)

Literature search

Sobstyl et al. performed a literature search regarding the clinical efficacy of ANT DBS. They discussed the surgical technique of the implantation of DBS electrodes with special attention paid to the targeting methods of the ANT. Moreover, they present in detail the clinical efficacy of ANT DBS, with a special emphasis on the stimulation parameters, a stimulation mode, and polarity. They also report all adverse events and present the current limitations of ANT DBS.

In general, the safety profile of DBS in intractable epilepsy patients is good, with a low rate of surgery, hardware-related, and stimulation-induced adverse events. No significant cognitive declines or worsening of depressive symptoms was noted. At long-term follow-up, the quality-of-life scores have improved. The limitations of ANT DBS studies include a limited number of patients treated and mostly open-label designs with only one double-blind, randomized multicenter trial. Most studies do not report the etiology of intractable epilepsy or they include nonhomogeneous groups of patients affected by intractable epilepsy. There are no guidelines for setting initial stimulation parameters. All the variables mentioned may have a profound impact on the final outcome.

ANT DBS appears to be a safe and efficacious treatment, particularly in patients with refractory partial seizures (three-quarters of patients gained at least 50% seizure reduction after 5 years). ANT DBS reduces most effectively the seizures originating in the temporal and frontal lobes. The published results of ANT DBS highlight promise and hope for patients with intractable epilepsy 3).

A literature review discusses the rationale, mechanism of action, clinical efficacy, safety, and tolerability of ANT-DBS in drug-resistant epilepsy patients. A review using systematic methods of the available literature was performed using relevant databases including Medline, Embase, and the Cochrane Library pertaining to the different aspects ANT-DBS. ANT-DBS for drug-resistant epilepsy is a safe, effective and well-tolerated therapy, where a special emphasis must be given to monitoring and neuropsychological assessment of both depression and memory function. Three patterns of seizure control by ANT-DBS are recognized, of which a delayed stimulation effect may account for an improved long-term response rate. ANT-DBS remotely modulates neuronal network excitability through overriding pathological electrical activity, decrease neuronal cell loss, through immune response inhibition or modulation of neuronal energy metabolism. ANT-DBS is an efficacious treatment modality, even when curative procedures or lesser invasive neuromodulative techniques failed. When compared to VNS, ANT-DBS shows slightly superior treatment response, which urges for direct comparative trials. Based on the available evidence ANT-DBS and VNS therapies are currently both superior compared to non-invasive neuromodulation techniques such as t-VNS and rTMS. Additional in-vivo research is necessary in order to gain more insight into the mechanism of action of ANT-DBS in localization-related epilepsy which will allow for treatment optimization. Randomized clinical studies in search of the optimal target in well-defined epilepsy patient populations, will ultimately allow for optimal patient stratification when applying DBS for drug-resistant patients with epilepsy 4).

Case series

Bilateral ANT electrodes were implanted into 18 patients suffering from focal, pharmacoresistant epilepsy. Antiepileptic treatment was kept unchanged from three months prior to operation. The Liverpool seizure severity scale (LSSS) was used to measure the burden of epilepsy.

Results: There was no significant difference between the 2 groups at the end of the blinded period at 6 months. However, when considering all patients and comparing 6 months of stimulation with baseline, there was a significant, 22% reduction in the frequency of all seizures (P = 0.009). Four patients had ≥50% reduction in total seizure frequency and 5 patients ≥50% reduction in focal seizures after 6 months of stimulation. No increased effect over time was shown. LSSS at 6 months compared to baseline showed no significant difference between the 2 groups, but a small, significant reduction in LSSS was found when all patients had received stimulation for 6 months.

Conclusions: Our study supports results from earlier studies concerning DBS as a safe treatment option, with effects even in patients with severe, refractory epilepsy. However, our results are not as encouraging as those reported from many other, mainly unblinded, and open studies 5).

Case reports

A case of relapsing herpes simplex encephalitis (HSE) as a newly reported and potentially fatal stimulation-related adverse effect following stimulation of the anterior thalamic nucleus (ANT-DBS) accompanied by fever, confusion, and cognitive impairment in a 32-year-old epileptic patient with a history of herpes meningoencephalitis 31 years earlier. The T2-weighted/FLAIR high-signal intensity in the temporal lobe developed at a “distance” from the stimulation target. The positive polymerase chain reaction of herpes virus deoxyribonucleic acid in the cerebrospinal fluid confirmed the diagnosis. The condition improved partially on acyclovir and stimulation stopped. Seizures disappeared and then returned after few months. The unique case report presents a rationale for considering history of herpes encephalitis as a relative contraindication for ANT-DBS, and HSE relapse should be suspected in patients with post-stimulation fever and/or altered consciousness 6).

1)

Salanova V, Witt T, Worth R, Henry TR, Gross RE, Nazzaro JM, Labar D, Sperling MR, Sharan A, Sandok E, Handforth A, Stern JM, Chung S, Henderson JM, French J, Baltuch G, Rosenfeld WE, Garcia P, Barbaro NM, Fountain NB, Elias WJ, Goodman RR, Pollard JR, Tröster AI, Irwin CP, Lambrecht K, Graves N, Fisher R; SANTE Study Group. Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy. Neurology. 2015 Mar 10;84(10):1017-25. doi: 10.1212/WNL.0000000000001334. Epub 2015 Feb 6. PMID: 25663221; PMCID: PMC4352097.
2)

Fisher R, Salanova V, Witt T, Worth R, Henry T, Gross R, Oommen K, Osorio I, Nazzaro J, Labar D, Kaplitt M, Sperling M, Sandok E, Neal J, Handforth A, Stern J, DeSalles A, Chung S, Shetter A, Bergen D, Bakay R, Henderson J, French J, Baltuch G, Rosenfeld W, Youkilis A, Marks W, Garcia P, Barbaro N, Fountain N, Bazil C, Goodman R, McKhann G, Babu Krishnamurthy K, Papavassiliou S, Epstein C, Pollard J, Tonder L, Grebin J, Coffey R, Graves N; SANTE Study Group. Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia. 2010 May;51(5):899-908. doi: 10.1111/j.1528-1167.2010.02536.x. Epub 2010 Mar 17. PMID: 20331461.
3)

Sobstyl M, Stapińska-Syniec A, Iwański S, Rylski M. Clinical Efficacy and Safety Profile of Anterior Thalamic Stimulation for Intractable Epilepsy. J Neurol Surg A Cent Eur Neurosurg. 2021 Jun 14. doi: 10.1055/s-0041-1725954. Epub ahead of print. PMID: 34126641.
4)

Bouwens van der Vlis TAM, Schijns OEMG, Schaper FLWVJ, Hoogland G, Kubben P, Wagner L, Rouhl R, Temel Y, Ackermans L. Deep brain stimulation of the anterior nucleus of the thalamus for drug-resistant epilepsy. Neurosurg Rev. 2019 Jun;42(2):287-296. doi: 10.1007/s10143-017-0941-x. Epub 2018 Jan 6. PMID: 29306976; PMCID: PMC6502776.
5)

Herrman H, Egge A, Konglund AE, Ramm-Pettersen J, Dietrichs E, Taubøll E. Anterior thalamic deep brain stimulation in refractory epilepsy: A randomized, double-blinded study. Acta Neurol Scand. 2019 Mar;139(3):294-304. doi: 10.1111/ane.13047. Epub 2018 Dec 11. PMID: 30427061.
6)

Hamdi H, Robin E, Stahl JP, Doche E, Azulay JP, Chabardes S, Bartolomei F, Regis J. Anterior Thalamic Stimulation Induced Relapsing Encephalitis. Stereotact Funct Neurosurg. 2019;97(2):132-136. doi: 10.1159/000499072. Epub 2019 May 3. PMID: 31055582.

Developmental venous anomaly

Developmental venous anomaly

Key concepts

● a vascular malformation that is part of the venous drainage of the involved area with intervening brain present. Therefore direct treatment is rarely indicated

● low-flow, low-pressure

● usually demonstrable on angiography as a starburst pattern

● rarely symptomatic: seizures rare, hemorrhage even more uncommon. Venous infarcts may occur (controversial)

● may have an associated cavernous malformation which is more likely to be symptomatic

Developmental venous anomaly (DVA) AKA venous malformation or (developmental) venous angioma. A tuft of medullary veins that converge into an enlarged central trunk that drains either to the deep or superficial venous system. The veins lack large amounts of smooth muscle and elastic. No abnormal arteries are found. There is neural parenchyma between the vessels. Most common in regions supplied by the MCA or in the region of the vein of Galen. They may be associated with a cavernous malformation.

Non hereditary. These are low-flow and low-pressure.

Most are clinically silent, but rarely seizures and even less frequently hemorrhage may occur. Venous infarcts have been described, but maybe coincidental. If symptoms are present, look for an associated cavernous malformation (GRASS MRI images may reveal some cavernous malformations that might otherwise be occult).

They have mostly supplanted the more pedestrian venous angioma 1).

Congenital malformation of veins which drain normal brain. They were thought to be rare before cross-sectional imaging but are now recognised as being the most common cerebral vascular malformation, accounting for ~55% of all such lesions.

A venous anomaly is characterized by the caput medusae sign of veins draining into a single larger collecting vein, which in turn drains into either a dural sinus or into a deep ependymal vein. The appearance has also been likened to a palm tree.

Pathology

The aetiology of VAs remains uncertain, but may relate to arrested development of venous structures

Histologically they consist of a number of abnormally thickened veins with normal feeding arteries and capillaries

Classification

The most common locations are:

frontoparietal region (36-64%) 1, usually draining towards the frontal horn of the lateral ventricle

cerebellar hemisphere (14-27%) draining towards the fourth ventricle

However, DVAs can be seen anywhere, draining either superficially or deep.

see Spinal cord venous angioma.

Associations

Lesions are usually solitary (75%), except in blue rubber bleb naevus syndrome

~20% (range 8-33%) of cases 2 are associated with cavernous malformations and are referred to as mixed vascular malformations (MVM) there is an association with venous malformations of the head and neck.

Diagnosis

Developmental venous anomaly diagnosis.

Treatment

In general, these should not be treated, as they are the venous drainage of the brain in that vicinity. If surgery is indicated for associated cavernous malformations, the angioma should be left alone. Surgery for the angioma itself is reserved only for documented bleeding or for intractable seizures that can be definitely attributed to the lesion.

Case series

Fifty-two children (20 boys and 32 girls [median age: 6 years] were identified with DVAs. Their age distribution was as follows: 1.9% neonates (< 1 month), 11.5% infants (1 month to 1 year), 30.8% 1-5 years, 30.8% 5-12 years and 25% 12-16 years. The majority (92.3%) presented with asymptomatic DVAs identified incidentally. Overall, anatomical distribution revealed predilection for frontal region (42.3%) with other common sites being posterior fossa (17.3%) and basal ganglia (13.5%). Temporal (11.5%), parietal (9.6%) and occipital (5.8%) were the remainder. Associated cavernous malformations (CMs) were present in 3/52 (5.8%), and no DVAs were associated with aneurysms or arteriovenous malformations (AVMs). Three patients had more than one DVA. There were three deaths unrelated to DVAs over median follow-up of 3.8 years. Four patients (7.7%) suffered DVA-related intracranial haemorrhage presenting with neurological deficits. The ages of the children with DVA-related haemorrhages were 21 days, 2 years and 6 months, 7 years and 1 month and 11 years and 7 months. Left-sided DVA haemorrhages predominated (3/4, 75%). The relative risk of a cerebellar DVA haemorrhage compared to its supratentorial counterpart was 5.35 (OR 6.8, 95% CI 0.8-58).

DVA-related haemorrhage is sevenfold greater in the paediatric cohort compared to adults and is significantly associated with a cerebellar location and cavernous malformations. There were no haemorrhages over a median period of 3.8 years of prospective follow-up 2).

Case reports

A 27-year-old woman who presented with a sensorineural hearing loss followed by facial paresis. Magnetic resonance imaging (MRI) and computed tomography (CT) angiography revealed hematoma with adjacent converging veins showing a typical “caput medusa” sign in the left middle cerebellar peduncle, in favor of DVA. Due to the compression effect of hematoma, she underwent surgery. Hearing loss and facial paresis improved significantly during the postoperative follow-up.

Although DVA is mostly benign and asymptomatic, complications such as hemorrhage rarely occur. Hearing loss is an extremely rare presentation that can be attributable to the compression effect on the cranial nerve VII to VIII complex. In the case of compression effect or progression of symptoms, surgical intervention is necessary. A good clinical outcome could be expected postoperatively 3).

Although the association of developmental venous anomalies (DVAs) with cavernous malformations is well documented, the association with arteriovenous malformations (AVM) is unusual. The aim is to report an additional case and to review the concepts associated with these mixed malformations in order to guide patient management.

A case of AVM associated with a DVA was identified and a literature review was performed according to PRISMA guidelines.

Case report: In an 18-year-old man presented with sub-acute headache but with a normal neurological examination, the MRI-scan showed a right occipital DVA associated with hemosiderin spots evocative of earlier asymptomatic bleedings. The Digital Subtraction Angiography revealed a right parieto-occipital Spetzler-Martin Grade III AVM, fed by branches from the right middle and posterior cerebral arteries, with a superficial drainage flowing into a DVA that then joined the superior sagittal sinus. Multistep embolization was performed, leading to a partial reduction of the nidus, but preserving the DVA permeability. After a six-year follow-up. bleeding did not recur and the MRI aspect of the malformation was perfectly stable.

The co-occurrence of a DVA and an AVM is rare but has a higher bleeding risk than AVM alone (69% vs 38%) and must consequently be suspected when a DVA is revealed by a hemorrhage, in the absence of associated cavernoma. These mixed malformations represent a therapeutic challenge that has to be tailored to the venous anatomy and to the malformation Spetzler-Martin grade. DVA permeability should be preserved to avoid deleterious venous infarction 4)

1)

Lasjaunias P, Burrows P, Planet C, et al. Developmental venous anomalies (DVA): the so-called venous angioma. Neurosurg Rev 1986;9:233–42.
2)

Silva AHD, Wijesinghe H, Lo WB, Walsh AR, Rodrigues D, Solanki GA. Paediatric developmental venous anomalies (DVAs): how often do they bleed and where? Childs Nerv Syst. 2020 Jan 3. doi: 10.1007/s00381-019-04460-1. [Epub ahead of print] PubMed PMID: 31900628.
3)

Ebrahimzadeh K, Tavassol HH, Mousavinejad SA, Ansari M, Kazemi R, Bahrami-Motlagh H, Jalili Khoshnoud R, Sharifi G, Samadian M, Rezaei O. The Sensorineural Hearing Loss Related to a Rare Infratentorial Developmental Venous Angioma: A Case Report and Review of Literature. J Neurol Surg A Cent Eur Neurosurg. 2021 Jun 14. doi: 10.1055/s-0041-1725960. Epub ahead of print. PMID: 34126638.
4)

Picart T, Dumot C, Guyotat J, Eker O, Berhouma M, Pelissou-Guyotat I. Arteriovenous malformation drained into a developmental venous anomaly: a case report and up-dated literature review. Neurochirurgie. 2020 Oct 10:S0028-3770(20)30404-5. doi: 10.1016/j.neuchi.2020.08.003. Epub ahead of print. PMID: 33049289.

Diffuse midline glioma H3 K27M-mutant MRI

Diffuse midline glioma H3 K27M-mutant MRI

T1: decreased intensity

T2: heterogeneously increased

T1 C+ (Gd): usually minimal (can enhance post-radiotherapy)

DWI/ADC: usually normal, occasionally mildly restricted

Extensive spread is relatively frequent, both craniocaudally to involve the cerebral hemispheres and spinal cord, as well as leptomeningeal spread 1)

A study included 66 cases (40 in men, 26 in women) of H3 K27M-mutant glioma in adult patients. Tumors were found in the following sites: thalamus (n = 38), brainstem (n = 6), brainstem with cerebellar or thalamic involvement (n = 4), whole-brain (n = 8), corpus callosum (n = 3), hypothalamus (n = 1), hemispheres (n = 2), and spinal cord (n = 4). All pure brainstem lesions were located posteriorly, and all corpus callosal lesions were in the genu. Most spinal tumors were long-segment lesions. Hemispheric lesions mimicked gliomatosis cerebri in presentation, with the addition of traditional midline structure involvement. Most tumors were solid with relatively uniform signals on plain MRI. Of the 61 cases with contrast-enhanced MR images, 36 (59%) showed partial to no enhancement, whereas 25 (41%) showed diffuse or irregular peripheral enhancement. Hemorrhage and edema were rare. Most lesions were solid and showed mild diffusion restriction on diffusion-weighted imaging. Tumor dissemination to the leptomeninges (n = 8) and subependymal layer (n = 3) was observed.

Qiu et al. described the MRI features of diffuse midline glioma with H3 K27M mutation in the largest study done to date in adult patients. Tumors were found in both midline and nonmidline structures, with the thalamus being the most common site. Although adult H3 K27M-mutant gliomas demonstrated highly variable presentations in this cohort of patients, the authors were able to observe shared characteristics within each location 2).

The radiographic features of diffuse midline gliomas with histone H3 K27M mutation were highly variable, ranging from expansile masses without enhancement or necrosis with large areas of surrounding infiltrative growth to peripherally enhancing masses with central necrosis with the significant mass effect but little surrounding T2/FLAIR hyperintensity. When we compared diffuse midline gliomas on the basis of the presence or absence of histone H3 K27M mutation, there was no significant correlation between enhancement or border characteristics, infiltrative appearance, or presence of edema 3)

Zhuo et al. from the Beijing Tiantan Hospital aimed to predict H3K27M mutation status by Amide proton transfer imaging (APTw) and radiomic features.

Methods: Eighty-one BSG patients with APTw imaging at 3T MR and known H3K27M status were retrospectively studied. APTw values (mean, median, and max) and radiomic features within manually delineated 3D tumor masks were extracted. Comparison of APTw measures between H3K27M-mutant and wildtype groups was conducted by two-sample Student’s T/Mann-Whitney U test and receiver operating characteristic curve (ROC) analysis. H3K27M-mutant prediction using APTw-derived radiomics was conducted using a machine learning algorithm (support vector machine) in randomly selected train (n = 64) and test (n = 17) sets. Sensitivity analysis with additional random splits of train and test sets, 2D tumor masks, and other classifiers were conducted. Finally, a prospective cohort including 29 BSG patients was acquired for validation of the radiomics algorithm.

Results: BSG patients with H3K27M-mutant were younger and had higher max APTw values than those with wildtype. APTw-derived radiomic measures reflecting tumor heterogeneity could predict H3K27M mutation status with an accuracy of 0.88, the sensitivity of 0.92, and specificity of 0.80 in the test set. Sensitivity analysis confirmed the predictive ability (accuracy range: 0.71-0.94). In the independent prospective validation cohort, the algorithm reached an accuracy of 0.86, the sensitivity of 0.88, and specificity of 0.85 for predicting H3K27M-mutation status.

Conclusion: BSG patients with H3K27M-mutant had higher max APTw values than those with wildtype. APTw-derived radiomics could accurately predict an H3K27M-mutant status in BSG patients 4).

Piccardo et al., from Genoa, retrospectively analyzed 22 pediatric patients with DMG histologically proved and molecularly classified as H3K27M-mutant (12 subjects) and wild-type (10 subjects) who underwent DWI, Proton magnetic resonance spectroscopic imaging, and ASL performed within 2 weeks of 18F-FDOPA PET. DWI-derived relative minimum apparent diffusion coefficient (rADC min), 1H-MRS data choline/N-acetylaspartate (Cho/NAA), choline/creatine (Cho/Cr), and presence of lactate and relative ASL-derived cerebral blood flow max (rCBF max) were compared with 18F-DOPA uptake Tumor/Normal tissue (T/N) and Tumor/Striatum (T/S) ratios, and correlated with histological and molecular features of DMG. Statistics included Pearson’s chi-squared test and Mann-Whitney U tests, Spearman’s rank correlation and receiver operating characteristic (ROC) analysis.

The highest degrees of correlation among different techniques were found between T/S, rADC min and Cho/NAA ratio (p < 0.01), and between rCBF max and rADC min (p < 0.01). Significant differences between histologically classified low- and high-grade DMG, independently of H3K27M-mutation, were found among all imaging techniques (p ≤ 0.02). Significant differences in terms of rCBF max, rADC min, Cho/NAA and 18F-DOPA uptake were also found between molecularly classified mutant and wild-type DMG (p ≤ 0.02), even though wild-type DMG included low-grade astrocytomas, not present among mutant DMG. When comparing only histologically defined high-grade mutant and wild-type DMG, only the 18F-DOPA PET data T/S demonstrated statistically significant differences independently of histology (p < 0.003). ROC analysis demonstrated that T/S ratio was the best parameter for differentiating mutant from wild-type DMG (AUC 0.94, p < 0.001).

Advanced MRI and 18F-DOPA PET characteristics of DMG depend on histological features; however, 18F-DOPA PET-T/S was the only parameter able to discriminate H3K27M-mutant from wild-type DMG independently of histology 5).

References

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Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007 Aug;114(2):97-109. doi: 10.1007/s00401-007-0243-4. Epub 2007 Jul 6. Erratum in: Acta Neuropathol. 2007 Nov;114(5):547. PMID: 17618441; PMCID: PMC1929165.
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Qiu T, Chanchotisatien A, Qin Z, Wu J, Du Z, Zhang X, Gong F, Yao Z, Chu S. Imaging characteristics of adult H3 K27M-mutant gliomas. J Neurosurg. 2019 Nov 15:1-9. doi: 10.3171/2019.9.JNS191920. Epub ahead of print. PMID: 31731269.
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Aboian MS, Solomon DA, Felton E, Mabray MC, Villanueva-Meyer JE, Mueller S, Cha S. Imaging Characteristics of Pediatric Diffuse Midline Gliomas with Histone H3 K27M Mutation. AJNR Am J Neuroradiol. 2017 Apr;38(4):795-800. doi: 10.3174/ajnr.A5076. Epub 2017 Feb 9. PMID: 28183840; PMCID: PMC5394943.
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Zhuo Z, Qu L, Zhang P, Duan Y, Cheng D, Xu X, Sun T, Ding J, Xie C, Liu X, Haller S, Barkhof F, Zhang L, Liu Y. Prediction of H3K27M-mutant brainstem glioma by amide proton transfer-weighted imaging and its derived radiomics. Eur J Nucl Med Mol Imaging. 2021 Jun 16. doi: 10.1007/s00259-021-05455-4. Epub ahead of print. PMID: 34131804.
5)

Piccardo A, Tortora D, Mascelli S, Severino M, Piatelli G, Consales A, Pescetto M, Biassoni V, Schiavello E, Massollo M, Verrico A, Milanaccio C, Garrè ML, Rossi A, Morana G. Advanced MR imaging and (18)F-DOPA PET characteristics of H3K27M-mutant and wild-type pediatric diffuse midline gliomas. Eur J Nucl Med Mol Imaging. 2019 Apr 27. doi: 10.1007/s00259-019-04333-4. [Epub ahead of print] PubMed PMID: 31030232.

Cleidocranial dysostosis

Cleidocranial dysostosis

Cleidocranial dysplasia is a rare genetic condition that affects teeth and bones, such as the skull, face, spine, collarbones, and legs. The bones in people with CCD might be formed differently or might be more fragile than normal, and certain bones such as collarbones may be absent.

Runx2, also known as Cbfa1, is a multifunctional transcription factor essential for osteoblast differentiation. It also plays a major role in chondrocyte maturation, mesenchymal stem cell differentiation, cleidocranial dysplasia, and the growth and metastasis of tumors.

Review

A review encountered several cases of orthodontic implications but a few cases on cranial defect approach.

The articles present literature that is unanimous on the recommendation of expectant conduct in children since the cranial block can occur spontaneously, even if the delayed form 1).

Case reports

Hypophosphatasia (HPT) and cleidocranial dysplasia (CCD) are characterized by both defective ossification and bone mineralization. Patients usually present with craniosynostosis and cranial defects which in many cases require surgical repair.

There re only 2 reported case of combined HPT and CCD in the literature.

The reported case of Blionas et al. involves a 3.5-year-old girl with concomitant homozygous CCD and heterozygous HPT. The child had an extended cranial defect since birth which improved with the administration of Strensiq and was followed until preschool age. Bone defects were relatively minor on revaluation. Due to the limited final defect, we decided not to intervene. In HPT-CCD patients, bone defects are overestimated due to osteomalacia, and thus, management strategy should be less aggressive. They should undergo surgical repair with cranioplasty with the use of cement and/or titanium meshes in case of extended final defects 2).

A case of posterior fossa subdural hematoma (PFSDH) after vaginal delivery in a neonate with CCD, which presented with several clinical symptoms such as apnea, vomiting, and bradycardia. Our patient, who had a family history of CCD, developed apnea and vomiting shortly after birth; PFSDH was detected by head computed tomography, and the patient recovered well following standard medical treatment.

The prognosis of intracranial hemorrhage in neonates with CCD is generally poor. In neonates, PFSDH occurs by the following mechanism: the distortion of the infant’s cranium during delivery, by the strong force, causes elongation of the falx and angulation of the tentorium that leads to tears in the posterior fossa venous structures, which then cause bleeding into the subdural space. In CCD, the forces occurring during vaginal delivery may cause excessive distortion of the fragile skull. An awareness of CCD is hence important to avoid vaginal delivery in prenatally diagnosed CCD cases with a family history of CCD 3).

A 40-yr-old woman presented with sensory disturbance on the left side of the body. Magnetic resonance imaging (MRI) revealed cerebellar tonsil herniation into the foramen magnum with cervical syringomyelia, and computed tomography additionally revealed skull anomalies: fontanel closure insufficiencies, cranial dysraphism, thin cranial bone, and dentition abnormalities. We diagnosed as symptomatic CM1 with syringomyelia associated with cleidocranial dysplasia, which is a dominantly inherited autosomal bone disease. Cerebral angiography revealed a developed right occipital sinus and hypoplasia of the bilateral transverse sinus. We performed FMD, paying special attention to the developed occipital sinus using ICG-VA to ensure a safe duraplasty. The angiography clearly highlighted a right-sided occipital sinus with a high contrast ratio, and no left-sided occipital sinus was visible. After a dural incision in a unilateral curvilinear fashion was safely completed, expansive duraplasty was performed. The sensory disorders experienced by the patient disappeared postoperatively. Postoperative MRI revealed elevation of the cerebellar tonsil and decreasing of the syringomyelia.

Conclusion: Additional assessment using intraoperative ICG-VA provides useful information for a safe FMD, particularly in patients with complicated cerebral venous circulation anomalies 4).

A rare case of successful cranioplasty using a modified split calvarial graft technique in a patient with cleidocranial dysplasia 5).

1)

Azevedo Almeida LC, Faraj de Lima FB, Matushita H, Valença MM, Ferreira Castro TL, de Mendonça RN. Cleidocranial dysplasia, a rare skeletal disorder with failure of the cranial closure: case-based update. Childs Nerv Syst. 2020 Dec;36(12):2913-2918. doi: 10.1007/s00381-020-04831-z. Epub 2020 Jul 30. PMID: 32734401.
2)

Blionas A, Friehs GM, Zerris VA. Hypophosphatasia and cleidocranial dysplasia-a case report and review of the literature: the role of the neurosurgeon. Childs Nerv Syst. 2021 Jun 15. doi: 10.1007/s00381-021-05261-1. Epub ahead of print. PMID: 34131769.
3)

Nagasaka S, Suzuki K, Saito T, Tanaka K, Yamamoto J. Posterior fossa subdural hematoma in a neonate with cleidocranial dysostosis after a spontaneous vaginal delivery: a case report. Childs Nerv Syst. 2021 Feb;37(2):683-686. doi: 10.1007/s00381-020-04689-1. Epub 2020 Jun 5. PMID: 32504170.
4)

Omoto K, Takeshima Y, Nishimura F, Nakagawa I, Motoyama Y, Park YS, Nakase H. Additional Assessment of Developed Occipital Sinus Using Intraoperative Indocyanine Green Videoangiography for a Safe Foramen Magnum Decompression-Technical Case Report. Oper Neurosurg (Hagerstown). 2020 Oct 15;19(5):E533-E537. doi: 10.1093/ons/opaa125. PMID: 32421802.
5)

Jung YT, Cho JI, Lee SP. Cranioplasty Using a Modified Split Calvarial Graft Technique in Cleidocranial Dysplasia. J Korean Neurosurg Soc. 2015 Jul;58(1):79-82. doi: 10.3340/jkns.2015.58.1.79. Epub 2015 Jul 31. PMID: 26279819; PMCID: PMC4534745.