Update: Asymptomatic Meningioma

Asymptomatic Meningioma

Asymptomatic intracranial meningioma is a benign disease; however, nearly two-thirds of patients experience tumor growth and one-third of untreated patients eventually require neurosurgical interventions during watchful waiting 1).

In the series of Jadid et al., long-term tumour growth of incidentally detected asymptomatic meningiomas appeared to be much higher than expected. This information needs to be considered when discussing surgery, since the indication for surgery may be stronger than previously stated, especially for younger patients with tumours that can be reached at low risk 2).

Niiro et al., stated that in elderly patients with asymptomatic meningiomas, careful clinical follow up with imaging studies is important. The imaging features mentioned in his article may contribute to prediction of tumour growth 3).

For Yoneoka et al., clinical and radiological observations would be advisable for these patients (especially young patients and patients with a large tumour), in view of the presence of rapidly growing tumours in some of the patients 4).

Hashimoto et al., observed that Skull base incidental meningiomas (IDM) tend not to grow, which is different from non-skull base tumors. Even when IDMs grow, the rate of growth is significantly lower than that of non-skull base tumors. The same conclusion with regard to biological behavior was confirmed in symptomatic cases based on MIB-1 index analyses. This findings may impact the understanding of the incidental intracranial meningioma natural history, as well as strategies for management and treatment of IDMs and symptomatic meningiomas 5).

Asymptomatic meningioma treatment

Asymptomatic meningioma case series

References

1)

Kim KH, Kang SJ, Choi JW, Kong DS, Seol HJ, Nam DH, Lee JI. Clinical and radiological outcomes of proactive Gamma Knife surgery for asymptomatic meningiomas compared with the natural course without intervention. J Neurosurg. 2018 May 18:1-10. doi: 10.3171/2017.12.JNS171943. [Epub ahead of print] PubMed PMID: 29775154.
2)

Jadid KD, Feychting M, Höijer J, Hylin S, Kihlström L, Mathiesen T. Long-term follow-up of incidentally discovered meningiomas. Acta Neurochir (Wien). 2015 Feb;157(2):225-30. doi: 10.1007/s00701-014-2306-3. Epub 2014 Dec 14. PubMed PMID: 25503298.
3)

Niiro M, Yatsushiro K, Nakamura K, Kawahara Y, Kuratsu J. Natural history of elderly patients with asymptomatic meningiomas. J Neurol Neurosurg Psychiatry. 2000 Jan;68(1):25-8. PubMed PMID: 10601396; PubMed Central PMCID: PMC1760589.
4)

Yoneoka Y, Fujii Y, Tanaka R. Growth of incidental meningiomas. Acta Neurochir (Wien). 2000;142(5):507-11. PubMed PMID: 10898357.
5)

Hashimoto N, Rabo CS, Okita Y, Kinoshita M, Kagawa N, Fujimoto Y, Morii E, Kishima H, Maruno M, Kato A, Yoshimine T. Slower growth of skull base meningiomas compared with non-skull base meningiomas based on volumetric and biological studies. J Neurosurg. 2012 Mar;116(3):574-80. doi: 10.3171/2011.11.JNS11999. Epub 2011 Dec 16. PubMed PMID: 22175721.

Update: Friedreich’s ataxia

Friedreich’s ataxia

Friedreich’s ataxia (FA) is the most frequent hereditary ataxia syndrome, while painful muscle spasms and spasticity have been reported in 11-15% of FA patients.

A report describes the successful management of painful spasms in a 65-year-old woman with Friedreich’s ataxia (FA) via intrathecal baclofen(ITB) therapy following unsuccessful medical treatments.

To Kalyvas et al., knowledge, this is the third reported case in the literature. Unfortunately, the pathophysiological characteristics of muscle spasms in FA are not well explored and understood while the therapeutic mechanisms of the different treatments are rather vague. Taking into consideration the suggested spinal atrophy in FA, the clinical resemblance of FA and chronic spinal injury muscle spasms, together with the rapid ITB therapy effectiveness in alleviating FA muscle spasms, they attempted to suggest a putative pathophysiological mechanism acting at the spinal level and possibly explained by the presence of independent spinal locomotor systems producing muscle spasms. Specifically, overexcitement of these centers, due to loss of normal regulation from upper CNS levels, may result in the uncontrolled firing of secondary motor neurons and may be the key to producing muscle spasms. However, further research under experimental and clinical settings seems to be necessary 1).


A 50-year-old female patient with Friedreich ataxia (FA) was treated successfully with an intrathecal baclofen (ITB)-delivering pump for painful spasms. This is the second reported case of FA where ITB relieved painful and disabling spasms. Berntsson et al., suggest that ITB should be considered in the treatment of disabling spasms in patients with FA 2).


Ben Smail et al.,reported a patient suffering from Friedreich’s ataxia (FA) with very painful and disabling spasms that were improved markedly by intrathecal baclofen infusion. This is the first report of an intrathecal baclofen-delivering pump implantation in an FA patient 3).

1)

Kalyvas AV, Drosos E, Korfias S, Gatzonis S, Themistocleous M, Sakas DE. Intrathecal Baclofen Therapy for Painful Muscle Spasms in a Patient with Friedreich’s Ataxia. Stereotact Funct Neurosurg. 2018 Jun 8:1-4. doi: 10.1159/000489220. [Epub ahead of print] PubMed PMID: 29886479.
2)

Berntsson SG, Holtz A, Melberg A. Does intrathecal baclofen have a place in the treatment of painful spasms in friedreich ataxia? Case Rep Neurol. 2013 Nov 21;5(3):201-3. doi: 10.1159/000356823. eCollection 2013. PubMed PMID: 24348400; PubMed Central PMCID: PMC3861848.
3)

Ben Smail D, Jacq C, Denys P, Bussel B. Intrathecal baclofen in the treatment of painful, disabling spasms in Friedreich’s ataxia. Mov Disord. 2005 Jun;20(6):758-9. PubMed PMID: 15756654.

Update: Minocycline

Minocycline

Minocycline attenuates brain swelling and blood brain barrier (BBB) disruption via an iron-chelation mechanism1)

Minocycline has beneficial effects in early brain injury (EBI) following subarachnoid hemorrhage (SAH).

Minocycline treatment significantly reduced germinal matrix hemorrhage (GMH)-induced brain edema, hydrocephalus and brain damage. Minocycline also suppressed upregulation of ferritin after GMH.

Iron plays a role in brain injury following GMH and that minocycline reduces iron overload after germinal matrix hemorrhage (GMH) and iron-induced brain injury 2).


Brain iron overload is involved in brain injury after intracerebral hemorrhage (ICH). There is evidence that systemic administration of minocyclinereduces brain iron level and improves neurological outcome in experimental models of hemorrhagic and ischemic stroke. However, there is evidence in cerebral ischemia that minocycline is not protective in aged female animals. Since most ICH research has used male models, this study was designed to provide an overall view of ICH-induced iron deposits at different time points (1 to 28 days) in aged (18-month old) female Fischer 344 rat ICH model and to investigate the neuroprotective effects of minocycline in those rats. According to our previous studies, we used the following dosing regimen (20 mg/kg, i.p. at 2 and 12 h after ICH onset followed by 10 mg/kg, i.p., twice a day up to 7 days). T2-, T2⁎-weighted and T2⁎ array MRI was performed at 1, 3, 7 and 28 days to measure brain iron content, ventricle volume, lesion volume and brain swelling. Immunohistochemistry was used to examine changes in iron handling proteins, neuronal loss and microglial activation. Behavioral testing was used to assess neurological deficits. In aged female rats, ICH induced long-term perihematomal iron overload with upregulated iron handling proteins, neuroinflammation, brain atrophy, neuronal loss and neurological deficits. Minocycline significantly reduced ICH-induced perihematomal iron overload and iron handling proteins. It further reduced brain swelling, neuroinflammation, neuronal loss, delayed brain atrophy and neurological deficits. These effects may be linked to the role of minocycline as an iron chelator as well as an inhibitor of neuroinflammation 3).

Complications

Consumption of minocycline have been described among the causes associated with idiopathic intracranial hypertension 4).

A 13-year old female patient with a history of acne treated with minocycline who began with severe headache, diplopia and blurred vision. The diagnosis of pseudotumor cerebri was made, indicating the immediate antibiotic suspension and the beginning of the treatment with acetazolamide. Although the pathogenesis of pseudotumor cerebri is not fully known, an association with minocycline has been observed. This antibiotic is often used by health professionals for the management of acne, so it is important to consider its complications before being prescribed 5).

Subarachnoid hemorrhage

The molecular mechanisms underlying these effects have not been clearly identified.

SAH was induced by the filament perforation model of SAH in male Sprague Dawley rats. Minocycline or vehicle was given via an intraperitoneal injection 1 h after SAH induction. Minocycline treatment markedly attenuated brain edema secondary to blood-brain barrier (BBB) dysfunction by inhibiting NLRP3 inflammasome activation, which controls the maturation and release of pro-inflammatory cytokines, especially interleukin-1β (IL-1β). Minocycline treatment also markedly reduced the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cells. To further identify the potential mechanisms, we demonstrated that minocycline increased Bcl2 expression and reduced the protein expression of P53, Bax, and cleaved caspase-3. In addition, minocycline reduced the cortical levels of reactive oxygen species (ROS), which are closely related to both NLRP3 inflammasome and P53 expression. Minocycline protects against NLRP3 inflammasome-induced inflammation and P53-associated apoptosis in early brain injury following SAH. Minocycline’s anti-inflammatory and anti-apoptotic effect may involve the reduction of ROS. Minocycline treatment may exhibit important clinical potentials in the management of SAH 6).

Case series

To predict the feasibility of conducting clinical trials of acute SCI within Canada, Thibault-Halman et al., have applied the inclusion/exclusion criteria of six previously conducted SCI trials to the RHSCIR dataset and generated estimates of how many Canadian individuals would theoretically have been eligible for enrollment in these studies. Data for SCI cases were prospectively collected for RHSCIR at 18 acute and 13 rehabilitation sites across Canada. RHSCIR cases enrolled between 2009-2013 who met the following key criteria were included: non-penetrating traumatic SCI; received acute care at a RHSCIR site; age >18- <75 years, and had complete admission single neurological level of injury data. Inclusion and exclusion criteria for the Minocycline in Acute Spinal Cord injury (Minocycline), Riluzole, Surgical Timing in Acute Spinal Cord Injury Study (STASCIS), Cethrin, Nogo antibody study (NOGO) and Sygen studies were applied retrospectively to this dataset. The numbers of patients eligible for each clinical trial were determined. 2166 of the initial 2714 cases (79.8%) met the key criteria and were included in the dataset. Projected annual numbers of eligible patients for each trial was: Minocycline 117 cases; Riluzole 62 cases; STASCIS 109 cases; Cethrin 101 cases; NOGO 82 cases; and Sygen 70 cases. An additional 8.0% of the sample had a major head injury (GCS≤ 12) and would have been excluded from the trials. RHSCIR provides a comprehensive national dataset which may serve as a useful tool in the planning of multicentre clinical SCI trials 7).

References

1)

Zhao F, Xi G, Liu W, Keep RF, Hua Y. Minocycline Attenuates Iron-Induced Brain Injury. Acta Neurochir Suppl. 2016;121:361-5. doi: 10.1007/978-3-319-18497-5_62. PubMed PMID: 26463975.

2)

Guo J, Chen Q, Tang J, Zhang J, Tao Y, Li L, Zhu G, Feng H, Chen Z. Minocycline-induced attenuation of iron overload and brain injury after experimental germinal matrix hemorrhage. Brain Res. 2015 Jan 12;1594:115-24. doi: 10.1016/j.brainres.2014.10.046. Epub 2014 Oct 31. PubMed PMID: 25451129.

3)

Dai S, Hua Y, Keep RF, Novakovic N, Fei Z, Xi G. Minocycline attenuates brain injury and iron overload after intracerebral hemorrhage in aged female rats. Neurobiol Dis. 2018 Jun 4. pii: S0969-9961(18)30173-6. doi: 10.1016/j.nbd.2018.06.001. [Epub ahead of print] Review. PubMed PMID: 29879529.

4) , 5)

González Gili LO, Buffone IR, Carrara LE, Coto MB, Fortunatti EA, Dejtera M, García Elliot MF, Giacone A, Luncio AC, Masnicoff SD, Oviedo Crosta MB, Parroua M, Romano M. [Pseudotumor cerebri secondary to consumption of minocycline in a pediatric patient]. Arch Argent Pediatr. 2016 Apr 1;114(1):e78-e83. doi: 10.5546/aap.2016.e78. Epub 2016 Apr 1. Spanish. PubMed PMID: 27079408.

6)

Li J, Chen J, Mo H, Chen J, Qian C, Yan F, Gu C, Hu Q, Wang L, Chen G. Minocycline Protects Against NLRP3 Inflammasome-Induced Inflammation and P53-Associated Apoptosis in Early Brain Injury After Subarachnoid Hemorrhage. Mol Neurobiol. 2015 Jul 5. [Epub ahead of print] PubMed PMID: 26143258.

7)

Thibault-Halman G, Rivers CS, Bailey C, Tsai E, Drew B, Noonan V, Fehlings M, Dvorak MF, Kuerban D, Kwon BK, Christie S. Predicting recruitment feasibility for acute spinal cord injury clinical trials in Canada using national registry data. J Neurotrauma. 2016 Sep 14. [Epub ahead of print] PubMed PMID: 27627704.

Update: HeadSense medical

HeadSense medical

HeadSense Medical develops inexpensive, easy-to-use devices for patient monitoring and diagnosis of cerebral dysfunction. The HS-1000 is the first product of the company.

The author and the developer of the device, as well as the co-founder and scientific director of the company is Surik Papyan, who is originally from Armenia and currently resides in Israel.


What are the advantages of the HS-1000 over the existing invasive and noninvasive ICP monitoring methods?

Figuratively speaking, the HS-1000 “listens” to our brains.

“The brain, just like the rest of the body, makes a noise when it works. This noise is at “low frequencies,” so we do not hear it. The sound of our circulatory system can be compared with the sounds of running water. The blood makes a different noise when it passes through too narrow or too wide vessels,” Surik Papyan explained.

We can “hear” these “sounds” only when we put a microphone in the ear canal, because of the fact that the outer ear canal, being hermetically sealed, becomes a unique resonator, something like an “organ pipe,” according to Alexander Khachunts, who is the head of the Laboratory of Psychophysiology of the National Academy of Sciences of Armenia and also took part in this project.

Just as a skilled mechanic can detect faults in a vehicle by listening to the sound of the engine, the HS-1000 can identify problems in the brain by listening to its sounds. The mathematical algorithms implemented in the device allow to dynamically measure and display the value of intracranial pressure.

The HS-1000 is equipped with a microphone, which is placed in the ear and records the mixed acoustic signal, which is formed by hemodynamic and liquorodynamic processes in the brain. It also records the air flow in the upper airways.

The acoustic signal is transmitted from the microphone to a tablet, PC or a mobile device with a special application installed. This application calculates the level of intracranial pressure and the physiological parameters needed to assess the patient’s condition. Then the results are displayed.

see more https://med.news.am/eng/news/9852/new-noninvasive-method-of-intracranial-pressure-monitoring-hs-1000-listens-to-the-brain.html


In a study a new method of Noninvasive intracranial pressure monitoring performed using algorithms to determine ICP based on acoustic properties of the brain was applied in patients undergoing invasive intracranial pressure monitoring, and the results were analyzed.

In patients with traumatic brain injury and subarachnoid hemorrhage who were undergoing treatment in a intensive neurocritical care unit, Ganslandt et al., from the Department of Neurosurgery, Klinikum Stuttgart; and Department of Neurosurgery, University of ErlangenGermanyrecorded ICP using the gold standard method of invasive external ventricular drainage or intraparenchymal monitoring. In addition, they simultaneously measured the ICP noninvasively with a device (the HS-1000) that uses advanced signal analysis algorithms for acoustic signals propagating through the cranium. To assess the accuracy of the NI-ICP method, data obtained using both I-ICP and NI-ICP monitoring methods were analyzed with MATLAB to determine the statistical significance of the differences between the ICP measurements obtained using NI-ICP and I-ICP monitoring.

Data were collected in 14 patients, yielding 2543 data points of continuous parallel ICP values in recordings obtained from I-ICP and NI-ICP. Each of the 2 methods yielded the same number of data points. For measurements at the ≥ 17-mm Hg cutoff, which was arbitrarily chosen for this preliminary analysis, the sensitivity and specificity for the NI-ICP monitoring were found to be 0.7541 and 0.8887, respectively. Linear regression analysis indicated that there was a strong positive relationship between the measurements. Differential pressure between NI-ICP and I-ICP was within ± 3 mm Hg in 63% of data-paired readings and within ± 5 mm Hg in 85% of data-paired readings. The receiver operating characteristic-area under the curve analysis revealed that the area under the curve was 0.895, corresponding to the overall performance of NI-ICP monitoring in comparison with I-ICP monitoring.

This study provides the first clinical data on the accuracy of the HS-1000 NI-ICP monitor, which uses advanced signal analysis algorithms to evaluate properties of acoustic signals traveling through the brain in patients undergoing I-ICP monitoring. The findings of this study highlight the capability of this NI-ICP device to accurately measure ICP noninvasively. Further studies should focus on clinical validation for elevated ICP values1).

1)

Ganslandt O, Mourtzoukos S, Stadlbauer A, Sommer B, Rammensee R. Evaluation of a novel noninvasive ICP monitoring device in patients undergoing invasive ICP monitoring: preliminary results. J Neurosurg. 2018 Jun;128(6):1653-1660. doi: 10.3171/2016.11.JNS152268. Epub 2017 Aug 8. PubMed PMID: 28784032.

Update: Cranioplasty timing

Cranioplasty timing

There is an increasing body of evidence in the recent literature, which demonstrates that cranioplasty may also accelerate and improve neurological recovery. Although the exact pathophysiological mechanisms for this improvement remain essentially unknown, there are a rapidly growing number of neurosurgeons adopting this concept.

Cranioplasty performed between 15 and 30 days after initial craniectomy may minimize infectionseizure, and bone flap resorption, whereas waiting > 90 days may minimize hydrocephalus but may increase the risk of seizure 1).


Communicating hydrocephalus is an almost universal finding in patients after hemicraniectomy. Delayed time to cranioplasty is linked with the development of persistent hydrocephalus, necessitating permanent CSF diversion in some patients.

Waziri et al., propose that early cranioplasty, when possible, may restore normal intracranial pressure dynamics and prevent the need for permanent CSF diversion in patients after hemicraniectomy 2).

Factors

One modifiable factor that may alter the risk of cranioplasty is the timing of cranioplasty after craniectomy. Case series suggest that early cranioplasty is associated with higher rates of infection while delaying cranioplasty may be associated with higher rates of bone resorption.

When considering ideal timing for cranioplasty, predominant issues include residual brain edema, brain retraction into the cranial vault, risk of infection, and development of delayed post-traumatic hydrocephalus.


Waiting to perform cranioplasty is important to prevent the development of devitalized autograft or allograft infections.

It is generally accepted to wait 3 to 6 months before reconstructive surgery. If there is an infected area, this waiting period can be as long as one year.

Cranioplasty is performed after craniectomy when intracranial pressure is under control for functional and aesthetic restorations and for protection, but it may also lead to some neurological improvement after the bone flap placement 3) 4) 5).

Timing of cranioplasty after decompressive craniectomy for trauma

The optimal timing of cranioplasty after decompressive craniectomy for trauma is unknown.

After decompressive craniectomy for trauma, early (<12 weeks) cranioplasty does not alter the incidence of complication rates. In patients <18 years of age, early (<12 weeks) cranioplasty increases the risk of bone resorption. Delaying cranioplasty (≥12 weeks) results in longer operative times and may increase costs 6).

Timing of cranioplasty after decompressive craniectomy for malignant middle cerebral artery infarction

Patients with malignant middle cerebral artery infarction frequently develop hydrocephalus after decompressive hemicraniectomy. Hydrocephalus itself and known shunt related complications after ventriculoperitoneal shunt implantation may negatively impact patients outcome.

A later time point of cranioplasty might lead to a lower incidence of required shunting procedures in general 7).

References

1)

Morton RP, Abecassis IJ, Hanson JF, Barber JK, Chen M, Kelly CM, Nerva JD, Emerson SN, Ene CI, Levitt MR, Chowdhary MM, Ko AL, Chesnut RM. Timing of cranioplasty: a 10.75-year single-center analysis of 754 patients. J Neurosurg. 2018 Jun;128(6):1648-1652. doi: 10.3171/2016.11.JNS161917. Epub 2017 Aug 11. PubMed PMID: 28799868.
2)

Waziri A, Fusco D, Mayer SA, McKhann GM 2nd, Connolly ES Jr. Postoperative hydrocephalus in patients undergoing decompressive hemicraniectomy for ischemic or hemorrhagic stroke. Neurosurgery. 2007 Sep;61(3):489-93; discussion 493-4. PubMed PMID: 17881960.
3)

Honeybul S, Janzen C, Kruger K, Ho KM. The impact of cranioplasty on neurological function. Br J Neurosurg. 2013;27:636–641. doi: 10.3109/02688697.2013.817532.
4)

Jelcic N, De Pellegrin S, Cecchin D, Della Puppa A, Cagnin A. Cognitive improvement after cranioplasty: a possible volume transmission-related effect. Acta Neurochir (Wien) 2013;155:1597–1599. doi: 10.1007/s00701-012-1519-6.
5)

Di Stefano C, Sturiale C, Trentini P, Bonora R, Rossi D, Cervigni G, et al. Unexpected neuropsychological improvement after cranioplasty: a case series study. Br J Neurosurg. 2012;26:827–831. doi: 10.3109/02688697.2012.692838.
6)

Piedra MP, Nemecek AN, Ragel BT. Timing of cranioplasty after decompressive craniectomy for trauma. Surg Neurol Int. 2014 Feb 25;5:25. doi: 10.4103/2152-7806.127762. PubMed PMID: 24778913; PubMed Central PMCID: PMC3994696.
7)

Finger T, Prinz V, Schreck E, Pinczolits A, Bayerl S, Liman T, Woitzik J, Vajkoczy P. Impact of timing of cranioplasty on hydrocephalus after decompressive hemicraniectomy in malignant middle cerebral artery infarction. Clin Neurol Neurosurg. 2016 Dec 9;153:27-34. doi: 10.1016/j.clineuro.2016.12.001. [Epub ahead of print] PubMed PMID: 28012353.

Update: Pupil Reactivity Score

Pupil Reactivity Score

The GCS Pupils Score (GCS-P) was described by Paul Brennan, Gordon Murray and Graham Teasdale in 2018 as a strategy to combine the two key indicators of the severity of traumatic brain injury into a single simple index.

How do I calculate the GCS-P?

The GCS-P is calculated by subtracting the Pupil Reactivity Score (PRS) from the Glasgow Coma Scale (GCS) total score:

GCS-P = GCS – PRS

The Pupil Reactivity Score is calculated as follows.

see more at http://www.glasgowcomascale.org/what-is-gcs-p/


Information about early GCS scores, pupil responses, late outcomes on the Glasgow Outcome Scale, and mortality were obtained at the individual patient level by reviewing data from the CRASH (Corticosteroid Randomisation After Significant Head Injury; n = 9,045) study and the IMPACT(International Mission for Prognosis and Clinical Trials in TBI; n = 6855) database. These data were combined into a pooled data set for the main analysis.

Methods of combining the Glasgow Coma Scale and pupil reaction data varied in complexity from using a simple arithmetic score (GCS score [range 3-15] minus the number of nonreacting pupils [0, 1, or 2]), which Brennan et al., called the GCS Pupils score (GCS-P; range 1-15), to treating each factor as a separate categorical variable. The content of information about patient outcome in each of these models was evaluated using Nagelkerke R2.

Separately, the GCS score and pupil response were each related to outcome. Adding information about the pupil response to the GCS score increased the information yield. The performance of the simple GCS-P was similar to the performance of more complex methods of evaluating traumatic brain damage. The relationship between decreases in the GCS-P and deteriorating outcome was seen across the complete range of possible scores. The additional 2 lowest points offered by the GCS-Pupils scale (GCS-P 1 and 2) extended the information about injury severity from a mortality rate of 51% and an unfavorable outcome rate of 70% at GCS score 3 to a mortality rate of 74% and an unfavorable outcome rate of 90% at GCS-P 1. The paradoxical finding that GCS score 4 was associated with a worse outcome than GCS score 3 was not seen when using the GCS-P.

A simple arithmetic combination of the GCS score and pupillary response, the GCS-P, extends the information provided about patient outcome to an extent comparable to that obtained using more complex methods. The greater range of injury severities that are identified and the smoothness of the stepwise pattern of outcomes across the range of scores may be useful in evaluating individual patients and identifying patient subgroups. The GCS-P may be a useful platform onto which information about other key prognostic features can be added in a simple format likely to be useful in clinical practice 1).

1)

Brennan PM, Murray GD, Teasdale GM. Simplifying the use of prognostic information in traumatic brain injury. Part 1: The GCS-Pupils score: an extended index of clinical severity. J Neurosurg. 2018 Jun;128(6):1612-1620. doi: 10.3171/2017.12.JNS172780. Epub 2018 Apr 10. PubMed PMID: 29631516.

Update: Overshunting associated myelopathy

Overshunting associated myelopathy” is a rare complication of CSF diversion that should be familiar to physicians who routinely evaluate patients with intracranial shunts 1) 2).

Only 12 previous cases have been reported in the literature 3).

OSAM has to be considered according to the Monro-Kellie hypothesis and is affected by an engorgement of the cervical epidural venous plexus, which can produce cervical myelopathy. Since it can be treated simply by increasing the shunt resistance, surgeons should be aware of the rarely detected overdrainage complication 4).

Classically, patients present with positional headache, but less common symptoms include neck pain and cranial nerve palsies.


A 45-year-old-patient with shunt-dependent, congenital hydrocephalus presented with an 8-year history of progressive tetraparesis and gait disorder in the Department of Neurosurgery, University of Tübingen, Germany. The patient was wheelchair-dependent. A new MRI scan of the head revealed slit ventricle syndrome and dural enhancement due to shunt overdrainage. An MRI and a CT-Phlebography of the cervical spine revealed engorgement of the epidural venous plexus with secondary compression of the spinal cord and myelomalacia. Surgery was performed during which we implanted a shunt valve. The patient recovered from surgery without any new deficits. The tetraparesis improved during the inpatient hospital stay. CT-Phlebography was performed 5 days after surgery and showed that the epidural venous plexus anterior to the cervical spinal cord had returned to nearly normal size. On follow-up examination 3 month after surgery, the patient´s strength had improved, and he was able to walk short distances with assistance and with ankle foot orthosis on the right side.

OSAM has to be considered according to the Monro-Kellie doctrine and is affected by an engorgement of the epidural cervical venous plexus, which can produce cervical myelopathy. Since it can be treated simply by increasing the shunt resistance, surgeons should be aware of the rarely detected overdrainage complication 5).


Ho et al., presented 2 cases of cervical myelopathy produced by engorged vertebral veins due to overshunting. Overshunting-associated myelopathy is a rare complication of CSF shunting. Coexisting cervical degenerative disc disease may further increase the difficulty of diagnosing the condition. Neurosurgeons and others who routinely evaluate patients with intracranial shunts should be familiar with this rare but possible diagnosis 6).


A 26-year-old woman with shunt-dependent, congenital hydrocephalus, presented with rapidly progressive cervical myelopathy following ventriculoperitoneal shunt revision. Imaging revealed engorgement of the cervical epidural venous plexus and mass effect on the cervical spinal cord. “Over-shunting associated myelopathy” is a rare complication of CSF diversion that should be familiar to physicians who routinely evaluate patients with intracranial shunts 7).

1) , 7)

Howard BM, Sribnick EA, Dhall SS. Over-shunting associated myelopathy. J Clin Neurosci. 2014 Dec;21(12):2242-4. doi: 10.1016/j.jocn.2014.05.014. Epub 2014 Jul 25. PubMed PMID: 25070631.

2) , 6)

Ho JM, Law HY, Yuen SC, Yam KY. Overshunting-associated myelopathy: report of 2 cases. Neurosurg Focus. 2016 Sep;41(3):E16. doi: 10.3171/2016.7.FOCUS16179. PubMed PMID: 27581312.

3) , 4) , 5)

Adib SD, Hauser TK, Engel DC, Tatagiba M, Skardelly M, Ramina K. Over-shunting associated myelopathy (OSAM) in a patient with bilateral jugular vein occlusion. World Neurosurg. 2018 Jun 1. pii: S1878-8750(18)31129-X. doi: 10.1016/j.wneu.2018.05.175. [Epub ahead of print] PubMed PMID: 29864573.

Update: Intramedullary spinal cord abscess

Intramedullary spinal cord abscess

Intramedullary spinal cord abscess due to congenital dermal sinus (CDS) is rare and often co-exists with an inclusion tumor such as dermoid/epidermoid cyst.

CDS are the commonest cause of intramedullary spinal cord abscess (IMSCA) 1).

Prasad et al. did a literature review to analyze all cases of pediatric IMSCA secondary to CDS by searching online databases starting from the oldest case reported.

Only 50 cases have been reported and were analyzed. Mean age was 22.6 months (range 1 month-15 years). Fever, acute flaccid lower limbweakness, and urinary disturbances were the most common presenting features. Dermal sinus was commonest in lumbosacral region. Inclusion cysts were observed in 50% of cases. Staphylococcus aureus was the most the common organism. Mean follow-up duration was 18.2 months (range 1 week-156 months). Majority of the cases underwent multilevel laminectomy with myelotomy and drainage of abscess. Outcome was good-to-excellent in around 60% cases with four deaths. Presence of fever and limb weakness was significantly associated with poor outcomes.

Intramedullary abscess secondary to CDS is very rare. Complete sinus tract excision, myelotomy and drainage of abscess, and decompression of co-existent inclusion cysts with prolonged antibiotic therapy remain the standard treatment. Approximately 60% cases achieve good outcomes. Fever and limb weakness portend poorer outcomes than those without 2).

1)

Kanaheswari Y, Lai C, Raja Lope RJ, Azizi AB, Zulfiqar MA. Intramedullary spinal cord abscess: The result of a missed congenital dermal sinus. J Paediatr Child Health. 2014 Aug 7. doi: 10.1111/jpc.12707. [Epub ahead of print] PubMed PMID: 25099316.

2)

Prasad GL, Hegde A, Divya S. Spinal Intramedullary Abscess Secondary to Dermal Sinus in Children. Eur J Pediatr Surg. 2018 Jun 1. doi: 10.1055/s-0038-1655736. [Epub ahead of print] PubMed PMID: 29857348.

Update: Central nervous system high grade neuroepithelial tumor with BCOR alteration

Central nervous system high grade neuroepithelial tumor with BCOR alteration

Central nervous system high grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR) is a rare entity, identified as a small fraction of tumors previously institutionally diagnosed as so-called CNS primitive neuroectodermal tumors. Their genetic characteristic is a somatic internal tandem duplication in the 3′ end of BCOR (BCOR ITD), which has also been found in clear cell sarcomas of the kidney (CCSK) and soft tissue undifferentiated round cell sarcomas/primitive myxoid mesenchymal tumors of infancy (URCS/PMMTI), and these BCOR ITD-positive tumors have been reported to share similar pathological features.

CNS HGNET-BCOR display pathological overlap with CNS-PNET and other histological entities 1).

The high expression of IGF-2 may be a common feature of HGNET-BCOR and ependymoma and may represent a target for new approaches. Several monoclonal antibodies and TKIs for IGF1R are being tested in preclinical and early phase clinical studies and may become relevant in the management of this new and aggressive tumor entity 2).

High expression of altered BCOR transcripts in CNS HGNET-BCOR tumors suggests a different mechanism from BCOR loss-of-function mutations reported in other malignancies, such as medulloblastoma 3) 4).

Yoshida et al., performed a clinicopathological and molecular analysis of six cases of CNS HGNET-BCOR, and compared them with their counterparts in the kidney and soft tissue. Although these tumors had histologically similar structural patterns and characteristic monotonous nuclei with fine chromatin, CNS HGNET-BCOR exhibited glial cell morphology, ependymoma-like perivascular pseudorosettes and palisading necrosis, whereas these features were not evident in CCSK or URCS/PMMTI. Immunohistochemically, diffuse staining of Olig2 with a mixture of varying degrees of intensity, and only focal staining of GFAP, S-100 protein and synaptophysin were observed in CNS HGNET-BCOR, whereas these common neuroepithelial markers were negative in CCSK and URCS/PMMTI. Therefore, although CNS HGNET-BCOR, CCSK and URCS/PMMTI may constitute a group of BCOR ITD-positive tumors, only CNS HGNET-BCOR has histological features suggestive of glial differentiation. In conclusion, we think CNS HGNET-BCOR are a certain type of neuroepithelial tumor relatively close to glioma, not CCSK or URCS/PMMTI occurring in the CNS 5).

Kirkman et al., describe a pediatric male patient with CNS HGNET-BCOR who developed seeding of the tumor into the site of the surgical wound within months of surgery for resection of a residual posterior fossa tumor.

This case emphasises three important points. First, CNS HGNET-BCOR can be aggressive tumors that necessitate close clinical and radiological surveillance. Second, surveillance imaging in such cases should incorporate the surgical incision site into the field of view, and this should be closely scrutinised to ensure the timely detection of wound site seeding. Third, wound site seeding may still occur despite the use of meticulous surgical techniques 6).

Appay et al., reported in 2017, 3 new CNS HGNET-BCOR cases sharing common clinical presentation and pathologic features. The 3 cases concerned children aged 3 to 7 years who presented with a voluminous mass of the cerebellum. Pathologic features included proliferation of uniform spindle to ovoid cells with fine chromatin associated with a rich arborizing capillary network. Methylation profiling classified these cases as CNS HGNET-BCOR tumors. Polymerase chain reaction analysis confirmed the presence of internal tandem duplications in the C-terminus of BCOR (BCOR-ITD), a characteristic of these tumors, in all 3 cases. Immunohistochemistry showed a strong nuclear BCOR expression. In 2 cases, local recurrence occurred within 6 months. The third case, a patient who received a craniospinal irradiation after total surgical removal followed by a metronomics maintenance with irinotecantemozolomide, and itraconazole, is still free of disease 14 months after diagnosis. In summary, CNS HGNET-BCOR represents a rare tumor occurring in young patients with dismal prognosis. BCOR nuclear immunoreactivity is highly suggestive of a BCOR-ITD. Whether CNS HGNET-BCOR should be classified among the category of “embryonal tumors” or within the category of “mesenchymal, nonmeningothelial tumors” remains to be clarified. Because CNS HGNET-BCOR share pathologic features and characteristic BCOR-ITD with clear cell sarcoma of the kidney, these tumors may represent local variants of the same entity 7).

1)

Sturm D, Orr BA, Toprak UH, Hovestadt V, Jones DTW, Capper D, Sill M, Buchhalter I, Northcott PA, Leis I, Ryzhova M, Koelsche C, Pfaff E, Allen SJ, Balasubramanian G, Worst BC, Pajtler KW, Brabetz S, Johann PD, Sahm F, Reimand J, Mackay A, Carvalho DM, Remke M, Phillips JJ, Perry A, Cowdrey C, Drissi R, Fouladi M, Giangaspero F, Łastowska M, Grajkowska W, Scheurlen W, Pietsch T, Hagel C, Gojo J, Lötsch D, Berger W, Slavc I, Haberler C, Jouvet A, Holm S, Hofer S, Prinz M, Keohane C, Fried I, Mawrin C, Scheie D, Mobley BC, Schniederjan MJ, Santi M, Buccoliero AM, Dahiya S, Kramm CM, von Bueren AO, von Hoff K, Rutkowski S, Herold-Mende C, Frühwald MC, Milde T, Hasselblatt M, Wesseling P, Rößler J, Schüller U, Ebinger M, Schittenhelm J, Frank S, Grobholz R, Vajtai I, Hans V, Schneppenheim R, Zitterbart K, Collins VP, Aronica E, Varlet P, Puget S, Dufour C, Grill J, Figarella-Branger D, Wolter M, Schuhmann MU, Shalaby T, Grotzer M, van Meter T, Monoranu CM, Felsberg J, Reifenberger G, Snuderl M, Forrester LA, Koster J, Versteeg R, Volckmann R, van Sluis P, Wolf S, Mikkelsen T, Gajjar A, Aldape K, Moore AS, Taylor MD, Jones C, Jabado N, Karajannis MA, Eils R, Schlesner M, Lichter P, von Deimling A, Pfister SM, Ellison DW, Korshunov A, Kool M. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs. Cell. 2016 Feb 25;164(5):1060-1072. doi: 10.1016/j.cell.2016.01.015. PubMed PMID: 26919435; PubMed Central PMCID: PMC5139621.
3)

Jones DT, Jäger N, Kool M, Zichner T, Hutter B, Sultan M, Cho YJ, Pugh TJ, Hovestadt V, Stütz AM, Rausch T, Warnatz HJ, Ryzhova M, Bender S, Sturm D, Pleier S, Cin H, Pfaff E, Sieber L, Wittmann A, Remke M, Witt H, Hutter S, Tzaridis T, Weischenfeldt J, Raeder B, Avci M, Amstislavskiy V, Zapatka M, Weber UD, Wang Q, Lasitschka B, Bartholomae CC, Schmidt M, von Kalle C, Ast V, Lawerenz C, Eils J, Kabbe R, Benes V, van Sluis P, Koster J, Volckmann R, Shih D, Betts MJ, Russell RB, Coco S, Tonini GP, Schüller U, Hans V, Graf N, Kim YJ, Monoranu C, Roggendorf W, Unterberg A, Herold-Mende C, Milde T, Kulozik AE, von Deimling A, Witt O, Maass E, Rössler J, Ebinger M, Schuhmann MU, Frühwald MC, Hasselblatt M, Jabado N, Rutkowski S, von Bueren AO, Williamson D, Clifford SC, McCabe MG, Collins VP, Wolf S, Wiemann S, Lehrach H, Brors B, Scheurlen W, Felsberg J, Reifenberger G, Northcott PA, Taylor MD, Meyerson M, Pomeroy SL, Yaspo ML, Korbel JO, Korshunov A, Eils R, Pfister SM, Lichter P. Dissecting the genomic complexity underlying medulloblastoma. Nature. 2012 Aug 2;488(7409):100-5. doi: 10.1038/nature11284. PubMed PMID: 22832583; PubMed Central PMCID: PMC3662966.
4)

Pugh TJ, Weeraratne SD, Archer TC, Pomeranz Krummel DA, Auclair D, Bochicchio J, Carneiro MO, Carter SL, Cibulskis K, Erlich RL, Greulich H, Lawrence MS, Lennon NJ, McKenna A, Meldrim J, Ramos AH, Ross MG, Russ C, Shefler E, Sivachenko A, Sogoloff B, Stojanov P, Tamayo P, Mesirov JP, Amani V, Teider N, Sengupta S, Francois JP, Northcott PA, Taylor MD, Yu F, Crabtree GR, Kautzman AG, Gabriel SB, Getz G, Jäger N, Jones DT, Lichter P, Pfister SM, Roberts TM, Meyerson M, Pomeroy SL, Cho YJ. Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations. Nature. 2012 Aug 2;488(7409):106-10. doi: 10.1038/nature11329. PubMed PMID: 22820256; PubMed Central PMCID: PMC3413789.
5)

Yoshida Y, Nobusawa S, Nakata S, Nakada M, Arakawa Y, Mineharu Y, Sugita Y, Yoshioka T, Araki A, Sato Y, Takeshima H, Okada M, Nishi A, Yamazaki T, Kohashi K, Oda Y, Hirato J, Yokoo H. CNS high-grade neuroepithelial tumor with BCOR internal tandem duplication: a comparison with its counterparts in the kidney and soft tissue. Brain Pathol. 2017 Dec 11. doi: 10.1111/bpa.12585. [Epub ahead of print] PubMed PMID: 29226988.
6)

Kirkman MA, Pickles JC, Fairchild AR, Avery A, Pietsch T, Jacques TS, Aquilina K. Early wound site seeding in a patient with CNS high-grade neuroepithelial tumor with BCOR alteration: A case report. World Neurosurg. 2018 May 30. pii: S1878-8750(18)31112-4. doi: 10.1016/j.wneu.2018.05.158. [Epub ahead of print] PubMed PMID: 29859355.
7)

Appay R, Macagno N, Padovani L, Korshunov A, Kool M, André N, Scavarda D, Pietsch T, Figarella-Branger D. HGNET-BCOR Tumors of the Cerebellum: Clinicopathologic and Molecular Characterization of 3 Cases. Am J Surg Pathol. 2017 Sep;41(9):1254-1260. doi: 10.1097/PAS.0000000000000866. PubMed PMID: 28704208.