UpToDate: Fluorescence guided surgery of glioma

Fluorescence guided surgery of glioma

It must be remembered that intraoperative visualization of fluorescence depends on the sensitivity of both the microscope filters and the cameraused 1).


The use of the optical contrast agent sodium fluorescein (NaFl) to guide resection of gliomas has been under investigation for decades. Although this imaging strategy assumes the agent remains confined to the vasculature except in regions of blood brain barrier (BBB) disruption, clinical studies have reported significant NaFl signal in normal brain tissue, limiting tumor-to-normal contrast. A possible explanation arises from earlier studies, which reported that NaFl exists in both pure and protein-bound forms in the blood, the former being small enough to cross the BBB.

A study of Folaron et al. from the Thayer School of Engineering and Department of Surgery Geisel School of Medicine, Dartmouth College, Hanover; and Section of Neurosurgery, and Norris Cotton Cancer Center, Dartmouth Hitchcock Medical CenterLebanonNew Hampshire, aimed to elucidate the kinetic binding behavior of NaFl in circulating blood and its effect on NaFl accumulation in brain tissue and tumor contrast. Additionally, they examined the blood and tissue kinetics, as well as tumor uptake, of a pegylated form of fluorescein selected as a potential optical analog of gadolinium-based MRI contrast agents.

Cohorts of mice were administered one of the following doses/forms of NaFl: 1) high human equivalent dose (HED) of NaFl, 2) low HED of NaFl, or 3) pegylated form of fluorescein. In each cohort, groups of animals were euthanized 15, 30, 60, and 120 minutes after administration for ex vivo analysis of fluorescein fluorescence. Using gel electrophoresis and fluorescence imaging of blood and brain specimens, the authors quantified the temporal kinetics of bound NaFl, unbound NaFl, and pegylated fluorescein in the blood and normal brain tissue. Finally, they compared tumor-to-normal contrast for NaFl and pegylated-fluorescein in U251 glioma xenografts.

Administration of NaFl resulted in the presence of unbound and protein-bound NaFl in the circulation, with unbound NaFl constituting up to 70% of the signal. While protein-bound NaFl was undetectable in brain tissue, unbound NaFl was observed throughout the brain. The observed behavior was time and dose dependent. The pegylated form of fluorescein showed minimal uptake in brain tissue and improved tumor-to-normal contrast by 38%.

Unbound NaFl in the blood crosses the BBB, limiting the achievable tumor-to-normal contrast and undermining the inherent advantage of tumor imaging in the brain. Dosing and incubation time should be considered carefully for NaFl-based fluorescence-guided surgery (FGS) of glioma. A pegylated form of fluorescein showed more favorable normal tissue kinetics that translated to higher tumor-to-normal contrast. These results warrant further development of pegylated-fluorescein for FGS of glioma 2).


Senders et al., systematically review all clinically tested fluorescent agents for application in FGS for glioma and all preclinically tested agents with the potential for FGS for glioma.

They searched the PubMed and Embase databases for all potentially relevant studies through March 2016.

They assessed fluorescent agents by the following outcomes: rate of gross total resection (GTR), overall and progression free survival, sensitivity and specificity in discriminating tumor and healthy brain tissue, tumor-to-normal ratio of fluorescent signal, and incidence of adverse events.

The search strategy resulted in 2155 articles that were screened by titles and abstracts. After full-text screening, 105 articles fulfilled the inclusion criteria evaluating the following fluorescent agents: 5 aminolevulinic acid (5-ALA) (44 studies, including three randomized control trials), fluorescein(11), indocyanine green (five), hypericin (two), 5-aminofluorescein-human serum albumin (one), endogenous fluorophores (nine) and fluorescent agents in a pre-clinical testing phase (30). Three meta-analyses were also identified.

5-ALA is the only fluorescent agent that has been tested in a randomized controlled trial and results in an improvement of GTR and progression-free survival in high-grade gliomas. Observational cohort studies and case series suggest similar outcomes for FGS using fluorescein. Molecular targeting agents (e.g., fluorophore/nanoparticle labeled with anti-EGFR antibodies) are still in the pre-clinical phase, but offer promising results and may be valuable future alternatives. 3).


Mounting evidence suggests that a more extensive surgical resection is associated with an improved life expectancy for both low grade glioma and high grade glioma patients. However, radiographically complete resections are not often achieved in many cases because of the lack of sensitivityand specificity of current neurosurgical guidance techniques at the margins of diffuse infiltrative gliomas. Intraoperative fluorescence imaging offers the potential to improve the extent of resection and to investigate the possible benefits of resecting beyond the radiographic margins.

Liu et al., in 2014 provided a review of wide-field and high-resolution fluorescence-imaging strategies that are being developed for neurosurgical guidance, with a focus on emerging imaging technologies and clinically viable contrast agents. The strengths and weaknesses of these approaches will be discussed, as well as issues that are being addressed to translate these technologies into the standard of care 4).


322 patients aged 23-73 years with suspected malignant glioma amenable to complete resection of contrast-enhancing tumour were randomly assigned to 20 mg/kg bodyweight 5-aminolevulinic acid for fluorescence-guided resection (n=161) or to conventional microsurgery with white light (n=161). The primary endpoints were the number of patients without contrast-enhancing tumour on early MRI (ie, that obtained within 72 h after surgery) and 6-month progression-free survival as assessed by MRI. Secondary endpoints were volume of residual tumour on postoperative MRI, overall survival, neurological deficit, and toxic effects. We report the results of an interim analysis with 270 patients in the full-analysis population (139 assigned 5-aminolevulinic acid, 131 assigned white light), which excluded patients with ineligible histological and radiological findings as assessed by central reviewers who were masked as to treatment allocation; the interim analysis resulted in termination of the study as defined by the protocol. Primary and secondary endpoints were analysed by intention to treat in the full-analysis population. The study is registered at http://www.clinicaltrials.gov as NCT00241670.

FINDINGS: Median follow-up was 35.4 months (95% CI 1.0-56.7). Contrast-enhancing tumour was resected completely in 90 (65%) of 139 patients assigned 5-aminolevulinic acid compared with 47 (36%) of 131 assigned white light (difference between groups 29% [95% CI 17-40], p<0.0001). Patients allocated 5-aminolevulinic acid had higher 6-month progression free survival than did those allocated white light (41.0% [32.8-49.2] vs 21.1% [14.0-28.2]; difference between groups 19.9% [9.1-30.7], p=0.0003, Z test). Groups did not differ in the frequency of severe adverse events or adverse events in any organ system class reported within 7 days after surgery.

INTERPRETATION: Tumour fluorescence derived from 5-aminolevulinic acid enables more complete resections of contrast-enhancing tumour, leading to improved progression-free survival in patients with malignant glioma 5).

References

1)

Moiyadi A, Syed P, Srivastava S. Fluorescence-guided surgery of malignant gliomas based on 5-aminolevulinic acid: paradigm shifts but not a panacea. Nat Rev Cancer. 2014 Feb;14(2):146. doi: 10.1038/nrc3566-c1. PubMed PMID: 24457418.
2)

Folaron M, Strawbridge R, Samkoe KS, Filan C, Roberts DW, Davis SC. Elucidating the kinetics of sodium fluorescein for fluorescence-guided surgery of glioma. J Neurosurg. 2018 Sep 7:1-11. doi: 10.3171/2018.4.JNS172644. [Epub ahead of print] PubMed PMID: 30192200.
3)

Senders JT, Muskens IS, Schnoor R, Karhade AV, Cote DJ, Smith TR, Broekman ML. Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results. Acta Neurochir (Wien). 2017 Jan;159(1):151-167. doi: 10.1007/s00701-016-3028-5. Review. PubMed PMID: 27878374; PubMed Central PMCID: PMC5177668.
4)

Liu JT, Meza D, Sanai N. Trends in fluorescence image-guided surgery for gliomas. Neurosurgery. 2014 Jul;75(1):61-71. doi: 10.1227/NEU.0000000000000344. Review. PubMed PMID: 24618801; PubMed Central PMCID: PMC4062574.
5)

Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ; ALA-Glioma Study Group. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 2006 May;7(5):392-401. PubMed PMID: 16648043.

UpToDate: Decompressive craniectomy for intracerebral hemorrhage

Decompressive craniectomy for intracerebral hemorrhage

Systematic review

Yao et al. conducted a systematic review to verify the effects of decompressive craniectomy (DC) on improving outcome in spontaneous intracerebral hemorrhage.

Through searching several electronic databases, they screened eligible publications. Respective risk ratio (RR) and its 95% confidence interval (CI) were calculated, data were synthesized with a fixed-effect model, and sensitivity analyses and subgroup analyses were performed. Publication bias was measured with Begg and Egger tests.

Overall effect showed that DC significantly reduced the poor outcome compared with the control group (RR, 0.91; 95% CI, 0.84-0.99; P = 0.03). But in the subgroup analyses, only studies published after 2010, studies using hematoma evacuation as control, and studies measuring outcome with Glasgow outcome score showed better outcomes in the DC group than in the control group. The other subgroup analyses and sensitivity analyses achieved inconsistent results. Compared with the control group, DC effectively decreased mortality (RR, 0.67; 95% CI, 0.53-0.85; P = 0.0008). The sensitivity analyses and subgroup analyses achieved consistent results.

The application of DC effectively reduced mortality in patients with sICH. DC might improve functional outcomes in certain populations and needs further verification. DC is not associated with increased incidences of postoperative rebleeding and hydrocephalus 1).

Experimental work

Marinkovic et al. from Helsinki, Finland, used the model of autologous blood injection into the basal ganglia in rats. After induction of ICH and then magnetic resonance imaging, animals were randomly allocated to groups representing no craniectomy (n = 10) or to craniectomy at 1, 6, or 24 hours. A fifth group without ICH underwent craniectomy only. Neurological and behavioral outcomes were assessed on days 1, 3, and 7 after ICH induction. Furthermore, terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells were counted.

After 7 days, compared with the ICH + no craniectomy group, all craniectomy groups had strikingly lower mortality (P < 0.01), much better neurological outcome (P < 0.001), and more favorable behavioral outcome. A trend occurred in the ICH + no craniectomy group toward more robust apoptosis.

Decompressive craniectomy performed up to 24 hours improved outcome after experimental ICH, with earlier intervention of greater benefit 2).

Case series

Rasras et al. from the Department of Neurosurgery, Ahvaz Jundishapur University of Medical Sciences, AhvazIran, sought to assess the preliminary utility of decompressive hemicraniectomy (DHC) without clot evacuation in patients with deep-seated supratentorial ICH.

Patients with deep seated spontaneous intracerebral hemorrhage who were admitted to the Golestan Hospital, of Ahvaz, from November 2014 to February 2016, were prospectively enrolled in a study. A prospective clinical trial where 30 patients diagnosed having large hypertensive ICH was randomly allocated to either group A or B using permuted-block randomization. These patients (n = 30), who all had large deep seated supratentorial ICH with surgery indications, were randomly divided to two groups. ultimately, in one group (n = 13), large DHC was performed without clot evacuation, while in the other (n = 17), craniotomy with clot evacuation was done. Data pertaining to the patients characteristics and treatment outcomes were prospectively collected.

There was no statistically significant difference between two treatment groups (P > 0.05). No significant difference was observed between the two groups in terms of mortality and GOS at 6 months (P > 0.05); nevertheless, the good outcome (Glasgow Outcome Scale = 4-5) for patients with hematoma evacuation was slightly higher (35.3%) as compared to the DHC patients without clot evacuation (30.7%).

Decompresive craniectomy without clot evacuation in deep seated ICH can be accomplished with identical mortality and outcome in comparison to patient that undergone clot evacuation 3).


A total of 54 eligible patients with spontaneous supratentorial hemorrhage (median age, 55 years; interquartile range, 47-64 years) who underwent decompressive craniectomy were retrospectively matched to 72 patients managed with best medical treatment (median age, 58 years; interquartile range, 32-74 years). Glasgow Outcome Scale (GOS) scores were dichotomized into favorable and unfavorable outcomes. Survival and functional outcomes were analyzed at discharge, 3, 6, and 12 months.

Survival in the craniectomy group was significantly higher compared with the medical treatment group at 30 days, 6, and 12 months (76%, 70%, and 70% vs. 60%, 57%, and 52% respectively; all P ≤ 0.05). There was no difference in functional outcomes at discharge, 3, 6, or 12 months after hemorrhage (all P > 0.05). Decompressive craniectomy was associated with longer hospital stay (median of 30 days vs. 7 days in the control group; P < 0.001). Hospital adverse events were more frequent in the craniectomy group than in the control group (76% vs. 33%; P < 0.001), the commonest adverse events being pneumonia and urinary tract infections.

They showed that decompressive craniectomy significantly improved survival compared with medical treatment with lasting benefits. This improvement came at a cost of increased length of hospital stay and related adverse events. There was no improvement in functional outcome 4).


Decompressive craniectomy is associated with a significant increase in perihematomal edema compared to patients who have been treated conservatively. Perihematomal edema itself lasts about 60 days if it is not treated, but decompressive craniectomy ameliorates the mass effect exerted by the intracerebral hemorrhage plus the perihematomal edema, as reflected by the reduced midline shift 5).


Of 21 patients who underwent DC for hemispheric hypertensive ICH in the Department of Neurosurgery, National Defense Medical College, Tokorozawa, Saitama, Japan, eleven of the patients were male and 10 were female, with an age range of 22-75 years (mean, 56.6 years). Their preoperative Glasgow Coma Scale scores ranged from 3 to 13 (mean, 6.9). The hematoma volumes ranged from 33.4 to 98.1 mL (mean, 74.2 mL), and the hematoma locations were the basal ganglia in 10 patients and the subcortex in 11 patients. Intraventricular extensions were observed in 11 patients. With regard to the complications after DC, postoperative hydrocephalus developed in ten patients, and meningitis was observed in three patients. Six patients had favorable outcomes and 15 had poor outcomes. The mortality rate was 10 %. A statistical analysis showed that the GCS score at admission was significantly higher in the favorable outcome group than that in the poor outcome group (P = 0.029). Our results suggest that DC with hematoma evacuation might be a useful surgical procedure for selected patients with large hemispheric hypertensive ICH 6).


Fung et al. compared consecutive patients (November 2010-January 2012) with supratentorial ICH treated with DC without hematoma evacuation and matched controls treated by best medical treatment. DC measured at least 150 mm and included opening of the dura. We analyzed clinical (age, sex, pathogenesis, Glasgow Coma Scale, National Institutes of Health Stroke Scale), radiological (signs of herniation, side and size of hematoma, midline shift, hematoma expansion, distance to surface), and surgical (time to and indication for surgery) characteristics. Outcome at 6 months was dichotomized into good (modified Rankin Scale 0-4) and poor (modified Rankin Scale 5-6).

Twelve patients (median age 48 years; interquartile range 35-58) with ICH were treated by DC. Median hematoma volume was 61.3 mL (interquartile range 37-83.5 mL) and median preoperative Glasgow Coma Scale was 8 (interquartile range 4.3-10). Four patients showed signs of herniation. Nine patients had good and 3 had poor outcomes. Three patients (25%) of the treatment group died versus 8 of 15 (53%) of the control group. There were 3 manageable complications related to DC.

DC is feasible in patients with ICH. Based on this small cohort, DC may reduce mortality. Larger prospective cohorts are warranted to assess safety and efficacy 7).


Records of 12 consecutive patients with hypertensive ICH treated with decompressive hemicraniectomy were reviewed. The data collected included Glasgow Coma Scale (GCS) score at admission and before surgery, ICH volume, ICH score, and a clinical grading scale for ICH that accurately risk-stratifies patients regarding 30-day mortality. Outcome was assessed as immediate mortality and modified Rankin Score (mRS) at the last follow-up.

Of the 12 patients with decompressive hemicraniectomy, 11 (92%) survived to discharge; of those 11, 6 (54.5%) had good functional outcome, defined as a mRS of 0 to 3 (mean follow-up: 17.13 months; range: 2-39 months). The mean age was 49.8 years (range: 19-76 years). Three of the 7 patients with pupillary abnormalities made a good recovery; of the 11 patients with intraventricular extensions (IVEs), 7 made a good recovery. The clinical finding (which was present in all 3 patients with mRS equal to 5 and which was not present in patients with mRS less than 5) was abnormal occulocephalic reflex. Of the 10 patients with an ICH score of 3, 9 (90%) survived to discharge, 4 (44%) had good functional outcome (mRS: 1-3). Hematoma volume was 60 cm3 or greater in eight patients, four (50%) of whom had good functional outcome (mRS: 0-3).

Decompressive hemicraniectomy with hematoma evacuation is life-saving and improves unfavorable outcomes in a select group of young patients with large right hemispherical ICH 8).

References

1)

Yao Z, Ma L, You C, He M. Decompressive Craniectomy for Spontaneous Intracerebral Hemorrhage: A Systematic Review and Meta-analysis. World Neurosurg. 2018 Feb;110:121-128. doi: 10.1016/j.wneu.2017.10.167. Epub 2017 Nov 10. Review. PubMed PMID: 29129764.
2)

Marinkovic I, Strbian D, Pedrono E, Vekovischeva OY, Shekhar S, Durukan A, Korpi ER, Abo-Ramadan U, Tatlisumak T. Decompressive craniectomy for intracerebral hemorrhage. Neurosurgery. 2009 Oct;65(4):780-6, 1 p following 786; discussion 786. doi: 10.1227/01.NEU.0000351775.30702.A9. PubMed PMID: 19834384.
3)

Rasras S, Safari H, Zeinali M, Jahangiri M. Decompressive hemicraniectomy without clot evacuation in supratentorial deep-seated intracerebral hemorrhage. Clin Neurol Neurosurg. 2018 Aug 23;174:1-6. doi: 10.1016/j.clineuro.2018.08.017. [Epub ahead of print] PubMed PMID: 30172088.
4)

Lo YT, See AAQ, King NKK. Decompressive Craniectomy in Spontaneous Intracerebral Hemorrhage: A Case-Control Study. World Neurosurg. 2017 Jul;103:815-820.e2. doi: 10.1016/j.wneu.2017.04.025. Epub 2017 Apr 17. PubMed PMID: 28427977.
5)

Fung C, Murek M, Klinger-Gratz PP, Fiechter M, Z’Graggen WJ, Gautschi OP, El-Koussy M, Gralla J, Schaller K, Zbinden M, Arnold M, Fischer U, Mattle HP, Raabe A, Beck J. Effect of Decompressive Craniectomy on Perihematomal Edema in Patients with Intracerebral Hemorrhage. PLoS One. 2016 Feb 12;11(2):e0149169. doi: 10.1371/journal.pone.0149169. eCollection 2016. PubMed PMID: 26872068; PubMed Central PMCID: PMC4752325.
6)

Takeuchi S, Takasato Y, Masaoka H, Hayakawa T, Yatsushige H, Shigeta K, Nagatani K, Otani N, Nawashiro H, Shima K. Decompressive craniectomy with hematoma evacuation for large hemispheric hypertensive intracerebral hemorrhage. Acta Neurochir Suppl. 2013;118:277-9. doi: 10.1007/978-3-7091-1434-6_53. PubMed PMID: 23564148.
7)

Fung C, Murek M, Z’Graggen WJ, Krähenbühl AK, Gautschi OP, Schucht P, Gralla J, Schaller K, Arnold M, Fischer U, Mattle HP, Raabe A, Beck J. Decompressive hemicraniectomy in patients with supratentorial intracerebral hemorrhage. Stroke. 2012 Dec;43(12):3207-11. doi: 10.1161/STROKEAHA.112.666537. Epub 2012 Oct 30. PubMed PMID: 23111437.
8)

Murthy JM, Chowdary GV, Murthy TV, Bhasha PS, Naryanan TJ. Decompressive craniectomy with clot evacuation in large hemispheric hypertensive intracerebral hemorrhage. Neurocrit Care. 2005;2(3):258-62. PubMed PMID: 16159072.

UpToDate: Spontaneous posterior fossa subdural hematoma

Spontaneous posterior fossa subdural hematoma

Posterior fossa subdural hematomas may be spontaneous, with no previous trauma. These cases are usually secondary to bleeding from an underlying pathology such as arteriovenous malformation (AVM), aneurysm 1),tumor or coagulation disorder2) 3).

see also Spontaneous retroclival subdural hematoma.

Posterior fossa craniectomy may be preferable in terms of diagnosis and safe treatment 4).

Outcome

Prognosis seems to be related to the clinical condition of the patient at the moment of surgery, according to the GCS. Patients with mild symptomatology usually have a good outcome, whereas, in most cases, there is no improvement if a moderate or severe neurologic deficit has already been established 5) 6).

Case reports

Finger G, Martins OG, Basso LS, Ludwig do Nascimento T, Schiavo FL, Cezimbra Dos Santos S, Stefani MA. Acute spontaneous subdural hematoma in posterior fossa: case report with great outcome. World Neurosurg. 2018 Aug 1. pii: S1878-8750(18)31700-5. doi: 10.1016/j.wneu.2018.07.220. [Epub ahead of print] PubMed PMID: 30077031.


A 69-year-old woman was admitted with nausea, headache, and mild consciousness disturbance. Computed tomography and magnetic resonance imaging showed bilateral pCSH. To prevent further neurological deterioration, we performed surgery under general anesthesia by midline suboccipital craniectomy. Unexpected bleeding from a developed circuitous occipital sinus was stopped with hemoclips. After hematoma removal, she recovered and was transferred to a rehabilitation hospital. By the 19(th) postoperative day, she had developed no neurologic deficits.

This experience demonstrates the risk of blind surgical therapy in patients with pCSH. In such patients, posterior fossa craniectomy may be preferable in terms of diagnosis and safe treatment 7).


A 83-year-old woman was admitted with recent sudden headache and dizziness. Magnetic resonance imaging showed a thin collection of blood in the subdural space adjacent to the clivus, along the wall of the posterior fossa, and at the cervical spine level. A right posterior communicating artery aneurysm was diagnosed using computed tomography angiography and digital subtraction angiography. The aneurysm had two lobes, one of which was attached to the right dorsum sellae. The aneurysm was occluded by stent-assisted coil embolization. The patient was discharged 3 weeks after admission with absence of neurological deficit.

A ruptured aneurysm of the posterior communicating artery may cause an acute SDH 8).


A rare case of concomitant cranial and spinal subdural haematoma (SDH) in a 12-year-old boy with severe thrombocytopenia due to aplastic anaemia, and review the available literature. Magnetic resonance (MR) imaging at presentation revealed a cranial SDH confined to the posterior fossa, and spinal SDH extending from the C1 to S3 segments. The child was managed conservatively due to his poor general condition and lack of any neurological deficit. Repeat MR imaging done at six weeks showed complete resolution of the spinal SDH and partial resolution of the cranial SDH. Although rare, a spontaneous spinal SDH can occur simultaneously with a cranial SDH. Urgent surgical decompression is considered the treatment of choice for spinal SDH; however, a conservative approach may succeed in patients with poor general condition, and/or mild/no neurological deficit 9).


Berhouma M, Houissa S, Jemel H, Khaldi M. Spontaneous chronic subdural hematoma of the posterior fossa. J Neuroradiol. 2007 Jul;34(3):213-5. PubMed PMID: 17572494 10).


Usul et al., present a spontaneous posterior fossa subdural hematoma in a term neonate and discuss conservative management 11).


A case of spontaneous acute subdural haematoma in the posterior fossa following anticoagulation 12).


The association of the posterior fossa chronic subdural hematoma with spontaneous parenchymal hemorrhage without anticoagulation therapy was never related in the literature. Costa et al., describe a case of a 64 year-old woman who suffered a spontaneous cerebellar hemorrhage, treated conservatively, and presented 1 month later with a chronic subdural posterior fossa hematoma 13).


Miranda et al., present a case of a posterior fossa acute subdural hematoma occurring in an anticoagulated patient who was preoperatively misdiagnosed as an intracerebellar hemorrhage 14).


A 52-year-old woman treated for acute myeloproliferative disease developed progressive stupor. CT showed obstructive hydrocephalus resulting from unexplained mass effect on the fourth ventricle. MRI revealed bilateral extra-axial collections in the posterior cranial fossa, giving high signal on T1- and T2-weighted images, suggesting subacute subdural haematomas. Subdural haematomas can be suspected on CT when there is unexplained mass effect. MRI may be essential to confirm the diagnosis and plan appropriate treatment 15).


A 70 year old female presented with progressive dizziness, vertigo and gait ataxia. She was on anticoagulation therapy for heart disease. Neuro-imaging revealed bilateral infratentorial subdural masses. The subdural masses were suspects for chronic subdural haematomas by neuroradiological criteria. Because of the progressive symptomatology, the haematomas were emptied through burrhole trepanations. Chocolate-colored fluid, not containing clotted components, gushed out under great pressure. The source of bleeding could not be identified. The patient recovered well from surgery, but died 4 months later shortly after admission to another hospital from heart failure.

The chronic subdural haematomas in this patient may have been due to rupture of bridging veins caused by a very mild trauma not noticed by the patient and possibly aggravated by the anticoagulation therapy. Infratentorial chronic subdural haematoma should at least be a part of the differential diagnosis in elderly patients with cerebellar and vestibular symptomatology even without a history of trauma 16).


A case of spontaneous acute subdural hematoma complicated with idiopathic thrombocytopenic purpura was reported. He was hospitalized complaining of sudden onset of headache and nasal bleeding without neurological deficit. CT scan revealed subdural hematoma in the posterior fossa especially below the tentorium cerebelli. Further hematological examination proved very low platelet count (1,000/mm3) and antiplatelet antibody in confirmation of a diagnosis of idiopathic thrombocytopenic purpura. As his neurological status was good, he was treated medically. His symptoms and platelet count improved gradually with corticosteroid therapy. Reviewing the literature, acute subdural hematoma with idiopathic thrombocytopenic purpura was quite rare and only three cases reported 17).


Aicher KP, Heiss E, Gawlowski J. [Spontaneous subdural hematoma in the posterior cranial fossa]. Rofo. 1988 Dec;149(6):669-70. German. PubMed PMID: 2849170 18).


Kanter et al., report a patient in whom a spontaneous subdural hematoma developed in the posterior fossa during anticoagulation therapy for mitral valve disease. This rare complication of anticoagulation has been reported in only three other patients 19).


A case of spontaneous posterior fossa subdural hematoma secondary to anticoagulation therapy with definitive diagnosis made by vertebral angiography is reported. Vertebral angiographic findings are illustrated and demonstrate primarily mass effect from posterior compartment of posterior fossa and avascular area. Carotid angiography did not show hydrocephalus. A review of the literature was made and this appears to be the first reported case in which a posterior fossa subdural hematoma has been diagnosed by vertebral angiography 20).


A report of spontaneous posterior fossa subdural haematoma associated with anticoagulation therapy. The possibility of posterior fossa lesions related to spontaneous haemorrhage is suggested by the combination of severe headache and increasing disturbance of consciousness associated with signs of brain-stem decompensation. A thorough neurological evaluation including appropriate contrast studies will help rule out a supratentorial lesion. This is a neurological emergency which can be successfully treated by early detection and prompt surgical decompression. This is the second reported case of spontaneous subdural haematoma of the posterior fossa occurring during anticoagulant therapy 21).

References

1) , 8)

Kim MS, Jung JR, Yoon SW, Lee CH. Subdural hematoma of the posterior fossa due to posterior communicating artery aneurysm rupture. Surg Neurol Int. 2012;3:39. doi: 10.4103/2152-7806.94287. Epub 2012 Mar 24. PubMed PMID: 22530173; PubMed Central PMCID: PMC3327002.
2) , 16)

Stendel R, Schulte T, Pietilä TA, Suess O, Brock M. Spontaneous bilateral chronic subdural haematoma of the posterior fossa. Case report and review of the literature. Acta Neurochir (Wien). 2002 May;144(5):497-500. Review. PubMed PMID: 12111507.
3) , 10)

Berhouma M, Houissa S, Jemel H, Khaldi M. Spontaneous chronic subdural hematoma of the posterior fossa. J Neuroradiol. 2007 Jul;34(3):213-5. PubMed PMID: 17572494.
4) , 7)

Takemoto Y, Matsumoto J, Ohta K, Hasegawa S, Miura M, Kuratsu J. Bilateral posterior fossa chronic subdural hematoma treated with craniectomy: Case report and review of the literature. Surg Neurol Int. 2016 May 6;7(Suppl 10):S255-8. doi: 10.4103/2152-7806.181979. eCollection 2016. PubMed PMID: 27213111; PubMed Central PMCID: PMC4866054.
5) , 14)

Miranda P, Alday R, Lagares A, Pérez A, Lobato RD. Posterior fossa subdural hematoma mimicking intracerebellar hemorrhage. Neurocirugia (Astur). 2003 Dec;14(6):526-8. PubMed PMID: 14710308.
6) , 15)

Pollo C, Meuli R, Porchet F. Spontaneous bilateral subdural haematomas in the posterior cranial fossa revealed by MRI. Neuroradiology. 2003 Aug;45(8):550-2. Epub 2003 May 22. PubMed PMID: 12761603.
9)

Jain V, Singh J, Sharma R. Spontaneous concomitant cranial and spinal subdural haematomas with spontaneous resolution. Singapore Med J. 2008 Feb;49(2):e53-8. Review. PubMed PMID: 18301828.
11)

Usul H, Karaarslan G, Cakir E, Kuzeyl K, Mungan L, Baykal S. Conservative management of spontaneous posterior fossa subdural hematoma in a neonate. J Clin Neurosci. 2005 Feb;12(2):196-8. PubMed PMID: 15749432.
12)

Pal D, Gnanalingham K, Peterson D. A case of spontaneous acute subdural haematoma in the posterior fossa following anticoagulation. Br J Neurosurg. 2004 Feb;18(1):68-9. PubMed PMID: 15040720.
13)

Costa LB Jr, de Andrade A, Valadão GF. Chronic subdural hematoma of the posterior fossa associated with cerebellar hemorrhage: report of rare disease with MRI findings. Arq Neuropsiquiatr. 2004 Mar;62(1):170-2. Epub 2004 Apr 28. PubMed PMID: 15122456.
17)

Saito K, Sakurai Y, Uenohara H, Seki K, Imaizumi S, Katakura R, Niizuma H. [A case of acute subdural hematoma in the posterior fossa with idiopathic thrombocytopenic purpura]. No To Shinkei. 1992 Apr;44(4):377-81. Review. Japanese. PubMed PMID: 1633035.
18)

Aicher KP, Heiss E, Gawlowski J. [Spontaneous subdural hematoma in the posterior cranial fossa]. Rofo. 1988 Dec;149(6):669-70. German. PubMed PMID: 2849170.
19)

Kanter R, Kanter M, Kirsch W, Rosenberg G. Spontaneous posterior fossa subdural hematoma as a complication of anticoagulation. Neurosurgery. 1984 Aug;15(2):241-2. PubMed PMID: 6483141.
20)

McClelland RR, Ramirez-Lassepas M. Posterior fossa subdural hematoma demonstrated by vertebral angiography. Neuroradiology. 1976;10(1):181-5. PubMed PMID: 1256644.
21)

Capistrant T, Goldberg R, Shibasaki H, Castle D. Posterior fossa subdural haematoma associated with anticoagulant therapy. J Neurol Neurosurg Psychiatry. 1971 Feb;34(1):82-5. PubMed PMID: 5313648; PubMed Central PMCID: PMC493691.

UpToDate: Cervical transverse process fracture

Cervical transverse process fracture

Cervical transverse process fractures have a strong association with other cervical spine fractures and blunt cerebrovascular injury 1).

With the advent of whole body computed tomography of trauma patients, the radiologic diagnosis of transverse process fractures (TPF) has increased. Spine service (neurosurgical or orthopedic) consultation is frequently requested for patients with these fractures, stressing constraints on these practices.

When TPF are identified, diligence in searching for a spine injury or abdominal injuries should be exercised, as these associated injuries occur frequently 2).

Isolated cervical transverse process fracture (TPF) of the subaxial cervical spine can be considered as clinically insignificant and do not require treatment 3)

Clinicians should maintain high indices of suspicion for associated injuries in patients with isolated transverse process fractures especially after high-velocity mechanisms 4).

1.- Fracture of the right transverse process of C2 involving the transverse foramen.

2.- Similar fracture passing through right transverse foramen of C3.

Vertebral artery angiography should be considered when patients with transverse process fractures extending into the transverse foramen develop signs and symptoms of vertebrobasilar disease 5).

A case report demonstrates the severity of injury after minor trauma in the context of ankylosing spondylitis, the capacity for full recovery in oesophageal perforations in spinal trauma, and that clinical suspicion of such injuries allows early diagnosistreatment and reduced complications6).

Case series

The Ronald Reagan UCLA Medical Center patient database was queried (years 2005-2016) using International Classification of Diseases, Ninth Revision, code 805: fracture of the vertebral column without mention of spinal cord injury.

A total of 129 patients with isolated transverse process fractures (ITPFs) were identified. Mean age was 38.1 years (range 15-92 years). Women were more likely to present with abdominal pain and associated kidney injury (P = 0.018 and P = 0.012, respectively). Motor vehicle accident (MVA) was the most common mechanism of injury (n = 81, 62.8%) and was associated with thoracic (P = 0.032) and lower extremity pain/injury (P = 0.005). Back pain was the most common presenting symptom (n = 71, 64.6%) and was associated with intraabdominal and lower extremity injuries (P = 0.032 and P = 0.016, respectively). Chest and neck pain were associated with vascular injuries (P < 0.001 and P = 0.001, respectively). Spine consult (neurosurgery or orthopedic surgery) was frequent (n = 94, 72.9%) and was more common after MVA versus fall (P = 0.018).

Several factors were identified as significant markers of associated injuries, including female sex, MVA, and presenting symptoms. Neck and chest pain were significantly associated with vascular injuries. Clinicians should maintain high indices of suspicion for associated injuries in patients with ITPFs, especially after high-velocity mechanisms 7).


21 patients (2.4%) had 25 isolated TPFs of the subaxial cervical spine. The seventh vertebra was involved predominantly (76%). The initial treatment regimen was unrestricted movement in all patients. No associated adverse events were observed. A follow-up of 13 to 39 months was available in 14 patients. Follow-up showed a stable and intact subaxial cervical spine in all patients’ radiographs, a patient satisfaction of 9.3 (SD 1.48), a Cybex measured range of motion in the sagittal plane of 109 degrees (SD 12.5, 95-129), the frontal plane of 70 (SD 17.8, 37-100) and the transverse plane of 144 (SD 12.5, 116-164), and a mean neck disability index score of 3.93 (SD 8.24).

The incidence of isolated TPFs of the subaxial cervical spine was 2.4%. Unrestricted movement resulted in satisfying functional, anatomic, and neurologic outcomes without associated adverse events. This study confirms that isolated TPFs of the subaxial cervical spine can be considered as clinically insignificant and do not require treatment 8).


Patients for a retrospective, institutional review board-approved study were identified by reviewing the daily neurosurgical census from July 2004 to February 2007. Data were collected by chart review on all patients with TPF-grouped into isolated fractures (iTPF) and fractures with other associated spinal injuries (aTPF). Other parameters evaluated included fracture location, other spinal injuries, nonspinal injuries, mechanical stability, neurologic findings, pain, and treatment (surgical stabilization or decompression or bracing or both).

Eighty-four patients with one or more TPF were identified-47 with iTPF and 37 with aTPF. All iTPF and aTPF patients were found to be neurologically intact. No patients with iTPF required surgery or bracing for spinal stability, but 4 aTPF needed surgery and 18 aTPF required bracing with a total of 22 requiring neurosurgical intervention (p < 0.0001). However, none of these patients received treatment for the TPF. Twenty-five patients had associated abdominal injuries (16 of 46 iTPF, 9 of 37 aTPF, p = 0.3335).

iTPF are not associated with neurologic deficit or structural instability requiring spine service intervention. Therefore, conservative management without neurosurgical or orthopedic consultation is appropriate. When TPF are identified, diligence in searching for other spinal injuries or abdominal injuries should be exercised, as these associated injuries occur frequently 9).


In a retrospective study of 216 patients with cervical fractures evaluated by plain films and computed tomography, Woodring et al., found that transverse process fractures were common. Transverse process fractures were present in 24% of patients with cervical fractures and accounted for 13.2% of all cervical fractures. Cervical radiculopathy and brachial plexus palsy were present in 10% of patients with transverse process fractures. In 78% of transverse process fractures, CT scanning showed that the fracture extended into the transverse foramenVertebral artery angiography, performed in eight patients with fractures involving the transverse foramen, showed dissection or occlusion of the vertebral artery in seven (88%) instances. Two of these seven patients had clinical evidence of vertebral-basilar artery stroke. Vertebral angiography should be considered when patients with transverse process fractures extending into the transverse foramen develop signs and symptoms of vertebrobasilar disease 10).


A 66 year old man fell backwards from the first rung of a ladder sustaining a cervical transverse process fracture of C6 vertebral body and a new diagnosis of ankylosing spondylitis. He was taken for surgical fixation, however his oesophagus was discovered entrapped within the fracture at the time of surgery. Despite the severity of the injury, with surgical reduction, fixation and oesophageal exclusion this patient made a full recovery.

This case demonstrates the severity of injury after minor trauma in the context of ankylosing spondylitis, the capacity for full recovery in oesophageal perforations in spinal trauma, and that clinical suspicion of such injuries allows early diagnosistreatment and reduced complications11).


A 40-year-old building and construction male worker who slipped and fell on an iron rod that resulted in penetrating wound on the right side of the anterior neck a week prior to presenting at our facility. He pulled out the iron rod immediately. Computer tomography angiography (CTA) done revealed C2-C4 transverse process fractures on the right side and a fracture at the right lamina of C3 and right common carotid artery dissection with stenosis. He was successfully treated with stenting via endovascular approach.

Richard et al., adopted the view that patient should never pull out objects that result in Penetrating neck injuries (PNI) because of complex neurovascular architecture of the neck. The mortality rate of the patient will have doubled if the iron rode penetrated the common carotid artery. The gold standard treatment option for carotid artery dissection and stenosis is endovascular approaches 12).

References

1)

Green NE, Swiontkowski MF. Skeletal Trauma in Children: Expert Consult – Print and Online, 4e. Saunders. ISBN:1416049002.
2) , 9)

Bradley LH, Paullus WC, Howe J, Litofsky NS. Isolated transverse process fractures: spine service management not needed. J Trauma. 2008 Oct;65(4):832-6; discussion 836. doi: 10.1097/TA.0b013e318184d30e. PubMed PMID: 18849799.
3) , 8)

Schotanus M, van Middendorp JJ, Hosman AJ. Isolated transverse process fractures of the subaxial cervical spine: a clinically insignificant injury or not?: a prospective, longitudinal analysis in a consecutive high-energy blunt trauma population. Spine (Phila Pa 1976). 2010 Sep 1;35(19):E965-70. doi: 10.1097/BRS.0b013e3181c9464e. PubMed PMID: 20479701.
4) , 7)

Bui TT, Nagasawa DT, Lagman C, Jacky Chen CH, Chung LK, Voth BL, Beckett JS, Tucker AM, Niu T, Gaonkar B, Yang I, Macyszyn L. Isolated Transverse Process Fractures and Markers of Associated Injuries: The Experience at University of California, Los Angeles. World Neurosurg. 2017 Aug;104:82-88. doi: 10.1016/j.wneu.2017.04.137. Epub 2017 Apr 28. PubMed PMID: 28461275.
5) , 10)

Woodring JH, Lee C, Duncan V. Transverse process fractures of the cervical vertebrae: are they insignificant? J Trauma. 1993 Jun;34(6):797-802. PubMed PMID: 8315673.
6) , 11)

Vonhoff CR, Scandrett K, Al-Khawaja D. Minor trauma in ankylosing spondylitis causing combined cervical spine fracture and oesophageal injury. World Neurosurg. 2018 Jul 30. pii: S1878-8750(18)31658-9. doi: 10.1016/j.wneu.2018.07.180. [Epub ahead of print] PubMed PMID: 30071342.
12)

Richard SA, Zhang CW, Wu C, Ting W, Xiaodong X. Traumatic Penetrating Neck Injury with Right Common Carotid Artery Dissection and Stenosis Effectively Managed with Stenting: A Case Report and Review of the Literature. Case Rep Vasc Med. 2018 Jun 10;2018:4602743. doi: 10.1155/2018/4602743. eCollection 2018. PubMed PMID: 29984035; PubMed Central PMCID: PMC6015681.

UpToDate: Merkel cell carcinoma

Merkel cell carcinoma (MCC)

Merkel cell carcinoma (MCC) is a rare cutaneous malignancy of neuroendocrine origin.

Harary et al., from the Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA, conducted a systematic review of the literature to identify cases reporting on management of distant MCC brain metastases (BM). A pooled survival analysiswas performed on the institutional and literature cases to assess predictors of OS.

Forty cases were included for analysis, describing operative [14] and non-operative [26] management. Median time to central nervous systeminvolvement was 17.0-mos (interquartile range 10.5-26.5), and most patients had a single BM (62.5%). Management of intracranial disease included radiotherapy (82.5%), systemic therapy (59.5%) and surgical resection (35%). Operative management was associated with a lower intracranial disease burden (DB), but similar DB. Both neurosurgery (hazard ratio [HR] 0.18, 95% confidence interval [CI]: 0.06-0.54, p = 0.002), having RT (HR 0.37, 95% CI: 0.14:0.93, p = 0.04) and having a single BM (extensive intracranial DB: HR 2.51, 95% CI: 1.12-5.6, p = 0.03) conferred an OS benefit on risk-unadjusted analysis. Only, neurosurgical resection was an independent predictor of OS (HR 0.12, 95% CI: 0.03-0.49, p = 0.003), controlling for age, DB and radiotherapy.

Resection of MCC BM may confer a survival benefit given appropriate patient selection. Prospective investigation of multimodal management of neurometastatic MCC is warranted, especially given the promise of new immunotherapy agents in treating MCC 1).

Case reports

A 59-year-old woman was admitted with a 4-month history of progressive and severe dorsal back pain, without neurological signs. The patient had been surgically treated for a recidivated MCC in the occipital region in 2007, 2011, and 2013. (In 2013, the surgical treatment also included lateral cervical lymph node dissection). Chemotherapy and radiotherapy had come after the treatments. Magnetic resonance imaging (MRI) of the dorsal spine showed metastatic vertebral involvement with cord impingement of the T7-T8 levels. A total body CT scan revealed lungs and liver metastases, besides vertebral district. After a multidisciplinary consult a palliative surgery was decided and a posterior dorsal approach was employed: Radiofrequency (RF) thermoablation was followed by the injection of cement of T7 and T8 and transpedicle fixation T5-T9. The postoperative course was uneventful and followed by a further adjuvant therapy.

Spinal metastases from MCC are described in literature only exceptionally. The clinical course is presented, along with a review of literature 2).


This case is particularly unusual in that, not only was no established primary lesion identified, but also the patient has survived for 10 years following initial diagnosis and for 9 years following excision of a single brain metastasis 3).


A case of Merkel cell carcinoma of the spine and evaluate the treatment paradigms utilized in the prior reports. Result A 76-year-old man with a history of Merkel cell carcinoma presented with 2-week history of progressive difficulty ambulating and a solitary T5 epidural mass encasing the spinal cord. The patient underwent a T5 corpectomy with cage placement and T3 to T7 posterior fusion with postoperative neurologic improvement and a return to ambulation. Three weeks postoperatively, the patient re-presented with new-onset weakness and widespread metastatic spinal disease with epidural compression at the T8 level. Six weeks postoperatively, he was placed in hospice care. Conclusion Prior reports in the literature demonstrated a poor prognosis for Merkel cell carcinoma metastasis to the spine with survival ranging from 1 to 9 months after diagnosis. Although neurologic decline necessitates a surgical intervention, the assessment of operative benefit should take into account the prognosis associated with the primary tumor subtype 4).


In this report Jacob et al., propose a novel approach to treat merkel cell carcinoma (MCC) brain metastases and present a review of the literature in an attempt to establish a treatment algorithm and provide prognosis. MCC is a rare neuroendocrine malignancy affecting the aging population. This malignancy has a very aggressive behavior with frequent metastases. We report a 61-year-old man with a prior history of MCC who presented with diplopia. Brain MRI revealed a single right thalamic lesion consistent with metastasis. In the two weeks following GammaKnife stereotactic radiosurgery (Elekta, Stockholm, Sweden) the diplopia improved. A brain MRI demonstrated shrinkage of the tumor. From our literature search we found only six other patients with MCC brain metastases. The majority of these patients were treated with whole brain radiation in conjunction with chemotherapy. We propose that stereotactic radiosurgery can be used as a first line therapy for patients with MCC metastatic brain disease 5).


A case of Merkel cell carcinoma displaying unique patterns of differentiation in the primary focus and brain metastasis. The skin primary was almost uniformly small cell carcinoma positive for epithelial and neuroendocrine markers, with a few glial fibrillary acidic protein- and cytokeratin 20-positive cells. The neoplasm contained giant cells immunoreactive for neurofilament and negative for epithelial markers. The neck lymph node metastasis was a typical neuroendocrine Merkel cell carcinoma positive for cytokeratin 20. A solitary dural intracranial metastasis displayed features of aggressive ganglioneuroblastoma, expressing many neuronal antigens with no evidence of glial or epithelial differentiation. After total gross resection, the tumor recurred within 3 months, and the patient developed skeletal metastases and died 6 months after craniotomy 6).


Madden et al., report a rare case of MCC metastatic to the spine in an immunocompromised patient. Methods A 55-year-old male with previously resected MCC, immunocompromised due to cardiac transplant, presented with sharp mid-thoracic back pain radiating around the trunk to the midline. Computed tomography of the thoracic spine showed a dorsal epidural mass from T6 to T8 with compression of the spinal cord. Laminectomy and subtotal tumor resection were performed, and pathology confirmed Merkel cell tumor through immunohistochemistry staining positive for cytokeratin 20 and negative for thyroid transcription factor-1. Results Further treatment with radiation therapy was initiated, and the patient did well for 4 months after surgery, but returned with a lesion in the cervical spine. He then opted for hospice care. Conclusions With an increasing number of immunocompromised patients presenting with back pain, MCC should be considered in the differential diagnosis of spinal metastatic disease 7).


A case of a 78-year-old male with intracranial extra-axial metastatic MCC involving the left cerebellopontine angle is presented.

A retrosigmoid craniectomy was performed with complete resection of the metastatic focus. Adjuvant treatment included whole-brain radiation therapy followed by etoposide and carboplatin chemotherapy. Seven months postoperatively, the patient was free of metastatic disease.

Surgical resection should be performed when feasible to prevent local recurrence. This may be followed by early adjuvant fractionated whole-brain radiotherapy and systemic chemotherapy; however, no clinical trials have been performed to demonstrate a survival benefit 8).


A unique case of a pituitary metastasis of MCC in a 65-year-old patient with a history of pituitary adenoma. This case is particularly novel due to the fact that the primary site of the MCC is unknown 9).


A rare case of Merkel cell carcinoma with extra-dural spinal metastasis causing paraplegia. There are only four reported cases in literature. A 57-year-old lady presented with a breast lump, multiple truncal skin swellings, low back pain and rapidly progressive paraplegia. MRI showed multiple epidural soft tissue masses causing neural compression. A biopsy from the truncal skin lesion was diagnosed as Merkel cell carcinoma (MCC). Posterior decompression and tumor debulking at all three sites of neural compression was performed. Histopathology of the epidural tumor was consistent with MCC and the diagnosis was confirmed by immuno-histochemistry staining for cytokeratin-20. She was started on chemotherapy and radiotherapy. One month after diagnosis she died due to extensive metastasis. The short term palliative response seen in our patient demonstrates the poor prognosis for patients with spinal metastasis 10).


An unusual case of Merkel cell carcinoma presenting as a frontal scalp mass with apparent invasion into underlying brain parenchyma through grossly intact calvaria. Despite wide local excision, craniectomy, intracranial tumor resection, and postoperative adjuvant irradiation, widespread systemic metastases resistant to chemotherapy developed, and the patient died 9 months after surgery. This case report confirms that Merkel cell carcinoma of the head and neck, already known to be an aggressive tumor, has the capacity for rapid intracranial extension. We propose that in this case, the mechanism of intracranial metastasis was via communicating veins rather than through bone destruction or systemic metastasis. Appropriate preoperative imaging should be carried out to define the extent of this tumor when it is adjacent to the skull. We found contrast-enhanced magnetic resonance imaging to be superior to computed tomography for defining soft tissue extent and marrow space involvement within underlying bone 11).


A 63-year-old man presented with a rare metastatic Merkel cell carcinoma (MCC) involving the lumbosacral spine and causing nerve root compression. Magnetic resonance (MR) imaging revealed an extradural soft tissue mass at the L5-S1 levels. The tumor was subtotally removed and chemotherapy was administered, but he died of multiple metastases from the primary epigastric tumor. Lumbosacral metastatic epidural tumor can manifest as lumbar disc disease symptoms, but MR imaging can non-invasively and rapidly reveal the presence of spinal epidural tumor and any extension to the spinal canal. Extradural MCC metastasis in the lumbosacral area should be considered in the differential diagnosis of radicular symptoms caused by disc herniation 12).


A 48-year-old woman with MCC of the left elbow and a right cerebellar metastasis. After the right cerebellar mass was totally resected, radiation treatment and chemotherapy were performed. Eight cases of brain metastasis have been reported in the literature, but only 5 have been presented in sufficient detail for analysis. Therapy for brain metastases has always been palliative whole-brain irradiation and chemotherapy except for our patient, who underwent total removal of the tumor and survived for 11 months without neurological deficit. Except in the case of 1 with a particularly radiosensitive MCC, the patients with brain metastases died within 9 months after detection of the brain lesions. If possible, aggressive excision of brain metastases as well as of the primary lesion should be done 13).


A 57-year-old female, who had been complaining of anosmia for 8 years, was admitted to the otolaryngological department because an intranasal tumor was found. Then, removal of the tumor and radiotherapy was carried out. After these procedures, the patient suffered from a high fever and CSF rhinorrhea. At this stage, our neurosurgical department was consulted. CT scan revealed a partially calcified low density mass with a slight enhancement effect at the left frontal base. Under the diagnosis of intracranial invasion by intranasal neuroendocrine carcinoma, the patient was operated on. Through bifrontal craniotomy and a combination of extra- and intradural approach, the tumor was excised. After that, the dura and the skull base were reconstructed. On histological examination, the tumor was found to consist of NSE positive cells forming some glandular structures. Electron microscopic study disclosed neurosecretory granules in the cytoplasmic process. These findings are typical of neuroendocrine carcinoma and compatible to those of the intranasal tumor previously removed. Neuroendocrine carcinoma is rare in itself and there have been reported only two cases of its invasion of the skull base. The clinical features, diagnostic procedures, pathological findings, and treatment of this tumor are discussed in this report 14).


A case arising in the calvarium and involving the bone, dura, and underlying brain is presented. The histopathology and immunohistochemical staining characteristics of tumor were consistent with those of Merkel cell tumor. The natural history and histopathology of this tumor are discussed, along with the possible explanation for the origin of this tumor in the calvarium 15).


Alexander et al., reported a case of Merkel cell carcinoma with proven brain metastases and a solid choroidal tumor. The patient responded well to radiation and chemotherapy and is alive and neurologically intact three years after diagnosis. All previous patients with metastatic Merkel cell carcinoma to the brain died within two months of the diagnosis. They used this case to discuss possible routes of metastatic dissemination and to review the treatment options in patients with distant metastatic disease. This is the first reported case of presumed choroidal metastasis of Merkel cell carcinoma and the longest documented survival in a patient with brain involvement 16).

References

1)

Harary M, Kavouridis VK, Thakuria M, Smith TR. Predictors of survival in neurometastatic Merkel cell carcinoma. Eur J Cancer. 2018 Jul 30;101:152-159. doi: 10.1016/j.ejca.2018.07.002. [Epub ahead of print] PubMed PMID: 30071443.
2)

Maugeri R, Giugno A, Giammalva RG, Gulì C, Basile L, Graziano F, Iacopino DG. A thoracic vertebral localization of a metastasized cutaneous Merkel cell carcinoma: Case report and review of literature. Surg Neurol Int. 2017 Aug 10;8:190. doi: 10.4103/sni.sni_70_17. eCollection 2017. PubMed PMID: 28868202; PubMed Central PMCID: PMC5569392.
3)

Honeybul S. Cerebral metastases from Merkel cell carcinoma: long-term survival. J Surg Case Rep. 2016 Oct 7;2016(10). pii: rjw165. doi: 10.1093/jscr/rjw165. PubMed PMID: 27765804; PubMed Central PMCID: PMC5055286.
4)

Goodwin CR, Mehta AI, Adogwa O, Sarabia-Estrada R, Sciubba DM. Merkel Cell Spinal Metastasis: Management in the Setting of a Poor Prognosis. Global Spine J. 2015 Aug;5(4):e39-43. doi: 10.1055/s-0034-1398488. Epub 2015 Jan 7. PubMed PMID: 26225292; PubMed Central PMCID: PMC4516752.
5)

Jacob AT, Alexandru-Abrams D, Abrams EM, Lee JY. Stereotactic radiosurgery for merkel cell carcinoma brain metastases. J Clin Neurosci. 2015 Sep;22(9):1499-502. doi: 10.1016/j.jocn.2015.03.013. Epub 2015 May 11. PubMed PMID: 25975493.
6)

Lach B, Joshi SS, Murty N, Huq N. Transformation of Merkel cell carcinoma to ganglioneuroblastoma in intracranial metastasis. Hum Pathol. 2014 Sep;45(9):1978-81. doi: 10.1016/j.humpath.2014.03.021. Epub 2014 May 28. PubMed PMID: 24996688.
7)

Madden NA, Thomas PA, Johnson PL, Anderson KK, Arnold PM. Thoracic spinal metastasis of merkel cell carcinoma in an immunocompromised patient: case report. Evid Based Spine Care J. 2013 Apr;4(1):54-8. doi: 10.1055/s-0033-1341597. PubMed PMID: 24436699; PubMed Central PMCID: PMC3699249.
8)

Seaman B, Brem S, Fromm A, Staller A, McCardle T, Jain S. Intracranial spread of Merkel cell carcinoma to the cerebellopontine angle. J Cutan Med Surg. 2012 Jan-Feb;16(1):54-60. Review. PubMed PMID: 22417997.
9)

Feletti A, Marton E, Rossi S, Canal F, Longatti P, Billeci D. Pituitary metastasis of Merkel cell carcinoma. J Neurooncol. 2010 Apr;97(2):295-9. doi: 10.1007/s11060-009-0025-z. Epub 2009 Oct 6. PubMed PMID: 19806319.
10)

Vijay K, Venkateswaran K, Shetty AP, Rajasekaran S. Spinal extra-dural metastasis from Merkel cell carcinoma: a rare cause of paraplegia. Eur Spine J. 2008 Sep;17 Suppl 2:S267-70. Epub 2007 Dec 4. PubMed PMID: 18057968; PubMed Central PMCID: PMC2525916.
11)

Barkdull GC, Healy JF, Weisman RA. Intracranial spread of Merkel cell carcinoma through intact skull. Ann Otol Rhinol Laryngol. 2004 Sep;113(9):683-7. PubMed PMID: 15453522.
12)

Turgut M, Gökpinar D, Barutça S, Erkuş M. Lumbosacral metastatic extradural Merkel cell carcinoma causing nerve root compression–case report. Neurol Med Chir (Tokyo). 2002 Feb;42(2):78-80. PubMed PMID: 11944594.
13)

Ikawa F, Kiya K, Uozumi T, Yuki K, Takeshita S, Hamasaki O, Arita K, Kurisu K. Brain metastasis of Merkel cell carcinoma. Case report and review of the literature. Neurosurg Rev. 1999;22(1):54-7. Review. PubMed PMID: 10348209.
14)

Manome Y, Yamaoka R, Yuhki K, Hano H, Kitajima T, Ikeuchi S. [Intracranial invasion of neuroendocrine carcinoma: a case report]. No Shinkei Geka. 1990 May;18(5):483-7. Japanese. PubMed PMID: 2385325.
15)

Wojak JC, Murali R. Primary neuroendocrine (Merkel cell) carcinoma presenting in the calvarium: case report. Neurosurgery. 1990 Jan;26(1):137-9. PubMed PMID: 2294466.
16)

Alexander E 3rd, Rossitch E Jr, Small K, Rosenwasser GO, Abson P. Merkel cell carcinoma. Long term survival in a patient with proven brain metastasis and presumed choroid metastasis. Clin Neurol Neurosurg. 1989;91(4):317-20. PubMed PMID: 2555091.

UpToDate: Diabetes insipidus diagnosis

Diabetes insipidus diagnosis

The indirect water deprivation test is the current reference standard for the diagnosis of diabetes insipidus. However, it is technically cumbersometo administer, and the results are often inaccurate.

A study of Fenske et al.,from the University of Leipzig,Würzburg,MunichLübeck Basel St. GallenBernLucerneAarauBelo Horizonte and the Department of Neurosurgery, University Hospital Hamburg-Eppendorf, compared the indirect water-deprivation test with direct detection of plasma copeptin, a precursor-derived surrogate of arginine vasopressin.

From 2013 to 2017, they recruited 156 patients with hypotonic polyuria at 11 medical centers to undergo both water-deprivation and hypertonic saline infusion tests. In the latter test, plasma copeptin was measured when the plasma sodium level had increased to at least 150 mmol per liter after infusion of hypertonic saline. The primary outcome was the overall diagnostic accuracy of each test as compared with the final reference diagnosis, which was determined on the basis of medical history, test results, and treatment response, with copeptin levels masked.

A total of 144 patients underwent both tests. The final diagnosis was primary polydipsia in 82 patients (57%), central diabetes insipidus in 59 (41%), and nephrogenic diabetes insipidus in 3 (2%). Overall, among the 141 patients included in the analysis, the indirect water-deprivation test determined the correct diagnosis in 108 patients (diagnostic accuracy, 76.6%; 95% confidence interval [CI], 68.9 to 83.2), and the hypertonic saline infusion test (with a copeptin cutoff level of >4.9 pmol per liter) determined the correct diagnosis in 136 patients (96.5%; 95% CI, 92.1 to 98.6; P<0.001). The indirect water-deprivation test correctly distinguished primary polydipsia from partial central diabetes insipidus in 77 of 105 patients (73.3%; 95% CI, 63.9 to 81.2), and the hypertonic saline infusion test distinguished between the two conditions in 99 of 104 patients (95.2%; 95% CI, 89.4 to 98.1; adjusted P<0.001). One serious adverse event (desmopressin-induced hyponatremia that resulted in hospitalization) occurred during the water-deprivation test.

The direct measurement of hypertonic saline-stimulated plasma copeptin had greater diagnostic accuracy than the water-deprivation test in patients with hypotonic polyuria. (Funded by the Swiss National Foundation and others; ClinicalTrials.gov number, NCT01940614 .) 1).


Antidiuretic hormone (ADH) appears as hyperintensity (HI) in the pituitary stalk and the posterior lobe of the pituitary gland on T1-weighted magnetic resonance (MR) imaging. Its disappearance from the posterior lobe occurs with DI, indicating a lack of ADH. The appearance of HI in the pituitary stalk indicates disturbances in ADH transport 2).


An increase in serum sodium of ≥2.5 mmol/L is a positive marker of development of diabetes insipidus (DI) with 80% specificity, and a postoperative serum sodium of ≥145 mmol/L is a positive indicator with 98% specificity. Identifying perioperative risk factors and objective indicators of DI after ETSS will help physicians care for patients postoperatively 3).

References

1)

Fenske W, Refardt J, Chifu I, Schnyder I, Winzeler B, Drummond J, Ribeiro-Oliveira A Jr, Drescher T, Bilz S, Vogt DR, Malzahn U, Kroiss M, Christ E, Henzen C, Fischli S, Tönjes A, Mueller B, Schopohl J, Flitsch J, Brabant G, Fassnacht M, Christ-Crain M. A Copeptin-Based Approach in the Diagnosis of Diabetes Insipidus. N Engl J Med. 2018 Aug 2;379(5):428-439. doi: 10.1056/NEJMoa1803760. PubMed PMID: 30067922.
2)

Hayashi Y, Kita D, Watanabe T, Fukui I, Sasagawa Y, Oishi M, Tachibana O, Ueda F, Nakada M. Prediction of postoperative diabetes insipidus using morphological hyperintensity patterns in the pituitary stalk on magnetic resonance imaging after transsphenoidal surgery for sellar tumors. Pituitary. 2016 Dec;19(6):552-559. PubMed PMID: 27586498.
3)

Schreckinger M, Walker B, Knepper J, Hornyak M, Hong D, Kim JM, Folbe A, Guthikonda M, Mittal S, Szerlip NJ. Post-operative diabetes insipidus after endoscopic transsphenoidal surgery. Pituitary. 2013 Dec;16(4):445-51. doi: 10.1007/s11102-012-0453-1. PubMed PMID: 23242859.

UpToDate: Glioma biomarker

Glioma biomarker

see also Glioblastoma biomarker.

Gliomas are difficult to classify precisely because of interobserver variability during histopathologic grading. Identifying biological signatures of each glioma subtype through protein biomarker profiling of tumor or tumor-proximal fluids is therefore of high priority. Such profiling not only may provide clues regarding tumor classification but may identify clinical biomarkers and pathologic targets for the development of personalized treatments.

In the past, differential proteomic profiling techniques have utilized tumor, cerebrospinal fluid, and plasma from glioma patients to identify the first candidate diagnostic, prognostic, predictive, and therapeutic response markers, highlighting the potential for glioma biomarker discovery. The number of markers identified, however, has been limited, their reproducibility between studies is unclear, and none have been validated for clinical use.

Technological advancements in methodologies for high-throughput profiling, which provide easy access, rapid screening, low sample consumption, and accurate protein identification, are anticipated to accelerate brain tumor biomarker discovery. Reliable tools for biomarker verification forecast translation of the biomarkers into clinical diagnostics in the foreseeable future 1).

Glioma shed extracellular vesicles (EVs), which invade the surrounding tissue and circulate within both the cerebrospinal fluid and the systemic circulation. These tumor-derived EVs and their content serve as an attractive source of biomarkers.

In a review, Hochberg et al., discuss the current state of the art of biomarkers for glioma with emphasis on their EV derivation 2).


A study identified an 18-cytokine signature for distinguishing glioma sera from normal healthy individual sera and also demonstrated the importance of their differential abundance in glioma biology 3).


Shi et al., from Hangzhou, Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai. Department of Neurosurgery, Huai’an Second People’s Hospital, The Affiliated Huai’an Hospital of Xuzhou Medical University, Huai’an, China, extracted data sets from the Gene Expression Omnibus data set by using “glioma” as the keyword. Then, a coexpression module was constructed with the help of Weighted Gene Coexpression Network Analysis software. Besides, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the genes in these modules. As a result, the critical modules and target genes were identified. Eight coexpression modules were constructed using the 4,000 genes with a high expression value of the total 141 glioma samples. The result of the analysis of the interaction among these modules showed that there was a high scale independence degree among them. The GO and KEGG enrichment analyses showed that there was a significant difference in the enriched terms and degree among these eight modules, and module 5 was identified as the most important module. Besides, the pathways it was enriched in, hsa04510: Focal adhesion and hsa04610: Complement and coagulation cascades, were determined as the most important pathways. In summary, module 5 and the pathways it was enriched in, hsa04510: Focal adhesion and has 04610: Complement and coagulation cascades, have the potential to serve as glioma biomarkers 4).

References

1)

Kalinina J, Peng J, Ritchie JC, Van Meir EG. Proteomics of gliomas: initial biomarker discovery and evolution of technology. Neuro Oncol. 2011 Sep;13(9):926-42. doi: 10.1093/neuonc/nor078. Review. PubMed PMID: 21852429; PubMed Central PMCID: PMC3158015.

2)

Hochberg FH, Atai NA, Gonda D, Hughes MS, Mawejje B, Balaj L, Carter RS. Glioma diagnostics and biomarkers: an ongoing challenge in the field of medicine and science. Expert Rev Mol Diagn. 2014 May;14(4):439-52. doi: 10.1586/14737159.2014.905202. Review. PubMed PMID: 24746164; PubMed Central PMCID: PMC5451266.

3)

Nijaguna MB, Patil V, Hegde AS, Chandramouli BA, Arivazhagan A, Santosh V, Somasundaram K. An Eighteen Serum Cytokine Signature for Discriminating Glioma from Normal Healthy Individuals. PLoS One. 2015 Sep 21;10(9):e0137524. doi: 10.1371/journal.pone.0137524. eCollection 2015. PubMed PMID: 26390214.

4)

Shi T, Chen J, Li J, Yang BY, Zhang QL. Identification of key gene modules and pathways of human glioma through coexpression network. J Cell Physiol. 2018 Aug 1. doi: 10.1002/jcp.27059. [Epub ahead of print] PubMed PMID: 30067869.

UpToDate: Internal carotid artery segments

Internal carotid artery segments

The course of the internal carotid artery (ICA) and its segment classifications were reviewed by means of a new and freely available interactive 3D model of the artery and the skull base, based on human neuroimages, that can be freely downloaded at the Public Repository of the University of Barcelona ( http://diposit.ub.edu/dspace/handle/2445/112442 ) and runs under Adobe Acrobat Reader in Mac and Windows computers and Windows 10 tablets. The 3D-PDF allows zoom, rotation, selective visualization of structures, and a predefined sequence view. Illustrative images of the different classifications were obtained 1).

In 1938 Fischer, described five internal carotid artery segments in the opposite direction to the blood flow 2).

These segments were based on the angiographic course of the intracranial ICA rather than its arterial branches or anatomic compartments. Subsequent attempts to apply modern nomenclature to these numerical segments failed to recognize Fischer’s original intent of describing patterns of arterial displacement by tumors and, therefore, resulted in a nomenclature that was anatomically inaccurate. Fischer’s system was further limited, because segments were numbered opposite the direction of blood flow and the extracranial ICA was excluded 3).


Gibo et al. in 1981 studied the microsurgical anatomy of the supraclinoid portion of the internal carotid artery (ICA) in 50 adult cadaver cerebral hemispheres using X 3 to X 40 magnification. The ICA was divided into four parts: the C1 or cervical portion; the C2 or petrous portion; the C3 or cavernous portion; and the C4 or supraclinoid portion.

The C4 portion was divided into three segments based on the origin of its major branches: the ophthalmic segment extended from the origin of the ophthalmic artery to the origin of the posterior communicating artery (PCoA); the communicating segment extended from the origin of the PCoA to the origin of the anterior choroidal artery (AChA); and the choroidal segment extended from the origin of the AChA to the bifurcation of the carotid artery. Each segment gave off a series of perforating branches with a relatively constant site of termination. The perforating branches arising from the ophthalmic segment passed to the optic nerve and chiasminfundibulum, and the floor of the third ventricle. The perforating branches arising from the communicating segment passed to the optic tract and the floor of the third ventricle. The perforating branches arises from the choroidal segment passed upward and entered the brain through the anterior perforated substance. The anatomy of the ophthalmic, posterior communicating, anterior choroidal, and superior hypophyseal branches of the C4 portion was also examined. Gibo-Rothon (J Neurosurg 55:560-574, 1981) follow the blood flow, incorporated the cervical and petrous portions, and divided the subarachnoid course-supraclinoid-in ophthalmic, communicating, and choroidal segments, enhancing transcranial microscopic approaches 4).


see Bouthillier classification.

Bouthillier et al. described in 1996 a seven segment internal carotid artery (ICA) classification system. It remains the most widely used system for describing ICA segments.


The Kassam’s group (2014), with an endoscopic endonasal perspective, introduces the “paraclival segment,” including the “lacerum segment” and part of the intracavernous ICA, and details surgical landmarks to minimize the risk of injury 5).

see also Carotid Siphon

AC: anterior clinoid process; ICA: internal carotid artery; LT: lamina terminalis; ON: optic nerve; OlN; olfactory nerve; SW: sphenoid wing; TS: tuberculum sellae; A1: A1 segment of the Anterior Cerebral Artery; A2: A2 segment of the Anterior Cerebral Artery; M1: M1 segment of the Middle Cerebral Artery

Endoscopic classification

Based on anatomic correlations, the ICA may be described as 6 distinct segments:

(1) parapharyngeal (common carotid artery bifurcation to carotid canal)

(2) petrous (carotid canal to posterolateral aspect of foramen lacerum)

(3) paraclival (posterolateral foramen lacerum to the superomedial aspect of the petrous apex)

(4) parasellar (superomedial petrous apex to the proximal dural ring)

(5) paraclinoid (from the proximal to the distal dural rings)

(6) intradural (distal ring to ICA bifurcation).

Corresponding surgical landmarks included the Eustachian tube, the fossa of Rosenmüller, and levator veli palatini for the parapharyngeal segment; the vidian canal and V3 for the petrous segment; the fibrocartilage of foramen lacerumforamen rotundummaxillary strut, lingular process of the sphenoid bone, and paraclival protuberance for the paraclival segment; the sellar floor and petrous apex for the parasellar segment; and the medial and lateral opticocarotid and lateral tubercular recesses, as well as the distal osseous arch of the carotid sulcus for the paraclinoid segment 6).

see Intracavernous internal carotid artery.

References

1)

Melé MV, Puigdellívol-Sánchez A, Mavar-Haramija M, Juanes-Méndez JA, Román LS, De Notaris M, Catapano G, Prats-Galino A. Review of the main surgical and angiographic-oriented classifications of the course of the internal carotid artery through a novel interactive 3D model. Neurosurg Rev. 2018 Jul 26. doi: 10.1007/s10143-018-1012-7. [Epub ahead of print] Review. PubMed PMID: 30051302.
2)

Fischer E. Die Lageabweichungen der vorderen hirnarterie im gefässbild. Zentralbl Neurochir. 1938;3:300–313.
3)

Bouthillier A, van Loveren HR, Keller JT. Segments of the internal carotid artery: a new classification. Neurosurgery. 1996 Mar;38(3):425-32; discussion 432-3. PubMed PMID: 8837792.
4)

Gibo H, Lenkey C, Rhoton AL Jr. Microsurgical anatomy of the supraclinoid portion of the internal carotid artery. J Neurosurg. 1981 Oct;55(4):560-74. PubMed PMID: 7277004.
5) , 6)

Labib MA, Prevedello DM, Carrau R, Kerr EE, Naudy C, Abou Al-Shaar H, Corsten M, Kassam A. A road map to the internal carotid artery in expanded endoscopic endonasal approaches to the ventral cranial base. Neurosurgery. 2014 Sep;10 Suppl 3:448-71. doi: 10.1227/NEU.0000000000000362. PubMed PMID: 24717685.

UpToDate: Osteoporotic vertebral fracture treatment

Osteoporotic vertebral fracture treatment

Initial therapy for osteoporotic vertebral compression fractures (OVCF) are bed rest, orthotic devices and pain medication 1) 2).

However, some patients fail to benefit from these treatment modalities and disease-related morbidity and mortality persists. Conservatively treated OVCF’s are cured with partial relief of pain and quality of life within 2 to 12 weeks 3) 4)

Kyphoplasty was developed to restore vertebral height and improve sagittal alignment. Several studies have shown these theoretical improvements cannot be transferred universally to the clinical setting.

see Vertebral augmentation.

The treatment of osteoporotic vertebral compression fractures using transpedicular cement augmentation has grown significantly since 1990s.

The treatment of painful vertebral compression fractures has changed substantially since the introduction of vertebroplasty in the mid-1980s and balloon kyphoplasty in the late 1990s. Both procedures were widely accepted with the vertebral fractures treated reaching 150,000 per annum in 2009 prior to the publication of 2 randomized controlled trials comparing vertebroplasty with a sham treatment published in the New England Journal of Medicine in August 2009. Since then, there has been a flood of information on vertebral augmentation and balloon kyphoplasty. It is worth evaluating this information especially because it relates to current recommendations that are often followed blindly by medical and administrative groups unfamiliar with either the procedure or the high level of evidence surrounding vertebral augmentation 5).


In a multicenter study, Kallmes et al., randomly assigned 131 patients who had one to three painful osteoporotic vertebral compression fractures to undergo either vertebroplasty or a simulated procedure without cement (control group). The primary outcomes were scores on the modified Roland Morris Disability Questionnaire (RDQ) (on a scale of 0 to 23, with higher scores indicating greater disability) and patients’ ratings of average painintensity during the preceding 24 hours at 1 month (on a scale of 0 to 10, with higher scores indicating more severe pain). Patients were allowed to cross over to the other study group after 1 month.

All patients underwent the assigned intervention (68 vertebroplasties and 63 simulated procedures). The baseline characteristics were similar in the two groups. At 1 month, there was no significant difference between the vertebroplasty group and the control group in either the RDQ score (difference, 0.7; 95% confidence interval [CI], -1.3 to 2.8; P=0.49) or the pain rating (difference, 0.7; 95% CI, -0.3 to 1.7; P=0.19). Both groups had immediate improvement in disability and pain scores after the intervention. Although the two groups did not differ significantly on any secondary outcome measure at 1 month, there was a trend toward a higher rate of clinically meaningful improvement in pain (a 30% decrease from baseline) in the vertebroplasty group (64% vs. 48%, P=0.06). At 3 months, there was a higher crossover rate in the control group than in the vertebroplasty group (51% vs. 13%, P<0.001) [corrected]. There was one serious adverse event in each group.

Improvements in pain and pain-related disability associated with osteoporotic compression fractures in patients treated with vertebroplasty were similar to the improvements in a control group 6).

On the other hand a randomized controlled trial (Fracture Reduction Evaluation [FREE] trial) which took place at 21 sites in eight countries and included 149 patients assigned to balloon kyphoplasty showed that in patients with acute, painful, vertebral fractures, balloon kyphoplasty improved quality of life, function, mobility, and pain more rapidly than did nonsurgical management, with significant differences in improvement between the groups at 1 month 7).

References

1)

Riek AE, Towler DA. The pharmacological management of osteoporosis. Mo Med. 2011;108:118–123.

2)

Rapado A. General management of vertebral fractures. Bone. 1996;18:191S–196S.

3)

Brown CJ, Friedkin RJ, Inouye SK. Prevalence and outcomes of low mobility in hospitalized older patients. J Am Geriatr Soc. 2004;52:1263–1270.

4)

Babayev M, Lachmann E, Nagler W. The controversy surrounding sacral insufficiency fractures: to ambulate or not to ambulate? Am J Phys Med Rehabil. 2000;79:404–409.

5)

Beall DP, McRoberts WP, Berven SH, Ledlie JT, Tutton SM, Parsons BP. Critique of the Analysis of UpToDate.com on the Treatment of Painful Vertebral Compression Fractures: Time to Update UpToDate. AJNR Am J Neuroradiol. 2014 Nov 20. [Epub ahead of print] PubMed PMID: 25414003.

6)

Kallmes DF, Comstock BA, Heagerty PJ, Turner JA, Wilson DJ, Diamond TH, Edwards R, Gray LA, Stout L, Owen S, Hollingworth W, Ghdoke B, Annesley-Williams DJ, Ralston SH, Jarvik JG. A randomized trial of vertebroplasty for osteoporotic spinal fractures. N Engl J Med. 2009 Aug 6;361(6):569-79. doi: 10.1056/NEJMoa0900563. Erratum in: N Engl J Med. 2012 Mar 8;366(10):970. PubMed PMID: 19657122; PubMed Central PMCID: PMC2930487.

7)

Wardlaw D, Cummings SR, Van Meirhaeghe J, Bastian L, Tillman JB, Ranstam J, Eastell R, Shabe P, Talmadge K, Boonen S. Efficacy and safety of balloon kyphoplasty compared with non-surgical care for vertebral compression fracture (FREE): a randomised controlled trial. Lancet. 2009 Mar 21;373(9668):1016-24. doi: 10.1016/S0140-6736(09)60010-6. Epub 2009 Feb 24. PubMed PMID: 19246088.

UpToDate: Pituicytoma

Pituicytoma

Pituicytoma is a rare glial sellar/suprasellar neoplasm arising in the neurohypophysis with a possible origin from the folliculostellate cells of the adenohypophysis which are non-endocrine spindled cells expressing S-100 and Bcl-2 1) 2).

Pituicytoma is considered to be a distinct Grade I neoplasm 3).

Although usually intra-sellar, pituicytomas can have suprasellar extension; however, purely suprasellar examples although rare have been reported 4).

Epidemiology

PTs had a higher prevalence in the fifth and sixth decades of life, with a slight male predominance. 5).

Clinical features

The presenting symptoms are due to the mass effect of the tumor and include visual disturbances caused by direct compression on the optic chiasm, headaches, endocrinological symptoms and rarely diabetes insipidus 6).

Diagnosis

Radiologically, PTs were found anywhere along the hypothalamic-pituitary axis mimicking other, more frequent tumors growing in this anatomical region 7).

The MRI features are non-specific with most case reports showing a solid, homogenous mass, iso-intense on T1-weighted images and hyper-intense on T2-weighted images with homogenous contrast enhancement 8).

Amongst the various sellar tumors, pituicytoma and spindle cell oncocytoma (SCO) have considerable overlap in histological, Immunohistochemical (IHC) profile and can have extensive intraoperative bleeding making complete excision difficult with increased chances of recurrence. It is important to differentiate pituicytoma from SCO since the former is associated with a slightly better prognosis with recurrence being uncommon after complete surgical excision. Till 2013, out of 29 cases of pituicytoma with a detailed follow-up, recurrence was seen in six cases, all of which were found to have an incomplete resection during the first surgery 9).

SCO on the other hand have a tendency to recur even after complete excision. Hence, it is advocated to combine surgery with adjuvant radiotherapy in all cases of SCO to reduce the chances of recurrence. EMA is strongly positive in SCO, thus it can help to differentiate pituicytoma from SCO 10).

Subtypes

TTF-1 Expressing Sellar Neoplasm with Ependymal Rosettes and Oncocytic Change: Mixed Ependymal and Oncocytic Variant 11).

Treatment

Review

Less than 50 cases have been reported in the world literature till 2013 12).

Salge-Arrieta et al., from the Hospital Universitario Ramón y Cajal Madrid, Spain, published a retrospective review of case reports published in the scientific literature to 2018, including a new illustrative example treated.

116 cases were collected. PTs had a higher prevalence in the fifth and sixth decades of life, with a slight male predominance. Main symptoms, which tended to be progressive, included visual field defects and pituitary-hypothalamic dysfunction. Radiologically, PTs were found anywhere along the hypothalamic-pituitary axis mimicking other, more frequent tumors growing in this anatomical region. Surgical treatment included both transcranial or transsphenoidal approaches, and resulted in gross total resection and morbidity rates of 46.8 and 59%, respectively; the latter essentially consisted in anterior and posterior pituitary dysfunction, with limited impact on daily quality of life.

Due to both low frequency and the absence of pathognomonic clinical and/or radiological features, formulating a suspicion diagnosis of PT represents a considerable challenge even for experienced professionals. The indication for treatment should be made on an individual basis, but it is inescapable in the presence of a visual field defect. The surgical approach has to be tailored according to the topography of the tumor and preoperative symptoms; the greatest challenges in accomplishing a gross total removal are represented by the degree of adherence and vascularization of the PT 13).

Case series

Lefevre et al., from the Groupe Hospitalier Pitié-Salpêtrière, Paris, France published a retrospective multicenter study, reporting the clinical manifestations, radiological characteristics, histopathological features, treatment strategies and long-term outcomes of patients who have been treated for a Pituicytoma at various institutions in Paris, France over the past 10 years. In addition, they compared the results to the world literature in order to identify similarities concerning the radiographic diagnosis and the treatment strategies of these tumors.

Eight patients were operated on in four different hospitals. Misdiagnosis was constant before surgery, pituitary adenoma or craniopharyngioma being suspected. During surgery (transsphenoidal approach: six cases, transcranial approach: two cases) unusual tumors were noted, with important bleeding in most cases. Complete resection could be obtained in five patients. Pathological diagnosis was confirmed in all cases. During the follow up two recurrences occurred. One was subsequently treated with radiotherapy, the other underwent a second surgery.

Recent updates concerning the histological diagnosis of pituicytomas should be generalized to our practice in order to provide a better understanding of this rare pathology and its natural course 14).

References

1)

Phillips JJ, Misra A, Feuerstein BG, Kunwar S, Tihan T. Pituicytoma: Characterization of a unique neoplasm by histology, immunohistochemistry, ultrastructure, and array-based comparative genomic hybridization. Arch Pathol Lab Med 2010;134:1063-9.

2)

Koutourousiou M, Gardner PA, Kofler JK, Fernandez-Miranda JC, Snyderman CH, Lunsford LD. Rare infundibular tumors: clinical presentation, imaging findings, and the role of endoscopic endonasal surgery in their management. J Neurol Surg B Skull Base. 2013 Feb;74(1):1-11. doi: 10.1055/s-0032-1329619. Epub 2012 Dec 31. PubMed PMID: 24436883; PubMed Central PMCID: PMC3699169.

3)

Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 2007;114:97-109.

4)

Zhang F, Chen J, You C. Pituicytoma: Case report and review of the literature. Neurol India 2010;58:799-801.

5) , 7) , 13)

Salge-Arrieta FJ, Carrasco-Moro R, Rodríguez-Berrocal V, Pian H, Martínez-San Millán JS, Iglesias P, Ley-Urzáiz L. Clinical features, diagnosis and therapy of pituicytoma: an update. J Endocrinol Invest. 2018 Jul 20. doi: 10.1007/s40618-018-0923-z. [Epub ahead of print] Review. PubMed PMID: 30030746.

6) , 8)

Chu J, Yang Z, Meng Q, Yang J. Pituicytoma: Case report and literature review. Br J Radiol 2011;84:e55-7.

9) , 10)

Ogiwara H, Dubner S, Shafizadeh S, Raizer J, Chandler JP. Spindle cell oncocytoma of the pituitary and pituicytoma: Two tumors mimicking pituitary adenoma. Surg Neurol Int 2011;2:116.

11)

Saeed Kamil Z, Sinson G, Gucer H, Asa SL, Mete O. TTF-1 Expressing Sellar Neoplasm with Ependymal Rosettes and Oncocytic Change: Mixed Ependymal and Oncocytic Variant Pituicytoma. Endocr Pathol. 2013 Nov 16. [Epub ahead of print] PubMed PMID: 24242699.

12)

Shenoy AS, Desai HM, Mehta JK. Pituicytoma: a case report with literature revisited. Indian J Pathol Microbiol. 2013 Apr-Jun;56(2):180-1. doi: 10.4103/0377-4929.118695. PubMed PMID: 24056664.

14)

Lefevre E, Bouazza S, Bielle F, Boch AL. Management of pituicytomas: a multicenter series of eight cases. Pituitary. 2018 Jul 31. doi: 10.1007/s11102-018-0905-3. [Epub ahead of print] PubMed PMID: 30062665.