Brain metastases recurrence diagnosis

Brain metastases recurrence diagnosis

It is difficult to differentiate local brain metastases recurrence from radiation induced-changes in case of suspicious contrast enhancement. New advanced MRI techniques (perfusion and spectrometry) and Amino Acid Positron Emission tomography allow to be more accurate and could avoid a stereotactic biopsy for histological assessment, the only reliable but invasive method.

Whereas positron emission tomography (PET) with the widely used 18F-2-deoxy-2-fluoro-D-glucose (18F-FDG) has low diagnostic accuracy after SRS, the use of radiolabelled amino acids or amino acid analogues such as L-methyl-11C-methionine (11C-MET) and O-(2-18F-Fluoroethyl)-L-Tyrosine (18F-FET) reaches sensitivity and specificity values in the range of 78 and 100 % rendering especially 18F-FET a highly reliable tracer in glioma imaging.


In patients with MRI-suspected tumor recurrence after focused high dose radiotherapy, 18F-FET PET has a high sensitivity and specificity for the differentiation of vital tumor tissue and radiation-induced lesions 1).


Tran et al. performed a feasibility study to prospectively evaluate 11C methionine positron emission tomography and11C PBR28 positron emission tomography in 5 patients with 7 previously SRS-treated brain metastases demonstrating regrowth to differentiate tumor regrowth (TR) from radiation necrosis (RN).

Sequential imaging with dual tracers was well-tolerated. [11C]methionine was accurate for detecting pathologically confirmed TR in 7/7 lesions, whereas [11C]PBR28 was only accurate in 3/7 lesions. Tumor PBRTSPO expression was elevated in both melanoma and lung cancer cells, contributing to lack of specificity of [11C]PBR28-PET.

Sequential use of PET tracers is safe and effective. [11C]Methionine was a reliable TR marker, but [11C]PBR28 was not a reliable marker of RN. Studies are needed to determine the causes of post-radiation inflammation and identify specific markers of RN to improve diagnostic imaging 2).

The multimodal MRI has greatly contributed to refine the differential diagnosis between tumour recurrence and radionecrosis, which remains difficult. The FDG PET is helpful, in favour of the diagnosis of local tumour recurrence when a hypermetabolic lesion is found. Others tracers (such as carbon 11 or a fluoride isotope) deserve interest but are not available in all centres. Stereotactic biopsy should be discussed if any doubt remains 3).

An increase in FLAIR signal of the fluid within the resection cavity might be a highly specific and early sign of local tumor recurrence/tumor progression also for brain metastases. 4).


1)

Romagna A, Unterrainer M, Schmid-Tannwald C, Brendel M, Tonn JC, Nachbichler SB, Muacevic A, Bartenstein P, Kreth FW, Albert NL. Suspected recurrence of brain metastases after focused high dose radiotherapy: can [18F]FET- PET overcome diagnostic uncertainties? Radiat Oncol. 2016 Oct 21;11(1):139. doi: 10.1186/s13014-016-0713-8. PMID: 27769279; PMCID: PMC5073742.
2)

Tran TT, Gallezot JD, Jilaveanu LB, Zito C, Turcu G, Lim K, Nabulsi N, Huang H, Huttner A, Kluger HM, Chiang VL, Carson R. [11C]Methionine and [11C]PBR28 as PET Imaging Tracers to Differentiate Metastatic Tumor Recurrence or Radiation Necrosis. Mol Imaging. 2020 Jan-Dec;19:1536012120968669. doi: 10.1177/1536012120968669. PMID: 33147119.
3)

Patsouris A, Augereau P, Tanguy JY, Morel O, Menei P, Rousseau A, Paumier A. [Differentiation from local tumour recurrence and radionecrosis after stereotactic radiosurgery for treatment of brain metastasis.]. Cancer Radiother. 2014 Jan 13. pii: S1278-3218(13)00444-7. doi: 10.1016/j.canrad.2013.10.013. [Epub ahead of print] French. PubMed PMID: 24433952.
4)

Bette S, Gempt J, Wiestler B, Huber T, Specht H, Meyer B, Zimmer C, Kirschke JS, Boeckh-Behrens T. Increase in FLAIR Signal of the Fluid Within the Resection Cavity as Early Recurrence Marker: Also Valid for Brain Metastases? Rofo. 2017 Jan;189(1):63-70. doi: 10.1055/s-0042-119686. PubMed PMID: 28002859.

Cerebrospinal fluid shunt malfunction diagnosis

Cerebrospinal fluid shunt malfunction diagnosis

The diagnosis of cerebrospinal fluid shunt malfunction based on a careful clinical history, examination, and investigations such as computed tomography (CT) scanning and plain X-ray shunt series is not always straightforward 1).

For example, ventricular size may not change in cases with a blocked shunt. Pumping a shunt prechamber is notoriously unreliable and potentially dangerous 2).

Admission for observation is expensive and excessive CT scanning carries a radiation burden. Many patients may be admitted and subjected to CT scanning on multiple occasions. There is a need to develop more reliable methods of assessing shunt function and monitoring intracranial pressure (ICP) 3) 4) 5) 6) 7) 8).

Optic nerve sheath diameter may be assessed using ultrasound or magnetic resonance imaging (MRI). Implantable ICP sensors within a shunt system have been blighted by poor long-term stability. Long-term studies of the recently introduced Raumedic NEUROVENT-P-tel and the Miethke SENSOR RESERVOIR are awaited with a keen interest 9).


Several attempts have been made to measure the cerebrospinal fluid flow velocity utilizing different Phase contrast magnetic resonance imaging techniques. In a study, König et al. evaluated 3T (Tesla) MRI scanners for their effectiveness in determining of flow in the parenchymal portion of ventricular shunt systems with adjustable valves containing magnets.

At first, an MRI phantom was used to measure the phase-contrasts at different constant low flow rates. The next step was to measure the CSF flow in patients treated with ventricular shunts without suspected malfunction of the shunt under observation.

The measurements of the phantom showed a linear correlation between the CSF flow and corresponding phase values. Despite many artifacts resulting from the magnetic valves, the ventricular catheter within the parenchymal portion of shunt was not superimposed by artifacts at each PC MRI plane and clearly distinguishable in 9 of 12 patients. Three patients suffering from obstructive hydrocephalus showed a clear flow signal.

Cerebrospinal fluid flow detected within the parenchymal portion of the shunt by phase contrast magnetic resonance imaging may reliably provide information about the functional status of a ventricular shunt. Even in patients whose hydrocephalus was treated with magnetic adjustable valves, the CSF flow was detectable using PC MRI sequences at 3 T field strength 10).


Non-invasive techniques to assess ‘semi-quantitatively’ whether intracranial pressure is raised or not include optic nerve sheath diameter (ultrasound or MRI), tympanic membrane displacement and transcranial Doppler but none have yet been shown to be sufficiently accurate for routine clinical use in patients with potential shunt malfunction. Provision of a separate subcutaneous CSF reservoir is of proven benefit in allowing access to the cerebral ventricles to measure ICP and allow removal of CSF in an emergency


Various invasive diagnostic test procedures for the verification of shunt function have been described:

Invasive CSF pressure and flow measurements

CSF tap test and drip interval test

Infusion tests

Radioactive shuntogram.

By comparison, publications addressing the noninvasive pumping test are rare.

Noninvasive pumping test of all formerly published results are values derived from tests with a variety of reservoirs and valves (at least 2 types).

In a few reports, the shunt/reservoir type used is not even specified, although the technical parameters of such reservoirs and valves are obviously essential.

To judge occlusions distally from the reservoir other authors have had to close the pVC transcutaneously by manual compression.

This is never possible with a sufficient certainty and, if ever undertaken, it usually does provide a source of error.


Rapid cranial MRI was not inferior to CT for diagnosing ventricular shunt malfunction and offers the advantage of sparing a child ionizing radiation exposure 11).


1)

Spirig JM, Frank MN, Regli L, Stieglitz LH (2017) Shunt agerelated complications in adult patients with suspected shunt dysfunction . A recommended diagnostic workup. 1421–1428
2)

Bromby A, Czosnyka Z, Allin D, Richards HK, Pickard JD, Czosnyka M (2007) Laboratory study on “intracranial hypotension” created by pumping the chamber of a hydrocephalus shunt. Cerebrospinal Fluid Res 9:1–9
3)

Dupepe EB, Hopson B, Johnston JM, Rozzelle CJ, Oakes WJ, Blount JP, Rocque BG (2016) Rate of shunt revision as a function of age in patients with shunted hydrocephalus due to myelomeningocele. Neurosurg Focus 41(November):1–6
4)

Korinek AM, Fulla-Oller L, Boch AL, Golmard JL, Hadiji B, Puybasset L (2011) Morbidity of ventricular cerebrospinal fluid shunt surgery in adults: an 8-year study. Neurosurgery 68(4):985–994
5)

Paulsen AH, Lundar T, Lindegaard KF (2015) Pediatric hydrocephalus: 40-year outcomes in 128 hydrocephalic patients treated with shunts during childhood. Assessment of surgical outcome, work participation, and health-related quality of life. J NeurosurgeryPediatrics 16(6):633–641
6)

Richards H, Seeley H, Pickard J (2009) Who should perform shunt surgery? Data from the UK Shunt Registry. Cerebrospinal Fluid Res 6:S31
7)

Spiegelman L, Asija R, Da Silva SL, Krieger MD, McComb JG (2014) What is the risk of infecting a cerebrospinal fluid–diverting shunt with percutaneous tapping? J Neurosurg Pediatr 14(4):336– 339
8)

Tamber MS, Klimo P, Mazzola CA, Flannery AM (2014) Pediatric hydrocephalus: systematic literature review and evidence-based guidelines. Part 8: management of cerebrospinal fluid shunt infection. J Neurosurg Pediatr 14(Suppl1):60–71
9)

Antes S, Stadie A, Müller S, Linsler S, Breuskin D, Oertel J (2018) Intracranial Pressure–Guided Shunt Valve Adjustments with the Miethke Sensor Reservoir. World Neurosur 642–650
10)

König RE, Stucht D, Baecke S, Rashidi A, Speck O, Sandalcioglu IE, Luchtmann M. Phase-Contrast MRI Detection of Ventricular Shunt CSF Flow: Proof of Principle. J Neuroimaging. 2020 Nov 4. doi: 10.1111/jon.12794. Epub ahead of print. PMID: 33146931.
11)

Boyle TP, Paldino MJ, Kimia AA, Fitz BM, Madsen JR, Monuteaux MC, Nigrovic LE. Comparison of rapid cranial MRI to CT for ventricular shunt malfunction. Pediatrics. 2014 Jul;134(1):e47-54. doi: 10.1542/peds.2013-3739. Epub 2014 Jun 2. PubMed PMID: 24918222.

Lumbar spinal stenosis diagnosis

Lumbar spinal stenosis diagnosis

Diagnosing lumbar spinal stenosis or herniated intervertebral disc is usually helpful only in potential surgical candidates 1).

Boden et al., performed magnetic resonance imaging on sixty-seven individuals who had never had low back pain, sciatica, or neurogenic claudication. The scans were interpreted independently by three neuro-radiologists who had no knowledge about the presence or absence of clinical symptoms in the subjects. About one-third of the subjects were found to have a substantial abnormality. Of those who were less than sixty years old, 20 per cent had a herniated nucleus pulposus and one had spinal stenosis. In the group that was sixty years old or older, the findings were abnormal on about 57 per cent of the scans: 36 per cent of the subjects had a herniated nucleus pulposus and 21 per cent had spinal stenosis. There was degeneration or bulging of a disc at at least one lumbar level in 35 per cent of the subjects between twenty and thirty-nine years old and in all but one of the sixty to eighty-year-old subjects. In view of these findings in asymptomatic subjects, they concluded that abnormalities on magnetic resonance images must be strictly correlated with age and any clinical signs and symptoms before operative treatment is contemplated 2).


Results of a survey suggested that there are no broadly accepted quantitative criteria and only partially accepted qualitative criteria for the diagnosis of lumbar spinal stenosis. The latter include disk protrusion, lack of perineural intraforaminal fat, hypertrophic facet joint degeneration, absent fluid around the cauda equine, and hypertrophy of the ligamentum flavum 3).

There is still no widely accepted diagnostic or classification criteria for the diagnosis of Lumbar spinal canal stenosis LSS and as a consequence studies use widely differing eligibility criteria that limit the generalizability of reported findings 4).

There are no universally accepted radiographic definitions for the diagnosis of central, lateral recess and foraminal stenosis.


Most studies of Lumbar central canal spinal stenosis diagnosis (LCCSS) rely on criteria published by Verbiest et al. 5). He defined relative spinal stenosis as a diameter between 10 and 12 mm whereas absolute stenosis was a diameter less than 10 mm. This method has been criticized for ignoring the trefoil shape of the LSS and the intrusion of ligamentum flavum and disc material in degenerative stenosis 6).

Magnetic resonance imaging

Magnetic resonance imaging (MRI) is most commonly used for the clinical assessment of degenerative LCCSS. LCCSS is a quantitative diagnosis that is made when the measurement of an individual is outside the range of normal. Thus, the criteria for LCCSS should be compared from an analysis of a normative distribution of measurements 7) 8)

In a meta-analysis, CT and MRI were found to have similar accuracy for the assessment of central stenosis 9).

By using a combination of magnetic resonance imaging (MRI) and computed tomography (CT) of the lumbar spine, it is possible to distinguish between spinal stenosis caused by bone compression and specific soft tissue epidural intraspinal lesions that cause localized spinal canal stenosis and neural compression. Examples include facet cysts and yellow ligament hypertrophy 10).

Because imaging findings of lumbar spinal stenosis (LSS) may not be associated with symptoms, clinical classification criteria based on patient symptoms and physical examination findings are needed 11).

Magnetic resonance imaging (MRI) has replaced myelography, now considered an old-fashioned technique. In selected cases with multilevel lumbar spinal stenosis, functional myelography revealed the highest precision in reaching a correct diagnosis. It resulted in a change in the surgical approach in every fifth patient in comparison with the MRI and proved most helpful, especially in elderly patients 12).

Cross sectional area

Narrowing of the lumbar dural sac cross sectional area (DSCSA) and spinal canal cross-sectional area (SCCSA) have been considered major causes of lumbar central canal spinal stenosis (LCCSS). DSCSA and SCCSA were previously correlated with subjective walking distance before claudication occurs, aging, and disc degeneration. DSCSA and SCCSA have been ideal morphological parameters for evaluating LCCSS.

To evaluate lumbar central canal spinal stenosis (LCCSS) patients, pain specialists should more carefully investigate the dural sac cross-sectional area (DSCSA) than spinal canal cross-sectional area (SCCSA) 13).

Schonstrom et al. showed that neurogenic claudication due to LSS was better defined by the cross-sectional area (CSA) of the dural sac, but that the CSA of the lumbar vertebral canal was unrelated to that of the dural sac 14). From in vitro 15) and in situ 16) studies, the authors postulated that constrictions above the critical size 70 to 80 mm2 would be unlikely to cause symptoms and signs of cauda encroachment. Subsequently, conflicting results have been published concerning the relationship between symptom severity and dural CSA. Even after axial loading, no statistically significant correlations were found in some studies 17). However, in another study, the use of the minimal CSA of the dural sac in central stenosis was found to be correlated with neurogenic claudication assessed measuring the maximum tolerated walking distance 18).

Electrodiagnostic studies

Patients with symptoms, physical examination and imaging findings consistent with LSS do not require additional testing. Although there is little evidence in the literature, electrodiagnostic evaluation is used in some patients with symptoms and findings that are equivocal or conflicting with imaging results and in whom procedures are being considered. Electrodiagnostic criteria for stenosis have been proposed:(47) mini-paraspinal mapping with a one side score > 4 (sensitivity 30%, specificity 100%), fibrillation potential in limb muscles (sensibility 33%, specificity 88%), absence of tibial H-wave (sensitivity 36%, specificity 92%). Better sensitivity was found for a composite limb and paraspinal fibrillation score (sensitivity 48%, specificity 88%) 19).

Diagnostic Screening

Jensen et al. developed a self-administered diagnostic screening questionnaire for lumbar spinal stenosis (LSS) consisting of items with high content validity and to investigate the diagnostic value of the questionnaire and the items.

The screening questionnaire was developed based on items from the existing literature describing key symptoms of LSS. The screening questionnaire (index test) was to be tested in a cohort of patients with persistent lumbar and/or leg pain recruited from a Danish publicly funded outpatient secondary care spine clinic with clinicians performing the reference test. However, to avoid unnecessary collection of data if the screening questionnaire proved to be of limited value, a case-control design was incorporated into the cohort design including an interim analysis. Additional cases for the case-control study were recruited at two Danish publicly funded spine surgery departments. Prevalence, sensitivity, specificity and diagnostic odds ratio (OR) were calculated for each individual item, and AUC (area under the curve) was calculated to examine the performance of the full questionnaire.

A 13-item Danish questionnaire was developed and tested in 153 cases and 230 controls. The interim analysis was not in favour of continuing the cohort study, and therefore, only results from the case-control study are reported. There was a positive association for all items except the presence of back pain. However, the association was only moderate with ORs up to 3.3. When testing the performance of the whole questionnaire, an AUC of 0.72 was reached with a specificity of 20% for a fixed sensitivity of 95%.

The items were associated with LSS and therefore have some potential to identify LSS patients. However, the association was not strong enough to provide sufficient accuracy for a diagnostic tool. Additional dimensions of symptoms of LSS need identification to obtain a reliable questionnaire for screening purposes 20).

References

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Boden SD, Davis DO, Dina TS, Patronas NJ, Wiesel SW. Abnormal magnetic-resonance scans of the lumbar spine in asymptomatic subjects. A prospective investigation. J Bone Joint Surg Am. 1990 Mar;72(3):403-8. PubMed PMID: 2312537.
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Mamisch N, Brumann M, Hodler J, Held U, Brunner F, Steurer J; Lumbar Spinal Stenosis Outcome Study Working Group Zurich. Radiologic criteria for the diagnosis of spinal stenosis: results of a Delphi survey. Radiology. 2012 Jul;264(1):174-9. doi: 10.1148/radiol.12111930. Epub 2012 May 1. PubMed PMID: 22550311.
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Genevay S, Atlas SJ, Katz JN. Variation in eligibility criteria from studies of radiculopathy due to a herniated disc and of neurogenic claudication due to lumbar spinal stenosis: a structured literature review. Spine (Phila Pa 1976). 2010 Apr 1;35(7):803-11. doi: 10.1097/BRS.0b013e3181bc9454. Review. PubMed PMID: 20228710; PubMed Central PMCID: PMC2854829.
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Verbiest H. Pathomorphologic aspects of developmental lumbar stenosis. Orthop Clin North Am. 1975 Jan;6(1):177-96. PubMed PMID: 1113966.
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Eisenstein S. The trefoil configuration of the lumbar vertebral canal. A study of South African skeletal material. J Bone Joint Surg Br. 1980 Feb;62-B(1):73-7. PubMed PMID: 7351439.
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Chatha DS, Schweitzer ME. MRI criteria of developmental lumbar spinal stenosis revisited. Bull NYU Hosp Jt Dis 2011;69:303–7.
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Premchandran D, Saralaya VV, Mahale A. Predicting lumbar central canal stenosis—a magnetic resonance imaging study. J Clin Diagn Res 2014;8:RC01–4.
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Kent DL, Haynor DR, Larson EB, Deyo RA. Diagnosis of lumbar spinal stenosis in adults: a metaanalysis of the accuracy of CT, MR, and myelography. AJR Am J Roentgenol. 1992 May;158(5):1135-44. PubMed PMID: 1533084.
10)

Jacobson RE, Granville M, Hatgis DO J. Targeted Intraspinal Radiofrequency Ablation for Lumbar Spinal Stenosis. Cureus. 2017 Mar 10;9(3):e1090. doi: 10.7759/cureus.1090. PubMed PMID: 28413736; PubMed Central PMCID: PMC5388364.
11)

Genevay S, Courvoisier DS, Konstantinou K, Kovacs FM, Marty M, Rainville J, Norberg M, Kaux JF, Cha TD, Katz JN, Atlas SJ. Clinical classification criteria for neurogenic claudication caused by lumbar spinal stenosis. The N-CLASS criteria. Spine J. 2017 Oct 12. pii: S1529-9430(17)31052-5. doi: 10.1016/j.spinee.2017.10.003. [Epub ahead of print] PubMed PMID: 29031994.
12)

Morgalla M, Frantz S, Dezena RA, Pereira CU, Tatagiba M. Diagnosis of Lumbar Spinal Stenosis with Functional Myelography. J Neurol Surg A Cent Eur Neurosurg. 2018 Jan 18. doi: 10.1055/s-0037-1618563. [Epub ahead of print] PubMed PMID: 29346832.
13)

Lim YS, Mun JU, Seo MS, Sang BH, Bang YS, Kang KN, Koh JW, Kim YU. Dural sac area is a more sensitive parameter for evaluating lumbar spinal stenosis than spinal canal area: A retrospective study. Medicine (Baltimore). 2017 Dec;96(49):e9087. doi: 10.1097/MD.0000000000009087. PubMed PMID: 29245329; PubMed Central PMCID: PMC5728944.
14)

Schonstrom NS, Bolender NF, Spengler DM. The pathomorphology of spinal stenosis as seen on CT scans of the lumbar spine. Spine (Phila Pa 1976). 1985 Nov;10(9):806-11. PubMed PMID: 4089655.
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Schönström N, Bolender NF, Spengler DM, Hansson TH. Pressure changes within the cauda equina following constriction of the dural sac. An in vitro experimental study. Spine (Phila Pa 1976). 1984 Sep;9(6):604-7. PubMed PMID: 6495030.
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Schönström N, Hansson T. Pressure changes following constriction of the cauda equina. An experimental study in situ. Spine (Phila Pa 1976). 1988 Apr;13(4):385-8. PubMed PMID: 3406845.
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Lohman CM, Tallroth K, Kettunen JA, Lindgren KA. Comparison of radiologic signs and clinical symptoms of spinal stenosis. Spine (Phila Pa 1976). 2006 Jul 15;31(16):1834-40. PubMed PMID: 16845360.
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Ogikubo O, Forsberg L, Hansson T. The relationship between the cross-sectional area of the cauda equina and the preoperative symptoms in central lumbar spinal stenosis. Spine (Phila Pa 1976). 2007 Jun 1;32(13):1423-8; discussion 1429. PubMed PMID: 17545910.
19)

Genevay S, Atlas SJ. Lumbar spinal stenosis. Best Pract Res Clin Rheumatol. 2010 Apr;24(2):253-65. doi: 10.1016/j.berh.2009.11.001. Review. PubMed PMID: 20227646; PubMed Central PMCID: PMC2841052.
20)

Jensen RK, Lauridsen HH, Andresen ADK, Mieritz RM, Schiøttz-Christensen B, Vach W. Diagnostic Screening for Lumbar Spinal Stenosis. Clin Epidemiol. 2020;12:891-905. Published 2020 Aug 19. doi:10.2147/CLEP.S263646
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