Radiation necrosis diagnosis

Radiation necrosis diagnosis

Unfortunately, symptomatic radiation necrosis is notoriously hard to diagnose and manage. The features of RN overlap considerably with tumor recurrence and misdiagnosing RN as tumor recurrence may lead to deleterious treatment which may cause detrimental effects on the patient 1)

Differentiating radiation necrosis from tumor progression on standard magnetic resonance imaging (MRI) is often difficult and advanced imaging techniques may be needed to make an accurate diagnosis.

Mayo et al. performed a literature review addressing the radiographic modalities used in the diagnosis of radiation necrosis.

Differentiating radiation necrosis from tumor progression remains a diagnostic challenge and advanced imaging modalities are often required to make a definitive diagnosis. If diagnostic uncertainty remains following conventional imaging, a multi-modality diagnostic approach with perfusion MRImagnetic resonance spectroscopy (MRS), positron emission tomography (PET), single photon emission spectroscopy (SPECT), and radiomics may be used to improve diagnosis.

Several imaging modalities exist to aid in the diagnosis of radiation necrosis. Future studies developing advanced imaging techniques are needed 2).

Mangesius et al. provide the experience of a tertiary tumor center with this important issue in neurooncology and provide an institutional pathway for dealing with this problem 3).


Vellayappan B, Tan CL, Yong C, Khor LK, Koh WY, Yeo TT, Detsky J, Lo S, Sahgal A. Diagnosis and Management of Radiation Necrosis in Patients With Brain Metastases. Front Oncol. 2018 Sep 28;8:395. doi: 10.3389/fonc.2018.00395. PMID: 30324090; PMCID: PMC6172328.

Mayo ZS, Halima A, Broughman JR, Smile TD, Tom MC, Murphy ES, Suh JH, Lo SS, Barnett GH, Wu G, Johnson S, Chao ST. Radiation necrosis or tumor progression? A review of the radiographic modalities used in the diagnosis of cerebral radiation necrosis. J Neurooncol. 2023 Jan 12. doi: 10.1007/s11060-022-04225-y. Epub ahead of print. PMID: 36633800.

Mangesius J, Mangesius S, Demetz M, Uprimny C, Di Santo G, Galijasevic M, Minasch D, Gizewski ER, Ganswindt U, Virgolini I, Thomé C, Freyschlag CF, Kerschbaumer J. A Multi-Disciplinary Approach to Diagnosis and Treatment of Radionecrosis in Malignant Gliomas and Cerebral Metastases. Cancers (Basel). 2022 Dec 19;14(24):6264. doi: 10.3390/cancers14246264. PMID: 36551750; PMCID: PMC9777318.

Delirium Diagnosis

Delirium Diagnosis

Unlike dementiadelirium has an acute onset, motor signs (tremormyoclonusasterixis), slurred speech, altered consciousness (hyperalert/agitated or lethargic, or fluctuations), hallucinations may be florid.

Consultation-liaison psychiatry could improve the recognition rate of postoperative delirium in elderly patients, and shorten hospitalization time. The training of mental health knowledge for non-psychiatrists could improve the ability of early identify and treatment of delirium 1).

It is a corollary of the criteria that a diagnosis of delirium usually cannot be made without a previous assessment, or knowledge, of the affected person’s baseline level of cognitive function. In other words, a mentally disabled person who is suffering from this will be operating at their own baseline level of mental ability and would be expected to appear delirious without a baseline mental functional status against which to compare.

Early detection is crucial because the longer a patient experiences delirium the worse it becomes and the harder it is to treat. Currently, identification is through intermittent clinical assessment using standardized tools, like the Confusion Assessment Method for the Intensive Care Unit. Such tools work well in clinical research but do not translate well into clinical practice because they are subjective, intermittent, and have low sensitivity. As such, healthcare providers using these tools fail to recognize delirium symptoms as much as 80% of the time.

EEG shows pronounced diffuse slowing.

Delirium-related biochemical derangement leads to electrical changes in electroencephalographic (EEG) patterns followed by behavioral signs and symptoms. However, continuous EEG monitoring is not feasible due to the cost and the need for skilled interpretation. Studies using limited-lead EEG show large differences between patients with and without delirium while discriminating delirium from other causes. The Ceribell is a limited-lead device that analyzes EEG. If it is capable of detecting delirium, it would provide an objective physiological monitor to identify delirium before symptom onset. This pilot study was designed to explore relationships between Ceribell and delirium status. Completion of this study will provide a foundation for further research regarding delirium status using the Ceribell data 2).

Hut SC, Dijkstra-Kersten SM, Numan T, Henriquez NR, Teunissen NW, van den Boogaard M, Leijten FS, Slooter AJ. EEG and clinical assessment in delirium and acute encephalopathy. Psychiatry Clin Neurosci. 2021 May 16. doi: 10.1111/pcn.13225. Epub ahead of print. PMID: 33993579.

Early neutrophil-to-lymphocyte ratio (NLR) elevation may also predict delayed-onset delirium, potentially implicating systemic inflammation as a contributory delirium mechanism 3).

Older age, headache, coagulopathy, decreased level of consciousness, seizures, and history of falls. Conversely, infection was associated with a reduced yield.

In higher-risk patients and settings, there should be a push toward earlier neuroimaging as indicated by clinical examinations and individual risk factors. In the meta-analysis, the yield of head CT was higher in ICU patients and those who had focal neurological deficits in addition to altered mental status and was especially high in neuro ICU settings 4)

Neuroimaging should not replace a clinical exam, even in ICU settings; ICU patients should have their sedation reduced to properly test for delirium 5).

Delirium has a complex and fluctuating course with underlying causes that are often multifactorial; identifying a CNS lesion does not necessarily exclude other causes, and vice-versa 6).

The risks of neuroimaging need to be considered in the decision-making process 7).

The use of CT head to diagnose the etiology of delirium and AMS varied widely and yield has declined. Guidelines and clinical decision support tools could increase the appropriate use of CT head in the diagnostic etiology of delirium/AMS 8).


Xie Q, Liu XB, Jing GW, Jiang X, Liu H, Zhong BL, Li Y. The Effect of Consultation-Liaison Psychiatry on Postoperative Delirium in Elderly Hip Fracture Patients in the General Hospital. Orthop Surg. 2023 Jan 3. doi: 10.1111/os.13501. Epub ahead of print. PMID: 36597675.

Mulkey MA, Hardin SR, Munro CL, Everhart DE, Kim S, Schoemann AM, Olson DM. Methods of identifying delirium: A research protocol. Res Nurs Health. 2019 May 30. doi: 10.1002/nur.21953. [Epub ahead of print] PubMed PMID: 31148216.

Reznik ME, Kalagara R, Moody S, Drake J, Margolis SA, Cizginer S, Mahta A, Rao SS, Stretz C, Wendell LC, Thompson BB, Asaad WF, Furie KL, Jones RN, Daiello LA. Common biomarkers of physiologic stress and associations with delirium in patients with intracerebral hemorrhage. J Crit Care. 2021 Mar 23;64:62-67. doi: 10.1016/j.jcrc.2021.03.009. Epub ahead of print. PMID: 33794468.

MadsenTE, KhouryJ, Cadena R, et al. Potentially missed diagnosis of ischemic stroke in the Emergency Department in the Greater Cincinnati/Northern Kentucky stroke study.Acad Emerg Med. 2016;23(10):1128-1135. doi:10.1111/acem.13029

Venkat A, Cappelen-Smith C, Askar S, et al. Factors associated with stroke misdiagnosis in the emergency department: a retrospective case-control study. Neuroepidemiology. 2018;51(3–4):123-127. doi:10.1159/000491635

The 2019 American Geriatrics Society Beers Criteria®UpdateExpert Panel. American Geriatrics Society 2019 updated AGSbeers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2019;67(4):674-694. doi:10.1111/jgs.15767

Reznik ME, Rudolph JL. “Yield” to the time-brain dilemma: The case for neuroimaging in delirium. J Am Geriatr Soc. 2023 Jan 6. doi: 10.1111/jgs.18206. Epub ahead of print. PMID: 36606371.

Akhtar H, Chaudhry SH, Bortolussi-Courval É, Hanula R, Akhtar A, Nauche B, McDonald EG. Diagnostic yield of CT head in delirium and altered mental status-A systematic review and meta-analysis. J Am Geriatr Soc. 2022 Nov 26. doi: 10.1111/jgs.18134. Epub ahead of print. PMID: 36434820.

Moyamoya Disease Diagnosis

Moyamoya Disease Diagnosis

Diagnosis of Moyamoya disease requires bilateral symmetrical stenosis or occlusion of the terminal portion of the internal carotid arterys (ICA)s as well as the presence of dilated collateral vessels at the base of the brain 1). (If unilateral, the diagnosis is considered questionable, 2) and these cases may progress to bilateral involvement).

Other characteristic findings include:

  1. stenosis/occlusion starting at the termination of ICA and at origins of ACA and MCA

  2. abnormal vascular network in the region of BG (intraparenchymal anastomosis).

  3. transdural anastomosis(rete mirabile), AKA “vault moyamoya.”Contributing arteries: anterior falcial, middle meningeal, ethmoidal, occipital, tentorial, STA

  4. moyamoya collaterals may also form from the internal maxillary artery via ethmoid sinus to the forebrain in the frontobasal region.

Work-up in suspected cases typically begins with a non-enhanced head CT. Up to 40% of ischemic cases have normal CT. Low-density areas (LDAs) may be seen, usually confined to cortical and subcortical areas (unlike atherosclerotic disease or acute infantile hemiplegia which tend to have LDAs in basal ganglia as well). LDAs tend to be multiple and bilateral, especially in the PCA distribution (poor collaterals), and are more common in children.

Magnetic resonance imaging for Moyamoya Disease Diagnosis.

In addition to helping to establish the diagnosis, angiography also identifies suitable vessels for revascularization procedures and unearths associated aneurysms. The angiography-related complication rate is higher than with atherosclerotic occlusive disease. Avoid dehydration prior to and hypotension during the procedure. Six angiographic stages of MMD are described by Suzuki and Takaku 3) that tend to progress up until adolescence and stabilize by age 20.

1 stenosis of suprasellar ICA, usually bilateral

2 development of moyamoya vessels at the base of the brain; ACA MCA & PCA dilated

3 increasing ICA stenosis & prominence of moya-moya vessels (most cases diagnosed at this stage); maximal basal moyamoya

4 entire circle of Willis and PCAs occluded, extracranial collaterals start to appear, moyamoya vessels begin to diminish

5 further progression of stage 4

6 complete absence of moyamoya vessels and major cerebral arteries.

Non-specific in the adult. Juvenile cases: high-voltage slow waves may be seen at rest, predominantly in the occipital and frontal lobes. Hyperventilation produces a normal buildup of monophasic slow waves (delta-bursts) that return to normal 20–60 seconds after hyperventilation. In >50%of cases, after or sometimes continuous with buildup is a second phase of slow waves (this characteristic finding is called “rebuild up”) which are more irregular and slower than the earlier waves, and usually, normalize in ≤10 minutes 4).

CBF is decreased in children with MMD, but relatively normal in adults. There is a shift of CBF from the frontal to the occipital lobes 5) probably reflecting the increasing dependency of CBF on the posterior circulation. Children with MMD have impaired autoregulation of CBF to blood pressure and CO2 (with more impairment of vasodilatation in response to hypercapnia or hypotension than vasoconstriction in response to hypocapnia or hypertension) 6). Xenon (Xe-133) CT can identify areas of low perfusion. Repeating the study after an acetazolamide challenge (which causes vasodilatation) evaluates the reserve capacity of CBF and can identify areas of “steal” which are at high risk of future infarction.

Ultrasound parameters are independently correlated with ipsilateral cerebral stroke in patients with Moyamoya disease (MMD). Ultrasound provides a new way to identify stroke in MMD patients. Future prospective cohort studies are needed to verify the clinical value of ultrasound in identifying patients with MMD at high risk of stroke 7).


Smith ER, Scott RM. Surgical management of moyamoya syndrome. Skull Base. 2005; 15:15–26

Nishimoto A. Moyamoya Disease. Neurol Med Chir. 1979; 19:221–228

Suzuki J, Takaku A. Cerebrovascular “moyamoya” disease. Disease showing abnormal net-like vessels in base of brain. Arch Neurol. 1969 Mar;20(3):288-99. PubMed PMID: 5775283.

Kodama N, Aoki Y, Hiraga H, et al. Electroencephalographic Findings in Children with Moyamoya Disease. Arch Neurol. 1979; 36:16–19

Ogawa A, Yoshimoto T, Suzuki J, Sakurai J. Cerebral Blood Flow in Moyamoya Disease. Part 1. Correlation with Age and Regional Distribution. Acta Neurochir. 1990; 105:30–34

Ogawa A, Nakamura N, Yoshimoto T, Suzuki J. Cerebral Blood Flow in Moyamoya Disease. Part 2. Autoregulation and CO2 Response. Acta Neurochir. 1990; 105:107–111

Zheng S, Wang F, Cheng L, Li R, Zhang D, He W, Zhang W. Ultrasound parameters associated with stroke in patients with moyamoya disease: a logistic regression analysis. Chin Neurosurg J. 2022 Oct 11;8(1):32. doi: 10.1186/s41016-022-00300-5. PMID: 36221122.

Spontaneous intracranial hypotension diagnosis

Spontaneous intracranial hypotension diagnosis

Spontaneous intracranial hypotension diagnosis have evolved due to improved understanding of spontaneous intracranial hypotension pathophysiology and implementation of advanced myelography techniques. Farnsworth et al. synthesized recent updates and contextualize them in an algorithm for diagnosis and treatment of SIH, highlighting basic principles and points of practice variability or continued debate. This discussion includes finer points of SIH diagnosis, spontaneous cerebrospinal fluid fistula classification systems, less common types and variants of CSF leaks, Brain MRI Bern scoring for intracranial hypotension diagnosis, potential spontaneous intracranial hypotension complications, key technical considerations, and positioning strategies for different types of Dynamic CT myelography. 1).

The diagnosis of spontaneous intracranial hypotension or cerebrospinal fluid (CSF) hypovolemia syndrome requires a high index of suspicion and meticulous history taking, demonstration of low CSF pressure and/or neuroimaging features.

Diagnostic criteria of headache attributed to low cerebrospinal fluid pressure (per IHS Classification (ICHD-III)):

  1. any headache that developed in temporal relation to low CSF pressure or cerebrospinal fluid fistula or has led to its discovery

  2. low CSF pressure (< 6 cm of water) and/or evidence of CSF leakage on imaging

  3. not better accounted for by another ICHD-III

Radiographic criteria are not required for diagnosis since no characteristic findings are seen in 20– 25% of patients.

The median delay from presentation to the diagnosis of SIH is 4 months.

This delay may be detrimental to patient outcomes. Therefore, brain MRI without and with contrast is recommended in patients with new-onset orthostatic headaches.

The diagnosis requires a high index of suspicion and meticulous history taking, demonstration of low CSF pressure and/or neuroimaging features.

Intracranial hypotension is associated with simple clinical presentation, orthostatic headache, and characteristic MRI findings. Misdiagnosed, it leads to unnecessary procedures 2).

The primary diagnostic factor relies on confirmation of cerebrospinal fluid leakage based on reduced spinal fluid pressure. Determining the specific leakage site is the most important issue for effective treatment but remains a difficult task. Although CT myelogram, radionuclide cisternography, and MRI are commonly performed in the diagnosis of CSF hypovolemia, these techniques can rarely identify the precise leakage site.

Therefore, an epidural blood patch is performed in the lumbar spine in many cases.

The identification of the site of CSF leak in the spinal canal can be very challenging. In some cases, the site cannot be identified.

Magnetic resonance imaging for intracranial hypotension diagnosis

Continuous intracranial pressure monitoring is definitive for documenting abnormally negative intracranial pressures.

A 31-year-old male, presented with subacute onset moderate occipital and sub-occipital headaches precipitated by upright posture and relieved on recumbency and neck pain for 2 years. There was no trauma, cranial/spinal surgery. Clinical examination was normal and CSF opening pressure and laboratory study were normal. Magnetic resonance imaging (MRI) brain showed thin subdural hygroma. Another patient, 41-year-old male presented with 1 month of subacute onset severe bifrontal throbbing orthostatic headaches (OHs). CSF opening pressure was normal. Contrast MRI brain showed the presence of bilateral subdural hygromas, diffuse meningeal enhancement, venous distension, sagging of the brain, and tonsillar herniation. We report two cases of “spontaneous OHs” with normal CSF pressures who were successfully treated with epidural blood patching after poor response to conservative management 3).

Repeated measurements of the optic nerve sheath diameter (ONSD) using B-mode sonography were performed before treatment initiation, during medical treatment, and during a course of repeated placement of epidural blood patches.

On admission, transorbital sonography revealed a decreased ONSD of 4.1 mm on the right and 4.3 mm on the left side. After 8 months of treatment with caffeine and computed tomography-guided epidural blood patches a gradual distension of the ONSD into the normal range was bilaterally observed (right: 5.2 mm; left: 5.3 mm).

The ultrasound-based evaluation of the optic nerve sheath may be helpful in detecting CSF hypovolemia and for determination of treatment effects. This report should be seen as a basis for future investigations on the sonographic assessment of the optic nerve sheath in diagnosis and treatment of intracranial hypotension 4).

Symptomatic patients with SIH showed a significant decrease of ONSD, as assessed by ultrasound, when changing from the supine to the upright position. Ultrasound assessment of the ONSD in two positions may be a novel, non-invasive tool for the diagnosis and follow-up of SIH and for elucidating the pathophysiology of SIH 5).


Farnsworth PJ, Madhavan AA, Verdoorn JT, Shlapak DP, Johnson DR, Cutsforth-Gregory JK, Brinjikji W, Lehman VT. Spontaneous intracranial hypotension: updates from diagnosis to treatment. Neuroradiology. 2022 Nov 7. doi: 10.1007/s00234-022-03079-5. Epub ahead of print. PMID: 36336758.

Louhab N, Adali N, Laghmari M, Hymer WE, Ben Ali SA, Kissani N. Misdiagnosed spontaneous intracranial hypotension complicated by subdural hematoma following lumbar puncture. Int J Gen Med. 2014 Jan 15;7:71-3. doi: 10.2147/IJGM.S48656. eCollection 2014. PubMed PMID: 24470768; PubMed Central PMCID: PMC3896286.

Hassan KM, Prakash S, Majumdar SS, Banerji A. Two cases of medically-refractory spontaneous orthostatic headaches with normal cerebrospinal fluid pressures responding to epidural blood patching: Intracranial hypotension versus hypovolemia and the need for clinical awareness. Ann Indian Acad Neurol. 2013 Oct;16(4):699-702. doi: 10.4103/0972-2327.120461. PubMed PMID: 24339614; PubMed Central PMCID: PMC3841635.

Bäuerle J, Gizewski ER, Stockhausen Kv, Rosengarten B, Berghoff M, Grams AE, Kaps M, Nedelmann M. Sonographic assessment of the optic nerve sheath and transorbital monitoring of treatment effects in a patient with spontaneous intracranial hypotension: case report. J Neuroimaging. 2013 Apr;23(2):237-9. doi: 10.1111/j.1552-6569.2011.00640.x. Epub 2011 Sep 1. PubMed PMID: 21883624.

Fichtner J, Ulrich CT, Fung C, Knüppel C, Veitweber M, Jilch A, Schucht P, Ertl M, Schömig B, Gralla J, Z’Graggen WJ, Bernasconi C, Mattle HP, Schlachetzki F, Raabe A, Beck J. Management of spontaneous intracranial hypotension – Transorbital ultrasound as discriminator. J Neurol Neurosurg Psychiatry. 2016 Jun;87(6):650-5. doi: 10.1136/jnnp-2015-310853. Epub 2015 Aug 18. PubMed PMID: 26285586; PubMed Central PMCID: PMC4893146.

Epilepsy diagnosis

Epilepsy diagnosis

The accurate diagnosis of seizures is essential as some patients will be misdiagnosed with epilepsy, whereas others will receive an incorrect diagnosis. Indeed, errors in diagnosis are common, and many patients fail to receive the correct treatment, which often has severe consequences

Imaging is pivotal in the evaluation and management of patients with seizure disorders.

Positron emission tomography (PET) is the most commonly performed interictal functional neuroimaging technique that may reveal a focal hypometabolic region concordant with seizure onset. Single photon emission computed tomography (SPECT) studies may assist the performance of ictal neuroimaging in patients with pharmacoresistant focal epilepsy being considered for neurosurgical treatment 1).

Elegant structural neuroimaging with magnetic resonance imaging (MRI) may assist in determining the etiology of focal epilepsy and demonstrating the anatomical changes associated with seizure activity. The high diagnostic yield of MRI to identify the common pathological findings in individuals with focal seizures including mesial temporal sclerosis, vascular anomalies, Low-grade glioma and malformations of cortical development has been demonstrated.

Positron emission tomography (PET) imaging in epilepsy is an in vivo technique that allows the localization of a possible seizure onset zone (SOZ) during the interictal period. Stereo-electro-encephalography (SEEG) is the gold standard to define the SOZ. The objective of aresearch was to evaluate the accuracy of PET imaging in localizing the site of SOZ compared with SEEG.

Seven patients with refractory temporal lobe epilepsy (Ep) and 2 healthy controls (HC) underwent 2 PET scans, one with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) and another with 2′-[18F]fluoroflumazenil (FFMZ), acquired 1 day apart. FDG was acquired for 10 min (static scan) 1 h after administration. An FFMZ scan was acquired for 60 min from radiopharmaceutical administration in a dynamic mode. Each brain PET image was segmented using a standard template implemented in PMOD 3.8. The pons was used as the reference region for modeling of the nondisplaceable binding potential (BPND)for FFMZ, and to obtain uptake ratios for FDG. SEEG studies of patients were performed as a part of their surgical evaluation to define the SOZ.

Well-defined differences between HC and Ep were found with both radiopharmaceuticals, showing the utility to identify abnormal brain regions using quantitative PET imaging. Lateralization of the SOZ findings by PET (lower uptake/binding in a specific brain hemisphere) matched in 86% for FFMZ and 71% for FDG with SEEG data.

Quantitative PET imaging is an excellent complementary tool that matches reasonably well with SEEG to define SOZ in presurgical evaluation 2).

Cerebrospinal fluid analysis for epilepsy

Automatic seizure detection.

Results of a cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcome3).


Cendes F, Theodore WH, Brinkmann BH, Sulc V, Cascino GD. Neuroimaging of epilepsy. Handb Clin Neurol. 2016;136:985-1014. doi: 10.1016/B978-0-444-53486-6.00051-X. PubMed PMID: 27430454.

Avendaño-Estrada A, Velasco F, Velasco AL, Cuellar-Herrera M, Saucedo-Alvarado PE, Marquez-Franco R, Rivera-Bravo B, Ávila-Rodríguez MA. Quantitative Analysis of [18F]FFMZ and [18F]FDG PET Studies in the Localization of Seizure Onset Zone in Drug-Resistant Temporal Lobe Epilepsy. Stereotact Funct Neurosurg. 2019 Nov 13:1-9. doi: 10.1159/000503692. [Epub ahead of print] PubMed PMID: 31722358.

McKnight D, Morales A, Hatchell KE, Bristow SL, Bonkowsky JL, Perry MS, Berg AT, Borlot F, Esplin ED, Moretz C, Angione K, Ríos-Pohl L, Nussbaum RL, Aradhya S; ELEVIATE Consortium, Haldeman-Englert CR, Levy RJ, Parachuri VG, Lay-Son G, de Montellano DJD, Ramirez-Garcia MA, Benítez Alonso EO, Ziobro J, Chirita-Emandi A, Felix TM, Kulasa-Luke D, Megarbane A, Karkare S, Chagnon SL, Humberson JB, Assaf MJ, Silva S, Zarroli K, Boyarchuk O, Nelson GR, Palmquist R, Hammond KC, Hwang ST, Boutlier SB, Nolan M, Batley KY, Chavda D, Reyes-Silva CA, Miroshnikov O, Zuccarelli B, Amlie-Wolf L, Wheless JW, Seinfeld S, Kanhangad M, Freeman JL, Monroy-Santoyo S, Rodriguez-Vazquez N, Ryan MM, Machie M, Guerra P, Hassan MJ, Candee MS, Bupp CP, Park KL, Muller E 2nd, Lupo P, Pedersen RC, Arain AM, Murphy A, Schatz K, Mu W, Kalika PM, Plaza L, Kellogg MA, Lora EG, Carson RP, Svystilnyk V, Venegas V, Luke RR, Jiang H, Stetsenko T, Dueñas-Roque MM, Trasmonte J, Burke RJ, Hurst ACE, Smith DM, Massingham LJ, Pisani L, Costin CE, Ostrander B, Filloux FM, Ananth AL, Mohamed IS, Nechai A, Dao JM, Fahey MC, Aliu E, Falchek S, Press CA, Treat L, Eschbach K, Starks A, Kammeyer R, Bear JJ, Jacobson M, Chernuha V, Meibos B, Wong K, Sweney MT, Espinoza AC, Van Orman CB, Weinstock A, Kumar A, Soler-Alfonso C, Nolan DA, Raza M, Rojas Carrion MD, Chari G, Marsh ED, Shiloh-Malawsky Y, Parikh S, Gonzalez-Giraldo E, Fulton S, Sogawa Y, Burns K, Malets M, Montiel Blanco JD, Habela CW, Wilson CA, Guzmán GG, Pavliuk M. Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice. JAMA Neurol. 2022 Oct 31. doi: 10.1001/jamaneurol.2022.3651. Epub ahead of print. PMID: 36315135.

Glioblastoma Pseudoprogression Differential diagnosis

Glioblastoma Pseudoprogression Differential diagnosis

The suspicious lesion may represent post-treatment radiation effects (PTRE) such as pseudoprogression, radiation necrosis or Glioblastoma recurrence 1).

A study aimed to investigate whether perioperative markers could distinguish and predict PsP from TeP in de novo isocitrate dehydrogenase (IDH) wild-type GBM patients. Methods: New or progressive gadolinium-enhancing lesions that emerged within 12 weeks after CCRT were defined as early progression. Lesions that remained stable or spontaneously regressed were classified as PsP, otherwise persistently enlarged as TeP. Clinical, radiological, and molecular information were collected for further analysis. Patients in the early progression subgroup were divided into derivation and validation sets (7:3, according to operation date). Results: Among 234 consecutive cases enrolled in this retrospective study, the incidences of PsP, TeP, and neither patterns of progression (nP) were 26.1% (61/234), 37.6% (88/234), and 36.3% (85/234), respectively. In the early progression subgroup, univariate analysis demonstrated female (OR: 2.161, P = 0.026), gross total removal (GTR) of the tumor (OR: 6.571, P < 001), located in the frontal lobe (OR: 2.561, P = 0.008), non-subventricular zone (SVZ) infringement (OR: 10.937, P < 0.001), and methylated O-6-methylguanine-DNA methyltransferase (MGMT) promoter (mMGMTp) (OR: 9.737, P < 0.001) were correlated with PsP, while GTR, non-SVZ infringement, and mMGMTp were further validated in multivariate analysis. Integrating quantitative MGMTp methylation levels from pyrosequencing, GTR, and non-SVZ infringement showed the best discriminative ability in the random forest model for derivation and validation set (AUC: 0.937, 0.911, respectively). Furthermore, a nomogram could effectively evaluate the importance of those markers in developing PsP (C-index: 0.916) and had a well-fitted calibration curve. Conclusion: Integrating those clinical, radiological, and molecular features provided a novel and robust method to distinguish PsP from TeP, which was crucial for subsequent clinical decision making, clinical trial enrollment, and prognostic assessment. By in-depth interrogation of perioperative markers, clinicians could distinguish PsP from TeP independent from advanced imaging 2).

Conventional structural MRI is insufficient for distinguishing pseudoprogression from true progressive disease, and advanced imaging is needed to obtain higher levels of diagnostic certainty. Perfusion MRI is the most widely used imaging technique to diagnose pseudoprogression and has high reported diagnostic accuracy. Diagnostic performance of MR spectroscopy (MRS) appears to be somewhat higher, but MRS is less suitable for the routine and universal application in brain tumor follow-up. The combination of MRS and diffusion-weighted imaging and/or perfusion MRI seems to be particularly powerful, with diagnostic accuracy reaching up to or even greater than 90%. While diagnostic performance can be high with appropriate implementation and interpretation, even a combination of techniques, however, does not provide 100% accuracy. It should also be noted that most studies to date are small, heterogeneous, and retrospective in nature. Future improvements in diagnostic accuracy can be expected with harmonization of acquisition and postprocessing, quantitative MRI and computer-aided diagnostic technology, and meticulous evaluation with clinical and pathological data 3).

The key features pseudoprogression will demonstrate include:

Magnetic resonance perfusion imaging: reduced cerebral blood volume (viable tumor will usually have increased rCBV)

Proton magnetic resonance spectroscopic imaging

low choline

ratio Cho/NAA ratio ≤1.4

increased lactate peak

increased lipid peak

the trace may also be generally flat (hypometabolic)

Apparent diffusion coefficient

tumors that respond to treatment and result in pseudoprogression will have elevated ADC values due to cell death ADC mean values ≥1300 x 10-6 mm2/s 8

Moassefi et al. reported the development of a deep learning model that distinguishes PsP from TP in GBM patients treated per the Stupp protocol. Further refinement and external validation are required prior to widespread adoption in clinical practice 4).

Incorporating all available MRI sequences into a sequence input for a CNN-LSTM model improved diagnostic performance for discriminating between pseudoprogression and true tumor progression 5).

see Glioblastoma progression.


Parvez K, Parvez A, Zadeh G. The diagnosis and treatment of pseudoprogression, radiation necrosis and brain tumor recurrence. Int J Mol Sci. 2014 Jul 3;15(7):11832-46. doi: 10.3390/ijms150711832. PMID: 24995696; PMCID: PMC4139817.

Li M, Ren X, Dong G, Wang J, Jiang H, Yang C, Zhao X, Zhu Q, Cui Y, Yu K, Lin S. Distinguishing Pseudoprogression From True Early Progression in Isocitrate Dehydrogenase Wild-Type Glioblastoma by Interrogating Clinical, Radiological, and Molecular Features. Front Oncol. 2021 Apr 20;11:627325. doi: 10.3389/fonc.2021.627325. Erratum in: Front Oncol. 2021 May 19;11:700599. PMID: 33959496; PMCID: PMC8093388.

Thust SC, van den Bent MJ, Smits M. Pseudoprogression of brain tumors. J Magn Reson Imaging. 2018 May 7;48(3):571–89. doi: 10.1002/jmri.26171. Epub ahead of print. PMID: 29734497; PMCID: PMC6175399.

Moassefi M, Faghani S, Conte GM, Kowalchuk RO, Vahdati S, Crompton DJ, Perez-Vega C, Cabreja RAD, Vora SA, Quiñones-Hinojosa A, Parney IF, Trifiletti DM, Erickson BJ. A deep learning model for discriminating true progression from pseudoprogression in glioblastoma patients. J Neurooncol. 2022 Jul 19. doi: 10.1007/s11060-022-04080-x. Epub ahead of print. PMID: 35852738.

Lee J, Wang N, Turk S, Mohammed S, Lobo R, Kim J, Liao E, Camelo-Piragua S, Kim M, Junck L, Bapuraj J, Srinivasan A, Rao A. Discriminating pseudoprogression and true progression in diffuse infiltrating glioma using multi-parametric MRI data through deep learning. Sci Rep. 2020 Nov 23;10(1):20331. doi: 10.1038/s41598-020-77389-0. PMID: 33230285; PMCID: PMC7683728.

Dysembryoplastic neuroepithelial tumor differential diagnosis

Dysembryoplastic neuroepithelial tumor differential diagnosis

The differential diagnosis of DNET includes oligodendrogliomas, low-grade gliomas, gangliogliomas and pleomorphic xanthoastrocytomas (PXA). Clinical features, imaging findings, and histologic findings are key in making the diagnosis

Low-grade epilepsy-associated neuroepithelial tumors (LEATs) create a diagnostic challenge in daily practice and intraoperative pathological consultation (IC) in particular.

Specific DNT is a homogeneous group of tumours sharing characteristics of pediatric low-grade gliomas: a quiet genome with a recurrent genomic alteration in the RASMAPKsignalling pathway, a distinct DNA methylation profile, a good prognosis but showing progression in some cases. The “non-specific/diffuse DNTs” subgroup encompasses various recently described histo-molecular entities, such as PLNTY and Diffuse astrocytoma MYB or MYBL1 altered 1).

Intraoperative squash smear cytology are extremely useful for accurate diagnosis; however, the knowledge of cytopathologic features of LEATs is based on individual case reports. Kurtulan et al. discuss the 3 most common and well-established entities of LEATs: ganglioglioma (GG), dysembryoplastic neuroepithelial tumor (DNT), and papillary glioneuronal tumor (PGNT).

Thirty patients who underwent surgery for GG, DNT, and PGNT between 2001 and 2021 were collected. Squash smears prepared during intraoperative consultation were reviewed by 1 cytopathologist and an experienced neuropathologist.

Among the 30 tumors, 16 (53.3%) were GG, 11 (36.6%) DNT, and 3 (10%) PGNT. Cytomorphologically, all of the 3 tumor types share 2 common features such as dual cell population and vasculocentric pattern. GG smears were characteristically composed of dysplastic ganglion cells and piloid-like astrocytes on a complex architectural background of thin- to thick-walled vessels. DNT, on the other hand, showed oligodendroglial-like cells in a myxoid thin fibrillary background associated with a delicate capillary network. Common cytological features of PGNT were hyperchromatic cells with narrow cytoplasm surrounding hyalinized vessels forming a pseudopapillary pattern and bland cells with neuroendocrine nuclei dispersed in a neuropil background.

A higher diagnostic accuracy can be obtained when squash smears are applied with frozen sections. However, it is important to integrate clinical and radiologic features of the patient as well as to know the cytopathologic features of the LEAT spectrum in the context of differential diagnosis to prevent misinterpretation in the IC 2).

A 29-year-old male from Bolivia, who lived in Spain, presented seizures and a multicystic brain lesion, initially suspected to be a dysembryoplastic neuroepithelial tumor (DNET). He underwent gross total resection of the mixed solid/cystic lesion. Pathology revealed gliosis, multiple interconnected cystic cavities with fibrous walls, inflammatory cell infiltration and no necrotizing granulomatous reaction. Inside the cavities, a parasitic form was identified as the larva of the cestode Spirometra mansoni. At 1-year follow-up, the patient had no deficits and was seizure free. Clinicians should be alerted to the possible existence of this rare entity in Europe, especially in patients from endemic areas with a possible infection history as well as “wandering lesions” on the MRI 3).

14-year-old woman admitted due to a right temporal lobe tumor.

She was transferred from other Hospital after finding a right temporal lesion on MRI in the context of seizures.

Unprovoked focal seizure. Paroxysmal episodes of blank stare, unresponsiveness, Orofacial Dyskinesia, Guttural sounds, and hypersalivation lasting approximately 30 seconds. Transient global amnesia. He refers to a similar episode a month ago.

Cranial magnetic resonance imaging without and with intravenous contrast (8ml gadovist) was performed with the usual protocol: sagittal T1 TSE, axial T2 TSE, coronal T2 TSE, axial T2 FLAIR, axial T2 EG and axial diffusion.

A signal alteration centered on the anterior pole of the right temporal lobe of approx. 2.2×2.7×1.7cm (TxAPxCC) associates diffuse cortical thickening and the presence of a heterogeneous lesion with a solid and microcystic component that is hypointense in the T1 sequences and hyperintense in the T2 sequences, it also presents a hyperintensity of the peritumoral signal and an increase in diffusion in DWI sequences without presenting signal drop in the ADC. The perfusion sequences did not show an increase in cerebral perfusion at this level with ADC: 1.3. This lesion presents a heterogeneous contrast uptake, drawing attention to the presence of a solid pole adjacent to the dura that presents intense enhancement, but does not present dural enhancement. These findings may be related to a dysembryogenic neuroepithelial tumor (DNET) or to a Ganglioglioma as the main differential diagnoses. No microbleeds were seen in the gradient echo T2 sequence or calcifications. The rest of the cerebral, cerebellar and brainstem parenchyma show no morphological or signal alterations. Middle line centered. Free basal and perimesencephalic cisterns. Centered ventricular system with preserved ventricular size. The main arterial and intracranial venous vessels show a caliber and signal void within normality. Unoccupied paranasal sinuses and mastoid cells. Slight descent of the cerebellar tonsils not significant (2 mm).

Diagnostic impression:

Heterogeneous lesion centered on the anterior temporal pole of the right temporal lobe with a solid / cystic component and enhancement after contrast administration, with tumor characteristics suggesting a Dysembryoplastic neuroepithelial tumor (DNET) or a ganglioglioma as the main differential diagnoses.


Pagès M, Debily MA, Fina F, Jones DTW, Saffroy R, Castel D, Blauwblomme T, Métais A, Bourgeois M, Lechapt-Zalcman E, Tauziède-Espariat A, Andreiuolo F, Chrétien F, Grill J, Boddaert N, Figarella-Branger D, Beroukhim R, Varlet P. The genomic landscape of dysembryoplastic neuroepithelial tumours and a comprehensive analysis of recurrent cases. Neuropathol Appl Neurobiol. 2022 Jul 14:e12834. doi: 10.1111/nan.12834. Epub ahead of print. PMID: 35836307.

Kurtulan O, Bilginer B, Soylemezoglu F. Challenges in the Intraoperative Consultation of Low-Grade Epilepsy-Associated Neuroepithelial Tumors by Cytomorphology in Squash Preparations. Acta Cytol. 2022 Jan 11:1-7. doi: 10.1159/000521249. Epub ahead of print. PMID: 35016169.

Lo Presti A, Aguirre DT, De Andrés P, Daoud L, Fortes J, Muñiz J. Cerebral sparganosis: case report and review of the European cases. Acta Neurochir (Wien). 2015 Sep;157(8):1339-43. doi: 10.1007/s00701-015-2466-9. Epub 2015 Jun 18. PubMed PMID: 26085111.

Positional Plagiocephaly Differential Diagnosis

Positional Plagiocephaly Differential Diagnosis

General practitioners (GPs) have an important role in assessment, diagnosis and referral for paediatric skull deformities. GPs are well placed to clinically differentiate between deformational plagiocephaly and craniosynostosis and provide timely referrals to optimise patient outcomes 1).

The child with unilateral lambdoid synostosis has a thick ridge over the fused suture, with compensatory contralateral parietal and frontal bossing 2). There is an ipsilateral occipitomastoid bulge, with a posteroinferior displacement of the ipsilateral ear. These characteristics are opposite to the findings in the children with deformational plagiocephaly. In the view from above, the shape of the head will be trapezoid in lambdoid synostosis and parallelogram in deformational plagiocephaly. A 3D CT will confirm the diagnosis. Torticollis is most commonly associated with deformational plagiocephaly. Chiari malformation can be present with lambdoid synostosis.


Lun KK, Aggarwala S, Gardner D, Hunt J, Jacobson E, Reddy R, Gianoutsos M, Rtshiladze M. Assessment of paediatric head shape and management of craniosynostosis. Aust J Gen Pract. 2022 Jan-Feb;51(1-2):51-58. doi: 10.31128/AJGP-09-20-5638. PMID: 35098275.

Huang MH, Gruss JS, Clarren SK, Mouradian WE, Cunningham ML, Roberts TS, Loeser JD, Cornell CJ. The differential diagnosis of posterior plagiocephaly: true lambdoid synostosis versus positional molding. Plast Reconstr Surg. 1996 Oct;98(5):765-74; discussion 775-6. doi: 10.1097/00006534-199610000-00001. PMID: 8823012.

Parasagittal Meningioma Differential Diagnosis

Parasagittal Meningioma Differential Diagnosis

see also Meningioma Differential Diagnosis.

Intracerebral schwannoma 1) 2) 3) 4).

Extra-axial ependymoma 5) 6).

Fibrous histiocytoma 7).

Rosai-Dorfman disease 8).

A 14-year-old female mosaic for the de novo p.R108H pathogenic variant in the PIK3CA gene was found to have a large tumor involving the superior sagittal sinus with mass effect on the motor cortex most consistent with a parafalcine meningioma. She underwent surgical resection with pathology demonstrating a venous malformation. PIK3CA pathogenic variants have been identified in nonsyndromic extracranial venous and lymphatic malformations as well in brain tumors, including glioma and meningioma. However, PIK3CA variants have not previously been identified in purely intracranial venous malformations. This distinction is relevant to treatment decisions, given that mTOR inhibitors may provide an alternative option for noninvasive therapy in cases of suspected venous malformation 9).


Li M, Mei J, Li Y, Tao X, Hong T. Intracerebral schwannoma mimicking meningioma: case report. Can J Neurol Sci. 2013 Nov;40(6):881-4. PubMed PMID: 24257236.

Ma L, Yang SX, Wang YR. Intracerebral schwannoma mimicking parasagittal meningioma. J Craniofac Surg. 2013 Nov;24(6):e541-3. doi: 10.1097/SCS.0b013e31828601bf. PubMed PMID: 24220461.

Bristol RE, Coons SW, Rekate HL, Spetzler RF. Invasive intracerebral schwannoma mimicking meningioma in a child. Childs Nerv Syst. 2006 Nov;22(11):1483-6. Epub 2006 Sep 22. PubMed PMID: 17021734.

Takei H, Schmiege L, Buckleair L, Goodman JC, Powell SZ. Intracerebral schwannoma clinically and radiologically mimicking meningioma. Pathol Int. 2005 Aug;55(8):514-9. PubMed PMID: 15998381.

Singh V, Turel MK, Chacko G, Joseph V, Rajshekhar V. Supratentorial extra-axial anaplastic ependymoma mimicking a meningioma. Neurol India. 2012 Jan-Feb;60(1):111-3. PubMed PMID: 22406799.

Salunke P, Kovai P, Sura S, Gupta K. Extra-axial ependymoma mimicking a parasagittal meningioma. J Clin Neurosci. 2011 Mar;18(3):418-20. doi: 10.1016/j.jocn.2010.04.042. Epub 2011 Jan 13. PubMed PMID: 21236682.

Tsutsumi M, Kawano T, Kawaguchi T, Kaneko Y, Ooigawa H, Yoshida T. Intracranial meningeal malignant fibrous histiocytoma mimicking parasagittal meningioma–case report. Neurol Med Chir (Tokyo). 2001 Feb;41(2):90-3. PubMed PMID: 11255634.

Kattner KA, Stroink AR, Roth TC, Lee JM. Rosai-Dorfman disease mimicking parasagittal meningioma: case presentation and review of literature. Surg Neurol. 2000 May;53(5):452-7; discussion 457. Review. PubMed PMID: 10874144.

Filippidis A, Lidov H, Al-Ibraheemi A, See AP, Srivastava S, Orbach DB, Fehnel KP. Intracranial venous malformation masquerading as a meningioma in PI3KCA-related overgrowth spectrum disorder. Am J Med Genet A. 2021 Dec 2. doi: 10.1002/ajmg.a.62570. Epub ahead of print. PMID: 34854542.

Glioblastoma Differential Diagnosis

Glioblastoma Differential Diagnosis

Tumors are classically distinguished based on biopsy of the tumor itself, as well as a radiological interpretation using diverse MRI modalities.

As its historical name glioblastoma multiforme implies, glioblastoma is a histologically diverse, World Health Organization grade IV astrocytic neoplasm. In spite of its simple definition of presence of vascular proliferation and/or necrosis in a diffuse astrocytoma, the wide variety of cytohistomorphologic appearances overlap with many other neoplastic or non-neoplastic lesions 1).

General imaging differential considerations include:

Intracranial metastases

may look identical

both may appear multifocal

metastases usually are centered on grey-white matter junction and spare the overlying cortex rCBV in the ‘edema‘ will be reduced

Primary central nervous system lymphoma should be considered especially in patients with AIDS, as in this setting central necrosis is more common otherwise usually homogeneously enhancing

Cerebral abscess central restricted diffusion is helpful, however, if GBM is hemorrhagic then the assessment may be difficult presence of smooth and complete SWI low-intensity rim presence of dual rim sign

Anaplastic astrocytoma should not have central necrosis consider histology sampling bias

Tumefactive demyelination lesion can appear similar often has an open ring pattern of enhancement usually younger patients

Subacute cerebral infarction history is essential in suggesting the diagnosis should not have elevated choline should not have elevated rCBV

Cerebral toxoplasmosis especially in patients with AIDS

In a study, Samani et al. of the overarching goal are to demonstrate that primary glioblastomas and secondary (brain metastases) malignancies can be differentiated based on the microstructure of the peritumoral region. This is achieved by exploiting the extracellular water differences between vasogenic edema and infiltrative tissue and training a convolutional neural network (CNN) on the Diffusion Tensor Imaging (DTI)-derived free water volume fraction. They obtained 85% accuracy in discriminating extracellular water differences between local patches in the peritumoral area of 66 glioblastomas and 40 metastatic patients in a cross-validation setting. On an independent test cohort consisting of 20 glioblastomas and 10 metastases, we got 93% accuracy in discriminating metastases from glioblastomas using majority voting on patches. This level of accuracy surpasses CNNs trained on other conventional DTI-based measures such as fractional anisotropy (FA) and mean diffusivity (MD), which have been used in other studies. Additionally, the CNN captures the peritumoral heterogeneity better than conventional texture features, including Gabor filter and radiomic features. The results demonstrate that the extracellular water content of the peritumoral tissue, as captured by the free water volume fraction, is best able to characterize the differences between infiltrative and vasogenic peritumoral regions, paving the way for its use in classifying and benchmarking peritumoral tissue with varying degrees of infiltration 2).


Gokden M. If it is Not a Glioblastoma, Then What is it? A Differential Diagnostic Review. Adv Anat Pathol. 2017 Nov;24(6):379-391. doi: 10.1097/PAP.0000000000000170. PMID: 28885262.

Samani ZR, Parker D, Wolf R, Hodges W, Brem S, Verma R. Distinct tumor signatures using deep learning-based characterization of the peritumoral microenvironment in glioblastomas and brain metastases. Sci Rep. 2021 Jul 14;11(1):14469. doi: 10.1038/s41598-021-93804-6. PMID: 34262079.