Publications by authors named "Calvin Soh"

18 Publications

  • Page 1 of 1

Spinal cord compression from hypertrophic nerve roots in chronic inflammatory demyelinating polyradiculoneuropathy - A case report.

Surg Neurol Int 2021 24;12:114. Epub 2021 Mar 24.

Department of Neurosurgery, Salford Royal NHS Foundation Trust, Greater Manchester, United Kingdom.

Background: Spinal cord compression secondary to nerve root hypertrophy is often attributed to hereditary neuropathies. However, to avoid misdiagnosis, rare immune-mediated neuropathy such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) should not be overlooked. This report presents a case of multilevel nerve root hypertrophy leading to significant cord compression from CIDP.

Case Description: We report a 56-year-old gentleman with type two diabetes mellitus who presented with subacute cervical cord syndrome following a fall. Mixed upper and lower motor neuron features were noted on examination. Magnetic resonance imaging showed significant pan-spinal proximal nerve root hypertrophy, compressing the cervical spinal cord. Initial radiological opinion raised the possibility of neurofibromatosis type 1 (NF-1), but neurophysiology revealed both axonal and demyelinating changes that were etiologically non-specific. C6 root and sural nerve biopsies taken at cervical decompression displayed striking features suggestive for CIDP. Although NF-1 is the most observed condition associated with root hypertrophy, other important and potentially treatable differentials need to be entertained.

Conclusion: While rare, CIDP can cause significant spinal cord compression. Furthermore, clinical manifestations of CIDP can mimic those of inherited peripheral neuropathies. Neurologists and neurosurgeons should be aware of this condition to optimize subsequent therapeutic decision-making.
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http://dx.doi.org/10.25259/SNI_35_2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053436PMC
March 2021

Leukoencephalopathy with calcifications and cysts: Genetic and phenotypic spectrum.

Am J Med Genet A 2021 01 7;185(1):15-25. Epub 2020 Oct 7.

Department of Paediatric Neurology, University Hospital of Wales, Cardiff, UK.

Biallelic mutations in SNORD118, encoding the small nucleolar RNA U8, cause leukoencephalopathy with calcifications and cysts (LCC). Given the difficulty in interpreting the functional consequences of variants in nonprotein encoding genes, and the high allelic polymorphism across SNORD118 in controls, we set out to provide a description of the molecular pathology and clinical spectrum observed in a cohort of patients with LCC. We identified 64 affected individuals from 56 families. Age at presentation varied from 3 weeks to 67 years, with disease onset after age 40 years in eight patients. Ten patients had died. We recorded 44 distinct, likely pathogenic, variants in SNORD118. Fifty two of 56 probands were compound heterozygotes, with parental consanguinity reported in only three families. Forty nine of 56 probands were either heterozygous (46) or homozygous (three) for a mutation involving one of seven nucleotides that facilitate a novel intramolecular interaction between the 5' end and 3' extension of precursor-U8. There was no obvious genotype-phenotype correlation to explain the marked variability in age at onset. Complementing recently published functional analyses in a zebrafish model, these data suggest that LCC most often occurs due to combinatorial severe and milder mutations, with the latter mostly affecting 3' end processing of precursor-U8.
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http://dx.doi.org/10.1002/ajmg.a.61907DOI Listing
January 2021

Clinical and neuroradiological characterisation of spinal lesions in adults with Neurofibromatosis type 1.

J Clin Neurosci 2020 Jul 13;77:98-105. Epub 2020 May 13.

Neurosurgery, Salford Royal Foundation Trust, Manchester, United Kingdom. Electronic address:

Neurofibromatosis type 1 (NF1) manifests itself in many ways in the spine. This study aims to report the types of spinal lesions, clinical and demographic data in a large cohort from a complex NF1 centre. The characteristics of those with spinal neurofibromatosis, where neurofibromas are present on every spinal nerve root, were sought for comparison with the wider group of NF1 patients. This is a retrospective review of MDT minutes of 303 patients from a UK NF1 centre and the largest reported series of NF1 patients based on radiological data. Prevalence of each symptom and lesion was calculated and statistically significant associations were established. The most reported findings were cutaneous lesions (44.9%) and neurological deficit (27.4%). 28.4% had dural ectasia, 52.5% had some form of spinal deformity. 57.8% had spinal nerve root tumours, the most common of which were at C2. The most progressive lesions were spinal nerve root tumours (29.1%). The only statistically significant association found was between dural ectasia and spinal deformity (P < 0.003), where dural ectasia is associated with a 32.6% increase in spinal deformity incidence. This is the largest descriptive study of spinal lesions in NF1. Spinal tumours and spinal deformity are prevalent in NF1. The predilection of spinal tumours for flexible spinal regions suggests that repetitive movement might be an important factor in pathogenesis. Physicians and patients should be alert to the observation that although many spinal neurofibromatosis patients display no neurological deficit, they often have significant lesions which require monitoring and sometimes surgery.
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http://dx.doi.org/10.1016/j.jocn.2020.05.014DOI Listing
July 2020

Multiple primary malignancies associated with a germline SMARCB1 pathogenic variant.

Fam Cancer 2019 10;18(4):445-449

Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University Hospitals Foundation Trust, Manchester, M13 9WL, UK.

A 51-year old presented with a 6-month history of increasing pelvic/lower back pain with nocturnal waking and episodes of anorexia and vomiting. Examination revealed right torticollis and Horner's syndrome, and a large abdominal mass arising from the pelvis. Magnetic resonance and positron emission tomography imaging revealed (A) a 14 cm heterogeneous enhancing mass, abutting the left kidney with standardised uptake value max = 2.9, (B) a large heterogeneous enhancing pelvic mass (C) mesenteric adenopathy standardised uptake value max = 10.3 and (D) 6 cm right lung apex mass standardised uptake value max = 4.3. Computerised tomography-guided biopsy of lesion A was reported as neurofibroma with occasional atypia, lesion B a benign uterine leiomyoma and lesion C follicular lymphoma world health organisation Grade 2. Although she had been given the diagnosis of Neurofibromatosis Type-1 (NF1) 25-years previously following removal of an intradural extramedullary schwannoma she had no cutaneous stigmata of NF1. Genetic analysis of blood lymphocyte DNA identified a pathogenic variant in SMARCB1 confirming a diagnosis of schwannomatosis. Following 6-months chemotherapy for lymphoma, surgery was performed to remove lesion A. Histology revealed a malignant peripheral nerve sheath tumour with areas of low and high-grade change. An incidental, well-differentiated small bowel neuroendocrine carcinoma was also excised. Close surveillance continues with no recurrence after 6 years. This case study describes a novel finding of three separate synchronous primary malignancies in a patient with schwannomatosis and a proven SMARCB1 pathogenic variant.
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http://dx.doi.org/10.1007/s10689-019-00138-4DOI Listing
October 2019

C2 neurofibromas in neurofibromatosis type 1: genetic and imaging characteristics.

J Neurosurg Spine 2018 10;30(1):126-132

2Manchester Academic Health Sciences Centre, Division of Evolution and Genomic Sciences, The University of Manchester, United Kingdom.

OBJECTIVEC2 nerve root neurofibromas have been reported frequently in patients with neurofibromatosis type 1 (NF1), although their genetic and imaging characteristics are unexplored. The aim of this study was to characterize genetic and spinal imaging findings in a large cohort of NF1 patients with C2 neurofibromas.METHODSThe authors performed a review of national NF1 referrals between 2009 and 2016. Inclusion criteria were at least 1 C2 root neurofibroma and cervical-spine or whole-spine MRI scans available for analysis. Blinded imaging review was performed by a neuroradiologist with an interest in NF1.RESULTSFifty-four patients with 106 C2 neurofibromas were included. The median age was 32.5 years (range 15-61 years), and there were slightly more male patients (33 vs 21 female patients). Splice-site (30%) and missense (20%) variants were frequent. Spinal neurofibromas were distributed in all spine regions (65%) or in the cervical spine alone (22%). Most (93%) C2 neurofibromas were visible on MRI scans of the head. Intradural invasion and cord compression in the cervical spine included the C2 level in 95% and 80% of patients, respectively. Compared with all other cervical spine neurofibromas in these patients, C2 neurofibromas had higher rates of intraspinal extension (75% vs 32%; OR 6.20, 95% CI 3.85-9.97; p < 0.001), intradural invasion (53% vs 26%; OR 3.20, 95% CI 2.08-4.92; p < 0.001), and cord compression (25% vs 13%; OR 2.26, 95% CI 1.35-3.79; p = 0.002). However, C2 neurofibromas had lower rates of extraforaminal growth beyond the transverse process (12% vs 62%; OR 0.09, 95% CI 0.05-0.16; p < 0.001).CONCLUSIONSC2 neurofibromas are associated with an aggressive intraspinal phenotype, limited growth outside the spinal canal, and an uncommon genetic profile. These observations require future study.
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http://dx.doi.org/10.3171/2018.7.SPINE171340DOI Listing
October 2018

Correction to: Assessing size of pituitary adenomas: a comparison of qualitative and quantitative methods on MR.

Acta Neurochir (Wien) 2018 07;160(7):1491-1492

Department of Neurosurgery, Greater Manchester Neurosciences Centre, Salford Royal Foundation Trust, Stott Lane, Salford, Manchester, M6 8HD, UK.

We have incorrectly described the ellipsoid equation as being calculated using maximal diameters. It is in fact calculated using half the maximal diameter, i.e. the maximal radii. The diameter is initially recorded on the MRI images (as per Fig. 1), as the lesions do not have a defined midpoint.
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http://dx.doi.org/10.1007/s00701-018-3553-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829694PMC
July 2018

Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts.

Nat Genet 2016 10 29;48(10):1185-92. Epub 2016 Aug 29.

Department of Clinical Genetics, Liverpool Women's NHS Foundation Trust, Liverpool, UK.

Although ribosomes are ubiquitous and essential for life, recent data indicate that monogenic causes of ribosomal dysfunction can confer a remarkable degree of specificity in terms of human disease phenotype. Box C/D small nucleolar RNAs (snoRNAs) are evolutionarily conserved non-protein-coding RNAs involved in ribosome biogenesis. Here we show that biallelic mutations in the gene SNORD118, encoding the box C/D snoRNA U8, cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts (LCC), presenting at any age from early childhood to late adulthood. These mutations affect U8 expression, processing and protein binding and thus implicate U8 as essential in cerebral vascular homeostasis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045717PMC
http://dx.doi.org/10.1038/ng.3661DOI Listing
October 2016

Circumferential intradural meningioma of the thoracic spinal cord.

Spine J 2016 07 3;16(7):e479-83. Epub 2016 Mar 3.

Department of Neurosurgery, Salford Royal Hospital, Stott Lane, Greater Manchester, England M6 8HD, United Kingdom.

Background And Context: There are very few reported cases of a meningioma circumferentially surrounding the spinal cord. To date, this entity has only been described at the conus medullaris and in the cervical cord. Herewith, the authors describe a case of an intradural extramedullary meningioma that completely encircled the thoracic spinal cord.

Case Report: A 40-year-old woman with progressive numbness of the lower limbs and spasticity of gait following a fall presented to our hospital. Magnetic resonance imaging of the spine demonstrated an abnormality at T6-T7 completely encircling the spinal cord. The patient underwent a T6-T8 laminectomy and subtotal resection of the intradural partially calcified lesion. Resection of the anterolateral portion was not feasible. Histology revealed psammomatous meningioma (WHO Grade 1). The patient recovered well and was discharged with improved gait but some residual numbness of her feet and right hemithorax.

Conclusion: This is the first reported case of an intradural extramedullary meningioma completely encircling the thoracic spinal cord. Achieving complete resection of this circumferential meningioma was not possible via a posterior approach. The optimum management of this condition is unknown; clearly, achieving symptomatic relief with adequate cord decompression is paramount; however, the long-term outcome and risk of recurrence in these cases, given their rarity and the difficulties in achieving complete resection, is unknown.
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http://dx.doi.org/10.1016/j.spinee.2016.02.053DOI Listing
July 2016

Assessing size of pituitary adenomas: a comparison of qualitative and quantitative methods on MR.

Acta Neurochir (Wien) 2016 Apr 29;158(4):677-683. Epub 2016 Jan 29.

Department of Neurosurgery, Greater Manchester Neurosciences Centre, Salford Royal Foundation Trust, Stott Lane, Salford, M6 8HD, Manchester, UK.

Background: A variety of methods are used for estimating pituitary tumour size in clinical practice and in research. Quantitative methods, such as maximum tumour dimension, and qualitative methods, such as Hardy and Knosp grades, are well established but do not give an accurate assessment of the tumour volume. We therefore sought to compare existing measures of pituitary tumours with more quantitative methods of tumour volume estimation.

Method: Magnetic resonance imaging was reviewed for 99 consecutive patients with pituitary adenomas awaiting surgery between 2010 and 2013. Maximal tumour diameter, Hardy and Knosp grades were compared with tumour volume estimates by the ellipsoid equation, [4/3π (a,b,c)], (i.e. ellipsoid volume) and slice-by-slice perimetry (i.e. perimeter volume).

Results: Ellipsoid and perimeter methods of tumour volume estimation strongly correlated (R(2) = 0.99, p < 0.0001). However the correlation was less strong with increasing tumour size, with the ellipsoid method slightly underestimating. The mean differences were -0.11 (95 % CI, -0.35, 0.14), -0.74 (95 % CI, -2.2, 0.74) and -1.4 (95 % CI, -6.4, 3.7) for micro-tumours, macro-tumours and giant tumours respectively. Tumour volume correlated with maximal diameter, following a cubic distribution. Correlations of tumour volume with Hardy and Knosp grades was less strong.

Conclusions: Perimeter and ellipsoid methods give a good estimation of tumour volume, whereas Knosp and Hardy grades may offer other clinically relevant information, such as cavernous sinus invasion or chiasmal compression. Thus the different methods of estimating tumour size are likely to have different clinical utilities.
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http://dx.doi.org/10.1007/s00701-015-2699-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791475PMC
April 2016

Leukoencephalopathy with calcifications and cysts: a purely neurological disorder distinct from coats plus.

Neuropediatrics 2014 Jun 9;45(3):175-82. Epub 2014 Jan 9.

Department of Paediatric Neurology, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom.

Objective: With the identification of mutations in the conserved telomere maintenance component 1 (CTC1) gene as the cause of Coats plus (CP) disease, it has become evident that leukoencephalopathy with calcifications and cysts (LCC) is a distinct genetic entity.

Patients And Methods: A total of 15 patients with LCC were identified from our database of patients with intracranial calcification. The clinical and radiological features are described.

Results: The median age (range) at presentation was 10 months (range, 2 days-54 years). Of the 15 patients, 9 presented with epileptic seizures, 5 with motor abnormalities, and 1 with developmental delay. Motor abnormalities developed in 14 patients and cognitive problems in 13 patients. Dense calcification occurred in the basal ganglia, thalami, dentate nucleus, brain stem, deep gyri, deep white matter, and in a pericystic distribution. Diffuse leukoencephalopathy was present in all patients, and it was usually symmetrical involving periventricular, deep, and sometimes subcortical, regions. Cysts developed in the basal ganglia, thalamus, deep white matter, cerebellum, or brain stem. In unaffected areas, normal myelination was present. No patient demonstrated cerebral atrophy.

Conclusion: LCC shares the neuroradiological features of CP. However, LCC is a purely neurological disorder distinguished genetically by the absence of mutations in CTC1. The molecular cause(s) of LCC has (have) not yet been determined.
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http://dx.doi.org/10.1055/s-0033-1364180DOI Listing
June 2014

Seizure-induced MRI changes mimicking metastatic brain disease.

J Clin Neurosci 2014 May 23;21(5):869-72. Epub 2013 Aug 23.

Department of Neurology, Greater Manchester Neurosciences Centre, Salford Royal Hospital, Manchester, UK.

Non-convulsive status epilepticus (NCSE) can present with heterogeneous clinical manifestations including prolonged confusion. MRI of the brain may demonstrate enhancing signal abnormalities that can mimic various pathologies including disease progression in patients with brain tumour. These neuroimaging changes are usually reversible and have been attributed to a combination of cytotoxic and vasogenic oedema. We report an interesting patient with a past history of prostatic rhabdomyosarcoma and brain metastasis presenting with NCSE where brain MRI demonstrated marked left hemispheric signal abnormalities, raising concerns about tumour recurrence. However the neuroimaging changes resolved following treatment with intravenous anticonvulsants, confirming that they were an effect rather than the cause of seizures. Recognition of seizure-related imaging abnormalities is important to institute prompt appropriate treatment, and to avoid diagnostic ambiguity and unnecessary treatment and/or investigations.
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http://dx.doi.org/10.1016/j.jocn.2013.06.012DOI Listing
May 2014

Malignant transformation of a Schneiderian papilloma presenting with isolated sixth nerve palsy.

Br J Neurosurg 2013 Apr 17;27(2):262-3. Epub 2012 Dec 17.

Department of Neurology, Greater Manchester Neurosciences Centre, Salford, UK.

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http://dx.doi.org/10.3109/02688697.2012.717982DOI Listing
April 2013

Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus.

Nat Genet 2012 Jan 22;44(3):338-42. Epub 2012 Jan 22.

Manchester Academic Health Science Centre, University of Manchester, Genetic Medicine, UK.

Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous γH2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the α-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-α primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity.
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http://dx.doi.org/10.1038/ng.1084DOI Listing
January 2012

Haemorrhagic synovial cyst presenting as thoracic cord compression: a case report and review of the literature.

Br J Neurosurg 2012 Feb 18;26(1):120-2. Epub 2011 Jul 18.

Department of Neurosurgery, Greater Manchester Neurosciences Centre, Salford Royal Hospital, Salford, Greater Manchester, UK.

Synovial cysts are often incidental findings on spinal imaging. They can present with back pain and radicular symptoms; rarely, they can rupture causing an epidural haematoma and thecal sac compression. We present the first reported case of a haemorrhagic synovial cyst causing thoracic cord compression, and review the pertinent literature.
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http://dx.doi.org/10.3109/02688697.2011.591853DOI Listing
February 2012

Radiotherapy-induced supratentorial primitive neuroectodermal tumour in a 17-year-old female: a case report and review of the literature.

Acta Neurochir (Wien) 2011 Feb 2;153(2):413-7. Epub 2010 Dec 2.

Department of Neurosurgery, Greater Manchester Neurosciences Centre, Salford Royal Hospital, UK.

We report a case of a 17-year-old female who presented with a CNS primitive neuroectodermal tumour 12 years after cranial radiotherapy for relapsed childhood acute lymphoblastic leukaemia. In this article, we discuss the association of these rare tumours with previous craniospinal irradiation and review the pertinent literature.
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http://dx.doi.org/10.1007/s00701-010-0890-4DOI Listing
February 2011

Tumour enhancing fraction (EnF) in glioma: relationship to tumour grade.

Eur Radiol 2009 Jun 7;19(6):1489-98. Epub 2009 Feb 7.

Wolfson Molecular Imaging Centre, Imaging Science and Biomedical Engineering, University of Manchester, 27 Palatine Road, Withington, Manchester, M20 3LJ, UK.

The aim of this research was to determine whether the proportion of a tumour that enhances (enhancing fraction, EnF) and changes in EnF with enhancement threshold differ between low and high grade glioma. Forty-four patients (45 gliomas comprising 16 grade II, 5 grade III and 24 grade IV) were studied. Imaging included pre- and post-contrast-enhanced T(1)-weighted sequences and T(1)-weighted DCE-MRI. Thresholded enhancement maps were generated for each tumour by using a range of values of the initial area under the contrast concentration curve (IAUC). A plot of EnF versus threshold value was generated. We examined the relationship between tumour grade and enhancement metrics including: EnF (threshold IAUC > 0 mMol s), EnF (threshold IAUC > 2.5 mMol s), initial slope of the EnF/threshold curve (partial differentialEnF), IAUC, and two previously described signal-intensity-based metrics. EnF, defined as the proportion of tumour showing any enhancement (threshold IAUC > 0 mMol s), showed no difference between low and high grade glioma. All other measures demonstrated significant differences between grade II and IV, and low (grade II) and high grade (grades III/ IV) gliomas (p < 0.01). Two measures, partial differentialEnF and Pronin's measure of enhancement, showed differences between grade III and IV (p < 0.05). No measure separated grade II from III. Metrics which describe the enhancing fraction and its variation with enhancement threshold partial differentialEnF show considerably different behaviour in low and high grade tumours. These observations suggest that these metrics may provide important biological information concerning tumour biology and therapeutic responses and encourage further research to characterise and validate these novel biomarkers.
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http://dx.doi.org/10.1007/s00330-008-1288-zDOI Listing
June 2009

Reliability assessment of computerized tomography scanning measurements in intracerebral hematoma.

Neurosurg Focus 2003 Oct 15;15(4):E6. Epub 2003 Oct 15.

Department of Neurosurgery, Newcastle General Hospital, Newcastle upon Tyne, United Kingdom.

Object: As one of the aspects of the International Surgical Trial in Intracerebral Haemorrhage (STICH), prerandomization computerized tomography (CT) scans were collected. In the present study the authors determined the inter-and intraobserver variability of various parameters pertinent to CT scans obtained in patients with intracerebral hematomas (ICHs).

Methods: A protocol was devised to analyze CT scans in a uniform and systematic manner. Each observer evaluated the same set of scans twice, with a minimum 2-month interval between assessments. In addition to noting the side and the sites of involvement, the observers measured the scale present on the scan itself and the length, breadth, height, and depth of the spontaneous ICH as well as the midline shift. The intraclass correlation was very high (kappa 0.8-1) for the measurements of volume, depth, and midline shift. Good interobserver agreement (kappa 0.8-1) was demonstrated with regard to involvement of basal ganglia or thalamus, presence of intraventricular extension, and the side of the hematoma. Agreement was substantial (kappa 0.61-0.8) with regard to identifying primary involvement of particular lobes. Agreement was moderate (kappa 0.41-0.6) on the presence or absence of hydrocephalus. When comparing the first and the second sets of readings, the intraobserver agreement was good (80-100%).

Conclusions: The study quantifies the degree of inter- and intraobserver agreement regarding evaluation of CT scans in patients with ICH when conducted in accordance with a set protocol.
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http://dx.doi.org/10.3171/foc.2003.15.4.6DOI Listing
October 2003
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