Intratumoral histological and molecular heterogeneity in an adult diffuse glioma.

Adult-type diffuse gliomas are the most prevalent type of malignant adult brain tumors. Intratumoral heterogeneity can hinder accurate diagnosis and subsequent treatment. This case report documents a tumor with intratumoral heterogeneity, both histologically and by methylation analysis, located within the left cerebral hemisphere of a 29-year-old female. She presented after a witnessed generalized tonic clonic seizure at home. Two years prior she had a witnessed seizure; however, no brain imaging was done at the time. Magnetic resonance imaging (MRI), on this admission, showed a mass lesion in the left frontal operculum with poorly identified margins and right-sided midline shift. Sampling from the left temporal lobe showed an IDH-mutant, ATRX-mutant astrocytoma, which appeared grade 4 in the enhancing anterior portion and grade 2 in the left temporal lobe. Methylation analysis confirmed this heterogeneity. In summary, this is an excellent example of tumor heterogeneity both histologically and by molecular analysis. It is probable, given the clinical history of presentation 2 years prior, that this tumor originated as a low-grade glioma and subsequently evolved.

Establishing a committee for antemortem reviews of suspect Creutzfeldt-Jakob disease cases in Ireland.

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a rapidly progressive, neurodegenerative disease. In Ireland, clinical diagnostics and laboratory testing remain the responsibility of the managing clinician and the Neuropathology Department at the Beaumont Hospital, respectively. Centralized review of individual cases is not undertaken. AIMS: To determine how diagnostic processes for CJD could be improved in Ireland and to outline the structure and referral process for a new CJD review panel at the Beaumont Hospital. METHODS: We surveyed Irish neurologists' experiences on the management of CJD in Ireland. We measured turnaround times (TAT) for CSF samples referred for diagnostic CJD testing. Finally, we retrospectively reviewed imaging of autopsy-proven CJD cases to compare with initial reports. RESULTS: Ninety-three percent of neurologists supported a national central review of suspect CJD cases. A second clinical opinion was considered to be of likely benefit by 79%. Additionally, 93% reported that a centralized review of neuroradiology would be useful. All respondents felt that expediting turnaround of CSF analysis would be of benefit. The average TAT for CSF testing was 35.4 days. In retrospective review of imaging, all patients demonstrated MRI findings consistent with CJD. However, in only one of these cases were the initial pre-autopsy radiological findings reported as being consistent with CJD. CONCLUSIONS: These findings support the need for improvements to the Irish National CJD Surveillance Unit to maximize antemortem diagnostic accuracy. On foot of this, a clinical CJD Multidisciplinary Team (CJD MDT) has been established to provide a second opinion on (i) the patient's clinical history, (ii) neuroradiology and (iii) and neurophysiology reports (where available).

Sinonasal outcomes associated with the use of BioGlue® in endoscopic transsphenoidal pituitary surgery.

Concerns have been raised in the neurosurgical literature regarding the use of BioGlue®, a tissue sealant initially developed for cardiothoracic surgery, due to reports of an increased incidence of infection, wound breakdown, and CSF fistulae. The aim of this study was to determine if the use of BioGlue® in skull base repair impacts on the sinonasal outcomes and the incidence of post-operative infection following endoscopic pituitary surgery. SNOT-22 questionnaires were completed pre-operatively, and at 6, 12, and 24 weeks post-operatively by 50 patients. Pre- and post-operative MRI scans were reviewed and assessed for evidence of post-operative sinusitis. Patient records were consulted to ascertain the incidence of post-operative infection. Repeated measures ANOVA and Wilcoxon signed rank test were used for data analysis. Statistical analysis revealed a significant difference in the mean SNOT-22 scores across the four time intervals (F(1.605, 78.642) = 9.180, p = 0.001). This difference was powered by a deterioration at 6 weeks that recovered completely by 12 weeks. The mean SNOT-22 score in the study cohort at 24 weeks was 16.84/110 (range 0-57, ± 2.04) which was lower than the mean pre-operative score and is consistent with mild rhinosinusitis. There were no cases of post-operative meningitis and 1/50 (2%) case of post-operative sinusitis in this cohort. The use of BioGlue® in endoscopic endonasal pituitary surgery does not appear to lead to significant sinonasal morbidity. Previous concerns about the use of BioGlue® in transcranial procedures may not apply to extradural application of this tissue sealant in endoscopic transnasal surgery.

Neuroimaging of central diabetes insipidus.

Central diabetes insipidus (CDI) occurs secondary to deficient synthesis or secretion of arginine vasopressin peptide from the hypothalamo-neurohypophyseal system (HNS). It is characterized by polydipsia and polyuria (urine output >30mL/kg/day in adults and >2l/m2/24h in children) of dilute urine (<250mOsm/L). It can result from any pathology affecting one or more components of the HNS including the hypothalamic osmoreceptors, supraoptic or paraventricular nuclei, and median eminence of the hypothalamus, infundibulum, stalk or the posterior pituitary gland. MRI is the imaging modality of choice for evaluation of the hypothalamic-pituitary axis (HPA), and a dedicated pituitary or sella protocol is essential. CT can provide complimentary diagnostic information and is also of value when MRI is contraindicated. The most common causes are benign or malignant neoplasia of the HPA (25%), surgery (20%), and head trauma (16%). No cause is identified in up to 30% of cases, classified as idiopathic CDI. Knowledge of the anatomy and physiology of the HNS is crucial when evaluating a patient with CDI. Establishing the etiology of CDI with MRI in combination with clinical and biochemical assessment facilitates appropriate targeted treatment. This chapter illustrates the wide variety of causes and imaging correlates of CDI on neuroimaging, discusses the optimal imaging protocols, and revises the detailed neuroanatomy required to interpret these studies.

Predicting post-operative cerebrospinal fluid (CSF) leak following endoscopic transnasal pituitary and anterior skull base surgery: a multivariate analysis.

BACKGROUND: Post-operative CSF leak is the major source of morbidity following endoscopic transsphenoidal surgery. The purpose of this study was to identify factors associated with post-operative CSF leak in patients undergoing this surgery and facilitate the prospective identification of patients at higher risk of this complication. METHODS: A review of a prospectively maintained database containing details of 270 endoscopic transsphenoidal operations performed by the senior author over a 9-year period was performed. Univariate analysis was performed using the Chi-squared and Fisher's exact tests, as appropriate. A logistic regression model was constructed for multivariate analysis. RESULTS: The rate of post-operative CSF leak in this series was 9%. On univariate analysis, previous surgery, resection of craniopharyngiomas, adenomas causing Cushing's disease and intra-operative CSF leaks were associated with an increased risk of post-operative CSF leak. The use of a vascularised nasoseptal flap and increasing surgical experience were associated with a decreased rate of CSF leak. On multivariate analysis, a resection of tumour for Cushing's disease (OR 5.79, 95% CI 1.53-21.95, p = 0.01) and an intra-operative CSF leak (OR 4.56, 95% CI 1.56-13.32, p = 0.006) were associated with an increased risk of post-operative CSF leak. Increasing surgical experience (OR 0.14, 95% CI 0.04-0.46, p = 0.001) was strongly associated with a decreased risk of post-operative CSF leak. CONCLUSIONS: Increasing surgical experience is a strong predictor of a decreased risk of developing post-operative CSF leak following endoscopic transsphenoidal surgery. Patients with Cushing's disease and those who develop an intra-operative CSF leak should be managed with meticulous skull base repair and close observation for signs of CSF leak post-operatively.

Early repatriation post-thrombectomy: a model of care which maximises the capacity of a stroke network to treat patients with large vessel ischaemic stroke.

BACKGROUND AND PURPOSE: Healthcare systems are challenged to provide access to thrombectomy in acute stroke patients. Either the "drip and ship" or "mothership" models result in increased numbers of patients in the endovascular stroke centre (ESC). We describe our approach for a "drip, ship, retrieve and leave" model repatriating patients immediately or within 24 hours of thrombectomy. METHODS: We included consecutive patients who underwent thrombectomy from January 2016 to June 2018. Patients from local region primary stroke centres (PSC) are immediately repatriated and those from remote region PSCs are admitted for 24 hours before repatriation. Key parameters recorded included clinical, radiological and timeline data as well as 90-day modified Rankin Scale (mRS). Patients who stayed beyond the intended time period in the ESC were analysed. RESULTS: From January 2016 to June 2018, 435 patients were transferred, with 352 patients in the local region group and 83 in the remote region group. The median NIHSS was 16 with a median ASPECTS of 9. Good functional outcome was seen in 47% of patients with a mortality rate of 19%. The local region group that were repatriated at the intended time period had a 90-day mRS 0-2 of 47% compared with 20% of those admitted to the ESC (P=0.006). Mortality rates were 20% and 27% respectively (P=0.377). The remote region group, repatriated at 24 hours' post-emergency endovascular thrombectomy had 90-day mRS 0-2 of 65% compared with 41% in the group admitted (P=0.042). Mortality rates were 4% and 22% respectively (P=0.007). CONCLUSION: This model enables the treatment of large numbers of patients with large vessel occlusion acute ischaemic stroke with thrombectomy within a national stroke service and system of care which would not otherwise be facilitated.

CNS lymphoma, the Irish experience: A retrospective review of neuropathologically confirmed cases over 10 years.

BACKGROUND: Central nervous system (CNS) lymphoma is rare, representing 2% of all brain tumors. The commonest subtype is diffuse large B-cell lymphoma (DLBCL), with primary T-cell lymphomas (PCNSTL) accounting for ~ 2%. OBJECTIVE: To determine the frequency and describe the key features of CNS lymphoma over a 10-year period in an Irish population. MATERIALS AND METHODS: This retrospective review was carried out using the neuropathology database in Beaumont hospital, the largest of two national neurosurgical centers, to identify all cases of CNS lymphoma from 2007 to 2017. Clinical, radiological, morphological, immunophenotype, and molecular information was recorded where available. RESULTS: We identified 149 cases of CNS lymphoma from 2007 to 2017, which equated to a cumulative incidence rate of 0.4/100,000 persons. Median age at diagnosis was 66 years, and 46% were male. 86% were classified as DLBCL (n = 128), 10% immunodeficiency-associated CNS lymphoma (n = 15), 3% PCNSTL (n = 4), and 1% (n = 2) cases of intravascular large B-cell lymphoma. Location in declining frequency was as follows: supratentorial (n = 125), infratentorial (n = 22), spinal (n = 1), and orbital (n = 1). CONCLUSION: This is the first study in an Irish population to determine a cumulative incidence rate of CNS lymphoma, which is in line with larger international population-based registries. No significant trends in incidence rate have been observed from 2007 to 2017. DLBCL is the commonest subtype encountered. Rare variants including PCNSTL can pose a significant diagnostic challenge, and in this setting, molecular studies can be useful to confirm diagnoses.

IgG4 hypophysitis - a rare and underdiagnosed cause of pituitary gland and stalk mass-like thickening.

Our aim is to present a typical case of IgG4-related hypophysitis, which will offer insight into the aetiology and pathogenesis of this relatively newly described disease. IgG4 Related Disease is a protean systemic condition that mimics inflammatory, infectious, and malignant processes. Biopsy of affected organs will show a typical histopathological pattern.

Vertebroplasty for acute painful osteoporotic vertebral compression fractures: An update.

Vertebral compression fractures (VCFs) are a common cause of back pain and disability and are usually osteoporotic in nature. Therapy aims to adequately control pain and allow early mobilisation and return of function while preventing additional fractures. A proportion of patients do not achieve adequate pain relief using conservative measures alone. Unwanted adverse effects from medications may also ensue. Vertebroplasty represents an alternative treatment option for VCFs. Patients with acute VCFs (≤6 weeks old) may gain the most benefit from vertebroplasty as healed fractures are not as amenable to cement injection. High-quality studies have reported conflicting results regarding the use of vertebroplasty in the treatment of acute VCFs. Despite high-quality evidence, varying study designs and heterogenous patient cohorts make interpretation of this data difficult. Only one sham-controlled randomised controlled trial (RCT) has evaluated vertebroplasty exclusively in patients with acute VCFs, reporting favourable results. Pooled data from RCTs also suggest vertebroplasty to be safe. This article provides a concise and critical review of the current literature regarding vertebroplasty for the treatment of acute VCFs.

Direct carotid puncture for endovascular thrombectomy in acute ischemic stroke.

BACKGROUND: Mechanical thrombectomy is the standard of care for acute ischemic strokes with proximal intracranial occlusion. Arterial access is commonly achieved with femoral artery puncture, although this is not always possible. In this case series, we describe 11 cases of anterior circulation stroke where direct carotid puncture was used to obtain vascular access. METHODS AND MATERIALS: A review of a prospectively maintained thrombectomy database over a 2-year period (August 2016 - August 2018) was undertaken to identify cases where direct carotid access was performed. CT and angiographic imaging were reviewed. Indications for carotid access, techniques used, technical success of procedure, recanalization rates, procedure-related complications, and patient outcomes were assessed. RESULTS: Eleven patients out of 498 overall thrombectomy procedures (2.2% thrombectomies) underwent direct carotid access. Median National Institutes of Health Stroke Scale was 20. Seventy three percent of patients received intravenous thrombolysis. The direct carotid approach was performed following the failed femoral approach due to unfavorable aortic arch anatomy, vessel tortuosity, and severe atherosclerotic disease. Direct carotid puncture was successful in 10 patients, and unsuccessful in one. Successful recanalization (TICI 2b-3) was achieved in eight patients. One patient had spontaneously recanalized on angiography. There was failed recanalization in one patient with tandem ICA and M1 occlusion. Carotid access complications included one patient with both neck hematoma and asymptomatic ICA dissection, and one of delayed central retinal artery occlusion. CONCLUSION: This case series highlights direct carotid puncture as a successful alternative when the femoral approach is not possible, allowing thrombectomy in patients who would otherwise be unsuitable.

Acute multiple sclerosis lesion pathology does not predict subsequent clinical course-a biopsy study.

BACKGROUND: Knowledge of the clinical outcome in tumefactive demyelination remains limited. AIMS: This study aims to characterise the natural history of biopsy-proven, pathogen-free, cerebral demyelination in an adult Irish population. METHODS: We identified all patients with biopsy-proven demyelination in a single neuropathology centre between 1999 and 2017. A baseline, and at least one follow-up MRI scan was available in each instance (mean of 3 scans per patient), together with both the presenting and most recent clinical details including disability level and disease-modifying drugs. RESULTS: In 21 patients, white matter biopsies showed the following: macrophages with myelin debris, myelin-axonal dissociation, reactive astrocytes and occasional lymphocytes. During a mean follow-up time of 8 years (± 4.4), 17 patients developed MS, confirmed both clinically and on MRI, using the 2010 McDonald criteria: 11 relapsing remitting (RR) MS, four secondary progressive and two primary progressive MS. Four patients had a monophasic illness with lesion regression, without clinical or radiological evidence of any further disease activity on follow-up. The patients with progressive MS had significantly higher levels of physical disability than either the RRMS or monophasic patients. CONCLUSION: Uniform white matter subacute demyelination is associated with a diverse clinical course ranging from a monophasic illness to progressive MS, suggesting that extraneous factors distinct from the basic pathology significantly influence the clinical course in MS.

Decreasing incidence of subarachnoid hemorrhage.

OBJECTIVE: To determine the incidence and trends in subarachnoid hemorrhage in Ireland using data from a national database. MATERIALS AND METHODS: We performed a retrospective nationwide query of the Irish Hospital In-patient Enquiry System (HIPE). This is a national database of all in-patient activity in acute public hospitals in Ireland. Each HIPE entry records one episode of in-patient care. The study period ranged from 1997 to 2015. Population data was obtained from the Irish Central Statistics Office, and the annual prevalence of smoking from the Irish National Tobacco Control Office. We were therefore able to calculate both crude annual acute subarachnoid hemorrhage (SAH) incidence rates, as well as population-standardized rates, and compared them with trends in the annual smoking rates. RESULTS: The mean number of SAH cases per year is 549, with 465 cases in 1997 and 517 in 2015 (range: 465-624). The absolute incidence of SAH, therefore, remained relatively stable. Due to population increases over time, the population-adjusted rate of SAH therefore decreased, from 126.9/million people/year in 1997 to 111.5/million people/year in 2015. Nationally, there was a decrease in smoking prevalence, from 31% in 1998 to 19.2% in 2015. There was a statistically significant correlation between decreasing smoking rates and decreasing population-adjusted incidence of SAH (P=<0.0001). CONCLUSIONS: Our data suggests that the incidence of non-traumatic subarachnoid hemorrhage in our population appears to be decreasing, a decrease which is correlated with decreasing smoking rates. This provides important data both in terms of the epidemiology of SAH, as well as the possible role of public-health interventions in tackling both smoking and declining rates of SAH.

Predictors of early progression of surgically treated atypical meningiomas.

BACKGROUND: Clinical behaviour of atypical meningiomas is not uniform. While, as a group, they exhibit a high recurrence rate, some pursue a more benign course, whereas others progress early. We aim to investigate the imaging and pathological factors that predict risk of early tumour progression and to determine whether early progression is related to outcome. METHODS: Adult patients with WHO grade II meningioma treated in three regional referral centres between 2007 and 2014 were included. MRI and pathology characteristics were assessed. Gross total resection (GTR) was defined as Simpson 1-3. Recurrence was classified into early and late (≤ 24 vs. > 24 months). RESULTS: Among the 220 cases, 37 (16.8%) patients progressed within 24 months of operation. Independent predictors of early progression were subtotal resection (STR) (p = 0.005), parafalcine/parasagittal location (p = 0.015), peritumoural oedema (p = 0.027) and mitotic index (MI) > 7 (p = 0.007). Adjuvant radiotherapy was negatively associated with early recurrence (p = 0.046). Thirty-two per cent of patients with residual tumour and 26% after GTR received adjuvant radiotherapy. There was a significantly lower proportion of favourable outcomes at last follow-up (mRS 0-1) in patients with early recurrence (p = 0.001). CONCLUSIONS: Atypical meningiomas are a heterogeneous group of tumours with 16.8% patients having recurrence within 24 months of surgery. Residual tumour, parafalcine/parasagittal location, peritumoural oedema and a MI > 7 were all independently associated with early recurrence. As administration of adjuvant radiotherapy was not protocolised in this cohort, any conclusions about benefits of irradiation of WHO grade II meningiomas should be viewed with caution. Patients with early recurrence had worse neurological outcome. While histological and imaging characteristics provide some prognostic value, further molecular characterisation of atypical meningiomas is warranted to aid clinical decision making.

Machine learning: a useful radiological adjunct in determination of a newly diagnosed glioma's grade and IDH status.

INTRODUCTION: Machine learning methods have been introduced as a computer aided diagnostic tool, with applications to glioma characterisation on MRI. Such an algorithmic approach may provide a useful adjunct for a rapid and accurate diagnosis of a glioma. The aim of this study is to devise a machine learning algorithm that may be used by radiologists in routine practice to aid diagnosis of both: WHO grade and IDH mutation status in de novo gliomas. METHODS: To evaluate the status quo, we interrogated the accuracy of neuroradiology reports in relation to WHO grade: grade II 96.49% (95% confidence intervals [CI] 0.88, 0.99); III 36.51% (95% CI 0.24, 0.50); IV 72.9% (95% CI 0.67, 0.78). We derived five MRI parameters from the same diagnostic brain scans, in under two minutes per case, and then supplied these data to a random forest algorithm. RESULTS: Machine learning resulted in a high level of accuracy in prediction of tumour grade: grade II/III; area under the receiver operating characteristic curve (AUC) = 98%, sensitivity = 0.82, specificity = 0.94; grade II/IV; AUC = 100%, sensitivity = 1.0, specificity = 1.0; grade III/IV; AUC = 97%, sensitivity = 0.83, specificity = 0.97. Furthermore, machine learning also facilitated the discrimination of IDH status: AUC of 88%, sensitivity = 0.81, specificity = 0.77. CONCLUSIONS: These data demonstrate the ability of machine learning to accurately classify diffuse gliomas by both WHO grade and IDH status from routine MRI alone-without significant image processing, which may facilitate usage as a diagnostic adjunct in clinical practice.

Endovascular thrombectomy beyond 12 hours of stroke onset: a stroke network's experience of late intervention.

BACKGROUND: Selected patients with proximal anterior circulation ischemic stroke who demonstrate limited infarct and sufficient penumbra may benefit from endovascular thrombectomy (EVT) beyond conventional time limits. OBJECTIVE: To perform a retrospective review of all cases of EVT performed at our institution for proximal anterior circulation acute ischemic stroke with onset >12 hours. MATERIALS AND METHODS: Patients were assessed with non-contrast CT brain and multiphase CT angiography, with Alberta Stroke Program Early CT Score (ASPECTS) and collateral grade informing patient selection. Data, including patient demographics, workflow, neuroimaging findings, procedural details, recanalization rates, and 90-day functional outcomes, were collected. RESULTS: Of the 542 consecutive endovascular thrombectomy cases performed during the study period, 25 (4.6%) were >12 hours from stroke onset. Median age was 69 years (IQR 55-80), median National Institute of Health Stroke Scale score on presentation was 14 (IQR 11-18.5), median ASPECTS was 8 (IQR 8-9), and rate of moderate-good collateral status was 96% (n=24). Median time to groin puncture was 14 hours 40 min (IQR 12 hours 36 min - 16 hours 18 min). Rate of successful recanalization (modified Thrombolysis in Cerebral infarction 2b-3) was 88% (n=22). Rate of functional independence (90-day modified Rankin Scale score 0-2) was 52% (n=13). There were no cases of symptomatic intracranial haemorrhage and 90-day mortality rate was 12% (n=3). CONCLUSION: With the use of ASPECTS and collateral grade to guide patient selection, good functional outcome with acceptable safety parameters may be achieved in patients undergoing EVT beyond 12 hours from stroke onset.

Reactive gliosis mimicking tumor recurrence - a case series documenting MRI abnormalities and neuropathological correlates.

The aim of this study is to identify, in our center, all cases of foreign-body reactions to hemostatic agents or other prostheses resulting in a radiological suspicion of tumor recurrence. We interrogated our internal database to identify all such cases and systematically evaluated the MRI brain scans of patients: (i) at the time of initial tumor diagnosis, (ii) postoperatively, (iii) and at the time of suspected tumor recurrence. In addition, we reviewed each patient's operative notes and reviewed the histology of all cases following a second surgical intervention. In total, we identified 8 patients, 7 of whom had a WHO grade II glioma at initial surgery. We did not identify any distinguishing radiological abnormalities from the initial diagnostic brain scan to the suspected recurrence, and histologically all cases were characterized by extensive gliosis; with both macrophages and reactive astrocytes present throughout. The cause of gliosis was identified as being relating to hemostatic agents in 4 cases; in the other 4 cases, the foreign-body reaction was presumed to be caused be materials used in a craniotomy or cranioplasty. This study highlights the difficulty in radiologically diagnosing a foreign-body reaction and also identifies that such a gliotic reaction may occur as a consequence of exogenous materials used in a craniotomy or cranioplasty.
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The DNA copy number landscape of a collision tumor.

Intracranial collision tumors are composed of two histologically distinct but merging components, and are rare. Their genetic profile has rarely been described. Comparative genome hybridization of a combined meningioma and oligodendroglioma demonstrated deletion of chromosome 22q and of 19q in both tumors. Somatic deletion of chromosome 22q and 19q is associated with development of an intracranial collision tumor.
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EBV driven natural killer cell disease of the central nervous system presenting as subacute cognitive decline.

Brain biopsy in patients presenting with subacute encephalopathyis never straightforward and only undertaken when a 'treatable condition' is a realistic possibility. This 63 year old right handed, immunocompetent Caucasian woman presented with an 8 month history of rapidly progressive right-sided hearing impairment, a 4 month history of intermittent headaches, tinnitus, 'dizziness', dysphagia, nausea and vomiting, with the subsequent evolution of progressive gait ataxia and a subacute global encephalopathy. The possibility of CJD was raised. Brain biopsy was carried out. Western blot for prion protein was negative. She died 9 days later and autopsy brain examination confirmed widespread subacute infarction due to an EBV positive atypical NK/T-cell infiltrate with positivity for CD3, CD56, granzyme B, perforin and EBER with absence of CD4, CD5 and CD8 expression. Molecular studies for T-cell clonality were attempted but failed due to insufficient DNA quality. Serology was consistent with past EBV infection (EBV VCA and EBNA IgG Positive). There was no evidence of disease outside the CNS. Primary central nervous system NK/T-cell lymphoma is extremely rare. The rare reported cases all present with a discrete intracranial mass, unlike the diffuse infiltrative pattern in this case. Whilst the diffuse interstitial pattern is reminiscent of chronic active EBV infection (CAEBV) seen in other organ systems such as the liver and bone marrow, the clinical presentation and epidemiologic profile are not typical for CAEBV.

CJD surveillance in the Republic of Ireland from 2005 to 2015: a suggested algorithm for referrals.

Definitive diagnosis of Creutzfeldt Jakob disease (CJD) remains tissue-based. Possible and probable CJD are useful clinical terms but may be used indiscriminately. The aim of this study was to assess the effectiveness of the Irish surveillance system and to ascertain how diagnostic accuracy in identifying clinically "definite" cases might be improved. We reviewed the clinical information, relevant investigations, and samples n = 100; (autopsy n = 87; biopsy n = 13) in 96 patients between January 1, 2005 and December 31, 2015. In 4 cases both a biopsy and autopsy were performed. CJD was confirmed in 50 patients (45 at autopsy and 5 at biopsy). Sporadic CJD (sCJD) accounted for 90% of cases (n = 45); variant CJD (vCJD) for 6% (n = 3) with 1 case each of familial CJD and iatrogenic CJD. CSF 14-3-3, EEG, and MRI investigations were helpful but not available on all patients. CJD mimics (n = 46) fell into the following categories: neurodegenerative (n = 22), immune mediated (n = 3), cerebrovascular disease (n = 5), tumor (n = 5), dual pathology (n = 3), and miscellaneous (n = 8). The Irish surveillance system fulfils its main objective as all clinically suspicious cases are being referred. CJD was confirmed in 52% (n = 50/96) of referrals. Based on this, we propose an algorithm for CJD referrals to reduce both infection control and diagnostic difficulties encountered in CJD surveillance.
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