E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious.

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Encephalitis Benedict Daniel Michael Benedict Michael (NIHR Doctoral Research Registrar in Neurology) works at the Institute of Infection ad Global Health, University of Liverpool and the Walton Centre for Neurology NHS Foundation Trust, Liverpool. He has a particular interest in both clinical practice and research into neurological infectious diseases and the para-infectious neuroimmunological response. He is also involved in the development and dissemination of national guidelines for neurological diseases. Edited by Prof Tom Solomon and Dr Agam Jung This session provides an overview of issues relating to the clinical features, acute investigation, diagnosis and management of encephalitis.

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Learning Objectives By the end of this session you will be able to: State the pathogenesis of encephalitis Describe the clinical features which should raise suspicion of encephalitis Define the appropriate acute investigations which should be performed for patients with suspected encephalitis Explain the appropriate treatment for encephalitis

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Overview This session explores the aetiology, clinical features, acute investigations and treatment of patients with suspected encephalitis. First it examines why cases of encephalitis are missed or diagnosed and treated late. This is important as mortality rates are 70% in untreated cases and can be as low as 10-20% if patients are treated early. Image from: http//pathology.mc.duke.edu/neuropath/CNSlecture2/hsv.jp Then it explains how pitfalls in missing or delaying diagnosis can be avoided. Finally, it provides a clear, structured approach to investigation, diagnosis and treatment of encephalitis. The first section begins with an overview of encephalitis.

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Pathogenesis of encephalitis I Encephalitis is defined as inflammation of the brain parenchyma. This is most commonly due to infection, typically with viruses, or less commonly, intracellular bacteria and mycobacteria. The most common viral causes of encephalitis are: Herpes simplex virus (HSV)1 Varicella zoster virus (VZV) These account for approximately 19% and 5% of cases respectively. Other causes of encephalitis include an 'acute disseminated encephalomyelitis' (ADEM) in approximately 11%, where encephalitis follows infection or vaccination. Additionally, antibody-mediated causes for encephalitis have been identified, most commonly those due to anti-NMDA and anti-VGKC antibodies, which account for 4% and 3% of cases respectively. The former is often a paraneoplastic process.

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Pathogenesis of encephalitis II The aetiology of encephalitis varies widely by age, geographical location and immune status. The table below demonstrates the findings of a recent Health Protection Agency study of 203 patients in the UK. ADEM= Acute disseminated encephalomyelitis; ANT= Antibody-associated cause; HSV= Herpes simplex virus; MTB= Mycobacterium tuberculosis; VZV=Varicella zoster virus

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Unknown Aetiology In approximately 40% of cases, the aetiology remains unknown. Urgent and thorough investigation, particularly examination of the cerebrospinal fluid (CSF) by performing a lumbar puncture (LP), maximises the chance of identifying the cause. This figure is derived from a systematic review of studies of encephalitis by country demonstrating the proportion of cases in which a pathogen is not identified.

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Causes of Encephalitis I Encephalitis can be caused by a wide range of pathogens in the immunocompetent and an even wider variety in the immunocompromised. Variation between the proportion of cases due to the common pathogens in the immunocompetent and the immunocompromised are outlined in a table on the following page from a recent study conducted in England. There is significant global variation in the incidence of causal pathogens reflecting endemic rates of human immunodeficiency virus (HIV) and tuberculosis infection, malnutrition and vaccination programmes. Additionally, viral vector prevalence is particularly important for arbovirus encephalitis, such as Japanese encephalitis virus and West Nile virus. Although this is typically limited to developing countries, recent outbreaks of the latter virus have been seen in the USA and southern Europe.

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Causes of Encephalitis II

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Suspicious clinical features I The classical clinical features are headache or altered or reduced consciousness or personality or behaviour change in a patient with a fever or history of a febrile illness. However, as demonstrated in the table on the following page, approximately 28% of patients with encephalitis are not febrile on admission. Indeed, in the same study 11% of patients with proven HSV encephalitis were not febrile on admission. Additionally, encephalitis should be considered for patients with new onset seizures, particularly if refractory. Altered consciousness, personality or behaviour should not be attributed to an infection outside of the central nervous system, such as a urinary tract infection, in an otherwise healthy patient unless there is strong evidence for this. Indeed, many patients with proven encephalitis will have gastrointestinal, respiratory or urinary symptoms.

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Suspicious clinical features II Adapted from Granerod et al. 2010

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Suspicious clinical features III The wide range of clinical features require that many patients are investigated. In a recent study, of 217 patients with suspected CNS infections at 10 hospitals, 44 had the diagnosis confirmed. Clinical features supporting the diagnosis of a CNS infection are outlined in the table below.

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Suspicious clinical features IV Often there is both clinical and histopathological overlap between encephalitis and meningitis and the term 'meningoencephalitis' is often used. Nevertheless, clinical features reflecting involvement of the brain parenchyma may point towards a diagnosis of encephalitis: Seizures Focal neurological signs (including movement disorders) Neuropsychiatric features Do not rely on a low Glasgow coma score as this is a very crude proxy of cerebral dysfunction. Indeed, in the two recent studies described only 5 of 13 (38%) had a GCS<15 and 37 of 203 (18%) had a GCS <8. Instead get a collateral history and assess this and the patient carefully for evidence of altered personality, behaviour and cognition, including neuro- psychiatric features. Never dismiss the statement of a friend or relative that a patient is 'not quite themselves'. Perform a full neurological examination, including mental state assessment and fundoscopy.

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Acute Diagnosis I A diagnostic algorithm can be found on the following page. CSF examination from a lumbar puncture (LP) is the most important investigation as this can confirm or refute the diagnosis and direct treatment towards a viral, bacterial or mycobacterial pathogen. Lumbar Puncture: An LP should be performed urgently for all patients in whom encephalitis is suspected unless there are clinical contraindications, as outlined on the following page. These clinical features have been found to be reliable and sensitive at identifying which patients are likely to have brain shift precluding an LP. CT scan: If the clinical contraindications are present, a computed tomography (CT) scan of the brain should be arranged urgently and if this does not show the outlined features, an urgent LP performed. Coagulation abnormalities Patients with coagulation abnormalities should these corrected before performing a LP and platelet count should be >100x109/L.

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Acute Diagnosis II

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Investigations I Often clinicians inappropriately request a CT to 'rule out raised intracranial pressure before an LP'. However, a CT scan cannot do this and indeed an LP may be safe in patients with raised intracranial pressure. The CT should only be performed before an LP to identify if significant brain shift is present, thereby precluding an LP in those patients in whom it is likely, as determined by the clinical features outlined. Delays in performing the LP have been demonstrated to delay the diagnosis and treatment in acute CNS infections and this results in increased morbidity and mortality. The routine CSF parameters and interpretation are shown in the table on the following page. The first CSF white cell count may be normal in approximately 10% of cases. If the clinical suspicion remains, the LP should be repeated 24- 48 hours later.

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Investigations II

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment A staged approach to pathogen detection I Although a wide range of pathogens can cause encephalitis, a staged approach to pathogen identification as outlined in the table below provides a pragmatic way to proceed:

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment A staged approach to pathogen detection II The ancillary investigations outlined in the table opposite can establish concomitant systemic infection, but not necessarily the cause of the encephalitis. Samples from sterile sites, such as vesicle swabs for VZV are more likely to represent active infection than non-sterile sites, such as faeces for enteroviruses, as this may represent asymptomatic shedding.

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment MRI and EEG Additionally, euro-imaging, preferably magnetic resonance imaging (MRI), can identify evidence of brain parenchymal inflammation. This may also point towards the aetiology, for example: Fronto-temporal changes may be seen in HSV encephalitis Hippocampal changes in limbic encephalitis, such as that due to VGKC antibodies Basal ganglia changes in some arboviral encephalitides Brain stem changes are seen in rhombencephalitis, such as that due to Listeria monocytogenes Electroencephalography (EEG) should be requested when subtle-motor or non-convulsive status epilepticus is suspected, for example a patient with fluctuating levels of consciousness, or if subtle motor features such as eye lid movement, are present.EEG can also be useful if it is unclear if the presentation is due to a primary psychiatric cause or encephalitis.

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Appropriate treatment for encephalitis Attention should be given to: Oxygenation Fluid and hydration Nasogastric or parenteral feeding Treating the complications, such as pneumonia Patients with a reduced coma score or impaired gag reflex, should be assessed by an intensive care team. In most immunocompetent patients, aciclovir (10mg/kg three times/day) should be given intravenously as soon as there is a strong suspicion of viral encephalitis, based on the clinical presentation and initial CSF and/or imaging findings. If performing these investigations is likely to lead to long delays and the clinical suspicion is strong, then treatment should be started at once. Aciclovir is a nucleoside analogue that reduces mortality from around 70% to 10-20% when encephalitis is due to herpes viruses including HSV and VZV. However, approximately 60% of survivors have significant neurological and neuro-psychiatric morbidity.

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Renal Function Renal function should be monitored closely and adequate hydration maintained because of the rare risk of renal failure. Other rare adverse effects include local inflammation at the site of the intravenous cannula, hepatitis, and bone marrow failure. As it is often not possible to determine whether the infection is due to a virus or bacteria in the acute phase, it is reasonable to commence both aciclovir and a 3rd generation cephalosporin. Nevertheless, due to the risks of opportunistic infection, antibiotic resistance and nephrotoxicity, the prescription of antimicrobials should be regularly reviewed in the light of test results.

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Treatments in use Antibody-mediated encephalitis, such as that due to voltage-gated potassium channel or N-methyl D-apartate receptor antibodies, often respond well to immune suppression. This includes plasma exchange or intravenous steroids in the acute phase and prolonged immunesuppression, such as with cyclosporin, to maintain remission. However, there is currently no consensus clinical guidance as to which treatments to use. Therefore, these patients should be managed under specialist neurology supervision. Patients and their family should be put in contact with patient-orientated support services, such as the Encephalitis Society, so that they have improved access to information, neuropsychological and social support.

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment 2012 guidelines for the management of suspected viral encephalitis Click below to view a flow chart summary of the most recent guidelines on the management of encephalitis: For the full guidelines see: Journal of Infection 2012, 64; issue 4: 347–373 (adult) and issue 5: 449-477 (children). Association of British Neurologists and British Infection Association guidelines 2012 on management of suspected viral encephalitis in adults and children

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Key Points Encephalitis is an important neurological emergency because early diagnosis and treatment decreases the risk of mortality and significant neurological morbidity. There are a wide range of clinical features that can be seen, but the presence of acute alteration or reduction in consciousness, or personality or behaviour change should raise suspicion of encephalitis. Not all patients will be febrile or have a history of fever. If clinical suspicion remains, two lumbar punctures, performed 24-48 hours apart are required to exclude the diagnosis. The lumbar puncture does not have to be delayed for neuro- imaging unless specific clinical contraindications are present

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Summary Having completed this session you will now be able to: State the pathogenesis of encephalitis Describe the clinical features which should raise suspicion of encephalitis Define the appropriate acute investigations which should be performed for patients with suspected encephalitis Explain the appropriate treatment for encephalitis References and further reading: 1.Solomon T, Hart I, Beeching NJ. Viral Encephalitis: A clinician's guide. Practical Neurology 2007; 7:288-305. 2.Granerod J, Ambrose HE, Davies NWS, Clewley JP et al. Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infectious Diseases 2010; 10: 835–44. 3.Michael BD, Sidhu M, Stoeter D, Roberts M, et al. The Epidemiology and Management of Adult Suspected Central Nervous System Infections - a retrospective cohort study in the NHS Northwest Region. Quarterly Journal of Medicine 2010; doi:10.1093/qjmed/hcq121. 4.Granerod J, Tam CC, Crowcroft NS, et al. Challenge of the unknown : A systematic review of acute encephalitis in non-outbreak situations. Neurology 2010;75;924.

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Question 1 Which one of the below statements is correct? a)All patients with encephalitis have a fever on admission or a history of fever.All patients with encephalitis have a fever on admission or a history of fever. b)The Glasgow Coma Scale (GCS) is a sensitive marker of brain dysfunction.The Glasgow Coma Scale (GCS) is a sensitive marker of brain dysfunction. c)A computed tomography (CT) scan cannot exclude raised Intracranial Pressure (ICP).A computed tomography (CT) scan cannot exclude raised Intracranial Pressure (ICP). d)Raised ICP is a contraindication to Lumbar Puncture.Raised ICP is a contraindication to Lumbar Puncture. e)If the initial LP shows a normal white cell count and clinical suspicion remains the LP should be repeated 6 days later.If the initial LP shows a normal white cell count and clinical suspicion remains the LP should be repeated 6 days later. Which one of the below statements is correct? a)All patients with encephalitis have a fever on admission or a history of fever.All patients with encephalitis have a fever on admission or a history of fever. b)The Glasgow Coma Scale (GCS) is a sensitive marker of brain dysfunction.The Glasgow Coma Scale (GCS) is a sensitive marker of brain dysfunction. c)A computed tomography (CT) scan cannot exclude raised Intracranial Pressure (ICP).A computed tomography (CT) scan cannot exclude raised Intracranial Pressure (ICP). d)Raised ICP is a contraindication to Lumbar Puncture.Raised ICP is a contraindication to Lumbar Puncture. e)If the initial LP shows a normal white cell count and clinical suspicion remains the LP should be repeated 6 days later.If the initial LP shows a normal white cell count and clinical suspicion remains the LP should be repeated 6 days later.

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Question 1 a) INCORRECT Many patients do not have a fever on admission or a history of fever. Please choose another option a) INCORRECT Many patients do not have a fever on admission or a history of fever. Please choose another option Which one of the below statements is correct? a)All patients with encephalitis have a fever on admission or a history of fever.All patients with encephalitis have a fever on admission or a history of fever. b)The Glasgow Coma Scale (GCS) is a sensitive marker of brain dysfunction.The Glasgow Coma Scale (GCS) is a sensitive marker of brain dysfunction. c)A computed tomography (CT) scan cannot exclude raised Intracranial Pressure (ICP).A computed tomography (CT) scan cannot exclude raised Intracranial Pressure (ICP). d)Raised ICP is a contraindication to Lumbar Puncture.Raised ICP is a contraindication to Lumbar Puncture. e)If the initial LP shows a normal white cell count and clinical suspicion remains the LP should be repeated 6 days later.If the initial LP shows a normal white cell count and clinical suspicion remains the LP should be repeated 6 days later. Which one of the below statements is correct? a)All patients with encephalitis have a fever on admission or a history of fever.All patients with encephalitis have a fever on admission or a history of fever. b)The Glasgow Coma Scale (GCS) is a sensitive marker of brain dysfunction.The Glasgow Coma Scale (GCS) is a sensitive marker of brain dysfunction. c)A computed tomography (CT) scan cannot exclude raised Intracranial Pressure (ICP).A computed tomography (CT) scan cannot exclude raised Intracranial Pressure (ICP). d)Raised ICP is a contraindication to Lumbar Puncture.Raised ICP is a contraindication to Lumbar Puncture. e)If the initial LP shows a normal white cell count and clinical suspicion remains the LP should be repeated 6 days later.If the initial LP shows a normal white cell count and clinical suspicion remains the LP should be repeated 6 days later.

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Question 1 b) INCORRECT The GCS is insensitive and personality or behaviour change and neuro-psychiatric features are common. Please choose another option b) INCORRECT The GCS is insensitive and personality or behaviour change and neuro-psychiatric features are common. Please choose another option Which one of the below statements is correct? a)All patients with encephalitis have a fever on admission or a history of fever.All patients with encephalitis have a fever on admission or a history of fever. b)The Glasgow Coma Scale (GCS) is a sensitive marker of brain dysfunction.The Glasgow Coma Scale (GCS) is a sensitive marker of brain dysfunction. c)A computed tomography (CT) scan cannot exclude raised Intracranial Pressure (ICP).A computed tomography (CT) scan cannot exclude raised Intracranial Pressure (ICP). d)Raised ICP is a contraindication to Lumbar Puncture.Raised ICP is a contraindication to Lumbar Puncture. e)If the initial LP shows a normal white cell count and clinical suspicion remains the LP should be repeated 6 days later.If the initial LP shows a normal white cell count and clinical suspicion remains the LP should be repeated 6 days later. Which one of the below statements is correct? a)All patients with encephalitis have a fever on admission or a history of fever.All patients with encephalitis have a fever on admission or a history of fever. b)The Glasgow Coma Scale (GCS) is a sensitive marker of brain dysfunction.The Glasgow Coma Scale (GCS) is a sensitive marker of brain dysfunction. c)A computed tomography (CT) scan cannot exclude raised Intracranial Pressure (ICP).A computed tomography (CT) scan cannot exclude raised Intracranial Pressure (ICP). d)Raised ICP is a contraindication to Lumbar Puncture.Raised ICP is a contraindication to Lumbar Puncture. e)If the initial LP shows a normal white cell count and clinical suspicion remains the LP should be repeated 6 days later.If the initial LP shows a normal white cell count and clinical suspicion remains the LP should be repeated 6 days later.

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Question 1 Which one of the below statements is correct? a)All patients with encephalitis have a fever on admission or a history of fever. b)The Glasgow Coma Scale (GCS) is a sensitive marker of brain dysfunction. c)A computed tomography (CT) scan cannot exclude raised Intracranial Pressure (ICP). d)Raised ICP is a contraindication to Lumbar Puncture. e)If the initial LP shows a normal white cell count and clinical suspicion remains the LP should be repeated 6 days later. Which one of the below statements is correct? a)All patients with encephalitis have a fever on admission or a history of fever. b)The Glasgow Coma Scale (GCS) is a sensitive marker of brain dysfunction. c)A computed tomography (CT) scan cannot exclude raised Intracranial Pressure (ICP). d)Raised ICP is a contraindication to Lumbar Puncture. e)If the initial LP shows a normal white cell count and clinical suspicion remains the LP should be repeated 6 days later. c) CORRECT A CT cannot exclude raised ICP. Many patients do not have a fever on admission or a history of fever, whilst the GCS is insensitive and personality or behaviour change and neuro-psychiatric features are common. A LP is contraindicated when there is brain shift or tight basal cisterns, but may be safe if these features are not present, but there is raised ICP. If the white cell count is normal the LP should be repeated after 24-48 hours. Click here to move onto the next questionClick here to move onto the next question c) CORRECT A CT cannot exclude raised ICP. Many patients do not have a fever on admission or a history of fever, whilst the GCS is insensitive and personality or behaviour change and neuro-psychiatric features are common. A LP is contraindicated when there is brain shift or tight basal cisterns, but may be safe if these features are not present, but there is raised ICP. If the white cell count is normal the LP should be repeated after 24-48 hours. Click here to move onto the next questionClick here to move onto the next question

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Question 1 d) INCORRECT A LP is contraindicated when there is brain shift or tight basal cisterns, but may be safe if these features are not present, but there is raised ICP. Please choose another option d) INCORRECT A LP is contraindicated when there is brain shift or tight basal cisterns, but may be safe if these features are not present, but there is raised ICP. Please choose another option Which one of the below statements is correct? a)All patients with encephalitis have a fever on admission or a history of fever.All patients with encephalitis have a fever on admission or a history of fever. b)The Glasgow Coma Scale (GCS) is a sensitive marker of brain dysfunction.The Glasgow Coma Scale (GCS) is a sensitive marker of brain dysfunction. c)A computed tomography (CT) scan cannot exclude raised Intracranial Pressure (ICP).A computed tomography (CT) scan cannot exclude raised Intracranial Pressure (ICP). d)Raised ICP is a contraindication to Lumbar Puncture.Raised ICP is a contraindication to Lumbar Puncture. e)If the initial LP shows a normal white cell count and clinical suspicion remains the LP should be repeated 6 days later.If the initial LP shows a normal white cell count and clinical suspicion remains the LP should be repeated 6 days later. Which one of the below statements is correct? a)All patients with encephalitis have a fever on admission or a history of fever.All patients with encephalitis have a fever on admission or a history of fever. b)The Glasgow Coma Scale (GCS) is a sensitive marker of brain dysfunction.The Glasgow Coma Scale (GCS) is a sensitive marker of brain dysfunction. c)A computed tomography (CT) scan cannot exclude raised Intracranial Pressure (ICP).A computed tomography (CT) scan cannot exclude raised Intracranial Pressure (ICP). d)Raised ICP is a contraindication to Lumbar Puncture.Raised ICP is a contraindication to Lumbar Puncture. e)If the initial LP shows a normal white cell count and clinical suspicion remains the LP should be repeated 6 days later.If the initial LP shows a normal white cell count and clinical suspicion remains the LP should be repeated 6 days later.

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Question 1 e) INCORRECT LP should be repeated 24-48hours later. Please choose another option e) INCORRECT LP should be repeated 24-48hours later. Please choose another option Which one of the below statements is correct? a)All patients with encephalitis have a fever on admission or a history of fever.All patients with encephalitis have a fever on admission or a history of fever. b)The Glasgow Coma Scale (GCS) is a sensitive marker of brain dysfunction.The Glasgow Coma Scale (GCS) is a sensitive marker of brain dysfunction. c)A computed tomography (CT) scan cannot exclude raised Intracranial Pressure (ICP).A computed tomography (CT) scan cannot exclude raised Intracranial Pressure (ICP). d)Raised ICP is a contraindication to Lumbar Puncture.Raised ICP is a contraindication to Lumbar Puncture. e)If the initial LP shows a normal white cell count and clinical suspicion remains the LP should be repeated 6 days later.If the initial LP shows a normal white cell count and clinical suspicion remains the LP should be repeated 6 days later. Which one of the below statements is correct? a)All patients with encephalitis have a fever on admission or a history of fever.All patients with encephalitis have a fever on admission or a history of fever. b)The Glasgow Coma Scale (GCS) is a sensitive marker of brain dysfunction.The Glasgow Coma Scale (GCS) is a sensitive marker of brain dysfunction. c)A computed tomography (CT) scan cannot exclude raised Intracranial Pressure (ICP).A computed tomography (CT) scan cannot exclude raised Intracranial Pressure (ICP). d)Raised ICP is a contraindication to Lumbar Puncture.Raised ICP is a contraindication to Lumbar Puncture. e)If the initial LP shows a normal white cell count and clinical suspicion remains the LP should be repeated 6 days later.If the initial LP shows a normal white cell count and clinical suspicion remains the LP should be repeated 6 days later.

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Question 2 Match the statements to the most appropriate numbers below. To see if you are correct click on the number you believe to match with the statement in bold on each page. Approximate percentage of cases of unknown cause Dose of aciclovir (in mg/kg) required 3 times a day HSV type that is the most common viral cause of encephalitis Immunocompromised patients should be tested for this Herpes subtype. Number of hours after a normal LP that it should be repeated Below this platelet count a LP should not be performed (x10 9 /l) Approximate % mortality in untreated HSV encephalitis Approximate % cases due to HSV Approx % due to voltage-gated potassium channel antibodies 24-4824-48 6 10019 40 110 70 461001940110704 Approximate percentage of cases of unknown cause Dose of aciclovir (in mg/kg) required 3 times a day HSV type that is the most common viral cause of encephalitis Immunocompromised patients should be tested for this Herpes subtype. Number of hours after a normal LP that it should be repeated Below this platelet count a LP should not be performed (x10 9 /l) Approximate % mortality in untreated HSV encephalitis Approximate % cases due to HSV Approx % due to voltage-gated potassium channel antibodies 24-4824-48 6 10019 40 110 70 461001940110704

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Question 2 INCORRECT Try one of the alternative answers in order to progress or read more by using the links on the left hand side INCORRECT Try one of the alternative answers in order to progress or read more by using the links on the left hand side Approximate percentage of cases of unknown cause Dose of aciclovir (in mg/kg) required 3 times a day HSV type that is the most common viral cause of encephalitis Immunocompromised patients should be tested for this Herpes subtype. Number of hours after a normal LP that it should be repeated Below this platelet count a LP should not be performed (x10 9 /l) Approximate % mortality in untreated HSV encephalitis Approximate % cases due to HSV Approx % due to voltage-gated potassium channel antibodies 24-4824-48 6 10019 40 110 70 461001940110704 Approximate percentage of cases of unknown cause Dose of aciclovir (in mg/kg) required 3 times a day HSV type that is the most common viral cause of encephalitis Immunocompromised patients should be tested for this Herpes subtype. Number of hours after a normal LP that it should be repeated Below this platelet count a LP should not be performed (x10 9 /l) Approximate % mortality in untreated HSV encephalitis Approximate % cases due to HSV Approx % due to voltage-gated potassium channel antibodies 24-4824-48 6 10019 40 110 70 461001940110704

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Question 2 Approximate percentage of encephalitis cases of unknown cause Dose of aciclovir (in mg/kg) required 3 times a day HSV type that is the most common viral cause of encephalitis Immunocompromised patients should be tested for this Herpes subtype. Number of hours after a normal LP that it should be repeated Below this platelet count a LP should not be performed (x10 9 /l) Approximate % mortality in untreated HSV encephalitis Approximate % cases due to HSV Approx % due to voltage-gated potassium channel antibodies 24-4824-48 6 10019 40 110 70 461001940110704 Approximate percentage of encephalitis cases of unknown cause Dose of aciclovir (in mg/kg) required 3 times a day HSV type that is the most common viral cause of encephalitis Immunocompromised patients should be tested for this Herpes subtype. Number of hours after a normal LP that it should be repeated Below this platelet count a LP should not be performed (x10 9 /l) Approximate % mortality in untreated HSV encephalitis Approximate % cases due to HSV Approx % due to voltage-gated potassium channel antibodies 24-4824-48 6 10019 40 110 70 461001940110704 CORRECT Move on to the next statement: CORRECT Move on to the next statement:

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Question 2 INCORRECT Try one of the alternative answers in order to progress or read more by using the links on the left hand side INCORRECT Try one of the alternative answers in order to progress or read more by using the links on the left hand side Approximate percentage of encephalitis cases of unknown cause Dose of aciclovir (in mg/kg) required 3 times a day HSV type that is the most common viral cause of encephalitis Immunocompromised patients should be tested for this Herpes subtype. Number of hours after a normal LP that it should be repeated Below this platelet count a LP should not be performed (x10 9 /l) Approximate % mortality in untreated HSV encephalitis Approximate % cases due to HSV Approx % due to voltage-gated potassium channel antibodies 24-4824-48 6 10019 40 110 70 461001940110704 Approximate percentage of encephalitis cases of unknown cause Dose of aciclovir (in mg/kg) required 3 times a day HSV type that is the most common viral cause of encephalitis Immunocompromised patients should be tested for this Herpes subtype. Number of hours after a normal LP that it should be repeated Below this platelet count a LP should not be performed (x10 9 /l) Approximate % mortality in untreated HSV encephalitis Approximate % cases due to HSV Approx % due to voltage-gated potassium channel antibodies 24-4824-48 6 10019 40 110 70 461001940110704

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Question 2 Approximate percentage of encephalitis cases of unknown cause Dose of aciclovir (in mg/kg) required 3 times a day HSV type that is the most common viral cause of encephalitis Immunocompromised patients should be tested for this Herpes subtype. Number of hours after a normal LP that it should be repeated Below this platelet count a LP should not be performed (x10 9 /l) Approximate % mortality in untreated HSV encephalitis Approximate % cases due to HSV Approx % due to voltage-gated potassium channel antibodies 24-4824-48 6 10019 40 110 70 46100194011070 4 Approximate percentage of encephalitis cases of unknown cause Dose of aciclovir (in mg/kg) required 3 times a day HSV type that is the most common viral cause of encephalitis Immunocompromised patients should be tested for this Herpes subtype. Number of hours after a normal LP that it should be repeated Below this platelet count a LP should not be performed (x10 9 /l) Approximate % mortality in untreated HSV encephalitis Approximate % cases due to HSV Approx % due to voltage-gated potassium channel antibodies 24-4824-48 6 10019 40 110 70 46100194011070 4 CORRECT Move on to the next statement: CORRECT Move on to the next statement:

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Question 2 INCORRECT Try one of the alternative answers in order to progress or read more by using the links on the left hand side INCORRECT Try one of the alternative answers in order to progress or read more by using the links on the left hand side Approximate percentage of encephalitis cases of unknown cause Dose of aciclovir (in mg/kg) required 3 times a day HSV type that is the most common viral cause of encephalitis Immunocompromised patients should be tested for this Herpes subtype. Number of hours after a normal LP that it should be repeated Below this platelet count a LP should not be performed (x10 9 /l) Approximate % mortality in untreated HSV encephalitis Approximate % cases due to HSV Approx % due to voltage-gated potassium channel antibodies 24-4824-48 6 10019 40 110 70 46100194011070 4 Approximate percentage of encephalitis cases of unknown cause Dose of aciclovir (in mg/kg) required 3 times a day HSV type that is the most common viral cause of encephalitis Immunocompromised patients should be tested for this Herpes subtype. Number of hours after a normal LP that it should be repeated Below this platelet count a LP should not be performed (x10 9 /l) Approximate % mortality in untreated HSV encephalitis Approximate % cases due to HSV Approx % due to voltage-gated potassium channel antibodies 24-4824-48 6 10019 40 110 70 46100194011070 4

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious clinical features Acute diagnosis Investigations Staged approach to pathogen detectionStaged approach to pathogen detection MRI & EEG Key management Renal Function Other treatments 2012 Guidelines Key Points Summary Self assessment Question 2 Approximate percentage of encephalitis cases of unknown cause= 40 Dose of aciclovir (in mg/kg) required 3 times a day= 10 HSV type that is the most common viral cause of encephalitis= 1 Immunocompromised patients should be tested for this Herpes virus subtype= 6 Number of hours after a normal LP that it should be repeated= 24-48 Below this platelet count a LP should not be performed (x10 9 /l)= 100 Approximate % mortality in untreated HSV encephalitis= 70 Approximate % cases due to HSV= 19 Approx % due to voltage-gated potassium channel antibodies= 4 Approximate percentage of encephalitis cases of unknown cause= 40 Dose of aciclovir (in mg/kg) required 3 times a day= 10 HSV type that is the most common viral cause of encephalitis= 1 Immunocompromised patients should be tested for this Herpes virus subtype= 6 Number of hours after a normal LP that it should be repeated= 24-48 Below this platelet count a LP should not be performed (x10 9 /l)= 100 Approximate % mortality in untreated HSV encephalitis= 70 Approximate % cases due to HSV= 19 Approx % due to voltage-gated potassium channel antibodies= 4 CORRECT Review the summary below then click here to finish the session.click here to finish the session CORRECT Review the summary below then click here to finish the session.click here to finish the session

Congratulations on completing this module and thank you for using NeuroID: elearning. We hope to see you at a NeuroID: Liverpool Neurological Infectious Diseases Course soon. Download a certificateDownload a certificate and then CLICK HERE to finish the module.CLICK HERE

Liverpool Medical Institution, UK Provisional date: May 2013 NeuroID 2013: Liverpool Neurological Infectious Diseases Course Ever struggled with a patient with meningitis or encephalitis, and not known quite what to do? Then the Liverpool Neurological infectious Diseases Course is for you! For Trainees and Consultants in Adult and Paediatric Neurology, Infectious Diseases, Acute Medicine, Emergency Medicine and Medical Microbiology who want to update their knowledge, and improve their skills. For more information and to REGISTER NOW VISIT: www.liv.ac.uk/neuroidcoursewww.liv.ac.uk/neuroidcourse Presented by Leaders in the Field Commonly Encountered Clinical Problems Practical Management Approaches Rarities for Reference Interactive Case Presentations State of the Art Updates Pitfalls to Avoid Controversies in Neurological Infections To learn more about neurological infectious diseases… Convenors: Prof Tom Solomon, Dr Enitan Carrol, Dr Rachel Kneen, Dr Nick Beeching, Dr Benedict Michael Feedback from previous course: “Would unreservedly recommend to others” “An excellent 2 days!! The best course for a long time”

E NCEPHALITIS Learning Objectives Overview Pathogenesis Cases of unknown aetiologyCases of unknown aetiology Causes Suspicious clinical featuresSuspicious.

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