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V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations.

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Presentation on theme: "V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations."— Presentation transcript:

1 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Viral Meningitis Dr Fiona McGill Dr Fiona McGill is a specialist registrar in infectious diseases and medical microbiology in the Yorkshire and Humber Deanery and a clinical research fellow with the Liverpool Brain Infections Group at the University of Liverpool. Edited by Prof Tom Solomon and Dr Agam Jung Viral meningitis is a common illness in the UK and abroad. It is often quoted as being a benign, self-limiting illness. Although the disease is rarely fatal in adults, there is mounting evidence that it can cause important complications in certain patients. This session will present the current evidence and clinical guidelines to guide the management of patients with viral meningitis. Adapted with kind permission from: McGill F, Michael B, Solomon T. Viral meningitis in adults – a practical approach. BMJ Learning 2012

2 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Learning Objectives After completing this module, you should know: That viral meningitis is a common problem in the UK The important causes of aseptic meningitis How to manage a patient with meningism and a raised lymphocyte count in their cerebrospinal fluid How to differentiate between viral and bacterial causes of meningitis The difference between viral meningitis and viral encephalitis The possible outcomes for patients with viral meningitis.

3 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Overview Meningitis is inflammation of the meninges which surround the brain and spinal cord. It is normally due to an infection and can be caused by viruses, bacteria or fungi. This module focuses on viral meningitis. Viral meningitis is an important cause of morbidity. You must be able to differentiate viral meningitis from both bacterial meningitis and viral encephalitis. This is because bacterial meningitis and viral encephalitis are associated with a higher mortality and morbidity rate than viral meningitis. You should not use the terms viral meningitis and aseptic meningitis interchangeably. In a patient with symptoms of meningism, aseptic meningitis is defined as: a cerebrospinal fluid (CSF) with a white cell count of over 5 x 10 6 /L (>5 cells/mm 3 ) with a negative bacterial culture of the CSF RIGHT: The meninges of the central nervous system consist of the dura mater, arachnoid and pia mater

4 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Causes of Aseptic Meningitis Viral meningitis is a type of aseptic meningitis. Aseptic meningitis has many other causes in addition to viruses. Some common and less common causes of aseptic meningitis are shown in the below table. Causes of aseptic meningitis (adapted from Meningitis, Chapter 41, Brain’s Diseases of the Nervous System by T. Solomon).

5 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Epidemiology Although viral meningitis is a notifiable disease, the exact incidence is unknown as it is probably under-diagnosed and under-reported. In England and Wales in 2009, 260 episodes of viral meningitis were notified to the Health Protection Agency (HPA). More detailed epidemiological studies have estimated that the true rate of disease may be about 10 to 14 times this number. So the number of notified episodes is likely to be a gross underestimate. In the UK, the most common viruses that cause viral meningitis are the enteroviruses and the herpes viruses. Other viruses, such as enterovirus serotype 71, may be the cause in people who are on holiday or resident in other countries. Some other tropical viruses can cause an aseptic meningitis, but more frequently cause encephalitis than meningitis. These include dengue, Japanese encephalitis, and West Nile virus. These are beyond the scope of this module.

6 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Features Patients with viral meningitis present with signs of meningeal irritation, termed ‘meningism’, and fever. Meningism refers to neck stiffness, headache and photophobia. Fever is often the most common presenting feature and neck stiffness the least common,but viral meningitis can and does occur in the absence of fever. Other non-specific symptoms are often also present, including diarrhoea and vomiting, muscle pain, and sore throat. There is usually no reduced conscious level in patients with viral meningitis. An alteration in conscious level suggests an alternative diagnosis, for example: Bacterial meningitis Encephalitis (inflammation of the brain substance) Encephalopathy due to infection outside the central nervous system, which is termed ‘septic encephalopathy’. Sometimes a patient does not present clearly with either meningitis or encephalitis and this is termed meningoencephalitis, implying involvement of the brain substance as well as the meninges.

7 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Approach to Investigation There are several British and international guidelines on meningitis and encephalitis in adults from: The British Infection Association (BIA) The BIA and Association of British Neurologists (the National Encephalitis Guideline). Infectious Diseases Society of America This section outlines the best approach to investigations, as recommended by these guidelines.

8 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Lumbar Puncture I It is difficult to differentiate viral meningitis from bacterial meningitis on clinical grounds alone, as patients can present with meningism and fever in both diseases. Therefore a lumbar puncture is necessary to confirm the diagnosis of meningitis and look for a causative agent. Unless there are specific clinical contraindications to lumbar puncture, a CT brain is NOT necessary before proceeding to lumbar puncture. You should send CSF to the laboratory and request the following tests on it: Microscopy and culture (2 bottles) – this will also give the white and red cell counts with a white cell differential Protein Glucose (you must also perform a simultaneous blood glucose) You should send a further sample of CSF to the laboratory for storage. If an increase in lymphocytes (lymphocytosis) is identified, you should then send this CSF for PCR (polymerase chain reaction). This will look for causative viruses. Depending on the results from the CSF, further tests may be necessary.

9 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Lumbar Puncture II Features that suggest viral meningitis include: A raised white cell count in the CSF (>5 cells/mm 3 in adults) with a predominance of lymphocytes (although neutrophils may predominate if the lumbar puncture is done early in the disease) Mildly raised protein (0.5 to 1 g/L) Normal ratio of glucose in CSF:blood (>66%) (Most textbooks quote 66% as the normal ratio, but only values of <50% are likely to be clinically important, e.g. bacterial meningitis.) PCR is now the gold standard for diagnosing the causative agent in viral meningitis. Most laboratories in the UK will test for enteroviruses, herpes simplex viruses (HSV) types 1 and 2, and varicella zoster virus (VZV). Some laboratories also test for parechoviruses and other less common viruses. No cause is found in around 35% of patients with lymphocytic meningitis

10 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Lumbar Puncture III Normal white cell count in the CSF It is sometimes possible to detect virus in the CSF even if there is no elevation in white cells. This does not always mean that the patient has meningitis. You need to look at the patient’s clinical features to see if it is possible that there could be neurological infection without a rise in white cells in the CSF. For example, a patient with shingles but no signs of meningism may have detectable levels of VZV in their CSF despite the white cell count in their CSF being normal. This patient may not necessarily have meningitis. An immunocompromised patient with neck stiffness and photophobia may have the same CSF findings as the patient with shingles, but is more likely to have meningitis.

11 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Other Investigations Blood tests The white cell count and C-reactive protein (CRP) may be normal or mildly raised in patients with viral meningitis. HIV test Aseptic meningitis can be a presenting feature of HIV seroconversion. So you should offer an HIV test to all patients with aseptic meningitis.

12 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Differentiating encephalitis and meningitis I There can be confusion between encephalitis and meningitis when a patient has a lymphocytic CSF. The clinical picture will help you to differentiate between the two. Features that suggest involvement of the brain substance (parenchyma) and therefore encephalitis are: Focal neurological weakness Seizures or movement disorder Change in personality, behaviour, cognition or consciousness In a patient with a lymphocytic CSF and an impaired conscious level, you should start treatment for presumed herpes simplex encephalitis. Herpes simplex encephalitis is a medical emergency and prompt treatment with aciclovir has been shown to reduce mortality and morbidity. You may wish to consider antibiotics as well until the definitive diagnosis is made. Other causes of a lymphocytic CSF include tuberculosis, listeriosis, partially treated bacterial meningitis and all the causes of aseptic meningitis.

13 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Differentiating encephalitis and meningitis II

14 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Treatment There are currently no treatments of proven benefit for the common causes of viral meningitis. Some clinicians treat patients who have herpes meningitis with aciclovir or valaciclovir, but to date, there have been no trials to support or refute this practice. Treatment should be supportive and reassuring. As viral meningitis is often difficult to differentiate from bacterial meningitis based on clinical features alone, it is possible that the patient will be on antibiotics before the viral aetiology is determined. Once the diagnosis has been established as viral meningitis, you should stop antibiotics, if they have been prescribed, and prioritise discharge from hospital. If HSV-2 is diagnosed, you should consider referring the patient to a sexual health clinic. The most common specific causes of viral meningitis are considered on the following slides.

15 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Enteroviral Meningitis I In most studies, enteroviruses are the most common cause of viral meningitis. Diagnosis has improved greatly since the widespread use of PCR. By using molecular techniques to obtain a definitive diagnosis, the length of hospital stay and duration of antibiotics can both be reduced. Enteroviruses are a group of viruses that include polioviruses, echoviruses, coxsackie viruses and the numbered enteroviruses. Viral meningitis is caused mainly by the coxsackie viruses and echoviruses. As the name suggests, enteroviruses are carried in the gastrointestinal tract and can be found on PCR of stool samples and throat swabs. The viruses tend to be carried in the throat during the acute episode. So if a patient with symptoms of meningism and raised white cells in their CSF has a positive throat swab for enterovirus, this is strongly suggestive as the cause of their meningitis. However, the same is not true of stool samples, as the virus can be excreted in the stool in well individuals as well as those with meningitis. These tests do not confirm the cause of meningitis, so you must perform a lumbar puncture for PCR analysis of the CSF.

16 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Enteroviral Meningitis II There is a seasonal variation in enteroviral meningitis, with most cases occurring in the summer/autumn in the Northern Hemisphere. Most immunocompetent adults recover from enteroviral meningitis without complication. But there is some evidence that patients may be left with neuropsychological dysfunction, for example, problems with attention or cognition. There is also evidence that enteroviral meningitis can leave people with fatigue and sleep problems. Enteroviral meningoencephalitis in neonates can be fatal. There is no current, licensed treatment for enteroviral meningitis.

17 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Herpes Virus Meningitis Several herpes viruses can cause meningitis. HSV-2 is normally the most common (one study found VZV to be the most common). Although a common casue of encephalitis, HSV-1 is an uncommon cause of aseptic meningitis. Outside the perinatal period, HSV-2 is normally acquired sexually. Most people with HSV-2 meningitis do not have concurrent genital herpes and usually have no history of such either. Recurrent lymphocytic meningitis, also known as Mollaret’s meningitis, is a rare disease that is estimated to have a prevalence of 2.7 per 100,000 population. HSV-2 is the most common cause of recurrent lymphocytic meningitis, being responsible for 84% of recurrent meningitis in one study. However, most patients who have one episode of HSV-2 meningitis do not go on to have a recurrence. Although aciclovir is used for other illnesses caused by herpes viruses, there is currently no strong evidence for or against its use in herpes meningitis. Treatment of herpes meningitis, including the use of aciclovir, varies greatly within the UK and the US, and there is a need for well conducted clinical trials. A recent trial looked at the role of valaciclovir in the prevention of recurrent episodes of HSV-2 meningitis, but no benefit was shown.

18 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Varicella Zoster Virus Meningitis Meningitis caused by varicella zoster virus (VZV) can occur during either primary infection with the virus (chickenpox) or reactivation (shingles), or after the live vaccine. Aseptic meningitis has been shown to be the most common neurological manifestation of VZV infection. VZV meningitis presents with the classic symptoms of meningism, although less frequently than in other forms of viral meningitis according to one study. Rash is also more common with VZV than with herpes or enteroviruses. But VZV meningitis can occur in the absence of skin lesions. Aciclovir has activity against VZV, but there are no trials to support its use in the setting of meningitis. But if there is clinical or radiographic evidence of meningoencephalitis in the patient, experts recommend the use of aciclovir. Right: The rash of Herpes Zoster infection

19 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment HIV and neurological illness HIV is an important cause of neurological illness, both due to direct involvement, as in HIV seroconversion, and secondary to opportunistic infections, such as VZV and cryptococcus. Aseptic meningitis can be caused by HIV, especially at the time of seroconversion. In one study, symptoms of meningitis occurred in 24% of patients presenting with primary HIV infection. This study also showed that most of these patients presenting with typical symptoms of primary HIV infection were not diagnosed at the initial medical encounter. Therefore, you should offer an HIV test to all patients with aseptic meningitis. Other studies have also shown that aseptic meningitis or encephalitis can present in established HIV infection as well as primary disease.

20 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment HIV and neurological illness In the UK, about one third of people who have HIV are currently undiagnosed and unaware of their infection. In addition, HIV is still often diagnosed late. In a recent British HIV Association (BHIVA) audit, over half of patients had a CD4 count of less than 350 cells/mm 3 when diagnosed. A CD4 count of 350 cells/mm 3 is the threshold below which treatment for HIV should be started. Many patients who were diagnosed late had had a previous, missed opportunity for HIV testing. In a previous audit of mortality in patients with HIV, a quarter of deaths were reported as being due to the diagnosis of HIV being made too late for effective treatment. It is for these reasons that national guidelines on HIV testing have been produced which indicate when to offer an HIV test. These can be found by following the below link.

21 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Complications Viral meningitis is often reported as a benign, self-limiting illness. But there is mounting evidence that the disease may have longer term effects, such as cognitive dysfunction, sleep disturbances and persistence of headaches. One study showed that patients who had viral meningitis have significantly lower global cognitive scores than control patients. Another study showed that headache occurs in up to 34% of patients. Memory, attention and speed of cognitive and psychomotor performance are the domains most affected. No studies have been conducted into whether these complications reduce over time. HSV-2 and other viruses can cause recurrent episodes of meningitis (Mollaret’s meningitis).

22 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Key Points I Viral meningitis is a common problem in the UK and can have important complications Herpes viruses (including HSV-2) and the enteroviruses are the most common causes of viral meningitis in the UK Viral meningitis and viral encephalitis are usually separate entities and the diagnostic approaches and management are different You should offer an HIV test to all adult patients with aseptic meningitis By diagnosing the specific (viral) pathogen causing the symptoms, you can reduce the length of hospital stay and amount of inappropriate antibiotics given

23 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Key Points II Below are some key clinical tips to bear in mind in the approach to viral meningitis: You should arrange a lumbar puncture for all patients with suspected meningitis, unless there are clinical contraindications, in order to differentiate bacterial from viral causes A CT head before a lumbar puncture is normally unnecessary and unhelpful You should refer patients with HSV-2 meningitis to a centre for sexual health You should notify all episodes of viral meningitis to your local Health Protection Unit

24 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Summary You should now know: That viral meningitis is a common problem in the UK The important causes of aseptic meningitis How to manage a patient with meningism and a raised lymphocyte count in their cerebrospinal fluid How to differentiate between viral and bacterial causes of meningitis The difference between viral meningitis and viral encephalitis The possible outcomes for patients with viral meningitis. Further resources f uidelines/Infections_by_Organ_System/Central_Nervous_System_(CNS)/Bacterial_M eningitis.aspx

25 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Summary II References 1.Schmidt H, Cohrs S, Heinemann T, Goerdt C, Djukic M, Heimann B, et al. Sleep disorders are long-term sequelae of both bacterial and viral meningitis. Journal of Neurology, Neurosurgery and Psychiatry. 2006;77: Schmidt H, Heimann B, Djukic M, Mazurek C, Fels C, Wallesch CW, et al. Neuropsychological sequelae of bacterial and viral meningitis. Brain. 2006;129: Sittinger H, Muller M, Schweizer I, Merkelback S. Mild cognitive impairment after viral meningitis in adults. Journal of Neurology. 2002;249: Khetsuriani N, Quiroz ES, Holman R, Anderson LJ. Viral Meningitis-Associated Hospitalisations in the United States, Neuroepidemiology. 2003;22: Landry ML, Greenwold J, Vikram HR. Herpes Simplex type-2 Meningitis: Presentation and Lack of Standardized Therapy. The American Journal of Medicine. 2009;122: Michael B, Sidhu M, Stoeter D, Roberts M, Beeching N, Bonington A, et al. Acute central nervous system infections in adults—a retrospective cohort study in the NHS North West region. QJM. [Original Paper] /07/2010;103:10. 7.Rantakallio P, Leskinen M, Von Wendt L. Incidence and Prognosis of Central Nervous System Infections in a Birth Cohort of Children. Scand Journal of Infectious Diseases. 1986;18: Kupila L, Vuorinen T, Vainionpaa R, Hukkanen V, Marttila RJ, Kotilainen P. Etiology or aseptic meningitis and encephalitis in an adult population. Neurology. 2006;66:6. 9.Solomon T. Meningitis. In: Donaghy M, editor. Brain's Diseases of the Nervous System. 12th ed: Oxford University Press; p Chadwick D. Viral meningitis. Br Med Bull. 2005;75-76: Logan S, MacMahon E. Viral meningitis. BMJ. 2008;336: Brabazon ED, O'Farrell A, Murray CA, Finnegan P. Trends in viral meningitis hospitalisations and notifications in the North Eastern Health Board ( ): a cause for concern? Irish Medical Journal. 2004;97(10): Rotbart HA. Enteroviral Infections of the Central Nervous System. Clinical Infectious Diseases. 1995;20:

26 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Summary III References 14.Ihekwaba UK, Kudesia G, McKendrick M. Clinical Features of Viral Meningitis in Adults: Significant Differences in Cerebrospinal Fluid Findings among Herpes Simplex Virus, Varicella Zoster Virus and Enterovirus Infections. Clinical Infectious Diseases. 2008;47: Desmond RA, Accortt NA, Talley L, Villano SA, Soong SJ, Whitley RJ. Enteroviral Meningitis:Natural history and Outcome of Pleconaril Therapy. Antimicrobial Agents and Chemotherapy. 2006;50(7): Brivet FG, Ducuing S, Jacobs F, Chary I, Pompier R, Prat D, et al. Accuracy of Clinical Presentation for differentiating bacterial from viral meningitis in adults: a multivariate approach. Intensive Care Medicine. 2005;31: Heyderman RS, Lambert HP, O'Sullivan I, Stuart JM, Taylor BL, Wall RA, et al. Early Management of Suspected Bacterial Meningitis and Meningococcal Septicaemia in Adults. Journal of Infection. 2003;46: Hasbun R, Abrahams J, Jekel J, Quagliarello VJ. Computed tomography of the Head before Lumbar Puncture in Adults with Suspected Meningitis. New England Journal of Medicine. 2001;345: Solomon T, Hart I, Beeching N. Viral Encephalitis: A Clinician's guide. Practical Neurology. 2007;7: Jeffrey KJ, Bangham CRM. Recent Advances in the laboratory diagnosis of central nervous system infections. Current Opinion in Infectious Diseases. 1996;9: Jeffrey KJ, Read SJ. Diagnosis of viral infections of the Central nervous system: Clinical interpretation of PCR results. Lancet. 1997;349(9048): Nowak DA, Boehmer R, Fuchs HH. A retrospective clinical, laboratory and outcome analysis in 43 cases of acute aseptic meningitis. European Journal of Neurology. 2003;10: British HIV Association, British Association of Sexual Health and HIV, British Infection Society. UK National HIV Testing Guidelines for HIV testing Solomon T, MIchael BD, Smith PE, Sanderson F, Davies NWS, Hart I, et al. National ABN/BIA guideline for the management of encephalitis for adults. Journal of Infection. 2012;In press.

27 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Summary IV References 25.Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, Scheld M, et al. Practice Guidelines for the management of Bacterial Meningitis. Clinical Infectious Diseases. 2004;39: Smith J, Robinson J. Age-Specific Prevalence of Infection with herpes Simplex Types 2 and 1: A Global Review. Journal of Infectious Diseases. 2002;186 (Suppl1):S3-S Kallio-Laine K, Seppanen M, Kautiainen H, Lokki ML, Lappalainen M, Valtonen V, et al. Recurrent Lymphocytic Meningitis Positive for Herpes Simplex Virus Type 2. Emerging Infectious Diseases. 2009;15: Chadwick D, Lever A. The impact of new diagnostic methodologies in the management of meningitis in adultsat a teaching hospital. QJM. 2002;95: Schuffenecker I, Mirand A, Antona D, Henquell C, Chomel JJ, Archimbaud C, et al. Epidemiology of human enterovirus 71 infections in France, Journal of Clinical Virology. 2011;50: Skoldenberg B, Alestig K, Burman L, Forkman A, Lovgren K, Norrby R, et al. Acyclovir versus vidaribine in Herpes Simplex Encephalitis. The Lancet. 1984;324(8405): Kupila L, Vainionpaa R, Vuorinen T, Marttila RJ, Kotilainen P. Recurrent Lymphocytic Meningitis. Arch Neurol. 2004;61: Koskiniemi M, Rantalaiho T, Piiparinen H, Bonsdorff CH von, Farkkila M, Jarvinen A, et al. Infections of the central nervous system of suspected viral origin: A colloaborative study from Finland. Journal of Neurovirology. 2001;7: Aurelius E, Franzen-Rohl E, Glimaker M, Akre O, Grillner L, Jorup-Ronstrom C, et al. Long term valacyclovir suppressive treatment after herpes simplex virus type-2 meningitis:a double blind, randomized controlled trial. Clinical Infectious Diseases. 2012;54: Whitley RJ, Alford CA, HIrsch MS, Schooley RT, Luby JP, Aoki FY, et al. Vidarabine versus Acyuclovir Therapy in Herpes Simples Encephalitis. New England Journal of Medicine. 1986;314: McGrath N, Anderson NE, Croxson MC, Powell KF. Herpes Simplex encephalitis treated with acyclovir: diagnosis and long term outcome. Journal of Neurology, Neurosurgery and Psychiatry 1997;63:321-6.

28 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Summary V 36.Fujimoto H, Asaoka K, Imaizumi T, Ayabe M, Shoji H, Kaji M. Epstein-Barr Virus Infections of the Central Nervous System. Internal Medicine. 2003;42(1): KOskiniemi M, Piiparinen H, Rantalaiho T, Eranko P, Farkkila M, Raiha K, et al. Acute Central Nervous System complications in varicella zoster virus infections. Journal of Clinical Virology. 2002;25: Pahud BA, Glaser CA, Dekker CL, Arvin AM, Schmid DS. Varicella Zoster Disease of the Central Nervous System: Epidemiological, Clinical and Laboratory Features 10 Years after the Introduction of the Varicella Vaccine. Journal of Infectious Diseases. 2011;203: Persson A, Bergstrom T, Lindh M, Namvar L, Studahl M. Varicella-zoster virus CNS disease - viral load, clinical manifestations and sequels. Journal of Clinical Virology. 2009;46: Schaker T, Collier AC, Hughes J, Shea T, Corey L. Clinical and Epidemiological Features of Primary HIV Infection. Annals of Internal Medicine. 1996;125(4): Villar del Saz S, Sued O, Falco V, Aguero F, Crespo M, Pumarola T, et al. Acute meningoencephalitis due to human inmmunodeficiency virus type 1 infection in 13 patients: clinical description and follow-up. Journal of neurovirology. 2008;14: Health Protection Agency, Infections. Cf. Testing times. HIV and other sexually transmitted infections in the United Kingdom: British HIV Association. Clinical Audit Report British HIV Association. BHIVA guidelines for the treatment of HIV-1 positive adults with antiretroviral therapy In Press Lucas SB, Curtis H, Johnson MA. National Review of Deaths among HIV-infected adults. Clinical Medicine. 2008;8(3): Begg N, Cartwright KAV, Cohen J, Kaczmarski EB, Innes JA, Leen CLS, et al. Consensus Statement on Diagnosis, Investigation, Treatment and Prevention of Acute Bacterial Meningitis in Immunocompetent Adults. Journal of Infection. 1999;39: Michael B, Menezes B, Cunniffe J, Miller A, Kneen R, Francis G, et al. Effect of delayed lumbar punctures on the diagnosis of acute bacterial meningitis in adults. Emerg Med J. 2010;27: Health Protection Agency. UK Standards for Microbiology Investigations - Investigation of Viral Encephalitis and Meningitis. 2011:1-29.

29 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 1 You are called to see an 18 year old man in the emergency department. He has a headache, photophobia and a sore throat. He has been unwell for just over 24 hours. On examination, he is alert and talking to you, although he has difficulty keeping his eyes open. He has no signs of focal neurological weakness and he has not had any seizures. His temperature is 39.0 °C. The rest of his examination is normal and his blood tests are all within the normal range. You have already sent blood cultures. What should you do now? A.CT scanCT scan B.Lumbar PunctureLumbar Puncture C.MRI brainMRI brain What should you do now? A.CT scanCT scan B.Lumbar PunctureLumbar Puncture C.MRI brainMRI brain

30 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 1 What should you do now? A.CT scan B.Lumbar Puncture C.MRI brain What should you do now? A.CT scan B.Lumbar Puncture C.MRI brain A.INCORRECT A CT brain is rarely useful or necessary prior to lumbar puncture in this situation. Indications on when to perform a CT before a lumbar puncture are: Immunocompromise (e.g. HIV infection, immunosuppressive drugs or transplantation) New onset seizures in preceding week Papilloedema Abnormal level of consciousness Focal neurological deficit Click here to move on to the next scenario A.INCORRECT A CT brain is rarely useful or necessary prior to lumbar puncture in this situation. Indications on when to perform a CT before a lumbar puncture are: Immunocompromise (e.g. HIV infection, immunosuppressive drugs or transplantation) New onset seizures in preceding week Papilloedema Abnormal level of consciousness Focal neurological deficit Click here to move on to the next scenario

31 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 1 What should you do now? A.CT scan B.Lumbar Puncture C.MRI brain What should you do now? A.CT scan B.Lumbar Puncture C.MRI brain B.CORRECT You must perform a lumbar puncture in order to find the cause of this patient’s meningism. The history does not suggest any obvious features of bacterial illness or sepsis, but some clinicians may give antibiotics in this situation. Indications on when to perform a CT before a lumbar puncture are: Immunocompromise (e.g. HIV infection, immunosuppressive drugs or transplantation) New onset seizures in preceding week Papilloedema Abnormal level of consciousness Focal neurological deficit Click here to move onto the next scenario B.CORRECT You must perform a lumbar puncture in order to find the cause of this patient’s meningism. The history does not suggest any obvious features of bacterial illness or sepsis, but some clinicians may give antibiotics in this situation. Indications on when to perform a CT before a lumbar puncture are: Immunocompromise (e.g. HIV infection, immunosuppressive drugs or transplantation) New onset seizures in preceding week Papilloedema Abnormal level of consciousness Focal neurological deficit Click here to move onto the next scenario

32 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 1 What should you do now? A.CT scan B.Lumbar Puncture C.MRI brain What should you do now? A.CT scan B.Lumbar Puncture C.MRI brain C.INCORRECT You must perform a lumbar puncture in order to find the cause of this patient’s meningism. Imaging is rarely useful or necessary prior to lumbar puncture in this situation. An MRI is not necessary and indications on when to perform a CT before a lumbar puncture are: Immunocompromise (e.g. HIV infection, immunosuppressive drugs or transplantation) New onset seizures in preceding week Papilloedema Abnormal level of consciousness Focal neurological deficit Click here to move onto the next scenario C.INCORRECT You must perform a lumbar puncture in order to find the cause of this patient’s meningism. Imaging is rarely useful or necessary prior to lumbar puncture in this situation. An MRI is not necessary and indications on when to perform a CT before a lumbar puncture are: Immunocompromise (e.g. HIV infection, immunosuppressive drugs or transplantation) New onset seizures in preceding week Papilloedema Abnormal level of consciousness Focal neurological deficit Click here to move onto the next scenario

33 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 1, part B He has had a lumbar puncture. The CSF results are phoned through to you: What is the most likely diagnosis? A.Enteroviral meningitisEnteroviral meningitis B.HSV encephalitisHSV encephalitis C.HSV meningitisHSV meningitis What is the most likely diagnosis? A.Enteroviral meningitisEnteroviral meningitis B.HSV encephalitisHSV encephalitis C.HSV meningitisHSV meningitis You are called to see an 18 year old man in the emergency department. He has a headache, photophobia and a sore throat. He has been unwell for just over 24 hours. On examination, he is alert and talking to you, but he has difficulty keeping his eyes open. He has no signs of focal neurological weakness and he has not had any seizures. His temperature is 39.0 °C. The rest of his examination is normal and blood tests are all within the normal range.

34 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 1, part B What is the most likely diagnosis? A.Enteroviral meningitis B.HSV meningitis C.HSV encephalitis What is the most likely diagnosis? A.Enteroviral meningitis B.HSV meningitis C.HSV encephalitis A.CORRECT The CSF findings are consistent with viral meningitis, with a mildly raised white cell count and protein, and a normal CSF:blood glucose ratio (>66%). The patient also has clinical evidence of meningism, with headache and photophobia. In most studies to date, enteroviruses are the most common cause of viral meningitis. Click here to move on to the next scenario A.CORRECT The CSF findings are consistent with viral meningitis, with a mildly raised white cell count and protein, and a normal CSF:blood glucose ratio (>66%). The patient also has clinical evidence of meningism, with headache and photophobia. In most studies to date, enteroviruses are the most common cause of viral meningitis. Click here to move on to the next scenario

35 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 1, part B What is the most likely diagnosis? A.Enteroviral meningitis B.HSV meningitis C.HSV encephalitis What is the most likely diagnosis? A.Enteroviral meningitis B.HSV meningitis C.HSV encephalitis B.INCORRECT While HSV encephalitis does cause a lymphocytic CSF, there will typically be some clinical evidence of involvement of the brain substance, such as focal neurological weakness or reduced conscious level. There is nothing in this patient’s history to suggest this. Encephalitis is a medical emergency, so it is important to be able to differentiate it from viral meningitis. Viral meningitis is generally not an emergency in adults. Enteroviruses are the most common cause. Click here to move on to the next scenario B.INCORRECT While HSV encephalitis does cause a lymphocytic CSF, there will typically be some clinical evidence of involvement of the brain substance, such as focal neurological weakness or reduced conscious level. There is nothing in this patient’s history to suggest this. Encephalitis is a medical emergency, so it is important to be able to differentiate it from viral meningitis. Viral meningitis is generally not an emergency in adults. Enteroviruses are the most common cause. Click here to move on to the next scenario

36 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 1, part B What is the most likely diagnosis? A.Enteroviral meningitis B.HSV meningitis C.HSV encephalitis What is the most likely diagnosis? A.Enteroviral meningitis B.HSV meningitis C.HSV encephalitis C.INCORRECT HSV-2 can cause meningitis in men, but it is much more common in sexually active women. As this is a young man, enteroviral meningitis is more likely. Click here to return to the question C.INCORRECT HSV-2 can cause meningitis in men, but it is much more common in sexually active women. As this is a young man, enteroviral meningitis is more likely. Click here to return to the question

37 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 2 A 35 year old woman presents to the emergency department with a 3 day history of headache, fever and photophobia. She had a previous episode of viral meningitis about 5 years ago. She has a male partner and has not had any other partners in the last 5 years. She has no history of sexually transmitted diseases as far as she knows. She is alert and orientated with a Glasgow Coma Scale (GCS) of 15/15. Her vital signs are all normal. Blood tests are also normal. She has had a lumbar puncture which shows the following: What is the most likely diagnosis? A.Bacterial meningitisBacterial meningitis B.Enteroviral meningitisEnteroviral meningitis C.HSV encephalitisHSV encephalitis D.HSV-2 meningitisHSV-2 meningitis What is the most likely diagnosis? A.Bacterial meningitisBacterial meningitis B.Enteroviral meningitisEnteroviral meningitis C.HSV encephalitisHSV encephalitis D.HSV-2 meningitisHSV-2 meningitis

38 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 2 A.INCORRECT Bacterial meningitis would normally produce a predominance of neutrophils in the CSF and a low CSF:blood glucose ratio. Partially treated bacterial meningitis may present with a predominance of lymphocytes, but this woman has not been treated for bacterial meningitis. Click here to return to the question A.INCORRECT Bacterial meningitis would normally produce a predominance of neutrophils in the CSF and a low CSF:blood glucose ratio. Partially treated bacterial meningitis may present with a predominance of lymphocytes, but this woman has not been treated for bacterial meningitis. Click here to return to the question What is the most likely diagnosis? A.Bacterial meningitis B.Enteroviral meningitis C.HSV encephalitis D.HSV-2 meningitis What is the most likely diagnosis? A.Bacterial meningitis B.Enteroviral meningitis C.HSV encephalitis D.HSV-2 meningitis

39 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 2 B.INCORRECT This is possible, but the history given points more to one of the other diagnoses. Click here to return to the question B.INCORRECT This is possible, but the history given points more to one of the other diagnoses. Click here to return to the question What is the most likely diagnosis? A.Bacterial meningitis B.Enteroviral meningitis C.HSV encephalitis D.HSV-2 meningitis What is the most likely diagnosis? A.Bacterial meningitis B.Enteroviral meningitis C.HSV encephalitis D.HSV-2 meningitis

40 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 2 C.INCORRECT HSV encephalitis does cause a lymphocytic CSF. But if this was HSV encephalitis, there would be some impairment of consciousness or behavioural change to indicate involvement of the brain parenchyma. The clinical picture in this woman is not consistent with HSV encephalitis. Click here to return to the question C.INCORRECT HSV encephalitis does cause a lymphocytic CSF. But if this was HSV encephalitis, there would be some impairment of consciousness or behavioural change to indicate involvement of the brain parenchyma. The clinical picture in this woman is not consistent with HSV encephalitis. Click here to return to the question What is the most likely diagnosis? A.Bacterial meningitis B.Enteroviral meningitis C.HSV encephalitis D.HSV-2 meningitis What is the most likely diagnosis? A.Bacterial meningitis B.Enteroviral meningitis C.HSV encephalitis D.HSV-2 meningitis

41 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 2 D.CORRECT Given that this is a sexually active woman with a previous history of meningitis, HSV-2 meningitis is the most likely diagnosis. HSV-2 is the most common cause of recurrent lymphocytic meningitis Click here to move on to the next scenario D.CORRECT Given that this is a sexually active woman with a previous history of meningitis, HSV-2 meningitis is the most likely diagnosis. HSV-2 is the most common cause of recurrent lymphocytic meningitis Click here to move on to the next scenario What is the most likely diagnosis? A.Bacterial meningitis B.Enteroviral meningitis C.HSV encephalitis D.HSV-2 meningitis What is the most likely diagnosis? A.Bacterial meningitis B.Enteroviral meningitis C.HSV encephalitis D.HSV-2 meningitis

42 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 3 You see a 61 year old woman in the emergency department. She has a headache, vomiting and fevers. She has no focal neurological signs and no impairment of consciousness. She has not been treated with antibiotics yet. A lumbar puncture shows the following: What is the most likely cause of her symptoms? A.Epstein Barr VirusEpstein Barr Virus B.Streptococcus pneumoniaeStreptococcus pneumoniae C.Neisseria meningitidisNeisseria meningitidis D.Varicella Zoster VirusVaricella Zoster Virus What is the most likely cause of her symptoms? A.Epstein Barr VirusEpstein Barr Virus B.Streptococcus pneumoniaeStreptococcus pneumoniae C.Neisseria meningitidisNeisseria meningitidis D.Varicella Zoster VirusVaricella Zoster Virus

43 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 3 What is the most likely cause of her symptoms? A.Epstein Barr Virus B.Streptococcus pneumoniae C.Neisseria meningitidis D.Varicella Zoster Virus What is the most likely cause of her symptoms? A.Epstein Barr Virus B.Streptococcus pneumoniae C.Neisseria meningitidis D.Varicella Zoster Virus A.INCORRECT Acute Epstein-Barr virus infection rarely causes meningitis. Click here to return to the question A.INCORRECT Acute Epstein-Barr virus infection rarely causes meningitis. Click here to return to the question

44 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 3 What is the most likely cause of her symptoms? A.Epstein Barr Virus B.Streptococcus pneumoniae C.Neisseria meningitidis D.Varicella Zoster Virus What is the most likely cause of her symptoms? A.Epstein Barr Virus B.Streptococcus pneumoniae C.Neisseria meningitidis D.Varicella Zoster Virus B.INCORRECT Pneumococcal meningitis normally presents with a predominance of neutrophils in the CSF with a lower CSF:blood glucose ratio. Click here to return to the question B.INCORRECT Pneumococcal meningitis normally presents with a predominance of neutrophils in the CSF with a lower CSF:blood glucose ratio. Click here to return to the question

45 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 3 What is the most likely cause of her symptoms? A.Epstein Barr Virus B.Streptococcus pneumoniae C.Neisseria meningitidis D.Varicella Zoster Virus What is the most likely cause of her symptoms? A.Epstein Barr Virus B.Streptococcus pneumoniae C.Neisseria meningitidis D.Varicella Zoster Virus C.INCORRECT With meningococcal meningitis (caused by Neisseria meningitidis), you would normally expect a predominance of neutrophils in the CSF, especially if no antibiotics have been given. Bacterial meningitis can present with a lymphocytic CSF, especially early in the course of the illness, but there would usually be higher numbers of white cells and a low CSF:blood glucose ratio. If there is any doubt as to the diagnosis, you should give antibiotics until a more definitive diagnosis is reached. Click here to return to the question C.INCORRECT With meningococcal meningitis (caused by Neisseria meningitidis), you would normally expect a predominance of neutrophils in the CSF, especially if no antibiotics have been given. Bacterial meningitis can present with a lymphocytic CSF, especially early in the course of the illness, but there would usually be higher numbers of white cells and a low CSF:blood glucose ratio. If there is any doubt as to the diagnosis, you should give antibiotics until a more definitive diagnosis is reached. Click here to return to the question

46 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 3 What is the most likely cause of her symptoms? A.Epstein Barr Virus B.Streptococcus pneumoniae C.Neisseria meningitidis D.Varicella Zoster Virus What is the most likely cause of her symptoms? A.Epstein Barr Virus B.Streptococcus pneumoniae C.Neisseria meningitidis D.Varicella Zoster Virus D.CORRECT This patient has meningism, a lymphocytic CSF, and a normal CSF:blood glucose ratio, so varicella zoster virus meningitis is the most likely cause of her symptoms from the list provided. This patient also has a high red cell count in her CSF which can be a feature of VSV meningitis. Click here to move on to the next scenario D.CORRECT This patient has meningism, a lymphocytic CSF, and a normal CSF:blood glucose ratio, so varicella zoster virus meningitis is the most likely cause of her symptoms from the list provided. This patient also has a high red cell count in her CSF which can be a feature of VSV meningitis. Click here to move on to the next scenario

47 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 4 You are reviewing a 60 year old woman with a 3 day history of confusion and odd behaviour. Her temperature is 38.5 °C. She has no signs of focal neurological weakness. She is normally fit and well and works as an office manager. She has not received any antibiotics. Her full blood count is normal, CRP is 35, urea, creatinine and electrolytes are normal. Urine dipstick shows no abnormality. Her chest x ray is normal. She has an urgent CT head which is also normal. Her lumbar puncture results are as follows: What is the most likely diagnosis? A.Bacterial meningitisBacterial meningitis B.Viral encephalitisViral encephalitis C.Viral meningitisViral meningitis What is the most likely diagnosis? A.Bacterial meningitisBacterial meningitis B.Viral encephalitisViral encephalitis C.Viral meningitisViral meningitis

48 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 4 What is the most likely diagnosis? A.Bacterial meningitis B.Viral encephalitis C.Viral meningitis What is the most likely diagnosis? A.Bacterial meningitis B.Viral encephalitis C.Viral meningitis A.INCORRECT Bacterial meningitis would normally have a predominance of neutrophils in the CSF and a low CSF:blood glucose ratio. Traditionally, the normal value for CSF:blood glucose ratio is quoted as >66%, but a bacterial meningitis would have a much lower ratio (probably <50% or lower). Partially treated bacterial meningitis may present with a predominance of lymphocytes, but this patient has not been treated for bacterial meningitis. The changes in cognition and behaviour suggest a diagnosis of encephalitis rather than meningitis Click here to move on to the next scenario A.INCORRECT Bacterial meningitis would normally have a predominance of neutrophils in the CSF and a low CSF:blood glucose ratio. Traditionally, the normal value for CSF:blood glucose ratio is quoted as >66%, but a bacterial meningitis would have a much lower ratio (probably <50% or lower). Partially treated bacterial meningitis may present with a predominance of lymphocytes, but this patient has not been treated for bacterial meningitis. The changes in cognition and behaviour suggest a diagnosis of encephalitis rather than meningitis Click here to move on to the next scenario

49 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 4 What is the most likely diagnosis? A.Bacterial meningitis B.Viral encephalitis C.Viral meningitis What is the most likely diagnosis? A.Bacterial meningitis B.Viral encephalitis C.Viral meningitis B.CORRECT This patient has evidence of changes in cognition and behaviour as well as a lymphocytic CSF. This suggests a diagnosis of encephalitis rather than meningitis. Click here to move on to the next scenario B.CORRECT This patient has evidence of changes in cognition and behaviour as well as a lymphocytic CSF. This suggests a diagnosis of encephalitis rather than meningitis. Click here to move on to the next scenario

50 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 4 What is the most likely diagnosis? A.Bacterial meningitis B.Viral encephalitis C.Viral meningitis What is the most likely diagnosis? A.Bacterial meningitis B.Viral encephalitis C.Viral meningitis C.INCORRECT This patient has evidence of changes in cognition and behaviour as well as a lymphocytic CSF. This suggests a diagnosis of encephalitis rather than meningitis. Click here to move on to the next scenario C.INCORRECT This patient has evidence of changes in cognition and behaviour as well as a lymphocytic CSF. This suggests a diagnosis of encephalitis rather than meningitis. Click here to move on to the next scenario

51 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 4 Part 2 You are reviewing a 60 year old woman with a 3 day history of confusion and odd behaviour. Her temperature is 38.5 °C. She has no signs of focal neurological weakness. She is normally fit and well and works as an office manager. She has not received any antibiotics. Her full blood count is normal, CRP is 35, urea, creatinine and electrolytes are normal. Urine dipstick shows no abnormality. Her chest x ray is normal. She has an urgent CT head which is also normal. Her lumbar puncture results are as follows: What should be your initial treatment? A.Supportive treatmentSupportive treatment B.Oral aciclovirOral aciclovir C.Intravenous aciclovir and intravenous antibioticsIntravenous aciclovir and intravenous antibiotics What should be your initial treatment? A.Supportive treatmentSupportive treatment B.Oral aciclovirOral aciclovir C.Intravenous aciclovir and intravenous antibioticsIntravenous aciclovir and intravenous antibiotics

52 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 4 Part 2 What should be your initial treatment? A.Supportive treatment B.Oral aciclovir C.Intravenous aciclovir and intravenous antibiotics What should be your initial treatment? A.Supportive treatment B.Oral aciclovir C.Intravenous aciclovir and intravenous antibiotics A.INCORRECT This would be the correct course of action if the patient had viral meningitis. But she has evidence of changes in cognition and behaviour as well as a lymphocytic CSF. So you should start urgent treatment with intravenous aciclovir for suspected viral encephalitis, as well as intravenous antibiotics until PCR confirms viral encephaltitis or a bacterial cause is found. Click here to move on to the next scenario A.INCORRECT This would be the correct course of action if the patient had viral meningitis. But she has evidence of changes in cognition and behaviour as well as a lymphocytic CSF. So you should start urgent treatment with intravenous aciclovir for suspected viral encephalitis, as well as intravenous antibiotics until PCR confirms viral encephaltitis or a bacterial cause is found. Click here to move on to the next scenario

53 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 4 Part 2 What should be your initial treatment? A.Supportive treatment B.Oral aciclovir C.Intravenous aciclovir and intravenous antibiotics What should be your initial treatment? A.Supportive treatment B.Oral aciclovir C.Intravenous aciclovir and intravenous antibiotics B.INCORRECT You should start urgent treatment with intravenous aciclovir for suspected viral encephalitis, as well as intravenous antibiotics until PCR confirms viral encephaltitis or a bacterial cause is found. Click here to move on to the next scenario B.INCORRECT You should start urgent treatment with intravenous aciclovir for suspected viral encephalitis, as well as intravenous antibiotics until PCR confirms viral encephaltitis or a bacterial cause is found. Click here to move on to the next scenario

54 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 4 Part 2 What should be your initial treatment? A.Supportive treatment B.Oral aciclovir C.Intravenous aciclovir and intravenous antibiotics What should be your initial treatment? A.Supportive treatment B.Oral aciclovir C.Intravenous aciclovir and intravenous antibiotics C.CORRECT This patient has evidence of changes in cognition and behaviour as well as a lymphocytic CSF. You should start urgent treatment with intravenous aciclovir for suspected viral encephalitis. Although viral encephalitis is the most likely diagnosis in this patient, bacterial meningoencephalitis could present in a similar way. So you should also give intravenous antibiotics until PCR confirms viral encephalitis or a bacterial cause is found. Click here to move on to the next scenario C.CORRECT This patient has evidence of changes in cognition and behaviour as well as a lymphocytic CSF. You should start urgent treatment with intravenous aciclovir for suspected viral encephalitis. Although viral encephalitis is the most likely diagnosis in this patient, bacterial meningoencephalitis could present in a similar way. So you should also give intravenous antibiotics until PCR confirms viral encephalitis or a bacterial cause is found. Click here to move on to the next scenario

55 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 5 You see a 55 year old bank manager in the emergency department. He has a 12 hour history of headache, sweats and photophobia. Neurological examination, including fundoscopy, is normal apart from marked neck stiffness. There is no rash. He is pyrexial at 38.5 °C. His heart rate is 110 beats per minute and his blood pressure is 120/65 mmHg. His abnormal blood results are: White cell count:23 x 10 9 /L with a neutrophil predominance Haemoglobin:13 g/dl Platelets:140 x 10 9 /L INR:1.3 seconds Urea:14 mmol/L Creatinine:245 µmol/L CRP:235 mg/L Blood cultures have already been taken. What should be the next management step? A.Intravenous antibiotics and lumbar punctureIntravenous antibiotics and lumbar puncture B.Intravenous aciclovir and lumbar punctureIntravenous aciclovir and lumbar puncture C.CT headCT head What should be the next management step? A.Intravenous antibiotics and lumbar punctureIntravenous antibiotics and lumbar puncture B.Intravenous aciclovir and lumbar punctureIntravenous aciclovir and lumbar puncture C.CT headCT head

56 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 5 What should be the next management step? A.Intravenous antibiotics and lumbar puncture B.Intravenous aciclovir and lumbar puncture C.CT head What should be the next management step? A.Intravenous antibiotics and lumbar puncture B.Intravenous aciclovir and lumbar puncture C.CT head A.CORRECT This patient has meningism as well as signs of sepsis, and this suggests bacterial meningitis. You must start urgent antibiotics in a patient with suspected bacterial meningitis. You must also perform a lumbar puncture in order to confirm the causative agent and establish its susceptibility to antibiotics Click here to move on to the next scenario A.CORRECT This patient has meningism as well as signs of sepsis, and this suggests bacterial meningitis. You must start urgent antibiotics in a patient with suspected bacterial meningitis. You must also perform a lumbar puncture in order to confirm the causative agent and establish its susceptibility to antibiotics Click here to move on to the next scenario

57 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 5 What should be the next management step? A.Intravenous antibiotics and lumbar puncture B.Intravenous aciclovir and lumbar puncture C.CT head What should be the next management step? A.Intravenous antibiotics and lumbar puncture B.Intravenous aciclovir and lumbar puncture C.CT head B.INCORRECT This patient has meningism as well as signs of sepsis, and this suggests bacterial meningitis. You must start urgent antibiotics in a patient with suspected bacterial meningitis and also perform a lumbar puncture. Click here to move on to the next scenario B.INCORRECT This patient has meningism as well as signs of sepsis, and this suggests bacterial meningitis. You must start urgent antibiotics in a patient with suspected bacterial meningitis and also perform a lumbar puncture. Click here to move on to the next scenario

58 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 5 What should be the next management step? A.Intravenous antibiotics and lumbar puncture B.Intravenous aciclovir and lumbar puncture C.CT head What should be the next management step? A.Intravenous antibiotics and lumbar puncture B.Intravenous aciclovir and lumbar puncture C.CT head C.INCORRECT There are no features in this patient to suggest the need for a CT head, such as papilloedema or immunocompromise. This patient has meningism as well as signs of sepsis, and this suggests bacterial meningitis. You must start urgent antibiotics in a patient with suspected bacterial meningitis and also perform a lumbar puncture. Click here to move on to the next scenario C.INCORRECT There are no features in this patient to suggest the need for a CT head, such as papilloedema or immunocompromise. This patient has meningism as well as signs of sepsis, and this suggests bacterial meningitis. You must start urgent antibiotics in a patient with suspected bacterial meningitis and also perform a lumbar puncture. Click here to move on to the next scenario

59 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 6 You see a 37 year old woman in your surgery. She was admitted to hospital 6 weeks ago with a diagnosis of viral meningitis. Her lumbar puncture showed a lymphocytosis with a normal level of protein and a normal CSF:blood glucose ratio. The PCR of her CSF was positive for enterovirus. Her HIV test was negative and her CT head was normal. She is still experiencing headaches, lack of concentration and difficulty sleeping. Her neurological examination, including fundoscopy, is normal. What should you do for her? A.Admit her to hospital, this is likely to be a recurrence of her meningitisAdmit her to hospital, this is likely to be a recurrence of her meningitis B.Reassure her and explain that these symptoms can occur after viral meningitisReassure her and explain that these symptoms can occur after viral meningitis C.Start her on a an antidepressantStart her on a an antidepressant What should you do for her? A.Admit her to hospital, this is likely to be a recurrence of her meningitisAdmit her to hospital, this is likely to be a recurrence of her meningitis B.Reassure her and explain that these symptoms can occur after viral meningitisReassure her and explain that these symptoms can occur after viral meningitis C.Start her on a an antidepressantStart her on a an antidepressant

60 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 6 What should you do for her? A.Admit her to hospital, this is likely to be a recurrence of her meningitis B.Reassure her and explain that these symptoms can occur after viral meningitis C.Start her on a an antidepressant What should you do for her? A.Admit her to hospital, this is likely to be a recurrence of her meningitis B.Reassure her and explain that these symptoms can occur after viral meningitis C.Start her on a an antidepressant A.INCORRECT Headaches and changes in cognition and sleep have been reported with varying frequencies following viral meningitis. While recurrences of viral meningitis are possible, particularly with HSV-2, there are no symptoms here (meningism) to suggest a recurrence. Click here to move on to the questions section A.INCORRECT Headaches and changes in cognition and sleep have been reported with varying frequencies following viral meningitis. While recurrences of viral meningitis are possible, particularly with HSV-2, there are no symptoms here (meningism) to suggest a recurrence. Click here to move on to the questions section

61 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 6 What should you do for her? A.Admit her to hospital, this is likely to be a recurrence of her meningitis B.Reassure her and explain that these symptoms can occur after viral meningitis C.Start her on a an antidepressant What should you do for her? A.Admit her to hospital, this is likely to be a recurrence of her meningitis B.Reassure her and explain that these symptoms can occur after viral meningitis C.Start her on a an antidepressant B.CORRECT Changes in cognition, sleep and headaches have all been reported with varying frequencies following viral meningitis. Click here to move on to the questions section B.CORRECT Changes in cognition, sleep and headaches have all been reported with varying frequencies following viral meningitis. Click here to move on to the questions section

62 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Clinical Scenario 6 What should you do for her? A.Admit her to hospital, this is likely to be a recurrence of her meningitis B.Reassure her and explain that these symptoms can occur after viral meningitis C.Start her on a an antidepressant What should you do for her? A.Admit her to hospital, this is likely to be a recurrence of her meningitis B.Reassure her and explain that these symptoms can occur after viral meningitis C.Start her on a an antidepressant C.INCORRECT This patient’s symptoms are also consistent with depression, but it is more likely at present that these are complications of her recent viral meningitis. If these symptoms persist, you may consider depression in this patient at a later stage. Click here to move on to the questions section C.INCORRECT This patient’s symptoms are also consistent with depression, but it is more likely at present that these are complications of her recent viral meningitis. If these symptoms persist, you may consider depression in this patient at a later stage. Click here to move on to the questions section

63 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Question 1 Answer the following question true or false Viral meningitis is a notifiable condition in the UK? TRUE FALSE Viral meningitis is a notifiable condition in the UK? TRUE FALSE

64 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Question 1 Answer the following question true or false Viral meningitis is a notifiable condition in the UK? TRUE FALSE Viral meningitis is a notifiable condition in the UK? TRUE FALSE CORRECT All meningitis is notifiable in the UK – this includes viral meningitis and aseptic meningitis. It is likely that viral meningitis is grossly underreported in the UK. Click here to move on to the next question CORRECT All meningitis is notifiable in the UK – this includes viral meningitis and aseptic meningitis. It is likely that viral meningitis is grossly underreported in the UK. Click here to move on to the next question

65 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Question 1 Answer the following question true or false Viral meningitis is a notifiable condition in the UK? TRUE FALSE Viral meningitis is a notifiable condition in the UK? TRUE FALSE INCORRECT All meningitis is notifiable in the UK – this includes viral meningitis and aseptic meningitis. It is likely that viral meningitis is grossly underreported in the UK. Click here to move on to the next scenario INCORRECT All meningitis is notifiable in the UK – this includes viral meningitis and aseptic meningitis. It is likely that viral meningitis is grossly underreported in the UK. Click here to move on to the next scenario

66 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Question 2 Select the single best answer from the options below Which of the following viruses do most laboratories test for in patients with likely viral meningitis in the UK? A.HSV-2HSV-2 B.Influenza virusInfluenza virus C.HIVHIV D.Hepatitis BHepatitis B Which of the following viruses do most laboratories test for in patients with likely viral meningitis in the UK? A.HSV-2HSV-2 B.Influenza virusInfluenza virus C.HIVHIV D.Hepatitis BHepatitis B

67 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Question 2 Select the single best answer from the options below Which of the following viruses do most laboratories test for in patients with likely viral meningitis in the UK? A.HSV-2 B.Influenza virus C.HIV D.Hepatitis B Which of the following viruses do most laboratories test for in patients with likely viral meningitis in the UK? A.HSV-2 B.Influenza virus C.HIV D.Hepatitis B CORRECT The HPA recommends testing for enterovirus, HSV-1 and HSV-2 and VZV by PCR on the CSF of patients with suspected viral meningitis or encephalitis. Influenza A has rarely been known to be associated with neurological sequelae but is not normally isolated from the CSF. Click here to move on to the next scenario CORRECT The HPA recommends testing for enterovirus, HSV-1 and HSV-2 and VZV by PCR on the CSF of patients with suspected viral meningitis or encephalitis. Influenza A has rarely been known to be associated with neurological sequelae but is not normally isolated from the CSF. Click here to move on to the next scenario

68 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Question 2 Select the single best answer from the options below INCORRECT Please try an alternative answer INCORRECT Please try an alternative answer Which of the following viruses do most laboratories test for in patients with likely viral meningitis in the UK? A.HSV-2HSV-2 B.Influenza virusInfluenza virus C.HIVHIV D.Hepatitis BHepatitis B Which of the following viruses do most laboratories test for in patients with likely viral meningitis in the UK? A.HSV-2HSV-2 B.Influenza virusInfluenza virus C.HIVHIV D.Hepatitis BHepatitis B

69 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitisEnteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Question 3 Select the single best answer from the options below Which of the following usually causes a predominance of neutrophils in the CSF? A.Enteroviral meningitisEnteroviral meningitis B.HSV-1 meningitisHSV-1 meningitis C.Pneumococcal meningitisPneumococcal meningitis D.Varicella Zoster meningitisVaricella Zoster meningitis Which of the following usually causes a predominance of neutrophils in the CSF? A.Enteroviral meningitisEnteroviral meningitis B.HSV-1 meningitisHSV-1 meningitis C.Pneumococcal meningitisPneumococcal meningitis D.Varicella Zoster meningitisVaricella Zoster meningitis

70 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Question 3 Select the single best answer from the options below INCORRECT Please try an alternative answer INCORRECT Please try an alternative answer Which of the following usually causes a predominance of neutrophils in the CSF? A.Enteroviral meningitisEnteroviral meningitis B.HSV-1 meningitisHSV-1 meningitis C.Pneumococcal meningitisPneumococcal meningitis D.Varicella Zoster meningitisVaricella Zoster meningitis Which of the following usually causes a predominance of neutrophils in the CSF? A.Enteroviral meningitisEnteroviral meningitis B.HSV-1 meningitisHSV-1 meningitis C.Pneumococcal meningitisPneumococcal meningitis D.Varicella Zoster meningitisVaricella Zoster meningitis

71 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Question 3 Which of the following usually causes a predominance of neutrophils in the CSF? A.Enteroviral meningitis B.HSV-1 meningitis C.Pneumococcal meningitis D.Varicella Zoster meningitis Which of the following usually causes a predominance of neutrophils in the CSF? A.Enteroviral meningitis B.HSV-1 meningitis C.Pneumococcal meningitis D.Varicella Zoster meningitis CORRECT The initial cell count of the CSF will be the first result you have back after performing a lumbar puncture. These results can give important clues to the cause of the illness. Bacterial meningitis normally presents with a predominance of neutrophils. Exceptions to this include Listeria meningitis and bacterial meningitis that has been partially treated with antibiotics. These may be associated with a predominance of lymphocytes. Viral meningitis usually presents with a lymphocytic CSF. Occasionally, if the lumbar puncture is performed early in the disease, viral meningitis may present with a predominance of neutrophils in the CSF. Click here to move on to the next scenario CORRECT The initial cell count of the CSF will be the first result you have back after performing a lumbar puncture. These results can give important clues to the cause of the illness. Bacterial meningitis normally presents with a predominance of neutrophils. Exceptions to this include Listeria meningitis and bacterial meningitis that has been partially treated with antibiotics. These may be associated with a predominance of lymphocytes. Viral meningitis usually presents with a lymphocytic CSF. Occasionally, if the lumbar puncture is performed early in the disease, viral meningitis may present with a predominance of neutrophils in the CSF. Click here to move on to the next scenario

72 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Question 4 Select the single best answer from the options below A 35 year old man has aseptic meningitis and all of the routine PCR tests on his CSF are negative (HSV-1, HSV-2, VZV and enterovirus). What should you do now? A.Offer a HIV testOffer a HIV test B.Repeat the lumbar puntcureRepeat the lumbar puntcure C.Consider the possibility of a false negitive PCRConsider the possibility of a false negitive PCR D.Perform a swab for genital HSV-2Perform a swab for genital HSV-2 E.No other actions are needed- reassure and discharge the patientNo other actions are needed- reassure and discharge the patien A 35 year old man has aseptic meningitis and all of the routine PCR tests on his CSF are negative (HSV-1, HSV-2, VZV and enterovirus). What should you do now? A.Offer a HIV testOffer a HIV test B.Repeat the lumbar puntcureRepeat the lumbar puntcure C.Consider the possibility of a false negitive PCRConsider the possibility of a false negitive PCR D.Perform a swab for genital HSV-2Perform a swab for genital HSV-2 E.No other actions are needed- reassure and discharge the patientNo other actions are needed- reassure and discharge the patien

73 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Question 4 A 35 year old man has aseptic meningitis and all of the routine PCR tests on his CSF are negative (HSV-1, HSV-2, VZV and enterovirus). What should you do now? A.Offer a HIV test B.Repeat the lumbar puntcure C.Consider the possibility of a false negitive PCR D.Perform a swab for genital HSV-2 E.No other actions are needed- reassure and discharge the patient A 35 year old man has aseptic meningitis and all of the routine PCR tests on his CSF are negative (HSV-1, HSV-2, VZV and enterovirus). What should you do now? A.Offer a HIV test B.Repeat the lumbar puntcure C.Consider the possibility of a false negitive PCR D.Perform a swab for genital HSV-2 E.No other actions are needed- reassure and discharge the patient CORRECT Many patients who present with meningism and have a lymphocytic CSF have a negative panel of tests for causative agents. For many people (35%), the diagnosis remains unknown. But one important, treatable cause of aseptic meningitis is HIV infection. So you should offer an HIV test to all patients with aseptic meningitis. It is unlikely that another lumbar puncture would give any more information. Laboratory quality controls prevent false negative PCRs being a real problem in clinical practice. There is no evidence for the use of genital swabs in this situation and discharge would not be appropriate. Click here to move on to the next scenario CORRECT Many patients who present with meningism and have a lymphocytic CSF have a negative panel of tests for causative agents. For many people (35%), the diagnosis remains unknown. But one important, treatable cause of aseptic meningitis is HIV infection. So you should offer an HIV test to all patients with aseptic meningitis. It is unlikely that another lumbar puncture would give any more information. Laboratory quality controls prevent false negative PCRs being a real problem in clinical practice. There is no evidence for the use of genital swabs in this situation and discharge would not be appropriate. Click here to move on to the next scenario

74 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Question 4 Select the single best answer from the options below INCORRECT Please try an alternative answer INCORRECT Please try an alternative answer A 35 year old man has aseptic meningitis and all of the routine PCR tests on his CSF are negative (HSV-1, HSV-2, VZV and enterovirus). What should you do now? A.Offer a HIV testOffer a HIV test B.Repeat the lumbar puntcureRepeat the lumbar puntcure C.Consider the possibility of a false negitive PCRConsider the possibility of a false negitive PCR D.Perform a swab for genital HSV-2Perform a swab for genital HSV-2 E.No other actions are needed- reassure and discharge the patientNo other actions are needed- reassure and discharge the patien A 35 year old man has aseptic meningitis and all of the routine PCR tests on his CSF are negative (HSV-1, HSV-2, VZV and enterovirus). What should you do now? A.Offer a HIV testOffer a HIV test B.Repeat the lumbar puntcureRepeat the lumbar puntcure C.Consider the possibility of a false negitive PCRConsider the possibility of a false negitive PCR D.Perform a swab for genital HSV-2Perform a swab for genital HSV-2 E.No other actions are needed- reassure and discharge the patientNo other actions are needed- reassure and discharge the patien

75 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Question 5 Select the single best answer from the options below What treatment should you give to a patient with a lymphocytic CSF, a GCS of 13 and a history of recent behavioural changes? A.Intravenous antibioticsIntravenous antibiotics B.Intravenous aciclovirIntravenous aciclovir C.Intravenous antiretroviralsIntravenous antiretrovirals D.Supportive care onlySupportive care only What treatment should you give to a patient with a lymphocytic CSF, a GCS of 13 and a history of recent behavioural changes? A.Intravenous antibioticsIntravenous antibiotics B.Intravenous aciclovirIntravenous aciclovir C.Intravenous antiretroviralsIntravenous antiretrovirals D.Supportive care onlySupportive care only

76 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Question 5 Select the single best answer from the options below INCORRECT Please try an alternative answer INCORRECT Please try an alternative answer What treatment should you give to a patient with a lymphocytic CSF, a GCS of 13 and a history of recent behavioural changes? A.Intravenous antibioticsIntravenous antibiotics B.Intravenous aciclovirIntravenous aciclovir C.Intravenous antiretroviralsIntravenous antiretrovirals D.Supportive care onlySupportive care only What treatment should you give to a patient with a lymphocytic CSF, a GCS of 13 and a history of recent behavioural changes? A.Intravenous antibioticsIntravenous antibiotics B.Intravenous aciclovirIntravenous aciclovir C.Intravenous antiretroviralsIntravenous antiretrovirals D.Supportive care onlySupportive care only

77 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Question 5 What treatment should you give to a patient with a lymphocytic CSF, a GCS of 13 and a history of recent behavioural changes? A.Intravenous antibiotics B.Intravenous aciclovir C.Intravenous antiretrovirals D.Supportive care only What treatment should you give to a patient with a lymphocytic CSF, a GCS of 13 and a history of recent behavioural changes? A.Intravenous antibiotics B.Intravenous aciclovir C.Intravenous antiretrovirals D.Supportive care only CORRECT As in most clinical situations, the history is the most important determinant in deciding what treatment is needed. If a patient is systemically well and presents mainly with symptoms of meningism, it is likely that they have viral meningitis and immediate treatment is not necessary. If a patient presents with a change in behaviour or cognition, then encephalitis is more likely and you should consider urgent treatment with antivirals, with or without antibiotics. Once the diagnosis is confirmed as viral encephalitis via PCR of the CSF, you can stop any antibiotics. There is good evidence for the use of aciclovir in herpes encephalitis, with a reduction in mortality from 70% to less than 30%. You should not start antiretrovirals unless a definitive diagnosis of HIV has been made. Click here to move on to the next scenario CORRECT As in most clinical situations, the history is the most important determinant in deciding what treatment is needed. If a patient is systemically well and presents mainly with symptoms of meningism, it is likely that they have viral meningitis and immediate treatment is not necessary. If a patient presents with a change in behaviour or cognition, then encephalitis is more likely and you should consider urgent treatment with antivirals, with or without antibiotics. Once the diagnosis is confirmed as viral encephalitis via PCR of the CSF, you can stop any antibiotics. There is good evidence for the use of aciclovir in herpes encephalitis, with a reduction in mortality from 70% to less than 30%. You should not start antiretrovirals unless a definitive diagnosis of HIV has been made. Click here to move on to the next scenario

78 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Question 6 Select the single best answer from the options below Which of the following is a recognised complication of viral meningitis? A.Recurrent episodesRecurrent episodes B.Secondary bacterial meningitsSecondary bacterial meningits C.Brain abscessBrain abscess D.Multiple sclerosisMultiple sclerosis Which of the following is a recognised complication of viral meningitis? A.Recurrent episodesRecurrent episodes B.Secondary bacterial meningitsSecondary bacterial meningits C.Brain abscessBrain abscess D.Multiple sclerosisMultiple sclerosis

79 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Question 6 Which of the following is a recognised complication of viral meningitis? A.Recurrent episodes B.Secondary bacterial meningits C.Brain abscess D.Multiple sclerosis Which of the following is a recognised complication of viral meningitis? A.Recurrent episodes B.Secondary bacterial meningits C.Brain abscess D.Multiple sclerosis CORRECT HSV-2 in particular, but also other viruses, have been shown to cause recurrent episodes of meningitis (Mollaret’s meningitis). Although viral meningitis is normally thought of as a benign, self- limiting illness, there is mounting evidence that there are important complications following viral meningitis. Studies have reported changes in various domains of cognition, for example memory and attention. Click here to finish the session CORRECT HSV-2 in particular, but also other viruses, have been shown to cause recurrent episodes of meningitis (Mollaret’s meningitis). Although viral meningitis is normally thought of as a benign, self- limiting illness, there is mounting evidence that there are important complications following viral meningitis. Studies have reported changes in various domains of cognition, for example memory and attention. Click here to finish the session

80 V IRAL M ENINGITIS Learning Objectives Overview Causes of aseptic meningitisCauses of aseptic meningitis Epidemiology Clinical Features Investigations Lumbar puncture Blood tests Viral meningitis vs encephalitisViral meningitis vs encephalitis Treatment Enteroviral meningitis Herpes meningitis VSV meningitis HIV infection Complications Key points Summary Clinical scenarios Self assessment Question 6 Select the single best answer from the options below INCORRECT Please try an alternative answer INCORRECT Please try an alternative answer Which of the following is a recognised complication of viral meningitis? A.Recurrent episodesRecurrent episodes B.Secondary bacterial meningitsSecondary bacterial meningits C.Brain abscessBrain abscess D.Multiple sclerosisMultiple sclerosis Which of the following is a recognised complication of viral meningitis? A.Recurrent episodesRecurrent episodes B.Secondary bacterial meningitsSecondary bacterial meningits C.Brain abscessBrain abscess D.Multiple sclerosisMultiple sclerosis

81 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 certificate Download a certificate and then to finish the session CLICK HERE.CLICK HERE

82 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: 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”


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