E. Lee Murray, MD
CHAPTER CONTENTS
◦Variant CJD and Bovine Spongiform Encephalopathy
•Herpes Zoster and Post-herpetic Neuralgia
•Progressive Multifocal Leukoencephalopathy
OVERVIEW
Infectious diseases are a common cause of hospital neurology consultation either because infection has directly involved nervous structures or patients with infection have developed a neurologic condition.
Neurologic complications of sepsis were discussed in Chapter 11. Detailed discussion of cerebrospinal fluid (CSF) analysis and interpretation is presented in Chapter 40.
MENINGITIS
Meningitis is most commonly first seen in the ED; hospital-acquired meningitis is rare in the absence of instrumentation. The most common cause is viral, with bacterial being less common, and fungal being quite rare and usually seen in an immunocompromised host.
Symptoms of meningitis depend on etiology, but the classic triad is fever, headache, and neck pain. Chronic meningitis will not be expected to have all of these, and nonbacterial meningitis may not be associated with fever. Altered mental status is common with meningitis of any cause.
Meningeal signs: Signs of meningeal inflammation depend on etiology. Meningeal signs are more often absent than present, but they are still commonly evaluated.
•Kernig sign: Supine patient has hip and knee flexed, then the knee is straightened so that the foot points upward. Sign is positive if there is resistance to straightening of the knee.
•Brudzinski sign: Supine patient has neck passively flexed to the chest. Sign is positive if there is reactive flexion of the hip.
•Neck rigidity is the most important of these signs. This is decreased mobility of the cervical spine because of muscle rigidity. This is often tested by attempts at active or passive flexion of the neck to the chest.
Viral Meningitis
Viral meningitis has many possible pathogens. The most common are enteroviruses, responsible for about 85% of viral meningitides, followed by herpes simplex virus 2 (HSV2). A list of encephalitides that are likely to be seen includes:
•Enterovirus (e.g., coxsackievirus, echovirus)
•California encephalitis virus
•Lymphocytic choriomeningitis virus
Routes of infection are varied and depend on the specific agent. Some are seasonal, with the common enteroviruses predominating in summer and early fall.
PRESENTATION is with a constellation of symptoms that can include headache, neck pain, nausea, and vomiting, usually with fever. Rash and photophobia can occur. Prodromal symptoms with malaise and myalgias can occur. Encephalopathy can occur, but seizures are uncommon.
DIAGNOSIS is suspected when patients present with headache and fever, especially with mental status change. Blood WBC is usually increased. CSF analysis makes the diagnosis.
Computed tomography (CT) or magnetic resonance imaging (MRI) brain is often done. It is obligatory if encephalopathy or seizure develops. Contrast enhancement can show meningeal enhancement.
CSF findings:
•CSF appearance: Usually clear
•Opening pressure: Normal or mildly elevated
•WBC: Usually in the range of 10–1,000 cells/μL, usually lymphocytic but may be polymorphonuclear early
•Glucose: usually normal but may be reduced in HSV encephalitis
•Protein: Usually mildly elevated
•Polymerase chain reaction (PCR): May be positive for selected viruses, including HSV, VZV, West Nile virus (WNV), enterovirus
•Cultures and smears: Seldom revealing for viral meningitis
Electroencephalogram (EEG) can be normal or show diffuse slowing. Periodic discharges can be seen with HSV encephalitis but would not be expected with meningitis.
MANAGEMENT is supportive for most viral meningitides. Most are self-limited disorders. The main opportunity is treating meningitis due to HSV and HIV, and for treating patients in whom the meningitis might be bacterial.
•HSV meningitis is treated with acyclovir.
•HIV meningitis is treated with antiretroviral agents.
•Cytomegalovirus (CMV) meningitis in immunocompromised patients is treated beginning with ganciclovir.
Bacterial meningitis may be suspected at the time of presentation because there is an overlap in CSF WBC counts, and not all patients with bacterial meningitis have low glucose. Empiric therapy1 may be given as if the patient had bacterial meningitis:
•Vancomycin + either ceftriaxone or cefotaxime
•Ampicillin is added if listeria is suspected.
Dexamethasone is routinely used for patients with bacterial meningitis; if there is concern about a bacterial cause at the time of initial evaluation, then administration is recommended. A common protocol is dexamethasone 10 mg IV q6h for 4 days.
Bacterial Meningitis
Bacterial meningitis is much more acute than viral meningitis for most patients. Important organisms include:
•Strep pneumoniae (Pneumococcal meningitis): Most common
•Haemophilus influenzae: Less common since vaccine
•Neisseria meningitidis (meningococcal meningitis): Especially with high-density housing (e.g., college dorms)
•Listeria monocytogenes: Especially in alcoholics; immunosuppressed; pregnant; chronic diseases such as hepatic and renal failure, and diabetes; and elderly
•Gram-negative bacilli: Especially after neurosurgical procedures, immunosuppressed, elderly (e.g., Escherichia coli, Klebsiella pneumoniae)
•Staphylococci: Especially after head injury, neurosurgical procedure, shunts
•Group B Streptococcus: with immunocompromised state, alcoholism, pregnancy, hepatic or renal failure, pregnancy
PRESENTATION is with various combinations of fever, headache, nausea/vomiting, and neck pain, stiffness, or rigidity. Rash is common with meningococcal meningitis. Symptoms can be subtle initially, especially with an immunocompromised state. With more severe meningitis, cerebral symptoms may develop—delirium, confusion, progressing to seizures and/or coma. Cranial nerve palsies can occur.
DIAGNOSIS is suspected by headache with signs of inflammation such as fever or increased blood WBC. Diagnosis is confirmed by lumbar puncture (LP).
•Patients with sinuses as a source may have active sinusitis at the time of presentation, and this should be looked for using sinus CT.
•Brain imaging with CT or MRI should be done emergently and prior to the LP if there are signs of encephalopathy, cranial nerve palsy, or seizure. If none of these is present, LP can be done as soon as meningitis is considered so CSF can be obtained prior to urgent administration of antibiotics.
CSF findings:
•Appearance is clear or cloudy depending on cell count.
•Opening pressure is elevated.
•WBC is typically in the thousands with bacterial meningitis, although levels down into the low 100s can be seen. Polymorphonuclear predominance favors bacterial etiology.
•Glucose is typically low, and very low levels signify a poor prognosis.
MANAGEMENT begins with empiric therapy immediately after suspicion of bacterial meningitis. Antibiotics are usually ordered as soon as meningitis is suspected and given as soon as the LP is completed. If there must be a delay in LP because of pending imaging, logistics, or otherwise, then antibiotics are given immediately. Consultation with infectious disease is recommended since local antibiograms differ and recommendations made here may be replaced by updated information since publication.
Empiric therapy for suspected bacterial meningitis at the time of writing is as follows:
◦Vancomycin + either ceftriaxone or cefotaxime
– Listeria is suspected on the basis of disorders listed at the beginning of this section
•Post-neurosurgery, penetrating injury, or CSF shunt
– Cefepime, or ceftazidime, or meropenem
Doses depend on a number of factors including size, age, and comorbid conditions, so please consult published prescribing information. Organism-specific therapy is guided by identification and sensitivities; our infectious disease colleagues should be consulted for assistance.
Steroids have become part of standard therapy for bacterial meningitis. A standard dose is dexamethasone 10 mg IV q6h for 4 days.
Intrathecal antibiotics are sometimes considered for patients who have had recent neurosurgery or instrumentation and who have not responded to IV antibiotics.
Some patients with severe bacterial meningitis develop cerebral edema with risk for herniation. Standard measures for increased intracranial pressure (ICP) are commonly given (Chapter 41).
Seizures are treated with standard antiepileptic drugs (AEDs), usually parenteral, including fosphenytoin, valproate, or levetiracetam. Midazolam or propofol can be given for status epilepticus.
Fungal Meningitis
Fungal meningitis is uncommon in immunocompetent patients. Cryptococcus neoformans is the most common organism. Other notable agents are Aspergillus, Histoplasma capsulatum, Blastomyces, and Coccidioides immitis.
PRESENTATION is usually subacute to chronic with cognitive changes. Headache and fever often occur, but this is not invariable. Deficits can include ataxia, weakness of extremities, and occasionally cranial nerve palsies, especially with cryptococcal meningitis.
DIAGNOSIS is usually considered when a patient with confusion and/or ataxia has negative imaging and basic lab studies. Since most cases are immunocompromised, this history is helpful.
Brain imaging with CT or MRI often shows hydrocephalus, especially with cryptococcal meningitis. Contrast reveals meningeal inflammatory change in many patients.
CSF findings:
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