Neurologic Infections

Stephen Krieger

Central nervous system (CNS) infections are significant causes of morbidity and mortality, and must be addressed with diagnostic and therapeutic urgency. CNS infections can be broadly categorized as meningitis, encephalitis, abscesses, and infections of the spinal cord.

Case Example

You are called to the emergency department to see a 46-year-old woman for “altered mental status.” On arrival, you find an Asian woman complaining of headache, nausea, and vomiting. Her examination is notable for fever, lethargy, papilledema, and nuchal rigidity.

Questions

Has the patient traveled outside the country recently?
Does she have any pets?
Any sick contacts?
Has she had any spells that may be seizures?

Urgent Orders

Order a head computed tomography (CT) scan without and with contrast
Perform a lumbar puncture, optimally prior to antibiotic administration.
Start empiric antibiotics (ceftriaxone, vancomycin, and acyclovir ± ampicillin).
Administer Dexamethasone prior to or in conjunction with administration of antibiotics if bacterial meningitis is suspected.

History and Examination

History

Time course of symptoms: Acute (<48 hour is often bacterial), subacute (often viral, can be anything), chronic/smoldering (often fungal, parasitic, or noninfectious)
History of, risk factors for, and prior testing for human immunodeficiency virus (HIV)
If HIV positive: CD4 count, highly active antiretroviral treatment (HAART) history, opportunistic infection history, and prophylaxismedication compliance
Other immunocompromised states: malignancy, malnutrition, immunosuppressive drugs, diabetes, alcoholism, renal replacement therapy, and splenectomy
Travel history, exposures, vaccinations/inoculations
Time of year:
- Summer/fall: Enteroviruses, arboviruses, Lyme disease, Rocky Mountain spotted fever
- Winter: Influenza
- Winter/spring: Measles, mumps, rubella, meningococcus, lymphocytic choriomeningitis

Physical Examination

Vitals: Full set, including accurate rectal temperature

Head, eyes, ears, nose, and throat (HEENT): Be attentive for facial rash (trigeminal zoster); ear canal vesicles (Ramsay-Hunt); thrush (HIV); parotiditis (mumps); dentition/dental abscesses; mastoid tenderness

Evaluate carefully for nuchal rigidity, meningismus, and range of motion.

Brudzinski’s sign: neck flexion elicits flexion of hips and/or knees
Kernig’s sign: flex hip and knee with thigh against abdomen, then extend knee—note pain or resistance
Both signs have poor sensitivity and are meaningful only in their presence and not their absence.

Dermatologic: Examine the patient for rashes: erythema migrans (Lyme disease), petechiae (Rocky Mountain spotted fever), purpura (meningococcemia with or without meningitis), vesicles (varicella zoster virus [VZV]), maculopapular rash (measles, rubella, lymphocytic choriomeningitis), Osler nodes (red-purple, slightly raised, tender lumps on the digits), and Janeway lesions (nontender, often hemorrhagic, flat lesions mostly on the palms and soles. Both Osler nodes and Janeway lesions are clues to endocarditis).

Neurologic Examination

A full neurologic examination, including assessment of mental status, cranial nerves, motor skills, and reflexes, as well as a sensory and cerebellar exam, should be performed on all patients.
Mental status: Assess for encephalopathy and level of attentiveness, (Can the patient do the months backward, count 20 to 1 backward?)
- Assess for aphasia, neglect, apraxia, or other cortical signs.
- Be alert for ictal or postictal states.
Cranial nerves: Cranial neuropathies are a clue to brainstem/meningeal processes (base of skull meningitis such as tuberculosis (TB) or carcinomatous meningitis, or rhombencephalitis such as caused by Listeria), hydrocephalus (sixth nerve palsy), or herniation syndromes (third nerve palsy). Assess the funduscopic exam for papilledema or macular star (as seen in neuroretinitis due to Lyme disease, Bartonella, or syphilis).
Motor/sensory: Assess for focal deficits (epidural/parenchymal abscess, empyema, tuberculoma).
Cerebellar: Assess for prominent cerebellar signs (consider varicella cerebellitis).

Differential Diagnosis

The differential diagnosis of various neurologic infections is given in Table 10.1.

Life-Threatening Diagnoses Not to Miss

Bacterial meningitis
Herpes simplex virus (HSV) encephalitis

Diagnostic Evaluation

Laboratory studies

Complete blood count (CBC), chemistry panel, liver function tests (LFTs), prothrombin time/partial prothrombin time (PT/PTT), human immunodeficiency virus (HIV), RPR/FTA, Lyme antibodies, and PPD (tuberculin skin test) placement

Blood cultures, urinalysis (UA)/urine cultures and toxicology, sputum culture

Chest x-ray, electrocardiogram (ECG), cardiac/hemodynamic monitoring; consider transesophageal echocardiogram (TEE)

Lumbar puncture—make sure international normalized ratio (INR) <1.5, PTT<40, platelets >50; always check opening pressure and closing pressure (if large-volume 30 mL tap)

Tube #1 cells and differential

Tube #2 glucose and protein

Tube #3 gram stain and culture

Consider: Acid-fast and/or tuberculosis polymerase chain reaction (TB PCR), Cryptococcal antigen and India ink stains, fungal cultures, angiotensin converting enzyme (ACE), VDRL (if serum positive), Lyme antibody (if serum positive), PCR for HSV, cytomegalovirus (CMV), VZV, human herpes virus 6 (HHV-6), JC virus, and Epstein-Barr virus (EBV)

Tube #4 cells and differential

Traumatic tap: red blood cells/white blood cells (RBC: WBC) = 700:1, 1000 RBC account for 1 mg of cerebrospinal fluid (CSF) protein

CSF findings can be found in Table 10.2.
Imaging studies
- Head CT should be performed prior to lumbar puncture (LP) if the patient is >60 years old, has a history of CNS disease, has altered mental status, an inability to answer two consecutive commands, focal neurologic signs, a seizure in the past week, or a history of HIV or immunosuppression.¹ In reality, most patients will receive a head CT.
- Magnetic resonance imaging/magnetic resonance angiography/magnetic resonance spectroscopy (MRI/MRA/MRS) with gadolinium is preferred to identify enhancing meninges, abscess, or possible vasculitis. Diffusion-weighted imaging (DWI) is particularly useful as it is bright with high sensitivity in bacterial and fungal abscesses.
- Digital subtraction angiography (DSA) can be considered if vasculitis is suspected.
Neurophysiologic testing
- EEG: Look for temporal periodic lateralized epileptiform discharges (PLEDS) with HSV. PLEDS are nonspecific and can occur with a variety of different etiologies.