CNS Infections- Case 2-9

Question 1

Let’s take another case This 30 year old man suffered a headache for one week. The headache was worse at night. Suddenly there was a change in the character of the headache, becoming much worse and associated with neck stiffness, lethargy and confusion.

Exam disclosed papilledema suggesting raised intracranial pressure. He had a heart murmur. The neurological exam showed no lateralizing signs. The skin lesions are shown on the next several slides.

Answer 1

There were needle tracks indicating intravenous drug use.

Question 2

He had splinter hemorrhages underneath his nail beds and distal purpuric lesions in his toes, both suggesting septic embolism.

Question 3

What is the likely diagnosis?

Answer 3

Bacterial endocarditis- The patient had septic emboli from infectious vegetations on the heart valves as shown in this picture.

Question 4

Bacterial endocarditis can be acute or subacute. It can affect the brain in four ways. Namely:

Answer 4

Through sepsis, it can cause a metabolic encephalopathy producing confusion, delirium and coma.

It can occlude a large cerebral blood vessel and cause acute ischemic stroke.

It can produce a focal brain area of ischemia and inflammation, so called cerebritis that precedes the development of an abscess. The abscess may be single or multiple, large or small.

Finally, a septic embolism to a distal cerebral artery can cause a focal inflammatory erosion of the vessel wall and produce a mycotic aneurysm. This can rupture and cause a subarachnoid hemorrhage.

Question 5

The pathogen in bacterial endocarditis is usually due to:

Answer 5

a gram positive organism.

Streptococcus viridans is responsible for about 50% of subacute bacterial endocarditis cases. Staphylococcus aureus and enterococcus are two other agents that infect the heart valves.

Question 6

This patient had a large cerebral abscess of the left temporal lobe that was missed on the clinical exam. Why would that happen?

Answer 6

The temporal lobe is a relatively silent area of the brain in so far as lateralizing motor and sensory signs go. However, a temporal abscess very likely would impinge on Myers loop, the white matter tract that sends visual information from the lateral geniculate body to the calcarine cortex.

If the patient had been cooperative to visual confrontation testing, the examiner should have detected a right superior quadrantic hemianopsia. In other words, the patient would have missed the wiggling fingers in the right upper visual field quadrant of each eye.

Question 7

It’s understandable that when a patient is acutely ill, visual field testing may be omitted or performed in haste. But not all is lost since we have CT and MRI, and imaging would have readily detected the mass lesion. Would you want to do an LP?

Answer 7

No. Importantly, a lumbar puncture in this patient could have precipitated a transtentorial herniation with all of its dire consequences. This is in contrast to the first patient , the young boy, who also had raised intracranial pressure and papilledema but no mass effect. He could safely tolerate the procedure.

In fact the consequent lowering of intracranial pressure by CSF removal and by tearing holes in the dura that would hopefully continue to leak CSF may have actually reduced the headache and improved cerebral perfusion, a good thing. The clinical pearl here is: get a CT prior to an LP whenever you suspect raised intracranial pressure or do a very careful neuro-exam.

Question 8

Why was the patient’s headache worse at night? Why did its character suddenly change?

Answer 8

Recall that the venous drainage of the brain and head is a valve-less system so that on lying down, one loses the effect of gravity on venous outflow and there is a back pressure that causes the distensible venous system to increase in blood volume intracranially.

When the intracranial contents are taut inside the skull, that small increase in venous blood volume causes an exponential rise in intracranial pressure and increases tension on the pain sensitive structures of the brain namely the dura, the large veins and dural sinuses, the circle of Willis and the proximal third of the ACA, MCA and PCA. This is identical to a so-called “tumor headache” or intracranial mass headache that is worse on awakening in the morning and improves with upright posture. The character of the headache changed when the abscess ruptured its contents into the CSF to cause an acute meningitis.

Question 9

Other clinical clues of bacterial endocarditis, acute or subacute, include:

Answer 9

Osler’s nodes,

Janeway lesions and

Roth’s spots

Question 10

How is subacute bacterial endocarditis tx?

Answer 10

Treatment is with antibiotics, but sometimes the heart valves need to be replaced. It is critical that the dentist prescribes antibiotics before any kind of dental work in someone who has known valvular disease or has a mechanical heart valve.

Question 11

Here are some examples of more subtle splinter hemorrhages. What do you think a urine-analysis or U/A would show?

Answer 11

Blood

Question 12

Here a some examples of Roth’s spots. These are hemorrhages with central clearing.

Answer 12

Osler’s nodes are painful “nodes” or pustules on the pads of the fingers and the toes. In contrast, Janeway lesions are painless red macular areas on the palms of the hand and soles of the feet.

Question 13

How do you suspect a brain abscess clinically so that you can order the CT scan to make the diagnosis?

Answer 13

The clues include the “tumor” headache pattern made worse on lying down.

With raised intracranial pressure, there is papilledema.
With sudden movements, up or down or sideways, the patient may experience a sudden blurring of vision. This is due to the movement triggering a so-called CSF pressure wave. The movement somehow triggers a steep rise in CSF pressure which then causes a transient visual obscuration or TVO.

Question 14

Why is vision affected by a pressure wave with a brain abscess?

Answer 14

The posterior circulation is a lower pressure system compared to the anterior circulation and is more susceptible to CSF pressure effects.

Question 15

What are some other clues to suspect a cerebral abscess?

Answer 15

Like any mass lesion, an abscess can irritate nearby cortex and induce a focal seizure with or without secondary generalization.

The CT shows a contrast enhancing ring-like lesion with surrounding edema shown by the asterisk.

Question 16

What are the risk factors for developing a brain abscess?

Answer 16

IV drug use,

sepsis,

local sinusitis,

penetrating skull fractures,

pulmonary arteriovenous shunts as occur with hereditary hemorrhagic telangiectasia.

Question 17

How do you treat brain abscess?

Answer 17

Antibiotics such as ceftriaxone or cefotaxime cover most pathogens, many of which are anaerobes, but they do not affect Bacteroides fragilis which requires the addition of metronidazole.

With serial CT or MRI, you can monitor the need for neurosurgical removal. Large abscesses and subdural empyemas usually need surgical extirpation, with empyemas requiring immediate drainage

Question 18

Question 19

Let’s look at another case. A 55 year old woman developed progressively increasing low thoracic back pain made worse on lying down. The pain became so severe that on the night prior to her visit to the ED, she slept standing up, hunched over a pillow on her grand piano. She had a low grade fever and had develop difficulty walking and urinary incontinence.

Her upper low back at T10 was exquisitely tender to percussion and palpation. Her legs were weakened so she could now barely support her weight without holding on to something. Rectal tone was reduced. Pin prick felt dull below the umbilicus. Both plantar responses were extensor.

So where is the lesion and what is going on?

Answer 19

The leg weakness, umbilical sensory level, urinary incontinence, reduced rectal tone and bilateral extensor plantar responses suggest a spinal cord lesion at T10. The mild fever suggests a subacute infectious process. The periodontal surgery could certainly have provided a bacteremia.

Question 20

So the patient presents a classic case of an epidural mass lesion, in this case an abscess. How do we know the problem was not caused by tumor or by a hematoma or something else?

Answer 20

We don’t, so we need additional information. For an epidural abscess, there is often point tenderness, which the patient demonstrated, and elevated white count and an elevated ESR, which is a non-specific index of an inflammatory process.

Question 21

How is a spinal epidural abscess diagnosed?

Answer 21

Imaging is the way to the diagnosis since tumors often causes bony destruction that is distinct from osteomyelitis that may or may not be present.

Question 22

T or F. Tumors of the spine destroy the bone but spares the intervertebral disc (nucleus pulposus) while infection often involves the disc (discitis) and relatively spares the surrounding bone, albeit not completely.

Answer 22

T.

Question 23

How do we clinically suspect an epidural abscess and order the correct imaging study without ordering a $2000 MRI on everybody with worsening back pain?

Answer 23

A key feature is the worsening of pain with recumbency.

Question 24

Why would an epidural abscess cause pain with recumbency?

Answer 24

Recall the pathophysiology underlying a tumor headache made worse with recumbency? The answer here is similar.

On lying down, the Batson’s venous plexus that drains the lower thoracic and lumbar cord has no valves. On lying down, the patient experiences increased venous back pressure that extends to inflamed areas of the dura and other pain sensitive structures.

Question 25

Also helpful in the diagonis of an epidural abscess is the point tenderness. Touch the spot and the patient jumps and claws the ceiling. Other clues include: .

Answer 25

fever and general malaise Once the patient starts to complain of gait difficulties including frequent falls, disaster is not far behind. Impotence is often an early sign but once bowel and bladder function are affected, there is a window of 24 to 48 hours in which treatment can save the spinal cord. Paraparesis or quadriparesis depending on level sensory level defect (absent pin prick sensation below the level of involvement)

Question 26

What lab values suggest an epidural abscess?

Answer 26

a high ESR or SED rate, an elevated white count with a left shift, and positive blood cultures.

Question 27

To make the diagnosis of epidural abscess, you need:

Answer 27

a spinal MRI. If the patient is too large to fit into the MRI scanner, or has a cardiac pacemaker or some other reason that prevents MRI imaging, a CT myelogram can be performed in its place. Below: spinal epidural abscess at L3-L4. It is posterior and is actually compressing the cauda equina rather than the spinal cord. Symptoms are very similar except one sees lower motor neuron signs such as reduced reflexes and plantar responses are not extensor

Question 28

What causes most spinal epidural abscesses?

Answer 28

Staph aureus (90%)

Question 29

What are the risk factors for a spinal epidural abscess?

Answer 29

1. Skin infection (IV drugs) - staphylococcus 2. Trauma (surgery) - staphylococcus 3. Osteomyelitis - staphylococcus 4. GU instrumentation - Gram negative (elderly) 5. Sepsis or prior dental work 6. Often accompanied by local discitis and osteomyelitis.

Question 30

How are epidural abscesses tx?

Answer 30

Treatment should include high dose steroids to reduce the vasogenic edema before the spinal cord is compressed so much that it infarcts and produces cytotoxic edema. Vancomycin is used to cover Staph and other antibiotics to cover anaerobes. It used to be thought that surgical drainage was indicated in all cases, but a study by Siddiq et al in the Archives of Internal Medicine published in December 2004 showed that medical management with antibiotics, sometimes with CT guided needle drainage, was effective treatment in about half of their 57 patients. Serial MRI and the patient’s clinical condition need to be followed carefully but many patients can be spared surgery

Question 31

A 15 year old boy developed a fever to 101, myalgia, headache, lethargy and a rash over his distal extremities. The neuro-exam was negative. Because of concern for meningitis, he had a lumbar puncture that disclosed only a modestly elevated protein level in the CSF.

Answer 31

Question 32

The great concern in this case is meningococcal meningitis but the CSF is free of any white cells. What does the presentation suggest?

Answer 32

The peripheral rash is much more characteristic for Rocky Mountain Spotted Fever than meningococcemia.

Question 33

RMSF is caused by what?

Answer 33

rickettsia. These are small gram negative organisms that live and proliferate only in living cells, specifically vascular endothelial cells. This leads to a systemic vasculitis that attacks the brain parenchyma and can cause confusion and seizures, as well as focal deficits. The rickettsia are transmitted by ticks and the disorder is not limited to the Rocky Mountain area but shows up in Memphis and even the Bronx.

Question 34

How do you recognize RMSF clinically?

Answer 34

Early on, the symptoms of fever, headache and flu-like symptoms are indistinguishable from the prodrome that often precedes bacterial meningitis, viral meningitis and encephalitis. The history of a tick bite is helpful, and the pattern of the skin rash is distinctive in so far that the peripheral extremities are often affected first before spreading proximally. Remarkably the CSF is usually benign or shows a modest increase in cells and protein.

Question 35

How is RMSF diagnosed and tx?

Answer 35

Immunohistochemistry can be used to identify the organism, and treatment is often empirical with intravenous doxycycline.

Question 36

Question 37

The patient had Lyme disease confirmed by Elisa and Western blot testing. Neuro-imaging was unremarkable. Following a prolonged but standard course of antibiotics, he showed incomplete cognitive improvement, and the CSF profile returned almost to normal.

Question 38

What causes Lyme disease?

Answer 38

Lyme disease is caused by a spirochete called Borrelia that is transmitted by ticks. It is endemic in the Northeast and is increasing on the west coast but has been only occasionally seen in the Memphis area. Importantly, for **the tick to transmit the spirochete, it must stay attached to the host for at least 36 hours**.

Question 39

How do Lyme disease present?

Answer 39

Two days to one month later, a characteristic skin rash called erythema migrans appears at the bite site. There is a round target-like area of redness with a central clearing that gradually expands over the ensuing days, hence the term erythema migrans. Weeks after the bite, the patient experiences flu-like symptoms, malaise, arthritis and aseptic meningitis and meningo-radiculitis in which the patient may have radicular or bandlike sensations of electric shock. Facial nerve paresis is usually bilateral and more commonly caused by Lyme disease than Bell's in the Northeast. Months later, the patient can show cognitive decline.

Question 40

How is Lyme disease tx?

Answer 40

Treatment is with IV ceftriaxone for 6 to 8 weeks but oral doxycycline is used successfully in Europe for a very similar illness.

Question 41

Here is a picture of the spirochete under immunofluorescence. The tick that transmits Lyme disease is also shown, before and after engorgement.

Answer 41

Here are two examples of erythema migrans. The rash is red and migrates peripherally from the original site of the tick bite.

Question 42

A 22 year old bisexual male, known to be HIV positive had a generalized convulsion. MRI disclosed a right parietal contrast enhancing lesion. The CSF showed a mild lymphocytic pleocytosis. Toxo titers were negative but Toxo was still strongly suspected. The patient received 2 weeks of empirical anti-toxo antibiotics. Serial MRI showed the lesion to increase in size. Primary brain lymphoma was suspected but a biopsy failed to show it. Subsequently, serum VDRL and serum fluorescent treponemal antibody were checked and found to be positive. 10 days of IV penicillin caused the lesion to disappear within one month. The patient had a syphilitic cerebral gumma initially misdiagnosed as CNS toxoplasmosis.

Question 43

What are the stages of a syphilis (treponemal pallidum) infection?

Answer 43

Primary syphilis refers to the painless genital chancre that appears at the site of inoculation within 3 weeks of exposure. Secondary syphilis is characterized by a rash, adenopathy, headache, fatigue and a mild meningitis. In HIV patients with compromised immunity, meningitis and vascular inflammation leading to ischemic stroke are more prominent. Since it is rare for an individual to live through many years without receiving antibiotics for some purpose, tertiary syphilis has become rare, including general paresis and tabes dorsalis. HIV patients are at much higher risk for syphilis and its complications.

Question 44

The syphilitic rash can range from macular, maculopapular to pustular. It is generalized, nonpruritic and heals without scarring. It often involves the palms and soles.

Question 45

How is the diagnosis of neurosyphilis made?

Answer 45

by clinical assessment and supporting serologic tests, including a serum VDRL, FTA, RPR, CSF VDRL, or a CSF pleocytosis.

Question 46

The presence of HIV can complicate the interpretation of the abnormal CSF changes seen in neurosyphilis, since HIV can alter the CSF profile by itself. A schema has been proposed for HIV patients:

Answer 46

the combination of a positive serum FTA and positive CSF VDRL means definite neurosyphilis. If the FTA is positive, but the CSF VDRL is negative, one diagnoses probable neurosyphilis if there is a CSF lymphocytic pleocytosis (more than 20 cells) or elevated CSF protein (greater than 60) and the clinical history is consistent with neurosyphilis, such as the occurrence of cranial palsies or stroke.

Question 47

How is neurosyphillis tx?

Answer 47

With high dose IV penicillin. In HIV patients, the CSF should be monitored every 6 months to look for improvement in abnormal parameters.

Question 48

The right panel shows a treponemal silver stain outlining spirochetes within the brain parenchyma. Meningovascular syphilis can appear in secondary syphilis or years later. Many years later, one may see the rarer complications of tertiary syphilis including gumma formation, tabes dorsalis and general paresis causing atrophy and dementia.

Question 49

A 36 year old immigrant from India complained of a low grade fever and a severe headache that brought him to the ED on two occasions. His physical exam was said to be normal. On his 3rd visit, papilledema was noticed, as were multiple cranial nerve deficits. A head CT showed early hydrocephalus. How would you analyze and diagnose this case?

Answer 49

The papilledema and headache point to raised intracranial pressure. The pressure appears to be diffuse in so far that no focal or lateralizing deficits are described and the CT does not show any mass lesion. The CT does show evidence for obstructed CSF outflow that is diffuse as might occur with damage to the arachnoid villi that resorb CSF.

Question 50

So, what additional testing might you do for case 7?

Answer 50

A spinal tap may be not only diagnostic but therapeutic when hydrocephalus and raised intracranial pressure do not show a focal structural obstruction of CSF flow.

Question 51

An example of structurally obstructed CSF flow would be:

Answer 51

an Arnold –Chiari malformation. Here thecerebellar tonsils sag into the foramen magnum. Patients complain of a headache and have a stiff neck. An LP could cause sudden herniation of the lower brainstem into the foramen magnum, distort the medulla's respiratory centers and cause a respiratory arrest. In this patient, the CT ruled that possibility out.

Question 52

Case 7: The LP showed increased intracranial pressure and provided headache relief to the patient. The CSF profile was abnormal with a predominantly lymphocytic pleocytosis, modest depression of the CSF glucose level, a very high protein, and negative gram stain. This is classic pattern for:

Answer 52

TB subacute or chronic meningitis. Clues to the diagnosis include the patient's 3rd world origin, abnormal chest x-ray, and characteristic CSF profile.

Question 53

How do you confirm the suspected diagnosis of TB?

Answer 53

Traditionally, you would stain for acid fast bacilli or AFB and send away CSF for culture. Immune fluorescence stain is easier to detect but for both staining and culture, detection is volume dependent. On average, you need about 30 cc of CSF to confirm the diagnosis through culture, and that takes 4 - 8 weeks to complete. PCR is now available but there is no standardization to the test, and labs differ in their sensitivity in detecting TB in the CSF.

Question 54

If untreated, TB produces a granulomatous meningitis that is especially severe at the base of the brain. That causes entrapment of multiple cranial nerves and blocks CSF flow, causing hydrocephalus and raised intracranial pressure.

Question 55

What are the clinical symptoms of chronic meningitis?

Answer 55

1. Fever (low grade) 2. Headache 3. Lethargy 4. Poor appetite/weight loss 5. Cranial neuropathy 6. Personality change 7. Cognitive impairment

Question 56

How does TB meningitis occur?

Answer 56

The dissemination of the pathogen from a primary infection in the lung or GI tract occurs via the blood. The bacteria lodge in the vascular periphery and form small, miliary tubercles, some of which stud the cortical surface. These tubercles are encapsulated by the host's immune response, but can later be reactivated and seed the meninges. Below: TB tubercles can be seen studding the brain surface on the left. Thick basal meninges can be seen trapping various cranial nerves on the right.

Question 57

In addition to meningitis, TB can cause what in the brain?

Answer 57

a vasculitis with vessel thrombosis and brain infarction. Some tubercles grow to a great size to produce caseating granulomas and act as mass lesions in the brain.

Question 58

How can you confirm the diagnosis of TB?

Answer 58

Ideally you would like to culture the organism, if only to determine its drug sensitivities. There is a new ribosomal RNA PCR test that may prove to be more reliable than other PCR tests in the past (results back in three days)

Question 59

How good are CXR or PPDs in diagnosing TB? Neuroimaging?

Answer 59

A tuberculum skin test or PPD can be useful but should always include a control, such as Candida or Trichophyton, to make certain that the patient is not anergic. Only positive in 50% of pts. The chest x-ray is abnormal/positive in 75% of patients. Neuro-imaging detects tubercles in a minority of cases and has its chief utility in eliminating other considerations from the differential.

Question 60

What is the TB CSF profile?

Answer 60

elevated opening pressure, lymphocytic pleocytosis, modestly decreased glucose, high protein

Question 61

What are the risk factors for TB meningitis?

Answer 61

3rd world, HIV, homeless alcoholics

Question 62

How is TB meningitis tx?

Answer 62

Treatment consists of isoniazid, rifampin and pyrazinamide plus a 4th drug such as streptomycin or ethambutol. Although somewhat controversial, corticosteroids do appear to improve neurological outcome and reduce mortality when the meningitis is moderate or severe (taper dexamethasone over 6 weeks)

Question 63

A young football player developed a fever to 102, stiff neck and headache over a three day period. There was no rash. Except for the nuchal rigidity and an absence of retinal venous pulsations, his exam and CT scan were normal. The spinal tap disclosed a moderately elevated opening pressure, 75 white cells, most of which were lymphocytic and essentially normal glucose and protein. Where is the lesion?

Answer 63

The neck stiffness points to meningeal irritation, which is confirmed with the spinal tap. Note that the absence of confusion, lethargy, seizures or other neurological deficits means that the brain parenchyma is spared. **This is a classic case of aseptic meningitis which is usually caused by viruses.**

Question 64

T or F. Viral etiologies are more common than bacterial causes of meningitis.

Answer 64

T.

Question 65

Among the more common pathogens of viral meningits are:

Answer 65

ones that live in your gut, including the enterovirus Echo, Coxsackie and enterovirus 71. These viruses sometimes cause mini-epidemics within a family. **The viruses are spread by the hand-oral-fecal route and the spread can be prevented with regular hand-washing and good hygiene habits.**

Question 66

One type of recurrent meningitis associated with so-called Mollaret cells in the CSF is due to a persistent infection with what?

Answer 66

Herpes simplex virus type 2 that causes genital herpes. Often the patients are unaware of genital infection, but require continuous therapy with acyclovir or one of its closely related drugs to prevent recurrence of the viral meningitis. Note also that HIV seeds the meninges early after infection and may cause an aseptic meningitis at the time of seroconversion. HIV may also trigger later episodic or chronic meningitis.

Question 67

Notes about viral meningitis etiology

Answer 67

- more common than bacterial - pts dont present extremely ill, are not encephalopathic - 80% causd by enterovirus and 7% via Mumps

Question 68

How do you recognize viral meningitis?

Answer 68

Patients develop fever, malaise, neck stiffness and low back pain that is commonly forgotten because **the headache is so much worse**. There may be a prodromal URI. The disorder subsides without specific treatment in a week or two (self-limiting). If recurrent, probably due to Herpes simplex 2 (HSV2 that causes genital herpes)

Question 69

How is viral meningitis diagnosed?

Answer 69

The CSF opening pressure is usually raised (180+ mm H₂O) and the CSF exhibits a lymphocytic pleocytosis, normal glucose and mildly increased protein. **Gram stains and bacterial cultures are negative**. Acute and convalescing titers for IgG Index against specific viruses is often helpful. There are many PCR tests being developed for viral identification

Question 70

How is viral meningitis tx?

Answer 70

Treatment is symptomatic. Most cases are self-limited and resolve without any specific treatment. However, early in the course, it is sometimes unclear whether one is dealing with early onset bacterial meningitis, Rocky Mountain Spotted Fever, or a viral encephalitis that has yet to but will involve the brain parenchyma. One option, perhaps the best, is to start the first round of treatment and then withdraw antibiotics as test results return to exclude certain pathogens. If the patient does not look particularly sick, one may hold off treatment until the CSF results come back to guide therapy. It is a clinical judgment call. Some experts warn they have been burned by a wait and watch decision to see what happens because after a few stable hours, the deterioration just took off.

Question 71

When HSV2 causes recurrent meningitis, how should it be tx?

Answer 71

valacyclovir, famciclovir or acyclovir is prescribed. The former two are somewhat easier to take requiring fewer doses per day than the five with acyclovir.

Question 72

Now for the last case. A 36 year old woman develops URI type symptoms and is treated for the “flu”. However, three days later, she becomes disoriented and forgetful. Then she has a generalized convulsion.

Answer 72

The exam shows that she is febrile to 40.5 degrees celsius. Has no rash. She does have evidence of raised intracranial pressure in so far that her retinal venous pulsations are absent and there is early obscuration of the optic disc margins. There is moderate nuchal rigidity. She is stuporous but will open her eyes to her name. The exam is essentially non-focal except that the eyes are tonically deviated to the right.

Question 73

What do you make of the eye deviation to the right in Case 9?

Answer 73

There are several possibilities. First, she may have had a right hemispheric injury that included the right frontal eye fields so that the left intact eye fields are tonically driving the eyes to the right. Against this is the absence of other right hemispheric neurologic deficits such as a left hemiplegia. Alternatively, the left frontal eye fields may be hyperactive, discharging abnormally as an epileptogenic focus and thereby driving the eyes to the right. That certainly is possible if there were any additional evidence for a focal initiation of seizure arising in the left hemisphere. Finally, the brainstem’s left horizontal gaze may be out of commission, so that the eyes would deviate to the right due to unopposed right horizontal gaze center pulling the eyes tonically to the right.

Question 74

The peripheral CBC and differential do not support a bacterial or purulent pathology. The head CT is useful in excluding various structural lesions. The early cerebral edema is not that specific. The LP, on the other hand, is very helpful. There is a modest increase in intracranial pressure but **more importantly, there is a striking lymphocytic pleocytosis with a few neutrophils that are slightly but abnormally increased.** The protein is mildly raised but the glucose is normal and all of the conventional bacterial and fungal players that can be detected by stains and wet mounts are absent. Where does this leave us?

Answer 74

First of all, we know the brain parenchyma is involved so this by definition is consistent with an encephalitis. Secondly bacterial and fungal causes appear to be made unlikely, while viruses are a real possibility. **So a viral encephalitis would appear to rise to the top of the differential at this point.** This is where the MRI can be especially helpful because it can detect early brain changes that the CT misses. Let’s see what the MRI shows on the next slide.

Question 75

The MRI on T2 imaging discloses areas of edema that the CT missed. It shows evolving edema in the right temporal lobe and extending into the base of the right frontal lobe (not shown here). **This patient’s MRI shows the classic picture for herpes simplex type 1 encephalitis.** Importantly, it rules out cerebral abscess, cerebral venous thrombosis and subarachnoid hemorrhage that can sometimes mimic herpes encephalitis.

Answer 75

Hence we would hope that the patient was already on acyclovir before these pictures were ever taken since the history was quite consistent with a viral encephalitis. If acyclovir is started after the patient has lapsed into coma, the prognosis is very poor. Again, the earlier you treat the better the outcome. So treat empirically when you are not sure of the diagnosis but suspect CNS infection.

Question 76

What is the most common cause of viral encephalitis?

Answer 76

Roughly one third of encephalitides are due to arborviruses, which means that they are transmitted by mosquitoes.

Question 77

More on arbovirus induced viral encephalitis

Answer 77

These cases of encephalitis occur in the spring, summer and early fall when mosquitoes are active, and it is children who play outdoors who are most likely to be bitten by the mosquitoes and develop the encephalitis. **When you are bitten by an infected mosquito, however, the chances of your coming down with encephalitis is still quite small.** Take the example of West Nile virus. The original outbreak was first recognized in Long Island, New York, but it became rapidly clear that thousands of people had been infected and had suffered a mild to moderate flu-like syndrome. Only a few patients actually came down with serious neurological symptoms.

Question 78

The Asian equivalent for West Nile, by the way, is:

Answer 78

Japanese B virus, which causes a very similar disease to West Nile.

Question 79

What are some other causes of viral encephalitis?

Answer 79

About a quarter of encephalitis cases are attributable to enterovirus, the same group that ordinarily causes a self-limited viral meningitis. **What you should really focus your attention on, however, is herpes simplex type 1 encephalitis (27% of cases).** This virus accounts for about a third of all viral encephalitis cases, occurs sporadically throughout the year, and is a real killer if left untreated. Fortunately, acyclovir has dramatically improved prognosis if the antiviral drug is started early in the course of the infection, before the patient lapses into coma.

Question 80

So what happens to patients with viral encephalitis in which natural history takes its course?

Answer 80

The illness typically has a prodromal period with URI symptoms, followed by fever, headache, lethargy and confusion. Seizures are often followed by stupor and coma and ultimately death. T_his clinical picture is virtually indistinguishable from bacterial meningitis and Rocky Mountain Spotted Fever_. Hence, the reason to treat empirically, before you have figured out the diagnosis, and to treat vigorously since the patient’s life really does depend upon your prompt action.

Question 81

What should be on the DDx for viral encephalitis?

Answer 81

Note that CNS vasculitis often shows fluctuation in space and time so that some areas of the brain are recovering while other areas are worsening over time.

Question 82

What is Post-infectious or post-vaccine immune mediated encephalitis?

Answer 82

resemble an attack of multiple sclerosis except that huge areas of the brain are affected.

Question 83

How is viral encephalitis diangosed?

Answer 83

Making the diagnosis involves the clinical history and for viral identification, IgM titers and PCR are often the best tests available. IgM for West Nile, for example, is the way to go with the diagnosis.

Question 84

What is the prognosis of viral encephalitis?

Answer 84

Prognosis depends on the virus and severity of the inflammatory response by the host. Some etiologies are treatable, such as the encephalitis caused by HSV-1 (acyclovir) and CMV (ganciclovir). Other etiologies have no specific treatment but ICU support may permit a modicum of recovery. Certain infections such as rabies are virtually always fatal.

Question 85

Here is a pathological specimen of hemorrhagic necrosis in the temporal lobe due to herpes encephalitis. Usually, the damage is far more extensive than seen here.

Question 86

Since herpes encephalitis is treatable much as any bacterial infection, I will summarize the most important points. Treat early and don’t be fooled by potential mimics. MRI is the best tool to make an early diagnosis. PCR results are usually definitive but not always so the test results must always be interpreted in the context of the clinical presentation

Question 87

Herpes Zoster is certainly a virus that has the potential for causing a great deal of neurological grief. How?

Answer 87

It lies latent in sensory ganglia for years and then becomes activated. Depending on the sensory ganglion, it can cause shingles or ophthalmic zoster.

Question 88

What else can HZV cause?

Answer 88

Sensory ganglion neurons are bipolar and that the virion can be transported into the nervous system too to produce zoster myelitis or zoster encephalitis. There is sensory input to the proximal third of the large intracranial arteries, so inflammation can involve them as well to cause giant cell arteritis of the CNS and ischemic stroke.

Question 89

What are the risk factors for herpes zoster reactivation?

Answer 89

Most of us have been previously infected with herpes zoster which lies dormant in our sensory ganglia. For unclear reasons, the latent virus becomes reactivated. Risk factors: \>50 yrs of age, immunosuppression (HIV, lymphoma).

Question 90

What happens when herpes zoster becomes reactivated?

Answer 90

More virion particles are synthesized in the cell body, transported down the axon and secreted into the subcutaneous space. Once out, the virus particles induce a marked inflammatory response that results in the characteristic rash. **Shingles is the term used for the rash which typically involves one or two dermatomes**. After the vesicular eruption heals, some patients develop a pain syndrome called post-herpetic neuralgia that can be incapacitating and very difficult to treat.

Question 91

When Zoster affects the ophthalmic division of the trigeminal nerve,\_\_\_\_\_\_\_\_\_\_\_\_\_\_ results.

Answer 91

Zoster ophthalmicus or ophthalmic Zoster The chief danger is ulceration of the cornea. Treatment with acyclovir and steroids prevents this complication.

Question 92

HIV causes neurological disease in two major ways. Namely:

Answer 92

It can act directly as the agent that induces acute or chronic meningitis, and causes dementia, myelopathy, neuropathy and myopathy. It can also act indirectly by altering immunity so as to place the patient at risk for a variety of unusual infectious and noninfectious complications resulting in AIDS.

Question 93

By suppressing the CD4 cellular immune system, HIV infection indirectly causes a variety of neurological disorders that lead to the diagnosis of AIDS. Among these, __________________ is by far the most frequent complication seen.

Answer 93

brain infection with toxoplasmosis

Question 94

Other infectious processes seen with HIV include:

Answer 94

cryptococcal meningitis, TB and progressive multifocal leukodystrophy or PML. HIV can induce a vasculitis. Primary CNS lymphoma and Kaposi’s sarcoma are two neoplastic complications associated with HIV. There are nutritional and metabolic disorders and drug toxicity that results from long term use of anti-retroviral therapy. HAART therapy has revolutionized the treatment of HIV so that life expectancy has increased dramatically.

Question 95

Question 96

Shown above is a histological specimen of toxoplasma parasite. These can invade the brain in multiple sites but have a predilection for the basal ganglia. On the right is a T1 MRI showing typical scattered lesions.