CNS Infections- Case 2-9 Flashcards
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.
There were needle tracks indicating intravenous drug use.
He had splinter hemorrhages underneath his nail beds and distal purpuric lesions in his toes, both suggesting septic embolism.
What is the likely diagnosis?
Bacterial endocarditis- The patient had septic emboli from infectious vegetations on the heart valves as shown in this picture.
Bacterial endocarditis can be acute or subacute. It can affect the brain in four ways. Namely:
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.
The pathogen in bacterial endocarditis is usually due to:
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.
This patient had a large cerebral abscess of the left temporal lobe that was missed on the clinical exam. Why would that happen?
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.
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?
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.
Why was the patient’s headache worse at night? Why did its character suddenly change?
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.
Other clinical clues of bacterial endocarditis, acute or subacute, include:
Osler’s nodes,
Janeway lesions and
Roth’s spots
How is subacute bacterial endocarditis tx?
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.
Here are some examples of more subtle splinter hemorrhages. What do you think a urine-analysis or U/A would show?
Blood
Here a some examples of Roth’s spots. These are hemorrhages with central clearing.
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.
How do you suspect a brain abscess clinically so that you can order the CT scan to make the diagnosis?
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.
Why is vision affected by a pressure wave with a brain abscess?
The posterior circulation is a lower pressure system compared to the anterior circulation and is more susceptible to CSF pressure effects.
What are some other clues to suspect a cerebral abscess?
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.
What are the risk factors for developing a brain abscess?
IV drug use,
sepsis,
local sinusitis,
penetrating skull fractures,
pulmonary arteriovenous shunts as occur with hereditary hemorrhagic telangiectasia.
How do you treat brain abscess?
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
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?
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.
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?
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.
How is a spinal epidural abscess diagnosed?
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.
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.
T.
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?
A key feature is the worsening of pain with recumbency.
Why would an epidural abscess cause pain with recumbency?
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.
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: .
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)
What lab values suggest an epidural abscess?
a high ESR or SED rate,
an elevated white count with a left shift, and
positive blood cultures.
To make the diagnosis of epidural abscess, you need:
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
What causes most spinal epidural abscesses?
Staph aureus (90%)
What are the risk factors for a spinal epidural abscess?
- Skin infection (IV drugs) - staphylococcus
- Trauma (surgery) - staphylococcus
- Osteomyelitis - staphylococcus
- GU instrumentation - Gram negative (elderly)
- Sepsis or prior dental work
- Often accompanied by local discitis and osteomyelitis.
How are epidural abscesses tx?
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
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.
The great concern in this case is meningococcal meningitis but the CSF is free of any white cells. What does the presentation suggest?
The peripheral rash is much more characteristic for Rocky Mountain Spotted Fever than meningococcemia.
RMSF is caused by what?
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.
How do you recognize RMSF clinically?
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.
How is RMSF diagnosed and tx?
Immunohistochemistry can be used to identify the organism, and treatment is often empirical with intravenous doxycycline.
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.
What causes Lyme disease?
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.
Here is a picture of the spirochete under immunofluorescence. The tick that transmits Lyme disease is also shown, before and after engorgement.
Here are two examples of erythema migrans. The rash is red and migrates peripherally from the original site of the tick bite.
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.
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.
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.
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?
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.
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:
TB subacute or chronic meningitis. Clues to the diagnosis include the patient’s 3rd world origin, abnormal chest x-ray, and characteristic CSF profile.
How do you confirm the suspected diagnosis of TB?
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.
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.
How does TB meningitis occur?
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.
In addition to meningitis, TB can cause what in the brain?
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.
How can you confirm the diagnosis of TB?
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)
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?
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.
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.
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.
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?
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.
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.
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.
What should be on the DDx for viral encephalitis?
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.
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.
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
Herpes Zoster is certainly a virus that has the potential for causing a great deal of neurological grief. How?
It lies latent in sensory ganglia for years and then becomes activated. Depending on the sensory ganglion, it can cause shingles or ophthalmic zoster.
What else can HZV cause?
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.
When Zoster affects the ophthalmic division of the trigeminal nerve,______________ results.
Zoster ophthalmicus or ophthalmic Zoster
The chief danger is ulceration of the cornea. Treatment with acyclovir and steroids prevents this complication.
HIV causes neurological disease in two major ways. Namely:
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.
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.
