Neuro ID

Question 1

Answer 1

Meningitis
Purulent material in the subarachnoid space from abundant PMNs

Question 2

Answer 2

Abscess(bottom)
– Occur at the gray-white junction often with marked edema out of proportion to the size of the abscess.
– Necrotic core surrounded by a thick wall of fibroblasts (circle) and proliferating blood vessels

Question 3

Answer 3

Granulomas
Composed of epitheliod macrophages (closed arrow), multinucleate giant cells (circle), lymphocytes (open arrow)
Caused by:
– Tuberculosis
– Fungi
– Spirochetes
– Sarcoidosis(non-caseating)
– Foreignbody

Question 4

Answer 4

TB meningitis
Subacute to chronic course
Tuberculosis, fungus, and spirochetes have a predilection for the base of the brain.
Tuberculosis and other mycobacterium are acid- fast bacteria (arrow).

Question 5

Answer 5

Fungi as hyphae

Aspergillus
– Presents most commonly as infarction (since it is angioinvasive) and less frequently as an abscess usually in immuno- compromised patients
– Narrow regular hyphae branching at acute angles (arrow) invading blood vessels.

A for acute

This patient has aspergillosis, which is caused by the aspergillus fungus. This organism is capable of causing various manifestations, such as allergic syndromes, respiratory tract infections, and sinusitis. However, it may also cause an invasive syndrome that can spread to the CNS, especially in neutropenic patients, immunocompromised patients, or those chronically on steroids.Aspergillus fumigatus is the organism that causes most of the invasive syndromes, invading blood vessels, causing stroke-like syndromes, infarcts, and hemorrhagic transformation. A vasculitis- type phenomenon occurs as the fungus invades the vessel walls and may eventually progress to parenchymal disease, forming granulomas, and abscesses. This fungus may invade multiple other organs and cause systemic disease.

Histopathologically, invading hyphae are detected in blood vessels, with the findings of necrosis, hemorrhage, and inflammation. The specimen shown in Figure 15.8 is a Gomori methenamine silver stain demonstrating septate hyphae that branch at acute angles, which is consistent with aspergillus infection. Aspergillosis does not typically present with meningitis.

Cryptococcus causes meningitis and not typically a vasculitis-type syndrome. Histoplasmosis causes pulmonary disease more frequently, but when it invades the CNS, it can produce a form of basilar meningitis, focal cerebritis, or granulomas. Candidiasis can also cause systemic disease, with histopathological findings of budding yeasts and pseudohyphae. This patient does not have clinical features or pathologic findings of HSV encephalitis (discussed in question 37).

Question 6

Answer 6

Fungi as hyphae

Mucormycosis (bottom)
– Presents with rhinocerebral disease typically in diabetics, transplant patients, hematologic malignancies
– Triad of DKA, blackened nares, and ophthalmoplegia
– Can also cause infarcts since it is angioinvasive.
– Broad irregular hyphae branching at 90 degrees (circle).
– High mortality: 44%

A zygomycosis.

This fungus tends to enter through the respiratory tract, producing nasal and sinus disease and pulmonary infections. In the presence of predisposing factors and trauma, it may invade blood vessels and gain entry into the CNS, where it can produce an acute necrotizing reaction and vascular thrombosis, including venous sinus thrombosis, especially affecting the cavernous sinus.

Externally, patients have a destructive inflammatory and necrotizing lesion affecting the face, especially in the nasal and maxillary areas.

Diabetes mellitus and diabetic ketoacidosis are major and frequent risk factors for this condition. Other predisposing conditions include malignancies, high-dose steroids, organ transplantation, immunosuppression, and iron chelation therapy (with deferoxamine).

The organisms causing this infection are mucor, rhizopus, and rhizomucor, which are fungi and not acid-fast bacilli. These fungi are seen as infrequently septated or nonseptated hyphae on histopathologic specimens.

Question 7

Answer 7

Fungi as yeast

Cryptococcus
– Most common CNS fungal infection
– Presents as meningitis with increased ICP or mass lesion (cryptoccocoma)
– large (2-15 mm) budding yeast with a thick carbohydrate capsule (arrow)
– Often forms microabcessess.
– Predilection for the perivascular spaces

Encapsulated yeast

Histopathologic specimen demonstrates budding yeasts near blood vessels and surrounded by an inflammatory infiltrate

Seen in immunocompromised patients with CD4 count<100

S(x)s: fever, headache, neck stiffness, personality and behavioral changes, and altered mental status. Brain CT scan and MRI are performed to rule out other conditions and may demonstrate hydrocephalus, gelatinous pseudocysts, infarcts, or cryptococcomas. Lumbar puncture demonstrates an increased opening pressure, and CSF analysis shows mononuclear lymphocytosis with increased protein and low glucose levels. India ink smear is not very sensitive; however, it is useful when it is positive. Cryptococcal antigen detection in the CSF is rapid, sensitive and specific, and clinically useful, since fungal culture may take several days to weeks for a positive result to be obtained.

The initial treatment regimen is amphotericin plus flucytosine for 2 to 3 weeks. These patients should be monitored closely, since amphotericin is associated with renal failure, hypokalemia, and hypomagnesemia; and flucytosine may cause hematologic abnormalities. If the patient is doing well on amphotericin and flucytosine, or the meningitis is mild, the treatment can be switched to fluconazole 200 mg twice daily for 8 to 10 weeks. Afterward, the patient should be kept on long-term maintenance therapy with fluconazole 200 mg daily to prevent recurrences. Highly active antiretroviral therapy, by promoting immune reconstitution, plays a major role in the long-term treatment of HIV patients with cryptococcal meningitis, after the acute infection has cleared.

Mortality rate in the acute setting may be related to elevated intracranial pressure, which should be treated. Patients with increased intracranial pressure may need frequent CSF drainage by repeated lumbar punctures or even ventriculostomy.

Question 8

Answer 8

Fungi existing as yeast

Candidiasis
Rare CNS pathogen
Presents as meningitis or abscess
Multiple yeast may connect to each other mimicking branching hyphae (pseudohyphae)

Question 9

Coccidioides

Answer 9

Dimorphic fungi: Hyphae at 25 degrees celsius, yeast at 37 degrees celsius

Second most common CNS fungal infection usually a meningitis in normal host from Southwest
Small yeast with large spherical endospore (arrow).

Question 10

Histoplasma

Answer 10

Rare CNS pathogen
Presents as meningitis or abscess usually in AIDS patient from Ohio or upper Mississippi Valley

Question 11

Blastomyces

Answer 11

Rare CNS pathogen
Presents as meningitis or abscess in normal host from lower Mississippi Valley

Question 12

Answer 12

Presents as mass lesions or less commonly a solitary lesion in deep nuclei, posterior fossa, or gray- white junction in immuno- compromised patients.
Exists in 2 forms
– Psuedocystfilledwithslow- growing round bradyzoite (circle)
– Active-growingbasophiliic comma-shaped tachyzoites
– Alsoseechronic inflammation (lymphocytes and plasma cells)

Question 13

Answer 13

Neurocystricosis

Caused by the larval form of the pork tapeworm, Taenia solium, which is endemic in Latin America, Sub-Sahran Africa, and parts of Asia and accounts for almost 30% of epilepsy in those regions.
initially can present as an inflammatory reaction to a mass lesion
Chronically presents as seizures secondary to parenchymal calcified granulomas.
Multiple small cysts (less than 1 cm) located in parenchyma, ventricles, and basal cisterns.
Ventricular lesions can cause hydrocephalus
The punctate structure in the cyst is the scolex (arrow).

Question 14

Microglial nodules

Answer 14

Nonspecific findings common in encephalitis
Hypercellular cluster containing microglia and reactive astrocytes (circle).

Question 15

Perivascular cuffing

Answer 15

Nonspecific finding common in encephalitis
Lymphocytes surrounding blood vessel (arrow).
• Similar findings in demyelinating disease and CNS lymphoma

Question 16

Cowdry A

Answer 16

Neuronal intranculear inclusions
– Single, large inclusion surrounded by a halo that efface the nucleus (circle).
– Seen in HSV, CMV, VZV, and SSPE.

Question 17

Cowry B

Answer 17

Neuronal intranuclear inclusions

Multiple, small inclusions without a halo that do not efface the nucleus (arrows).
Seen in Polio or normally in the substantia nigra (Marinesco body)

Question 18

Answer 18

HSV encephalitis
HSV has a predilection for the temporal lobes/ basal forebrain (circle).
Classically presents as a hemorrhagic encephalitis

Question 19

Answer 19

Rabies

Characterized by eosinophilic intracytoplasmic inclusions within pyramidal cell neurons (Negri bodies) (circles).

Carried by:
– Raccoons
– Skunks
– Bats
– Foxes
– Coyotes

Question 20

PML

Answer 20

Necrotic demyelination beginning in the white matter within a cortical gyrus (circle).
Characterized by:
– Ground glass inclusions in oligodendroglia nuclei (blue arrow)
– Bizzarre astrocytes (black arrow)

Question 21

Bacterial meningitis by age

Answer 21

In order of prevalence?
Neonate: GNRs, Group B Strep, Listeria
1 mo - 15 year: H influenzae, N meningitidis, S pneumo
15 - 50 year old: S pneumo, N meningitidis, staphlococci
>50 years old: S pneumo, Listeria, GNRs

Different way to memorize it
Neonate: GNRs, Listeria, Group B Strep,
1 mo - 15 year: H influenzae, N meningitidis, S pneumo
15 - 50 year old: Staphylococci, N meningitidis, S pneumo
>50 years old: GNRs, Listeria, S pneumo

Question 22

Dexamethasone in bacterial meningitis

Answer 22

Suggested for adults with suspected/confirmed pneumococcal meningitis, no evidence of harm in meningococcal meningitis
Best survival difference in Europeans>55
Modest reduction in hearing loss

Adds Hib meningitis in children

Dose: 10 mg q6h x 4 days

Question 23

CSF Hypoglcorrhachia

Answer 23

Cancer
Bacterial
TB
Neurosarcoidosis
Sometimes HSV
Someties fungal

Question 24

Meningococcal disease prevention if exposure

Answer 24

Rifampin PO 2 days, children<1 mo 5 mg/kg q12h, > 1 mo 10 mg/kg q12h, adults 500 mg q12h

Question 25

Meningococcal disease prevention if exposure

Answer 25

Rifampin PO 2 days, children<1 mo 5 mg/kg q12h, > 1 mo 10 mg/kg q12h, adults 500 mg q12h
Ciprofloxacin single PO dose of 500 mg
Ceftriaxone singe dose IM 125 mg if <15 yo, 250 if>15 yo

Rifampin not rec’d during pregnancy (teratogen), may interfere with OCP
Ciprofloxacin not rec’d <18 yo or pregnancy due to cartilage damage
Cipro resistant strains are emerging
Exposed but previously vaccinated should chemoprophylaxis since immunity wanes

Question 26

Meningococcal vaccines

Answer 26

Serogroup B is not covered by either Menomune (polysaccharide) or Menactra (conjugate) vaccines: 2 new FDA approved group B vaccines

Question 27

Answer 27

Rhombencephalitis
Listeria
Seen in AIDs patient but decrease with prophylaxis for PCP
Transplant patients within 1 month - 2/2 CMV reactivation, GVH disease

Question 28

Answer 28

TB meningitis: axial cut shows ventricular dilation (asterisks) as well as inflammatory exudate in the ambient cisterns (black arrows) and multiple foci of vasculitis-associated necrosis

Treatment: Isoniazid (w/pyridoxine), ethambutol (optic neuropathy), pyrazinamide, rifampin

Question 29

Answer 29

Pyogenic abscess
Rim is hypointense on T2WI
T1 contrast enhancement of smooth walled rim
DWI/ADC show restricted diffusion within abscess cavity areas, bright on DWI here
Dx: No LP, get BCxs, HIV test, chest CT, TTE/TEE, if c/f fungal infection obtain Aspergillus galactomannan assay, surgery - drainage/cultre
Rx: PenG, Vanc/CTX/Flagyl

Question 30

Answer 30

Subdural empyema
Pyogenic exudate usually due to direct extension from surgical procedure or abscess, osteomyelitis, mastoiditis
CT, no LP (herniation)
Antibiotics
Surgical drainage required

Question 31

Answer 31

Subdural empyema
Pyogenic exudate usually due to direct extension from surgical procedure or abscess, osteomyelitis, mastoiditis
CT, no LP (herniation)
Antibiotics
Surgical drainage required

Question 32

Answer 32

Infective endocarditis

Question 33

Decision making in IE

Answer 33

Question 34

Infectious causes of peripheral facial weakness

Answer 34

2/3 cases: Bell’s palsy - median age of 40, equal gender incidence, rare recurrence
Other associated conditions: HIV, Lyme, Ramsay Hunt, WNV, intranasal flu vaccine, sarcoidosis, Sjogren’s, parotid disorders, amyloidosis, pregnancy, DM, HTN,
If recurrent: Lyme, sarcoid, lymphoma, pontine lesion, myasthenia

Question 35

Treatment of Bell’s palsy

Answer 35

Question 36

Treatment of Bell’s palsy

Answer 36

Question 37

Lyme syndromes and treatment options

Answer 37

Question 38

Neurosyphillis:

Answer 38

Treponema pallidum infects CSF within 3-8 months of primary infection
Meningitis in 25-40% of patients, cranial neuritis
Arteritis: 2-5 years from primary infection
Late complications: time frame compressed for HIV patients - gamma, tabes dorsals (demyelination of DCML), optic neuropathy, dementia - vascular: endarteritis

Question 39

Neurosyphillis:

Answer 39

Treponema pallidum infects CSF within 3-8 months of primary infection
Meningitis in 25-40% of patients, cranial neuritis
Arteritis: 2-5 years from primary infection
Late complications: time frame compressed for HIV patients - gamma, tabes dorsals (demyelination of DCML), optic neuropathy, dementia - vascular: endarteritis

Dx: serum VDRL, FTA-ABS, MHA-TP plus CSF VDRL (false positive unlikely), OCBs, pleiocytosis; NR treponemal test means no syphilis ever, VDRL titers will fall with appropriate treatment but may remain + for months - successful treatment judged by normalization of pleiocytosis and bands

Treatment: 2 weeks 3-4 million units penicillin q4h plus benzathine penicillin G 2.4 units IM weekly for 3 weeks OR procaine penicillin G 2.4 million U IM daily with 500 mg oral probenecid 4 times daily for 10-14 days with benzathine penicillin G 2.4 million units IM weekly for 3 weeks

Question 40

Whipple’s disease

Answer 40

Neurologic: oculomasticatory myorhythmia, cognitive decline, hypothalamic features, supranuclear vertical gaze impairment
Systemic: malabsorption, polyarthalgias, fever, lymphadenopathy

Diagnosis: MRI, Blood/CSF PCR T. Whippeli, duodenal biopsy, brain biopsy

Rx: Ceftriaxone and steptomycin for two weeks parenterally; one year of oral CTX

Question 41

Answer 41

Neurocysticercosis:
RX: Albendazole or praziquantel (and steroids for clinical deterioration or ventricular disease)
Antiparasitic RX improves seizures
Intraventricular lesions typically require surgical removal

Question 42

Leprosy

Answer 42

Question 43

With cystitis -> red urine

Answer 43

Schistosomiasis
Tx: Praziquantel+steroids if edema present
Check for cord/conus/cauda lesions -> may require surgery

Question 44

Dengue virus

Answer 44

Flavivirus
Primary infections with 1/4 serotype gives lifelong protection
Secondary infection with different serotype -> risk for severe disease
Nonmosquito transmission: blood, sexual transmission, maternal-fetal
Neurological complications: GBS+microcephaly

Question 45

Ddx of rapidly progressive dementia and myoclonus

Answer 45

Question 46

CJD

Answer 46

PRNP gene on chromosome 20

Question 47

CJD on MRI

Question 48

sCJD vs vCJD

Answer 48

Question 49

Gerstmann Straussler

Answer 49

Prion disease
AD, onset at 50-60 yo
5-10 yrs: insomnia, euphoria, pyramidal signs, supranuclear gaze palsy
Cerebella atrophy, Fe in BG

Question 50

Kuru

Answer 50

Cannibalism-associated
Fore people
Leg pain
Euphoria, amyloid plaques in cerebellum

Question 51

Fatal familial insomnia

Answer 51

AD, onset age 50, duration 13-15 months
Insomnia, ataxia, dysautonomia, memory loss, degeneration of VA and MD thalamic subnuclei

Question 52

Inactivated vaccines

Answer 52

Injected influenza, cholera, bubonic plague, intramuscular polio (Salk), hepatitis A, rabies, HPV
Toxic-immune reactions, influenza->rare GBS, safe in MS, Salk->fever, no paralysis, rabies ->Japanese B encephalitis

Question 53

Toxoid vaccines

Answer 53

Tetanus, diphtheria

Question 54

Subunit vaccines

Answer 54

Hepatitis B vaccine, HBV, influenza

Question 55

Conjugate vaccines

Answer 55

Hemophilus influenzae type B, Meningococcal

Question 56

Live attenuated vaccines

Answer 56

Intranasal influenza, VZV (Zostavax and Varivax), oral polio (Sabin), yellow fever, measles, mumps, rubella, typhoid, BCG, Yersinia pestos
Mimic natural disease: polio (OPV) -> rare paralytic disease, measles -> febrile seizures in infants, rare encephalitis, mumps -> aseptic meningitis 15-35 days after, rubella - ok if patient not pregnant, varicella ->acute cerebellar ataxia (reversible)
Tetanus -> GBS, brachial plexitis (infants, reversible)

Question 57

Neurology of vaccines pearls

Answer 57

Question 58

Metronidazole neurotoxicity

Answer 58

Reversible cerebellar toxicity - dentate nuclei

Question 59

Linezolid neurotoxicity

Answer 59

PRES, ischemic optic neuropathy, serotonin syndrome, peripheral neuropathy

Question 60

Roxithromycin neurotoxicity

Answer 60

PRES

Question 61

Posaconazole neurotoxicity

Answer 61

Enhances vincristine toxicity (inhibitor CYP3A4 enzyme)

Question 62

Cefepime neurotoxicity

Answer 62

Encephalopathy, myoclonus, NCSE +/- renal failure

Question 63

Meropenem neurotoxicity

Answer 63

Lowers VPA levels

Question 64

Fluoroquinolones - neurotoxicity

Answer 64

Mania, insomnia, delirium, seizures, dyskinesias

Question 65

Bactrim neurotoxicity

Answer 65

Tremor - resting and postural

Question 66

Beta-lactams neurotoxicity

Answer 66

Seizures

Question 67

Zidovudine

Answer 67

Myopathy

Question 68

Efavirenz

Answer 68

>50% dreams, headaches, paranoia, psychosis, IRIS

Question 69

HIV aseptic meningitis

Answer 69

Acute HIV aseptic meningitis is a syndrome that may occur during the initial stages of HIV infection as part of the seroconversion syndrome. Patients with acute HIV meningitis present with a febrile illness, headache, and symptoms of meningeal irritation. By definition, alertness and cognition are preserved. The CSF of these patients usually shows a lymphocytic pleocytosis (but usually less than 25 cells/μL) and mildly increased protein level (less than 100 mg/dL), with normal glucose levels.

It is a diagnosis of exclusion
It may be a challenging diagnosis to make in the early stages of infection, during which HIV antibodies may not be detected

What distinguishes it from encephalitis and meningoencephalitis? Preservation of alertness and cognition

Question 69

HIV aseptic meningitis

Answer 69

Acute HIV aseptic meningitis is a syndrome that may occur during the initial stages of HIV infection as part of the seroconversion syndrome. Patients with acute HIV meningitis present with a febrile illness, headache, and symptoms of meningeal irritation. By definition, alertness and cognition are preserved. The CSF of these patients usually shows a lymphocytic pleocytosis (but usually less than 25 cells/μL) and mildly increased protein level (less than 100 mg/dL), with normal glucose levels.

It is a diagnosis of exclusion
It may be a challenging diagnosis to make in the early stages of infection, during which HIV antibodies may not be detected

What distinguishes it from encephalitis and meningoencephalitis? Preservation of alertness and cognition

Question 70

CNS manifestations of Lyme

Answer 70

Caused by borrelia burgdorferi, a spirochete transmitted by the deer tick Ixodes, frequently seen in the NE USA

Stage 1 (localized infection) (within first 4 weeks of the tick bite): erythema chronicum migrans, which is a “bull’s eye rash” (not erythema marginatum, which is seen in rheumatic fever). Patients may have constitutional symptoms during this stage.
Stage 2 (disseminated infection) (days to weeks after the rash): systemic manifestations, with fever, chills, migratory musculoskeletal pain, arthralgias, fatigue. Cardiac involvement may also be present (cardiac conduction blocks). After weeks or months, some patients may develop lymphocytic meningitis, and neuropathies, including cranial and peripheral neuropathies.
Stage 3 (persistent infection) (months after the secondary stage): Intermittent episodes of oligoarthritis, encephalomyelitis, encephalopathy, and dementia. An axonal polyneuropathy may also occur.

The presence of anti–B. burgdorferi antibodies in the serum and CSF, with intrathecal production of these antibodies, are helpful in making the diagnosis. PCR is also available. MRI studies may show leptomeningeal enhancement in some cases.

Treatment - Patients with CNS abnormalities should be treated with intravenous antibiotics such as ceftriaxone or penicillin G for up to 2 to 4 weeks. If CSF findings are unremarkable and there are no neurologic manifestations or cardiac involvement, oral doxycycline may be sufficient.

Question 71

HIV associated dementia

Answer 71

AKA HIV-associated neurocognitive disorder

The spectrum of this cognitive disorder includes asymptomatic neurocognitive impairment (ANI), minor neurocognitive disorder (MND), and HIV-associated dementia (HAD). Usually, HAD is seen in patients with CD4 counts below 200 cells/mm3, with a diagnosis of AIDS. The etiology of this condition is the retrovirus itself rather than an opportunistic infection. Progressive cognitive decline and prominent psychomotor dysfunction are the main clinical manifestations. These patients have significant difficulties with attention and concentration, along with fine motor dysfunction, gait incoordination, and tremors. However, focal neurologic deficits are not common.

CSF - nonspecific, frequently mild lymphocytic pleocytosis and slightly elevated protein levels, europathological studies show diffuse white matter pallor, mononuclear infiltrates, multinucleated giant cells, and vacuolar changes in the brain. The main findings are in the subcortical region, and the cerebral cortex is relatively spared.

Neuropsychologic testing is useful in the diagnosis and follow-up of these patients, as well as to monitor them while on therapy.

HIV-associated dementia can be prevented by adequate early treatment of HIV with highly active antiretroviral therapy (HAART), with the goals of attaining higher CD4 counts and suppressing the virus. Treatment of patients with HIV-associated dementia leads to improvements in neuropsychological performance. However, the prognosis is generally poor, likely given the late stage of HIV in which this condition develops.

Successful treatment with HAART requires the simplest drug regimen possible to ensure compliance

Question 72

WNV encephalitis

Answer 72

An arboviral infection that spreads in the summer months, can occur in epidemics, and is transmitted by mosquitoes of the genus Culex. Most infected patients are asymptomatic, up to 20% may show signs of a febrile viral illness, and less than 1% develop a severe neurologic presentation. Patients with severe neurologic presentation will have manifestations of encephalitis; however, WNV can also invade the anterior horn cells leading to flaccid weakness with arreflexia, similar to poliomyelitis. WNV infection may also manifest with cranial neuropathies and tremors. Elderly patients are particularly at risk for neurologic disease, especially encephalitis, however, meningitis and flaccid paralysis may also occur in young and middle-aged patients.

WNV encephalitis is diagnosed by serology and detection of immunoglobulin M (IgM) antibodies in the CSF. CSF PCR is less sensitive, but is diagnostic when positive. MRI is nondiagnostic. Treatment is supportive.

Question 73

Toxoplasmosis of the CNS

Answer 73

Caused by toxoplasma gondii, an intracellular protozoan (single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic tissues and debris, represents a parasitic infection)

The histopathologic findings showing a microglial nodule, in which an encysted bradyzoite can be seen surrounded by an inflammatory infiltrate.

The organism is usually acquired earlier in life and remains dormant until the immune system declines and T. gondii becomes active. This occurs in advanced stages of immunodeficiency in the setting of CD4 counts of less than 100/μL.

S(x)s: headaches, focal neurologic deficits, seizures, and altered mental status that in late stages can progress to coma.

Brain MRI typically demonstrates multiple ring enhancing lesions with surrounding edema. Since these cases present with a mass lesion in the brain, the differential diagnoses include primary CNS lymphoma, tuberculomas, fungal masses, or bacterial abscesses. Definitive diagnosis is made with brain biopsy; however, this is not commonly performed, and patients are typically treated empirically.

Standard therapy is sulfadiazine plus pyrimethamine. Both affect folate metabolism pathways, folinic acid should be provided to avoid hematologic complications.

An alternative therapy is clindamycin, especially in patients who are allergic to the sulfa components and cannot take sulfadiazine.

Long-term suppressive therapy is needed to prevent relapses. Highly active antiretroviral therapy promotes immune reconstitution, and patients whose CD4 counts rise above 200/μL may not need further suppressive therapy.

Trimethoprim-sulfamethoxazole is used for prophylaxis. Patients with HIV and CD4 counts of less than 100/μL with positive IgG antibodies to toxoplasma should be given prophylaxis.

Question 74

Primary CNS lymphoma (PCNSL) in the setting of AIDS.

Answer 74

S(x)s and d(x): focal neurologic manifestations, which progress slowly over days to weeks. Since PCNSL in AIDS patients is frequently associated with Epstein–Barr virus, positive CSF PCR for this virus helps to make the diagnosis. CSF findings usually demonstrate a lymphocytic pleocytosis, elevated protein, and low to normal glucose levels. Cytology may detect atypical cells; however, this test has low sensitivity. Flow cytometry is helpful in making the diagnosis showing monoclonal B lymphocytes. CT scan has poor sensitivity, and MRI is a better tool, showing one or more lesions usually in the periventricular and deep regions of the brain. Th_ese lesions may have contrast enhancement, surrounding edema, and produce mass effect. Definitive diagnosis is done with brain biopsy_.

Corticosteroids are helpful in the treatment of edema and mass effect, and the lesion itself tends to shrink with this treatment. However, the use of steroids may alter the results and the sensitivity of the brain biopsy. Whenever possible, their use should be delayed until after the biopsy is obtained. The use of chemotherapy is controversial in this setting, and may not be optimal in patients with a baseline poor performance status related to the underlying disease. Radiation therapy is used as palliative treatment. The use of highly active antiretroviral therapy has improved the overall prognosis in patients with AIDS and PCNSL.

Question 75

PML

Answer 75

Secondary to JC virus, which is a polyomavirus. PML occurs in patients with end-stage AIDS. A large percentage of the general population has antibodies against this virus, certainly without linical manifestations; and therefore, the presence of serum antibodies is not helpful for the diagnosis. Only those patients with severe immunosuppression develop clinical manifestations; PML in immunocompetent individuals is exceedingly rare but can occur.

PML is a demyelinating condition and presents with a gradually progressive course of multiple focal neurologic manifestations, with visual field deficits and visual agnosias being common, given the predominant involvement of parieto-occipital regions. Hemiparesis, sensory deficits, language disorders and ataxia may occur.

The diagnosis can be suspected with the history and clinical manifestations, supported with MRI findings and CSF JC virus DNA PCR, and confirmed with brain biopsy (though brain biopsy is not necessary in the setting of typical clinical, imaging, and CSF findings).

MRI shows multiple white matter nonenhancing lesions that tend to coalesce and predominate in the parieto-occipital regions. Brain biopsy is the gold standard diagnostic test; neuropathologic findings include myelin loss, giant astrocytes, and altered oligodendrocytes, with enlarged nuclei and viral inclusions. On electronic microscopy, the viral particles give a “spaghetti and meatballs” appearance. The specimen shown in attached image demonstrates enlarged oligodendrocytes with intranuclear inclusions consistent with PML. CSF JC virus DNA PCR is specific for the diagnosis, and brain biopsy is rarely necessary when this test is positive.

Patients with PML have poor prognosis, as it denotes the presence of an already severely altered immune system. There is no specific therapy for this condition; however, some patients may improve with antiretroviral therapy and immune reconstitution. There are no specific EEG findings in PML, and acyclovir does not treat this condition.

Question 76

HIV neuropathy

Answer 76

This patient has HIV neuropathy, which is a distal sensory neuropathy seen in patients with HIV, more frequently as the CD4 count drops. This condition is a predominantly sensory, axonal length-dependent symmetric polyneuropathy. It is thought to be related to direct effects of the virus and cytokine upregulation. These patients should continue antiretroviral therapy for virus suppression, and the treatment is symptomatic for the neuropathic pain.

Vs nucleoside analog-associated neuropathy occurs over weeks following the initiation of therapy, and the treatment is to discontinue the offending drug.

Vs acute inflammatory demyelinating polyradiculoneuropathy, seen at the time of seroconversion

Vs CMV polyradiculomyelitis is an uncommon syndrome seen in patients with very low CD4 counts, presenting with leg pain, sensory symptoms, and weakness, along with areflexia and sphincteric dysfunction evolving over days.

Vs mononeuropathy multiplex can occur with HIV disease, more frequently late in the course of the illness, and may be associated with superimposed infection, lymphomatous infiltration, or vasculitis.

Question 77

HIV myopathy

Answer 77

HIV does not invade muscle fibers directly, rather it induces major histocompatibility complex I expression with autoimmune muscle fiber injury. T

This myositis can occur at any time during HIV infection. P

atients on zidovudine can develop a mitochondrial myopathy.

Pyomyositis is a purulent infection of skeletal muscle that arises from hematogenous spread, usually with abscess formation. It is rare, but since the HIV epidemic, it has been more frequently seen.

Patients with end-stage AIDS may develop a muscle wasting syndrome known as AIDS cachexia.

Question 78

Bacterial meningitis by age group (Chin-Chin)

Answer 78

<1 months: Escherichia coli, other enteric gram-negative bacilli, Listeria monocytogenes, and group B streptococci

1 to 23 months: H influenza, Neisseria meningitidis, Streptococcus pneumoniae, {Streptococcus agalactiae, and Escherichia coli}

2 to 50 years: Staphylococci, Neisseria meningitidis, Streptococcus pneumoniae

>50 years: GNRs, Listeria, {N meningitidis}, Streptococcus pneumonia

In the setting of CNS instrumentation, these same agents and Propionibacterium acnes should be considered (also think of a. Staphylococcus aureus b. Staphylococcus epidermidis c. Pseudomonas aeruginosa). Unlike in community- acquired meningitis, Streptococcus pneumoniae is not a common cause of hospital-acquired meningitis.

Empiric antibiotic therapy should be started early and before specific organisms can be identified from CSF cultures. Usually, vancomycin and a third-generation cephalosporin (such as ceftriaxone) are initiated in adult patients with suspicion for bacterial meningitis caused by Streptococcus pneumoniae, Neisseria meningitidis, and/or Haemophilus influenzae. In the extremes of life (younger and older patients) and in immunocompromised patients, Listeria monocytogenes should be considered and, therefore, ampicillin should be added to the empiric therapy.

Pruitt
Neonate: GNRs, Listeria, Group B Strep,
1 mo - 15 year: H influenzae, N meningitidis, S pneumo
15 - 50 year old: Staphylococci, N meningitidis, S pneumo
>50 years old: GNRs, Listeria, S pneumo

Question 79

Pott’s disease

Answer 79

Tuberculosis can affect the spine, more specifically the vertebral column (Pott’s disease). The most commonly affected region is the thoracic spine. Patients frequently present with constitutional symptoms, back pain, spinal tenderness, and muscle spasms, sometimes with findings of compressive radiculopathy or myelopathy.

Spinal involvement from Mycobacterium tuberculosis occurs from hematogenous spread to the vertebral bodies, usually starting in the anterior region of the vertebral bodies, not at the spinous processes. The infectious process later spreads to the central part of the vertebral body and intervertebral disk. With progression of the infection there is disruption of the bone and the intervertebral spaces, leading to vertebral body destruction and collapse, as well as vertebral column deformities with kyphosis and scoliosis.

Question 80

Sensitivity of gram stain for different CNS infections

Answer 80

Gram stain results depend on multiple factors, such as the CSF concentration of bacteria and the specific bacterial agent. Approximately 90% of meningitis cases caused by Streptococcus pneumoniae, 86% of those caused by Haemophilus influenzae, 75% of those caused by Neisseria meningitidis, 50% of those caused by gram-negative bacilli, and 33% of cases caused by Listeria monocytogenes have positive Gram stain results.

Question 81

Leprosy

Answer 81

AKA Hansen disezse

This disease has a long incubation period (from years to decades) and is caused by Mycobacterium leprae, which is thought to spread through the respiratory tract but does not typically produce a respiratory illness. This mycobacterium has tropism toward peripheral nerves, especially in cooler areas of the body.

Leprosy has two major variants 1) a lepromatous variant: in patients with impaired cell- mediated immunity, making it possible for the organism to spread to the skin and peripheral nerves, causing a maculopapular rash, nodules, and poorly demarcated skin lesions. The manifestations can be systemic, and patients present with sensory loss predominantly in the coolest regions of the body, such as the pinna of the ear, tip of the nose, dorsal surfaces of the hands, forearms and feet, and dorsolateral surface of the legs. and 2) a tuberculoid variant: n patients with good cellular immunity, in which the disease is less disseminated, the skin lesions are better localized, and the patient will also have asymmetric peripheral neuropathies with thickened nerves. The ulnar nerve is commonly affected, and the syndrome may resemble mononeuritis multiplex. Other commonly involved nerves include the greater auricular, radial, common peroneal, and sural nerves.

The tuberculoid variant presents in patients with strong cell-mediated immunity and an intense delayed hypersensitivity reaction, causing destruction of peripheral nerves and inflammatory lesions in the skin. These patients typically have demarcated hypopigmented lesions and areas of sensory loss, especially to temperature and pinprick. Peripheral nerves are involved, indurated, hypertrophic, and palpable, and sensory loss may be prominent, leading to trauma. Nerves predominantly involved are the ulnar, radial, common peroneal, sural, and greater auricular. Claw-hand from ulnar involvement and footdrop from common peroneal involvement may be present.

The lepromatous form is present in patients with poor cell- mediated immunity with proliferation of the mycobacteria as they invade the tissues. It is characterized by skin infiltration by the mycobacteria, leading to diffuse cutaneous involvement in the coolest regions such as the pinna of the ear, tip of the nose, and dorsum of the hands and feet. Nerves may also be involved but usually at later stages.

The diagnosis is suspected based on clinical and epidemiologic data. Skin and/or nerve biopsies are often necessary, demonstrating inflammatory granulomas with epithelioid and mononuclear infiltrates and acid-fast organisms.

Chronic therapy is usually needed, using rifampin, dapsone, and clofazimine.

As opposed to tuberculosis, pulmonary illness is uncommon in Hansen disease.

Most cases in the United States occur in immigrants, especially from Asia, the South Pacific, India, South America, and certain parts of Africa. Mycobacterium leprae is transmitted after prolonged and close contact with a patient with the disease, with an incubation period that is very long, lasting for years. The organism is thought to spread through the respiratory tract, from where it disseminates to other regions, especially the skin and superficial nerves, and mainly to cooler regions of the body. When invading the peripheral nerves, the mycobacterium tends to involve the Schwann cells preferentially.

Question 82

Neisseria meningitidis treatment

Answer 82

Treatment → third-generation cephalosporin, either ceftriaxone or cefotaxime, and the recommended duration of treatment is 7 days.

Question 83

Streptococcus pneumoniae treatment

Answer 83

Treatment→ vancomycin and ceftriaxone, and the duration of treatment is between 10 and 14 days.

Question 84

Listeria monocytogenes treatment

Answer 84

Treatment → ampicillin for more than 21 days.

Question 85

Haemophilus influenzae treatment

Answer 85

Treatment → ampicillin if the organism is β-lactamase negative; however, if it is β-lactamase positive, a third-generation cephalosporin should be used.

Question 86

Pseudomonas aeruginosa treatment

Answer 86

Usually a hospital-acquired infection and is typically resistant to ceftriaxone. Ceftazidime and cefepime have been used to treat this infection with a duration of treatment of at least 21 days.

Question 87

Brain abscess

Answer 87

These lesions originate from invasion of brain parenchyma by bacterial organisms, commonly polymicrobial, with a combination of streptococci, staphylococci, enterobacteria, and anaerobes. The bacterial agents spread via hematogenous routes or from a contiguous infected site, such as the sinuses, ears, or teeth. They also can be encountered after open trauma or neurosurgical interventions.

Patients may present with fever, headaches, neck stiffness, focal neurologic findings, and altered mental status. The diagnosis is made on the basis of clinical suspicion and the presence of risk factors, along with clinical and radiologic findings, with the MRI showing ring enhancing lesions with surrounding edema.

Lumbar puncture may be contraindicated in the presence of mass effect, and therefore CSF may not be available.

Brain abscesses evolve through different stages

• Initial cerebritis in the first few days then…
• The formation of central necrosis with surrounding vasogenic edema, and the subsequent formation of a capsule.
• The abscess eventually matures, with the development of collagenous tissue in the capsule and regression of the vasogenic edema.
• Caseating granulomas are not seen in cerebral bacterial abscesses.

Optimal treatment requires drainage of the abscess in combination with intravenous antibiotics. Given that these lesions are most commonly polymicrobial, the treatment of choice is a combination of antibiotics, usually a third-generation cephalosporin (for streptococci and gram-negative bacilli), metronidazole (for anaerobes), and vancomycin (for staphylococci). The IV antibiotic regimen is continued for 6 to 8 weeks, and subsequent continuous oral antibiotics may be required beyond the initial treatment period.

Question 88

Septic cavernous sinus thrombosis

Answer 88

This patient has septic cavernous sinus thrombosis, which can be a complication of bacterial sinus infections, and manifests with proptosis, compromise of the cranial nerves (CNs) traveling within the sinus (CNs V1 and V2, III, IV, and VI), retinal vein engorgement with retinal hemorrhages, and papilledema.

Patients with intracranial infections may also develop thrombosis of other sinuses such as the superior sagittal or the transverse sinuses. Diagnosis is based on clinical suspicion and radiologic studies. Brain MRI, MRV and/or angiography with visualization of the venous phase may be useful. Treatment involves antibiotic therapy, covering gram-positive agents, staphylococci, gram- negative organisms, and anaerobes.

Question 89

TB meningitis

Answer 89

TB meningitis is caused by Mycobacterium tuberculosis, which is an aerobic mycobacterium that spreads via respiratory droplets leading to a primary infection (usually pulmonary) and subsequent reactivation (commonly in the setting of immunosuppression). TB meningitis tends to affect the base of the brain and frequently presents with fever, headache, neck stiffness, multiple cranial neuropathies (due to involvement of the basal aspect of the brain) and altered mental status. Focal neurologic manifestations and seizures may also occur.

CSF demonstrates elevated protein level, low glucose level, and lymphocytic pleocytosis. Opening pressure is usually elevated but may be normal. Acid-fast bacillus (AFB) smear is diagnostic in 10% to 30% of the cases, and CSF cultures may be positive in 45% to 70%; however, the results may take between 6 and 8 weeks to become positive. PCR has higher sensitivity and may be helpful to make a diagnosis earlier. Brain MRI may be normal or may demonstrate meningeal enhancement, especially on the basal surface. Pathologic specimens show caseating granulomas, mononuclear inflammatory infiltrates, and multinucleated giant cells as described in this case.

Combinations of multiple anti-TB agents are used to kill the organisms and avoid inducing resistance. Commonly used medications are isoniazid, rifampin, pyrazinamide, streptomycin, and ethambutol. Usually, four drugs are initially administered for 2 months, after which the regimen can be reduced to two drugs that can be continued for several months.

Mycobacterium tuberculosis can affect the spinal cord and the brain parenchyma, where it can lead to the formation of tuberculomas. These lesions behave like space-occupying lesions, and the treatment is with anti-TB medications.

Question 90

Syphillis

Answer 90

This patient has manifestations of neurosyphilis, more specifically meningovascular syphilis. Syphilis is caused by the spirochete Treponema pallidumn (like in Lyme), which transmits vertically from mother to child or via sexual contact. In infected adults, three phases with a latent period and various neurologic complications are described:

• Primary syphilis is characterized by the development of a painless chancre at the site of entry (genital region). There is asymptomatic systemic spread of the organism, and the chancre eventually disappears.
• Secondary syphilis develops approximately 2 to 12 weeks after the exposure, with manifestations of systemic dissemination, including constitutional symptoms, lymphadenopathy, and rash (classically palms and soles). Syphilitic meningitis and cranial neuropathies may occur in this second stage.
• Latent period is an asymptomatic phase with serologic evidence of the disease, which may last for years.
• Tertiary syphilis is characterized by cardiovascular complications (such as aortitis), gummatous complications, and neurologic complications.

Major neurologic complications include pure meningeal syphilis, meningovascular syphilis, tabes dorsalis, and parenchymatous neurosyphilis. Meningeal invasion of the treponemes can lead to meningitis and meningovascular syphilis, in which there is endarteritis obliterans and vasculitis, which can lead to strokes in different arterial distributions; this can occur at any stage but often occurs within the first 4 to 7 years of infection with syphilis. Tabes dorsalis is the classical myelopathy with areflexia, lightning pains, sensory ataxia, loss of pain and temperature sensation, and relatively preserved strength, leading to gait instability and the development of Charcot joints. Parenchymatous syphilis (general paresis) is the encephalitic form in which patients develop progressive dementia, neuropsychiatric manifestations, speech disturbance, and pupillary abnormalities.

Argyll-Robertson pupils, which accommodate but do not react to light, may be seen in patients with neurosyphilis. Manifestations of neurosyphilis may overlap in the same patient, usually presenting with a combination of findings. sensory ataxia, loss of pain and temperature sensation, and relatively preserved strength, leading to gait instability and the development of Charcot joints.

Question 91

Whipple disease

Answer 91

This patient has Whipple disease, caused by Tropheryma whippelii. Whipple disease is a multisystemic disease, initially affecting the gastrointestinal tract, producing abdominal pain, diarrhea, and weight loss. It can also produce arthritis, cutaneous hypopigmentation, adrenal insufficiency, and various neurologic manifestations, including dementia, supranuclear ophthalmoplegia, ataxia, oculomasticatory myorhythmia (such as described in this case), meningitis, neuropathy, and myopathy. Some patients with Whipple disease may present only with CNS manifestations, without the characteristic diarrhea and joint symptoms.

The diagnosis is made on the basis of gastrointestinal biopsy demonstrating periodic acid Schiff-positive macrophage inclusions. CSF-PCR for Tropheryma whippelii can also be helpful.

Intravenous ceftriaxone for 2 weeks, followed by a prolonged course of trimethoprim-sulfamethoxazole is the treatment of choice.

Question 92

CJD

Answer 92

A transmissible spongiform encephalopathy.

CJD is a prion disease, caused by conformational changes of the prion protein from cellular prion protein (PrPC) to scrapie prion protein (PrPSc), which has an increased β-sheet content. This leads to physico-chemical changes in the protein, making it resistant to proteinases, poorly soluble, and with a tendency to polymerize, which eventually may lead to neuronal death. PrPSc has the ability to bind to PrPC and induce its conformational change, therefore making this agent infective.

CJD can be sporadic or familial, caused by mutations in the prion protein gene. The familial form can be inherited in an autosomal dominant fashion. EEG is helpful in making the diagnosis, showing a repetitive sharp and wave periodic pattern.

The MRI shown in Figure 15.6 demonstrates restricted diffusion of the cortex (cortical ribboning) and the head of the caudate, which are findings not seen in the diagnoses provided in the other options. Other MRI findings seen in some CJD variants include bilateral signal hyperintensity in both thalami (especially in the pulvinar region, known as the pulvinar sign) and in the anterior portions of the putamen. The combination of anterior putamen and caudate head hyperintensity is known as the “hockey-stick” sign.

Patients with CJD present clinically with a rapidly progressive dementia, neuropsychiatric symptoms, cerebellar ataxia, and myoclonus. These patients deteriorate rapidly and inexorably die within months. The diagnosis is suspected on the basis of clinical features and supported by ancillary tests such as MRI, EEG, and CSF studies. EEG shows a typical periodic pattern. The presence of CSF 14-3-3 protein is helpful but not specific for this condition, as it can be seen in many other causes of neuronal destruction. Other potentially useful CSF biomarkers include total Tau, Neuron- specific enolase, and S100B. Neuropathologic evaluation may be required in some cases and demonstrates significant spongiform degeneration with neuronal loss, vacuolar changes, and astrocytosis (discussed in Chapter 12).

Question 93

Primary CNS lymphoma in HIV vs not

Answer 93

Primary CNS lymphoma (PCNSL) is more frequently diagnosed in immunocompromised patients, especially in patients with AIDS. Almost all of these cases are associated with Epstein–Barr virus (EBV), and CSF EBV PCR is helpful in the diagnosis. In contrast, PCNSL in immunocompetent patients is not commonly associated with EBV. It is not possible to differentiate PCNSL in immunocompromised patients versus immunocompetent patients only on the basis of imaging, CSF findings, cytology, or response to steroids.

Question 94

Serum and CSF studies for neurosyphilis

Answer 94

The diagnosis of syphilis is based on clinical manifestations along with supportive laboratory evidence. There are treponemal and nontreponemal tests. Nontreponemal tests are the Venereal Disease Research Laboratory (VDRL) test and the Rapid Plasma Reagin test. These tests are more sensitive but less specific than treponemal tests and become negative sometime after treatment. Treponemal antibodies remain positive for life and include the fluorescent treponemal antibody and microhemagglutination assay among others. For the diagnosis of neurosyphilis, CSF should be analyzed, usually showing mononuclear pleocytosis with elevated protein levels. CSF VDRL is very specific for neurosyphilis but may be negative in as many as 25% of cases. Intrathecal antibody production against Treponema pallidum, oligoclonal bands, and PCR are also helpful for the diagnosis.

Question 95

Treatment of neurosyphilis

Answer 95

Treatment of neurosyphilis involves intravenous antibiotics, and the first choice is penicillin G 4 million units every 4 hours for 14 days. Antibiotic therapy may clear the infection; however, it may not reverse already established neurologic manifestations of tertiary syphilis. Follow-up CSF analysis is recommended to assess the response to therapy.

Question 96

HSV encephalitis

Answer 96

This patient has HSV encephalitis, likely from HSV type 1, which is the most common cause of fatal sporadic viral encephalitis in the United States. This virus spreads to the CNS, where it tends to affect the orbitofrontal and temporal regions. Patients present with fever, headaches, behavioral changes, altered mental status, focal neurologic findings, and seizures. CSF analysis demonstrates pleocytosis with lymphocytic predominance (10 to 1,000 WBCs/ μL), moderately elevated protein and normal glucose levels. Increased RBC count in the CSF or xanthochromia is seen frequently; however, this finding is neither sensitive nor specific. CSF HSV PCR has very high sensitivity and specificity for this condition; however, there may be false-negative results if the CSF is sampled in the first 24 hours of the illness. The MRI (shown in Fig. 15.7) demonstrates FLAIR T2 hyperintensities and restricted diffusion in the temporal regions—in this case, on the right side. Treatment with intravenous acyclovir 10 mg/kg every 8 hours should be started as soon as possible and continued for a minimum of 14 days.

Question 97

Fatal familial insomnia

Answer 97

A prion disorder characterized by progressive intractable insomnia and symptoms of sympathetic hyperactivity such as hypertension, tachycardia, hyperthermia, and hyperhidrosis. Patients may also have cognitive impairment, tremor, ataxia, hyperreflexia, and myoclonus.

CJD exists in different variants, including sporadic, familial, iatrogenic, and new variant forms. (The sporadic form is the typical form that was described in question 33). The familial variant is similar to the sporadic form; however, it may present earlier, and the course is more protracted and insidious. The iatrogenic form is very rare and has been described in the past in patients who received cadaver-derived human growth hormone, and after neurosurgical procedures or corneal transplants.

Question 98

Gerstmann–Straussler–Scheinker

Answer 98

Gerstmann–Straussler–Scheinker is an inherited prion disease that progresses slowly over years. It is characterized by cerebellar ataxia and dysarthria, sometimes extrapyramidal features followed by dementia. The new variant CJD was first described in 1996 and is believed to occur from infection through consumption of cattle products contaminated with the agent of bovine spongiform encephalopathy. In contrast to traditional forms of CJD, new variant CJD affects younger patients (third to fourth decades of life), and the duration is more protracted.

Question 99

SSPE

Answer 99

Subacute sclerosing panencephalitis (SSPE) is a rare and late complication of measles, which is not an arbovirus (but WNV is!). Measles can cause four major neurologic syndromes:

• Acute encephalitis.
• Postviral encephalomyelitis.
• Measles inclusion body encephalitis, which occurs in patients with cell-mediated immunodeficiency, 1 to 6 months after measles exposure. It is characterized by a rapidly progressive dementing process with seizures, myoclonus, mental status changes, and coma.

• SSPE, which is caused by defective measles virus maturation in neural cells.

Children infected in the first 2 years of life are the ones at the greatest risk for SSPE, which may develop 2 to 12 years after the infection. It begins with behavioral and personality changes, later causing seizures, myoclonus, spasticity, ataxia, choreoathetoid movements, optic atrophy, quadriparesis, autonomic instability, akinetic mutism, and eventually coma.

EEG shows periodic slow-wave complexes at regular intervals and a background of depressed activity. MRI demonstrates T2 hyperintensity in the gray and subcortical white matter more in the posterior regions. Neuropathologically, neurons contain nuclear and cytoplasmic viral inclusion bodies, and levels of CSF and serum antibodies are elevated.

Question 100

Arboviruses

Answer 100

Regarding the arboviruses, these are arthropod-borne viruses, transmitted by mosquitoes. More than 500 arbovirus-transmitted RNA viruses exist, including Saint Louis encephalitis virus, West Nile virus, La Crosse encephalitis virus, Japanese encephalitis virus, and Eastern and Western Equine encephalitis viruses.

Question 101

Infections→vasculitis

Answer 101

Syphillis, aspergillosis, VZV; mucormycosis is angioinvasive but manifestations→acute necrotizing reaction and vascular thrombosis

Question 102

Neurocysticercosis

Answer 102

Neurocysticercosis is caused by the pork tapeworm Taenia solium and has a worldwide distribution, being endemic in Latin America, Africa, India, and other parts of Asia.

Human ingestion of undercooked pork meat containing cysticerci may lead to infection with the intestinal tapeworms but does not cause the manifestations of neurocysticercosis, which occurs only with infection at a specific stage of the tapeworm life cycle. When the adult tapeworm resides in the small bowel of either the pig or the human, proglottids are released and excreted in to the feces. The eggs in these proglottids are infective to humans and animals. After humans ingest these eggs, larvae are released which penetrate the intestinal wall, migrating to various tissues, causing cysticercosis and neurocysticercosis. Clinical manifestations may occur years later, including seizures, focal neurologic symptoms, a vasculitic-type syndrome with strokes, increased intracranial pressure, headaches, hydrocephalus, and rarely coma.

Neuroimaging is helpful in the diagnosis of neurocysticercosis, showing cystic lesions that may have contrast enhancement and calcifications. The treatment of choice is albendazole. Praziquantel is an alternative. Since patients commonly have seizures, antiepileptic agents are often required.

Question 103

Indian ink stain

Answer 103

Microbiologists use India ink to stain a slide containing micro-organisms. The background is stained while the organisms remain clear. This is called a negative stain. India ink, along with other stains, can be used to determine if a cell has a gelatinous capsule.^[24] A common application of this procedure in the clinical microbiology laboratory is to confirm the morphology of the encapsulated yeast Cryptococcus spp. which cause cryptococcal meningitis.

Question 104

Grocott methenamine silver (GMS)

Answer 104

Grocott methenamine silver (GMS) stain is commonly used for the identification of fungi on cytosmears and tissue sections.

Question 105

Amebic meningoencephalitis

Answer 105

This patient has amebic meningoencephalitis. The diagnosis is based on clinical history and epidemiological factors and is confirmed by the histopathologic specimen, which shows an inflammatory infiltrate and trophozoites, consistent with an amebic infection.

Amebic meningoencephalitis is caused by free-living amebae, such as Naegleria fowleri, Acanthamoeba, and Balamuthia mandrillaris. Patients acquire the amebae by swimming in contaminated lakes or ponds. The parasites enter the brain by passing through the cribriform plate and along the olfactory nerve to enter the frontal lobes and cause a necrotizing inflammation with destruction. Acanthamoeba can also enter the CNS through hematogenous dissemination and from a primary corneal infection acquired by using contact lenses stored in contaminated solution.

Patients with amebic encephalitis present with headaches, fever, neck stiffness, nausea, and vomiting and eventually develop focal neurologic findings, seizures, and altered mental status. T_he progression is rapid, and the disease is usually fatal._

CSF opening pressure is increased, and CSF analysis shows a neutrophilic pleocytosis, increased protein, and decreased glucose levels. Gram stain will not show the organism, but trophozoites may be seen on a wet preparation of unspun spinal fluid. Pathologically, there are findings consistent with purulent meningitis, with microabscesses and necrotizing destruction of the parenchyma. A polymorphonuclear inflammatory infiltrate and trophozoites can be seen, such as in the histopathologic specimen

Question 106

Lyme

Answer 106

This patient has Lyme disease, which has a broad variety of neurologic presentations, and is caused by Borrelia burgdorferi, a spirochete. It is more commonly acquired in the Northeastern United States and is transmitted by a tick bite, more specifically the Ixodes tick. Lyme disease has an early phase and a late phase, and neurologic complications occur in both. In the early phase, patients may have a rash called erythema migrans, which is characteristic and has a “bull’s eye” appearance. They are further outlined below

• Stage 1 (localized infection) (within first 4 weeks of the tick bite): erythema chronicum migrans, which is a “bull’s eye rash” (not erythema marginatum, which is seen in rheumatic fever). Patients may have constitutional symptoms during this stage.
• Stage 2 (disseminated infection) (days to weeks after the rash): systemic manifestations, with fever, chills, migratory musculoskeletal pain, arthralgias, fatigue. Cardiac involvement may also be present (cardiac conduction blocks). After weeks or months, some patients may develop lymphocytic meningitis, and neuropathies, including cranial and peripheral neuropathies.
• Stage 3 (persistent infection) (months after the secondary stage): Intermittent episodes of oligoarthritis, encephalomyelitis, encephalopathy, and dementia. An axonal polyneuropathy may also occur.

Neurological manifestations in the early phases include

• Aseptic meningitis: these patients have a mononuclear pleocytosis and mild elevation of protein levels in the CSF, as well as intrathecal production of antibodies against Borrelia burgdorferi.
• Cranial neuropathy: commonly cranial nerve VII, and this can be uni- or bilateral.
• Peripheral nervous system: including mononeuritis multiplex, peripheral neuropathy, polyradiculopathy, or even a Guillain– Barré type presentation (which is not common).

Neurologic presentations in the late phase are encephalopathy, encephalomyelitis, and peripheral neuropathy. Bacterial meningitis with neutrophilic predominance is unlikely to occur. Subdural empyema is not seen in Lyme disease. The diagnosis of CNS Lyme disease is based on clinical and epidemiological suspicion, supported by the presence of positive serology, CSF abnormalities, and intrathecal production of antibodies. Serology may be positive in small percentage of people living in endemic areas, and this should be taken into account. The treatment is antibiotic therapy with intravenous ceftriaxone, up to 2 g daily, or penicillin G for 2 to 4 weeks. For late presentations, a longer course may be required. Oral antibiotic therapy with doxycycline can be used in patients without CSF abnormalities.

Other nonneurologic manifestations include carditis, arthralgias, lymphadenopathy, and fever.

Question 107

VZV

Answer 107

VZV produces a variety of manifestations, and delayed neurologic syndromes. Chickenpox is caused by VZV primary infection, and after this, the virus remains latent in dorsal root ganglia, autonomic ganglia, and cranial nerve ganglia. The virus reactivates years later producing various neurologic manifestations:

Herpes zoster: Occurs more commonly in older patients, and in those with some degree of immunodeficiency, but can occur in anyone. Usually starts with hyperesthesia, tingling and burning sensation in the involved dermatomes (usually one to three dermatomes), followed by the zoster rash, which is a vesicular rash in that same region. The rash gradually heals over several days, but patients experience pain and sensory impairment that can last weeks to months. The most commonly involved dermatomes are in the mid-thoracic region.

Zoster sine herpete: In this variant, the patient experiences the sensory symptoms without the rash.

Herpes zoster ophthalmicus: This involves reactivation of the virus in the ophthalmic division of the trigeminal nerve, and causing sensory symptoms and rash in the distribution of this nerve division. In this distribution, the cornea and conjunctiva can be involved, causing keratitis, which can lead to blindness.

Ramsay–Hunt syndrome: Characterized by facial palsy combined with herpetic rash in the external auditory meatus, sometimes with vertigo, tinnitus, and deafness_. This syndrome is secondary to geniculate ganglion involvement_.

Other cranial nerves can be affected by reactivation of the virus, with various cranial neuropathies resulting from this.

Necrotizing retinitis leading to visual loss.

VZV vasculopathy: Small and large intracranial vessels are involved, leading to ischemic strokes, TIAs, and sometimes aneurysmal dilatations with resulting subarachnoid or intracranial hemorrhages.

Myelitis: this can be a one-time event leading to paraparesis, or present as a gradually progressive myelitis.

Question 108

VZV vasculopathy

Answer 108

This patient has VZV vasculopathy causing a stroke. VZV vasculopathy is a multifocal disease and affects small and large intracranial vessels. It can affect immunocompetent and immunocompromised patients, manifesting with TIAs and strokes, and less commonly with aneurysmal dilatation leading to subarachnoid and intracranial hemorrhage. Typical angiographic findings include multifocal segmental narrowing with poststenotic dilatation. These findings can sometimes be seen on noninvasive imaging such as CTA and MRA.

CSF may be abnormal, with mild mononuclear pleocytosis, slightly elevated protein but normal glucose levels. Virologic confirmation is required, and the value of detecting anti-VZV IgG in the CSF has been demonstrated to be superior to the detection of VZV DNA. Even though a positive VZV DNA in the CSF is helpful, a negative PCR does not exclude the diagnosis.

Patients with VZV vasculopathy should be treated with acyclovir 10 to 15 mg/kg IV three times a day for at least 2 weeks. Steroids may be required. Use of antiplatelet agents may be reasonable in patients with intracranial stenosis and ischemic strokes or TIAs, but should not be used alone without specific antiviral therapy in these cases.

Question 109

Rabies

Answer 109

This patient had rabies, which is caused by a viral infection, not a fungal infection. The virus is inoculated in humans by an animal bite, with most common reservoirs being bats, raccoons, skunks, foxes, and unimmunized dogs. Occasionally the source is not identified or recalled by the patient.

_Incubation period ranges from 1 to 3 months, but may be shorte_r. Symptoms begin with fever, malaise, headache, and followed by psychomotor hyperactivity. Patients subsequently experience dysarthria and dysphagia, with prominent spasms in the pharyngeal, facial and neck muscles. These oropharyngeal spasms may be triggered by attempts to swallow water, leading to hydrophobia. The inability to swallow associated with salivation may produce the described “frothing” in the mouth. Progression of the disease is associated with increased attack frequency, agitation, hallucinations, seizures, and coma. A paralytic form called “dumb” rabies may progress from paresthesias and weakness of the bitten limb, to quadriplegia. This paralytic form is more common from bat rabies.

Neuropathologically, there are characteristic cytoplasmic eosinophilic inclusions known as Negri bodies, which are found mainly in Purkinje cells and pyramidal cells of the hippocampus, but can also be seen in neurons in other parts of the brain and spinal cord.

After exposure, patients should receive HDCV (human diploid cell vaccine) on days 0, 3, 7, 15 and 28. Also they should receive human rabies immunoglobulin (20 IU/kg) as soon as possible, at least half of the dose around the wound and the rest intramuscularly.

This condition is very serious, but some patients may survive if they receive postexposure prophylaxis and adequate intensive supportive care and mechanical ventilatory support.

Question 110

Infective endocarditis

Answer 110

Patients with infective endocarditis can have a variety of neurologic complications, most likely from embolization of infected particles from the valvular vegetations.

These neurologic manifestations include ischemic and hemorrhagic strokes, meningitis, encephalitis, abscesses, vasculitis, and mycotic aneurysms, which can lead to subarachnoid hemorrhage if they rupture. The exact mechanism of formation of mycotic aneurysms is not well known, but it is likely that they form secondary to septic emboli involving distal vessels, affecting their vasa vasorum, with destruction and weakening of the arterial wall and subsequent aneurysmal dilatation. These mycotic aneurysms are usually very distal in the arterial tree, and commonly seen in distal bifurcations. They are not typically seen in the proximal circle of Willis. The subarachnoid hemorrhage resulting from rupture of these small aneurysms is usually cortical and superficial, and is not generally associated with vasospasm.

Patients who suffer subarachnoid hemorrhage in the setting of infective endocarditis, should have a diagnostic cerebral angiogram to evaluate for the presence of mycotic aneurysms (or other potential cause of the subarachnoid hemorrhage). Some advocate for cerebral angiogram in patients with endocarditis and ischemic strokes or other signs of neurologic involvement, since mycotic aneurysms may be silent, however, this practice is still not widely recommended. Ruptured mycotic aneurysms should be treated surgically or endovascularly.

Patients with infective endocarditis should be properly treated with early antibiotic therapy, which is mainstay of treatment. Antibiotics not only treat the cardiac infection but also prevents neurologic complications, and may potentially lead to resolution of unruptured mycotic aneurysms.

Anticoagulants are generally contraindicated given the risk of rupture of silent or known mycotic aneurysms, as well as potential risk of hemorrhagic transformation of embolic strokes.

Question 111

Erythema chronicum migrains

Answer 111

Lyme disease

Question 112

Bilateral facial nerve palsies

Answer 112

Consider Lyme disease as well as non-infectious etiologies: MS, sarcoidosis

Question 113

Meningitis, positive India ink +/- budding yeasts

Answer 113

Cryptococcus

Question 114

AIDs and MRI with ring enhancing lesions with edema

Answer 114

Consider toxoplasmosis and CNS lymphoma

Question 115

AIDs with mass lesion and positive EBV virus PCR

Answer 115

Primary CNS lymphoma

Question 116

Answer 116

JC virus, PML

Question 117

Meningitis in the very young or very elderly

Answer 117

Listeria

Question 118

Hypopigmented lesions and enlarged peripheral nerves

Answer 118

Myobacecterium leprae

Question 119

Oculomasticatory myorrhythmia

Answer 119

Whipple disease

Question 120

Answer 120

CJD

Question 121

Encephalitis and bilateral temporal hemorrhage

Answer 121

HSV encephalitis

Question 122

Nasal and maxillary necrotizing lesion and diabetic ketoacidosis

Answer 122

Mucormycosis

Question 123

Answer 123

Consider West Nile virus

Question 124

Basal meningitis

Answer 124

Consider TB

Question 125

Tabes dorsalis, Argyll-Roberston pupil

Answer 125

Syphillis

Question 126

Septate hyphae with acute angle branches

Answer 126

Aspergillosis

Question 127

Patient from underdeveloped country with seizures and cystic and calcified parenchymal lesions

Answer 127

Neurocysticercosis

Question 128

Negri bodies

Answer 128

Rabies