Autoimmune encephalitis + Cryptococcal Meningitis + Hepatic Encephalopathy

Question 1

what is the usual course of autoimmune encephalitis

Answer 1

usually, but not always, SUBACUTE (timeline of sx onset usually over course of several weeks)

Question 2

what is the incidence of all encephalitis, both infectious and autoimmune encephalitis

Answer 2

5-10 per 100 000 in high income countries

Question 3

why is early diagnosis of autoimmune encephalitis so important

Answer 3

so therapy can begin quickly

early tx is associated with decreased seizure frequency, faster cognitive improvement and IMPROVED SURVIVAL

Question 4

define encephalitis

Answer 4

INFLAMMATION of the brain parenchyma

assoc. with neurologic dysfunction (i.e altered mental status, behavioural changes)

can be infectious or non infectious

Question 5

define encephalopathy

Answer 5

refers to neuro dysfunction but can be with OR WITHOUT inflammation of brain tissue

i.e wernicke encephalopathy

Question 6

what should be considered in a patient presenting with rapidly progressive memory impairment, behavioural or psychiatric changes or seizures of unknown etiology

Answer 6

autoimmune limbic encephalitis

Question 7

name some of the autoimmune encephalitis examples

Answer 7

autoimmune limbic encephalitis

acute disseminated encephalomyelitis

anti-NMDA receptor encephalitis

Bickerstaff’s brainstem encephalitis

Question 8

what 3 criteria need to be met to diagnose autoimmune encephalitis

Answer 8

1. SUBACUTE onset–> rapid progression of less than 3 months of WORKING MEMORY deficits (short term memory loss), altered mental status or psych symptoms
2. at least 1 of:
   –new FOCAL CNS findings
   –seizures not explained by a previously known seizure disorder
   –CSF pleocytosis (WBC count more than 5 cells per mm3)
   –MRI findings suggestive of encephalitis
3. reasonable exclusion of alternative causes

Question 9

what number of WBCs in the CSF is considered “pleocytosis”

Answer 9

more than 5 cells per mm3

Question 10

what would be considered MRI findings suggestive of encephalitis

Answer 10

hyperintense signal on T2 weight fluid-attenuated inversion recovery sequences highly restricted to one or both medial temporal lobes (autoimmune limbic encephalitis)

or

hyperintense signal on T2 weighted fluid-attenuated inversion recovery sequences in multifocal areas involving grey matter, white matter, or both compatible with demyelination or inflammation

Question 11

what causes the symptoms of autoimmune limbic encephalitis

Answer 11

dysfunction in the limbic structures of the brain

Question 12

what symptoms can be caused by autoimmune limbic encephalitis

Answer 12

ST memory impairment

behavioural changes

anxiety

depression

psychosis

seizures

Question 13

in which population does autoimmune limbic encephalitis most commonly occur

Answer 13

middle aged adults–but can occur in all ages

Question 14

what 4 criteria must be met to diagnose autoimmune limbic encephalitis

Answer 14

1. subacute onset of sx suggesting involvement of limbic structures
2. BILATERAL brain abnormalities that is HIGHLY RESTRICTED to the MEDIAL TEMPORAL LOBES on T2 weighted FLAIR MRI
3. at least one of:
   –CSF pleocytosis
   and/or
   –EEG with epileptic or slow wave activity involving the temporal lobes
4. reasonable exclusion of alternative causes

**if one of first 3 not met, must find antibodies against cell surface, synaptic or onconeural proteins to make the definite autoimmune limbic encephalitis diagnosis

Question 15

what might be seen on EEG in autoimmune limbic encephalitis

Answer 15

epileptic or slow wave activity involving temporal lobes

Question 16

what other brain imaging technique may actually be more sensitive to autoimmune limbic encephalitis

Answer 16

18F-FDG PET–> may show increased FDG uptake in otherwise normal appearing medial temporal lobes thus indicating autoimmune limbic encephalitis

Question 17

what is acute disseminated encephalomyelitis

Answer 17

a monophasic CNS inflammatory disease

Question 18

in what population does acute disseminated encephalomyelitis most commonly occur

Answer 18

children and adults under age 40

Question 19

what can trigger acute disseminated encephalomyelitis

Answer 19

can be triggered by acute systemic infection or vaccination

Question 20

list symptoms of acute disseminated encephalomyelitis

Answer 20

cranial nerve palsies

ataxia

hemiparesis

myelopathy

optic neuritis

Question 21

what types of antibodies may be found in those with acute disseminated encephalomyelitis

Answer 21

myelin oligodendrocyte glycoprotein (MOG) antibodies

can be found in up to 50% of children with acute disseminated encephalomyelitis

Question 22

what 5 criteria must be met to diagnose definite acute disseminated encephalomyelitis

Answer 22

1. a first, MULTIFOCAL, clinical CNS event of presumed inflammatory demyelinating cause
2. encephalopathy that cannot be explained by fever
3. abnormal brain MRI
4. NO NEW clinical or MRI findings after 3 months of symptom onset
5. reasonable exclusion of alternative causes

Question 23

what brain abnormalities would be seen in MRI in acute disseminated encephalomyelitis

Answer 23

DIFFUSE, poorly demarcated, LARGE (bigger than 1-2cm) LESIONS predominantely involving the CEREBRAL WHITE MATTER in T2-weighted FLAIR imaging that can be present in the supratentorial white matter, basal ganglia, brainstem, cerebellum, and spinal cord (with or without contrast enhancement)

T1-hypointense lesions in the white matter in rare cases

deep grey matter abnormalities (i.e thalamus or basal ganglia) can be present

Question 24

what antibodies are associated with anti-NMDA receptor encephalitis

Answer 24

CSF IgG antibodies against the GluN1 subunit of the NMDA receptor

Question 25

what symptoms characterize the presentation of anti-NMDA receptor encephalitis

Answer 25

prominent psychiatric manfestations--> can delay diagnosis and treatment

Question 26

what 3 criteria must be met for a "probable" diagnosis of anti-NMDA receptor encephalitis

Answer 26

1. rapid onset of at least 4 of the following 6 major groups of symptoms: --abnormal (psychiatric) behaviour or cognitive dysfunction --speech dysfunction (pressured speech, verbal reduction, mutism) --seizures --movement disorder, dyskinesias, or rigidity/abnormal postures --decreased level of consciousness --autonomic dysfunction or central hypoventilation 2. at least 1 of the following: --abnormal EEG --CSF with pleocytosis or oligoclonal bands 3. reasonable exclusion of alternative causes **can also be made in the presence of 3/6 of the above symptoms clusters + presence of a SYSTEMIC TERATOMA

Question 27

what abnormalities may be seen on EEG in anti-NMDA receptor encephalitis

Answer 27

focal or diffuse slow or disorganized activity, epileptic activity or extreme delta brush

Question 28

when can a DEFINITE diagnosis of anti-NMDA receptor encephalitis be made

Answer 28

in the presence of ONE OR MORE of the 6 major groups of symptoms PLUS IgG anti-GluN1 antibodies (including CSF testing) after reasonable exclusion of other disorders

Question 29

what is the period of onset of symptoms associated with Bickerstaff's Brainstem Encephalitis

Answer 29

subacute--> LESS THAN 4 WEEKS

Question 30

what is the symptom pattern seen in Bickerstaff's Brainstem Encephalitis

Answer 30

progressive impairment of CONSCIOUSNESS + ATAXIA + bilateral, mostly symmetrical OPHTHALMOPARESIS frequently develop pupillary abnormalities, bilateral facial palsy, babinskis sign and bulbar palsy --> generalized limb weakness can occur and overlap with features of GBS

Question 31

when can a diagnosis of definitely Bickerstaff's Brainstem Encephalitis be made

Answer 31

in presence of + IgG anti-GQ1b antibodies --> even if bilateral ophthalmoplegia is not complete or ataxia cannot be assessed or if recovery occured within 12 weeks after onset

Question 32

what two criteria must be met to diagnose probable Bickerstaff's Brainstem Encephalitis

Answer 32

1. subacute onset (rapid progression of less than 4 weeks) of ALL of the following: decreased LOC + bilateral external ophthalmoplegia + ataxia 2. reasonable exclusion of alternative dx

Question 33

what factors can be elevated in those with hashimotos encephalitis/encephalopathy

Answer 33

anti-TPO antibodies anti-thyroglobulin antibodies anti-dsDNA antibodies

Question 34

what 6 criteria must be met for diagnosis of hashimotos encephalitis/encephalopathy

Answer 34

1. encephalopathy with seizures, myoclonus, hallucinations or stroke-like episodes 2. subclinical or overt THYROID DISEASE 3. brain MRI NORMAL or with nonspecific abnormalities 4. presence of SERUM THYROID ANTIBODIES (thyroid peroxidase, thyroglobulin) 5. absence of well characterized neuronal antibodies in serum or CSF 6. reasonable exclusion of alternative causes

Question 35

is hashimotos encephalitis/encephalopathy usually associated with hyper or hypothyroidism

Answer 35

usually hypothyroidism

Question 36

what is normally seen on MRI in hashimotos encephalitis/encephalopathy

Answer 36

usually normal or with nonspecific abnormalities

Question 37

list RED FLAGS for suspicion of autoimmune encephalitis in patients with PSYCHOSIS

Answer 37

1. infectious prodrome 2. new onset severe headache or clinically significant change in headache pattern 3. rapid progression 4. adverse response to antipsychotics or presence of NMS 5. insufficient response to antipsychotics 6. movement disorder i.e catatonia or dyskinesia 7. focal neuro disease 8. decreased LOC 9. autonomic disturbance 10. aphasia, mutism or dysarthria 11. seizures 12. presence of a tumor or hx of recent rumor 13. hyponatremia (not explained by side effects of medication) 14. other autoimmune disorders 15. parethesia

Question 38

what is required for a diagnosis of DEFINITE autoimmune psychosis

Answer 38

meet criteria for probable autoimmune psychosis + presence of IgG class anti-neuronal antibodies in CSF (criteria for probable autoimmune psychosis include rapid progression of sx + symptom clusters + CSf WBC/MRI abn/EEG changes/CSF oligoclonal bands/serum anti-neuronal antibodies)

Question 39

list the NO paraneoplastic encephalopathies

Answer 39

hashimotos encephalopathy sarcoidosis lupus sjogrens celiac Bechet's anti-VGKC encephalitis

Question 40

what is paraneoplastic limbic encephalitis

Answer 40

rare neuro syndrome assoc with cancer selectively affects limbic system structures--hippocampus, hypothalamus, amygdala caused by altered immune response to a malignancy that has antigens that resemble limbic antigens

Question 41

paraneoplastic limbic encephalitis is usually associated with what type of cancer

Answer 41

small cell lung cancer

Question 42

ddx for autoimmune encephalitis

Answer 42

HSV encephalitis HHV-6 encephalitis glioma status epilepticus neurosyphillis whipples HIV CNS infections septic encephalopathy metabolic encephalopathy drug toxicity epileptic disorders prion diseases CVD mitochondrial disorders inborn errors of metabolism kleine-levin

Question 43

what signs would indicate HSV encephalitis

Answer 43

fever + MRI hemorrphagic lesions usually unilateral MRI changes

Question 44

what is a sign/symptom that is considered pathognomonic for autoimmune limbic encephalitis

Answer 44

faciobracial dystonic seizures --> involuntary movements--> brief contractions affetcing ipsilateral face, arm or leg--> can last several seconds, and can occur hundreds of times a day --> often refractory to treatment with anti seizure meds

Question 45

is there usually unilateral or bilateral involvement shown on MRI in the limbic encephalitises

Answer 45

usually bilateral (though can be unilateral or MRI can be normal)

Question 46

what EEG change is most specific for anti-NMDA receptor encephalitis

Answer 46

extreme delta brush

Question 47

what type of antibodies are associated with autoimmune encephalitises

Answer 47

all are IgG

Question 48

anti-NMDA receptor encephalitis predominantely affects what population

Answer 48

under age 45 more females

Question 49

what is the main tumor association with anti-NMDA receptor encephalitis

Answer 49

ovarian teratoma

Question 50

what receptor is associated with limbic encephalitis

Answer 50

AMPA receptor

Question 51

what tumors are more associated with limbic encephalitis

Answer 51

thymoma small cell lung cancer

Question 52

what is first line therapy for autoimmune encephalitis

Answer 52

(if theres a tumor, treat the tumor first--this will be most important tx) otherwise... IV steroids (methylprednisone) IVIG Plasma exchange/PLEX or both IVIG + PLEX (second line = rituximab and cyclophosphamide)

Question 53

how do symptoms generally progress in anti-NMDA receptor encephalitis

Answer 53

initially prominent PSYCHIATRIC symptoms then progresses to seizures, movement disorders, autonomic dysfunction, hypoventilation *older adults may present with cognitive decline and catatonic feaures

Question 54

you have a young person admitted with psychosis, and they display antipsychotic intolerance--what should you consider

Answer 54

anti-NMDA receptor encephalitis those with anti-NMDA receptor encephalitis often have antipsychotic intolerance i.e fever, unusual EPS rigidity, decreased alertness

Question 55

what other encephalitis can precede anti-NMDA receptor encephalitis

Answer 55

HSV encephalitis--> seroconversion rate of up to 30%

Question 56

what should you do if you have a patient who presents with a relapse of symptoms after recovering from HSV encephalitis

Answer 56

CSG analysis for anti-NMDA receptor encephalitis--> MANDATORY in these cases due to high seroconversion rate **ask about hx of HSV encephalitis in patient presenting with new psychosis relapsing HSV encephalitis affects 20% of patients

Question 57

in which populations should you suspect cryptococcal meningitis

Answer 57

those with HIV can also affect other people who are immunosuppressed

Question 58

what psychiatric disorder can be misdiagnosed in those who actually have cryptococcal meningitis

Answer 58

dementia

Question 59

what are the most common clinical symptoms of cryptococcal meningitis

Answer 59

subacute headache and confusion (less than 20% have the neck stiffness that we assoc. with meningitis)

Question 60

do people with cryptococcal meningitis usually present acutely

Answer 60

no--> subacute meningitis is the most common presentation--> can be steadily progressive up to years

Question 61

what are the symptoms of hepatic encephalopathy

Answer 61

cognitive impairment ataxia altered LOC

Question 62

what investigations should be done if you suspect hepatic encephalopathy

Answer 62

ammonia levels abdominal U/S EEGs (look for encephalopathy)

Question 63

in a patient on VPA, what should you consider if they present with decreasing LOC, focal neuro deficits, cognitive slowing, vomiting, drowsiness, lethargy

Answer 63

consider hyperammonemic encephalopathy--> check ammonia levels can occure even when VPA levels are normal and LFTs are normal