Autoimmune encephalitis + Cryptococcal Meningitis + Hepatic Encephalopathy Flashcards
what is the usual course of autoimmune encephalitis
usually, but not always, SUBACUTE (timeline of sx onset usually over course of several weeks)
what is the incidence of all encephalitis, both infectious and autoimmune encephalitis
5-10 per 100 000 in high income countries
why is early diagnosis of autoimmune encephalitis so important
so therapy can begin quickly
early tx is associated with decreased seizure frequency, faster cognitive improvement and IMPROVED SURVIVAL
define encephalitis
INFLAMMATION of the brain parenchyma
assoc. with neurologic dysfunction (i.e altered mental status, behavioural changes)
can be infectious or non infectious
define encephalopathy
refers to neuro dysfunction but can be with OR WITHOUT inflammation of brain tissue
i.e wernicke encephalopathy
what should be considered in a patient presenting with rapidly progressive memory impairment, behavioural or psychiatric changes or seizures of unknown etiology
autoimmune limbic encephalitis
name some of the autoimmune encephalitis examples
autoimmune limbic encephalitis
acute disseminated encephalomyelitis
anti-NMDA receptor encephalitis
Bickerstaff’s brainstem encephalitis
what 3 criteria need to be met to diagnose autoimmune encephalitis
- SUBACUTE onset–> rapid progression of less than 3 months of WORKING MEMORY deficits (short term memory loss), altered mental status or psych symptoms
- 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 - reasonable exclusion of alternative causes
what number of WBCs in the CSF is considered “pleocytosis”
more than 5 cells per mm3
what would be considered MRI findings suggestive of encephalitis
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
what causes the symptoms of autoimmune limbic encephalitis
dysfunction in the limbic structures of the brain
what symptoms can be caused by autoimmune limbic encephalitis
ST memory impairment
behavioural changes
anxiety
depression
psychosis
seizures
in which population does autoimmune limbic encephalitis most commonly occur
middle aged adults–but can occur in all ages
what 4 criteria must be met to diagnose autoimmune limbic encephalitis
- subacute onset of sx suggesting involvement of limbic structures
- BILATERAL brain abnormalities that is HIGHLY RESTRICTED to the MEDIAL TEMPORAL LOBES on T2 weighted FLAIR MRI
- at least one of:
–CSF pleocytosis
and/or
–EEG with epileptic or slow wave activity involving the temporal lobes - 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
what might be seen on EEG in autoimmune limbic encephalitis
epileptic or slow wave activity involving temporal lobes
what other brain imaging technique may actually be more sensitive to autoimmune limbic encephalitis
18F-FDG PET–> may show increased FDG uptake in otherwise normal appearing medial temporal lobes thus indicating autoimmune limbic encephalitis
what is acute disseminated encephalomyelitis
a monophasic CNS inflammatory disease
in what population does acute disseminated encephalomyelitis most commonly occur
children and adults under age 40
what can trigger acute disseminated encephalomyelitis
can be triggered by acute systemic infection or vaccination
list symptoms of acute disseminated encephalomyelitis
cranial nerve palsies
ataxia
hemiparesis
myelopathy
optic neuritis
what types of antibodies may be found in those with acute disseminated encephalomyelitis
myelin oligodendrocyte glycoprotein (MOG) antibodies
can be found in up to 50% of children with acute disseminated encephalomyelitis
what 5 criteria must be met to diagnose definite acute disseminated encephalomyelitis
- a first, MULTIFOCAL, clinical CNS event of presumed inflammatory demyelinating cause
- encephalopathy that cannot be explained by fever
- abnormal brain MRI
- NO NEW clinical or MRI findings after 3 months of symptom onset
- reasonable exclusion of alternative causes
what brain abnormalities would be seen in MRI in acute disseminated encephalomyelitis
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
what antibodies are associated with anti-NMDA receptor encephalitis
CSF IgG antibodies against the GluN1 subunit of the NMDA receptor
what symptoms characterize the presentation of anti-NMDA receptor encephalitis
prominent psychiatric manfestations–> can delay diagnosis and treatment
what 3 criteria must be met for a “probable” diagnosis of anti-NMDA receptor encephalitis
- 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 - at least 1 of the following:
–abnormal EEG
–CSF with pleocytosis or oligoclonal bands - 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
what abnormalities may be seen on EEG in anti-NMDA receptor encephalitis
focal or diffuse slow or disorganized activity, epileptic activity or extreme delta brush
when can a DEFINITE diagnosis of anti-NMDA receptor encephalitis be made
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
what is the period of onset of symptoms associated with Bickerstaff’s Brainstem Encephalitis
subacute–> LESS THAN 4 WEEKS
what is the symptom pattern seen in Bickerstaff’s Brainstem Encephalitis
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
when can a diagnosis of definitely Bickerstaff’s Brainstem Encephalitis be made
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
what two criteria must be met to diagnose probable Bickerstaff’s Brainstem Encephalitis
- subacute onset (rapid progression of less than 4 weeks) of ALL of the following:
decreased LOC
+
bilateral external ophthalmoplegia
+
ataxia - reasonable exclusion of alternative dx
what factors can be elevated in those with hashimotos encephalitis/encephalopathy
anti-TPO antibodies
anti-thyroglobulin antibodies
anti-dsDNA antibodies
what 6 criteria must be met for diagnosis of hashimotos encephalitis/encephalopathy
- encephalopathy with seizures, myoclonus, hallucinations or stroke-like episodes
- subclinical or overt THYROID DISEASE
- brain MRI NORMAL or with nonspecific abnormalities
- presence of SERUM THYROID ANTIBODIES (thyroid peroxidase, thyroglobulin)
- absence of well characterized neuronal antibodies in serum or CSF
- reasonable exclusion of alternative causes
is hashimotos encephalitis/encephalopathy usually associated with hyper or hypothyroidism
usually hypothyroidism
what is normally seen on MRI in hashimotos encephalitis/encephalopathy
usually normal or with nonspecific abnormalities
list RED FLAGS for suspicion of autoimmune encephalitis in patients with PSYCHOSIS
- infectious prodrome
- new onset severe headache or clinically significant change in headache pattern
- rapid progression
- adverse response to antipsychotics or presence of NMS
- insufficient response to antipsychotics
- movement disorder i.e catatonia or dyskinesia
- focal neuro disease
- decreased LOC
- autonomic disturbance
- aphasia, mutism or dysarthria
- seizures
- presence of a tumor or hx of recent rumor
- hyponatremia (not explained by side effects of medication)
- other autoimmune disorders
- parethesia
what is required for a diagnosis of DEFINITE autoimmune psychosis
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)
list the NO paraneoplastic encephalopathies
hashimotos encephalopathy
sarcoidosis
lupus
sjogrens
celiac
Bechet’s
anti-VGKC encephalitis
what is paraneoplastic limbic encephalitis
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
paraneoplastic limbic encephalitis is usually associated with what type of cancer
small cell lung cancer
ddx for autoimmune encephalitis
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
what signs would indicate HSV encephalitis
fever + MRI hemorrphagic lesions
usually unilateral MRI changes
what is a sign/symptom that is considered pathognomonic for autoimmune limbic encephalitis
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
is there usually unilateral or bilateral involvement shown on MRI in the limbic encephalitises
usually bilateral (though can be unilateral or MRI can be normal)
what EEG change is most specific for anti-NMDA receptor encephalitis
extreme delta brush
what type of antibodies are associated with autoimmune encephalitises
all are IgG
anti-NMDA receptor encephalitis predominantely affects what population
under age 45
more females
what is the main tumor association with anti-NMDA receptor encephalitis
ovarian teratoma
what receptor is associated with limbic encephalitis
AMPA receptor
what tumors are more associated with limbic encephalitis
thymoma
small cell lung cancer
what is first line therapy for autoimmune encephalitis
(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)
how do symptoms generally progress in anti-NMDA receptor encephalitis
initially prominent PSYCHIATRIC symptoms
then progresses to seizures, movement disorders, autonomic dysfunction, hypoventilation
*older adults may present with cognitive decline and catatonic feaures
you have a young person admitted with psychosis, and they display antipsychotic intolerance–what should you consider
anti-NMDA receptor encephalitis
those with anti-NMDA receptor encephalitis often have antipsychotic intolerance i.e fever, unusual EPS rigidity, decreased alertness
what other encephalitis can precede anti-NMDA receptor encephalitis
HSV encephalitis–> seroconversion rate of up to 30%
what should you do if you have a patient who presents with a relapse of symptoms after recovering from HSV encephalitis
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
in which populations should you suspect cryptococcal meningitis
those with HIV
can also affect other people who are immunosuppressed
what psychiatric disorder can be misdiagnosed in those who actually have cryptococcal meningitis
dementia
what are the most common clinical symptoms of cryptococcal meningitis
subacute headache and confusion
(less than 20% have the neck stiffness that we assoc. with meningitis)
do people with cryptococcal meningitis usually present acutely
no–> subacute meningitis is the most common presentation–> can be steadily progressive up to years
what are the symptoms of hepatic encephalopathy
cognitive impairment
ataxia
altered LOC
what investigations should be done if you suspect hepatic encephalopathy
ammonia levels
abdominal U/S
EEGs (look for encephalopathy)
in a patient on VPA, what should you consider if they present with decreasing LOC, focal neuro deficits, cognitive slowing, vomiting, drowsiness, lethargy
consider hyperammonemic encephalopathy–> check ammonia levels
can occure even when VPA levels are normal and LFTs are normal
