Emily

Barnes
PM 530
Mac
Jeffrey
Angela
Reyes

July 29,
2016

Initial Symptoms
13 year old had one week of altered mental status
8 days prior to admission (PTA) reported headaches, ear
pain, and auditory hallucinations
Had to be sent home from school with headaches and
earache 7 days PTA
Had trembling and a tensing of the left hand
Back pain
Discussion: initial thoughts on symptoms?

Past Medical History

Possible hyperthyroidism, was referred to Endocrinologist,
tested normal
No past surgeries
No developmental delays
Good diet, not a picky eater
No allergies
No medications taken at home
Vaccinations up to date

Family History
She has a healthy mother, and three healthy
siblings. Her father has type 2 diabetes.
*No red flags

Social History

Lives at home with her mother, father, and three siblings

No smokers at home
Two outdoor dogs
Born in Central Valley California
No history of travel outside of the USA
No recent visitors from outside of the USA

Discussion: Why are the dogs a red flag?

Review of Symptoms
Neuro

Const

ENT

Resp

GI

Repro

Headaches
(not
described
well),
hallucinations

No weight
loss, no
change in
appetite

Ear pain

No cough, no
runny nose,
no chest pain,
no difficulty
breathing

No diarrhea,
no
constipation

Last period was

1 week PTA

*No recent history of traveling, bug bites, or sick contacts

Discussion: What else could cause these symptoms if not Lyme Disease?

ER (first treatment center)

7 days PTA had head CT, blood test, and urine cath test at a local community
hospital. All results normal:

*CSF negative for enterovirus, HSV, Cocci, AFB, WNV, Fungal and bacterial cx, EBV,
CMV
*Blood: negative for EBV, CMV, HIV, ANA, pregnancy, Mycoplasma Igm, RPR, Cocci
*Negative hepatitis B DNA PCR

She was then transferred to a tertiary care medical center because she started
displaying bizarre behavior, concerns of her being a danger to herself

Discussion: Why did safety concerns necessitate a transfer in the case of this patient?

Lab Results (second treatment center)

WBC 11.3 with 81.7% neutrophils

Urine Toxicity Screen was negative
CSF showed 34 WBC with 96% monocytes
TSH 0.164
T4 10.2

Physical Exam (second treatment center)

Temp: 37.3 (~99 F), Pulse 120, BP 135/77, Respiration rate 21, WT 60.7 Kg, HT 152
Cm
Waxing and waning lucid states
Would become oriented, but could not make eye contact with examiner and could
only mumble underneath her breath
Extraocular movements intact, PERRL (pupils equal, round, reactive to light)
Tongue was making odd, repetitive movements
Heart rate regular
Lungs sound healthy
Abdomen soft, but not tender. Bowel sounds present.
Neuro showed deep tendon reflex
Extremities were in soft restraints

Physical Exam (continued)

Extremity exam unable to do; speech mostly

unintelligible of patient
Patient does not follow commands so hard to
test strength and gait
Not responsive to tactile stimuli because just
received dose of Zyprexa

Psychiatric Facility (third treatment center)

BY 5 days pta she got a bed in a psychiatric facility
Parents were not permitted to visit her prior to transfer to psychiatric
facility
In psychiatric facility mother reported she was sedated with meds and
disorganized in her actions

She stayed 2 days in psychiatric facility and was then transferred

downstate to another medical center because she spiked a fever to 100.2

Discussion: Why would one restrict parental visitation? Why

would a fever necessitate transfer?

Fourth (and final) Treatment Center

Patient was combative and attempted to assault staff at new center
She was disoriented and slow to respond
EEG showed poorly reactive high amplitude delta activity without an
anterior-posterior gradient suggestive of a diffuse encephalopathic
process
She was started on ceftriaxone (an antibiotic) and acyclovir (antiviral
used to treat viruses in the herpes family)
Discussion: Why do you think the patient was treated with these drugs?

They get an interesting phone call...

The third treatment center where she just came from called to let the doctors know
that her LP (spinal tap) results came back and showed a titer of the NMDA receptor
antibody at 1:160 (reference interval <1:10). A repeat LP showed consistent results.
*This piece of information solved the case.

Anti-NMDA Receptor Encephalitis

NMDA = N-methyl-D-aspartate
glutamate receptor and ion channel protein in nerve cells

Treatment

Treated with pulse steroids (high doses of steroids given over 3-5 days)
Patient also needed rituximab infusion (drug that destroys B cells) for the
encephalopathic process that she experienced
Patients status improved after treatment

Discussion: Why were these drugs used to treat the patient? Why did the patients
illness respond to these treatments?

Before we tell you more about the final

diagnosis, heres some helpful background
information:

Delirium vs. Psychosis

DIFFERENCE
between
Dementia and
Delirium:
ONSET
Rapid versus Slow
(months to years)

Delirium

Psychosis

Rapid

Rapid

Fluctuating

Stable

No

No

ATTENTION

Disordered

Delusional

COGNITION

Disordered

Selectively Impaired

SPEECH

Incoherent

Rapid pressured

ONSET
PATTERN
ORIENTED

What can cause Delirium?

Acute medical illness (UTI, influenza)
A brain event (stroke or bleeding from an unrecognized head injury)
Adverse reaction to medication, mix of meds
Withdrawal from abruptly stopping a medication, alcohol, or nicotine

What can increase susceptibility?

Normal brain aging

Electrolyte imbalance
Dehydration
Malnutrition

Hearing/vision impairment
Multiple medications
Use of certain meds
Prior stroke or brain injury

What can cause Psychosis?

Each case is different -- exact cause is not always clear

Triggers include

Drug use
Lack of sleep
Environmental factors
Stress

Brain diseases (Parkinsons,

Huntingtons disease)
Some chromosomal disorders
Brain tumors or cysts

What can increase susceptibility?

Family history
Genetic mutation 22q11.2 deletion syndrome

Teaching Point | Differentiating Delirium vs Psychosis

Delirium can be treated and it goes away.
- Disturbed consciousness and changes in cognition
- Acute illness
- Fluctuates
Psychosis may not be as simple to eradicate.
-

Characterized by hallucinations and delusions

Cognitive faculties intact, but loss of reality
May be genetically predisposed
Stable

Inflammatory
Brain
Diseases
Mater, H. V. (2014). Pediatric
inflammatory brain diseases.
Current Opinion in Rheumatology,
26(5), 553-561. doi:10.1097/bor.
0000000000000092

Anti-NMDA Receptor Encephalitis Background

Disease officially named and categorized in 2007,

though existed under various names and
symptom categorizations
Incidence and etiology is not very well
understood
In some cases, has been mistaken for demonic
possession

More about the Final Diagnosis

Anti-NMDA Receptor Encephalitis
Occurs when antibodies produced by the bodys own immune system attack NMDA
receptors in the brain. NMDA receptors are proteins that control electrical impulses in
the brain. Their functions are critical for judgement, perception of reality, human
interaction, the formation and retrieval of memory, and the control of unconscious
activities (such as breathing, swallowing, etc).
Cause: Unknown, but probably due to a bacterial infection. The Ceftriaxone could have
eliminated the infection.
*Usually caused by tumors, but that theory was dismissed by negative test results for
tumors in problem areas associated with this disease (ovaries, lung, etc).

Anti NMDA-receptor Encephalitis

May see white matter lesions in MRI

- Serial MRI changes after treatment of

plasma exchange have been presented in a
case report
- white matter lesions on FLAIR (fluidattenuated inversion recovery) and DWI
(diffuse weighted images)
- Possible Tx for lesions= Plasma exchange,
though difficult to do in children

Teaching Point | anti-NMDA Receptor Encephalitis

Classic clinical presentation:

Acute psychiatric symptoms

Low-grade fever
Decreased consciousness
Dyskinesias
Seizures

Most common in young women and

children.

Diagnosis

anti-NMDA receptor antibodies

in serum and CSF
MRI may be normal or abnormal

Over half of the patients have

associated tumor
- Most common: ovarian teratoma

Final Treatment Overview

Patient continued to be encephalopathic and had intermittent episodes of agitation. To
gain control of her agitation, she was started on Tegretol (mood stabilizer), Dilaudid
(for possible pain), and Clonazepam (sedative). After this, she no longer needed
restraints. With regards to her treatment of NMDA Encephalitis, she is s/p (statuspost) 5 days of Methylprednisone (steroid) and s/p 5 days of intravenous
immunoglobulin (for antibody deficiencies). She has also received two more doses of
Rituximab.
Discussion: Why do you think this particular disease process responded to steroids and
Rituximab?

Teaching Point | Role of Cortisol

Steroids cortisol
Cortisol = hormone of adrenal cortex
Secreted in stress situations
Different functions

Promotes efficient use of nutrients

Increase use of fats and excess amino acids for energy instead
of glucose conserves glucose for use by brain
Inflammatory effect
Blocks effects of histamine, preventing tissue destruction

So, how is she now?

Her delirium improved with the interventions and
she was eventually discharged to go home after an
inpatient rehabilitation of approximately two
months after her initial signs of illness.
Discussion: What are the benefits of completing inpatient vs.
outpatient rehab?

So, how is she now? (continued)

The patient was hospitalized in 2013, and

as of February 2015 she has regained all
functions completely.