A case discussion of Acute Demyelinating Encephalitis

1. Acute Confusion & Ataxia
Frank W Meissner MD, RDMS, RDCS, FACP, FACC, FCCP, FASNC
PGY-2 Psychiatry Resident
Neurology/Radiology
Teaching Conference
1 May 2017

2. HPI
30 year old Right Handed Hispanic Female, longstanding Bipolar Illness on Chronic Lithium
Therapy to Emergency department by POV for evaluation of confusion & falling.
The patient has acute encephalopathy. Her Provider provides history. The patient had been
group home resident for 7 months and was free of any previous episodes of confusion,
disequilibrium, headache, complaints of focal neurological symptoms or unexplained
vomiting. The patient usual state of good physical health on Friday 21 April. Saturday
morning about 10 AM, patient experienced repetitive episodes violent vomiting, according to
the provider 10-12 episodes in the day time. Patient remained miserable but her behavior
appeared normal. However, 2 AM on Sunday morning she began to display progressive
confusion, gait ataxia, and experienced frequent falls on her way to the bathroom. Her
speech deteriorated becoming garbled and incomprehensible. On Monday morning condition
deteriorated, patient now unable to take fluids arrived at UMC ED at 7 AM. She was totally
incomprehensible in her speech, and was unable to walk without assistance. ROS was
unobtainable.
Past Medical History:
Bipolar disorder 1st diagnosed at age 18 with superimposed polysubstance abuse and a total
of 8 separate hospitalizations at EPPC. Her last psychiatric hospitalization was 23Jun2010 at
which time she had a MMSE score of 30/30.
Medications:
Lithium since Y2010, Haloperidol, Propranolol.
Family History: Unobtainable
Social history: Previous history of substance abuse (alcohol, M-J, Cocaine, occasional rare use

3. Vitals: Temp 38.1 C (100.6 ° F), BP 145/83, HR 97/min, RR 16/min, O2 Sat
96% RA
General appearance – WDWN, mildly obese, hirsute, somnolent & poorly
interactive, yawning through out interview. Diffuse soft-tissue contusion &
bruising of the upper and lower extremities. Face had various scrapes and
bruising asymmetrical more prominent on the right face.
Eyes: pupils equally round and reactive to light, can’t cooperate for
accommodation. EOMI at initial exam, about 2 hr later, has a prominent L
gaze preference. Can’t cooperate for VA or visual fields.
Cardiovascular: RRR, no murmurs, POC Echo essentially normal.
Respiratory : CTA bilaterally, POC Pulmonary US Type I, No effusions
Physical Examination

4. Neurological Examination
Oriented to person, situation, & year, attempts to communicate but
vocalizations incomprehensible due to speech being heavily mumbled.
Cranial nerves: Eyes as above, no facial asymmetry, facial sensory intact to
sharp.
Can’t cooperate for cerebellar testing – no nystagmus or evidence of
movement D/O.
Motor : 5/5 at all sites, no abnormal motor tone.
Reflex: 1+ at all sites. Babinski/Hoffman (-). No elicited Frontal Release
signs.
Sensory : Intact sensation to sharp.
Gait: Not assessed. But markedly abnormal by history.

5. Initial Lab/Evaluation
CBC 12.15 with 34 bands, 2 metamyelocytes
Renal BUN 46/ Creat 4.02, Glucose 125, CO2 16, Na 128, K 3.8
TSH 8.11, T4 1.19, HCG negative, Ammonia < 10, Lactic Acid 1.1,
Alcohol 4, Acetaminophen <2, Salicylate <17, BNP 21, Troponin I
0.057, UDS negative
Lithium 0.75 (admit) 0.65 (24 hr postAdmit) 0.47 (5th hosp day)
CXR nml, CT scan abnml (to be shown)
HIV & RPR negative
EEG diffuse slowing => encephalopathy
LP 1 WBC/50 RBC, CSF Glucose 77, CSF Protein 70, Bactogen
negative, Crypto AG/VDRL negative
MRI (to be shown)

6. Dx Impressions
Non-infective Demyelinating
Encephalitis
Acute Kidney Injury - ?
Etiology

7. Wide Differential Diagnosis
Acute Disseminated Encephalomyelitis
Para-neoplastic Encephalitis (NDMR Receptor Encephalitis)
Subacute Sclerosing Panencephalitis
NMO Vs MS
Toulene Encephalopathy
MELAS
Hashimoto’s Encephalopathy
Hypersensitivity Vasculitis or other Vasculitis
HSV Encephalitis
Lyme Disease
Neuro-Sarcodosis
Neuro-Bechet’s Disease
Neuro-Syphillis
SILENT (Syndrome of Irreversible Lithium-effectuated Neurotoxicity

8. Acute Disseminated
Encephalomyelitis
(ADEM)

9. Inflammatory demyelinating disorder of the subcortical white
matter
Autoimmune demyelinating disease of the CNS via cross
reactivity an antiviral antibody with a myelin auto-antigen
M > F
The onset is acute
Often rapidly progressive

10. ADEM
Often involves antecedent infection or
immunization
Viruses associated with ADEM include:
HSV, HIV, HSV6, MEASLES,
HEPATITIS, INFLUENZA, EBV

11. ADEM
A symptom lag of 2-10 days, but may be 4 wks distant from immunological
insult
Signs:
Pyramidal signs (60- 90%)
Acute hemiplegia (76%)
Seizures (35%)
Fevers, headaches, AMS
Lymphocytosis, raised CPR and ESR.
CSF may have elevated protein but can be normal.
CT brain – normal.
MRI: T2 weighted images shows area of prolonged T2 in subcortical
white matter - asymmetrical.

13. Treatment
Initial therapy - IV methylprednisolone 500 mg QD X 5d
If no response IV-IG, 0.4 g/kg X 5d
Or Plasma exchange

14. ADEM vs MS
New lesion with relapse –alert possibility of MS
ADEM classical occurs as a single instance
MS-has no prodromal viral illness & no fever or
meningismus at presentation.
MS present as mono-symptomatic syndrome, i.e. optic
neuritis or myelopathy and develops a relapsing remitting
course.

15. Prognosis
Most make excellent prognosis over a period of
days, weeks & months with no subsequent
neurological impairment
Minority have neurological impairment : motor
disability, visual/cognitive or behavioral
impairment

16. Another Hypothesis

17. Lithium intoxication – S/S
Mild: Sleepy, Proximal Muscle Weakness,
Impaired memory, GI: nausea, vomiting, diarrhea.
Moderate: Neurotoxic: Delirium, Convulsion,
Coma, Incontinence, Hyperreflexia,
Fasciculation, Parkinson-like s/s : Ataxia.
Dyscoordination.
Severe: Nephrotoxic: Nocturia, Distal tubular
acidosis,Impaired Renal Function Tests.
Cardiotoxic: ST-T change, QT prolong, Flat T
waves, Conduction delay, Hypotension.
Acute intoxication– Less CNS depression.

18. Long-term neurologic
sequelae
In some cases, neurologic complications
persist despite lithium removal by
hemodialysis.
The Syndrome of Irreversible Lithium
Effectuated Neurotoxicity (SILENT) consists
of prolonged neurologic and
neuropsychiatric symptoms following
lithium toxicity . In typical cases of SILENT,
neurologic toxicity develops along with an
elevated lithium concentration, but
symptoms persist despite successful
removal of the drug.

19. SILENT patients have been show
to demonstrate
Demyelination at Path Evaluation

20. Long-term neurologic
sequelae
Cerebellar dysfunction, extrapyramidal
symptoms, brainstem dysfunction, and
dementia can develop as part of SILENT
(Syndrome of Irreversible Lithium Effectuated
Neurotoxicity)
Other neurologic sequelae may include
nystagmus, choreoathetoid movements,
myopathy, and blindness.
A review of 90 published cases identified
cerebellar dysfunction as the most common
sequelae, and proposed that demyelination at
multiple sites in the CNS may be the cause .
SILENT can continue for months & in rare cases
effects persist for years.