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1. Case and Discussion:
Chronic and Acute
Confusional States
Connie Chen, MD
Neurology Consultants of Dallas

2. Overview
 Case presentation
 Differential diagnosis
 Clinical approach
 Results and findings
 Follow-up
 Discussion

3. Case Presentation
 61 yo woman
– episode of presyncope
– “wobbly” when standing
– “slow thinking” over 6 months
– noted after administration of BP meds (SBP
200’s lowered to 120’s)
 NRO exam non-focal. MS not extensively
tested, some memory loss noted
 Hyponatremic: Na=117

4. Case Continued
 Diuretic stopped
 BP raised slightly
 PT d/c’d to home after Na normalized

5. Case Continued
 2 weeks later
– Episodic worsening of confusion
– Lost while driving
– Worsening short-term memory
– Episodes of paranoia
– New delusions:
 CT scanner trying to transport her to the future
 Aliens trying to abduct daughter
 After watching “Manchurian Candidate,” she was
also involved in a conspiracy

6. Case Continued
 NRO exam:
– MS:
 Poor memory, attention, not oriented
 Labile affect
 Intact calculations, language
 Delusional
– CN, motor, sensation, cerebellar, and gait are
normal

7. Differential diagnosis:
Chronic confusional state
 Progressive decline of memory, cognition:
– Degenerative dementias
– Multi-infarct dementia
– Chronic infection (TB meningitis, syphilis, HIV)
– Hypothyroidism
– Vitamin deficiencies (B12, thiamine)
– Toxins
– Other: seizures, neoplastic, paraneoplastic,
“pseudo-dementia”

8. Differential diagnosis:
Acute confusional state
 Delirium
– “Metabolic states”:
 Medications/drugs
 Endocrine: thyroid, glucose, hyper/hypoadrenalism
 Electrolytes: Na, Ca
 Vitamins: B12, thiamine
 Organ failure: liver, renal (uremia, “dialysis
disequilibrium”), respiratory failure (hypoxia)

9. Acute Confusional State
– Cerebrovascular:
 stroke/TIA
 hypertensive encephalopathy, hypotension
 DIC, TTP
– Infectious: meningitis
– Seizures
– Head trauma
– Neoplasm
– Other: (Systemic disease: rheumatologic,
paraneoplastic)

10. Clinical approach
 Systematic approach
 Indications for studies
 Don’t stop with one diagnosis:
– “Think outside the box”
– “What am I missing?”
– Tailor your work-up, you can always expand
later

11. Our case: Results and Findings
 Chronic confusional state (>6 month decline)
– Degenerative dementias:
 Diagnosis of exclusion
 Requires memory loss in addition to another “cognitive
sphere” with functional decline
– Multi-infarct dementia: no evidence of infarction.
– Chronic infection: LP negative ( mild protein
elevation), RPR negative, HIV negative.
– Hypothyroidism: nl TSH
– Vitamin deficiencies (B12, thiamine): low B12, normal
homocysteine
– Toxins: negative tox screen

12. Results Continued
 Acute confusional state:
– Metabolic:
 Meds: none
 Endocrine: TSH normal, normo-glycemia
 Infections: LP negative except elevated protein,
RPR negative, HIV negative.
 Vitamins: B12 low but homocysteine normal (MMA
pending), thiamine given.
 Electrolytes: Na 131, dropped to 127.
 Organ failure: organs normal, no respiratory
failure.

13. Results Continued
 Cerebrovascular: no focality to suggest stroke/TIA, not
hyper or hypotensive, no evidence DIC/TTP.
 Seizure: left temporal sharp wave. No seizure.
 Neoplasm: normal head CT.

14. What else am I missing?
 Delirium with new onset pyschosis :
– Antiphospholipid antibody syndrome
– Limbic encephalitis (paraneoplastic syndrome)
– Porphyria

15. More Results
 ESR, ANA, anticardiolipin antibodies
negative.

16. More Results
 Chest CT:
– right paratracheal node
– 0.8 cm nodular opacity right upper lobe.
 Biopsy of node: small cell lung cancer.

17. Follow-up
 Treatment with XRT and CMTx.
 Psychotic symptoms resolved.
 Memory loss remains.

18. Discussion
 Limbic encephalitis:
“a paraneoplastic syndrome marked by
degeneration of neurons in the medial
temporal lobe.”

19. Limbic encephalitis
– Incidence: unknown (rare)
– Symptoms:
 Acute confusional states
 Memory loss
 Seizures
 “Psychiatric” symptoms
 Dementia
– Antineuronal antibodies: anti-Hu, anti-Ta,
(anti-Ma, others)

20. Limbic encephalitis
– Often presents before tumor diagnosis
– Tumor associations
 Lung (small cell, non-small cell)
 Testicular
 Breast

21. Limbic encephalitis:
Studies
 EEG: temporal lobe seizures, sharp waves,
normal.
 CSF: (can be normal)
 Mild pleocytosis
 Mildly elevated protein
 Radiographic:
– MRI: (can be normal)
 medial temporal lobe: “bright” on T2, enhances
with contrast.
 brainstem
 hypothalamus
– ** r/o HSV encephalitis**

22. Limbic encephalitis:
Treatment
 Treatment: underlying tumor
 Immune modulatory treatments attempted:
– Steroids
– Cyclophosphamide
– IV IG
– Plasmapheresis
 Improvement of symptoms only with tumor
treatment
 If diagnosed- search for tumor!