Case and Discussion Chronic and Acute Confusional States

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

Overview n Case presentation n Differential diagnosis n Clinical approach n Results and findings n Follow-up n Discussion

Case Presentation n 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) n NRO exam non-focal. MS not extensively tested, some memory loss noted n Hyponatremic: Na=117

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

Case Continued n 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

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

Differential diagnosis: Chronic confusional state n Progressive decline of memory, cognition: – Degenerative dementias – Multi-infarct dementia – Chronic infection (TB meningitis, syphilis, HIV) – Hypothyroidism – Vitamin deficiencies (B 12, thiamine) – Toxins – Other: seizures, neoplastic, paraneoplastic, “pseudo-dementia”

Differential diagnosis: Acute confusional state n Delirium – “Metabolic states”: § Medications/drugs § Endocrine: thyroid, glucose, hyper/hypoadrenalism § Electrolytes: Na, Ca § Vitamins: B 12, thiamine § Organ failure: liver, renal (uremia, “dialysis disequilibrium”), respiratory failure (hypoxia)

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

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

Our case: Results and Findings n 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 (B 12, thiamine): low B 12, normal homocysteine – Toxins: negative tox screen

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

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.

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

More Results n ESR, ANA, anticardiolipin antibodies negative.

More Results n Chest CT: – right paratracheal node – 0. 8 cm nodular opacity right upper lobe. n Biopsy of node: small cell lung cancer.

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

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

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

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

Limbic encephalitis: Studies n EEG: temporal lobe seizures, sharp waves, normal. n CSF: (can be normal) § Mild pleocytosis § Mildly elevated protein n Radiographic: – MRI: (can be normal) § medial temporal lobe: “bright” on T 2, enhances with contrast. § brainstem § hypothalamus – ** r/o HSV encephalitis**

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