Case and Discussion: Chronic and Acute Confusional States Connie Chen, MD Neurology Consultants of Dallas Overview Case presentation Differential diagnosis Clinical approach Results and findings Follow-up Discussion 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 Case Continued Diuretic stopped BP raised slightly PT d/c’d to home after Na normalized 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 Case Continued 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 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” 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) Acute Confusional State – Cerebrovascular: stroke/TIA hypertensive encephalopathy, hypotension DIC, TTP – Infectious: meningitis – Seizures – Head trauma – Neoplasm – Other: (Systemic disease: rheumatologic, paraneoplastic) 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 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 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. 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? Delirium with new onset pyschosis : – Antiphospholipid antibody syndrome – Limbic encephalitis (paraneoplastic syndrome) – Porphyria More Results ESR, ANA, anticardiolipin antibodies negative. More Results Chest CT: – right paratracheal node – 0.8 cm nodular opacity right upper lobe. Biopsy of node: small cell lung cancer. Follow-up Treatment with XRT and CMTx. Psychotic symptoms resolved. Memory loss remains. Discussion 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 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** 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!