# Clinical Cases: Limbic System ## Case 1: Wernicke-Korsakoff Syndrome ### Patient Presentation **Demographics:** 58-year-old male **Chief Complaint:** Confusion and inability to walk straight for 3 days **History of Present Illness:** The patient was brought to the emergency department by his landlord who found him confused and stumbling around his apartment. The patient has a long history of alcohol use disorder, drinking approximately a fifth of vodka daily for the past 20 years. He reports poor appetite and has been eating minimally for the past several weeks. He is unable to provide a coherent history and appears disoriented. His landlord reports the patient seemed "not himself" for about a week before becoming acutely worse. **Physical Examination:** - Vital signs: BP 142/88, HR 98, T 37.4C, RR 18 - General: Thin, disheveled male, mildly confused - Neurological: - Mental status: Alert but disoriented to time and place; confabulates when asked about recent events (claims he went fishing yesterday when landlord confirms he has not left apartment) - Cranial nerves: Horizontal nystagmus bilaterally; limited lateral gaze in both eyes (CN VI weakness); pupils reactive - Motor: 5/5 strength in all extremities - Gait: Wide-based ataxic gait; unable to perform tandem walk - Coordination: Dysmetria on finger-to-nose testing bilaterally **Workup:** - **Basic metabolic panel:** Glucose 78, sodium 131 (low), otherwise unremarkable - **Complete blood count:** MCV 104 fL (elevated, macrocytic) - **Liver function tests:** AST 89, ALT 52, GGT 287 (elevated) - **Thiamine level:** 45 nmol/L (low; normal 70-180) - **MRI brain:** Symmetric T2/FLAIR hyperintensity in the bilateral medial thalami and periaqueductal gray matter; mammillary bodies appear atrophic with increased signal **Diagnosis:** Wernicke encephalopathy progressing to Korsakoff syndrome **Treatment:** - High-dose IV thiamine (500 mg three times daily for 3 days, then 250 mg daily) - Thiamine administered BEFORE glucose-containing IV fluids - Magnesium supplementation (cofactor for thiamine utilization) - Nutritional rehabilitation - Alcohol cessation counseling **Clinical Course:** After 5 days of treatment, the patient's eye movement abnormalities and ataxia improved significantly. However, he continued to demonstrate anterograde amnesia and confabulation, consistent with Korsakoff syndrome. At discharge to rehabilitation, he could not recall any of the medical staff despite daily interactions. **Clinical Pearl:** The classic Wernicke triad is confusion, ophthalmoplegia, and ataxia, but the complete triad is present in only about 30% of cases. Thiamine must ALWAYS be given before glucose in suspected cases, as glucose metabolism consumes thiamine and can precipitate or worsen the syndrome. The mammillary bodies and medial thalami are preferentially affected due to their high metabolic demands and role in the Papez circuit. --- ## Case 2: Herpes Simplex Encephalitis with Limbic Involvement ### Patient Presentation **Demographics:** 34-year-old female **Chief Complaint:** Fever, confusion, and strange behavior for 2 days **History of Present Illness:** The patient's husband reports she developed a fever and headache three days ago, which she attributed to a flu. Over the following two days, she became increasingly confused, had difficulty finding words, and exhibited bizarre behavior including repeatedly asking the same questions and becoming agitated when watching television, saying the people on screen were "talking about her." She had one episode witnessed by her husband where she "stared blankly and smacked her lips" for about 2 minutes followed by confusion. **Physical Examination:** - Vital signs: BP 128/76, HR 102, T 38.9C, RR 20 - General: Appears unwell, intermittently agitated - Neurological: - Mental status: Oriented to person only; unable to remember three words after 5 minutes; paraphasic errors; intermittent agitation - Cranial nerves: Intact - Motor: Right arm drift, 4+/5 strength right upper extremity - Sensory: Intact - Reflexes: Brisk on right side **Workup:** - **CT head without contrast:** Subtle hypodensity in left temporal lobe - **MRI brain:** T2/FLAIR hyperintensity involving the left medial temporal lobe (hippocampus, parahippocampal gyrus, amygdala) with extension to the insular cortex; mild enhancement; similar but less extensive changes on the right - **Lumbar puncture:** Opening pressure 180 mmH2O; WBC 125/mm3 (85% lymphocytes); protein 78 mg/dL; glucose 58 mg/dL (serum 102); RBC 450/mm3 - **CSF HSV PCR:** Positive for HSV-1 **Diagnosis:** Herpes simplex encephalitis (HSE) with bilateral medial temporal lobe involvement **Treatment:** - IV acyclovir 10 mg/kg every 8 hours for 21 days - Levetiracetam for seizure prophylaxis - Supportive care in ICU **Clinical Course:** The patient's fever resolved within 48 hours. Her agitation improved over 5-7 days. At discharge after 3 weeks, she demonstrated significant anterograde amnesia, being unable to form new memories of events during hospitalization. At 6-month follow-up, she had persistent memory impairment and required assistance with complex tasks but could perform basic activities of daily living independently. **Clinical Pearl:** HSV-1 has a predilection for the medial temporal lobes (limbic structures) due to viral latency in the trigeminal ganglion with spread along meningeal branches. The bilateral hippocampal involvement explains the severe anterograde amnesia seen in survivors. Early acyclovir treatment significantly improves outcomes, so empirical treatment should begin immediately when HSE is suspected. --- ## Case 3: Transient Global Amnesia ### Patient Presentation **Demographics:** 62-year-old male **Chief Complaint:** Wife reports patient has been "asking the same questions over and over" for 4 hours **History of Present Illness:** The patient's wife reports that they were gardening this morning when her husband suddenly began asking "What are we doing?" repeatedly. Despite answering him multiple times, he would ask again within minutes. He knows who he is and recognizes family members but cannot recall what he did this morning or why he is at the hospital. He has asked "Why are we here?" approximately 15 times during the emergency department evaluation. He denies headache, and there was no witnessed seizure activity. He was straining while lifting heavy bags of mulch just before symptom onset. **Physical Examination:** - Vital signs: BP 154/88, HR 72, T 36.8C - General: Anxious appearing, well-groomed male - Neurological: - Mental status: Alert; oriented to person and place; knows the year but not the exact date; cannot recall any of three objects at 5 minutes despite multiple trials; long-term memory intact (recalls wedding date, children's names, career history); repeatedly asks "What happened to me?" - Cranial nerves: Intact - Motor: 5/5 throughout - Sensory: Intact - Coordination and gait: Normal **Workup:** - **CT head without contrast:** No acute abnormality - **MRI brain with DWI:** Small punctate areas of restricted diffusion in bilateral hippocampi (particularly CA1 regions), each measuring approximately 2-3 mm - **Basic metabolic panel:** Normal - **ECG:** Normal sinus rhythm **Diagnosis:** Transient global amnesia (TGA) **Treatment:** - Observation and reassurance - No specific treatment required **Clinical Course:** Over the next 6 hours, the patient gradually began retaining new information. By 8 hours after onset, he could recall three objects at 5 minutes. At discharge 10 hours after symptom onset, he had returned to baseline cognitive function. He had complete amnesia for the episode itself and approximately 2 hours before onset (the gardening). At 1-month follow-up, neurological examination was normal and the patient had returned to all usual activities. **Clinical Pearl:** TGA is a benign, self-limited episode of anterograde amnesia typically lasting 4-8 hours (maximum 24 hours). Patients characteristically ask repetitive questions while retaining personal identity and procedural abilities. The hippocampus (particularly CA1, which is vulnerable to metabolic stress) shows transient dysfunction. Precipitants may include physical exertion, emotional stress, immersion in cold water, or Valsalva maneuver. The condition is not associated with increased stroke risk, and recurrence is uncommon (approximately 5-25%). --- ## Clinical Image ![Wernicke encephalopathy MRI](case_01_image.jpg) **Image Description:** Axial FLAIR MRI demonstrating symmetric hyperintensity in the bilateral medial thalami, a characteristic finding in Wernicke encephalopathy due to thiamine deficiency. This pattern reflects the selective vulnerability of mammillary bodies, medial thalami, and periaqueductal gray matter - key structures in the Papez circuit essential for memory formation. **Attribution:** Image from Radiopaedia (https://radiopaedia.org/), Creative Commons Attribution-NonCommercial-ShareAlike 3.0 license.