Clinical Problem Solving Harry Hollander, MD Department of - PowerPoint PPT Presentation

6/20/2018 Chief Complaint Department of Medicine  CC: Headache and confusion Clinical Problem Solving Harry Hollander, MD Department of Medicine Peter Barish, MD June 20th, 2018 History of Present Illness History of Present Illness Department Department of Medicine of Medicine • 33 year old healthy male • Most HPI is obtained from wife, with contributions from patient • 3 days ago developed mild headache • Improved with Tylenol • Patient walking normally without • Returned in the evening after yard work apparent deficits in strength. No facial • Low grade fever noted by wife changes • Given Nyquil and Dayquil • Wife notes new word-finding difficulties • Per wife, this AM patient “saying weird things” and may be hallucinating. 1

6/20/2018 • PMH • Family Hx: • NASH • Father: HTN, DM2 Department of Medicine • HTN • GERD • Soc ial Hx: Lives with his wife and daughter and • Meds works construction and as a • Naproxen PRN snowplower. • Ibuprofen PRN Clinical Problem • Former smoker • Fluoxetine • Social alcohol use Solving • Vitamin e • No other recreational drugs • Omega-3 Fatty Acids • Omeprazole 20mg • Zolpidem 5 mg June 20 th , 2018 Department of Medicine Stop 1 • No allergies Physical Exam Review of Systems Department Department BP 155/90 | Pulse 93 | Temp 37.9 C (100.2 F) | Resp 16 of Medicine of Medicine |SpO2 98% | BMI 36.38 kg/m² Positive for fever and malaise/fatigue, and Positive for headache. • Gen : Patient is nontoxic-appearing. He sits up in bed and is conversational but needs redirection. Otherwise ROS is negative • HEENT : Atraumatic. PERRL. Optic disks was visualized partially in both right and left eye and no edema was noted. • CV : RRR, no m/g/r • Pulm : Lungs clear without crackles/rales. Normal effort. • Abd : Soft. NABS. No TTP, guarding, distension 2

6/20/2018 Neurologic Exam Department of Medicine Mental Status:  He is alert. He is disoriented. Patient knows the town but not that he is in a hospital. He intermittently remembers his wife but can't say her name.  Repeats 3/3 words. 0/3 in short- and long-term recall. Clinical Problem  Speech is fluent but he has word finding difficulties. Solving He is able to follow multistep commands.  He attempts to follow conversation but gets frustrated when trying to speak. June 20 th , 2018 Department of Medicine CN : II-XII intact Stop 2 Strength, Sensation, Coordination, Gait: Normal Labs and Studies Labs and Studies Department Department of Medicine of Medicine Ca: 9.2 CT Head 132 16 98 18.3 There is subtle low-attenuation within the left temporal lobe. 144 8.5 257 22 0.8 3.6 49.7 There is no midline shift. There is no mass effect. There is no hemorrhage. There is no extra axial fluid collection. LFTs: WNL MRI is recommended 3

6/20/2018 Labs and Studies Department Department of Medicine of Medicine MRI Brain  Include MRI brain image here There is increased T2 signal within the medial left temporal lobe and to a lesser extent extending to the insular cortex. Following gadolinium administration, there is enhancement of the medial aspect of the temporal lobe and to a lesser extent the midportion of the insular cortex. No other pathologic enhancing process. Department of Medicine CSF Studies: • Clear, colorless fluid • RBC 125 cells/uL • WBC 845 cells/uL (5% PMN, 95% mononuclear cells) Clinical Problem • Glucose 87 • Protein 71.2 Solving • CSF Gram stain is negative June 20 th , 2018 Department of Medicine Stop 3 4

6/20/2018 Initial Admission - OSH Hospital Course Department Department of Medicine of Medicine Empirically the patient is started on vancomycin, • Treated with IV acyclovir, completes a 21 day course ceftriaxone and azithromycin IV and admitted to • Course complicated by episodes of “staring off into Hospital Medicine space” with right sided weakness, concerning for seizure • Repeat MRI with small temporal lobe hemorrhage • Keppra is initiated for seizure CSF Studies • HSV1 PCR Positive Patient is discharged to acute rehab • HSV2 PCR Negative • Cognitive deficits improve over next 2 weeks • Bacterial Culture Negative • Patient returns to work 4 h/day Clinical Course Department of Medicine In following 3 weeks:  Wife notes more irritability, increased anger, reduced sociability, inappropriately affectionate behaviors  Anger/irritability progress and patient develops Clinical Problem hypersexual behavior Solving New seizure-like activity: wife notes episodes of RUE extension, R head turn, brief LOC • Keppra dose is increased June 20 th , 2018 Department of Medicine • Phenytoin is added Stop 4 5

6/20/2018 Readmission to OSH Transfer to UCSF and Additional Hx Department Department of Medicine of Medicine • Initial signs of fluctuating short term memory, poor sleep, LP Repeated frequent agitation. • WBC 36, Protein 68, Gluc 67 • Mood was altered incl inappropriate laughing, crying. • New hyperphagia and hypersexuality, inappropriate • HSV1 PCR in CSF is Negative behavior, lack of inhibition • Short attention span; less socially engaged with decreased verbal output. • Wife noticed unstable gait, decreased use of R arm at times and new mild R facial droop since April 9th. • No change in comprehension. Able to follow through tasks without difficulty. Physical Exam EEG Department Department of Medicine of Medicine BP 156/105 | P 91 | Temp 36.8 C | RR 17 | SpO2 96% IMPRESSION: This is an abnormal long-term video-EEG monitoring study due to mild diffuse MS: A&O to self, DOB, place. Answers most questions background slowing. "Frijoles" + inappropriate laughing; One step command following requires frequent repetition and redirection. Speech is limited to one word answers. Naming intact for high frequency objects, can only repeat one word. Reading Comment : Mild slowing of the background is a intact. Inappropriately affectionate, stating ”I love you” to nonspecific indicator of mild global cerebral team. dysfunction of numerous potential etiologies. CN : +mild R facial droop, otherwise normal Strength : 5/5 throughout Reflexes : 3+ throughout; 4 beats R ankle clonus Coordination : intact FTN Gait , Sensation : intact, normal 6

6/20/2018 7 Department Department of Medicine of Medicine MRI FINDINGS: Interval evolution of the prior predominantly left temporal lobe T2/FLAIR hyperintensity and edema with increased encephalomalacia now involving the mesial and anterior left temporal lobe. There are multiple areas of abnormal enhancement with ring-enhancing lesions involving the medial aspect of the left temporal lobe with a small amount of internal reduced diffusion, concerning for small abscesses. Department of Medicine Clinical Problem Solving June 20 th , 2018 Department of Medicine Stop 5 7

Slide 25 7 Pare this slide down Quinny Cheng, 6/19/2018

6/20/2018 More Labs Department of Medicine All Negative: CSF Studies • HIV Ag/Ab  WBC 7, glu 85, prot 50 • RPR  VDRL – negative • Beta D glucan  VZV IgG and IgM – • Galactomannan negative Clinical Problem • ANA  EBV – negative • Cryptococcal antigen Solving  HHV6 – negative  Rapid HSV-1 PCR – • Peripheral BCx Positive • TTE June 20 th , 2018 Department of Medicine • CT C/A/P Stop 6 A diagnostic test returns… Department of Medicine A. Recurrent HSV encephalitis 39% B. Hashimoto’s encephalitis 30% C. Autoimmune encephalitis Clinical Problem D. Creutzfeldt-Jakob Disease 18% Solving E. Levetiracetam (Keppra) toxcity 12% F. Paraneoplastic encephalitis 0% 0% June 20 th , 2018 Department of Medicine Hashimoto’s encephalitis Autoimmune encephalitis Creutzfeldt-Jakob Disease Paraneoplastic encephalitis Recurrent HSV encephalitis Levetiracetam (Keppra) t... Stop 7 8

6/20/2018 Clinical Course Department Department of Medicine of Medicine NMDA Receptor Antibody (IgG) The patient was treated with IVIG 2g/kg over 3 days and Solumedrol 1G IV x5 days followed by a Serum and CSF - Positive 1:320 prednisone taper. Keppra discontinued to avoid any HSV-1 PCR Quant returns <50 neuropsychiatric side effects. All bacterial Cx remain negative Completed another 14d course of IV acyclovir Discharged to acute rehab, showing slow improvement in cognitive deficits Anti-NMDA Receptor Encephalitis Anti-NMDA Receptor Encephalitis Department Department of Medicine of Medicine Clinical Features: Prodromal Fever, HA, viral like process, Treatment – based on observational studies with rapid (<3 month) development of: • Methylprednisolone • Abnormal (psychiatric) behavior or cognitive dysfunction • IVIG or Plasma Exchange • Speech dysfunction • 2 nd line • Seizures • Rituxumab • Movement disorder, dyskinesias, or rigidity/abnormal • Cyclophosphamide postures • Decreased level of consciousness Known Association with HSV Encephalitis • Autonomic dysfunction or central hypoventilation  In small studies, up to 20% with recurrent sx post HSVE Diagnosis : above symptoms + have anti-NMDA antibodies • CSF pleocytosis, abnormal ECG, MRI FLAIR  High clinical suspicion necessary for diagnosis hyperintensity • IgG Antibodies to NMDA Receptor (CSF or Serum) 9

6/20/2018 Final Diagnosis Department of Medicine Post-herpetic NMDA Receptor Encephalitis Clinical Problem Solving Harry Hollander, MD Department of Medicine Peter Barish, MD June 20 th , 2018 10