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

6/20/2018 1

Department of Medicine

Clinical Problem Solving

Harry Hollander, MD Peter Barish, MD

June 20th, 2018

Department

• f Medicine

Chief Complaint

• CC: Headache and confusion

Department

• f Medicine

History of Present Illness

• 33 year old healthy male
• 3 days ago developed mild headache
• Improved with Tylenol
• Returned in the evening after yard work
• Low grade fever noted by wife
• Given Nyquil and Dayquil
• Per wife, this AM patient “saying weird

things” and may be hallucinating.

Department

• f Medicine
• Most HPI is obtained from wife, with

contributions from patient

• Patient walking normally without

apparent deficits in strength. No facial changes

• Wife notes new word-finding difficulties

History of Present Illness

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Department

• f Medicine
• PMH
• NASH
• HTN
• GERD
• Meds
• Naproxen PRN
• Ibuprofen PRN
• Fluoxetine
• Vitamin e
• Omega-3 Fatty Acids
• Omeprazole 20mg
• Zolpidem 5 mg
• No allergies
• Family Hx:
• Father: HTN, DM2
• Social Hx: Lives with his

wife and daughter and works construction and as a snowplower.

• Former smoker
• Social alcohol use
• No other recreational drugs

Department of Medicine

Clinical Problem Solving

June 20th, 2018 Stop 1

Department

• f Medicine

Review of Systems

Positive for fever and malaise/fatigue, and Positive for headache. Otherwise ROS is negative

Department

• f Medicine

Physical Exam

BP 155/90 | Pulse 93 | Temp 37.9 C (100.2 F) | Resp 16 |SpO2 98% | BMI 36.38 kg/m²

• Gen: Patient is nontoxic-appearing. He sits up in

bed and is conversational but needs redirection.

• 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

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Department

• f Medicine

Neurologic Exam

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.
• Speech is fluent but he has word finding difficulties.

He is able to follow multistep commands.

• He attempts to follow conversation but gets frustrated

when trying to speak. CN: II-XII intact Strength, Sensation, Coordination, Gait: Normal

Department of Medicine

Clinical Problem Solving

June 20th, 2018 Stop 2

Department

• f Medicine

Labs and Studies

18.3 8.5 257 3.6 144 132 98 22 0.8 16 49.7

Ca: 9.2

LFTs: WNL

Department

• f Medicine

Labs and Studies

CT Head

There is subtle low-attenuation within the left temporal lobe. There is no midline shift. There is no mass effect. There is no hemorrhage. There is no extra axial fluid collection. MRI is recommended

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Department

• f Medicine
• Include MRI brain image here

Department

• f Medicine

Labs and Studies

MRI Brain 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

Clinical Problem Solving

June 20th, 2018 Stop 3

Department

• f Medicine

CSF Studies:

• Clear, colorless fluid
• RBC 125 cells/uL
• WBC 845 cells/uL (5% PMN, 95% mononuclear cells)
• Glucose 87
• Protein 71.2
• CSF Gram stain is negative

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Department

• f Medicine

Initial Admission - OSH

Empirically the patient is started on vancomycin, ceftriaxone and azithromycin IV and admitted to Hospital Medicine CSF Studies

• HSV1 PCR Positive
• HSV2 PCR Negative
• Bacterial Culture Negative

Department

• f Medicine

Hospital Course

• Treated with IV acyclovir, completes a 21 day course
• Course complicated by episodes of “staring off into

space” with right sided weakness, concerning for seizure

• Repeat MRI with small temporal lobe hemorrhage
• Keppra is initiated for seizure

Patient is discharged to acute rehab

• Cognitive deficits improve over next 2 weeks
• Patient returns to work 4 h/day

Department of Medicine

Clinical Problem Solving

June 20th, 2018 Stop 4

Department

• f Medicine

Clinical Course

In following 3 weeks:

• Wife notes more irritability, increased anger, reduced

sociability, inappropriately affectionate behaviors

• Anger/irritability progress and patient develops

hypersexual behavior New seizure-like activity: wife notes episodes of RUE extension, R head turn, brief LOC

• Keppra dose is increased
• Phenytoin is added

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Department

• f Medicine

Readmission to OSH

LP Repeated

• WBC 36, Protein 68, Gluc 67
• HSV1 PCR in CSF is Negative

Department

• f Medicine

Transfer to UCSF and Additional Hx

• Initial signs of fluctuating short term memory, poor sleep,

frequent agitation.

• Mood was altered incl inappropriate laughing, crying.
• New hyperphagia and hypersexuality, inappropriate

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.

Department

• f Medicine

Physical Exam

BP 156/105 | P 91 | Temp 36.8 C | RR 17 | SpO2 96% MS: A&O to self, DOB, place. Answers most questions "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

• intact. Inappropriately affectionate, stating ”I love you” to

team. 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

Department

• f Medicine

EEG IMPRESSION: This is an abnormal long-term video-EEG monitoring study due to mild diffuse background slowing. Comment: Mild slowing of the background is a nonspecific indicator of mild global cerebral dysfunction of numerous potential etiologies.

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Department

• f 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.

7

Department

• f Medicine

Department

• f Medicine

Department of Medicine

Clinical Problem Solving

June 20th, 2018 Stop 5

Slide 25 7 Pare this slide down

Quinny Cheng, 6/19/2018

6/20/2018 8

Department

• f Medicine

More Labs All Negative:

• HIV Ag/Ab
• RPR
• Beta D glucan
• Galactomannan
• ANA
• Cryptococcal antigen
• Peripheral BCx
• TTE
• CT C/A/P

CSF Studies

• WBC 7, glu 85, prot 50
• VDRL – negative
• VZV IgG and IgM –

negative

• EBV – negative
• HHV6 – negative
• Rapid HSV-1 PCR –

Positive

Department of Medicine

Clinical Problem Solving

June 20th, 2018 Stop 6

Department

• f Medicine

A diagnostic test returns…

• A. Recurrent HSV encephalitis
• B. Hashimoto’s encephalitis
• C. Autoimmune encephalitis
• D. Creutzfeldt-Jakob Disease
• E. Levetiracetam (Keppra) toxcity
• F. Paraneoplastic encephalitis

Recurrent HSV encephalitis Hashimoto’s encephalitis Autoimmune encephalitis Creutzfeldt-Jakob Disease Levetiracetam (Keppra) t... Paraneoplastic encephalitis

39% 0% 12% 0% 18% 30% Department of Medicine

Clinical Problem Solving

June 20th, 2018 Stop 7

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Department

• f Medicine

NMDA Receptor Antibody (IgG) Serum and CSF - Positive 1:320 HSV-1 PCR Quant returns <50 All bacterial Cx remain negative

Department

• f Medicine

Clinical Course

The patient was treated with IVIG 2g/kg over 3 days and Solumedrol 1G IV x5 days followed by a prednisone taper. Keppra discontinued to avoid any neuropsychiatric side effects. Completed another 14d course of IV acyclovir Discharged to acute rehab, showing slow improvement in cognitive deficits

Department

• f Medicine

Anti-NMDA Receptor Encephalitis

Clinical Features: Prodromal Fever, HA, viral like process, with rapid (<3 month) development of:

• Abnormal (psychiatric) behavior or cognitive dysfunction
• Speech dysfunction
• Seizures
• Movement disorder, dyskinesias, or rigidity/abnormal

postures

• Decreased level of consciousness
• Autonomic dysfunction or central hypoventilation

Diagnosis: above symptoms +

• CSF pleocytosis, abnormal ECG, MRI FLAIR

hyperintensity

• IgG Antibodies to NMDA Receptor (CSF or Serum)

Department

• f Medicine

Anti-NMDA Receptor Encephalitis

Treatment – based on observational studies

• Methylprednisolone
• IVIG or Plasma Exchange
• 2nd line
• Rituxumab
• Cyclophosphamide

Known Association with HSV Encephalitis

• In small studies, up to 20% with recurrent sx post HSVE

have anti-NMDA antibodies

• High clinical suspicion necessary for diagnosis

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Department

• f Medicine

Final Diagnosis

Post-herpetic NMDA Receptor Encephalitis

Department of Medicine

Clinical Problem Solving

Harry Hollander, MD Peter Barish, MD

June 20th, 2018