196. Rasmussen Encephalitis: Clinical Features, Pathophysiology, and Management Strategies—A Comprehensive Literature Review

Article type: Literature Review

Article title: Rasmussen Encephalitis: Clinical Features, Pathophysiology, and Management Strategies—A Comprehensive Literature Review

Journal: Medicina
Year: 2024
Authors: Ana Leticia Fornari Caprara, Jamir Pitton Rissardo, Eric P. Nagele
E-mail: jamirrissardo@gmail.com

ABSTRACT
Rasmussen encephalitis (RE) is a rare and progressive form of chronic encephalitis that typically affects one hemisphere of the brain and primarily occurs in pediatric individuals. The current study aims to narratively review the literature about RE, including historical information, pathophysiology, and management of this condition. RE often occurs in individuals with normal development, and it is estimated that only a few new cases are identified each year in epilepsy centers. Approximately 10% of cases also occur in adolescents and adults. The hallmark feature of RE is drug-resistant focal seizures that can manifest as epilepsia partialis continua. Also, patients with RE usually develop motor and cognitive impairment throughout the years. Neuroimaging studies show progressive damage to the affected hemisphere, while histopathological examination reveals T-cell-dominated encephalitis with activated microglial cells and reactive astrogliosis. The current therapy guidelines suggest cerebral hemispherotomy is the most recommended treatment for seizures in RE, although significant neurological dysfunction can occur. Another option is pharmacological management with antiseizure medications and immunomodulatory agents. No significant progress has been made in understanding the pathophysiology of this condition in the last decades, especially regarding genetics. Notably, RE diagnosis still depends on the criteria established by Bien et al., and the accuracy can be limited and include genetically different individuals, leading to unexpected responses to management.

Keywords: rasmussen encephalitis; rasmussen syndrome; encephalitis; epilepsy; hypometabolism; epilepsia partialis continua; refractory epilepsy; cerebral hemiatrophy

Citation
Fornari Caprara AL, Rissardo JP, Nagele EP. Rasmussen Encephalitis: Clinical Features, Pathophysiology, and Management Strategies—A Comprehensive Literature Review. Medicina 2024; 60:1858.
Figure 1. The natural history of Rasmussen’s encephalitis.

Figure 2. Schematic diagram of the proposed mechanisms for the drugs related to Rasmussen’s encephalitis management. 1—Inhibition of lymphocyte T proliferation (tacrolimus, mycophenolate mofetil, and azathioprine). 2—Diapedesis blockage (natalizumab). 3—Pro-inflammatory cytokines blockage (adalimumab, anakinra, and infliximab). 4—Antibody blockage/ clearance (intravenous immunoglobulin, plasmapheresis, and adsorption). 5—Inhibition of lymphocyte B proliferation (rituximab). 6—Inhibition of T and B lymphocytes (alemtuzumab, mitoxantrone, cyclophosphamide). 7—Unknown etiology (ganciclovir). 8—Broad-spectrum anti-inflammatory action (corticosteroids).

Figure 3. Management of Rasmussen’s encephalitis. First, surgery eligibility should be assessed. Second, medical treatment can be used independent of the indication of the surgical procedure. The first-line therapies are corticosteroids ± intravenous immunoglobulin (IVIg) ± plasmapheresis/immunoadsorption. Second-line therapies are related to targeting lymphocytes, pro-inflammatory cytokines, and other mechanisms. The data is scarce in providing specific definitions for most second-line therapies in RE.

Table 1. Histological classification proposed by Robitaille et al. (1991)

Table 2. Neuroimaging stages of Rasmussen’s encephalitis proposed by Bien et al. (2005)



Table 3. Clinical criteria for Rasmussen encephalitis, adapted from Bien et al. (2005)

Table 4. Critical analysis of cases described by Olson et al. (2013)

Table 5. Medical treatment of Rasmussen’s encephalitis.

Table 6. Seizure outcomes in children with Rasmussen’s encephalitis undergoing resective or hemispheric epilepsy surgery.

Table 7. Cognitive outcome after hemispherectomy in patients with RE.

Table 8. Differential diagnosis of RE and explorations, adapted from Bien et al. (2005)

Table 9. Neuroimaging of some cerebral hemi-atrophy causes.

Visual syndromes & cortical blindness

Visual syndromes related to cortical blindness

Syndromes
Anton syndrome
Balint syndrome
Charles Bonet
Capgras delusion
Cortical blindness
Fregoli syndrome
Prosopagnosia
Riddoch syndrome
Subjective doubles
Visual agnosia


Anton versus Charles Bonet
Anton - no insight, cortical lesion
Charles bonnet - insight, cataracts

Stroke - Lipids

Stroke - Lipids

Atorvastatin
10 mg/d - no stroke and LDL at goal, or stroke and low LDL
20 mg/d - stroke and LDL is at goal
80 mg/d -  stroke and LDL high or undefined

DSA - Preprocedure

Digital subtraction angiography - Pre-procedure
António Caetano de Abreu Freire Egas Moniz
Portuguese neurologist and the developer of cerebral angiography

Definition
- DSA means that everything that is not moving is subtracted

Pre-procedure
- anesthesia evaluation
> NPO for 6 hours
- informed consent
> if medical emergency, consent can be waived
- foley catheter insertion after anesthesia
- proper patient positioning
- handwashing
- cleaning of puncture site
- draping

Instrumentation
- test equipament w/ NS heparinized

Access needle
- size 18/19 G
- one versus two versus micro-puncture
one-piece
> sharp, guidewire direct introduction, both A&V access
two-piece
> blunt, before guidewire remove stylet, arterial access
micro-puncture
> small access, use dilator
- dilator
> plastic catheter for dilation

Sheaths
> open at one end w/ capped hemostatic valve in the other
> prevent bleeding

Guidewires
- double-cover, preventing unwinding if it breaks
- lower G than access
- SIM1, SIM2

Contrast
- normal eGFR - up to 800 ml omnipaque
- CKD - iodixanol

Radiation safety
- lead apron
- radiation monitoring batch

Technique
- every time you remove the catheter, you need to double-flush
- long-run or road map
- only two ways to manipulate cattheter, in-out or rotation

Stroke - Afib and LAAL and LAAO

Stroke - Afib and LAAL and LAAO

Considerations
- stroke due to Afib after full anticoagulation
- stroke due to Afib and cannot use anticoagulation

LAAO and LAAL
LAAO
- watchman and amulet

LAAL
- lariat and sierra


Clinical trial - APLS and stroke

Clinical trial - APLS and stroke

Clinical trials
APASS-WARSS (2004)
- warfarin has the same effect of ASA in preventing ischemic episodes

RAPS (2016)
- warfarin has the same effect of rivaroxaban in preventing ischemic episodes

TRAPS (2018)
- warfarin is superior to rivaroxaban in preventing ischemic episodes

ASTRO-APS (2022)
- warfarin is superior to rivaroxaban in preventing ischemic episodes

RISAPS (ongoing)
- warfarin versus rivaroxaban

Clinical trial - apixaban and stroke

Clinical trial - apixaban and stroke

Clinical trials
ARISTOTLE (2011)
- apixaban is superior to warfarin in stroke prevention and lower bleeding

AVERROES (2011)
- apixaban is superior to ASA in stroke prevention and same bleeding risk

ARISTOTLE INR (2014)
apixaban is superior to warfarin in stroke prevention and lower bleeding

AUGUSTUS (2019)
- apixaban monotherapy is superior to VKA or a combination of apixaban to ASA, regarding bleeding risk

Stroke - ICH

Stroke - ICH

Hemorrhagic transformation scale


Clinical trial - aortic atheroma and stroke management

Clinical trial - aortic atheroma and stroke management

Considerations
- > 4 mm is high grade

Clinical trials
ARCH (2014)
- Aortic Arch-Related Cerebral Hazard
- ASA + clopidogrel is superior to warfarin


EEG - Basics

EEG Basics

International 10-20 system
> nasion & inion
> LORE system - left is odd, and right is even

How to place a routine EEG
- paper rule for 10-20 system
- mark w/ the pen the locations
- cotton swab to open the hair, place the gel, and place the paste, and last the sticker
> gel is nuprep (green); pasta is ten20
- start by middle back going to the front, then place the right, and after the left, and by last the ECG
- take the leads from near the machine, and follow to the end of the lead
- look at the monitor needs to turn green in machine
- last two leads are cardiac, one on each side of the thorax
- considerations
> can wrap the head, if the leads fall off; can wrap two times if needed
> can place the leads together near and distal, and place a wrap in all the cables
> eyelids leads are localized at sides


How to do a routine EEG
- calibrate the machine, and test impedance
- ask to open and close eyes
- ask orientation questions like the MMSE
- calm background sound to sleep, especially for kids
- photic stimulation, which does different photic frequencies, with eyes open and close
- channel test at the end
- remove leads with water
- considerations:
> all the modifications and patient positions should be described in the reading

Differences in home LTM EEG
- leads
> no eyelid leads or Fpz lead
> x1-x2 are ECG leads
> gel, paste, glue, and pressurized air
> to remove the leads you need the remover
- ground-ref: can be placed at any spot, usually on forehead
- RULL system: right lead is up, and left lead is low
- needs a backpack and a battery
- before patient leave, do a 30 minutes monitoring
- look at the machine, should be green, and blinking yellow

Cable length
- rEEG: 40 cm; home LTM EEG: 60 cm

Types of monitoring
- routine EEG (30 min)
- continuous EEG inpatient
- continuous EEG inpatient (EMU)
> look at LTM order about what to do
> CBC & BMP at arrival
> it is not a real admission, but it can be converted
- continuous EEG outpatient at home

Mechanism
- differential amplifier
- EEG is always relative

Montages
- channels; a mix of channels is called a chain
- average is used to look at where is coming the spike

- pediatric montages:
> double-banana peds
> reference peds
> trans peds

- adult montages:
> double-banana peds
> reference peds
> transversal (PFOT) peds

- other montages:
> bipolar montage
> common average reference montage