Anti-NMDA Receptor Encephalitis

By: Arben Memed, SPTA

Morton College
PTA Program
 Learning Objectives
❏ To understand the causes, diagnosis, common signs and symptoms, prognosis, and medical
treatments of Anti-NMDA Receptor Encephalitis

❏ To provide insight to physical therapists on how to specifically assist patients with this
diagnosis to meet the goals within the established plans of care and provide physical
therapists with a variety of intervention ideas to adapt to the patients' needs.

❏ To obtain a variety of intervention ideas for patients with this diagnosis

 Why did we choose this topic?
❏ May 9th, 2021: (Mother’s Day)
❏ Preparing for final exams
❏ Emergency phone call - Sister was admitted into the ER.
❏ During Nursing Clinicals
❏ Presentation fluctuated
❏ Extreme depression, crying, fear of impending death
❏ Manic, extremely happy and stating that she was “okay”
❏ With bouts of mental clarity was able to recognize something was wrong

For a couple weeks we didn’t know what was wrong… Until finally a team of
Neurologists took on her case and diagnosed my sister with Anti-NMDA Receptor
Encephalitis.
 Cause of Anti-NMDA Receptor Encephalitis
❏ “Anti-N-methyl D-aspartate (NMDA) receptor (anti-NMDAR) encephalitis,
caused by immunoreactivity against the NMDA receptor 1 (NR1) subunit of
the NMDA receptor, is one of the most common autoimmune encephalitides,
first described in 2007 by Dalmau and colleagues in which psychiatric and
neurologic symptoms were found in women with ovarian teratomas” (Ford et
al., 2019).
❏ Autoimmune reaction caused by antibodies to the NMDA receptor, which is
found most densely on the surface of the neurons in the hippocampus of the
brain. These antibodies disrupt the functioning of the ligand-gated cation
channels formed by the NMDAR, which result in profound psychiatric and
neurologic disturbances.” (Thomas et al., 2019)
❏ Limited research:
❏ Genetic factors
❏ Environmental factors
Which impairment is most common in those with Anti-NMDA Receptor Encephalitis?

A. Behavior/cognition

B. Speech disorder

C. Movement disorder

D. Seizures
 Signs and Symptoms
❏ Can present weeks/months prior to onset.

❏ Psychiatric disturbances and manifestation of Schizophrenia: Visions,

hallucinations, agitation, paranoia

❏ Viral symptoms such as a headache, fatigue, or fever

❏ Suicidal thoughts

❏ Memory impairments (Anterograde amnesia)

❏ Autonomic disorders: Increased HR, decreased RR

 Clinical Presentation
❏ Behavioral/Cognitive

❏ Catatonia

❏ Impairments with memory and consciousness

❏ Disorders of speech (Aphasia)

❏ Seizures

❏ Dyskinesias

❏ Autonomic symptoms (ie. Temp, RR, HR)

❏ “As the disease progresses, the symptoms become medically urgent and often include autonomic
dysfunction, hypoventilation, cerebellar ataxia, loss of feeling on one side of the body, loss of
consciousness, or catatonia.” (Thomas et al., 2019)
 Catatonia
❏ A complex syndrome of bizarre motor behavior, impaired volition, and vegetative abnormalities

❏ Up to 40 different signs and symptoms have been associated with catatonia

❏ These signs may be summarized in 4 groups:
❏ Pure motor signs
❏ Disturbances of volition
❏ Inability to suppress complex motor activities
❏ Autonomic instability

❏ Neuroimaging reports pointed to reduced resting state activity and reduced task activation in
motor areas of the frontal and parietal cortex” (Walter & Strik, 2016).

❏ ECT
 Diagnosis

❏ Anti-NMDAR encephalitis is based on the detection of IgG antibodies to the

NMDAR, based on cell-based serum antibody analysis..

❏ “An individual with a positive serum antibody test result should have it confirmed by
testing their cerebrospinal fluid via lumbar puncture for high antibody levels which
would indicate an underlying tumor.” (Thomas et al., 2019)

❏ Patients in whom there is a strong clinical suspicion of anti-NMDAR encephalitis

even if the serum assay results are negative, CSF fluids should be tested.

❏ Electroencephalogram (EEG) is abnormal in almost 90% of patients with this

condition.
 Prognosis

❏ When a curable tumor is identified, such as a teratoma of the ovary, the prognosis for
remission is improved because of the high probability of complete tumor removal.

❏ “In high-risk patients, such as females above 12 years of age, a 6-monthly screening MRI
of the pelvis and abdomen for 4 years is recommended.” (Perelman School of Medicine, 2022)

❏ It is also important to recognize that any abnormal behavior of new onset in a patient who
had anti-NMDAR encephalitis may be a sign of relapse of the condition.
 Medical Treatments
Treatment of anti-NMDA receptor encephalitis varies amongst patients but can include a combination
of:
First Line Treatment:

❏ Tumor removal (if tumor is present)

❏ Steroids
❏ Plasma Exchange (plasmapheresis)
❏ Intravenous immunoglobulin (IVIG)

Second Line Treatment:

❏ CellCept
❏ Rituximab
❏ Cytoxan
 Physical Therapy Treatments/Interventions
❏ Pt/Caretaker education

❏ Bed mobility
❏ Transfer training
❏ Balance re-education
❏ Gait training
❏ Age-appropriate functional tasks
❏ Adaptations for functional deficits
❏ Assistance with community integration
Case Study #1: Northwestern Hospital Patient
D.W.

Physical Therapy Interventions:

Cognitive Exercises to increase arousal and focus

Weight shifting via reaching activities, lateral shifting, forward and backwards shifting to engage core
musculature while challenging seated balance, maintaining upright posture, and stimulating vestibular
input.

Transfers: Sit to stands to promote weight bearing through BLE’s, increase strength of BLE.

* All interventions performed to improve functional independence and promote cognitive

engagement.
Case Study #2
❏ 14-year-old female

❏ Symptom progression within 2 days:

❏ Blister, rash, headache, high temperature
❏ Hallucinations and paranoia
❏ Physically threatening

❏ Symptom progression at 2 days:

❏ Hyperactivity, irritability, increased speech, insomnia, paranoia

❏ Symptom progression at 1 week:

❏ Tonic-clonic seizure, declining cognition and neurological status, bowel/bladder incontinence, decreased
feeding, word-finding difficulty

❏ Symptom progression from 1-8 months:

❏ Dystonia, diskinesia, spastic/cogwheel rigidity, hyperreflexia, periods of decreased tone, symptoms
consistent with symptomatic catatonia
Case Study #2 (continued)
❏ Extensive medical work-up
❏ Imaging: unremarkable.
❏ Creatine kinase elevated
❏ CSF positive for anti NMDAR antibodies

❏ Treatment
❏ ECT (7 sessions)
❏ Pharmacological management
❏ PLEX
 Summary
❏ Anti-NMDA receptor encephalitis affects 1 out of 1.5 million people
(0.0000666666666667%)
❏ Suspicion of this pathology should cause health care professionals to take a deeper
look by administering diagnostic techniques that revolve around the analysis of CSF
fluid to see if high levels of antibodies are detected.
❏ Fortunately, prognosis for this condition can be good assuming the tumor is removed
and the patient is able to undergo several medical treatments to restore the bodies lab
values.
❏ As you learned in the previously mentioned case studies, physical therapy plays a big
role in the rehabilitation of both low level and high functioning victims of Anti-
NMDA Receptor Encephalitis.
 References
Center for Autoimmune Neurology. Anti-NMDAR Encephalitis. (n.d.). Retrieved May 8, 2022, from

https://www.med.upenn.edu/autoimmuneneurology/nmdar-encephalitis.html#:~:text=al.%2C%202013-,Diag

nosis,%2D800%2DPENN%20LAB).

Ford. B. McDonald. A., & Srinivasan. S. (2019). Anti-NMDA receptor encephalitis: a case study and illness overview

Drugs in context. 8. 212589. https://doi.org/10.7573/dic.212589

Houtrow, A. J., Bhandal, M., Pratini, N. R., Davidson, L., & Neufeld, J. A. (2012). The rehabilitation of children with

anti–N-methyl-D-aspartate–receptor encephalitis. American Journal of Physical Medicine & Rehabilitation,

91(5), 435–441. https://doi.org/10.1097/phm.0b013e3182465da6

Kennedy, C., O'Shea, R., & De Ranieri, D. (2021). Physical therapy interventions and outcome measures for a

patient diagnosed with Anti-NMDA receptor encephalitis. Pediatric Annals, 50(10).

https://doi.org/10.3928/19382359-20210917-01
 References
Luchini F, Medda P, Mariani MG, Mauri M, Toni C, Perugi G. Electroconvulsive therapy in catatonic patients:

Efficacy and predictors of response. World J Psychiatry. 2015 Jun 22;5(2):182-92. doi:

10.5498/wjp.v5.i2.182. PMID: 26110120; PMCID: PMC4473490.

Mann, A., Machado, N. M., Liu, N., Mazin, A.-H., Silver, K., & Afzal, K. I. (2012). A multidisciplinary approach to the

treatment of Anti-NMDA-Receptor antibody encephalitis: A case and review of the literature. The

Journal of Neuropsychiatry and Clinical Neurosciences, 24(2), 247–254.

https://doi.org/10.1176/appi.neuropsych.11070151

Martin, S., & Kessler, M. (2021). Neurologic interventions for physical therapy (4th ed.). Elsevier.

Peery, Harry E., et al. “Anti-NMDA Receptor Encephalitis. The Disorder, the Diagnosis and the

Immunobiology.” Autoimmunity Reviews, vol. 11, no. 12, 2012, pp. 863–72. Crossref,

https://doi.org/10.1016/j.autrev.2012.03.001.
 References
Perelman School of Medicine. “Anti-NMDAR Encephalitis | Center for Autoimmune Neurology | Perelman

School of Medicine at the University of Pennsylvania.” Perelman School of Medicine at the University of

Pennsylvania, www.med.upenn.edu/autoimmuneneurology/nmdar-encephalitis.html. Accessed 9 May

2022.

Thomas, Liji, MD. “Diagnosis of Anti-NMDA Receptor Encephalitis.” News-Medical.Net, 27 Feb. 2019,

www.news-medical.net/health/Diagnosis-of-Anti-NMDA-Receptor-Encephalitis.aspx.

Walther, S., & Strik, W. (2016). Catatonia. CNS Spectrums, 21(4), 341-348. doi:10.1017/S1092852916000274