Symptoms & Phases
Autoimmune encephalitis (AE) can produce a very wide range of neuropsychiatric symptoms. A major challenge in diagnosis is that different symptoms may appear at different times and different levels of intensity, so that the disease may mimic many other disorders. Some patients initially present with either neurological or psychiatric symptoms, further complicating diagnosis. Approximately 75% of patients presenting with psychiatric symptoms are first seen by a psychiatrist or psychologist. Because AE mimics bipolar disorder and schizophrenia, patients often go misdiagnosed. Focus on raising awareness of AE among these medical specialties is of vital importance to mitigate misdiagnosis at the onset of first episode of psychosis (FEP). A high level of suspicion is necessary and a lumbar puncture should be performed to rule out an organic cause as autoimmune encephalitis is treatable with immunotherapy.
An otherwise unexplained mixture of these neuropsychiatric symptoms may be a clue that the underlying cause is autoimmune encephalitis.
The signs and symptoms of most antibody-mediated neurologic diseases start suddenly and progress rapidly over several weeks or months. Specific signs and symptoms vary between diseases. In the classic presentation, there is often a distinct phase or period of time where the illness is developing. This is called the prodromal stage. In Autoimmune Encephalitis, the prodromal symptoms, if they occur, are flu-like symptoms which include: headache, fever, nausea, vomiting, diarrhea, or upper respiratory tract symptoms.
Frequently the dominant feature that is seen in children following this first phase is seizure activity. Young children typically present with insomnia, seizures, abnormal movements, or a change in behavior such as irritability, temper tantrums, agitation, and reduction of verbal output. While teenagers and adults more often present with psychiatric symptoms, including agitation, aggression, inappropriate sexual behaviors, panic attacks, compulsive behaviors, euphoria, or fear, hallucinations, delusions, and psychomotor slowing, (a visible slowing of physical and emotional reactions, including speech and affect), which may lead to hospital admission for psychosis.
The disease progresses in a period of days or weeks to include reduction of speech, memory deficit, orofacial and limb dyskinesias, seizures, decreased level of consciousness, and autonomic instability manifested as excess salivation, hyperthermia, fluctuations in blood pressure, tachycardia, or central hyperventilation. One month after disease onset, regardless of the symptoms at presentation, most children and adults have a syndrome that combines several of the above-mentioned symptoms. In approximately 5% of patients, the disease may remain monosymptomatic.
Psychiatric Symptoms may fluctuate rapidly coming on and receding in severity and length of time. Cognitive impairments or abnormalities such as thinking, memory loss, especially the ability to retain new information may be impaired, seizures, problems with concentration, and reasoning are severe enough that they interfere with daily functioning.
There is a progressive decrease in the level of consciousness which can progress to coma. All these signs and symptoms are often occurring within the first few days to several weeks of the disease appearing.
Symptoms associated with AE can include:
Memory disturbance, weakness or numbness of part of the body, loss of balance, slowed or blurred speech or loss of ability to speak, ataxia, autoimmune pain, involuntary movements, distorted vision, cognitive impairment, decreased level of consciousness – to the point of unresponsiveness, catatonia or coma, seizures – (either self-evident, or smaller seizures that show up on an EEG reading), behavior change, (aggression, panic attacks, compulsive behaviors, euphoria or fear), partial or complete loss of appetite for long periods, food and drink tasting inedible or triggering nausea, excessive eating without feeling sated, agitation, inability to sleep, loss of inhibition, inappropriate sexual behaviors, rapid, pressured, or involuntary speech, psychosis, hallucinations (visual or auditory) and delirium, paranoid thoughts, severe anxiety, depression.
Presenting Phases of Autoimmune Encephalitis
If you go to the ER during Phase 1 – of Autoimmune Encephalitis:
The first phase of the disease is a nonspecific prodromal phase with flu like symptoms which include headache, fever, nausea, vomiting, diarrhea, or upper respiratory tract symptoms, low fever, muscle pain, and fatigue.
You may be treated with IV fluids for dehydration, medication for nausea and possibly medication for headache. It’s your basic “Take two aspirin and call me in the morning.” treatment. The patient is stabilized and discharged for home.
If you go to the ER during Phase 2 – of Autoimmune Encephalitis:
The second phase is characterized by neurologic and psychiatric symptoms. Adult patients often show overt first time psychosis with different combinations of psychomotor agitation, delusions, catatonia, violence and aggression. Involuntary muscle movements that are most often facial dyskinesia, is almost universal in the most common Autoimmune Encephalitis, ANMDARE, and may be present at this phase or may first appear during phase three. It seems very likely that these patients will pass through an Emergency Department, and unfortunately many case reports of Autoimmune Encephalitis describe patients who presented to a physician in phase two and were diagnosed with either organic or drug-induced psychotic disorders, bipolar disorder or possible schizophrenia if the age of the patient coincides with the onset of those mental illnesses. They are referred to psychiatric institutions.
The Emergency Department will usually Admit to psych during Phase 2 and ask the question: “Who gave this patient ketamine?”
This is due to the overt psychosis dissociative state that is “similar to that elicited by ketamine”. The physician has been trained to look for the most common cause and fails to evaluate for encephalitis and possible inflammation occurring in the central nervous system.
The signs of ketamine use are so pronounced that they are very hard to miss. For this reason, a person abusing ketamine who does not want family members to know will probably abuse the drug out of sight of family. It is very often used as a party drug, or it may be used in isolation.
Ketamine causes distortions to perceptions, and at lower dosages, a sort of mellowness. The user will feel out of control of himself, and to a greater or lesser degree dissociated from their body. The user may also experience hallucinations similar to those of a person using LSD. Because the symptoms are not long-lasting, the person who uses the drug at a party may have recovered by the time he gets home. For the patient with Autoimmune Encephalitis, symptoms may fluctuate rapidly. Family and friends may report a ‘waxing and waning’ of symptoms which may indicate to the Emergency Room Attending that the episode was drug induced.
One of the challenges of the physicians who first see the patient when onset occurs is that autoimmune encephalitis mimics these common mental illnesses or the appearance of a person who has misused drugs. It is for these reasons and the fact that autoimmune encephalitis is not well recognized within the medical community or still thought to be rare rather than under recognized, that patients suffering are frequently sent home without a neurological evaluation or neurologist called in to consult. Usually they are discharged from the ER and told to follow up with a psychiatrist or they are admitted as a psychiatric patient in a psychiatric institution. All too often patients with Autoimmune Encephalitis are put on a psychiatric hold which now prevents further neurological evaluations. Misdiagnosed as bipolar or schizophrenic with overt first time psychosis, they face becoming legally committed where they remain untreated and the disease is allowed to progress. Catatonia, low levels of consciousness and coma may occur leading to irreversible brain injury and eventual death if an accurate medical diagnosis and treatment does not occur.
If you go to the ER during Phase 3 – of Autoimmune Encephalitis:
During phase 3, patients often present with abnormal or fluctuating blood pressure (hemodynamic instability) and hypoventilation/hypoxia. Again, patients are likely to present to an ED in this stage, from either home or a psychiatric institution.
The Emergency Department declares: “Medically Cleared No More.”
Unfortunately, the diagnosis is not an easy one to make and it requires a skilled, Emergency Attending, Neurologist or Psychiatrist to tease out this diagnosis and separate it from any underlying pre-existing psychiatric condition. As such, patients with this disease may progress past the earlier psychiatric presentation into a more neurologic presentation.
When the disease progresses to this stage, almost half of these patients will require prolonged ICU stays and mechanical ventilation. Many develop autonomic dysregulation (disturbances, abnormalities) such as combinations of tachycardia, bradycardia, hypertension, hypotension, fever or hypothermia, or hyperthermia. Dyskinesia, hyper salivation that may interfere with airway management, no memory of events, also common is the development of seizure like motor activity, although EEG typically does not show changes consistent with epileptic activity. Mild neurologic symptoms such as facial twitching, as well as catatonia, seizures, mutism, or development of extrapyramidal symptoms when placed on an antipsychotic agent.