“Education is a progressive discovery of our
own ignorance”
Will Durant
Since the inception of human
society, people have been intrigued about the mystery of human behavior and
emotions. Scholars came up with different explanations based on existing belief
system, knowledge and evidences. Greek philosopher Aristotle believed heart as
center of intelligence and emotions. Few centuries later, another Greek
philosopher Galen explained that animal spirit originates in the heart and
travels via the circulatory system to brain. Galen described his assumptions
based on dissection of corpse, and further elaborated that cerebral ventricles
are the epicenter of reasons and emotions.
In the medieval period, accurate
reproduction of images by artists like Da Vinci, Michelangelo and Rembrandt as
well as rapid dissemination of knowledge by printing press, led to better
understanding of human neuroanatomy and neurophysiology. As a result, by the
end of eighteenth century, knowledge of human psyche had evolved from
theoretical philosophy to evidence based neuroscience.
In 1848, while treating a young
patient, who suffered penetrating injury to brain with an iron rod, Harlow and
Vermont observed that damage to prefrontal cortex causes behavioral changes in
human beings.
Twelve years later, Broca proposed
the concept of cerebral dominance and concluded that inferior frontal gyrus in
dominant cerebral hemisphere is the center of speech, while examining brain of
one of his patients. He coined the term ‘Great Limbic Lobe’.
in 1939 Kluver and Bucy, in Chicago
USA, showed that removal of both temporal lobes in monkeys markedly changed
their aggressive behavior and converted them into submissive and obedient
creatures. This was termed as temporal lobe syndrome and later renamed as
Kluver-Bacy syndrome.
In the early years of twentieth
century, Papez and Maclean correlated limbic system with emotions in different
experiments. Papez described Circuit of Papez, a neural connection between
cortex and hypothalamus responsible for generating emotions. Finally, Mclean
coined the term limbic system as a complex connection of cortical and
subcortical structures, functioning together to produce human emotions. His
intention of limbic system was more of a functional concept than anatomical
one.
Thus limbic system is more of a
functional concept. Anatomically it is represented by Ring of interconnected
structures around the "stem" that connects the cerebral hemispheres
to the top end of the brain stem. It includes amygdala, hippocampus, fornix,
mammillary body, mediodorsal thalamic nuclei, anterior nucleus of thalamus,
cingulate gyrus and prefrontal cortex.
Disorders of the limbic system
manifests as neuropsychiatric symptomatology. In many societies, initial
psychiatric behavior is either ignored or considered spirit or demonic
possession, treated by witchcraft before meeting fatal outcome. In learned
societies, these patients take frequent visits to psychiatry ward, treated by various
combinations of antipsychotics, before they manifest the neurological symptoms,
which becomes difficult to differentiate from adverse drug reaction related to
antipsychotic medications.
Till the middle of twentieth
century, patients who were diagnosed as encephalitis, but manifested mainly
neuropsychiatric symptoms, were labeled as atypical encephalitis. In 1960,
Brierly and colleague described temporal lobe inflammation in three patient of
atypical encephalitis. Eight years later, Corselis found similar finding in temporal
lobes of three patients with bronchial carcinoma who suffered atypical
encephalitis. He reviewed eight previously reported similar cases, and
suggested correlation between malignancy and encephalitis and coined the term
limbic encephalitis.
For the next twenty years, it was
considered that limbic encephalitis is a rare disorder and almost always
associated with malignancy and thus described as paraneoplastic disease
(paraneoplastic limbic encephalitis). But it was going to change soon due to
the advancements in neuroradiology and neurochemistry.
Gultekin and Rosenfeld tested
antineural antibodies in patients of paraneoplastic limbic encephalitis and
found autoantibodies against various intraneuronal antigens, in sixty percent
cases. This led to the assumption of autoimmune basis of limbic encephalitis
(autoimmune limbic encephalitis).
With the refinement in imaging
technology, cases of autoimmune limbic encephalitis were reported in patients who
either had benign neoplasm or did not have at all. But MRI imaging of brain in
these patients revealed similar hyperintensities in temporal lobes as in
patients with paraneoplastic limbic encephalitis. More interesting was the
finding that, non-neoplastic autoimmune limbic encephalitis patients responded dramatically to
immunotherapy than neoplastic limbic encephalitis patients, who behaved refractory to
immunotherapy and tumor removal.
Over the next few years, more case of
limbic encephalitis with different neuronal autoantibodies were reported in
literature, which refuted the assumption that limbic encephalitis is a rare
disease.
In 2005, four young women with of
paraneoplastic limbic encephalitis were reported, who were found to have antibodies against the
NMDA receptor. NMDA receptor (N-methyl-D-aspartate
receptor) is a neuronal excitatory glutamate receptor, which plays important
role in controlling synaptic plasticity and memory function.
Characteristic finding of anti NMDA
receptor limbic encephalitis is its affiliation for young women and hypoventilation.
Ultrasonography may reveal pelvic cyst, often ovarian dermoid or teratoma.
These patients are difficult to wean from mechanical ventilator due to central
hypoventilation. Response to immunotherapy and removal of ovarian cyst is
dramatic. Recovery starts within two to three week of treatment and often these
patient return to their baseline physical and mental activity.
Since time immemorial, in every
society and culture, people with symptoms suggestive of limbic encephalitis,
had been either persecuted or revered under the presumption of demonic
possession or spiritual awakening.
These are the few example of people, who
suffered anti NMDAR encephalitis, some of them died because of our ignorance
while others survived, thanks to our knowledge.
In 1970 Germany, a young woman
Anneliese Michel died in mysterious circumstances, following a year of exorcism
by catholic church. Her symptoms were strongly suggestive of anti NMDAR
encephalitis. Ironically, the first case of limbic encephalitis was described
10 years before her painful and ultimate demise.
Two movies "The Exorcism of
Emily Rose" and "Requiem" are based on her.
Amobi Okoye, a football player in Dallas
Cowboy, USA was diagnosed anti-NMDAR encephalitis. He remained in deep sedation
for 3 months, and recovered in 17 months. Despite experiencing a 145-day memory
gap and profound weight loss, he returned to practice on October 23, 2014.
Susannah Cahalan, New York Post
reporter suffered anti NMDAR encephalitis. She fought it bravely, recovered and
recounted her experience in a book titled ‘Brain on Fire: My Months of Madness’.
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