Post-Encephalitic Parkinsonism 

In the early twentieth century, a global illness called Encephalitis Lethargica (EL) caused a global pandemic, leaving thousands of individuals with long-term effects. The main symptoms of this illness include high fever, lethargy and somnolence, that progressed into a chronic neuronal disease similar to post-encephalitic parkinsonism in many cases (Hoffman and Vilensky, 2017). Survivors often exhibited severe and persistent neurological sequelae, including motor rigidity, tremors, and loss of voluntary movement and speech in extreme cases. Many patients became unresponsive to external stimuli, existing in a prolonged state of semi-catatonia (Dale et al., 2004). The conditions of these patients were recorded by Awakenings (Oliver Sacks, 1973), which also documented the therapeutic responses in the latter half of the century. Although the exact cause of EL remains unknown, proposed explanations include autoimmune mechanisms, viral infections, and post-infectious inflammatory damage to the central nervous system (Dale et al., 2004). 

 Using L-Dopa as a Treatment 

The discovery and therapeutic application of L-Dopa (levodopa) in the 1960s was a major breakthrough in the treatment of parkinsonism. L-Dopa is a biochemical precursor of dopamine, which is the reduced neurotransmitter in Parkinson’s diseases and post-encephalitic Parkinsonism. The lack of dopamine results in abnormities in motor functions in patients. L-Dopa is capable of being transported into the central nervous system through blood brain barrier, in cascade converted into dopamine by the enzyme aromatic L-amino acid decarboxylase (Birkmayer and Hornykiewicz, 1961). The mechanism allowed direct restore of deficient dopamine to relief patients from tremors, rigidity and bradykinesia (Fahn, 1996). The widely use of L-Dopa in patients exhibited rapid improvements in mobility, speech and cognitive engagement. In clinical, patients ‘awakening’ from neurological stasis, validated the dopamine deficient as a main cause of diseases. In addition, L-Dopa became a powerful tool in treatment of motor disorders and gave hope to patients that considered incurable (Fahn, 1996). 

 Impact of L-Dopa as a Long-Term Treatment 

However, beyond the initial transient success of L-Dopa, Awakenings vividly illustrates its serious long-term side effects. While patients exhibited improvements in regaining speech, mobility and emotional expression, these improvements soon become unstable. In the movie, Leonard Lowe, one of the most responsive patients to L-Dopa, develops facial tics and emotional disturbances as his dosage increases. These symptoms in the film closely mirror real-life presentations of L-Dopa induced dyskinesias and distressing movements. Nowadays, these side effects have been recognized from the long-term L-Dopa therapy (Marsden and Parkes, 1977). The motor complications arise due to overstimulation of dopamine receptors in basal ganglia; and the emotional disturbances arise from overstimulation of non-motor areas, such as mesolimbic system (Marsden and Parkes, 1977). In addition to these pharmacological effects, this film also reveals the psychological and existential impact on patient’s re-entry into consciousness after neurological isolation. Leonard was distressed and emotionally overwhelmed by the unfamiliar external world around him. These emotional responses are not direct side effects of the drug, reflect a broader psychosocial effect. This theme is supported by findings in the clinical literature, where patients experience identity disruption and anxiety as they attempt to reintegrate into a world that has significantly changed (Turner et al., 2011). These emotional effects highlight the interplay between biological treatment effects and the social and emotional challenges faced by patients when they are reawakened after decades of isolation. 

 Evolution of Schizophrenia Treatment During Nash’s Life 

John Nash was born in 1928 and passed away in 2015 at 86 years old (Kelley, 2015). During his lifetime, schizophrenia treatment changed dramatically.  Although Nash managed to learn to live with his hallucinations, better treatment meant that towards the end of his life he was able to take medication long-term. He was unwilling to take previous medications, due to the side-effects. This is a major issue with schizophrenia treatment, as many patients refuse treatment because of the side-effects. 

Especially in the early twentieth century, many treatments were quite brutal and could often lead to lifelong disabilities or death. Treatments from this time include fever therapy, insulin therapy, lobotomies, and electroconvulsive therapy (ECT) (Kyziridis, 2005). Fever therapy involved deliberately inducing fever in the patient. This could be done by infecting the patient with malaria or by injecting the patient with oil and sulphur. Insulin therapy involved injecting the patient with large amounts of insulin to induce a coma. A lobotomy was performed by severing connections in the pre-frontal cortex. Due to the unpleasant experience and high risk of permanent side effects or death, these were usually administered without the consent of the patient. Additionally, none of these treatments had much evidence for being an effective treatment for schizophrenia. ECT uses electricity to induce seizures in a patient. The seizures could be violent, but there has been evidence for its efficacy. ECT is still used to treat schizophrenia, but only when other medications have failed (Patel et al., 2014). Now, it is performed with the use of anaesthesia.  

Then, a breakthrough came in the fifties with the first antipsychotic drugs. These were the first generation or typical antipsychotics.  The first was chlorpromazine, which the medication Nash took. In the sixties, both chlorpromazine and haloperidol were commonly used (Tueth, 1995). Despite being effective at managing hallucinations, these drugs have a low compliance rate due to the side effects. Chlorpromazine can cause weight gain and has a higher risk of extrapyramidal symptoms. It is also one of the antipsychotics with the highest sedation potential (Patel et al., 2014). Because of side effects like sedation and cognitive impairments, many patients, including Nash, refuse to take them. 

At the same time that the first-generation antipsychotics were becoming widely used, the use of counselling and behavioural therapies began to gain traction (Kyziridis, 2005). A wide range of psychotherapies are still used today. These therapies help patients learn to manage their symptoms and many also focus on family support which improves social functioning (Patel et al., 2014). Many with this treatment also tend to more compliant with taking their medications. Patients obviously must be willing to go to a therapist. They are usually receptive because this treatment does not involve unpleasant side effects like they may have experienced from medication. 

Second generation or atypical antipsychotic drugs came around in the nineties with clozapine and risperidone being the first to come on the market (Tueth, 1995). These drugs have become the first line treatment as they have fewer extrapyramidal symptoms compared to previous drugs (Patel et al., 2014). 

 Examples of the Impact of Schizophrenia Treatment 

‘A Beautiful Mind’ elaborates John Nash’s experience with schizophrenia, a condition marked by hallucinations and delusions. Early in the film, Nash undergoes insulin shock therapy, a now-obsolete treatment that involved injecting high doses of insulin to induce comas and to “reset” the brain. The therapy was based on the idea that shock or coma could reset brain function and alleviate psychiatric symptoms. Some doctors reported temporary improvements in patients with schizophrenia.  Insulin therapy involved administering high doses of insulin to deliberately lower blood sugar levels, inducing a hypoglycaemic coma. This procedure could lead to a range of dangerous complications, including severe hypoglycaemia itself, seizures, permanent brain damage, and even death if the patient’s blood sugar dropped too far or recovery was delayed. The physical strain on the body and the potential for unpredictable reactions during the coma further contributed to its high-risk profile. I highly doubt that any patient would welcome the idea of experiencing such discomfort even at the prospect of treating schizophrenia, whose symptoms appear far less intense than those to be endured in insulin shock therapy.  Other treatments like ECTs were shown to be more effective than insulin shock therapy but were known for causing memory loss and confusion. One of the treatments Nash uses in the movie is the antipsychotic, chlorpromazine. It was shown to effectively reduce hallucinations, but John becomes emotionally detached and unbale to connect with Alicia, his wife. This mirrors real world side effects as the drug has been known to cause involuntary muscle spasms and cognitive blunting. His eventual decision to stop medication is something that I think a lot of people face because patients are obviously going to reject treatments when side effects outweigh the benefits, even if it means having to endure their illness.   

One of the worst treatments for a disease was transorbital lobotomy, which was conducted by Dr Walter Freeman to schizophrenia patients. This method inflicted greater harm than the illnesses they intended to cure. Dr Freeman’s method only took minutes and required no sterile operating room and involved physically severing brain connections with the intention of ‘calming’ schizophrenia patients. This obviously had catastrophic consequences as many of the patients were left in either a vegetative state, emotionally hollow or permanently disabled, as was the case with Rosemary Kennedy who was reduced to infant-like dependency. I think patients would have been better off without this treatment at all because it failed to address the root cause of schizophrenia, and it basically stripped patients of their identity. 

References 

1. Birkmayer, W. and Hornykiewicz, O., 1961. The L-3,4-dioxyphenylalanine (DOPA)-effect in Parkinson-akinesia. Wiener Klinische Wochenschrift, 73(40), pp.787–788. 

2. Dale, R.C., Church, A.J., Surtees, R.A., et al., 2004. Encephalitis lethargica syndrome: 20 new cases and evidence of basal ganglia autoimmunity. Brain, 127(1), pp.21–33. 

3. Fahn, S., 1996. The history of dopamine and levodopa in the treatment of Parkinson’s disease. Movement Disorders, 11(S1), pp.4–10. 

4. Hoffman, L.A. and Vilensky, J.A., 2017. Encephalitis lethargica: 100 years after the epidemic. Brain, 140(8), pp.2246–2251. 

5. Kelley, M., 2015. John F. Nash, Jr. | Math.  Princeton.edu.  

6. Kyziridis, T.C., 2005. Notes on the History of Schizophrenia. German Journal of Psychiatry. 

7. Marsden, C.D. and Parkes, J.D., 1977. "On-off" effects in patients with Parkinson's disease on chronic levodopa therapy. The Lancet, 309(8007), pp.292–296. 

8. Patel, K.R., Cherian, J., Gohil, K. and Atkinson, D., 2014. Schizophrenia: Overview and Treatment Options. Pharmacy and Therapeutics, 39(9), p.638 

9. Sacks, O., 1973. Awakenings. London: Duckworth. 

10. Tueth, M.J.,1995. Schizophrenia: Emil Kraepelin, Adolph Meyer, and beyond. Journal of Emergency Medicine, 13(6), pp.805–809.  

11. Turner, B., Fleming, J., Ownsworth, T. and Cornwell, P., 2011. Reconstructing self after brain injury: A theoretical model of identity change. Neuropsychological Rehabilitation, 21(2), pp.188–209.