THE DIGITAL REVOLUTION
patient and the physician alike soon after initiation of treatment with L-Dopa when it became available for clinical use in 1970 . This is also illustrated so well in the movie Awakenings , with Robert De Niro portraying patient Leonard Lowe , who was afflicted by post-encephalitic PD and oculogyric crises . The movie is based on the must-read book , also Awakenings , published in 1973 by the famous neurologist and author , Dr . Oliver Sacks .
While we are still in the 1950s and 60s let us look at a remarkable incident that serendipitously pointed to potential surgical approaches to PD . In 1953 , Dr . Irving Cooper , a neurosurgeon in New York , while performing cerebral pedunculotomy , accidentally injured the anterior choroidal artery of a patient with Parkinson ’ s disease and was forced to ligate it to prevent bleeding . The patient experienced striking improvement in tremor on the contralateral side . The procedure was later widely used but apparently caused mortality in 10 % of patients . Dr . Cooper later developed the first cryosurgical probe to treat PD and other movement disorders . Soon , stereotactic surgical procedures for lesioning of globus pallidus and ventral nucleus of thalamus followed , but the miraculous effect of L-Dopa treatment hampered further progress . Nevertheless , it became clear that patients may stop responding to levodopa after several years and the side effects may be too severe , observations which encouraged exploration of more advanced treatment . It is fascinating to point out that Dr . Cooper ’ s fame does not stop with stereotactic surgery as he was the first to implant a deep brain stimulator in a patient with pain and spasticity , which may have eventually led to similar measures in PD , making him a pioneer in functional neurosurgery . 2
Another serendipitous incident provided further insight into PD . In 1982 , seven young adults developed features of severe Parkinson ’ s disease after self-injection of synthetic heroin that contained MPTP ( 1 Methyl 4 phenyl 1-2-3-6 tetrahydropyridine ), a metabolite MPP + that destroys substantia nigra . This led to development of an excellent animal model of PD .
Recent years have seen significant advances in deep brain stimulation ( DBS ) techniques , which have enabled patients with Parkinson ’ s disease to have less tremor and improved ability to ambulate . Stereotactic lesioning has been given a new life with the use of high intensity focused ultrasound in combination with MRI guidance , which has obviated the need for placing a burr hole in the skull . Therapeutic advances , although less spectacular , have also been made , the latest being the use of a pump for subcutaneous infusion of levodopa and carbidopa . This helps to avoid the most annoying end-dose and peak-dose dyskinesias that accompany use of oral levodopa in patients with advanced PD .
Parkinson ’ s disease is still a clinical diagnosis ; the trained physician ’ s use of his / her eye ( observing the facial appearance , tremor , gait and bradykinesia ), the ear ( listening to the speech pattern ) and hand ( feeling the typical cogwheel type rigidity ) can make the diagnosis within minutes . The FDA approval of DaTscan in 2011 was a milestone as the first test to became available . It involves the use of a radioactive chemical , loflupane , which attaches to the dopamine transporter in the brain . The test is valuable for differentiating PD from look-alikes like essential tremor . The next milestone is the discovery of biomarkers to detect PD early or to differentiate it from other clinically similar disorders : the SYNTap test looks at the CSF and the Syn-One test at a skin biopsy specimen to detect phosphorylated synuclein . The biomarker era for PD is just beginning and hopefully a simple blood test will become available soon .
We are going through a phase of momentous advances in medicine especially with the increasing use of gene editing , thanks to Jennifer Doudna who won the Nobel prize ( Chemistry ) in 2020 for the development of CRISPR-Cas9 technique . In the 1990s , mutations in the SNCA gene , which is important for alpha synuclein synthesis , were detected in families with autosomal dominant PD . Other genetic abnormalities in PD include mutations in PINK1 , LRRK2 , PRKN and PARK7 . Gene therapies together with DBS is an approach already being explored to see if dopamine production could be enhanced . Other promising research is aimed at gaining insight into the roles of the gut microbiome / quality of diet in the onset and progression of PD . A recent study by Kwon et al . 3 suggests that a healthy diet may support the gut microbiome to have a positive influence on PD risk and progression .
In the next several decades , the entire approach for the management of PD will be revolutionized by ongoing research . Routine use of highly sensitive and specific biomarkers will detect potential risk of developing PD at the pre-clinical stage , which will trigger genetic tests to detect specific mutations that may be correctable and thereby stop further progression . Dietary and other measures to optimize the gut microbiome and potentially prevent onset / progression of PD will become a routine step . Administration of specific drugs that can hinder the formation of phosphorylated alpha synuclein is likely to prevent progression of the disease . These measures are likely in the future to obviate the need for replenishing dopamine and for measures like deep brain stimulation and stereotactic surgery .
Let me finish the back to the future Parkinson journey with a quote credited to the great H . G Wells , regarded by many as the Father of Science Fiction : “ The past is the beginning of the beginning and all that is and has been is but the twilight of the dawn .”
References
1
York GK . The history of James Parkinson and his disease . J Neurol Sci . 2017 ; 381 : S35
2
Rosenow J et al . Irving S . Cooper and his role in intracranial stimulation for movement disorders and epilepsy . Stereotact Funct Neurosurg . 2002 ; 78 ( 2 ): 95-112
3
Kwon D et l . Diet and gut microbiome in patients with Parkinson ’ s disease . npj Parkinsons Dis . 10 , 89 ( 2024 ). https :// doi . org / 10.1038 / s41531-024-00681-7
Dr . Iyer practices at the Neurodiagnostic Center of Louisville and is a retired professor of neurology at the University of Louisville School of Medicine .
November 2024 9