Anatomy, Etiology & Treatment

Although early anatomists demarcated the cortex, brainstem, and spinal cord, the subcortical areas and specifically the striatum, were later discoveries.  Thomas Willis (1664) identified the basal ganglia and linked their function to the control of movement.

Charcot classified Parkinson’s disease as a névrose, or neurological condition without a known organic lesion.  As with all primary neurological conditions, Parkinson’s disease was considered to have a hereditary basis in that patients inherited a susceptibility to neurological disease, but the condition itself was not transmitted from generation to generation.  Environmental conditions, including trauma, extreme cold and emotional stress could influence the onset and severity.  Toxic etiologies of parkinsonian syndromes were posited early in the nineteenth century, and in 1837, Couper documented that manganese produced tremor, bent posture, and hypophonia.

Three years after Charcot’s death in 1895, Edouard Brissaud, alluded to midbrain involvement in Parkinson’s disease, and Trétiakoff and Foix further pursued these studies with detailed pathological analyses.  The Lewy body was first described in 1912, and the most complete pathological descriptions of nigral degeneration were performed by Greenfield and Bosanquet.  These studies removed Parkinson’s disease from the category of the névroses and established the structural basis of the primary neurodegenerative disorder.

Because the biochemical lesion of Parkinson’s disease was not established until the 1960’s early treatments were empiric.  Charcot used anticholinergic agents and rye-based products that may have been related to ergot-based dopaminergic agonists.  Several non-pharmacological therapies involved vibratory treatments that specifically abated tremor, including carriage rides, special vibration chairs to shake the body, and vibratory helmets to shake the brain.

Early surgery for movement disorders was pioneered by Victor Horsley and his engineering colleague, RH Clarke.  They developed early stereotaxic equipment to target brain nuclei, though their early surgeries dealt with hyperkinetic disorders rather than Parkinson’s disease per se.  Meyers first focused on the basal ganglia as a lesion target for abating parkinsonian tremor in the 1940’s with subsequent advances by Cooper and other neurosurgeons.

Andreas Vesalius (1514-1564)

Vesalius’ drawing of the corpus striatum
In outlining the structure that would later become known as the coprus striatum (streaked body), Andreas Vesalius (1514-1564) comments in to C and D: “Lines visible everywhere corresponding to those of the three preceding figures. The lines here mark the yellowish or grayish substance of the brain.” Figure VII from Vesalius De humani corporis fabrica (1542). [Public domain]

Thomas Willis (1621-1675)
Thomas Willis introduced experimental studies of the nervous system, and his Cerebri anatome, published in 1664, marked the transition between medieval and modern concepts of brain function. He identified the basal ganglia and linked their function to the control of movement. Working with illustrators, Christopher Wren and Richard Lower, he produced seven important anatomical texts in spite of the political turmoil of the English Civil War and Restoration period. Courtesy of the National Library of Medicine.

Engraving from Finger S. (1994)  Origins of Neuroscience A History of Explorations
into Brain Function, Figure 2.9, p. 23.  New York, Oxford University Press.

Charles Estienne (Stephanus) (1505-1564) composed the seminal anatomical text, De dissectione partium corporis humani…. in 1545 with elaborate engravings. Several concern neuroanatomy and this figure shows a primitive rendition of the corpus striatum, termed glutia or buttocks (E) as they project against the wall of the lateral ventricle.

Francisco Piccolomini (1520-1604)
Piccolomini drew the distinction between cortex, white matter and subcortical nuclei. From Illustrium Virorum Elogia, 1630 Tomasini IP.

Private Collection, courtesy of MDS Member, Christopher G. Goetz, MD, Chicago, IL.

Jean-Martin Charcot found the onset of Parkinson’s disease to be often associated with “damp cold, such as that arising from a prolonged exposure to a badly ventilated apartment.”  Citing a case where tremor began after a patient was attacked by a Cossack and left in the snow, he included “fright, terror the sudden communication of bad news” as possible precipitating influences. Always reflective, however and convinced that primary neurological conditions also always related to hereditary  influences, he commented in a different context: 

“And all this is fine, but I must not prevent you from pushing your investigations further to find the true cause.  Take a look backwards, for neurological diseases are almost all cases dominated by hereditary influences from prior generations.”

William Richard Gowers

William Gowers (1903) listed prolonged anxiety and emotional shock as the most common antecedents of Parkinson’s disease and recommended removing
all causes of mental strain and of physical exhaustion….Life should be quiet and regular, freed, as far as may be, from care and work.

Photo from Bernard, A-M (ed.) (2002)  The World of Proust
as Seen by Paul Nadar, p. 117.  Cambridge: The MIT Press.

Édouard Brissaud (1852-1909)
Édouard Brissaud was Charcot’s student and held the chair immediately after Charcot’s death.  In his lectures, he made the first allusion to possible midbrain involvement in Parkinson’s disease:   “A lesion of the locus niger could very well be the anatomic sustrate of Parkinson’s disease (1895)”.

Courtesy, Library of the College of Physicians of Philadelphia.

Charcot Prescription
Whereas dopaminergic/cholinergic striatal balance was not proposed until the twentieth century, Charcot used the combination of ergot drugs, the basis of some of the modern dopamine agonists, and belladonna alkaloids that are anticholinergic in his early treatment of Parkinson's disease.  This prescription, located in the Philadelphia College of Physicians, is signed by Charcot 1877 and directed the patient to consume hyocyamine and Pearson’s solution, a rye-based syrup.

Nouv Iconographie de la Salpêtrière, 1892 ;5 :265-275.

Vibrating helmet (from Scientific America 1892).  In Goetz, C.G., Bonduelle, M.,
and Gelfand, T. (1995).  Charcot: Constructing Neurology, Figure 5-9, p. 162.
New York:  Oxford University Press.

Helmet and vibratory chair
Vibratory chair (above) was used at the Salpetriere for the treatment of paralysis agitans.  The vibratory helmet (above) was used as a portable adaptation of the chair.

Robert Henry Clark

Victor Horsley

Private Collection, courtesy of MDS Member, Christopher G. Goetz, MD, Chicago, IL.

Early Surgical Interventions
Victor Horsley was a celebrated British surgeon who attempted a surgical intervention on a movement disorder patient with athetosis in 1909. He excised motor cortex with substantial improvement in involuntary movements. Working in London with his physiologist colleague, Robert Henry Clarke, he developed early stereotaxic equipment, first for animal experiments and then for humans. This daunting surgical apparatus taken from their reports in Brain in 1908 guided them to deep brain centers including the basal ganglia and the cerebellum.

Lewy FH (1912):  Paralysis agitans I pathologische anatomie in:  Lewandowsky: Handbuch de Neurologie.  Berlin, Springer.

Lewy's first illustration of microscopical changes In paralysis agitans from Lewandowsky's Handbuch der Neurologie (1912)

Friedrich Heinrich Lewy (1885-1950) described the inclusion body that bears his name in 1912 and though he studied Parkinson’s disease subjects, neither he nor his contemporaries appreciated the close links between Lewy body, nigral degeneration, and Parkinson’s disease. 

Private Collection, Courtesy of MDS Member, Christopher G. Goetz, MD, Chicago, IL.

Early Pallidotomy and Pallidal Deep Brain Stimulation
Surgery to the cortex and cerebellum dominated the field in the early 1900’s and the first systematic attention to the basal ganglia was the work of Meyers in the 1940’s. He examined the effects of lesions in the caudate nucleus and globus pallidus and noted he could improve parkinsonian tremor and rigidity without inducing weakness. Hyperkinesias could likewise be treated with pallidal lesions, and these reports, forgotten for decades, are the solid foundation for treating Parkinson’s disease with pallidotomy or pallidal deep brain stimulation. Irving Cooper and Joseph Waltz’s largely publicized work expanded on these early observations but the advent of levodopa eclipsed the pursuit of neurosurgical studies for three decades.

Traditional Indian Medicine, Parkinson’s disease and Ayurvedic medicines
Description of Parkinson’s disease in Sanskrit under the name of Kapavata in the ancient Indian text Basavarajiyam in 1400 AD. Several natural products used in Indian medicine:

1. Mucina Pruriens. (above) These seeds are called as Kapiketchu or Naikurna and patients powder this and take it. It is said to be an aphrodisiac but it has been shown to contain levodopa.
2. Hysocyamus niger: These seeds have an anticholinergic property.
3. Withnia Somnifera (Ashvagandha). This is believed to have a calming effect on the central nervous system and is used as a “Brain Tonic.”
4. Sida Cordifolia (Bala). This too is considered a “Brain Tonic”.

Text provided courtesy of MDS member, BV Manyam, Texas, USA. Photographs
provided courtesy of MDS member, U Muthane, Bangalore, India.

Photographs of mancerina provided courtesy of MDS Member
Christopher G. Goetz (Chicago, IL USA); mancerina was given as a gift
to Dr. Goetz by MDS Member Esther Cubo (Spain).

Mancerina (Cup Holder)
Mancerinas can be distinguished from other tableware items because of their characteristic central cavity that was used to hold silver, china, or porcelain cups or glasses, while the surrounding saucer served as a pastry tray.
According to legend, the name mancerina came from the Viceroy Antoinio Sebastián de Toledo, the Marquis of Macera, who suffered from an illness that made his hands shake, making him spill the hot chocolate he was so fond of drinking. Thus, he had this special device designed, which prevented the liquid from spilling. One can conjecture on whether his tremor was parkinsonian, essential or toxic in origin. Regardless, this quaint legend is disproved because the mancerina was already popular in the Marquis’ lifetime in many parts of Europe, where it was also known as a “temblorosa”, “tasse tremblante” or “shaker”.

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