Early Atypical Parkinsonian Syndromes

Variants of Parkinson’s disease attracted the attention of Charcot who used such cases to define the breadth and clinical scope of typical Parkinson's disease.  He recognized that some patients shared features of Parkinson's disease, but were atypical in other ways: absence of tremor, predominance of axial rigidity without flexed posture, or seeming weakness or severe inability to use the more parkinsonian side.  Progressive supranuclear palsy, multiple system atrophy, and corticobasal degeneration were specifically described and differentiated much later in the mid-twentieth century when more sophisticated microscopic techniques became available to  neuropathologists.  An array of early documents exist, however, to demonstrate that atypical parkinsonism was appreciated in the nineteenth century and served as a foundation for the later separation of various parkinsonism-plus syndromes. Establishing these diagnoses from clinical descriptions, early photographic archives and pathology descriptions remains inferential, but nonetheless, important to understanding the overall history of these disorders.

Encephalitis lethargica
Von Economo wrote in 1918:  It seems strange when sleep appears as a symptom of an illness. Sleeping sickness where people fall asleep while eating or working was first described in two cases in our clinic in Vienna in 1916.  Usually headache, nausea and fever were followed, often within one day, by sleeping that frequently occurred in the most uncomfortable positions.
Photograph from Barcelona clinic of L. Barraquer Ferré (c. 1919) showing a somnolent, encephalitic patient.  Lent by MDS member, L. Barraquer-Bordas, Barcelona.

Photograph from Barcelona clinic of L. Barraquer Ferré (c. 1930) showing a patient
with post-encephalitic parkinsonism. Lent by MDS member, L. Barraquer-Bordas, Barcelona.

Post-encephalitic parkinsonism of von Economo’s disease
Among the late sequelae, parkinsonism was particularly common. Von Economo wrote, “the amyostatic-akinetic form…characterized by a rigidity, without a real palsy and without symptoms arising from the pyramidal tract…To look at these patients one would suppose them to be a state of profound secondary dementia. Emotions are scarcely noticeable in the face, but they are mentally intact.”

Photograph from Barcelona clinic of L. Barraquer Ferré (c. 1940) showing various forms of dystonia. Lent by MDS member, L. Barraquer-Bordas, Barcelona.

Dystonia and other hyperkinesias in post-encephalitics
Von Economo wrote in 1929: “In the winter of 1920, a very large group of hyperkinetic cases appeared, first in Italy and then in Austria. Chorea and hemichorea as well as myoclonic twitches were seen and some progressed into wild gyrations. In other instances, the disorder was expressed as a generalized, curious restlessness of an anxious or hypomanic type. In most of these cases, a very distinct sleep disturbance occurs in which there is troublesome insomnia.” Dystonic spasms also occurred with regularity.

Horizontal section of cerebrum showing bilateral and symmetrical degeneration and atrophy of lenticular nuclei. Normal thalamus. From Brain xxxiv. From the National Hospital, Queen’s Square, published originally in Brain xxxiv.

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

Early documents exist to demonstrate that atypical parkinsonism was appreciated in the nineteenth century and served as the foundation for the later separation of the various Parkinsonism-plus syndromes.

Charcot wrote:  “Studying archetypes is the fundamental task of nosography, Duchenne de Boulonge practiced it instinctively, and many others have done it before and after him.  It is indeispensable and the only way to extract from the chaos of imprecision a specific pathologic state.  The history of medicine, which is long and gran, shows this truth well.  But once the archetype is established, the second nosographic operation begins:  dissect the archetype and analyze its parts.  One must in other words, learn how to recognize the imperfect cases, the formes frustes, or examples where only one feature occurs in isolation.  Using this second method, the phsysician will see the archtypical illness in an entirely new light.  One’s cope enlarges, and the illness becomes much more important in the doctor’s daily practice.  To the patient’s benefit, the doctor becomes attentive and sensitive to recognizing a disease, even when it is in its earliest developmental stages.”

Drawing from Goetz, C.G. (1987) Charcot, The Clinician.  New York: Raven Press.
Private Collection of MDS Member, Christopher G. Goetz, MD, Chicago, IL.

Atypical parkinsonism—likely early examples of Progressive Supranuclear Palsy
Drawing from Charcot’s original lesson, given on June 12, 1888, where he presented a typical case of Parkinson’s disease (L) and his patient, Bachère  (R), whose Parkinsonian variant included the absence of tremor and the extended posture.  Charcot regularly taught his students by comparing and contrasting cases of patients from the Salpêtrière inpatient and outpatient services.

Charcot commented:  “There is something else unusual here worth noting.  Look how he stands.  I present him in profile so you can see the inclination of the head and trunk, well described by Parkinson.  All this is typical.  What is atypical however is that Bachère’s forearms and legs are extended, making the extremities like rigid bars, whereas in the ordinary case, the same body parts are partly flexed.  One can say then tht in the typical case of Parkinson's disease, flexion is the predominant feature, whereas, here, extension predominates and accounts for the unusual presentation.  The difference is even more evident when the patient walks (1888)”.

Drawing from Goetz, C.G. (1987) Charcot, The Clinician.  New York: Raven Press.
Private Collection of MDS Member, Christopher G. Goetz, MD, Chicago, IL.

These four drawings from the same lesson, show the distinctive facial features of patients with atypical Parkinson’s disease. A: Portrait of Bachère, drawn by Charcot.  B: Forehead muscles and superior obicularis in simultaneous contraction. C: Activation of the palpebral portion of the orbicularis. D: Combined activation of frontalis superior portion of the orbicularis and platysma, giving a frightened expression in contrast to the placid, blank stare of typical Parkinson’s disease patients.  

Image shown is Figure 4 (case 2) – Spastic face and fixed staring gaze from Steele, J.C., Richardson, J. C., and Olszewski, J. (1964) Progressive Supranuclear Palsy. Archives of Neurology, 10, p. 336. Reference Steele, J.C., Richardson, J. C., and Olszewski, J. (1964) Progressive Supranuclear Palsy. Archives of Neurology, 10, p.333-359.

Image shown is Figure 5 (case 4) – Resting posture of upturned head and eyes (not a posed upward fixation of gaze) from Steele, J.C., Richardson, J. C., and Olszewski, J. (1964) Progressive Supranuclear Palsy. Archives of Neurology, 10, p. 338.

Image shown is Figures 12 (case 4) and 13 (case 4) from Steele, J.C., Richardson, J. C., and Olszewski, J. (1964) Progressive Supranuclear Palsy. Archives of Neurology, 10, p. 352.

Supranuclear Palsy
Steele, Richardson and Olszewski presented their seminal description of Progressive Supranuclear Palsy (PSP) in 1963 emphazing the combination of parkinsonism, supranuclear ocular paresis and extended neck posture.  They stressed the brain stem lesions and particularly demylinating lesions of the superior colleculi.

From Dutil A.  Sur un cas de paralysis agitante à forme hemiplégique
avec attidtude anormale de la tête et du tronc (extension).
Nouvelle Iconographie de la Salpêtrière 1889 ;2 :165-169.

Progressive Supranuclear Palsy
vs. Corticobasal Degeneration

Patient presented by A. Dutil as an atypical case of Parkinson’s disease for two reasons, first she presented as a highly asymmetrical case of hemiplegic features, and second because of her extended posture.  This case has been reviewed and published as a possible case of progressive supranuclear palsy, but the asymmetry of motor features and the flexed elbow and wrist suggest that corticobasal degeneration is another possibility.  No autopsy information is available.  The photos show a frontal view with asymmetry of arm posture, and profile view with truncal extension.  

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

PSP in Literature
Historical research on early medical diagnoses has occasionally benefited from non-medical sources, especially literary descriptions.  Because movement disorders are particularly visual in their character, it is reasonable to search the writings of celebrated authors known for their picturesque descriptive writings.  In this context, Larner proposed that Charles Dickens captured the essential features of progressive supranuclear palsy in his description of a character in The Lazy Tour of Two Idel Apprentices.  Dickens wrote:

A chilled, slow, earthy, fixed old man.  A cadaverous man of measured speech.  An old man who seemed as unable to wink, as if his eyelids had been nailed to his forehead.  An old man whose eyes – two spots of fire – had no more motion than if they had been connected with the back of his skull by screws driven through it and riveted and bolted outside, among his grey hair.  He had come in an shut the door, and he now sat down.  He did not bend himself to sit, as other people do, but seemed to sink bold upright, as if in water until the chair stopped him.

Chavany portrait

From Chavany JA, van Bogaert L, Godlewski S. Sur un syndrome de rigidité,
à prédominance axiale avec perturbation des automatismes oculo-palpébraux d’origine
encèphalopatique. Presse Médicale 1951;50:958-962. [Copyright Masson, Paris].

Though Steele, Richardson and Olszewski wrote their landmark article on Progressive Supranuclear Palsy in the mid 1960’s an earlier case study by Chavany published in the Revue Neurologique (1951) likely represents the same condition.

From Lhermitte J, Lévy G, Kyriaco N.  Les perturbations de la representation
spatial ches les apraxiques.  Rev Neurolog (Paris) 1925;2:586-600.

Early Photograph of
Possible Corticobasal Degeneration
In 1925, J. Lhermitte reported a case to the French Neurological Society:  A carpenter retired at age 67 because of progressive right hand clumsiness.  At age 72, he could no longer walk independently and ambulated with a wide-based, shuffling gait with the right arm flexed.  In addition, his right arm moved involuntarily “like a foreign body”.  In spite of normal primary sensation, he could not recognize objects placed in his right hand.  Although the patient did not have an autopsy, the clinical picture is highly suggestive of corticobasal degeneration.  

Kayser-Fleischer Ring
Kayser-Fleischer ring as shown in SA Kinnier Wilson’s original textbook, Neurology (1940). Reference Image shown is Plate IX from SA Kinnier Wilson (1940) Neurology Volume II. A. Ninian Bruce (Ed). Reproduced by Hafner Publishing Co., Inc., New York, NY (1970). Chapter XXXVI Progressive Lenticular Degeneration, 806-831.

Amplitude of Tremor in Wilson’s Disease
Patient with Wilson’s disease who attempts to hold his hands outstretched. A light has been attached to the fingertips and light-sensitive film superimposed on the static photograph allows the measurement of the tremor amplitude.

Reprinted from Walshe JM, Handbook of Clinical Neurology, Vol. 49, Elsevier, Amsterdam, © (1986), with permission from Elsevier.

Hand Dystonia in Wilson’s Disease Hand dystonia in a patient with Wilson’s disease.

Reprinted from Walshe JM, Handbook of Clinical Neurology, Vol. 49, Elsevier, Amsterdam, © (1986), with permission from Elsevier.

Typical Facial Expression of Progressive Lenticular Degeneration from SA Kinnier Wilson’s textbook Neurology (1940) showing the characteristic facies and expression in progressive lenticular degeneration in an early stage.

Figure 131 (page 812) from SA Kinnier Wilson (1940) Neurology Volume II. A. Ninian Bruce (Ed). Reproduced by Hafner Publishing Co., Inc., New York, NY (1970). Chapter XXXVI Progressive Lenticular Degeneration, 806-831.

Olivopontocerebellar Atrophy
In 1900 Dejerine and Thomas described Olivopontocerebellar atrophy presenting clinical cases and extensive pathological material. From Dejerine J., Thomas A. (1900) L’atrophie olivo-ponto cerébélleuse. Nouvelle Iconographie de la Salpêtrière, 13, p. 330-370. Photograph taken by Christopher G. Goetz, Chicago.

Multiple System Atrophy
Shy and Drager described orthostatic hypotension in association with parkinsonism or cerebellar features in 1960 drawing note to the marked degeneration of automonic ganglia and spinal cord lesions. Figures 2-5, p. 47-48 from Shy, M. and Drager, G.A. (1960) A Neurological Syndrome Associated with Orthostatic Hypotension: A Clinical-Pathologic Study. AMA Archives of Neurology, 2, p.41-57.

Striatal Nigral Degeneration
Adams, van Bogaert and van der Eecken described striatal nigral degeneration presenting a series of expertly prepared pathological specimens. From Adams, R.D., vanBogaert L., van der Eecken, H. (1964) Striato-nigral degeneration. J Neuropathol Exp Neurol, 23, p. 584-608.

These entries were coalesced under the rubric Multiple System Atrophy (MSA) in the seminal article by Graham and Oppenheimer (1969).


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