Hans Förstl


Otto Binswanger


Die Abgrenzung der progressiven Paralyse.

Berliner Klinische Wochenschrift. 31, 1137, 1182-1184

The definition of progressive paralysis (p. 1137)


First  I will address a relatively small group of cases. Since I became aware of this condition 11 years ago, I have only observed eight such cases. In them we find a pronounced atrophy of the hemispheric white matter, either restricted to one or more gyri in one brain area or several hemispheric regions with variable severity. In the most advanced cases the entire white matter of a lobe may disappear a1most completely so that the opposite gyri are touching, for example in the area of the insula, or are only demarcated on the interior by the thickened ependyma of the enlarged ventricles. These changes are most clearly apparent in the area of the occipital and temporal lobes, so that the temporal and occipital horns are widened into bag-like cavities, while the anterior portion of the lateral ventricle shows relatively little enlargement and the frontal white matter is a1most unaffected by the disease process.1 The fact that the posterior brain areas are the main focus of disease distinguishes these cases from general paralysis. The clinical features and the course of disease yield reliable criteria for its differentiation from paralysis.

We will call this form of disease 'Encephalitis subcorticalis chronica progressiva' (the term 'encephalitis' is used according to Thoma's concept in the wider sense of 'brain disease' and not 'inflammation'). The cortex does not show any remarkable macroscopic change apart from a slight narrowing. Granular ependymitis was present in four observations only. Onset of the disease process can sometimes occur at the same age as paralysis, ie in the second half of the forties. There is no doubt that it more frequently begins at the threshold of old age, at the beginning of the fifties.
Invariably these cases show a severe atheromatosis of the cerebral arteries. It is an obvious assumption that the subcortical loss of fibres is produced by the disturbances of nutrition which are caused by arteriosclerosis. As I observed only a few days ago, we can also find a loss of white matter restricted to individual parts of the brain in older patients with severe dementia senilis.

An intellectually outstanding man of 74 years, who had administered his affairs responsibly until two years previously, fell prey to a rapidly progressive intellectual decay, characterized by paraphasia. His post-mortem revealed a severe loss of white matter in the area of the occipital and temporal lobe. The occipital and temporal horns showed an enormous corresponding widening and the ependyma was tough and thickened.
(pp. 1182-1184) I would like to illustrate the clinical distinction of encephalitis subcorticalis chronica progressiva from general paralysis with a case example.
A factory director had been infected with syphilis 26 years earlier, had suffered from sciatic pain 12 years earlier, and had hypersalivation, visual impairment on his right side (choreoiditis disseminata) and vertigo. He developed severe left-sided headache, formication in his right arm and leg, and impairment of fine coordinated movements of his right hand and fingers, which manifested as uncertainty, c1umsiness and increased fatigability when writing, dressing or undressing. A decreased touch and pain sensitivity could not be demonstrated in the affected extremities. Pressure, position, and tactile sensitivity were not notably reduced. Gross motor strength on the right side was not impaired. Moreover, the patient complained of language difficulties: he would frequently lack the words to express his thoughts concisely and c1early, and would often have to express himself in a roundabout way because the most obvious words did not occur to him. There was no disturbance of articulation and no paralytic disturbance of language. He suffered from sleeplessness, a miserable hypochondriacal mood and a fear of becoming insane. He was particularly tormented not only by losing the correct words during a conversation but by sudden general failures of his memory. For example, when he reported his experiences during the German-French, war, he suddenly forgot where he had been on this or that occasion and what he had seen or done. He could consistently and correctly remember recent experiences, his own and his family's situation, and he was well aware of his condition. It was striking that he had difficulties calculating with multidigit numbers.
Antisyphilitic treatment led to a relative improvement.
His headaches decreased, the disturbances in the extremities and the aphasic disturbances diminished. It was only during periods of physical or mental fatigue that his language failed for short periods. The patient continued his former business but he lacked his earlier mental freshness. Not only did he tire sooner, but his performance was of poorer quality, as his brother, who was also working in the company, confirmed. The aphasic disturbances did not change significantly during the antisyphilitic treatment. Impairment of his intellectual capacities increased during the following years. He became more forgetful, particularly for recent events. His judgement of business matters deteriorated more and more. The language disturbance increased and became clearly paraphasic. His affect was highly irritable and he displayed states of angry or anxious-tearful excitement. In his fiftyfourth year he had to be admitted to an asylum because of more violent states of excitement. The patient got up at night-time to look for thieves, would mutter in an excited, incomprehensible and inconsistent manner, was completely disoriented, wanted to run out on the street, and became extremely furious when he was stopped.
The following information is taken from his case notes. Scar at the right tonsil and at the left velum palatinum; scar left of the frenulum praeputii; no glandular swellings; mild periostitic superimpositions over both tibiae, arteries remarkably tortuous, more rigid on the right than on the left; pulse 94; cardiac sounds feeble, but of normal quality; normal cardiac percussion; urine acidic and free of protein. Pupils of average diameter, equal, all reactions prompt; lids equal; left facial nerve slightly stronger innervation at rest and during activity than the right; slight deviation of the tongue to the right, but can also be stuck out at the side of the mouth; no tremor; motor strength of the upper extremities bilaterally only mildly reduced; dynamometric measure of hand grip 75, 77, 95, 100, 86 on the right, and 55, 80, 73, 70, 80 on the left; fine tremor of the hands; fine hand and arm movements, e.g. buttoning, well preserved on both sides; bilaterally reduced motor strength of the lower extremities, right worse than left; walking normal; no Rombergism.
Language. He always speaks incoherently and incomprehensibly by joining words together in a completely meaningless manner. He calls a spoon a 'school', shakes his head and evidently looks for the right word. When he is told 'spoon', he immediately agrees and murmurs the word several times. His repetition appears generally intact and the understanding of simple tasks appears relatively well preserved. A number of items are placed in front of the patient and he is asked to give a clearly named item to the physician. He mostly finds the correct item. More rarely, e.g. when asked for a 'pencil', he looks at the physician in astonishment and does not point to the pencil in front of him. Once he mixed up pencil and penholder. He res ponds correctly when asked to show his tongue or to extend his left or right hand.
Physician: 'Where is my ring?' Patient: 'My - your ring?' (Looks at his hand.)
Physician: 'Show me my ring!' The patient draws a ring in the air with his finger.
Physician: 'Point to my ring on my left hand.' The patient looks at his left hand.
The designation of presented items appears inconsistent as demonstrated by the following sequence. (Watch):  'This is ... I really don't know that – Erfurt - in Erfurt.' (Hat): 'A hat.' (Ring): 'This is also a hat.' (Glove): 'This is a dog- show-shof.' (Ink pot): 'Bread.' Physician: 'But that is not a bread.' Patient: 'Nooee, the blue one-.' (The ink pot is blue.) (Penholder): 'Pen-nib.' (Wallet): 'That is-I don't know-that is 200 and so and so much. That is beautiful.' Even when touching the wallet he does not find the name. (Dollar): 'A dollar.' (A pound coin): 'That is a twenty (twenty note?)- a silver penny, no two.' (Cuff): 'Cuff (quickly). He cannot name a key, but makes the correct mime of unlocking.
If items are put into his hand to fee! while his eyes are closed, he names them as correctly or paraphasically wrong as often as if he could see them. It must be concluded that his sense is intact, because even if he gives the wrong name, he can correctly observe 'this is the same thing' if he puts the item from one hand into the other.
Alexia. When reading, the patient skips words and interprets others fantastically. Instead of' We wouId have preferred it if she had chosen a Frenchman of her own religious demonination, but her heart has spoken and we agree' (newspaper headline), he read 'We had a black of own faith-this is a disgusting story-and her heart yes black spoke until early to us.' This is aggravated by new disturbances as the patient now jumps from line to line.
He does not obey the following written command even if he is able to read it slowly and correctly: 'Give me your right hand'. He can usually read three-digit numbers correctly: transpositions and confusions occur with four digit numbers.
Agraphia. He can often write his name spontaneously and correctly, but sometimes single letters are omitted or inappropriate letters are interposed. On dictation he writes, for example, 'moustache' as 'mustaurrda', and at the next attempt 'mud ... ' a number of completely illegible and incomprehensible letters follow. The patient can write the word 'light' correctly on dictation. Even copying is severely impaired. Instead of 'moustache' he writes 'neighbour builderer' and then 'nennhbarbobiterin', and fina1ly illegible signs.
Sensitivity to pain is generally preserved; sensitivity to touch cannot be adequately examined. He obviously smells Perubalsam and NH3 on both sides. Words spoken low can be heard in the right and left ear at a distance of half a metre. He hears the ticking of a watch with closed eyes and concludes promptly: 'This is a watch'. No gross disturbance of taste to be verified.
Facial expression rather intelligent, a little perplexed and astonished. When somebody smiles at him or offers his hand, he smiles obligingly and shakes the hand with perfect courtesy, bowing correctly. Sometimes he suddenly clasps his hands and his face assumes a pitiful expression. He looks upwards and tries to explain something to the physician; however, his paraphasia is of such a degree that he cannot be understood.
24.II. Very restless at night, mostly out of his bed, moves urgently towards the door.
25.II.. Physician: 'Who am I? Patient: 'You are Mr .. .' Physician: 'Priest?' Patient: 'No.' Physician: 'Physician?' Patient: 'Yes.'
Now he is frequently tearful and timid in the daytime.
He often keeps repeating some words automatically from questions he has been asked.
28.II. Sings the melody 'A bird comes flying ... ' (without words) and adds 'I used to make music'.
3.III. The patient shows increasing restlessness. He rarely sits quiet for a couple of minutes; taking large steps he walks around everywhere as if searching for something. When somebody tries to stop him he says: 'By God, so let me go. I have all day long-some other time (?), do me a favour'.
4.III. (3x2?): '7.' (3x3?): '9.' (7x8?): '3x3, 3x3 = 9.'
7.III. The patient cannot play the piano any more. 12.111. When addressed forcefully, he can sometimes utter words which he otherwise forgets.
15.III. There is no consistency in his mistakes. The patient frequently uses conventional phrases instead of what he wanted to say. When reading his own paragraphic writing, he realizes his mistakes.
21.III. Frequently puts on his clothes in the wrong sequence.
27.III. Often walks up to this or that fellow patient and pays a compliment. His behaviour gives the impression that he believes himself to be at a social gathering.
l.V. Sometimes mild inclination of body to the right side.
1. VI. A night frequently very noisy.
12..VIII. To judge by his facial expression he recognizes a relative probably correctly, but calls him by the wrong name.
1890. 4.III. Has apparently recognized his former physician during a visit.
l.V. Now repeats spoken words wrongly. Often makes scrubbing movements with his hands over his limbs.
1. VII. Cannot write his correct name any more.
l89l. 10.IV. Testing verbal comprehension as after admission. (Weimar newspaper): 'Newspaper- ... .' (Official News): 'official .. .'-the patient does not read further. On dictation he can only write single letters correctly; writing spontaneously, he can only write single letters and then illegible lines. Copying, he can only write the first letter correctly-strange letters are added. The patient is often unclean.
1892. 18.II. Epileptic seizure with initial cry in the morning, short-lasting clonic-tonic, then coordinated hitting and kicking followed by several hours of sleep. Temperature 37.4°C. Vomiting at 2.00 pm. 4.30 pm defaecation.
19.II. Restless and unclean at night, undisturbed skin and tendon reflexes. Symmetrical reaction after stitches with muscle innervation on the right and left side. No gross impairment of the visual field and of hearing. Slightly staggering gait.
7. VI. Second epileptic seizure. Violent postictal excitement. The patient throws himself about in his bed and lashes out.
6'x1I. Knew jerks cannot be elicited. In the evening 39.2°C. Diarrhoea.
1893. 10.1. The patent is dull, apathetic, very frail. 10.111. Direct and indirect pupillary reaction preserved on both sides; slightly less prompt. Strabismus divergens sinister. Moderately strong knee jerk on both sides. Generally preserved sensitivity to pain. Does not respond to the most simple commands. Does not name any items presented to him. Repeats 'book' and 'hat'. Severe wast¬ing. Has to be fed. Completely unclean. During the fol¬lowing days frequent fever in the evening hours.
3. VI. Decubitus. 39.3 °C. Slowed respiration. Face very red.
6.VI. 9.00 pm. Exitus letalis.

Postmortem 7.VI.1893, 11.00 am (Prof. Müller).
Abbreviated from the neuropathology report: Medulla spinalis: roots white. Cervical medulla: even, substance very pale, dorsal roots in a narrow zone besides the Raphe pale greyish-yellow. Upper thoracic medulla: anterior columns white, lateral columns almost complete radial grey-reddish discoloration apart from the middle lateral parts; dorsal columns grey. Lower thoracic medulla: Anterior columns white, reddish-grey discoloration pronounced in the posterior third of the right lateral column more than the left; dorsal columns of the anterior half pale reddish-grey, in the posterior half yellowish-grey; grey substance very pale. Lumbar medulla: plain; anterior columns white, lateral columns showing reddish-grey stripes particularly towards the grey substance; dorsal columns grey; grey substance very pale; central canal nowhere visible. Leptomeninges delicate apart from single unremarkable opacities of the arachnoid; severe external hydrocephalus. Frontal gyri obviously increasingly narrowed towards the front; the basal dura mater of the anterior and middle fossa covered with reddish-yellow gelatinous dots. Brain weight 1285 g.
Only single, unremarkable white opacities at the basal arteries. The lateral ventricles significantly enlarged, particularly in the temporal horn. Hemispheres generally pale; grey matter narrowed in the frontal part.
The white matter of the lower parietal lobe and of the upper and lateral part of the temporal lobe is extraordinarily narrowed, particularly in the left side. The enlargement of the lateral ventricles therefore primarily affects the occipital and temporal horns. Their ependym is remarkably thickened. No sign of a focal disease can be found anywhere (the accurate examination of the brain with serial cuts for the delineation of the extent of the fibre loss will be published later in connection with the reporting of similar cases). In these parts the decay of the white matter can most clearly be seen in the brain fixed by potassium chromate.
The posterior half of the hemispheres is much small on the left than on the right. A frontal cut through the right hemisphere through the middle of the posterior branch of the Sylvian fissure at the posterior margin of the operculum shows a maximum diameter of 8.7 cm, whereas the diameter on the left is only 7.3 cm.
These observations can be summarized as follows. Syphilitic disease in the mid-twenties; first disturbances of the nervous system (sciatic nerve?) in the forty-first year and hypersalivation lasting 1.5 years in the forty-fifth year. Choreoiditis disseminata in the forty-ninth year; at the same time, symptoms of brain disease among which motor aphasia and paraphasia are most characteristic. Paraphasia, dysgraphia, paralexia and dyslexia. Increasing memory impairment, disorientation, incoherence, states of excitation during which disturbances of language remain fairly stable. In the fifty-seventh year two epileptic attacks. Increasing intellectual decay. Wasting and exitus letalis in the fifty-eighth year. Postmortem: mild arteriosclerosis, diffuse affection of the spinal cord, no macroscopically detectable syphilitic affection of the brain arteries, no remarkable leptomeningitis, severe wasting of the white matter in the parietal and temporal lobes, particularly on the left side, moderate cortical atrophy of the frontal lobes.
It can be concluded from the development and course in this case that the disease process has primarily affected the myelin fibres of the left hemisphere and particularly the connecting pathways:
1.    Between the centres of visual representation and acoustic language and the reading and writing centres
2.    Between the reading and writing centres and the acoustic language centre.
3.    Between the acoustic and motor language centres
According to this widespread but functionally and anatomically incomplete destruction of association fibres, the aphasic symptom complex is complicated and not simple. It contains mixed features of transcortical and intercentral conduction aphasia. Of course it is completely impossible at this stage, before the brain has been investigated in greater detail, to state whether we are only dealing with the destruction of association of callosal fibres or with projection fibres also. The latter can be concluded from the macroscopical findings with some certainty. Apart of the language disturbance could then be related to the latter and therefore be explained by incomplete agnostic sensory aphasia and alexia (throughout this paper I have employed the terms for the individual aphasic disturbances as used by Ziehen in his c1ear and comprehensive article on aphasia; Real Encyclopaedia, IIIrd edn., chapter 'Aphasia'). During the further course of disease the fibre loss was certainly not restricted to the brain areas mentioned above. The final intellectual decay indicates that innumerable pathways have been affected and ultimately destroyed in the white matter of both hemispheres. Only a more thorough histological examination will reveal details about the involvement of intracortical fibres. As the postmortem has shown, the spinal cord was also involved in the degenerative process.
I am concentrating here on this individual example. I hope to publish a more extensive work on this subject which will be based on observations in eight such cases. They show differences in several particulars. The general features typical of this disorder are the following: the disease begins at the onset of senility (early in the fifties) or in advanced old age (early in the sixties); there is slow impairment of intellectual capabilities manifested primarily by the progressive impairment and ultimate loss of the association between cortical sensory and motor areas; most frequently observed are aphasic disturbances (as in the present ease), hemiamblyopia or hemianopia, and hemiparesis with loss of the sense of pressure, position or touch. These circumscribed deficits are of a stable character during the fully developed disease and they are combined with the slow and relentless progression of intellectual deterioration. The mental operations are later confined to a very limited area. Superior mental interests are lost and ultimately the most severe dementia develops in which the patients lack any spontaneous will and lie dull and staring in their beds or, once they are washed and dressed, run around in their rooms without aim or purpose. They resemble the decerebrate laboratory animals of Goltz - if this comparison may be permitted.
Severe apoplectic attacks occur in the course of disease, which present as dizziness or fainting in their milder forms or-in their more severe forms as shorter or longer lasting unconsciousness, hemiparesis with signs of cortico-motor excitation (clonic jerking) in the paretic muscles, fully developed aphasic phenomena (motor or sensory aphasia, dyslexia, cortical blindness [Seelenblindheit, literally 'blindness of the mind']. agraphia), etc. Fully developed epileptic seizures can even occur during the disease. Moreover, protracted states of psychic excitement, lasting from weeks to months, may develop, during which the patients display an increased motor agitation (restless running around, loud shouting), sleeplessness, angry irritability, complete incoherence and disorientation with accelerated imagination and massive sensory deception. The course of the disease is extremely protracted in the majority of cases (10 or more years). Often the disease comes to a standstill lasting for years. Because of the localized and stable deficits, this state may then by misdiagnosed as a focal disease (softening, bleed, embolism) of certain cortical areas with consequent dementia. Death occurs from an apoplectic attack, from eventually intercurrent diseases, or from decubitus, from marasmus with cardiac paralysis in the terminal stage of the dementia.
These cases can be distinguished from general paralysis first by the stability of their deficits, secondly by the peculiar development of the cognitive defect (decrease of partial memories, disturbed and disrupted cortico-motor and cortico-sensory association), thirdly by a peculiar course (average duration of illness longer than in typical paralysis) and fourthly by the autopsy findings.
The clinical differentiation from arteriosclerotic brain degeneration is based on the following characteristics: the focal symptoms (in arteriosclerotic brain degeneration; translator's note) are transitory and indicate a diffuse brain disorder from the early stages of disease. The disease process (in subcortical encephalitis; translator's note) displays circumscribed deficits limited to certain hemispheric areas; therefore the isolated deficits which were described above are predominant from the on set of illness. Because of the close relationship of the pathoanatomical process, intermediate forms of illness are undoubtedly present. In those forms the stable deficits limited to certain sensory and motor functions are less clearly pronounced and are masked by the global cognitive impairment which is caused by a general fibre loss of association pathways.

(translated by H. Förstl, R. Howard, and R. Levy;
a commented version was published in the International Journal of Geriatric Psychiatry, 1991:)

In 1894 Qtto Binswanger described a disease of the hemispheric white matter which he called 'encephalitis subcorticalis chronica progressiva'. He examined eight patients who had shown a slow but relentless cognitive decay that began in middle or old age and lead to severe dementia, characterized in the early stages by a disturbance of association of cortical sensory and motor areas, by aphasia, hemiamblyopia, hemianopia, hemiparesis and a loss of the sense of pressure, position and touch. At postmortem the patients showed white matter atrophy most pronounced in the temporal and occipital lobes. Binswanger proposed that this subcortical fibre loss was due to cerebral arteriosclerosis, which was almost invariably demonstrated. 'Binswanger's disease' has gained topical importance following the introduction of sensitive imaging techniques which have led to the frequent detection of white matter disease during life. This full account of his original observations may contribute to the clarification of contemporary terminological issues.
Otto Binswanger began his work on the histopathology of general paralysis of the insane while working in Breslau. From 1882 to 1919 he held the chair of neuropsychiatry in Jena. He published his influential monograph on 'The Pathological Histology of the Cortical Disease in General Paralysis of the Insane' in 1983 (Binswanger, 1893). Binswanger thought that the clinical and pathological investigation of this disorder was the most urgent task in psychiatry. Work in this field had indeed led to remarkable discoveries during the following years. One of them was the description of' encephalitis subcorticalis chronica progressiva', which he presented at the yearly congress of the Society of German Alienists in Dresden in 1894 (where Alois Alzheimer read his paper on 'arteriosclerotic brain atrophy', which addressed closely related issues; Alzheimer, 1895). Binswanger's paper concerning the 'Differentiation of General Paralysis' was published in three parts at the end of the same year in the Berlin Weekly Clinical Journal (Binswanger, 1894). The consideration of 'subcortical encephalitis' as an important option in the differential diag- nosis of 'general paralysis' was extensively covered in parts II and III of the article. Binswanger announced that he planned to describe the histopathologic details of the eases which he had collected by 1894, but he never published such a paper. It is possible that he lost confidence in the significance of his observations. This might be suggested by several inconclusive details which become apparent in his paper. Alois Alzheimer (1902) and Franz Nissl (1920) took up Binswanger's initial concept, provided histological details and coined the term 'Binswanger's disease'. Excerpts from Binswanger's, Alzheimer's and Nissl's writings on this topic were published in 1962 (Olszewski, 1962) and rekindled interest in this condition.
CT scanning and later magnetic resonance imaging demonstrated white matter changes in a variety of aetiologically distinct disorders, for example multiple sclerosis, vascular dementia, dementia of the Alzheimer type, depression in old age and even in clinically normal individuals (Babikian and Ropper, 1987; Revesz et al., 1989). The frequent radiological demonstration of such white matter lesions, i.e. 'leuko-araiosis' (Pachinko et al., 1987), their clinical significance and their relationship (if any) to Binswanger's original descriptions of explicitly rare eases have become controversial (Hunt et al., 1989; Roman, 1987).