Wilhelm Uhthoff--a phenomenon 1853-1927.
Abstract: The name of Wilhelm Uhthoff is associated with several aspects of progress in neurology in the 19th and 20th Century but is best known for his contribution to the pathophysiology of transient visual disturbance. Uhthoff was born on 31 July 1853 in Klein Warin, Germany and died on 21 March 1927 in Breslau, Germany. This ophthalmologist described for the first time that increased body temperature from physical exertion may lead to transient impairment of vision in patients with multiple sclerosis.

KEY WORDS: UHTHOFF, MULTIPLE SCLEROSIS, UHTHOFF PHENOMENON, OPTIC NEURITIS
Article Type: Report
Subject: Stress (Psychology)
Presidents (Organizations)
Ophthalmology
College teachers
Multiple sclerosis
Authors: Stutzer, P.
Kesselring, J.
Pub Date: 11/01/2008
Publication: Name: The International MS Journal Publisher: PAREXEL MMS Europe Ltd. Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2008 PAREXEL MMS Europe Ltd. ISSN: 1352-8963
Issue: Date: Nov, 2008 Source Volume: 15 Source Issue: 3
Accession Number: 221274689
Full Text: Biography

Wilhelm Uhthoff was born on 31 July 1853 in Klein Warin, Grand Duchy of Mecklenburg-Schwerin (now Mecklenburg-Vorpommern). He grew up in the countryside with six brothers and two sisters and attended senior school in Wismar, Mecklenburg. He studied medicine from 1873 at the universities of Tubingen, Gottingen, Rostock and Berlin. As his father had nine children and therefore great financial difficulties, Wilhelm had to borrow money for his exams. As an assistant physician he regularly sent money home at the expense of his personal requirements. His promotion to Doctor Medicinae took place in 1877 in Berlin and he decided to specialize in ophthalmology. Early in 1878 he took his final exams and went to Berlin as an assistant physician to Professor Heinrich Leopold Schoeller at the former clinic of Albrecht von Graefe. During the 10 years of his work there he was habilitated as Privatdozent for the specialty of ophthalmology in 1885. (1) In 1890, at the age of 37 years, Wilhelm Uhthoff was appointed Ordinary Professor to the Chair of Ophthalmology in Marburg as successor of Hermann Schmidt-Rimpler (1838-1915). Six years later he went to Breslau as successor to Professor Carl Friedrich Richard Forster (1825-1902) and took over the direction of the University Eye Clinic, (2) where he later was also rector of the Silesian Friedrich Wilhelm University. Even when he did not feel well, and even with a high fever he gave his lectures, proving his conscientiousness and sense of duty, as well as his passion for teaching! A great number of experienced ophthalmologists, including some of the most prominent at universities, enjoyed his tutelage. The German Ophthalmologic Society elected him following the death of Theodore Leber, its first president, and the university of Breslau elected him as rector for the year 1908/09. (1) In spite of several calls for appointments to the universities of Vienna, Bonn and Berlin he remained loyal to Breslau and remained active there until his retirement in 1923. After his retirement he worked on his collection of private material which gave rise to his last papers. (1) Wilhelm Uhthoff died of a heart attack as a consequence of influenza on 21 March 1927 in Breslau. His sudden death cut short his intense practical and scientific endeavours.

A few days after his death his paper: "On hemianopia and flickering scotoma" (uber Hemianopsie und Flimmerskotom) appeared in the Klinische Monatsblatter. Among his possessions a second finished paper was found as a manuscript: "On squint amblyopia" (zur Schiel-Amblyopie).

Uhthoff's Publications

* 1890: Contribution to the pathology of optic nerves and retina in general diseases

* MS patient with reversible amblyopia during physical exercises

* 1 894: On ocular disturbances occurring in syphilis of the central nervous system

* On recent progress in bacteriology related to conjunctivitis and carotids of humans

* 1907: On the treatment of retinal detachment

* 1908: On blind people

* 1908: On vision and disturbances of vision and their relationship to the brain

* 1911: Ocular disturbances in intoxications

* 1915: On the ocular symptoms in diseases of the nervous system

* 1915: Stereoscopic ophthalmologic atlas

* 1915: Ocular symptoms in brain tumours (Foster-Kennedy syndrome)

His Influence on Neurology

The scientific work of Uhthoff covers almost all fields of ophthalmology. His special interest was neuro-ophthalmology dating to his time as a consultant at the clinic for nervous diseases at the Charite in Berlin under Westphal. There he worked alongside his assistants Moehli, Oppenheim, Wallenberg, Thompson and Siemerling, which led to successful collaborations over many years. Wilhelm Uhthoff was interested in the relationship of ocular symptoms with other diseases. He concentrated in particular on nervous system intoxications. In 1819 in the Archives of Psychiatry and Nervous Diseases he described for the first time, in four of 100 patients with multiple sclerosis (MS), the phenomenon which later was named after him: "Marked deterioration of visual acuity during physical exercise and exhausting". (3) Furthermore, he investigated in depth the diagnostic and aetiologic importance of various papillary disturbances, optic nerve atrophies and papilleoedema. In Marburg he wrote the paper: "On ocular disturbances occurring during syphilis of the central nervous system"; in 1887 the classic work "On damage of the optic nerve due to alcohol abuse"; 1890, the "Investigations on ocular disturbances occurring during multiple focal sclerosis". (3) During his time in Breslau he wrote the following chapters for the Handbook of Ophthalmology, edited by Von Graefe-Saemisch: "Ocular disturbances in diseases of the nervous system" and "Ocular disturbances in intoxications". Uhthoff himself described the result of this period as his "life work". Further focal points of his scientific work were problems of optics as well as of physiology and psychology of facial perception, but also on ophthalmologic microsurgery (glaucoma).

[FIGURE 1 OMITTED]

Siemerling described as astonishing the assiduousness with which Uhthoff continued his clinical and pathologic-anatomical investigations as well as his extended medical work at the Clinic of Schoeller and his intensive teaching duties. The success of these works by Uhthoff were founded on sound pathologic-anatomical investigations which contributed greatly to the understanding of retinal, choroidal and corneal diseases. With his eldest student, Axenfeld, Uhthoff was also involved in bacteriology. Siemerling recalls the pleasure Uhthoff took in the examination of the longitudinal section across the optic nerves in multiple sclerosis (Figure 2).

In 1961 G Ricklefs created the eponym of Uhthoff for the transient deterioration of symptoms or the new appearance of symptoms with increasing body temperature in patients with demyelinating diseases. (4) For a long time it was not clear whether the nervous conduction velocity in demyelinated fibres is influenced directly by heat (5) (Figure 3) or whether it is due to indirect phenomena, e.g. temperature-dependent production of nitrite oxide.

Smith et al described the main mechanism of temperature depended conduction block in the central nervous system, whereby the "blocking temperature" depends on the degree of demyelination. (6) This leads to a change of properties of ion channels. Until 1983 "the hot bath test", first reported by Tom Guthrie, was accepted as a clinical test and used for diagnosing MS, (7) later replaced by more specific investigations. (8)

[FIGURE 2 OMITTED]

[FIGURE 3 OMITTED]

The Uhthoff phenomenon and the characteristic deterioration of multiple sclerosis symptoms by increased body temperature due to physical exercise may also be observed with triggering factors such as fever, hot meals, weather, menstruation, but also smoking and psychological stress. (9)

Based on the Uhthoff phenomenon, therapeutic trials with cooling vests are investigated and developed. (10)

Apart from Wilhelm Uhthoff's achievements as a physician and internationally appreciated scientist, it is worth emphasizing that he created the requirements in his clinic with great personal commitment so that each assistant could work scientifically in the clinic as well as in the laboratory. Uhthoff was an excellent diagnostician and surgeon but also warm-hearted philanthropist who never forgot that the "interesting case" was also a suffering person anxious to keep their eyesight. Uhthoff wanted to alleviate the lot of blind people and introduce prevention of war blindness and he was one of the foremost and successful pioneers for prevention of war blindness.

"A life rich on arduousness and successes finished. Uhthoff was not spared sorrow and grief but a benevolent fate preserved his workforce until a high age and granted him the pleasure and pride of the successes in scientific and medical endeavours until the end". (11)

Key Points

* Wilhelm Uhthoff (1853-1927) was a famous German professor of ophthalmology at the Universities of Marburg and later in Breslau

* In 1890 he described temporary vision loss associated with optic neuritis linked to physical exercise

* This condition is known as Uhthoff's phenomenon and was later found to be caused by a rise in body temperature

Received: 23 May 2008

Accepted: 1 July 2008

References

(1.) Siemerling E. Wilhelm Uhthoff. Eur Arch Psychiatry Clin Neurosci 1927; 1: 293-296.

(2.) Ruprecht KW, Weik R. Wilhelm Uhthoff und das Uhthoffsche Zeichen. Jubilaumsband:10 Jahre Julius-Hirschberg-Gesellschaft; Halle 1 996: 1 8-27.

(3.) Uhthoff W. Untersuchungen uber die bei der Multiplen Herdsklerose vorkommenden Augenstorungen. Archiv Psychiatrie und Nervenkrankheiten 1890; 21: 303-410.

(4.) Ricklefs G. On Uhthoff's symptom in multiple sclerosis. Klin Monatsblatter Augenheil Augenarztl Fortbild 1961; 139: 385-390.

(5.) Schauf CL, Davis FA. Impulse conduction in multiple sclerosis: a theoretical basis for modification by temperature and pharmacological agents. J Neurol Neurosurg Psychiatry 1974; 37: 152-161.

(6.) Smith KJ, McDonald WI. The pathophysiology of multiple sclerosis: the mechanisms underlying the production of symptoms and the natural history of the disease. Phil Trans R Soc Lond B Biol Sci 1999; 354: 1649-1673.

(7.) Poser C M, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983; 13: 227-231.

(8.) Humm AM, Beer S, Kool J, Magistris MR, Kesselring J, Rosler KM. Quantification of Uhthoff's phenomenon in multiple sclerosis: a magnetic stimulation study. Clin Neurophysiol 2004; 11 5: 2493-2501.

(9.) Lepore FE. Uhthoff's symptom in disorders of the anterior visual pathways. Neurology 1994; 44: 1036-1038.

(10.) Meyer-Heim AD, Rothmaier M, Weder M, Kool J, Kesselring J. Advanced lightweight cooling garment technology: functional improvement in thermosensitive patients with Multiple Sclerosis. Mult Scler 2006; 12: 1-6.

(11.) Bielschowsky A. Wilhelm Uhthoff. J Mol Med 1 927; 6: 879.

P Stutzer, J Kesselring

Department of Neurology and Neurorehabilitation, Rehabilitation Centre, Val ens, Switzerland

Address for correspondence:

Jurg Kesselring

Department of Neurology and Neurorehabilitation

Rehabilitation Centre, CH 7317 Valens

Switzerland

Phone: +41 (0)81 303 14 08

Fax: +41 (0)81 303 14 10

Email: kesselring.klival@spin.ch
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