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From pseudotumour cerebri to idiopathic intracranial hypertension
  1. J M S Pearce
  1. Correspondence to J M S Pearce, Emeritus Consultant Neurologist, Department of Neurology, Hull Royal Infirmary, Anlaby Road, Hull HU3 2JZ, UK; jmspearce{at}freenet.co.uk

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The terms “pseudotumour cerebri”1 and “benign intracranial hypertension”,2 respectively introduced by Nonne in 1904 and Foley in 1955, were originally applied to patients with raised intracranial pressure in whom no tumour was found and whose course was benign (table 1). But the natural history proved to be not always benign. Buchheit et al,3 finding progressive visual loss in several patients, challenged the terms “benign” and “pseudotumour” in 1969: “The syndrome is neither a benign process nor a false tumour.” The terminology was then changed to “idiopathic intracranial hypertension”.3, 4

Table 1

Table 1 Early diagnostic terminology

In an excellent monograph, Johnston and colleagues5 drew attention to some of the earliest possible examples of the syndrome which had been recorded in a long section on diseases of the optic nerve in the Transactions of the Ophthalmological Society UK 1880–1881. This was before the introduction of lumbar puncture (see below) so it was impossible to measure intracranial pressure. Papilloedema was then usually referred to as optic neuritis. For example, Hughlings Jackson mentioned reports by ophthalmologists of “…a recoverable optic neuritis in young women suffering from uterine derangement”.6 Gowers too in 1881 described optic neuritis associated with “chlorosis”, most often caused by nutritional iron deficiency anaemia7 but his account is not typical of idiopathic intracranial hypertension. Broadbent reported in the same issue of the BMJ, a 12-year-old girl with a 2 year history of headache and vomiting with “double optic neuritis” associated with amenorrhoea whose symptoms resolved and menstrual regularity was restored although she remained blind from the sequelae of the papilloedema.

In 1900, Williamson and Roberts described8 100 cases of “double optic neuritis” which is “the first good description of pseudotumour within the prevailing diagnostic limitations”.2 In their groups IX and X were 21 cases, including 13 females of average age 16.8 years. In this era, the essential features were optic neuritis, obesity and menstrual irregularities. In fact many reports9 probably included instances of intracranial hypertension caused by various meningitides or intracranial venous sinus thrombosis due to otitis media.

Nonne reported 18 patients, stressing not a disease entity, but a syndrome easily mistaken for a brain tumour, hence his designation “pseudotumour cerebri”. The papers of Nonne and Quincke were important; however, there were several causes of the clinical syndrome and not all were necessarily what we would now call “idiopathic”.

Max Nonne (1861–1959)

Nonne10 (fig 1) was a neurologist in Hamburg, a pupil of Erb. He introduced the term “pseudotumour cerebri” in 1904 when he reported on 18 patients although they did not conform to the modern definition of idiopathic intracranial hypertension.

Figure 1

Max Nonne (1861–1959).

For example, the first was a 25-year-old man who was concussed during a fight. Soon afterwards he developed severe headache and third, fourth and sixth cranial nerve palsies, bilateral papilloedema and a CSF pressure of 60 cm H2O. After six lumbar punctures, each draining 15–20 ml of fluid, he recovered from probable traumatic intracranial venous sinus thrombosis. The second, a 27-year-old woman, had a 2 year history of suppurative otitis media followed by 2 weeks of headache, dizziness, vomiting and diplopia. She had bilateral papilloedema and a left sixth nerve palsy. A cerebral abscess was suspected but operative exploration showed left lateral sinus thrombosis. Remarkably, she subsequently recovered. Nonne rightly concluded that she had hydrocephalus secondary to sinus thrombosis caused by otitis—in keeping with Sir Charles Symond’s later otitic hydrocephalus.11

Nonne wrote authoritatively on Syphilis and the Nervous System (3rd edition 1915) and described the Nonne–Apelt reaction for CSF globulins and Nonne–Milroy–Meige disease, familial lymphoedema. He was one of the four physicians who attended Vladimir Ilich Lenin (1870–1924) in his final illness.

Heinrich Irenaeus Quincke (1842–1922)

Quincke (fig 2) was the son of a Berlin physician. He was born in Frankfurt-an-ser-Oder, read medicine at Berlin, Würzburg and Heidelberg, and became a doctor in 1863. His influential teachers were Frerichs, Virchow and von Kölliker. Quincke held chairs in Berne and then in Kiel. Much of his work was on lung disease but he also observed the angio-oedema of anaphylaxis—Quincke’s oedema. He described the pulsation of nail bed capillaries in aortic regurgitation (Quincke’s sign). Studying the CSF in dogs and rabbits in 1872, he injected the red sulphide of mercury (cinnabar) into the subarachnoid space to demonstrate flüssigkeit or CSF flow.

Figure 2

Heinrich Irenaeus Quincke (1842–1922).

Despite earlier instances of non-tumourous intracranial hypertension, the first report of idiopathic intracranial hypertension is usually ascribed to Quincke, who described it in 1893 under the name “meningitis serosa”.12 Two years previously, Quincke and Wynter had independently described lumbar puncture and so were able for the first time to measure intracranial pressure.13 Quincke himself had reported the technique of lumbar puncture to the 10th Congress of Internal Medicine at Wiesbaden in April 189114 and in 1902 published a monograph, Die Technik der Lumbalpunktion. He reported 10 cases (seven women and three men) but only two women conformed to current criteria for idiopathic intracranial hypertension. Both suffered headache, papilloedema and raised CSF pressure, with normal composition. Impaired visual acuity was evident in one. Quincke postulated an increase in CSF secretion mediated by the autonomic nervous system. He listed possible causes as head injury, stress, excessive alcohol, pregnancy, influenza and otitis media which shows that, in keeping with modern concepts, he intended to describe a syndrome, not a disease entity.

Evolving clinical concepts

Idiopathic intracranial hypertension has an annual incidence of about 1–2 per 100 000, mostly women. The aetiology is obscure. Right from the earliest accounts, obesity, menstrual irregularities and endocrine disorders were described as common associations. To make the diagnosis requires CSF pressure and content measurements, visual field charts and brain imaging.15 16 By definition, it excludes patients with space occupying lesions and those with dilated ventricles. It has been associated with many aetiologies such as hypervitaminosis A, arteriovenous malformations, systemic lupus erythematosus as well as oral contraceptives and steroid withdrawal. Symptoms are dangerously non-specific but classically consist of postural, early morning raised pressure headaches in 94%, variably accompanied by vomiting.17 More serious are characteristic obscurations of vision on changing posture in 68%, which signify critical papilloedema with enlarged blind spots. Pulsatile tinnitus (58%), diplopia (38%) and visual loss (30%) are also common.18 Both CSF pressure and the symptoms tend to fluctuate, with spontaneous remissions—sometimes permanently.

Walter Dandy first proposed diagnostic criteria in 1937.19 Smith modified them in 198520 and Friedman and Jacobson in 200221 (table 2).

Table 2

Table 2 Dandy’s criteria (modified20 21) for intracranial pressure without brain tumour

In the past 40 years CT and MRI have shown normal or small lateral ventricles, suggesting brain swelling. Cerebrospinal fluid pressure at lumbar puncture is raised, but CSF protein, glucose and cells are all normal. MRI and MR venography should exclude intracranial venous sinus thrombosis before making the diagnosis of idiopathic intracranial hypertension.

Mechanisms

Two mechanisms have been postulated: increased production of CSF or reduced reabsorption. Increased production might be caused by vasogenic extracellular brain oedema.22 However, when brain water diffusion and proton longitudinal relaxation time were measured,23 no significant abnormality was found. This suggests that diffuse brain oedema is not a necessary feature. Alternatively, reduced reabsorption due to low conductance of CSF outflow at the arachnoid villi or intracranial venous hypertension24 has been postulated. Venous sinus stenting was therefore used in 12 patients; five became asymptomatic, two were improved and five were unchanged.16 Although venous dysfunction is probable, its exact cause remains obscure.

Weight reduction, corticosteroids, acetazolamide and repeated lumbar punctures have been traditionally used and there is anecdotal but variable evidence of intracranial pressure control. But these treatments do not always work. Thus if progressing visual loss develops, optic nerve fenestration or CSF shunting is needed.5

REFERENCES

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Footnotes

  • Competing interests None.

  • Provenance and peer review Commissioned; not externally peer reviewed.

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