Meningitis

Cellular and Molecular Basis

Myron Christodoulides, Myron Christodoulides

• Publisher: CAB International
• Year: 2013
• ISBN:
  9781789244205
• Topic: Medizin
• Subtopic: Medizinische Mikrobiologie & Parasitologie

Examining meningitis mainly from a bacterial perspective, but also including an overview of viral, fungal and chronic meningitis, this book describes the anatomy of the meninges and clinical signs and symptoms of this disease. Individual organisms that cause meningitis worldwide are dealt with in specific chapters, describing in detail how these pathogens interact with the human host at both a molecular and cellular level. The book provides a thorough understanding of bacterial virulence factors, adhesion and invasion mechanisms, the nature of known host cell receptors and the host cell response.

1 A History of Bacterial Meningitis from Antiquity to Modern Times

Myron Christodoulides*
University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK

1.1 Introduction

The history of central nervous system (CNS) infections is as old as humankind itself, and tantalizing evidence of CNS infections can be found in collections of anthropological specimens and archaeological artefacts dating back to the Neolithic Revolution (10,000–3000BC). The first known description of the word ‘brain’ is to be found in the Edwin Smith Papyrus, an Egyptian medical and surgical text, dating from c.1500BC. The papyrus was bought by the Egyptologist Edwin Smith in 1862 and eventually translated by James H. Breasted in 1930 (Breasted, 1930). The papyrus contains 27 cases of head injury, six cases of throat and neck injury and one case of spinal injury: significantly for neuroanatomists, it also contains the earliest descriptions of cranial sutures, the meninges, cerebrospinal fluid and the external surface of the brain (Wilkins, 1964).

1.2 From Hippocrates to the Renaissance

There were primitive discussions about the nervous system in pre-Hippocratic Greece by ‘philosopher-physicians’, but this medical literature only survives in fragments or in the quotations and testaments of later scribes (Rose, 1994). It is Hippocrates (c.460–370BC) that scholars of history and medicine turn to for the first recorded descriptions of CNS afflictions. The Corpus Hippocraticum contains the surviving medical treatises attributed to Hippocrates, to his students and to his followers since antiquity. Between 1839 and 1861, the French physician and philologist Maximilien Paul Emile Littré (1801–1881) provided a Greek edition and a French translation interpreted with authority (Litré, 1839). Contemporaneously and with a heavy debt to Littre, the English physician Francis Adams (1796–1861) was commissioned by the Sydenham Society to translate ‘the genuine works of Hippocrates’, which was invaluable in reinforcing the Hippocratic tradition in England and America (Adams, 1849).¹

Within the Corpus Hippocraticum (Section VII) are the Seven Books of Epidemics, which consist mainly of histories and cases of diseases, many ending with fatality. Although his descriptions cannot be taken as conclusive proof of meningism, particular cases are compelling. Fever is a constant, and nuchal rigidity is suggested. In The First Book of Epidemics, Section II, Year 2, Hippocrates describes:

Pains and heavinesses about the head and neck, with or without a fever, in phrenitic cases denote convulsions; and æruginous vomitings succeed. Some of these die presently. But in burning fevers and others, a pain of the neck, a heaviness of the temples, a dimness of the sight … Children are generally attacked thus, and mostly affected with convulsions in these cases.

In The Third Book of Epidemics:

He that had a phrensy and was laid up the fifth day … and had a weight and pain in the head and neck … was very feverish … and at night was convulsed. The third (day), was worse in all respects. The fourth, died.

The son of Cydis exhibited a suppurative ear discharge with ‘fever, headache, vomiting, mental confusion, intense neck rigidity …’, which has been suggested to describe meningitis secondary to otitis (Nutton, 1986).

Although Hippocrates was aware of the membranes surrounding the brain – as was the Greek polymath Aristotle (384–322BC) in his anatomical studies of animals (The History of Animals) – it was Herophilus of Calcedon (330–260BC; the ‘Father of Anatomy’) and his pupil Erasistratus of the School of Alexandria who named precisely the dura mater and pia mater of the meninges (von Staden, 1989; Rose, 1994). Hippocrates was also aware of the importance of not damaging the meninges during the treatment of head injuries. In ‘On Wounds of the Head’ in the Corpus Hippocraticum, Hippocrates describes the necessary cleansing steps to prevent infection and inflammation of head wounds, and he was equally clear on the method of trepanning.

Medical teaching in Europe ceased after the fall of the Roman Empire, but the Hippocratic tradition extended by Claudius Galen (129–217AD) and others was collected, preserved and added to by Arab scholars. Galen gave an accurate description of the dura and pia mater and is credited with using the term ‘meninx’ to specifically mean the coverings of the brain, rather than the membranes that generally covered all organs. The most famous Arab physician, Abu Ali al-Husayn ibn Abd Allah ibn Sina (Latin: Avicenna 980–1037AD), described meningitis in his Kitab al-Qanun fial-tibb (The Canon of Medicine) as an ‘inflammation or tumour of the envelopes of the brain’. The Canon was compulsory reading through the Renaissance to the 17th century. It is also worth noting the publication De Contagione et Contagiosis Morbis et Eorum Curatione (1546) by the Italian physician and poet Girolamo Fracastoro (1478–1553), which contains remarkable insight into the transmission of infectious disease and presents the first evidence of a ‘germ theory’. In his lifetime, Fracastoro’s fame would not relate to meningitis directly but to his poem of 1530, Syphilis sive morbus Gallicus (‘Syphilis or The French Disease’). In the Libri Tres of the poem, Fracastoro’s eponymous hero is the shepherd boy Syphilus, who unfortunately is made to suffer with the disease that bears his name.²

1.3 Phresny and Dropsy

The Corpus Hippocraticum frequently referred to patients who suffered phrensy or who were phrenitic, from which we derive our modern word ‘frenzy’. In Greco-Roman times, these terms were given to patients with ‘acute inflammation of the mind and body’, i.e. exhibiting fever and chill, nuchal rigidity and headache, and voiding scanty urine. In particular, continuous delirium attended phrensy prior to death. The English physician Thomas Willis (1621–1675), in his London Practice of Physick (posthumously published in 1685), in a section titled ‘Of the phrensy’, offered ‘meningitis’ as the modern diagnosis of phrensy/phrenitis. Moreover, Willis clearly described the pathology of compression of the brain as a consequence of meningeal inflammation and also mentions an epidemic of meningitis in the chapter ‘An account of an epidemic fever, reigning An.1661, which chiefly infested the brain and the genus nervosum’ (Willis, 1685). In his magnus opus, De Sedibus et Causis Morborum per Anatomen Indagatis (1761),³ the Italian anatomist Giovanni Battista Morgagni (1682–1771) presented and analysed 640 autopsies. In one autopsy, he recognized how the infectious process in otitis media and mastoiditis advanced to the meninges and produced meningitis (Klotz, 1932).

In ‘On Diseases’ (Section V, Book II, De Morbis), Hippocrates writes of ‘water upon the brain’ (and suggests, as a last resort, an opening of the cranium in order to discharge the fluid), which we recognize today as hydrocephalus or dropsy that can be acute or chronic. In 1768, the Scottish physician Robert Whytt (1714–1766) published a seminal book Observations on the Dropsy in the Brain⁴ in which he related the history of dropsy and described cases that appeared to result from tuberculous (chronic) meningitis. Whytt‘s Scottish physician colleagues and contemporaries (the ‘Edinburgh School’), David MacBride (1726–1778), John Cheyne (1777–1836), John Fothergill (1712–1780), William Cullen (1710–1790) and John Abercrombie (1781–1844) (Tyler, 2010), all made contributions to the study of hydrocephalus.

1.4 The Swiss and the French

Major contributions towards understanding meningitis were made by the Swiss-Geneva physicians Jean-Francois Coindet (1774–1834), Louis Odier (1748–1814), Gaspard Vieusseux (1746–1814), Jacques-Andre Matthey (1778–1842), Francois-Louis Senn (1799–1873) and Frederic Rillet (1814–1861) (Mullener, 1965), and by the French clinicians Francois Herpin (dates unknown), Louis Guersent (1777–1848) and Antoine Bayle (1799–1858). In his thesis, the French army surgeon Herpin (1803) described cases of CNS infection complicating head injuries in soldiers, particularly noting the presence of pus (suppuration) in the meninges at autopsy. Herpin termed the infection ‘meningitis’ to describe this ‘inflammation of the membranes of the brain’ and distinguished this from ‘phrenitis’ due to the absence of delirium in many of the patients. Back in Edinburgh, the neuropathologist Abercrombie (1828) recognized that meningeal inflammation was the primary pathology in meningitis and was centred specifically on the arachnoid and pia mater and did not involve the dura mater.

1.5 Pathological Subtypes of Meningitis

Abercrombie, in 1828, also recognized that several pathological subtypes of meningitis could present, with inflammation involving the base of the brain (basilar), the surface of the brain (classical) and extending into the ventricles (ventriculitis). In 1839, Louis Guersent proposed a classification of meningitis into (i) tuberculous and (ii) simple, non-tuberculous, which encompassed acute meningitis, chronic meningitis, meningitis following trauma, epidemic meningitis and general paresis of the insane (also known as syphilitic meningitis) (Guersent, 1839). In 1822, the French physican Antoine Laurent Bayle (1799–1858) was the first to comprehensively describe general paresis or ‘maladie de Bayle’ (Mullener, 1965).

In 1779, Odier described an ‘epidemic of meningitis’ that occurred in Geneva, with 16 cases and 12 deaths, commenting that this disease occurred every year with this frequency (Odier, 1779). In 1789, Odier described post-mortem results on a boy and a girl, on whom dissection showed hydro-cephalus and ‘green and yellow pus between the meninges’ (‘hydrocephale combine avec l’inflammation des meninges’). But Vieusseux is generally credited with the first detailed description of epidemic meningitis, oc...