50450ournal ofNeurology, Neurosurgery, and Psychiatry 1996;60:504-509 Chronic fatigue and minor psychiatric morbidity J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.60.5.504 on 1 May 1996. Downloaded from after viral meningitis: a controlled study Matthew Hotopf, Norman Noah, Simon Wessely Abstract Viral meningitis is usually considered to be a Objective-To test the hypotheses that benign illness. It is most commonly caused patients exposed to viral meningitis would now by enteroviruses, as mumps has be at an increased risk of developing decreased in incidence.' Enteroviral infection chronic fatigue syndrome and would have has been suggested as a cause of fatigue and an excess of neurological symptoms and chronic fatigue syndrome, sometimes called physical impairment. postviral fatigue syndrome or myalgic Methods-Eighty three patients were fol- encephalomyelitis (ME). A range of serological lowed up 6-24 months after viral meningi- and viral markers of infection in patients has tis and a postal questionnaire was used to been examined in case-control studies. Early compare outcome with 76 controls who results suggested a relation between these had had non-enteroviral, non-CNS viral markers of infection and current symptoms.2 7 infections. These studies have been criticised8 for their Results-For the 159 patients and con- use of inappropriate control groups, and selec- trols the prevalence of chronic fatigue tion and ascertainment biases. More recent syndrome was 12-6%, a rate higher than studies, which have overcome these method- previously reported from primary care ological problems, suggest that the relation is attenders, suggesting that moderate to less compelling than previously thought,9 '3 severe viral infections may play a part in although one well conducted study found evi- the aetiology of some fatigue states. Those dence for a relation.'4 with a history of meningitis showed a One problem is the difficulty of defining slight, non-significant increase in preva- exposure given the frequency of enteroviral lence of chronic fatigue syndrome (OR infections in the community. We hypothesised 1-4; 95% CI 0.5-3.6) which disappeared that if enteroviral infection is a true risk factor when logistic regression analysis was used for chronic fatigue syndrome, then this effect to correct for age, sex, and duration of will be strongest in a sample of patients follow up (OR 1-0; 95% CI 0 3-2 8). exposed to enteroviral infection of the CNS. Controls showed marginally higher psy- Patients with viral meningitis represent such a chiatric morbidity measured on the gen- sample: in the United Kingdom enteroviruses eral health questionnaire-12 (adjusted OR are the commonest cause of viral meningitis.'5 http://jnnp.bmj.com/ 0-6; 95% CI 0-3-1.3). Both groups had If enteroviruses cause chronic fatigue syn- similar rates of neurological symptoms drome we would expect patients recovering and physical impairment. The best pre- from viral meningitis to be at increased risk of dictor of chronic fatigue was a prolonged abnormal fatigue. Viral meningitis is also said duration of time off work after the illness to be benign and without neurological seque- (OR 4-93, 95% CI 1-3-18-8). The best pre- lae and this was also examined in this study. dictor of severe chronic fatigue syndrome There are two large studies that followed up diagnosed by Center for Disease Control patients with viral meningitis. Lepow et all6 in on October 2, 2021 by guest. Protected copyright. criteria was past psychiatric illness (OR an uncontrolled study found that two thirds of 7-82, 95% CI 1-8-34.3). Duration of viral patients were at risk of fatigue, headaches, and illness, as defined by days in hospital, did clumsiness three months after the illness, but not predict chronic fatigue syndrome. the impression was of recovery at one year, The of follow was Muller Institute of Psychiatry, Conclusions-(l) prevalence although up incomplete. et Denmark Hill, chronic fatigue syndrome is higher than al'7 traced 238 patients with aseptic meningitis London, UK expected for the range of viral illnesses and followed them up for two to 12 years. M Hotopf examined; (2) enteroviral infection is They could detect no difference between their S Wessely unlikely to be a specific risk factor for its mental health and that of healthy controls. King's College School of Medicine and development; (3) onset of chronic fatigue These two studies did not aim to examine Dentistry, London, UK syndrome after a viral infection is pre- patients specifically for fatigue; nor did they N Noah dicted by psychiatric morbidity and pro- use standardised assessments of symptoms. S Wessely longed convalescence, rather than by the The aims of this study were: (a) to examine Correspondence to: Dr M Hotopf, Department severity of the viral illness itself. whether patients with viral meningitis are at of Psychological Medicine, greater risk of subsequent chronic fatigue syn- Institute of Psychiatry, 103 Denmark Hill, London, SE5 (J Neurol Neurosurg Psychiatry 1 996;60:504-509) drome, psychiatric morbidity, and neurologi- 8AZ, UK. cal complications than a control group of Received 31 January 1995 patients who had non-enteroviral, non-CNS, and in final revised from 1 September 1995 Keywords: chronic fatigue syndrome; viral meningitis; viral illnesses; (b) to attempt to find predictors Accepted 4 September 1995 psychiatric morbidity of fatigue and psychological symptoms. Chronic fatigue and minor psychiatric morbidity after viral meningitis: a controlled study 505 Methods ral infections, and infectious mononucleosis J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.60.5.504 on 1 May 1996. Downloaded from CASE SELECTION (which has been shown to be a risk factor for Cases were identified from four virology labo- fatigue'8) were also excluded. Controls with ratories and from the records of a hospital spe- any evidence of "meningism" (nuchal rigidity cialising in infectious diseases. These and photophobia) or a history of lumbar punc- represented a mix of urban and rural popula- ture during the acute illness were excluded. tions. In the virology laboratories records of samples of CSF in the routine day books over CASE NOTE INFORMATION the previous two years (July 1 99 1-June 1993) For all subjects, case notes or hospital dis- were used to identify patients, whose hospital charge summaries were examined to gather case notes were then obtained and examined. baseline sociodemographic information and For cases at the infectious diseases hospital the details regarding current and past physical and disease cards (which document by disease psychiatric illness. Information on the nature each admission to the hospital) were used to of the illness leading to admission to hospital identify cases of viral meningitis and the rele- was also collected on a checklist of symptoms vant case notes were then checked. and signs. Investigations performed in hospital In all cases the following inclusion criteria were recorded as well as any information on were met: age 16-65; a clinical diagnosis of the clinical state of the patient at discharge. acute onset meningitis (characterised by pyrexia, headache, photophobia, and neck POSTAL SURVEY stiffness) leading to admission to hospital; A questionnaire was designed to elicit sociode- spontaneous resolution of symptoms; evidence mographic details and information regarding of lymphocytic meningitis as defined by lym- medical and psychiatric history and service phocytes in the CSF (> 8 per cm3). Cases use. Current psychiatric health was measured were excluded if there was any evidence of a using the general health questionnaire- 12 bacterial or other non-viral cause of the (GHQ-12)19 and the Beck depression inven- meningitis from microscopy and culture of the tory.20 Fatigue was measured on a validated CSF. Further exclusion criteria included seri- questionnaire used in several studies of ous medical illnesses, which would be a poten- chronic fatigue and chronic fatigue syn- tial cause of fatigue, and patients with a history drome.21 Somatic symptoms were identified of psychosis, substance misuse, or eating dis- on a checklist of 32 symptoms. Finally, func- order. Other psychiatric disorders were not tional impairment and quality of life were excluded. Cases with illness that had appeared assessed on the medical outcome survey short in the context of recent travel outside Europe form (SF-36) scored according to predeter- and North America were also excluded. mined thresholds.22 Table 1 gives the defini- Finally, cases were excluded if there was a tions of the different fatigue syndromes. clinical suspicion or definite confirmation of Chronic fatigue syndrome is defined according HIV infection. to the Green College criteria23 or to the Center for Disease Control (CDC) criteria (chronic CONTROL SELECTION fatigue syndrome +).24 Controls were identified from one virology laboratory and the infectious diseases hospital. http://jnnp.bmj.com/ Those identified from the laboratory were Results proved cases of self limiting viral infections Of 255 eligible patients, 159 (62%) which the laboratory had identified from sam- responded. Of the remainder, 49 had changed ples other than chronic fatigue syndrome. address and could not be traced. If these were From this information hospital casenotes or removed from the sample the response rate general practice records were examined. was 77%. The remaining non-responders Controls were identified from the infectious either failed to return a questionnaire despite diseases hospital using the disease cards and reminders or retumed the questionnaire on October 2, 2021 by guest. Protected copyright. casenotes. Inclusion criteria were of self limit- uncompleted. There were no differences ing viral illness which had led to admission to between responders and non-responders in hospital or consultation with a general practi- terms of age and sex. A similar proportion of tioner in the past two years in patients aged persons in each group responded.