Mollaret's meningitis

Definition

This is a form of benign, recurrent, aseptic meningitis. It was first described by Pierre Mollaret (1898-1987) in 1944¹.

Diagnostic criteria

G W Bruyn refined the clinical diagnostic criteria in 1962²:

• Recurrent episodes of severe headache, meningismus and fever.

• Cerebrospinal fluid (CSF) pleocytosis with large 'endothelial' cells, neutrophils and lymphocytes.

• Attacks separated by symptom-free periods of weeks to months.

• Spontaneous remission of symptoms and signs.

• No causative aetiological agent identified.

Pathogenesis

In recent years there has been increasing evidence to implicate the herpes simplex virus 2 (HSV-2) in many cases³.

It has been suggested that if the strict criteria above are followed, these cases should be excluded, and the term Mollaret's meningitis reserved for true idiopathic cases. However, this appears not to be rigorously applied.

Epidemiology

It is very rare and the literature is very limited.

Presentation

• There is a rapid onset of symptoms that are typical of meningitis - eg, fever, headache and neck stiffness.

• The symptoms last between one and seven days.

• Symptoms resolve without any residual defect.

• Symptom-free periods may last from weeks to years, but the characteristic feature of this disease is the tendency to recur.

• The clinical picture can be variable:
  

  • Some have been reported without fever, with transient neurological signs and symptoms, and with raised gammaglobulin in the CSF.

  • More severe cases can occur with neurological abnormalities, including seizures, diplopia, abnormal reflexes, cranial nerve palsy, hallucinations and coma.

  • This may occur in as many as half of all patients, but full recovery is usual

Investigations

Head CT or MRI scanning is done before lumbar puncture if a brain mass is suspected - eg, from focal neurological signs or papilloedema.

• The classical feature is the appearance of 'fantomes cellulaires' (cell ghosts) in the CSF⁴:

• After the first 24 hours the cells are predominantly lymphocytes, numbering fewer than 3,000 mm³.

• In about a third of cases the CSF glucose is low.

• Polymerase chain reaction (PCR) of the CSF to determine any underlying viral cause¹.

• Other causes of meningitis should be excluded.

Differential diagnosis

Other acute aseptic meningitis:

• Viral - enteroviruses (poliomyelitis, Coxsackievirus, echovirus), HSV-1 and HSV-2, varicella-zoster virus, adenovirus, Epstein-Barr virus, lymphocytic choriomeningitis virus (LCMV), human immunodeficiency virus (HIV), and influenza A and B viruses.

• Bacterial - partially treated meningitis, parameningeal infection, endocarditis, mycoplasma, tuberculosis, ehrlichiosis, borrelia, syphilis, and brucella.

• Fungi.

• Parasites - toxoplasma and cysticercosis.

• Non-infectious:
  

  • Drugs - non-steroidal anti-inflammatory drugs, co-trimoxazole, amoxicillin, azathioprine, high-dose intravenous immunoglobulin, isoniazid, intrathecal methotrexate and cystine arabinoside, vaccination, allopurinol.

  • Systemic disease - sarcoidosis, leptomeningeal cancer, systemic lupus erythematosus (SLE), granulomatosis with polyangiitis, Behçet's disease, post-transplantation, lymphoproliferative disorder, Vogt-Koyanagi-Harada syndrome.

  • Miscellaneous - arachnoiditis, migraine, postinfectious syndrome.

  • Small, recurrent bleeds of subarachnoid haemorrhage.

• Of the above, causes of recurrent meningitis include Behçet's disease, Vogt-Koyanagi-Harada syndrome, sarcoidosis, SLE, and undiagnosed viral - eg, encephalomyocarditis

Management

• Pain and temperature should be treated in the usual way.

• Intravenous fluid may be required.

• Colchicine and indometacin have been used and clinical observation suggests effectiveness⁵.

• Randomised controlled trials on the the use of antiviral agents are lacking. (This is probably because the disease is so rare that it is impossible to get even a small series.)

• Aciclovir if HSV is shown on PCR testing¹.

Prognosis

• Herpes simplex encephalitis is a rare but very serious condition with a mortality around 70% that usually leaves survivors with neurological deficits.

• This is in contrast to Mollaret's meningitis, which may be recurrent and unpleasant in the acute attack but does not leave residual damage.