Important Information for Physicians
- Herpes simplex virus (HSV) 1 – 2 polymerase chain reaction (PCR) test is not always positive, particularly if done more than 3-4 days after onset of acute illness.
- Duration of recurrent meningeal signs / symptoms can be variable.
- Pain management is an important component of treatment since meningitis can be extremely painful for patients.
What is Mollaret’s meningitis?
“Mollaret meningitis is a rare type of viral meningitis that is characterized by repeated episodes of fever, stiff neck (meningismus), muscle aches, and severe headaches separated by weeks or months of no symptoms. About half of affected individuals may also experience long-term abnormalities of the nervous system that come and go, such as seizures, double vision, abnormal reflexes, some paralysis of a cranial nerve(paresis), hallucinations, or coma. Mollaret meningitis is poorly understood and the exact cause remains unknown. However, recent data suggests that herpes simplex virus (HSV-2 and, less frequently, HSV-1) may cause some, if not most cases. Other causes may include trauma and viral infections other than herpes simplex. There is no specific treatment, so management involves supportive measures such as rest, fluids, and medicine to relieve the fever or headache.” – Genetic and Rare Diseases Information Center
Mollaret’s Meningitis can be diagnosed through lumbar puncture (spinal tap) in order to examine the cerebrospinal fluid (the clear, colorless liquid that fills and surrounds the brain and the spinal cord and provides a mechanical barrier against shock). Diagnosis is made by detecting Herpes simplex virus DNA in the cerebrospinal fluid. Early diagnosis may prevent prolonged hospital admissions, unnecessary investigations, and exposure to unnecessary medications, along with their associated costs. If a patient has had a recent head injury or a problem with their immune system, they may not qualify for a lumbar puncture because of a possible fatal brain herniation; therefore, a CT or MRI scan may be performed prior to any lumbar puncture. All of the different types of meningitis (viral, bacterial, fungal and parasitic) are diagnosed by the growing presence of bacteria in the spinal fluid, a sample of which is collected with the help of a lumbar puncture. The fluid will reveal if the CSF (cerebral spinal fluid) has raised or lowered white blood cell production.
There are no vaccines currently available to prevent the development of viral meningitis. Many people who have a rare disease understandably want to find healthcare professionals or researchers with knowledge of their condition. However, with a condition as rare as Mollaret’s Meningitis, it can be extremely difficult to find medical professionals who have treated more than one or two cases.
Symptoms of a full-blown Mollaret’s infection include severe headaches, fever, nausea, vomiting, sensitivity to light and/or sound, malaise, and neck rigidity. Rarer symptoms include tachycardia, double vision and hallucinations. Because of the similarity in symptoms to benign migraine headache, sufferers of Mollaret’s have often been misdiagnosed by medical personnel. Without proper care, symptoms can escalate to seizures and even coma. Thus, a greater understanding and knowledge of this disease will facilitate better patient care in emergency situations.
Periods of severe illness usually last 3-4 days, separated by weeks or months between recurrences. However, many sufferers experience milder relapses, which although debilitating, do not necessitate hospitalization.
Unfortunately, along with each recurrence, whether mild or severe, comes the risk of further disability. Nearly half of those with the disease experience long-term negative effects of the nervous system. Permanent disabilities that can develop over time include memory loss, difficulty retaining information, lack of concentration, abnormal reflexes, clumsiness, coordination problems, loss of balance, residual headaches, hearing problems, tinnitus, speech problems, dizziness, learning difficulties (ranging from temporary learning deficiencies all the way to long term mental impairment), tachycardia, epilepsy, seizures, paralysis, muscle spasms, cerebral palsy, loss of sight, and changes in sight.
Currently, Acyclovir is the treatment of choice for Mollaret’s meningitis. Acyclovir has proven helpful in many cases, particularly when administered intravenously, where it can cross the blood/brain barrier. It is often the immediate treatment of choice for recurrences that require hospitalization. Some have also seen a reduction in recurrences from daily oral administration of Acyclovir, but it hasn’t been shown to definitively alter the recurrence of the Mollaret’s Meningitis.
Valcyclovir is another medication similar to Acyclovir that has also been found helpful. Other common medications also administered for the subsequent pain during recurrences include NSAIDS (Motrin, Advil), Hydrocodone (Norco, Vicodin Lortab), morphine, and hydromorphone (Dilaudid). Anti-seizure medications such as Gabapentin (Neurontin), Pregabalin (Lyrica), Lamotrigine (Lamictal) have also been used.
With Mollaret’s meningitis, it is difficult to measure the effectiveness of any drug therapy because the very nature of the disease is spontaneous and recurrent. The rarity of the disease also makes it difficult to create solid documentation of clinical trials studying the effectiveness of different antiviral drugs. However, there are some medications known to be contraindicated for the treatment of Mollaret’s meningitis, those being phenylbutazonum, steroids, antihistamines, colchicine, and estrogen.
For those that have obtained an allergy to Acyclovir, and other antivirals, Lysine seems to be effective at helping to minimize symptoms.
Drug-Induced Aseptic Meningitis
The incidence of drug-induced meningitis (DIAM) is unknown. Many antimicrobials, such as trimethoprim-sulfamethoxazole, ciprofloxacin, cephalexin, metronidazole, amoxicillin, penicillin, and isoniazid, are causes of aseptic meningitis. In addition, the xanthine oxidase inhibitor allopurinol has been implicated in causing aseptic meningitis. DIAM is a complication in which numerous other drugs, namely nonsteroidal anti-inflammatory drugs (NSAIDs), ranitidine, carbamazepine, vaccines against hepatitis B and mumps, immunoglobulins, OKT3 monoclonal antibodies (ie, directed against the T3 receptor and, therefore, pan T-cell antibodies), co-trimoxazole, radiographic agents, and muromonab-CD3, also have been associated. A high index of suspicion is needed to make an accurate diagnosis of DIAM. Diagnostic accuracy in clinical care depends on a complete history and physical examination.
The clinical presentation does not help in differentiating DIAM from infectious meningitis. The CSF profile (ie, neutrophilic pleocytosis) does not allow DIAM to be distinguished from infectious meningitis. Systemic lupus erythematosus is the single most frequent underlying condition associated with DIAM. Recurrent DIAM is well known; females usually predominate, and the frequency varies with the different underlying conditions.
We have created a pamphlet that gives information about this disease for providers. We have also created a document with known causes for recurrent meningitis not necessarily virally caused.