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Epileptic Disord 2006; 8 (S1): S59-67

Seizures, epilepsy and infectious of the

Hervé Vespignani1, A. Al Najjar1, Stéphane Kremer2, Louis Maillard1 1 Service de Neurologie, CHU de Nancy, France 2 Service de Neuroradiologie, CHU de Nancy, France

ABSTRACT – The recent onset of partial epileptic , secondary general- ized partial seizures, or tonic-clonic generalized seizures are often diagnostic indicators of (, , single or multiple abscesses, sub-dural empyema). The occurrence of status epilepti- cus (SE) from an is a serious factor to be considered in therapeutic management. CT-scan or MRI examinations are used to establish its parasitic, mycotic, bacterial or viral etiology. These studies also serve to confirm or modify the clinical diagnosis and the topographical origin of the infection. Nevertheless normal morphological examinations do not rule out a recent infection as a causative factor in epileptic seizures. This is especially true for meningitis in all age groups but particularly in children. Indeed, epileptic onset in patients with meningitis is an indication of the presence of a cerebral abscess. In the phase, antiepileptic treatments are the rule of thumb. Their indication in the follow up phase with the purpose of preventing further seizures will depend upon the nature of the infection and availability of access to antiinfectious treatments. The risk of subsequent epileptic seizures is most common in patients with encephalitis and cerebral abscesses. In cases of trauma, infections affecting the central nervous system increase the risk of posttraumatic epileptic seizures. Keywords: seizures, epilepsy, infectious diseases, nervous system

Epileptic seizures constitute one of the less of age (15%), and particularly in most common presenting events of children: 37% up to age 4 years, 40% central nervous system infections. In between 5 and 14 years. A second infectious etiologies overall, onset by frequency peak occurs in the elderly an epileptic seizure is seen in 70% of (Annegers et al., 1995). cases of encephalitis, 40% of cerebral In the setting of seizures as the first abscesses and 20% of cases of menin- presenting symptom, many diagnostic gitis (Lahar and Harden, 1997). The and therapeutical issues should be occurrence of initial or early status considered: epilepticus is also a vital indication of • envisage and look for an infectious Correspondence: H. Vespignani immediate severity of the , and origin in cases of epileptic seizure or CHU de Nancy, serves to establish functional and co- as the presenting 29 av. du Maréchal de Lattre-de-Tassigny, gnitive (Vespignani et al., symptom of the clinical picture; CO n° 34, 1995). At the same time, infection is • know the most common infectious 54035 Nancy Cedex, France one of the most common etiologies of aetiologies, in order to choose suitable symptomatic epileptic seizures regard- anti-infectious treatment;

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• in the acute phase, determine the appropriate antiepi- particularly resistant and remain infectious for a very long leptic and the duration of treatment; time in pork. These eggs produce embryos that are en- • determine whether or not chronic antiepileptic treat- cysted in different parts of the body, under the skin or, most ment is indicated to limit the risk of subsequent epileptic particularly, in the muscles, as well as in the brain or in the seizures and, accordingly define the criteria for choice of bone marrow. Encystment in the produces hy- antiepileptic . drocephalus in addition to arteritic changes at the base of Infections also constitute a frequent etiological factor in the skull and secondary vascular complications. symptomatic , at all ages. Knowing that 40% of Cerebral location of cysts is responsible for epileptic sei- epilepsies are symptomatic, infectious aetiologies (viral zures, 72% of which are partial, according to Medina encephalitis, cerebral abscess, AIDS, neurocysticerosis) (Medina et al., 1990), and associated with a normal neu- represent 3% of all epilepsies (Annegers et al., 1988). This rological exam in 80% of patients. Paraclinical diagnosis percentage is about the same as that for traumatic causes. is easy to be made. The scan shows a number of small Although the percentage varies considerably depending cysts, rounded and covered with calcifications. Solitary on age, it seems to be most dependent on geographic brain lesions have been observed; they consist of a large region. In many countries (Latin America, Asia, Africa), hypodense or isodense cyst surrounded by perilesional neurocysticerosis (NCC) represents over half of the etiolo- . Cyst evolution is described in four stages: stage 1 gies of initial seizures in adults (Medina et al., 1990). (thin-walled cyst), 2 (cyst with thicker walls, with or with- In the presence of symptomatic epilepsy, manifesting in out scolex), 3 (poorly limited cystic degeneration), 4 (pres- repeated spontaneous epileptic seizures, the objectives ence of calcifications). pursued are: The presence of myalgia can lead to identification of • to link the epileptic events to a more or less remote characteristic muscular calcifications. infectious cause. Today, this problem has been solved in An antiparasitic drug (albendazole), is more specifically large part by morphologic brain imaging; keeping in mind, indicated in forms without calcifications. Long-term prog- however, that if an infectious etiology is suspected, a nosis of epilepsy is uncertain, given the subsequent risk of normal MRI does not necessarily exclude this possibility; seizure recurrence observed after ending treatment in over • to determine criteria for choosing the most appropriate half the cases during the first three months, among 40 antiepileptic drugs and specify subsequent prognostic ele- patients studied by Del Brutto (Del Brutto et al., 1992), ments in cases at risk to progress towards a drug resistant despite a 2-year, seizure-free period. The choice of anti- epilepsy. epileptic therapy must take into account the possibility of In order to attain these objectives, we will examine suc- reduced praziquantel blood levels due to the - cessively parasitic, viral, fungal and bacterial etiologies, inducing effect of antiepileptic drugs (Bittencourt, 1992). specifying for each one the involved pathophysiological mechanism, as well as clinical and paraclinical diagnostic Paludism elements. Paludism is the most common fatal parasitic disease in the world. 80% of patients die of cerebral complications. In , where paludism is endemic, one third of epileptic Parasitic etiologies seizures with in children are caused by this disease (Asindi et al., 1993). The agent responsible, a hematozoon Neurocysticerosis (NCC) - of the most common falciparum type, the most Neurocysticerosis is the most common parasitic disease in serious, or more rarely, of the vivax type, ovale, malariae, Central and South America. After paludism, it is the most transmitted by female Anopheles in Asia, Africa and Latin common parasitosis; it should be considered in subjects America – multiplies in the liver before invading red blood who lived in Latin America, in black Africa or in Asia. NCC cells, where successive cycles provoke febrile attacks represents 10% of etiologies of neurologic emergency concomitant with antigen release. Changes in the central cases. Epilepsy is the most common symptom, occurring nervous system correspond to multiple necrotic and hem- in two thirds of patients (Del Brutto et al., 1992). orrhagic foci produced by contact with fine thrombosed In Mexico, NCC is the most common cause of adult onset capillaries rich in parasites. epilepsy, representing half of all cases (Medina et al., The characteristic symptom is an attack of paludism. Cere- 1990). In Europe, foci have been observed in the Mediter- bral is the serious, mortal form of the attack. ranean region, particularly in Sicily. In France, few cases It must be remembered that cerebral malaria never takes have been seen, although diagnosis is easy, given that the form of meningitis or , but ap- neuroradiologic images are characteristic (Planque et al., pears instead as a very serious , without 1990). NCC is due to infection of a human (final host) by CSF changes, with convulsive seizures and with con- , whose intermediary host is the pig. Pigs are sciousness and tonus problems. Although euphoria is the contaminated by eating eggs found in human feces. It is usual mode of presentation, hyperalgic forms do also exist possible for humans to absorb these eggs, which are (Dumas, 1997). This diagnosis should be systematically

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considered in travelers returning from black Africa, from Diagnosis is more difficult when the CT scan shows a Central and South America, from South-East Asia. EEG single image suggestive of abscess, or when normal. toxo- recordings are not helpful. But we must be aware of the plasma contributes little to the diagnosis. Excep- forms of the disease characterized by periodic activity, tionally, IgMs are found; more often, traces of IgG are since they could suggest a false diagnosis of necrotizing found. , whose usefulness should be encephalitis. It is urgent to look for Plasmodium falcifarum decided based on location and size of cysts, as well as on by performing a blood smear or by microscopic observa- the presence of intracranial hypertension, may show mod- tion, knowing that the parasite will not always be found. erate cellular reaction, with low CSF . The MRI When in doubt, it is best to treat with quinine IV. Paludism detects multiple T2 hypersignals with mass effect. can be prevented by taking an antimalarial drug 10 days Brain biopsy, performed less often nowadays, shows areas before leaving, throughout the duration of stay in these of necrosis with parasitic infestation. A very important regions, and for three months after return. Antimalarials, argument favoring the diagnosis is the effectiveness of the such as mefloquine (Lariam®) can lower convulsive specific treatment (Malocide®, Adiazine®, Lederfoline®), threshold and reduce sodium blood levels by 30 resulting in clinical and imaging resolution in over 80% of to 40%. cases (Lahar and Harden, 1997). Onset of epileptic sei- Therefore, it is useful to check, and if need be to change, zures motivates the choice of non enzyme-inducing anti- the sodium valproate dosages of epileptics traveling in epileptics. endemic regions. Other parasitoses worms include nematodes (non- Toxoplasma gondii, an intracellular protozoon, is trans- segmented, cylindrical), cestodes (flat, segmented) and mitted in food contaminated with oocysts from cat feces, trematodes (flat, non-segmented). since the cat is the only known definitive host. Transmis- Nematodes that infect humans are for the most part intes- sion can also take place by ingestion of undercooked meat tinal parasites: ascaris, oxyuris, trichocephalus, ankylosto- of bovines or ovines infected with cysts. After passing mas, and strongyloid threadworm. They can cause head- through the digestive system, the parasite invades the body aches, , apathy, insomnia and, exceptionally, through the hematopoietic system, and spreads to a mul- of non-epileptic origin. In general, their role in titude of cells. The infection can remain quiescent, exist- neuropsychiatric disorders is ambiguous. It is not possible ing in a microcystic intracellular form that is virtually to assert that a parasitic origin of this type is responsible for asymptomatic. The advent of immunosuppression may epilepsy in a child with oxyuris or ascaris, unless the reactivate the cysts. Nervous system complications in- infection is massive, and there are predisposing factors. clude encephalitis, large brain lesions in the course of The cause-effect relationship is very different in cases of AIDS and, rarely, , polyradiculoneuritis and poly- filaria and trichiuria, which can cause neurological com- myositis. In a pregnant woman, infection during the first plications through larval migration. Filaria infections are two trimesters of can result in a massive ubiquitous in tropical regions. Nervous complications like to the fetal encephalon, producing brain malformations, meningoencephalitis or epileptic seizures are very rare , psychomotor delay and chorioretinitis. (Dumas et al., 1986). Children can subsequently develop epilepsy, whose origin Trichinosis exists world-wide. Short epidemics have oc- will be revealed rapidly by the presence of characteristic curred in France. The infection is transmitted through the calcifications on a brain CT scan, or even a simple x-ray. ingestion of undercooked boar or meat that contains There has been renewed interest in this infection among Trichina spiralis larvae; it causes systemic illness with AIDS patients, because toxoplasmosis is a in hypereosinophilia and myositis, including cardiac myosi- about 30% of cases, representing half of all neurological tis (Fourestié et al., 1993). Nervous complications arise diseases associated with AIDS (Porter and Sande, 1992). very suddenly, a few days after ingestion of the contami- Thus, toxoplasmosis is the most common neurological nated meal; they manifest as diffuse with or complication of AIDS, appearing at a late stage of this without epileptic seizures, with paralysis of variable inten- disease. sity and location. CSF is normal or shows only a high Epileptic seizures may be the initial manifestation in 18 to level. The CT scan reveals the presence of numer- 29% of cases of toxoplasmosis complicating AIDS (Porter ous small and diffuse, “contrast enhancing” hypodensities, and Sande, 1992, Ragnaud et al., 1993). The CT scan is in the white matter or the cortex. Treatment consists of a very suggestive as it shows multiple ring-enhancing cysts combination of benzymidazoles and corticoids. Prognosis surrounded by perilesional edema. This very characteris- depends on the extent of cardiac involvement. Chronic image in the case of immunocompromised hosts justi- antiepileptic therapy is not indicated beyond the acute fies the institution of specific antiparasitic therapy. Diag- phase. nosis is confirmed by resolution of clinical signs and brain Other nematode parasitoses exist in the Far East and in the lesions in response to treatment. Pacific. One is particularly frequent in Thailand: gnathos-

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tomiasis caused by Gnathostoma spinigeruna, a parasite . Entamoeba histolytica, the agent of amebic dys- of the cat, and of rats infesting uncooked fish and shellfish entery, can cause cerebral abscess, usually single and very meals. The disease manifests with sudden, intense pain large. This diagnosis is suggested by intestinal symptoms. whose location is variable, painful paralyses and convul- Entamoeba naegleria causes a very serious purulent men- sions, in a context of often fatal encephalitis. ingoencephalitis, due to penetration by the amoeba into Cestoda are taenias. Taenia saginata, the most common, the olfactory tract of swimmers in the lukewarm or warm particularly in France, does not cause neurologic compli- stagnant waters of lakes, ponds or even poorly maintained cations, except at the stage of general complications. swimming pools. Taenia solium is the agent responsible for . Diagnosis is made upon discovery of the amoeba at direct Taenia ecchinococcus, which causes hydatid cysts (hy- phase-contrast microscopy, or after culture. Evolution is datidosis) exists world-wide and advances along with often extremely rapid. Entamoeba acanthamoelva is re- sheep farming (intermediary host). Adult taenias live in the sponsible for subacute meningoencephalitis that can in- intestines of . Humans are contaminated by ingesting clude epileptic seizures in immunocompromised patients. eggs shed with taenia rings. Cerebral localization of tae- The main sanguineous protozoon is the agent of paludism. nias causes the development of a large, hypodense cystic Trypanosomiasis is also secondary to infestation by a lesion, as evident on CT scan imaging. The lesion may sanguineous protozoan; Trypanosomiasis is transmitted by result in intracranial hypertension and symptomatic epi- the tsetse fly (Glossina), only in intertropical black Africa. leptic seizures. Treatment is surgical. Subsequently, This parasite, presently in full recrudescence, causes men- chronic antiepileptic treatment must be maintained for ingoencephalitis with altered , which is several months, even two years. quickly fatal if untreated (melarsoprol is the therapy of Alveolar echinococcosis (Echinococcus multilocularis)is choice). The clinical picture presents subacute or chronic a particular form of echinococcosis; this infection is ubiq- meningoencephalitis, with epileptic seizures in rare cases, uitous, also seen in France, especially in the East (Weber et more often with altered consciousness, extrapyramidal al., 1988). The echinococcus lives in the intestines of rigidity, and psychic problems. The CSF is foxes; humans are contaminated by eating wild berries. quite characteristic, with increased levels of gamma Larvae are encysted as poly lobar nodules that appear as globulin and IgM, as shown by using immunofluorescence bunches of grapes in the meningeal spaces and sometimes (Dumas, 1997). in the cerebral parenchyma, particularly in the temporal In summary, epileptic seizures can be responsible for the region. Epileptic seizures can be the initial symptoms. discovery of intracranial parasitosis, or can complicate a is largely based on CT scan findings, chronic infestation. Epileptic events are always partial and includes metastases or glioblastomas, mostly in the seizures or tonic-clonic seizures generalized from the presence of a unique lesion. Blood hypereosinophilia outset. They can occur together to constitute status epilep- should attract attention toward parasitic origin. ticus. As far as trematodes are concerned, neuropsychic compli- When an epileptic seizure is isolated and constitutes an cations involve Distoma and . Among Dis- initial event, diagnosis depends on geographical of origin toma parasites, Fasciola hepatica, responsible for hepatic and CT scan findings: distomatosis, is the most likely to cause meningeal syn- • single cyst in France: hydatidosis, dromes with CSF eosinophilia. Epileptic seizures are un- • multiple small cysts in Latin America, black Africa, Asia, usual. Southern Europe: , Paragonimiases are of interest because of the neurologic • multiple or single cysts in France: alveolar echinococ- manifestations seen in 30 to 50% of patients, with pre- cosis, toxoplasmosis, dominance of encephalitis and secondary epileptic sei- • multiple, “soap bubble” cysts in South-East Asia, black zures. In addition, the “soap bubble” appearance of scan Africa: , images is particularly characteristic. This Far East parasite • single cyst in North Africa: amebiasis, causes pneumopathy responsible for purulent bloody spu- • encephalopathies: pernicious paludism, tum containing parasite eggs. The clinical picture presents • meningoencephalitis: filariasis, trichinosis, toxoplasmo- as , but the diagnosis can be corrected rapidly sis. by a systematic search for eggs in the sputum. From the therapeutic perspective, antiparasitic treatments act as diagnostic tests (toxoplasmosis, paludism) and are Protozoans generally very active if the diagnosis is made early Intestinal telluric protozoa responsible for amebiasis, and enough. Onset of early epileptic seizures requires antiepi- sanguineous protozoa causing paludism and trypanoso- leptic therapy at the acute phase (). Sur- miasis belong to the category of protozoa with neurologi- gical treatment could be indicated in cases of single local- cal tropism. ization of large, accessible cyst. Follow-up with chronic Epileptic seizures can be symptomatic of cerebral amebia- antiepileptic therapy is necessary in case of single or sis. The clinical picture varies depending on the type of multiple localization of sequel cyst, with or without calci-

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fication. The drugs of choice are non-enzyme-inducing of confusion, with or without fever. Absence of fever antiepileptics which do not interfere with antiparasitic should not eliminate the suspicion of encephalitis. In the treatment. same way, absence of a clinical meningeal is almost universal. However, these signs are obviously highly indicative of a Mycotic etiologies diagnosis of encephalitis, in the presence of recent-onset epileptic seizures, if infection is present, if skin irritation is Central nervous system mycoses are rare but one of them, noted, or if there are highly suggestive epidemiological cryptococcosis, has attracted attention because of its fre- data. quent association with AIDS. Cryptococcosis caused by yeasts ( neoformans) represents about 10% The herpes of neurological affections associated with AIDS (Belec and Gray, 1990). Clinically they may present as a subacute Necrotizing encephalitis caused by herpes virus (HSV1) is meningeal syndrome, meningoencephalitis with cranial the most common, one of the most serious in the absence nerve involvement; and sometimes as pseudo tumoral of specific treatment (over 70% death rate, high . The clinical picture may consist only of mod- of serious sequelae among survivors), and especially the erate fever or persistent , due to meningitis. most important to recognize early because of the thera- Epileptic seizures may complicate evolution. MRI is very peutic possibilities that have completely altered the prog- suggestive and may show symmetrical hypersignal nodu- nosis of this very serious entity. lar lesions, in the Virchow Robin spaces of the basal The herpes virus invades preferentially the ganglia. A systematic search for and the orbito-frontal cortex, bilaterally, probably through (direct India ink CSF staining, culture, antigen identifica- olfactory fibers. It rapidly causes inflammation accompa- tion) is essential. nied by edema responsible for rapid and massive destruc- The hypothesis of a mycotic origin must be considered in tion of the . This preferred localisation every case of subacute or chronic meningitis, meningoen- accounts for early onset of epileptic seizures, for possible cephalitis or single, or more often multiple, abscesses in a phasic problems, and for the rapid appearance of mental patient with lowered defenses (immunocompromised, confusion and diminished alertness. Epileptic seizures are with serious chronic infection) after catheterization or both early and numerous, which explains the frequency of placement of prosthesis (nosocomial infection). It also indicative status epilepticus. should be considered in the differential diagnosis of cen- Characteristically, the possibility of herpes encephalitis tral nervous system tuberculosis and cacinomatous men- should be considered first in the presence of seizures ingitis. The responsible agents are cryptococci, Aspergil- appearing to be of temporal origin, very recent and numer- lus (aspergillosis), (candidiasis), more rarely ous from the outset, in a subfebrile or altered alertness histoplasmosis or coccidi-oidiomycosis in cases of men- context. Perioral herpetic lesions are observed in less than ingitis. Diagnosis is based largely on neuroradiological 5% of cases. findings. Presence of one or several abscesses can be the The diagnostic procedure should take the following facts consequence of dermatomycosis (single, blackish ab- into account: cess,), nocardiosis (ubiquitous distribution), and blasto- • antiherpetics are more effective if administered early; (endemic in the United States). • the value of presumptive treatment combining antiher- In the acute phase, antiepileptic treatment with benzodi- petics with wide spectrum (antiherpetic, anti azepines can be necessary, followed by chronic antiepi- , antituberculosis) has been proven; leptics to avoid the high risk of seizures relapse. Drugs to • for the purposes of early diagnosis, a CT scan is not as drugs interactions and the patient general status may inter- useful as a brain MRI, which shows, as early as the second fere with the choice of anti epileptic drugs. day, a T2 hypersignal at both temporal lobes, keeping in mind that the MRI can be normal prior to this (in practice, this can only be done when access to MRI is easy in an Viral etiologies emergency); • diagnostic proof is provided by a CSF study (presence of Epileptic seizures are a common symptom of viral en- viral DNA and levels of alpha interferon). Results for viral cephalitis. They can be generalized tonic-clonic, but also, DNA can be obtained relatively early, within 24 to 48 very characteristically, frequently recurrent, recent onset hours, but a negative PCR does not exclude this diagnosis partial seizures. Serial seizures, and even initial status (Jambon, 2001). epilepticus, are not unusual. In general, a diagnosis of Interferon-alpha levels indicate the presence of a virus, acute encephalitis should be considered in the presence of and results can be obtained in about 8 days. As for an epileptic seizures in a context of recent altered alertness emergency CSF test, the classic traps must be kept in mind: and impaired consciousness, in the course of a recent state normal results in 10% of cases; reaction with polymorpho-

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nuclear predominance that could orient the diagnosis partial complex seizures. In addition, at EEG, periodic toward other etiologies, particularly bacterial. lateralized epileptiform discharges (PLED) can resemble For all these reasons, the EEG is useful, although neurora- periodic activity, adding to the difficulty; diologic investigations are now given priority. The EEG is • other : diagnostic errors in favor of useful when an MRI cannot be performed, when MRI herpetic encephalitis are not harmful, since the other viral images are not clearly indicative or are ambiguous, when etiologies do not respond to treatment. The diagnosis is lesions are unilateral, signs are atypical, or there is ab- corrected by performing viral biologic investigations, be- sence of biological concordance. cause these clinical and neuroradiologic profiles can be The EEG is even more important in cases of misleading similar; clinical forms (apyretic forms, psychiatric forms), or in • non viral encephalitis, particularly acute disseminated cases where the CSF is normal (10%) or atypical (poly- , where epileptic seizures are excep- nucleated cells in over 40% of cases, hemorrhagic forms). tional and lesions manifest through white matter anoma- The characteristic EEG in an indicative clinical context lies revealed by MRI; paraneoplastic , shows localized short period periodic activity. Periodic called Corsellis encephalitis (Ducrocq et al., 1992); or activity is a regularly repeated paroxysmal activity occur- transient limbic encephalitis of dysimmune origin, associ- ring in stereotypical fashion for a long period, usually ated with antibodies to cortical voltage-gated potassium lasting several minutes. When the period, that is, the time channels (Thieben et al., 2004). Acute onset, without between the start of each complex, is less than 4 seconds, fever, in a context of altered consciousness, behavioral the activity is classified as short; it is classified as long problems, or cognitive deficit, with temporal lobe epilep- when it exceeds 4 seconds. In herpetic encephalitis, peri- tic seizures rapidly becoming numerous, may point to- odic activity is short and localized in temporal or fronto- ward herpetic encephalitis, but there is no periodic activ- temporal regions. Becoming visible, in general, between ity and focal epileptic seizures are often in alternating the second and the fifteenth day, this activity can be labile locations on the same EEG tracing or on different tracings. and, at first, can consist of a few fragments that are MRI shows bi-temporal T2 signal abnormalities, predomi- repeated over a few dozen seconds, and that should be nating or appearing exclusively in the . looked for in an indicative context (Vespignani et al., 2002). This uniform or bilateral periodic activity appears In practice, it is only when performing a brain MRI is over a slow background which is proportional to impaired impossible, and when the MRI is normal or MRI images consciousness. The periodic activity is interrupted by focal are unclear, that differential diagnosis is considered, but or rapidly generalized epileptic seizures. We must keep in without delaying presumptive therapy that combines an mind that spontaneous evolution takes place through the antiherpetic ( IV, 30 to 45 mg per kg and per day gradual replacement of all periodic activity by a low for ten days), an anti-listeria (amoxicillin + aminoside or voltage activity, which indicates necrosis and irreversible cotrimoxazole alone), an antituberculous (isoniazide- lesions. rifampicine) if there are clinical indications of tuberculo- The usefulness of the EEG for diagnosis has been illus- sis. trated in a series of 18 cases of herpes encephalitis, and in Subsequent evolution will lead to stopping antitubercu- 31 cases of presumed viral, but not herpetic, encephalitis. lous treatment if clinical improvement is rapid (a few In the herpetic encephalitis group, the EEG is normal less days), to stopping antiherpetics if the herpes PCR is nega- often than in the non herpetic group (8% versus 23%) and tive and the interferon alpha is normal. temporal abnormalities are more frequent (75% versus As for antiepileptic treatment, the choice is between an 19%). Periodic activity is only found in less than 3% of intravenous () or IV sodium cases of non herpetic encephalitis, and can exist in spite of valproate; the latter might be preferred in order to better normal MRI (Clinque et al., 1996). However, it is not monitor consciousness and alertness. In case of status constant, since the same series only shows it in 28% of epilepticus resistant to this therapy, fosphenytoine (Dilan- cases, and remarks on its transient, labile character, and on tin®) is useful. The risk of epileptic sequelae is 16 times the need to repeat the EEG in case of suspicion of herpetic higher than that in the general population, and this risk encephalitis. persists for almost 15 years (Annegers et al., 1988). Risk of Differential diagnosis is only considered, in practice, after epilepsy in encephalitis patients with early epileptic sei- institution of presumptive treatment based on MRI clinical data. In this situation, the EEG is important once again in zures is 10% in the first five years, and 22% during the 20 order to detect: years after the initial infectious episode. • pathologies other than encephalitis, particularly cere- For patients with encephalitis without early epileptic sei- bral thrombophlebitis whose clinical profile can be simi- zures, the cumulative risk over 20 years is 10%. For lar, with generalized tonic-clonic epileptic seizures, ap- patients with bacterial meningitis with or without early parently from the outset or, more often, partial and epileptic seizures, the cumulative risk over 20 years is 13 secondarily generalized; partial motor seizures rather than and 2% respectively (Annegers et al., 1995).

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Other herpes coccus B, and in the neonatal period; Haemophilius influenzae, The cytomegalovirus (CMV) is transmitted through the meningitidis and pneumonia after the age blood, particularly during with extracorporeal cir- of six years. culation. The CMV also plays a pathogenic role in many should be considered separately neurological syndromes, and in the late stages of AIDS, because seizures are very common in the course of its where it is ubiquitous. Apart from retinal lesions, it can evolution. This pathology is seen more often in adults and cause subacute encephalitis close to “AIDS ”, in the elderly. The typical form is subacute meningeal and is responsible for partial or generalized tonic-clonic syndrome, with lymphocytic-type cellular reactions, low epileptic seizures. MRI is suggestive, showing an abnor- cerebrospinal fluid and high proteins. Alertness mal T2 hypersignal lining the ventricular walls (Gastaut, problems appear early, as do EEG abnormalities related to 1997). In exceptional cases, the Epstein-Barr virus is re- diffuse and often significant slowing of background sponsible for acute encephalitis that can bear a clinical rhythm. Life threatening forms are not rare; they are char- resemblance to herpetic encephalitis (Bale, 1993). acterized by subfebrile confusion, persistent headaches, generalized tonic-clonic or partial seizures, in a cephala- The other viruses lgic and subfebrile context. Tuberculous meningitis is as- Arboviroses are transmitted by mosquitoes or ticks and sociated with epileptic seizures in 10 to 15% of cases. The belong, for the most part, to intertropical pathology. Cen- seizures are secondary to severe CSF inflammation, and tral nervous system injury occurs most often during a associated . Tuberculoma, a late-developing ce- second febrile episode. Seizures can occur in a very rebral abscess is not discovered at this stage. variable clinical context, depending on the agent in- In the acute phase of acute bacterial meningitis, seizure volved. A few cases among natives have been docu- onset requires urgent antiepileptic therapy with benzodi- mented. Encephalitis caused by ticks is generally associ- azepines or sodium valproate IV, depending on the state of ated with peripheral paralysis. Epileptic seizures are consciousness; follow-up with a chronic antiepileptic unusual (Garcia-Monco and Benach, 1995). treatment should be decided based on the risk of subse- quent epileptic sequelae to the acute meningeal episode. Rabies Epidemiologic data on this point has been clearly estab- lished, as witnessed by the historical Rochester series In France, rabies is an imported pathology, since the (Annegers et al., 1995), which documents increased risk of disease is virtually eradicated in animals. But it is present epilepsy. This risk is independent of age at the time of in neighboring regions as in Central Europe and North infection, but varies considerably depending on type of Africa. It is responsible for encephalitis that is rapidly fatal. infection and on the presence of early seizures. Epileptic seizures, usually generalized tonic-clonic and Patients with do not have added risk of convulsive are part of an indicative clinical picture that subsequent epilepsy. Patients with bacterial meningitis includes hydrophobia (Dupont and Earle 1966). have a five times higher risk compared to the general population, with particularly highest risk during the first two years following infection. This risk contributes to risk Bacterial etiologies factors for possible head trauma, causative or associated, corresponding to a supplementary risk factor for post- Acute meningitis traumatic epilepsy. Onset of epileptic seizures in the course of bacterial meningitis should alert to the possibility of an abscess or Cerebral abscess the development of cerebral thrombophlebitis. These hy- Diagnostic and therapeutic procedures related to cerebral potheses must be eliminated before a physiopathology of abscess have been considerably modified by the advent of “irritative” meningeal inflammation, or release of epilep- the brain CT scan, keeping in mind that cerebral abscess togenic bacterial toxins can be considered. This rule incidence was greatly reduced with the introduction of should motivate a brain CT scan and, if need be, an MRI, antibiotics (Nielsen et al., 1983). As is the case for all in the event of seizures in the context of bacterial menin- infectious pathologies, prognosis depends primarily on gitis. early diagnosis. Initial or early partial or partial second- Seizures are common, observed in nearly 30% of cases of arily generalized seizures occur in nearly one third of bacterial meningitis, with no visible cerebral lesions (Du- cases. Symptomatology is directly related to the location rand et al., 1993). They are more frequent in young of single or multiple cerebral abscesses. children, being often the presenting clinical sign of men- Although considerable progress has been made in terms of ingitis, in febrile children (Green et al., 1993). The agent diagnostic techniques, the physiopathologic mechanisms responsible is mainly Haemophilus influenzae, but the of cerebral abscesses are still unknown. The point of entry bacterium varies depending on the child’s age: Strepto- of the infection is otic (chronic otitis, more rarely ),

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either through a hematogenous pathway originating in a 1995). Residual risk of epileptic sequelae is high and leads locus of chronic pulmonary suppuration, or by means of a to the prescription of antiepileptic therapy over several congenital cardiopathy with right-to-left shunt. The shunt years. It is only after 5 to 10 years that ending therapy can can be responsible for infection through venous blood be considered, keeping in mind that even a long time after contaminated by infected teeth or tonsils. Similarly, the the initial episode the risk of seizure recurrence remains clinical picture is classic in patients with Rendu-Osler significant. disease, vascular dysplasia with telangiectasias, some- Tuberculoma is a rare and particular form of . times associated with pulmonary angiomas, causing sup- It consists of a solid mass representing a granuloma made purative emboli. It is not known why the cerebral infection of epithelioid cells and caseum. At CT scan, the tubercu- is sometimes diffuse (meningeal type) and at other times loma resembles a pyogenic abscess. It usually originates localized; or why the localized form is sometimes intrac- along vasculitic lesions and almost always it follows mas- erebral (cerebral abscess) and sometimes located in the toiditis. Scanographic findings are non-specific. Treatment subdural space (subdural empyema). In 10 to 20% of consists of evacuating the abscess (aspiration or cran- cases, an exact point of entry is not found. The organisms iotomy) and administering prolonged antituberculous involved are very diverse, aerobic and anaerobic. They chimotherapy. Antiepileptic treatment is required in the cause intracellular suppuration, with collection sur- acute phase and follow-up with an antiepileptic drug is rounded by a zone of inflammation, itself surrounded by indicated, at least for the duration of the antituberculous edema. Abscess evolution results in the creation of a treatment (12 to 18 months or more, depending on scano- fibrous shell. graphic evolution). Choice of must take into The clinical picture reflects a tumoral syndrome possibly account possible drug interactions and the possibility of associated with deficits and/or intracranial hypertension. enzyme induction, particularly when the drug prescribed When seizures are the exposing event, they can be either is isoniazide (INH). M isolated or part of the tumoral picture. The important element to keep in mind is that the infectious syndrome with fever, and blood inflammatory syndrome, is not con- References stant and can be discrete. Moreover, discovery of a pos- sible source of infection is definitely not the rule, at least Asindi A, Ekamen E, Ibia E, Nwangwa M. Upsurge of malaria- related in a resistant Plasmodium falciparum. Trop not during the initial diagnostic procedures. Therefore, it is Geogr Med 1993; 45: 110-3. the brain CT scan that makes it possible to identify a single or multiple abscesses. Annegers JF, Hauser WA, Beghi E, Nicolas A, Kurland LT. The Diagnostic difficulties are of two types. Erring on the side risk of unprovoked seizures after encephalitis and meningitis. 1988; 38: 1407-10. of caution, that is, diagnosing an abscess too quickly and instituting wide spectrum treatment, has no Annegers JF, Hauser WA, Lee JRJ, Rocca N. Incidence of acute serious consequences, and the diagnosis is rapidly cor- symptomatic seizures in Rochester, Minnesota 1935-1984. Epi- rected by the evolution of clinical signs and by scan lepsia 1995; 36: 327-33. results. By contrast, erring by default is serious because it Bale J. Viral encephalitis. Med Clin North Am 1993; 77: 25-42. delays treatment. A diagnosis of meningitis can be main- Belec L, Gray F. Infections du système nerveux central par le tained when meningeal signs are predominant and the virus de l’immunodéficience humaine et le cytomégalovirus. neurological deficit is discrete. As a rule, the occurrence of Névraxe 1990; 1: 133-53. any seizures in the course of a meningeal syndrome is Bittencourt P, Gracia C, Martin R, Fermandes A, Diekmann H, reason for performing a brain scan. The scan images can Jung W. and decrease bioavailability lead to making a diagnosis of : glioblastoma or of praziquantal. Neurology 1992; 42: 492-6. single or multiple metastases in case of subacute evolution Clinque P, Cleator GM, Weber T. The role of laboratory investi- and discrete infectious syndrome. Treatment is medical gation in the diagnosis and management of patients with sus- and/or surgical, by puncture and institution of local anti- pected herpes simplex encephalitis: a consensus report. J Neurol biotic therapy, combined with systemic antibiotic therapy. Neurosurg Psychiatrie 1996; 61: 339-45. Occurrence of initial or early epileptic seizures requires Del Brutto O, Sanribanez R, Noboa C, Aguirre R, Diaz E, antiepileptic treatment with benzodiazepin or sodium val- Alarcon T. Epilepsy due to of 203 patients. proate; partial or generalized status epilepticus is not rare Neurology 1992; 42: 389-92. ® and can require prescribing fosphenytoine (Dilantin ). Ducrocq X, Anxionnat R, Lacour JC, Maillard S, Vespignani H, Follow-up with a chronic antiepileptic treatment is obliga- Barroche G. L’encéphalopathie limbique paranéoplasique de tory in all cases. Risk of subsequent seizures is almost Corsellis. À propos de deux observations. Ann Med Nancy Est constant (Legg et al., 1973). 1992; 31: 121-5. This risk is greater in the context of possible post-traumatic Dumas M, Léger JM, Pestre-Alexandre M. Manifestations neu- origin. Brain abscess is an additional risk factor for the rologiques et psychiatriques des parasitoses. 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