SE or RSE in Different Types of Encephalitis

4.8.8.1 SE/RSE in Herpes Simplex Encephalitis

Herpes simplex encephalitis (HSE) is the most common type of virus encephalitis. According to different reports, the incidence of seizures in patients with HSE ranges from 75 to 89% [443, 444], including SE or even RSE. The onset of SE not only occurs in the initial stage as new-onset RSE [26] but also occurs after the viral infec-tion as post-infectious autoimmune encephalitis [445] (please see the chapter on RSE in patients with autoimmune encephalitis). Patients with HSE can present with GCSE [26], but more fre-quently present with NCSE [446, 447]. Since HSE usually affects the limbic system, including the anterior/median temporal lobe, orbital fron-tal lobe, and insular lobe, the EEGs of patients with HSE are significantly more likely to exhibit periodic discharges and focal slowing in the fron-totemporal and occipital regions compared with the EEGs of patients with encephalitis of other etiologies [448, 449]. The neuroimaging data from most patients are abnormal, and the clas-sic presentations on the MRI show asymmetric hyperintense T2 signals in the mesiotemporal and orbitofrontal lobes and the insular cortex, which are corresponding to edema of these regions [450]. Most patients with HSE respond to acy-clovir [450] and have a good prognosis after treatment with antiepileptic and antiviral agents [26]. However, malignant RSE has also been observed. Bick et al. [439] had reported a case study of a 60-year- old male patient who devel-oped SRSE caused by HSVE. He continued to have NCSE after empirical treatments with anti-bacterial and antiviral agents and a three-level anti-SE treatment. His seizures were eventually controlled by ATL.

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4.8.8.2 SE/RSE in Japanese Encephalitis Japanese encephalitis is a common type of encephalitis in Southeast Asia. According to previous reports, the incidence of seizures in patients with Japanese encephalitis was 46–54%

[444, 451], which was only second to HSE [444], whereas the occurrence of SE was not common.

Patients with Japanese encephalitis predomi-nantly present primary focal seizures with sec-ondary generalization. In a study by Misra et al.

[451], 30 of 65 patients with Japanese encepha-litis experienced a seizure within a week, includ-ing 17 GTCSs and 13 partial motor seizures with secondary generalization. Eleven patients had a single seizure, eight had two seizures, 11 had multiple seizures, and only two patients devel-oped SE, both of whom presented partial motor seizures with secondary generalization and not RSE. However, in a study by Kalita et al., nine of the 30 patients with SE caused by encepha-litis were diagnosed with Japanese encephaencepha-litis [432]. The interictal EEG more likely showed focal slowing and was less likely to exhibit epi-leptiform discharges. In a study of 65 patients with Japanese encephalitis by Misra et al. [451], the interictal EEG of the patients with seizures revealed theta to delta slow waves in all patients, but epileptiform discharges were only observed in four patients. The prognosis of the patients with Japanese encephalitis who had seizures was poorer than that of patients without seizures.

In a study by Misra et al. [451], three of the 23 patients with Japanese encephalitis and seizures exhibited a complete recovery, eight exhibited a partial recovery, nine exhibited a poor recovery, and three died. Among the 34 patients without seizures, 17 patients exhibited a complete recov-ery, five exhibited a partial recovrecov-ery, seven exhib-ited a poor recovery, and five died. In the study of Kalita et al. [432], four of the nine patients with Japanese encephalitis and seizures died.

4.8.8.3 SE/RSE in Human

Metapneumovirus Encephalitis Since its initial discovery in 2001 [452], human metapneumovirus (hMPV) has been established as a common pathogen of respiratory tract infections with a global distribution. Although

most hMPV infections are mild to moderate, several case reports of severe infections, such as encephalitis, have been published. Most patients with hMPV encephalitis had seizures. In the California Encephalitis Project, the nasopharyn-geal swabs from five patients were positive, and three of these patients presented seizures [453].

Among the 13 patients included in published case reports, ten patients presented seizures, includ-ing three cases of SE [437, 453–459]. HMPV encephalitis often occurs in children and is usu-ally accompanied by severe lung infections. The seizure type may be generalized seizures [455]

or partial seizure [437]. The interictal EEG may be normal or exhibit focal sharp waves, and the neuroimaging examinations are usually normal [437, 455]. Most patients with hMPV encepha-litis have a good prognosis after treatment with appropriate anti-infectious and antiseizure agents [437, 456]. Webster et al. [455] had reported a case study of two patients with hMPV encephali-tis who presented SE accompanied by respiratory failure. Between these patients, one was a previ-ously healthy 15-month-old female who became abnormally excited during the night and then presented uncontrolled full body twitching and eye deviation to the right after 2 days of nausea.

After treatment with rectal diazepam followed by intravenous lorazepam, fosphenytoin, and finally phenobarbital, her clinical seizure was eventually controlled 35 min after onset. Another 18-month- old female toddler with a history of one simple febrile seizure presented GTCS after several hours of decreased oral intake and fever.

After treatment with midazolam, lorazepam, and fosphenytoin, the patient’s SE was eventually controlled 45 min after onset. Both patients had lung infections and gradually developed respira-tory failure, but both had a good prognosis after receiving the antiviral and antibacterial treat-ments. Vehapoglu et al. [437] reported a case study of a 4-month-old male infant who devel-oped hMPV encephalitis and suddenly displayed twitching of the right extremity and eye devia-tions to the right after 3 days of mild rhinorrhea, cough, and fever. He was somnolent soon after the seizures occurred, with a right frontal sharp wave discharge in the EEG and a normal cerebral

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MRI. His seizure was not controlled by AEDs, including levetiracetam, phenytoin, phenobar-bital, and midazolam and anti-infectious drugs, including ceftriaxone and acyclovir. Finally, the seizure was gradually controlled by a thiopental sodium infusion, and the infant eventually had a good prognosis.

4.8.8.4 SE/RSE in WNV Encephalitis WNV is a mosquito-borne subgroup of arbo-viruses that was, in 1937, first isolated from the blood of a febrile woman in the West Nile province of Uganda in 1937, and WNV began to play a more prominent role in clinical prac-tice since its first outbreak in the US in 1999.

According to different reports, the incidence of seizure in patients with WNV encephalitis is approximately 0–9% [460–462]. WNV encepha-litis usually symmetrically affects the brain stem and midbrain. The most common type of SE is NCSE; the most frequent abnormality in the EEG is symmetric generalized slowing with a frontal predominance and occasionally with a bilateral or asymmetric temporal predominance. The cere-bral MRI often exhibits bilateral symmetrical T2 hypertension in the brain stem and midbrain [463]. Most patients with WNV encephalitis have a good prognosis, with the exception of several severe cases, which have a poor progno-sis. Older patients and/or patients in a profound coma tend to have a poor prognosis. During the epidemic of WNV encephalitis in the southeast district of Tunis in 1997, 25 of the 30 patients recovered completely, one had a persistent head-ache and asthenia, one had persistent arm tremor, and three substantially older (mean age 62 ± 2 vs.

53.3 ± 23.3 years, p < 0.05) who were in a pro-found coma died [464]. However, reports about the relationship between seizures and the progno-sis of WNV encephalitis are not available. Bagic et al. [465] reported a case study of a patient with WNV encephalitis who presented RSE. The patient initially experienced chills and fever and gradually experienced asymmetric leg weakness, double vision, and dysphagia and soon had a dis-turbance of consciousness. On the fourteenth day after onset, the patient began to exhibit “fast eye movements with eyelid flickering.” The cerebral

MRI exhibited symmetrical abnormalities in the bilateral hippocampus, substantia nigra, central pontine, and dentate nucleus in the cerebellum.

The EEG displayed moderate diffuse slowing with a poly-spike wave discharge. After treat-ment with lorazepam, fosphenytoin, phenobarbi-tal, propofol, valproic acid, and carbamazepine, the electrical SE was eventually controlled.

Unfortunately, the patient ultimately died.

4.8.8.5 SE/RSE in Patients with Human Parvovirus B19 Encephalitis

As a pathogen of erythema infectiosum, human parvovirus B19 (hPVB19) usually causes a benign and self-limited disease. However, in immunodeficient subjects or children, it can also cause a severe disease. According to the study by Barah et al. [466], hPVB19 caused 4.3% of cases of undetermined meningoencephalitis during its epidemic outbreak between 1997 and 1998. The incidence of seizure in patients with hPVB19 encephalitis is very low. In a study by Barah et al.

[466], only two of the 12 patients with hPVB19 encephalitis presented seizures. According to published reports [466–469], the SE types observed in patients with hPVB19 encephalitis include GTCS, partial seizure, or partial seizure with subsequent generalization. SE may be con-vulsive SE or NCSE, with diffuse slowing or a focal slow wave with epileptiform discharges.

The cerebral MRI usually does not show abnor-malities. The pathogenesis is usually considered related to autoimmune inflammatory reactions, and the patient usually has a good prognosis after receiving immunoregulatory, antiviral, and anti-epileptic treatments. Erol et al. [469] reported a case study of a 10-year-old girl who was even-tually diagnosed with hPVB19 and presented RSE. The patient displayed confusion and GTCS at onset, with diffuse slowing and epileptiform discharges in the left hemisphere in the EEG and a normal cerebral CT/MRI. Her electrical SE persisted after treatment with valproic acid, midazolam, and pentobarbital and was eventu-ally controlled with high-dose corticosteroids. In another case report by Skaff et al. [468], a pre-viously healthy 27-year-old woman initially dis-played an erythematous, maculopapular rash over

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her cheeks, frontal headache with intermittent, low-grade fevers, myalgias, anorexia, and leth-argy and developed psychiatric symptoms, including depression, hallucinations, and confu-sion 5 days after onset. She began to have seizure activity with facial twitching and eye blinking and progressed to CSE, with diffuse slowing on the EEG and no significant abnormalities in the cerebral MRI. She continued to have NCSE after treatment with phenytoin and phenobarbital. A right frontal lobe biopsy was performed 6 weeks after the onset of her illness and showed minimal, chronic, leptomeningeal inflammations and mild, superficial, cortical gliosis. Since the serologic evaluation for HPVB19 on day 53 was positive for both IgM and IgG, she was diagnosed with HPVB19 encephalitis. After multiple treatments, including acyclovir, carbamazepine, lorazepam, topiramate, phenobarbital, VNS, and rehabilita-tion, she eventually exhibited a near complete recovery. Palermo et al. [467] also reported a case study of a previously healthy 18-year-old male patient who initially presented with headache, fever, sleepiness, and irritability 7 days after an erythematous rash involving all four limbs occurred. Five days later, the patient developed GTCS preceded by auditory sensations, version of the head to the right, and hyperextension of the right arm. The EEG exhibited diffuse and persistent slow delta activity with subcontinuous recruiting sharp theta activity that was prevalent over the right frontotemporal region, whereas the cerebral CT and MRI were normal. After receiv-ing levetiracetam, phenobarbital, and clonaz-epam treatments, he continued to present eyelid flickering and GTCS. Since the serological tests for the PVB19 DNA, IgG, and IgM were all posi-tive, the patient was diagnosed with HPVB19 encephalitis, and all symptoms, with the excep-tion of ictal epilepsy, recovered after receiving immunoglobulin treatments.

4.8.8.6 SE/RSE in EBV Encephalitis

The Epstein-Barr virus (EBV) is a lymphocyte virus belonging to Herpesviridae and is the patho-gen responsible for infectious mononucleosis and is closely related to the occurrence of nasopha-ryngeal carcinoma and childhood lymphoma.

It can also lead to acute, severe diseases, such as myocarditis and complications of the CNS, including meningitis, encephalitis, and neuritis.

In a study by Mazur-Melewska et al. [470], ten of the 194 patients with EBV infections had infec-tions in the CNS, and five of these patients devel-oped seizures, including four cases of GTCSs and one case of partial seizures. EBV encepha-litis often affects the unilateral or bilateral basal ganglion or thalamus [470–472], but it may also affect the temporal and occipital lobes [438] or the brain stem, midbrain, and corpus callosum [473]. The presentations in the EEG include dif-fuse or focal slow waves, fast beta activity with high-amplitude sharp waves, low- voltage activity with spike-wave discharges, high-amplitude slow waves with unilateral or bilateral spikes, and spike slow waves complexes appearing singly or in a group [438, 470]. The cerebral MRI may show T2 hyperintense in the unilateral or bilat-eral basal ganglion and thalamus or tempo-occip-ital region [470–472]. Most patients have a good prognosis after receiving antiviral and antiepilep-tic treatments; however, a few have a persistent neurological dysfunction [438, 470–473]. Greco et al. [438] reported a case study of a 4-year-old girl who initially presented with NCSE that began with 3 days of fever and sore throat. After 1 month, the patient had a complex motor partial seizure involving the arms and left leg that lasted for less than 5 min and a subsequent acute con-fused state that lasted for 3 h. The EEG showed a generalized high- amplitude slow wave activ-ity with unilateral or bilateral spikes and spike slow waves complexes that appeared singly or in a group. The cerebral MRI showed subcortical T2 hypertension in the right occipital lobe. Since the patient’s serum was positive for IgM and IgG antibodies and the EBV DNA was detected in the CSF using a nested PCR, she was diagnosed with EBV encephalitis and eventually recovered after treatment with acyclovir and other agents. Nishie et al. [474] reported a case study of a 37-year-old female patient with RSE that was thought to be caused by EBV. She initially presented with fever and headache followed by RSE 10 days later, with a diffuse slow-wave outbreak and bilateral paroxysmal diffuse sharp wave on the EEG. She

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was treated with anesthetic agents for as long as 2 months but ultimately had a good prognosis.

Delgado et al. [473] reported a case study of a 55-year-old female patient with EBV encepha-litis who had undergone renal transplantation and had been treated with immunosuppressive therapy for more than 7 years. She initially com-plained of dizziness and influenza-like symp-toms and then experienced visual hallucinations, a disturbance of consciousness, and continuous motor partial seizures in the left limbs. The MRI showed T2 hyperintense in the medulla, fornix, midbrain, left thalamus, and around the corpus callosum. Since the serological test for the EBV DNA was negative, the patient was diagnosed with EBV encephalitis and had a good prognosis after treatment with ganciclovir.

4.8.8.7 SE/RSE in Patients

with Mycoplasma pneumoniae Encephalitis

Mycoplasma pneumoniae (M. pneumoniae) is also a common pathogen that causes encephali-tis, particularly in children. Among 43 patients with suspected encephalitis who presented with RSE in California Encephalitis Project, five were diagnosed with probable M. pneumoniae encephalitis [434]. In a retrospective study by Lin et al. [436], SE was present in all nine cases of M. pneumoniae encephalitis occurring in children between 2002 and 2008 (100%), and the most frequent initial seizure type was partial seizure with subsequent generalization (4/9, 44%), followed by complex partial seizures (3/9, 33%) and GTCSs (2/9, 22%). Six patients developed RSE, including four patients with partial seizures and subsequent generalization, one patient with complex partial seizures, and one patient with GTCS. The presentations in the EEG included focal epileptiform discharges in two patients, multifocal epileptiform discharges in three patients, diffuse epileptiform discharges in two patients, and cortical dysfunction in two patients. Cerebral MRI was performed on seven patients, and the abnormalities included atrophy in three patients, T2 hyperintense in the bilateral hippocampus in two patients, acute dissemi-nated encephalitis in one patient, and increased

leptomeningeal enhancement at the 6th day from onset in one patient. The overall prognosis was poor. Two patients died (one had RSE), two patients were in a persistent vegetative state (both had RSE), three patients experienced persistent, severe neurological dysfunction (two had RSE), and two patients experienced a mild to moderate neurological dysfunction (one had RSE).

4.8.8.8 SE/RSE in Patients

with Bartonella Encephalitis A type of gram-negative bacilli, Bartonella henselae, is the etiological agent of cat-scratch disease. It can also infect the CNS and cause neu-rological symptoms including seizure, encepha-lopathy, neuroretinitis, and vasculitis. According to published reports [475–478], the incidence of seizure in Bartonella encephalitis is approxi-mately 50–79%. It may occur within 6 weeks and may present as GCSE or NCSE, partial seizures, or generalized seizures. The EEG abnormali-ties include focal slow waves, sharp waves, or spike- waves. The cerebral MRI may exhibit T2 and DWI hypertension in the bilateral pulvinar or tempo-occipital region. If Bartonella encephali-tis is diagnosed early and effectively treated with antibiotics, such as erythromycin and rifampi-cin, and antiepileptic agents, most patients have a good prognosis. Singhal et al. [477] reported a case study of two patients with Bartonella encephalitis. The first was a 27-year-old female patient with convulsive RSE whose cerebral MRI exhibited T2 and DWI hypertension in the bilat-eral pulvinar region. The patient had recently received scratches from her pet cat, and her serum and CSF were both positive for anti-Bartonella IgG. Thus, she was diagnosed with Bartonella encephalitis and gradually recovered after treat-ment with intravenous erythromycin followed by intravenous trimethoprim. The other case was a 66-year-old female patient who initially presented with sudden right arm clumsiness and developed right arm and facial twitching that gradually pro-gressed to RSE. The cerebral MRI showed T2 and DWI hypertension in the left frontal lobe and parieto-occipital cortices. Based on a cat-scratch history and positive serological anti-Bartonella IgG test, she was diagnosed with Bartonella

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encephalitis and was treated with ofloxacin for 2 weeks, followed by minocycline for 3 weeks, multiple antiepileptic agents, corticoids, electrical shock, and eventually underwent surgical resec-tion of the lesions with subpial transecresec-tions in the left pre- and postcentral gyri. Upon discharge to rehabilitation at 4.5 months, she had recurrent partial and generalized seizures and neurologi-cal disabilities, including profound aphasia and right-hand dystonia. Laswell et al. [478] reported a case study of a 28-year-old female patient who presented with new-onset RSE and had a history of recent exposure to a new cat and a positive serological test for Bartonella. Thus, the patient was diagnosed with Bartonella encephalitis. She continued to experience NCSE after treatment with benzodiazepines, fosphenytoin, propofol, and levetiracetam and eventually recovered after receiving a combination of doxycycline, rifampi-cin, and high-dose corticosteroids.

4.9 Epilepsy and Refractory