Encephalitis Of Unknown Origin Research Articles

Biomarkers of Neurological Injury for Emerging Viral Threats and Post Viral Disease

Abstract Neurotropic viral infection and the ensuant immune response are a significant cause of morbidity and mortality worldwide, which can range in severity from mild to permanent central nervous system (CNS) damage and death. Encephalitic alphaviruses include Venezuelan and eastern equine encephalitis viruses (VEEV and EEEV; Alphavirus; Togaviridae). Injury to the CNS is an important determinant of poor outcome and tools to predict this outcome are lacking. Neurons are the primary target cells of encephalitic alphaviruses where cytopathology plays a major role in CNS dysfunction. Proteins are released following cell death, such as ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) are neuromarkers of CNS tissue injury which could serve as biomarkers to assess injury severity, monitor disease progression, direct treatment, and as reliable endpoints to help develop novel medical countermeasures. Recent advances in the use of blood-based biomarkers for diagnosis of traumatic brain injury (TBI) which have FDA approved assays have provided a scientific foundation for expanding the biomarker technology to brain damage caused by other CNS pathologies like viral encephalitis. Here we evaluated the ability to detect these biomarkers for encephalitic alphaviruses, encephalitis of unknown origin, and hospitalized patients with severe coronavirus disease (COVID-19). Higher levels of specific biomarkers were detected in patients diagnosed with alphavirus or unknown encephalitis which may be useful in prognosis and treatment guidance of post viral disease. Collectively, our results suggest that these blood-based biomarkers may be a good indicator for brain injury resulting from viral infection.

Diagnostic Approach and Treatment Regimens in Adult Patients Suffering from Antibody- mediated or Paraneoplastic Encephalitis.

Identification of patients with antibody-mediated encephalitis poses a diagnostic challenge, and any delay in that aspect will increase the interval until the initiation of immunotherapy and may negatively affect the patient´s clinical outcome. Within this review, we focus on therapeutic strategies in antibody-mediated encephalitis and propose how to proceed with patients who are suspected of having encephalitis of unknown origin. We further briefly outline differences in the treatment of paraneoplastic and antibody-mediated encephalitis according to its pathomechanisms.

Improved diagnosis of viral encephalitis in adult and pediatric hematological patients using viral metagenomics.

Metagenomic sequencing is a powerful technique that enables detection of the full spectrum of pathogens present in any specimen in a single test. Hence, metagenomics is increasingly being applied for detection of viruses in clinical cases with suspected infections of unknown etiology and a large number of relevant potential causes. This is typically the case in patients presenting with encephalitis, in particular when immunity is impaired by underlying disorders. In this study, viral metagenomics has been applied to a cohort of hematological patients with encephalitis of unknown origin. Because viral loads in cerebrospinal fluid of patients with encephalitis are generally low, the technical performance of a metagenomic sequencing protocol with viral enrichment by capture probes targeting all known vertebrate viral sequences was studied. Subsequently, the optimized viral metagenomics protocol was applied to a cohort of hematological patients with encephalitis of unknown origin. Viral enrichment by capture probes increased the viral sequence read count of metagenomics on cerebrospinal fluid samples 100 - 10.000 fold, compared to unenriched metagenomic sequencing. In five out of 41 (12%) hematological patients with encephalitis, a virus was detected by viral metagenomics which had not been detected by current routine diagnostics. BK polyomavirus, hepatitis E virus, human herpes virus-6 and Epstein Barr virus were identified by this unbiased metagenomic approach. This study demonstrated that hematological patients with encephalitis of unknown origin may benefit from early viral metagenomics testing as a single step approach.

Opportunistic diseases in patients with HIV infection in the intensive care unit

The aim of the study was to analyze the incidence and prevalence of opportunistic diseases and comorbidities in patients admitted in the intensive care unit. Materials and methods. A specialized intensive care unit (ICU) for patients with severe HIV infection was set up in 2014 at the infectious diseases 2nd state hospital Moscow. It provides intensive care and treatments for HIV patients with severe co-morbidities and opportunistic infections. Retrospective analysis of medical records from 2014-2016 was carried out. Also carried out was a comparative study of the most common presentation of secondary diseases with available data of HIV patients in Russia from 1993-1997. Results. The number of patients treated increased from 455 to 852, and the death rate in the department decreased from 64.8 to 50.2% since it began operating. The opportunistic infections noted were cytomegalovirus, pneumocystis pneumonia, esophageal candidiasis, tuberculosis and toxoplasmosis of the brain. The most common comorbidities were chronic hepatitis C and mixed form of chronic hepatitis with cirrhosis complications. Despite the vast diagnostic possibilities, bacterial pneumonia and encephalitis of unknown origin significantly occurred. Comparative study of secondary disease since the early 1990s revealed a significant increase in cerebral toxoplasmosis (from 1.7 to 10.4%), pneumocystis pneumonia (from 5.2 to 16.0%) and encephalitis of unspecified etiology (from 13.8 to 39.4%) Conclusion. Disease severity among HIV patients is increasing. CMV and pneumocystis pneumonia were predominant opportunistic diseases. There were significant changes in the presentation of secondary diseases compared to data from 1993-1997.

Encephalitis of Unknown Origin in Horses From Brazil

Encephalitis of Unknown Origin in Horses From Brazil

P485: Event-related potentials in patients with primary Sjögren’s syndrome

s of Poster Presentations / Clinical Neurophysiology 125, Supplement 1 (2014) S1–S339 S179 Abstract P484 – Figure 2P484 – Figure 2 neuropathy with a high variable clinical course and outcome. Despite immunotherapy up to 20% of patients remain severely disabled and mortality in the first year is approximately 4%. Aim of this study is to perform an epidemiological analysis of clinical and electrophysiological features of patients admitted in our ward for GBS in last ten years; to test the incidence of different GBS subtypes and their clinical and electrophysiological evolution; to test on our sample the prognostic value of variables known in literature and we suggested integration with new prognostic markers. We collected data prospectively from 89 patients regarding: demographic features, previous infections, clinical manifestations, kind of therapy received, motor deficit and disability (evaluated respectively with MRC sumscore and GBS disability score (GBSDS)). We measured dosage of protein in the cerebrospinal fluid (CSF). Serial nerve conduction studies (NCS) were performed. Differences between groups were compared by Fisher’s exact test. Potential prognostic factors were tested in uni and multivariable logistic analysis and was estimated by regression analysis. 19% of GBS were acute motor axonal neuropathy (AMAN) and showed more severe prognosis. High age was predictive of poor prognosis in acute inflammatory demyelinating neuropathy (AIDP) but not in AMAN. High GBSDS at nadir and cranial nerves involvement were predictive of being enable to run at 1 year. Conduction block did not have a significant distribution in GBS subtypes and showed no correlation with clinical outcome. In NCS performed between 30 and 90 days from the clinical onset, a pathological distal cMAP duration (DcMAPD) represented a distinctive marker of primary demyelinating pathophysiological mechanism, in our sample of GBS. The endurance of pathological DcMAPD showed a predictive value on long term disability in AIDP. This study confirms the key-role of serial NCS for a proper diagnosis of GBS subtypes. Further clinical-electrophysiological studies are necessary to define more inclusive work-up in GBS enabling forecasting of the patients with poorest long term outcome.

P486: Immune-modulating therapies for encephalitis of unknown origin – importance of early application for improving clinical outcomes. 2 cases of encephalitis of unknown origin who had similar clinical findings and with serial electrocencephalogram (EEG) follow up, who had considerably different outcome according to whether immune-modulating therapy was applied or not

P486: Immune-modulating therapies for encephalitis of unknown origin – importance of early application for improving clinical outcomes. 2 cases of encephalitis of unknown origin who had similar clinical findings and with serial electrocencephalogram (EEG) follow up, who had considerably different outcome according to whether immune-modulating therapy was applied or not

Persistent Intrathecal Antibody Synthesis 15 Years After Recovering From Anti– N-methyl-D-aspartate Receptor Encephalitis

Anti- N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune disorder characterized by high intrathecal antibody synthesis. Little is known about the long-term follow-up of the cerebrospinal fluid antibody status. To describe persistent intrathecal antibody synthesis in a clinically healthy person 15 years after recovering from anti-NMDAR encephalitis. Case report. Academic medical center. A 40-year-old woman who had been diagnosed as having encephalitis of unknown origin in 1995. Clinical evaluation and NMDAR antibody testing. On reexamination in 2011, the patient had fully recovered. Investigation of archived as well as follow-up serum and cerebrospinal fluid samples revealed intrathecal synthesis of NMDAR antibodies. This is the longest follow-up on a patient with anti-NMDAR encephalitis. Our findings emphasize that intrathecal antibody synthesis does not necessarily reflect disease activity and that the significance of NMDAR antibody titers needs to be interpreted for each patient according to the clinical context.

Anti-NMDA-receptor encephalitis presenting as postpartum psychosis in a young woman, treated with rituximab

A severe paraneoplastic form of acute encephalitis associated with antibodies against the N-methyl D-aspartate (NMDA) receptor typically occurs in young individuals and is associated, but not always, with an underlying tumor. If diagnosed early, initiation of immunotherapy and tumor removal (if present) may result in recovery. We report a case in a 25-year-old young woman who presented to our medical center with postpartum psychosis. Treatment with rituximab (a chimeric monoclonal antibody against the protein CD20) resulted in gradual improvement in mental status and resolution of seizure activity episodes. A year after diagnosis and treatment, the patient was doing well without recurrences, and no tumors appeared. This is the first described case of anti–NMDA-receptor antibodies encephalitis that presented initially as a postpartum psychosis disorder and was successfully treated with rituximab.

Disappearance of a deadly disease acute hepatomyoencephalopathy syndrome from Saharanpur

Sir, Apropos our earlier correspondence1, there has been a drastic reduction of the deadly disease affecting young children of Saharanpur district of western Uttar Pradesh (UP). The outbreaks of this unexplained acute brain disease in children was recurring every year, with very high (70-80%) fatality for over two decades. It was earlier known as “Saharanpur encephalitis” or “acute viral encephalitis of unknown origin”. However, it was later found not encephalitis, but a multi-system disease affecting liver, muscle and brain and re-named “acute hepatomyoencephalopathy (HME) syndrome” caused by phytotoxins2. Later, the source of toxicity was found to be to the consumption of beans of a ubiquitous herb Cassia occidentalis by unsupervised young children of poor families3,4. Cases occurred only in September through December every year coinciding with the poding season of this annual plant. After publication of these studies, a meeting of all stakes-holders that comprised paediatricians, general physicians, local health and district administrations, health agencies, and media representatives was conducted in 2007 at the district headquarter city of Saharanpur, the worst affected district. Later, the local unit of Indian Academy of Pediatrics, with support from the health agencies [mainly UNICEF and National Polio Surveillance Project (NPSP)], district administration, and media launched a massive educational campaign in and around Saharanpur district to educate people about the poisonous nature of the weed. Pamphlets in local language were printed and distributed; the ‘live weed’ was exhibited/displayed at the registration counters of all hospitals and nursing homes, frequently-visited government offices, and at other public places. The task of massive uprooting of the weed was taken by the forest and Public Works departments. Instructions were given to village ‘Pradhans’ to employ labourers for destroying the weed from the neighbourhoods. Regular meetings were organized with ‘Gram Panchayat’ members and villagers were educated regarding the toxic nature of the plant. Media played a significant role in creating awareness among rural population. The entire operation was supervised by the district magistrate of Saharanpur. This massive campaign, sustained over 2 years led to drastic reduction in the number of cases in the district. As evident from the Table, the total number of admissions in Saharanpur district hospital which has a special ‘encephalitis ward’ to admit these cases, fell from 100-200 cases admitted annually up to 2007 to 15-30 in 2008 and 2009 and to nil in 2010. Table Numbers of admitted cases and deaths in Saharanpur District Hospital, 2002-2010 There is an urgent need to carry out similar awareness/education campaigns in all other affected districts of western UP and Uttarakhand. The lessons learnt are that there is no substitute to systematic and professional investigation of any outbreak of unknown cause2–4. This experience deserves wider publicity and public understanding. Healthcare professionals both in private and public sectors should have inquisitive mind and motivation to solve local problems by team approach. Public-private partnership in health sector can help achieving some difficult, unattainable targets. And, media can also play a very important constructive role in raising awareness among general public.

Retrospective analysis of NMDA receptor antibodies in encephalitis of unknown origin

Anti-NMDA-receptor (NMDAR) encephalitis is a severe disorder that occurs in association with antibodies to the NR1 subunit of the NMDAR and results in a characteristic syndrome. To determine in a single institution setting whether patients previously diagnosed with encephalitis of unknown origin had anti-NMDAR encephalitis. Charts of 505 patients aged 18 to 35 years admitted to the intensive care unit (ICU) during a 5-year period were retrospectively reviewed for criteria of encephalitis of unknown etiology. These included encephalitic signs with psychiatric symptoms (agitation, paranoid thoughts, irritability, or hallucinations); seizures; CSF inflammation; and exclusion of viral or bacterial infection. Archived serum and CSF samples of patients fulfilling these criteria were examined for NMDAR antibodies. Follow-up visits allowed the analysis of the natural disease course and estimation of prognosis. Seven patients (all women) fulfilled the indicated criteria; 6 of them had NMDAR antibodies. Ovarian teratomas were detected in 2 patients, in one 3 years after the onset of encephalitis. Outcome was favorable in all patients. One patient without teratoma improved spontaneously along with disappearance of NMDAR antibodies. Anti-NMDAR encephalitis represented 1% of all young patients' admissions to the ICU. Six of 7 cases with the indicated clinical criteria had anti-NMDAR encephalitis. NMDAR antibodies should be tested in all patients with encephalitis who fulfill these criteria.

Under the Radar:BalamuthiaAmebic Encephalitis

We present data from 9 years (1999-2008) of tests for Balamuthia mandrillaris, an agent of amebic encephalitis that were conducted as part of the California Encephalitis Project. Specimens obtained from patients with encephalitis were sent to the California Encephalitis Project for diagnostic testing; a subset of these specimens were tested for Balamuthia species. Tests included indirect immunofluorescent staining of sections for amebae, fluorescent antibody staining and enzyme-linked immunosorbent assay for serum titers, and polymerase chain reaction for Balamuthia 16S mitochondrial DNA. Cerebrospinal fluid (CSF) samples obtained from patients with diverse types of encephalitis were also tested for a broad range of cytokines. Of >3500 cases referred to the California Encephalitis Project, 10 were found to be amebic encephalitis on the basis of serologic and CSF tests and examination of stained tissue sections. Most of these cases would have been described as "encephalitis of unknown origin" if it were not for the California Encephalitis Project. Nine of the 10 patients were male; ages ranged from 1.5 to 72 years. All patients had abnormal neuroimaging findings and abnormal CSF composition. The more common symptoms at presentation included headache, seizures, cranial nerve palsies, and lethargy. CSF specimens from patients with Balamuthia infection had significant elevations in the levels of cytokines IL-6 and IL-8, compared with specimens obtained from persons with viral or noninfectious encephalitides. Balamuthiasis is difficult to diagnose, and it is likely that cases go unrecognized because clinicians and laboratorians are unfamiliar with the disease. Alerting the medical community to this disease may lead to earlier diagnosis and improve the chances of survival.

Specific in vitro IgG subclass synthesis and lymphocyte proliferation responses in herpes virus encephalitis

Cerebrospinal fluid, peripheral blood lymphocytes (PBL) and sera from 5 patients with herpes simplex encephalitis (HSVE), 3 with varicellae zoster (VZV) meningoencephalitis and 5 with encephalitis of unknown origin (NUD) were analyzed. Lymphocytes from both blood and CSF were shown to synthesize anti-VZV IgG subclasses in VZV meningoencephalitis and anti-HSV IgG subclasses in HSVE. The subclass patterns of CSF and in vitro synthesized anti-viral IgG were similar, suggesting that a considerable portion of the antiviral IgG subclasses detected are synthesized in the CNS compartment. Antigen presentation in vitro seemed to produce a heterologous IgG4 and/or 3 response in 3 patients. Lymphocyte proliferation was detectable in response to HSV and VZV, respectively.

P02-47 Catatonia in autism and other neurodevelopmental disorders

Objective:This paper reviews the presence of catatonia in neurodevelopmental disorders, with emphasis on autism spectrum disorders. Clinical presentations are reviewed, followed by catatonia treatment algorithms including lorazepam and ECT.Method:A literature review of catatonia in autistic, developmentally disabled and neurologically impaired populations was conducted. This was combined with the author's experience with patients with autism as well as traumatic, infectious and congenital brain injuries, all of whom developed frank catatonia.Results:Catatonia is a unique neurobiological syndrome with multiple psychiatric, neurological, medical and drug-related etiologies. Most commonly associated with bipolar affective illness, catatonia has also been found in 12-17% of patients with autism. Other neurodevelopmental disorders may similarly present with catatonia. Blueprints for treatment of catatonia include lorazepam and electroconvulsive therapy. While current literature supports the appropriateness, safety and efficacy of ECT for catatonia in autistic and developmentally disabled populations, treatment barriers may persist. The following cases are presented:Pt 1: A 14 year-old female with encephalitis of unknown origin and profound catatonia. Cultural barriers prevented treatment.Pt 2: A 20 year-old male with high-functioning autism and catatonia characterized by alternating stupor and extreme psychomotor agitation with self-injury.Pt 3: A 15 year-old male with congenital agenesis of the cerebellum and vermis in frank catatonic stupor mistakenly attributed to his disability.Conclusion:Catatonia is readily diagnosed in a variety of neurodevelopmental conditions including autism, and is eminently treatable with lorazepam and/or ECT in this population. Treatment barriers should be recognized and remedied.

In vivo detection of hepatitis C virus (HCV) RNA in the brain in a case of encephalitis: evidence for HCV neuroinvasion

We report here a 27-year-old woman who presented with encephalitis of unknown origin. Magnetic resonance imaging (MRI) of the brain revealed leukoencephalopathy, cerebrospinal fluid showed signs of inflammation. Serum and brain biopsy tissue was tested positive for hepatitis C virus (HCV). Neuropathological investigation supported the hypothesis of viral encephalitis. C3, C4 and cryoglobulins as well as cerebral MR-angiography were normal. Neurological complications of HCV infection other than hepatic encephalopathy are generally attributed to parainfectious phenomena. This is the first case of HCV-RNA detection in vivo in human brain in literature and it raises the possibility that HCV is able to induce encephalitis caused by neurotrophism. This is supported by the fact that there is a growing body of literature on HCV-induced cerebral dysfunction and laboratory findings indicating HCV neuroinvasion.

A patient with bilateral immature ovarian teratoma presenting with paraneoplastic encephalitis

Background. Teratomas can be accompanied by a paraneoplastic syndrome with severe neurological and psychiatric manifestations or even death as a result. These symptoms mostly precede the gynecological diagnosis. Case. We present a case of a 32-year-old woman with paraneoplastic encephalitis. The gynecologic oncologist was consulted because of suspicion on a pelvic mass. Physical examination and transvaginal ultrasound (TVU) showed enlarged ovaries. Bilateral salpingo-oophorectomy and complete staging were performed resulting in FIGO stage Ib grade 1 immature teratoma. After surgery her neurological condition improved significantly. Conclusion. In case a young woman presents with encephalitis of unknown origin she should also be referred to the gynecologist to rule out ovarian pathology, especially since surgical removal of a teratoma may result in clinical improvement or even complete recovery.

Persistent vegetative state with encephalitis in a pregnant woman with successful fetal outcome

Case report A 28 year old woman, gravida 3, para 2, consulted her physician at 22 weeks of gestation for a flulike syndrome. Pharyngitis was suspected and antibiotics were given. Vomiting, vertigo, left sided paraesthesia and dysarthria developed over the next few days. The patient was referred to our centre in December 2001. At the first examination, she was conscious, with confusion and fever. She had an internuclear ophthalmoplegia with monocular nystagmus; her gait was ataxic, without dysmetria. She presented left hemiparesis, dysphagia and false passage. During the next week, the neurological status worsened: the patient was able to open her eyes but unable to respond to simple commands; she became unconscious with finally a persistent vegetative status. The patient was admitted to the Department of Neurosurgery, which is located immediately beside the obstetric unit at our institution. Her neurological status remained unchanged for 10 weeks. The brain magnetic resonance imaging (MRI) showed numerous hypersignals in the cerebral trunk, corpus callosum and basal hemispheric brain (Fig. 1). Routine biochemical tests were normal. The analysis of the cerebrospinal fluid showed a non-specific reaction (normal glucose, 1.5 g/L protein, 11–30 leucocytes/mm 3 ). The immunologic tests found high concentrations of IgM against Epstein–Barr virus and cytomegalovirus and an antiprothrombin-like circulating anticoagulant. The direct viral and bacteriological cultures were negative. The diagnosis was therefore encephalitis of unknown origin. The patient was separated and not married to the father of the fetus. Her parents were the legal decision makers in this case. They received complete information on medical findings and data of the literature, and we told them that in our opinion, the pregnancy should be continued. However, the parents wrote to political and medical authorities to request for the pregnancy to be terminated. We asked a judge to appoint an independent arbiter. We also asked for an opinion from the National Academy of Medicine and National Committee of Ethics. All these authorities agreed

Retrospective identification of three undiagnosed cases of measles encephalitis.

It has long been recognised that neuroinvasion may occur as a rare complication of measles. According to cases reported in the medical literature [1], measles virus (MV) can persist in the central nervous system producing chronic neurological disease without systemic viremia [2, 3]. In most industrialised countries, the introduction of live attenuated measles vaccines has resulted in the virtual disappearance of measles as a common childhood disease and strongly reduced the numbers of patients with MV-related neurological disease. However, measles did not completely disappear: occasional clinical cases are still observed due to importation of MV from endemic areas [4], and larger outbreaks continue to occur amongst clusters of unvaccinated individuals [5]. It is difficult to assess how many people are exposed to wild-type MV as a result of these cases, but the virus is only rarely considered as a possible cause of neurological symptoms. The aim of the present study was to identify undiagnosed cases of MV-related encephalitis. Combined evaluation of clinical data, results of diagnostic serological tests and reverse transcriptase polymerase chain reactions carried out on cerebrospinal fluid and bronchoalveolar lavage specimens may shed light on the aetiology of these cases of encephalitis. A retrospective analysis was performed on 53 patients admitted to our hospital during 1998 with encephalitis of unknown origin. Their mean age was 48 years (range, 19–74 years). Clinical features included fever, headache, facial weakness, altered mental status, seizures, impaired hearing, motor disturbances, limb paralysis and respiratory distress. Patients were tested for several viral infections that may be associated with encephalitis including herpes simplex viruses 1 and 2, cytomegalovirus, Epstein-Barr virus, JC virus (the causative agent of progressive multifocal leukoencephalopathy), tick-borne encephalitis virus, dengue virus, HIV-1 and HIV-2 and Mycoplasma pneumoniae. All patients were negative for all of these agents. In the present study, serum and cerebrospinal fluid samples were tested for the presence of MV-specific IgM and IgG antibodies using a commercially available IgM capture enzyme immunoassay (Meddens Diagnostics, The Netherlands) and an enzyme immunoassay developed in-house based on whole virus, respectively. Two patients, 29 and 48 years of age, were found to be MV IgM-positive in both serum and cerebrospinal fluid, and in one 73-year-old patient borderline levels of MV-specific IgM serum antibodies were detected. This last patient had chronic lymphatic leukaemia and was undergoing immunosuppressive treatment. During the previous 2 years he had suffered recurrent opportunistic infections, with fever and pneumonia, zoster, vasculitis, and hepatitis. Serum samples collected 1 year before his encephalitis was diagnosed were MV IgM-negative and contained low levels of MV-specific IgG antibodies. An MV-specific reverse transcriptase polymerase chain reaction [6] was carried out on a bronchoalveolar lavage sample to diagnose the cause of the patient’s pneumonia that had developed during his encephalitis and was found positive. Sequence analysis of the amplicon demonstrated that the virus belonged to genotype C2 (GenBank, http://www.ncbi.nlm.nih.gov/Genbank/; accession number AF519493), which was a common European genotype during the last decade of the previous century. Blast analysis identified a virus isolated in 1992 in Tilburg, The Netherlands, as the only identical sequence in the GenBank database, but almost identical viruses were involved in a measles outbreak in Luxembourg in 1996 [7]. The results of the present study strongly suggest that undiagnosed encephalitis may be associated with MV infection: in 2 of 53 undiagnosed encephalitis cases, MVspecific IgM antibodies were found in serum and cerebrospinal fluid, strongly indicating that these patients were suffering from an MV infection. In a third patient,

Predictors and underlying causes of medically intractable localization-related epilepsy in childhood

The goal of this study is to clarify the prognostic factors in childhood localization-related epilepsy in a tertiary medical center. Children (n = 113) with symptomatic and cryptogenic localization-related epilepsy were divided into groups of intractable patients (average seizure frequency: one or more per month during the 6 months before the last follow-up; n = 40) and well-controlled patients (no seizures for at least 1 year before the last follow-up; n = 73). Clinical and electroencephalogram (EEG) factors were examined to elucidate prognostic factors. The subtypes of epilepsies and causes were also investigated. Univariate analyses indicated that the following factors were correlated with seizure outcome: (1) seizure type at the first visit; (2) seizure frequency; (3) underlying cause; (4) age at onset of epilepsy; (5) status epilepticus occurring as the first seizure and before the first visit; and (6) diffuse epileptic discharges on first visit interictal EEGs. Multivariate analyses revealed that seizure type at the first visit, seizure frequency, status epilepticus before the first visit, and underlying causes were significant independent predictive factors. The rate of intractable patients was highest in multilobar epilepsy, followed by frontal-lobe epilepsy. Regarding etiologies, the intractable group contained nine patients with encephalitis of unknown origin and three each with localized cortical malformation and mesial temporal sclerosis.