Anti-NMDA receptor encephalitis presenting as isolated aphasia in an adult

ABSTRACT

Anti-NMDA receptor (NMDA-r) encephalitis is a relatively rare cause of autoimmune encephalitis with divergent clinical presentations. We report a case of an adult patient with anti-NMDA-r encephalitis presenting with isolated, abrupt-onset aphasia. Her condition remained unaltered over a period of 6 months. The patients’ electroencephalogram findings were typical for NMDA-r encephalitis; however, her magnetic resonance imaging and cerebrospinal fluid analysis were normal. She responded well to immunotherapy, and aphasia eventually resolved. The natural course of the present case contradicts the rapidly progressive nature of typical NMDA-r encephalitis. Furthermore, it broadens the clinical spectrum of anti-NMDA-r encephalitis, to incorporate isolated, nonprogressive aphasia.     

Cerebrospinal fluid in acute necrotizing encephalitis. Hypochlorrhachia as a diagnostic aid

The chemical and microscopic findings in the cerebrospinal fluid (CSF) were compared in patients with acute necrotizing encephalitis (due to herpes simplex virus), nonherpetic aseptic meningoencephalitis and tuberculous meningitis. The prominent findings in the CSF of the patients with herpes simplex encephalitis were an increase in white and red blood cells, increased protein, normal glucose and low chloride levels. The latter finding differentiates this disease from other forms of viral encephalitis and may be helpful in the establishment of early diagnosis and treatment.     

A case of Balamuthia mandrillaris meningoencephalitis

Balamuthia mandrillaris is a newly described pathogen that causes granulomatous amebic encephalitis, an extremely rare clinical entity that usually occurs in immunosuppressed individuals. We report a case of pathologically proven Balamuthia encephalitis with unusual laboratory and radiologic findings. A 52-year-old woman with idiopathic seizures and a 2-year history of chronic neutropenia of unknown cause had a subacute illness with progressive lethargy, headaches, and coma and died 3 months after the onset of symptoms. Cerebrospinal fluid (CSF) glucose concentrations were extremely low or unmeasurable, a feature not previously described (to our knowledge). Cranial magnetic resonance imaging scans showed a single large temporal lobe nodule, followed 6 weeks later by the appearance of 18 ring-enhancing lesions in the cerebral hemispheres that disappeared after treatment with antibiotics and high-dose corticosteroids. The initial brain biopsy specimen and analysis of CSF samples did not demonstate amebae, but a second biopsy specimen and the postmortem pathologic examination showed Balamuthia trophozoites surrounded by widespread granulomatous inflammation and vasculitis. The patient's neutropenia and antibiotic use may have caused susceptibility to this organism. Amebic meningoencephalitis should be considered in cases of subacute meningoencephalitis with greatly depressed CSF glucose concentrations and multiple nodular lesions on cerebral imaging. Arch Neurol. 2000;57:1210-1212     

A case of measles meningoencephalitis with marked increase of plasma cells in cerebrospinal fluid

Marked increase of plasma cells in cerebrospinal fluid (CSF) was observed in a 22-year-old female patient with measles meningoencephalitis. Typical measles exanthema was followed, 3 days later, by neurological abnormalities such as confusion, severe meningeal signs and bilateral pyramidal signs. Immunological examination showed slight elevation of IgG, normal T cell subsets and NK cell activity in peripheral blood. The antibody titer of measles was 32x in serum (4x after 2 months). CSF contained 167 cells/mm3, 66% of which was plasma cells. Total protein was 75 mg/dl, and IgG (24.5 mg/dl) showed high values. The antibody titer of measles was 4x (1x after 2 months). The antibody index was 7.15 (N = 2). The anti-myelin antibody was 8x. Oligoclonal band in CSF was negative. The appearance of large number of plasma cells in CSF in viral meningoencephalitis is extremely rare in the literature. However, B cell activation in peripheral blood in measles encephalitis has been reported. Therefore, immunologically abnormal findings in CSF of this case suggest marked B cell activation occurring in the central nervous system in measles meningoencephalitis.     

Chemotherapy-induced autoimmune-mediated encephalitis during germinoma treatment

BackgroundAutoimmune mediated encephalitis (AME), which includes autoantibody-associated encephalitis and acute disseminated encephalomyelitis, is a common cause of encephalitis as well as infectious encephalitis in children. AME may be triggered by autoimmune responses to paraneoplastic syndromes and infections. Infectious encephalitis associated with an immunocompromised status caused by anti-cancer chemotherapy is well recognized; however, there have been few reports on the relationship between AME and chemotherapy.Case reportA ten-year-old previously healthy, developmentally normal girl was diagnosed with a pure germinoma in the suprasellar region. Following 30 days of induction chemotherapy, she developed a depressed level of consciousness with accompanying right hemiplegia, aphasia, and unexplained fever. Cerebrospinal fluid (CSF) analysis revealed positive oligoclonal bands and elevated neopterin levels. Neither atypical cells suggesting tumor exacerbation nor pathogens known to cause encephalitis were identified in the CSF. She was administrated immunosuppressive therapy and her symptoms rapidly improved. No known autoantibodies associated with autoantibody-associated encephalitis were identified in blood or CSF. However, the presence of oligoclonal bands and elevated neopterin levels in the CSF, and the favorable response to immunosuppressive therapy were consistent with an AME diagnosis. Thirteen days after the third course of chemotherapy, the patient developed a depressed level of consciousness again. Due to the recurrence of encephalitis, re-administration of immunosuppressive therapy was performed, which led to improvement in her symptoms. Recurrence of encephalitis has not occurred for 1 year after completion of chemotherapy.ConclusionThe chemotherapy-induced abnormal immune response might have triggered the AME.     

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.     

Clinical signs as a guide for performing HSV-PCR in correct diagnosis of herpes simplex virus encephalitis

BACKGROUND: Clinical criteria (symptoms) are not reliable enough to differentiate between different causes of encephalitis. The clinical presentation of herpes simplex virus encephalitis (HSVE) is not classically constant and in such a patient, therefore, it is vital to make early diagnosis. AIMS: To investigate satisfactory and crucial clinical signs as guide to perform HSV-PCR in a rapid diagnosis of herpes simplex virus encephalitis. MATERIAL AND METHODS: A total of 156 CSF specimens from 70 patients with clinically suspected HSVE or meningoencephalitis were tested. The criteria for cases suspected of HSVE were fever >380C, altered mental status and other critical manifestations. CSF features, irregularity in brain CT scan and MRI findings were also assessed. All the specimens were collected before and after Acyclovir treatment. Polymerase chain reaction was performed using primers, which amplified DNA sequences for both HSV-1 and HSV-2. STATISTICAL ANALYSIS: To analyze data, two-tailed Fisher's exact test and the X2-test with Yates' correction were used as appropriate. The odds ratio was used to express the strength of association between the clinical factors and the PCR results. RESULTS: HSV-DNA was detected in 18% of the specimens, belonging to 25.7% of the patients. Results indicate that the majority of the clinical symptoms are not specific to definitive clinical diagnosis of HSVE, except alteration in the level of consciousness--odds ratio [0.27 (0.07-0.96) (P=0.033)]; and lateralization sign--odds ratio [4.7 (0.98-22.6) (P=0.023)]. However, laboratory data, including total white blood cell count, especially the number of lymphocytes, and MRI findings could be suggested for HSV-PCR examination. CONCLUSION: At the first admission, a preliminary finding of at least two important clinical features mentioned above along with the pattern of CSF cell and differential counts could be sufficient to perform HSV-PCR which could ultimately result in a rapid and correct diagnosis of herpes simplex encephalitis.     

Enteroviral encephalitis leading to a locked-in state.

Millions of children are infected by enteroviruses each year, usually exhibiting only mild symptoms. Although enteroviruses are a common cause of community-acquired aseptic meningitis, enteroviral meningitis usually has a benign course. We describe a 14-year-old patient with enteroviral meningoencephalitis diagnosed by polymerase chain reaction. Her level of consciousness declined rapidly after hospital admission and resulted in a locked-in state. Although she experienced slow neurologic improvement, residual neurologic deficits remain. Although there is a general awareness of the characteristics of enteroviralencephalitis, this case report is significant in presenting a case of unusual severity and sequelae. To our knowledge, this is the first published report of an enterovirus encephalitis leading to a locked-in-state.     

Quantitative CSF PCR in Epstein-Barr virus infections of the central nervous system

Acute Epstein-Barr virus (EBV) infection of the central nervous system (CNS) is associated with meningoencephalitis and other neurological syndromes and with CNS lymphomas (CNSLs). Diagnosis is based on serological studies and more recently on detection of EBV DNA in cerebrospinal fluid (CSF) by polymerase chain reaction (PCR). We measured EBV DNA by quantitative PCR and EBV mRNA by RT-PCR in the CSF in patients with EBV-associated neurological disorders. EBV was identified as the cause of CNS infection in 28 patients: 14 with CNSL, 10 with encephalitis, and 4 with postinfectious neurological complications. CSF analysis showed that patients with CNSL had high EBV load (mean +/- standard error of 4.8 +/- 0.2 log(10) DNA copies/ml) and low leukocyte counts (22 +/- 7 cells/microl); encephalitis was characterized by high EBV load (4.2 +/- 0.3 log(10) DNA copies/ml) and high leukocyte counts (143 +/- 62 cells/microl); and patients with postinfectious complications showed low EBV load (3.0 +/- 0.2 log(10) DNA copies/ml) with high leukocyte counts (88 +/- 57 cells/microl). Lytic cycle EBV mRNA, a marker of viral replication, was identified in 10 CSF samples from patients with CNSL and encephalitis. These studies demonstrate the utility of quantitative CSF PCR and establish the presence of lytic cycle EBV mRNA in CSF of patients with EBV-associated neurological disease.     

Status epilepticus revealing syphilitic meningoencephalitis

The incidence of seizures in neurosyphilis ranges from 14 to 60%, however, neurosyphillis presenting with status epilepticus (SE) is rare. We report the case of a 49 year old man with no history of epilepsy and with a 9-year history of untreated syphilitic chancre. He presented in October 2005 with four stereotyped epileptic seizures lasting less than 2 minutes followed by a prolonged seizure lasting 20 minutes without recovery of consciousness. He regained consciousness after admission in intensive care unit for SE management. Brain CT scan showed disappearance of cortical sulci with collapse of ventricles. Ophthalmological examination revealed papillary hyperemia. Interictal EEG showed bi-frontal bi- and triphasic spikes. Syphilitic serology in blood then in cerebrospinal fluid (CSF) confirmed the diagnosis of neurosyphilis. The clinical course was favorable after early administration of penicillin and carbamazepine with total remission of seizures. We underline the rarity of neurosyphilis vasculitis as possible etiology of SE and underline the crucial value of syphilitic serology in blood then in CSF, especially within any atypical presentation of encephalitis, meningoencephalitis; or encephalitis and vasculitis. We highlight the very good prognosis if treated precociously.     

Acute onset of tuberculous meningoencephalitis presenting with symmetric linear lesions in the bilateral thalamus: a case report]

A 18-year-old woman was admitted to our hospital because of high fever and headache. Nuchal stiffness was present, and a CSF examination showed lymphocyte-domonant pleocytosis and a decreased level of glucose. Although antibiotics, aciclovir and an antimycotic drug were administered, disturbance of consciousness, involuntary movements, and pyramidal tract signs appeared. Soon after the medications were changed to antituberculous medicines, the meningoencephalitis started to subside, and was finally cured. Judging from the clinical findings, the CSF findings, the effectiveness of antituberculous medicines, an elevated ADA level in CSF, and positive conversion in tuberculin tests, the final diagnosis was made as tuberculous meningoencephalitis. At the severest stage of the disease, a brain MRI showed symmetric, linear lesions without the effect of Gd-enhancement in the bilateral thalamus, which thereafter disappeared along with the healing of the illness. From all these things, we conclude that thalamic and other parenchymal lesions should be kept in mind in case of acute tuberculous meningoencephalitis.     

Acute meningoencephalitis caused by Streptococcus pneumoniae, mimicking acute disseminated encephalomyelitis]

A 57-year old woman had a five-day history of cough and high fever followed by abnormal behavior and headache with signs of meningeal irritation. A cerebrospinal fluid (CSF) exam revealed polymorphonuclear pleocytosis. Streptococcus pneumoniae was cultured from the patient's CSF and serum. Clinical features and laboratory investigations supported a diagnosis of pneumococcal meningoencephalitis. After treatment with intravenous meropenem (MEPM), the patient's laboratory data improved and her neck stiffness disappeared, but a brain MRI showed white matter lesions in the bilateral frontal and temporal lobes. The patient responded to pulse therapy with intravenous methylprednisolone (1 g/day), carried out over three days: she recovered neurological function and her MRI lesions resolved. We report a case of acute meningoencephalitis caused by Streptococcus pneumoniae, mimicking acute disseminated encephalomyelitis (ADEM). We suggest that pneumococcal infection is one of the pathogenetic factors in ADEM.     

A case of non-herpetic acute encephalitis with autoantibodies for ionotropic glutamate receptor delta2 and epsilon2]

We report a 45-year-old woman admitted to our hospital due to fever, consciousness disturbance, and severe seizures. Based on her signs and symptoms and clinical course, a diagnosis of non-herpetic acute encephalitis was made. She received antibiotic drugs, acyclovir, gamma-globulin, and steroid pulse therapy (methylprednisolone 1 g/day, 3 days). The patient's signs, symptoms and severe seizure showed marked improvement, but she still showed monthly seizure attacks and both anterograde and retrograde amnesia Viral infection and autoimmune response after viral infection may have been involved in non-herpetic acute encephalitis in our patient. Recently, autoantibodies to GluRepsilon2 and VGKC were reported in cases of non-herpetic acute limbic encephalitis (NHALE). In our patient, we detected IgM type autoantibody to GluRdelta2 and epsilon2 in both the CSF and serum, and these antibodies normalized in the CSF with the clinical course. Autoantibodies to GluRdelta2 and epsilon2 may be involved in the clinical symptoms and pathogenesis of non herpetic acute limbic encephalitis. This is the first report of MRI-positive non-herpetic acute encephalitis with autoantibodies to GluRdelta2 and epsilon2.     

Periodic EEG complexes in infectious mononucleosis encephalitis.

The presence of periodic EEG complexes in patients with an acute viral encephalitis is generally held to suggest that infection is due to herpes simplex. We now report a patient with clinical and laboratory findings of infectious mononucleosis, and neurologic involvement manifested by lymphocyte meningitis, coma, seizures, aphasia, hemiparesis and hemianopsia. Serial EEGs showed periodic, predominantly left-sided slow wave complexes occurring every 4 to 5 seconds, which disappeared with clinical resolution of the illness. In view of our findings and the similar findings reported previously by others in another case of infectious mononucleosis encephalitis, an EEG showing periodic complexes in the clinical setting of acute viral encephalitis should not be considered pathognomonic of herpes encephalitis, and infectious mononucleosis should be included in the differential diagnosis.     

Listeriosis of the central nervous system

Listeriosis of the CNS is an inflammatory disease of the central nervous system that occurs mostly sporadically or occasionally as a limited epidemic. The pathogens are generally ingested with the food. Whether or not the infection becomes manifest in an exposed person depends on the number of pathogens ingested, on the virulence of the Listeria strain and on the individual disposition. It appears to be of decisive importance for an infection that the cellular immunodefense mediated by the T cells is disturbed; however, even persons without any previous disease worth mentioning may be affected. The characteristics of the various CNS manifestations are demonstrated via the case histories of 12 own patients (acute meningitis and meningoencephalitis, brain stem encephalitis, brain abscess, meningoencephalitis with infected cerebral infarct, chronic recidivating encephalitis). Early neurological focal signs and symptoms, combined with CSF findings atypical for bacterial CNS disease, should not be taken lightly and may point to listeriosis even though they are not specific for CNS listeriosis. The decisive criterion is the proof of the pathogen in the blood or CSF or the proof of antibody titre changes in the serum. Recent CSF diagnostic methods such as CSF lactate determination and the identification of IgG-positive B lymphocytes are useful in differentiating between viral and noninflammatory CNS disease; most important for follow-up are repeat CSF examinations. High-dosage ampicillin or amoxycillin treatment combined with gentamycin is the therapy of choice in CNS listeriosis. The bactericidal effect achieved thereby is desirable especially if immunodefense is disturbed. Prognosis of CNS listeriosis depends on the underlying disease in each case. The high mortality even among persons who had been healthy before the infection, is at least in part due to delayed diagnosis.     

Electrofocusing and electrophoresis of cerebrospinal fluid proteins in CNS disorders of known or probable infectious etiology.

The CSF and sera of 17 patients with meningoencephalitis or encephalitis, 10 with meningitis or meningomyelitis, 5 subjects with postencephalitic sequelae and 2 with arachnoiditis were studied. Diseases involving the intracranial CNS parenchyma were found to give CSF electrofocusing findings differing from those of the other diagnostic subgroups. Differences regarding subfraction patterns of the gamma-globulin region seemed to be influenced of whether supra- or infratentorial structures were affected. The present study seems to indicate that the abnormal CSF-protein patterns found on electrofocusing were not only influenced by temporal but also by spatial factors.     

The clinical usefulness of MRI diffusion weighted images in herpes simplex encephalitis-like cases]

We examined the serial MRI diffusion weighted images (DWIs) in two patients with acute viral encephalitis similar to herpes simplex encephalitis (HSE). Patient 1. A 27-year-old woman was admitted to the psychiatry ward for her confusional state and convulsions. Because of abnormal CSF findings she was transferred to the neurology ward, and the infusion of acyclovir was started. On disease day 5. MRI demonstrated high signal intensity in the left lateral lobe both on T2 weighted images (T2WIs) and DWIs. On day 18, MRI showed progression of the lesions, so acyclovir was changed to ara-A. On day 26, no improvement was seen clinically or radiologically. Then, combination therapy with acyclovir, ara-A and gamma-globulin was began. On day 36, she recovered completely, and abnormal intensity in MRI disappeared both on T2WIs and DWIs. Therefore, antiviral agent therapy was discontinued. Patient 2. A 31-year-old man was admitted for headache, fever and aphasia. On the next day, acyclovir was started and both DWIs and T2WIs of MRI demonstrated a high signal intensity in the left temporal lobe. Ten days later, he became perfectly well, and the increased signal intensity disappeared on DWIs, but not on T2WIs. Treatment was therefore discontinued. No relapse was in either patient. We concluded that serial MRI DWIs may be useful to determine when to discontinue the treatment in encephalitis.     

A fatal case of coxsackievirus B4 meningoencephalitis

BACKGROUND: Coxsackieviruses and echoviruses are common causes of aseptic meningitis, but they rarely cause life-threatening illness. We report a fatal case of coxsackievirus B4 meningoencephalitis in a woman who developed extrapyramidal symptoms suggestive of encephalitis lethargica. The exact causative agent of encephalitis lethargica has rarely been found, but most cases of the syndrome are assumed to be of viral origin. CASE DESCRIPTION: A 33-year-old woman previously treated with methylprednisolone and cyclophosphamide for Henoch-Sch?nlein purpura was transferred from a referring hospital because of sore throat, fever, and chills. Her neurologic findings progressed from headache with mild photophobia to lethargy, cogwheeling, increased tone in all 4 limbs, and brisk reflexes. The patient was diagnosed as having coxsackievirus B4 meningoencephalitis and, despite treatment with the experimental antiviral agent pleconaril, died of an overwhelming central nervous system infection and myocarditis. Magnetic resonance imaging showed focal hyperintense lesions in the substantia nigra that corresponded to the location of pathological changes seen at autopsy. CONCLUSIONS: This patient had a fulminant coxsackievirus B4 viral meningoencephalitis with a clinical pattern reminiscent of encephalitis lethargica and striking focal abnormalities in the substantia nigra identified on magnetic resonance imaging. The magnetic resonance imaging findings correlated with pathological changes identified at autopsy that were similar to the pathological findings observed in patients with encephalitis lethargica and postencephalitic parkinsonism. It is likely that the patient's immunocompromised state led to an overwhelming infection from an otherwise relatively innocuous viral infection.     

Autoantibodies against glutamate receptor epsilon2-subunit detected in a subgroup of patients with reversible autoimmune limbic encephalitis

We investigated the presence of autoantibodies against glutamate receptor (GluR) epsilon2 in serum and cerebrospinal fluid (CSF) samples from 12 consecutive patients with acute encephalitis/encephalopathy by immunoblotting using recombinant GluR epsilon2 as antigen. In 4 patients, IgM autoantibodies against GluR epsilon2 were detected in CSF in the early phase of the disease but were not detectable after several months. Seizures and psychiatric symptoms were noted during the acute phase of the disease in these 4 patients, who showed various degrees of residual amnesia. Immunotherapy was performed on 3 patients (patients 1, 3 and 4), and they showed marked improvements. Immunohistochemistry using these patients' sera showed that immunoreactivity is specifically detected in the cytoplasm of rat hippocampal and cortical neurons. The clinical features and neuroimaging findings of patients with IgM autoantibodies against GluR epsilon2 in CSF resemble those of patients with reversible autoimmune limbic encephalitis.     

A case of primary Sj?gren's syndrome presenting with aseptic meningoencephalitis associated with sarcoidosis]

A 64-year-old Japanese woman with sarcoidosis and primary Sj?gren's syndrome was admitted to our hospital in January 1998 for consciousness loss. Physical examination revealed meningeal signs and hyperreflexia in the lower limbs. Laboratory investigations showed hypergammaglobulinemia and high titers of autoantibodies such as RF, ANA, anti SS-A and SS-B antibody. In addition, she had keratoconjunctivitis, and an apple-tree pattern was observed in sialography, but serum ACE was normal. In the cerebrospinal fluid (CSF), the cell count, total protein, and interleukin 6 (IL-6) were increased, but ACE in CSF was normal. We diagnosed the case as primary Sj?gren's syndrome presenting with aseptic meningoencephalitis. After treatment with prednisolone, her manifestations and CSF findings including IL-6 resolved. Therefore, the level of IL-6 in CSF may be an indicator for the activity of primary Sj?gren's syndrome associated with central nervous manifestations.