Fulminant acute disseminated encephalomyelitis in children

Acute disseminated encephalomyelitis (ADEM) is a typically monophasic inflammatory demyelinating disease of the central nervous system with a favorable outcome. However, 2% of ADEM involves acute hemorrhagic leukoencephalitis (AHLE), which is a fulminant and hyperacute variant of ADEM with a poor outcome and high mortality. There are limited case reports of fulminant ADEM including AHLE in children. Herein, we report two pediatric cases of fulminant ADEM. Both cases had a rapid deterioration of consciousness, repetitive seizures, and brain edema on neuroimaging, in addition to atypical neuroradiological findings on magnetic resonance imaging (MRI), a reversible splenial lesion in case 1, and bilateral frontal and occipital cortical lesions in case 2. Both cases were treated with early high-dose methyl-prednisolone and immunoglobulin, while therapeutic hypothermia was also initiated in case 2 after the patient exhibited a decerebrate posture and irregular breathing pattern. Both cases had a favorable outcome. Further case reports on pediatric fulminant ADEM are required to clarify the various clinical types, and to examine the efficacy of various treatment modalities for fulminant ADEM and AHLE in children.     

Akathisia in association with herpes simplex encephalitis relapse and opercular syndrome in children

We report a 2-year-old boy with herpes simplex virus type 1 encephalitis (HSE) and opercular syndrome who presented with clinical relapse characterized by chorea-like involuntary movements that suggest akathisia. The patient initially presented with multiple focal seizures that cause epilepsia partialis continua, polymerase chain reaction (PCR) for herpes simplex virus type 1 was positive. He developed hypersalivation, speech and swallowing difficulties within 30 days. Based on these findings the patient was diagnosed as having opercular syndrome due to HSE. He developed akathisia on 44th day of admission as a relapse and he was successfully treated with propranolol.     

Acute Hemorrhagic Leukoencephalopathy Associated with Influenza A (H1N1) Virus

Background

Acute hemorrhagic leukoencephalopathy (AHLE) is a rare condition associated with H1N1. In this condition the infection triggers an autoimmune response which results in perivascular demyelination and hemorrhage in the brain parenchyma.

Methods

We report a case of a patient who developed brain edema and herniation as a result of AHLE.

Results

A 27-year-old presented to a community hospital with fever, dyspnea, and malaise and was found to have H1N1-associated pneumonia. Despite treatment he progressed to acute respiratory distress syndrome and required mechanical ventilation. Due to failure on conventional ventilation, he was transferred to our hospital and was placed on high-frequency oscillatory ventilation. He was showing improvement until day 6 of transfer to our hospital when he was suddenly noted to have a rise in his blood pressure followed by hypotension. The following morning he was noted to have non-reactive pupils and was declared brain dead. Autopsy of the brain was consistent with AHLE.

Conclusions

This case emphasizes the importance of awareness of this disease. The non-specific signs and symptoms, and the use of sedatives, make diagnosis challenging in the early stages of this disease. If suspected early, appropriate imaging can aid in the diagnosis. Treatment with immunosuppressive agents and plasmapheresis may prevent rapid progression and death. This is the first published case of AHLE in association with H1N1 that has been confirmed pathologically.     

Evidence of axonal damage in human acute demyelinating diseases

Substantial axon damage, detected by immunostaining for beta amyloid precursor protein (betaAPP) has been demonstrated in acute demyelinating lesions in multiple sclerosis. AIMS: The present study aimed to determine if this was also the case in the other human acute demyelinating diseases, acute hemorrhagic leucoencephalitis (AHLE), acute disseminated encephalomyelitis (ADEM) and central pontine myelinolysis (CPM). METHODS: BetaAPP immunostaining was used as a marker of axonal damage in autopsy material from these conditions. RESULTS: Axonal damage was detected in all these conditions. Its extent varied within and between them. Axonal damage was largely confined to tissue adjacent to veins and venules in AHLE and ADEM but was unrelated to proximity to these vessels in CPM. CONCLUSION: Substantial axon damage occurs in fatal cases of AHLE, ADEM and CPM.     

Acute polyradiculoneuritis during primary herpes simple virus infection

The herpes virus family, particularly cytomegalovirus and Epstein-Barr virus, are often associated with acute polyradiculoneuritis (APRN). APRN following primary herpes simplex virus infection is much more uncommon, viral reactivation generally being involved. We report a patient who developed APRN following herpes simplex virus primary infection, probably HSV II.     

Viral encephalitis. Experiences with 53 patients in Middle Hessia

Clinical symptoms, course of disease, cerebrospinal fluid (CSF) and cranial CT of 53 patients suffering from acute or subacute encephalitis were evaluated retrospectively. The virus could be identified in 21 (39%) patients. Nine of them had herpes simplex virus-encephalitis. 16 patients, eight with herpes simplex virus-encephalitis, died due to the disease. Complete restitution could be observed in 73% of survivors. Disturbance of consciousness and severe focal neurological deficit worsened prognosis towards letality and functional recovery. Most patients had initially elevated number of cellular elements and/or pathological protein concentration in CSF. CSF protein profile showed disturbance of blood-CSF-barrier function in a great number of patients during the first week of the disease whereas autochthonous production of immunoglobulin G was observed predominantly during the second and third week. Elevated concentration of CSF-lactate was seen in herpes simplex virus-encephalitis and in letal cases. 28 (53%) patients had pathological CT-findings. Generalized brain edema, focal hypodensities, focal and cortical contrast enhancement and hemorrhagic imbibation were observed. With one exception patients with herpes simplex virus-encephalitis had hypodense lesions in the temporal lobe. Besides this CT-findings did not allow conclusions regarding the etiology of encephalitis. Prognosis of encephalitis caused by other than herpes simplex virus was worse in case of pathological CT.     

Herpes simplex encephalitis originating from bilateral thalamic lesions with hemorrhagic component]

A 71-year-old woman with hypertension and hypothyroidism was transferred to our hospital from a nearby hospital because of right thalamic hemorrhage evident on CT. She had been suffered from fever and headache for five days. Neurological examination on admission revealed somnolence, rigidity in the neck and extremities, and bilateral Babinski signs. Then she developed decorticate rigidity in a day. On brain MRI four hours after admission, T2-hyperintese lesions were demonstrated in the bilateral thalamus in addition to hemorrhagic change of the right thalamus on the initial CT. No pleocytosis was evident on cerebrospinal fluid examination at admission. Follow-up MRI on the fifth hospital day, however, revealed expansion of the lesions bilaterally to the medial temporal lobes including amygdala, hippocampus and insular cortex. The diagnosis of herpes simplex encephalitis was established by PCR of cerebrospinal fluid on the same day. After immediate treatment with acyclovir and ara-A, she gradually became conscious and could respond to simple conversation. This was an unusual case of herpes simplex encephalitis originating from bilateral thalamic lesions on brain imaging. We should consider thalamus as a primary lesion in herpes simplex encephalitis.     

Herpes simplex encephalitis presenting with exclusively frontal lobe involvement

The authors report a patient with herpes simplex encephalitis who presented with magnetic resonance imaging (MRI) lesions exclusively in the frontal lobes, including the bilateral anterior cingulate gyri. She is making a good recovery after therapy with intravenous acyclovir. A similar presentation with a fatal outcome was previously reported by Rose et al (Neurology 42: 1809-1812, 1992). MRI shows temporal lesions in most patients with herpes simplex encephalitis, whereas occasional patients have normal imaging. A high index of suspicion for the diagnosis of herpes simplex encephalitis should be maintained when a patient presents with fever and brain lesions involving extratemporal limbic system structures.     

Chronic granulomatous herpes simplex encephalitis in children

Herpes simplex encephalitis is usually a monophasic acute illness but can cause chronic disease, particularly in children. Little information is available as to the histological substrate. We report the findings in 3 children. In 2 children, herpes encephalitis had occurred during the first 2 years, but both later developed intractable epilepsy that led to neurosurgery. The biopsies showed chronic granulomatous inflammation with foci of mineralization. One child made a good post-operative recovery. The other was found post-operatively to have herpes simplex virus type 1 (HSV-1) DNA and elevated titers of HSV IgM antibodies in the CSE He was given acyclovir but after initial improvement developed hemiparesis, with extensive signal change on MRI. Repeat biopsy revealed florid granulomatous inflammation with necrosis. The third patient was an infant who had had a cutaneous facial HSV-2 eruption soon after birth. This was treated with topical acyclovir, after which she remained well until 2 months, when she presented with a relatively non-specific illness, developed blisters of the right hand and foot, and died a few days later. Necropsy revealed severe granulomatous encephalitis, most extensive in the temporal lobe and insula, and associated with mineralization. Our findings indicate that herpes simplex encephalitis in children can be complicated by chronic granulomatous inflammation with mineralization. This pattern of disease may be an under-recognized complication of herpes simplex infection during the first few years of life.     

Craniectomy in herpetic encephalitis

The morbidity and mortality of herpes simplex encephalitis have decreased since the 1980s with the use of antivirals, but have remained stable in the last couple of years. One cause of morbidity is the development of focal hemorrhagic necrosis and edema in the temporal lobe, giving rise to space-occupying lesions, with a subsequent elevation of intracranial pressure. In some cases, the necrosis and edema can be refractory to medical treatment, with fatal outcome. Under these circumstances, some authors proposed decompressive craniectomy to treat severe intracranial hypertension and prevent serious neurologic deficits. We report the clinical outcomes of 2 adolescents affected with herpes simplex encephalitis who developed, during the course of their illness, severe intracranial hypertension refractory to medical treatment. Decompressive surgery was undertaken, with good outcomes in both patients.     

Herpes encephalitis during natalizumab treatment in multiple sclerosis

In this case report we describe the first non-fatal herpes simplex virus encephalitis (HSE) case with natalizumab for multiple sclerosis (MS). A 36-year-old woman, previously treated with immunomodulatory and immunosuppressive drugs for MS, developed acute encephalitis after 6 monthly natalizumab perfusions. Brain imaging demonstrated suggestive bi-temporal lesions. Herpes simplex virus type-1 DNA was detected in cerebrospinal fluid. The patient improved gradually after a 21-day course of intravenous acyclovir, but neuropsychiatric changes remained 5 months later. Our non-fatal case of HSE and other reported cases of herpes infections provide evidence of an increased risk with natalizumab and point to the need for clinicians to maintain awareness.     

Neurosyphilis

Diagnosis of herpes simplex encephalitis in the acute stage is based on clinical symptoms (nonspecific prodromi, neuropsychological deficits, epileptic seizures) in combination with typical CSF abnormalities (lymphomonozytic pleocytosis) and MR imaging abnormalities assumed to be typical for herpes simplex encephalitis (increased fluid-attenuated inversion recovery and T2 hyperintensities in the mesiotemporal lobe region). Definite diagnosis of herpes simplex encephalitis is based on positive polymerase chain reaction in the CSF, usually available some days after hospital admission. Suspected herpes simplex encephalitis requires immediate treatment with acyclovir. Bacterial encephalitis caused by spirochetes may present with similar features but requires different treatment. This should therefore be considered in the differential diagnosis of herpes simplex encephalitis. We report a young patient with neurosyphilis whose correct diagnosis could be made only several days after beginning specific treatment.     

Herpes simplex virus specific antibody determined by immunoblotting in cerebrospinal fluid of a patient with the Guillain-Barré syndrome.

The Guillain-Barré syndrome is often preceded by a herpes virus infection. Herpes simplex virus, however, has rarely been observed as the causative agent. A patient is described with a herpes simplex virus infection followed by a Guillain-Barré syndrome. Immunoblotting was used to detect herpes simplex virus-specific antibodies in serum and cerebrospinal fluid.     

巢式聚合酶链反应检测脑脊液中单纯疱疹病毒DNA

应用巢式聚合酶链反应(PCR)检测患者脑脊液(CSF)中单纯疱疹病毒1型(HSV-1)DNA。23例经鞘内HSV-1特异性IgG抗体检测阳性的“HSV-1型性脑炎(HSE)”中19例PCR阳性,4例阴性患者病程均超过1个月。22例IgG阴性的“散发性脑炎”中7例PCR阳性,此7例皆于发病1周内检查CSF,其中2例取材于发病当日。1周后复查7例患者,CSF PCR仍为阳性,IgG皆阴性,提示PCR适用于HSE的早期诊断。     

Relapsing herpes simplex encephalitis: pathological confirmation of viral reactivation

This case is reported to raise awareness of herpes simplex encephalitis as a persisting brain disorder. A 66 year old immunocompetent man developed status epilepticus and died of pneumonia in the course of progressive hemiparesis, cognitive decline, and atrophy of the brain over a five year period after herpes simplex encephalitis. In addition to a completely destroyed left temporal lobe, necropsy revealed active encephalitis consisting of necrosis and lymphocyte infiltration with a large number of intranuclear inclusions in the neurones and glial cells in the markedly oedematous parenchyma of the right frontal and parietal lobes. Herpes simplex virus type 1 (HSV-1) antigen was detected by immunohistochemistry, HSV-1 DNA by in situ hybridisation, and herpes simplex virus nucleocapsids by electronmicroscopy. These clinical and pathological findings suggest that direct viral reactivation might result in a relapse of herpes simplex encephalitis, causing progressive clinical deterioration associated with the persistence of HSV-1 in the brain. This is the first case report demonstrating HSV-1 antigen, HSV-1 DNA, and herpes simplex virus nucleocapsids in a case of relapsing herpes simplex encephalitis.     

Natalizumab and HSV meningitis

Natalizumab (Tysabri, Biogen Idec and Elan Pharmaceuticals) is a monoclonal antibody approved for use in patients with relapsing multiple sclerosis (MS) as well as moderate to severe Crohn’s disease. We report the first case of a patient with a history of MS, on monthly natalizumab, who developed HSV-2 meningitis. We discuss the mechanism of action of natalizumab and review what is known about the reactivation of herpes infection in association with this medication. The question of herpes simplex virus (HSV) and varicella zoster virus (VZV) prophylaxis for patients is raised.     

Prognostic value of intrathecal antibody production and DNA viral load in cerebrospinal fluid of patients with herpes simplex encephalitis

Herpes simplex encephalitis is a devastating disease. In the early 1980s our group conducted a nationwide clinical trial of acyclovir versus vidarabine in patients with herpes simplex encephalitis in whom intrathecal herpes simplex virus (HSV) antibodies were assayed. The purpose of this study was to investigate if antibody levels and viral load correlate with outcome in herpes simplex encephalitis. We have analysed the prognostic value of HSV antibody levels in serum and cerebrospinal fluid (CSF) at the start of antiviral treatment in the 53 included patients. Frozen samples from a subset of patients were analysed with quantitative polymerase chain reaction (PCR) to assess the prognostic value of the viral load in CSF. IgG-levels in CSF at presentation were significantly higher in vidarabine-treated patients with a favourable outcome than in those treated with vidarabine but with an unfavourable outcome. The intrathecal viral load at presentation showed no correlation with outcome. However, the duration of positive HSV-PCR in CSF was longer in vidarabine-treated than in acyclovir-treated patients. These findings indicate that the B-cell response is important in the pathogenetic process of herpes simplex encephalitis. However, neither antibody levels nor viral load at presentation are useful as prognostic markers for the individual patient in this study.     

Relapsing herpes simplex encephalitis following antiviral therapy

Although treatment for herpes simplex virus (HSV) encephalitis with antiviral agents has improved survival, occasional patients experience unexplained clinical exacerbations. This report presents evidence that some relapses may occur from recurrent viral encephalitis. An adult male developed the classic symptoms of HSV encephalitis. The cerebrospinal fluid (CSF), electroencephalogram, and isotope brain scan suggested a localized encephalitis involving the left temporal lobe. The pateint was treated for 10 days with high doses of cytosine arabinoside instead of the currently recommended adenine arabinoside. Progression of encephalitis stopped, and clinical recovery occurred. The HSV antibody titer increased eightfold. Fifty-four days after the initial encephalitis, the patient relapsed with a subacute progressive encephalitis involving the same brain area. The CSF demonstrated oligoclonal bands, elevated immunoglobulin G levels (100 mg/dl), and a high HSV antibody titer (1:8,192 by indirect hemagglutination test). From a left temporal lobe biopsy taken 74 days after onset of the initial encephalitis, herpes simplex virus type 1 was isolated. Without renewed antiviral drug therapy, the patient slowly recovered.     

A polymerase chain reaction assay of cerebrospinal fluid in patients with suspected herpes simplex encephalitis.

A polymerase chain reaction (PCR) was used to detect herpes simplex virus (HSV) deoxyribonucleic acid (DNA) in CSF of 109 patients with possible herpes simplex encephalitis. HSV DNA was found in 20/109 patients. In 14 of these patients the diagnosis was confirmed by a rise in CSF antibodies, isolation of HSV from the brain, or both. In 3 patients CSF antibodies did not rise and 3 patients did not have a follow up lumbar puncture or a brain biopsy. In 19/20 patients HSV DNA was present in the first CSF specimen. The virus was identified as HSV I in 15 patients and HSV II in 4; the virus was not typed in the other patient. A possible diagnosis of herpes simplex encephalitis was not confirmed in the 89 PCR-negative patients. HSV DNA was present in CSF of 3 patients who had meningitis with herpetic genital infections but it was not found in 24 patients with other neurological diseases. The results suggest that the detection of HSV DNA in CSF using a PCR assay will be an accurate method of early diagnosis of herpes simplex encephalitis.     

Granulomatous Herpes Simplex Encephalitis in an Infant With Multicystic Encephalopathy: A Distinct Clinicopathologic Entity?

BackgroundHerpes simplex virus encephalitis can manifest as a range of clinical presentations including classic adult, neonatal, and biphasic chronic-granulomatous herpes encephalitis.MethodWe report an infant with granulomatous herpes simplex virus type 2 encephalitis with a subacute course and multicystic encephalopathy.CaseA 2-month-old girl presented with lethargy and hypothermia. Computed tomography scan of the head showed multicystic encephalopathy and calcifications. Cerebrospinal fluid analysis by polymerase chain reaction testing for herpes simplex virus 1 and 2, enterovirus, and cytomegalovirus was negative. Normal cerebrospinal fluid interferon-α levels argued against Aicardi-Goutières syndrome. The patient died 2 weeks after presentation. At autopsy, multicystic encephalopathy was confirmed with bilateral gliosis, granulomatous inflammation with multinucleated giant cells, and calcifications. Bilateral healing necrotizing retinitis suggested a viral etiology, but retina and brain were free of viral inclusions and immunohistochemically negative for herpes simplex virus-2 and cytomegalovirus. However, polymerase chain reaction analysis showed herpes simplex virus-2 DNA in four cerebral paraffin blocks. Subsequent repeat testing of the initial cerebrospinal fluid sample using a different polymerase chain reaction assay was weakly positive for herpes simplex virus-2 DNA.ConclusionGranulomatous herpes simplex virus encephalitis in infants can present with subacute course and result in multicystic encephalopathy with mineralization and minimal cerebrospinal fluid herpes simplex virus DNA load. Infectious etiologies should be carefully investigated in the differential diagnosis of multicystic encephalopathy with mineralization, in particular if multinucleated giant cells are present.