Neurosyphilis mimicking herpes simplex encephalitis

We report the case of a 34-year old man who presented with confusion and temporal lobe symptoms and signs without motor neuron involvement, suggesting herpes simplex encephalitis, as a reminder to "think syphilis" in all patients with unexplained neurologic deficits.     

Treatment of acute herpes simplex encephalitis

Combined subjective and objective nutritional assessment was performed on admission in 127 patients with oral and maxillofacial malignancies. On the basis of the nutritional assessment result, three typical nutritional parameters-body weight (BW) (X1), mid-upper-arm circumference (MAC) (X2), and hand grip strength (HGS) (X3) were used to establish a new nutritional assessment method that was developed by a computer-based discriminant analysis. The established model was as follows: Y1 = -126 + 1.09X1 + 1.34X2 + 0.23X3; Y2 = -95.63 + 0.96X1 + 1.17X2 + 0.19X3. In the model Y1 was regarded as good nutrition and Y2 as malnutrition. The larger value of Y stood for the patient's nutritional status (i.e. Y1 > Y2, well nourished; Y1 < Y2 malnourished). The new nutritional assessment correlates well with the combined subjective and objective nutritional assessment with a total agreement rate of 88.2%. With its simplicity and accuracy, the new nutritional assessment deserves a wide application in clinical situation.     

Chronic herpes simplex encephalitis initially presenting with persistent myoclonus

A 59-year-old female patient with atypical chronic herpes simplex encephalitis was reported. Initial symptom was persistent myoclonus involving the trunk and limb muscles, and later lateral gaze palsy to the left side, cerebellar ataxia, consciousness disturbance and other brainstem symptoms including absence of corneal and gag reflex and vocal cord palsy developed. The patient was successfully treated with high dose of acyclovir. Electroencephalogram was normal in the initial stage but later showed diffuse slow waves. Although CT scan and MRI showed no abnormal finding in the cerebral cortex, brainstem lesion was observed on PD weighted image of MRI. Lumbar puncture yielded a clear cerebrospinal fluid, with slightly elevated protein, increased lymphocytes, and elevated titer of herpes simplex virus type I. The serological data, albumin ratio (10.3), antibody index (12.3) and antibody ratio (7.1) were consistent with herpes simplex encephalitis. Ten days' administration of acyclovir, 1,200 mg a day and repeated three times, was prominently effective for the myoclonus and consciousness disturbance. A diagnosis of chronic herpes simplex encephalitis initially presenting with brainstem encephalitis was made. Judging from the clinical and EEG findings, the brainstem lesion was initially thought to be a cause of myoclonus in this case. However, somatosensory evoked potential (SPE) of both upper and lower extremities revealed enlarged amplitude (giant SEP), and long loop reflex was enhanced (C-reflex) on the left. Giant SEP and C-reflex imply cerebral cortex as the origin of the myoclonus. Brainstem inflammatory lesion might have involved the ascending inhibitory system, thus disinhibiting the cortical sensorimotor area and causing cortical myoclonus.     

Altered tryptophan metabolism in mice with herpes simplex virus encephalitis: increases in spinal cord quinolinic acid

Mice infected with the herpes simplex virus, type-1, developed a paralysis which was associated with increased levels of the neurotoxin quinolinic acid (QUIN). The largest increases in QUIN were observed in the spinal cord with much smaller changes in the rostral forebrain or serum. The time course for the paralysis coincided with the increase in spinal cord QUIN, a maximal 40-fold elevation, at 7-10 days post infection. The time course suggested that the increases in QUIN were due to its local synthesis. Consistent with this possibility, herpes virus-infected mice had increased activities of indoleamine 2,3-dioxygenase and kynurenine hydroxylase (two key enzymes in QUIN formation), when compared to non-infected controls. Since QUIN is formed by activated macrophages, these new data are consistent with QUIN formation as part of the host response to a pathogen whose importance is discussed.     

Failure of acyclovir sodium therapy in herpes simplex encephalitis

Herpes simplex encephalitis is an important disease characterized by focal haemorrhagic necrosis of the temporal and frontal lobes of the brain. The mortality rate may be as high as 70% of untreated cases. Isolation of the virus from brain tissue is the most reliable means of diagnosis. Although some non-invasive diagnostic modalities have been investigated, none is as reliable as brain tissue sampling. Despite acceptance that acyclovir sodium is the most effective drug for treatment, there is not a consensus on the dosage and duration of the antiviral therapy because some patients fail to respond and sometimes there is recurrence following therapy. We report a case of encephalitis in a previously normal host who died after a 13-day course of acyclovir therapy with isolation of HSV-type 1 from the brain post mortem.     

Gerstmann's syndrome following an acute herpes simplex encephalitis

The authors present a rare clinical case of a woman who developed Gerstmann's syndrome following an acute Herpes simplex viral encephalitis. Clinical observation and laboratory evaluation were performed during the acute phase of the disease. After that the follow-up continued for one-year period. The localization of the pathologic process was determined by computerized tomography, conducted periodically. The characteristics of the clinical picture are interpreted in the context of the contemporary concepts of the topical diagnosis of Gerstmann's syndrome. The possibility of a sudden onset of acute Herpes simplex viral encephalitis without a preceding febrile-intoxication syndrome is worth noting. Conclusions are drawn stressing the need of an early etiologic treatment and the importance of the rehabilitation activities during the convalescence period.     

Distribution of herpes simplex virus DNA in the brains of human long-term survivors of encephalitis

The influence of morphine on proliferation of human tumor K562 and lymphoid cells was studied and compared with that on the mitogen-induced proliferation of human peripheral blood mononuclear cells (PBMC). Morphine was shown to act as a suppressor of both cellular DNA synthesis (50% and more as compared to control) and the cellular population growth of mitogen-induced PBMC, B-lymphoma Namalva cells and EBV-transformed lymphocytes. Morphine activated proliferation of myeloid K562 and T-lymphoma Yurkat cells 1.5-fold. It is supposed that the opposite effects of morphine on proliferation of cell lines of immune origin reveal the difference in modulation of diverse immune cell types by morphine.     

Magnetic resonance imaging of herpes simplex virus encephalitis: reversible asymmetric basal ganglia lesions

We report a patient with herpes simplex virus type 1 encephalitis (HSE) who showed abnormal magnetic resonance imaging (MRI) signals in the basal ganglia. The lesions were asymmetric and became apparent with relapse of the neurological symptoms, but they completely disappeared, concomitantly with improvement of the illness.     

Atypical herpes simplex virus encephalitis diagnosed by PCR amplification of viral DNA from CSF

The caspases are cysteine proteases that have been implicated in the execution of programmed cell death in organisms ranging from nematodes to humans. Many members of the Bcl-2 family, including Bcl-XL, are potent inhibitors of programmed cell death and inhibit activation of caspases in cells. Here, we report a direct interaction between caspases and Bcl-XL. The loop domain of Bcl-XL is cleaved by caspases in vitro and in cells induced to undergo apoptotic death after Sindbis virus infection or interleukin 3 withdrawal. Mutation of the caspase cleavage site in Bcl-XL in conjunction with a mutation in the BH1 homology domain impairs the death-inhibitory activity of Bcl-XL, suggesting that interaction of Bcl-XL with caspases may be an important mechanism of inhibiting cell death. However, once Bcl-XL is cleaved, the C-terminal fragment of Bcl-XL potently induces apoptosis. Taken together, these findings indicate that the recognition/cleavage site of Bcl-XL may facilitate protection against cell death by acting at the level of caspase activation and that cleavage of Bcl-XL during the execution phase of cell death converts Bcl-XL from a protective to a lethal protein.     

Anterior opercular syndrome, caused by herpes simplex encephalitis

Bilateral frontal and parietal opercular lesions cause a syndrome characterized by paralysis of the masticatory, facial, pharyngeal, and tongue muscles (the anterior opercular syndrome). The anterior opercular syndrome can occur in patients with herpes simplex encephalitis (HSE), but in most of these patients the diagnosis of HSE was not confirmed. We describe the anterior opercular syndrome in four patients with HSE. In two of these patients, the anterior opercular syndrome dominated the clinical picture, but in the other two patients it was overshadowed by other manifestations of HSE. The diagnosis of HSE was confirmed by detection of herpes simplex virus (HSV) DNA in the CSF (two patients), culture of the HSV from a brain biopsy (one patient), and elevated HSV antibody titers in the CSF (one patient). Our patients made a partial recovery. Acute onset of weakness of masticatory, facial, pharyngeal, and glossal muscles, accompanied by fever, headache, and partial motor seizures of the face should suggest HSE.     

Gastritis secondary to herpes simplex virus

Gastric infection with herpes simplex virus is rare, with only two cases previously reported. At the time of the previous reports, the virus could not be cultured, and the diagnosis was based on histological findings. Two cases of culture positive herpes simplex virus gastritis are presented, emphasizing the importance of routine gastric biopsies and viral cultures in immunodeficient patients with dyspeptic symptoms.     

Cytokines and other markers of intrathecal immune response in patients with herpes simplex encephalitis

Sequential samples of serum and cerebrospinal fluid (CSF), from 9 patients with herpes simplex encephalitis (HSE), were analyzed for cytokines and soluble cytokine receptors. The response to herpes simplex virus was characterized by a vigorous compartmentalized immune response. The intrathecal response comprised three different phases: an acute stage (first week of illness), characterized by elevated CSF levels of interleukin (IL)-6 and interferon-gamma; an early convalescence stage (weeks 2-6 after onset of disease), associated with peaking levels of tumor necrosis factor-alpha and late markers of the specific T cell-mediated immune response, soluble IL-2 receptor, and soluble CD8 antigen (sCD8); and finally, a late convalescence stage, lasting months to years and associated with persistently increased levels of sCD8 in particular. These findings show the compartmentalization and kinetics of the inflammatory response in HSE and demonstrate persistence of the intrathecal inflammatory process, which may have implications for antiviral and antiinflammatory therapy.     

Early diagnosis of herpes simplex virus encephalitis by single photon emission computed tomography (SPECT) in patients with normal MRI

Since treatment of herpes simplex virus encephalitis (HSVE) is most effective when started early, a sensitive and specific method for early diagnosis would be of great benefit. MRI and CT are commonly used for this purpose. In this study, we presented two patients who had serologically confirmed HSVE and had normal CT and MRI, but were diagnosed as having HSVE by means of SPECT in the early stage. Case 1 was a 56-year-old man who suddenly developed alexia. On admission, physical and neurological examination were unremarkable except for alexia, agraphia, acalculia, and left-right disorientation. Brain CT, MRI, and cerebral angiography were all normal. However, SPECT showed hyperaccumulation of 99m Tc-HM-PAO in the right temporal-occipital area. On the 5th hospital day, he became comatose. CSF study revealed marked pleocytosis. Even then, MRI including Gd-enhanced study was normal while SPECT continued to show hyperaccumulation. Detection of herpes simplex virus DNA in CSF by polymerase chain reaction was negative. Anti-HSV antibody titer in CSF and serum confirmed intrathecal production of the antibody on the 14th hospital day. Abnormal accumulation of tracer in SPECT returned to normal on the 31st day when he was alert but still had a mild Gerstman syndrome. Case 2 was a 61-year-old man with disturbance of consciousness, mental dysfunction, and generalized convulsion. He was diagnosed as having HSVE by means of CSF pleocytosis, detection of HSV DNA in CSF by polymerase chain reaction, and presence of anti-HSV antibody in the CSF. CT and MRI again revealed no abnormality while SPECT clearly showed hyperaccumulation in the left temporal lobe in an early stage. Hyperaccumulation of lipophilic tracer on SPECT study, especially in the temporal lobes, has been reported in the early stage of HSVE by previous investigators. Unlike MRI or enhanced CT, the increased tracer accumulation in SPECT does not reflect disruption of the blood-brain-barrier or inflammatory edema, but reflects hyperperfusion or some other HSVE related abnormality which is currently unknown. From these observations, we suggest that local hyperperfusion occurs before local inflammation, and that SPECT is the most useful scanning method for early diagnosis of HSVE when this disease is clinically suspected.     

Cellular protein interactions with herpes simplex virus type 1 oriS

The herpes simplex virus type 1 (HSV-1) origin of DNA replication, oriS, contains an AT-rich region and three highly homologous sequences, sites I, II, and III, identified as binding sites for the HSV-1 origin-binding protein (OBP). In the present study, interactions between specific oriS DNA sequences and proteins in uninfected cell extracts were characterized. The formation of one predominant protein-DNA complex, M, was demonstrated in gel shift assays following incubation of uninfected cell extracts with site I DNA. The cellular protein(s) that comprises complex M has been designated origin factor I (OF-I). The OF-I binding site was shown to partially overlap the OBP binding site within site I. Complexes with mobilities indistinguishable from that of complex M also formed with site II and III DNAs in gel shift assays. oriS-containing plasmid DNA mutated in the OF-I binding site exhibited reduced replication efficiency in transient assays, demonstrating a role for this site in oriS function. The OF-I binding site is highly homologous to binding sites for the cellular CCAAT DNA-binding proteins. The binding site for the CCAAT protein CP2 was found to compete for OF-I binding to site I DNA. These studies support a model involving the participation of cellular proteins in the initiation of HSV-1 DNA synthesis at oriS.     

Serial MRI, SPECT and 1H-MRS findings in a case of herpes simplex encephalitis

Thyroid-associated ophthalmopathy (TAO) is a progressive eye disorder associated with Graves' hyperthyroidism, which is generally considered to have an autoimmune etiology. Eye muscle membrane proteins of 64 kd are good markers of ophthalmopathy in patients with thyroid autoimmunity. The 64-kd protein is now shown from a partial sequence to be the flavoprotein subunit (Fp) of mitochondrial succinate dehydrogenase. Hyperthyroidism due to Graves' disease is increasing in incidence among urban black female Africans, possibly because of exposure to environmental risk factors such as increased dietary iodine ingestion and stress. Ophthalmopathy is frequently observed in this clinical context, but its association with serum autoantibodies reactive with Fp has not been examined. We studied 19 black South African patients with Graves' disease during the course of prolonged antithyroid drug administration, of whom 10 had congestive ophthalmopathy, but no clinical evidence for eye muscle damage at the onset. Anti-Fp antibodies were detected in 2 of these patients, as well as in 2 of the 9 patients who did not have overt eye disease. Additionally, the antibodies became positive in 3 patients with ophthalmopathy in whom tests were negative initially, remained positive in 1 patient throughout the study period and became negative in 1 patient with positive tests initially. Ophthalmopathy did not develop in any of the 9 patients who lacked this complication on presentation. The reasons why we failed to demonstrate a close relationship between anti-Fp antibodies and the eye muscle component of ophthalmopathy are unclear although one possibility is that ocular myopathy is an uncommon manifestation in African thyrotoxic patients compared with those of Caucasian origin. The relationship between anti-Fp antibodies and eye muscle inflammation in patients with thyroid autoimmunity of different ethnic origins and environmental settings, needs to be addressed in a large prospective study.     

BK virus encephalitis in an immunocompetent patient

OBJECTIVES: To describe a previously healthy patient now suffering from monophasic encephalitis caused by a primary infection with BK virus and to discuss possible risk factors for developing BK virus encephalitis. DESIGN: Case report. SETTING: Referral hospital. PATIENT: The patient was examined on referral. MAIN OUTCOME MEASURES: The main diagnostic tests performed were serology, polymerase chain reaction on cerebrospinal fluid samples, and cranial magnetic resonance imaging. RESULTS: During the course of the patient's encephalitis, an IgM titer developed against polyomavirus, followed by anti-polyomavirus IgG. Wild-type BK virus was demonstrated in cerebrospinal fluid samples. Cranial magnetic resonance imaging showed diffuse reversible white matter changes most prominent on T2-weighted images. CONCLUSION: We conclude that diagnostic tests for BK, a human polyomavirus, should be included in the screening program for encephalitogenic pathogens.