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.     

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.     

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.     

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.     

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.     

Treatment of herpes simplex & varicella zoster infection

Fourteen patients underwent pancreaticoduodenectomy between January 1991 and February 1995 for periampullary carcinoma. In the first 8 patients pancreaticojejunostomy was performed; two of them developed pancreatic leak and died. In the subsequent 6 patients, pancreaticogastrostomy was performed; in this group there was no pancreatic leak and no perioperative mortality. THere was no difference between the two groups in preoperative bilirubin level, duration of jaundice, diameters of the common bile duct and pancreatic duct at surgery, operative time and blood loss. Postoperatively, the patients undergoing pancreaticogastrostomy fared better; they were started on oral feeds earlier (6.0 +/- 0.6 vs 10.2 +/- 0.8 days, p < 0.001), became ambulatory earlier (7.2 +/- 0.4 vs 12.3 +/- 1.5 days, p < 0.001) and had less loss of body weight at the time of discharge (2.2 +/- 0.2 vs 3.8 +/- 0.4 Kg, p < 0.001).     

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.     

Discordance of technetium-99m-HMPAO and technetium-99m-ECD SPECT in herpes simplex encephalitis

Technetium-99m-hexamethyl propyleneamine oxime (HMPAO) and 99mTc-ethyl cysteinate dimer (ECD) accumulate in brain tissue in proportion to regional cerebral blood flow in healthy subjects and in patients with a variety of neurological diseases. We report on four patients with herpes simplex encephalitis and the discordance between these two approved cerebral perfusion imaging radiopharmaceuticals. CONCLUSION: SPECT images showed unilateral regional increase of 99mTc-HMPAO uptake and decrease of 99mTc-ECD uptake in the affected temporal lobe.     

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.     

A case of neuro-Beh?et's encephalitis with pleds as distinct from herpes simplex encephalitis: a differential diagnosis

We report a male patient with neuro-Beh?et's disease who had somnolence, mild motor aphasia and periodic lateralized epileptiform discharge. SPECT study showed decreased cerebral blood flow in the left frontal and temporal lobes. An MRI scan of the head showed only mild brain stem atrophy. His clinical signs were markedly improved after administration of prednisolone. We propose that some cases of neuro-Beh,cet's disease may have very similar clinical features to herpes simplex encephalitis and that SPECT and MRI examinations can be very useful in distinguishing the ischemic lesion of neuro-Beh?et's from the inflammatory lesion of herpes simplex encephalitis.     

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.     

A case of chronic encephalitis due to double infection with herpes simplex and measles viruses

In a healthy 49-year-old man, a decrease in job efficiency was noticed along with bizarre behavior. On admission, he was euphoric, childish, superficial and had increased libido. Neurological findings were normal. There were no abnormal findings on routine blood tests, hematochemistry or urine analysis. MRI showed no abnormal findings. However, single photon emission CT (SPECT) showed diffuse hypoaccummulation of tracer from the temporal to frontal regions. Lumbar puncture showed clear cerebrospinal fluid (CSF) with pleocytosis and an elevated protein level. Moreover, antibody IgG titers to herpes simplex virus (HSV) and measles virus were elevated, according to EIA [serum HSV -1,202.2x, measles virus 47.1x: CSF HSV-116.1x, measles virus 9.9x]. The ratio of serum to CSF antibody titers of HSV and measles virus were 12.5 and 4.75, respectively. The antibody index values of HSV and measles virus IgG titers were 8.42 and 22.22. The ratio of albumin was 105.7. Chronic, progressive HSV encephalitis is rare, and there have been very few reports of encephalitis due to double infection by HSV and another virus. Our patient was diagnosed as having encephalitis due to double infection with HSV and measles virus, because the ratio of serum to CSF antibody titers was less than 20 and the antibody index values were over 1.91. Moreover, since the IgG index was elevated and the ratio of albumin was not low, it was suggested that the blood-brain-barrier had not been disrupted, and antibodies were being produced chronically in the medullary cavity. Hyperaccummulation of tracer on SPECT studies has been reported in the early stages of HSV encephalitis. In our case, while CT and MRI showed no abnormal findings, SPECT showed diffuse hypoaccummulation. SPECT appears to be a useful tool in the diagnosis of this disorder. In case of chronic, progressive personality change in middle-aged adults, we must be aware of double virus infection of the brain as a possible causal factor.     

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.     

Diagnosis of herpes simplex diseases

The diagnosis of herpes simplex diseases will be made on ground of the typical clinical symptoms in more than 90% of all cases. A very easy additional procedure is the Tzanck test. If possible, immunofluorescent microscopy and electron microscopy of negatively stained virus particles may be helpful. Remaining questions should be solved by further virological examination in special laboratories. Information about sampling and shipment of the diagnostic material (vesicle fluid, swabs from mouth and genital ulcers, blood etc.) should be obtained prior to collection.     

Interleukin-18 protects mice against acute herpes simplex virus type 1 infection

We examined the effects of interleukin-18 (IL-18) in a mouse model of acute intraperitoneal infection with herpes simplex virus type 1 (HSV-1). Four days of treatment with IL-18 (from 2 days before infection to 1 day after infection) improved the survival rate of BALB/c, BALB/c nude, and BALB/c SCID mice, suggesting innate immunity. One day after infection, HSV-1 titers were higher in the peritoneal washing fluid of control BALB/c mice than in that of IL-18-treated mice. A genetic deficiency of gamma interferon (IFN-gamma), however, diminished the survival rate and the inhibition of HSV-1 growth at the injection site in the mice. Anti-asialo GM1 treatment had no influence on the protective effect of IL-18 in infected mice. IL-18 augmented IFN-gamma release in vitro by peritoneal cells from uninfected mice, while no appreciable IFN-gamma production was found in uninfected mice administered IL-18. Although IFN-gamma has the ability to induce nitric oxide (NO) production by various types of cells, administration of the NO synthase inhibitor NG-monomethyl-L-arginine resulted in superficial loss of the improved survival, but there was no influence on the inhibition of HSV-1 replication at the injection site in IL-18-treated mice. Based on these results, we propose that IFN-gamma produced before HSV-1 infection plays a key role as one of the IL-18-promoted protection mechanisms and that neither NK cells nor NO plays this role.