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#1
20.05.2007, 18:15
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Вот как бывает: Normal MRI findings in herpes simplex virus encephalitis
Peter Höllinger Lukas MatterMatthias Sturzenegger
Normal MRI findings in herpes simplex virus encephalitis Received: 21 December 1999 Received in revised form: 13 April 2000 Accepted: 2 May 2000 Sirs: Signs and symptoms of herpes simplex virus encephalitis (HSVE) are manifold and do not allow a firm diagnosis based on clinical findings alone [10]. Diagnosis remains a challenge despite several refined methods of investigation, including magnetic resonance imaging (MRI), electroencephalography (EEG), and analysis of cerebrospinal fluid (CSF) with polymerase chain reaction (PCR) and antibody titers. The former gold standard of diagnosis was brain biopsy, which nowadays has largely been replaced by PCR [6]. Due to the ease of performance and widespread availability of the method, there is agreement that PCR analyses of CSF specimens will redefine the spectrum of HSV infections of the CNS [2, 5]. Cerebral MRI is believed to be the most sensitive neuroimaging method for the diagnosis of HSVE [1, 8, 9]. Definite diagnosis of HSVE relies on a synopsis of clinical findings and additional investigations, which all have limited sensitivity and specificity [6,10]. Establishing a firm diagnosis remains an important issue, since the effective treatment of HSVE with acyclovir is associated with remarkable costs [3]. On the other hand, prompt initiation of treatment is essential for improvement in outcome [10]. A 21-year-old farmer suffered from bifrontal headache with slightly elevated body temperature and malaise for approximately 2weeks. One day before admission involuntary jerking of the right cheek occurred for about 30 s. The following day he suddenly noticed myoclonic jerks of his right arm with rapid progression to a generalized tonic-clonic seizure of about 1 min duration. On admission he was febrile (up to 39°C), with slight somnolence and a motor hemisyndrome on the right side with mixed aphasia. Results of laboratory investigations are listed in Table 1. CSF essentially showed mononuclear pleocytosis and a positive PCR for HSV–1. This is an unnested PCR amplifying a 200-bplong fragment of 5-regulatory DNA sequences of the thymidine kinase gene with an analytical sensitivity of five DNA-copies (Institute for Medical and Molecular Diagnostics, Zurich). In addition, normal values in blood were obtained for antibodies against Mycoplasma pneumoniae, varicella zoster virus, cytomegalovirus, human immunodeficiency virus 1, Treponema pallidum, Borrelia burgdorferi, rubella, measles, and mumps. MRI (1.5T, Siemens, Germany) of the brain was performed on the second hospital day and included the following sequences: T1 axial (TR 528/TE 12) and sagittal (440/12), T2 axial (3176/98) and coronal (3640/96), proton weighted axial (3176/16), contrast-enhanced T1 in three planes and axial fluidattenuated inversion recovery images. Careful examination of temporal lobes, opercular regions, and the cingulate gyri revealed no signal abnormalities. EEG on that day showed bifrontotemporal delta waves with preponderance on the left side without periodic complexes. 
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#2
20.05.2007, 18:17
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Approximately 7 h after the generalized seizure antiviral therapy with
intravenous acyclovir (10 mg/kg) every 8 h was started and continued for 12 days. Under a prophylactic treatment with 100 mg diphenylhydantoin three times daily no further clinical seizure activity was observed. On the second hospital day only a palsy of the right corner of the mouth and slightly elevated body temperatures persisted. Cerebral MRI performed on the sixth hospital day remained completely normal. CSF 1 week after admission showed regression of pleocytosis and negative PCR. Serum IgA antibody titers against HSV at that time remained positive without a significant titer change. After 2 weeks in the hospital the patient was discharged without any focal neurological deficit. CSF 1 month later showed 12 mononuclear cells with negative PCR. One year after the initial encephalitic episode he complained of persistently reduced physical performance and excessive daytime sleepiness. The Epworth Sleepiness Score was 17, polysomnography revealed a normal result, and the multiple sleep latency test was clearly pathological with an average sleep latency of 4 min 42 s and one sleep-onset REM episode. CSF, EEG, and MRI at that time were normal. The HLA-DRB1*15 antigene (associated with narcolepsy) was not found. Under a symptomatic treatment with methylphenidate sleepiness could be overcome when necessary. Our patient presented with fever and a secondarily generalized tonicclonic seizure followed by an acute neurological deficit for several hours, which therefore perhaps corresponds to a postictal paresis of Todd. This focal neurological sign together with mononuclear CSF pleocytosis allowed the clinical diagnosis of focal encephalitis [10]. EEG showed focal slowing over temporal regions of both hemispheres with intermittent epileptic discharges, findings which are not specific but typical of HSVE [4]. PCR from CSF performed on the day of admission was positive for HSV–1 and therefore allowed an etiological diagnosis to be established. Repeated PCR after 8 days of ongoing acyclovir treatment was negative, which is in good agreement with the findings of previous studies [5, 10]. Antibody titers were suggestive of HSV reactivation; however, they did not show a course over time with the encephalitic syndrome. Intrathecal antibody production was not documented since there were no detectable IgA antibodies against HSV in the CSF. Diagnostic antibody titer changes in HSVE have been reported only in about 66–80 % of definite cases [5, 10]. Interestingly, our patient had normal cerebral MRI, including T2- weighted and fluid-attenuated inversion recovery images in axial and coronal planes as well as diffusionweighted imaging performed on days 2, 6, and again14 months after the acute onset of symptoms. This is in contrast to previous studies reporting a high sensitivity of MRI in the early diagnosis of HSVE [1, 2, 8, 9]. However, to our knowledge, the sensitivity and specificity of the various imaging modalities in the diagnosis of human HSVE have not been quantified or related to the time point with respect to disease course. Especially, there are no comparisons with virological methods such as brain biopsy or PCR [10]. From animal experiments with nasal inoculation of HSV it is known that cerebral MRI can remain normal in about 5% [7]. Reports on human HSVE generally describe clearcut pathological findings on cerebral MRI, but a patient with normal MRI, CSF pleocytosis, and positive HSV-PCR has obviously not yet been described [2]. We think that our patient falls into this rare category and fulfills those diagnostic criteria. As outlined above the firm diagnosis of HSVE is based on several elements of clinical presentation and additional investigations, which must be integrated for a firm diagnosis. These various findings in our patient allowed the diagnosis of HSVE, despite the normal MRI. Another typical but rare element is the occurrence of organic hypersomnia 1 year after the acute encephalitic episode. In the acute phase of HSVE a rapid decision concerning acyclovir therapy must be taken due to the favorable prognostic consequences of early treatment [10]. HSVE with at least initially normal CSF cell count is well known from the literature [2]. We would like to emphasize that even normal MRI of the brain can occur throughout the course of confirmed HSVE. MRI as a structural imaging method is a secondary tool in the diagnosis of HSVE, but never a proof of this entity. On the other hand, normal MRI should not prevent the clinician from initiating acyclovir therapy.
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