Neurol Sci DOI 10.1007/s10072-014-1984-1
LETTER TO THE EDITOR
Cryptococcal encephalitis with fulminant intracranial hypertension mimicking anti-NMDA receptor encephalitis Mirko Piola • Nerina Mascoli • Salvatore Barca Marco Arnaboldi • Vincenzo Belcastro
•
Received: 2 September 2014 / Accepted: 14 October 2014 Ó Springer-Verlag Italia 2014
A 25-year-old woman was admitted to the emergency room for headache, behavioural change with psychomotor agitation, memory impairment and chewing automatisms. Her medical history was unremarkable. On admission the hematocrit, haemoglobin level, and results of renal and liver function tests were normal. A computed tomographic (CT) scan of the head, obtained without the administration of contrast material, was normal, as was a chest radiograph. On examination, the patient was awake, alert, and oriented with respect to her name and her father but not the place or time; she answered ‘‘yes’’ or ‘‘no’’ to questions but often cried with unintelligible words. The vital signs were normal. There was no nuchal rigidity. An electroencephalographic (EEG) recording showed diffuse background slowing and delta activity with superimposed bursts of rhythmic beta frequency activity on frontal and temporal regions, a pattern known as extreme delta brush (EDB) (Fig. 1a). Over the first 2 days after admission, the patient fluctuated between episodes of normal lucidity and episodes of unresponsiveness and stereotyped movements. These episodes were interpreted as complex seizures and antiepileptic began (levetiracetam 500 mg bid). Magnetic resonance imaging (MRI) of the head was performed after the administration of gadolinium and revealed only mild leptomeningeal enhancement without brain lesion (Fig. 1b). Lumbar puncture was performed and cerebrospinal fluid (CSF) analysis was unremarkable with normal opening
M. Piola N. Mascoli S. Barca M. Arnaboldi V. Belcastro (&) Neurology Unit, Department of Medicine, S. Anna Hospital, via Ravona, 22100 Como, Italy e-mail:
[email protected]
pressure (17 cmH2O). Herpes viruses (HSV 1–2, CMV, EBV, VZV), HIV, JCV, West Nile virus, fleboviruses, and enteroviruses were excluded. On the basis of the clinical picture [1] and EEG findings of EDB [2] an anti-N-methyl-D-aspartate (NMDA) receptor encephalitis was suspected. Thus, intravenous methylprednisolone 500 mg daily was started. Noteworthy, 3 days after admission, she suddenly worsened developing comatose state with a Glasgow Coma Scale score of 3 points. At this stage, a CT scan of the brain showed diffuse brain oedema with a radiological pattern of pseudotumor cerebri-like syndrome (Fig. 1c). Surgical monitoring of intracranial pressure (ICP) revealed severe hypertension (110 cmH2O) and a brain angiography showed no intracranial flow. The same day in which the brain death was declared Cryptococcus neoformans was cultured from CSF, blood and urine. Autopsy revealed disseminated neoformans cryptococcosis.
Discussion In our presumably immunocompetent patient, the acute onset of memory impairment, headache, partial seizures, behavioural change and the presence of EDB on EEG strongly suggested a possible diagnosis of anti-NMDA receptor encephalitis [1]. However, unlike the common clinical course of anti-NMDA receptor encephalitis, our patient suddenly worsened and brain death occurred 3 days after admission. A diagnosis of disseminated cryptococcosis was revealed by autopsy. Cryptococcus neoformans is the most common cause of life threatening fungal infection and the most common cause of meningitis in patients with AIDS. Notably, cryptococcal
123
Neurol Sci Fig. 1 EEG recording shows diffuse background slowing and delta activity with superimposed bursts of rhythmic beta frequency activity (arrows) on frontal and temporal regions (a). Brain MRI reveals mild leptomeningeal enhancement without brain lesion in T1weighted sequence (b). CT scan of the brain showed diffuse brain oedema (c)
encephalitis is a rare condition in immunocompetent patients frequently leading to wrong diagnoses [3, 4]. Typical MRI features for cryptococcosis in immunocompetent patients is that of clustered enhancing cysts or nodules in bilateral basal ganglia usually associated with diffuse leptomeningeal enhancement [5], while CSF findings usually reveal high opening pressure (median 27 cmH2O) with increased leukocyte count and protein level [4]. In our patient, brain MRI showed only mild leptomeningeal enhancement and CSF findings were unremarkable. Noteworthy, in our patient, EEG recording showed a particular pattern known as EDB that is considered as a
123
unique electrographic marker for a subset of patients with severe anti-NMDA receptor encephalitis. Moreover, its presence in the correct clinical context is considered as a strong suspicion of the diagnosis [2]. To the best of our knowledge, EDB has been not reported in patients with cryptococcal encephalitis. EDB is characterised by continued delta activity with superimposed beta activity riding on each delta wave (Fig. 1a). The patient was not receiving treatment with barbiturates or benzodiazepines, thus the beta activity could not be attributed to these medications. The aetiology of EDB is undetermined, but a plausible hypothesis is that delta activity is a reflection of focal
Neurol Sci
dysfunction and the superimposed beta activity is the consequence of altered glutamatergic activity. Cryptococcal encephalitis is often associated with intracranial pressure C200 mmH2O in more than 50 % of cases. The mechanism is hypothesised to be the obstruction of CSF outflow by a large burden of yeasts and polysaccharide plugging the arachnoid villi [6]. Our patient likely had severe intracranial hypertension that was evident on CT imaging with a radiological pattern of pseudotumor cerebri-like syndrome. Cryptococcal encephalitis in immunocompetent patient at onset may resemble anti-NMDA receptor encephalitis representing a challenging diagnosis. Although EDB is considered as a specific EEG pattern in anti-NMDA receptor encephalitis, its presence could predict a more aggressive course as observed in cryptococcal encephalitis. A delay in anti-mycotic treatment plays a key role in high mortality rate in these patients. Conflict of interest
The authors declare no conflict of interest.
References 1. Dalmau J, Gleichman AJ, Hughes EG, Rossi JE, Peng X, Lai M et al (2008) Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 7:1091–1098 2. Schmitt SE, Pargeon K, Frechette ES, Hirsch LJ, Dalmau J, Friedman D (2012) Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis. Neurology 79:1094–1100 3. Kiertiburanakul S, Wirojtananugoon S, Pracharktam R, Sungkanuparph S (2006) Cryptococcosis in human immunodeficiency virus-negative patients. Int J Infect Dis 10:72–78 4. Zafer Ecevit I, Clancy CJ, Schmalfuss IM, Hong Nguyen M (2006) The poor prognosis of central nervous system cryptococcosis among nonimmunosuppressed patients: a call for better disease recognition and evaluation of adjuncts to antifungal therapy. Clin Infect Dis 42:1443–1447 5. Scozzafava J, Block H, Asdaghi N, Siddiqi ZA (2007) Teaching NeuroImage: cryptococcal brain pseudocysts in an immunocompetent patient. Neurology 69:E6–7 6. Denning DW, Armstrong RW, Lewis BH, Stevens DA (1991) Elevated cerebrospinal fluid pressures in patients with cryptococcal meningitis and acquired immunodeficiency syndrome. Am J Med 91:267–272
123 View publication stats
