- Email: [email protected]
Recurrent leukoencephalopathy in a cocaine abuser
NeuroToxicology 32 (2011) 410–412
Contents lists available at ScienceDirect
NeuroToxicology
Brief communication
Recurrent leukoencephalopathy in a cocaine abuser Federico Bianco *, Elisa Iacovelli, Emanuele Tinelli, Chiara Lepre, Flavia Pauri Department of Medical-Surgical Sciences and Biotechnologies, Neurology Section, University of Rome, ‘‘Sapienza’’, Viale Universita` 30, 00185 Rome, Italy
A R T I C L E I N F O
A B S T R A C T
Article history: Received 21 January 2011 Accepted 15 March 2011 Available online 22 March 2011
We report the case of a cocaine abuser who presented two consecutive episodes of acute leukoencephalopathy, documented by serial MRI, with favourable outcome. Clinical findings and brain imaging led to the diagnosis of cocaine-induced toxic leukoencephalopathy and other possible mimickers have been excluded on the basis of clinical assessment. The patient’s unexpected recovery on neurological and neuropsychological examination, despite initially severe neurological symptoms, is striking and differs from more common reports of a rapid progression to death. Of note, case presented in the peculiar form of recurrent episodes of acute leukoencephalopathy, with favourable outcome, which, to our knowledge, has not been described yet. We speculate about the aetiology of this condition, which is still poorly understood. ß 2011 Elsevier Inc. All rights reserved.
Keywords: Cocaine Toxic leukoencephalopathy Posterior reversible encephalopathy syndrome Magnetic resonance imaging
1. Introduction Toxic leukoencephalopathy is a structural alteration of cerebral white matter, in which myelin suffers the most damage, that may be caused by exposure to a wide variety of agents, including cranial irradiation, therapeutic agents, drugs of abuse, and environmental toxins (Filley and Kleinschmidt-DeMasters, 2001). In cocaine abusers, toxic leukoencephalopathy particularly involves white matter tracts devoted to higher cerebral functions causing clinical features that range from inattention, forgetfulness and changes in personality to dementia and the clinical course may be fatal (Kondziella et al., 2007; Ryan et al., 2005). Physiopathology of this condition continues to be elusive and neuropathological findings support different hypotheses. We report the case of a cocaine abuser, who underwent two consecutive episodes of acute leukoencephalopathy, documented by serial MRI, with favourable outcome.
2. Case report A 30 year-old male restaurant keeper was admitted two weeks after the sudden onset of left arm weakness. On admission, neurological examination revealed left-sided hemiparesis and normal plantar responses. The mental status was normal haematological and biochemical tests as well as cerebrospinal
* Corresponding author. Tel.: +39 0649914809; fax: +39 0649914456. E-mail addresses: [email protected] (F. Bianco), [email protected] (E. Iacovelli), [email protected] (E. Tinelli), [email protected] (C. Lepre), fl[email protected] (F. Pauri). 0161-813X/$ – see front matter ß 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.neuro.2011.03.005
fluid (CSF) and multimodal evoked potentials were normal. The patient’s relatives reported cocaine abuse for a few years and hair drug testing (gas chromatography/mass spectrometry method; limit of detection: 0.1 ng/mg) was positive for cocaine and its metabolite benzoylecgonine (BEG): cocaine 12 ng/mg; BEG 23 ng/ mg. MRI showed bilateral areas of hyperintense signal in the periventricular white matter, better appreciated on fluid attenuated inversion recovery (FLAIR) sequence (Fig. 1 A) and no gadolinium enhancement. Diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) mapping as well as magnetic resonance angiography were normal. Corticosteroid treatment based on a possible presence of cocaine-induced cerebrovascular inflammation was performed. Complete clinical recovery occurred into two weeks and at the three-month follow-up MRI, the hyperintense areas in the periventricular white matter were significantly reduced (Fig. 1 A1). Six months after the initial admission, the patient’s behaviour rapidly changed and he presented negativism, associated to mutism, which alerted his relatives. On admission, he was stuporous and neurological examination showed bilateral hyperreflexia, moderately increased muscle tone and normal plantar responses. His relatives admitted he continued cocaine abuse and hair drug testing was positive for cocaine (16 ng/mg) and BEG (24 ng/mg). Haematological and biochemical tests were unremarkable. Blood pressure as well as CSF examination including cytological analysis were normal. Serological tests for infective agents such as human immunodeficiency virus, herpes virus and JC virus were negative, as were CSF viral and bacterial cultures. EEG demonstrated severe slowing over the frontal regions. Diffuse symmetrical hyperintensity of the periventricular white matter was evident on FLAIR-MRI (Fig. 1 B) and DWI. ADC mapping
F. Bianco et al. / NeuroToxicology 32 (2011) 410–412
411
Fig. 1. MRI appearance of cocaine-induced recurrent leukoencephalopathy. First episode. Axial fluid-attenuated inversion recovery (FLAIR) MRI (6000/100) showing bilateral areas of hyperintense signal in the periventricular white matter (A). Three months later, axial FLAIR-MRI (6000/100) showed significant reduction of the hyperintense areas in the periventricular white matter (A1). Second episode. Axial FLAIR-MRI (6000/100) showed diffuse symmetrical hyperintensity of the periventricular white matter (B). Six months later, axial FLAIR-MRI (6000/100) showed significant reduction of the hyperintense signal in the periventricular white matter (B1).
showed reduced values in the periventricular white matter, where magnetic resonance spectroscopy (MRS) showed decrease in Nacetylaspartate peak, increase of choline peak and evidence of lactate-lipids peaks. The diagnosis of cocaine-induced toxic leukoencephalopathy was hypothesized and supportive treatment was only performed. During the next four weeks, symptoms gradually improved and the patient started to communicate in a simple way. After a six-month rehabilitation program, his clinical condition significantly improved with mild residual impairment of short term memory and visuospatial functions. On FLAIR-MRI, the hyperintense signal in the periventricular white matter was significantly reduced (Fig. 1 B1). At the present time, two years after onset of symptoms, mild deficit in cognitive functions still persists, but patient has been able to return to his previous work at the counter of his restaurant. 3. Discussion Although characteristic leukoencephalopathy associated with heroin exposure is well documented, leukoencephalopathy associated with cocaine usage has been less frequently described. Cocaine-induced brain damage can be divided into primary neurotoxic effects causing toxic leukoencephalopathy, secondary effects of compromised cerebral blood flow resulting in ischemic and haemorrhagic stroke, cerebral vasculitis and vasospasm and tertiary effects due to hypoxia as result of cardiopulmonary collapse (Kondziella et al., 2007). Clinical findings and brain imaging led to the diagnosis of cocaine-induced toxic leukoencephalopathy in the reported case.
The histological picture of cocaine-induced toxic leukoencephalopathy demonstrates widespread confluent vacuolar degeneration of the deep white matter, with profound axonal loss and axonal injury in adjacent normal appearing white matter. This may suggest that the axonal injury precedes the myelin vacuolar change. For the most part, however, the axonal injury and vacuolar change appear to parallel each other (Ryan et al., 2005). Neuroimaging shows diffuse symmetrical white matter involvement with sparing of the subcortical U fibres (Ryan et al., 2005). There is no involvement of the brain stem and cerebellar white matter, which are typical features of heroin vapour inhalation (Keogh et al., 2003). Brain changes are best appreciated on FLAIR-MR imaging and no contrast enhancement is observed following administration of a paramagnetic agent. Brain MRI of our patient demonstrated a pattern of involvement closely resembling that of previous reports of cocaine-induced toxic leukoencephalopathy (Kondziella et al., 2007; Ryan et al., 2005). In fact, FLAIR-MRI showed diffuse bilateral lesions of high signal intensity in the subcortical white matter, particularly evident in the frontal lobes, without cerebellar and brain stem involvement. The aetiology of this condition is poorly understood. A defect in mitochondrial function has been suggested in two cases of leukoencephalopathy associated with heroin vapour inhalation where increased white matter lactate and a favourable response to antioxidants have been reported (Kriegstein et al., 1999). In addition to a direct toxic effect on myelin and mitochondrial dysfunction, hypoxic injury may also contribute to the axonal damage and spongiform white matter change.
412
F. Bianco et al. / NeuroToxicology 32 (2011) 410–412
The clinical presentation varies widely. There may be an altered level of consciousness, spasticity, or the development of a bradykinetic rigid state. In some cases, there is rapid progression to death and complete recovery rarely occurs (Maschke et al., 1999). There is not general consensus about treatment of toxic leukoencephalopathy. It has been suggested that coenzyme Q10 and vitamins E and C supplements may be of benefit in heroin vapor inhalation leukoencephalopathy (Kriegstein et al., 1999). Nevertheless, little published data exist on treating cocaine toxic leukoencephalopathy, whose treatment remains primarily supportive (Keogh et al., 2003). In our case, corticosteroid treatment was performed on the first admission on the basis of a possible presence of cocaine-induced cerebrovascular inflammation, as previously suggested (Diez-Tejedor et al., 1998). Indeed, we do not believe that corticosteroid therapy played a major role in clinical recovery. On the second admission, the diagnosis of cocaine-induced toxic leukoencephalopathy was established and supportive treatment was only performed. The patient’s unexpected recovery on neurological and neuropsychological examination, despite severe neurological symptoms, is striking and differs from the findings of other reports of a rapid progression to death (Kondziella et al., 2007; Ryan et al., 2005). Of note, case presented with two consecutives episodes of acute leukoencephalopathy and, to our knowledge, recurrent episodes of cocaine-induced toxic leukoencephalopathy, with favourable outcome, have not been described yet. Kriegstein et al. (1999) suggested that there may be a dose dependent severity of the disease when caused by inhaling heroin pyrolysate. This may also be the case for the cocaine abuse we reported, whose increasing severity in the clinical presentation and MRI lesions is likely due to the dose of cocaine used. Progressive multifocal leukoencephalopathy could be considered in the differential diagnosis, but the patient was not immunodepressed and test for JC virus was negative. Other possible mimickers such as adrenoleukodystrophy, multiple sclerosis and ischemia were excluded on the basis of clinical assessment. Since case presented in the unusual form of recurrent leukoencephalopathy, with favourable outcome, posterior reversible encephalopathy syndrome (PRES) needs to be excluded too. As it has been recently reminded, it is important to distinguish toxic leukoencephalopathy from PRES, which may be caused by many of the same medications or drugs and possible overlap between PRES and toxic leukoencephalopathy has been admitted, in some cases (McKinney et al., 2009). PRES is characterized by vasogenic oedema in the posterior regions of the cerebral hemispheres and usually presents symptoms of headache, seizures and cortical visual disturbances, associated with hypertension (Hinchey et al., 1996). Nevertheless, ‘‘atypical’’ forms of PRES are
being reported with increasing frequency in the current literature. These ‘‘atypical’’ forms can be: not reversible; not associated with hypertension; not characterized by classic symptoms of headache, seizures, cortical visual disturbances or blindness; not restricted to the posterior regions of the cerebral hemispheres (Bhagavati and Choi, 2008; Ahn et al., 2004; Ay et al., 1998). DWI may show either vasogenic or cytoxic oedema, in some cases (Covarrubias et al., 2002). Of note, a recurrent form of PRES has been also described (Hagemann et al., 2004). Indeed, growing experience is indicating that PRES could actually represent a non-specific reaction of the brain, triggered by different pathologies, taking the form of an encephalopathy characterized by acute onset of cerebral oedema, either vasogenic or even cytotoxic, with variable outcome (Bianco, 2005). Conflict of interest statement The authors declare that there are no conflicts of interest. References Ahn KJ, You WJ, Jeong SL, Lee JW, Kim BS, Lee JH, et al. Atypical manifestations of reversible posterior leukoencephalopathy syndrome: findings on diffusion imaging and ADC mapping. Neuroradiology 2004;46:978–83. Ay H, Buonanno FS, Schaefer PW, Le DA, Wang B, Gonzalez RG, et al. Posterior leukoencephalopathy without severe hypertension: utility of diffusion-weighted MRI. Neurology 1998;51:1369–76. Bhagavati S, Choi J. Atypical cases of posterior reversible encephalopathy syndrome. Clinical and MRI features. Cerebrovasc Dis 2008;26:564–6. Bianco F. Reversible posterior leukoencephalopathy syndrome: a changing concept. Neuroradiology 2005;47:703–4. Covarrubias DJ, Luetmer PH, Campeau NG. Posterior reversible encephalopathy syndrome: prognostic utility of quantitative diffusion-weighted MR images. Am J Neuroradiol 2002;23:1038–48. Diez-Tejedor E, Frank A, Gutierrez M, Barreiro P. Encephalopathy and biopsy-proven cerebrovascular inflammatory changes in a cocaine abuser. Eur J Neurol 1998;1:103–7. Filley CM, Kleinschmidt-DeMasters BK. Toxic leukoencephalopathy. N Engl J Med 2001;345:425–32. Hagemann G, Ugur T, Witte OW, Fitzek C. Recurrent posterior reversible encephalopathy syndrome (PRES). J Hum Hypertens 2004;18:287–9. Hinchey J, Chaves C, Appignani B, Breen J, Pao L, Wang A, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996;334:494–500. Keogh CF, Andrews GT, Spacey SD, Forkheim KE, Graeb DA. Neuroimaging features of heroin inhalation toxicity: ‘‘chasing the dragon’’. Am J Roentgenol 2003;180:847– 50. Kondziella D, Danielsen ER, Arlien-Soeborg P. Fatal encephalopathy after an isolated overdose of cocaine. J Neurol Neurosurg Psychiatry 2007;78:437–8. Kriegstein AR, Shungu DC, Millar WS, Armitage BA, Brust JC, Chillrud S, et al. Leukoencephalopathy and raised brain lactate from heroin vapor inhalation (‘‘chasing the dragon’’). Neurology 1999;53:1765–73. Maschke M, Fehlings T, Kastrup O, Wilhelm HW, Leonhardt G. Toxic leukoencephalopathy after intravenous consumption of heroin and cocaine with unexpected clinical recovery. J Neurol 1999;246:850–1. McKinney AM, Kieffer SA, Paylor RT, Santa Cruz KS, Kendi A, Lucato L. Acute toxic leukoencephalopathy: potential for reversibility clinically and on MRI with diffusion-weighted and FLAIR imaging. Am J Roentgenol 2009;193:192–206. Ryan A, Molloy FM, Farrell MA, Hutchinson M. Fatal toxic leukoencephalopathy: clinical, radiological, and necropsy findings in two patients. J Neurol Neurosurg Psychiatry 2005;76:1014–6.
Contents lists available at ScienceDirect
NeuroToxicology
Brief communication
Recurrent leukoencephalopathy in a cocaine abuser Federico Bianco *, Elisa Iacovelli, Emanuele Tinelli, Chiara Lepre, Flavia Pauri Department of Medical-Surgical Sciences and Biotechnologies, Neurology Section, University of Rome, ‘‘Sapienza’’, Viale Universita` 30, 00185 Rome, Italy
A R T I C L E I N F O
A B S T R A C T
Article history: Received 21 January 2011 Accepted 15 March 2011 Available online 22 March 2011
We report the case of a cocaine abuser who presented two consecutive episodes of acute leukoencephalopathy, documented by serial MRI, with favourable outcome. Clinical findings and brain imaging led to the diagnosis of cocaine-induced toxic leukoencephalopathy and other possible mimickers have been excluded on the basis of clinical assessment. The patient’s unexpected recovery on neurological and neuropsychological examination, despite initially severe neurological symptoms, is striking and differs from more common reports of a rapid progression to death. Of note, case presented in the peculiar form of recurrent episodes of acute leukoencephalopathy, with favourable outcome, which, to our knowledge, has not been described yet. We speculate about the aetiology of this condition, which is still poorly understood. ß 2011 Elsevier Inc. All rights reserved.
Keywords: Cocaine Toxic leukoencephalopathy Posterior reversible encephalopathy syndrome Magnetic resonance imaging
1. Introduction Toxic leukoencephalopathy is a structural alteration of cerebral white matter, in which myelin suffers the most damage, that may be caused by exposure to a wide variety of agents, including cranial irradiation, therapeutic agents, drugs of abuse, and environmental toxins (Filley and Kleinschmidt-DeMasters, 2001). In cocaine abusers, toxic leukoencephalopathy particularly involves white matter tracts devoted to higher cerebral functions causing clinical features that range from inattention, forgetfulness and changes in personality to dementia and the clinical course may be fatal (Kondziella et al., 2007; Ryan et al., 2005). Physiopathology of this condition continues to be elusive and neuropathological findings support different hypotheses. We report the case of a cocaine abuser, who underwent two consecutive episodes of acute leukoencephalopathy, documented by serial MRI, with favourable outcome.
2. Case report A 30 year-old male restaurant keeper was admitted two weeks after the sudden onset of left arm weakness. On admission, neurological examination revealed left-sided hemiparesis and normal plantar responses. The mental status was normal haematological and biochemical tests as well as cerebrospinal
* Corresponding author. Tel.: +39 0649914809; fax: +39 0649914456. E-mail addresses: [email protected] (F. Bianco), [email protected] (E. Iacovelli), [email protected] (E. Tinelli), [email protected] (C. Lepre), fl[email protected] (F. Pauri). 0161-813X/$ – see front matter ß 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.neuro.2011.03.005
fluid (CSF) and multimodal evoked potentials were normal. The patient’s relatives reported cocaine abuse for a few years and hair drug testing (gas chromatography/mass spectrometry method; limit of detection: 0.1 ng/mg) was positive for cocaine and its metabolite benzoylecgonine (BEG): cocaine 12 ng/mg; BEG 23 ng/ mg. MRI showed bilateral areas of hyperintense signal in the periventricular white matter, better appreciated on fluid attenuated inversion recovery (FLAIR) sequence (Fig. 1 A) and no gadolinium enhancement. Diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) mapping as well as magnetic resonance angiography were normal. Corticosteroid treatment based on a possible presence of cocaine-induced cerebrovascular inflammation was performed. Complete clinical recovery occurred into two weeks and at the three-month follow-up MRI, the hyperintense areas in the periventricular white matter were significantly reduced (Fig. 1 A1). Six months after the initial admission, the patient’s behaviour rapidly changed and he presented negativism, associated to mutism, which alerted his relatives. On admission, he was stuporous and neurological examination showed bilateral hyperreflexia, moderately increased muscle tone and normal plantar responses. His relatives admitted he continued cocaine abuse and hair drug testing was positive for cocaine (16 ng/mg) and BEG (24 ng/mg). Haematological and biochemical tests were unremarkable. Blood pressure as well as CSF examination including cytological analysis were normal. Serological tests for infective agents such as human immunodeficiency virus, herpes virus and JC virus were negative, as were CSF viral and bacterial cultures. EEG demonstrated severe slowing over the frontal regions. Diffuse symmetrical hyperintensity of the periventricular white matter was evident on FLAIR-MRI (Fig. 1 B) and DWI. ADC mapping
F. Bianco et al. / NeuroToxicology 32 (2011) 410–412
411
Fig. 1. MRI appearance of cocaine-induced recurrent leukoencephalopathy. First episode. Axial fluid-attenuated inversion recovery (FLAIR) MRI (6000/100) showing bilateral areas of hyperintense signal in the periventricular white matter (A). Three months later, axial FLAIR-MRI (6000/100) showed significant reduction of the hyperintense areas in the periventricular white matter (A1). Second episode. Axial FLAIR-MRI (6000/100) showed diffuse symmetrical hyperintensity of the periventricular white matter (B). Six months later, axial FLAIR-MRI (6000/100) showed significant reduction of the hyperintense signal in the periventricular white matter (B1).
showed reduced values in the periventricular white matter, where magnetic resonance spectroscopy (MRS) showed decrease in Nacetylaspartate peak, increase of choline peak and evidence of lactate-lipids peaks. The diagnosis of cocaine-induced toxic leukoencephalopathy was hypothesized and supportive treatment was only performed. During the next four weeks, symptoms gradually improved and the patient started to communicate in a simple way. After a six-month rehabilitation program, his clinical condition significantly improved with mild residual impairment of short term memory and visuospatial functions. On FLAIR-MRI, the hyperintense signal in the periventricular white matter was significantly reduced (Fig. 1 B1). At the present time, two years after onset of symptoms, mild deficit in cognitive functions still persists, but patient has been able to return to his previous work at the counter of his restaurant. 3. Discussion Although characteristic leukoencephalopathy associated with heroin exposure is well documented, leukoencephalopathy associated with cocaine usage has been less frequently described. Cocaine-induced brain damage can be divided into primary neurotoxic effects causing toxic leukoencephalopathy, secondary effects of compromised cerebral blood flow resulting in ischemic and haemorrhagic stroke, cerebral vasculitis and vasospasm and tertiary effects due to hypoxia as result of cardiopulmonary collapse (Kondziella et al., 2007). Clinical findings and brain imaging led to the diagnosis of cocaine-induced toxic leukoencephalopathy in the reported case.
The histological picture of cocaine-induced toxic leukoencephalopathy demonstrates widespread confluent vacuolar degeneration of the deep white matter, with profound axonal loss and axonal injury in adjacent normal appearing white matter. This may suggest that the axonal injury precedes the myelin vacuolar change. For the most part, however, the axonal injury and vacuolar change appear to parallel each other (Ryan et al., 2005). Neuroimaging shows diffuse symmetrical white matter involvement with sparing of the subcortical U fibres (Ryan et al., 2005). There is no involvement of the brain stem and cerebellar white matter, which are typical features of heroin vapour inhalation (Keogh et al., 2003). Brain changes are best appreciated on FLAIR-MR imaging and no contrast enhancement is observed following administration of a paramagnetic agent. Brain MRI of our patient demonstrated a pattern of involvement closely resembling that of previous reports of cocaine-induced toxic leukoencephalopathy (Kondziella et al., 2007; Ryan et al., 2005). In fact, FLAIR-MRI showed diffuse bilateral lesions of high signal intensity in the subcortical white matter, particularly evident in the frontal lobes, without cerebellar and brain stem involvement. The aetiology of this condition is poorly understood. A defect in mitochondrial function has been suggested in two cases of leukoencephalopathy associated with heroin vapour inhalation where increased white matter lactate and a favourable response to antioxidants have been reported (Kriegstein et al., 1999). In addition to a direct toxic effect on myelin and mitochondrial dysfunction, hypoxic injury may also contribute to the axonal damage and spongiform white matter change.
412
F. Bianco et al. / NeuroToxicology 32 (2011) 410–412
The clinical presentation varies widely. There may be an altered level of consciousness, spasticity, or the development of a bradykinetic rigid state. In some cases, there is rapid progression to death and complete recovery rarely occurs (Maschke et al., 1999). There is not general consensus about treatment of toxic leukoencephalopathy. It has been suggested that coenzyme Q10 and vitamins E and C supplements may be of benefit in heroin vapor inhalation leukoencephalopathy (Kriegstein et al., 1999). Nevertheless, little published data exist on treating cocaine toxic leukoencephalopathy, whose treatment remains primarily supportive (Keogh et al., 2003). In our case, corticosteroid treatment was performed on the first admission on the basis of a possible presence of cocaine-induced cerebrovascular inflammation, as previously suggested (Diez-Tejedor et al., 1998). Indeed, we do not believe that corticosteroid therapy played a major role in clinical recovery. On the second admission, the diagnosis of cocaine-induced toxic leukoencephalopathy was established and supportive treatment was only performed. The patient’s unexpected recovery on neurological and neuropsychological examination, despite severe neurological symptoms, is striking and differs from the findings of other reports of a rapid progression to death (Kondziella et al., 2007; Ryan et al., 2005). Of note, case presented with two consecutives episodes of acute leukoencephalopathy and, to our knowledge, recurrent episodes of cocaine-induced toxic leukoencephalopathy, with favourable outcome, have not been described yet. Kriegstein et al. (1999) suggested that there may be a dose dependent severity of the disease when caused by inhaling heroin pyrolysate. This may also be the case for the cocaine abuse we reported, whose increasing severity in the clinical presentation and MRI lesions is likely due to the dose of cocaine used. Progressive multifocal leukoencephalopathy could be considered in the differential diagnosis, but the patient was not immunodepressed and test for JC virus was negative. Other possible mimickers such as adrenoleukodystrophy, multiple sclerosis and ischemia were excluded on the basis of clinical assessment. Since case presented in the unusual form of recurrent leukoencephalopathy, with favourable outcome, posterior reversible encephalopathy syndrome (PRES) needs to be excluded too. As it has been recently reminded, it is important to distinguish toxic leukoencephalopathy from PRES, which may be caused by many of the same medications or drugs and possible overlap between PRES and toxic leukoencephalopathy has been admitted, in some cases (McKinney et al., 2009). PRES is characterized by vasogenic oedema in the posterior regions of the cerebral hemispheres and usually presents symptoms of headache, seizures and cortical visual disturbances, associated with hypertension (Hinchey et al., 1996). Nevertheless, ‘‘atypical’’ forms of PRES are
being reported with increasing frequency in the current literature. These ‘‘atypical’’ forms can be: not reversible; not associated with hypertension; not characterized by classic symptoms of headache, seizures, cortical visual disturbances or blindness; not restricted to the posterior regions of the cerebral hemispheres (Bhagavati and Choi, 2008; Ahn et al., 2004; Ay et al., 1998). DWI may show either vasogenic or cytoxic oedema, in some cases (Covarrubias et al., 2002). Of note, a recurrent form of PRES has been also described (Hagemann et al., 2004). Indeed, growing experience is indicating that PRES could actually represent a non-specific reaction of the brain, triggered by different pathologies, taking the form of an encephalopathy characterized by acute onset of cerebral oedema, either vasogenic or even cytotoxic, with variable outcome (Bianco, 2005). Conflict of interest statement The authors declare that there are no conflicts of interest. References Ahn KJ, You WJ, Jeong SL, Lee JW, Kim BS, Lee JH, et al. Atypical manifestations of reversible posterior leukoencephalopathy syndrome: findings on diffusion imaging and ADC mapping. Neuroradiology 2004;46:978–83. Ay H, Buonanno FS, Schaefer PW, Le DA, Wang B, Gonzalez RG, et al. Posterior leukoencephalopathy without severe hypertension: utility of diffusion-weighted MRI. Neurology 1998;51:1369–76. Bhagavati S, Choi J. Atypical cases of posterior reversible encephalopathy syndrome. Clinical and MRI features. Cerebrovasc Dis 2008;26:564–6. Bianco F. Reversible posterior leukoencephalopathy syndrome: a changing concept. Neuroradiology 2005;47:703–4. Covarrubias DJ, Luetmer PH, Campeau NG. Posterior reversible encephalopathy syndrome: prognostic utility of quantitative diffusion-weighted MR images. Am J Neuroradiol 2002;23:1038–48. Diez-Tejedor E, Frank A, Gutierrez M, Barreiro P. Encephalopathy and biopsy-proven cerebrovascular inflammatory changes in a cocaine abuser. Eur J Neurol 1998;1:103–7. Filley CM, Kleinschmidt-DeMasters BK. Toxic leukoencephalopathy. N Engl J Med 2001;345:425–32. Hagemann G, Ugur T, Witte OW, Fitzek C. Recurrent posterior reversible encephalopathy syndrome (PRES). J Hum Hypertens 2004;18:287–9. Hinchey J, Chaves C, Appignani B, Breen J, Pao L, Wang A, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996;334:494–500. Keogh CF, Andrews GT, Spacey SD, Forkheim KE, Graeb DA. Neuroimaging features of heroin inhalation toxicity: ‘‘chasing the dragon’’. Am J Roentgenol 2003;180:847– 50. Kondziella D, Danielsen ER, Arlien-Soeborg P. Fatal encephalopathy after an isolated overdose of cocaine. J Neurol Neurosurg Psychiatry 2007;78:437–8. Kriegstein AR, Shungu DC, Millar WS, Armitage BA, Brust JC, Chillrud S, et al. Leukoencephalopathy and raised brain lactate from heroin vapor inhalation (‘‘chasing the dragon’’). Neurology 1999;53:1765–73. Maschke M, Fehlings T, Kastrup O, Wilhelm HW, Leonhardt G. Toxic leukoencephalopathy after intravenous consumption of heroin and cocaine with unexpected clinical recovery. J Neurol 1999;246:850–1. McKinney AM, Kieffer SA, Paylor RT, Santa Cruz KS, Kendi A, Lucato L. Acute toxic leukoencephalopathy: potential for reversibility clinically and on MRI with diffusion-weighted and FLAIR imaging. Am J Roentgenol 2009;193:192–206. Ryan A, Molloy FM, Farrell MA, Hutchinson M. Fatal toxic leukoencephalopathy: clinical, radiological, and necropsy findings in two patients. J Neurol Neurosurg Psychiatry 2005;76:1014–6.