Journal of Clinical Neuroscience xxx (2015) xxx–xxx

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Journal of Clinical Neuroscience
journal homepage: www.elsevier.com/locate/jocn

Case Report

Synthetic cannabinoids revealing adrenoleukodystrophy
Avi Fellner ⇑, Felix Benninger, Ruth Djaldetti
Department of Neurology, Rabin Medical Center, Beilinson Hospital, 39 Jabotinski Street, Petah Tikva 49100, Israel
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

a r t i c l e

i n f o

Article history:
Received 16 July 2015
Accepted 23 July 2015
Available online xxxx
Keywords:
Adrenoleukodystrophy
Cannabinoids
Leukodystrophies
MRI
Seizures

a b s t r a c t
We report a 41-year-old man who presented with a first generalized tonic-clonic seizure after recent consumption of a synthetic cannabinoid. MRI showed extensive bilateral, mainly frontal, white matter
lesions. Blood analysis for very long chain fatty acids was compatible with adrenoleukodystrophy, and
a missense mutation in the ABCD1 gene confirmed the diagnosis. We hypothesize that cannabinoid
use might have contributed to metabolic decompensation with subacute worsening of the underlying
condition.
Ó 2015 Elsevier Ltd. All rights reserved.

1. Case report
A 41-year-old man presented to the emergency department
with a first generalized tonic-clonic seizure. On arrival he was confused and disoriented with disinhibited behavior and frontal
release signs. Spastic quadriparesis, bilateral ankle clonus and
bilateral extensor plantar response were noticed.
The patient’s family reported learning difficulties from childhood and an acute depressive episode with a single suicide attempt
4 years earlier. He smoked cannabis on a regular basis and was
recently consuming a synthetic cannabinoid street drug termed
‘‘Nice Guy”. During the month prior to admission, behavioral
changes were noted with easy irritability and aggressive outbursts
as well as bizarre incoherent behavior, including shaving half of his
face and talking to himself.
Toxic screen on admission was positive for benzodiazepines and
tetrahydrocannabinol. Blood tests were unremarkable, except for
an elevated creatine kinase [1,928 units/l (normal range: 20–
200 units/l)]. MRI following head CT scan showed hyperintense
symmetric bilateral, mainly frontal, lesions, with symmetric linear
restricted diffusion and gadolinium enhancement in part of the
lesion (Fig. 1).
Human immunodeficiency virus testing was negative. Cerebrospinal fluid (CSF) analysis showed four white cells, elevated
protein level of 74 mg/dl (normal range: 15–45 mg/dl), and glucose
of 76 mg/dl (normal range: 40–70 mg/dl), and was negative for
venereal disease research laboratory test, treponema pallidum
⇑ Corresponding author. Tel.: +972 54 541 1771; fax: +972 3 937 6355.
E-mail address: avi.fellner@gmail.com (A. Fellner).

hemagglutination test, cryptococcal antigen, polymerase chain
reaction for John Cunningham virus and toxoplasma. CSF showed
two monoclonal bands which were stronger in the CSF than in
the serum. Free light chain analysis in the serum demonstrated
normal kappa to lambda ratio. Total body positron emission
tomography-CT scan was normal. Electroencephalogram showed
bilateral frontal slowing in the theta range.
The patient was treated with antiepileptic medication without
recurrent seizures. Motor weakness resolved spontaneously. He
was left with bilateral extensor plantar response, frontal disinhibition and incoherent behavior.
Blood analysis for very long chain fatty acids levels demonstrated increased C24:22 ratio of 1.663 and increased C26:22 ratio
of 0.092, compatible with the diagnosis of adrenoleukodystrophy
(ALD). A missense mutation in the ABCD1 gene confirmed the
diagnosis.

2. Discussion
We present a case of leukodystrophy in a patient who came to
medical attention after a first epileptic seizure following synthetic
cannabinoid consumption. Synthetic cannabinoids abuse is associated with seizures [1] and leukodystrophy diagnosis in this case
could be incidental. Nevertheless, we hypothesize that cannabinoids use might have contributed to metabolic decompensation
with subacute worsening of the underlying condition. Lesions in
cerebral ALD involve the parieto-occipital lobes or, as in this case,
the frontal lobes [2]. The demyelinating lesions of ALD are initially
not of active inflammatory origin, with absence of gadolinium

http://dx.doi.org/10.1016/j.jocn.2015.07.020
0967-5868/Ó 2015 Elsevier Ltd. All rights reserved.

Please cite this article in press as: Fellner A et al. Synthetic cannabinoids revealing adrenoleukodystrophy. J Clin Neurosci (2015), http://dx.doi.org/
10.1016/j.jocn.2015.07.020

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Case Report / Journal of Clinical Neuroscience xxx (2015) xxx–xxx

enhancement. Patients often have no neurologic deficits, except
mild progressive cognitive impairment, until the disease turns to
an active inflammatory state with gadolinium enhancement of
the lesions followed by rapid clinical deterioration [2]. Gadolinium
enhancement of the lesions in our patient may represent progression from indolent ALD to clinically overt disease possibly
triggered by synthetic cannabinoid abuse.
Conflicts of Interest/Disclosures
The authors declare that they have no financial or other
conflicts of interest in relation to this research and its publication.
References
[1] Harris CR, Brown A. Synthetic cannabinoid intoxication: a case series and
review. J Emerg Med 2013;44:360–6.
[2] Kemp S, Berger J, Aubourg P. X-linked Adrenoleukodystrophy: clinical,
metabolic, genetic and pathophysiological aspects. Biochim Biophys Acta
2012;1822:1465–74.

Fig. 1. Axial brain CT scan showing bilateral hypodense confluent lesion involving
periventricular frontal areas (A) and the corpus callosum, with mild peripheral
contrast enhancement (B). Axial MRI showing hyperintense bilateral symmetric
lesion on T2-weighted imaging (C), with symmetric linear restricted diffusion (not
shown) and gadolinium enhancement in part of the lesion on T1-weighted imaging
(not shown) and on fluid attenuated inversion recovery sequence (D).

Please cite this article in press as: Fellner A et al. Synthetic cannabinoids revealing adrenoleukodystrophy. J Clin Neurosci (2015), http://dx.doi.org/
10.1016/j.jocn.2015.07.020