232 Case Reports / Journal of Clinical Neuroscience 34 (2016) 232–234

Combined endovascular and microsurgical treatment of a complex

spinal arteriovenous fistula associated with CLOVES syndrome in an
adult patient
Mohammad R. Boroumand 1, M. Yashar S. Kalani 1, Robert F. Spetzler ⇑
Department of Neurosurgery, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, United States

a r t i c l e i n f o a b s t r a c t

Article history: CLOVES (congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and scoliosis/skele-
Received 24 June 2016 tal/spinal anomalies) syndrome is a congenital and almost exclusively pediatric syndrome associated
Accepted 12 September 2016 with vascular malformations of the neuroaxis. We report the case of a complex spinal arteriovenous fis-
tula in an adult woman with CLOVES syndrome treated using a multidisciplinary approach with endovas-
cular embolization and microsurgical technique, and review the medical literature on this disease.
Keywords:
Ó 2016 Elsevier Ltd. All rights reserved.
CLOVES
Malformation
Spinal
Vascular

1. Introduction CLOVES syndrome may be apparent on ultrasound in late preg-

CLOVES (congenital lipomatous overgrowth, vascular malfor-
mations, epidermal nevi, and spinal deformation) syndrome is a
rare disorder usually diagnosed in children. We present the first
adult case with combined endovascular and microsurgical man-
agement of a symptomatic complex arteriovenous fistula.
2. Case presentation and diagnostics
A 54-year-old woman presented with neck pain and myelo-
pathy. Cervical spine MRI revealed flow voids and C5-C6 disc com-
pression of the spinal cord (Fig. 1A). Spinal angiography revealed
an extraspinal arteriovenous fistula (C7 to T2), fed by branches of
the left thyrocervical and costocervical trunks and draining trans-
durally into intradural spinal veins (Fig. 1B and C). Examination
revealed nevi over the back (Fig. 1D), a large midline lipoma
extending to the left scapula, and an enlarged left leg and foot.
Two-stage endovascular embolization with polyvinyl alcohol
(Onyx) and n-butyl cyanoacrylate glue was used for the arterial
pedicles to the fistula. Remaining arterial feeders were discon-
nected microsurgically at the spinal dura level without intradural
exploration. Intraoperatively, arterial branches to the fistula were
noted passing through the lipoma.
Postoperative imaging demonstrated complete disconnection of
the fistula (Fig. 1E).
3. Discussion
CLOVES syndrome was described in 2007 by Sapp et al. [1] for a
subgroup of 7 patients diagnosed with Proteus syndrome, a rare
congenital disorder involving gigantism of hands and feet, epider-
mal nevi, hemihypertrophy, subcutaneous tumors, macrocephaly,
and lipomatosis. It has a postnatal onset, is progressive, and occurs
sporadically [2].
⇑ Corresponding author at: c/o Neuroscience Publications, Barrow Neurological
Institute, St. Joseph’s Hospital and Medical Center, 350 W. Thomas Rd., Phoenix, AZ
85013, United States. Fax: +1 602 406 4104.
E-mail address: Neuropub@dignityhealth.org (R.F. Spetzler).
1
These authors contributed equally to this report.
nancy. Skeletal deformations appear more ballooning than dis-
torted. However, distortion may occur after corrective surgery.
The course of the disease is nonprogressive or mildly progressive
[1].
Patients are typically born with thoracic and abdominal wall
lipomatous masses. Musculoskeletal manifestations include leg-
length discrepancy, dislocated knees, scoliosis, wide hands and
feet, furrowed soles, sandal gap toe, and hemihypertrophy. Neuro-
logical and cutaneous manifestations include neural tube defect,
tethered cord, capillary malformation, and epidermal nevi [1,3].
Other overgrowth disorders are Klippel-Trenaunay, Cobb Parkes
Weber, Bannayan-Riley-Ruvalcaba, and Lhermitte-Duclos syn-
dromes [4]. Understanding the differences among overgrowth
disorders may facilitate management and advance research on
causes and treatments [1].
In 2010 Alomari et al. [5] reported that CLOVES syndrome
would be a more adequate description for many patients diag-
nosed with Cobb syndrome. They identified 7 cases, including a
19th-century case, that likely were CLOVES syndrome instead of
Cobb syndrome [6].
Patients with CLOVES syndrome and vascular malformations
generally have truncal fatty overgrowth with capillary stains and
skeletal asymmetry (spinal deformities and/or megalodactyly).
Alomari et al. [3] reported on 6 CLOVES patients with complex
spinal-paraspinal, fast-flow lesions presenting with a hypervascu-
lar paraspinal fatty structure and communicating vessels to para-
spinal arteriovenous shunts.
Causes of overgrowth syndromes with vascular malformations
are unknown. Detailed genetic analysis shows a somatic mosaic
PIK3CA gene mutation in CLOVES, as in Klippel-Trenaunay syn-
drome and fibro-adipose vascular anomaly. The mutation causes
increased phosphoinositide-3-kinase activity [7]. Rare sporadic
and asymmetric phenotypes may result from genetic mutations,
which would be lethal in the autosomal form [8].
The coexistence of fatty tissue overgrowth and fast-flow
shunts suggests an association between adipocytes and endothe-
lial cells, potentially during embryonic development. Adipose
tissue growth is angiogenesis-dependent, and angiogenesis inhi-
bitors decrease endothelial cell proliferation and increase adipose
apoptosis [9].
 Case Reports / Journal of Clinical Neuroscience 34 (2016) 232–234 233

Fig. 1. (A) Sagittal T2-weighted MRI demonstrates flow voids. Spinal angiography confirms a spinal fistula fed by (B) thyrocervical and (C) costocervical trunks. (D)
Intraoperative photographs demonstrate skin nevi and soft tissue lipoma. (E) Postoperative angiography demonstrates fistula disconnection. Used with permission from Barrow
Neurological Institute, Phoenix, Arizona.

Vascular malformations can be challenging to treat. Many clas- Financial support

sifications are available for spinal vascular lesions [10]. Extradural
feeders shunting to spinal canal veins lead to mass effect, compres- None.
sion of nerve roots and spinal cord, and ultimately CLOVES symp-
toms. Individualized by lesion, treatment can include embolization
and microsurgical disconnection. Acknowledgment

We thank the staff of the Neuroscience Publications office at

4. Conclusion Barrow Neurological Institute.

For this adult with CLOVES syndrome, we combined endovascu-

References
lar embolization and microsurgical disconnection for a complex
spinal arteriovenous fistula. Despite its pediatric predominance,
CLOVES syndrome should be considered in the differential when
evaluating adults with prototypical characteristics.
Disclosures
None.
[1] Sapp JC, Turner JT, van de Kamp JM, et al. Newly delineated syndrome of
congenital lipomatous overgrowth, vascular malformations, and epidermal
nevi (CLOVE syndrome) in seven patients. Am J Med Genet A
2007;143A:2944–58.
[2] Biesecker LG, Sapp JC. Proteus Syndrome. In: Pagon RA, Adam MP, Ardinger HH,
Wallace SE, Amemiya A, Bean LJH, et al., editors. GeneReviews. Seattle,
WA: University of Washington; 1993–2016.
[3] Alomari AI, Chaudry G, Rodesch G, et al. Complex spinal-paraspinal fast-flow
lesions in CLOVES syndrome: analysis of clinical and imaging findings in 6
patients. AJNR Am J Neuroradiol 2011;32:1812–7.
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[4] Uller W, Fishman SJ, Alomari AI. Overgrowth syndromes with complex [8] Happle R. Lethal genes surviving by mosaicism: a possible explanation for
vascular anomalies. Semin Pediatr Surg 2014;23:208–15. sporadic birth defects involving the skin. J Am Acad Dermatol
[5] Alomari AI, Thiex R, Mulliken JB. Hermann Friedberg’s case report: an early 1987;16:899–906.
description of CLOVES syndrome. Clin Genet 2010;78:342–7. [9] Rupnick MA, Panigrahy D, Zhang CY, et al. Adipose tissue mass can be
[6] Alomari AI. Characterization of a distinct syndrome that associates complex regulated through the vasculature. Proc Natl Acad Sci U S A 2002;99:10730–5.
truncal overgrowth, vascular, and acral anomalies: a descriptive study of 18 [10] Kim LJ, Spetzler RF. Classification and surgical management of spinal
cases of CLOVES syndrome. Clin Dysmorphol 2009;18:1–7. arteriovenous lesions: arteriovenous fistulae and arteriovenous
[7] Kurek KC, Luks VL, Ayturk UM, et al. Somatic mosaic activating mutations in malformations. Neurosurgery 2006;59:S195–201 [discussion S3-13].
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http://dx.doi.org/10.1016/j.jocn.2016.09.001

Tardily accelerated neurologic deterioration in two-step thallium

intoxication
Hiroshi Kuroda a,⇑, Yoshiyuki Mukai b, Shuhei Nishiyama a, Takayuki Takeshita c, Maki Tateyama a,
Atsushi Takeda d, Masashi Aoki a
a
Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan
b
Department of Neurology, Izumi Hospital, Sendai, Japan
c
Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Japan
d
National Hospital Organization Nishitaga Hospital, Sendai, Japan

a r t i c l e i n f o a b s t r a c t

Article history: Thallium intoxication was reported in cases with accidental ingestion, suicide attempt, and criminal
Received 27 May 2016 adulteration. Reported cases were mostly one-time ingestion, therefore, the clinical course of divisional
Accepted 15 September 2016 ingestion has not been fully known. Here, we report a case with two-step thallium intoxication manifest-
ing as tardily accelerated neurologic deterioration. A 16-year-old adolescent was cryptically poisoned
with thallium sulfate twice at an interval of 52 days. After the first ingestion, neurologic symptoms
Keywords: including visual loss, myalgia, and weakness in legs developed about 40 days after the development of
Optic neuropathy
acute gastrointestinal symptoms and alopecia. After the second ingestion, neurologic symptoms deteri-
Peripheral neuropathy
Alopecia
orated rapidly and severely without gastrointestinal or cutaneous symptoms. Brain magnetic resonance
Mees’ line imaging exhibited bilateral optic nerve atrophy. Nerve conduction studies revealed severe peripheral
neuropathies in legs. Thallium intoxication was confirmed by an increase in urine thallium egestion.
Most of the neurologic manifestations ameliorated in two years, but the visual loss persisted. The source
of thallium ingestion was unraveled afterward because a murder suspect in another homicidal assault
confessed the forepast adulteration. This discriminating clinical course may be attributable to the cumu-
lative neurotoxicity due to the longer washout-time of thallium in the nervous system than other organs.
It is noteworthy that the divisional thallium intoxication may manifest as progressive optic and periph-
eral neuropathy without gastrointestinal or cutaneous symptoms.
Ó 2016 Elsevier Ltd. All rights reserved.

1. Introduction 2. Case report

Thallium is a heavy metal, used as industrial and medical mate-
rials, and rodenticide. Thallium intoxication was reported in cases
with accidental ingestion, suicide attempt, and criminal adulter-
ation [1,2]. Acute intoxication manifests as gastrointestinal, cuta-
neous, cardiovascular, and neurologic symptoms; chronic
intoxication manifests as mainly neurologic symptoms including
encephalopathy, optic neuropathy, and peripheral neuropathy
[1]. Reported cases were mostly one-time ingestion, therefore,
the clinical course of divisional ingestion has not been fully known.
Here, we report a case with two-step thallium intoxication mani-
festing as tardily accelerated neurologic deterioration.
⇑ Corresponding author at: Department of Neurology, Tohoku University
Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai 980-8574, Japan.
Fax: +81 22 717 7192.
E-mail address: dakuro@med.tohoku.ac.jp (H. Kuroda).
A 16-year-old adolescent without previous illness developed
abdominal pain and diarrhea (day 0). The gastrointestinal symp-
toms lasted several days and gradually ameliorated. Hair loss
began at day 7 and peaked at day 24. He felt blurred vision at
day 39; felt myalgia and weakness in legs at day 42. The blurred
vision and weakness rapidly deteriorated from day 44. He felt pro-
gressive numbness in legs from day 56. After visiting several doc-
tors’ office, he consulted our hospital at day 56. Physical
examination revealed recovering alopecia and white transverse
bands in hand nails, so-called ‘‘Mees’ lines” (Fig. 1a). Ophthalmo-
logic examination revealed impaired visual acuity (both: counting
finger) with bilateral central scotoma. Neurologic examination
revealed distal predominant weakness in legs (Medical Research
Council Scale: 4/5 in proximal muscles, 0/5 in distal muscles) to
be non-ambulatory, absent Achilles tendon reflexes, and
stocking-type dysesthesia. Blood, urine, and cerebrospinal fluid
examinations were normal. Brain magnetic resonance imaging
exhibited no parenchymal abnormalities but enlarged perineural