A different type of blocking (Fig 1, right) was seen
eight and nine months after onset. Here, a single late
component was present in an on-off fashion for 30 or
more consecutive impulses. An analogous finding has
been reported at regions of low conduction safety in
single primary afferent fibers of the cat, with impulses
undergoing alternating periods of block and conduction [I]. This raises the possibility that following the
attack of myoglobinuria, a recently myelinated sprout
acted as a region of low conduction safety, thereby
giving rise to on-off blocking. Further studies may
help resolve this point.
I am grateful to Drs M. J. Aminoff, H. L. Fields, and D. A. Riley, of
the University of California, San Francisco, for review of the manuscript and valuable suggestions.

References
1. Chung S-H, Raymond SA, Letwin JY: Mulaple meanings in

single visual units. Brain Behav Evol 3:72-101, 1970
2. Dennis MJ: Physiological properties of junctions berween nerve
and muscle developing during salamander limb regeneration. J
Physiol (Lond) 244:683-702, 1975
3. Desmedt JE, Borenstein S: Regeneration in Duchenne muscular
dystrophy.

Electromyographic

evidence.

Arch

Neurol

33:642-650, 1976
4. Edds M V : Collateral nerve regeneration. Q Rev Biol 28:260276, 1953
5. Hall-Crams ECB: Hyperinnervation of muscle following treatment with bupivacaine. Anat Rec 184:420-421, 1976
6. Staberg E, 'Ihiele B: Transmission block in terminal nerve
twigs: a single fibre electromyographic finding in man. J Neurol
Neurosurg Psychiatry 35:52-59, 1972
7 . Trojaborg W: Prolonged conduction block with axonal degeneration. An electrophysiological study. J Neurol Neurosurg
Psychiatry 40:50-57, 1977

Blue Rubber Bleb
Nevus Syndrome with
CNS Involvement and
Thrombosis of a Vein of
Galen Malformation
E. A. Waybright, MD, J. B. Selhorst, MD,
W. 1. Rosenblum, MD, and C. G. Suter, M D

A patient is described with the dermatological features
of blue rubber bleb nevus syndrome (BRBNS), focal
seizures, and lateralized neurological signs. CAT scan
demonstrated a nonenhanced density in the region of
the vein of Galen. Neuropathological examination
showed that this density was a clot within a vein of
Galen malformation. Hemangiomas that grossly resembled the skin lesions of BRBNS were seen on the
cerebral surface. Many of these hemangiomas were
thrombosed and overlay patchy zones of infarction.
Numerous vascular malformations of varying histological types were also found within the brain and systemic organs.
Bluish, compressible, often raised hemangiomas of
the skin should alert physicians to the BRBNS and the
potential for vascular malformations to occur within
the brain as well as systemic organs. Diagnosis of
BRBNS involving the brain may assist in interpretation of radiographic findings. T h e tendency of these
malformations to thrombose may account for focal
neurological deficits.
Waybright EA, Selhorst JB, Rosenblum WI, et al:
Blue rubber bleb nevus syndrome with CNS
involvement and thrombosis of a vein of Galen
malformation. Ann Neurol 3:464-467, 1978
In 1958 Bean [ 13 described a disorder with distinctive
hemangiomas of the skin and gastrointestinal tract. He
termed the condition the blue rubber bleb nevus syndrome (BRBNS). We wish to draw attention to brain
involvement in BRBNS by describing a patient who
presented with focal seizures, lateralized neurological
signs, and bluish hemangiomas of the skin. In this
patient computerized tomography (CAT scan) revealed a high density in the region of the vein of
Galen. T h e nature of this high density and the cause of
the neurological signs were not fully evident until
pathological examination.
From the Departments of Neurology and Pathology, Medical College of Virginia, Richmond, VA.
Accepted for publication Dec 13, 1977.
Address reprint requests to D r Selhorst, Box 698, Medical College
of Virginia. L c h m o n d , VA 23298.

464 0364-5134/78/0003-0521$01.00 @ 1978 by E. A. Waybright

Four months before admission a 19-year-old man described
a brief clonic twitch of his left arm. Subsequently he complained of several severe, throbbing bifrontal headaches.
O n e such headache lasted three days. Two clonic seizures of
the left arm prompted admission. Careful review of the
family history did not reveal similar skin lesions in any
member.
The patient was 1.52 m tall and weighed 91.9 kg. Blood
pressure was 154/104. His skin had scattered, spiderlike
telangiectasias and blue, bleblike, rubbery hemangiomas of
the left upper eyelid, lower lip (Fig l ) , buccal mucosa, and
palm. These had been present from birth. General physical
examination was unremarkable. Neurological examination
disclosed total left homonymous hemianopia, broad-based
gait, and slightly decreased strength in the left arm. Astereognosis and extinction to double, simultaneous tactile
stimuli were found in the left hand. Ocular motility was full.
There were no abnormal eye movements. Funduscopic examination after application of a mydriatic agent was unremar kable .
Laboratory data revealed an increased red cell mass
(hemoglobin, 18.7 g d d l , hematocrit, 54.5%) with low to
normal platelet count and normal white cell count. Lactic
dehydrogenase and alkaline phosphatase were elevated.
Other liver function indicators were normal after transient
mild elevations. Urinalysis showed proteinuria and slightly
positive reaction for blood without microscopic hematuria.
An electrocardiogram recorded first-degree atrioventricular
block and right ventricular hypertrophy. With the patient
breathing 100% oxygen, a right-to-left pulmonary shunt of
1.3% was found.
Roentgenograms of the chest, hand, skull, and long bones
were normal. An electroencephalogram showed spike discharges and theta rhythm in the right posterior hemisphere.
CAT scan revealed a small, high density in the posterior
midline that was not enhanced after injection of contrast
material. Prominent basal veins and a straight sinus were
seen (Fig 2A). An angiogram of the right carotid and left
vertebral arteries showed dilated basal veins and superficial

draining veins over the right hemispheric cortex. The
thalamostriate and internal cerebral veins and the vein of
Galen were not visualized. Using subtraction techniques
neither arterial shunts, hypervascular stains, nor early-filling
veins were identified about the vein ofGalen or the cerebral
surface.
After consultation a clinical diagnosis of BRBNS of skin
and brain was made. Phenytoin therapy was begun. Several
phlebotomies were performed to ameliorate secondary
polycythemia. Three days after discharge the patient died at
home in his sleep.

F i g I . Raised bluish heniangiomas w i t h a rubbery consistency
are Jeen on the eyelid, lip, and angle ofthe mouth. Spontmeous
perspiration occurred on the upper lip.

Discussion

Postmortem Findings
The patient had multiple vascular malformations of the skin,
esophagus, right atrium, pericardium, and parietal pleura.
These malformations were variously capillary telangiectasias, cavernous and venous hemanfiiomas, and arteriovenous malformations. Abnormal pulmonary vessels were
also seen. The cause of death was not apparent.
Numerous bluish, ectatic vessels up to 1.0 cm in diameter
were scattered over the posterior half of the right hemispheric surface (Fig 3). These hemangiomas grossly resembled the skin lesions o n the face. Histological examination
showed these ectatic vessels to be large, dilated channels
with walls of varying thickness. Many of the channels were
thrombosed. Multiple tortuous arteries were present adjacent to these walls. In one section a small artery entered the
dilated vein. Moderate-sized venous channels were also
seen deep in sulci. Along the surfaces of the right posterior
parietal and occipital lobes, underlying the thrombosed
hemangiomas, were multiple softened, yellowish areas.
These thin, discolored patches consisted of necrotic gray
and white matter. In the region ofthe vein ofGalen was a 2.0
cm bluish mass that was fed by the internal cerebral veins
(Fig 2B). This mass was a venous aneurysm which contained a large thrombus. Several small arteries were found
adjacent to it. Capillary telangiectasias and cavernous
hemangiomas were also found near the surface of the right
cerebrum and cerebellum.

C a v e r n o u s hemangiomas, blood sacs with a rubbery
consistency a n d bluish color, and irrcgular blue marks

Case Report: Waybright et al: Blue Rubber Bleb Nevus Syndrome 465

Fig 2. (A)CAT scan with contrast s h m s venouJ drainage into
the straight sinus and around a small midline density that was
not enhancedafier injection of contrast. (B) This density was a
clot within a 2.0 cm, bluish bleb in the region of the vein of
Galen (arrows).

A

466 Annals of Neurology Vol 3 No 5 May 1978

B
F i g 3. Anterior surface (A)andposterior surface (B) of serial
sectionsfrom the posterior right hemisphere show severallarge
and smallthrombosed malformations on the cerebral surface and
i n the sulci. Multiple dilated vessels are seen within brain
parenchyma. Awws indicate softened, discolored margins of
several gyri.

were all described by Bean as part of BRBNS [ l ] .
These lesions are often, but not invariably, elevated.
Occasionally pain or hyperhidrosis further distinguishes the skin lesion [ 4 ] .Histological section shows
large and small cavernous spaces lined with endothelium and separated by varying amounts of collagenous and fibrous tissues [ 1, 2,4]. T h e most frequent serious complication of BRBNS is hemorrhage
from gastrointestinal tract hemangiomas [2]. Hemangiomas in other abdominal organs and the lungs have
also been reported. In three families BRBNS has been
reported to be genetically transmitted [2, 81.
Because of scattered telangiectasias and pulmonary
shunting, a diagnosis of Osler-Weber-Rendu disease
or hereditary hemorrhagic telangiectasia (HHT) was
considered in our patient during his hospitalization.
This diagnosis was discarded because of the presence
of skin lesions more typical for BRBNS and absence
of the inherited flat, reddish pinhead angiomas of
HHT. Furthermore, our review of the neuropathology of HHT failed to disclose vascular lesions within
the brain that grossly resembled those in our patient.
Three past reports of multiple hemangiomatosis
involving brain might now be recognized as manifesting dermatological features of BRBNS. Jaffe [71 described a patient with skin, thyroid, lung, intestine,
spleen, cervical anterior nerve root, and asymptomatic
leptomeningeal hemangiomas which resembled those
of our patient. Wood and associates [lo] reported
similar coincidental hemangiomas of brain, skin, liver,
spleen, and kidney in an elderly woman with acerebral
infarction. Burke et al [3] found multiple hemangiomas of the brain in an infant with seizures, hydrocephalus, and many large, protuberant skin
hemangiomas. To our knowledge this is the first patient described with focal neurological signs accompanying the now established BRBNS.
Thrombosis in the malformations of the cerebral
surface and vein of Galen in o u r patient were remarkable neuropathological findings. Thrombosis in the
skin hemangiomas of BRBNS has been described
[ 4 ] .Thus, discovery of thrombi in similar appearing
vascular malformations of the brain is not unex-

pected. Polycythemia possibly contributed further to
thrombus formation. The composite of multiple
patchy zones of necrotic cerebrum underlying the
thrombosed malformations on the cerebral surface
accounted for the left homonymous hemianopia and
spike discharges.
Spontaneous thrombosis of an arteriovenous malformation is rare. There are only 2 reports of complete thrombosis of a vein of Galen aneurysm [5,
91. In both reports the histological description is incomplete. A thrombosed cavernous hemangioma in
the pineal region of a patient without skin lesions was
recently described. That report is relevant to our patient because of a remarkably similar C A T scan [6]. In
each patient with a thrombosed vein of Galen
aneurysm, as in our own, angiography failed to reveal
internal cerebral veins o r the vein of Galen. Recognition of the vascular lesions of BRBNS, the possible
association with vascular malformations in the brain,
and the tendency of the latter to thrombose should
assist proper interpretation of similar radiographic
findings in the future.
References
1. Bean WR: Vascular Spiders and Related Lesions of the Skin.

Springfield, IL, Charles C Thomas, 1958, pp 178-185
2. Bedyne GM, Berlyne N : Anemia due to "blue-rubber-bleb'
nevus disease. Lancet 2:1275-1277, 1960
3. Burke EC, Winkelmann RK, Strickland MK: Disseminated
hemangiomarosis. Am J Dis Child 108:418-424, 1964
4. Fretzin DF, Potter B: Blue rubber bleb nevus. Arch Intern
Med 116924-929. 1965
5. Heinz ER, Schwartz JF, Sears RA: Thrombosis in the vein of
Galen malformation. Br J Radio1 41:424-428, 1968
6. Hubschmann 0, Kasoff S, Doniger D: Cavernous hemangioma in the pineal region. Surg Neurol 6:349-351, 1976
7. Jaffe RH: Multiple hemangiomas ofrhe skin and of the internal
organs. Arch Pathol 7:44-54, 1929
8. Walshe MM, Evans CO, Warin RF': Blue rubber bleb nevus.
Br Med J 2:931-932, 1966
9. Weir BKA, Allen PBR, Miller J D R Excision of thrombosed
vein of Galen aneurysm in an infant. J Neurosurg 29:619622, 1968
10. Wood MW, White RJ, Kernohan JW: Cavernous hemangiomatosis involving the brain, spinal cord, heart, skin, and
kidney. Proc Mayo Clin 32:249-254, 1957

Case Report: Waybright et al: Blue Rubber Bleb Nevus Syndrome 467