SCIENCE sciencemag.org 21 DECEMBER 2018 • VOL 362 ISSUE 6421 1341PHOTO: JAMES AKENA/REUTERS
A
disease mystery with no shortage of
leads now has an intriguing new one.
Since the 1960s, thousands of chil-
dren in poor, war-torn regions of East
Africa have developed epilepsy-like
seizures in which their heads bob to
their chest; over time, the seizures worsen,
cognitive problems develop, and the victims
ultimately die. Researchers have proposed
causes for nodding syndrome that include
malnutrition, parasites, and viruses, but
have not proved a clear link to any of them.
Now, the first published examination of the
brains of children who died
after developing the condition
suggests it has a key similarity
to certain brain diseases of old
age, such as Alzheimer’s and
Parkinson’s: It leaves victims’
brains riddled with fibrous
tangles containing a protein
called tau.
“Nodding syndrome is a
tauopathy,” concludes Michael
Pollanen, a pathologist at the
University of Toronto in Can-
ada who is lead author of a
report published last month
in Acta Neuropathologica.
Pollanen believes the finding
“suggests a totally new line
of investigation” into the syn-
drome. As significant as the
discovery of the tangles may be what his
group of Canadian and Ugandan research-
ers didn’t find: any sign of the brain inflam-
mation that might be triggered by a parasite
or virus. “Our hypothesis is that nodding
syndrome is a neurodegenerative disease,
like Alzheimer’s,” Pollanen says.
Some who study the condition are skep-
tical, but the possibility excites researchers
working on other tauopathies including
Alzheimer’s. Childhood forms of those dis-
eases are exceedingly rare, but the nodding
syndrome finding “means [tau deposition]
is not an age-dependent problem,” says John
Hardy, of the UK Dementia Research Insti-
tute at University College London. Some-
thing else must have triggered the tauopathy
in these children. And because nodding syn-
drome struck a small region of East Africa,
over a specific time period—in Uganda, the
condition appears to be vanishing—its trig-ger might be relatively easy to identify, and
could shed light on the causes of diseases
like Alzheimer’s, Hardy and others say.
First, though, the researchers need to
convince others who have studied nodding
syndrome for years that they are right.
Originally reported in Tanzania, the dis-
ease spread to what is now South Sudan
in the 1990s and to northern Uganda after- Uganda has reported 3000 cases, but
no new ones since 2014. The current study
was done on the brains of five Ugandan
children who fell ill while living in camps
for internally displaced persons between
2005 and 2010, when Joseph Kony’s Lord’s
Resistance Army was terrorizing the re-
gion, and later died.
The brains are among a dozen obtained
by U.S. and Ugandan researchers between
2014 and 2017, overcoming challenges such
as persuading relatives, harvesting the or-
gans promptly after death, and transport-
ing them from remote areas in a tropical
climate. Initial investigations done in the
United States were never published—it’s not
clear why—and the brains were returned to
Uganda, where Pollanen’s group studied all- They hope to publish their analyses of
the remaining seven soon.
The current paper is thin on detail and
lacks important controls, cautions neuro-
logist Avindra Nath of the U.S. National In-
stitute of Neurological Disorders and Stroke
in Bethesda, Maryland, who has studied
nodding syndrome. It does not describe the
brain pathology in children from the same
population who died of other forms of epi-
lepsy, for example.
Robert Colebunders, an infectious dis-
ease expert at the University of Antwerp in
Belgium who has long worked on nodding
syndrome, says he has still-unpublished post-
mortem findings from seven children who
fell ill at the same time, in the same camps,
but survived longer because they received
better care and experienced fewer seizures.
None of them shows tauopathy, he says. “My
conclusion is that tau [deposition] is a conse-
quence of seizures, not a cause.”
Colebunders favors a long-standing theory
that the ultimate cause of nodding syndrome
is infection by a parasitic
worm called Onchocerca vol-
vulus, which is endemic to
the same regions. There is no
evidence that the worm itself
penetrates the brain, but last
year, Nath and others pro-
posed that a protein in the
worm triggers the produc-
tion of antibodies that attack
a similar protein on neu-
rons, in a misdirected auto-
immune response (Science,
17 February 2017, p. 678).
It’s dangerous to propose
that nodding syndrome is a
neurodegenerative disease,
Colebunders says, because it
could divert resources away
from much-needed efforts to
eradicate the worm and to improve care for
children with the illness. “With good care and
nutrition, the epilepsy can be controlled and
the children can go back to school without
suffering any cognitive deficit,” he says.
But Peter Spencer, a neurotoxicologist at
Oregon Health & Science University in Port-
land, suspects the worm is a bystander. He
suggests it opportunistically infects people
who have another condition that also triggers
seizures and tau deposition. How it all fits to-
gether is unclear, but tau gives investigators
one more piece of the puzzle, Spencer says.
“We have an opportunity here to discover the
primary cause of this disease, and then to do
primary prevention.” Not only will that ben-
efit affected children, Spencer adds, “It will
potentially open up our understanding of
other tauopathies, too.” jLaura Spinney is a journalist in Paris.Protein tangles hint that childhood illness is a degenerative disease of the brain
N E U R O L O GYLink to Alzheimer’s seen in nodding syndrome
By Laura SpinneyA 2012 image from Uganda shows an 1 1 - year-old boy suffering from nodding syndrome.NEWS | IN DEPTHPublished by AAASon December 20, 2018^http://science.sciencemag.org/Downloaded from