Handbook of Clinical Neurology, Vol.

113 (3rd series)

Pediatric Neurology Part III
O. Dulac, M. Lassonde, and H.B. Sarnat, Editors
2013 Elsevier B.V. All rights reserved

Chapter 178

Progressive myoclonus epilepsy

JEAN-MARIE GIRARD, JULIE TURNBULL, NIVETHA RAMACHANDRAN, AND BERGE A. MINASSIAN*
Division of Neurology, Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto, Canada

INTRODUCTION Myoclonus is distal, erratic, triggered by light and sound

Progressive myoclonus epilepsy (PME) is a dreaded cate-
gory of pediatric epilepsy. The term progressive distin-
guishes among countless epileptic children the few who
will not get better, but will get worse in a continuous unin-
terrupted fashion and ultimately die. Progressive also
implies neurodegenerative. Amidst the neurodegenera-
tion of PME, there is dramatic prominence of two partic-
ular symptoms, myoclonus and epilepsy, suggesting that
in this group of diseases there is either particular degener-
ation of neural pathways related to myoclonus and epi-
lepsy, or that the underlying genetic disturbances are,
separate from being neurodegenerative, also myoclono-
and epileptogenic.
Most pediatric PME are genetic diseases inherited in
autosomal recessive fashion. Exceptions are some cases
of mitochondrial disease, reviewed in Chapter 168, and
the most severely affected members of families with
the autosomal dominant Huntingtons disease, and denta-
torubropallidoluysian atrophy (Yamada et al., 2006).
A nongenetic PME occurs in the course of subacute
sclerosing panencephalitis (SSPE), discussed in Chapter
123. Autosomal recessive PME can be subgrouped patho-
logically into nonlysosomal PME (Lafora disease and the
newly characterized ataxia-PME disease) and lysosomal
PME (UnverrichtLundborg disease and certain forms
of sialidosis, Gaucher disease, and the vast family of
neuronal ceroid lipofuscinoses (NCL)). This chapter
reviews the autosomal recessive PME, with the exception
of the NCL, which merit their own section, Chapter 173.
LAFORA DISEASE
Onset of Lafora disease is between 8 and 18 years of age.
The first symptoms are headaches, difficulties in school,
myoclonic jerks, generalized seizures, and in many cases
visual hallucinations of both epileptic and psychotic origin.
stimulation, and enhanced with emotion. EEG shows slow-
ing of background activity, generalized irregular spike-
waves with photosensitivity and low amplitude spikes in
posterior head regions (Figure 178.1). The myoclonus, sei-
zures, and hallucinations gradually worsen and become
intractable. For many years, patients maintain contact
and communication, interrupted by extremely frequent
myoclonic absence seizures. They remain conscious of
their deterioration until late in the course of the disease
and often exhibit depression. Gradually, dementia sets
in and by the tenth year after onset the patient is in
near-continuous myoclonus with absences, frequent
generalized seizures, and profound dementia. Death is
frequently secondary to aspiration pneumonia during sta-
tus epilepticus (Lafora, 1911; Minassian, 2001; Andrade
et al., 2005; Striano et al., 2008).
Gonzalo Rodriguez-Lafora, an eminent Spanish neu-
rologist and student of Cajal, Marie, Dejerine, Alzheimer,
Oppenheim, and Kraeplin, described Lafora disease when
he was a neuropathologist at the Government Hospital for
the Insane in Washington DC (Nanduri et al., 2008). He not
only discovered the pathognomonic inclusion bodies in
the brain which later took his name, he also fully described
the disease clinical features, course, and inheritance pat-
tern. The only major neurological facet he did not address
was the EEG, which had not yet been invented. Figure 178.2
shows drawings of Lafora bodies made by Lafora in his
first publication (Lafora, 1911). Lafora bodies are dense
accumulations of malformed and insoluble glycogen mol-
ecules termed polyglucosans that differ from normal gly-
cogen in lacking the symmetric branching that allows
glycogen to be soluble. They are present in all brain regions
and in most neurons, specifically in neuronal cell bodies
and dendrites (Fig. 178.3) (Lafora, 1911; Van Heycop Ten
Ham, 1975; Cavanagh, 1999; Minassian, 2001; Striano
et al., 2008). They are not present in glia. Remarkably,

*Correspondence to: Berge A. Minassian, MD, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G
1X8. E-mail: berge.minassian@sickkids.ca
1732 J.-M. GIRARD ET AL.

Fig. 178.1. Ten seconds of EEG on a 14-year-old girl with Lafora disease at earliest onset of symptoms. Note the slow occipital
background, irregular and wide generalized spike-waves, and low amplitude and posterior location of spikes. At the time of
EEG, the child was experiencing frequent headaches and a decline in school performance. The first myoclonia and generalized
convulsions appeared soon after this EEG. The EEG was done because her older sister, 23 years of age, had florid Lafora disease.
A homozygous mutation in the EPM2A gene was found in both girls (c.799-800insA; N267fs). This was the first ever Lafora dis-
ease mutation.

even this was noted by Lafora, at a time when pathological

Fig. 178.2. The first ever Lafora bodies seen. Drawings of
Lafora bodies by Lafora (Lafora, 1911).
distinction of neurons and glia was only starting to be
made. It is currently thought that the gradual occupation
of dendrites by Lafora bodies leads eventually to the onset
and then the irrevocable progression of the epilepsy and
the other neurological symptoms. The dendritic location
is considered important, because in the only other disease
in which Lafora bodies are found, adult polyglucosan
body disease, caused by mutations in the glycogen branch-
ing enzyme gene, the bodies are in axons and the patients
have dementia, upper and lower neuron signs, but no epi-
lepsy (Robitaille et al., 1980; Lossos et al., 1998).
Extraneural tissues, including skeletal muscle, heart,
liver and skin, also contain Lafora bodies in Lafora dis-
ease, but these organs are not clinically affected in the life
span of the patient. In skin, biopsy of which is often used
for diagnosis, Lafora bodies are present in two very par-
ticular locations: in ducts of eccrine sweat glands and in
the myoepithelium surrounding apocrine sweat glands.
Interpretation of skin biopsy is prone to an important pit-
fall (Fig. 178.4) (Andrade et al., 2003), which if avoided
makes this an excellent diagnostic modality next to gene
sequencing.
Lafora disease is caused by autosomal recessively
inherited mutations in either the EPM2A or EPM2B gene,
encoding respectively the laforin carbohydrate-binding
dual-specificity phosphatase and the malin ubiquitin E3
ligase (Minassian et al., 1998; Chan et al., 2003). Mutations
in each gene contribute approximately equally (45%) to
cases of Lafora disease (Lafora Gene Mutation Database:
Ianzano et al., 2005). The remaining 10% is thought to be
caused by mutations in an as yet undiscovered gene (Chan
et al., 2004; Singh et al., 2008). Based on the disease genes a
 PROGRESSIVE MYOCLONUS EPILEPSY 1733

Fig. 178.3. Lafora bodies in the brain. (A) Several large Lafora bodies are labeled LB. Note in the one to the right of the image the
typical juxtanuclear location and the denser core of the structure. Numerous pink puncta are Lafora bodies in neuronal processes,
usually in dendrites. Stain, periodic acid-Schiff with diastase pretreatment. Diastase is amylase which digests normal glycogen, but
in the short time of these preparations is unable to digest the densely packed polyglucosans comprising the Lafora bodies. Bar,
50 mm. The mutation in this patient is homozygous EPM2B c.C205G (P69S). This is the most common Lafora disease mutation
in the EPM2B gene. (B) Electron micrograph of Lafora bodies (LB) in neuronal processes. Note the fibrillar nature of the poly-
glucosans. Several axons are recognized by their synaptic vesicles. Bar, 500 nm. Note the absence of LB in the axons. The mutation
in this patient is EPM2B c.T98C (F33S). This was the first EPM2B mutation identified.

that have excessively long strands and inadequate branch-

ing. This abnormal glycogen, polyglucosan, is insoluble
and precipitates and accumulates to form the Lafora bod-
ies (Lohi et al., 2005; Vilchez et al., 2007). In the second
pathogenic model, laforin acts directly on glycogen,
dephosphorylating its excess phosphate. In the absence
of laforin, the excess phosphate distorts the double helices
of glycogen strands and the molecules symmetric branch
pattern, both of which are necessary for its solubility.
Again, the abnormal glycogen precipitates and accumu-
lates into Lafora bodies (Gentry et al., 2007; Tagliabracci
et al., 2009). Whether both processes are important and
complementary or not awaits further studies.

Fig. 178.4. Lafora bodies in apocrine glands. The Lafora bod-
ies are in the myoepithelium of the gland, that is at the base of
the gland (arrow). Periodic acid-Schiff structures at the lumi-
nal side (arrowhead) should not be confused with Lafora bod-
ies. They are normal secretory material. Bar, 50 mm.
large amount of work has been done, which presently
brings forth two chief pathogenic hypotheses. In the first,
the laforinmalin complex is suggested to regulate glyco-
gen synthase. In the absence of either protein, glycogen
synthase is overactive, exceeding glycogen branching
enzyme activity and thus resulting in glycogen molecules
UNVERRICHT^LUNDBORG DISEASE
(UNVERRICHT DISEASE)
Onset of Unverricht disease is between 6 and 13 years of
age. This disease differs from other PME in that it is pro-
gressive only in adolescence, with dramatic and increas-
ing myoclonus in the first 6 years. Jerks consist of action
myoclonus triggered by any attempt to voluntary move-
ment, posture, stress, and external stimulation; the ado-
lescent is sometimes suspected of conversion, and is
soon confined to the wheelchair. Seizures occur more
often on awakening and usually respond to medications
during this time, but myoclonus does not. EEG shows
generalized spike-waves triggered by photic stimulation,
but the basic background rhythm remains normal.
1734 J.-M. GIRARD ET AL.
Treatment at that stage by a combination of valproate,
zonisamide, levetiracetam and especially high dose
piracetam may be effective. By adulthood, the disease
stabilizes and myoclonus and ataxia may improve.
Seizures remain controlled and there is minimal or no
cognitive decline. Adulthood is characterized by ongo-
ing, sometimes severe, but no longer progressive myo-
clonus, almost normal cognitive functions, controlled
epilepsy, and the possibility of a normal life span
(Unverricht, 1891; Magaudda et al., 2006; Kalviainen
et al., 2008; Santoshkumar et al., 2008).
Unverricht described the neurological features and
the autosomal recessive inheritance pattern of this dis-
ease in detail in a large Baltic family from present-day
Estonia (Unverricht, 1891). He did not describe patho-
logical findings, and there are none beyond nonspecific
apoptotic cell loss and brain atrophy. The disease is rel-
atively common in Finland (1:20 000) (Kalviainen et al.,
2008) and was known as Baltic myoclonus until it was
shown that Mediterranean and other populations with
the same phenotype have the same genotype. Lundborg
described a Swedish family with an altogether different
disease with, in addition to myoclonus, progressive
tremor, rigidity, and ultimately paralysis resembling
in his words, paralysis agitans (Parkinsons disease)
(Puschmann, 2008). Lundborg was racist (Puschmann,
2008) above and beyond the racism so prevalent in
the Europe he lived in. Whether this disqualifies him
from an eponym can be discussed, but clearly, even
though he wrote extensively on PME, given that he
did not describe a family with UnverrichtLundborg
disease, and that his own term for PME was Unver-
richts myoclonus (Lundborg, 1903), it seems that a
simplification of the name of this disease to Unverricht
disease is warranted.
Unverricht disease was the first of the PME to be
described. In the time of Unverricht and Lundborg, in
the absence of effective antiepileptic and antimyoclonic
medications, it was clearly a progressive disease. Later,
when patients were treated with phenytoin, they devel-
oped a dramatic progressive ataxia, because, as we
now know, their cerebellar Purkinje cells are dramati-
cally vulnerable to this medication. In our time, as
described above, this prototypical PME has thankfully
all but lost its progressive status.
The Unverricht disease gene is CSTB (alias EPM1)
(Pennacchio et al., 1996). The disease is due to massive
downregulation (to less than 10% of normal) but not
complete loss of CSTB. The cause of the downregulation
is a particularity of the human genome in the promoter
of CSTB, the presence of a dodecamer repeat that occa-
sionally expands, and when it does so drastically reduces
transcription of the gene. Few patients have other muta-
tions within the gene, but only on one allele. An
Unverricht disease patient necessarily has the dodecamer
repeat expansion in at least one of the two alleles
(Virtaneva et al., 1997; Joensuu et al., 2008).
The CSTB product is cystatin B, so named because it
interacts with and inactivates certain lysosomal prote-
ases, cathepsins B, L, S, and H (Turk and Bode, 1991).
It is thought that cystatin B protects cells from these
cathepsins if they find their way out of the lysosome.
Recently, a new function of the protein has been delin-
eated, namely protection of the cell against oxidative
stress (Lehtinen et al., 2009). Whether the two functions,
protection against lysosomal hydrolases and protection
against oxidants, are separate or part of a yet unknown
interconnection between cathepsins and oxidative cell
damage awaits further study.
ATAXIA-PME DISEASE
Between 2005 and 2006, three groups described an
autosomal recessive neurological disease in three sepa-
rate large Arab families from nearby villages straddling
the northern IsraelJordan border. In one family, the
patients were adolescents and adults exhibiting primar-
ily a PME, so closely resembling Unverrichts disease
that it was called EPM1B (Berkovic et al., 2005). In
the other two families, the affected individuals were
children manifesting an ataxia (Straussberg et al.,
2005; El-Shanti et al., 2006). A collaborative re-
evaluation of the families showed that two shared the
same last name, that the children who had presented
with ataxia were exhibiting myoclonus as they grew
older, and that the adolescents and adults with myoclo-
nus had in fact had ataxia earlier in life. All patients had
the same missense mutation (R104Q) in the PRICKLE1
gene (Bassuk et al., 2008). The phenotype appears to be
as follows: ataxia soon after walking in the first half of
the second year of life, tremor starting at 3 or 4 years of
age, seizures after 8 years, and myoclonus soon after.
Most patients also have upward gaze palsy, and some
have exhibited a sensory neuropathy. The core features
of ataxia and myoclonus are progressive and the adults
are wheelchair-dependent with florid myoclonus. Sei-
zures are well controlled and there is no dementia.
MRI shows no atrophy even of the cerebellum. Periph-
eral tissues exhibit no inclusions material, and brain has
not yet been studied (Berkovic et al., 2005; Straussberg
et al., 2005; El-Shanti et al., 2006; Bassuk et al., 2008).
The gene product appears to influence the REST
and Wnt pathways, separate signaling cascades that
regulate gene expression, including neuronal genes
(Bassuk et al., 2008). The questions of which genes
are controlled by PRICKLE1 and how their dysregula-
tion causes a progressive neurological disease without
brain atrophy wait to be tackled.
 PROGRESSIVE MYOCLONUS EPILEPSY
TYPE I SIALIDOSIS (CHERRY-RED SPOT
MYOCLONUS SYNDROME) AND TYPE
IIIA GAUCHER DISEASE
Mutations of the gene encoding neuraminidase, a lyso-
somal enzyme that removes sialic acid from various mac-
romolecules, cause severe infantile disease with bony
deformities, dysmorphism, myoclonus, cherry-red spot
in the fundus, and early lethality. Some mutations cause
a variant phenotype (type I sialidosis) which presents
as typical PME with a wide range of age of onset. This
seems to have a higher frequency of occurrence in Italian
patients, but has also been seen elsewhere (Chen et al.,
2006). Ataxia is prominent, and the presence of a
cherry-red spot on funduscopy is highly indicative of
the disease in the context of a PME. The disease can be
diagnosed by the presence of sialo-oligosaccharides in
urine (Bonten et al., 2000).
Gaucher disease, caused by mutations of GD1, which
encodes the glucocerebrocidase lysosomal enzyme, is
characterized by hepatosplenomegaly, anemia, throm-
bocytopenia, bone pain, and other systemic features.
In some patients, the central nervous system is involved,
and in a subgroup of these patients the neurological pre-
sentation is a typical PME (type IIIA Gaucher disease).
Occasionally, the systemic disease in this type is so mild
that it is unrecognized and the PME is initially confused
for juvenile myoclonic epilepsy, and then for Lafora
disease (Filocamo et al., 2004). Splenomegaly, even mild,
and upward gaze palsy, are important clues towards
considering type IIIA Gaucher disease in a patient
with PME.
CONCLUSION
At the present time, some 120 years after the writings of
Unverricht and Lundborg on PME, the first PME, Unver-
richt disease, is no longer considered to be progressive,
because we have worked out which seizure medications
to use and which not to use. Lafora disease is, however,
just as progressive and fatal as ever. From Unverricht
disease we have teased out a new phenotype with its
own genotype (ataxia-PME disease), and we have dis-
cerned PME in a fraction of patients with sialidosis
and the common Gaucher disease. We have likewise clar-
ified the PME phenotypes within the large multifaceted
neuronal ceroid lipofuscinoses, mitochondrial cytopa-
thies, and trinucelotide repeat expansion diseases, and
we have immunized most of humanity against SSPE.
Finally, we have exposed the causes of all these disorders
and are now racing to use this knowledge to eliminate
them. We expect that Lundborg would agree that we
have not done so badly as a human race. Hopefully,
we will all achieve what remains to be done fast.
1735
ACKNOWLEDGMENTS
This work was supported by funds from the Canadian
Institutes for Health Research and the Canada Research
Chairs Program. We thank Drs. Cameron Ackerley and
Pasquale Striano for the biopsy and autopsy samples and
Ms. Nela Pencea for help with preparing the images.
Dr. Berge Minassian holds the University of Toronto
Michael Bahen Chair in Epilepsy Research.
REFERENCES
Andrade DM, Ackerley CA, Minett TS et al. (2003). Skin
biopsy in Lafora disease: genotype-phenotype correlations
and diagnostic pitfalls. Neurology 61: 16111614.
Andrade DM, del Campo JM, Moro E et al. (2005). Non-epileptic
visual hallucinations in Lafora disease. Neurology 64:
13111312.
Bassuk AG, Wallace RH, Buhr AR et al. (2008). A homozy-
gous mutation in human PRICKLE1 causes an autosomal
recessive progressive myoclonic epilepsy-ataxia syn-
drome. Am J Hum Genet 83: 572581.
Berkovic SF, Mazarib A, Walid S et al. (2005). A new
clinical and molecular form of UnverrichtLundborg dis-
ease localized by homozygosity mapping. Brain 128:
652658.
Bonten EJ, Arts WF, Beck M et al. (2000). Novel mutations in
lysosomal neuraminidase identify functional domains and
determine clinical severity in sialidosis. Hum Mol Genet 9:
27152725.
Chan EM, Young EJ, Ianzano L et al. (2003). Mutations in
NHLRC1 cause progressive myoclonus epilepsy. Nat
Genet 35: 125127.
Chan EM, Omer S, Ahmed M et al. (2004). Progressive myoc-
lonus epilepsy with polyglucosans (Lafora disease): evi-
dence for a third locus. Neurology 63: 565567.
Chen CM, Lai SC, Chen IC et al. (2006). First report of two
Taiwanese siblings with sialidosis type I: a 10-year
follow-up study. J Neurol Sci 247: 6569.
Cavanagh JB (1999). Corpora-amylacea and the family of poly-
glucosan diseases. Brain Res Brain Res Rev 29: 265295.
El-Shanti H, Daoud A, Sadoon AA et al. (2006). A distinct
autosomal recessive ataxia maps to chromosome 12 in an
inbred family from Jordan. Brain Dev 28: 353357.
Filocamo M, Mazzotti R, Stroppiano M et al. (2004). Early
visual seizures and progressive myoclonus epilepsy in neu-
ronopathic Gaucher disease due to a rare compound hetero-
zygosity (N188S/S107L). Epilepsia 45: 11541157.
Gentry MS, Dowen RH, 3rd., Worby CA et al. (2007). The
phosphatase laforin crosses evolutionary boundaries and
links carbohydrate metabolism to neuronal disease. J Cell
Biol 178: 477488.
Ianzano L, Zhang J, Chan EM et al. (2005). Lafora progressive
Myoclonus Epilepsy mutation database-EPM2A and
NHLRC1 (EPM2B) genes. Hum Mutat 26: 397.
Joensuu T, Lehesjoki AE, Kopra O (2008). Molecular back-
ground of EPM1UnverrichtLundborg disease. Epilepsia
49: 557563.
1736 J.-M. GIRARD ET AL.
Kalviainen R, Khyuppenen J, Koskenkorva P et al. (2008).
Clinical picture of EPM1UnverrichtLundborg disease.
Epilepsia 49: 549556.
Lafora GR (1911). Uber das vorkommen amyloider kor-
perchen im innern der ganglienzellen: zugleich en beitrag
zum stadium der amyloiden substanz im nervensystem.
Virchows Arch Pathol Anat Physiol Klin Med 205: 295303.
Lehtinen MK, Tegelberg S, Schipper H et al. (2009). Cystatin B
deficiency sensitizes neurons to oxidative stress in progres-
sive myoclonus epilepsy, EPM1. J Neurosci 29: 59105915.
Lohi H, Ianzano L, Zhao XC et al. (2005). Novel glycogen
synthase kinase 3 and ubiquitination pathways in progres-
sive myoclonus epilepsy. Hum Mol Genet 14: 27272736.
Lossos A, Meiner Z, Barash V et al. (1998). Adult polygluco-
san body disease in Ashkenazi Jewish patients carrying
the Tyr329Ser mutation in the glycogen-branching enzyme
gene. Ann Neurol 44: 867872.
Lundborg H (1903). Die progressive Myoklonus-Epilepsie
(Unverrichts Myoklonie). Almqvist und Wiksells
Buchdruckerei-A-G, Uppsala.
Magaudda A, Ferlazzo E, Nguyen VH et al. (2006).
UnverrichtLundborg disease, a condition with self-
limited progression: long-term follow-up of 20 patients.
Epilepsia 47: 860866.
Minassian BA (2001). Laforas disease: towards a clinical, path-
ologic, and molecular synthesis. Pediatr Neurol 25: 2129.
Minassian BA, Lee JR, Herbrick JA et al. (1998). Mutations in a
gene encoding a novel protein tyrosine phosphatase cause
progressive myoclonus epilepsy. Nat Genet 20: 171174.
Nanduri AS, Kaushal N, Clusman H et al. (2008). The maestro
don Gonzalo Rodriguez-Lafora. Epilepsia 49: 943947.
Pennacchio LA, Lehesjoki AE, Stone NE et al. (1996).
Mutations in the gene encoding cystatin B in progressive
myoclonus epilepsy (EPM1). Science 271: 17311734.
Puschmann A (2008). UnverrichtLundborg disease a mis-
nomer? Mov Disord 24: 629630.
Robitaille Y, Carpenter S, Karpati G et al. (1980). A distinct
form of adult polyglucosan body disease with massive
involvement of central and peripheral neuronal processes
and astrocytes: a report of four cases and a review of the
occurrence of polyglucosan bodies in other conditions such
as Laforas disease and normal ageing. Brain 103: 315336.
Santoshkumar B, Turnbull J, Minassian BA (2008).
UnverrichtLundborg progressive myoclonus epilepsy in
Oman. Pediatr Neurol 38: 252255.
Singh S, Satishchandra P, Shankar SK et al. (2008). Lafora
disease in the Indian population: EPM2A and NHLRC1
gene mutations and their impact on subcellular localization
of laforin and malin. Hum Mutat 29: E1E12.
Straussberg R, Basel-Vanagaite L, Kivity S et al. (2005). An
autosomal recessive cerebellar ataxia syndrome with
upward gaze palsy, neuropathy, and seizures. Neurology
64: 142144.
Striano P, Zara F, Turnbull J et al. (2008). Typical progression
of myoclonic epilepsy of the Lafora type: a case report. Nat
Clin Pract Neurol 4: 106111.
Tagliabracci VS, Girard JM, Segvich D et al. (2009).
Abnormal metabolism of glycogen phosphate as a cause
for Lafora disease. J Biol Chem 283: 3381633825.
Turk V, Bode W (1991). The cystatins: protein inhibitors of
cysteine proteinases. FEBS Lett 285: 213219.
Unverricht H (1891). Die Myoclonie. Leipzig and Vienna,
Franz Deuticke.
Van Heycop Ten Ham M (1975). Lafora disease, a form of pro-
gressive myoclonus epilepsy. In: PJ Vinken, GW Bruyn
(Eds.), The Epilepsies. Handbook of Clinical Neurology.
vol.15. Elsevier, Amsterdam, pp. 382422.
Vilchez D, Ros S, Cifuentes D et al. (2007). Mechanism
suppressing glycogen synthesis in neurons and its demise
in progressive myoclonus epilepsy. Nat Neurosci 10:
14071413.
Virtaneva K, DAmato E, Miao J et al. (1997). Unstable min-
isatellite expansion causing recessively inherited myoclo-
nus epilepsy, EPM1. Nat Genet 15: 393396.
Yamada M, Shimohata M, Sato T et al. (2006). Polyglutamine
disease: recent advances in the neuropathology of
dentatorubral-pallidoluysian atrophy. Neuropathology 26:
346351.