Thesis (DMed (Medicine. Internal Medicine))--University of Stellenbosch, 2009. / ENGLISH ABSTRACT: Progressive Myoclonic Epilepsies (PME) are characterized by progressive neurological
impairment with myoclonus, seizures and dementia. In contradistinction, Familial Adult
Myoclonic Epilepsy (FAME) is characterized by a benign course with rare seizures and
cortical tremor. Both conditions have neurophysiological features suggestive of a cortical
origin for their myoclonus.
This dissertation reports on a novel form of PME. Many of those who were affected had no
or minimal progression of their illness, low seizure frequency and were cognitively intact,
suggestive of non-progressive disorders linked to the FAME loci.
The majority of patients had features of cortical myoclonus, with generalized spike and wave
discharges on electroencephalography, enlarged evoked potentials, enhanced C reflexes,
and evidence of cortical excitability with magnetic stimulation. However, there was evidence
of cerebellar dysfunction both pathologically and on imaging. With regard to similar
conditions, dentatorubral pallidoluysian atrophy and Unverricht-Lundborg syndrome were
excluded by linkage analysis. Similarly, linkage was not present for either the FAME 1 or
FAME 2 loci.
This syndrome is both clinically and genetically novel, and has a nosology which is difficult to
characterize, in which the condition appears to lie on the spectrum between FAME and
PME. The dissociation between the pathological and radiological findings which suggest
subcortical dysfunction, and the neurophysiological findings of cortical myoclonus is striking.
Review of the literature associated with the neurophysiology of related conditions associated
with PME and FAME suggests that:
1. The assumption that generalized forms of myoclonic disorders represent multifocal
forms of focal cortical discharges is an oversimplification.
2. The dissociation between initial and later components of the evoked potential is less
robust than is generally supposed, and that subcortical inputs may affect later
components of the evoked potential.
3. In a high proportion of cases the latency from cortical spike discharge to myoclonic
jerk obtained with jerk locked averaging is incompatible with a cortical origin for the
spike discharge.
4. The proposal that myoclonus is a form of long latency reflex and that myoclonus
represents a reflex arising from subclinical sensory input, is unproven. / AFRIKAANSE OPSOMMING: Progressiewe Miokloniese Epilepsie (PME) word gekenmerk deur progressiewe
neurologiese agteruitgang met mioklonus, konvulsies en demensie. Daarenteen word
Familiële Volwasse Miokloniese Epilepsie (FAME) gekenmerk deur 'n benigne verloop met
ongereelde konvulsies en kortikale tremor. Beide entiteite het neurofisiologiese kenmerke
suggestief van 'n kortikale oorsprong vir die mioklonus.
Hierdie manuskrip beskryf 'n nuwe vorm van PME. Baie van die aangetaste persone toon
geen of min agteruitgang van die siekte oor tyd nie, met 'n lae frekwensie van konvulsies en
is kognitief intak, wat suggestief is van 'n nie-progressiewe siekte gekoppel aan die FAME
loci.
Die oorgrote meerderheid van pasiente het kenmerke van kortikale mioklonus gehad, met
algemene spits en boog ontladings op elektroensefalografie, hoë amplitude ontlokte
potensiale, versterkte C-reflekse, en tekens van kortikale eksiteerbaarheid met magnetiese
stimulasie. Met neurobeelding en patologie was daar egter bewyse van serebellêre
disfunksie. Soortgelyke toestande, naamlik dentatorubro-pallidoluysiese atrofie en
Unverricht-Lundborg sindroom is uitgeskakel deur middel van koppelingsanalise. Koppeling
met die FAME1 of FAME2 loci kon ook nie aangetoon word nie.
Die sindroom is beide klinies sowel as geneties nuut en het 'n nosologie wat moeilik
gekaraktiseer kan word. Dit wil voorkom of die siekte op 'n spektrum lê tussen FAME en
PME. Die dissosiasie tussen die patologiese en radiologiese bevindinge, wat suggestief is
van subkortikale disfunksie, en die neurofisiologiese bevindinge van kortikale mioklonus is
opmerklik.
’n Oorsig van die literatuur in verband met die neurofisiologie van toestande geassosieer
met PME en FAME suggesteer die volgende:
1. Die aanname dat algemene vorme van miokloniese toestande multifokale vorme van
fokale kortikale ontladings verteenwoordig, is ’n oorvereenvoudiging.
2. Die dissosiasie tussen inisiële en latere komponente van die ontlokte potensiaal is
minder robuust as wat algemeen aanvaar word, en subkortikale invoer mag latere
komponente van die ontlokte potensiaal beïnvloed.
3. In ’n groot proporsie van gevalle is die latensie van kortikale spits ontlading tot
miokloniese ruk, verkry deur “jerk locked averaging”, nie verenigbaar met met ’n
kortikale oorsprong vir die spits ontlading nie.
4. Geen bewyse bestaan vir die teorie dat mioklonus ’n vorm van ’n lang latensie refleks
is en dat mioklonus ’n refleks is wat ontstaan uit subkliniese sensoriese invoer nie.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:sun/oai:scholar.sun.ac.za:10019.1/1201 |
| Date | 12 1900 |
| Creators | Carr, Jonathan |
| Contributors | Brink, P.A., University of Stellenbosch. Faculty of Health Sciences. Dept. of Medicine. Internal Medicine. |
| Publisher | Stellenbosch : University of Stellenbosch |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Rights | University of Stellenbosch |
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