Notesale: Turn your study into money

Document Preview

Extracts from the notes are below, to see the PDF you'll receive please use the links above

---

Epilepsy  and  Anticonvulsants  
Epilepsy  can  be  defined  by  the  following  characteristics:  
§
§
§
§
§

A  sudden  excessive  high  frequency  neuronal  discharge;  high  number  of  neurons  carrying  out  
the  same  action  
Not  random  but  highly  synchronous  
A   disorder   of   the   cerebral   cortex;   epilepsy   largely   arises   from   here,   with   the   possibility   of  
cerebral  atrophy
...
 

Facts  and  figures  of  epilepsy:  
§
§
§
§
§
§
§

0
...
   
20%-­‐30%  refractory  to  surgery  
1000  deaths  per  year;  50%  sudden  unexplained  death  in  epilepsy  (SUDEP)  
60-­‐90%  undiagnosed  or  untreated  in  developing  countries;  about  half  have  no  precipitated  
cause
...
 
Patients  with  an  IGE  subtype  are  typically  otherwise  normal  and  have  no  structural  brain  
abnormalities
...
  IGE   tends   to   manifest   itself   between   early  
childhood   and   adolescence   although   it   can   be   eventually   diagnosed   later
...
 
Genetic  (rare  familial  disorders)  
Congenital   epilepsy-­‐   Children   are   born   with   the   disorder   and   may   be   due   to   structural  
abnormalities  within  the  brain  
 Birth  trauma-­‐  ischaemia;  inadequate  blood  supply  during  the  pregnancy  at  foetal  stages  
could  affect  the  development  of  the  brain
...
 

 
Recording  Epilepsy  
The  most  common  methods  to  record  epilepsy  are  EEG  and  MEG
...
 
MEG  and  EEG  both  work  by  being  applied  to  the  scalp  in  order  to  measure  the  afferent  axon  activity  
under  the  pia  mater
...
 Seizures  are  often  brought  
on   by   factors   such   as   stress,   alcohol   abuse,   flickering   light,   or   a   lack   of   sleep,   among   others
...
 
Seizure  threshold  is  lowered  in  epilepsy
...
 This   results   in   a   wave   of   depolarization   known   as   a  paroxysmal   depolarizing   shift
...
 This  is  due  in  
part   to   the   effect   of   inhibitory   neurons,   electrical   changes   within   the   excitatory   neuron,   and   the  
negative  effects  of  adenosine
...
 Some  types  of  seizures  may  change  brain  structure,  while  others  appear  to  have  little  
effect
...
   
Primary  generalized  seizures:  
Primary   generalized   epilepsy   is   a   form   of  epilepsy  characterised   by   generalised   seizures   with   no  
apparent   cause
...
   
Generalized   epilepsy   is  primary  because   the   epilepsy   is   the   originally   diagnosed   condition   itself,   as  
opposed   to  secondary  epilepsy,   which   occurs   as   a   symptom   of   a   diagnosed   condition
...
 
Where  do  the  seizures  arise?  
They  can  arise  anywhere,  however  it  is  rare  to  get  a  seizure  in  the  subcortical
...
  The   latter   is   the  
most  prone,  with  a  prevalence  rate  of  30-­‐40%;  within  this  region  it  effects  mainly  the   hippocampus,  
entorhinal  cortex  and  amygdala
...
 

 

•

 

They  can  fluctuate  and  become  
pathologically  altered  to  the  level  of  
individual  neurons    

K+  counteracts  the  depolarising  influxes  by  
repolarising  the  membrane,  thus,  reducing  the  
frequency  of  the  firing  rate  of  action  
potentials
...
 
In  normal  synaptic  balance,  the  
inhibition  counteracts  the  excitation,  
however  during  epilepsy  there  may  
be  reduced  inhibition,  thus,  there  is  
too  m uch  excitation  

 
 
 
 
 

 
 
 
 
 
 

These  neurons  can  be  interconnected  
and  cause  recurrent  excitations,  
allowing  for  back  and  forth  
communication  between  1000’s  of  
neurons
...
 
Taking  away  these  interneurons  will  
induce  excessive  excitation  

 
 
 
 
 
 

 
 
Summary  of  cortical  networks  
•
•
•
•
•
•
•

Pyramidal  neurons  are  excited  by  glutamate  inputs  
Pyramidal  neurons  excite  interneurons  
Interneurons  inhibit  pyramidal  cells  
Pyramidal  neurons  can  excite  each  other  
Loss  of  inhibition  can  result  in  increased  excitation  
Increased  excitation  can  override  inhibition  
An  over  activation  of  AMPA  glutamate  receptor  kicks  off  the  seizure  and  promotes  a  cascade  
of  discharge  to  the  NMDA  receptor
...
 
Accordingly,  many  studies  suggesting  axonal  sprouting  in  GABAergic  circuitry  have  used  markers  for  
GABA   content   including   GABA,   its   synthesizing   enzyme,  glutamic   acid   decarboxylase  (GAD),   or  
the  presynaptic  neuronal   GABA   transporter,   GAT-­‐1
...
  Studies   suggesting   axonal   sprouting   of  
GABAergic  neurons  often  have  used  a  combination  of  these  classifications
...
 
A   majority   of   reports   suggesting   axonal   sprouting   of   GABAergic   neurons   have   focused   on   the  
dendritic  regions  of  dentate  granule  cells
...
  These   data   are  
consistent  with  the  early  partial  loss  of  GABAergic  interneurons  in  the  pilocarpine  model
...
  Likewise,   GAD   immunoreactivity   was   increased   in   the   inner   molecular   layer  
and,  to  a  lesser  degree,  in  the  outer  molecular  layer  at  times  ⩾2  months  following  initial  pilocarpine-­‐
induced  status  epilepticus
...
 
Increased   GAD   or   GAT-­‐1   immunoreactivity   has   been   documented   in   the   inner   molecular   layer   in  
the  kainic   acid,   electrical   stimulation-­‐induced   status   epilepticus,   and   pilocarpine  models   and   in   the  
outer  molecular  layer  in  the  pilocarpine  and  electrical  stimulation-­‐induced  status  epilepticus  models
...
  Taken   together,   these   data   suggest   an   early   loss   of  
innervation  followed  by  sprouting  in  GABAergic  circuitry  in  the  dendritic  regions  of  dentate  granule  
cells
...
 
Epilepsy  treatment  
•
•
•

•

Block  destabilising  currents  
Increase  stabilising  currents  
Reduce  synaptic  excitation  
§ Block  glutamate  release    
§ Block  glutamate  receptors  
Increase  synaptic  inhibition  
§ Increase  GABA  release  
§ Potentiate  GABA  receptors  

No   anti-­‐epileptic   drugs   can   repair   the   network   but   they   will   prevent   the   occurrence   of   another  
seizure
...
 
Blocking  voltage  gated  Na-­‐channels  blocks  depolarisations  and  drugs  that  do  this  include:  phenytoin,  
carbamazepine,  iamotrigine  and  sodium  and  valproate
...
  Drugs   that   block   glutamate   block   Na  
channels  and  Ca  channels

---