Mesial Temporal Sclerosis and psychosis

1. By
Shokry Alemam, MD
Case presentation

2. Ms S is a 32 year old female patient, single, unemployed,
educated till 3rd
year of secondary school.
Presented for the first time to my clinic 2 years ago by:
Hearing voices threatening her, thinking that her maid
will hurt her and watches her (as voices tell her),
disturbed sleep in the form of difficulty to fall asleep,
and frequent wakening up.
Her sister reported that Ms S had many bouts of
agitation, social withdrawal, with inappropriate
behaviors, neglected self hygiene, and bouts of
disorientation to time, and place.

3. All these symptoms started 17 years ago by insidious
onset, and progressive course, with no specific
precipitating or relieving factors.
She sought medical advice 17 years ago and was
diagnosed as schizoaffective, and her last medications
before presenting to our clinic were, Prozac 20 mg,
Risperdal consta 50 mg IM every 2 weeks, Topamax 100
mg daily, lamictal 100 mg BID.
•No past medical history.
•Positive family history as her cousin (maternal) has
similar presentation.
•Premorbid personality, she was introverted, socially
retarded, and poor school performance.

4. By examination, Ms S was obese, with psychomotor
slowing, staring look poor concentration, coherent
speech of decreased volume and pressure, euthymic
mood and blunt affect, concrete thinking with poverty
of thoughts, delusion of reference and persecution,
poor insight and judgment, no suicidal thoughts, plans
or intent.

5. What is your possible diagnosis?

6. She was diagnosed as schizophrenia
The plan was to continue on
Risperdal consta 50 mg/ 2 weeks
Prozac 20 mg
Topamax 100 mg
Start Risperdal 3 mg nocturnal
But
The next visit after 2 months, the patient reported that she developed
galactorrhea with no improvement of her symptoms, so the plan was
to D/C Risperdal tablets and start Seroquel 200 mg and abilify 10 mg

7. After 4 months the patient still the same regarding
delusions and hallucinations with severe irritability, and
started to complain of dry mouth, abdominal pain, and
poor appetite.
So the plan was to D/C Topamax and Prozac and start
haloperidol 5 mg BID and Cogentin 2 mg BID
RFT, HbA1c were done and were normal.
After 4 months no improvement, and the patient still
complaining of dry mouth, abdominal pain, and
developed hirsutism and skin pigmentation in her back,
legs, and arms, smelling bad odor and stopped
haloperidol by herself, so we started zyprexa 15 mg
nocte, and stellasil 5 mg BID

8. ll the endocrine profile was investigated with RFT, LFT,
CBC, glucose profile, and electrolyte profile, and all the
results were normal.
he final medications she was on were Abilify 30 mg,
Risperdal consta 50 mg/ 2 weeks, Zyprexa 15 mg,
Glucophage 500 BID, Cogentin 1 mg BID, and Stellasil 5
mg BID
And the patient showed no improvement

9. What do you think?!!!
What is your next step?!!!!
What if all the previous diagnoses and management
are wrong?!!!

10. The next step was to reevaluate the case discovering the
detailed history of the previous 15 years which revealed:
•The patient developed galactorrhea twice before once she took
risperdal tablets either with or without risperdal injection
•She showed some improvement on Depakine 500 BID mg and
Seroquel 900 mg by improvement of concentration only in 2003.
•She did pituitary MRI and was free
•CT brain with contrast which showed venous malformation at
right side of cerebellum ( not clinically significant) in 3/2011
•In 7/2011she was referred to do MRI due to possible complex
partial seizures, which showed decreased volume of right
hippocampus, and right mesial temporal sclerosis
•EEG was done and was free

11. y further history of possible complex partial seizures,
the mother reported that it is always present and
happens many times per day.
he next step was to wash out all the antipsychotics
and keep patient only on clonazepam with close
observation and do MRI, CT, and EEG again.
he investigations confirmed the previous findings
through MRI brain only
n the clinical base the patient is much improved on
clonazepam with better concentration, activity, sleep,
and less delusions and hallucinations.

12. • After confirmation of diagnosis of mesial temporal
sclerosis and complex partial seizures, we increased
the dose of clonazepam to 3 mg at bed time, and
started on carbamazepine 200 mg at bed time.
• After 2 weeks of improvement the patient showed
racing thoughts, hyperactivity, delusion of
grandiosity, disinhibition, aggressive
behavior,olfactory hallucinations, but sleeps well, so
we decided to decrease the dose of Clonazepam
gradually, and up titrating of Carbamazepine to 400
mg at bed time, and start Seroquel gradually till the
dose of 800 mg daily.

13. WHAT HAPPENED?
WHY THIS PATIENT IS RESISTANT TO
MEDICATIONS?
WHAT ARE THE POSSIBLE TREATMENTS
OF SUCH A PATIENT

14. MESIAL TEMPORAL SCLEROSIS

15. • Mesial temporal sclerosis is the commonest cause of
partial complex seizures.
• The etiology of this condition is controversial, but it is
postulated that both acquired and developmental
processes may be involved. Familial cases have also
been reported.
• Magnetic resonance imaging (MRI) is the imaging
investigation of choice for the diagnosis and has been
shown to be highly sensitive and specific(1)
1. Marchetti RL, Tavares AG, Gronich G, et al. Complete remission of epileptic psychosis after temporal
lobectomy: case report. Arq Neuropsiquiatr 2001 Sep;59:802–805

16. T2 weighted MRI. This image demonstrates an abnormality in the right mesial temporal lobe. It is shrunken and malformed
with enlargement of the temporal horn of the lateral ventricle. There is also a small area of abnormal high T2 signal within
the right hippocampus. The left hippocampus is relatively normal.

17. The T1 weighted image demonstrates the lesion with somewhat better anatomical detail

18. esial temporal sclerosis is the most common
pathologic entity associated with refractory
temporal lobe epilepsy (TLE); it is seen in as
many as 60% to 80% of cases.(2)
. BronenRA,FulbrightRK,SpencerDD,etal.Refractoryepilepsy:comparisonofMRimaging,CT,andhistopathologicfindingsin117patients.Radiology

19. ecause epilepsy is a disorder of distributed neural
networks,(3)
recent advances in brain network analysis
have been used to explore network abnormalities in
patients with TLE. Evidence for altered brain networks
in TLE has been accumulating through both structural(4)
and functional(5)
network analyses.
.EngelJJr,ThompsonPM,SternJM,etal.Connectomicsandepilepsy.CurrOpinNeurol2013;26:186–194.
.ConchaL,KimH,BernasconiA,etal.Spatialpatternsofwaterdiffusionalongwhitemattertractsintemporallobeepilepsy.Neurology2012;79:455–462.

20. edical treatment is successful in 25% of cases,
whilst anterior temporal lobectomy (Tailored
resection strategies including selective
amygdala-hippocampectomy are established )
is effective in 70 - 95% of patients, with up to
80% postoperative seizure freedom within the
first 2 years.(6)
.vonLeheM,LutzM,KralT,SchrammJ,ElgerCE,Clus-mannH(2006)Correlationofhealth-relatedqualityoflifeaftersurgeryformesialtemporallobeepilepsywithtwosei-zureoutcomescales.EpilepsyBehav

21. Psychosis and Epilepsy
he prevalence of psychotic illness in people with
epilepsy is at least 4%.(7)
diagnosis of temporal lobe epilepsy does not seem to
confer additional risk.(8)
ntipsychotics have been associated with
hyponatraemia, and seizures may occur if this is
severe.(9)
Some antipsychotics and antidepressants can reduce
the seizure threshold, and the risk is dose-related(10)

22. ext Anticonvulsants are associated with the
onset of psychotic symptoms:
arbamazepine, ethosuximide, gabapentin,
lamotrigine,(11)
levetiracetam,(12)
piracetam,
pregabalin, primidone, tiagabine, topiramate,(13)
valproate, vigabatrin and zonisamide.(14)
1. BrandtCetal.Developmentofpsychosisinpatientswithepilepsytreatedwithlamotrigine:reportofsixcasesandreviewoftheliterature.EpilepsyBehav2007; 11:133–139.
2.BhardwajRetal.Levetiracetam-inducedpsychosis.EpilepsyBehav2010;17:614.

23. lectroconvulsive therapy (ECT) has
anticonvulsive properties and is worth consid-
ering in the treatment of depression in patients
with unstable epilepsy.
CT does not appear to cause epilepsy.(15)

24. Drug Safety in
epilepsy
Special considerations
Trifluoperazine/
haloperidol
Good choice Low pro-convulsive effect
Carbamazepine increases the metabolism of some
antipsychotics and larger doses of an antipsychotic may be
required
Sulpiride/amisul
pride
Good choice Low pro-convulsive effect, very few reports of
suspected drug-related seizures.
No known interactions with anticonvulsants
Risperidone/Ola
nzapine/Quetia
pine
Care required Doubts about safety in epilepsy
Olanzapine may affect EEG, and myoclonic seizures have
been reported
Seizures rarely reported with quetiapine, but also shown
to have anticonvulsant activity in ECT
Both olanzapine and quetiapine may increase the seizure
threshold up to two-fold, and are linked
to higher rates of drug-related seizure
Aripiprazole Care required Very limited data and clinical experience Seizures
have been reported rarely

25. Drug Safety in
epilepsy
Special considerations
Clozapine Avoid if
possible
very epileptogenic
Approximately 5% who receive more than 600 mg/ day develop
seizures
Sodium valproate or lamotrigine are the anticonvulsant of choice
as they have a lower incidence of leucopenia than carbamazepine
Lurasidone,
asenapine
Avoid if
possible
Not thought to affect seizure threshold but experience is
limited
Chlorpromazine Avoid Most epileptogenic of the older drugs Ideally best avoided
completely
Depot
antipsychotics
Avoid None of the depot preparations currently available are
thought to be epileptogenic, however: the kinetics of
depots are complex (seizures may be delayed)
if seizures do occur, the offending drug may not be
easily withdrawn. Depots should be used with extreme
care

26. Thank you