Secondary Schizophrenia (33 page)

focal epilepsy, especially in the preictal and postictal
Between the last seizure and the psychosis there
periods
[29].
Neurons in the medial temporal region
is usually a nonpsychotic period, which ranges from
in temporal lobe epileptic patients have higher firing
a few hours to a few days. This period lasted 12 to
rates, more frequent burst discharges, and stronger
72 hours in the Kanner study
[35]
and up to 1 week
synchrony than neurons in nonepileptic regions, espe-according to Logsdail and Toone
[31].
Some clouding
cially during sleep
[30].
Second, rapid synchronized
of consciousness is often present in this period, and it
neuronal discharges, which form the basis of epilep-may extend to the initial period of psychosis or even
tic discharges, occur normally in the limbic structures,
the whole episode. The psychotic symptoms are pleo-hypothalamus, and brainstem in association with vital
morphic (persecutory, grandiose, referential, somatic,
functions such as parturition, milk ejection, growth
and religious delusions, catatonia, hallucinations, etc.),
hormone release, and orgasm
[5].

and affective symptoms (manic or depressive) are often
prominent
[31,
39].
First-rank symptoms of Schnei-

Postictal psychosis

der can occur but are rare
[35].
Postictal psychoses
resolve within a few days, with the mean duration in
The behavioral disturbances that may follow a seizure,
the study by Kanner and colleagues
[35]
being about
or a bout of seizures, have received increased attention
70 hours (range
=
24–144), and all resolving within
in the last two decades
[31,
32, 33, 34, 35, 36, 37, 38, 39,

1 month in the study by Savard and colleagues
[33].

40, 41].
Postictal psychosis (PIP) as a special instance
A few reports of longer duration of PIP have been
of such disturbance has been recognized for centuries,
published, but at which point the diagnosis should
but its clinical importance has been overshadowed by
be changed to interictal psychosis is debatable. The
the interictal psychoses. Indeed, a literary reference to
proposal of the Subcommission on Classification of
postictal psychosis occurs in Shakespeare’s Othello (IV,
the ILAE Commission on Epilepsy and Psychobiology
I, 42, 43, 44, 45, 46, 47, 48):

was that PIP lasting more than a month may require
IAGO: My Lord is fall’n into a epilepsy. This is his second fit; he
reconsideration of diagnosis and a change to interictal
had one yesterday.

psychosis
[36].

CASSIO: Rub him about the temples.

Although the resolution of PIP is generally spontaneous, it is aided by neuroleptic medication, usu-IAGO: No, forbear; the lethargy must have his quiet course; if
ally in small doses. A further seizure may exacerbate
not, he foams at the mouth; and bye and bye breaks out to
the psychosis, and anticonvulsant treatment should be
savage madness . . .

carefully monitored. The brief psychosis may recur, at
Because PIPs are brief and occur in close proxima frequency of 2 to 3 episodes per year in two stud-

83

ity with seizures, they are ideal for the investigation
ies
[35, 49],
and in some patients (15% in one study
Organic Syndromes of Schizophrenia – Section 3

[31])
these episodes may become chronic. More lon-neocortex. Mathern and colleagues
[54]
reported two
gitudinal studies of patients with PIP are needed to
patients, one of whom had unilateral postictal dis-examine its course, its likelihood of recurrence, and
charges, but on autopsy was found to have bilateral
factors that predispose a transition into chronic inter-hippocampal neuronal loss, although the pathology
ictal psychosis.

was asymmetric. Some authors also report low intelli-The predisposing factors of PIP are poorly under-gence as a predisposing factor for PIP
[39, 50],
suggest-stood. A question that has been frequently posed in
ing the presence of more widespread brain abnormal-the published literature is whether PIP is associated
ity. In summary, the weight of the evidence supports
with a specific type of epilepsy, that is, with a temporal
a stronger association with complex partial epilepsy,
focus, and whether independent bilateral disturbance
especially of temporal lobe origin, in which there is
is more commonly represented than unilateral abnor-bilateral pathology, although this relationship is not
mality. The majority of reported patients suffer from
exclusive.

partial complex seizures that are secondarily general-The
pathogenetic

mechanisms

are

unclear,

ized. Epilepsy has often been present for more than 10

although the proximity of these psychoses to seizures
years before the onset of psychosis
[31,
35, 37].
EEG

and their frequent occurrence in epilepsy centers
abnormalities persist in the majority of patients dur-while patients are being monitored make them
ing the psychosis in the majority of cases
[31].
In a
ideal candidates for the exploration of underlying
case report by So and colleagues
[32]
, the patient with
mechanisms. The finding of chronic frequent subictal
postictal psychosis demonstrated frequent bitemporal
discharges suggests that ictal activity in the temporal
independent epileptiform discharges on depth record-lobe may be directly related to this kind of psychosis.

ing that were maximal in the mesial limbic regions. On
Changes in monoamines, particularly postsynaptic
the other hand, another report presented two patients
dopamine receptor sensitivity, have been suggested
with PIP who had repeated EEGs during the psychosis
as the mediating mechanism
[32]
. Some support for
showing that their habitual focal epileptiform abnor-the dopamine mechanism came from a single photon
malities were absent
[50]
– suggestive of “forced nor-emission computed tomography (SPECT) study using
malization” (discussed later). Although Kanner and
[(123)
I]iodobenzamide that demonstrated low levels
colleagues
[35]
found no specific predisposing fac-of striatal dopamine D2 receptors in patients with
tors that differentiated their psychotic group from a
periictal psychosis
[55].
Low folic acid levels have
comparable nonpsychotic epilepsy group, Savard and
been suggested to have a role
[56],
but firm evidence is
colleagues
[33]
were impressed with a high rate of
lacking. The significance of a report of hyponatremia
ictal fear, bilateral independent discharges, and gross
in these patients is also unknown
[35].

structural lesions (6 out of 9 patients), including the
More importantly, it would be fruitful to exam-presence of alien tissue tumors. Kanemoto and col-ine PIP in the context of the homeostatic mecha-leagues
[39]
also noted frequent psychic auras, and
nisms that are brought about in the brain to con-Umbricht and colleagues
[51]
noted frequent bitem-trol seizures, which have been divided into electro-poral foci in their subjects. In contrast with the other
physiological mechanisms, cerebral blood flow (CBF)
literature, Devinsky and colleagues
[52]
found sim-changes, and neurotransmitter and receptor changes
ilar rates of PIP in partial and primary generalized
[40].
Postictal psychosis in this context has been con-epilepsies, although they did note bilateral indepen-ceptualized as a phenomenon akin to Todd’s paralysis,
dent interictal discharges in those with partial seizures.

indicating the postictal inactivation of cortical regions
PIP has also been associated with frontal lobe epilepsy,
involved in the ictal event, which usually include bilat-accounting for 3 out of 11 cases in one series
[53].

eral medial temporal structures
[17].
A simple electro-Five of the 14 patients studied by Logsdail and Toone
physiological explanation – that the postictal state is
[31]
had abnormalities on brain computerized tomog-caused by “neuronal exhaustion” – is not supported by
raphy (CT). In the MRI study of Kanemoto and col-experimental evidence
[57].
A second possible expla-leagues
[37],
postictal psychosis was most likely to
nation – also lacking evidence – is that of neurotrans-occur in patients with resistant TLE stemming from
mitter depletion due to repeated firing
[40].
An impor-mesial temporal sclerosis, especially on the left side.

tant aspect of seizure termination is active inhibition,
These patients with left-side mesial temporal sclero-in which a number of mechanisms are involved. A
84

sis were also likely to have atrophy of the temporal
hierarchy of inhibition is produced by fast inhibitory
Chapter 6 – Schizophrenia-like psychosis and epilepsy

postsynaptic potential (IPSP) mediated by gamma
Table 6.2
Possible pathogenetic mechanisms of the postictal
amino butyric acid-A (GABA

state with relevance to postictal psychosis
A) receptors, a later

hyperpolarizing potential mediated by GABAB recep-1. Electrophysiological:
tors
[40],
and after hyperpolarization produced by
a. Continuous ictal discharges leading to psychomotor
calcium-activated potassium currents. Although these
change

inhibitory mechanisms are brief, prolonged inhibition
b. Neuronal “exhaustion” from a seizure cluster
of neuronal activity can be produced by hyperpolariz-2. Neurotransmitter changes:
ing pumps, whose object is to restore the steady-state
a. Catecholamine depletion

ionic balance after neuronal activity. Seizures lead to
b. Increased postsynaptic dopamine sensitivity
increased extracellular K
+
, and levels higher than 20

to 30 mm produce a spreading depression and cessa-c. Increased endogenous opiates
tion of neuronal activity, which may account for the
d. Increased adenosine

postictal state
[58].
Seizures also cause lactic acido-e. Increased nitric oxide
sis and low pH, and the H
+
ions compete with other
3. Postictal inhibitory mechanisms:

ions at the ion channel associated with N-methyl-D-a. Fast inhibitory postsynaptic potential (GABAA mediated)
aspartic acid (NMDA) receptors.

b. Later hyperpolarizing potential (GABA
Seizures cause a release of a number of other
B mediated)

neurotransmitters that include acetylcholine, cate-c. After hyperpolarization due to calcium-activated
potassium currents

cholamines, serotonin, opiates, adenosine, and nitric
oxide (NO). Endogenous opiates appear to play a sped. Na-K hyperpolarizing pumps
cial role in the postictal state
[43].
Naloxone is noted
e. Increased extracellular K
+

to reverse post-seizure catalepsy in rats subjected to
f. H
+
induced attenuation of NMDA receptors
electroshock
[44]
and to increase the rate of interictal
g. Increased opiates, adenosine and NO

spiking in humans
[45],
but the evidence is not entirely
4. Cerebral blood flow alterations due to poor autoregulation
consistent
[46, 47].
Adenosine and NO are neuromod-5. Other:
ulators that may act as endogenous anti-seizure agents.

It is possible that the repeated release of neurotrans-a. Low folic acid
mitters during seizure activity leads to postsynaptic
b. Hyponatraemia

receptor changes, as has been demonstrated for ben-zodiazepine receptors
[48],
and this may be relevant
to PIP.

Seizures lead to substantial changes in CBF that
demonstrated for postictal hemiparesis
[61].
Hyper-may have a relevance to PIP, although the precise
perfusion in PIP, therefore, cannot necessarily be con-mechanism is unknown. Ipsilateral to the temporal
strued as hypermetabolism, although regional varia-lobe seizure, there is a rise of CBF to twice the base-tions after correction for global change in perfusion
line at about 5 min, but by 1 hour, the CBF is below
cannot be dismissed. Moreover, increased perfusion is
baseline. A SPECT study of four patients with TLE

equally likely to be related to increased inhibition or
and postictal psychosis demonstrated mesial frontal
excitation, and the primary disturbance may be local
hyperperfusion during the psychosis
[34].
Another
or remote. Metabolic studies, combined with neu-report from the same group suggested hyperperfusion