Discussion:
Patients with TSC may develop a variety of neuropsychiatric disorders
called TAND. Neurodevelopmental disorders such as autism spectrum
disorder (40–50%) and attention deficit hyperactivity disorder
(30–50%) are the most common psychiatric diagnoses made[8].
According to a recent study that enrolled 2216 participants with TSC
from 170 sites across 31 countries to explore TAND syndrome, psychiatric
disorders are underdiagnosed and potentially diagnosed late. Psychosis
and hallucinations were nonfrequent manifestations but significantly
higher in adults than children (10.3% vs 0.6%, p <
0.001) [9].
This case represents a form of TAND, where psychiatric symptoms,
suggesting a psychotic disorder, occurred after many years of disease’s
evolution. Several etiological factors can be identified, and some
hypotheses can be generated.
First, psychotic symptoms can be associated with epilepsy. It’s known
that early and multiple seizures are associated with a poor
neurodevelopmental outcome which may increase the risk of psychosis.
Furthermore, psychosis may be precipitated by longer duration of
epilepsy and higher frequency of seizures. In fact, frequent subclinical
epileptic discharges, and repeated altered consciousness may cause
structural and functional damage, including neuronal changes,
neurophysiological and blood flow abnormalities in the brain network
across neocortical, limbic, and subcortical regions which may result in
pathological mental phenomena leading to developing psychotic symptoms.
As a matter of fact, this patient had EEG abnormality in the temporal
lobe and associated epileptic seizures which are considered as risk
factors for psychosis. According to a recent meta-analysis, the pooled
prevalence of psychosis in epilepsy is 5.6%, and 7% in temporal lobe
epilepsy[10]. Psychotic disorders identified in patients with
epilepsy are commonly referred to in the medical literature as psychosis
of epilepsy (POE) [11]. Epilepsy and POE have a complex and
bidirectional relation. Not only are patients with epilepsy at increased
risk of developing a psychotic disorder, but patients with a psychotic
disorder are also at greater risk of developing epilepsy. POE generally
exhibits mood disorder, anxiety, hallucinations, delusions, and
disorders of consciousness. It can be classified according to the
temporal relationship to the seizures as ictal, postictal, and
interictal psychosis. The risk factors for postictal psychosis include
temporal lobe epilepsy, earlier epilepsy onset, and impaired
intellectual function, all of which were present in this case. However,
clinical amelioration of seizures and psychotic symptoms, without a
significant improvement in EEG patterns suggests that psychiatric
manifestations might be an independent component in this case.
Second, psychotic symptoms may also be caused by organic lesions due to
TSC [7]. The literature lacks knowledge about the pathogeny of these
symptoms. Few cases reported the onset of psychiatric manifestations.
According to Andrej N Ilanković et al, 5 patients with the average age
of 35, 7 years, from different part of Yugoslavia, who were admitted
between 2013 and 2016, developed paranoid psychotic episodes one year
before being hospitalized [12]. In fact, hallucinations and
delusions are explained based on tubers impinging upon various limbic
structures. Subependymal calcification, giant cell tumors, and retinal
phakomas might be also the cause. However, there were not any overt
modification in the cerebral imaging within the time course which made
this hypothesis less possible.
Third, the occurrence, in this patient, of a first psychotic episode
triggered by a stressful event, comorbid with his organic pathology,
remains highly probable. Indeed, all symptoms were reported to emerge in
the month following the global emergence of the COVID-19 pandemic.
Although no explanation of the relationship between the pandemic and
this case can be considered definitive, we suggest that a combination of
social isolation, longer duration of quarantine reduced individual
liberty, inadequate supplies, financial loss, fear of the infection
itself , feeling insecure, a loss of control and poor quality of sleep
might have triggered an intense psychobiological stress reaction leading
to the psychosis onset [13,14].
This acutely stressful scenario could play an important role in the
emergence of new-onset psychoses and might also be a major risk factor
for clinical decompensation in individuals with previous chronic
disorders who are considered as being vulnerable to psychiatric
diseases[15, 16]. As a matter of fact, a recent study made by María
José Valdés-Florida and al, including all the hospitalized patients with
reactive psychoses during the first two weeks of quarantine, show that
relapses were directly triggered by stress derived from the COVID-19
pandemic [2]. Also, Zulkifli et al identified a case report from
Malaysia, of an acute episode of psychosis seemingly precipitated by
fear and distress associated with the COVID-19 pandemic, in 31-year-old
male patient without previous history of mental disorder, nor substance
use [12]. About medical care, there is not a specific treatment for
psychosis seen in TSC [17]. In literature, a case was reported
responding well to risperidone without side effects [17]. Our
patient received olanzapine with marked improvement in psychotic
symptoms.