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.