Toxic-Induced Encephalopathy Following Chemsex in a Young HIV-Positive Male: A Complex Case of Acute Cognitive Impairment with Anterograde Amnesia and Behavioral Alterations

Intoxications related to chemsex are becoming more prevalent among individuals with HIV, and their use as neurochemical substances as sexual boosters (chemsex is a term used to describe the intentional use of drugs to enhance or facilitate sexual activity) has become popular in this population [1, 2]. Neurological complications are the most prevalent in some European cohorts [3]. In this setting, emergencies occasionally bring forth rare clinical events known as acute amnestic syndromes [4]. Pinpointing the cause can be complex, given the array of potential origins. While some cases may be fully recoverable, others can come with additional neurological symptoms, leading to severe, permanent brain injury. The hippocampus plays a critical role in memory. Its alteration, either structural or functional, can alter memory. One common manifestation is transient global amnesia, distinguished by a swift onset of anterograde amnesia that lasts less than 24 h, devoid of other neurological indicators. Another brief memory disturbance is transient epileptic amnesia, attributed to localized seizure activity [4]. Memory impairments can also arise suddenly from strokes that affect crucial memory sites. Beyond neurological origins, amnesia can also signal psychiatric conditions like dissociative amnesia. It is essential to consider traumatic brain injuries, autoimmune encephalitis, and acute toxic metabolic disorders as potential causes of amnesia; for this discussion, we highlight the importance of toxic-induced disorders [5, 6].

This report presents a challenging case involving a 28-year-old male with a background of well-controlled HIV and documented substance use. Following an episode of heavy consumption of cannabis, poppers, methamphetamine, and cocaine within chemsex, the patient exhibited alarming neurological and cognitive symptoms, chiefly characterized by acute cognitive impairment and predominant anterograde amnesia. This case provides an opportunity to examine the potential neurological ramifications of substance use, especially in individuals with underlying conditions. It stresses the importance of prompt and comprehensive clinical assessments in understanding and managing such difficult presentations.

Twenty-eight-year-old male patient with no known drug allergies. Educational background: He completed a degree in social communication in his home country (Colombia). Worked as a salesperson in stores and as a waiter. The patient is a heavy consumer of cannabis (weekly), poppers (weekly), smoked methamphetamine (monthly), and occasional alcohol in social settings and no slamming.

Past medical history: HIV infection diagnosed in November 2014. Started treatment in Colombia with switching from efavirenz/tenofovir/emtricitabine EFV/TDF/FTC after diagnosis (unknown CD4 nadir and viral load at diagnosis), apparently good adherence and tolerance. There was no history of virological failures or opportunistic infections. He arrived in Spain in 2021, EFV/TDF/FTC to dolutegravir/lamivudine (DTG/3TC). The patient showed reasonable immunovirological control with a CD4 count of 646 cells/mm³ and a viral load of less than 50 copies/ml, with no data before hospitalization.

On the night of July 14–15, he consumed cocaine, poppers, and cannabis in a recreational-sexual context, starting the same day with symptoms of sweating, holocranial headache (widespread headache), and general discomfort, which his partner initially interpreted as a result of partying, leading him to sleep most of the day. On July 16, around 11:00 am, he started experiencing language impairment (according to his partner, dysarthria "as if his tongue was tied"), and upon returning home, he began experiencing memory lapses, not remembering what had happened during the morning. Consequently, he was taken to the emergency room for assessment. A stroke code was activated due to possible neurological focal symptoms, but it was dismissed due to the temporal and progressive nature of the symptoms.

A blood test showed a slight elevation in acute-phase reactants with leukocytosis and a PCR of 3 mg/dl. Urine toxicology was positive for cannabis and amphetamines. A brain CT scan showed signs of toxic encephalopathy with bilateral and symmetrical hypodensity of both hippocampi and pale globes (Fig. 1) and reduced intensity in the bilateral occipital lobe, suggesting toxic-metabolic encephalopathy. A lumbar puncture revealed minimal hyperproteinorrachia, glucose within range, 200 red blood cells, and eight nucleated cells. Empirical coverage with acyclovir was initiated and discontinued as LCR multiplex PCR was negative.

Nevertheless, the patient’s condition rapidly deteriorated in the hospital ward, with worsening dysarthria, neuropsychiatric alterations, and exacerbated anterograde amnesia. An EEG showed findings consistent with diffuse cerebral dysfunction. Doppler ultrasound and angio-MRI showed no abnormalities in the carotid territory. During the early hours of July 19, he developed significant psychomotor agitation about memory lapses, requiring mechanical and pharmacological restraint. Due to the progressive neurological deterioration and the likely need for sedation for a brain MRI, he was admitted to the ICU. After the MRI, he was transferred back to the conventional Infectious Diseases ward.

Neuroimaging (cranial CT Fig. 1 and cerebral MRI Fig. 2) showed lesions in the globus pallidus, cerebellum, and hippocampi. Upon reassessment, he presented primarily anterograde amnesia, increased response latency, childlike behavior, and a lack of awareness of his deficits. He occasionally confabulated. A MoCA test was performed, yielding a score of 19/30 (visuospatial/executive function 3/5; identification 3/3; attention 6/6; language 2/3; abstraction 2/2; delayed recall 0/5; orientation 3/6), primarily indicating a deficit in episodic memory with a score of 1/15 on the memory index scale (MIS). The patient’s neuropsychological assessment had indicated a pronounced presence of anterograde amnesia, accompanied by retrograde memory challenges and compromised executive functions, all consistent with the hallmarks of toxic encephalopathy.

Upon admission, in-depth neuropsychological screening, documented as Table 1, revealed significant anterograde amnesia, attention deficits, and executive function challenges. This was closely followed by further assessments, outlined in Table 2, at 38 days post-onset, where certain cognitive deficits persisted despite slight improvements in memory retention and retrieval. After 120 days, as detailed in Table 3, the patient still exhibited anterograde amnesia, impairment in complex visuospatial functions, yet showed some recovery in language function and cognitive flexibility with slight improvements in memory encoding and retention noted since the initial evaluation. Additionally, there has been a consolidation in the retrieval of retrograde information. The patient’s spontaneous language normalized, and attention remains average. Complementing these findings, MRI results 33 days post-onset (Fig. 3) revealed marked improvement in the globus pallidi’s signal alteration, with ongoing but diminished signal changes in the cerebellum and both hippocampi. These cognitive deficits, particularly anterograde amnesia, significantly impair the patient’s autonomy and ability to manage self-care, increasing vulnerability in personal decision-making.

In recent years, like many other major cities worldwide, Barcelona has seen a significant rise in drug use, especially within chemsex [1, 11, 12]. This growing phenomenon raises not only concerns about the direct health consequences of drug misuse, such as addiction and overdose, but also the increased incidence of atypical presentations of diseases and a higher incidence of sexually transmitted infections or the recently described associated methicillin-resistant Staphylococcus aureus infection [2, 13].

In this case, the severe clinical presentation of the 28-year-old male offers a profound insight into the interplay between substance use and neurological implications. Neuroimaging shows lesions in the globus pallidus, cerebellum, and hippocampus, which merit a detailed neuroscientific exploration. These brain regions are integral to a range of cognitive functions: the globus pallidus plays a crucial role in regulating voluntary movement, the cerebellum contributes to motor control and mental functions such as attention and language, and the hippocampus is fundamentally involved in memory formation and retrieval. The pronounced anterograde amnesia observed in the patient is elucidating, given the hippocampal damage evidenced by neuroimaging. This aligns with the existing literature regarding the hippocampus’s role in consolidating new memories. The patient’s neurological state is characterized by significant memory deficits, neuropsychiatric alterations, and cognitive disturbances. The heavy consumption of these substances, especially within the setting of chemsex, can potentiate their neurotoxic effects. These side effects are not dose-dependent.

The precise mechanism behind these lesions is unclear, but potential causes include ischemia, direct toxicity, or their combination. Anoxia often leads to ischemic hippocampal injuries [14], resulting in marked anterograde amnesia. While anoxia-induced bilateral lesions in the basal ganglia are less common [15, 16], they can also arise from carbon monoxide exposure [17, 18]. Hippocampal lesions from anoxic events usually hint at a bleak prognosis [19, 20]. Research on rat models indicates that hypoxia can induce hyperpolarization and neuronal injury within the CA1 region of the hippocampus [21]. The unilateral counterpart usually shows less pronounced memory deficits than bilateral hippocampal damage [22]. Different conditions can induce ischemia and hypoxia in the hippocampus, and each carries its prognosis. For example, post-cardiac arrest ischemia often has a limited potential for memory recovery [19]. Though rare, cocaine-induced vasospasm and carbon monoxide intoxication are recognized instigators of bilateral ischemia in the hippocampus [23]. In this patient, we postulate that multiple drug exposures led to anoxia, culminating in bilateral hippocampal damage.

Stimulants, specifically cocaine, can produce ischemic lesions from vasospasm. There are prior cases of bilateral basal ganglia lesions in stimulant use. For example, there is a case of bilateral basal ganglia lesions following MDMA use [24] and an additional case involving methadone, cocaine, and amphetamines [25] producing basal ganglia lesions. A combination of cocaine and alcohol resulting in unconsciousness has also produced bilateral basal ganglia lesions [26]. Between 2012 and 2016 in Massachusetts, an unusual group of 14 cases emerged, each presenting with sudden amnesia due to acute and total bilateral ischemia in the hippocampus. While the exact cause remains uncertain, 13 of the 14 cases either tested positive for opioids or had a record of opioid use in their medical history at the time of their initial assessment [27]. In this particular situation, the patient tested negative for opioids, and there is no known current use of these substances within the chemsex context in Barcelona. In other studies, from a series studying bilateral globus pallidus necrosis, drug overdose was the cause in ten out of 27 cases, surpassing any other reason [28].

In a case echoing ours, a 55-year-old man presented with bilateral hippocampal and basal ganglia lesions following a myocardial infarction induced by cocaine and 3,4-methylenedioxy-methamphetamine consumption, resulting in explicit and procedural anterograde amnesia. Notably, both patients exhibited a similar memory impairment type – anterograde amnesia for explicit and implicit/procedural memory, which we attribute to bilateral lesions in the hippocampus and basal ganglia due to drug use [29].

Furthermore, bilateral hippocampal lesions have been observed concerning cocaine use, stemming from vasospasm without anoxia [30, 31]. It is also noteworthy to touch upon the patient’s childlike behavior and lack of awareness of his deficits. Such presentations may suggest frontal lobe involvement, a brain region responsible for executive functions, judgment, and self-awareness. Though not explicitly mentioned, the observed executive dysfunctions in the neuropsychological evaluation hint at possible frontal cortex implications.

Regarding neuroimaging findings in 50% of patients suffering from acute amnesic syndrome, MRI T2-fluid-attenuated inversion recovery (FLAIR) sequences reveal hyperintense lesions in locations such as the fornix, medial thalamus, mammillary bodies, and periventricular area around the third ventricle, and periaqueductal areas [4]. In our specific patient, the findings contrast with this, as we observed a definitive change in signal in both globus pallidus. The FLAIR sequences for this patient also detected signal variations in the cerebellum and hippocampus. Hence, the distinct findings centered around the cerebellum, hippocampi, and the globus pallidus. Postmortem examinations have detailed the neuropathological consequences of carbon monoxide (CO) toxicity. They reveal damage to the globus pallidus, diffuse white matter lesions, and encephalopathic changes [32]. We could not detect carboxyhemoglobin due to our patient’s delayed arrival time to the ER (the half-life of carboxyhemoglobin is about 74 min) [33].

Despite experiencing a severe outcome, our patient on dolutegravir and lamivudine was not exposed to the amplified risks of boosted ART. In a study of 172 HIV-positive chemsex participants, 30% used boosted ART. Of 2048 identified potential drug–drug interactions, 23% were deemed concerning, with 88% due to boosted ART [34]. Therefore, for the HIV chemsex community, it is crucial to consider non-boosted ART as a safer alternative to minimize potential drug interactions.

In our patient, while the underlying cause is likely drug toxicity, established ischemia is evident both on brain scanning and MRI, coupled with bilateral involvement. Medical literature extensively documents that anoxic damage causing hippocampal lesions predicts a less optimistic prognosis [19, 20]. Specifically, bilateral hippocampal damage tends to induce more profound memory deficits than unilateral lesions [22]. Numerous circumstances can precipitate ischemia and hypoxia in the hippocampus, each presenting its prognosis. As referenced from literature-based case reports and some case series, it is notable that patients who suffer from hypoxia but show no signs of ischemia, as well as those with histotoxic hypoxia stemming from incidents like carbon monoxide poisoning, might stand a better chance of recovery, irrespective of how severe the initial imaging might appear [35]. For example, post-cardiac arrest ischemia often culminates in a bleak outlook for memory recovery [19]. Even though rare, both cocaine-induced vasospasm and carbon monoxide poisoning are recognized precipitators for bilateral ischemia in the hippocampus [23, 36].

A notable limitation of this study is the inability to definitively identify the pathophysiological mechanisms underlying the neurological impairments observed in the patient, such as the exact cause of lesions in the brain regions like the globus pallidus, cerebellum, and hippocampus – this gap in understanding limits the ability to develop targeted interventions. Additionally, the lack of long-term follow-up is a significant limitation, as recovery from neurological impairments, particularly those involving memory and cognitive functions, can be prolonged. Insights into the patient’s recovery trajectory and the effectiveness of interventions over time are therefore unavailable. Another fundamental limitation is the absence of specific medical interventions or rehabilitation programs to enhance cognitive recovery in the patient’s care plan. Such interventions could aid in recovery, especially given the nature of the neurological deficits. The report also does not elaborate on rehabilitative or supportive care provided, which is crucial for recovery in cases involving drug misuse and neurological damage. Lastly, while the complexity of drug interactions in chemsex is acknowledged, the potential for underestimating the synergistic effects of multiple drugs used concurrently might limit a comprehensive understanding of the patient’s condition.

In this case, temporary legal safeguards have been considered essential to protect the patient’s health and welfare, with adjustments to be made according to clinical developments. Although the chances of complete recovery remain uncertain, it is advised to conduct a subsequent neuropsychological evaluation and begin specialized neuropsychological rehabilitation to optimize the potential for rehabilitation.

The adverse consequences of substances, particularly cocaine, cannabis, and poppers (alkyl nitrites), seem to be exacerbated when consumed in high doses, as observed in chemsex settings. While anoxia appears to be a plausible cause behind the observed injuries, considering the link between drug overdose and ischemia in specific brain regions, it is evident that multiple factors, such as direct toxicity or ischemia, contribute to the outcome. It is also vital to recognize the potential association of substance-induced ischemia without the involvement of anoxia. Noteworthy neuroimaging findings, particularly lesions in crucial brain regions such as the globus pallidus, cerebellum, and hippocampi, correspond with observed severe anterograde amnesia.

The complexity of drug interactions, especially in chemsex, brings forth multifaceted clinical implications that the modern healthcare system must adeptly navigate. Chemsex is a complex and dynamic phenomenon that, as demonstrated in this instance, can have potentially detrimental effects on a person’s life in a variety of ways. A proactive approach to public health, encompassing thorough research, targeted interventions, education, and public awareness, is tailored to the specific needs of this vulnerable population.