Severe Sleep Research Articles

Sleep Loss Promotes Astrocytic Phagocytosis and Microglial Activation in Mouse Cerebral Cortex.

We previously found that Mertk and its ligand Gas6, astrocytic genes involved in phagocytosis, are upregulated after acute sleep deprivation. These results suggested that astrocytes may engage in phagocytic activity during extended wake, but direct evidence was lacking. Studies in humans and rodents also found that sleep loss increases peripheral markers of inflammation, but whether these changes are associated with neuroinflammation and/or activation of microglia, the brain's resident innate immune cells, was unknown. Here we used serial block-face scanning electron microscopy to obtain 3D volume measurements of synapses and surrounding astrocytic processes in mouse frontal cortex after 6-8 h of sleep, spontaneous wake, or sleep deprivation (SD) and after chronic (∼5 d) sleep restriction (CSR). Astrocytic phagocytosis, mainly of presynaptic components of large synapses, increased after both acute and chronic sleep loss relative to sleep and wake. MERTK expression and lipid peroxidation in synaptoneurosomes also increased to a similar extent after short and long sleep loss, suggesting that astrocytic phagocytosis may represent the brain's response to the increase in synaptic activity associated with prolonged wake, clearing worn components of heavily used synapses. Using confocal microscopy, we then found that CSR but not SD mice show morphological signs of microglial activation and enhanced microglial phagocytosis of synaptic elements, without obvious signs of neuroinflammation in the CSF. Because low-level sustained microglia activation can lead to abnormal responses to a secondary insult, these results suggest that chronic sleep loss, through microglia priming, may predispose the brain to further damage.SIGNIFICANCE STATEMENT We find that astrocytic phagocytosis of synaptic elements, mostly of presynaptic origin and in large synapses, is upregulated already after a few hours of sleep deprivation and shows a further significant increase after prolonged and severe sleep loss, suggesting that it may promote the housekeeping of heavily used and strong synapses in response to the increased neuronal activity of extended wake. By contrast, chronic sleep restriction but not acute sleep loss activates microglia, promotes their phagocytic activity, and does so in the absence of overt signs of neuroinflammation, suggesting that like many other stressors, extended sleep disruption may lead to a state of sustained microglia activation, perhaps increasing the brain's susceptibility to other forms of damage.

Mindfulness-Based Intervention Does Not Influence Cardiac Autonomic Control or the Pattern of Physical Activity in Fibromyalgia During Daily Life: An Ambulatory, Multimeasure Randomized Controlled Trial.

Fibromyalgia (FM) is a syndrome characterized by severe pain, fatigue and sleep disturbance. There is evidence of central hyper-responsiveness to sensory stimulation and impaired cardiovascular autonomic control. Laboratory investigations suggest that mindfulness-based stress reduction (MBSR) may improve autonomic functioning in FM. However, these findings may not reflect what occurs during naturalistic conditions, and MBSR studies during real-life functioning are lacking. We conducted a randomized controlled, 3-armed study with 168 female FM patients. This report describes cardiac, respiratory, and physical activity findings. Eight-week MBSR was compared with wait-list and active control intervention. Ambulatory accelerometry and cardiorespiratory function were monitored over 24-h periods at 3 time points: preintervention, postintervention, and at the 8-week follow-up. Also, baseline levels were compared with an age-matched group of 33 healthy women. Activity heart rate, respiratory sinus arrhythmia, and ventilation were measured. Comparison with controls confirmed differences in cardiac autonomic tone and activity pattern among patients. Most measures also showed effects of time of day and point of measurement. Regarding the intervention study, there were no effects of treatment. In addition, there were no relations between patient-reported clinical improvement and objective physiological or accelerometry parameters. Intervention-related benefits in wellbeing were not associated with changes in daytime cardiorespiratory measures or pattern of physical activity. MBSR did not produce cardiac autonomic benefits or changes in daily activity in FM. Furthermore, the lack of an association between patient-experienced clinical improvement and objective physiological measures suggests that subjective changes in the wellbeing of FM patients over time are not related to alterations in the cardiorespiratory autonomic function or activity levels.

1223 Severe sleep apnea in an infant treated with high-flow nasal cannula therapy.

1223 Severe sleep apnea in an infant treated with high-flow nasal cannula therapy.

Use of buspirone in selective serotonin reuptake inhibitor-induced sleep bruxism

Sleep bruxism is characterized by the involuntary clenching or grinding of the teeth during sleep and can cause severe health problems, including the destruction of tooth structure, temporo-mandibular joint dysfunction, myofascial pain, and severe sleep disturbances. Iatrogenic sleep bruxism may be common during treatment with psychotropic medications, such as anti-psychotics and antidepressants, especially selective serotonin reuptake inhibitors (SSRIs). Bruxism is a common movement disorder that affects 8–21% of the population. The majority of bruxism symptoms are mild or moderate, although rare but severe cases may lead to serious periodontal damage, temporo-mandibular dysfunction, sleep disturbances, jaw pain, and stiffness. As a result, such cases must be treated with medication. It has been hypothesized that the mechanism of SSRI-induced bruxism may involve excessive serotonergic action on the meso-cortical neurons arising from the ventral tegmental area. It has been argued that,the addition of buspirone, was necessitated by the high level of residual anxiety. As a result, these symptoms may have been prevented through the use of buspirone alone. Buspirone, is an agonist of the 5-HT1A receptor that increases dopaminergic neuron, firing in the ventral tegmental area and increases the synaptic release of dopamine in the prefrontal cortex. These effects ameliorate drug-induced bruxism. Buspirone can also ameliorate extrapyramidal side effects, such as akathisia and tardive dyskinesia, and this property may be an additional explanation for the bruxism-related effects of the drug. Furthermore, buspirone may be an effective treatment for the bruxism associated with the use of these medications.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Assessment of interfering factors in non-adherence to oral appliance therapy in severe sleep apnea.

Oral appliances (OA) are recommended for patients with severe obstructive sleep apnea who fail to comply with continuous positive airway pressure (CPAP) therapy. This mixed-methods study aimed to quantify adherence to OA therapy and evaluate subjective reasons associated with non-adherence. The medical records of 52 patients with an apnea-hypopnea index (AHI) ≥ 40, treated with OA after discontinuation of CPAP treatment, were examined for OA adherence. Patients were divided according to usage at the time of a phone interview. The USER group included all forms of usage, whereas those who completely ceased using the OA were in the NUSE group. The timing of the phone interview was from five months to six years (average 44.63±17.17months) after OA delivery. The overall adherence rate was 57.7% (30/52 patients). The mean usage times were 10.07±8.96 and 44.30±17.3months in the NUSE and NUSE groups, respectively. The main factors associated with non-adherence were concerns about the effects of the OA on teeth (22%) and insufficient efficacy (22%). Other factors were discomfort (15%) and improved well-being following weight loss (15%). The overall number of interfering and discontinuity factors was significantly higher in the NUSE group than in the USER group (P=0.041). Nine (17.3%) of 52 patients resumed CPAP use. Subjective and objective outcomes, determined by using a second sleep test with OA in 69.2%of patients, were related to the continuation of treatment. On-adherence to OA is strongly associated with patient reservations regarding the effects of the device on teeth, possible lack of efficacy, and discomfort. Clinicians should closely monitor adherence patterns and assess potential interfering factors during their diagnostic workup. Patients should be reassured regarding device safety, particularly following dental work that may interfere with the insertion of the OA.

ICARUS study: prevalence and clinical features of impulse control disorders in Parkinson’s disease

BackgroundImpulse control disorders/other compulsive behaviours (‘ICD behaviours’) occur in Parkinson’s disease (PD), but prospective studies are scarce, and prevalence and clinical characteristics of patients are insufficiently defined.ObjectivesTo assess the presence...

Severe sleep apnea resistant to all treatments

Severe sleep apnea resistant to all treatments

Security sovereignty and the preemption of low-risk detainees: A look into ‘battlelab’ torture techniques used at Guantanamo Bay

This study conceptualizes a new sovereign power following controversial interrogation practices used at Guantanamo Bay. I conceptualize this new sovereign, referred to as security sovereignty, as a new style of governance that draws commonalities and differences with logics of security and sovereignty. While security logics aim to preempt future danger and sovereignty seeks to violently retaliate against those that break the law, security sovereignty uses violent measures against low-level risks that have not been charged or convicted of wrongdoing. This new concept can be used to help explain why high-ranking officials in the Bush Administration authorized controversial interrogation methods against low-value detainees at Guantanamo Bay and CIA black sites. Indeed, President Bush and high-ranking officials at Guantanamo Bay created a secret interrogation program at Guantanamo Bay, referred to as ‘battlelab’ interrogations by Major General Michael Dunlavey, to develop the most sophisticated psychological and physical torture techniques. Battlelab experimentation techniques were used on select detainees to develop useful truth extraction methods that could later be used on high-value targets captured on the battlefield. Such practices included severe sleep deprivation, the use of psychosis-inducing drugs, forced enemas and medications, and prolonged IV feedings that resulted in involuntary bowel movements. This study uses battlelab experimentations as substantive support to theorize a new sovereign power that exercises the absolute right to torture detainees that do not pose a threat to U.S. national security.

Parental Reports of Prodromal Psychopathology in Pediatric Bipolar Disorder.

: Objectives: Early psychopathology in children diagnosed with Bipolar Disorder (BD) remains poorly characterized. Parental retrospective reports provide helpful details on the earliest manifestations and their evolution over time. These symptoms occur early in the course of BD, often before a formal diagnosis is made and/or treatment is implemented, and are of great importance to early recognition and prevention.Methods: Parents of pre-pubertal children and adolescents with DSM-IV diagnoses of BD attending an outpatient mood disorders clinic provided retrospective ratings of 37 symptoms of child psychopathology. Stability and comorbidity of diagnoses were evaluated, and severity of symptoms for each subject was assessed by identifying the earliest occurrence of the reported symptoms causing impairment.Results: Severe mood instability, temper tantrums, anxiety symptoms, sleep disturbances and aggression were among the most common signs of psychopathology reported in children diagnosed with BD before puberty. Symptoms were already apparent in the first three years in 28%, and formal diagnoses were made before the age of 8 y in the majority of cases.Conclusions: Retrospective parental reports of early symptoms of psychopathology in pre-pubertal children with BD revealed a very early occurrence of affective precursors (irritability and mood dysregulation) and clinical risk factors like impulsive aggression and anxiety that can precede the syndromal onset of mania by several years. These findings support previous reports suggesting a progression of symptoms from abnormal, non-specific presentations to sub-threshold and finally syndromal BD. The importance of early identification and intervention is discussed.

A predictive model for obstructive sleep apnea and Down syndrome.

Obstructive sleep apnea (OSA) occurs frequently in people with Down syndrome (DS) with reported prevalences ranging between 55% and 97%, compared to 1-4% in the neurotypical pediatric population. Sleep studies are often uncomfortable, costly, and poorly tolerated by individuals with DS. The objective of this study was to construct a tool to identify individuals with DS unlikely to have moderate or severe sleep OSA and in whom sleep studies might offer little benefit. An observational, prospective cohort study was performed in an outpatient clinic and overnight sleep study center with 130 DS patients, ages 3-24 years. Exclusion criteria included previous adenoid and/or tonsil removal, a sleep study within the past 6 months, or being treated for apnea with continuous positive airway pressure. This study involved a physical examination/medical history, lateral cephalogram, 3D photograph, validated sleep questionnaires, an overnight polysomnogram, and urine samples. The main outcome measure was the apnea-hypopnea index. Using a Logic Learning Machine, the best model had a cross-validated negative predictive value of 73% for mild obstructive sleep apnea and 90% for moderate or severe obstructive sleep apnea; positive predictive values were 55% and 25%, respectively. The model included variables from survey questions, medication history, anthropometric measurements, vital signs, patient's age, and physical examination findings. With simple procedures that can be collected at minimal cost, the proposed model could predict which patients with DS were unlikely to have moderate to severe obstructive sleep apnea and thus may not need a diagnostic sleep study.

Effects of Sleep Loss on Subjective Complaints and Objective Neurocognitive Performance as Measured by the Immediate Post-Concussion Assessment and Cognitive Testing.

This study examined the effects of total and partial sleep deprivation on subjective symptoms and objective neurocognitive performance, as measured by the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) in a sample of healthy adults. One-hundred and two, right-handed, healthy participants (between ages 18 and 30 years old) completed three consecutive nights in the sleep laboratory with concurrent continuous polysomnography monitoring. Night 1 served as a baseline night. Prior to Night 2, they were randomly assigned to one of three sleep conditions: undisrupted normal sleep (N = 34), sleep restriction (50% of habitual sleep, N = 37), or total sleep deprivation (N = 31). Participants slept undisturbed on Night 3. ImPACT was administered on three separate occasions. Sleep loss was associated with increased severity of subjectively reported affective, cognitive, physical, and sleep symptoms. Although objective neurocognitive task scores derived from the ImPACT battery did not corroborate subjective complaints, sleep loss was associated with significant differences on tasks of visual memory, reaction time, and visual motor speed over time. While self-report measures suggested marked impairments following sleep loss, deficits in neurocognitive performance were observed only on three domains measured with ImPACT. ImPACT may capture subtle changes in neurocognitive performance following sleep loss; however, independent and larger validation studies are needed to determine its sensitivity to acute sleep loss and recovery sleep. Neurocognitive screening batteries may be useful for detecting the effects of more severe or chronic sleep loss under high-stress conditions that mimic high-risk occupations.

Highlights in this issue

An apparent life-threatening event (ALTE) is when a baby demonstrates one or more of the following for less than a minute: bluish skin, poor breathing, weakness or poor responsiveness. Monti et al 1 used a regional database to study the occurrence of ALTEs in Northern Italy from 2002 to 2006. The incidence was 4.1 cases per 1000 live births, and the presence of gastroesophageal reflux and a family history of sudden death were found to be significant risk factors. If an ALTE is unexplained after a thorough investigation, the recommended term is now a brief resolved unexpected event (BRUE), and if it occurs immediate after birth, the term sudden unexpected postnatal collapse (SUPC) is used. See the accompanying editorial by Herlenius 2. This issue contains two papers on food allergies. Strinnholm et al 3 investigated adolescents’ experiences after a double-blind placebo-controlled food challenge. Reintroduction failure was common and was associated with fear of reactions, not appreciating the taste of the food and living a normal life without the challenged food. In the second study, Kukkonen et al 4 looked at peanut oral immunotherapy in a double-blind, placebo-controlled trial of children aged 6–18 years. They found that it was effective for severe allergies and did not have any negative effects on airway inflammation. All women with preterm labours between 24 and 34 weeks of gestation should receive antenatal corticosteroid prophylaxis to improve the lung maturation of their offspring. However, Gagliardi et al 5 found that 15% of women delivering very preterm infants in a highly organised network of hospitals in Tuscany, Italy, did not receive antenatal corticosteroids. Late hospital admission and migrant status were the main factors associated with missed prophylaxis. Cuttini 6 comments on the findings. Acute rhinosinusitis is common in young children, and in certain cases, it may lead to serious bacterial infections with orbital and intracranial complications. Schollin Ask et al 7 studied the incidence of acute rhinosinusitis in tertiary care in Stockholm County, Sweden, between 2003 and 2007 and surveyed the clinical outcomes. They found that most children hospitalised for acute rhinosinusitis had an orbital complication and that this was more common in children under the age of two years and in boys. Severe postseptal complications were rare. This Swedish study describes how parents of 86 infants perceived their own sleep while their infant was in a neonatal intensive care unit and after discharge. Mothers were more likely to report severe insomnia than fathers during their infants’ hospitalisation, and the higher insomnia severity scores were associated with more severe infant sleep problems after discharge. Thernström Blomqvist et al 8 concluded that parents need support to optimise their sleep, as parents’ sleeping problems seem to affect their child's sleeping pattern.

Adipsic diabetes insipidus in adult patients.

Adipsic diabetes insipidus (ADI) is a very rare disorder, characterized by hypotonic polyuria due to arginine vasopressin (AVP) deficiency and failure to generate the sensation of thirst in response to hypernatraemia. As the sensation of thirst is the key homeostatic mechanism that prevents hypernatraemic dehydration in patients with untreated diabetes insipidus (DI), adipsia leads to failure to respond to aquaresis with appropriate fluid intake. This predisposes to the development of significant hypernatraemia, which is the typical biochemical manifestation of adipsic DI. A literature search was performed to review the background, etiology, management and associated complications of this rare condition. ADI has been reported to occur in association with clipping of an anterior communicating artery aneurysm following subarachnoid haemorrhage, major hypothalamic surgery, traumatic brain injury and toluene exposure among other conditions. Management is very difficult and patients are prone to marked changes in plasma sodium concentration, in particular to the development of severe hypernatraemia. Associated hypothalamic disorders, such as severe obesity, sleep apnoea and thermoregulatory disorders are often observed in patients with ADI. The management of ADI is challenging and is associated with significant morbidity and mortality. Prognosis is variable; hypothalamic complications lead to early death in some patients, but recent reports highlight the possibility of recovery of thirst.

Pacemaker-detected severe sleep apnea predicts new-onset atrial fibrillation.

Sleep apnea (SA) diagnosed on overnight polysomnography is a risk factor for atrial fibrillation (AF). Advanced pacemakers are now able to monitor intrathoracic impedance for automatic detection of SA events. We enrolled 160 consecutive recipients of a dual-chamber pacemaker endowed with the ApneaScan algorithm (Boston Scientific). If the pacemaker-measured Respiratory Disturbance Index was ≥30 episodes per hour for at least one night during the first week after implantation, SA was defined as severe. Patients were considered to have experienced AF episodes if the device detected a cumulative AF burden ≥6 h in a day. Sixteen patients in AF at the time of implantation were excluded from our analysis. During follow-up, AF burden ≥6 h/day was documented in 35 (24%) of the patients included in the analysis and in 12 (13%) of the 96 patients with no history of AF. Severe SA was detected in 89 patients during the first week after implantation; 58 of these had no history of AF. Severe SA at the baseline was associated with a higher risk of AF both in the whole population (log-rank test, hazard ratio: 2.38; 95% CI: 1.21-4.66; P = 0.025) and among patients with no previous history of AF (log-rank test, hazard ratio: 2.80; 95% CI: 1.10-7.10; P = 0.047). Moreover, severe SA at the time of follow-up device interrogation predicted AF occurrence within the next 3 months (log-rank test, hazard ration: 2.13; 95% CI: 1.11-4.08; P = 0.036). In pacemaker patients, device-diagnosed severe SA was independently associated with a higher risk of AF (≥6 h/day) and new-onset AF. In particular, severe SA on follow-up data review identified patients who were ∼2-fold more likely to experience an AF episode in the next 3months.

Obesity Hypoventilation Syndrome and Pulmonary Hypertension Case with Excessive Daytime Sleepiness

Obesity and pulmonary hypertension (PH) are two conditions that frequently coexist in clinical practice and also the association between obesity and hypersomnolence has long been recognized. Pulmonary hypertension is more common (50% vs. 15%) and more severe in patients with OHS than in patients with OSAS. Here, we present an obese man with very severe excessive daytime sleep and very serious pulmonary hypertension, who only gave respond to AVAPS and oxygen treatment.

Treatment of a severe sleep apnea case with Down syndrome and high obesity

Treatment of a severe sleep apnea case with Down syndrome and high obesity

Obstructive Sleep Apnoea in Patients Having Atrial Fibrillation Ablation: Prevalence, Severity and Association with Arrhythmia Phenotype

Background: Despite evidence that obstructive sleep apnoea treatment (OSA) is critical for optimal atrial fibrillation (AF) ablation outcomes, OSA prevalence, severity and correlation with AF phenotype, remain poorly characterised. We sought to 1)characterise the prevalence and severity of OSA in an AF ablation population and 2)describe the association of OSA severity with the AF phenotype. Methods: Consecutive AF ablation patients were evaluated for OSA utilising formal overnight polysomnography. Respiratory events were evaluated and classified based on American Academy of Sleep Medicine criteria. OSA severity was determined using the apnoea-hypopnoea index (AHI) (0-5 nil, 5-15 mild, 15-30 moderate and >30 severe). Univariable and multivariable predictors of persistent AF were determined to explore the relationship between OSA severity and AF phenotype. Results: One hundred and thirty-eight consecutive patients (female 28, age 60 ± 9yr) having ablation were assessed (paroxysmal 77, persistent 61). OSA was diagnosed in 85.5% (29% mild, 29% moderate, 27.5% severe) with median AHI 15.3(IQR 7.7-30.7). Persistent AF was associated with more severe sleep apnoea compared with paroxysmal AF (AHI 22.2(IQR 11.9-40.3) vs 11.8(IQR 5.9-22.7),p < 0.001). Persistent AF was strongly associated with OSA severity (17% increase risk persistent AF/5-unit increase AHI (95%CI 8-30),p = 0.002). This association persisted even after adjusting for age, gender and body mass index (14.5%(95%CI 5-29),p = 0.01). Conclusions: The prevalence of OSA in a symptomatic AF ablation cohort is high. Increased OSA severity is independently associated with prevalent persistent AF. This data highlights that OSA screening is critical among patients considered for AF ablation, to treat under-recognised OSA and improve ablation outcomes.

Are job strain and sleep disturbances prognostic factors for low-back pain? A cohort study of a general population of working age in Sweden

The aim of this study was to determine whether job strain, i.e. a combination of job demands and decision latitude (job control), and sleep disturbances among persons with occasional low-back pain are prognostic factors for developing troublesome low-back pain; and to determine whether sleep disturbances modify the potential association between job strain and troublesome low-back pain. A population-based cohort from the Stockholm Public Health Cohort surveys in 2006 and 2010 (= 25,167) included individuals with occasional low-back pain at baseline 2006 (= 6,413). Through logistic regression analyses, potential prognostic effects of job strain and sleep disturbances were studied. Stratified analyses were performed to assess modification of sleep disturbances on the potential association between job strain and troublesome low-back pain. Those exposed to job strain; active job (odds ratio (OR) 1.3, 95% confidence interval (95% CI) 1.1-1.6), or high strain (OR 1.5, 95% CI 0.9-2.4) and those exposed to severe sleep disturbances (OR 3.0, 95% CI 2.3-4.0), but not those exposed to passive jobs (OR 1.1, 95% CI 0.9-1.4) had higher odds of developing troublesome low-back pain. Sleep disturbances did not modify the association between job strain and troublesome low-back pain. These findings indicate that active job, high job strain and sleep disturbances are prognostic factors for troublesome low-back pain. The odds of developing troublesome low-back pain due to job strain were not modified by sleep disturbance.

Therapeutic Efficacy of Mandibular Advancement Devices in Patients with Severe Sleep Apnea: A Preliminary Report.

Obstructive sleep apnea (OSA) is defined as episodes of upper airway obstructions during sleep. The method of choice in conservative treatment of OSA is the use of devices that produce positive airway pressure (CPAP). In patients with mild-moderate form of OSA, intraoral mandibular advancement devices (MAD) are applied. The aim of the study was to evaluate the therapeutic efficacy of MAD in patients with severe OSA who were unable to use CPAP. In this preliminary study three patients from a group of 25 severe OSA sufferers who failed to use CPAP, were included. The three patients underwent a triple polysomnographic (PSG) investigation: on CPAP, before MAD treatment, and during MAD. The patients completed the Epworth Sleepiness Scale questionnaire twice. We found significant improvements of subjective symptoms and PSG-evaluated variables after application of MAD in all three patients in comparison with both baseline and CPAP-recorded data. We conclude that MAD can be an alternative treatment option for severe OSA patients who are non-compliant with CPAP therapy.

A CHALLENGING NEUROLOGICAL COMPLICATION IN A YOUNG HIV-INFECTED WOMAN

Background: The management of HIV infected patients with immune reconstitution inflammatory syndrome (IRIS) represents a challenge, especially in those with cerebral opportunistic infections. Case description: We present a 26 year-old woman, diagnosed with HIV infection and admitted in our hospital with severe anemia, depression and anxiety. Lab screens showed severe anemia and immunosuppression (CD4 cell count 63 cells/mm3 ) and high plasma HIV-RNA (6.25 log10 copies/mL). After one month treatment with lamivudine 3TC, tenofovir (TDF) and raltegravir RAL and important immune recovery (CD4 192 cells/mm3 ) and significant decay in HIV viral load to 1.5 log10 copies/mL were noticed. The initial clinical evolution was unfavorable with the appearance of generalized seizures, movement disturbances, auditory hallucinations and right hemiparesis. CSF exam was normal with negative bacterial and fungal cultures but with detectable HIV-RNA – 82 copies/mL (1.90 log10 copies/mL). Brain MRI showed hyperintense lesions on T2 and FLAIR sequences and hypointense on T1 sequences, localized in fronto-temporal areas, right cerebellum and pons. In evolution, there was a continuing worsening of psychiatric and neurological symptoms with severe tremor, axial hypotonia, generalized weakness and severe sleep disturbances. Atypical brain MRI lesions in the presence of severe psychiatric symptoms raised difficulties in establishing the cause of the neurological complication. The important progression of the lesion in the white matter, the appearance of contrast enhancement and the presence of JC – DNA in CSF suggested the diagnosis of PML IRIS. The patient was treated with high doses of cortisone, antipsychotic drugs and continued cART, with a slow clinical recovery and brain MRI improvement starting with 4 months of treatment. Conclusion: The diagnosis of the neurological complication was difficult due to the atypical onset, the presence of concomitant psychiatric symptoms and the atypical initial brain imaging.