The exact incidence of neurological complications from coronavirus disease 2019 (COVID-19) infection remains unknown. Neurological symptoms are more common with severe form of the disease. Through neuro-invasion, the virus can affect both neurons and glial cells and induce wide range of neurological pathologies.

To systematically assess the neurological manifestations in patients diagnosed with COVID-19.

A systematic literature search of the PubMed, Scopus, and Cochrane databases was performed. Randomized controlled trials, nonrandomized controlled trials, observational studies of neurological manifestations in patients diagnosed with COVID-19.

All three-database search identified 89 publications. A total of 22 full-text articles assessed for eligibility with 12 articles excluded. Altogether, the included studies reported 290 patients with neurological manifestations. Neurological manifestations were subdivided into central causes (CNS) and peripheral causes (PNS). CNS symptoms is commoner representing 91% of all neurological patients with 9% only with PNS. Headache represented the commonest neurological symptoms in regard to number of patients, meanwhile dizziness has the highest incidence with 11.9%. Neurological manifestations were divided according to COVID-19 severity into: (1) nonsevere and (2) severe; with all CNS manifestations were more in severe patients except headache were more in nonsevere patients. All included studies were on adult patients except one study in pediatric patients with limited number of participants.

From the descriptive analyses and available data of relatively small sample-sized studies, it can be concluded that in spite of the aforementioned limitations, that a wide spectrum of neurological manifestations including CNS and PNS can occur in COVID-19 patients.

Blood platelets, due to shared biochemical and functional properties with presynaptic serotonergic neurons, constituted, over the years, an attractive peripheral biomarker of neuronal activity. Therefore, the literature strongly focused on the investigation of eventual structural and functional platelet abnormalities in neuropsychiatric disorders, particularly in depressive disorder. Given their impact in biological psychiatry, the goal of the present paper was to review and critically analyze studies exploring platelet activity, functionality, and morpho-structure in subjects with depressive disorder.

According to the PRISMA guidelines, we performed a systematic review through the PubMed database up to March 2020 with the search terms: (1) platelets in depression [Title/Abstract]”; (2) “(platelets[Title]) AND depressive disorder[Title/Abstract]”; (3) “(Platelet[Title]) AND major depressive disorder[Title]”; (4) (platelets[Title]) AND depressed[Title]”; (5) (platelets[Title]) AND depressive episode[Title]”; (6) (platelets[Title]) AND major depression[Title]”; (7) platelet activation in depression[All fields]”; and (8) platelet reactivity in depression[All fields].”

After a detailed screening analysis and the application of specific selection criteria, we included in our review a total of 106 for qualitative synthesis. The studies were classified into various subparagraphs according to platelet characteristics analyzed: serotonergic system (5-HT2A receptors, SERT activity, and 5-HT content), adrenergic system, MAO activity, biomarkers of activation, responsivity, morphological changes, and other molecular pathways.

Despite the large amount of the literature examined, nonunivocal and, occasionally, conflicting results emerged. However, the findings on structural and metabolic alterations, modifications in the expression of specific proteins, changes in the aggregability, or in the responsivity to different pro-activating stimuli, may be suggestive of potential platelet dysfunctions in depressed subjects, which would result in a kind of hyperreactive state. This condition could potentially lead to an increased cardiovascular risk. In line with this hypothesis, we speculated that antidepressant treatments would seem to reduce this hyperreactivity while representing a potential tool for reducing cardiovascular risk in depressed patients and, maybe, in other neuropsychiatric conditions. However, the problem of the specificity of platelet biomarkers is still at issue and would deserve to be deepened in future studies.

Obsessive-compulsive disorder (OCD) is a prevalent and disabling condition with frequent chronic course. Staging models applied to psychiatric disorders seek to define their extent of progression at a particular time-point and differentiate early, milder clinical phenomena from those characterizing illness progression and chronicity. In OCD patients, a staging model has been recently proposed but not tested yet. This was the aim of the present study.

From an overall sample of 198 OCD patients, recruited across two psychiatric clinics in Northern Italy, 70 patients on stable treatment completed a follow-up assessment ranging from 12 to 24 months. At follow-up initiation, patients had been divided into four staging groups, according to the model proposed by Fontenelle and Yucel. At the end of the follow-up, patients were subdivided into three groups (no stage change, improved stage, or worsened stage) compared with statistical analyses.

At the end of the follow-up, 67.1% patients showed no stage changes, 24.3% a stage improvement, and 8.6% a stage progression. Worsened patients showed higher rates of comorbid disorders and higher rates of unfavorable employment characteristics compared to the other subgroups (P < .05). Patients with worsened stage showed higher prevalence of somatic obsessions (P < .05), while patients with improved stage showed higher rates of magical thinking and violence/harm obsessions compared to other groups (P < .05).

The present results provide epidemiologic and clinical correlates of the first application of a staging model in a sample of OCD patients, encouraging further studies to assess the utility of this approach in the field.

Schizophrenia-related, health, social, and fiscal consequences are substantial, affecting patients, caregivers, and society. The incidence of health, social, and fiscal outcomes are frequently reported for the overall schizophrenia population, not stratified by remission or relapse status.

This study aimed to assess healthcare resource use, employment status, and housing circumstances for patients with schizophrenia in remission or relapse, compared to the overall schizophrenia population.

The Adelphi Schizophrenia Disease Specific Programme was a point-in-time survey conducted across the USA between July and October 2019. Remission was defined using Clinical Global Impression-Severity (CGI-S) score of 1-3 (stable), with relapse defined as a CGI-S score of 4-7 (unstable). Outcome-specific rate ratios were calculated by dividing the cumulative incidence for those in remission or relapse by the cumulative incidence of the overall schizophrenia population. Ratios greater than 1 indicate a higher probability of the event.

Psychiatrists (n = 124) provided data for 409 patients in remission and 609 patients in relapse. Patients with schizophrenia in remission were more likely to be employed (1.66, 95% confidence interval [1.46-1.90]) and to live with a partner or family (1.08 [1.01-1.17]) compared to the overall schizophrenia population, whereas patients in relapse were more likely to experience hospitalizations in the previous 12 months (1.34 [1.19-1.15]), disability-related unemployment (1.38 [1.25-1.51]), sick leave absences (1.23 [0.66-2.31]), need to support housing (1.39 [1.08-1.79]), and homelessness (1.47 [0.95-2.27]).

Schizophrenia patients in relapse were more likely to experience hospitalizations, unemployment, and have unfavorable housing circumstances compared to the overall schizophrenia population. Identifying patients at risk of relapse may aid physicians in targeting interventional support, thereby reducing the burden of schizophrenia.

Sunovion Pharmaceuticals

To investigate the association between cognitive impairment and hospitalizations, quality of life and satisfaction with life among patients with schizophrenia.

A point-in-time survey was conducted between July and October 2019 via the Adelphi Schizophrenia Disease Specific Programme across the United States of America. Patients were stratified as mild or severe based on the level of cognitive impairment reported by their psychiatrist (normal, mild = mild; moderate, severe, very severe = severe). Multiple regression analysis was used to model the association between cognitive impairment and outcomes, adjusting for baseline characteristics.

Data were provided by 124 psychiatrists for 651 mildly and 484 severely impaired patients with schizophrenia; PSCs were completed by 349 mildly and 206 severely impaired patients. Severe cognitive impairment was associated with increased odds of hospitalization due to schizophrenia relapse since diagnosis (2.10 odds ratio [OR], P = .004) and within 12 months (1.95 OR, P < .001) compared to mild impairment. Moreover, patients with severe cognitive impairment had poorer quality of life according to the EuroQoL 5-dimension (EQ-5D) Health Index (−0.085 coefficient, P < .001) and EQ-5D Visual Analogue Scale (−6.24 coefficient, P = .041) compared to patients with mild cognitive impairment. Severe cognitive impairment was also associated with lower overall life satisfaction according to the Quality-of-Life Enjoyment and Satisfaction Questionnaire (−8.13 coefficient, P = .006) compared to mild cognitive impairment.

Schizophrenia patients with severe cognitive impairment had more hospitalizations due to relapse than patients with mild cognitive impairment. Additionally, patients with severe cognitive impairment had significantly lower quality of life and overall satisfaction with life compared to patients with mild cognitive impairment.

Sunovion Pharmaceuticals

Schizophrenia is associated with health, social, and financial burdens for patients, caregivers, and society. Major systemic changes, reforms, and technological advances have happened in the USA since the prior estimate of the societal cost of schizophrenia, $155.7B in 2013. This study analyzes the most recent data and literature to update this estimate.

Direct and indirect costs associated with schizophrenia in the US in 2019 were estimated using a prevalence-based approach (ICD-10 codes: F20, F25). Direct healthcare costs were assessed retrospectively using a matched cohort design in the IBM Watson Health MarketScan Commercial, Medicare, and Medicaid databases from October 1, 2015, through December 31, 2019. Patients were matched to controls on demographics, insurance type, and index year. Direct nonhealthcare costs were estimated using published literature and government data. Indirect costs were estimated using a human capital approach and the value of quality-adjusted life years lost. Cost offsets were applied to account for basic living costs avoided. Excess costs, comparing costs for individuals with and without schizophrenia, were reported in 2019 USD.

The estimated excess economic burden of schizophrenia in the US in 2019 was $330.6B, including $62.3B in direct healthcare costs (19%), $19.7B in direct nonhealthcare costs (5%), and $251.9B in excess indirect costs (76%). The largest drivers of indirect costs were caregiving ($112.3B), premature mortality ($77.9B), and unemployment ($54.2B).

The estimated societal burden of schizophrenia in the USA in 2019 was $330.6B, which represented a 93.5% increase from 2013 to 2019, after accounting for inflation. This study underscores the increasing and apparent burden of schizophrenia not only on the patient, but also on caregivers and society.

Sunovion Pharmaceuticals

Extrapyramidal symptoms (EPS) affect 15% to 30% of patients with schizophrenia treated with antipsychotics and have been associated with poor patient outcomes.

To examine the incidence and economic burden of EPS in patients with schizophrenia initiating treatment with atypical antipsychotics (AAPs).

Patients with schizophrenia newly initiating AAPs with no prior EPS were identified in the MarketScan Commercial and Medicare Supplemental database from January 1, 2012 to December 31, 2018. Incidence of EPS (new diagnosis or medication) was assessed in the year following AAP initiation. Patients were classified as developing (EPS cohort) or not developing (non-EPS cohort) EPS. All-cause and schizophrenia-related healthcare resource use and costs were compared between cohorts over the year following the first EPS claim (EPS) or randomly assigned index date (non-EPS). Multivariate models were developed for total healthcare costs and inpatient admissions.

A total of 3558 patients qualified for the study; 22.1% developed EPS in the year following AAP initiation (incidence: 26.9 cases/100-person-years). Multivariate analyses demonstrated that EPS patients had a 34% higher odds of all-cause (OR:1.3361, 95% CI:1.0770-1.6575, P < .01) and 84% increased odds of schizophrenia-related (OR:1.8436, 95% CI:1.0434-2.4219, P < .0001) inpatient admissions, as well as significantly higher all-cause (EPS: $26,632 vs non-EPS: $21,273, P < .001) and schizophrenia-related (EPS: $9018 vs non-EPS: $4475, P < .0001) total costs compared to the non-EPS cohort.

Approximately 20% of patients developed EPS in the year following AAP initiation. The significant increases in healthcare resource utilization and costs in the EPS cohorts highlight the need for treatments that effectively target schizophrenia symptoms while reducing the risk of EPS.

Sunovion Pharmaceuticals

Cotard’s syndrome is a nihilistic delusion where the individual believes they are dead, partly dead, or replaced by an animal. The delusion that their body has been replaced by a purely inanimate azooic (but physical entity), such as a robot or a droid, has not hitherto been described.

Case study: This 60-year-old, right-handed, female, with a past history of schizophrenia presented with complaints of depression, irritability, and anger. When confronted with commitment papers signed by her father, she denied their truthfulness, insisting that he had been replaced by an imposter. This belief persisted unabated, despite treatment with 20 mg of haloperidol per day. Over time, she expressed the belief that she had been replaced by another person, whom she refused to identify. The following day she refused all food and water proclaiming that she had died and been replaced by a machine revealing, “I am not her. I am a robot.” Soon thereafter she developed tremulousness, stiffness, and rigidity. After haloperidol was decreased and benztropine started, these parkinsonism symptoms subsided, but her delusions persisted.

Abnormalities in physical examination: General: decreased blink frequency. Neurologic examination: Mental status examination: bradyphrenia, hypoverbal, blunted affect. Oriented ×2. Motor examination: bradykinetic, cogwheel rigidity in both upper extremities. Gait examination: slow shuffling gait, reduced bilateral arm swing. Cerebellar examination: resting tremor in both upper extremities at 3 cycles per second. Other: EEG: focal sharp transients in the left temporal region. MRI with and without contrast: normal. Toxicological, metabolic, endocrine screening: normal.

This illustrated sequential presentations of three delusions of misidentification. Upon presentation, she exhibited Capgras syndrome, the delusional belief that a familiar person has been replaced by a double. The nidus for this may have been the discovery that her father had signed her commitment papers. This was followed by the belief she was a double of herself, which is the syndrome of Reverse Subjective Doubles. Finally, she manifested Cotard’s syndrome in a previously undescribed manner, believing she had died and become a robot. Cotard’s and Capgras syndromes are known to present sequentially rather than concurrently, whereas the patient presented concurrently with all three syndromes. Drug-induced parkinsonism may have made the patient subjectively feel stiff, which she interpreted as being rigid like a robot. She was bradykinetic, did not eat or drink, and had rigidity, suggesting that these were somatic manifestations of her underlying delusion of being a robot or alternatively, may have been the somatic nidus for the delusion. Those who present with Cotard’s syndrome warrant evaluation for underlying medical conditions, serving as a substrate for this delusion.

No funding

Many patients suffer from comorbid HIV and Schizophrenia diagnoses. Patients with schizophrenia and other psychosis are at increased risk of contracting HIV due to numerous psychosocial factors including increased frequency of drug use, increased rates of victimization, and increased propensity for high-risk sexual behaviors. In addition to deficits in functioning related to psychiatric illness, patients with HIV also suffer from virus-related neurocognitive insults. It is quite possible that inflammation associated with an untreated HIV infection could compound the pre-existing neurocognitive decline seen in patients with schizophrenia and other psychosis, creating poor outcomes and treatment-resistant pathology. The benefit of clozapine treatment for schizophrenia patients with comorbid HIV extends beyond just symptomatic control. Long-term and consistent treatment of schizophrenia can be a stepping-stone for the improvement of many psychosocial aspects of life. Patients with well-controlled schizophrenia can lead relatively unaffected lives with improved insight and self-care. Improved insight allows patients to better understand their illness, treatment regimen, and follow-up needs. Improved self-care contributes to increased adherence to treatment regimens and overall health. It is likely that patients who are consistently treated for their schizophrenia will have an increased capacity to understand their HIV diagnosis. With gained understanding, these patients may be more likely to adhere to HAART therapy for HIV and to attend follow-up appointments with infectious disease or primary care. Furthermore, with adherence to HAART therapy, patients can enjoy an improved quality and duration of life by raising CD4 counts and preventing progression to AIDS or succumbing to AIDS-related opportunistic infections.

A patient with schizophrenia and HIV diagnosis was monitored and interviewed with repeated MOCA scoring over a lengthy hospitalization period. During this time, he was titrated to an effective dose of clozapine totaling 400 mg at bedtime. His MOCA scores were compared over this period.

In this case, we have observed that starting a patient on clozapine with therapeutic levels for adequate period has improved MOCA scores. Low MOCA scores could be due to untreated HIV, untreated underlying psychosis. Improved MOCA scores have led the patient to gain insight into his HIV diagnosis. For the first time, he felt the need to be on antiretroviral medication and understood the chronic nature of his illness.

In conclusion, this case describes a patient with untreated HIV and comorbid schizophrenia who is started on clozapine to gain insight into his medical conditions and become more adherent with HIV HAART. The patient shows improvement in PANSS and MOCA scores, supporting an increased awareness of his illness and an increased ability to remain on treatment.

No funding

Elimination of olfactory sensory perception with a reduction in odor-induced migraine has not heretofore been reported.

Case study: A 64-year-old right-handed woman presented with a history of common migraines since childhood. The headaches were bilateral, throbbing, pulsatile, and without aura and were associated with lightheadedness, photophobia, sonophobia, nausea, and vomiting. They would be precipitated by ambient aromas, such as perfumes and bath products, and she became agoraphobic, fearful of going out of her domicile and being exposed to odors. She avoided stores, perfume counters, and public places; scared that it would initiate a disabling headache. Twenty-five years prior to presentation, the patient fell on ice, striking her head and causing a transient loss of consciousness and persistent absence of smell and taste. From that point forwards, while she would have an occasional headache independent of an odor, she no longer experienced odor-induced headaches. Her agoraphobia had resolved. Since the head trauma, her smell remained at 10% to 20%. Her taste remained at 30% of normal.

Abnormalities on neurological examination: Motor examination: Drift testing: Right pronator drift with right abductor digiti minimi sign. Cerebellar examination: Bilateral finger-to-nose dysmetria. Rapid alternating movements: decreased in the left upper extremity. Reflexes: Bilateral upper extremity 3+. Absent bilateral ankle jerks. Bilateral palmomental and Hoffmann reflexes present. Chemosensory testing: Olfaction: Brief Smell Identification Test (B-SIT): 7 (hyposmia), Alcohol Sniff Test: 0 (anosmia). Retronasal Olfaction: Retronasal Smell Index: 4 (hyposmia). Gustation: Propylthiouracil Disc Taste Test: 10 (normogeusia). While performing the B-SIT and sniffing the aroma of rose, the patient noted the sudden onset of a headache, even though she could not detect any odor present.

The temporal relationship between loss of sense of smell and elimination of odor-induced migraines suggests a causal relationship. Conscious recognition of odor may induce a stimulus-response paradigm, whereby migraine occurs. Head trauma-induced anosmia, by elimination of conscious perception of the odor, may thus be the modality whereby her headaches resolved. Alternatively, odors may induce an autonomic response, and conscious recognition of such autonomic response may induce a headache. To tergiversate, that the rose aroma in the B-SIT induced a headache, without any conscious detection of the odor, implies that either unconscious perception is enough to precipitate a headache or that these odors act not as odorants, but rather as an exogenous ambient chemical inducing headaches. Possibly the production of temporary anosmia by use of nose clips may be utilized as a prophylactic device for those with odor-induced migraines. Further investigation into this is warranted.

No funding

The COVID-19 pandemic substantially impacted care of patients with schizophrenia treated with long-acting injectable antipsychotics (LAIs). This study examined how clinics adapted operations to maintain a standard of care for these patients after pandemic onset.

Online surveys were completed in October-November 2020 by one principal investigator (PI) or PI-appointed designee at 35 clinics participating in OASIS (NCT03919994). Items concerned pandemic impacts on clinic operations, particularly telepsychiatry, and on the care of patients with schizophrenia treated with LAIs.

All 35 clinics reported using telepsychiatry; 20 (57%) implemented telepsychiatry after pandemic onset. Telepsychiatry visits increased from 12%-15% to 45%-69% across outpatient visit types after pandemic onset; frequency of no-show and/or canceled telepsychiatry visits decreased by approximately one-third. Nearly half of clinics increased the frequency of telepsychiatry visits for patients with schizophrenia treated with LAIs. Approximately one-third of participants each reported switching patients treated with LAIs to longer injection interval LAIs or to oral antipsychotics. The most common system/clinic- and patient-related barrier for telepsychiatry visits was lower reimbursement rate and access to technology/reliable internet, respectively. Almost all participants (94%) were satisfied with telepsychiatry for maintaining care of patients with schizophrenia treated with LAIs; most predicted a hybrid of telepsychiatry and office visits post-pandemic.

Changes made by clinics after pandemic onset were viewed by almost all participants as satisfactory for maintaining a standard of care for patients with schizophrenia treated with LAIs. Most participants predicted continuing telepsychiatry to support patient care post-pandemic; equitable access to telepsychiatry will be important in this regard.

Alkermes, Inc.

Amphetamines are a first-line treatment for ADHD. The dextroamphetamine transdermal system (d-ATS) was developed as an alternative to oral amphetamine formulations. A randomized controlled trial of d-ATS in children and adolescents with ADHD was conducted, and its primary and key secondary endpoints were met. Here, we report secondary endpoints of the study, further assessing the efficacy and safety of d-ATS.

This study comprised a 5-week, open-label dose optimization period (DOP) followed by a 2-week, randomized, cross-over double-blind treatment period (DBP). All eligible patients received d-ATS 5 mg/9 h and were evaluated weekly for a possible dose increase to 10 mg/9 h, 15 mg/9 h, and 20 mg/9 h. Once reached, the optimal dose was maintained for the DOP and utilized during the DBP. Secondary objectives for this study included assessment of efficacy via Permanent Product Measure of Performance-Attempted and -Correct (PERMP-A, PERMP-C), ADHD-RS-IV, Conners Parent Rating Scale Revised Short Form (CPRS-R:S), and Clinical Global Impression (CGI) scores in a laboratory classroom setting. Efficacy was analyzed using a mixed-model repeated-measures (MMRM) approach. Safety assessments included treatment-emergent adverse events (TEAEs) and dermal safety.

In total, 110 patients were enrolled in the DOP, and 106 patients were randomized in the DBP. Patients receiving d-ATS demonstrated significant improvement vs placebo in PERMP-A and -C scores in the DBP consistently from 2 to 12 hours post-dose (P < .001 for all timepoints). ADHD-RS-IV total scores improved during the DOP and improved further during the DBP, with a least-squares mean (95% CI) difference for d-ATS vs placebo of −13.1 (−16.2, −10.0; P < .001). Significant differences between placebo and d-ATS in the DBP were also observed for the CPRS-R:S and CGI scales (P < .001). Most TEAEs were mild or moderate, with 3 TEAEs (abdominal pain, irritated mood, and appetite loss) leading to study discontinuation in the DOP and none in the DBP. No patients were discontinued due to dermal reactions in either phase.

d-ATS was effective in the treatment of ADHD in children and adolescents, meeting its primary endpoint (reported elsewhere) and all secondary endpoints. d-ATS was safe and well-tolerated, with minimal dermal reactions.

Noven Pharmaceuticals, Inc.

Olfactory reference syndrome (ORS) is a delusion in which a person believes that he or she exudes a displeasing body aroma that others perceive negatively. The axilla has been reported as a single primary source in only one patient. Furthermore, ORS is rarely reported to be associated with food odor. In these instances, the food is not edible. Delusions of ORS presenting as alliaceous edible food aromas have not heretofore been described.

One week after undergoing catheter ablation for atrial fibrillation, this 42-year-old right-handed male experienced a sudden onset of loss of smell and taste. This has persisted on presentation and he described a complete lack of smell, only being able to smell different spices and herbs. Over time, his sense of smell selectively improved such that he was able to smell alliaceous substances, including onion and garlic, as well as a few other aromas. At the same time his smell returned, he noted that his own body exuded a smell of garlic. This occurred especially while weightlifting at the gym. He noticed that the shirts he had worn working out, in the axillary regions, were encumbered with a garlic/onion miasma. He was fearful that this mephitic aroma was being secreted through his armpits, and that others would recognize his tragomaschalia. As a result, he restricted his activities. Over a few months, his smell ability gradually worsened back to the condition he was in after the ablation. Coincident with this, his perception that he was exuding an alliaceous aroma resolved.

Motor examination: Drift testing: mild left pronator drift. Left abductor digiti minimal sign. Olfactory testing prior to the development of ORS: Alcohol Sniff Test (AST): 0 (anosmia). Brief Smell Identification Test (B-SIT): 3 (anosmia). Olfactory testing during ORS: AST: 16 (hyposmia). B-SIT: 9 (hyposmia). Olfactory testing after resolution of ORS: AST: 0 (anosmia).

This could be explained by a physiologic axillary odor or malodor, which he could not detect before or after the ORS. During the ORS, the odor may have been misperceived in a dysosmic manner due to his underlying olfactory deficit. Such dysosmia may have then been interpreted as the aroma of an alliaceous vegetable. The intensity of the aroma may have been greatest at the axillary area if compared to the other sources, but due to his underlying hyposmia, he was able to perceive only the axilla as a sole source of the aroma. Besides, psychodynamic preoccupation with bodily physique may have explained his hypersensitivity to minor flaws and his excessive preoccupation with possible harassment from others. He may have consequently misinterpreted individuals’ benign observations and attitudes to presume the presence of aroma. In individuals with olfactory deficit, this investigation for the presence of ORS with traditionally unpleasant food aromas or the presence of ORS in those with chemosensory dysfunction is warranted.

No funding

Meningitis causes inflammation of the meninges and when bacteria are not the cause may be considered aseptic. Drug-induced aseptic meningitis (DIAM) can arise from the use of certain medications. The pathophysiology of DIAM is not well understood. Within the antiepileptic medication class, only lamotrigine, carbamazepine, and levetiracetam have been associated with DIAM via documented cases. Common presentation of DIAM involves fever, headache, meningismus, and mental status changes (abnormal consciousness and focal neurological deficits). Other clinical features may include neck stiffness, photophobia, nausea, vomiting, abdominal pain, bone pain, hypotension, edema (facial and optic nerve), rash, and seizures. Case reports of DIAM with varying or limited symptomology exist. Therefore, the presentation alone will not allow for a DIAM diagnosis, prompting further analysis and diagnostic exclusion.

A middle-aged male presented with a 48-hour history of confusion, disorientation, unresponsiveness, and hypersomnolence. Past medical history included hypertension, hyperlipidemia, type-2 diabetes, and seizures. Home medication included chlorthalidone, levetiracetam, lisinopril, metformin, potassium chloride, rosuvastatin with no medication allergies reported. Upon admission, the patient denied fever, headache, nausea, neck pain, vomiting, and rash. Somnolence, dysarthria, and obtundation were noted during the physical evaluation. Hospital medications included home medications along with enoxaparin, correctional dose insulin lispro, and IV lactated ringers. Vitals and labs were unremarkable. On hospital day (HD) 1 the MRI scan was unremarkable, ruling out a demyelinating process. Serology tests (ie, ANA and dsANA) were negative. Neurology was consulted, and a lumbar puncture was performed. On HD-2 AEIM was suspected, prompting levetiracetam discontinuation and lacosamide initiation (50 mg by mouth twice daily). The CSF analysis was notable for pleocytosis (lymphocytic predominance at 96%), elevated protein (100 mg/dL), and slightly elevated glucose (79 mg/dL). The CSF VDRL was negative, ruling out neurosyphilis. Bacterial meningitis was ruled out based on the CSF analysis (WBC 144 × 103 and glucose) and the lack of bacterial growth on gram stain. Inasmuch, antibiotic therapy was not initiated. Empiric acyclovir 1000 mg IV every 8 hours was initiated as viral meningitis had not been eliminated, due to the lack of viral meningeal PCR testing. By HD-3, the CSF culture resulted without growth and the patient was alert and oriented. By HD-4 the patient was discharged, having received 6 doses of IV acyclovir, with 7 more days of oral therapy.

In 2018, McDonald et al documented the first case of probable levetiracetam-related antiepileptic induced meningitis (AEIM). The mainstay of treatment is discontinuing the offending agent. Resolution of symptoms is typically 2 to 3 days after drug discontinuation as seen in this patient case report. Symptomatic resolution within days of stopping the suspected offending drug has been observed in all reported cases of AEIM where 1 to 2 weeks is generally seen with viral meningitis. Applying the Naranjo Scale yields a score of 4, which indicates possible levetiracetam-induced meningitis in this adult patient. Providers should be cognizant when prescribing antiepileptics to assess and monitor for aseptic meningitis that may appear with atypical symptoms.

No funding