We report a case of posterior reversible encephalopathy syndrome (PRES) during treatment for alcohol withdrawal syndrome with gabapentin and clonidine. The patient developed severe hypertension, confusion and tremor, culminating in bilateral vision loss and a seizure. Imaging revealed posterior cerebral edema. Treatment with benzodiazepines, antihypertensives, and anti-seizure medications led to resolution. One year later, imaging showed resolution of the findings. We review the associated literature and propose the recognition of a PRES sub-entity, Alcohol-Related PRES (ARPRES), which can appear in the setting of alcohol withdrawal syndrome, chronic alcohol use, and acute alcohol intoxication, with or without hypertension.

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BACKGROUND: The influence of hybrid solvation models on the molecular structures and vibrational characteristics of g-aminobutyric acid (GABA) and a-aminoisobutyric acid (AIB) zwitterions was assessed by employing a variety of Density Functional Theory (DFT). The quantum chemical methods included the B3LYP and B3PW91 hybrid functionals and the 6‑311++G(d,p) basis set.
METHODS: The most stable conformation derived from the potential energy surface (PES) scans using the B3LYP/6-311++G(d,p) model chemistry for each studied molecule was predicted within a continuum environment represented by the COSMO and SMD solvation models. The stable structures were subsequently immersed in explicit/COSMO and explicit/SMD hybrid solvation models, where 10 and 8 water molecules were explicitly positioned around the functional groups of the GABA and AIB zwitterions, respectively. The number of water molecules chosen was sufficient to prevent proton transfer among the carboxylate group (COO-) and the ammonium group (NH3+) within each molecule under investigation. After optimizing the geometry of each hydrated complex, the normal vibrational modes were determined. The scaled theoretical frequencies obtained from the various model chemistries were then compared to available experimental data from infrared (IR) and Raman spectroscopy.
RESULTS: In the case of GABA and AIB molecules, the comparisons revealed that the B3LYP/6-311++G(d,p) model chemistry yielded wavenumber values that closely matched the experimental IR and Raman data, particularly when the explicit/SMD solvent was employed. The computed results indicate deviations of less than 4% when compared to the experimental data for the two molecules under investigation.

Numerous studies reported an association between GABAA R subunit genes and epilepsy, eating disorders, autism spectrum disorders, neurodevelopmental disorders, and bipolar disorders. This study was aimed to find some potential positive allosteric modulators and was performed by combining the in silico approach with further in vitro evaluation of its real activity. We started from the GABAA R-diazepam complexes and assembled a lipid embedded protein ensemble to refine it via molecular dynamics (MD) simulation. Then we focused on the interaction of α1β2γ2 with some Z-drugs (non-benzodiazepine compounds) using an Induced Fit Docking (IFD) into the relaxed binding site to generate a pharmacophore model. The pharmacophore model was validated with a reference set and applied to decrease the pre-filtered Enamine database before the main docking procedure. Finally, we succeeded in identifying a set of compounds, which met all features of the docking model. The aqueous solubility and stability of these compounds in mouse plasma were assessed. Then they were tested for the biological activity using the rat Purkinje neurons and CHO cells with heterologously expressed human α1β2γ2 GABAA receptors. Whole-cell patch clamp recordings were used to reveal the GABA induced currents. Our study represents a convenient and tunable model for the discovery of novel positive allosteric modulators of GABAA receptors. A High-throughput virtual screening of the largest available database of chemical compounds resulted in the selection of 23 compounds. Further electrophysiological tests allowed us to determine a set of 3 the most outstanding active compounds. Considering the structural features of leader compounds, the study can develop into the MedChem project soon.

OBJECTIVE: Phenibut (4-amino-3-phenyl-butyric acid) is a structural analog of GABA with central nervous system depressant and anxiolytic properties, developed in the former Soviet Union for anxiety, insomnia, and alcohol withdrawal. Its primary mechanism of action is believed to be a GABA-B receptor agonist-with high affinity at the α 2 δ subunit-containing voltage-dependent calcium channels and therefore gabapentinoid activity-as well as, to a lesser extent, GABA-A agonist activity. While not approved or regulated by the FDA, phenibut is easily obtainable online, where it is marketed as a nootropic, or cognitive enhancer. However, phenibut can lead to problems related to intoxication, dependency, and withdrawal, similar to other sedatives.
METHODS: We present a case of phenibut intoxication and withdrawal delirium that provided diagnostic and management challenges because of a patient that was initially not forthcoming about his phenibut use which resulted in five presentations to the hospital including two admissions.
RESULTS: Initial differential including adrenergic, serotonergic or anticholinergic toxidrome based on clinical picture and history reported at that time, however phenibut use of 50 g daily was eventually revealed, an amount exceeding the highest reported cases in our review of the English literature.
CONCLUSIONS: High-dose phenibut intoxication and withdrawal can appear as dramatic and dangerous as high-dose sedative withdrawal, however given its specified receptor affinity and binding profile we found that a pharmacotherapeutic approach targeting GABA-B, GABA-A, and gabapentenoid receptors were effective in stabilizing this patient, eventually leading to the patient\'s full and sustained recovery.

It is challenging to manage schizophrenic catatonia and comorbid chronic intestinal pseudo-obstruction (CIPO). The pathology of catatonia is unclear. There are few reports or research on this issue. In this case, we present a middle-aged woman diagnosed with schizophrenia with catatonic features and comorbid CIPO. In the treatment process, modified electroconvulsive therapy (mECT) improved her stupor and CIPO partially. Lorazepam alleviated her stupor and CIPO completely. It is the first report describing complete remission with lorazepam in patient suffering from comorbid schizophrenic catatonia and CIPO, which may benefit the exploration of pathophysiology and treatment of comorbidity of schizophrenia with catatonia and CIPO.

Durvalumab is an immune checkpoint Inhibitor (ICIs) that is used in the treatment of malignant tumors, such as lung cancer and melanoma. ICIs are associated with immune-related adverse events including autoimmune encephalitis, although both paraneoplastic phenomena and ICI treatment may lead to autoimmunity.
We describe a 72-year old male patient with small-cell lung cancer, who during adjuvant treatment with Durvalumab developed GABABR1 and GAD65 antibodies and both diabetes and autoimmune limbic encephalitis. Because he was followed prospectively as part of a treatment study, we had access to repeated serum samples and cognitive assessments over time prior to developing encephalitis and diabetes, in addition to later assessments. A high titer of GABABR1 antibodies appeared early, while GAD65 antibodies appeared later with a lower titer in parallel with the development of diabetes. As he subsequently developed clinical signs of encephalitis, verified by EEG and brain MRI, he also had CSF GABABR1 antibodies. Durvalumab was discontinued and steroid treatment with subsequent plasmapheresis were started, resulting in reduction of both CSF and serum antibody levels. Clinical signs of encephalitis gradually improved.
This case illustrates the importance of being aware of possible serious autoimmune adverse reactions, including neurological syndromes such as encephalitis, when treating patients with high risk of para-neoplasia with ICIs. In addition, the case shows the development of autoantibodies over time.

Background: Phenibut is a drug similar in structure to gabapentin and pregabalin. It is available online without prescription, often marketed as a dietary supplement or amino acid derivative. Little is known about phenibut use despite its increased popularity in the United States over the last decade.Objective: To clarify reasons for taking phenibut, circumstances, and effects of use.Methods: Reports of phenibut, gabapentin, and pregabalin use were downloaded from a publicly-available database, Erowid.org. A mixed methods approach utilizing qualitative content analysis was used.Results: Of 229 reports, 211 were from male authors. People usually purchased phenibut online and reportedly used it for recreation, to manage a medical or psychiatric problem (primarily insomnia, anxiety), as a substitute for other drugs (especially benzodiazepines), to manage withdrawal from another substance (including benzodiazepines, opioids), and/or for performance enhancement. While it shared many reported effects with pregabalin and gabapentin such as anxiolysis, increased talkativeness, and impaired motor coordination, reports of gastrointestinal distress and sedation were more commonly attributed to phenibut. Several people reported difficulty in restricting their use and managing withdrawal.Conclusions: Phenibut reports suggest that phenibut may have some benefits for some people. Use also, however, carries risks of adverse effects, a potentially dangerous withdrawal syndrome, and addiction. Not dissimilar to unprescribed gabapentin or pregabalin, self-medication is a common motive for phenibut use. Physicians should continue to ask their patients about use of any non-prescribed medications, dietary supplements, or \"amino acid derivatives.\"Abbreviation: PWUPh: people who use phenibut; PWUG: people who use gabapentin; PWUPr: people who use pregabalin.

Gabapentin (GBP) is a structural analog of gamma-aminobutyric acid (GABA) that is commonly used in palliative care for symptom management indications including neuropathic pain syndromes, hiccups, cough, and anxiety. An uncommon adverse effect of GBP is urinary incontinence (UI). We report the case of a 61-year-old male with metastatic non-small cell lung cancer who developed probable overflow UI while receiving 1200 mg/day of GBP for chemotherapy-induced peripheral neuropathy. The patient self-tapered GBP to 600 mg/day which resolved the overflow UI, but resulted in poorly controlled bilateral foot pain. The palliative care physician rotated the patient to pregabalin 150 mg/day and his bilateral foot pain improved after his regimen was titrated to 200 mg/day. The patient did not experience overflow UI while taking pregabalin despite the similar pharmacology and comparable doses to GBP. We believe this is the first case report to describe subsequent achievement of pain control by substituting pregabalin without recurrence of UI. Healthcare professionals should consider GBP as a potential cause when evaluating patients presenting with new onset overflow UI.

A 65-year-old man was admitted to our hospital with a 6-year history of painful muscle stiffness in his trunk and lower limbs, preventing him from walking. Stiff-person syndrome (SPS) was diagnosed because the patient had symptoms of painful muscle spasms elicited by tactile stimulation without joint contracture. Although SPS- related autoantibodies in the serum, including anti-glycine R, anti-amphiphysin, anti-glutamic acid decarboxylase (GAD), anti-dipeptidyl peptidase-like protein (DPPX) and anti-γ-aminobutyric acid-A (GABAA) R, were negative, the ACTH and cortisol levels were low. On the basis of additional loading tests for anterior pituitary function and ACTH, isolated ACTH deficiency (IAD) was diagnosed. Hormonal replacement therapy with hydrocortisone at 15 mg/day ameliorated the condition quickly, and the patient became asymptomatic after three months. Flexion contractures have been reported as musculoskeletal symptoms of IAD, but are not usually evident in patients with SPS. The present case illustrates that the painful muscle spasms elicited by tactile stimulation without joint contracture characteristic of SPS can also be symptoms of IAD.