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Alzheimer's is the most common neurodegenerative disease among the aging population, which has been a major global challenge. The pathogenesis of the disease is still undetermined but postulated to be involved in various mechanisms including oxidative stress, excitotoxicity, inflammation, cell death, genetic factors, protein accumulation, and degradation. There are few Food and Drug Administration (FDA)-approved drugs available for the treatment of Alzheimer's disease (AD) that have limited benefits along with associated adverse effects. A retrospective review of randomized double-blind controlled trials of various supplements used in AD patients was performed on a PubMed search from January 1983 to March 2022. We found 10 articles that have shown positive outcomes in various cognitive domains. We conclude that there should be a global standard to endorse the quality and safety of these supplements., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Chimakurthy et al.)

Magnetic resonance guided focused ultrasound (MRgFUS) thalamotomy targets the ventral intermediate nucleus of the thalamus and has been shown to be safe and effective to treat medication-resistant essential tremors. Improvement in tremor scores, posture and action scores, disability scores and quality of life scores have been reported in patients treated with this procedure. Adverse events are usually transient and non-severe. We present a patient who underwent MRgFUS thalamotomy of the left VIM and developed new-onset parkinsonian features predominantly on the right side and return of essential tremors a few years after the procedure. Changes in speech (hypophonia and dysarthria), gait imbalance and postural instability, bradykinesia, and cogwheeling rigidity occurred, likely due to involvement of the fiber tracts through the ventrolateral subnuclei and the adjacent ventral anterior thalamic nuclei and other surrounding structures. We describe side effects of MRgFUS thalamotomy in our patient compared to previous reports and review the thalamic nuclei and surrounding structures that can be affected during procedure, causing these effects., (© 2021 The Authors. Published by Elsevier B.V.)

Benzodiazepine withdrawal symptoms vary from mild anxiety to life-threatening delirium or seizures. In susceptible individuals, such as those with mood disorders, benzodiazepine withdrawal may also precipitate catatonia. A 26-year-old man with schizoaffective disorder (depressed type with catatonia) ran out of lorazepam and presented with catatonia, delirium, and seizures. He was taking olanzapine, venlafaxine, and trazodone for schizoaffective disorder. Lorazepam 2 mg twice daily kept him free of catatonia for 6 months. Besides catatonia and delirium, lorazepam withdrawal also triggered convulsive seizures and nonconvulsive status epilepticus. He was admitted to the intensive care unit where he underwent continuous video-EEG monitoring. Catatonia resolved with lorazepam on day 2. Seizures stopped with levetiracetam, lacosamide, and propofol on day 4. His mental status was normal when he was discharged on day 6. If not immediately recognized and treated, catatonia and delirium can lead to significant morbidity or mortality. Unfortunately, physicians tend to overlook catatonia and delirium, especially if both syndromes are present. At first, we suspected that our patient had ictal catatonia, but video-EEG showed no clear-cut correlation between catatonia, seizures, and epileptiform activity. As with prior observations, the patient's catatonia was more sensitive to benzodiazepine withdrawal and treatment than his seizures. The efficacy of benzodiazepines in aborting catatonia, seizures, and mixed delirium-catatonia syndromes suggests a key pathogenetic role of abnormal GABA neurotransmission in these brain disorders.

Objective: To describe and assess intraoperative and postoperative outcomes in the insertion of osseointegrated auditory implants with a newly designed surgical instrumentation set through a punch type technique., Study Design: Retrospective case series., Methods: Patients who underwent bone anchored auditory implant surgery using the Minimally Invasive Ponto Surgery (Oticon Medical, Somerset, NJ) surgical set through a punch technique at nine neurotology tertiary referral based practices were identified. Demographic data, skin thickness at implant site, implant used, duration of surgery, adverse intraoperative events, and postoperative outcomes were recorded., Results: Seventy-five patients comprised the study cohort (32 males, 43 females). Most patients (57. 3%) were aged 51 to 75 years while 30.7% of the cohort comprised those aged 18 to 50 years and 12% were over 75 years. All but two patients received 4 mm fixtured implants and 68% received the Oticon Medical BioHelix implant. Two patients received 3 mm fixture implants and 32% received the Oticon Medical Wide Ponto implant. Mean surgical time was 12.2 minutes (6-45 min, standard deviation of 6.88 min). In three instances, surgery was converted to a linear incision to control brisk bleeding. Skin condition was Holgers 0 to 1 in 91.8%, while 5.5% had Holgers 2, and 2.7% had Holgers 3 at the first postoperative visit. At second postoperative visit, 94.3% had Holgers 0 to 1, 4.3% had Holgers 2, and 1.4% had Holgers 3. All instances of adverse skin reactions were treated with topical or systemic antibiotics and/or local debridement. There were no instances of implant loss. One patient had his implant traumatically displaced to a 45-degree angle necessitating implant replacement at a second site., Conclusion: Punch technique placement of osseointegrated auditory implants using the Minimally Invasive Ponto Surgery surgical set represents a safe technique that further simplifies a progressively minimally invasive surgery.

A 39-year-old woman was incidentally found to have extensive bilateral basal ganglia calcifications after a motor vehicle accident. Laboratory work-up was unremarkable. She was diagnosed with idiopathic basal ganglia calcifications, formerly known as Fahr's disease. A brief review of the literature is presented.

In mice administered chronic stress--repeated overnight restraint stress for 7 days--there was a prolonged enhancement of dopamine (DA) uptake into synaptosomes. The mRNA for the DA transporter (DAT) was found to be concomitantly increased in the midbrain, as was the binding of the transporter ligand mazindol to DAT in the nucleus accumbens and caudate-putamen. Kinetic analysis showed an increase in Vmax for DA, with little change in Km. No changes in tyrosine hydroxylase activity and tissue DA or 3,4-dihydroxyphenylacetic acid (DOPAC) content were observed. However, homovanillic acid (HVA) was found to be increased in the striatum of the stressed animals. Enhanced DAT activity attributable to chronic stress was still observed in animals treated with the DA D2 receptor antagonist haloperidol or the glucocorticoid receptor antagonist mifepristone. Modulation of DAT activity may be a physiological mechanism for regulating the concentration of DA that reaches receptors, following periods of stress.

Objective: To assess the accuracy of computer-aided surgery for common neurotologic approaches to the temporal bone., Study Design and Setting: Cadaveric heads were dissected by using standard neurotologic approaches to the temporal bone including translabyrinthine, middle fossa, and retrosigmoid. Dissected anatomic landmarks from each approach were compared with CT images that were obtained before dissection on the VectorVision 2 system (BrainLAB Corp, Munich, Germany) and the variability measured from digital images. Each approach was performed 5 times, with each anatomic landmark measured 3 times from each approach., Results: The accuracy of the computer-aided surgery system was less than 1 mm for all anatomic points measured. Forty-two of the 49 measured points were accurate to less than 0.5 mm., Conclusions: Computer-aided surgery of the temporal bone using common neurotologic approaches can be performed accurately and reliably in cadaver specimens., Significance: The utility and limitations of computer-aided surgery in the temporal bone are discussed., Ebm Rating: B-2.

Objectives/hypothesis: Mutations in GJB2 are a common cause of congenital sensorineural hearing loss. Many children with these mutations receive cochlear implants for auditory habilitation. The purpose of the study was to compare the speech perception performance of cochlear implant patients with GJB2-related deafness to patients without GJB2-related deafness., Study Design: Retrospective case review., Methods: Pediatric cochlear implant recipients who have been tested for GJB2 mutation underwent chart review. All patients received cochlear implantation at a tertiary referral center, followed by outpatient auditory habilitation. Charts were reviewed for cause and duration of deafness, age at time of cochlear implantation, intraoperative and postoperative complications, duration of use, and current age. Results of standard tests of speech perception administered as a part of the patients' auditory habilitation were reviewed., Results: Twenty patients with GJB2 mutations were compared with 27 patients without GJB2 mutations. There was no statistical difference between patients with and without GJB2-related congenital sensorineural hearing loss with regard to open-set and closed-set speech recognition performance at 12, 24, and 36 months after cochlear implantation. Surgical complications were uncommon., Conclusion: Pediatric patients with congenital sensorineural hearing loss without other comorbid conditions (eg, developmental delay, inner ear malformations) perform well when they receive cochlear implantation and auditory habilitation. The presence or absence of GJB2 mutation does not appear to impact speech recognition performance at 12, 24, and 36 months after implantation.

Objective: To investigate the clinical utility of intraoperative plain radiographs in cochlear implant surgery., Study Design: Prospective., Setting: Tertiary referral center., Patients: Eighty consecutive adult and pediatric cochlear implant operations at a facility capable of intraoperative radiographs were evaluated over 12 months., Interventions: Intraoperative plain radiographs to assess implant location and surgeon questionnaire., Main Outcome Measures: Plain radiographic image interpretation and surgeon questionnaire., Results: In one revision surgery, the intraoperative plain radiograph was useful for confirming the cochleostomy site. In the remaining 79 operations, no changes in the electrode arrays were made on the basis of the information provided by intra-operative plain radiographs., Conclusions: In this cohort, intraoperative plain radiographs were not useful for uncomplicated implant operations; however, they may be useful for complicated operations. These results may have implications for surgical cost and patient radiation exposure.

Objective/hypothesis: To assess the audiologic and surgical outcomes for pediatric cochlear implant patients with inner ear malformations., Study Design: Retrospective review of 315 pediatric cochlear implant cases from 1994 to 2002., Methods: Twenty-eight pediatric cochlear implant patients with known inner ear malformations determined on high-resolution computed tomography (HRCT) of the temporal bone were the subjects of review. Results of HRCT findings, intraoperative findings, postoperative complications, and objective measures of both closed- and open-set testing of speech perception were analyzed., Results: Patients with the constellation of an incompletely partitioned (IP) cochlea, enlarged vestibular aqueduct (EVA), and a dilated vestibule (i.e., Mondini's malformation) as well as those with an isolated EVA or partial semicircular canal aplasia have relatively good levels of speech perception. Patients with total semicircular canal aplasia, isolated IP, cochlear hypoplasia, or common cavity demonstrated lower levels of performance. Poor performance may be related to associated developmental delays rather than labyrinthine anatomy alone. Complications of surgery were relatively limited., Conclusions: Cochlear implantation can be successfully performed in children with inner ear malformations. These children and their parents can expect significant auditory benefits from this intervention. The various types of inner ear malformations may have quite different prognoses for good auditory performance.

Cochlear implants have dramatically changed the treatment and prognosis for patients with profound sensorineural hearing loss. Deaf adults and children can be successfully (re)integrated into the hearing world through a multidisciplinary approach involving otolaryngologists, audiologists, and speech/language pathologists. As the technology of the cochlear prosthesis advances, the candidacy for these devices continues to broaden. This review addresses the basic technology, candidacy criteria, and important issues in the fields of adult and pediatric cochlear implantation. Cost utility and future directions in the treatment of the profoundly hearing impaired are discussed.

The appropriate management of labyrinthine fistulae has been debated in the literature for years. After several recent cases of labyrinthine fistulae at our institution, a review of the published data regarding hearing outcome with fistula management was undertaken. Results of this critical review were presented at departmental grand rounds. The grand rounds presentation, data and discussion are presented to better illuminate the topic of labyrinthine fistula management., (Copyright 2003, Elsevier Science (USA). All rights reserved.))

"Strong artificial life" refers to the thesis that a sufficiently sophisticated computer simulation of a life form is a life form in its own right. Can John Searle's Chinese room argument [12]-originally intended by him to show that the thesis he dubs "strong AI" is false-be deployed against strong ALife? We have often encountered the suggestion that it can be (even in print; see Harnad [8]). We do our best to transfer the argument from the domain of AI to that of ALife. We do so in order to show once and for all that the Chinese room argument proves nothing about ALife. There may indeed be powerful philosophical objections to the thesis of strong ALife, but the Chinese room argument is not among them.

Incubation with either of the protein kinase C activators phorbol 12-myristate 13-acetate (PMA) and sn-1,2 dioctanoylglycerol (DiC8) decreased the uptake of dopamine into striatal synaptosomes, whereas the inactive phorbol ester 4 alpha-PMA had no effect. Washout of PMA and DiC8 failed to reverse the decrease in uptake. Kinetic analysis showed a decrease in the apparent V(max) for the transporter without changes in the K(m). Neither PMA nor DiC8 affected mazindol binding to the dopamine transporter. Preincubation with the protein kinase inhibitor staurosporine prevented the DiC8-induced decrease of dopamine uptake. Furthermore, the protein phosphatase inhibitor okadaic acid decreased dopamine uptake by itself and enhanced the DiC8-induced reduction of uptake. These findings support a role for protein kinase C in modulating dopamine transporter activity.