Associations between Antiretrovirals and Cognitive Function in Women with HIV.

Cognitive complications persist in antiretroviral therapy(ART)-treated people with HIV. However, the pattern and severity of domain-specific cognitive performance is variable and may be exacerbated by ART-mediated neurotoxicity. 929 women with HIV(WWH) from the Women's Interagency HIV Study who were classified into subgroups based on sociodemographic and longitudinal behavioral and clinical data using semi-parametric latent class trajectory modelling. Five subgroups were comprised of: 1) well-controlled HIV with vascular comorbidities(n = 116); 2) profound HIV legacy effects(CD4 nadir <250 cells/µL; n = 275); 3) primarily <45 year olds with hepatitis C(n = 165); 4) primarily 35-55 year olds(n = 244), and 5) poorly-controlled HIV/substance use(n = 129). Within each subgroup, we fitted a constrained continuation ratio model via penalized maximum likelihood to examine adjusted associations between recent ART agents and cognition. Most drugs were not associated with cognition. However, among the few drugs, non-nucleoside reverse transcriptase inhibitor (NNRTIs) and protease inhibitors(PIs) were most commonly associated with cognition, followed by nucleoside reverse transcriptase inhibitors(NRTIs) and integrase inhibitors(IIs). Directionality of ART-cognition associations varied by subgroup. Better psychomotor speed and fluency were associated with ART for women with well-controlled HIV with vascular comorbidities. This pattern contrasts women with profound HIV legacy effects for whom poorer executive function and fluency were associated with ART. Motor function was associated with ART for younger WWH and primarily 35-55 year olds. Memory was associated with ART only for women with poorly-controlled HIV/substance abuse. Findings demonstrate interindividual variability in ART-cognition associations among WWH and highlight the importance of considering sociodemographic, clinical, and behavioral factors as an underlying contributors to cognition. Are antiretroviral agents a risk factor for cognitive complications in women with HIV? We examind associations between ART-agents and cognitive function among similar subgroups of women with HIV from the Women's Interagency HIV study. The patterns of associations depended on sociodemographic, clinical, and behavioral characteristics of women.

Garbled speech: a rare presentation of metronidazole-induced neurotoxicity.

Neurotoxicity is a rare but significant side effect of metronidazole. We present, here, a case of a 34-year-old man, presenting with garbled speech and word finding difficulty. He was taking metronidazole for the last 3 months for stage 4 decubitus ulcers. MRI of the brain showed abnormal signal intensities in the splenium of the corpus callosum and dentate nuclei of the cerebellum. The diagnosis of metronidazole-induced neurotoxicity was made based on MRI findings. The antibiotic was stopped leading to resolution of abnormal MRI findings. We advocate that metronidazole can be associated with severe neurotoxicity, but its prompt cessation leads to better outcome and prognosis.

Aminoglycoside-associated nonsyndromic deafness and speech disorder in mitochondrial A1555G mutation in a family: A case report.

RATIONALE: Mitochondrial DNA mutations have been associated with many maternal inherited diseases. A1555G mutation in mtDNA effects the gene code for rRNA, resulting in the structural change of human ribosome rending it susceptible to binding of the common antibiotic, aminoglycosides. Such mutation has linked with non-syndromic hearing loss and is one of the most common mtDNA mutations in Asian populations. PATIENT CONCERNS: A 50-year-old Taiwanese female visited our neurology department with concern for multiple members with hearing loss in her family, including herself. DIAGNOSES: Physical examination findings were not significant besides hearing loss and brain MRI did not reveal any lesions. BAEP confirmed bilateral peripheral sensory deficit. Given the multiple cases of hearing loss in the family, a genetic cause was suspected. Using PCR and sequences chromatogram technique we have identified A1555G mutation on her mtDNA affecting region codes for 12S rRNA. Additionally, we observed severe speech disorder in two young family members with the onset of hearing loss began in their early childhood. INTERVENTIONS: The patient declined any form of intervention at the time for personal reasons. OUTCOMES: The patient was satisfied with the diagnosis, her and her families are continuously followed by our neurology department. LESSONS: We report on a family with mtDNA mutation hearing loss that is related to exposure to aminoglycosides. Children with such mutation are at high risk for impaired linguistic function. Early identification and intervention with cochlear implant should be considered.

Doxylamine succinate overdose: Slurred speech and visual hallucination.

Derinöz-Güleryüz O. Doxylamine succinate overdose: Slurred speech and visual hallucination. Turk J Pediatr 2018; 60: 439-442. Doxylamine succinate is a commonly used antihistamine for respiratory allergies including allergic rhinitis as well as for the management of insomnia. As it is available over-the-counter like other nonprescription antihistamines and sleep aids, there is a risk of overdose. It is believed that doxylamine succinate has both peripheral and central activity with its anticholinergic properties. Delirium, seizures, and coma are among the central adverse effects that are rare. This case was presented since it is the first case in the literature who developed slurred speech and visual hallucination after high dose doxylamine succinate use and received antidotal therapy for anticholinergic side effects.

The effects of synthetic cannabinoid UR-144 on the human body-A review of 39 cases.

UR-144 [(1-pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone] is a synthetic cannabinoid, which has been detected in many 'legal highs', seized from the global drug market since the beginning of 2012. It has gained popularity as a 'legal' alternative to classic cannabis in countries where it was not controlled. Despite the widespread distribution of this substance, the data on its effects on the human body are scarce. Therefore, this paper describes the results of analysis and observed effects in 39 cases in which UR-144 was determined in blood. Symptoms were noted from the blood sampling forms filled out by the representative doctor. The determined concentrations of UR-144 were in the range of trace amounts (LOD-0.15ng/mL; LOQ-0.5ng/mL) up to 17ng/mL. The most common observed effects included slurred speech, dilated pupils, sluggish and abnormal pupillary reaction, cheerful behaviour, poor coordination, and staggering. Less frequently observed were: verbosity, narrow pupils, loss of consciousness, pale or reddened facial skin, blackout, euphoria, agitation, hallucinations, hindered communication, shaking hands, seizures, convulsions, somnolence, delayed movements, redness of the conjunctiva, and tachycardia. The discussed cases show the effects observed after UR-144 use. This study can assist in the recognition of possible effects caused by this substance.

Association of Selective Serotonin Reuptake Inhibitor Exposure During Pregnancy With Speech, Scholastic, and Motor Disorders in Offspring.

IMPORTANCE: Speech/language, scholastic, and motor disorders are common in children. It is unknown whether exposure to selective serotonin reuptake inhibitors (SSRIs) during pregnancy influences susceptibility to these disorders. OBJECTIVE: To examine whether SSRI exposure during pregnancy is associated with speech/language, scholastic, and motor disorders in offspring up to early adolescence. DESIGN, SETTING, AND PARTICIPANTS: This prospective birth cohort study examined national population-based register data in Finland from 1996 to 2010. The sampling frame includes 845 345 pregnant women and their singleton offspring with data on maternal use of antidepressants and depression-related psychiatric disorders during pregnancy. EXPOSURES: There were 3 groups of offspring: 15 596 were in the SSRI-exposed group, ie, had mothers diagnosed as having depression-related psychiatric disorders with a history of purchasing SSRIs during pregnancy; 9537 were in the unmedicated group, ie, had mothers diagnosed as having depression-related psychiatric disorders without a history of purchasing SSRIs during pregnancy; and 31 207 were in the unexposed group, ie, had mothers without a psychiatric diagnosis or a history of purchasing SSRIs. MAIN OUTCOMES AND MEASURES: Cumulative incidence of speech/language, scholastic, or motor disorders (829, 187, and 285 instances, respectively) from birth to 14 years. All hypotheses tested were formulated before data collection. RESULTS: Of the 56 340 infants included in the final cohort, 28 684 (50.9%) were male and 48 782 (86.6%) were 9 years or younger. The mean (SD) ages of children at diagnosis were 4.43 (1.67), 3.55 (2.67), and 7.73 (2.38) for speech/language, scholastic, and motor disorders, respectively. Offspring of mothers who purchased SSRIs at least twice during pregnancy had a significant 37% increased risk of speech/language disorders compared with offspring in the unmedicated group. The cumulative hazard of speech/language disorders was 0.0087 in the SSRI-exposed group vs 0.0061 in the unmedicated group (hazard ratio, 1.37; 95% CI, 1.11-1.70; P = .004). There was a significantly increased risk of these disorders in offspring in the SSRI-exposed and unmedicated groups compared with offspring in the unexposed group. For scholastic and motor disorders, there were no differences between offspring in the SSRI-exposed group and in the unmedicated group. CONCLUSIONS AND RELEVANCE: Exposure to SSRIs during pregnancy was associated with an increased risk of speech/language disorders. This finding may have implications for understanding associations between SSRIs and child development.

Delayed Antitoxin Treatment of Two Adult Patients with Botulism after Cosmetic Injection of Botulinum Type A Toxin.

BACKGROUND: Injection of botulinum toxin type A for cosmetic purposes is common. It is believed to be safe, but adverse reactions have been reported, including dysphagia, generalized paralysis, respiratory depression, and death caused by focal injection of the toxin. Early administration of antitoxin in patients with adverse reactions is the mainstay of management, but the time window for its clinical efficacy is not well defined. CASE REPORTS: Two female adult patients with clinical botulism after botulinum toxin type A injection are described. Both patients had received intramuscular injection of botulinum toxin type A in their calves at beauty shops for cosmetic reasons. They developed clinical botulism about 3 days postinjection. They presented late to the emergency department. Monovalent type A botulinum antitoxin was administered 7 and 9 days from symptom onset, respectively. Both patients showed clinical improvement after the antitoxin treatment. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Patients may present to the emergency department with systemic effects of botulinum toxin type A after cosmetic injection. Clinical efficacy of botulinum antitoxin treatment was observed in two patients who were given the drug 7 and 9 days after the occurrence of symptoms of botulism after cosmetic injection of botulinum toxin type A. It may be worthwhile to commence antitoxin treatment even if patients present late.

Evaluating the effect of risperidone on speech: A cross-sectional study.

Speech subsystems are susceptible to the effects of several factors including medications. The atypical antipsychotics can also adversely affect the speech because of its action on serotonin and dopamine neurotransmitters. The present study aims to analyze the speech characteristics associated with atypical antipsychotic risperidone. Speech of 92 patients on risperidone with or without trihexyphenidyl and/or clonazepam were compared with that of 31 persons who were not on any psychotropic medicines. Compared to control group, maximum phonation duration, sequential motion rate of diadochokinesia was reduced by about 3s and 1syllable/s respectively and s/z ratio was increased by 0.16 in patients with risperidone. Performance of larynx, lips and tongue sub-system and intelligibility of speech were also significantly reduced in risperidone group. Risperidone did impact the phonation and articulation sub-systems of speech mildly, which was independent of tardive dyskinesia and extrapyramidal symptoms. Randomized controlled prospective study looking into impact on speech and related effect on drug adherence, functioning and quality of life needs to be conducted with risperidone and other atypical antipsychotics.

Children and adolescents previously treated with glucocorticoids display lower verbal intellectual abilities.

AIM: Perinatal exposure to glucocorticoids has been associated with adverse cerebral effects, but little is known about their effect on cognitive development and exposure later in childhood. This study examined intellectual abilities, memory and behavioural problems in children previously treated with glucocorticoids. METHODS: We evaluated 38 children aged from seven to 16 years, who had been treated with glucocorticoids for rheumatic disease or nephrotic syndrome, together with 42 healthy controls matched for age, gender and parental education. The median cumulative dose of prednisolone equivalents was 158 mg/kg (range 21-723) and the mean time that had elapsed since treatment was three-and-a-half (standard deviation 2.2) years. Intellectual abilities were assessed with the Wechsler Intelligence Scale for Children and memory performance and behavioural problems with a pattern recognition memory task and the Child Behaviour Check List. RESULTS: There were no significant differences between the groups in pattern recognition memory, perceptual organisation index or behavioural problems, but patients had a significantly lower verbal comprehension index and this difference was present in both disease groups. There were no significant dose-response relationships regarding verbal intellectual abilities. CONCLUSION: Children and adolescents previously treated with glucocorticoids seemed to have lower intellectual verbal abilities than healthy controls.

A comparison of sedation-related events for two multiagent oral sedation regimens in pediatric dental patients.

PURPOSE: This study compared the incidence of adverse sedation-related events occurring with two different multiagent oral sedation regimens in pediatric dental patients. METHODS: Forty healthy patients (three to six years old), received either a sedation regimen of chloral hydrate, meperidine, and hydroxyzine with nitrous oxide (CH/M/H/N2O; N=19) or a regimen of midazolam, meperidine, and hydroxyzine with nitrous oxide (MZ/M/H/N2O; N=21). The two treating dentists answered a questionnaire regarding the perioperative period. Parents received two phone interviews at eight and 24 hours after sedation. Statistical analysis included chi-square, Pearson correlation coefficient, and t-test (P<.05). RESULTS: Children sedated with MZ/M/H/N2O showed a significant increase in hyperactivity during dental treatment, slurring/difficulty speaking, and difficulty walking postoperatively within eight hours after discharge. Children sedated with CH/M/H/N2O showed a significant increase in frequency of sleeping, talking less than normal after arriving home, and an increased need for postoperative pain medication. CONCLUSIONS: Different oral sedation regimens produce different adverse sedation-related events. The provider of pediatric oral sedation should select a sedative regimen with an adverse sedation-related profile that he/she believes is optimal for the patient being treated. Parents should be counseled as to possible postsedation effects anticipated based on the sedative regimen administered.

Characteristics and occurrence of speech impairment in Huntington's disease: possible influence of antipsychotic medication.

Although motor speech impairment is a common manifestation of Huntington's disease (HD), its description remains limited. The aim of the current study was therefore to estimate the occurrence and characteristics of speech disorder in HD and to explore the influence of antipsychotic medication on speech performance. Speech samples, including reading passage and monologue, were acquired from 40 individuals diagnosed with HD and 40 age- and sex-matched healthy controls. Objective acoustic analyses were used to evaluate key aspects of speech including vowel articulation, intensity, pitch and timing. A predictive model was constructed to detect the occurrence and most prominent patterns of speech dysfunction in HD. We revealed that 93% of HD patients manifest some degree of speech impairment. Decreased number of pauses, slower articulation rate, imprecise vowel articulation and excess intensity variations were found to be the most salient patterns of speech dysfunction in HD. We further demonstrated that antipsychotic medication may induce excessive loudness and pitch variations perceptually resembling excess patterns of word stress, and may also accentuate general problems with speech timing. Additionally, antipsychotics induced a slight improvement of vowel articulation. Specific speech alterations observed in HD patients indicate that speech production may reflect the pathophysiology of the disease as well as treatment effects, and may therefore be considered a valuable marker of functional disability in HD.

The influence of alcoholic intoxication on the short-time energy function of speech.

This study investigates rhythmic features based on the short-time energy function of speech signals with the aim of finding robust, speaker-independent features that indicate speaker intoxication. Data from the German Alcohol Language Corpus, which comprises read, spontaneous, and command&control speech uttered by 162 speakers of both genders and various age groups when sober and intoxicated, were analyzed. Energy contours are compared directly (Root Mean Squared Error, statistical correlation, or the Euclidean distance in the spectral space of the contour) and by parameterization of the contour using the Discrete Cosine Transform (DCT) and the first and second moments of the lower DCT spectrum. Contours are also analyzed by Principal Components Analysis aiming at fundamental "eigen contour" changes that might encode intoxication. Energy contours differ significantly with intoxication in terms of distance measures, the second and fourth DCT coefficients, and the first and second moments of the lower DCT spectrum. Principal Components Analysis did not yield interpretable "eigen contours" that could be used in distinguishing intoxicated from sober contours.

Herpes zoster encephalopathy or acyclovir neurotoxicity: a management dilemma.

This is a case report of a 69-year-old morbidly obese woman who presented with mental status changes after she was treated with acyclovir for shingles. The predominant symptoms were word-finding difficulties and visual hallucinations. Complicating her presentation was acyclovir-induced acute renal injury causing her creatinine level to rise up to 7.4 mg/dL. Acyclovir was discontinued on the suspicion of acyclovir neurotoxicity. Even though PCR for varicella zoster virus in the cerebrospinal fluid was positive, acyclovir was not restarted and the patient continued to improve and returned to her baseline.

The effect of moderate gestational alcohol consumption during pregnancy on speech and language outcomes in children: a systematic review.

BACKGROUND: Consensus has not been reached on safe alcohol consumption recommendations during pregnancy. The National Institutes for Care and Health Excellence (NICE) in the UK suggest that one to two drinks not more than twice per week is safe. However, the speech and language effects of even low levels of alcohol use among offspring are unknown. The aim of this study was to review systematically the evidence on studies of the effect of low to moderate levels of alcohol consumption during pregnancy (up to 70 grams of alcohol per week) compared to abstinence on speech and language outcomes in children. METHODS: Using medical subject headings, PubMed, Web of knowledge, Scopus, Embase, Cinahl and the Cochrane Library were searched from their inception up to March 2012. Case control and cohort studies were included. Two assessors independently reviewed titles, abstracts and full articles, extracted data and assessed quality. RESULTS: A total of 1,397 titles and abstracts were reviewed of which 51 full texts were retrieved. Three cohort studies totaling 10,642 women met the inclusion criteria. All three studies, (United States (2) and Australia (1)) indicated that language was not impaired as a result of low to moderate alcohol consumption during pregnancy. Two studies were judged to be of low quality based on a six-item bias classification tool. Due to heterogeneity, results could not be meta-analyzed. CONCLUSION: Studies included in this review do not provide sufficient evidence to confirm or refute an association between low to moderate alcohol use during pregnancy and speech and language outcomes in children. High quality, population based studies are required to establish the safety of low to moderate levels of alcohol use such as those set out by the NICE guidelines in the UK.

Butalbital and driving impairment.

Butalbital (Fiorinal(®)), used in the treatment of migraines and muscle pain, is the most commonly encountered barbiturate in impaired driving cases. It has central nervous system (CNS) depressant properties, including sedation, drowsiness, and feelings of intoxication, which can contribute to driving impairment. Twenty-six driving under the influence cases are reviewed including results from field sobriety tests and toxicology testing. Blood samples were screened using enzyme multiplied immunoassay technique immunoassay, and the presence of butalbital was confirmed and quantified using gas chromatography/mass spectrometry, gas chromatography with flame ionization detection, or gas chromatography nitrogen/phosphorus detection. Butalbital concentrations ranged from 1.0 to 30.2 mg/L, with a mean and median of 16.0 mg/L. General impairment indicators in these cases included horizontal and vertical nystagmus, lack of convergence, poor motor coordination, and balance and speech problems, which are common to CNS depressant intoxication, similar to that associated with alcohol. These findings indicate the importance of toxicological testing for butalbital in cases where CNS depressants are indicated.

Impaired verbal fluency under topiramate--evidence for synergistic negative effects of epilepsy, topiramate, and polytherapy.

BACKGROUND AND PURPOSE: Treatment with topiramate (TPM) is known to negatively affect executive functions and verbal fluency in particular. However, judgments of cognitive side effects under TPM rarely consider clinical conditions and possible effects of epilepsy, treatment, and drug load. METHODS: This retrospective cross-sectional study in large cohorts of patients with epilepsy evaluated the impact of TPM mono- and polytherapy on verbal fluency. To isolate TPM-induced effects from those of epilepsy and antiepileptic medication in general, verbal fluency under TPM (N = 421) was compared to the performance of a matched sample of patients with an antiepileptic medication other than TPM (N = 351), untreated patients (N = 108), and healthy controls (N = 100). RESULTS: Impaired verbal fluency performance was seen in 77% of the patients treated with TPM. Compared to healthy controls, verbal fluency in untreated patients was reduced by 22%, under monotherapy without TPM by 31% and under TPM monotherapy by 45%. With and without TPM, verbal fluency performance linearly decreased with each additional drug in polytherapy. On each level, performance under TPM was 21-28% worse than in the respective condition without TPM. Unimpaired performance under TPM was primarily associated with lower dose, higher education, and a later onset of epilepsy. CONCLUSIONS: The majority of patients under TPM shows reduced verbal fluency. However, when taking the cumulative negative effects of epilepsy, and the concomitant drug regimen into account, TPM is associated with a 21-28% poorer performance as compared with other drugs. Additionally, the data indicate an impact of dose and reserve capacity on the occurrence of impairments.