Abnormal Brainstem Research Articles

Lundberg and his Waves.

This historical vignette revisits the main contributions by Nils Lundberg, a neurosurgeon, that were published in the late 1950s and early 1960s. The Lundberg studies also definitively established that symptoms of abnormal brainstem function resulted from abnormal intracranial pressure (ICP), and moreover, even variations in ICP could produce clinical symptoms. The most innovative result of continuous monitoring was the discovery of plateau-shaped waves that produced paradoxical symptoms previously designated as "decerebrate" and "tonic fits" or "acute coning."

Lasmiditan: new drug for acute migraine

Migraine is ranked by the World Health Organization as the world’s second leading cause of disability. The current state of knowledge suggests that migraine is a neuronal process involving activation and sensitization of the trigeminal nociceptors and the trigeminocervical complex, as well as cortical spreading depression and abnormal brainstem activity. The present non vascular etiological basis has opened a new horizon in the treatment of acute migraine targeting the trigeminal pathways. Lasmiditan, a highly selective 5-HT1F receptor agonist, acts on the trigeminal system without causing vasoconstriction because of its low affinity for 5-HT1B receptors. The compound belongs to a new class of drugs “ditans” and its mechanism of action is neuronal without evidence of vasoactive effects as seen with triptans. It lowers plasma protein extravasation decreasing the neurogenic inflammation of the dura and suppress neuronal firing within the trigeminal nucleus caudalis. Also, 5HT1F agonists have shown to decrease c-fos activity within trigeminal nucleus thereby reducing the level of synaptic activation. The onset of action of lasmiditan is fast, shows rapid absorption, oral bioavailability of 40% and linear pharmacokinetics. Most common adverse reactions seen are dizziness, paresthesia, somnolence, nausea, fatigue and lethargy with dizziness being the most recurrently reported adverse event. Clinical trials for lasmiditan to date have been positive, and maiden results suggest that lasmiditan may be a new safe and effective option for acute migraine treatment, especially for patients refractory to or unable to tolerate triptans, and/or for patients with pre-existing cardiovascular disease. With Eli Lilly and Co. having already applied for US FDA approval in Nov 2018, lasmiditan may soon be a new addition to the mounting armoury of drugs against migraine.

Vestibular Evoked Myogenic Potentials Are Abnormal in Idiopathic REM Sleep Behavior Disorder

Objectives: To investigate brainstem function in idiopathic REM sleep Behavior Disorder (iRBD), a condition occurring as a result of a derangement of connections within brainstem structures, with a battery of Vestibular Evoked Myogenic Potentials (VEMPs), neurophysiological tools suited for the functional investigation of the brainstem. Neurophysiological data were correlated with clinical characteristics of patients.Methods: Twenty patients with iRBD and 22 healthy controls underwent cervical (cVEMP), masseter (mVEMP) and ocular (oVEMP) VEMP recording. Patients were assessed clinically according to presence of motor as well as non-motor symptoms such as constipation, depression, and hyposmia. Also, they were screened for postural instability through the Berg Balance Scale (BBS). VEMPs were categorized as for increasing degrees of abnormalities, namely latency delay, amplitude reduction and absence; a VEMP score was built accordingly.Results: Compared with controls, iRBD had higher rates of abnormalities both in the VEMP battery (iRBD 75%, Controls 23%; p < 0.01) as well as in each single VEMP (cVEMP: 45 vs. 5%; mVEMP: 65 vs. 13.6%; oVEMP: 50 vs. 5%; p < 0.01), which exhibited significantly lower amplitudes (cVEMP and oVEMP: p < 0.0001; mVEMP: p = 0.001) in iRBD. Within altered reflexes, absence was predominant in oVEMP (81%), amplitude reduction in mVEMP (50%) and cVEMP (70%). Severity of VEMP alterations was significantly higher in iRBD compared with controls (p < 0.05 for all VEMPs), as indicated by the larger VEMP scores in the former. The oVEMP score correlated inversely with poor performances on the BBS.Conclusion: VEMPs unveil consistent and extensive brainstem abnormalities in iRBD patients. Further studies are warranted for testing the potential of VEMPs in the monitoring of the evolution of iRBD over time.

289 MRI abnormalities in mog antibody disease

AimsTo analyse the MRI abnormalities of myelin oligodendrocyte glycoprotein-antibody (MOG-Ab) associated demyelinating disease.MethodsClinical records and 165 MRIs from 56 patients with MOG-Abs were reviewed.ResultsThe median age was 29(8–71) years and 52% percent were female. Common phenotypes included isolated optic neuritis (ON)=17, or transverse myelitis (TM)=16, ON+TM =12, and combinations of above groups with cerebral and/or brainstem involvement=11. Seventeen patients (30%) fulfilled NMOSD 2015 diagnostic criteria.All patients had brain imaging and 89% (50/56) had spinal imaging. Common areas of MRI brain abnormality involved brainstem(32%), hemispheric white matter(29%), corticospinal tracts(21%), and U-fibres(20%). Dawson’s fingers were not detected in any patients.Cord imaging showed longitudinally extensive myelitis in 69% (20/29) and atrophy in 4% (2/47). Optic nerve imaging was abnormal in 69% (18/26) of patients, with bilateral lesions in 33% and long lesions (orbital and/or canalicular) in 83%. On serial MRI, radiological improvement was observed in 76% (22/29; median interval- 14 months) and importantly asymptomatic new lesions were absent in 13 untreated patients after a median of 16.5 months.ConclusionsApart from optic nerve and spinal cord changes, brainstem and hemispheric white matter abnormalities are common in MOG-antibody disease. Irrespective of treatment, asymptomatic accrual of brain and/or spinal lesions is uncommon.

Hyperbilirubinemia in preterm infants in Japan: New treatment criteria.

In 1992, Kobe University proposed treatment criteria for hyperbilirubinemia in newborns using total serum bilirubin and serum unbound bilirubin reference values. In the last decade, chronic bilirubin encephalopathy has been found to develop in preterm infants in Japan because it can now be clinically diagnosed based on an abnormal signal of the globus pallidus on T2-weighted magnetic resonance imaging and abnormal auditory brainstem response with or without apparent hearing loss, along with physical findings of kinetic disorders with athetosis. We therefore revised the Kobe University treatment criteria for preterm hyperbilirubinemic infants in 2017. The three revised points are as follows: (i) newborns are classified under gestational age at birth or corrected gestational age, not birthweight; (ii) three treatment options were created: standard phototherapy, intensive phototherapy, and albumin therapy and/or exchange blood transfusion; and (iii) initiation of standard phototherapy, intensive phototherapy, and albumin therapy and/or exchange blood transfusion is decided based on the total serum bilirubin and serum unbound bilirubin reference values for gestational weeks at birth at <7days of age, and on the reference values for corrected gestational age at ≥7days of age. Studies are needed to establish whether chronic bilirubin encephalopathy can be prevented using the 2017 revised Kobe University treatment criteria for preterm infants in Japan.

Research progress on auditory neuropathy spectrum disorder and cochlear implantation in infants and young children

Auditory neuropathy is a disorder characterized by absent or severely abnormal auditory brainstem response (ABR) with intact outer hair cell function, as evidenced by the presence of evoked otoacoustic emissions and/or cochlear microphonics. Unlike patients with sensory hearing loss who show clinical evidence of impaired outer hair cell function. For ANSD patients, clinical rehabilitation is mainly limited to hearing aid wearing and cochlear implantation. However, the effect of cochlear implantation for ANSD patients may be difference. The outcome of cochlear implantation is related to the lesion location, the age of implantation and the diameter of cochlear nerve.

Auditory Brainstem Pathology in Autism Spectrum Disorder: A Review

Atypical responses to sound are common in individuals with autism spectrum disorder (ASD), and growing evidence suggests an underlying auditory brainstem pathology. This review of the literature provides a comprehensive account of the structural and functional evidence for auditory brainstem abnormalities in ASD. The studies reviewed were published between 1975 and 2016 and were sourced from multiple online databases. Indices of both the quantity and quality of the studies reviewed are considered. Findings show converging evidence for auditory brainstem pathology in ASD, although the specific functions and anatomical structures involved remain equivocal. Two main trends emerge from the literature: (1) abnormalities occur mainly at higher levels of the auditory brainstem, according to structural imaging and electrophysiology studies; and (2) brainstem abnormalities appear to be more common in younger than older children with ASD. These findings suggest delayed maturation of neural transmission pathways between lower and higher levels of the brainstem and are consistent with the auditory disorders commonly observed in ASD, including atypical sound sensitivity, poor sound localization, and difficulty listening in background noise. Limitations of existing studies are discussed, and recommendations for future research are offered.

Repeated Prenatal Exposure to Valproic Acid Results in Auditory Brainstem Hypoplasia and Reduced Calcium Binding Protein Immunolabeling

Auditory dysfunction is a common occurrence in individuals with autism spectrum disorder (ASD). While most cases of ASD are of unknown etiology, in utero exposure to the antiepileptic valproic acid (VPA) significantly increases risk. We have previously identified significant dysmorphology and hypoplasia in the auditory brainstem of humans with ASD and rodents exposed to VPA in utero. Further, we have identified abnormal c-Fos immunolabeling patterns after exposure to pure tone stimuli in VPA-exposed animals. Herein, we describe the impact of repeated exposure to VPA on key components of the auditory hindbrain, the ventral cochlear nucleus (VCN) and superior olivary complex (SOC). Specifically, we examined neuronal number, neuronal morphology, immunolabeling for the calcium binding proteins calbindin (CB) and calretinin (CR), dopaminergic innervation and the structure of calyx terminals in the medial nucleus of the trapezoid body (MNTB). VPA-exposed animals had significantly fewer neurons in both the VCN and SOC. VPA had a differential impact on the size of neurons in the VCN and SOC. VPA-exposed animals have reduced CB and CR immunolabeling and a lower density of dopaminergic terminals. Finally, we saw no difference in the surface area or volume of calyx terminals in the MNTB, although there was a relative increase in the surface area and volume of calyces in VPA-exposed animals. These results indicate hypotrophy of the auditory brainstem, abnormal calcium regulation and reduced dopaminergic input. Together, such alterations suggest abnormal brainstem circuitry and significant auditory dysfunction in VPA-exposed animals.

Auditory and non-auditory effects of asymmetrical hearing loss in animal models

Animal models offer an opportunity to investigate the consequences of asymmetrical hearing loss with a level of control over extraneous variables that is not possible with human listeners. Experimental manipulations to induce unilateral conductive or sensorineural hearing loss in animal models have demonstrated substantial and diverse changes in physiological function, anatomical reorganization of neural projections, and adverse effects on auditory behaviors. Our experiments in rodents exposed to acoustic trauma with one ear plugged result in asymmetrical hearing loss and abnormal auditory brainstem response waveforms that occur when either the unprotected or protected ear is stimulated. Susceptibility to auditory brainstem response deficits appears to differ between the right and left sides. Asymmetrical hearing loss is associated with increased startle reactivity to loud sounds, suggesting abnormal loudness perception or an increased emotional response to sound. These animals also show abnormal social interaction, and some subjects show reduced exploratory behavior in a novel environment indicative of heightened anxiety. These studies provide a framework for investigating the interplay between the auditory and non-auditory behavioral consequences of hearing loss, as well as the underlying neuropathology.Animal models offer an opportunity to investigate the consequences of asymmetrical hearing loss with a level of control over extraneous variables that is not possible with human listeners. Experimental manipulations to induce unilateral conductive or sensorineural hearing loss in animal models have demonstrated substantial and diverse changes in physiological function, anatomical reorganization of neural projections, and adverse effects on auditory behaviors. Our experiments in rodents exposed to acoustic trauma with one ear plugged result in asymmetrical hearing loss and abnormal auditory brainstem response waveforms that occur when either the unprotected or protected ear is stimulated. Susceptibility to auditory brainstem response deficits appears to differ between the right and left sides. Asymmetrical hearing loss is associated with increased startle reactivity to loud sounds, suggesting abnormal loudness perception or an increased emotional response to sound. These animals also show abnormal social i...

Trismus caused by paraneoplastic brainstem encephalitis

We discuss the assessment and differential diagnoses of a middle-aged man who presented with trismus, double vision and behavioural problems. MRI scan of the brain was initially normal, but a...

Hyperintense sensorimotor T1 spin echo MRI is associated with brainstem abnormality in chronic fatigue syndrome.

We recruited 43 Chronic Fatigue Syndrome (CFS) subjects who met Fukuda criteria and 27 healthy controls and performed 3T MRI T1 and T2 weighted spin-echo (T1wSE and T2wSE) scans. T1wSE signal follows T1 relaxation rate (1/T1 relaxation time) and responds to myelin and iron (ferritin) concentrations. We performed MRI signal level group comparisons with SPM12. Spatial normalization after segmentation was performed using T2wSE scans and applied to the coregistered T1wSE scans. After global signal-level normalization of individual scans, the T1wSE group comparison detected decreased signal-levels in CFS in a brainstem region (cluster-based inference controlled for family wise error rate, PFWE= 0.002), and increased signal-levels in large bilateral clusters in sensorimotor cortex white matter (cluster PFWE < 0.0001). Moreover, the brainstem T1wSE values were negatively correlated with the sensorimotor values for both CFS (R2 = 0.31, P = 0.00007) and healthy controls (R2 = 0.34, P = 0.0009), and the regressions were co-linear. This relationship, previously unreported in either healthy controls or CFS, in view of known thalamic projection-fibre plasticity, suggests brainstem conduction deficits in CFS may stimulate the upregulation of myelin in the sensorimotor cortex to maintain brainstem – sensorimotor connectivity. VBM did not find group differences in regional grey matter or white matter volumes. We argued that increased T1wSE observed in sensorimotor WM in CFS indicates increased myelination which is a regulatory response to deficits in the brainstem although the causality cannot be tested in this study. Altered brainstem myelin may have broad consequences for cerebral function and should be a focus of future research.

Clinical profile and the outcome of children admitted to a tertiary care hospital with non-traumatic coma

Objective: To study the clinical profile, the outcome and to determine clinical signs predictive of the outcome in pediatric patients admitted with non-traumatic coma. Methods: This prospective study was conducted over a period of two years on 150 children between age group 2 months and 14 years admitted with non-traumatic coma to the PICU of a tertiary care state government run hospital of eastern India. Clinical parameters at admission and at 48 hours were analysed. Relevant laboratory investigations and radiological studies were documented. Outcomes were analysed at the time of discharge or death. Results: CNS infection was the leading cause of coma in 57.3 % of the cases, out of which acute bacterial meningitis in 38.4% cases, encephalitis in 33.7% cases, cerebral malaria in 18.6% cases and tuberculous meningitis in 9.3% cases. The toxic-metabolic conditions (21.3%) were overall second followed by status epilepticus (7.4%), intracranial haemorrhage (4%), and others (10%). Among the 99 (66%) children survived, 59(39.3%) were normal, 17(11.3%) had mild, 17(11.3%) had moderate and 6(4%) had severe disability. Survival was highest in ischemic stroke patients (100%) followed by patients with CNS infection (71%). Poor pulse volume, abnormal blood pressure, respiratory pattern, poor GCS and abnormal brain stem reflexes at admission or at 48 hours showed significant correlation with mortality. The abnormal heart rate, abnormal motor pattern, the presence of papilledema and convulsion if present at 48 hrs were poor predictors of survival. Conclusion: CNS infection was the commonest aetiology and clinical signs at 48 hrs of admission were important predictors of mortality.

The effects of stimulus rate on ABR morphology and its relationship to P1 CAEP responses and auditory speech perception outcomes in children with auditory neuropathy spectrum disorder: evidence from case reports

Objective: Auditory neuropathy spectrum disorder (ANSD) affects approximately 5–15% of children with sensorineural hearing loss (SNHL). ANSD is characterized by the presence of otoacoustic emissions (OAE) and an absent or abnormal auditory brainstem response (ABR). The purpose of this study was to investigate the prognostic value of slow-rate ABR in predicting the auditory cortical development and auditory speech perception outcomes in case studies of children with ANSD.Design: ABR waveform characteristics were collected at slow stimulation rates (5.1 clicks/second) and a fast stimulation rates (>11–31.1 clicks/second, rates typically used in a clinical setting) in three case reports of children with ANSD. P1 CAEP responses and measures of auditory speech perception using the Infant Toddler Meaningful Auditory Integration Scale (IT-MAIS) were also collected in these children. Retrospective analysis was performed to evaluate the prognostic value of slow- versus fast-rate ABR in predicting P1 CAEP responses and auditory speech perception outcomes in these children.Study sample: Participants included case reports of three paediatric participants with a clinical diagnosis of ANSD.Results: Slow-rate ABR did not elicit significant improvements in waveform morphology compared to fast-rate ABR. P1 CAEP results were present in 2 out of 3 cases and were consistent with auditory speech perception outcomes.Conclusions: Even when ABR stimulation rates were slowed, ABR responses in these children with ANSD did not display any characteristic or replicable pattern, and ABR responses were not predictive of cortical auditory maturation or behavioural performance. In contrast, P1 CAEP responses provided valuable information regarding the maturational status of the auditory cortex and P1 CAEP responses were consistent with behavioural measures of auditory speech perception. Overall, results highlight the high prognostic value of P1 CAEP testing when used in conjunction with behavioural measures of auditory speech perception in children with ANSD.

Efficacy of antiviral treatment on abnormal auditory brainstem responses in congenital cytomegalovirus-infected infants

Efficacy of antiviral treatment on abnormal auditory brainstem responses in congenital cytomegalovirus-infected infants

“Kinks and Clefts”: A Review of Congenital Brain Stem Abnormalities

“Kinks and Clefts”: A Review of Congenital Brain Stem Abnormalities

Improving the efficiency of Auditory Brainstem Responses in newborns, using a 60 clicks/s stimulation rate

Recent evidence suggests that Auditory Brainstem Responses (ABR), in neonates with risk factors for neurological damage, may show auditory brainstem abnormalities, even in patients with normal hearing. To compare the recording and diagnostic accuracy of neonatal Auditory Brainstem Responses (ABR), using 10 and 60clicks/s stimulation rates, two groups of neonates were prospectively studied: 30 healthy full-term neonates, with no peri- or postnatal complications; and 30 high-risk newborns with two or more of the following conditions: hyperbilirubinemia, use of ototoxic drugs, birth weight inferior to 1500g, perinatal sepsis, intraventricular hemorrhage, and/or mechanical ventilation. Correlation between ABR trials, recording duration, and the absolute and interpeak latencies of ABR waves I, III and V, were measured. ROC-curve analysis assessed the diagnostic accuracy of both stimulation rates. The correlations between ABRs trials were significantly higher at 60clicks/s than at 10clicks/s (F(1,116)=14.5, p<0.0002). Recording duration at 60clicks/s was significantly lower (t=20.9, p<0.0001). ROC-curve comparisons showed increased diagnostic accuracy at the stimulation rate of 60clicks/s, for waves I (D=2.04, p=0.04), V (D=2.02, p=0.04), interpeak latencies III-V (D=2.2, p=0.02), and I-V (D=2.86, p=0.004). In neonates, the use of 60clicks/s stimulation rate permits a substantial shortening of the ABR recording, with greater diagnostic accuracy and replicability.

Clinical Characteristics of Severe Japanese Encephalitis: A Case Series from South Korea.

Japanese encephalitis (JE) virus is a major cause of devastating viral encephalitis, especially in Asia. Although a successful vaccination program led to its near-elimination over three decades in South Korea, the incidence of JE has increased since 2010. The present study investigated the clinical manifestations, laboratory findings, and factors affecting neurological outcomes of reemerging JE. We retrospectively reviewed medical records of laboratory-confirmed JE patients who presented with acute encephalitis syndrome at three tertiary hospitals between 2010 and 2015. A total of 17 patients with JE were identified. Their median age was 51 years, and 10 (58.5%) were men. The most common symptoms and signs were fever (94.1%), altered consciousness (94.1%), and headache (80.2%). Hyporeflexia (47.1%), seizures (35.2%), abnormal brainstem reflex (23.5%), and flaccid weakness (17.6%) were also noted. Brain imaging revealed thalamic lesions in all patients, with the hippocampus, midbrain, basal ganglia, and cerebral cortex affected to varying degrees. Sixteen patients (94.1%) required management in the intensive care unit with mechanical ventilation due to neurological deterioration. At the time of discharge, 11 (64.7%) had poor recovery, defined as Glasgow coma scale scores of less than 8, and remained ventilator dependent. Comparison between the two outcome groups indicated that midbrain involvement (P = 0.028) and rapid deterioration (P = 0.005) were associated with severe neurological sequelae. Given that JE is a vaccine-preventable disease, vaccination for adults should be considered in response to the reemergence of JE.

Transcranial sonography image characteristics in different Parkinson's disease subtypes.

Recently, Parkinson's disease (PD) has been classified into three subtypes: postural instability gait difficulty (PIGD), tremor dominate (TD), and indeterminate PD. Transcranial sonography (TCS) is considered to be an important tool to diagnose PD. However, it is uncertain that whether there are differences in TCS image characteristics in different PD subtypes, so 373 idiopathic PD (188 PIGD, 108 TD, 77 indeterminate PD) were registered and received TCS in our investigation; also, the association between clinical characteristics and TCS results in different PD subtypes was analyzed. In accordance with several previous studies, we detected substantia nigra (SN) by TCS in 85.4% of patients with idiopathic PD; we concluded that PIGD patients had more serious disease than TD and indeterminate PD group (p<0.05). They always had larger SN hyperechogenicity areas on TCS (p<0.05), and we found that there was no correlation between SN hyperechogenicity and disease duration or severity (p>0.05). Similarly, abnormal brainstem raphe signal was also more often in PIGD group than in TD and indeterminate PD group (p<0.05), which might imply that PIGD group was vulnerable to suffer from depression in the future.

BRAINSTEM NEURONAL LOSS OCCURRING INDEPENDENTLY FROM NEOCORTICAL ALZHEIMER, LEWY BODY, OR FOCAL ISCHEMIC LESIONS IS COMMON AND SIGNIFICANTLY ASSOCIATED WITH BOTH MOTOR AND COGNITIVE IMPAIRMENT IN AUTOPSIED HONOLULU-ASIA AGING STUDY DECEDENTS

The neuropathologic abnormalities to which aging-related cognitive impairment is commonly attributed include neocortical neurofibrillary tangles, neuritic amyloid plaques, cortical Lewy bodies, hippocampal sclerosis, and vascular brain injury with microinfarcts and/or lacunar infarcts. Motor impairments are very common with aging and occur often but not invariably with dementia. The brain abnormalities generally recognized as common and relevant to motor impairments are infarcts, hemorrhage, and Lewy bodies in the substantia nigra, Repeated cognitive and motor function assessments were carried out over two decades on Japanese-American male Honolulu-Asia Aging Study participants. This analysis was carried out on 774 HAAS decedents who received comprehensive, highly standardized brain autopsies at death. Cognitive assessments utilized the Cognitive Assessment and Screening Instrument. Grip strength, walking speed, stride length, turn around steps, turn around time, chair stands, and standing balance were assessed on 6 occasions. Analyses utilized graphic and tabular visual representation plus linear and logistic regression statistical modeling. Decedents with cognitive impairment but little or no motor impairment were found at autopsy to have neocortical neurofibrillary tangles and amyloid plaques, microinfarcts and/or lacunar infarcts, and hippocampal sclerosis, but negligible striatal, cerebellar, or brainstem abnormalities. Those who had both cognitive and motor impairments had these same lesions plus neocortical Lewy bodies, generalized brain atrophy, and striatal and brainstem neuronal loss and gliosis. In a subset of autopsied cases without neocortical Alzheimer lesions, Lewy bodies (brainstem or neocortex), microinfarcts, or hippocampal sclerosis, neuronal loss and gliosis observed in the brainstem was nonetheless significantly associated with both cognitive and motor impairments. These findings suggest that linked cognitive and motor impairments may be associated with brainstem neuronal injury due in part to currently undefined disease processes distinct from other neuropathologic processes represented by neocortical Alzheimer lesions, Lewy bodies, vascular brain injury, and/or hippocampal sclerosis.

Exposures to fine particulate matter (PM2.5) and ozone above USA standards are associated with auditory brainstem dysmorphology and abnormal auditory brainstem evoked potentials in healthy young dogs

BackgroundDelayed central conduction times in the auditory brainstem have been observed in Mexico City (MC) healthy children exposed to fine particulate matter (PM2.5) and ozone (O3) above the current United States Environmental Protection Agency (US-EPA) standards. MC children have α synuclein brainstem accumulation and medial superior olivary complex (MSO) dysmorphology. The present study used a dog model to investigate the potential effects of air pollution on the function and morphology of the auditory brainstem. MethodologyTwenty-four dogs living in clean air v MC, average age 37.1 ± 26.3 months, underwent brainstem auditory evoked potential (BAEP) measurements. Eight dogs (4 MC, 4 Controls) were analysed for auditory brainstem morphology and histopathology. ResultsMC dogs showed ventral cochlear nuclei hypotrophy and MSO dysmorphology with a significant decrease in cell body size, decreased neuronal packing density with regions in the nucleus devoid of neurons and marked gliosis. MC dogs showed significant delayed BAEP absolute wave I, III and V latencies compared to controls. ConclusionsMC dogs show auditory nuclei dysmorphology and BAEPs consistent with an alteration of the generator sites of the auditory brainstem response waveform. This study puts forward the usefulness of BAEPs to study auditory brainstem neurodegenerative changes associated with air pollution in dogs. Recognition of the role of non-invasive BAEPs in urban dogs is warranted to elucidate novel neurodegenerative pathways link to air pollution and a promising early diagnostic strategy for Alzheimer's Disease.