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There is international variability in whether neurological determination of death (NDD) is conceptually defined based on permanent loss of brainstem function or “whole brain death.” Canadian guidelines are not definitive. Patients with infratentorial stroke may meet clinical criteria for NDD despite persistent cerebral blood flow (CBF) and relative absence of supratentorial injury.
We performed a multicenter cohort study involving patients that died from ischemic or hemorrhagic stroke in Alberta intensive care units from 2013 to 2019, focusing on those with infratentorial involvement. Medical records were reviewed to determine the incidence and proportion of patients that met clinical criteria for NDD; whether ancillary testing was performed; and if so, whether this demonstrated the absence of CBF.
There were 95 (27%) deaths from infratentorial and 263 (73%) from supratentorial stroke. Sixteen patients (17%) with infratentorial stroke had neurological examination consistent with NDD (0.55 cases per million per year). Among patients that underwent confirmatory evaluation for NDD with an apnea test, ancillary test (radionuclide scan), or both, ancillary testing was more common with infratentorial compared with supratentorial stroke (10/12 (85%) vs. 25/47 (53%), p = 0.04). Persistent CBF was detected in 6/10 (60%) patients with infratentorial compared with 0/25 with supratentorial stroke (p = 0.0001).
Infratentorial stroke leading to clinical criteria for NDD occurs with an annual incidence of about 0.55 per million. There is variability in clinicians’ use of ancillary testing. Persistent CBF was detected in more than half of patients that underwent radionuclide scans. Canadian consensus is needed to guide clinical practice.
This chapter looks at the state of sleep and its biology. it begins by looking at what comprises the state of sleep, and examines comparatively which, and how, other animals sleep. It looks at circadian rhythms, and how the sleep--wake cycle is controlled, with melatonin manufactured by the pineal gland. There is emphasis on the electrophysiology of sleep (sleep EEG), and a description of the stages of sleep and how they are characterised by different EEG profiles, particularly the distinction between REM and non-REM sleep. The neurology of sleep looks at the role of structures such as the brainstem and reticular activating system, and the effect of damage at different levels of the brain on sleeping behaviour. The psychopharmacology of sleep looks at the changing role of neurotransmitters throughout the day and night, and in dreaming and dreamless sleep. The chapter then examines the range of sleep disorders, including problems getting to sleep, as well as sleep walking and sleep talking. It then looks at the effects of sleep deprivation. The chapter concludes with a discussion of why we sleep, covering the possible evolutionary functions of sleep, with focus on the role of sleep in learning and memory consolidation.
To determine the clinical significance of arachnoid cysts.
The scans of 6978 patients undergoing magnetic resonance imaging of the internal acoustic meatus for unilateral cochleovestibular symptoms were retrospectively reviewed. We identified the scans with arachnoid cysts, and assessed the statistical associations between the laterality, location and size of the arachnoid cyst, the laterality of symptoms, the patients’ age and gender.
In a total of 37 arachnoid cysts identified in 36 patients (0.5 per cent), no associations were identified between the laterality of symptoms and the laterality of the arachnoid cyst, regardless of its size or location. There were no significant associations between the location of the arachnoid cyst and the age (p = 0.99) or gender of the patient (p = 0.13), or size (p = 0.656) or side of the cyst (p = 0.61). None of the cysts with repeat imaging scans (17 cysts) demonstrated growth.
Our results suggest that most, if not all, arachnoid cysts are of no clinical significance. Given their indolent behaviour, even serial imaging is not essential.
To determine the characteristics of acute phase nystagmus in patients with cerebellar lesions, and to identify a useful indicator for differentiating central lesions from peripheral lesions.
Acute phase nystagmus and the appearance of neurological symptoms were retrospectively investigated in 11 patients with cerebellar stroke.
At the initial visit, there were no patients with vertical nystagmus, direction-changing gaze evoked nystagmus or pure rotatory nystagmus. There were four cases with no nystagmus and seven cases with horizontal nystagmus at the initial visit. There were no neurological symptoms, except for vertigo and hearing loss, in any cases at the initial visit. The direction and type of nystagmus changed with time, and neurological symptoms other than vertigo appeared subsequently to admission.
It is important to observe the changes in nystagmus and other neurological findings for the differential diagnosis of central lesions.
The nasal cycle exhibits mainly reciprocal changes in nasal airflow that may be controlled from centres in the hypothalamus and brainstem. This study aims to gather new knowledge about the nasal cycle to help develop a control model.
Right and left nasal airflow was measured in healthy human subjects by rhinomanometry. This was performed over 7-hour periods on 2 study days separated by approximately 1 week. The correlation coefficient for nasal airflow was calculated for day 1 and day 2.
Thirty subjects (mean age, 22.7 years) completed the study. The correlation coefficient for nasal airflow varied between r = 0.97 with in-phase changes in airflow and r = −0.89 with reciprocal changes in airflow. The majority of r values were negative, indicating reciprocal changes in airflow (50 out of 60). There was a tendency for r values to become more negative between day 1 and day 2 (p < 0.001).
A control model involving a hypothalamic centre and two brainstem half centres is proposed to explain both the in-phase and reciprocal changes in airflow associated with the nasal cycle.
The brainstem-derived neuropeptide S (NPS) has a multidirectional regulatory activity, especially as a potent anxiolytic factor. Accumulating data suggests that neuroleptics affect peptidergic signalling in various brain structures. However, there is no information regarding the influence of haloperidol on NPS and NPS receptor (NPSR) expression.
We assessed NPS and NPSR mRNA levels in brains of rats treated with haloperidol using quantitative real-time polymerase chain reaction.
Chronic haloperidol treatment (4 weeks) led to a striking upregulation of NPS and NPSR expression in the rat brainstem. Conversely, the NPSR mRNA expression was decreased in the hippocampus and striatum.
This stark increase of NPS in response to haloperidol treatment supports the hypothesis that this neuropeptide is involved in the dopamine-dependent anxiolytic actions of neuroleptics and possibly also in the pathophysiology of mental disorders. Furthermore, our findings underline the complex nature of potential interactions between dopamine receptors and brain peptidergic pathways, which has potential clinical applications.
Numerous findings of brain structural changes in obstructive sleep apnea (OSA) give strong support to the notion that the disorder does cause brain injury. This chapter describes findings by technique, influences of factors other than the sleep disordered breathing on structural changes in OSA, and a summary of the brain regions shown across multiple studies to be affected in the disorder. Psychological symptoms of depression and anxiety are associated with neural changes in non-OSA populations, so one can hypothesize that the structural changes in OSA would be exacerbated in the presence of these symptoms. Many areas in the brain show structural impairments in OSA, including cortical, limbic, brainstem and cerebellar regions. Neuroimaging methods give numerical measures that are associated with a variety of biological pathologies, and technical limitations due to scanning and analysis issues limit the interpretability of the data.
This chapter reviews brain imaging studies that comment on whether or not there is abnormal brain function in insomnia patients that may in some way relate to their difficulty in sleeping. It provides a systems neuroscience view of a hierarchical arousal network in the central nervous system. Human sleep neuroimaging studies in healthy subjects support the involvement of these basic arousal networks in non-rapid eye movement (NREM) sleep. Blood flow has been shown to correlate negatively with the presence of NREM sleep in the pontine reticular formation, and in the basal forebrain/hypothalamus. Pharmacotherapy for insomnia may have some of its mechanism of action on the limbic and paralimbic structures, especially the antidepressant medications. Traditional sedative-hypnotic approaches appear to target brainstem and hypothalamic arousal networks in insomnia patients while behavioral treatments and frontal cerebral hypothermia appear to target frontal hyperarousal in insomnia patients.
This chapter focuses on aspects of structural and functional neuroanatomy relevant to Behavioral Neurology & Neuropsychiatry (BN&NP). It considers the general structure of the brain from the brainstem through the cerebral cortex, including a review of white matter anatomy, the cerebral vasculature, and the ventricular system. The brainstem comprises the medulla oblongata, pons and cerebellum, and midbrain. Each of these areas and the neurobehaviorally salient structures they contain are reviewed briefly in the chapter. The reticular formation (which is contributed to by several brainstem substructures) and the cranial nerves (some, but not all, of which are located within the brainstem) also are discussed in the chapter. The diencephalon includes the thalamus, metathalamus (medial and lateral geniculate nuclei), epithalamus (habenula, stria medullaris, and pineal body), and subthalamus. The chapter considers briefly the thalamus, hypothalamus (and pituitary), and the epithalamus.
The advent of neuroimaging has allowed clinicians to improve clinico-anatomical correlations in stroke patients. Arterial trunks supplying the brainstem include: the vertebral artery, basilar artery, anterior and posterior spinal arteries, posterior inferior cerebellar artery, anterior inferior cerebellar artery, superior cerebellar artery, posterior cerebral artery, and anterior choroidal artery. The arterial supply of the medulla oblongata comes from the vertebral arteries that form the middle rami of the lateral medullary fossa, the posterior inferior cerebellar artery that gives rise to the inferior rami of the lateral medullary fossa, and the anterior and posterior spinal arteries. Different arterial trunks supply blood to the pons, including the vertebral arteries, anterior inferior cerebellar artery, superior cerebellar artery, and basilar artery. The leptomeningeal arteries consist of the terminal branches of the anterior, middle, and posterior cerebral arteries forming an anastomotic network on the surface of the hemispheres.
Severe ischemic stroke with progressive edema development is frequently life-threatening and associated with a poor prognosis due to limited expandability within the cranial cavity. This chapter describes the relevant aspects of supra- and infratentorial space-occupying strokes with particular emphasis on the role of decompressive surgery. Large ischemic infarction of the middle cerebral artery (MCA) territory can lead to a clinical syndrome called malignant MCA stroke. Cranial computed tomography (CT) is still the most widely used radiological modality to diagnose and monitor malignant MCA infarction. The only specific treatment option for this type of stroke with a solid base of evidence and major impact on the clinical course to date is decompressive surgery, that is, hemicraniectomy. Swelling of a large space-occupying cerebellar infarct appears within a few days from symptom onset and can lead to compression of the brainstem and midbrain or cause a hydrocephalus.
This chapter talks about a 54-year-old right-handed man who was brought to medical attention by his daughter because of progressive speech difficulty over the last 2 years. The patient was clinically diagnosed with fronto-temporal dementia with non-fluent progressive aphasia as well as behavioral symptoms. Sensory and motor nerve conduction studies were normal. EMG needle electromyography showed mixed denervation pattern in the right FDI and left biceps with 2_ fasciculation potentials, positive sharp waves, and fibrillations. Motor units were polyphasic with increase in sharp waves. External examination of the formalin-fixed brain showed no obvious cerebral atrophy or no focal lesions. The base of the brain was unremarkable apart from mild patchy atherosclerosis. Serial coronal sections through the cerebral hemispheres showed a normal ventricular system and deep gray structures. Sections of the brainstem and cerebellum were also unremarkable apart from mild loss of pigmentation of substantia nigra.
Tinnitus is a disturbing symptom and is often the main reason for otology referral. It is usually associated with hearing loss of varying aetiology, and is thought to begin in the cochlea, with later abnormal central activity. We hypothesise that tinnitus without hearing loss may be caused by central and subcortical abnormalities and altered outer hair cell function.
To compare the auditory brainstem responses, middle latency responses and otoacoustic emissions in normal-hearing individuals with and without tinnitus.
The audiological test results of 25 normal hearing subjects with tinnitus (age 18–45 years) were determined, and compared with those of a control group.
A statistically significant difference was found between study group tinnitus ears vs control group ears, as regards wave I latency prolongation, shortening of wave V and absolute I–III and I–V interpeak latency, enlargement of wave Na and Pa amplitude, and distortion product and transient evoked otoacoustic emission signal-to-noise ratios. There was no statistically significant difference between unilateral vs bilateral tinnitus ears.
The pathogenesis and optimum management of tinnitus are still unclear. It often occurs with primary ear disease, usually associated with hearing loss, but may occur in patients with normal hearing. Observed changes in auditory brainstem and middle latency responses indicate central auditory alterations. Tinnitus involves both peripheral and central activity, and complete audiological and neurophysiological investigation is required. Management should be based on both audiological and neurophysiological findings.
Advances in medical technology and transplantation lead to the re-defining of death to include death by virtue of brain death. The determination of whole brain death requires the demonstration of three things: an irreversible comatose state; the loss of brainstem reflexes; and brainstem inactivity leading to apnea. Protocols for the clinical determination of brain death vary among institutions but must generally be made by more than one doctor in one of several relevant specialties. Neurophysiologic determinations of cerebral circulatory arrest include four-vessel cerebral angiography as well as various scintigraphic perfusion studies. In all countries where brain death is recognized legally, the diagnosis rests with physical examination, at times supported by further medical testing. Philosophical arguments for the integrity of brain death as a definition of death rest in historic religious and social concepts of what constitutes life, or with ideas that loss of personhood may be equivalent to death.
Following surgery in the USA in 1992 to remove a large right cerebello-pontine angle tumour, a 39-year-old woman developed severe brainstem and cerebellar infarction. This left her with severe visual impairment and ataxia. She became able to communicate by means of an adapted finger-spelling alphabet. She had total hearing loss in the right ear and a mild to moderately severe sensorineural hearing loss in the left ear, and severe tinnitus heard throughout the head. Additionally, she experienced hypersensitivity to sound above normal conversational levels, which evoked a synaesthetic feeling of coldness across her upper torso. Previous linear analogue hearing aid fitting had not been beneficial for either hearing or tinnitus. Careful fitting of a digital hearing aid, together with tinnitus counselling, inhibited the patient's tinnitus to 25 per cent of its former intensity after a six month acclimatisation period, and improved communication.
We compared the developmental periods in the mouse when projections from the two eyes become segregated in the dorsal lateral geniculate nucleus with the time when this nucleus becomes innervated by cholinergic fibers from the brainstem. Changes in labeling patterns of different tracers injected into each eye revealed that segregation of retinogeniculate inputs commences at postnatal day five (P5) and is largely complete by P8. Immunocytochemical staining showed that cholinergic neurons are present in the parabrachial region of the brain stem on the day of birth. However, cholinergic fibers are not evident in the geniculate until P5, and these are sparse at this age, increasing in density to form well-defined clusters by P12. These results indicate that segregation of eye-specific projections during normal development is unlikely to be regulated by cholinergic inputs from the brainstem.
There is some experimental evidence to support the existence of a connection between panic and respiration. However, only recent studies investigating the complexity of respiratory physiology have revealed consistent irregularities in respiratory pattern, suggesting that these abnormalities might be a vulnerability factor to panic attacks. The source of the high irregularity observed, together with unpleasant respiratory sensations in patients with panic disorder (PD), is still unclear and different underlying mechanisms might be hypothesized. It could be the result of compensatory responses to abnormal respiratory inputs or an intrinsic deranged activity in the brainstem network shaping the respiratory rhythm. Moreover, since basic physiological functions in the organism are strictly interrelated, with reciprocal modulations and abnormalities in cardiac and balance system function having been described in PD, the respiratory findings might arise from perturbations of these other basic systems or a more general dysfunction of the homeostatic brain. Phylogenetically ancient brain circuits process physiological perceptions/sensations linked to homeostatic functions, such as respiration, and the parabrachial nucleus might filter and integrate interoceptive information from the basic homeostatic functions. These physiological processes take place continuously and subconsciously and only occasionally do they pervade the conscious awareness as ‘primal emotions’. Panic attacks could be the expression of primal emotion arising from an abnormal modulation of the respiratory/homeostatic functions.
A novel auditory brainstem response (ABR) detection and scoring algorithm, entitled the Vector algorithm is described. An independent clinical evaluation of the algorithm using 464 tests (120 non-stimulated and 344 stimulated tests) on 60 infants, with a mean age of approximately 6.5 weeks, estimated test sensitivity greater than 0.99 and test specificity at 0.87 for one test. Specificity was estimated to be greater than 0.95 for a two stage screen. Test times were of the order of 1.5 minutes per ear for detection of an ABR and 4.5 minutes per ear in the absence of a clear response. The Vector algorithm is commercially availablefor both automated screening and threshold estimation in hearing screening devices.