Brainstem Functions and Reflexes No abstract available

Ocular Motor and Vestibular Disorders in Brainstem Disease Summary: The brainstem contains ocular motor and vestibular structures that, when damaged, produce specific eye movement disorders. In this review, we will discuss three brainstem syndromes with characteristic ocular motor and vestibular findings that can be highly localizing. First, we will discuss the lateral medullary (Wallenberg) syndrome, focusing on ocular lateropulsion, saccadic dysmetria, and the ocular tilt reaction. Second, we will review the medial longitudinal fasciculus syndrome including the ocular tilt reaction, nystagmus, and the vestibular-ocular reflex. Lastly, we will discuss hypertrophic olivary degeneration and oculopalatal tremor, which may develop weeks to months after a brainstem or cerebellar lesion. In these syndromes, the clinical ocular motor and vestibular examination is instrumental in localizing the lesion.

Eye Movement Disorders and the Cerebellum Summary: The cerebellum works as a network hub for optimizing eye movements through its mutual connections with the brainstem and beyond. Here, we review three key areas in the cerebellum that are related to the control of eye movements: (1) the flocculus/paraflocculus (tonsil) complex, primarily for high-frequency, transient vestibular responses, and also for smooth pursuit maintenance and steady gaze holding; (2) the nodulus/ventral uvula, primarily for low-frequency, sustained vestibular responses; and (3) the dorsal vermis/posterior fastigial nucleus, primarily for the accuracy of saccades. Although there is no absolute compartmentalization of function within the three major ocular motor areas in the cerebellum, the structural–functional approach provides a framework for assessing ocular motor performance in patients with disease that involves the cerebellum or the brainstem.

Spontaneous, Voluntary, and Reflex Blinking in Clinical Practice Summary: Blinking is one of the motor acts performed more frequently by healthy human subjects. It involves the reciprocal action of at least two muscles: the orbicularis oculi shows a brief phasic activation while the levator palpebrae shows transient inhibition. In clinical practice, noninvasive recording of the orbicularis oculi activity is sufficient to obtain useful information for electrodiagnostic testing. Blinking can be spontaneous, voluntary, or reflex. Although the analysis of spontaneous blinks can already furnish interesting data, most studies are based on reflex blinking. This article is a review of some of the alterations that can be observed in blinking, focusing in four patterns of abnormality that can be distinguished in the blink reflex: (1) afferent versus efferent, which allows characterization of trigeminal or facial lesions; (2) peripheral versus central, which distinguishes alterations in nerve conduction from those involving synaptic delay; (3) upper versus lower brainstem lesions, which indicates the lesions involving specific circuits for trigeminal and somatosensory blink reflexes; and (4) asymmetric abnormal excitability pattern, which shows a unilateral alteration in the descending control of excitability in brainstem circuits. The blink reflex excitability recovery curve to paired stimuli may provide information about other modulatory inputs to trigemino-facial circuits, such as those proposed for the connection between basal ganglia and trigeminal neurons. Finally, prepulse inhibition of blink reflex reflects the motor surrogate of subcortical gating on sensory volleys, which is still another window by which electrodiagnosis can document motor control mechanisms and their abnormalities in neurologic diseases.

Differential Diagnosis of Chronic Neuropathic Orofacial Pain: Role of Clinical Neurophysiology Summary: Orofacial pain syndromes encompass several clinically defined and classified entities. The focus here is on the role of clinical neurophysiologic and psychophysical tests in the diagnosis, differential diagnosis, and pathophysiological mechanisms of definite trigeminal neuropathic pain and other chronic orofacial pain conditions (excluding headache and temporomandibular disorders). The International Classification of Headache Disorders 2018 classifies these facial pain disorders under the heading Painful cranial neuropathies and other facial pains. In addition to unambiguous painful posttraumatic or postherpetic trigeminal neuropathies, burning mouth syndrome, persistent idiopathic facial and dental pain, and trigeminal neuralgia have also been identified with neurophysiologic and quantitative sensory testing to involve the nervous system. Despite normal clinical examination, these all include clusters of patients with evidence for either peripheral or central nervous system pathology compatible with the subclinical end of a continuum of trigeminal neuropathic pain conditions. Useful tests in the diagnostic process include electroneuromyography with specific needle, neurography techniques for the inferior alveolar and infraorbital nerves, brain stem reflex recordings (blink reflex with stimulation of the supraorbital, infraorbital, mental, and lingual nerves; jaw jerk; masseter silent period), evoked potential recordings, and quantitative sensory testing. Habituation of the blink reflex and evoked potential responses to repeated stimuli evaluate top-down inhibition, and navigated transcranial magnetic stimulation allows the mapping of reorganization within the motor cortex in chronic neuropathic pain. With systematic use of neurophysiologic and quantitative sensory testing, many of the current ambiguities in the diagnosis, classification, and understanding of chronic orofacial syndromes can be clarified for clinical practice and future research.

The CPM Effect: Functional Assessment of the Diffuse Noxious Inhibitory Control in Humans Summary: The diffuse noxious inhibitory control, which has been investigated extensively in animals, consists of the inhibitory modulation of pain pathways after heterotopic noxious stimulation. The subnucleus reticularis dorsalis, which lies in the caudal part of the medulla, together with its descending projections to the wide-dynamic-range neurones, is responsible for the diffuse noxious inhibitory control. Many studies have investigated the diffuse noxious inhibitory control phenomenon in humans. However, owing to the complexity of the effect of descending modulation on human pain perception, expert opinion has recommended the term “conditioned pain modulation” to describe the psychophysical paradigm in which a heterotopic noxious stimulus is used to affect pain pathways in humans. In this narrative review, we present the current knowledge on the mechanisms underlying the diffuse noxious inhibitory control in animals and show how this phenomenon can be investigated in humans by using the conditioned pain modulation paradigm. We also demonstrate the relevance of conditioned pain modulation to the pathophysiology of pain.

Transcutaneous Auricular Vagus Nerve Stimulation Summary: Invasive vagus nerve stimulation (VNS) is an approved treatment for drug-resistant epilepsy. Besides recognized clinical efficacy in about 60% of patients, there are major drawbacks such as invasiveness and common side effects including hoarseness, sore throat, shortness of breath, and coughing. Invasive VNS applies electrical stimulation to the left cervical branch of the vagus nerve and excites thick-myelinated afferent nerve fibers. Peripheral vagus nerve afferent volley initiates brainstem activity in the nucleus of the solitary tract and provokes typical brainstem and cerebral activation patterns that mediate the anticonvulsive mode of action. Whereas invasive VNS is an established neuromodulatory treatment in drug-resistant epilepsy, transcutaneous VNS (tVNS) of the auricular branch of the vagus nerve is suggested to be an alternative access path to the same neuronal network without invasiveness. Preclinical and clinical studies indicate that especially the cymba conchae of the auricle is selectively supplied by the auricular branch of the vagus nerve. Recent anatomical data demonstrate existence and quantity of thick-myelinated afferent nerve fibers of the left auricular branch of the vagus nerve that carries 21% of thick-myelinated afferent nerve fibers counted in the left thoracic vagus nerve in humans. Projection of auricular branch of the vagus nerve afferents from the auricle to the nucleus of the solitary tract is known from histochemical and electrophysiological experiments in rodents and confirmed in humans by functional imaging. Cerebral activation patterns triggered by invasive and tVNS resemble each other in appearance. Clinical trials in patients address safety and performance of tVNS and provide evidence for application in drug-resistant epilepsy.

The Vagus and Glossopharyngeal Nerves in Two Autonomic Disorders Summary: The glossopharyngeal and vagus cranial nerves provide the brainstem with sensory inputs from different receptors in the heart, lung, and vasculature. This afferent information is critical for the short-term regulation of arterial blood pressure and the buffering of emotional and physical stressors. Glossopharyngeal afferents supply the medulla with continuous mechanoreceptive signals from baroreceptors at the carotid sinus. Vagal afferents ascending from the heart supply mechanoreceptive signals from baroreceptors in different reflexogenic areas including the aortic arch, atria, ventricles, and pulmonary arteries. Ultimately, afferent information from each of these distinct pressure/volume baroreceptors is all relayed to the nucleus tractus solitarius, integrated within the medulla, and used to rapidly adjust sympathetic and parasympathetic activity back to the periphery. Lesions that selectively destroy the afferent fibers of the vagus and/or glossopharyngeal nerves can interrupt the transmission of baroreceptor signaling, leading to extreme blood pressure fluctuations. Vagal efferent neurons project back to the heart to provide parasympathetic cholinergic inputs. When activated, they trigger profound bradycardia, reduce myocardial oxygen demands, and inhibit acute inflammation. Impairment of the efferent vagal fibers seems to play a role in stress-induced neurogenic heart disease (i.e., takotsubo cardiomyopathy). This focused review describes: (1) the importance of the vagus and glossopharyngeal afferent neurons in regulating arterial blood pressure and heart rate, (2) how best to assess afferent and efferent cardiac vagal function in the laboratory, and (3) two clinical phenotypes that arise when the vagal and/or glossopharyngeal nerves do not survive development or are functionally impaired.

Startle and the StartReact Effect: Physiological Mechanisms Summary: It has been well documented that a prepared response can be triggered at short latency following the presentation of a loud acoustic stimulus that evokes a reflexive startle response. Different hypotheses have been proposed for this so-called “StartReact” effect, although there is still much debate surrounding the physiological mechanisms involved in the observed reduction in reaction time (RT). In this review, we outline the various neurophysiological explanations underlying the StartReact effect and summarize the data supporting, and at times opposing, each possibility. Collectively, the experimental results do not unequivocally support a single explanation and we suggest the most parsimonious mechanism may involve a hybrid framework involving a distribution of neural pathways. Specifically, we propose that multiple node networks at the cortical, brainstem, and spinal levels are involved in response preparation and initiation, and the relative contributions of these structures depends on the type of stimulus delivered and the type of movement required. This approach may lead to greater understanding of the pathways involved in response preparation, initiation, and execution for both healthy and motor disordered populations.

Time Is Brain: The Use of EEG Electrode Caps to Rapidly Diagnose Nonconvulsive Status Epilepticus Objective: To perform a feasibility pilot study comparing the usefulness of EEG electrode cap versus standard scalp EEG for acquiring emergent EEGs in emergency department, inpatient, and intensive care unit patients. Background: Nonconvulsive status epilepticus (NCSE) is a neurological emergency diagnosed exclusively by EEG. Nonconvulsive status epilepticus becomes more resistant to treatment 1 hour after continued seizure activity. EEG technologists are alerted “stat” when there is immediate need for an EEG during oncall hours, yet delays are inevitable. Alternatively, EEG caps can be quickly placed by in-house residents at bedside for assessment. Design/Methods: EEG caps were compared with standard-of-care “stat” EEGs for 20 patients with suspected NCSE. After the order for a stat EEG was placed, neurology residents were simultaneously alerted and placed an EEG cap prior to the arrival of the on-call out-of-hospital technologist. Both EEG cap recordings and standard EEG recordings were visually reviewed at 10 and 20 minutes in a blinded manner by two electroencephalographers. The timing, accuracy of interpretation, and diagnosis between the two techniques were then compared. Results: Of the 20 adult patients, 70% (14 of 20) of EEG cap recordings were interpretable, whereas 95% (19 of 20) standard EEGs were interpretable; three had findings consistent with NCSE on both the EEG cap and standard EEG recordings. In the time analysis, 16 patients were included. EEG cap placement was significantly more time efficient than an EEG performed by technologist using the usual “stat” EEG protocol, with the median EEG cap electrode placement occurring 86 minutes faster than standard EEG (22.5 minutes vs. 104.5 minutes; P < 0.0001; n = 16). Conclusions: New rapid EEG recording using improved EEG caps may allow for rapid diagnosis and clinical decision making in suspected NCSE.