Introduction: the concept of brainstem dysfunction
Functional neuroanatomy of the brainstem
Anatomic structures | Function | |
---|---|---|
Gray matter | Nuclei of cranial nerves | Brainstem reflexes |
Nuclei of ascending reticular activating system (ARAS) | Arousal, sleep/wake cycles, and alertness | |
Nuclei of the extrapyramidal system | Automatic movements | |
Nuclei of the central autonomic system | Vital function regulation and homeostasis | |
White matter | Axons of ascending pathways: Posterior column-medial lemniscus pathway Spinothalamic tract and lateral lemniscus pathway | Sensory information: Fine touch, vibration, two-point discrimination, and proprioception Pain and temperature |
Axons of descending pathways: Pyramidal corticospinal and corticobulbar tracts Extrapyramidal tract (rubrospinal, pontine and medullary reticulospinal tract, lateral vestibulospinal and tectospinal tracts) | Voluntary motor control Reflexes, locomotion, complex movements, and postural control |
Brainstem syndromes and assessment
Brainstem motor and sensory deficits and cranial nerve palsy
Brainstem structures | Functions | Centers | Symptoms |
---|---|---|---|
Midbrain (rostral to the pons and caudal to the thalamus and the basal ganglia) | Eye movements | Cranial nerve nuclei: III oculomotor nerve (mainly motor) IV trochlear nerve (motor) | Oculomotor signs: Ptosis (III) Ophthalmoplegia (III, IV) |
Pupillary size: sphincter pupillae and muscles of the ciliary body, pupil light reflex | Cranial nerve nuclei: III oculomotor nerve | Pupillary anomalies: Myosis (sympathetic lesion) Mydriasis (parasympathetic lesion) Anisocoria | |
Movement control | Substantia nigra | Parkinsonian syndrome and movement disorders (hemichorea, hemiballism, dystonia, tremor, asterixis, pseudo-athetosis, non-epileptic myoclonus) | |
Posture tone | Red nucleus | Postural tone impairment | |
Posture/auditory and visual integration | Accessory optic tractus | Balance disorder | |
Posture and movement integration | Tectum (dorsal part) | Balance disorder | |
Posture and inhibitor motor centers | Tegmentum (ventral portion) (basal ganglia and thalamus connections) | Involuntary movements | |
Sleep/wake cycles, alertness, and arousal | ARAS: composed of almost 100 nuclei, including locus coeruleus-raphe nuclei with neocortex connections | Sleep disturbance Consciousness disorders | |
Central thermic regulation | ARAS-hypothalamus connections | Hypo/hyperthermia | |
Pons (between the medulla and the midbrain) | Facial sensitivity, muscles of mastication | Cranial nerve nuclei: V trigeminal nerve (sensory and motor) | Facial symptoms: Facial dysesthesia Oculomotor signs: Corneal/ciliary reflex impairment |
Facial muscles and taste from the anterior 2/3 of the tongue (VII) | Cranial nerve nuclei: VII facial nerve (sensory and motor) | Facial symptoms: Peripheral facial palsy | |
Eye movement (abduction) | Cranial nerve nuclei: VI abducens nerve (motor) | Oculomotor signs: Ophthalmoplegia | |
Posture, sensation of rotation, gravity, and sound | Cranial nerve nuclei: VIII vestibulocochlear nerve (mostly sensory) Cerebellum tract | Altered audition (VIII) Balance disorders (VIII and cerebellum tract) | |
Posture Posture and inhibitor motor center | Spinocerebellar tracts Tegmentum (thalamus and basal nuclei connections) | Cerebellar ataxia Involuntary movement | |
Motor efference integration Sensory efference integration | Tracts carrying signals to the thalamus | Motor deficit Sensory deficit | |
Consciousness, alertness, and sleep regulation | Tracts carrying signals to the thalamus | Sleep disturbance Consciousness disorders | |
Sleep/wake cycles, alertness, and arousal | ARAS: composed of almost 100 nuclei, including raphe nuclei and locus coeruleus-raphe nuclei-neocortex connections | Sleep disturbance Consciousness disorders | |
Emotion | ARAS: locus coeruleus and amygdala connections | Anxiety and post-traumatic stress disorder (PTSD) | |
Central thermic regulation | ARAS-hypothalamus connections | Hypo/hyperthermia | |
Respiratory drive: respiratory rate and tidal volume control | Pedunculopontine tegmentum, locus coeruleus, lateral parabrachial respiratory group, and Kölliker-Fuse nuclei | Respiratory drive dysfunction: Kölliker-Fuse and parabrachial nuclear: increase tidal volume, decrease respiratory rate Lower part/ponto-peduncular injury: respiratory asynchronism | |
Medulla (lower half of the brainstem, connects the higher levels of the brain to the spinal cord) | Taste from the posterior 1/3 of the tongue | Cranial nerve nuclei: IX glossopharyngeal (sensory and motor) | Tongue sensory impairment |
Pharyngo-laryngeal reflex | Cranial nerve nuclei: IX glossopharyngeal nerve X vagus nerve (sensory and motor) XI spinal nerve (motor) | Oro-pharyngo-laryngeal anomalies: Dysphagia (swallowing impairment) Dysphonia Velo-pharyngo-laryngeal impairment Absence of pharyngeal/gag reflex | |
Glossal muscles | XII hypoglossal (mainly motor) | Tongue motor impairment (fasciculation, motor deficit) | |
Cough | IX glossopharyngeal nerve X vagus nerve | Absence of cough reflex (IX, X) | |
Posture | Spinocerebellar tracts | Cerebellar ataxia | |
Regulation of autonomic nervous system: | Sympathetic nuclei Parasympathetic nuclei: vagus nerve (X) control of the heart, lung, digestive tracts | Autonomic dysfunction | |
Cardiac regulation | Sympathetic nuclei Parasympathetic nuclei: vagus nerve (X) control of the heart, lung, digestive tracts | Oculocardiac reflex impairment (X) Dysautonomia: tachycardia (parasympathetic impairment), bradycardia (sympathetic impairment), sudden death | |
Vasomotor regulation | Hemodynamic failure: Dysautonomia with hypertension (parasympathetic impairment), hypotension (sympathetic impairment) | ||
Gastrointestinal motility | Gastrointestinal motility anomalies | ||
Respiratory drive: respiratory rate and tidal volume control | Respiratory centers: dorsal respiratory complex | Respiratory drive dysfunction: respiratory rate irregularities and ataxic breathing, hyperventilation, respiratory-ventilator asynchronism, central apnea | |
Microbiota gut-brain axis, senses and peripheral inflammation modulation | Vagus nerve (X) | Maladaptive immune response, gut-brain axis impairment | |
Tracts all along the brainstem | Connection of the oculomotor nerves (see Fig. 1) | Medial longitudinal fasciculus | Internuclear ophthalmoplegia |
Motor information from the periphery to supratentorial structures | Corticospinal tract Pyramidal and extrapyramidal tracts | Motor deficit, locked-in syndrome Tetrapyramidal and extrapyramidal syndromes with movement disorders (tremor) Non-epileptic myoclonus | |
Sensory information from the periphery to supratentorial structures | Posterior column-medial lemniscus pathway and spinothalamic tracts | Sensory deficit | |
Oculosympathetic control | Centers control of the ciliary nerve, superior tarsal muscle, pupillary sphincter/dilator | Horner’s syndrome (ptosis, myosis, enophtalamos, anhidrosis) |
Reflex | Examination technique | Normal response | Afferent pathway | Brainstem centers | Efferent pathway |
---|---|---|---|---|---|
Physiological reflexes | |||||
Pupillary light reflex | Response to light | Direct and consensual myosis followed by mydriasis | Retina, optic nerve, chiasma, optic tract | Pupillo-constrictor: midbrain, pretectal olivary nucleus, Edinger-Westphall nucleus Pupillo-dilator: posterior-lateral hypothalamus, cervical ganglion, trigeminal ganglion, abducens | Sympathetic fibers of cranial nerve III (oculomotor) |
Cilio-spinal | Latero-cervical nociceptive stimulation | Uni- or bilateral irido-dilatation | Sensory ascending pathways to centro-spinal centers | Midbrain | Cranial nerve III |
Fronto-orbicular | Glabellar percussion | Eyes closing | Cranial nerve V (trigeminal) | Pons | Cranial nerve VII (facial) |
Oculocephalic | Turn head from side to side | Eyes move conjugately in direction opposite to head | Semicircular canals, Cranial nerve VIII (oculovestibular) | Pons, nucleus vestibularus, nucleus abducens | Cranial nerves III (oculomotor) and VI (abducens) |
Oculovestibular | Irrigate external auditory canal with 50 ml of cold water | Nystagmus | |||
Corneal | Stimulation of cornea with saline drops | Eyelid closure | Cranial nerve V (trigeminal) | Pons, trigeminal and facial nuclei | Cranial nerve VII (facial) |
Grimace/masseterian | Deep pressure on nail bed, supraorbital ridge, or temporo-mandibular joint | Facial grimace and limb movement | |||
Cough reflex | Stimulation of the carina with a suction tube | Cough | Cranial nerve IX (Glossopharyngeal) and X (vagal) | Medulla, nucleus tractus solitarius | Cranial nerve IX (glossopharyngeal) and X (vagal) |
Gag/pharyngeal reflex | Stimulation of the soft palate | Symmetrical rise of soft palate gag reflex | |||
Oculocardiac | Ocular globe compression | Decrease in heart rate | Cranial nerve V (trigeminal) | Pons, medulla | Cranial nerve X (vagal) |
Primitive reflexes | |||||
Palmo-mental | Pressure of the thenar eminence with a thin stick | Single twitch of the ipsilateral mentalis muscle | Posterior column-medial lemniscus pathway | Pons | Cranial nerve VII (facial) |
Corneo-mandibular | Corneal stimulation | Contralateral deviation of the jaw | Cranial nerve V (trigeminal) | Pons | Cranial nerve VII (facial) |
Other syndromes | |||||
Internuclear ophthalmoplegia (see Fig. 1) | Oculomotricity testing Can be observed during oculocephalogyric or oculovestibular tests | Disconjugate lateral gaze with a preserved convergence | Lesion of the medial longitudinal fasciculus | Connects the sixth nucleus with the contralateral third nucleus | |
Claude Bernard-Horner’s syndrome | Ptosis, myosis, enophtalamos, anhidrosis | Sympathetic pathway injury | |||
Vertical nystagmus, skew deviation | Midbrain or medulla injury | ||||
Ocular bobbing | Pons injury |
Causes of brainstem dysfunction | |
---|---|
Acute primary insult | |
Vascular injury | |
Ischemic: thrombotic or cardio-embolic, lacunar ischemia due to small vessel disease, vasculitis | |
Hemorrhage | |
Inflammatory | |
Multiple sclerosis (MS) | |
Acute disseminated encephalomyelitis (ADEM) | |
Neuromyelitis optica (NMO) (anti-MOG, anti-AQP4 antibodies, or seronegative types) | |
Birkenstaff encephalitis (anti-ganglioside GQ1b antibodies) | |
Behcet disease and rarely other autoimmune disease (lupus, neuro-sarcoidosis) | |
Langerhans cell histiocytosis | |
Traumatic: direct or indirect injury | |
Metabolic: central pontine myelinolysis | |
Infectious: rhombencephalitis, abscess, Listeria monocytogenes and enterovirus 68 and 71, followed by herpes simplex viruses and tuberculosis, Epstein-Barr virus (EBV), and human herpesvirus 6 (HHV6) | |
Paraneoplastic (anti-neuronal NMDA, AMPA, GABA, CASPR2, Hu, Ma2, Ri, Yo, CV2, amphiphysin, Lgi1,glycine, mGluR1/5, VGKC/VGCC, GAD antibodies) | |
Chronic primary insult | |
Tumoural | |
Degenerative/atrophic injury |
Impairment of consciousness
Variable | Score point |
---|---|
Absence of cough reflex | 1 |
Absence of pupillary light reflex | 1 |
Absence of corneal reflex | 2 |
Absence of grimacing to pain and absence of OCR | 1 |
Absence of grimacing to pain and presence of OCR | 3 |
BAEP waves | Anatomic localization |
I | Distal portion of the auditory nerve |
II | Proximal portion of the auditory nerve or cochlear nuclear complex, in the upper part of the medulla, ipsilateral to the stimulation side |
III | Cochlear nucleus or superior olivary complex in caudal pontine tegmentum, ipsilateral to the stimulation side |
IV | Superior olivary complex (lateral lemniscus), contralateral to the stimulation side |
V | Inferior colliculus located in the midbrain, contralateral to the stimulation side |
Blink test | Response |
After stimulation of the supraorbital nerve, three responses are recorded on eyelid orbicular muscles: an early ipsilateral (R1) response and the two (ipsi- and contralateral) late responses (R2) | R1 response generated at the level of the pons, R2 responses at the level of the trigeminal-spinal tract at the pons level, the medulla oblongata, and the caudal trigeminal-spinal nucleus |
Autonomic nervous system impairment
Neurogenic respiratory failure
Brainstem dysfunction in critically ill patients
Brainstem dysfunction | Differential diagnosis |
---|---|
Oculomotor anomalies (III, IV, VI cranial nerves nuclei) | Cranial nerve palsy Myopathy involving oculomotor muscles Neuromuscular disorders: myasthenia, Lambert-Eaton syndrome and botulism |
Pupillary size anomalies | Anisocoria: compressive lesion of the III cranial nerve such as herniation/intracranial hypertension and posterior communicative artery aneurysm |
Mydriasis: third nerve lesion | |
Claude Bernard-Horner’s syndrome (ptosis, myosis, enophtalmia, anhidrosis) | Pancoast tumor Carotid or aortic dissection |
Facial sensory anomalies (V cranial nerve nucleus) | Contralateral brain injury Cranial nerve palsy (V) |
Facial motor anomalies (VII cranial nerve nucleus) | Contralateral brain injury Cranial nerve palsy (VII) Myopathy with facial paralysis Neuro-muscular disorders: myasthenia, Lambert-Eaton syndrome and botulism |
Posture and movement anomalies | Uni- or bilateral basal ganglia lesions |
Motor and/or sensory deficit | Contralateral brain injury Critical illness neuromyopathy Guillain-Barre syndrome |
Motor deficit | Myopathy Neuro-muscular disorders: myasthenia, Lambert-Eaton syndrome and botulism |
Autonomic (sympathetic and parasympathetic) dyfunctions | Spine injury Guillain-Barre syndrome |
Respiratory control anomalies | Cervical spine injury (C3–C5) Phrenic nerve palsy Diaphragmatic injury Critical illness neuromyopathy Neuromuscular disorders: myasthenia, Lambert-Eaton syndrome and botulism |