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Pulm: Respirations
•normal resp rate is 20 bpm (J Emerg med.1989.7.129, BMJ.1982.284.626); this was also determined by Lambert
Quetelet in 1842, one of first people to compile vital and social statistics, who also developed our equation for the
BMI, known as the Quetelet index); many textbooks cite normal resp rate as 12-18, but w no data
Tachypnea
•various definitions (roughly 25)
•better predictor of subsequent cardiopulmonary arrest in hospitalized pts than tachycardia or abnormal BP
(JGIM.1993.8.354)
Bradypnea
•narcotics, sedatives, hypothyroidism, CNS dz (uncertain location)
Abnormal breathing patterns
General statements
•lack of animal to human correlation
•while existence of specific centers postulated, seems this is an oversimpification
•probably all patterns of breathing interrelated in some way
General nervous system contol
Anatomy and Physiology of the Respiratory Center
I. Brainstem signals
1. dorsal respiratory group (DRG) (dorsal medulla mostly in nucleus of tractus solitarius, some reticular substance)
2. ventral respiratory group (VRG) (ventral medulla)
3. pneumotaxic center (dorsal superior pons in nucleus parabrachialis)
?pathologic brain edema can decrease respiration
?brain injury can increase respiration
II. Chemoreceptors
carotid artery chemoreceptors
•sense hypoxia (they do sense pH, PaCO2, but the effect ~7 times less powerful than brainstem signal, but does
respond 5 times more quickly, therefore might be important at onset of excercise)
•afferents pass along carotid sinus nerve, join glossopharyngeal nerve, terminate in NTS of DRG
aortic body chemoreceptors
•sense hypoxia (pH, CO2, see above)
•afferents from aortic nerves to vagus to medulla
brainstem chemoreceptors
•sense hydrogen ion content of ECF of medulla
•BBB impermeable to H ions, but PaCO2 crosses and reacts to form more H ions
•the CSF has less protein buffer than brain interstitial fluid, therefore this is sensitive mechanism (occurs in seconds)
•chronic effects is smaller (kidneys increase bicarbonate to dec H ion concentration)
•unknown location (?ventral medulla)
III. Lung signals
stretch receptors
•affect depth and duration of breathing
•Herig-Breuer Inflation Reflex: stretch receptors in bronchi and bronchioloes transmit signal through vagus into
DRG when lungs become overstretched, switching off the inspiratory ramp signal; probably not activated until tidal
volume ~ 1.5L, therefore a protective control rather that a regularly operating mechanism
pulmonary epithelial cell irritant receptors
•coughing, sneezing, bronchoconstriction
J receptors
•exist at juxtaposition of alveolar wall and pulmonary capillary
•probablly play role for dyspnea in pulmonary edema
Voluntary, Automatic, and Limbic Respiration
Voluntary (Behavioral) respiration
•active during speech, swallowing (important clinical correlation with aspiration), breath-holding, voluntary
hyperventilation
•associated with activity in motor and premotor cortex (using PET scanning)
•not known if voluntary signals bypass the brainstem mechanisms, or are integrated there
Automatic (Metabolic) respiration
•locked-in syndrome occurs when both dorsal descending tracts offering voluntary control are interrupted, and then
automatic respiratory system maintains rate of ~ 16 with uniform tidal volumes
Limbic (Emotional) respiration
•laughter, coughing, anxiety
The patterns
Cheyne-Stokes (aka "periodic breathing")
- lesions anywhere along descending pathway between forebrain and upper pons
- cardiac disorders that prolong circulation time
- normal people during sleep or at high altitudes
- periodic, regular, sequentially increasing depth of respiration followed by periods of apnea
- RR constant during hyperpnea phase (does NOT gradually inc or dec as is often stated (Chest 1974.66.345)
- time bt 2 consec peaks is the "cycle length" or "period", and each cycle lenth divided into
hyperpnea phase: ~30sec
apnea phase ~25 sec
- pathophysiology is essentially a loss of normal fine tuning of respiratory centers to PaCO2; caused by
1)INCREASED sensitivity to CO2 and 2)circulatory delay bt lungs and chemorectors in arteries, which results in
constant over and undercompensation of the respiratory center (J Clin Invest.1962.41.42-52; Tobin
MJ.CCM.1984.12.882)
- John Cheyne, 1818 and William Stokes 1854 (J Emerg Med 1985.3.233)
- poor prognosis in heart failure (see McGee for refs)
Hyperpnea (Kussmaul) (increased RR and TV)
- metabolic acidosis (primarily diabetic, but also other AG met acidoses)
Hypopnea (low TV)
- obesity-hypoventilation
Biot's
- on a vague and semantic continuum with "ataxic" respirations (a=without, taxis=order or arrangement [G] and also
called "atactic" in some books); made even more vague by the lack of information about Biot the person (see
below); in some literature, Biot's seems to be more associated with hypoventilation, and ataxic tends to be more
completely irregular but i think this distinction is difficult
- medulla: (described in reticular formation of dorsomedial part) (usually vascular ("brainstem stroke") or
compression due to rapid increase in ICP
- irregular respiratory cycle of variable frequency and tidal volume alternating with periods of apnea which last
longer than breathing (almost spasmodic)
- Biot's life remains a mystery: only paper that I can find that cites his work is chest.2003;123:632, and that ref is
[Biot, MC Contribution a l’étude de phénomène respiratoire de Cheyne-Stokes. Lyon Med 1876;23,517-528];
however, dictionary of the history of medicine, and Dorlands, sites Camille Biot (b1878) as originator of the type of
respirations, seen in medullary compression of the brain stem. MC Biot, cited below, was alive and publishing in
1876, so I'm not sure: would need to get original paper in French and deduce what Biot actually meant).
- poor prognosis, and important sign of impending respiratory arrest
- notably, Biot's breathing progresses to the intermittent prolonged inspiratory gasps which are called Agonal or
Gasping; the exact physiology of these is unclear to me, but Webber and Speck showed that Biot's, gasping, and
apnea can be produced in the same cat with lesions in the dorsolateral pontine tegmentum by altering the depth of
anesthesia; i would turn to discussing in Neurology text pasted: [As pointed out by Fisher and by Plum and Posner,
when certain supratentorial lesions progress to the point of temporal lobe and cerebellar herniation, one may observe
a succession of respiratory patterns (CSR-CNH-Biot breathing), indicating an extension of the functional disorder
from upper to lower brainstem; but again, such a sequence is not always observed. Rapidly evolving lesions of the
posterior fossa may cause sudden respiratory arrest without any of the aforementioned abnormalities of breathing;
presumably this results from fulminant pontomedullary compression by the cerebellar tonsils.]
Short cycle periodic
(faster rhythm than Cheyne-Stokes, or short bursts of 7-10 rapid breaths, then one or two waning breaths, then apnea
without a waning or waxing prodrome - erroneously refferred to as Biot's)
- increased ICP
- lower pontine lesion
- expanding lesion of posterior fossa
Apneustic
- aka "short cycle CSR"
- pauses, either prolonged pause at full inspiration, or alternating brief end inspiratory and expiratory pauses
- pons: dorsolateral inferior half/bilateral tegmental (basilar artery occlusion)
Cluster
- clusters of breaths followed by apneic periods of variable duration
- high medullary damage (lower pontine tegmental)
Central neurogenic hyperventilation
- rare, associated with structural lesion (vascular, malignancy), usually in pons (lower midbrain-upper pontine
tegmentum) which can either be primary or secondary to tentorial herniation
- thought to represent a release of the reflex mechanisms for respiratory control in the lower brainstem, but exact
neurologic basis is uncertain, and one study failed to show a correlation between anatomic location and tachypnea
(North JB and Jennett 1974)
- rapid, regular hyperventilation which persists in face of alkalosis, raised PaO2, low PaCO2, and absence of any
pulmonary or airway disorder (PMJ.2001.77.700)
- note that mild hyperventilation is common post acute neurologic events, and therefore CNH must be distinguished
from hyperventialation caused by other illness (ex: pneumonia, acidosis)
Ondine's curse
•failure of automatic control of ventilation
•Central neurogenic hyperventilation is an idiopathic version of this)
•thought to represent failure of pathways that provide automatic respiration
•described in vascular evetns, encephalitis, in Leigh syndrome
•converse of this state (loss of voluntary control, but preserved automatic control) has also been described (Arch
Neurol.1991.48:1190) and components of this are observed in cases of "locked-in" state
•ondines are water nymphs, and one fell in love w a man and longed to be transformed into a female and acquire a
soul; however, the King of the Ondines warned his school of mermaids that an ondine who went mortal was on a
risky course: a disagreeable ending was in store if the ondine was then jilted for an ordinary human female; all
ondines knew this; notably, the would be mortal husbands didn't. each author who wrote about ondines described
different disagreeable endings: they vary from the ondine returning to the sea forever as a mermaid, the ondine
returning to the sea as foam, the ondine having to kill the unfaithful husband, the husband forfeiting his life, or the
husband commanding himself to perform all of his bodily functions that usually went on automatically (one of
which was breathing) (described by Giraudoux, Jean: Ondine. 1939). this is the one for which the curse is named,
but the word "curse" is a literary error: no ondine ever cursed the unfathful husband, it just happened. (see
Frankenstein, Pickwick, and Ondine paper)
Signs of respiratory muscle weakness
(usually appear when vital capacity has been reduced to about 10% of normal, or ~500mL for avg adult)
Paradoxic abdominal movements (aka abdominal paradox)
- both chest and abd usually rise in inspiration (a result of lung expansion, and contraction of the diaphragm which
pushes down abdominal content)
- when weak diaphragm, neg intrathoracic pres caused by acces musc pulls diaphragm into thorax, dec intraabdom
pres, causing paradoxical inward displacement of abd during inspiration (like after running 100y dash)
- detected by inspection, or by placing one hand over chest and other over abdomen and observing their rocking
motion
- one study of pts w dyspnea and neuromuscular dz, SN95 SP71 LR3.3 for MIP <30 cm H20 (Am Rev Resp
Dis.1988.137.877)
respiratory alternans
- when the diaphragm works for a few respirations, and then fatigues for a few, resulting in normal respirations
followed by the paridoxically inward-moving abdomen for a few respirations
asynchronous breathing
- results in chronic airflow obstruction
- abrupt inward and then outward abdominal movement during expiration which likely results from strong action of
accessory muscles during expiration which push the flattened diaphragm temporarily downward
(Chest.1975.67.553, Chest.1977.71.456)
- associated with poor prognosis
Orthopnea, Platypnea, and Trepopnea
orthopnea
•[G "straight" or "vertical"]
•likely caused partly by dec in lung compliance and vital capacity upon lying down
•one study of pts with known COPD, presence of orthopnea distinguished bt those w EF <50% with SN97 SP64
LR+2.7 LR-0.04; therefore suggesting that the presence of orthopnea has limited use, but the absence of orthopnea
argues for a normal EF (Chest.1984.85.59)
platypnea
"flat breathing"
platy [G] flat
pnea [G] breating
opposite of orthopnea
ortho [G] upright, straight
Caused by R-->L shunts
1. Cirrhosis, HRS (Pulmonary AVMs)
2. Intracardiac (ASD, PFO)
- preferential blood flow to septum due to altered inracardiac relationships?
- unequal diastolic compliance beteween L and R sides of heart?
- transient R-->L pressure gradients assoc w respiratory maneuvers?
3. Lung Dz s shunts (severe COPD, post-pneumonectomy)
this type of R -->L shunting is unique because assoc with normal PA pressures (most R -->L shunts have inc R
sided pressure)
Platypnea with orthodeoxia = platypnea-orthodeoxia syndrome
Platypnea without orthodeoxia=?
Dx of platypnea-orthodeoxia syndrome
1. erect and supine pulse ox
2. echo ot find intracardiac shunts
3. R and L cardiac cath
Tx
1. fix shunts
2. ?opiods
REFS
Chest. 112(6):1449-51, 1997
Heart 2000;83:221-223
Chest. 2000;118:553-557
trepopnea
1. R effusions of CHF (R side down)
2. Pleuritis (bad side down)
3. Mass lesions that compress normal lung, especially after partial resections
4. Infants (bad side down)
5. R atrial masses (myxomas/HCC/RCC)
6. Unilateral lung dz (usually good lung down, which enables more blood flow to healthy lung (see McGee)
? COPD
In CHF
Proposed mechanism
1. R atrium is lower if R side down, increasing venous return (corroborated with measurements of ANP in three
recumbent positions)
also possible that large heart does not compress L lung
?R side down dec sympathetic activity
?feeling of displaced PMI on L chest when L side down?
REFS
see McGee for complete list
Wood FC.Trepopnea.ArchIM.1959.104.966
OVERALL REFS
BOOKS
Mangione physical diagnosis secrets
McGee "RR and abnormal breathing patterns"
Adams and Victor's Principles of Neurology - 8th Ed. (2005) Ch. 17 Coma and Related Disorders of Consciousness
(obtainable through StatRef)
Guyton
Sapira
REVIEW
Howard RS et al. Pathophysiological and clinical aspects of breathing after stroke. PMJ.2001.77.700
LACK OF CORRELATION BT NEUROSURGICAL LESION AND TACHYPNEA
North JB, Jennett B: Abnormal breathing patterns associated with acute brain damage. Arch Neurol 32:338, 1974.
INTERRELATEDNESS OF BREATHING PATTERNS
Webber CL, Jr, Speck DF: Experimental Biot periodic breathing in cats: Effects of changes in PiO2 and PiCO2.
Respir Physiol 46:327, 1981.
CHEYNE-STOKES
McGee
Guyton
Sternbach GL. J Emerg Med.1985.3.233
Tobin MJ.CCM.1984.12.882
ArchIM.1971.127.712
NERVOUS SYSTEM CONTROL OF RESPIRATION
from Adams and Victor's Principles of Neurology - 8th Ed. (2005) Ch. 26
Introduction
Considering the fact that the act of breathing is entirely neurologic, it is surprising how little attention it has received
other than from physiologists. Every component of breathingthe lifelong automatic cycling of inspiration, the
transmission of coordinated nerve impulses to and from the respiratory muscles, the translation of systemic
influences such as acidosis to the neuromuscular apparatus of the diaphragmis under neural control. Moreover,
respiratory failure is one of the most disastrous disturbances of neurologic function in comatose states and in
neuromuscular diseases such as myasthenia gravis, Guillain-Barre syndrome, amyotrophic lateral sclerosis,
muscular dystrophy, and poliomyelitis. The major part of the treatment of these disorders consists of measures that
assist respiration (mechanical ventilators). Finally, deathor brain deathis now virtually defined in terms of the
ability of the nervous system to sustain respiration, a reversion to ancient methods of determining the cessation of all
vital forces. A full understanding of respiration requires knowledge of the mechanical and physiologic workings of
the lungs as organs of gas exchange; but here we limit our remarks to the nervous system control of breathing.
Neurologists should be familiar with the alterations of respiration caused by diseases in different parts of the nervous
system, the effects of respiratory failure on the brain, and the rationale that underlies modern methods of treatment.
The Central Respiratory Motor Mechanisms
It has been known for more than a century that breathing is controlled mainly by the lower brainstem, and that each
half of the brainstem is capable of producing an independent respiratory rhythm. In patients with poliomyelitis, for
example, the occurrence of respiratory failure was associated with lesions in the ventrolateral tegmentum of the
medulla (Feldman, Cohen). Until recently, thinking on this subject was dominated by Lumsden's scheme of the
breathing patterns that resulted from sectioning the brainstem of cats at various levels. He postulated the existence of
several centers in the pontine tegmentum, each corresponding to an abnormal breathing patterna pneumotaxic
center, an apneustic center, and a medullary gasping center. This scheme proves to be oversimplified when viewed
in the light of modern physiologic experiments. It appears that neurons in several discrete regions discharge with
each breath and, together, generate the respiratory rhythm. In other words, these sites do not function in isolation, as
individual oscillators, but interact with one another to generate the perpetual respiratory cycle and they each contain
both inspiratory and expiratory components.
Three paired groups of respiratory nuclei are oriented more or less in columns in the pontine and medullary
tegmentum (Fig. 26-7). They comprise (1) a ventral respiratory group (referred to as VRG), extending from the
lower to the upper ventral medulla, in the region of the nucleus retroambiguus; (2) a dorsal medullary respiratory
group (DRG), located dorsal to the obex and immediately ventromedial to the nucleus of the tractus solitarius
(NTS); and (3) two clusters of cells in the dorsolateral pons in the region of the parabrachial nucleus. From electrical
stimulation experiments, it appears that paired neurons in the dorsal pons may act as "on-off" switches in the
transition between inspiration and expiration.
FIGURE 26-7
The location of the main centers of respiratory control in the brainstem as currently envisioned from animal experiments and
limited human pathology. There are three paired groups of nuclei: A. The dorsal respiratory group (DRG), containing mainly
inspiratory neurons, located in the ventrolateral subnucleus of the nucleus of the tractus solitarius; B. A ventral respiratory group
(VRG), situated near the nucleus ambiguus and containing in its caudal part neurons that fire predominantly during expiration
and in its rostral part neurons that are synchronous with inspirationthe latter structure merges rostrally with the Botzinger
complex, which is located just behind the facial nucleus and contains neurons that are active mostly during expiration; C. A
pontine pair of nuclei (PRG), one of which fires in the transition between inspiration and expiration and the other between
expiration and inspiration. The intrinsic rhythmicity of the entire system probably depends on interactions between all these
regions, but the "pre-Botzinger" area in the rostral ventromedial medulla may play a special role in generating the respiratory
rhythm.(Adapted by permission from Duffin et al.)
Inspiratory neurons are concentrated in the dorsal respiratory group and in the rostral portions of the ventral group,
some of which have monosynaptic connections to the motor neurons of the phrenic nerves and the nerves to the
intercostal muscles. Normal breathing is actively inspiratory and only passively expiratory; however, under some
circumstances of increased respiratory drive, the internal intercostal muscles and abdominal muscles actively expel
air. The expiratory neurons that mediate this activity are concentrated in the caudal portions of the ventral
respiratory group and in the most rostral parts of the dorsal group. On the basis of both neuroanatomic tracer and
physiologic studies, it has been determined that these expiratory neurons project to spinal motor neurons and have
an inhibitory influence on inspiratory neurons.
The pathway of descending fibers that arises in the inspiratory neurons and terminates on phrenic nerve motor
neurons lies just lateral to the anterior horns of the upper three cervical cord segments. When these tracts are
damaged, automatic but not voluntary diaphragmatic movement on that side is lost. As noted below, the fibers
carrying voluntary motor impulses to the diaphragm course more dorsally in the cord. The phrenic motor neurons
form a thin column in the medial parts of the ventral horns, extending from the third through fifth cervical cord
segments. Damage to these neurons, of course, precludes both voluntary and automatic breathing.
The exact locus from which the breathing rhythm is generated, if there is such a site, is not known. The conventional
teaching has been that the dorsal respiratory group (DRG) was the dominant generator of the respiratory rhythm, but
the situation is certainly more complex. Animal experiments have focused attention instead on the rostral
ventrolateral medulla (VRG). This region contains a group of neurons in the vicinity of the "Botzinger complex"
(which itself contains neurons that fire mainly during expiration). Cooling of this area or injection with neurotoxins
causes the respiratory rhythm to cease (see the review by Duffin et al). It has been shown that the paired respiratory
nuclei in the pons that are thought to act as switches between inspiration and expiration also possess a degree of
autonomous rhythmicity, but their role in engendering cyclic breathing has not been clarified. Some workers are of
the opinion that two or more sets of neurons in the VRG create a rhythm by their reciprocal activity or that
oscillations arise within even larger networks (see Blessing for details). There are also centers in the pons that do not
generate respiratory rhythms but may, under extreme circumstances, greatly influence them. One pontine group, the
"pneumotaxic center," modulates the response to hypoxia, hyopcapnia, and lung inflation. In general, expiratory
neurons are located laterally and inspiratory neurons medially in this center, but there is an additional group that lies
between them and remains active during the transition between respiratory phases. Also found in the lower pons is a
group of neurons that prevent unrestrained activity of the medullary inspiratory neurons ("apneustic center"). In
addition to these ambiguities regarding a "center" for the generation of respiratory rhythm, there is the difficulty that
the nuclei described above are not well defined in humans.
As to the effects of a unilateral brainstem lesion on ventilation, numerous cases of hypoventilation or total loss of
automatic ventilation ("Ondine's curse"see further on) have been recorded (Bogousslavsky et al). We have
observed several such remarkable cases as well, due in most instances to a large lateral medullary infarction. If the
neural oscillators on each side were totally independent, such a syndrome should not be possible. The likely
explanation may be that a unilateral lesion interrupts the connections between each of the paired groups of nuclei,
which normally synchronize the two sides in the generation of rhythmic bursts of excitatory impulses to spinal
motor neurons. It is of interest that in a case of a very delimited metastasis to the NTS there was no apparent impact
on the breathing pattern until a terminal respiratory arrest (Rhodes and Wightman).
Voluntary Control of Breathing During speech, swallowing, breath-holding, or voluntary hyperventilation, the
automaticity of the brainstem mechanisms of respiration is arrested in favor of reflexive or of conscious control of
diaphragmatic contraction. The observations of Colebatch and coworkers, utilizing PET scanning, indicate that
voluntary control of breathing is associated with activity in the motor and premotor cortex. The experiments of
Maskill and associates demonstrated that magnetic cortical stimulation of a region near the cranial vertex activates
the diaphragm. Although automatic and voluntary breathing utilize the same pools of cervical motor neurons that
give rise to the phrenic nerves, the descending cortical pathways for voluntary breathing are distinct from those
utilized by automatic brainstem mechanisms. It is not known whether the voluntary signal bypasses the brainstem
mechanisms or is possibly integrated there. When both dorsal descending tracts subserving voluntary control are
interrupted, as in the "locked-in syndrome," the independent, automatic respiratory system in the medulla is capable
of maintaining an almost perfectly regular breathing rate of 16 per minute with uniform tidal volumes.
These essential facts do not fully depict the rich interactions between the neuronal groups governing respiration and
between the neurons for laryngeal and glottic activity that come into play during such coordinated acts as
swallowing, sneezing, and coughing, and speaking. The brainstem regions involved in holding breathing in
abeyance while swallowing occurs are pertinent to aspiration, a common feature of many neurologic diseases, as
discussed further on. The drive applied to these systems is damped in processes such as Parkinson disease and may
contribute to the problem of aspiration, as also discussed further on.
Afferent Respiratory Influences A number of signals that modulate respiratory drive originate in chemoreceptors
located in the carotid artery. These receptors are influenced both by changes in pH and by hypoxia. Chemoreceptor
afferents pass along the carotid sinus nerves, which join the glossopharyngeal nerves and terminate in the NTS.
Aortic body receptors, which are less important as detectors of hyopxia, send afferent volleys to the medulla through
the aortic nerves, which join the vagus nerves. There are also chemoreceptors in the brainstem, but their precise
location is uncertain. Their main locus is thought to be in the ventral medulla, but other areas that are responsive to
changes in pH have been demonstrated in animals. What is clear is that these regions are sensitive not to the pH of
CSF, as had been thought, but to the hydrogen content of the extracellular fluid of the medulla.
Numerous stretch receptors within smooth muscle cells of the airways also project via the vagus nerves to the NTS
and influence the depth and duration of breathing. Afferent signals from these specialized nerve endings mediate the
Hering-Breuer reflex, described in 1868a shortened inspiration and decreased tidal volume triggered by excessive
lung expansion. The Hering-Breuer mechanism seems not to be important at rest, since bilateral vagal section has no
effect on the rate or depth of respiration. These aspects of afferent pulmonary modulation of breathing have been
reviewed by Berger and colleagues. It is interesting, however, that patients with high spinal transections and
inability to breathe can still sense changes in lung volume, attesting to a nonspinal afferent route to the brainstem
from lung receptors, probably through the vagus nerves. In addition, there are receptors located between pulmonary
epithelial cells that respond to irritants such as histamine and smoke. They have been implicated in the genesis of
asthma. Also there are "J-type" receptors that are activated by substances in the interstitial fluid of the lungs. These
are capable of inducing hyperpnea and probably play a role in driving ventilation under conditions of pulmonary
edema. Both the diaphragm and the accessory muscles of respiration contain conventional spindle receptors, but
their role is not clear; all that can be said is that the diaphragm has a paucity of these receptors compared with other
skeletal muscles (a property shared with extraocular muscles) and is therefore not subject to spasticity with
corticospinal lesions or to the loss of tone in states such as REM sleep, in which gamma motor neuron activity is
greatly diminished.
Dyspnea The common respiratory sensations of breathlessness, air hunger, chest tightness, or shortness of breath, all
subsumed under the term dyspnea, have defied neurophysiologic interpretation. In animals, Chen and colleagues
from Eldridge's laboratory have demonstrated that neurons in the thalamus and central midbrain tegmentum fire in a
graduated manner as respiratory drive is increased. These neurons are influenced greatly by afferent information
from the chest wall, lung, and chemoreceptors and are postulated to be the thalamic representation of sensation from
the thorax that is perceived at a cortical level as dyspnea. However, functional imaging studies indicate that various
areas of the cerebrum are activated by dyspnea, mainly the insula and limbic regions.
Aberrant Respiratory Patterns Many of the most interesting respiratory patterns observed in neurologic disease
are found in comatose patients, and several of these patterns have been assigned localizing value, some of uncertain
validity: central neurogenic hyperventilation, apneusis, and ataxic breathing. These are discussed in relation to the
clinical signs of coma (Chap. 17) and sleep apnea (Chap. 19). Some of the most bizarre cadences of
breathingthose in which unwanted breaths intrude on speech or those characterized by incoordination of laryngeal
closure, diaphragmatic movement, or swallowing or by respiratory ticshave occurred in paraneoplastic brainstem
encephalitis. Similar incoordinated patterns occur in certain extrapyramidal diseases. Patterns such as episodic
tachypnea up to 100 breaths per minute and loss of voluntary control of breathing were, in the past, noteworthy
features of postencephalitic parkinsonism. In Leeuwenhoek disease, named for the discoverer of the microscope who
described and suffered from the disease, there is a continuous epigastric pulsation and dyspnea in association with
rhythmic bursts of activity in the inspiratory musclesa respiratory myoclonus akin to palatal myoclonus (Phillips
and Eldridge). Two such cases in our clinical material followed influenza-like illnesses and resolved slowly over
months.
Cheyne-Stokes breathing, the common and well-known waxing and waning type of cyclic ventilation reported by
Cheyne in 1818 and later elaborated by Stokes, has for decades been ascribed to a prolongation of circulation time,
as in congestive heart failure; but there are data that support a primary neural origin of the disorder, particularly the
observation that it occurs most often in patients with deep hemispheral lesions of the cerebral hemispheres.
Another striking aberration of ventilation is a loss of automatic respiration during sleep, with preserved voluntary
breathing ("Ondine's curse"). The term stems from the German myth in which Ondine, a sea nymph, condemns her
unfaithful lover to a loss of all movements and functions that do not require conscious will. Patients with this
condition are compelled to remain awake lest they stop breathing, and they must have nighttime mechanical
ventilation to survive. Presumably the underlying pathology is one that selectively interrupts the ventrolateral
descending medullocervical pathways that subserve automatic breathing. The syndrome has been documented in
cases of unilateral and bilateral brainstem infarctions, hemorrhage, encephalitis (neoplastic or infectiousfor
example, due to Listeria), in Leigh syndrome, and recovery from traumatic Duret hemorrhages. The issue of a loss
of automatic ventilation as a result of a unilateral brainstem lesion has been addressed above. The converse of this
state, in which there is complete loss of voluntary control of ventilation but preserved automatic monorhythmic
breathing, has also been described (Munschauer et al). Incomplete variants of this latter phenomenon are regularly
observed in cases of brainstem infarction or severe demyelinating disease and may be a component of the "locked-in
state."
The congenital central hypoventilation syndrome is thought to be an idiopathic version of the loss of automatic
ventilation (see Shannon et al). This rare condition begins in infancy with apneas and sleep disturbances of varying
severity or later in childhood with signs of chronic hypoxia leading to pulmonary hypertension. As mentioned on
page 345, several subtle changes in the arcuate nucleus of the medulla and a depletion of neurons in regions of the
respiratory centers have been found in this condition, but further study is necessary.
Neurologic lesions that cause hyperventilation are diverse and widely located throughout the brain, not just in the
brainstem. In clinical practice, episodes of hyperventilation are most often seen in anxiety and panic states. The
traditional view of "central neurogenic hyperventilation" as a manifestation of a pontine lesion has been brought into
question by the observation that it may occur as a sign of cerebral lymphoma, in which postmortem examination has
failed to show involvement of the brainstem regions controlling respiration (Plum).
Hiccup (singultus) is a poorly understood phenomenon. It does not seem to serve any useful physiologic purpose,
existing only as a nuisance, and is typically not associated with any particular disease. It may occur as a component
of the lateral medullary syndrome (page 678), with masses in the posterior fossa or medulla, and occasionally with
generalized elevation of intracranial pressure, brainstem encephalitis, or with metabolic encephalopathies such as
uremia. Rarely, singultation may be provoked by medication, one possible offender in our experience being
dexamethasone. Since the triggers of hiccup often seem to arise in epigastric organs adjacent to the diaphragm, it is
considered to be a gastrointestinal reflex, more than a respiratory one. A physiologic study by Newsom Davis has
demonstrated that hiccup is the result of powerful contraction of the diaphragm and intercostal muscles, followed
immediately by laryngeal closure. This results in little or no net movement of air. He concluded that the projections
from the brainstem responsible for hiccup are independent of the pathways that mediate rhythmic breathing. Within
a single burst or run of hiccups, the frequency remains relatively constant, but at any one time it may range
anywhere from 15 to 45 per minute. The contractions are most liable to occur during inspiration and they are
inhibited by therapeutic elevation of arterial carbon dioxide (CO 2) tension. We cannot vouch for the innumerable
home-brewed methods that are said to suppress hiccups (breath-holding, induced fright, anesthetization or
stimulation of the external ear canal or concha, etc.); but where the neurologist is asked to help in an intractable case
of unknown origin (usually male), baclofen is sometimes effective.
Disorders of Ventilation Due to Neuromuscular Disease
Failure of ventilation in the neuromuscular diseases presents as one of two symptom complexes: one occurs in
patients with acute generalized weakness, such as Guillain-Barre syndrome and myasthenia gravis, and the other in
patients with subacute or chronic diseases, such as motor neuron disease, certain myopathies (acid maltase,
nemaline), and muscular dystrophy. The review by Polkey and colleagues provides a more extensive list. Patients in
whom respiratory failure evolves rapidly, in a matter of hours, become anxious, tachycardic, and diaphoretic; they
exhibit the characteristic signs of diaphragmatic paralysis. They experience paradoxical respiration, in which the
abdominal wall retracts during inspiration, owing to the failure of the diaphragm to contract, while the intercostal
and accessory muscles create a negative intrathoracic pressure. Or, there is respiratory alternans, a pattern of
diaphragmatic descent only on alternate breaths (this is more characteristic of airway obstruction). These signs
appear in the acutely ill patient when the vital capacity has been reduced to approximately 10 percent of normal, or
approximately 500 mL in the average adult.
Patients with chronic but stable weakness of the respiratory muscles, demonstrate signs of CO2 retention, such as
daytime somnolence, headache upon awakening, nightmares, and, in extreme cases, papilledema. The accessory
muscles of respiration are recruited in an attempt to maximize tidal volume, and there is a tendency for the patient to
gulp or assume a rounded "fish mouth" appearance in an effort to inhale additional air. In general, patients with
chronic respiratory difficulty tolerate lower tidal volumes without dyspnea than do patients with acute disease, and
symptoms in the former may occur only at night, when respiratory drive is diminished and compensatory
mechanisms for obtaining additional air are in abeyance.
Treatment of the two conditions differs. The chronic type of respiratory failure may require only nighttime support
of ventilation, which can be provided by negative pressure devices such as a cuirass or preferably, by intermittent
positive pressure applied by a tight-fitting mask over the nose (BIPAP or CPAP). These measures may also be used
temporarily in acute situations, but in many cases there will be need of a positive-pressure ventilator that provides a
constant volume with each breath. This can be effected only through an endotracheal tube. In patients with chronic
weakness, the use of a cough-assist machine to provide an artificial cough three or four times a day is remarkably
effective in preventing pulmonary infection.
Typical ventilator settings in cases of acute mechanical respiratory failure, if there is no pneumonia, are for tidal
volumes of 8 to 10 mL/kg, depending on the compliance of the lungs and the patient's comfort, at a ventilator rate
between 4 and 12 breaths per minute, adjusted to the degree of respiratory failure. The tidal volume is kept relatively
constant in order to prevent atelectasis, and only the rate is changed as the diaphragm becomes weaker or stronger.
Decisions regarding the need for these mechanical devices are frequently difficult, particularly since patients with
chronic neuromuscular illnesses often become dependent on a ventilator. Further details regarding the management
of ventilation in acute neuromuscular weakness are given in the section on Guillain-Barre syndrome on page 1126.
The presence of oropharyngeal weakness as a result of the underlying neuromuscular disease may leave the patient's
airway unprotected and require endotracheal intubation before mechanical ventilation becomes necessary. It is also
difficult to decide when to remove the endotracheal tube in cases of oropharyngeal weakness. Because the safety of
the swallowing mechanism cannot be assessed with the tube in place, one must be prepared to reintubate the patient
or to have a surgeon prepared to perform a tracheostomy after extubation, in the event that aspiration occurs.
Not infrequently we encounter a patient in whom the earliest feature of neuromuscular disease is subacute
respiratory failure; this is manifest as dyspnea and exercise intolerance but without other overt signs of
neuromuscular disease. Most such cases turn out to have motor neuron disease, but rare instances of myasthenia
gravis, acid maltase deficiency, polymyositis, nemaline myopathy, Lambert-Eaton syndrome, or chronic
inflammatory demyelinating polyneuropathy may present in this way. The neurologist may be consulted in these
cases after other physicians have found no evidence of intrinsic pulmonary disease. The spirometric flow-volume
loop examination in mechanical-neuromuscular forms of respiratory failure shows low airflow rates with diminished
lung volumes that together simulate a restrictive lung disease. Among such patients we have also found instances of
an apparently isolated unilateral or bilateral phrenic nerve paresis, which had followed surgery or an infectious
illness. The problem is probably akin to brachial neuritis (Parsonage-Turner syndrome, page 1165), in which the
phrenic nerve can be implicated.
Neuromuscular Respiratory Failure in Critically Ill Patients Neurologists increasingly are being called upon to
address the question of an underlying neuromuscular cause for respiratory failure in a critically ill patient. Aside
from the acute neuromuscular diseases listed above, Bolton and colleagues have delineated a critical illness
polyneuropathy, which accounts for the majority of instances in which there is an inability to wean the patient from
a ventilator once the more conventional causes of pulmonary insufficiency such as malnutrition and hypokalemia
have been addressed. Such a critical illness polyneuropathy has been identified by electromyography (EMG) in as
many as 40 percent of patients in medical intensive care units. Most of the patients have had an episode of sepsis or
have had multiple-organ failure (see Chap. 46). Less often, a critical illness myopathy occuring in relation to
administration of high-dose corticosteroids (Chap. 51) has been the cause of generalized weakness and respiratory
failure. This unique polymyopathy occurs mainly in patients who are receiving neuromuscular postsynaptic blocking
drugs such as pancuronium with the high-dose steroids (page 1237). Severe hypophosphatemia is another cause of
acute generalized weakness.
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