12: Neurological status

Christine Iacovetta

BluePearl Veterinary Partners, Queens, New York

Introduction

Seizures, coma, paraplegia, quadriplegia, and generalized tremors are four of the most devastating neurological problems that necessitate early recognition and immediate therapeutic intervention for ICU patients (Figure 12.1). The end‐result of successful therapy is not just patient survival, but includes recovery from neurological dysfunction after injury. Whether the patient presents to the ICU with neurological signs or develops neurological signs later as a consequence of disease outside the nervous system, there is little room for error in diagnosis and administering treatments.

Flowchart of the prioritization and approach to severe neurological signs in the ICU patient. The four most critical are seizures, coma, paraplegia quadriplegia, and generalized tremors. — **Figure 12.1** Prioritization and approach to severe neurological signs in the ICU patient. The four most critical presentations or changes in neurological signs in the ICU patient are listed at the top of the algorithm with guidelines for immediate patient stabilization.

Neurological injury occurs in two phases. Primary injury occurs immediately and directly from the initial effects of the insult (e.g. mechanical tissue damage, contusion, infarction). Secondary injury occurs minutes to days later and results from intracranial and extracranial factors secondary to the primary insult.

Respiratory rate and effort, cardiac output, blood pressure, endocrine regulation, and basal organ functions depend upon the integrity of the brain and spinal cord. As the control center of the body, the nervous system requires a consistent amount of oxygen and glucose to preserve life‐sustaining metabolic functions. Metabolic and homeostatic changes such as hypotension, hypoxia, hypoglycemia or fever contribute to secondary damage (Table 12.1). Hypoxia and hypoglycemia are the two most devastating systemic abnormalities. Neural tissues become damaged due to lack of the energy source adenosine triphosphate (ATP). Cell membrane channels and pumps become dysfunctional, and ultimately, there is an intracellular influx of calcium and sodium ions. The resultant osmotic effect causes cellular and extracellular swelling. Edema of the nervous tissue occurs due to the release of inflammatory mediators, reactive oxygen species, and enzyme systems, each leading to cell death. Brain edema and swelling within an intact cranium can progress to life‐threatening brain herniation with coma and respiratory paralysis. It is therefore essential to monitor the neurological status of all ICU patients, giving particular attention to clinical signs of brain swelling, spinal cord compression, and systemic influences that may affect nervous tissue function.

Table 12.1 Systemic disorders that influence CNS function.

Parameter	Neurological derangement	Mechanism of effect on CNS	Treatment goal	Note
Oxygen PaO₂ ≤ 80 mmHg PaO₂ ≤ 60 mmHg = severe hypoxemia	Anxiety Dull mentation Seizures	Inadequate energy production	Oxygen support PaO₂ > 60 mmHg	Avoid nasal cannula if causes sneezing or agitation
Carbon dioxide Hypocarbia PCO₂ < 35 mmHg Hypercarbia PCO₂ > 45 mmHg	Anxiety Dull mentation Dull mentation Coma	Cerebral vasoconstriction Cerebral vasodilation, sympathetic stimulation	Normalize PCO₂ = 35–45 mmHg	Mechanical ventilation may be required to maintain normal PCO₂
pH Acidemia pH <7.35 Alkalemia pH >7.45	Dull mentation Dull mentation	Alterations in cerebral blood flow, cardiovascular effects, ROS	Normalize pH 7.34–7.40	Correct fluid deficits, ventilation and other abnormalities Administer sodium bicarbonate only if refractory metabolic acidemia
Glucose Hypoglycemia Hyperglycemia	Weakness Seizures Stupor Coma Weakness Stupor Coma Neuropathy	Alterations in cerebral blood flow, altered Na/K ATPase, increased intracellular calcium, ROS Lactate production, edema, excitatory amino acid release, ROS, altered cerebral blood flow	Euglycemia – <180 mg/dL	Supplementation with solutions greater than 7.5% dextrose should not be administered in a peripheral catheter. Monitor often to titrate needs
Potassium Decreased	Generalized weakness Paralysis Ventral flexion of neck in cats	Depressed muscle excitability causing severe weakness or paralysis	Normalize 3.5–5 mEq/L	Ventilation can be needed if paralysis of diaphragm; may be seen with chronic renal disease in cats. Replace no faster than 0.5 mEq/kg/h
Magnesium Increased Decreased	Lethargy Weakness Hyporeflexia Respiratory depression Arrhythmia Weakness Ataxia Tremors Seizures	Decreased acetylcholine release and neuromuscular blockade Increased acetylcholine release	Normalize Dogs: 1.9–2.5 mg/dL total or 0.4–0.6 mmol/L Cats: 1.8–2.9 mg/dL total or 0.4–0.7 mmol/L	Correct any potassium or calcium abnormalities as well as magnesium
Phosphorus Increased Decreased	Weakness Seizures Ataxia Seizures	Signs usually secondary to calcium sequestration leading to hypocalcemia Decreased cellular energy and 2,3‐DPG	Normalize 2.5–5.5 mg/dL Supplementation with KH₂PO_4.	Treat primary disease to correct Make sure to take into account the K amount given to avoid overdosing
Blood pressure Hypotension Hypertension	Weakness Ataxia Dull mentation Blindness Disorientation Seizures Head tilt	Decreased oxygen and energy supply Vascular inflammation and injury, altered blood flow	Systolic pressure: 100–150 mmHg	Patients with severe hypertension should have a stepwise decrease in pressure while hospitalized to avoid signs of hypotension
Thiamine Deficiency (B₁)	Bilateral vestibular signs Mydriasis Ventral flexion of neck in cats Lethargy Seizures	Deficiency in carbohydrate metabolism leading to energy depletion and neuronal necrosis	Supplement: 12.5–50 mg/dog 12.5–25 mg/cat IM, SC or PO daily	Seen with diets mainly of raw fish or diets heated to excessive temperatures
Thyroid Hypothyroidism Hyperthyroidism	Peripheral neuropathy Myxedema coma Hypertensive signs Thyroid storm Agitation Seizures Thyrotoxic periodic paralysis	Not completely understood – possibly depletion in energy metabolism and altered cerebral blood flow Increased stimulation of the cardiovascular and sympathetic systems	Supplementation to normal levels Normalize with drug therapy or radioactive iodine	An association also exists with: Peripheral vestibular signs Facial nerve paralysis Laryngeal paralysis Megaesophagus Treatment of thyroid storm will necessitate rapid reduction in hormone production and release as well as cardiovascular support
Body temperature Hypothermia Hyperthermia	Lethargy Dull mentation Dull mentation Seizures	Decreased metabolic demand and altered blood flow Increased metabolic demand and altered blood flow	Normalize body temperature 100–102.5 °F	Warming should be performed slowly with careful attention to blood pressure Cooling efforts should be stopped around 103 °F to avoid overshooting If a true fever exists, treatment should be aimed at the underlying disease, not active cooling
Coagulation Hypocoagulation Hypercoagulation	Dull mentation Seizures Dull mentation Seizures	Hemorrhage directly into or around nervous tissue leading to dysfunction and potential increased intracranial pressure Ischemia/infarct to nervous tissue, vascular effects altering blood flow	Monitor coagulation factor parameters and platelet numbers	Plasma is not recommended unless clinical risk of bleeding is high or there is active hemorrhage
Calcium Decreased Increased	Tremors Facial scratching Stiff gait Seizures Lethargy Weakness Ataxia Twitching Seizures	Decreased cell membrane threshold potential Increased cell membrane threshold potential	Normalize ionized calcium levels	Always measure ionized levels as other factors can affect total calcium levels
Sodium Decreased Increased	Dull mentation Seizures Coma Dull mentation Seizures Coma	Osmotic swelling of cells Osmotic shrinkage of cells	Normalization of sodium levels	Do not change serum sodium level faster than 0.5 mEq/L/h unless the disease is acute to avoid worsened neurological insult

ROS, reactive oxygen species generation.

Monitoring methods

Appropriate diagnostic tests and therapy can be initiated while working to minimize or eliminate the impact of systemic disorders on the nervous system. Important information is gained from the patient history, followed by thorough physical, orthopedic, and neurological examinations. Serial assessments of neurological function are important since patient status can rapidly change or deteriorate. Additional diagnostic and monitoring tools include routine and ancillary clinicopathological testing, neuroimaging, electrodiagnostic testing, and more invasive procedures such as cerebrospinal fluid (CSF) collection or intracranial pressure (ICP) monitoring. The choice of tests and the sequence in which they are performed will vary depending on patient status.

History

A review of the recent and past patient history should include signalment (age, breed, sex), prescribed medications (Table 12.2), recent or past seizures, head or spinal trauma, past loss of consciousness, known neurological diseases, liver, renal and thyroid function, environment, potential exposure to toxins, gagging or regurgitation, presence of other animals, past problems with anesthesia, known allergies, and diet. Information is gathered from other clinicians (neurologist, radiologist, and/or surgeon) interacting with the patient for details regarding previous patient history, examination and diagnostic findings, recent treatment, drugs or contrast agents administered, complications to anticipate and treatment recommendations.

Table 12.2 Potential CNS side‐effects of drugs frequently used in the ICU.

CNS signs	Drug	Therapy
Vestibular	Metronidazole Aminoglycosides	Discontinue – diazepam Discontinue if possible
Seizures	Enrofloxacin IV Lidocaine Dobutamine Iohexol contrast	Discontinue or change route of administration Discontinue, reduce dose, intralipid Discontinue, reduce dose Stop administration *For all cases, diazepam can be given to stop the immediate seizure
Depression/ sedation	Acepromazine Chlorpromazine Benzodiazepines Opiates Anticonvulsants Dexmedetomidine Mirtazapine Tramadol	Discontinue, reduce dose Discontinue, reduce dose Discontinue, reduce dose, flumazenil Discontinue, reduce dose, naloxone Wait for signs to improve, change drug Discontinue, reduce dose, atipamezole Discontinue, reduce dose, decrease frequency Discontinue, reduce dose
Agitation/ disorientation	Opiates Benzodiazapines Metoclopramide	Discontinue, reduce dose, naloxone, change drug Discontinue, reduce dose, flumazenil Discontinue, reduce dose
Ataxia	Any sedative drug Epidural/local block	Discontinue, reverse drug if possible Wait for effects of drug to wear off
Tremors	Avermectins Isoproterenol Epinephrine	Discontinue, intralipid Discontinue, reduce dose Discontinue, reduce dose

Physical and orthopedic examinations

Basic physical parameters to monitor begin with temperature, pulse, and respiration, which reflect central nervous system (CNS) energy demands, CNS perfusion capabilities, and brain control of ventilation. Changes in the breathing pattern may occur with disease of the cerebrum or one of the four parts of the brainstem (diencephalon, midbrain, pons, and medulla). Cheyne–Stokes respirations are cycles where respiration becomes increasingly deeper then increasingly shallower with possible apneic periods. Severe cerebral or diencephalic (cranial brainstem) lesions can result in Cheyne–Stokes respirations. Hyperventilation can occur with severe midbrain disease, but must be differentiated from hyperventilation associated with acidosis or pain. An apneustic breathing pattern is characterized by deep gasping inspirations held for 30–90 seconds then expelled. Irregular and apneustic breathing is often associated with caudal pontine or medulla oblongata lesions due to loss of the vagal nerve and pneumotaxic center function. Loss of consciousness and changes in posture and pupils discussed below usually accompany abnormal respirations. High cervical lesions can result in respiratory paresis or paralysis due to loss of intercostal and diaphragm motor function from compression, edema or hemorrhage and immediate ventilatory assistance may be required.

Careful examination for evidence of trauma, systemic disease, pain, bleeding or bruising should be performed to detect systemic problems that can impact the nervous system. Evaluation of the eyes may reveal chorioretinitis suggestive of infectious disease or neoplasia, papilledema suggestive of increased ICP, or scleral hemorrhage. Orthopedic examination is performed to detect bone, tendon, joint, or muscular disorders that can influence the response to neurological testing or contribute to further neurological injury. Neck or back pain is noted and affected animals are handled little until analgesics are given and vertebral fracture or dislocation is ruled out. Pain on manipulation of the neck or back can provide an initial localization of a spinal cord lesion.

Neurological examination

Goals of the neurological examination are to:

determine if there are neurological deficits present
localize the lesion(s)
determine lesion severity
monitor for changes over time.

An attempt should be made to explain all neurological deficits by a single lesion. If that is impossible then a multifocal neurological disorder is most likely present. It is best to perform the initial neurological examination prior to administration of sedatives or analgesics when possible, unless seizures, delirium or pain warrants medication sooner.

The neurological examination usually begins with an assessment of seizures, mentation, level of consciousness, cranial nerves, and basic body posture to identify and localize intracranial problems. Lesions of the brainstem have a poorer overall prognosis than those in the cerebrum and cerebellum. Asymmetrical neurological deficits suggest a more focal disorder, such as mass, infarct or hemorrhage. Multifocal lesions are more typical of inflammation or metastatic neoplasia. A guide for localization of intracranial lesions by neurological and clinical signs is provided in Table 12.3.

Table 12.3 Localization of neurological lesions in the brain by clinical signs.

Lesion location	Clinical signs	Note
Cerebrum and diencephalon CN I CN II	Seizures, behavior change, dementia, delirium, depression, stupor or coma with normal or miotic pupils; head pressing; pacing; circling; loss of smell (CN I); blind with dilated pupils (CN II) or normal pupils; Cheyne–Stokes breathing pattern	Acute lesions may have transient contralateral hemiparesis or quadriparesis; spinal reflexes normal or exaggerated
Midbrain CN III CN IV Rubronuclei (main flexor tract)	Stupor, coma, dilated (CN III) or midrange fixed pupils; ventrolateral strabismus (CN III); absent pupil light response (CN III); pupil rotation (CN IV)	Quardriparesis with bilateral lesion; decerebrate rigidity with severe lesion; spinal reflexes normal or exaggerated in all four limbs
Pons CN V	Depression, stupor, coma; miotic pupils with normal mentation; atrophy of temporal and masseter muscles or decreased facial sensation or hyperesthesia of face (CN V)	Ipsilateral hemiparesis; spinal reflexes normal or exaggerated in all four limbs
Cranial medulla oblongata CN VI CN VII CN VIII Reticulospinal tract (extensor tract) Vestibulospinal tract (extensor tract)	Depressed or normal mentation; stupor or coma; medial strabismus (CN VI); reduced blink, lip and ear reflex (CN VII); nystagmus and disequilibrium (CN VIII)	Ipsilateral hemiparesis; spinal reflexes normal or exaggerated in all four limbs
Caudal medulla oblongata CN IX CN X CN XI CN XII	Depressed or normal mentation; stupor or coma; hyperventilation; apneustic breathing; heart rate and blood pressure alterations; dysphagia (CN IX or X); megaesophagus (CN X); laryngeal paresis (CN X); tongue atrophy or paralysis (CN XII)	Ipsilateral hemiparesis; spinal reflexes normal or exaggerated in all four limbs
Cerebellum	Intention tremors and ataxia of the head; head tilt away from lesion; nystagmus; loss of menace response; ipsilateral or bilateral dysmetria; normal limb strength	Normal reflexes all four limbs unless opisthotonus or decerebellate rigidity (conscious animal)

CN, cranial nerve.

Seizures

Past or present seizures indicate a primary disease of the cerebrum or diencephalon or secondary effects of metabolic disease. The majority of seizures in dogs are generalized with loss of consciousness and tonic clonic movements. However, focal seizures may occur with or without the loss of consciousness and can have a wide variety of manifestations. Patients will often present with focal facial seizures that may progress to a more generalized seizure. A list of common toxins known to cause seizures or tremors is provided in Box 12.1. Prolonged seizures result in hypoxia, hypoglycemia, hyperthermia, and lactic acidosis and constitute a neurological emergency. The seizure must be stopped immediately to reduce the amount of secondary brain damage (see Seizure treatment and complications below).

Mentation and level of consciousness

The patient should be observed at rest and wandering around the examination room if ambulatory, noting their basic movements and response to the environment. Animals with lesions of the cerebrum and diencephalon may have a blank stare, wander aimlessly, compulsively pace, press their head against a corner or wall or circle (with no head tilt) or turn the head toward the side of the lesion.

Alterations of mentation and consciousness may be graded from 1 to 18 using a modified Glasgow Coma Scale (Table 12.4). A defined grading system provides a more objective means to determine the initial severity of intracranial disease and monitor for changes. The mentation can be classified as conscious with normal, hysterical, inappropriate, or obtunded behavior. Changes in levels of consciousness include stupor (laterally recumbent responsive only to noxious stimuli) or coma (unconscious, unresponsive to any stimuli) (Table 12.5). Stupor or coma can occur with lesions anywhere in the cerebrum or brainstem, due to dysfunction of the ascending reticular activating system (ARS). Input to the ARS normally alerts the brain, resulting in consciousness. Stimulation of sensory peripheral and cranial nerves projects impulses into the reticular formation within the medulla, pons, and midbrain, which then projects through the diencephalon to alert the cerebral cortex. Common causes of alterations in mentation and consciousness include brain trauma, neoplasia, and inflammation as well as systemic metabolic or inflammatory disease, intoxication or prescribed medications (see Table 12.2).

Table 12.4 Modified Glasgow Coma Scale. Within each category a score of 1–6 is assigned. A score of 18 is normal; as the score decreases from this, the severity of neurological injury increases [3]. A score of 8 at admission is associated with a 50% probability of survival [4].

Source: Platt SR, Radaelli ST, McDonnell JJ. The prognostic value of the Modified Glasgow Coma Scale in head trauma in dogs. J Vet Med. 2001;15(6):581–4. Open Access License, Wiley.

Motor activity	Score
Normal gait, normal spinal reflexes	6
Hemiparesis, tetraparesis, or decerebrate activity	5
Recumbent, intermittent extensor rigidity	4
Recumbent, constant extensor rigidity	3
Recumbent, constant extensor rigidity with opisthotonus	2
Recumbent, hypotonia of muscles, depressed or absent spinal reflexes	1
Brainstem eflexes
Normal pupillary reflexes and oculocephalic reflexes	6
Slow pupillary reflexes and normal to reduced oculocephalic reflexes	5
Bilateral unresponsive miosis and normal to reduced oculocephalic reflexes	4
Pinpoint pupils with reduced to absent oculocephalic reflexes	3
Unilateral, unresponsive mydriasis and reduced to absent oculocephalic reflexes	2
Bilateral, unresponsive mydriasis and reduced to absent oculocephalic reflexes	1
Level of consciousness
Occasional periods of alertness and responsive to environment	6
Depression or delirium, responsive, but response may be inappropriate	5
Semicomatose, responsive to visual stimuli	4
Semicomatose, responsive to auditory stimuli	3
Semicomatose, responsive only to repeated noxious stimuli	2
Comatose, unresponsive to repeated noxious stimuli	1
Total score

Table 12.5 Levels of consciousness in the cat and dog.

Level of consciousness	Definition
Normal	Exhibits a response typical of the “normal” temperament of the patient
Demented	Response is not typical of the “normal” temperament of the patient or is different from what is a normal expected response
Delirium	Irrational or uncontrollable emotional response
Obtunded	Decreased conscious response to external nonnoxious stimuli – subjectively is graded as mild, moderate or severe
Stupor	Conscious response only with the application of a noxious stimulus
Unconscious	Lack of any conscious response to any external stimuli limited to a brief period of time (seconds or minutes)
Coma	Prolonged lack of any conscious response to any external stimuli – spinal and cranial nerve reflexes may or may not be present depending on the location of the lesion

Mentation changes caused by systemic metabolic disorders should improve markedly as the systemic abnormalities are corrected unless secondary damage has occurred.

Cranial nerves

The functions of the cranial nerves (Table 12.6) are assessed to evaluate the health of the peripheral nerve and the area of the brainstem containing the nucleus of that nerve. Normal cranial nerve function reduces the likelihood of a lesion in a specific region of the brainstem. A change in mentation or level of consciousness with normal cranial nerve functions suggests cerebral and diencephalic disease.

Cranial nerve	Location of nuclei	Function	Testing	Note
I Olfactory	Diencephalon	Olfaction	Cover eyes and present food under nose	Not usually tested. Irritating substances should not be used to avoid stimulation of other nerves
II Optic	Diencephalon	Vision	Menace response Visual tracking of cotton ball/object	Note any anisocoria
III Oculomotor	Mesencephalon (midbrain)	Motor to extraocular muscles (lateral, medial, ventral rectus) Motor to levator palpebrae superioris Parasympathetic control to pupil	Look for strabismus – resting and positional Look for drop of the upper eyelid Look for mydriasis and response to light	Deficit results in ventrolateral strabismus
IV Trochlear	Mesencephalon (midbrain)	Motor to extraocular muscle (dorsal oblique)	Look for strabismus – resting and positional	Deficit results in medial strabismus
V Trigeminal	Metencephalon (pons)	Sensory to the face Three branches: maxillary nerve mandibular nerve ophthalmic nerve Motor to muscle of mastication	Corneal reflex – touch surface of cornea and look for withdrawal of head/globe Palpebral reflex – touch medial and lateral palpebral fissures and look for closure of the eyelid Facial sensation – pinch both sides of the rostral upper and lower lip and look for withdrawal of the lip and blinking; if there is no response insert a small blunt‐ended object into each nostril to evoke withdrawal of the head Palpate masseter and temporal muscle for symmetry and size. Mouth should be in a closed position	Motor response is due to CN VI and VII Motor response is due to CN VII Motor response is due to CN VII and neck muscles
VI Abducens	Myelencephalon (cranial medulla)	Motor to extraocular muscles (retractor bulbi and lateral rectus)	Look for strabismus – resting and positional Corneal reflex – touch surface of cornea and look for withdrawal of the globe backwards	Deficit results in top of eye rotated laterally – not obvious on dogs due to circular pupil Sensory response is due to CN V
VII Facial	Myelencephalon (cranial medulla)	Motor to muscle of facial expression Parasympathetic supply to lacrimal gland and sublingual and submandibular salivary gland Sensory and taste to rostral 2/3 of tongue	Look for facial symmetry Palpebral reflex – touch medial and lateral palpebral fissures and look for closure of the eyelid Facial sensation – pinch both sides of the rostral upper and lower lip; look for withdrawal of the lip and blinking Schirmer’s tear test can be used to test lacrimal innervation	Sensory response is due to CN V Sensory response is due to CN V
VIII Vestibulocochlear	Myelencephalon (cranial medulla)	Vestibular function and hearing	Ataxia with wide‐based stance Circling, head tilt Resting nystagmus Positional ventrolateral strabismus Vestibuloocular reflex – slowly move the nose to one side, the eyes should move in the opposite direction to stabilize the visual field forward (physiological nystagmus)	Usually toward lesion Fast phase away from lesion Same side as lesion Positional nystagmus should also be assessed by laying the patient on its back and looking for rapid eye movements Bilateral disease will not have a head tilt or nystagmus of any kind (including physiological) Cerebellar lesions will cause paradoxical vestibular signs, proprioceptive deficits used to decipher side of lesion
IX Glossopharnyngeal	Myelencephalon (caudal medulla)	Motor to larynx and pharynx Sensory supply to pharynx Sensory and taste to caudal 1/3 of tongue Parasympathetic supply to parotid and zygomatic salivary gland	Gag reflex	It is important to question the owner about changes in voice, or any dysphagia/regurgitation at home
X Vagus	Myelencephalon (caudal medulla)	Motor to larynx and pharynx Sensory supply to pharynx Parasympathetic supply to viscera	Gag reflex	Same for CN IX
XI Accessory	Myelencephalon (caudal medulla)	Motor to trapezius muscle	Look for trapezius atrophy	Difficult to assess
XII Hypoglossal	Myelencephalon (caudal medulla)	Motor to tongue muscles	Look for atrophy, asymmetry or deviation of the tongue	In chronic cases tongue will deviate to the affected side
Horner’s syndrome

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12: Neurological status

Introduction