Case History
A medical intensivist requests a neurologic consultation on a 56-year-old man who was admitted to the intensive care unit (ICU) for respiratory failure due to pneumonia 2 weeks ago and has failed to wean from the ventilator.

Decision Point A. A thorough history and chart review is necessary at this time. What questions are of particular relevance to your diagnosis and treatment plan?

A1. Admitting diagnosis
A2. Past history of neurologic disease
A3. Detailed list of medications used during the admission
A4. Hospital complications
A5. Laboratory review
He received a single injection of succinylcholine prior to endotracheal intubation and received only IV sedation throughout the remainder of the ICU stay. His hospital course was complicated by sepsis with renal failure for which he received vancomycin for methicillin-resistant Staphylococcus aureus. Currently the sepsis and pneumonia have resolved. Attempts at weaning from mechanical ventilation have been limited due to respiratory fatigue associated with increased blood concentration of carbon dioxide.

Decision Point B. To which of the following should you pay particular attention as you perform your neurologic examination?

B1. Spontaneous movements
B2. Mental status
B3. Cranial nerves
B4. Grimace to noxious stimulation
B5. Muscle stretch reflexes
B6. Muscle strength
B7. Sensory examination
On physical examination, the patient is intubated, mechanically ventilated, and not breathing above the ventilator set rate. There are no spontaneous movements of the extremities. On neurologic examination, he is awake and follows simple commands to move the eyes and blink. Cranial nerve examination reveals normal extraocular movements and facial strength. Motor examination reveals a flaccid quadriparesis with trace movements at the ankles and no movement of the toes. There is 2+ strength of the proximal upper and lower extremities. The muscle stretch reflexes are absent throughout the upper and lower extremities. Although there is no withdrawal to noxious stimulation applied to the distal fingers and toes, the patient has an unequivocal grimace.

Decision Point C. What laboratory testing is of particular relevance to the diagnosis?

C1. MRI of the brain
C2. MRI of the cervical spinal cord
C3. Electrolyte panel
C4. Renal and liver profile
C5. Creatine kinase
C6. Nerve conduction studies and EMG
C7. Repetitive nerve stimulation
C8. Muscle and nerve biopsy
All routine laboratories are normal, including a liver profile, creatinine, and creatine kinase. Motor nerve conduction studies reveal absent responses in the lower extremities and low-amplitude responses in the upper extremities. No electrophysiologic evidence of primary demyelinating features such as conduction block, temporal dispersion, or severe conduction velocity slowing is present. The sensory nerve conduction responses of the upper and lower extremities are absent. Needle examination of weak muscles in the upper and lower extremities shows widespread fibrillations and severely reduced recruitment of normal amplitude, normal duration motor unit potentials.

Decision Point D. What is the most likely diagnosis?

D1. Polymyositis
D2. Acute inflammatory demyelinating polyneuropathy
D3. Critical illness polyneuropathy
D4. Critical illness myopathy
The clinical and electrophysiologic features are consistent with an acute, severe generalized polyneuropathy with axonal features as seen with critical illness polyneuropathy.

Decision Point E. What interventions should you recommend at this time?

E1. Family and caregiver conference
E2. Treatment with IV immunoglobulin
E3. Treatment with IV methylprednisolone
E4. Tracheostomy and percutaneous endoscopic gastrostomy (PEG)
Decision Point F. A tracheostomy and PEG tube were placed. A family conference is arranged. What prognosis should be discussed with the patient?

F1. Recovery expected within 2 weeks
F2. Recovery with persistent neurologic deficits expected within 2 weeks
F3. Complete recovery expected after more than 1 year
F4. Recovery with persistent neurologic deficits expected after more than 1 year
WEIGHTS AND COMMENTS
EXPLANATION OF WEIGHTS:
* +5 Unequivocally required for diagnosis
* +3 Important for diagnosis but not immediately necessary
* +1 Potentially useful for diagnosis (routine studies fall into this category)
* 0 Neutral impact, neither clearly helpful nor harmful under given circumstances
* -1 Not harmful, but nonproductive, time-consuming, and not cost-effective
* -3 Nonproductive and potentially harmful
* -5 Totally inappropriate and definitely harmful; may threaten life
A1. Admitting diagnosis +3
A review of the admitting diagnosis and clinical presentation is essential to the evaluation of a patient who fails to wean from the ventilator. Signs and symptoms of neuromuscular disorders that lead to respiratory failure are usually noted upon admission. In cases where rapid progression of weakness occurs, however, acute inflammatory demyelinating polyneuropathy (AIDP), myasthenia gravis, spinal cord compression, and occasionally motor neuron disease may be initially missed.

A2. Past history of neurologic disease +3
It is important to determine whether the patient has a prior history of neurologic disease. Neuromuscular dysfunction identified during critical illness cannot be assumed to have developed during the hospitalization and may be a manifestation of preexisting disease. In some cases, such as in the setting of preexisting myasthenia gravis, the appropriate treatment may be delayed or not provided if the past neurologic history is unknown.

A3. Detailed list of medications used during the admission +1
Many medications used during critical illness have a mechanism of action upon nerve excitability or the neuromuscular junction. Some medications have a direct toxic effect on muscle. Aminoglycoside antibiotics and corticosteroids are associated with the development of acquired paresis during critical illness. Neuromuscular blocking agents may have a prolonged effect due to impaired metabolism and clearance associated with liver or renal failure.

A4. Hospital complications +5
The systemic inflammatory response syndrome, sepsis, and multiple organ failure are common complications in critically ill patients. These syndromes are associated with critical illness polyneuropathy (CIP), as well as critical illness myopathy (CIM).

A5. Laboratory review +1
Most laboratory assessments are of limited value. However, electrolyte disturbances, such as hypokalemia and hypocalcemia, can result in generalized weakness that is easily treated if recognized. An elevated creatine kinase (CK) level may suggest he presence of myopathy. When CK is markedly elevated, a necrotizing myopathy should be considered.

B1. Spontaneous movements +1
The absence of spontaneous limb movements may be the earliest sign of the development of acquired paresis in the ICU.

B2. Mental status +3
CIP and CIM do not directly impair the mental state. Patients are, however, commonly encephalopathic from sepsis, medications, or organ failure. When altered mental status is present in a patient with generalized weakness, the etiology of the encephalopathy should be considered in addition to the presence of peripheral nervous system dysfunction.

B3. Cranial nerves +3
The presence of cranial nerve involvement suggests a brainstem lesion as seen in stroke or central pontine myelinolysis. Although mild facial weakness may be present, cranial nerve signs are typically not associated with CIP or CIM.

B4. Grimace to noxious stimulation +3
The presence of encephalopathy, sedation, and confusion results in poor cooperation by the patient and limits sensory and motor testing. In this setting the absence of a limb withdrawal with an intact grimace to noxious stimulation may be the only clinical indication of paresis.

B5. Muscle stretch reflexes +3
Hyperreflexia is seen with lesions of the brain and spinal cord. Reduced or absent muscle stretch reflexes typically indicate a lesion in the peripheral nervous system. In many cases of acute myelopathy, however, the reflexes are initially lost (spinal shock) and upper motor neuron signs develop over subsequent weeks.

B6. Muscle strength +3
The pattern of muscle strength can help localize the lesion. Weakness of distal greater than proximal extremity muscle groups points to a length-dependent, axonal polyneuropathy. When proximal extremity muscle strength is weaker than distal muscle strength, a myopathy should be suspected. In cases of severe weakness due to either cause, proximal and distal muscles may be equally involved, and as a result neuropathy cannot be reliably distinguished from myopathy based on the motor examination.

B7. Sensory examination +3
An intact sensory examination excludes the presence of CIP and suggests CIM. In the majority of cases, however, a detailed sensory examination is limited by patient cooperation and not helpful.

C1. MRI of the brain -1
In a patient who is awake, quadriparetic, hyporeflexic, and without cranial nerve signs, an MRI of the brain is unlikely to reveal the etiology. Although noninvasive and without significant risk, an MRI is expensive and time-consuming when performed on a mechanically ventilated patient in the ICU.

C2. MRI of the cervical spinal cord +5
In this patient no cranial nerve signs are present; therefore, an acute high cervical spinal cord lesion presenting with "spinal shock" cannot be clinically excluded. An MRI of the cervical spine is warranted in this situation.

C3. Electrolyte panel +1
Although not helpful in the evaluation for CIP or CIM, the identification of hypokalemia or hypocalcemia may provide an alternate etiology for the patient's weakness.

C4. Renal and liver profile +1
Although not helpful in the evaluation for CIP or CIM, the presence of renal or liver failure may prolong the effects of neuromuscular blocking agents, which may in turn provide an alternate etiology for the patient's weakness.

C5. Creatine kinase +1
The presence of an elevated CK is suggestive of CIM. However, in CIM, the CK can be elevated or normal. A normal CK level, therefore, does not exclude the diagnosis of CIM. When markedly elevated, a necrotizing myopathy should be considered.

C6. Nerve conduction studies and EMG +5
Nerve conduction studies are essential to the identification of a neuromuscular etiology of acquired paresis. In addition to confirming the clinical suspicion of CIP and CIM, this procedure will help to exclude an alternative diagnosis such as a demyelinating polyneuropathy.

C7. Repetitive nerve stimulation +1
In cases where a high clinical suspicion for prolonged neuromuscular blockade is present, repetitive nerve stimulation provides an easy way to confirm the diagnosis at the bedside. However, this procedure is not helpful in confirming a diagnosis of CIP or CIM.

C8. Muscle and nerve biopsy +1
No histopathologic features of muscle and nerve are specific to CIM or CIP. When typical clinical and electrophysiologic features of CIM or CIP are found, routine muscle and nerve biopsy may not be necessary. In cases where an alternative diagnosis, such as inflammatory myopathy or peripheral nervous system vasculitis, is considered, a muscle and nerve biopsy should be obtained.

D1. Polymyositis -3
No clinical or electrophysiologic findings suggest a diagnosis of polymyositis. An incorrect diagnosis of polymyositis could lead to treatment with unnecessary and potentially harmful medications and treatment regimens, such as plasma exchange.

D2. Acute inflammatory demyelinating polyneuropathy -3
Although the findings on neurologic examination are consistent with a polyneuropathy, electrophysiologic features of a demyelinating neuropathy, such as conduction block, temporal dispersion, and conduction velocity slowing, were not found on the nerve conduction studies. As a result, AIDP is unlikely, and this incorrect diagnosis could lead to treatment with unnecessary and potentially harmful medications and treatment regimens, such as plasma exchange.

D3. Critical illness polyneuropathy +5
The clinical and electrodiagnostic findings are consistent with a diagnosis of CIP.

D4. Critical illness myopathy 0
The clinical and electrodiagnostic findings are not consistent with a diagnosis of CIM. A patient with CIM would be expected to have greater weakness in proximal muscles, intact sensation, and reduced but retained muscle stretch reflexes. Although this is an incorrect diagnosis, the supportive care and family/caregiver discussions that would occur with CIM are similar to that provided for CIP.

E1. Family and caregiver conference +5
A family conference is essential to the management of acquired paresis in the ICU. Issues regarding prognosis, preparation for long-term care, and need for physical rehabilitation should be discussed.

E2. Treatment with IV immunoglobulin -3
During the daytime, effective treatment of supine hypertension can be accomplished simply by avoiding the supine position. Sleeping with the bed head raised to the head-up tilt position reduces nocturnal sodium loss, which will improve orthostatic hypotension in the morning. Patients with persistent nighttime supine hypertension may require treatment with vasodilators taken at bedtime. Options include 50-mg hydralazine or nitroglycerine patch 0.1 mg/h, which is removed in the morning.

E3. Treatment with IV methylprednisolone -3
No evidence indicates that treatment with IV methylprednisolone is beneficial for either CIP or CIM.

E4. Tracheostomy and percutaneous endoscopic gastrostomy (PEG) +5
At this point it is important to plan for the long-term care of this patient. Recovery from CIM may take weeks to months. Placement of a tracheotomy for long-term mechanical ventilation and a PEG tube to allow feeding and medication administration may be necessary before transfer to a rehabilitation facility.

F1. Recovery expected within 2 weeks -1
Recovery from CIP is dependent on the extent of axonal degeneration. Due to the severity of this patient's axonal neuropathy, recovery is not expected within 2 weeks.

F2. Recovery with persistent neurologic deficits expected within 2 weeks -1
A severe polyneuropathy that results in extensive axonal loss is likely to result in persistent neurologic deficits. However, recovery that requires axonal regeneration will not occur within 2 weeks.

F3. Complete recovery expected after more than 1 year -1
Although severe cases of CIP with extensive axonal loss may take greater than 1 year to recover, persistent neurologic deficits are likely to occur.

Recovery with persistent neurologic deficits expected after more than 1 year +5
Due to the severity of this patient's axonal neuropathy, recovery is expected to occur over many months and in some cases beyond 1 year. It is likely that neurologic deficits, such as weakness and numbness, will persist long-term. This information allows the caregivers to have a realistic view of the future and make appropriate arrangements for rehabilitation and long-term care.

copyright for continuum of neurology