Approach
The diagnosis of an acute motor loss can be complex and difficult. In trying to reach a diagnosis, it is vital that some causes are identified or excluded rapidly because they may benefit from urgent intervention to minimize injury (e.g., thrombolysis for ischemic stroke) or require special handling to prevent worsening of the deficit (e.g., traumatic spinal injury).
A careful and thorough history is essential because there is a wide spectrum of conditions that can give rise to acute motor deficits. Although many motor deficits may be obvious and profound, others may be more subtle and may not be the only or most prominent feature of the condition.
In some instances, such as stroke or trauma, it is possible that the individual will not be able to give the history directly; in these cases, a history should be obtained from relatives, friends, or eyewitnesses, by phone if necessary.[7] Important information to illicit would include:
Whether anyone witnessed the individual having a seizure or convulsions.
Convulsions may be present with numerous conditions, including syncope, epilepsy, encephalitis, cerebral vein thrombosis (if there is cortical vein involvement), other structural brain lesions affecting the cerebral cortex or underlying white matter, metabolic disturbances (e.g., hypoglycemia, hyperglycemia, hyponatremia, hypocalcemia, hypomagnesemia, profound hepatic failure, uremia), hypertensive encephalopathy (including posterior reversible encephalopathy syndrome), the use of convulsant drugs or agents (cocaine, amphetamines, aminophylline, lidocaine, isoniazid), advanced neurodegenerative conditions, and psychogenic unresponsiveness (pseudoseizures/psychogenic seizures)
Any trauma
Whether there has been any recent overseas travel (may be suggestive of infection and encephalitis)
Whether the person has had a febrile illness or chills (suggesting a CNS or systemic infection)
Previous medical history, including any history of cancer, a history of drug or alcohol misuse, diabetes mellitus, adrenal, hepatic or renal failure, or immunosuppression (either drug-induced or acquired)
Medication history: this can reveal medications that may be responsible for drug-induced myopathies and/or neuropathies. For example:
myopathies without neuropathy (corticosteroids)
myopathies with neuropathy (colchicine, chloroquine, and hydroxychloroquine)
combinations of drugs (e.g., a fibrate and a statin, or cyclosporine and colchicine)
myasthenic syndromes (d-penicillamine, antibiotics, beta-blockers, immune checkpoint inhibitors)[19]
lipid-lowering drugs
The exact nature of the symptoms
Whether the symptoms involve motor function alone, or motor and sensory function, and whether the sensation of pain is affected
The muscles and motor functions affected and the distribution of any accompanying sensory deficits
Nature and timing of the onset of the deficit
What the person was doing when the deficit occurred
How the symptoms have changed or progressed since onset (e.g., ascending/descending deficit, transient, or worsening or improving)
Whether the person has suffered similar episodes in the past
One of the first goals of history-taking is to identify the likely part of the motor pathway responsible for the deficit. Motor function originates in the cortex, going through the axon pathways to the motor cells in the spinal cord. The pathway then proceeds via the anterior spinal roots to form the spinal nerves, which ultimately form peripheral nerves that innervate the relevant muscles.
In general terms, therefore, the levels of possible dysfunction are supraspinal lesions, spinal cord lesions, peripheral neuropathy, disorders of neuromuscular transmission, and muscle disorders. So, for example, if the face, arm, and leg on the same side are paralyzed, then the lesion is likely in the brain; if only an arm and leg are involved, then the lesion is likely in the upper spinal cord.
With the history suggesting a possible site or sites for the dysfunction (e.g., brain or high spinal cord), the next step is to consider the possible pathophysiologic causes.
An abrupt onset over seconds, minutes, or hours suggests a vascular disturbance (e.g., a transient ischemic attack [TIA] or a stroke), or certain toxic or metabolic disturbances.[22] Trauma may also cause sudden loss of motor function, usually associated with catastrophic damage to the CNS, spinal root avulsion, or local trauma to a peripheral nerve trunk.
A subacute onset over a few days is more generally associated with infection, autoimmune/inflammatory, or compressive processes.
A progressive increase in motor deficit from time of onset suggests a continuing activity of the underlying process. Progression that is episodic is suggestive of a vascular or inflammatory origin; steady progression suggests a neoplastic or degenerative origin.
Acute motor loss can have functional origins as well. History should consider factors such as comorbid pain and fatigue, psychiatric comorbidities, active psychosocial stressors, unhelpful behavioral responses, unhelpful illness beliefs.[23] A social-family history can supplement the diagnosis.[23][24]
Physical exam
A thorough and comprehensive neurologic exam is essential. Although many motor deficits may be obvious and profound, others may be more subtle and may not be the most prominent feature of the overall clinical picture.
Muscle bulk, strength, and tone in the limbs and torso should be assessed, along with a sensory assessment, including pain, thermal, and position sense. Neurologic exam should be supported by a general physical exam of all systems because this may suggest systemic disease(s) that may be the underlying cause of the motor deficit.
Acute motor loss is most often flaccid in tone; rarely there may be some spasticity at onset. Hemiplegia with accompanying sensory loss points to specific loci in the CNS where sensory and motor tracts are in close proximity (e.g., the cortex, the white matter tracts in the corona radiata, or the motor/sensory tracts in the upper spinal cord).
Monoplegia requires evaluation of the pulses in the affected extremity: a pulseless, painful, hypoesthesic leg might suggest compartment syndrome or trauma. Symmetrical loss of muscle bulk with normal sensory exam might suggest metabolic dystrophy.
Reflex testing is often not useful as a differentiating test because reflexes are absent in many cases of acute motor deficit. Pathologic signs such as meningismus are suggestive of hemorrhage or infection.
CNS signs such as Babinski sign, L'Hermitte sign, and Kernig sign, although not sensitive, are specific indicators of a CNS lesion:
Babinski sign: the hallux dorsiflexes and the other toes fan out when the lateral side of the foot is stroked firmly with a blunt point from heel to toes. The sign is present when the extension reflex is elicited. It reflects damage to the corticospinal tracts from a wide variety of pathologies including ischemia, mass lesion, or infection.
L'Hermitte sign: paresthesias, including tingling, buzzing, electric shocks, partial numbness, and sharp pains brought on by marked flexion or extension of the neck. It indicates pathology involving the caudal medulla or posterior columns of the spinal cord. A wide group of states can produce this sign: transverse myelitis, infections, metabolic issues affecting the posterior columns, and cord compression resulting from tumor or spondylosis.
Kernig sign: with the patient lying supine, the leg is fully bent at the hip and knee. Subsequent extension of the knee with the hip still flexed is painful and is resisted. Considered primarily to be a sign of meningismus, and likely meningitis, it is present in 5% of patients.[25]
Decreased rectal tone and priapism point to a spinal cord lesion. Following history and exam, and guided by the findings, laboratory and imaging tests are usually indicated.
Initial laboratory testing
Initial evaluation should include electrolytes, anion gap, glucose, blood urea nitrogen (BUN), creatinine, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum creatine kinase (CK), and liver function tests (LFTs).
Hematologic investigations such as complete blood count (CBC), prothrombin time (PT) and activated partial thromboplastin time (PTT), international normalized ratio (INR), and hypercoagulation panel also often necessary during the initial evaluation, particularly if a vascular diagnosis is under consideration. These tests may reveal findings that point toward particular diagnoses:
Glucose: hypoglycemic events can give global symptoms such as confusion or syncope, but can also lead to focal motor deficits that mimic stroke. Type 1 glycogen storage disease will also cause a low glucose level during fasting or acute illness. Serial measurements are often useful in this situation.[26]
Chemistry panel: severe hyponatremia may be seen, for example, in rickettsial infections and SIADH, and can trigger seizures and can be a cause of motor deficits. Extremely low potassium or high calcium can cause generalized weakness. These abnormalities are usually suggested by other elements of the history.
ESR and CRP: although nonspecific, ESR is elevated in >90% of patients with a brain abscess and is only rarely elevated in patients with a CNS neoplasm.[27] Likewise, elevation of CRP favors abscess over tumor. ESR and CRP are also elevated in about one-half of patients with dermatomyositis and polymyositis. Other infective and inflammatory causes will also likely show elevation of ESR and/or CRP.
Procalcitonin (PCT): this peptide is noted to be elevated in many infectious conditions. It correlates well with the severity of sepsis, has high sensitivity and specificity for bacterial infections (especially in the lungs), and is considered to be more sensitive than CRP or ESR for infections of extra-CNS origin.[28][29] It is also considered more sensitive to the resolution of the process under treatment, due to its relatively short half-life.[30][31]
LFTs: in 10% to 20% of patients with Guillain-Barre syndrome, LFTs are deranged during the first few days, with elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as high as 500 units/L; bilirubin may be transiently elevated but rarely high enough to cause jaundice. These rapidly normalize after 1 to 2 weeks.[32] Such elevation of hepatic enzymes is associated with a more severe disease.[33] The cause is unclear. Lactate dehydrogenase (LDH) and ALT may also be increased in idiopathic inflammatory myopathy or dermatomyositis.
Serum CK: Elevation of serum CK is often found in patients with Duchenne muscular dystrophy, although high levels are often not attained until the patient is >1 year old.[34] Serum CK is also frequently elevated in patients with dermatomyositis or idiopathic inflammatory myopathy. Although CK level may be elevated up to 50-fold in active dermatomyositis, it can be normal in some cases.[35] An elevated serum CK will also be detected in compartment syndrome where it reflects muscle cell lysis and necrosis.[36]
CBC: a high white blood cell (WBC) count can suggest infection as the cause of symptoms. The WBC count is elevated in up to 70% of cases of brain abscess and this elevation would favor abscess over, for example, brain tumor, especially if the patient has not yet received corticosteroids. Low platelet count suggests a secondary cause of hemorrhage.
PT, activated PTT, and INR: these tests can indicate whether coagulopathy is a cause or aggravating factor in cases of hemorrhagic stroke or other intracranial bleeding.[37]
Hypercoagulability panel: this can reveal thrombophilic states such as antiphospholipid antibody syndrome or hyperhomocysteinemia that may be associated with arterial thrombus and ischemic stroke.
In combination with the history and exam findings, the results of the initial routine blood tests will help focus on the most likely differentials. Additional, more specific and specialized laboratory tests may then be ordered to narrow the differential yet further.
Prognostic tests
Protein S-100 and neuron-specific enolase are used increasingly in patients with head injuries to allow for prognostication regarding degree of injury, and form part of the overall assessment of survivability. These complement some of the indirect markers, such as antiphospholipid antibodies in CNS lupus and other vasculitides. The presence of serum interleukin-8 is a marker for CNS injury after ischemia and trauma. These tests are not yet part of a routine laboratory package but represent second-line tests to confirm diagnostic considerations in the early phases of the evaluation.
Imaging
Imaging plays a key diagnostic role and should be employed early in most situations. For instance, noncontrast CT head is required if conditions such as stroke or intracranial hemorrhage are suspected.[7][8][37] Differentiating stroke or intracranial hemorrhage from brain abscess will result in different treatment cascades, and prompt and accurate identification is paramount in such circumstances.
For conditions in which soft tissue changes are likely, MRI is the most sensitive and specific test. Yield can be increased by techniques such as diffusion-weighted imaging, gradient-recalled echo, and short tau inversion recovery sequences. Magnetic resonance spectroscopy, single photon emission CT, functional MRI, and brain PET scans are specialist techniques that can be a valuable aid to diagnosing the underlying cause of encephalitis.
In the setting of suspected hemorrhage or bony pathology, CT is more sensitive. The history and physical exam will identify the regions that require imaging, with special attention paid to factors such as levels of sensory loss and whether symptoms are descending or ascending. The most frequently used imaging modality remains MRI, but in trauma settings, CT is preferred on grounds of speed. If MRI is unavailable or contraindicated, CT myelography can sometimes be used in the evaluation of spinal trauma and cord compression.
Detailed vascular images with CT angiography or MR angiography are adjuncts to initial studies in cases where a vascular cause is suspected.[7][8] Conventional invasive brain angiography (catheter intra-arterial digital subtraction angiography [DSA]) also has a role; it is recommended in patients with spontaneous intracerebral hemorrhage (ICH) and a CT or MR angiogram suggestive of a macrovascular cause (e.g. arteriovenous malformation or aneurysm).[37] In cases of ischemic stroke, if routine imaging studies fail to show arterial occlusion and if the ischemic tissue has features of venous occlusion (e.g., does not conform to a vascular territory), the patency of cerebral venous sinuses can then be assessed by CT or MR venography.[8]
Plain x-rays can be used to evaluate extracerebral infections (e.g., chest x-ray to evaluate pneumonia) and trauma of the spine, but their use is dwindling.
Doppler ultrasound scans of the carotids can be a valuable test if a transient ischemic attack is suspected.[8][22] The presence of ipsilateral carotid stenosis supports an artery-to-artery embolic event as the source of the acute motor deficit. In infants with open fontanelles, ultrasound may also be used to evaluate for brain abscess or hydrocephalus.
PET scans may be used later in the clinical course of encephalitis to aid the detection of any underlying cancers (e.g., lung, brain, or ovarian) that may be associated with limbic or brainstem encephalitis.
Lumbar puncture
In cases where the differential has focused toward an infectious or metabolic cause, lumbar puncture (LP) is indicated. It is also indicated to rule out an infection or metabolic cause in cases of epileptiform seizures.
Measuring cerebrospinal fluid (CSF) pressure and analysis of composition can assist in the diagnosis of many infectious, metabolic, and some hemorrhagic causes of motor deficit. The most accepted use is for analysis of CBC and composition, cell morphology, presence of infectious or parasitic agents, and immunologic findings.
Normal CSF is usually clear and colorless, with a WBC count of 0 to 5 cells/mm³ (60% lymphatic origin), RBC count of 0 to 5/mm³, protein level 15 to 45 mg/dL, and glucose level 45 to 80 mg/dL (ratio CSF/serum 0.60). There are normally no oligoclonal bands and the IgG serum:CSF ratio is greater than 1.
Normal CSF pressure, when measured in a lateral decubitus position, ranges from 3 to 15 cm of water. Polymerase chain reaction (PCR) is performed for suspected meningitis along with standard microbiologic testing (Gram stain and culture).
Although an important and helpful test, LP should not be undertaken lightly and there are several important contraindications and considerations:
Contraindications:
Coagulopathy (INR >1.5)
Thrombocytopenia (<50,000/microliter)
Infection/skin lesion over puncture site
Known elevated intracranial pressure
Before conducting an LP, the following considerations should prompt brain imaging (CT or MRI):
Patients ages over 60 years
Patients who are immunocompromised
Patients with known CNS lesions
Patients who have had a seizure within 1 week of presentation
Patients with abnormal level of consciousness
Patients with focal findings on neurologic exam
Patients with papilledema seen on physical exam with clinical suspicion of elevated intracranial pressure
How to perform a diagnostic lumbar puncture in adults. Includes a discussion of patient positioning, choice of needle, and measurement of opening and closing pressure.
Electrophysiologic testing
Relevant tests may include ECG, EMG, nerve conduction studies, evoked potentials (electrical signals generated by the nervous system in response to sensory stimuli), and EEG.
ECG: Detection of atrial fibrillation on ECG would indicate an increased risk for embolic cerebral ischemic stroke or TIA. Other abnormalities such as bundle branch blocks or ventricular hypertrophy are more nonspecific findings of underlying cardiac disease that may reflect CHF or common risk factors for atherosclerotic disease. Hemorrhagic stroke may be complicated by myocardial ischemia, although large inverted T waves in multiple coronary artery distributions suggest ECG changes of cerebral origin rather than acute coronary syndrome. Fifty percent of patients with subarachnoid hemorrhage have an abnormal ECG on admission. Abnormalities include arrhythmias, prolonged QTc and ST segment/T-wave abnormalities.
Evoked potential testing: This has widespread application in the assessment of acute motor deficits and can be used to assess peripheral nerves, spinal cord, and brain. Although there are several types of evoked potential test, the somatosensory test is most commonly used in the setting of acute motor deficit. Abnormalities of both the time taken to generate a waveform and the shape of a waveform can contribute to making a diagnosis. The entities that affect wave transmission involve demyelination of the affected axons or injury to the neurons involved in the signal production. A normal test in the setting of acute motor deficit suggests a muscle-based process.
EEG: May be appropriate in cases of suspected encephalitis, and background slowing is an early and sensitive indicator of cerebral involvement, although it is nonspecific. Later, more specific patterns may emerge that indicate particular types of encephalitis: temporal lobe abnormalities are frequently seen in viral encephalitides; periodic lateralized epileptiform discharges can be seen in HSV encephalitis; in subacute sclerosing panencephalitis, a typical generalized periodic EEG pattern repeating with intervals between 4 and 15 seconds, synchronous with the myoclonus of the patient, may be seen.[44][45]
EMG: This electrophysiologic test measures the conduction speed and muscle activity elicited following the application of a stimulus. It is useful in acute motor loss, despite the belief held by some that 3 weeks should pass before an EMG is undertaken. In cases of severe nerve injury (axonal loss/neuropraxia) the diminished motor response can be detected immediately. When the nerve degeneration is advanced (Wallerian loss) the test is more easily elicited with evidence of fibrillation potentials in the muscles tested.
Nerve conduction: This test allows for precise localization of a nerve injury. The nerve pathway is stimulated at several sites and the conduction block can be pinpointed between the 2 sites of stimulation. The waveform obtained is either absent, slowed, or of abnormal morphology. In the case of a partial nerve injury (neuropraxia), the most common finding is an abrupt change in the waveform.
Biopsy
For diagnosis of many of the myopathies, a muscle biopsy is warranted. This can also help distinguish certain peripheral neuropathies from myopathies. Muscle biopsy is indicated in the setting of weakness, loss of muscle bulk, severe cramping, and elevated CK. Muscle biopsy requires careful sampling and preparation of the specimen, and a pathologist familiar with these biopsies for accurate interpretation.
Although not routinely performed, brain biopsy is the criterion standard for diagnosis of encephalitis. Clinical or radiologic deterioration in patients with encephalitis of unknown origin is an indication for brain biopsy.[44] Immunocytochemistry, in situ hybridization, and PCR can be performed on biopsy/autopsy specimens, and have had a profound impact on the ability to diagnose the various etiologies of encephalitis.
Use of this content is subject to our disclaimer