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Part 2: Differential Diagnosis & Further Tests

A Strategy for Achieving Differential Diagnosis

In part 1, we reviewed the neurological examination. Now, in part 2, we review how these physical findings enable us to get into the "black box" of the nervous system. A simple strategy consists of determining 1) the anatomic localization and 2) the etiology of the disease. First, the history and physical are used to localize the problem along the neuro-axis: from the cortex, through the brainstem, down the spinal cord, out the peripheral nerves, and onto the muscles. Second, specific disease entities that could be acting at those sites are identified. Guided by this differential, further tests such as EEGs, CT scans, or MRIs may be used to help achieve a final diagnosis.

Localization

Neuroanatomy can be greatly simplified. Basically, we are reactive organisms. Information is picked up by our sensory receptors and passed on to our sensory cortex. Next, associative cortices decide what to do about it, and eventually pass instructions to our motor cortex. From there, neuroanatomy basically consists of a two neuron system: the upper and lower motor neurons. 1) The upper motor neuron starts with the Betz cell body in the motor cortex, sends out its axon through the centrum semiovale (the white matter), crosses in the medulla of the brainstem, travels down the spinal cord in the contralateral corticospinal tract, and synapses on the lower motor neuron. 2) The lower motor neuron starts with its cell body (known as the anterior horn cell), continues as the peripheral nerve, sends a message across the neuromuscular junction, and causes the muscle to act. Diseases may also act multi-focally or systemically.

Figure 1:  Physical Findings at Anatomical Locations

The pattern of physical findings typical for each site along the above pathway is summarized in figure 1. Upper motor neuron disease is associated with decreased strength. Acutely, there may be a decrease in muscle tone and reflexes, and the Babinski response may be silent. This is typically followed by increased muscle tone and reflexes, along with a positive Babinski. Brainstem pathology may be additionally associated with crossed cranial nerve findings, in which the cranial nerve findings are on the opposite side from the hemiparesis. Spinal cord disease may be associated with bladder and bowel symptoms.

Motor unit disease (disease localized anywhere from the lower motor neuron to the muscle) is usually associated with decreased strength, decreased tone, often decreased reflexes, and normal or silent Babinski responses. Additionally, pathology involving the lower motor neuron may result in muscle fasciculations. Diseases of the peripheral nerves may include sensory findings; these are often in a distal "stocking/glove" pattern, but may also follow dermatomal or other distributions. Myopathies tend to cause proximal weakness, which is best detected by watching the child get up from the floor or walk up stairs.

Etiology

Once we have arrived at the likely anatomic location(s) along the neuro-axis, we can next think of specific diseases that might occur at those sites. Using the symptom of hypotonia as an example, figure 1 gives some of the specific disease entities that might occur at each anatomic site.

Further Tests

After a differential diagnosis is achieved, further tests may be required. Here, we discuss caveats about the EEG, CT, and MRI.

An "interictal EEG" [a routine study obtained in between actual seizures] will pick up interictal spikes in only about 50% of known epileptic patients. Repeating the study a second time will increase the yield to about 75%. A third study increases the yield to 90%. After that, there are diminishing returns.

Continuous EEG monitoring may be the only way to capture a spell and determine if it is actually a seizure or not. There are occasionally false negatives even with this approach. Continuous EEG usually requires hospitalization for as long as it is likely for the child to have an event. If the patient is being evaluated for possible seizure surgery, it is necessary to capture multiple seizures in order to be certain that they all come from the same location.

The situation where the seizure occurred should be recreated, whenever possible. In particular, if a seizure occurred during sleep, the EEG should contain a segment recorded during sleep.

In general, EEGs should be obtained after sleep deprivation. Spikes can be activated by sleep deprivation, by the act of falling asleep during the EEG, and by the state of being asleep. In particular, children with Benign Rolandic Epilepsy may have totally normal EEGs during the waking state that become markedly abnormal during sleep. For younger children, limiting sleep to 4-5 hours the night before the test may be sufficient. Use clinical judgement.

Even children who will be sedated will benefit from sleep deprivation the night before, as the sedative works much better on children who are already sleepy.

Be certain that the EEG lab and EEG reader are experienced with children's EEGs. Normal findings vary with a child’s age

Best test for emergencies: CT scans are fast, readily accessible from emergency rooms, and accommodate respirators.

Best imaging test for fresh blood (<24-48 hours). Even with a normal CT, though, a lumbar puncture might still be needed to rule out subarachnoid or small hemorrhages.

CT scans are better than MRI for detecting calcifications.

Non-contrast studies are sufficient for immediately required information about most emergency problems (large bleed, shift, depressed fractures, etc.)

IV contrast studies are usually required in conditions such as headaches where the differential includes vascular malformations or breaks in the blood/brain barrier (such as tumor or abscess.)

A common strategy is to utilize a non-contrast CT as the emergency test, followed by an MRI. This approach will usually avoid the need for IV contrast.

In general, the MRI scan is the elective test of choice.

Compared to the CT, the MRI: 1) avoids ionizing radiation; 2) avoids iodinated IV contrast; 3) gives excellent views of the sinuses at the same time as the brain; and 4) gives better images—especially of the temporal lobes and posterior fossa where bone artifact make CT scans particularly unreliable.

MRIs are not good for detecting fresh blood or calcifications.

The FLAIR sequence, which does not require contrast, is particularly sensitive for small parenchymal lesions.

As of this writing, IV gadolinium contrast is not required for most children’s initial MRI.

MRA (Magnetic Resonance Angiography) and MRV (Magnetic Resonance Venography) are non-invasive tests which might supplement routine MRI.

MRI SPECT is a non-invasive MRI sequence which can analyze points of the brain for certain chemicals. For example, MRI SPECT can look for lactate peaks in mitochondrial disorders, or for choline and creatine peaks to help distinguish tumor from hamartoma.

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