Investigations in the Diagnosis and Management of Neurological Disease

The history and examination are key to making the diagnosis in a patient with neurological disease (see Chapter 1 ). However, ancillary testing is very important in diagnosis and management. Testing for specific disorders is addressed in detail in later chapters in Part III. This chapter provides a general overview of the principles that underlie obtaining investigations beyond the neurological examination.

Investigations beyond the history and examination should be directed to prove or disprove the hypothesis that a certain disease is responsible for the patient’s condition. They should not be used as a “fishing expedition.” Sometimes a physician who cannot formulate a differential diagnosis from the clinical history and examination is tempted to order a wide range of tests to see what might be abnormal. In addition to the high costs involved, this approach is likely only to add to the confusion, because “abnormalities” may be found that have no relevance to the patient’s complaints. For instance, many patients are referred to neurologists to determine whether they have multiple sclerosis (MS) because their physicians requested magnetic resonance imaging (MRI) of the brain for some other purpose, such as the investigation of headaches. If the MRI shows small T2-weighted bright abnormalities in the centrum semiovale (changes that are seen in a proportion of normal older adults and in those with hypertension and diabetes), the neuroradiologist will report that the differential diagnosis includes MS, despite the fact that the patient has no MS symptoms and is unlikely to have MS.

There have been significant advances in laboratory technology; as a result, genetic, immunological, and other blood tests are expanding the ability of clinicians to confirm the diagnosis of an increasing number of neurological disorders, obviating more invasive studies. A test may be diagnostic (e.g., the finding of cryptococci in the cerebrospinal fluid [CSF] of a patient with a subacute meningitis, a low vitamin E level in a patient with ataxia and tremor, a low serum vitamin B ₁₂ level in a patient with a combined myelopathy and neuropathy).One rapidly emerging area of diagnostic investigation is genetic testing. This can be targeted to a specific mutation when the level of suspicion for the genetic disorder is very high. However, there is an increasing utilization of new-generation diagnostic genetic testing such as whole-exome and whole-genome sequencing. The interpretation of these tests may require consultation with a geneticist and a genetic counselor. Another area of diagnostic testing that is rapidly expanding is immunology and testing for specific antibodies that may be involved in the pathogenesis of a variety of autoimmune and paraneoplastic disorders.

Results of laboratory tests can also be used to determine response to treatment. For instance, the high erythrocyte sedimentation rate (ESR) that is typically seen with giant cell arteritis falls with corticosteroid treatment and control of the condition. A rising ESR as the corticosteroid dosage is reduced indicates that the condition is no longer adequately controlled and that headaches and the risk of loss of vision may soon return.

Neuroimaging modalities have expanded remarkably, and the neurologist ordering these tests should be familiar with each one, so that appropriate sequences and methods are used to address the particular question presented by the patient’s history. Also, because of the increasing use of pacemakers, deep brain stimulators, and other devices, the neurologist should be aware that certain precautions must be taken before MRI scans are ordered. MRI has replaced computed tomography for most conditions, and MR angiography and venography have largely replaced conventional catheter-based studies for the imaging of blood vessels.

It is important to use ancillary tests judiciously and to understand their sensitivity, specificity, risks, and costs. The physician must understand how to interpret hematological, biochemical, and bacteriological studies and specific neurodiagnostic investigations. These last studies include clinical neurophysiology, neuroimaging, and the pathological study of biopsy tissue. Knowledge of the various DNA tests available and their interpretation is critical before they are ordered; their results may have far-reaching implications not only for the patient but also for all of the patient’s other family members.

The neurologist must know enough about each test to request it appropriately and interpret the results intelligently. As a rule, it is inappropriate to order a test if the result will not influence diagnosis or management. Tests should be used to diagnose and treat disease, not to protect against litigation. When used judiciously, investigations serve both purposes; when ordered indiscriminately, they serve neither. As we become more digitally advanced, functions in electronic medical record templates may suggest “best practices” as a guide to diagnostic investigations for given clinical presentations, but there is no substitute for physician-directed good clinical sense.

The neurologist must also have a working knowledge of several related disciplines that provide specific investigations to aid in a neurological diagnosis. These include neuropsychology, neuro-ophthalmology, neuro-otology, uroneurology, neuroepidemiology, clinical neurogenetics, neuroimmunology, neurovirology, and neuroendocrinology. Later chapters in Part II describe some of these disciplines and the investigations they offer.