Investigation Of The Nervous System
The key to investigating any patient is through their history and examination, as this will highlight the likely nature and site of the problem.
History and examination (see Chapters 50 and 51)
At the end of the history and examination one should have formulated a hypothesis of where the problem lies and what the problem could be, which will then guide investigations.
A large number of tests are available (see figure for examples).
Imaging (see also Chapter 53)
· Plain X-rays are rarely of value in the diagnosis of neurological disease, unless one suspects the patient has a related disease in another site such as the chest (e.g. lung cancer).
· Computed tomography (CT) gives detailed X-ray images of the brain, skull and lower spine. It is useful for diagnosing structural lesions such as tumours, major strokes or skull fractures. It is widely available but has limited resolution especially in the posterior fossa and cervicothoracic spinal cord.
· Magnetic resonance imaging (MRI) is a noisy, claustrophobic procedure which relies on patient cooperation. It provides detailed images of all parts of the brain and spinal cord and the use of different sequences has increased its utility and diagnostic strength. It does not involve any radiation.
· Magnetic resonance angiography and venography (MRA/MRV) scans delineate the major blood vessels to, within and from the brain. They are primarily used to look for significant narrowing (stenosis) of the extracranial carotid arteries in the neck, aneurysms in the brain and blockage of the major venous sinuses in the brain, but are not as sensitive as angiography.
· Angiography involves the passing of a small catheter to the origin of the major blood vessels of the brain (both carotid and vertebral arteries), and a small amount of dye is injected. The dye can then be followed using a video and images captured rapidly over time as the dye passes through the vascular tree. The proce- dure is invasive and carries a small risk of complication, but is useful in accurately delineating any vascular abnormalities (e.g. carotid stenoses, aneurysms, arteriovenous malformations and venous sinus thrombosis). It can also be used to look for specific vascular abnormalities in the spinal cord.
· Myelography is rarely used nowadays to delineate abnormalities in the spinal cord because of the non-invasiveness and resolution of MRI. However, it can be helpful in some circumstances and involves injecting a radio-opaque dye via a lumbar puncture into the subarachnoid space around the spine.
· Single photon emission computed tomography (SPECT) involves radioactive isotopes which typically provide information on per- fusion within the brain. It has low resolution.
· Positron emission tomography (PET) detects the release of positrons from specific substances that bind to certain chemical sites within the brain. It is only used to localize small occult tumours in patients with suspected paraneoplastic syndromes at the moment.
· Electrocardiography (ECG) is an electrical recording from the heart, and is performed in many patients with neurological disease, especially those with muscle disease, blackouts or some genetic disorders (e.g. myotonic dystrophy).
· Electroencephalography (EEG) measures the electrical activity and rhythms of the brain and is helpful in patients with decreased levels of consciousness, epilepsy (see Chapter 61) and some patients with sleep disorders (e.g. narcolepsy; see Chapter 43).
· Nerve conduction studies (NCS) involve stimulating both sensory and motor nerves and measuring the response. The general principle is that one stimulates at one site of the nerve and records at another site or the muscle it innervates. The size and speed of the response are important. Loss of myelin (demyelination) slows the speed of conduction, while a loss of axons gives a smaller response but normal conduction velocity. It is useful in determining whether the patient has a neuropathy, what type (demyelinating versus axonal) and the extent (focal or generalized).
· Electromyography (EMG) involves placing a needle into the muscle and recording the electrical activity within it. It is useful in the diagnosis of muscle disease and in patients with motor neuronal loss as occurs in motor neurone disease (MND) because EMG can show the extent of denervation, helping in the diagnosis.
· Evoked potentials (EPs) can be recorded from the visual pathway (visual-evoked potential or responses; VEP), auditory pathway (brainstem auditory-evoked potential BSAEP) or peripheral nerves in the arms or legs (somatosensory-evoked potential). The test involves stimulating the peripheral receptor (eye, ear or median/posterior tibial nerve) and measuring the cortical response.
This gives a measure of conduction that has both a peripheral and CNS component. The most commonly used test is VEP in multiple sclerosis to look for asymptomatic demyelination in visual pathways.
• Central motor conduction time (CMCT) measures the time from stimulating the motor cortex to measuring a muscle response in the periphery such as the hand. It is not routinely available and can be used as a measure of integrity of the descending corticospinal tract assuming that there is no dysfunction within the peripheral motor apparatus.
• Thermal thresholds are a subjective test designed to look at small fibre responses in patients. It relies on the patient detecting changes in temperature in the hands and feet. It is not routinely available.
Cerebrospinal fluid analysis
Cerebrospinal fluid (CSF) can be obtained from a number of sites but is routinely obtained by a lumbar puncture, which involves passing a small needle into the subarachnoid space in the lower lumbar spine. CSF should be clear and sent for analysis to include the following:
• Numbers of certain cell types are typically raised in infections (e.g. meningitis and encephalitis) as well as in malignant meningitis (where cancer cells seed themselves along the meninges).
• Culture of the CSF to look for infective organisms, including Gram staining in meningitis and polymerase chain reaction (PCR) for the causative organism in some infections of the CNS (e.g. herpes simplex virus in herpes encephalitis).
• Glucose levels, which can be low in certain types of infection or meningitis and metastatic tumours growing in the meninges.
• Protein levels, which can be raised in some types of neuropathy, tumour and in lesions blocking spinal CSF flow.
• Oligoclonal bands indicative of immunoglobulin synthesis specifically within the CNS, typically seen in multiple sclerosis.
In cases where there is evidence of nerve or muscle disease, a biopsy may be helpful in identifying the defect more specifically. Typical biopsy sites are the radial and sural nerves and the quadriceps and deltoid muscles.
This is routinely performed in patients with brain tumours to confirm the diagnosis and to some extent predict prognosis. In some cases of progressive neurological disease for which no obvious cause can be found, a biopsy looking specifically for inflammation in the blood vessels (vasculitis) as well as prion disease may be considered.