What investigations should be done for a patient presenting with progressive neurological symptoms?

Investigations for Progressive Neurological Symptoms

MRI of the brain (preferred over CT) should be performed as the initial imaging study to evaluate for structural abnormalities, patterns of atrophy, vascular lesions, and to exclude other etiologies such as autoimmune or infectious processes. 1

Initial Neuroimaging

• Brain MRI is the preferred initial imaging modality for patients with progressive neurological symptoms, as it is superior to CT for detecting patterns of atrophy, parenchymal abnormalities, substance deposition, and excluding structural or vascular lesions 1
• CT scanning has limited utility except for detecting large ischemic infarctions, hemorrhage, and parenchymal brain calcifications, and should be reserved when MRI is contraindicated or unavailable 1
• Advanced MRI techniques including diffusion tensor imaging and magnetization transfer ratio imaging may be useful for evaluating microstructural integrity of gray matter, white matter, and neural pathways 1

Vascular Imaging

• Non-invasive vascular imaging (CTA or MRA from aortic arch to vertex) should be completed when cerebrovascular etiology is suspected 1
• CTA including extracranial and intracranial vasculature is recommended as the ideal method to assess both circulations simultaneously 1
• Transcranial color-Doppler ultrasonography and MR angiography are acceptable alternatives based on availability and patient characteristics 1

Neurophysiological Testing

Electromyography (EMG) with nerve conduction studies (NCS) should be performed when motor neuron disease, peripheral neuropathy, or neuromuscular junction disorders are suspected. 1, 2

For Suspected Motor Neuron Disease (e.g., ALS):

• Standard NCS should include at least four sensory and four motor nerves in an arm and leg to exclude potentially treatable motor neuropathies 2
• At least three sites in three different nerves should be stimulated when searching for conduction blocks 2
• Needle EMG should examine at least two limbs (arm and leg; minimum five muscles each), thoracic paraspinal muscles, and bulbar muscles 2
• Characteristic findings include widespread non-myotomal denervation (acute and chronic) with fibrillations and fasciculations 2

For Suspected Peripheral Neuropathy:

• Electromyography with peripheral nerve neurophysiological tests is essential for all patients with suspected peripheral nerve involvement 1
• Histological peripheral nerve examination (mainly sural nerve biopsy) including intraepidermal nerve fiber density may be indicated when appropriate 1
• Sensory nerve conduction should involve two to three nerves to disclose coexistence of sensory neuropathy 3

Laboratory Investigations

Initial Bloodwork (should be obtained routinely):

• Complete blood count (hematology) 1
• Electrolytes 1
• Coagulation studies (aPTT, INR) 1
• Renal function (creatinine, eGFR) 1
• Random glucose 1
• Troponin 1
• Serum cryoglobulins when vasculitic neuropathy is suspected 1
• Alpha-fetoprotein (AFP) levels if ataxia-telangiectasia is considered 1

Subsequent Laboratory Tests:

• Lipid profile (fasting or non-fasting) 1
• Screening for diabetes with HbA1c or 75g oral glucose tolerance test 1
• Monoclonal component evaluation when cryoglobulinemia is suspected 1

Cardiac Evaluation

• 12-lead ECG should be obtained to assess cardiac rhythm and identify potential cardioembolic sources 1
• This is particularly important when cerebrovascular etiology is being considered 1

Specialized Testing Based on Clinical Presentation

For Rapidly Progressive Dementia:

• Brain imaging (CT or MRI) should be completed urgently 1
• 18F-fluoro-deoxyglucose PET scan may be useful for specific CNS manifestations 1
• Functional brain MRI studies could be employed for specific CNS manifestations 1

For Movement Disorders:

• Nuclear medicine studies can evaluate abnormal glucose metabolism patterns, buildup of abnormal proteins within neurons, or neurochemical deficits 1
• Quantitative volumetric analysis may be useful for assessing patterns of atrophy 1

For Suspected Neuromuscular Junction Disorders:

• 3Hz repetitive nerve stimulation to search for myasthenic syndrome 3
• Repeated short exercise testing (combined with cooling if necessary) for myotonic syndromes 3
• Long exercise test if periodic paralysis is suspected 3

Important Clinical Caveats

• Avoid ionizing radiation in patients with ataxia-telangiectasia due to increased cellular sensitivity to radiation 1
• Electrodiagnostic studies should primarily be performed in patients with unequivocal clinical signs of peripheral nervous system lesions, not as screening tools 4
• Normal nerve conduction studies do not exclude radiculopathy or nerve root compression 5
• The distribution of investigations should be guided by the specific clinical presentation and suspected etiology rather than ordering all tests indiscriminately 1