LABORATORY EVALUATION IN CNS DISEASE

Important investigations in neurological disease include: (a) CSF examination, (b) neuroimaging, (c) electrophysiological studies and (d) others, e.g. nerve or muscle biopsy, enzyme studies, etc.

CSF examination, from the fluid obtained via Lumbar puncture is the baseline investigation in most neurological disorders, specially indicated for:

• Diagnosis of meningitis, encephalitis, subarachnoid hemorrhage, etc.

• Assessment of CNS involvement in septicemia, leukemia, etc.

• D/D between poliomyelitis and Guillain-Barre syndrome

• CSF sample collection for antibody testing, metabolic disorders, etc.

• Therapeutic reduction in raised ICP.

Lumbar puncture (LP) is contraindicated in cases with:

(a) papilledema, (b) anatomical defect or local infection at the puncture site, (c) thrombocytopenia lt;20,000#8725;mm³, (d) midline-shift in CT brain, and (e) hemodynamic instability. Fundus exam for papilledema is essential before LP to exclude raised ICP, as sudden release of pressure may result in medullary coning and cardiorespiratory arrest.

Complications are rare after LP but some cases may develop—(a) sudden death due to coning of brain stem,

(b) iatrogenic meningitis (exogenous infection), and (c) local inclusion dermoid after many years. For procedural details of LP, see Ch 32.6.

Important CSF findings in normal children as well as common CNS infections (Table 18.6) include:

• Pressure (N: 80-100 mmH₂O) may be elevated in intracranial infections, tumors and crying child; while low pressure or dry tap indicates spinal block in extramedullary spinal tumors or due to thick pus in bacterial meningitis.

• Color: CSF is colorless, except in newborns who may have xanthochromic CSF due to high protein and bilirubin content. Common color abnormalities include: Xanthochromic in Froin syndrome or old sub-

TABLE 18.6: CSF findings in normal child and in common CNS infections

arachnoid bleed, Cloudy in pyogenic meningitis, straw­colored in tubercular meningitis and Red in traumatic or subarachnoid hemorrhage.

Differentiation between traumatic and hemorrhagic CSF is difficult, though progressive clearance of color during CSF collection in 2-3 different test tubes indicates traumatic LP.

• Cobweb formation after 2-3 hours (due to high fibrinogen content) indicates TBM.

• Elevated proteins (N: lt;40 mg/dl) indicate meningitis, though mild elevation (lt;100 mg/dl) is common in newborns, encephalitis, traumatic LP, subarachnoid bleeds, degenerative disorders and Guillain-Barre syndrome.

• Elevated cell count (N: lt;5 cells/mm³) indicates meningitis, though mild pleocytosis (lt;50 cell/mm³) may be seen in newborns, poliomyelitis, brain tumors, demyelinating diseases, etc. Presence of even a single polymorph in non-traumatic CSF indicates bacterial meningitis, except in newborns.

• Hypoglycorrhachia (#936;glucose) indicate bacterial con­sumption of glucose in meningitis. Normal CSF glucose is about 2/3^rd of blood levels.

• Bacteriological examination of CSF is indicated in all cases for gram staining, bacterial cultures and AFB staining/culture. Fungal cultures as well as viral studies, e.g. PCR are indicated in select cases.

• Selected samples may also be tested for antibodies (autoimmune encephalitis, SSPE) or metabolites, e.g. lactates (metabolic disorders).

Neuroimaging studies include plain skull skiagrams, cranial ultrasound, CT scan, MRI, brain scan with contrast and vascular studies, e.g. angiography or venogram.

Plain skull X-ray is rarely useful in neurodiagnosis, except in suspected skull fractures, chronic raised intracranial pressure (ICP) and calcifications. X-ray skull should be specially looked for:

• Sutural separation (#8593;ICP) or thickening/premature fusion (craniosynostosis).

• Diploe space narrowing (#8593; ICP) or widening (hemolytic anemia).

• Copper/silver beaten appearance (#8593;ICP) due to impressions of enhanced cortical sulci-gyri, pressing over inner table of skull (Fig. 18.1).

• Visible skull fractures.

• Calcifications (Intrauterine infections, Sturge-Weber syndrome).

• Eroded anterior clinoid process (craniopharyngioma).

• Mastoid sclerosis (chronic ear disease).

Cranial ultrasound is useful in newborns and infants with open fontanelle to assess central structures, e.g. ventricles and paraventricular region but peripheral

Fig. 18.1: X-ray skull: Silver-Beaten appearance in raised intracranial pressure.

cortex, subdural spaces and posterior fossa is not well visualized on USG.

Computerized tomography (CT) provides comparable information to MRI in intracranial structural lesions, which may be broadly classified as hypodense, isodense and hyperdense. Hypodense lesions are produced by presence of fluid, e.g. in edema, necrosis, infarcts, hydrocephalus, cysts etc while hyperdense lesions are seen in hemorrhage, calcifications, tumors, etc.

CT scan is preferred over MRI to visualize skull frac­tures and calcifications, while posterior fossa lesions and myelination disorders may be missed on CT. Radiation exposure is another risk with CT scan.

Contrast CT is useful in cases with altered vascularity, i.e. infarcts, cerebral edema, hemorrhage, tumors or abscesses.

CT angiography is often used to visualize cervical and intracranial vascular structures as high density lesions, specially in older children.

Magnetic resonance imaging (MRI) is generally preferred over CT scan for neuroimaging due to the advantage of structural as well as functional assessment without exposure to radiation. However, it is relatively costly and may need anesthesia in younger children.

MRI is preferred investigation in—(a) degenerative/ demyelinating disorders, (b) cerebral edema, (c) poste­rior fossa lesions, (d) spinal cord lesions, and (e) before neurosurgery. However, calcifications are not well visualized on MRI.

Different imaging sequences in MRI include T1 images for structural lesions, T₂ images mainly for function lesions and flair (Fluid attenuation inversion

recovery) images to detect CSF signals in peripheral and periventricular lesions.

MR-angiography or venography is the investigation of choice in suspected intracranial vascular malformations and strokes.

Functional MRI is a non-invasive technique to map neuronal activity based on cerebral blood flow and oxygenation, useful for pre-surgical localization of critical brain functions, e.g. before epilepsy surgery.

MR spectroscopy is a molecular imaging technique to assess neurochemical profile of a selected brain region, e.g. presence of N-acetylaspartate, creatine, lactate, etc. This information is useful in diagnosis of inborn errors of metabolism, cortical dysplasia, and hypoxic-ischemic injury. It also helps to differentiate tuberculoma (lipid peaks) from neurocysticercosis (amino acid peaks) and in pre-operative or post-therapeutic assessment of intracranial tumors.

Radionuclide brain scan with ⁹⁹Tc, positron emis­sion tomography (PET) or single photon emission computerized tomography (SPECT) helps to study regional blood flow and integrity of blood-brain barrier. Brain scans are specially useful in herpes encephalitis, autoimmune encephalitis, cerebrovascular disease and to localize small epileptic foci.

Cerebral angiography (with digital substraction) is useful for evaluation of vascular disorders of brain, though MR-angiography has reduced the need of more invasive angiographies in recent years.

Electrophysiological studies are useful to assess the functional status of neurons even in absence of structural abnormalities, specially in epilepsy and peripheral neuromuscular disorders, as follows:

Electroencephalography (EEG) is a continuous recording of electrical activity between two reference scalp electrodes, to study rate, amplitude, symmetry and morphology of electric rhythms.

Normal EEG waves are classified according to frequency as-delta (1-3/sec), theta (4-7/sec), alpha (8-12/sec) and beta (13-20/sec) waves. These waves are altered by many factors, e.g.

Uses: EEG is mainly useful to—(a) differentiate seizure from non-seizure disorders, (b) diagnose specific epileptic syndromes, (c) diagnose some degenerative (SSPE), infective (herpes encephalitis) or metabolic (pyridoxine dependency) disorders, and (d) decide about anticonvulsant therapy.

Important EEG abnormalities may be generalized, localized or lateralized, including either presence of epileptiform discharge (paroxysmal, sharp waves or spikes, high voltage) or abnormal slowing of rhythm. Important diagnostic abnormalities are seen in:

• Absence seizures: 3 per second spike and wave form.

• Infantile spasms: Hypsarrhythmia (high voltage, slow wave pattern) with superimposed spikes.

• SSPE: Repeated bursts of high-voltage, slow-wave complexes.

• Rolandic epilepsy: Repeated high amplitude spikes, originating from rolandic area.

• Herpes encephalitis: Periodic lateralized epileptiform discharges from centrotemporal regions

• Focal epileptiform discharges or slowing are seen in structural lesions, e.g. malformations, infarcts, tumors and other space occupying lesions.

• Diffuse background slowing usually indicates diffuse neuronal injury, e.g. in toxic or metabolic encephalopathies.

Caution: EEGs may be abnormal in ~2% of normal population and should be interpreted cautiously with clinical correlation. On the other hand, EEG may be occasionally normal during interictal phase in epilepsy.

EEG abnormalities may be precipitated by provocation procedures, e.g. sleep deprivation or photic stimulation. Polygraphic or video-EEG recordings for long periods are recent innovations in detection of subtle seizures and epileptic foci.

Electromyography (EMG) is mainly used to distinguish myopathies from neuropathies, though specific diagnosis of myopathic disorder is rarely possible on EMG.

Nerve conduction studies (NCS) is an age-dependent parameter, indicated in diagnosis of neuropathies and subclinical involvement in systemic disorders, based on parameters like amplitude, nerve conduction velocity (NCV) and latency. Decreased NCV is indicative of myelin injury whereas reduced amplitude indicates axonal injury.

Other electrophysiological studies, e.g. visual evoked potentials (VEP), brain stem auditory evoked potential (BAEP) and somatosensory evoked potentials (SSEP) are specially useful in young, uncooperative and comatose children for early diagnosis of neurological insults in high-risk cases.

18.3