Investigation of Neurological Disease

INVESTIGATION OF NEUROLOGICAL DISEASE Divided into:1. Tests of function. 2. Tests of structure (imaging). Tests of function:1. 2. 3. 4. Electroencephalography (EEG) Evoked potentials(EP). Nerve conduction studies (NCS) Electromyography (EMG) EEG • EEG is the recording and measurement of scalp electrical potentials to evaluate baseline brain functioning and paroxysmal brain electrical activity suggestive of a seizure disorder. • EEG is performed by securing 20 electrodes to the scalp at predetermined locations based on an international system that uses standardized percentages of the head circumference. • Each electrode is labeled with a letter and a number, the letter identifying the skull region (Fp = front polar; F = frontal; P = parietal; C = central; T =temporal; O = occipital) and the number identifying the specific location, with odd numbers representing left-sided electrodes and even numbers right sided electrodes. These electrodes are then connected in various combinations of pairs to generate voltage potential differences, and the potentials are recorded on a chart recorder. EEG • The EEG is analyzed with respect to symmetry between each hemisphere; wave frequency and amplitude; and the presence of spikes (20 to 70 msec)and sharp waves (70 to 200 msec), which may indicate a seizure focus. • When the eyes are shut, the most obvious frequency over the occipital cortex is 8-13 Hz; this is known as alpha rhythm, and disappears when the eyes are opened. • Other frequency bands seen over different parts of the brain in different circumstances are 1) beta (faster than 13/s). 2) theta (4-8/s). 3) delta (slower than 4/s). Lower frequencies predominate in the very young and during sleep. EEG Normal waves Primary generalised epileptic discharge Focal sharp waves Secondary epileptic discharge EEG The major usefulness of electroencephalography is for diagnosis and categorization of a seizure disorder. • EEGs are neither highly sensitive nor completely specific for diagnosis of seizures. • Because seizures are paroxysmal events, it is not unusual for an EEG to be normal—or only minimally abnormal—in a patient with epilepsy if it is recorded during an interictal phase (the period between seizures). • Only about 50% of patients with seizures show epileptiform activity on the first EEG. • Repeating the EEG with provocative maneuvers, such as:I. Sleep deprivation. II. Hyperventilation. III. Photic stimulation may increase this percentage to 90%. Onset of a tonic seizure showing generalized repetitive sharp activity with synchronous onset over both hemispheres Burst of repetitive spikes occurring with sudden onset in the right temporal region during a clinical spell characterized by transient impairment of external awareness Generalized 3-Hz spike-wave activity occurring synchronously over both hemispheres during an absence (petit mal) attack. The EEG may provide clues to the diagnosis of certain neurologic conditions, including viral encephalitis, prion disorders, and some forms of coma. Nerve Conduction Study(N C S) • NCS is helpful in documenting the existence of a neuropathy, quantifying its severity, and noting its distribution (i.e., whether it is distal, proximal, or diffuse). • It also can provide information on the modality involved (i.e., motor versus sensory) and can suggest whether the lesion is axonal or demyelinating. • The NCS is also helpful in diagnosis of compressive mononeuropathies, such as carpal tunnel syndrome, ulnar palsy, peroneal nerve palsy, and tarsal tunnel syndrome. Bipolar electrodes (R) Stimulation at the median nerve at the elbow (S1) Stimulation at wrist (S2). • By measuring the response latency to stimulation of a nerve at two different points along its length, it is possible to calculate nerve conduction velocities (NCVs). • This can be done for both sensory and motor nerves; typical values are 5060 m/s. Slowing of conduction velocity is suggestive of peripheral nerve demyelination, which may be either diffuse (as in a demyelinating peripheral neuropathy) or focal (as in pressure palsies or conduction block). Evoked potentials • EP are ways of measuring conduction velocities for sensory pathways in the CNS by means of computerized averaging techniques. • Three types of evoked potentials are routinely performed:I. Visual. II. Brain stem auditory (BAER ) . III. Somatosensory. A prolonged P 100 latency in one eye, in the absence of ocular disease, implies slowed conduction velocity in the optic nerve and suggests demyelination of that nerve (Multiple sclerosis ). BAER testing is helpful in diagnosis of acoustic schwannoma and other tumors in the cerebellopontine angle. Electromyography (EMG) • EMG involves recording compound motor action potentials (CMAPs) over muscles in response to motor nerve stimulation. • These are easier to record than nerve potentials because the muscle amplifies the response, typical amplitudes being 1-20 millivolts. • Fine concentric needle electrodes are inserted into muscle belly and the potentials from individual motor units recorded. It is also possible to record abnormal spontaneous activity arising from muscles at rest, such as fibrillations (a sign of denervation) or myotonic discharges. Abnormalities in the shape and size of muscle potentials can help in the differential diagnosis of denervation and structural muscle diseases.. EMG • EMG is helpful in evaluation to determine whether the weakness is due to anterior horn cell disease, nerve root disease, peripheral neuropathy, or an intrinsic disease of muscle itself (myopathy). • EMG can differentiate acute denervation from chronic denervation and may thus give an indication about the time course of the lesion causing the neuropathy. EMG • EMG can also be used to investigate the neuromuscular junction:Repetitive stimulation of a nerve with trains of electrical impulses at 3-15/s does not normally result in a significant fall-off in the amplitude of the resulting muscle action potential, However, such a decrement is seen in myasthenia gravis and provides one of the key diagnostic features. Augmentation of the response to repetitive stimulation is seen in the Lambert-Eaton myasthenic syndrome, though usually at higher stimulation frequencies. EMG Incremental Decremental Imaging study (structure) Is crucial to the identification of lesions of the nervous system in disease. These include:1. X-rays (plain X-rays, computed tomography (CT), CT angiography, myelography and angiography). 2. Magnetic resonance (MR imaging-MRI, or MR angiographyMRA,MRV, DWI, FLAIR). 3. Ultrasound (Doppler imaging of blood vessels) 4. Radioisotopes (single photon emission computed tomography-SPECT, and positron emission tomography-PET). MRI provides a non-invasive way of obtaining high-resolution images of both the vertebral column and the relevant neural structures whether for cervical, dorsal or lumbosacral. Cervical and thoracic spine  Plain X-rays are useful in the investigation of structural damage to vertebrae. Give information about intervertebral disc disease. it not provide detailed information about the spinal cord or nerve roots, for which myelography or MRI is used.  Myelography has declined with the advent of MRI.  Myelography is indicated in: 1. MRI is not available 2. MRI is contraindicated. 3. if the patient cannot tolerate lying within the scanner because of claustrophobia. Lumbo-sacral region  Plain X-rays are of value in the investigation of structural abnormalities of the lumbar spine. It of no value in the assessment of nerve roots or the spinal canal.  Radiculography :- contrast injection into the thecal space can be used to outline the lower nerve roots.  Myelography:- contast run up to outline the conus and spinal cord.  CT contrast give detailed informations following myelography.  Non-contrast CT of the lumbar spine can only be used to image the vertebrae and discs. Head and orbit imaging  Plain skull X-rays is largely restricted to the diagnosis of fractures and sinus disease.  CT or MRI is needed to image pathology inside the skull.  CT will show bone and calcium well, and will easily image collections of blood. It will also detect abnormalities of the brain and ventricles, such as atrophy, tumours, cysts, abscesses, vascular lesions and hydrocephalus. Diagnostic yield is often improved by the use of intravenous contrast and spiral CT methods. It is of limited in its ability to image the posterior fossa (because of the surrounding bone density). It is poor at detecting abnormalities of white matter and at allowing detailed analysis of grey matter. Head and orbit MRI • MRI is much more useful in the investigation of posterior fossa disease, as it is not affected by the surrounding bone. • It is much more sensitive than CT to abnormalities of white and grey matter and is therefore useful in the investigation of inflammatory conditions such as multiple sclerosis, and in investigating epilepsy. • Diffusion weighted MRI(DWI) is particularly useful in diagnosing acute ischaemic stroke. • It is also useful in imaging the orbits, where special imaging sequences can be used to compensate for orbital fat and thereby allow clear views of extraocular muscles, optic nerve and other orbital structures. Blood vessels imaging A. Doppler or duplex study :- noninvasive US to study stenosis ,ulcerated plaques in both intracranial &extra cranial arteries. B. Contrast study either IV or IA resolution can be enhanced by using of spiral CT or computer-assisted digital subtraction. IV need large amount of contrast than IA, but IA carry higher complication rate than IV. C. MR angiography (MRA,MRV) to study flowing of blood non invasively , although resolution still not comparable to that of intra-arterial angiography, but it replacing angiography in most diagnostic settings, except when MRI cannot be performed because of contraindications . Imaging the nervous system Technique X-ray Principle Attenuation of X-ray beam by radioopaque tissues and substances (bone, calcium, metal, iodinated contrast) Magnetic resonance imaging (MRI) Magnetic resonance Structural imagingHigh-quality soft Expensive Increasing application of different tissues MRA tissue imaging Less widely available Functional MR and depends largely on Functional MRI Good views of MRA looks at blood flow not spectroscopy still mainly free hydrogen/water MR spectroscopy posterior fossa and vessel anatomy research tools content; signals temporal lobes Scanners claustrophobic changed by No ionising radiation Pacemakers contraindicate MRI. movement (e.g. Non-invasive Complications of contrast flowing blood) (gadolinium) Ultrasound Echoes from highfrequency sound source localise structure; Doppler principle used to measure flow rate RadioRadio-labelled isotope isotopes Applications Plain X-rays CT, CTA Radiculography Myelography Intra-arterial angiography Doppler Duplex scans Advantages Widely available Relatively cheap Relatively quick Cheap Quick Non-invasive Isotope brain scan In vivo imaging of SPECT functional anatomy PET (ligand binding, blood flow) Disadvantages Ionising radiation Reactions to contrast Myelography and angiography are invasive and thus carry risk Comments X-rays only used for showing fractures or foreign bodies. CT investigation of choice for stroke Intra-arterial angiography still 'gold standard' for vascular lesions Operator-dependent Poor anatomical definition Useful as screening tool to assess need for carotid endarterectomy Poor spatial resolution Ionising radiation Expensive (especially PET) Not widely available Isotope scans obsolete. SPECT and PET mainly research tools but being introduced clinically for management of epilepsy and dementia Routine blood tests Thyroid function , SLE ,B12, Syphilis, Acanthocytes may assist in the diagnosis of neuroacanthocytosis, Creatine kinase in muscle diseases, and copper studies in Wilson's disease  Immunological tests:- Antibodies to acetylcholine receptors and muscle-specific tyrosine kinase (MuSK), seen in myasthenia gravis. Antibodies to voltage-gated calcium channels in Lambert-Eaton myasthenic syndrome. Antibodies to basal ganglia neurons are found in Sydenham's chorea and encephalitis lethargica.  Genetic testing:- Many inherited neurological diseases can diagnosed by DNA analysis. These include diseases caused by increased numbers of trinucleotide repeats, such as Huntington's disease, myotonic dystrophy and some types of spinocerebellar ataxia. Lumbar puncture By inserting a needle between lumbar spinous processes (usually between L3 and L4) through the dura and into the CSF under local anaesthetic. Normal Pressure Colour Subarachnoid haemorrhage Acute bacterial meningitis 50-250 mm Increased Normal/increased of water Clear Blood-stained Cloudy Xanthochromic Tuberculous meningitis Multiple sclerosis Normal Normal/increased Normal Clear Clear/cloudy Clear Viral meningitis Red cell count (× 106/L) 0--4 Raised Normal Normal Normal Normal White cell count (× 106/L) 0—4 Normal/slightly raised 1000-5000 polymorphs 10-2000 lymphocytes 50-5000 lymphocytes 0-50 lymphocytes > 60% of blood level < 0.45 g/L Normal Decreased Normal Decreased Normal Increased Increased Normal/increased Increased Normal/increased Sterile Sterile Ziehl-Nielson/auramine stain or tuberculosis culture positive Sterile Negative Negative Can be positive Often positive Glucose Protein Microbiology Oligoclonal bands Organisms on Gram Sterile/virus detected stain and/or culture Can be positive Can be positive CSF contraindications :1. Clinical suggestion of raised intracranial pressure (papilloedema). 2. Depressed level of consciousness. 3. Focal neurological signs suggesting a cerebral lesion. These need imaging study (CT or MRI ) to exclude brain SOL, because in IIH although there is papillodema but we can do LP safely for diagnostic & therapeutic purposes. 4. Thrombocytopenia or disseminated intravascular coagulation, and in those on warfarin or heparin therapy. A. B. C. Complications of LP Headache, which is thought to be due to reduced CSF pressure. The risk of this can be reduced by using smaller needles. Transient radicular pain, and pain over the lumbar region during the procedure. Infections such as meningitis are extremely rare following lumbar puncture, provided that an aseptic technique is used. Biopsy • This can be used for muscles, nerves, meninges & brain. • It carry high risk of morbidity & complications & because the availability of non invasive imaging study these investigations are rarely used