Nervous system: introduction 2

INVESTIGATION OF NEUROLOGICAL

DISEASES:

Nervous system: introduction 2

INVESTIGATION OF NEUROLOGICAL

DISEASES:

Dr. Mohammad Shaikhani.

INVESTIGATION OF NEUROLOGICAL DISEASE

INVESTIGATION OF NEUROLOGICAL DISEASE

1.TESTS OF FUNCTION (CLINICAL NEUROPHYSIOLOGY):

A. EEG. B. EPs. NCS/EMG. 2.Imagings. 3. Special tests: A. Blood tests. B. CSF testing C. Biopsies.

TESTS OF FUNCTION (CLINICAL NEUROPHYSIOLOGY)

TESTS OF FUNCTION (CLINICAL NEUROPHYSIOLOGY)

More restricted application than imagings. Essential in certain conditions. Include: EEG. Evoked potentials (EPs). Nerve conduction studies/electromyography

(NCS/EMG).

EEG:EEG:

When the eyes are shut, the most obvious frequency over the occipital cortex is 8-13/s( alpha rhythm) disappears when eyes opened.

Other frequency bands seen over different parts of the brain in different circumstances are beta (faster than 13/s), theta (4-8/s) & delta (slower than 4/s).

Lower frequencies predominate in the very young & during sleep.

clear right temporal sharp waves in two patients with right temporal lobe epilepsy

10-second EEGs: Seizure EvolutionN Pre

During Post

EEG: Indications in CNS diseases:

EEG: Indications in CNS diseases:

The management of epilepsy (the most important). A global increase in fast frequencies (beta) seen with

sedating drugs (e.g. benzodiazepines), Marked slowing over a structural lesion as a tumour

or an infarct, but with modern neuro-imaging, it had lost its use in localizing such lesions.

Still useful in; The management of patients with disturbance of

consciousness or sleep. The diagnosis of cerebral diseases as encephalitis. In certain dementias (e.g. sporadic CJD).

EEG In epilepsy:EEG In epilepsy: Only in rare circumstances EEG provide unequivocal

evidence of epilepsy It is not useful as a diagnostic test for the presence of

epilepsy because: 50% of patients with proven epilepsy will have a

normal 'routine' EEG. The presence of EEG changes often seen in association

with epilepsy does not make a diagnosis (although false +ve rate for clear-cut epileptiform features is < 1/1000).

Its use is predominantly to: Distinguish the type of epilepsy. Whether there is an epileptic focus, particularly if

surgery for epilepsy is contemplated.

EEG In epilepsy:EEG In epilepsy: It is often possible to detect 'epileptiform'

abnormalities in between seizures in the form of 'spikes' & 'sharp waves' that support a clinical diagnosis, enhanced by hyperventilation, photic flicker, sleep & some drugs.

During an epileptic seizure, high-voltage disturbances can be recorded, may be generalised, as in the 3 cycle/s 'spike & wave' of childhood absence epilepsy (petit mal), or more focal, as in partial epilepsies.

It is unusual to record a seizure itself, except in the case of childhood absence epilepsy.

EEG In epilepsy:EEG In epilepsy: Diagnostic value enhance by: 24 hours tape recorder instead of usual 30-min record. Video information to the EEG allows comparison of

behaviour with cerebral activity. In special circumstances, electrodes can be surgically

positioned, e.g. through the foramen ovale, to record from the inferior temporal surface.

Evoked potentials:Evoked potentials: EEG data from 100-1000 repeated stimuli are averaged

electronically, noise is removed & an evoked potential recorded & its latency (the time interval between stimulus onset & the maximum positive value of the evoked potential, P100) &amplitude can be measured.

Can be measured following visual, auditory or somatosensory.

Visual evoked potentials(VER), most commonly used. Abnormalities of the evoked potential indicate damage

to the relevant pathway, either in the form of a conduction delay (increased latency) or reduced amplitude, or both.

With MRI, evoked potentials is restricted to specialised indications, as a semi-objective measure of visual function.

Evoked potentials:Evoked potentials:

Nerve conduction studies & electromyography :Nerve conduction studies & electromyography :

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), for both sensory & motor nerves; typical values are 50-60 m/s.

Slowing of conduction velocity is suggestive of peripheral nerve demyelination & may be either diffuse (as in a demyelinating peripheral neuropathy) or focal (as in pressure palsies or conduction block).

Nerve conduction studies & electromyography :Nerve conduction studies & electromyography :

Indications: To identify damage to peripheral nerves. Whether the pathological process is focal or diffuse Whether the damage is principally axonal or

demyelinating or in the nerve roots. Fine concentric needle electrodes can be inserted into

muscle &record fibrillations (a sign of denervation) or myotonic discharges or structural muscle diseases.

Investigate the NMJ, a decrement is seen in myasthenia gravis.

Augmentation of the response to repetitive stimulation is seen in the Lambert-Eaton myasthenic syndrome, usually at higher stimulation frequencies.

Imagings:Imagings:

TECHNIQUES AVAILABLE FOR IMAGING THE NERVOUS SYSTEM

Technique Principle Applications Advantages Disadvantages Comments

X-ray radio-opaque tissues /substances (bone, calcium, metal, iodinated contrast)

Plain X-raysCT Radiculography MyelographyAngiography

Widely availableRelatively cheapRelatively quick

Ionising radiationReactions to contrastMyelography & angiography are invasive & carry risk

Plain X-rays only used for showing fractures or foreign bodiesCT is investigation of choice for stroke Intra-arterial X-ray contrast angiography still 'gold standard'

MRI depends on free hydrogen/water content; signals changed by movement (e.g. flowing blood)

Structural imaging MRAFunctional MRIMR spectroscopy

High-quality soft tissue imaging Good views of posterior fossa /temporal lobes No ionising radiation Non-invasive

ExpensiveLess widely availableMRA looks at blood flow not vessel anatomy

claustrophobicPacemakers C/I.

Increasing applicationFunctional MR / spectroscopy.

U/S Echoes from high- frequency sound source localise structure;Doppler principle usedto measure flow rate

DopplerDuplex scans

CheapQuickNon-invasive

Operator-dependentPoor anatomical definition

Useful as screening tool Increasingly used as basis for carotid endarterectomy

Radio- isotope Radio-labelled isotopes

Isotope brain scan SPECTPET

In vivo imaging of functional anatomy (e.g. ligand binding, blood flow)

Poor spatial resolution Ionising radiation Expensive (especiallyPET)Not widely available

Isotope scans now obsoleteSPECT &PET used increasingly in management of epilepsy/ dementia

Special testes: blood testsSpecial testes: blood tests

Systemic diseases affecting CNS as: Confusion due to hypothyroidism(TFTs) Stroke due to systemic lupus erythematosus (ANF etc). Ataxia due to vitamin B12 deficiency Myelopathy due to syphilis(VDRL). Haematological tests (e.g. looking for acanthocytes to

diagnose neuroacanthocytosis)

Special testes: blood testsSpecial testes: blood tests

Biochemical tests (e.g. creatine kinase in muscle diseases) Copper studies in Wilson's disease). tests to diagnose infections of the nervous system.

Special testes: blood testsSpecial testes: blood tests

A number of specific antibodies to: Acetylcholine receptors &muscle-specific tyrosine kinase

(MuSK), in myasthenia gravis Voltage-gated calcium channels in Lambert-Eaton

myasthenic syndrome. Different gangliosides in various types of neuropathy

including multifocal motor neuronopathy& Guillain-Barré syndrome (sp Miller-Fisher variant).

Antineuronal antibodies as a markers of paraneoplastic cerebellar or neuropathic syndromes.

Basal ganglia neurons found in Sydenham's chorea & encephalitis lethargica.

Special testes: blood testsSpecial testes: blood tests

DNA analysis: For diseases caused by increased numbers of

trinucleotide repeats, as Huntington's disease, myotonia dystrophy& some types of spinocerebellar ataxia.

Defects of mitochondrial DNA detected in many conditions as Leber's hereditary optic neuropathy& some syndromes causing epilepsy or stroke-like syndromes.

Special testes: LPSpecial testes: LP

Lumbar puncture is indicated in: CNS infections (e.g. meningitis or encephalitis) Subarachnoid haemorrhage. Inflammatory conditions (e.g. multiple sclerosis,

sarcoidosis, cerebral lupus) Neurological malignancies (e.g. carcinomatous

meningitis, lymphoma , leukaemia), Measure CSF pressure (e.g. in idiopathic intracranial

hypertension) Myelography. Therapeutic procedures, either to lower CSF pressure or

to administer drugs as Methotrexate in ALL.

Special testes: CSF testingSpecial testes: CSF testing

CSF is normally clear & colourless. Tests include: Centrifuging to determine the colour of the supernatant

(yellow, or xanthochromic, some hours after subarachnoid haemorrhage)

Biochemistry (glucose, total protein, protein electrophoresis to detect oligoclonal bands).

Microbiology (e.g. PCR for herpes simplex or TB), Immunology (e.g. paraneoplastic antibodies). Cytology (to detect malignant cells).

Special testes: risks of spinal tap.Special testes: risks of spinal tap.

If there is a SOL in the head, LP can result in a potentially fatal shift of intracerebral contents downwards, towards &into the spinal canal (coning).

LP is contraindicated until imaging head (by CT or MRI) has excluded a SOL or hydrocephalus, if there is:

Any suggestion of raised intracranial pressure (e.g. papilloedema),

Depressed level of consciousness. Focal neurological signs suggesting a cerebral lesion. The patient is likely to bleed, as in thrombocytopenia,

DIC or warfarin therapy, unless specific measures are taken to compensate for the clotting deficit on a temporary basis.

LP is not contraindicated in those on aspirin.

Special testes: spinal tap side effects.Special testes: spinal tap side effects.

30% followed by low-pressure headache, which can be severe.

Transient radicular pain during the procedure,pain over the lumbar region.

Infections as meningitis extremely rare if sterile procedures followed.

Needle between L3,4 or L4,5

CSF PARAMETERS IN HEALTH & SOME

COMMON DISORDERS CSF PARAMETERS IN HEALTH & SOME

COMMON DISORDERS

GlucoseGlucose

  NormalSubarachnoid haemorrhage

Acute bacterial meningitis

Viral meningitis

Tuberculous meningitis

Multiple sclerosis

Pressure 50-180 mm of water

Increased N/increased Normal N/increased Normal

Colour Clear Bloody/Xanthochromic

Cloudy Clear Clear/cloudy Clear

Red cell count 0-4 *106/l Raised Normal Normal Normal Normal

White cell count

0-4 *106/l N/slightly raised

1000-5000 polymorphs

10-2000 lymphocytes

50-5000 lymphocytes

0-50 lymphocytes

> 60% of blood level

N Decreased Normal Decreased Normal

Protein < 0.45 g/l Increased Increased Normal/increased

Increased N/increased

Microbiology Sterile Sterile Organisms on Gram stain &/or culture

Sterile/virus detected

ZN or TB culture positive

Sterile

Oligoclonal bands

Negative Negative Can be positive

Can be positive

Can be positive

Often +ve.

Xanthochromic CSF in SAH:

Biopsies: Nerve.Biopsies: Nerve.

Nerve biopsy at the ankle or radial nerve at the wrist, for histopathology, useful for;

Identify underlying causes in demyelinating neuropathies (e.g. vasculitic) or, occasionally, infiltration with abnormal substances as amyloid.

It is not performed unless it is reasonably likely to diagnose a potentially treatable condition as an inflammatory neuropathy, as there is an appreciable morbidity.

Biopsies: Muscle.Biopsies: Muscle.

Often quadriceps. Indications include the investigation of primary muscle

disease, to distinguish neurogenic wasting, for myositis or myopathy.

Histology /enzyme histochemistry can also be helpful in the diagnosis of more widespread metabolic disorders, as mitochondrial &some storage diseases.

Pain & infection can follow, much less than after nerve biopsy.

Biopsies: Brain.Biopsies: Brain.

In situations in which the nature of lesions is not clear,as in unexplained degenerative diseases (e.g. unusual dementias) to diagnose potentially treatable disease.

Brain biopsy stereotactically through a burrhole in the skull, complication much lower than open craniotomy, but haemorrhage, infection& death still occur.

Brain biopsy is only considered if a diagnosis cannot be reached in any other way.

Signs of motor neuron lesions:Signs of motor neuron lesions:

Lower motor neuron lesions: as in poliomyelitis. A. Flaccid weakness. B. Low tone. C. Absent reflexes. D. Babenski: equivocal. C. preserved superficial reflexes as abdominal reflex. Upper motor neuron lesions: as in CVA & Brain tumors. A. Spastic paralysis. B. High muscle tone (spastic). C. Exadurated reflexes. D. absent superficial reflexes as abdominal reflex. C. Dorsiflexed (upgoing) Babenski reflex.

Spasticity vs rigidity: both increase muscle toneSpasticity vs rigidity: both increase muscle tone

Spasticity: in upper motor neuron lesions. Of clasp-knife character. Rigidity: in parkinsonism, of 2 types. A. Lead pipe: increase tone throughout ranges of

movements, when rigidity predominates over tremor. B. Cog-wheel: increase tome intermittent, when tremor

predominates.