INVESTIGATION OF NEUROLOGICAL DISEASES:

Dr Rasol M Hasan

• Skull and spinal X-rays • These show: • fractures of the skull vault or base • skull lesions (e.g. metastases, osteomyelitis,

Paget's disease, abnormal skull foramina, fibrous dysplasia)

• enlargement or destruction of the pituitary fossa - intrasellar tumour, raised intracranial pressure

• intracranial calcification - tuberculoma, oligodendroglioma, wall of an aneurysm, cysticercosis.

• Spinal X-rays show fractures, congenital bone lesions (e.g. cysts), destructive lesions (infection, metastasis) or spondylosis (degenerative change).

• CT scanning demonstrates: • cerebral tumours • intracerebral haemorrhage and

infarction • subdural and extradural haematoma • free blood in the subarachnoid space

(subarachnoid haemorrhage) • lateral shift of midline structures and

displacement/enlargement of the ventricular system

• cerebral atrophy • spinal trauma (with CT myelography) • skull and scalp lesions.

• Limitations of CT • Lesions under 1 cm diameter may be missed. • Lesions with attenuation close to that of bone

may be missed if near the skull. • Lesions with attenuation similar to that of brain

are poorly imaged (e.g. MS plaques, isodense subdural haematoma).

• CT sometimes misses lesions within the posterior fossa.

• The spinal cord is not imaged directly by CT (contrast is necessary).

• Cooperation is required - a general anaesthetic is occasionally needed

• Advantages of MRI • MR distinguishes between brain white and grey

matter. • Spinal cord and nerve roots are imaged directly. • Pituitary imaging. • MRI has greater resolution than CT (around 0.5

cm). • No radiation is involved. • Magnetic resonance angiography (MRA) images

blood vessels without contrast. • It is useful in muscle disease, e.g. myositis.

• Indications for lumbar puncture (LP) are: • diagnosis of meningitis and encephalitis • diagnosis of subarachnoid haemorrhage

(sometimes) • measurement of CSF pressure, e.g. idiopathic

intracranial hypertension. • removal of CSF therapeutically, e.g. idiopathic

intracranial hypertension • diagnosis of miscellaneous conditions, e.g. MS,

neurosyphilis, sarcoidosis, Behçet's disease, neoplastic involvement, polyneuropathies

• intrathecal injection of contrast media and drugs.

• Contraindications for lumbar puncture • Suspicion of a mass lesion in the brain or spinal

cord. Caudal herniation of the cerebellar tonsils ('coning') may occur if an intracranial mass is present and the pressure below is reduced by removal of CSF.

• Any cause of raised intracranial pressure. • Local infection near the site of puncture. • Congenital lesions in the lumbosacral region

(e.g. meningomyelocele). • Platelet count below 40 × 109/L and other

clotting abnormalities, including anticoagulant drugs.

• Unconscious patients and those with papilloedema must have a CT scan before lumbar puncture.

• Specialized tests in specific diseases • Certain tests are employed in the diagnosis of

individual (and often rare) neurological diseases. Examples are:

• anticardiolipin and lupus anticoagulant antibody and detailed clotting studies in stroke

• antibody to acetylcholine receptor protein in myasthenia gravis

• serum copper and caeruloplasmin in Wilson's disease. • blood lactate studies (failure to rise on exercise) in

McArdle's syndrome . • serum phytanic acid (elevated) in Refsum's disease • serum long-chain fatty acid (present) in

adrenoleucodystrophy . • genetic studies - e.g. Huntington's disease, hereditary

sensorimotor neuropathies

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) • More restricted application than

imagings.• Essential in certain conditions.• Include:• EEG.• Evoked potentials (EPs).• Nerve conduction

studies/electromyography (NCS/EMG).

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:

• 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:• 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:• 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:• 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:• 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:

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 :

• 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:

• 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 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 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 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.

Special 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: 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 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.• 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.• 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

GlucoseGlucose

  Normal

Subarachnoid 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 *103/l N/slightly raised

1000-5000 polymorphs

10-2000 lymphocytes

50-5000 lymphocytes

0-50 lymphocytes

Glucose > 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.• 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.• 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.• 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:• 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 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 tone intermittently, when tremor predominates.