Unit 23.

Neuromuscular
diseases,

central and peripheral

nervous system
diseases
Objectives:
Tests for muscle weakness –
myopathies.
Tests for muscle damage -
rhabdomyolysis.
Tests in the common/serious
diseases with neuro-muscular
manifestations.
Symptoms of
neuromuscular weakness:
Muscle weakness or rigidity.
Cramp like pain
Swelling or twitching of muscles or a
skin. If there is a rash –
dermatomyositis.
Skeletal muscle weakness or atrophy –
myopathies.
Children – delays in sitting up or
walking.
Timing is important:
Sudden paralysis = vascular
disorders of CNS – stroke.
1-14 days paralysis =
poliomyelitis, Guillain-Barre
syndrome, porphyria.
Slowest = disease of the
muscle itself.
Causes of myopathies,
muscle diseases:
• Inherited
• Infections
• Structural: anoxia, infections, toxins,
drugs, trauma, overuse.
• Denervation: trauma, poliomyelitis,
metabolic, porphyrias.
• Metabolic: endocrine.
• Electrolyte imbalance: K, Ca, Mg.
Laboratory tests in
myopathies:
Na, K, Cl, HCO3.
CK, CK2, CK1, (AST, LD, aldolase)
Creatinine, (Creatine)
Urea
Liver function tests: AST, ALT, ALP,
GGT
Myoglobin
Ca, Pi,.
Laboratory tests in
myopathies (2)
Glucose
Ketones
Thyroid hormones
Adrenal hormones
Parathyroid hormone
Inflammatory disease markers.
 Creatine kinase in tissues:
Units/kg CK1,MM CK2,MB CK3,BB
Skeletal 25,000 95 <5 0
Cardiac 400 78 22 0
Brain 160 0 0 100
Uterus 50 2 1 97
Kidney 15 12 0 88
Liver 4 90 6 4
Special myopathy tests:
Ischaemic lactate.
Exercise test on patient.
Patient fasting then measure
organic acids for defects in
mitochondrial fatty acid oxidation.
Lead
Cocaine etc.
Myopathies, research
tests:
Biopsy.
Mitochondrial
biochemistry.
Magnetic resonance
spectroscopy.
Muscle weakness
investigation:
• Family history.
• Endocrine check.
• Drugs check.
• Infections.
Routine laboratory tests in
myopathies
Serum CK
Serum electrolytes
Serum or urine myoglobin,
Serum and urine creatinine
Rhabdomyolysis
investigation:
Urine blood/myoglobin.
Serum CK.
Serum myoglobin
Serum electrolytes: K, Ca, Mg
Renal shock: serum and urine
creatinine, osmolality.
Causes of rhabdomyolysis:
Primary muscle injury: trauma, alcohol.
Hypoxia.: ischaemia, carbon monoxide.
Abnormality of energy production:
exercise.
Infectious disease involving muscle:
virus, gangrene.
Miscellaneous: hypokalaemia, toxic
drugs.
Neuromuscular disease:
Central nervous system.
Peripheral nervous system
disease.
Interface: neuromuscular
junction.
Muscles.
Acute meningitis:
Commonest causes are Neisseria
meningitidis, streptococcus
pneumonia and Haemophilus
influenzae.
Other bacteria, fungi, parasites
and viruses can cause it.
Meningitis:
Fever,
Headache
Nausea,
Vomiting
Hyperaesthesia
Myalgia.
Stiffness, spasm of neck, back,
hamstring
Meningitis:
Petechial rash
Could be acute or over a period of days.
CSF: cells
Culture
Protein
Glucose
Lactate.
 Cerebrospinal fluid:
Colour protein glucose Etc.

Acute bacterial Increase Decrease IgM

meningitis.
Viral meningitis Normal Normal

Encephalitis Increase Normal

Hemorrhage Yellow Increase

Bacterial meningitis
Colonize nasopharynx
Invades blood
Invades CSF and meninges
Inflammation of cerebral vessels
Spasm and thrombosis
Hypoxia
Capillary damage, brain oedema
Degenerative disease,
nutritional dementia:
Laboratory work up:
Na, K, Cl, HCO3
Creatinine, urea.
TSH
Folate, vitamin B12.
Lipoprotein e variants for
Alzheimer’s
79 year-old woman,
hypertensive
Heart disease
Withdrawn.
Potassium 3.0 mmol/L (3.5-5.0)
Glucose 7.3 mmol/L (3.5-5.0)
Magnesium 0.5 mmol/L (0.8-1.5)
Albumin 30 g/L (35-50)
Calcium 2.1 mmol/L (2.2-2.6)
Betty Parker, 65 year-old
woman
Hands becoming shaky, tremour worse
in right hand.
Worsened by stress improved by sleep.
Handwriting small
Muscles stiff.
Blank facial expression, voice soft and
monotonous
Walking is slow to start, difficult to stop
Autoimmune disease,
multiple sclerosis
Muscular weakness due to decreased
neuromuscular signal transmission.
Blurred vision, environment moves.
Judgment impaired
Emotionally labile
Variable course
Differential diagnosis includes: hysteria,
drugs, SLE
Multiple sclerosis
Antibodies against myelin.
T cell mediated.
Women: men 2:1.
20-40 years of age.
In tropics 1/10,000
Canada 1/1,000
Relapse in 30-40%
32 year-old woman,
clinical chemist
Blurring of vision.
Muscular weakness.
Episodic symptoms.
Laboratory work:
Csf protein
Csf electrophoresis – oligoclonal
banding in gamma region.
Causes of peripheral
neuropathy:
Undetermined causes *
Diabetes mellitus*
Alcohol*
Vitamin B12 deficiency.
Drugs (such as isoniazid, vincristine)
Paraneoplastic arthritis.
Amyloidosis.
Peripheral neuropathy (2):
Hereditary (Peroneal [fibula or
outside of leg] muscular atrophy)
Post infective (Guillain-Barre
syndrome)
Tropics:
Leprosy*
Pellagra
Thiamine deficiency.
Peripheral neuropathy by
toxins
Uraemia
Nerve conduction slowed.
Check renal function.

Diabetes mellitus – glycation,

sorbitol?
Peripheral neuropathy:
Inherited, the most common is
Charcot-Marie-Tooth disease.
150,000 in USA.
Demyelinating neuropathy with
wasting below the knee, pes cavus
(foot arch) and hand
Laboratory work: genetic test for
CMT
Interface, autoimmune,
myasthenia gravis:
Muscle weakness on repetitive tasks.
Adults of all ages.
Women more than men.

Laboratory work: antibodies to acetyl

choline receptors
Thyroid test (13% of Myasthenia gravis)
Mia Graves, 40 year-old
woman, general weakness
Difficulty holding head up,
Difficulty eating
Voice is quieter.
Lost 3 kg in weight in last 6
months.
Laboratory tests: Antibody tests,
thyroid function tests.
Inherited disease,
muscular dystrophy
Male
1 in 3,500 live births
Becomes evident in 2-5 years of
age.

Laboratory work: CK much

increased but this is less and less
as the disease progresses.
Neoplasia:
Parathesia,
Pain,
Sensory loss,
Absent tendon reflexes,
Proximal muscle weakness.
Dragon boater woman,
treated for breast cancer
Serum calcium 3.5 mmol/L
(2.2-2.6)

What is the effect of such a

high calcium on her muscle
function?
Dermatomyositis and
polymyositis
Autoimmune, infections possible cause?
40-60 years of age.
Women > men
Variable course
Collagen disease
Facial oedema
Erythema, pink scaling eruption.
Dermatomyositis,
polymyositis
Laboratory work:
ESR increase
Alpha2 and gamma globulins increased,
ANA (SLE) negative
Urine creatinine (creatine) decreased
Calcification
ECG variable.
Dermatomyositis rash
Localized or diffuse erythema.
Maculopapular eruption. Scaling
eczematoid dermatitis.
Heliotrope (reddish purple/lilac)
discolouration over dorsum of finger
joints, round nail bed, eyelids, mouth,
nose, cheek, forehead.
Itching possible.
Periodic paralysis,
electrolyte problems:
Three types known with different
triggers such as:
Exercise
Food
Stress
Cold
Laboratory work: serum and urine K
During attack serum and urine K falls.
Trauma
• Physical injury

Laboratory work: CK,

myoglobin.
Lolita Bebe,12 year old,
collapses in marathon.
Urine dark brown
in colour
Serum CK
Urine “blood”
Urine or serum
myoglobin
Serum and urine
creatinine.
Johnny Liar, 35 years of
age athlete,
Ran 300 km in 24
hours.
Claims world record
Known liar
CK and AST

Clinica Chimica Acta,

JAMA 1981.
.
2. Muscle damage by toxic
trauma
Lead,
Porphyrins,
Cocaine,
Family history:
Succinyl choline
Halothane
Muscle damage by heat
Heat stroke.
Malignant
hyperthermia
Cardiac
arrhythmias
Muscle rigidity
Family history
28 year old man ran 8 km,
Australia, temperature 31oC high humidity.
Race delayed because of heat.
Collapsed at 7.4 km when in lead.
Taken to local hospital.
Acidotic and hot.
IV fluid with ice over arteries.
28 year old with heat stroke.
Later cool IV fluid given
Renal failure.
Acidosis body temperature 40oC.
12 days later sent to Sydney.
Serum calcium reduced then increased
Serum phosphate the opposite of calcium.
Serum CK increased to 20,000 IU/L (<100)
28 year old with heat stroke.
Liver and kidney failed.
Major muscles swollen for days.
Tawny colour on biopsy.
Med J Australia 153, 101-104 1990.
Muscle structural damage
- denervation
Inflammatory diseases
Infections
Polymyositis.

Laboratory tests:
ESR, ceruloplasmin, alpha-1-
antitrypsin, complement, C
reactive protein.
Metabolic diseases
involving muscle:
Endocrine:
Adrenal
Thyroid
Diabetes
Iatrogenic.
Genetic
52 year old woman, mild
fatigue
Muscle pain and
stiffness
Weight gain.
Work stress
Insomnia
Poor diet
Serum TSH 11 U/L
(0.5-5)
Serum thyroxine and
serum free thyroxine
normal
Metabolic disease -
genetic
Muscular dystrophies.
Glycogen storage diseases
16 year-old boy with
muscle cramps
On severe exercise.
Serum CK increased.
Serum lactate dehydrogenase
increased.
Haemolysis (CBC changes).
Myoglobinuria, myoglobinaemia.
Muscle biopsy done.
 16 year old boy, muscle
biopsy
glycogen Glucose-6 Fructose-6 Fructose
phosphate phoshate 1,6diphosp

16 yr 44 9 1.6 0.02
boy
Health 10 10.5 0.1 0.6
Muscle disease caused by
electrolytes’ milieu
Tetany
Stiff man
Cramps
Spasms
Laboratory work:
Na, K, H, Ca, Mg, PTH, renal
function tests.
Alcoholic myopathy – the
wrath of grapes.
Muscle weakness, especially legs.
Cramps
Swelling
Tenderness
Laboratory work includes:
Serum CK increases
Serum and urine myoglobulinaemia.
Alcohol and muscles
• Substrate use increases. ATP is used
but not regenerated because glucose
and oxygen is not sufficient.
• NADH increases so pyruvate is
converted to lactate, this blocks urate
excretion.
• Acetate is produced and ATP used up.
Alcoholic myopathy
Treatment:
Abstinence.
Laboratory monitoring:
Serum GGT or
Serum carbohydrate deficient
transferrin or
Serum methanol.
John Coors-Molson, 52
year old brewer
Difficulty walking
Impotent
Legs weak
Laboratory data:
Serum CK 950 U/L (<100)
Serum GGT 100 U/L (<55)
Urine: dark colour.
Boxcar Bertha, 40 years:
Homeless woman, an alcoholic.
Scuffle with Police whilst drunk.
She claims Police brutality but
there are concerns about her
having a myocardial infarction.
Laboratory work:
Serum CK 10,000 U/L (<120)
Tommy Atkins, 55 yrs old
Former soldier
Fired from job in
Africa after 20
years.
Weight loss.
Appetite loss
Muscles are weak,
wasting and
painful.
Tommy Aitkin,
Walks oddly, difficulty standing.
Skin has spider naevi.
Spleen and liver are enlarged.
Fading bruises over shins and arms
Ankle oedema.
Smoked 40 cigarettes a day.
Drinks whiskey regularly.
Atonic Betty, Moose Jaw
native, retired superhero
Chronic
fatigue.
Muscle pain.
Loss of
athletic
performance
Atonic Betty, differential
diagnosis:
Anaemia
Endocrine
Nutritional
Fluid and electrolyte
Hepatic disease
Chronic heart
disease
Chronic lung disease
Infections
Atonic Betty, differential
diagnosis:
Anxiety
Psychotic
depression.
Summary:
Tests for muscle weakness.
Tests for muscle
breakdown.
Test for common/serious
neuro- and neuromuscular
diseases.
Post script, running
performance and aging:
Theories
Lung capacity and or
Heart function and or
Neuromuscular problems, are they
chemical
structural
nerve?
Aging=weakness. Theories
No nerve connection?
Poisoned nerve?
Poisoned central nervous system?
Poisoned muscle?
Lack of mitochondria.
Changes in fibre structure.
?