Neuromuscular disorders

FM Brett MD., FRCPath

At the end of this lecture you should be able to:

Distinguish between UMN and LMN lesions

Understand the differences between a neuropathy and a myopathy

3. Know how MND presents

Know the common causes of a peripheral neuropathy

Know the importance of clinical history, f/x and examination in understanding muscle disease.

Sites of lesions producing neuromuscular pathologyEither the upper (1,2,3) or lower motor neurone pathway (4,5), N-M-J (6) or muscle (7) may be responsible

Sites of lesions producing neuromuscular pathologyCommonest causes trauma or vascular accidents (1,2) or demyelination (2,3,4,5)neuronal degeneration (4), transmission defects (6) and membrane, fibrillary or metabolic lesions (7).

The motor unitNMJMNeuroneAxon Diseases ofmotor neurones

PeripheralneuropathiesDiseases of neuromuscular transmissionPrimary muscledisease: myopathies

MND ALS~ generalised wasting & fasiculation

~ Bulbar muscle involvement common

~ Associated upper motor neurone symptoms and signs

~ No sensory symptoms

~ Steadily progressive and fatal

Clinical presentation of MND

Selective loss of LMN from pons, medulla and spinal cord, together with loss of UMN from the brain

Clinical picture varies depending on whether :upper or lower motor neurones are predominantly involved Which muscles are most affectedThe rate of cell loss

Aetiology of ALS

~ cause unknown

~ 5-10% AD and in familial cases usually starts 10 years earlier than sporadic cases

~ Mutations in the Cu/Zn superoxide dismutase gene on Ch 21q accounts for 25% of all familial cases

~ Mutations of the neurofilament heavy

~ Tunisian ALS uncommon AR disease linked to 2q33-q35

Macroscopic examination reveals

the anterior spinal nerve roots to

be shrunken and grey in appearance

Pathology

~ Loss of motor neurones and astrocytosis in spinal cord, brain stemand motor cortex~ Motor neurones in the pons and medulla are often involved in the disease process

The motor unitNMJMNeuroneAxon Diseases ofmotor neuronesPeripheralneuropathiesDiseases of neuromuscular transmissionPrimary muscledisease|: myopathies

Peripheral neuropathy

~ Axonal or demyelinating

~ Neurotransmission most impaired in long nerves because nerve impulse confronted by a greater number of demyelinated segments

~ Therefore symptoms distal in distribution~ Affects legs and feet more than arm and hand

axonmyelinNode of ranvierSpinal cordPeripheral nerveM

Common causes of peripheral neuropathyDeficiency Vit B1 alcoholic Vit B6 in pts taking isoniazid Vit B12 in patients with PA and bowel diseaseToxic AlcoholDrugs isoniazid, vincristine3. Metabolic DM, CRF4. Post-infectious Guillain- Barre syndrome5. Collagen vascular RA, SLE, PA 6. Hereditary Charcot- Marie Tooth disease7. Idiopathic Perhaps up to 50% cases

Guillane-Barree syndrome

~ Rapid evolution over several days~ Life threatening weakness~ Affects nerve roots as well as peripheral nerves~ Occurs within 2 weeks of an infection usually campylobacter, cytomegalo, EBV~ Auto-immune response~ Weakness and sensory symptoms which worsen daily for 1-2 weeks~ Demyelinating polyneuropathy and polyradiculopathy

Myasthenia GravisUMNLMNNMJM~ Muscle weakness without wasting ~ Fatiguability~ Ocular and bulbar muscles commonly involved~ Responds well to treatment

Muscle disease UMNLMNNMJM~ Muscle weakness and wasting the distribution of which dependson the type of disease but strong tendency to involve proximal musclesi.e trunk and limb girdles

~ Various causes

Classification

Inherited Acquired

Muscular dystrophies EndocrinopathiesMyotonic dystrophyDrug inducedCongenital myopathisIdiopathic inflammatory myopathyMetabolic myopathiesMetabolic myopathyChannelopathiesMyasthenia Gravis/LEMS

Aim of the history and examination

To identify mode of inheritance

Accompanying features

Key pattern of muscle involvement

Functional status

Minimum tests to establish a diagnosis

Diagnostic Consultation

F/x tree

Personal and f/x h/x

Observation

Functional assessment

Pattern of muscle involvement:

Specific in familial muscular dystrophies e.g fascioscapuloperoneal

Proximal weakness in the limbs in acquired diseases of muscle such as polymyositis

Distribution of onset of muscle weakness

Typical proximal (limb-girdle) distribution of a myopathic disorder(DMD)

More distal (glove and stocking) distribution of a neurogenic disorder (SMA)

FSH own distribution

SP - own distribution

Investigations of patients with generalised muscle weakness and wastingTEST

MNDPeripheral neuropathyMuscle diseaseCPKNNEMGNeuropathicNeuropathicMyopathicHistologyDenervationDenervationPrimary muscle disease

CONCLUSIONS

UMN lesions involving the corticospinal tract

LMN lesions involving brain stem and spinal cord MND may present with UMN and LMN signs

Peripheral neuropathy may be axonal or demyelinating

Muscle disease may be inherited or acquired