Neuromuscular disorders

FM Brett MD., FRCPath

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

1. Distinguish between UMN and LMN lesions

2. Understand the differences between a neuropathy and a myopathy

3. Know how MND presents

3. Know the common causes of a peripheral neuropathy

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

Sites of lesions producing neuromuscular pathology

Either 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 pathology

Commonest 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 unit

NMJ

M

Neurone Axon

Diseases ofDiseases ofmotor neuronesmotor neurones

Peripheralneuropathies

Diseases of neuromuscular transmission

Primary 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 :a) upper or lower motor neurones are predominantly involveda) Which muscles are most affectedb) The 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 unit

NMJ

M

Neurone Axon

Diseases ofmotor neurones

PeripheralPeripheralneuropathiesneuropathies

Diseases of neuromuscular transmission

Primary 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

axonmyelin

Node of ranvier

Spinal cord

Peripheral nerveM

Common causes of peripheral neuropathyCommon causes of peripheral neuropathy1. Deficiency – Vit B1 alcoholic

Vit B6 in pts taking isoniazid Vit B12 in patients with PA and bowel disease

2. Toxic AlcoholDrugs – isoniazid, vincristine

3. Metabolic – DM, CRF

4. Post-infectious – Guillain- Barre syndrome

5. Collagen vascular – RA, SLE, PA

6. Hereditary – Charcot- Marie – Tooth disease

7. 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 Gravis

UMN LMNNMJ

M

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

Muscle disease

UMN LMNNMJ

M

~ 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 Endocrinopathies• Myotonic dystrophy Drug induced• Congenital myopathis Idiopathic

inflammatory myopathy

• Metabolic myopathies Metabolic myopathy

• Channelopathies Myasthenia 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

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

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

C. FSH –own distribution

D. SP - own distribution

Investigations of patients with generalised muscle weakness and wasting

MND Peripheral neuropathy

Muscle disease

CPK N N

EMG Neuropathic Neuropathic Myopathic

Histology Denervation Denervation Primary muscle disease

TEST

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