MOTOR NEURONE DISEASES

AND OTHER MOTOR SYSTEM DISEASE

MND
UNKNOWN CAUSE

TRAUMA, EXCESSIVE EXERCISE, LEAD POISONING AND MERCURY POISONING, OCCULT NEOPLASIA AND VIRUSES HAVE ALL BEEN SPECULATIVELY LINKED WITH THE AETIOLOGY OF MND
AFFECTING ALL RACES YOUNG ADULT MAY BE AFFECTED, BUT MOST PATIENTS ARE 60 YEARS OR OLDER MALE : FEMALE = 1.5 : 1 THE AVERAGE DURATION OF SURVIVAL IS 3-4 YEARS

CLINICAL PRESENTATION
Difficulty performing specific task:
Turning a key, floppiness of a foot, a weak grip or wasting of some of the muscles of one hand

History of cramps, quivering of muscles, or heaviness, aching and stiffness of legs

DIAGNOSIS
IS SUGGESTED BY THE PRESENCE OF FASCICULATION OR WASTING WITH ENHANCED REFLEXES AND WITHOUT SENSORY SIGNS

CHARACTERIZED BY
Progressive degeneration of anterior horn cells corticospinal fibers, and motor nuclei in the medulla

Various levels of the nervous system: bulbar, cervical, and lumbar may be involved All level of the motor system are involved

The most common presentation:

AMYOTROPIC LATERAL SCLEROSIS
wasting in the upper limbs and spasticity in the lower limbs PROGRESSIVE MUSCULAR ATROPHY
SHOW PREDOMINANTLY LOWER MOTOR NEURONE CHANGES

PROGRESSIVE LATERAL SCLEROSIS

PYRAMIDAL TRACT DEGENERATION BEFORE MUSCULAR WASTING

PSEUDOBULBAR/BULBAR ; PROGRESSIVE BULBAR PALSY

BRAIN STEM INVOLVEMENT, PREDOMINANTLY SPASTIC: (PSEUDOBULBAR) PREDOMINANTLY FLACCID (BULBAR)

AMYOTROPIC LATERAL SCLEROSIS

the most common form of motor neuron disease

Atrophy, weakness and fasciculation in their limb muscle (indicating a lower motor neuron lesion) Hyperactive reflexes Extensor plantar responses No sensory signs It is this combination of upper and lower motor neuron signs in all limbs that hallmark of ALS

FASCICULATION OVER AN AREA MAY BE SEEN WITH

CERVICAL SPONDYLOSIS SYRINGOMYELIA ACUTE STAGE OF POLIOMYELITIS NEURALGIC AMYOTROPHY THYROTOXIC MYOPATHY

BULBAR SYMPTOMS:
SELECTIVE SWALLOWING DIFFICULTIES WEAKNESS AND NASAL SPEECH FASCICULATION AND ATROPHY THE TONGUE

DIAGNOSIS
CLINICAL FEATURES May leave a little doubt CONFIRMED BY ELECTROMYOGRAPHY If indicated muscle biopsy MYELOGRAM ?
(High cervical lesion)

CFS EXAMINATION
(Neurosyphilis)

PROGNOSIS
IF THE PATIENS ASKS IF THE CONDITION IS POTENTIALLY LETHAL, THE ANSWER MUST IN ALMOST EVERY CASE BE YES. Most patients remain mentally alert and are able to make rational decisions to cope with their increasing disability

PARALYTIC POLIO
Persons infected with polio: > 95% asymptomatic viremia and spontaneous clearing Flulike prodrome severe generalized myalgias with focal, often asymmetric fasciculation; followed by weakness that often is severe the legs often are most affected although any muscle or region can be involved including diaphragm and bulbar muscles

Recovery typically is incomplete, atrophy and asymmetric weakness is often permanent

POST-POLIO SYNDROME
Occasionally a syndrome develops in former paralytic polio victims several years following the initial attack Patients typically complain a diffuse myalgias and recurrence of weakness of muscles that were affected in the initial attack

The lag between the initial attack and development of so-called postpolio syndrome often is measured in decades

PARALYTIC POLIO POST-POLIO SYNDROME

MANAGEMENT ?

MYASTHENIA
An acquired autoimmune disorder causing skeletal muscle fatigue and weakness Autoantibodies against the acetylcholine receptor produce weakness that can affect the entire body or only eye movement Can begin at any time, from early childhood to extreme old age The cause of the autoantibodies is not known. The thymus is implicated in the inception and generation of the autoantibodies

Auto antibodies bind to the acetylcholine receptor and cause increased receptor degradation. The combination of the binding and the turnover effects results loss of receptor so that an action potential in the motor neuron does not always result in an action potential in the muscle fiber

Thymoma as present in some patients with myasthenia

Onset in non-thymoma cases: Peak incidence at 10-30 yeas of age, again at 60-70 yeas of age Myasthenia associated with thymoma: Peak incidence at 40-50 years of age Under 40 predominantly affects women

MYASTHENIA WHICH HAS A DIFFERENT MECHANISM

Neonatal myasthenia
Transient illness, lasting less than 1 month, 1 in 8 babies of myasthenic mothers

Juvenile myasthenia
Myasthenia in the younger age group, generally similar to those of myasthenia in young adults

Penicillamine-induced myasthenia
Usually resolves over several month after drug withdrawal

Lambert-Eaton myasthenic syndrome

A presynaptic disorder characterized by impaired release of Ach from the nerve terminal. 60% cases is associated with small cell lung carcinoma

Congenital myasthenia Familial myasthenia

SYMPTOMS AND SIGNS

weakness of skeletal muscle is characteristically increased by exercise, but is not associated with muscle pain (in contrast to physiological fatigue) emotional stress, pregnancy and infection can also cause an exacerbation of symptoms

Ocular muscles Limb weakness Bulbar muscle weakness Respiratory muscle involvement

CLINICAL CLASSIFICATION
Main groups of acquired myasthenia gravis Group I: ocular myasthenia gravis (symptoms may remain persistently confined to the ocular muscles, particularly when 2 years have elapsed since the onset

Group IIA, B: mild or moderately severe generalized myasthenia gravis

Group III: acute severe (fulminating) myasthenia gravis with respiratory muscle involvement Group IV: late (chronic) severe disease

INVESTIGATION
Anti-ACHR antibody Antistriated muacle antibody
Edrophonium chloride test (modification?) Electromyographic techniques Thymoma

MODES OF THERAPY
Anticholinesterase therapy:
Pyridostigmine, 30-120 mg orally Neostigmine bromide, 15-30 mg orally every 3 hours except at night Higher dose than those given above are seldom indicated and greatly increase the risk of cholinergic crisis. Side-effects are caused by para-sympatithetic stimulation and include: - pupillary constriction
colic diarrhoea Increased salivation Increased sweating Increased lacrimation Increased bronchial secretions

MODES OF THERAPY
Corticosteroids: Prednisolone - suitable - once daily on alternate days to avoid side-effects - initial dose 10 mg, increased slowly out patients: 5-10mg / week in patients: 5-10 mg / dose to avoid the exacerbation of symptoms that can occur when the drug is started at a high dose - Maximal dose: 1-1.5 mg / kg body weight - (or symptoms are controlled)

Thymectomy Intravenous immunoglobuln Plasma exchange

Improvement is expected although most patients are maintained on a low-dose corticosteroid after their initial tapering Crisis may develop requiring hospitalization, administration or IVIG or PE, and/or transient increases in corticosteroid

MYASTHENIC CRISIS
occurs with inadequate treatment and can be precipitated by infection.
Treatment consist of:

Control of the airway and assisted ventilation Anticholinesterase medication Immunosuppressive drug therapy and/or plasma exchange

CHOLINERGIC CRISIS
caused by excess anticholinesterase medication Treatment consist of: Control of the airway and assisted ventilation Temporary withdrawal of anticholinesterase drugs, with later reintroduction at a reduced dose regiment Immunosuppressive drug therapy and/or plasma exchange Atropine, if not already being given