Prepared by: Dr. Sarwer Jamal Bajalan M.B.Ch.B, F.I.B.M.S(Neurology) 2014

Essentials of diagnosis  Weakness  No sensory loss or sphincter disturbance  Progressive course.  No identifiable underlying cause other than genetic basis in familial cases.

General Considerations  Characterized clinically by weakness and variable wasting of affected muscles, without accompanying sensory changes.  MND generally commences between 30 and 60 years of age.  There is degeneration of: ○ Anterior horn cells in the spinal cord, the motor nucle of the lower cranial nerves, and ○ Corticospinal and corticobulbar pathways.  The disorder is usually sporadic, but familial cases may occur  Cigarette smoking may be one risk factor.

Classification Five varieties have been distinguished on clinical grounds.  A. Progressive Bulbar Palsy  B. Pseudobulbar Palsy  C. Progressive Spinal Muscular Atrophy  D. Primary Lateral Sclerosis  E. Amyotrophic Lateral Sclerosis (ALS) A mixed UMN and LMN deficit is found in the limbs.

 ALS (Prof Stephen Hawking( Infantile spinal muscular atropy SMA1

Symptoms and Signs  In Bulbar type ○ Dysphagia, dyspea, and dysarthria. ○ Drooping of the palate; a depressed gag reflex; pooling of saliva in the pharynx; a weak cough; and a wasted, fasciculating tongue.  In pseudobulbar palsy, the tongue is contracted and spastic and cannot be moved rapidly from side to side.  Weakness, stiffness, wasting & fasciculations (UMN &/or LMN)  No objective changes on sensory examination.  The sphincters are generally spared.  Cognitive changes or pseudobulbar affect may be present.  The disorder is progressive, and ALS is usually fatal within 3–5 years.  Death usually results from pulmonary infections.  Patients with bulbar involvement generally have the poorest prognosis,  Primary lateral sclerosis often have a longer survival.

Ix  EMG: chronic partial denervation, with abnormal spontaneous activity in the resting muscle and a reduction in the number of motor units under voluntary control.  Confident Diagnosis of ALS needs changes to be found in at least: o Three spinal regions (cervical, thoracic, lumbosacral) or o Two spinal regions and the bulbar musculature.  The serum creatine kinase may be slightly elevated.  Genitics:

 Monoclonal gammopathies.  Multifocal nmotor neuropathies with conduction block.  Hodgkin disease.  Infective anterior horn cell diseases (polio virus or West Nile virus infection). D Dx

Treatment  Riluzole, 50 mg orally twice daily, which reduces the presynaptic release of glutamate, may slow progression of amyotrophic lateral sclerosis. There is otherwise no specific treatment  Symptomatic and supportive measures may include: ○ Anticholinergic drugs (such as trihexyphenidyl, amitriptyline, or atropine). ○ Portable suction machine. ○ Physical therapy to prevent contractures. ○ Spasticity may be helped by baclofen or diazepam. ○ A semiliquid diet or nasogastric tube feeding

MYOPATHIC DISORDERS DISORDERS

Muscular Dystrophies Essentials of diagnosis ○ Muscle weakness, often in a characteristic distribution. ○ Age at onset and inheritance pattern depend on the specific dystrophy

General Considerations  These inherited myopathic disorders are characterized by progressive muscle weakness and wasting.  They are subdivided by mode of inheritance, age at onset, and clinical features.  In Duchenne Muscular Dystrophy: ○ Pseudohypertrophy of muscles frequently occurs at some stage; ○ Intellectual retardation is common; and there may be ○ Skeletal deformities, ○ Muscle contractures, and ○ Cardiac involvement. ○ X-linked recessive ○ Age at Onset 1-5 year ○ Pelvic, then shoulder girdle; later, limb and respiratory muscles are affected. ○ Rapid progression (death within about 15 years after onset).

Ix  The serum creatine kinase(CK) level is increased.  EMG & histopathology may help confirm that weakness is myopathic rather than neurogenic.  A genetic defect on the short arm of the X-chromosome has been identified in Duchenne dystrophy. The affected gene codes for the protein dystrophin, which is markedly reduced or absent from the muscle of patients with the disease.  Dystrophin levels are generally normal in the Becker variety, but the protein is qualitatively altered.

Facioscapulohumeral

 Gowers’ sign showing a patient using arms to climb up thelegs in attempting to get up from the floor

 Lordotic posturing

Managemennt  There is no specific treatment for the muscular dystrophies, but it is important to encourage patients to lead as normal lives as possible.  Prednisone (0.75 mg/kg orally daily) improves muscle strength and function in boys with Duchenne dystrophy, but side effects need to be monitored.  Prolonged bed rest must be avoided, as inactivity often leads to worsening of the underlying muscle disease.  Physical therapy and orthopedic procedures may help counteract deformities or contractures.

Myotonic Dystrophy(DM)  A slowly progressive, dominantly inherited disorder,  Usually manifests itself in the 3 rd or 4 th decade but occasionally appears early in childhood.  Myotonic dystrophy type 1 results from an expanded CTG repeat in a protein kinase gene on chromosome 19.  In Myotonic dystrophy type 2, the defect is a CCTG repeat expansion in the gene for zinc-finger protein-9 on chromosome 3.  EMG o Myotonic discharges o Myopathic changes

DM1

Clinical Features od MD1  Muscle stiffness is evidenced by the marked delay of relaxation after muscle contraction.  This can often be demonstrated clinically by delayed relaxation of the hand after sustained grip or by percussion of the belly of a muscle.  In addition, there is weakness and wasting of the facial, sternocleidomastoid, and distal limb muscles.  Associated clinical features include: ○ Ptosis ○ Cataracts, ○ Frontal baldness, ○ Testicular atrophy, ○ Diabetes mellitus, ○ Cardiac abnormalities, and ○ Intellectual changes.

Treatment  When myotonia is disabling, treatment with a sodium channel blocker—such as : ○ Phenytoin ○ Procainamide ○ Mexiletine  Neither the weakness nor the course of the disorder is influenced by treatment.

 INFLAMMATORY MYOPATHIES:  Inclusion Body Myositis  This disorder, of unknown cause, begins insidiously, usually after middle age, with progressive proximal weakness of first the lower and then the upper extremities, and affecting facial and pharyngeal muscles.  Weakness often begins in the quadriceps femoris in the lower limbs and the forearm flexors in the upper limbs.  Distal weakness is usually mild( small mm of the hands).  Serum CK levels may be normal or increased.  The diagnosis is confirmed by muscle biopsy.  Corticosteroid and immunosuppressive therapy is usually ineffective, but IVIG therapy is occasionally of mild benefit.  Polymyositis & Dermatomyositis -----

Myopathies Associated with Other Disorders  Muscle weakness may be caused by a range of metabolic, endocrine, toxic or inflammatory disorders.  Disorders affecting the muscles’ structural integrity can be distinguished by EMG from those caused by metabolic derangement.  In metabolic disorders, weakness is often acute and generalised, while a proximal myopathy predominantly affecting the pelvic girdle is a feature of some endocrine disorders. This may develop without other manifestations of hormonal disturbance.  A wide variety of drugs and toxins may cause myopathy

Causes of acquired proximal myopathy

PERIODIC PARALYSIS SYNDROMES (channelopathies)  Periodic paralysis may have a familial (dominant inheritance) basis.  Episodes of flaccid weakness or paralysis, sometimes in association with abnormalities of the plasma potassium level.  Strength is normal between attacks.  Hypokalemic periodic paralysis characterized by attacks that tend to occur on awakening, after exercise, or after a heavy meal and may last for several days. Patients should avoid excessive exertion.  Hyperkalemic periodic paralysis  Normokalemic periodic paralysis

Chanalopathies

Treatment of Hypokalemic PP  A low carbohydrate and low-salt diet may help prevent attacks, as may acetazolamide, 250–750 mg  An ongoing attack may be aborted by potassium chloride given orally or by intravenous drip, provided the ECG can be monitored and kidney function is satisfactory.  In young Asian men, it is commonly associated with hyperthyroidism.  Treatment of the endocrine disorder prevents recurrences.