DEGENERATIVE MOTOR NEURON DISEASES (MND)

1. Prepared by: Dr. Sarwer Jamal Bajalan M.B.Ch.B, F.I.B.M.S(Neurology) 2014 DEGENERATIVE MOTOR NEURON DISEASES(MND)

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

3. 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 • Corticospinaland corticobulbar pathways. • The disorder is usually sporadic, but familial cases may occur • Cigarette smoking may be one risk factor.

4. 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.

5. ALS (Prof Stephen Hawking( Infantile spinal muscular atropy SMA1

6. 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.

7. 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: • Three spinal regions (cervical, thoracic, lumbosacral) or • Two spinal regions and the bulbar musculature. • The serum creatine kinase may be slightly elevated. • Genitics:

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

9. 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

10. MYOPATHIC DISORDERSDISORDERS

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

12. 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. • InDuchenne Muscular Dystrophy: • Pseudohypertrophyof 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).

13. Ix • The serum creatinekinase(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. • Dystrophinlevels are generally normal in the Beckervariety, but the protein is qualitatively altered.

15. Facioscapulohumeral

16. Gowers’ sign showing a patient using arms to climb up thelegsin attempting to get up from the floor

17. Lordotic posturing

18. 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.

19. MyotonicDystrophy(DM) • A slowly progressive, dominantly inherited disorder, • Usually manifests itself in the 3rd or 4th 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 • Myotonic discharges • Myopathic changes

20. DM1

21. 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.

22. 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.

23. 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 -----

24. 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

25. Causes of acquired proximal myopathy

26. 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 • Normokalemicperiodic paralysis

27. Chanalopathies

28. 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.