Hereditary diseases of nervous system

1. Hereditary diseases of nervous system

2. Common syndromes • Status dysrhaphycus (skin and bone abnormalities) • The diseases begin in early childhood • The diseases have permanent progression(slowly progresses) • There are mental disorders in typical cases (psychiatric changes)

3. Diseases with involvement of nervous – muscle synapse: • Myasthenia • Myasthenic syndromes

4. Myasthenia gravis (MG) is caused by a defect of neuro-muscular transmission due to an antibody-mediated attack on nicotinic acetylcholine receptors (AchR) at neuro-muscular junctions. It is characterized by fluctuating weakness that is improved by inhibitors of cholinesterase.

5. Myasthenia gravis (MG) • Etiologyis unknown. How the autoimmune disorder starts is not known • In about 15% of patientsthere is an encapsulated benign tumor - thymoma. • There are few familial cases of the disease, but disproportionate frequency of some HLA haplotypes (B8, DR3, DQB1) in MG patients suggests that genetic predisposition may be important

6. Pathogenesis • Loss of receptors due to complement-mediated lysis of the membrane and to acceleration of normal degradative processes (internalization, endocytosis, lysosomal hydrolysis) with inadequate replacement by new synthesis • Loss of AChR and the erosion and simplification of the endplates • Abnormally sensitive to the competitive antagonist curare • Most AChR antibodies are directed against antigenic determinants other than the ACh binding site • Destruction of the receptors

7. Clinical features • According to the course of the disease: • Progressive • Stationary • Mysthenic episodes • Clinical forms: • Ophthalmic • Bulbar • Skeletal • General

8. Typical features: • Asymmetric lesion and dynamic symptoms (the signs increase in the evening) • Ophthalmoplegia is a very common symptom. • The other ones are: - Weakness of mimic muscles – especially oral muscles - Weakness of chewing muscles - Weakness of pharyngeal, laryngeal muscles and muscles of tongue, tongue function disorders - Breathing disturbances - Extremities function disturbances (especially proximal parts) - Neck muscles weakness – hanging of the head - Body muscles weakness that leads to duck – like gait • Sensory and pelvic disorders usually are not observed.

11. Provocation tests for disease revealing • The patient is asked to look upwards or inside during 30 seconds in order to cause ptosis • He is asked to read text aloud in order to cause dysarthria • The patient is asked to make 100 chewing movements in order to reveal the weakness of these muscles • Proserine test. Proserine is introduced in dose 1.5 – 2 ml s/c. In 20–40 min all the signs of myasthenia disappear. In 2–3 hours all the symptoms appear again

15. Diagnosis • EMG – myasthenic reaction. Test is positive in 85% of patients with skeletal form. • Muscle biopsy – muscle atrophy and signs of degeneration. • CT reveals timoma signs. In 90% of all patients antibodies to ACHR are found

18. Differential diagnosis • Botulism • Neurasthenia • LAS • Polineuropathy • Muscles dystrophy • Inflammatory myopathy • MS • Stroke in v/b region • Brain stem tumor

19. Treatment • Anticholinestherase medicines: - Caliminum – 30 mg 3 times per day - Proserinum – 0.5 – 1.5 mg s/c • K drugs 3 – 4 g per day • Corticoids – we start from 15–20 mg a day, than increase gradually on 5 mg every 3 day • Anabolics – Retabolil 50 mg once every 3 days, 5 – 6 injections • Immune suppressors – Asatioprinum in dose 50 – 150 – 200 mg per day • Plasmapheresis - at acute and progressive form • Radiation therapy of thymus • Methabolic drugs

20. Myasthenic crisis: • Plasmapheresis • Ig i/v (2 g per kg 2 – 5 days) • Corticoids (1000 mg prednisonum) • Proserinum 1 – 2 ml i/v • SLV, oxygen • Halloperidolum at excitation

21. Cholinergic crisis • There fasciculations, seizures, bradycardia, salivation, hyperhydrosis and abdominal pain. • Treatment – Atropinum 1 ml 0.1 % s/c or i/v.

22. Diseases with involvement of pyramidal system: • Hereditary Spastic paraplegia of Shtrumpel • Family spastic paralysis with amyotrophy, oligophrenia, retina degeneration (described by Kellin) • Family spastic paralysis with ichthyosis and oligophrenia

23. Spastic paraplegia of Shtrumpel • This disease is the result of pyramidal tracts and cerebellar connections degeneration. • Transmission:genetically recessive in most cases but in some families it show dominant inheritance

24. Clinical features • The first signs are observed at the age of 10–15 • Lower spastic paraplegia with increased muscle tonus, high stretch reflexes, pathological reflexes • Lesion of lower extremities is symmetrical • Sometimes motor disorders can be developed in upper extremities. • In some cases pseudobulbar symptoms are joined • The typical signs of the disease: • The dominance of spastic tonus over motor disorders • Well preserved abdominal reflexes • The absence of pelvic disorders

27. Diseases with involvement of extrapyramidal system: • Parkinson disease • Hepato – cerebral degeneration • Dystonia • Huntington disease • Double athetosis • Myoclonus – epilepsy • Tourette syndrome

28. Parkinsonism • is a chronic progressive neurodegenerative syndrome that is characterized by motor disorders as a result of extrapyramidal system involvement • Parkinson disease (PD)– is a chronic progressive degenerative disease of CNS that manifest as voluntary movements disorders.

29. Etiology Primary Parkinsonism: • Parkinson disease • Younger parkinsonism Secondary Parkinsonism: • Cerebral vessels sclerosis • Long lasting usage of neuroleptics, reserpinum medicines • Toxins • Viral infections • Metabolic encephalopathy • Severe cranial trauma • Tumors, hydrocephalus Parkinsonism as syndrome of other hereditary diseases

30. Clinical features • Hypokinesia • Rigidity • Resting trembling • Loss of postural reflexes

32. The main clinical forms • Trembling • Rigidity • Mixed Severity stages: • I – loss of activity, but that doesn’t influence on professional activity and working ability • II – moderate loss of professional activity • III – the patients need someone to look after him

33. Drug Therapy • Carbidopa is listed as the peripheral dopa decarboxylase inhibitor, but in many countries benserazide is also available • Amantadine, selegiline, and the anticholinergics are reviewed in following sections • Antidepressants are needed for treating depression

34. Triatment Basic therapy: • Nootrops • Cinnarizini • Cavintoni • Adequate dose of antiparkinsonic drugs Surgery therapy: • Stereotaxis operations • Deep electrostimulation of brain structures • Method for case of no effective of drug therapy

37. Hepatocerebral dystrophy (HCD) (Wilson – Konovalov disease) • This disease is connected with disorders of ceruloplasminum metabolism. Ceruloplasminum is a blood protein responsible for Cu transport. It is produced in liver. Pathologically there is accommodation of Cu in subcortical ganglions (especially n. Lenticularis), brain cortex, cerebellum, liver, spleen, iris. • Transmission:genetically autosomal – recessive. And it is observed in male and female with the same frequency.

38. Clinical signs • The first signs of the disease are observed in early childhood • neck stiffness • different hyperkinesis • psychiatric changes • Sometimes seizures can be observed • liver enlargement. • Kaizer – Fleishner ring in the iris

39. Konovalov classification types of the disease: • Rigid – arythmokinetic • Trembling – rigid • Trembling • Extrapyramidal – cortical Sometimes the disease manifests only as liver insufficiency and neurological signs are joined later.

40. Diagnosis • Family history • The typical signs of the disease – Kaizer – Fleishner ring • lesion of liver • low quantity of ceruloplasminum in the blood • increased quantity of Cu in urine

41. Differential diagnosis • Huntington disease • MS • Chronic stage of epidemic encephalitis

42. Torsion dystonia • The pathology of the disease includes degenerative changes of subcortical ganglions, subthalamic nuclei and n. Dentatus of cerebellum as a result of neuromediators production and metabolism disturbances. • Hyperkinetic form of the disease has autosomal – dominant type of inheritance. Rigid form of the disease is characterized by autosomal – recessive type of inheritance.

43. Clinical features • The disease begins in early childhood • permanent progression • hyperkinesis that increases with every movement • hyperkinesis may have a look of tonic body and extremities muscle straining • Spastic torticollis is one of the earliest symptoms of the disease. • There are no mental disorders in typical cases. • There are generalized form of the disease and local ones, such as spastic torticollis and chirospasm.

44. Diagnosis • Family history and the evaluation of pathological process dynamics are necessary for the diagnosis putting. Differential diagnosis • Atypical form of Economo encephalitis

48. Huntington disease • It is a progressive hereditary disorder that usually appears in adult life. It is the result of systemic degeneration of extrapyramidal structures and brain cortex. • It has autosomal – dominant type of inheritance.

49. Clinical features • Appears in adult life and it is very rare in children • Male and female can suffer from this disease • Choreic movements • Extrapyramidal rigidity • Slowly progressive dementia

50. Diagnosis • Clinical and genetic analysis • CT and MRI of brain (atrophic changes of brain hemispheres) • EEG • DNA – analysis Differential diagnosis • Chorea • Hepato – cerebral degeneration