Hereditary Hereditary diseases of diseases of

nervous nervous systemsystem

Common syndromesCommon syndromes Status dysrhaphycus (skin and Status dysrhaphycus (skin and

bone abnormalitiesbone abnormalities)) The diseaseThe diseasess begin in early begin in early

childhood childhood The diseases have The diseases have permanent permanent

progressionprogression ((slowly progressesslowly progresses)) There are mental disorders in There are mental disorders in

typical casestypical cases ( (psychiatric psychiatric changeschanges))

Diseases withDiseases with involvement involvement of nervous – muscle of nervous – muscle synapse:synapse:

– MyastheniaMyasthenia– Myasthenic Myasthenic

syndromessyndromes

Myasthenia gravis Myasthenia gravis (MG)(MG)

is caused by a defect of neuro-is caused by a defect of neuro-muscular transmission due to an muscular transmission due to an antibody-mediated attack on antibody-mediated attack on nicotinic acetylcholine receptors nicotinic acetylcholine receptors (AchR) at neuro-muscular (AchR) at neuro-muscular junctions. junctions.

It is characterized by fluctuating It is characterized by fluctuating weakness that is improved by weakness that is improved by inhibitors of cholinesterase.inhibitors of cholinesterase.

Myasthenia gravis Myasthenia gravis (MG)(MG)

EtiologyEtiology is unknown. is unknown. How the How the autoimmune disorder starts is not known autoimmune disorder starts is not known

IIn about 15% of patientsn about 15% of patients there is an there is an encapsulated benign tumorencapsulated benign tumor - - thymoma. thymoma.

There are few familial cases of the There are few familial cases of the disease, but disproportionate frequency disease, but disproportionate frequency of some HLA haplotypes (B8, DR3, DQB1) of some HLA haplotypes (B8, DR3, DQB1) in MG patients suggests that genetic in MG patients suggests that genetic predisposition may be importantpredisposition may be important

PathogenesisPathogenesis Loss of receptors due to complement-Loss of receptors due to complement-

mediated lysis of the membrane and to mediated lysis of the membrane and to acceleration of normal degradative acceleration of normal degradative processes (internalization, endocytosis, processes (internalization, endocytosis, lysosomal hydrolysis) with inadequate lysosomal hydrolysis) with inadequate replacement by new synthesis replacement by new synthesis

Loss of AChR and the erosion and Loss of AChR and the erosion and simplification of the endplatessimplification of the endplates

Abnormally sensitive to the competitive Abnormally sensitive to the competitive antagonist curareantagonist curare

Most AChR antibodies are directed against Most AChR antibodies are directed against antigenic determinants other than the ACh antigenic determinants other than the ACh binding sitebinding site

Destruction of the receptorsDestruction of the receptors

Clinical featuresClinical features According to the course of the According to the course of the

diseasedisease::– ProgressiveProgressive– StationaryStationary– Mysthenic episodesMysthenic episodes

Clinical forms:Clinical forms:– OphthalmicOphthalmic– BulbarBulbar– SkeletalSkeletal– GeneralGeneral

Typical features:Typical features: Asymmetric lesion and dynamic symptoms Asymmetric lesion and dynamic symptoms

(the signs increase in the evening)(the signs increase in the evening) Ophthalmoplegia is a very common symptom. Ophthalmoplegia is a very common symptom. The other ones are:The other ones are:- - Weakness of mimic muscles – especially oral musclesWeakness of mimic muscles – especially oral muscles- Weakness of chewing muscles- Weakness of chewing muscles- Weakness of pharyngeal, laryngeal muscles and - Weakness of pharyngeal, laryngeal muscles and

muscles of tongue, tongue function disordersmuscles of tongue, tongue function disorders- Breathing disturbances- Breathing disturbances- Extremities function disturbances (especially proximal - Extremities function disturbances (especially proximal

parts)parts)- Neck muscles weakness – hanging of the head- Neck muscles weakness – hanging of the head- Body muscles weakness that leads to duck – like gait- Body muscles weakness that leads to duck – like gait Sensory and pelvic disorders usually are not Sensory and pelvic disorders usually are not

observed.observed.

Provocation tProvocation tests for disease ests for disease revealingrevealing

The patient is asked to look upwards or The patient is asked to look upwards or inside during 30 seconds in order to inside during 30 seconds in order to cause ptosiscause ptosis

HHe is asked to read text aloud in order to e is asked to read text aloud in order to cause dysarthriacause dysarthria

The patient is asked to make 100 The patient is asked to make 100 chewing movements in order to reveal chewing movements in order to reveal the weakness of these musclesthe weakness of these muscles

Proserine test. Proserine test. Proserine is introduced Proserine is introduced in dose 1.5 – in dose 1.5 – 22 ml s/c. In 20–40 min all ml s/c. In 20–40 min all the signs of myasthenia disappear. In 2–the signs of myasthenia disappear. In 2–3 hours all the symptoms appear again 3 hours all the symptoms appear again

DiagnosisDiagnosis EMG – EMG – myasthenic reaction. myasthenic reaction.

Test is positive in 85% of Test is positive in 85% of patients with skeletal form.patients with skeletal form.

Muscle biopsy – Muscle biopsy – muscle muscle atrophy and signs of atrophy and signs of degeneration.degeneration.

CT CT reveals timoma signs. In reveals timoma signs. In 90% of all patients antibodies to 90% of all patients antibodies to ACHR are foundACHR are found

Differential diagnosisDifferential diagnosis BotulismBotulism NeurastheniaNeurasthenia LASLAS PolineuropathyPolineuropathy Muscles dystrophyMuscles dystrophy Inflammatory myopathyInflammatory myopathy MSMS Stroke in v/b regionStroke in v/b region Brain stem tumorBrain stem tumor

TreatmentTreatment Anticholinestherase medicinesAnticholinestherase medicines::- - Caliminum – 30 mg 3 times per dayCaliminum – 30 mg 3 times per day- - Proserinum – 0.5 – 1.5 mg s/cProserinum – 0.5 – 1.5 mg s/c K drugs K drugs 3 – 4 g per day3 – 4 g per day Corticoids – Corticoids – we start from 15–20 mg we start from 15–20 mg aa day, day,

than increase gradually on 5 mg every 3 than increase gradually on 5 mg every 3 ddayay Anabolics –Anabolics – Retabolil 50 mg once every 3 Retabolil 50 mg once every 3

days, 5 – 6 injectionsdays, 5 – 6 injections Immune suppressors –Immune suppressors – Asatioprinum in Asatioprinum in

dose 50 – 150 – 200 mg per daydose 50 – 150 – 200 mg per day Plasmapheresis -Plasmapheresis - at acute and progressive at acute and progressive

formform Radiation therapy of thymusRadiation therapy of thymus Methabolic drugsMethabolic drugs

MMyastheniyasthenicc crisis crisis::

– PlasmapheresisPlasmapheresis– Ig i/v (2 g per kg 2 – 5 days)Ig i/v (2 g per kg 2 – 5 days)– Corticoids (100Corticoids (10000 mg mg

prednisonum)prednisonum)– Proserinum 1 – 2 ml i/v Proserinum 1 – 2 ml i/v – SLV, oxygenSLV, oxygen– Halloperidolum at excitationHalloperidolum at excitation

Cholinergic crisisCholinergic crisis

There fasciculations, There fasciculations, seizures, bradycardia, seizures, bradycardia, salivation, hyperhydrosis salivation, hyperhydrosis and abdominal pain.and abdominal pain.

Treatment – Atropinum 1 Treatment – Atropinum 1 ml 0.1 % s/c or i/v.ml 0.1 % s/c or i/v.

Diseases withDiseases with involvement of involvement of

pyramidal systempyramidal system:: Hereditary Spastic paraplegia Hereditary Spastic paraplegia

of Shtrumpelof Shtrumpel Family spastic paralysis with Family spastic paralysis with

amyotrophy, oligophrenia, amyotrophy, oligophrenia, retina degeneration (described retina degeneration (described by Kellin)by Kellin)

Family spastic paralysis with Family spastic paralysis with ichthyosis and oligophreniaichthyosis and oligophrenia

Spastic paraplegia of Spastic paraplegia of ShtrumpelShtrumpel

This disease is the result of This disease is the result of pyramidal tracts and pyramidal tracts and cerebellar connections cerebellar connections degeneration.degeneration.

Transmission:Transmission: genetically genetically recessive in most cases recessive in most cases but but in some families it show in some families it show dominant inheritancedominant inheritance

Clinical featuresClinical features The first signs are observed at the age of 10–15The first signs are observed at the age of 10–15 Lower spastic paraplegia with increased muscle Lower spastic paraplegia with increased muscle

tonus, high stretch reflexes, pathological tonus, high stretch reflexes, pathological reflexesreflexes

Lesion of lower extremities is symmetricalLesion of lower extremities is symmetrical Sometimes motor disorders can be developed Sometimes motor disorders can be developed

in upper extremities. in upper extremities. In some cases pseudobulbar symptoms are In some cases pseudobulbar symptoms are

joinedjoined The typical signs of the disease:The typical signs of the disease: The dominance of spastic tonus over motor The dominance of spastic tonus over motor

disordersdisorders Well preserved abdominal reflexesWell preserved abdominal reflexes The absence of pelvic disordersThe absence of pelvic disorders

Diseases withDiseases with involvement of involvement of extrapyramidal systemextrapyramidal system::

– Parkinson diseaseParkinson disease– Hepato – cerebral degenerationHepato – cerebral degeneration– DystoniaDystonia– Huntington diseaseHuntington disease– Double athetosis Double athetosis – Myoclonus – epilepsyMyoclonus – epilepsy– Tourette syndromeTourette syndrome

ParkinsonismParkinsonism is a chronic progressive is a chronic progressive

neurodegenerative syndrome that is neurodegenerative syndrome that is characterized by motor disorders as characterized by motor disorders as a result of extrapyramidal system a result of extrapyramidal system involvementinvolvement

Parkinson disease (PD)Parkinson disease (PD) – – is a is a chronic progressive degenerative chronic progressive degenerative disease of CNS that manifest as disease of CNS that manifest as voluntary movements disorders.voluntary movements disorders.

EtiologyEtiologyPrimary Parkinsonism:Primary Parkinsonism: Parkinson diseaseParkinson disease Younger parkinsonismYounger parkinsonismSecondary Parkinsonism:Secondary Parkinsonism: Cerebral vessels sclerosisCerebral vessels sclerosis Long lasting usage of neuroleptics, Long lasting usage of neuroleptics,

reserpinum medicinesreserpinum medicines ToxinsToxins Viral infectionsViral infections Metabolic encephalopathyMetabolic encephalopathy Severe cranial traumaSevere cranial trauma Tumors, hydrocephalusTumors, hydrocephalusParkinsonism as syndrome of other Parkinsonism as syndrome of other

hereditary diseaseshereditary diseases

Clinical featuresClinical features

HypokinesiaHypokinesia RigidityRigidity Resting tremblingResting trembling Loss of postural reflexesLoss of postural reflexes

The main clinical formsThe main clinical forms TremblingTrembling RigidityRigidity MixedMixed

Severity stages:Severity stages: I – loss of activity, but that doesn’t I – loss of activity, but that doesn’t

influence on professional activity and influence on professional activity and working abilityworking ability

II – moderate loss of professional II – moderate loss of professional activityactivity

III – the patients need someone to III – the patients need someone to look after himlook after him

Drug TherapyDrug Therapy Carbidopa Carbidopa is listed as the is listed as the

peripheral dopa decarboxylase peripheral dopa decarboxylase inhibitor, but in many countries inhibitor, but in many countries benserazide benserazide is also availableis also available

Amantadine, selegiline, Amantadine, selegiline, and the and the anticholinergics are reviewed in anticholinergics are reviewed in following sectionsfollowing sections

Antidepressants are needed for Antidepressants are needed for treating depressiontreating depression

TriatmentTriatmentBasic therapyBasic therapy: : NootropsNootrops CinnariziniCinnarizini CavintoniCavintoni Adequate dose of antiparkinsonic drugsAdequate dose of antiparkinsonic drugsSurgery therapySurgery therapy:: Stereotaxis operationsStereotaxis operations Deep electrostimulation of brain Deep electrostimulation of brain

structuresstructures Method for case of no effective of drug Method for case of no effective of drug

therapytherapy

Hepatocerebral dystrophy Hepatocerebral dystrophy (HCD) (Wilson – Konovalov (HCD) (Wilson – Konovalov disease)disease)

This disease is connected with disorders of This disease is connected with disorders of ceruloplasminum metabolism. ceruloplasminum metabolism. Ceruloplasminum is a blood protein Ceruloplasminum is a blood protein responsible for Cu transport. It is produced in responsible for Cu transport. It is produced in liver. Pathologically there is accommodation of liver. Pathologically there is accommodation of Cu in subcortical ganglions (especially n. Cu in subcortical ganglions (especially n. Lenticularis), brain cortex, cerebellum, liver, Lenticularis), brain cortex, cerebellum, liver, spleen, iris. spleen, iris.

Transmission:Transmission: genetically autosomal – genetically autosomal – recessive. And it is observed in male and recessive. And it is observed in male and female with the same frequency.female with the same frequency.

Clinical signsClinical signs The The first signs of the diseasefirst signs of the disease

are observed in early childhood are observed in early childhood neck stiffnessneck stiffness different hyperkinesis different hyperkinesis psychiatric changespsychiatric changes Sometimes seizures can be Sometimes seizures can be

observedobserved liver enlargement. liver enlargement. Kaizer – Fleishner ring in the irisKaizer – Fleishner ring in the iris

Konovalov classification Konovalov classification types of the diseasetypes of the disease::

Rigid – arythmokineticRigid – arythmokinetic Trembling – rigidTrembling – rigid TremblingTrembling Extrapyramidal – corticalExtrapyramidal – cortical

Sometimes the disease manifests Sometimes the disease manifests only as liver insufficiency and only as liver insufficiency and neurological signs are joined later.neurological signs are joined later.

DiagnosisDiagnosis Family historyFamily history The typical signs of the disease The typical signs of the disease

– Kaizer – Fleishner ring – Kaizer – Fleishner ring lesion of liver lesion of liver low quantity of low quantity of

ceruloplasminum in the bloodceruloplasminum in the blood increased quantity of Cu in increased quantity of Cu in

urineurine

Differential diagnosisDifferential diagnosis

Huntington diseaseHuntington diseaseMSMSChronic stage of Chronic stage of epidemic encephalitisepidemic encephalitis

Torsion dystoniaTorsion dystonia The pathology of the disease includes The pathology of the disease includes

degenerative changes of subcortical degenerative changes of subcortical ganglions, subthalamic nuclei and n. ganglions, subthalamic nuclei and n. Dentatus of cerebellum as a result of Dentatus of cerebellum as a result of neuromediators production and neuromediators production and metabolism disturbances. metabolism disturbances.

Hyperkinetic formHyperkinetic form of the disease has of the disease has autosomal – dominant type of inheritance. autosomal – dominant type of inheritance. Rigid formRigid form of the disease is characterized of the disease is characterized by autosomal – recessive type of by autosomal – recessive type of inheritance.inheritance.

Clinical featuresClinical features The disease begins in early childhood The disease begins in early childhood permanent progressionpermanent progression hyperkinesis that increases with every hyperkinesis that increases with every

movement movement hyperkinesis may have a look of tonic body hyperkinesis may have a look of tonic body

and extremities muscle strainingand extremities muscle straining Spastic torticollis is one of the earliest Spastic torticollis is one of the earliest

symptoms of the disease. symptoms of the disease. There are no mental disorders in typical There are no mental disorders in typical

cases. cases. There are generalized form of the disease and There are generalized form of the disease and

local ones, such as spastic torticollis and local ones, such as spastic torticollis and chirospasm.chirospasm.

DiagnosisDiagnosis

Family history and the evaluation Family history and the evaluation of pathological process dynamics of pathological process dynamics are necessary for the diagnosis are necessary for the diagnosis putting.putting.

Differential diagnosisDifferential diagnosis Atypical form of Economo Atypical form of Economo

encephalitisencephalitis

Huntington diseaseHuntington disease

It is a progressive hereditary It is a progressive hereditary disorder that usually appears in disorder that usually appears in adult life. It is the result of adult life. It is the result of systemic degeneration of systemic degeneration of extrapyramidal structures and extrapyramidal structures and brain cortex. brain cortex.

It has autosomal – dominant type It has autosomal – dominant type of inheritance.of inheritance.

Clinical featuresClinical features AAppears in adult life and it is very ppears in adult life and it is very

rare in childrenrare in children Male and female can suffer from Male and female can suffer from

this diseasethis disease Choreic movementsChoreic movements Extrapyramidal rigidityExtrapyramidal rigidity Slowly progressive dementiaSlowly progressive dementia

DiagnosisDiagnosis

Clinical and genetic analysisClinical and genetic analysis CT and MRI of brain (atrophic changes CT and MRI of brain (atrophic changes

of brain hemispheres)of brain hemispheres) EEGEEG DNA – analysisDNA – analysis

Differential diagnosisDifferential diagnosis ChoreaChorea Hepato – cerebral degenerationHepato – cerebral degeneration

Hereditary ataxiaHereditary ataxia

– Spinal ataxia of Spinal ataxia of Fridreich Fridreich

– Hereditary cerebellar Hereditary cerebellar ataxia of Pier – Maryataxia of Pier – Mary

– Olivo – ponto – Olivo – ponto – cerebellar degenerationcerebellar degeneration

Spinal Fridreich ataxiaSpinal Fridreich ataxiaThe disease is characterized The disease is characterized

by spinal cord degeneration by spinal cord degeneration and degenerative – and degenerative – dystrophic changes in dystrophic changes in posterior and lateral columns.posterior and lateral columns.

TTransmission:ransmission: by autosomal – by autosomal – recessive type of inheritance.recessive type of inheritance.

Clinical features Clinical features :: The disease begins at the age of 10 – 12 The disease begins at the age of 10 – 12 slowly progressesslowly progresses sensitive – cerebellar ataxia, nystagmus sensitive – cerebellar ataxia, nystagmus muscle hypotonia and areflexiamuscle hypotonia and areflexia gait disordersgait disorders At the beginning of the disease there is deep At the beginning of the disease there is deep

sensation disorders according to the conductive sensation disorders according to the conductive type on lower extremities.type on lower extremities.

In the course of the disease coordination In the course of the disease coordination disorders, scan speech, body and upper disorders, scan speech, body and upper extremities ataxia appear. extremities ataxia appear.

some bone abnormalities some bone abnormalities cardiomyopathcardiomyopathyy mental disorders mental disorders symptoms of lesion of pyramidal tractssymptoms of lesion of pyramidal tracts

Hereditary cerebellar ataxia Hereditary cerebellar ataxia of Pier–Maryof Pier–Mary

The main signs of the disease are:The main signs of the disease are: The beginning at the age of 30 – The beginning at the age of 30 –

5050 Cereballar ataxiaCereballar ataxia DysarthriaDysarthria HyperreflexiaHyperreflexia and s and spastic pastic

muscle hypertoniamuscle hypertonia

TTransmission: byransmission: by autosomal – autosomal – dominantdominant type type..

Clinical featureClinical feature::

begins gradually with gait disordersbegins gradually with gait disorders disorders of coordination, nystagmus, disorders of coordination, nystagmus,

dysarthriadysarthria high reflexes, increased muscle tonus high reflexes, increased muscle tonus

spastic type (mainly in lower spastic type (mainly in lower extremities), pathologic reflexesextremities), pathologic reflexes

eeye movements disorders ye movements disorders mental, memory and emotional mental, memory and emotional

disordersdisorders tthe course of the disease is progressivehe course of the disease is progressive

Olivo-ponto-cerebellar Olivo-ponto-cerebellar degenerationdegeneration

It is the group of the diseases that It is the group of the diseases that are connected by system lesion of are connected by system lesion of cerebellar cortex, pons and lower cerebellar cortex, pons and lower olives. Sometimes the neurons of olives. Sometimes the neurons of anterior horns of the spinal cord anterior horns of the spinal cord and basal ganglia are involved.and basal ganglia are involved.

The inheritanceThe inheritance of the disease is of the disease is autosomal – dominant.autosomal – dominant.

Clinical featuresClinical features

BBegins at the age of 15 – 20, egins at the age of 15 – 20, sometimes 30 yearssometimes 30 years

Cerebellar symptoms dominateCerebellar symptoms dominate also extrapyramidal and pyramidal also extrapyramidal and pyramidal

symptomssymptoms peripheral polineuropathyperipheral polineuropathy Sometimes retina is involved in Sometimes retina is involved in

pathological processpathological process Mental disorders are often observedMental disorders are often observed

Diseases with involvement of Diseases with involvement of neuro – muscular junction:neuro – muscular junction:

Progressive muscular Progressive muscular dystrophydystrophy

– Dushen pseudo – hypertrophic Dushen pseudo – hypertrophic muscle dystrophymuscle dystrophy

– Late Bekker pseudo – hypertrophic Late Bekker pseudo – hypertrophic muscle dystrophymuscle dystrophy

– Shoulder – scapula – facial form of Shoulder – scapula – facial form of Landuzi – DegerinaLanduzi – Degerina

– Erba dystrophyErba dystrophy

Amyotrophy as a result of Amyotrophy as a result of peripheral neuron lesionperipheral neuron lesion

Spinal amyotrophy of Werding – Spinal amyotrophy of Werding – HoffmanHoffman

Proximal amyotrophy of Proximal amyotrophy of Kukelberg – WelanderKukelberg – Welander

Sharkot – Marie – Tooth diseaseSharkot – Marie – Tooth disease

Family – hereditary Family – hereditary myotonia:myotonia:

– Myotonia TomsenaMyotonia Tomsena– Atonic myotoniaAtonic myotonia

Hereditary Hereditary diseases with diseases with paroxysmal states:paroxysmal states:

– Paroxysmal family myoplegiaParoxysmal family myoplegia– Episodic hereditary adynamiaEpisodic hereditary adynamia