Transcript Hereditary diseases of nervous system Common syndromes

Hereditary
diseases of
nervous system
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)
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Diseases with involvement of
nervous – muscle synapse:
– Myasthenia
– Myasthenic syndromes
Myasthenia gravis (MG)
is caused by a defect of neuro-muscular
transmission due to an antibodymediated attack on nicotinic
acetylcholine receptors (AchR) at
neuro-muscular junctions.
It is characterized by fluctuating
weakness that is improved by inhibitors
of cholinesterase.
Myasthenia gravis (MG)
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Etiology is unknown. How the autoimmune
disorder starts is not known
In about 15% of patients there 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
Pathogenesis
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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
Clinical features
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According to the course of the
disease:
– Progressive
– Stationary
– Mysthenic episodes
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Clinical forms:
– Ophthalmic
– Bulbar
– Skeletal
– General
Typical features:
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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
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Sensory and pelvic disorders usually are not
observed.
Provocation tests for disease
revealing
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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
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
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Differential diagnosis
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Botulism
Neurasthenia
LAS
Polineuropathy
Muscles dystrophy
Inflammatory myopathy
MS
Stroke in v/b region
Brain stem tumor
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
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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
Cholinergic crisis
 There
fasciculations, seizures,
bradycardia, salivation,
hyperhydrosis and abdominal
pain.
 Treatment – Atropinum 1 ml
0.1 % s/c or i/v.
Diseases with involvement
of pyramidal system:
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Hereditary Spastic paraplegia of
Shtrumpel
Family spastic paralysis with
amyotrophy, oligophrenia, retina
degeneration (described by Kellin)
Family spastic paralysis with
ichthyosis and oligophrenia
Spastic paraplegia of
Shtrumpel
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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
Clinical features
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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
Diseases with involvement of
extrapyramidal system:
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Parkinson disease
Hepato – cerebral degeneration
Dystonia
Huntington disease
Double athetosis
Myoclonus – epilepsy
Tourette syndrome
Parkinsonism
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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.
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
Clinical features
 Hypokinesia
 Rigidity
 Resting
trembling
 Loss of postural reflexes
The main clinical forms
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Trembling
Rigidity
Mixed
Severity stages:
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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
Drug Therapy
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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
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
Hepatocerebral dystrophy (HCD)
(Wilson – Konovalov disease)
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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.
Clinical signs
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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
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.
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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
Differential diagnosis
 Huntington
disease
 MS
 Chronic
stage of epidemic
encephalitis
Torsion dystonia
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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.
Clinical features
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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.
Diagnosis
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Family history and the evaluation of
pathological process dynamics are
necessary for the diagnosis putting.
Differential diagnosis
Atypical form of Economo encephalitis
Huntington disease
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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.
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
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Diagnosis
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Clinical and genetic analysis
CT and MRI of brain (atrophic changes of
brain hemispheres)
EEG
DNA – analysis
Differential diagnosis
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Chorea
Hepato – cerebral degeneration
Hereditary ataxia
– Spinal ataxia of
Fridreich
– Hereditary cerebellar
ataxia of Pier – Mary
– Olivo – ponto –
cerebellar degeneration
Spinal Fridreich ataxia
The disease is characterized by
spinal cord degeneration and
degenerative – dystrophic
changes in posterior and lateral
columns.
Transmission: by autosomal –
recessive type of inheritance.
Clinical features :
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The disease begins at the age of 10 – 12
slowly progresses
sensitive – cerebellar ataxia, nystagmus
muscle hypotonia and areflexia
gait disorders
At the beginning of the disease there is deep sensation
disorders according to the conductive type on lower
extremities.
In the course of the disease coordination disorders,
scan speech, body and upper extremities ataxia appear.
some bone abnormalities
cardiomyopathy
mental disorders
symptoms of lesion of pyramidal tracts
Hereditary cerebellar ataxia of
Pier–Mary
The main signs of the disease are:
 The beginning at the age of 30 – 50
 Cereballar ataxia
 Dysarthria
 Hyperreflexia and spastic muscle
hypertonia
Transmission: by autosomal –
dominant type.
Clinical feature:
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begins gradually with gait disorders
disorders of coordination, nystagmus,
dysarthria
high reflexes, increased muscle tonus
spastic type (mainly in lower extremities),
pathologic reflexes
eye movements disorders
mental, memory and emotional disorders
the course of the disease is progressive
Olivo-ponto-cerebellar degeneration
It is the group of the diseases that are
connected by system lesion of
cerebellar cortex, pons and lower
olives. Sometimes the neurons of
anterior horns of the spinal cord and
basal ganglia are involved.
 The inheritance of the disease is
autosomal – dominant.
Clinical features
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Begins at the age of 15 – 20, sometimes 30
years
Cerebellar symptoms dominate
also extrapyramidal and pyramidal
symptoms
peripheral polineuropathy
Sometimes retina is involved in pathological
process
Mental disorders are often observed
Diseases with involvement of neuro
– muscular junction:
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Progressive muscular dystrophy
– Dushen pseudo – hypertrophic muscle
dystrophy
– Late Bekker pseudo – hypertrophic
muscle dystrophy
– Shoulder – scapula – facial form of
Landuzi – Degerina
– Erba dystrophy
Amyotrophy as a result of
peripheral neuron lesion
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Spinal amyotrophy of Werding –
Hoffman
Proximal amyotrophy of Kukelberg –
Welander
Sharkot – Marie – Tooth disease
Family – hereditary myotonia:
– Myotonia Tomsena
– Atonic myotonia
Hereditary diseases with paroxysmal
states:
– Paroxysmal family myoplegia
– Episodic hereditary adynamia