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AAA - Boli Neurodegenerative 2017 - Febr
AAA - Boli Neurodegenerative 2017 - Febr
Degenerare
?
declin inexplicabil de la un nivel
anterior considerat a fi normal la
un nivel inferior din punct de
vedere al functiei
AUTOFAGIA
situatie particulara: MITOFAGIA ( AUTOFAGIA MITOCONDRIALA )
Mechanisms of neurodegeneration
Genetic mechanisms
Thousands of gene mutations
Intracellular mechanisms
Usually are the consequence of the abnormalities induced by gene mutations
Specific for each disease, not completely elucidated
Common finding for many ND disorders: accumulation of insoluble protein aggregates
major histopathologic hallmark
protein aggregates contribute to neuronal death or they are merely secondary
bystanders ?
the inability to degrade protein aggregates could lead to cellular dysfunction, impaired
axonal transport and cell death by apoptotic mechanisms
Toxic Proteins in Neurodegenerative Disease, JP Taylor et al., Science, 296, 1991-1995, 2002
MECANISMELE INTRACELULARE
DE TRAFIC AL PROTEINELOR
7. Boli cu cecitate progresiva sau oftalmoplegie, cu sau fara alte anomalii neurologice
A. Boala Parkinson
B. Atrofia multi-sistem
C. Paralizia supranucleara progresiva ( PSP )
D. Boala Huntington
E. Achantocitoza cu miscari involuntare ( coree, distonie )
F. Degenerescenta cortico-bazala
G. Boala difuza cu corpi Lewy
H. Tremorul esential
I. Boala Gilles de la Tourette
4. Boli cu ataxie progresiva
7. Boli cu cecitate progresiva sau oftalmoplegie, cu sau fara alte anomalii neurologice
A. Degenerescenta retiniana pigmentara ( retinitis pigmentosa )
B. Boala Stargardt
C. Boli mitocondriale
Oftalmoplegia externa progresiva cu/ fara surditatesau alte atrofii de sisteme ( sd.
Kearns-Sayre )
Neuropatia optica ereditara Leber
Encefalopatia necrozanta Leigh
ATAXIILE
SPINOCEREBELOASE
CLASIFICARE CLINICA: ATAXIILE CEREBELOASE
PURE
ATAXIILE CEREBELOASE
COMPLICATE
ATAXIILE PROGRESIVE
Myocardial muscle fibers also show degeneration and are replaced by macrophages
and fibroblasts. Essentially, chronic interstitial myocarditis occurs with hypertrophy
of cardiac muscle fibers; fibers become hypertrophied and lose their striations. This
is followed by swelling and vacuolation and finally interstitial fibrosis. The nuclei
appear hyperchromatic and occasionally vacuolated. The cytoplasm appears
granular with frequent lipofuscin depositions.
Kyphoscoliosis is likely; it is secondary to spinal muscular imbalance.
BOALA (ATAXIA) FRIEDREICH
Data fiind natura progresiva a bolii, tabloul clinic devine de obicei complet numai dupa cativa ani de
la debut
BOALA (ATAXIA) FRIEDREICH
MANIFESTARI CLINICE ( ataxie cerebeloasa + spinala)
- ataxia mersului, astazo-abazie, alergatul dificil
- inabilitatea mainilor: dupa luni / ani de la aparitia tulburarilor de mers
- dizartrie cerebeloasa: dupa ataxia mb. superioare
- RAR: debut brusc, asimetric, dupa o boala febrila
- ROT abolite precoce, r. Babinski prezent
- pierderea precoce a sensibilitatii proprioceptive
- Proba Romberg (+) nesistematizat
- uneori nistagmus predominent orizontal
- amiotrofii, de regula moderate in stadiile tardive ( asociaza neuropatie )
- uneori: tulb. de vedere, de auz
- TRASATURI CLINICE ASOCIATE
* cifoscolioza
* pes cavus de obicei inaintea manifestarilor neurologice
* degete "in ciocan"
* CARDIOMIOPATIE asociata in >50% cazuri
deces prin aritmie cardiaca sau insuficienta cardiaca
- agravare prin insuficienta respiratorie ( cifoscolioza )
* cca. 10% dezvolta DIABET ZAHARAT
* cca. 10% au doar TOLERANTA ALTERATA LA GLUCOZA
PES CAVUS DEGETE "IN CIOCAN"
FRIEDREICH ATAXIA Ancillary investigations
The diagnosis of Friedreich ataxia is based upon clinical findings but should be confirmed by
genetic testing.
Neuroimaging of the brain and spinal cord with MRI is recommended for all patients
presenting with ataxia to exclude other causes (eg, tumor, infarction, hemorrhage) and to evaluate for
cerebellar atrophy.
MRI of the brain and spinal cord in patients with FA consistently shows atrophy of the cervical spinal cord with
minimal evidence of cerebellar atrophy
The absence of cerebellar atrophy on brain MRI is supportive of the diagnosis of Friedreich ataxia. The presence
of significant cerebellar atrophy suggests alternative forms of hereditary ataxia other than Friedreich ataxia
Genetic testing for GAA repeat expansions in the frataxin gene should be performed in all patients
with progressive cerebellar ataxia and autosomal recessive inheritance.
Electrocardiographic and echocardiographic abnormalities indicative of cardiac involvement
are supportive features.
Evidence of a sensory axonal neuropathy on electrodiagnostic testing is a supportive feature
A report of 115 patients from 90 families established the main clinical criteria for Friedreich ataxia,
which were autosomal recessive inheritance, onset before age 25 years, ataxia of all four
limbs, absence of lower limb reflexes, and presence of pyramidal signs!
FA
FRIEDREICH ATAXIA Management
There is no specific disease-modifying therapy for Friedreich ataxia
The management often requires a team of special services that includes neurology, physical
medicine, cardiology, orthopedics, endocrinology, and speech therapy.
A physical therapy program should be initiated early and modified over time to address the
progressive loss of balance and fine motor control; adaptive devices to assist in ambulation and
activities of daily living eventually will be needed.
Yearly cardiac evaluation for evidence of arrhythmia and cardiomyopathy is required. Although there
is no specific treatment for Friedreich ataxia-related cardiomyopathy, conventional drugs and device
implantation can be used to manage heart failure and arrhythmia
Swallowing should be evaluated at baseline and as needed thereafter depending upon symptoms,
with speech and swallowing therapy for patients with dysphagia
Scoliosis screening is recommended annually, followed by orthopedic referral for those with
musculoskeletal abnormalities
Patients should be screened annually for the development of diabetes
FRIEDREICH ATAXIA Prognosis
Severity of disease and rate of progression are variable, with more severe disease being associated
with a higher number of GAA repeats
The mean time from symptom onset to use of a wheelchair ranges from 11 to 25 years
Most patients die between the ages of 30 and 40, with a mean age of 37 years in some studies,
though some patients survive until the eight decade
With late-onset Friedreich ataxia, disease progression is generally slower
The major cause of death is cardiac dysfunction, typically congestive heart failure or arrhythmia.
Less often, death occurs from noncardiac causes, such as pneumonia due to bulbar dysfunction with
inability to protect the airway
BOALA NEURONULUI MOTOR
(SCLEROZA LATERALA AMIOTROFICA SLA;
Boala Charcot; Boala Lou Gehring)
Grup de boli neurodegenerative
leziuni ale neuronilor motori centrali ( cortexul motor )
+
leziuni ale neuronilor motori periferici ( spinali, bulbo-pontini )
debut cu deficit motor distal asimetric la un membru ( initial ca pierderea abilitatii ) cu extensie
spre proximal ( ms. centurilor afectata tardiv );
ulterior: afectarea ms. gatului, limbii, faringelui, laringelui, trunchiului (insuficienta respiratorie
progresiva, tulb. de deglutitie cu reflexele de fund de gat mult timp pastrate )
+ atrofii ms. progresive in teritoriul deficitar
caz particular: sd. Aran-Duchenne mana "scheletica", "cadaverica"
fasciculatii musculare ( f. caracteristic: pe limba ) niciodata izolate !
crampe musculare ( frecvent, adesea f. precoce, legate de actiune, sugestiv dar nespecific ! )
evolutie extensiva insidioasa ( luni ani ), in timp semnele apar bilateral si la toate membrele
ex. clinic:
asociere semne SD. PIRAMIDAL ( vivacitate ROT, r. patologice ) + SD. NMP
ALS- Clinical features of limb weakness
Lower extremity onset of ALS most often begins with distal leg weakness (foot drop).
Patients with proximal leg weakness often complain of difficulty climbing stairs and difficulty arising
from chairs.
Upper extremity onset is most often heralded by hand weakness but may begin in the shoulder
girdle muscles.
Patients with hand weakness may complain that they drop things and have difficulty with tasks
such as pinching, writing, typing, managing buttons or zippers, and picking up small objects.
Patients with shoulder girdle weakness may report difficulty using their arms in activities such as
washing or combing their hair as well as lifting things above their head.
Clinical features of bulbar weakness
Patients with dysarthria complain of slurring of speech that is often worse at the end of the day or
with more vigorous use of their voice.
Patients with dysphagia initially complain of difficulty swallowing thin liquids, and may report the
need to swallow multiple times in order to manage a single liquid bolus.
With progression, patients may choke or cough when drinking thin liquids and eventually develop
difficulty managing thicker liquids, their own secretions, and solids.
Patients with axial neck weakness complain of posterior neck pain or strain with a
gradually worsening tendency for head drop.
Patients with axial truncal weakness complain of difficulty maintaining an erect
posture when standing or walking. Some will support their trunk by placing their
hands in their front pants pockets or on their upper thighs.
ALS- Typical form
The triad:
1) atrophic weakness of the hands, arms or legs
2) generalized hyperreflexia
3) Coarse fasciculation evident in weakened muscles.
The muscle of the upper limb and shoulder girdles are typically involved later
Later the atrophic weakness spreads to the neck, tongue, pharyngeal and laryngeal muscles.
ALS- Uncommon forms
impreuna cu
B. ABSENTA:
(B:1) dovezilor electrofiziologice si patologice pentru alte procese patologice care pot explica semnele de
degenerescenta ale NMP si/ sau NMC
si
(B:2) dovezilor neuroimagistice in favoarea altor procese patologice care pot explica semnele clinice si
electrofiziologice observate.
Criteriile WFN - El ESCORIAL revizuite pentru
diagnosticul sclerozei laterale amiotrofice
SLA CLINIC DEFINITA:
doar dovezi clinice pentru semne de NMC si NMP in cel putin 3 regiuni diferite
SLA CLINIC PROBABILA:
doar dovezi clinice pentru semne de NMC si NMP in cel putin 2 regiuni diferite, cu necesitatea ca unele
semne de NMC sa fie localizate rostral de semnele de NMP
SLA CLINIC PROBABILA SUSTINUTA DE PROBE DE LABORATOR:
semne clinice de NMC si NMP doar intr-o singura regiune, sau doar semne de NMC prezente intr-o
singura regiune iar semnele de NMP definite prin criterii EMG sunt prezente la cel putin 2 membre, plus
utilizarea adecvata a neuroimagisticii si protocoalelor de laborator clinic pentru a exclude alte cauze.
SLA CLINIC POSIBILA:
semne clinice de NMC si NMP impreuna intr-o singura regiune / sau doar semne de NMC in 2 sau mai
multe regiuni;
sau,
semnele de NMP se gasesc rostral de semnele de NMC si diagnosticul de "SLA clinic probabila sustinuta
de probe de laborator" nu poate fi sustinut pe baze clinice asociate cu semne electrodiagnostice,
neurofiziologice, neuroimagistice sau studii de laborator clinic. Trebuie excluse alte diagnostice
pentru a accepta dg. de SLA clinic posibila.
SLA SUSPECTATA CLINIC:
sd. de NMP pur, in cadrul caruia dg. de SLA nu poate fi considerat suficient de sigur, pentru a include
pacientul intr-un studiu de cercetare ( dg. exclus din Criteriile revizuite El Escorial pt. SLA)
FORME CLINICE PARTICULARE
ATROFIA MUSCULARA PROGRESIVA
forma limitata: doar afectarea NM periferic
barbati: x4 mai frecvent decat femei
progresie mai lenta, supravietuire mai lunga ( > 15 ani )
cu neuropatii motorii cronice autoimune +/- bloc de conducere