Ernia discale L5-S1 destra

Author: Davide Russo
Date: 09/09/2013

Description

1) Definizione del paziente e della storia

sesso:*maschile*
Anno di nascita : 1978
Peso: 90 Statura: 1,76 BMI: 29

Anamnesi patologica prossima
da circa un anno il paziente lamenta lombosciatalgia ingravescente con parestesie ed ipoestesia lungo il territorio di innervazione L5-S1. Claudicatio neurogena. Il paziente assume Takidol a.b. ma senza miglioramento della sintomatologia. Viene eseguita una consulenza fisiatrica con indicazione ad eseguire una TC: ernia discale L5-S1 in posizione mediana-paramediana destra con sofferenza della radice S1. Indicazione ad eseguire cicli di FKT ed infiltrazioni con corticosteroidi. La sintomatologia si attenua ma al termine dei cicli di terapia aggravamento della sintomatologia dolorosa con grave compromissione delle normali attività quotidiane. A tal punto si richiede consulenza neurochirurgica con indicazione ad eseguire intervento di chemonucleolisi.

EON: Paziente vigile, collaborante ed orientato nello spazio e nel tempo; molto sofferente. Non si segnalano lesioni a carico del distretto cranico. Prove cerebellari correttamente eseguite. Lasègue positivo a 10° a destra, negativo a sinistra. Si segnala ipoestesia diffusa arto inferiore destro lungo il territorio di innervazione L5-S1. ROT simmetrici e normoelicitabili. Babinski assente. Non si rilevano deficit di forza. Deambulazione antalgica con claudicato neurogena.

Anamnesi patologica remota

8 anni:intervento di tonsillectomia
18 anni: varicocele; trattamento chirurgico di scleroembolizzazione
22 anni: cheratocono bilaterale; portatore LAC rigide

Anamnesi familiare
Nulla di rilevante

2) Le basi molecolari degli eventi descritti, tenendo conto di tutti i sintomi ed utilizzando i link alle informazioni pertinenti
La funzione del disco intervertebrale è di permettere un movimento stabile della colonna vertebrale e di supportare e distribuire i pesi durante il movimento.
La fuoriuscita del nucleo discale, la porzione più idratata e compatta del disco, è determinata dal cedimento degli strati periferici, da figurare come lamine concentriche (a buccia di cipolla) man mano meno idratate e più fibrose dal centro alla periferia. Tale cedimento avviene di solito nell'ambito di un processo lento degenerativo a carico di tutto il complesso osteo-articolare tra una vertebra e l'altra e quindi dovrebbe coinvolgere fasce di età medio-avanzata. Invece la vita sedentaria, il sovrappeso e il ripetersi di ripetuti micro-o macrotraumi sulla colonna vertebrale può provocare una precoce degradazione di tali strutture anatomiche e quindi portare al manifestarsi clinico in età anche giovanile. La genesi della sintomatologia clinica è dovuta all'estrinsecarsi dell'ernia in una direzione posteriore o postero-laterale alla situazione anatomica del disco intervertebrale, andando così a comprimere e danneggiare le strutture nervose. La degenerazione e quindi l'ernia del disco sono spesso legati a fattori congeniti genetico-familiari, attivati o rivelati poi da varie cause come stress e traumi vertebrali, protratte posture viziate, maldistribuzione di carichi sulla colonna ed altri. La responsabilità di fattori genetici spiega i moltissimi casi di degenerazioni discali nell'adolescenza. Il fumo, l'uso eccessivo dell'automobile ed il sovrappeso sono noti fattori favorenti l'usura del disco e quindi la formazione di un'ernia.
Basi molecolari della degenerazione discale: Degeneration of the intervertebral disk (IVD) is a major pathological process implicated in low back pain and is a prerequisite to disk herniation. Although mechanical stress is an important modulator of the degeneration, the underlying molecular mechanism remains unclear. The association of human IVD degeneration, assessed by magnetic resonance imaging, with annulus fibrosus cell apoptosis and anti-cytochrome c staining revealed that the activation of the mitochondria-dependent apoptosome was a major event in the degeneration process. Apoptosis is a genetically controlled mechanisms of cell death involved in the regulation of tissue homeostasis. The 2 major pathways of apoptosis are the extrinsic (Fas and other TNFR superfamily members and ligands) and the intrinsic (mitochondria-associated) pathways, both of which are found in the cytoplasm. The extrinsic pathway is triggered by death receptor engagement, which initiates a signaling cascade mediated by caspase-8 activation. Caspase-8 both feeds directly into caspase-3 activation and stimulates the release of cytochrome c by the mitochondria. Caspase-3 activation leads to the degradation of cellular proteins necessary to maintain cell survival and integrity. The intrinsic pathway occurs when various apoptotic stimuli trigger the release of cytochrome c from the mitochondria (independently of caspase-8 activation). Cytochrome c interacts with Apaf-1 and caspase-9 to promote the activation of caspase-3. Recent studies point to the ER as a third subcellular compartment implicated in apoptotic execution. Alterations in Ca2+ homeostasis and accumulation of misfolded proteins in the ER cause ER stress. Prolonged ER stress can result in the activation of BAD and/or caspase-12, and execute apoptosis.
Basi molecolari della sintomatologia del dolore neuropatico e delle parestesie: After a peripheral nerve lesion, aberrant regeneration may occur. Neurons become unusually sensitive and develop spontaneous pathological activity, abnormal excitability, and heightened sensitivity to chemical, thermal and mechanical stimuli. This phenomenon is called "peripheral sensitization". In "central sensitization," nociceptive neurons in the dorsal horns of the spinal cord become sensitized by peripheral tissue damage or inflammation. This type of sensitization has been suggested as a possible causal mechanism for chronic pain conditions. The changes of central sensitization occur after repeated trials to pain. Research from animals has consistently shown that when a trial is repeatedly exposed to a painful stimulus, the animal’s pain threshold will change and result in a stronger pain response. Researchers believe that there are parallels that can be drawn between these animal trials and persistent pain in people. For example, after a back surgery that removed a herniated disc from causing a pinched nerve, the patient may still continue to “feel” pain. Tissue injury results in the release of an inflammatory mediator pool that activates signaling cascades within nociceptors to produce periperhal sensitization. Acutely, these cascades posttranslationally modify stimulus transducing ion channels and voltage-gated ion channels to sensitize the transduction machinery and enhance excitability. PKC and PKA phosphorylation of TRPV1 reduces thermal threshold, enhances responses to suprathreshold stimuli, and diminishes receptor desensitization. Phosphorylation o voltagegate sodium and potassium channels work to potentially reduce action potentia threshold, decrease refractory period, and enhance repetitive firing. Phosphorylation of high-threshold voltage-gated calcium channels may also modulate excitability, but more importantly, decouples transmitter release from G-protein–mediated inhibition, thus enhancing neurogenic peptide release from peripheral nerve terminals. Endogenous reducing agents, such as L-cysteine, may directly potentiate TRPV1 and T-type calcium channels to enhance thermal transduction and excitability without activating intermediary signaling molecules. Thus, a host of concerted posttranslational molecular events act to rapidly produce peripheral sensitization. Although the discussion here has been limited to posttranslational modification of ion channels, it should be noted that posttranslational modifications, in particular phosphorylation, are also critical in the mechanisms underlying the activation of transcription factors, such as CREB (Ji and Rupp, 1997; Qiao and Vizzard, 2004) by inflammatory mediators. Thus, posttranslational mechanisms also serve to regulate pretranslational mechanisms of sensitization. Future studies should continue to identify posttranslational modifications of nociceptive and voltage-gated ion channels. The generation of biochemical tools, such as phospho-specific antibodies, and knock-in mice with point mutations at sites of posttranslational modification should directly identify and determine the in vivo function of specific posttranslational events. Interleukin-8, also, appears to be associated with development of radicular pain by back extension and to be activated on acute or subacute disc herniations. IL-8 seems to participate in the pathomechanism of nerve root inflammation in lumbar disc herniations, which implies that it may be considered a target for therapeutic intervention.
TRPV1 e IL-8 per approfondimenti visitare le sezioni dedicate in questo sito.

3) Eventuali proposte di terapia, volta al ripristino delle condizioni ottimali
Intervento di chemoucleolisi: acceptable treatment, but less efficacious than discectomy (open or micro). Chymopapain (Chymodiactin) is injected intradiscally under local or rather under general anaesthesia. Proven more effective than placebo injection. Typical succes rates: at 1 year 85% of patients undergoing discectomy had good or excellent results compared to 44% to 63% for chemonucleolysis (CNL). Althought sciatica improves in both groups, only the discectomy group had significant improvement in back pain. In one study, at 6 months 56% of patients initially having CNL had undergone surgery for unrelieved symptoms. Risk of the significant complication of anaphylaxis (sometimes fatal) may be reduced by skin-tests for allergic sensitivity to the agent. Other complications reported include: discitis, neurologic injury, vascular injury, thrombophlebitis, transverse myelitis.
Scheda tecnica della chymopapaina: link to http://merops.sanger.ac.uk/cgi-bin/pepsum?id=C01.002
Paracetamolo 1000 a.b.
Educazione posturale

Bibliografia:

Intervertebral disc degeneration: the role of the mitochondrial pathway in annulus fibrosus cell apoptosis induced by overload. Rannou F, Lee TS, Zhou RH, Chin J, Lotz JC, Mayoux-Benhamou MA, Barbet JP Chevrot A, Shyy JY. Division of Biomedical Sciences, University of California, Riverside, California 92521-0121, USA.
Mark S. Greenberg, Handbook of neurosurgery, Thieme, Seventh edition; cap. 18.1, 18.2, 18.3
http://www.genome.jp/keggbin/show_pathwaymap=hsa04210&show_description=show
http://en.wikipedia.org/wiki/Neuropathic_pain
http://en.wikipedia.org/wiki/Sensitization
Posttranslational Mechanisms of Peripheral Sensitization Gautam Bhave,1Robert W. Gereau IV21 Division of Neuroscience, Baylor College of Medicine, Houston, Texas 770302
http://journals.lww.com/spinejournal/Abstract/2002/05010/mRNA_Expression_of_Cytokines_and_Chemokines_in.5.aspx
http://en.wikipedia.org/wiki/TRPV1
http://en.wikipedia.org/wiki/Chymopapain
http://merops.sanger.ac.uk/cgi-bin/pepsum?id=C01.002

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Comments
2014-04-24T12:30:37 - Paolo Pescarmona

TRPV1

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