AGGIORNAMENTI IN MEDICINA VETERINARIA :questioni di clinica medica degli animali da compagnia Diagnosi caso 1: Il cane magro con il "pancione": un segno, tante cause Grazie alla raccolta anamnestica, la visita clinica e le indagini collaterali è stato possibile raggiungere la diagnosi di sospetto: epatite cronica di origine tossica causata dall'ingestione di parti velenose di Cycas Revoluta. Le epatiti croniche del cane, sono processi flogistici che si sviluppano principalmente a livello del parenchima epatico, con il conseguente innalzamento dei valori delle transaminasi. Si tratta di patologie che si riscontrano soprattutto in cani di età adulta (4-7 anni) ad eccezione delle forme ereditarie da accumulo di rame che possono insorgere anche in soggetti più giovani; risultano maggiormente interessate le femmine, e, pur potendo interessare tutte le razze, esiste maggiore predisposizione per Bedlington Terrier, Dalmata, Labrador Retriever, Whest Highland White Terrier, Dobermann e Spaniel. Dal punto di vista sintomatologico, i cani affetti da epatite cronica possono presentarsi asintomatici o con segni clinici del tutto aspecifici, quali poliuria e polidipsia, anoressia/disoressia, dimagramento, abbattimento e intolleranza agli sforzi, vomito, diarrea e nei, casi gravi, ascite, coagulopatie ed encefalopatia epatica. La visita clinica del paziente raramente porta al riscontro di qualche reperto indicativo ad eccezione di uno scadimento delle condizioni generali del soggetto, o condizioni più eclatanti come ittero o ascite. Anche le alterazioni di laboratorio risultano non sempre indicative: si riscontrano di norma aumenti delle transaminasi , meno costanti aumenti di fosfatasi alcalina e γ-glutamiltransferasi; nelle fasi avanzate è poi possibile evidenziare tutte le alterazioni indicative di un malfunzionamento epatico, come ipoalbuminemia, riduzione dei valori dell'urea, aumento degli acidi biliari, abbassamento del fibrinogeno. Tra le alterazioni ematologiche che si possono incontrare, ci sono lieve anemia, leucocitosi e piastrinopenia (da consumo, in associazione a coagulopatia) oltre all'aumento dei tempi coagulativi (tempo di protrombina (PT), e tempo di tromboplastina parziale, PTT). La diagnostica per immagini, ed in particolare l'ecografia addominale, può solo completare il quadro ma non fornisce la diagnosi di certezza, in quanto possono sia essere evidenziate alterazioni nella struttura epatica, soprattutto in caso di cirrosi, ma non necessariamente soggetti affetti da epatite cronica presentano alterazioni dell'ecostruttura rilevabili all'esame. Lo strumento diagnostico più indicato in caso di tali patologie, è rappresentato dall'esame istopatologico di un campione prelevato tramite biopsia (ovviamente va ricordato che, in caso di patologia avanzata, in cui fossero comparsi deficit coagulativi, quest'ultima risulta controindicata). Nel presente caso l'esame bioptico ed istopatologico non è stato eseguito in quanto il proprietario non ha dato il suo consenso alla procedura perché preoccupato degli elevati rischi anestesiologici dovuti alla grave condizione clinica del suo cane.
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intraoral orthoses and migraine
Intraoral splints are effective in migraine prevention. In this review, changes in the quality of
life of migraineurs treated with a palatal nonoccluding splint were measured. Using the
Migraine Specific Quality of Life Instrument (Version 2.1), it was found that the palatal
nonoccluding splint significantly improved the quality of life of migraineurs. The role of the
craniomandibular muscles in the pathophysiology of migraine is also discussed.
Expert Rev. Neurotherapeutics 5(3), 371–377 (2005) Migraine is a common disorder with a life- Materials & method
Materials & method
time prevalence of 16% worldwide, and a last-year prevalence of 10% [1,2]. It may sig- In total, 152 patients, 117 female and 35 male, Discussion
nificantly diminish quality of life, even were admitted to the study. The inclusion between attacks, and impairs quality of life Expert opinion
more than diabetes, hypertension and osteo- • Age of onset of migraine before 50 years Five-year view
arthritis [3–5]. Although the pathogenesis of • Subjects with all or most of their own teeth, Key issues
migraine headache remains poorly under- and who did not wear a removable dental References
stood, current theories suggest a primary, possibly genetically determined, CNS dys- Affiliation
function to be involved. There is activation • History of migraine of 1 year or more, with of the trigeminovascular system at least one attack per week in the previous is comprised of the meningeal vessels, trigeminal nerve and trigeminal nucleus, in • Headache free between attacks particular the trigeminal subnucleus • A diagnosis of migraine without aura caudalis .
(i.e., group 1.1 in the guidelines laid down Tenderness and dysfunction of the crani- by the Headache Classification Committee omandibular muscles is a common finding of the International Headache Society) in migraine [9–15]. Intraoral interocclusal To make the diagnosis of migraine without orthoses, used in the treatment of cranio- aura, the following criteria must be met : mandibular muscle dysfunction [16–21], arealso effective in preventing migraine A. At least five attacks fulfilling criteria B, C Their therapeutic muscle-relaxing effect is attributed to the fact that they encourage B. Headache attacks lasting 4–72 h (untreated the mandible to assume the physiologic rest or unsuccessfully treated) position, thereby altering habitual neu- C. Headache has at least two of the following The Headache Clinic, romuscular patterns within the mastica- characteristics: unilateral location, pulsat- Suite 256, P Bag X2600, tory muscles . When a nonoccluding Houghton, 2014, South Africa ing quality, moderate or severe intensity palatal orthosis is worn, there is increased Tel.: +27 114 840 933 (inhibits or prohibits daily activities), Fax: +27 114 840 982 resting length and relaxation of the cranio- aggravated by walking up stairs or similar mandibular muscles [25,26]. This study routine physical activity determined the effect of wearing a nonoc- KEYWORDS:
D. During the headache at least one of the fol- craniomandibular, migraine, cluding palatal orthosis on the quality of lowing: nausea and/or vomiting, muscle dysfunction, orthosis life of migraineurs.
photophobia and phonophobia 2005 Future Drugs Ltd
Factors that could influence the frequency or intensity of • Role function restriction, which measures the percentage of migraine, such as pregnancy, the use of prophylactic migraine time that the patient can perform normal daily activities medication or ergot derivatives, a history of drug or alcohol • Role function prevention, which measures the percentage abuse, or serious illness were exclusion criteria. All participants productivity while working were fully informed of the nature of the project and their prior • Emotional function, which measures the percentage of consent was obtained.
emotional and relationship disability Patients completed the MSQ before the start of treatment The posture-modifying appliance (PMA) was fabricated using and again 12 months later. Participants were instructed to the maxillary cast of the subject. It consisted of a 3 mm thick continue using palliative medication whenever necessary.
acrylic resin reinforced with a chrome cobalt strip (FIGURE 1).
The appliance covered the hard palate, with the exception of the anterior part where the tip of the tongue normally touches As there was no significant statistical difference between the during speech.
results for males and females, they were combined, and the The PMA was adjusted for fit and overall comfort. Patients average pretreatment and post-treatment scores for each were told that the PMA should not interfere with the free parameter were calculated. Analysis of the data using the Stu- movement of the tongue during speech. They were asked to dent's t-test showed statistically significant improvement in all speak with the PMA in situ using the words listed in three parameters. Role function restriction improved from which are phonetically balanced and designed to test the whole 54.6 to 91% (p < 0.0001), role function prevention improved range of English sounds in various combinations from 45.4 to 84.8% (p < 0.0001) and emotional function was then removed and the part that the tongue had touched improved from 45.4 to 91.2% (p < 0.0001).
during speech indicated by the patient. The offending acrylicwas ground away and the process repeated, until the patient was no longer aware of any interference with tongue move- Migraine is considered to be a neurovascular syndrome, with ment. The final shape and thickness of the PMA was, in most abnormal neuronal excitability in the cerebral cortex, peripheral patients, very different to the original sensitization of the trigeminovascular system and pain due to (FIGURE 2). Subjects were instructed to wear the PMA day and night, but to remove it dilation of intracranial blood vessels [30–32]. The triptans were during tooth brushing, eating and drinking, and when playing developed as cranial vasoconstrictors to mimic the desirable contact sports. Subjects were requested to return for adjustment effects of serotonin [33,34], while avoiding its side effects . An of the PMA if they experienced discomfort or speech difficulty.
important hindrance to the more widespread use of the triptansis the unsubstantiated perception that they have harmful Migraine specific quality of life measurement
vasoconstrictor effects .
The Migraine Specific Quality of Life Questionnaire (MSQ) Nociceptive input to the CNS is increased due to sensitiza- Version 2.1 was used to assess the efficacy of the PMA. The tion of peripheral sensory afferents, and the resultant barrage of MSQ is a 14-item, self-administered questionnaire, which nociceptive impulses results in sensitization of second- and measures three dimensions of headache-related quality of life third-order neurons in the CNS. In this way, sensitization may that are affected by migraine play a role in the initiation and maintenance of migraine Consequently, current research has focussed upon prejunctionaland presynaptic targets on nociceptive trigeminovascular neu-rons in an attempt to develop drugs that inhibit trigeminalnociceptive traffic and central sensitization withoutvasoconstrictor effects [32,37].
Central sensitization is induced by nociceptive afferent input from the intracranial dura mater travelling along thetrigeminovascular pain pathway . It results in [39–41]: • A reduction of the threshold to cell depolarization • Cellular activity that continues after cessation of the peripheral nociceptive input • A spread of cellular activity to neighbouring cells Noxious stimulation of muscle afferents also increases the excitability of spinal cord neurons . Persistent stimulationleads to cellular and molecular changes, which result in neuro- Figure 1. The posture-modifying appliance before adjusting
nal hyperexcitability, to the extent that pain is elicited by low- for speech.
threshold, normally non-noxious, stimuli [43–49]. After anincrease in central excitability produced by the activation of Expert Rev. Neurotherapeutics 5(3), (2005) Muscles and migraine
peripheral chemoreceptors, cells in the trigeminal nucleus cau-dalis that are normally nociceptive-specific begin to respond to Box 1. Phonetically balanced word list designed to test
low-threshold, primary afferent non-nociceptive mechano- the whole range of English sounds in various
receptors . Repeated stimulation of a dorsal root produces, in some neurons, a prolonged heterosynaptic facilitation withan augmentation of the response to the conditioning root (homosynaptic potentiation) as well as to adjacent test roots (heterosynaptic potentiation) Restoring a patient's ability to function normally is now recognized as the primary treatment goal, rather than merely . The results of this study show that relaxa- tion of the craniomandibular muscles by means of a PMA improves the quality of life of migraineurs. By reducing sen- sory input from the craniomandibular muscles, central sen- sitization is reduced. The probable mechanism is that intraoral splints may have therapeutic effects apart from • Volumetric analysis of the masseter and medial pterygoid those commonly attributed to the occlusal component .
muscles showed that the volume of masticatory muscles in This may be attributed to the fact that an intraoral appli- migraineurs is nearly 70% greater than in nonmigraineurs ance may encourage the mandible to assume the physiologic rest position, thereby altering habitual neuromuscular pat- terns within the masticatory muscles . Further research has shown that when a nonoccluding palatal appliance isworn there is an increase in the interocclusal distance and, • Sensory afferents from the craniomandibular muscles consequently, in the resting length of the masticatory project to the trigeminal sensory nuclei, and in particular muscles [55,56].
to the subnucleus caudalis. Subnucleus caudalis neurons, A limitation of this study is the lack of a placebo control including low-threshold mechanoreceptive, wide-dynamic group. There is, unfortunately, no remedy for this when range and nociceptive-specific neurons, are excited by the testing a physical intervention such as an intraoral appli- stimulation of craniomandibular muscle sensory ance, given the sensitivity of the intraoral structures. The possible placebo effect of the PMA cannot therefore be • The subnucleus caudalis also acts as a critical interneuronal measured, and its importance must remain the subject of relay site in craniofacial nociceptive reflex activity involving speculation. According to Occam's Razor, in science the sim- the craniofacial muscles [67–70].
plest theory that fits the facts of a problem is the one thatshould be selected. This is interpreted to mean that the sim- plest of two competing theories is preferable. If Occam's The following clinical findings have been determined: Razor is applied, then the most likely conclusion is that the • Pericranial muscle pain and tenderness are prominent PMA does have a beneficial nonplacebo effect. The possibil- features in migraine [71–73] ity of natural regression of the migraine in this group of • There is increased pericranial muscle electromyographic patients is minimal, given that all the subjects had been suf- activity in migraine fering for a long time frame without improvement until the PMA was fitted.
• Physical therapy can precipitate migraine attacks  Further corroborating evidence that the craniomandibular muscles play a role in the cascade of events in migraine pathogenesis is described below.
Treatment modalities that reduce craniomandibular muscletension are effective in the treatment of migraine and include: • Intraoral splints which reduce migraine intensity and • The middle meningeal artery, dura of the middle and ante- rior cranial fossae, and craniomandibular muscles, all receive • Biofeedback to induce muscle relaxation is widely used in sensory afferents from the mandibular division of the trigem- migraine prophylaxis. The positive treatment response to inal nerve. They all send sensory afferent input to the subnu- biofeedback/relaxation in migraine headache is not related to cleus caudalis, possibly enhancing central sensitization. The presence of changes in blood flow velocity .
middle meningeal artery and dura of the middle and anterior • Intramuscular trigger point injections are effective in the cranial fossae via its recurrent meningeal branch, and the treatment of acute migraine pain [84–86].
muscles via their individual branches [57,58].
findings suggest a relationship between migraine headaches onthe one hand and dysfunction of the craniomandibular muscleson the other. In this study, the quality of life of migraineurs wassignificantly enhanced by the use of an intraoral palatal nonoc-cluding appliance. This and other evidence, including anatomi-cal evidence, the projection of sensory afferents from the crani-omandibular muscles to the trigeminal subnucleus caudalis,clinical findings, treatment modalities designed to reduce mus-cle tension which also successfully treat migraine, and drug tri-als, provide a compelling argument that central sensitization inmigraineurs is enhanced by sensory input originating from thecraniomandibular muscles. Therefore, the best current treat-ment regimen must include assessment and treatment of thepericranial muscles.
Figure 2. Example of the posture-modifying appliance after adjusting
It is unlikely that this treatment regimen will gain much favor.
The reason being that medicine is divided into different disci-plines, each with its own sphere of interest. While the general • Resection of the corrugator supercillii muscles in patients public may believe that these disciplines share information at who respond positively to botulinum toxin A injection the highest level, in reality they rarely communicate with each results in prolonged and effective migraine other. The excellent results achieved with the use of intraoral splints in migraineurs have been on record for many years. Inspite of this, intraoral splints are rarely mentioned in the headache literature – there is not a single article on the subject Preliminary studies indicate that drugs such as botulinum in Headache or Cephalalgia in at least the last 3 years. Unfor- toxin A, baclofen and tizanidine, which reduce skeletal mus- tunately, despite the excellent clinical results, splint therapy cle spasm and tone, may be useful in migraine for migraine is still regarded with scepticism. In the words of prophylaxis .
Max Planck (Nobel Prize Physicist, 1918), "A new scientific Sumatriptan was developed as a cerebral vasoconstrictor, but truth does not triumph by convincing its opponents and it has also been shown to act on skeletal muscle [91–93]. It cannot making them see the light, but rather because its opponents be excluded, therefore, that the triptans may be effective in eventually die, and a new generation grows up that is familiar migraine due to altered muscle metabolism.
with it". It is improbable, therefore, that, despite the provenefficacy of intraoral splints, their use will be widely adopted within the next 5 years. In the next 50 years. perhaps? Current theories suggest that a primary, probably geneticallydetermined, CNS dysfunction is involved in the initiation of the migraine headache, with activation of the trigeminovascular The author would like to express sincere thanks to Daniel system and sensitization of neurons in the CNS . Clinical Shevel for his invaluable input in the writing of this review.
• Migraine is a common disorder.
• It is characterized by moderate-to-severe pain, with associated symptoms such as nausea, vomiting, photophobia and phonophobia.
• Migraine is associated with changes in the trigeminovascular system.
• Tenderness and dysfunction of the craniomandibular muscles is a common finding in migraine.
• Intraoral orthoses are used to relax the craniomandibular muscles and restore them to normal function.
• This review studies the effect on migraineurs of wearing a nonoccluding palatal orthosis.
• Placebo-controlled studies are not feasible when intraoral orthoses are used.
• The effect was therefore measured by comparing pretreatment with post-treatment quality of life.
• Statistical analysis of the results showed a significant improvement in quality of life when the orthosis was worn.
Expert Rev. Neurotherapeutics 5(3), (2005) Muscles and migraine
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More than twenty years ago, four college students asked each other: What if we could offer children from under-resourced communities individualized attention before they enter kindergarten, giving them the critical academic and social skills—the ‘jumpstart'—they need to succeed? The idea took hold and by 2015, Jumpstart had trained more than 40,000 college students and community volunteers, preparing over 87,000 children for kindergarten success. Jumpstart's program is replicated across the country in 14 states and the District of Columbia. We leverage partnerships with higher education institutions, Head Start, community-based preschools, and school districts to create sustainable solutions in order to close the kindergarten readiness gap.