Maxillofacial Musculoskeletal Diseases

    

    

    Figure 2:  (a) Neural, (b) Muscular, (c) Vascular origin and (d) Primary tumors
of maxillofacial musculoskeletal diseases.
    
    

Osteogenesis imperfecta

The disorder is inherited as an autosomal dominant/recessive or non hereditary pattern due to an abnormality in the type 1 collagen synthesis, which forms fragile and porous bone. Different types of Osteogenesis Imperfecta (OI) have been identified: OI type I and II, OI tarda, OI neonatal lethal, OI Vrolik, OI with blue scelera, OI progressively deforming with normal sclera/Type III, OI Type IV; all with a gene map locus at 17q21.31-q22.1. It features a triad of brittle bones, blue sclera and deafness (otosclerosis). Bone extremities are small/deformed and rib fractures are common. Calvarium is made of soft wormian bones that make them prone to intracranial hemorrhage and hydrocephalus. Muscular hypotony is due to the weak tendinous insertions into bones. Bone fractures are noticed form 2 to 4 years of age with several pseudoarthroses. Neural defects affecting cerebellum and pyramidal tracts arise from abnormal bone-nerve connections. Histologically, it has thin cortices and spongy bones, since osteoblasts are affected owing to defects in collagen synthesis. A variant of it; known as dentinogenesis imperfecta, shows defective dentition, maxillary hypoplasia, frontal bossing, cross bite and anterior open bite [6]. No definitive treatment exists for osteogenesis imperfecta, other than the interventions done for secondary infections. Type I cases survive, but Type IIs succumb to death in first year of life. For other groups, varying ranges of decreased life expectancy is seen.

Marfan syndrome

It is a connective tissue disorder; with an autosomal dominant mode of inheritance, where FBN1 gene on chromosome 15, bands q15-q23, which codes fibrillin/connective tissue protein, is affected. The classic triad of Marfan’s syndrome includes subluxated lenses, skeletal anomalies, and cardiovascular diseases. Aortic dilatation and aneurysms are common. It also involves the lungs, muscles, genitourinary system, and skin. Patients are tall with arm span being greater than the total height. Generally, hyper extensibility and habitual dislocations of joints, kyphosis and flat feet are seen. It shows long, narrow skull, high arch palate, malocclusion and temporomandibular joint disorders [7]. Though no specific treatment is available for the disease, cardiovascular complications are attended to reduce its morbidity and mortality.

Hypophosphatasia

This disorder affects patients of all age groups, where bone mineralization is disturbed due to alkaline phosphatases deficiency [8]. The gene is ALPL, placed at band 1p36.1-34. The ’perinatal’ type is lethal and ’infantile’ type has 50% mortality. Premature loss of teeth, defective root cementum and hypocalcified teeth are dental findings. No definite therapy exists for the disease.

Osteopetrosis

Defects in osteoclast bone resorption causes increase in bone mass but results in poor quality thick sclerotic bone. Three distinct types are noticed; infantile (malignant), adult onset (benign) and intermediate. The first has an autosomal recessive inheritance, manifested in early life and is usually lethal. Skull and pelvis are sclerosed and obliterate brain foramens to give rise to neurologic symptoms. Involvement of sella turcica cause pituitary dysfunctions. Cranial nerve palsies of 3rd, 4th, and 7th nerves are also found. Serum calcium and urinary hydroxyproline remains normal, irrespective of the abnormal

bone resorption. Medullary bone spaces are reduced making the maxillofacial bones vulnerable to osteomyelitis after dental infections. Jaw fracture during tooth extraction is a potential complication. Teeth are defective with enamel/dentinal abnormalities and arrested root development [9]. Radiographicaly; when the jaws are involved, tooth roots are not visible due to osteosclerosis. Treatment involves calcitriol therapy, which stimulate inactive osteoclasts towards bone resorption. Corticosteroids and gamma interferons are also used for stimulating bone resorption.

Mucopolysaccharidoses

They are a group of lysosomal storage diseases (Type I-VII) with autosomal recessive or X linked type II inheritance. Defect lies in the degradation of glycosaminoglycans. Skeletal findings include dwarfism, stiff joint articulations involving jaw bones [10]. Accumulation of keratin sulfate and chondroitin-6-sulfate in connective tissue causes abnormalities in dental tissues. No definitive treatment exists for mucopolysaccharidoses, other than symptomatic and supportive.

Rickets

It includes a group of disorders in the vitamin D-calciumphosphorus axis that forms hypomineralized bone matrix due to defective endochondral bone calcification [11]. The pitfalls in bone mineralization of growth plates show as growth retardation. Vitamin D deficient rickets occur in infants and children. Adults show osteomalacia with under-mineralized bones from abnormal metabolism of vitamin D and phosphate. Another variant; vitamin D resistant rickets is a form of hypophosphatemia with reduced body height. The dental tissues show characteristic features like hypocalcified globular dentin and elongated pulp horns making teeth prone to caries and infections. Other findings are gingival fistulas, defective cementum and poorly defined lamina dura around tooth root. Histolgically, hypertrophic zones of growth plates show large number of disorganized cells termed as rachitic metaphysis, illustrating interferences in the calcification of osteoid matrix. Renal rickets occurs because of the inability of kidneys to synthesize 1-a-hydroxylase and convert 25-hydroxycholecalciferol to the active metabolite of vitamin D.

Hyper and hypoparathyroidism

Primary type results from the adenoma/hypertrophy of the gland, which is common in Type I and II Multiple Endocrine Neoplasia (MEN) syndrome [12]. Secondary hyperparathyroidism is because of the hyperplastic parathyroid glands and low serum calcium. It can occur at any age, but more common in 5-6th decades with high predilection for females. Features are bone pain, tenderness, muscle fatigue, weakness, spontaneous fracture, myalgia and osteoporosis with concomitant involvement of jaw bones [13]. Hypoparathyroidism on the other hand causes hypocalcaemia and hyperphosphatemia, leading to neuromuscular excitability. Circumoral numbness, paresthesia of distal extremities, muscle cramping, and carpopedal spasm/tetany are also found. Management of hyperparathyroidism is centered on reducing hypercalcemia.

Fibrous dysplasia

The disease begins in childhood with no distinct pattern of inheritance. It is a syndrome with precocious puberty, dermal pigmentation, and generalized skeletal dysplasia. Defect occurs in the bone forming mesenchyme where osteoblast maturation and differentiation are affected. It is mainly due to the mutation in the GNAS1gene; 20q13.2. It leads to hyper function of affected endocrines, premature puberty, hyperthyroidism, overproduction of growth hormones and cortisol [14]. It also causes high proliferation of melanocytes to form café-au-lait spots with irregular margins. The meduallry bone is replaced in fibrous dysplasia; appears radiolucent on radiographs characteristically described as ground glass appearance [15]. The disease presents as monostotic, polystotic, craniofacial and cherubism. Monostotic is the predominant one in which craniofacial bones is affected. The polystotic forms manifest as a mild Jaffe’s type and a severe Albright syndrome [16]. Cherubism, an autosomal dominant inheritance pattern is seen more in children. It presents with a broad and protruding/ bulging jaw with premature exfoliation of primary teeth, delayed eruption of permanent teeth and resulting malocclusion. Skull and facial bones are affected causing disfigurement and functional (eye) deficits like in maxillo-sphenoethmoido- frontal bone disease. The eye signs are because of the compression of the optic nerve within the optic canal [17]. Treatment involves correction of underlying endocrine disorders and functional deformities. Vitamin D and bisphosphonates are also given for bony lesions.

Craniofacial syndromes

Crouzon’s syndrome belongs to the group of craniofacial deformities known as craniosynostosis; which shows premature fusion of cranial sutures making a brachiocephalic skull. Fibroblast growth factor receptor gene (FGFR)-2 mutations could be responsible for Crouzon syndrome. This in turn causes increased intracranial pressure - brain damage/blindness and head shape deformities [18]. It is inherited as an autosomal dominant condition with mutations in the fibroblast growth factor receptors. Generally, it shows maxillary hypoplasia, high arch palate and bifid uvula. Ocular abnormalities include shallow orbits, bilateral ocular proptosis, hypertelorism, divergent strabismus, optical atrophy, conjunctivitis and loss of visual accuracy. Nystagmus, coloboma of the iris, anisocoria, microcornea/ megalocornea, cataract, blue sclera, and glaucoma and globe luxation is also seen. Other intracranial abnormalities include anomalous venous drainage and hydrocephalus. Calcification of the stylohyoid ligament, cervical spine C2-5/elbow/hand abnormalities and skin lesions also occur [19]. Decompression of cranium is done in increased intracranial hypertension. Plastic/cosmetic surgery of the face can resolve facial deformities to a large extent.

Hemifacial microsomia

It shows features like mid face flattening, deviation of nasal bone and chin, hypoplastic mandible, canting of occlusal plane, upper eyelid colobomas and sometimes cleft lip/palate [20]. When present with syndactyly, it is termed as Goldenhar’s syndrome.

Treacher collins syndrome (Mandibulofacial dysostosis)

This syndrome includes a group of disorders of the head and face with an autosomal dominant pattern of inheritance. It results from the disturbances in the differentiation of maxillary mesoderm. Gene responsible is 5q32-q33.1. Symmetrical deformity of the face is present with anti-mongoloid palpebral fissures, lower eyelid coloboma, external and middle ear hypoplasia, defective zygoma/mandible and dental malocclusion with open bite. Macrostomia, high palate, facial clefts are features. Characteristically, patients present with ’bird faces’ [21]. Though, there is no specific treatment, prognosis is good with most patients able to lead a normal life.

Pierre robin syndrome

It presents in a triad of micrognathia, glossoptosis, and cleft palate [22]. For the newborns, breathing is compromised because of tongue pressure on the epiglottis. Cleft palate arises due to the trap of tongue between the palatine processes. Prognosis is good if early childhood survives respiratory problems. Micrognathia tend to become less noticed with growth. Aural and ocular anomalies, congenital heart disease, and malformation of the extremities are related findings. The complex facial features are addressed through a multidisciplinary approach; with main focus on maintaining the patency of airway.

Achondroplasia

The disease is transmitted as an autosomal domain trait. It is caused by the mutation in the gene for fibroblast growth factor receptor: FGFR3; mapped to band 4p16.3. It presents with short stature, mid face hypoplasia, frontal bossing and malocclusion. Maxilla is retruded because of the growth restriction in the base of the skull [23]. Congenitally missing teeth are also noticed. Failure of endochondral ossification is evident in histology. However, if the patients survive initial years of life, they tend to lead a normal life.

Cleidocranial dysplasia

It is a congenital disorder of bone showing clavicular hypoplasia with narrow thorax. There is late ossification of the skull, delayed closing of sutures with large open fontanels [24]. It has an autosomal dominant pattern of inheritance, with rearrangement of long arm of chromosome 8(8q22) and another arm of chromosome 6. Mutations occurring in core binding factor alpha 1 gene, located on chromosome 6p21. Brachycephalic or wide skull is the feature. Calvarial thickenings of frontal, temporal and occipital bones, faulty development of brain foramens, dysplasia of paranasal sinuses are also seen. Maxilla, lacrimal and zygomatic bones are underdeveloped with high arch palate. Prolonged retention of deciduous teeth and delay in the eruption of successor teeth are noticed. The tooth root cementum also has defects. Crypt formation around impacted teeth and ectopic teeth are other findings [25]. Therefore, a multidisciplinary dental care is important for the normal development of dentition.

Down syndrome

It is a frequent form of mental retardation with intelligence quotient of 25-30 with specific Mongoloid features and related somatic defects due to chromosomal aberrations. Trisomy 21, chromosomal translocation and mosaicism are the three cytogenetic types [26]. Brachycephalic head, short stature, broad and short hands are the skeletal anomalies. Abdominal protrusion, delayed and incomplete puberty, congenital defects of heart polydactylia/ syndactylia are also seen. Oral manifestations include small mouth, macroglossia, maxillary hypoplasia, delayed tooth eruption, partial anodontia, enamel hypoplasia cleft lip/palate and juvenile periodontitis. Fissuring and thickenings of lips and angular cheilitis are also found [27]. 25% of the patients die during the first year of life out of respiratory infections and congenital heart disease. Oral care has an important role in the development of dentition and face.

Paget’s disease

It is inherited as autosomal dominant/recessive form. Age of onset of the disease is usually after 4-5th decades. There is increased resorption of bone by multinucleated osteoclasts and formation of irregular bones, which makes weak and deformed bones. Its symptoms are generally related to the compression of abnormal osseous tissues on adjacent structures. Pain and deformity of the lower extremities and fracture of femur and tibia are common. Head size increase and deafness secondary to osteosclerosis of the auditory system are also found. Hemorrhage from brittle abnormal bone can cause epidural/subdural hematoma [28]. Pelvis and spine are commonly affected. Pathological fractures, platybasia; soft cranial base sinking into cervical spine causing pain, numbness, defective gait, bladder and bowel incontinence are also frequent. A potential complication of abnormal bone is its malignant change into osteosarcomas, fibrosarcomas or rarely into giant cell tumors [29]. Radiographicaly, the findings can be a localized thinning and demineralization of bone known as osteoporosis circumscripta or a generalized and bizarre deformity involving several bones. It is described as a cotton wool appearance. A characteristic biochemical abnormality in Paget’s disease is the highly elevated serum alkaline phosphatase level. The oral manifestations are enlarged maxilla with wide alveolar ridges, flat palate and expanding jaws. Defects in alveolar bone and cementum can cause pathologic migration of teeth, root resorption, malocclusion and sometimes tooth loss. The altered bone apposition and resorption affects the fit of the dentures [30]. Vitamin, hormone, calcitonin, bisphosphonates and radiation therapy are traditionally used for this condition marked by pathologic fractures and degenerative joint diseases.

Eosinophilic granuloma

(Multifocal Hand-Schuller-Christian Disease and unifocal skeletal and extra skeletal lesions): This occurs in early life, marked by histiocyte proliferation in the skeletal/extra skeletal sites. Punched out bone destruction in skull is characteristic with exophthalmos and diabetes insipidus. Dysfunction of pituitary gland causing polyuria, dwarfism and infantilism are also noticed. Other features are facial swelling and asymmetry, sore mouth, ulceration, premature exfoliation of teeth and alveolar bone loss [31]. Dental conditions are corrected by the bony curettage of the lesions or by radiation therapy.

Muscle hyperalgesia, referred pain and neck musculoskeletal disorders: Transition of pain in musculoskeletal diseases from acute to chronic states is through peripheral and central sensitization, which manifests as tenderness and referred pain over a wider segment. Work place factors and their relationships to musculoskeletal disorders have been investigated, which have shown a correlation specifically with maxillofacial/neck shoulder diseases. Casual associations are there between repetitive work of these tissues which involve prolonged static loads/contraction and extreme working postures. A classical example is the back, neck and shoulder pain seen among dentists [32]. Seronegtaive spondyloarthritis are a group of related inflammatory joint diseases distinct from rheumatoid arthritis, which shows considerable overlap in their clinical features. Ankylosing spondylitis, a prominent condition of this group, secondary to chronic inflammatory arthritis, affects sacroiliac joint and spine, progressing to bony fusion of spine [33]. Osteomyelitis of facial muscles consequent to staphylococci, pseudomonas and mycobacterium tuberculosis infections are another important group [34].

Temporomandibular joint (TMJ) disorders

TMJ connects temporal bone of skull with the condyle of the mandible. It is termed either as a ginglymoid (rotation) or an arthrodial (gliding) joint. The fibro cartilaginous joint surfaces are separated by an articular disc. The movements of the joint are highly dependent on the dental occlusion between maxilla and mandible [35]. Developmental defects of the TMJ can be aplasia and/or hypoplasia of the condyle. It is treated with the help of orthodontic appliances in minor disorders to osteoplasty in severe conditions. Traumatic disturbances cause luxation and subluxation (complete and incomplete dislocation). In such cases, reduction is accomplished through relaxation of muscles followed by guiding condylar head by downward and backward movement beneath articular eminence. Ankylosis is another severe form of the TMJ disease owing to forceps delivery, chin trauma forcing condyle to glenoid fossa, malunion of condylar fracture, congenital syphilis etc [36]. Surgery is the only option in these cases.

Osteoarthritis of TMJ is associated with aging; where weight bearing joints are affected first [37]. Since TMJ is not a weight bearing joint, changes are induced in late stages only. Osteoarthritis involves a gradual deterioration of the joint cartilage with proliferation and remodeling of underlying bone. Pain, stiffness and loss of function are the main features. Degeneration of TMJ cartilage causes pain, clicking and altered dental occlusion leading to limited jaw opening. Tenderness is present over muscles of mastication/ sternocleidomastoid/trapezius. Concomitant dentofacial deformities like short mandible, cross bite/open-bite/asymmetry are also present. The disease shows degeneration of articular cartilage/disc /synovium/ subchondral bone through the mediation of neuropeptides, cytokines, serotonin and free radicals [38]. Supportive, symptomatic treatment is done for pain and discomfort, while condylectomy is considered for severe conditions. Rheumatoid arthritis of TMJ is another group, where females are affected more. It involves the synovial tissue between bones and joints. Though it is less prevalent than osteoarthritis, it manifests through severe symptoms. It destroys the joint cartilage and cause erosion of adjoining bone. Other systemic involvement is in the renal, vascular, ophthalmic and dental tissues. It is considered to have an autoimmune etiology. Inflammation originating from adjacent structures like otitis media, mastoiditis, osteomyeltits of temporal or condyle and radiotherapy also contribute to it. Rheumatoid arthritis affects oral health in multiple ways. Due to the restricted joint movement of hands, oral hygiene maintenance becomes difficult, which in turn invites dental caries, gingivitis and periodontitis. It also deteriorates the functioning of temporomandibular joint [39]. In children, rheumatoid arthritis cause malocclusion of protuberant maxilla, open bite, deformation of mandible with short body and reduction in the height of ramus. Periarticular fibrosis is another feature. Histolgically, disease is associated with invasion of granular tissue over articular surface and destruction of articular cartilage. Cartilage cells exhibit degeneration and destruction with bony exostoses. Remarkable improvement is noticed with administration of cortisone. If joint movements are limited, condylectomy can regain mobility.

TMJ syndrome is a common cause of facial pain second to tooth ache [40]. They form a set of disorders involving the TMJ and masticatory muscles characterized by pain, tenderness, clicking and limited mouth opening. It has a higher prevalence among adult females. Joint overload is the key factor for the initiation of TMJ syndrome. Etiology is multifactorial and includes malocclusion, jaw clenching, bruxism, psychologic disorders, stress and trauma. Osteoarthritis, rheumatoid arthritis and ankylosis also lead to it [41]. Therefore, a combination therapy involving self care practices for relieving muscle spasms and restoring joint coordination is required. Non steroidal anti-inflammatory drugs can be of good help for symptomatic relief. Costen’s syndrome is a type of TMJ disorder where the joint pain is either due to the posterior displacement of condyle causing pressure on the auriculotemporal nerve or due to the eccentric position of the condyle in the temporal fossa [42]. Temporomandibular disorders also present with ear complaints. This is due to the common features of TMJ and ear in terms of embryology, anatomy and function. Mostly, it is due to the same trigeminal innervation and by the auditory tube dysfunction. Associated findings are vertigo and tinnitus [43]. Musculoskeletal diseases of the cervical spine also affect the temporomandibular jaw functions [44]. A long styloid process often causes cervicofacial pain near ear and temporomandibular region with difficulty in swallowing known as Eagle’s syndrome [45]. Osteoporosis is a generalized condition marked by reduced bone density with propensity towards fracture. Decline of eostrogen in post menopausal women, accumulation of fat in bone marrow, genetic/ environmental factors, endocrine, and drugs are the chief causes. It also affects the maxillofacial skeletal tissues including TMJ [46]. Screening radiographs like transcranial views/ panoramic films, arthrography and tomograms/3D reconstructions/ stereolithography would show abnormalities of condylar head and temporal bone ankylosis/dysplasia/growth aberrations/trauma/ tumors. Arthroscopy would help in synovial fluid analysis and getting biopsy specimens [47]. MRI can complement the clinical diagnosis by rightly identifying the osteoarthritic changes of temporomandibular joint [48]. Symptomatic treatment is basic to temporomandibular disorders. Pharmacotherapy is useful for acute pain. Occlusal splints are helpful in harmonizing neuromuscular dysfunctions arising out of dental occlusion. Behavioral therapy is also used for managing chronic pain. A variety of pharmacologic agents are used. Tranquilizers, muscle relaxants, sedatives, and narcotics are given in serious and refractory cases. Dental appliances like occlusal splints/ night guards are used to aid in bruxism. Physical therapy involves exercises, external massages and other psychological means to address stress. Surgical options include arthroscopy, arthrocentesis, condylotomy, arthrotomy, coronoidotomy, coronoidectomy, styloidectomy and joint replacements with alloplastic implants [49- 51]. From the foregoing, it follows that musculoskeletal dysfunctions cause a major amount of disability among different age groups of population: newborns, infants, pre-adolescent/adolescents, adults and elderly. Some of them are fatal, while most of them significantly affect the quality of life. They are also marked by specific oral findings, which are often hallmark of the disease. Surprisingly, no definitive treatment exists for individual entities of these groups; which has its pathogenesis related to wide ranging causes as shown in (Table 1). A common thread unifying these disease groups would be their multidisciplinary treatment protocol; found effective in ameliorating the oral symptoms and in reducing the morbidity associated with these disorders.

Craniofacial clefts

They occur due to the partial/complete failure of facial processes during intrauterine development. Cleft lip deformity is caused by the non fusion of the maxillary and median nasal processes, whereas cleft palate occurs due to the defects in the fusion of palatine process with maxillary process [20].

Systemic lupus erythematosus

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by chronic inflammation mediated by auto antibodies and immune complexes towards organ damage affecting skin, kidney, blood cells and neural tissues. It manifests as a cutaneous (erythematous patches over face) systemic disorder with frequent ups and downs. Oral mucous membrane shows lesions similar to skin [52]. Genetic, environment and hormones can precipitate the immune dysregulation seen in lupus. Patients with SLE have autoantibodies against DNA, nuclear materials, ribosomes, platelets, erythrocytes, leukocytes etc. Since being a lifelong illness with possibility of end organ damage to vital organs, patients require long term monitoring to maintain quality of life.

Systemic sclerosis

Systemic sclerosis is a multisystem autoimmune disease. It causes peripheral and visceral vasculopathy and progressive fibrosis of the skin and internal organs like heart, lungs and kidney. It shows induration of epidermis to underlying subcutaneous tissues. Tongue, soft palate and larynx are involved. Dysphagia, limitation in mouth opening and lymphocytic infiltration of minor salivary glands are also seen [53]. No adequate treatment is available for progressive systemic sclerosis, but partial remissions are seen with cortisone therapy.

Sjogren’s syndrome

It is an autoimmune disease with wide ranging systemic manifestations [54]. Decreased lacrimal/salivary gland function, xerostomia, keratoconjunctivitis sicca, and parotid gland enlargement are the main findings. Primary Sjogren’s presents alone, whereas secondary Sjogren’s occurs along with autoimmune rheumatic diseases. Joint disease in primary Sjogren’s is of an intermittent polyarticular arthropathy type with arthralgias and myalgias. Extreme fatigue is highly troublesome for the patients. Other systemic involvement is with lungs, liver, kidneys, vasculature, and blood. Dry skin is a major feature. The main pathophysiology of Sjogren’s is chronic immune stimulation. B cell hyper reactivity is expressed through hypergammaglobulinemia and circulating autoantibodies. Organ specific autoantibodies are against salivary ducts, thyroid gland, gastric mucosa, erythrocytes, pancreas, prostate and nerve cells and they contribute to tissue dysfunction before inflammation is apparent. Histologically, there is focal lymphocytic infiltrate; T, B and plasma cells, with a predominance of activated CD4+ helper T cells, around the glandular ducts. They produce interleukins and tumor necrosis factor. Cough is often the main respiratory symptom after xerotrachea. Other pulmonary complications are lymphocytic alveolitis, interstitial pneumonitis, fibrosis, and pseudo lymphoma. In the renal involvement, it affects kidney tubules causing renal tubular acidosis. Interstitial inflammation is predominantly lymphocytic with fibrosis and tubular atrophy.

Neural origin of maxillofacial musculoskeletal diseases

Trigeminal neuralgia is a short duration severe pain in the maxillofacial area over the anatomical distribution of 5^th cranial nerve [55]. It is usually initiated by trigger zones, where older adults are affected more with a greater female predilection. A similar and severe type is glossopharyngeal neuralgia [56]. Burning mouth syndrome is a diffuse burning sensation of mucosa, lips and tongue in the absence of specific mucosal lesions [57]. It has a psychosomatic association with etiology being dry mouth, mucosal disorders, gastro esophageal refluxes, vitamin deficiency, diabetes, menopause and psychologic disorders/stress. Auriculotemporal syndrome is due to the damage of auriculotemporal nerve and subsequent re-innervation of sweat glands by parasympathetic salivary fibers, which causes gustatory sweating; of the face and temporal area during eating [58]. Bell’s palsy or 7^th cranial nerve syndrome is due to an abrupt/isolated/ unilateral peripheral facial nerve paralysis without specific cause. The affected corner of the mouth droops with drooling saliva and watering of the eye. Inability to close or wink the eye leads to infections. When patient smiles; paralysis becomes more obvious because corners of mouth do not rise nor close. Patient has a masked appearance [59]. Motors system diseases are a group of disorders with unknown etiology. They manifest with progressive muscular atrophy, amyotrophic lateral sclerosis and progressive bulbar palsy. They all undergo corticospinal, anterior horn cell degeneration with tongue and pharyngeal involvement. Muscular weakness, reflex loss, sensory disturbances, difficulty in speaking/swallowing, hoarseness of voice and impairment of palatal movements are also present [60]. There is no specific treatment for the motor system disease; many times it is fatal, though temporary remissions are also noticed. Atypical facial pain is a group of conditions in which there is a vague deep and poorly localized pain in the region supplied by 5th and 9th cranial nerve and 2^nd and 3^rd cervical nerves. Unlike neuralgias, it do not show trigger zones and the pain persists for weeks [61]. Tricyclic antidepressants give reasonable relief.

Muscular origin of maxillofacial musculoskeletal siseases

Muscle dystrophy involves the progressive degeneration of skeletal muscle fibers albeit normal neuromuscular junctions. Important types are: severe generalized familial muscular dystrophy- which begins in early child hood with inability to walk or run. It is rapidly progressing with facial muscular enlargement and weakness of extremities. The mild restricted muscle dystrophy on the other hand is a slowly progressing one with inability to close eyes even during sleep because of weakness of facial muscles. Lips develop looseness and protrusion with myopathic facies where patients cannot smile and whistle [62]. No definitive treatment exists for these groups of diseases. Myotonias imply failure of muscles to relax after cessation of voluntary contraction. 3 forms are there: dystrophic, congenital and acquired. Dystrophic myotonia show facial muscle weakness, ptosis of eyelids and atrophy of masseter/sternocleidomastoid muscles [63]. Massetric atrophy is generally seen in the lower half of the face with pharyngeal/ laryngeal involvement. Histology has enlarged and scattered muscle fibers, centrally placed nuclei in long rows, hypertrophy of fibers and degenerative changes like muscle proliferation/intense basophilic cytoplasm/phagocytosis [64]. Hemifacial spasm involves repeated, rapid painless irregular, non rhythmic contraction of facial muscles in adults due to a peripheral facial nerve lesion. It starts as brief transitory twitching of periorbital muscles triggered by fatigue/ tension/facial activity followed by sustained spasm that later spreads to entire half of the face. Opposite to these is reduction or complete absence of tone in facial muscles manifested as congenital variants in atonic diplegia, lipoid/glycogen storage diseases, Mongolism, cretinism and achondroplasia. Infantile muscle atrophy and dystrophy show loss of muscle tone [63]. Myasthenias generally denote abnormal weakness and fatigue in muscles following activity. Myasthenia gravis is an acquired autoimmune disorder characterized by weakness of skeletal muscle and fatigability on exertion, mostly in the middle aged women. Antibodies are directed towards acetylcholine receptor at neuromuscular junctions. It can also be of an idiopathic origin. Muscles of mastication and facial expression are involved and cause drooping of jaw, difficulty in deglutition, slurring speech, altered taste sensation, diplopia and ptosis [65]. Myositis is the inflammation of muscle tissue with infections as well as certain physical and chemical injuries. It can also be of an unknown origin as in dermatomyositis which shows characteristic calcinosis cutis, erythematous skin eruptions, edema, progressive muscle weakness with abnormal electromyograms (EMG). Diffuse stomatitis/ pharyngitis with telangiectatic lesions of vermillion border of the lip/ jaw muscles/tongue/pharynx are usual [66]. Heterotopic ossification is bone formation at abnormal anatomical sites. Traumatic myositis ossificans is an important type of it, which is normally preceded by an injury or trauma of the muscle. Myositis ossificans of masseter and temporal muscles occur as calcified lesions causing difficulties in mastication [67]. Fibromyalgia is another important group in the musculoskeletal diseases [68]. It is associated with sleep inability, as seen with decreased delta sleep. This is due to abnormal peripheral and central pain amplifications done through spinal cord via altered cerebrospinal fluid substance-P, 5-HT hydroxytryptamine/serotonin. It can also be due to a decrease in blood flow at the caudate and thalamus.

Vascular origin of maxillofacial musculoskeletal diseases

Systemic vasculitis involves the inflammation of nerves and blood vessels with damage to skin, kidney lung, heart, brain, and gastro intestinal tract. Bechet’s syndrome is prominent of them with oral ulcers and erythematous skin lesions [69]. When large vessels are affected, it is called giant cell arteritis [70], medium vessel involvement is as in classical polyarteritis nodosa and those in smaller vessels form microscopic polyangiitis, Wegener’s granulomatosis and Henoch Schonlein purpura [71]. Specific treatment is seldom found for these cases.

Maxillofacial musculoskeletal diseases: Treatment options

These deformities are treated by a team of maxillofacial surgeons, neurosurgeons, plastic surgeons, psychologists, ophthalmologists, speech and language therapists, orthodontists, audiologists, geneticists and nursing assistants. Maxillary osteotomies include Le Fort I, II and III surgeries to correct deformities in the Anteroposterior/ vertical/transverse planes. Mandibular osteotomies are done most often at ramus for advancement and set back sagittal split surgeries. Interpositional bone grafts are at times combined with any of these osteotomies. Adjunctive procedures like genioplasty enable correction of chin deformities [72]. (Table 2) shows the medical and surgical treatment options for maxillofacial musculoskeletal diseases; which features a common approach, either medical or surgical.

  

    
Non steroidal anti inflammatory 
      
(NSAIDS) drugs 
    
Disease modifying anti rheumatic drugs 
    
Biologic disease modifying anti rheumatic drugs
    
Surgical procedures for MSK diseases
  
  

    
Celecoxib100-200mg
    
Hydroxychloroquine 200-400mg
    
Anti TNF
    
Soft tissue release
  
  

    
Etoricoxib 60-120mg
    
Sulfasalazine 2-4g
    
Rituximab
    
Tendon repairs
  
  

    
Ibuprofen 600-1600mg
    
D-penicillamine 250-750mg
    
Abatacept
    
Synovectomy
  
  

    
Meloxicam 7.5-15mg
    
Methotrexate 5-30mg
    
Anakinra
    
Osteotomy
  
  

    
Naproxen 500-1000mg
    
Gold 50mg/month i.m
    
Tocilizumab
    
Excision arthroplasty
  
  

    
Indomethacin 50-200mg
    
Azathioprine 50-150mg
    

    
Joint replacement arthroplasty
  
  

    
Ketoprofen 100-200mg
    
Cyclophosphamide 0.5-1g i.v
    

    
Arthrodesis
  
  

    
Piroxicam 20-30mg
    
Ciclosporin 150-300mg
    

    

  
  

    

    
Corticosteroids
    

    

  

Table 2:  Current treatment protocols in maxillofacial musculoskeletal (MSK) diseases.