Traditional indications of some
\r\n\t
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Dr. Li’s research focuses on the vibration, fatigue, damage, fracture, reliability, safety and durability of aircraft and aero engine. In this research area, he is the first author of 184 SCI journal publications (49 JCR Q1), 8 monographs, 3 edited books, 3 textbooks, 3 book chapters, 30 Chinese Patents, 2 US Patents, 2 Chinese Software Copyright, and more than 20 refereed conference proceedings. 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Kawsar Alam",coverURL:"https://cdn.intechopen.com/books/images_new/6805.jpg",editedByType:"Edited by",editors:[{id:"199691",title:"Dr.",name:"Md. Kawsar",surname:"Alam",slug:"md.-kawsar-alam",fullName:"Md. Kawsar Alam"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"54028",title:"Chemical Composition and Biological Activities of Mentha Species",doi:"10.5772/67291",slug:"chemical-composition-and-biological-activities-of-mentha-species",body:'\nThis family includes about 260 genera and more than 7000 species. Their characteristic features include the stems which are quadrangular (square) in cross-section and the bisexual, zygomorphic bilaterally symmetrical flowers, composed of five united and deeply lobed petals and five united sepals; typically, the lower petal is larger than the others. The fruit is dry and woody, a schizocarp or drup. The distinctive strongly aromatic leaves are opposite with successive pairs at right angles (i.e., decussate) with margins entire or lobed. Many species of this family, such as mints, have important commercial uses for the culinary, pharmaceutical, herbal, and ornamental industries [1].
\nThroughout history, a number of mint species have been used around the globe for various properties. Peppermint oil is one of the world’s oldest herbal medicines. The gathering of dried peppermint dates back to at least 1000 BC, and its use is documented in the ancient Egypt, Greece, and Rome; in traditional Chinese medicine, the use of a local mint species,
The taxonomy of the genus
Most
Within the section
The five basic species comprising the genus
Šarić-Kundalić et al. [9] suggest a differentiation of the section
Besides its culinary uses, mint is also used in traditional systems of medicine. Mints are mainly used to cure gastrointestinal disorders, but the spectrum of medical activities is broader [9]. Mint was originally used as a medicinal herb to treat stomachache and chest pains, and it is commonly used in the form of tea as a home remedy to stimulate digestion; alleviate stomach pain; and treat biliary disorders, dyspepsia, enteritis, flatulence, gastritis, gastric acidities, aerophagia, intestinal colic, and spasms of the bile duct, gallbladder, and gastrointestinal tract [7, 10, 11]. Mint also aids digestion, notably of fats; in recent years, it has been often recommended for treating obesity. Mint tea is also a strong diuretic [7].
\nThe essential oil from
Other therapeutic effects attributed to a series of
Brazil | For the expulsion of parasitic worms, mainly | [13] | |
Morocco | Leaf and stem infusion for headache and tiredness | [14] | |
India | Stimulant, carminative, antispasmodic, fever, remedy in infantile troubles; the boiled leaves extract is used to relieve hiccup, flatulence, giddiness and as remedy for inflammation, bronchitis, to control vomiting during pregnancy | [15] | |
Turkey | Three or four cups daily between meals can relieve gastrointestinal complaints. This herb is considered stimulant, carminative, antispasmodic, and antidote for poisons. It has been reported as a remedy for inflammation, fevers, bronchitis, infantile troubles, vomiting in pregnancy, and hysteria | [16] | |
India | The boiled leave extract was counseled in the viral hepatitis, as analgesic known for its ability to enhance memory. Leaves are given for fever and bronchitis and are used as lotion in aphthae, as stomachic and diuretic, for gas pain, rheumatism, toothache, muscle pain, and mouthwash | [11] | |
France | Acquires a very powerful action on the nervous system | [17] | |
India | The plant is typically used in the treatment of loss of appetite, common cold, bronchitis, sinusitis, fever, nausea, and vomiting | [10] | |
Brazil | For expulsion of parasitic worms; mainly | [13] | |
Algeria | Stomachic, carminative, antiemetic, antispasmodic, tonic, antitussive, and insecticidal | [18] | |
Iran | Antiseptic for treatment of cold, sinusitis, cholera, food poisoning, bronchitis, and tuberculosis | [19] | |
Iran | In the treatment of flatulent dyspepsia and intestinal colic | [7] | |
Spain | Hypotensive | [20] | |
Morocco | Leaf and stem decoction was used in cold and for system digestive | [14] | |
France | Tonic, stimulative, stomachic, carminative, analgesic, choleretic, antispasmodic, anti-inflammatory, sedative, hypotensive, and insecticidal | [21] | |
Iran | Different parts of the plant (leaves, flower, stem, bark, and seeds) have been used as antimicrobial, carminative, stimulant, antispasmodic, antirheumatic, anticatarrhal, wound healing, deworming, insect repellent, antiemetic, sedative, diuretic, aphrodisiac, blood purifier and for the treatment of headaches, digestive disorders, tonsillitis, diarrhea, dysentery, abdominal disorders, constipation, gall stone, jaundice, toothache, flatulence, asthma, cough, dyspnea, common cold, fever, headache, general weakness, and bladder and kidney stones | [22] | |
India | Peppermint oil (as well as peppermint leaf) has been used internally as an antispasmodic (upper gastrointestinal tract and bile ducts) and to treat irritable bowel syndrome, catarrh of the respiratory tract, and inflammation of the oral mucosa. Externally, peppermint oil has been used for myalgia and neuralgia To relieve menstrual cramps and used externally for neuralgia, myalgia, headaches, migraines, and chicken pox | [23] | |
India | Peppermint plants have been used for many conditions, including loss of appetite, common cold, bronchitis, sinusitis, fever, nausea, vomiting, and indigestion | [10] | |
Finland | Peppermint uses include irritable bowel syndrome, flatulence, indigestion, nausea, vomiting, cough, and bronchitis | [24] | |
USA | The odors of peppermint serve as central nervous system stimulant and are used to decrease fatigue | [25] | |
India | Possess abortifacient property | [10] | |
Australia | Decoctions were used to treat colds and coughs while inhaling the crushed mint to relieve headaches; the plant is also used as an abortifacient | [26] | |
China | Various parts of the plant are used to treat sores and rashes on the skin, headache, red eyes, common cold, superficial visual obstructions, sore throat, mouth ulcers, and distension and oppression in the chest and the hypochondrium | [27, 28] |
Traditional indications of some
Mint is also used for buccodental prevention. During the middle ages, powdered mint leaves were used to whiten teeth [7]. Fresh mint leaves are used in chewing, for mouth burns; in decoction, it is used as mouthwashes to reduce gingival pain [29]. Mint is used in making oral dentifrices as it can provide overall freshness in breath. More studies are being done as to whether or not it directly contributes to preventing caries and plaque; however, it is confirmed that it does create an unfavorable environment for bacteria [23]. Moreover, peppermint applied to the gums of teething babies can help relieve distress and clean teeth [4].
\nMint oil and its constituents and derivatives are also used as flavoring agents throughout the world in food, pharmaceutical, perfumery, and flavoring industry [23]. Essential oils isolated from
Although some healthcare professionals believe that herbal medicines, such as the essential oil from
On the basis of recent rodent chronic studies [31], target organs for pulegone and menthofuran are the liver and kidney, and a plausible mechanism for toxicity is the formation of reactive metabolites, which is also supported by in vitro experimental data. According to the Committee of Experts on Flavoring Substances (CEFS), provisional consumption limits were established for pulegone at 20 mg/kg in food and beverages [32].
\nMenthol causes hepatocellular changes in rats. Inhalation of menthol can cause apnea and laryngeal constriction, a risk for infants. Contact sensitivity to menthol and peppermint with oral symptoms including burning mouth syndrome, recurrent oral ulceration, or a lichenoid reaction has been reported. The excessive inhalation of mentholated preparation has caused reversible nausea, anorexia, cardiac problems, ataxia, and other central nervous system (CNS) problems. Peppermint oil is contraindicated in obstruction of the bile ducts, gallbladder inflammation, and severe liver failure [23].
\nDose-dependent hepatotoxicity and nephrotoxicity were reported for
In Wistar rats, depending on dosage, the
Due to the major decrease of the potentially harmful pulegone and menthone by oven-drying, it is recommended that this herb should be oven-dried or cooked before consumption in order to reduce toxicity. Eating of the raw plant should be discouraged, particularly in patients with a history of liver disease or those taking cytochrome P450-inducing drugs [22].
The majority of studies on mint constituents focus on essential oils. Indeed, these compounds are widely used in different industries. Moreover, major polyphenols have also been investigated for interesting biological properties.
\nEssential oils are natural and volatile secondary metabolites characterized by a strong odor and a complex composition. They are usually obtained by steam or hydro-distillation from various aromatic plants, generally localized in temperate to warm countries like Mediterranean and tropical countries where they represent an important part of the traditional pharmacopoeia [34].
\nSeveral species of
Peppermint leaves typically contain 1.2–3.9% (v/w) of essential oil, with more than 300 identified compounds. The terpenic class is the most represented, comprising about 52% of monoterpenes and 9% of sesquiterpenes, whereas other groups, such as aldehydes (9%), aromatic hydrocarbons (9%), miscellaneous (8%), lactones (7%), and alcohols (6%), have been shown to be present in a smaller proportion. Among monoterpenes, menthol is the major constituent (35–60%), followed by menthone (2–44%), menthyl acetate (0.7–23%), 1,8-cineole (eucalyptol) (1–13%), menthofuran (0.3–14%), isomenthone (2–5%), neomenthol (3–4%), and limonene (0.1–6%), whereas β-caryophyllene is the main sesquiterpene (1.6–1.8%) [36]. Most of peppermint oil medicinal properties are ascribed to menthol, their major active component, while esters, such as menthyl acetate, provide the familiar minty taste and associated aroma [4].
\nTable 2 presents published compositions of some widespread mint essential oils with a more limited commercial interest, including
Carvone | Tunisia (50), China (47–65), Greece (59), Japan(62), Israel(58), India (73), Portugal (76),South Africa (55), India (50–77), Serbia (50), Pakistan (60–63), Turkey (50), Algeria (59), Morocco (29), India (49), Algeria (49) | [6, 35, 37–51] | |
Pulegone | Brazil (55) | [52] | |
Piperitenone oxide | Greece (36) | [53] | |
Piperitone | Turkey (22–28) | [54] | |
Pulegone | Portugal (35), Algeria (39), Japan (51), Switzerland (20–35),Greece (45–50), Portugal (78–81), Uruguay (73), Morocco (80),Iran (38), Greece (33–76), India (66–83), Bulgaria (27–50), Egypt (44), Algeria (4–87), Spain (41–42), Tunisia (61),Iran (41), Morocco (70), Algeria, Bejaia (70); Algeria, Bouira (71) | [41, 47, 55–72] | |
Menthone | Portugal (36) | [73] | |
Piperitone | Austria (70), Iran (38) | [19, 74] | |
Piperitenone | Greece (84–97) | [75] | |
Menthol | Tunisia (41–52), Greece (61–78) | [76, 77] | |
Carvone | Argentina (43), Finland (62), | [78, 79] | |
Trans-piperitone oxide | Italy (41), Japan (18–26) | [80, 81] | |
Algeria (28–31) | [82] | ||
Piperitol | Spain (58) | [83] | |
Piperitenone oxide | Japan (46), Japan (8–84), Morocco (0.9–56), Algeria (24–39) | [38, 84–86] | |
Lippione | Senegal (80) | [87] | |
Pulegone | Morocco (85), Tunisia (32) | [88, 89] | |
2,4(8),6-p-Menthatrien-2,3-diol | Cuba (15) | [90] | |
Menthol | Morocco (41) | [91] | |
Piperitenone | Algeria (55) | [86] | |
Trans-piperitone epoxide | Algeria, Bejaia (30) | [71] | |
Piperitone | Yugoslavia (39) | [92] | |
Pulegone | Tunisia (47), Senegal (52 and 42) | [12, 68] | |
Cis-piperitone epoxide | Turkey (18) | [93] |
Major constituents of the essential oils of some
Phenolic compounds, secondary metabolites ubiquitously distributed in plants, include a large group of biologically active compounds, with over 8000 molecules, either small or large and complex molecules, presenting at least one aromatic ring with one or more hydroxyl groups attached. These compounds often appear in their natural sources as esters and glycosides [94].
\nSpecies of the genus
Regarding phenolic acids, the genus
In an older study, external lipophilic methylated flavonoids have been extracted from dried leaves of
The phenolic composition of other species of different origins is summarized in Table 3.
Phenolic acids | Rosmarinic acid | Japan | [101] |
Veratric acid | China | [102] | |
Vanillic, homovanillic, hydroxybenzoic, syringic, 4-hydroxy cinnamic, trans-hydroxy cinnamic, 2-hydroxy cinnamic, and ferulic acids | Greece | [103] | |
Gallic acid | Greece | [104] | |
Protocatechuic acid | China | [105] | |
Gallic, chlorogenic, caffeic, vanillic, syringic, | Finland | [106] | |
Protocatechuic and vanillic acids | China | [107] | |
4-Hydroxy benzoic, caffeic, | Algeria | [99] | |
Flavonoids | Diosmetin, diosmin, diosmin-7-glucoside | India | [108] |
6,4′-trihydroxy-7,3′-dimethoxyflavone | Spain | [109] | |
5-Desmethoxynobiletin, 5,6-dihydroxy-7,8,3′,4′-tetramethoxyflavone, thymonin, sideritiflavone | Japan | [101] | |
5-Hydroxy-3′,4′,6,7-tetramethoxyflavone and thymonin | China | [102] | |
Naringenin, luteolin | Greece | [103] | |
Apigenin, rutin, catechin | Greece | [104] | |
Chrysoeriol, 5, 6-dihydroxy-7, 8, 3′, 4′-tetramethoxyflavone and nodifloretin | China | [105] | |
Rutin, quercetin, luteolin | Greece | [110] | |
Rutin, scopoletin | Czech Republic | [111] | |
Catechin, epicatechin, rutin, myricetin, luteolin, apigenin, naringenin | Malaysia | [112] | |
Rutin, naringin, luteolin, diosmin, naringenin, kaempferol, and diosmetin | Algeria | [99] | |
Lignans | Spicatolignan A and spicatolignan B | China | [113] |
Phenolic acids | Rosmarinic acid | France | [114] |
Rosmarinic, caffeic, and lithospermic acids | Poland | [115] | |
Rosmarinic and lithospermic acids | Poland | [116] | |
Rosmarinic, salvianolic, and dehydro-salvianolic acids | [117] | ||
Caffeic, syringic, gallic, vanillic, | USA | [25] | |
Caffeic acid, salvianolic acid B, protocatechuic acid glucoside, isosalvianolic acid A, prolithospermic acid, salvianolic acids (E and H/I), danshensu | Iran | [118] | |
Protocatechuic acid glucoside, caffeic, chlorogenic, rosmarinic, prolithospermic acids, salvianolic acid H/I, isosalvianolic acid A, salvianolic acid B, salvianolic acid E, and danshensu | Different origins | [24, 30] | |
Caffeic, vanillic, ferulic, and chlorogenic acids | Iran | [119] | |
Caffeic, | Mexico | [98] | |
Rosmarinic, caffeic, gallic, syringic, | Croatia | [120] | |
Caffeic, chlorogenic, 3-O-caffeoylquinic acids, salvianolic acid B, and salvianolic acid L | Portugal | [94] | |
Flavonoids | Luteolin 7-O-rutinoside, isorhoifolin, eriodictyol 7-O-glucoside, hesperidin, eriocitrin, narirutin, diosmin | France | [114] |
5,6-Dihydroxy-7,8,3′,4′-tetramethoxyflavone, sorbifolin, thymosin, thymonin, sideritoflavone, ladanein, xanthomicrol, acacetin, salvigenin, 5-O-demethylnobiletin | France | [121] | |
Luteolin 7-O-β-glucuronide, luteolin 7-O-rutinoside, isorhoifolin, eriodictyol, eriodictyol 7-O-β-glucoside, hesperidin, eriocitrin, narirutin, naringenin-7-O-β-glucoside | Poland | [115] | |
Luteolin 7-O-glucuronide | Poland | [116] | |
Luteolin 7-glucoside, luteolin 7-O-rutinoside, isorhoifolin, pebrellin, eriodictyol 7-O-glucoside, eriodictyol-7-rutinoside, 5,6-dihydroxy-7,8,3′,4′-tetramethoxyflavone | Portugal | [97] | |
Luteolin O-diglucuronide, luteolin O-glucuronide, methylated luteolin-glucuronide, luteolin-glucopyranosyl-rhamnopyranoside, eriodictyol-glucopyranosyl-rhamnopyranoside | Poland | [117] | |
Luteolin, luteolin 7-O-neohesperidoside, tricetin 3′-O-glucoside, 5′-O-rhamnoside, pebrellin, hesperidin, eriocitrin, narirutin, eriodictyol-7-rutinoside, gardenin D, isosafrole, kaempferol 7-O-rutinoside, 4′-methoxykaempferol-7-O-rutinoside | USA | [122] | |
Catechin, (−)-epigallocatechin gallate | USA | [25] | |
Luteolin O-diglucuronide, luteolin O-glucuronide, luteolin O-rutinoside, eriocitrin, narirutin, diosmin, myricetin O-glucoside | Iran | [118] | |
Luteolin-di-O-glucuronide, eriocitrin, luteolin-O-glucuronide, luteolin-O-rutinoside, narirutin, apigenin-O-rutinoside, diosmin, luteolin-O-glucuronide, myricetin-O-glucoside | Different origins | [24] | |
Rutin | Iran | [119] | |
Catechin, quercetin-4′-glucoside, (−)-epicatechin | Croatia | [120] | |
Gallocatechin-gallate, rutin, quercetin, naringin, hesperidin | Mexico | [98] | |
Luteolin-7-O-rutinoside, luteolin-7-O-glucuronide, luteolin-O-diglucuronide, eriodictyol-O-rutinoside and eriodictyol-O-hexoside, naringenin-7-O-rutinoside, eriodictyol-7-O-rutinoside | Portugal | [94] | |
Lignans | Medioresinol, medioresinol sulfate | Iran | [118] |
Stilbenes | Trans-resveratrol | Croatia | [120] |
Phenolic acids | Caffeic acid | Egypt | [123] |
Caffeic, vanillic, and ferulic acids | Greece | [104] | |
4-Hydroxy benzoic, caffeic, | Algeria | [99] | |
Flavonoids | Diosmin | France | [124] |
Thymonin, jaceosidin, pectolinaringenin, ladanein, sorbifolin, pedalitin, 5,6,4′-trihydroxy-7,3′-dimethoxyflavone; 5,6-dihydroxy-7,3′,4′-trimethoxyflavone; 5-hydroxy-6,7,3′,4′-tetramethoxyflavone, apigenin, luteolin, chrysoeriol | Algeria | [125] | |
Acacetin 5-O- | Egypt | [123] | |
Luteolin, diosmin, and kaempferol | Algeria | [99] | |
Apigenin, luteolin, naringenin, catechin | Greece | [104] | |
Phenolic acids | Caffeic, | Spain | [126] |
Caffeic, | Algeria | [99] | |
Flavonoids | Apigenin, luteolinidin, elargonidin, cyanidin, delphinidin, petunidin, luteolin | Spain | [126] |
Thymonin, thymosin, 5,6-dihydroxy-7,8,3′,4′-tetramethoxyflavone, jaceosidin, hispidulin, ladanein, sorbifolin, nodifloretin, apigenin, luteolin, genkwanin | Algeria | [125] | |
Esculetin | Czech Republic | [127] | |
Luteolin, diosmin, naringenin, kaempferol, and diosmetin | Algeria | [99] | |
Phenolic acids | Rosmarinic, salvianolic acid L, dedihydro-salvianolic acid | Poland | [117] |
Flavonoids | Luteolin-glucuronide, luteolin-diglucuronide, luteolin-glucopyranosyl-rhamnopyranoside, eriodictyol- glucopyranosyl-rhamnopyranoside, methylated luteolin-glucuronide | Poland | [117] |
5-Hydroxy-6,7,3′,4′-tetramethoxyflavone | Turkey | [128] | |
Phenolic acids | Rosmarinic, chlorogenic, and caffeic acids | Australia | [26] |
Flavonoids | Neoponcirin, narirutin, biochanin A, apigenin, hesperetin, and naringenin | Australia | [26] |
Phenolic acids | Rosmarinic, caffeic acid | China, Finland | [27, 129] |
China | [130] | ||
Flavonoids | Isoraifolin, luteolin-7-glucoside, menthoside | China | [27] |
Eriocitrin, luteolin-7- | Finland | [129] |
Phenolic composition of
Various other classes of compounds have been characterized and quantified in the mints.
Triterpenoids and steroids were also isolated from mints. So, two triterpenoids ursolic acid and uvaol and three steroids stigmast-5-en-3-
On the other hand, different pigments were identified and quantified in
Mint was also reported to contain sugars, saponins, alkaloids, anthraquinones, and quinines [136], but these absolutely surprising HPTLC-based phytochemical data as well as the identity/purity of investigated samples should be thoroughly verified.
The research over the past several years has shown that mint and its constituents possess different biological activities including antioxidant, antimicrobial, insecticidal, anticancer, and anti-inflammatory properties [10].
\nVarious types of compounds from aromatic and medicinal plants are receiving particular attention due to their radical scavenging properties. Reactive oxygen species (ROS) are chemical species formed in the body during metabolism that are highly reactive and may have one or more unpaired electrons. Oxidative stress, i.e., an imbalance between ROS and antioxidant defenses, has deleterious effects, such as the peroxidation of membrane lipids and the attack on biomolecules (proteins, membrane enzymes, carbohydrates, and DNA) [137].
\nVarious
Other tests are less used in literature to evaluate the antioxidant potential/radical scavenger capacity of
Ethanolic | [99, 144, 148] | |
Essential oil | [6] | |
Essential oil | [51, 71, 147] | |
Water Essential oil | [69] | |
Methanolic | [145, 149] | |
Methanolic | [149] | |
Methanolic | [145] | |
Essential oil | [140] | |
Ethanolic | [150] | |
Ethanolic | [142] | |
Ethanol/water | [139] | |
Methanolic | [145] | |
Ethanolic | [142] | |
Methanolic | [151] | |
Essential oil | [138] | |
Ethanolic, water | [141] | |
Acetone, acetone/water methanol, methanol/water, ethanol, ethanol/water | [146] | |
Essential oil | [138] | |
Ethanol, water | [141] | |
Acetonic | [25] | |
Essential oils | [51, 71] | |
[151] | ||
Water, ethanolic | [73, 141] | |
Essential oil | [73] | |
Essential oil | [89] |
Different methods applied to evaluate the antioxidant properties of
The most studied species are
The antibacterial and antifungal activities of
Thus,
The essential oil of
Besides, the essential oils from
The antibacterial or antifungal activity of
Mint is also known to exhibit insecticidal activity against a wide variety of insects.
Varma and Dubey [158] reported complete inhibition of
Several studies have indicated that
The cytotoxicity of essential oils from four
In another study, aqueous extract of
Lv et al. [25] also evaluated the antiproliferative activity of a peppermint extract against the human tumor cell line HT-29 (effective doses 250 and 500 μg/mL). Similarly, the cytotoxic effect of
In vivo, pretreatment of albino mice and female Wistar rats with
As early as 1922, Harvey Cushing distinguished two types of meningiomas: spherical
While meningiomas account for approximately 20% of all intracranial tumors in males and 38% in females (with a 2:1 female-to-male ratio) [9, 10], SOMs comprise between 4% and 9% of all meningiomas [11]. In a meta-analysis of 38 retrospective studies about SOM that included a total of 1486 patients, Fisher
In a review of the literature, Apra
Patients typically present with progressive, unilateral, and nonpulsatile proptosis (84%), often associated with cosmetic deformity [12, 15]. The frequent optic nerve (ON) disturbances result in unilateral decreased visual acuity (46%), constricted visual field (31%), and sometimes loss of color vision (5%) [12]. Ophthalmoplegia is seen in 25% of patients with SOM, often due to cranial oculomotor nerves deficit (oculomotor nerve 11%; trochlear nerve 6%; abducens nerve 4%). Diplopia can also be caused by intraorbital compression of the oculomotor muscles. Deficits in other cranial nerves (trigeminal, vestibulocochlear, and facial nerves) are less common. Finally, other general neurological signs, such as headaches (25%) and epileptic seizures (4%), are observed in patients with SOM.
Skull radiographs were historically used to diagnose SOM by demonstrating unilateral sphenoid hyperostosis. With the emergence of computed tomography (CT) and magnetic resonance imaging (MRI), these techniques became the standard before any surgical procedure involving the removal of a SOM.
CT precisely demonstrates the bone features of the SOM, as well as its extension (Figures 1 and 2). Using CT, the involvement of the orbit walls, floor of the middle cranial fossa (including the foramens rotundum and ovale), SOF, ACP, and optic canal can be easily identified.
(a) Axial contrast-enhanced T1-weighted magnetic resonance imaging demonstrates thickening of the temporopolar dura mater on the right side, with a deviated optic nerve compared to the left side. A temporopolar arachnoid cyst is seen on the left side. (b) Axial computed tomographic scan shows hyperostosis of both the lesser and greater sphenoid wings, sparing the anterior clinoid process. Proptosis can be easily measured on axial brain slices passing through the lens on both sides, by firstly taking as reference the line joining the two lateral orbital margins. This line is then projected to the level of each cornea and the distance between these two new lines is measured, giving an accurate and relevant estimate of proptosis for follow-up.
(a) Axial contrast-enhanced T1-weighted magnetic resonance imaging demonstrates a large right spheno-orbital meningioma with middle sphenoid wing center, invading the temporal fossa (TF), the superior orbital fissure (SOF), and the orbit (O). There was no true invasion of the optic canal (OC) by the meningioma on thin-section MRI analysis. (b) Axial computed tomographic scan shows hyperostosis of the lesser and greater sphenoid wings (L&GSW) and anterior clinoid process (ACP) on the right side.
MRI completes the radiological assessment, showing the globoid or plaque-like shape of the intradural portion of the meningioma and its impact on the brain parenchyma (mass effect and edema). The epicenter of the tumor on the sphenoid wing is identified, and the specific involvement of the temporal and infratemporal fossae, orbit, SOF, optic canal, and CS is determined. At this stage, it is important to differentiate between simple involvement of the lateral wall of the CS and true intracompartment invasion. Similarly, the presence of meningioma within the optic canal or SOF should be similarly distinguished from tumor bony involvement of these structures (Figures 1 and 2). All of these details are critical, as they contribute to the planning of the upcoming surgical procedure for optimal tumor resection.
A comprehensive preoperative ophthalmological exam is mandatory and should include at least an objective assessment of visual acuity and field, a dilated-pupil fundus examination and ideally an optical coherence tomography (OCT). The Lancaster red-green test for assessment of oculomotor muscle function is performed according to the presence of diplopia. Accurate measurement of the proptosis can be achieved with an exophthalmometer or with correctly oriented cerebral imaging (Figure 1).
At this time, differential diagnosis for hyperostosis due to SOM should also be considered. These include fibrous dysplasia, osteoma, osteoblastoma, Paget’s disease, hyperostosis frontalis interna, osteoblastic metastases, and erythroid hyperplasia [15].
As with all other meningiomas, the decision-making process for SOM must be tailored to each patient. Mass effect of the tumor, age, general condition, comorbidities, symptomatology, its impact on daily life, and the patient’s wishes must be taken into account. In cases with absent or mild symptoms without mass effect on imaging, simple clinical and radiological monitoring can be chosen initially, with patient follow-up on a regular basis (every 3–6 months). In contrast, the presence of optic neuropathy, severe neurological symptoms, significant proptosis, or serious mass effect warrants surgical operation. Although a subject of debate, optimal surgical resection remains the current reference treatment for SOM, in accordance with the general EANO (European Association of Neuro-Oncology) guidelines for the management of meningiomas published in 2016 [16]. If the patient is in a fragile state of health or categorically refuses the operation, radiation treatment may be offered as an alternative. The choice of technique is then mainly based on the tumor volume, stereotactic radiosurgery being preferred for smaller tumors and radiotherapy being preferred for larger tumors. To summarize this reasoning, we propose a simple algorithm highlighting the main points to be taken into account during decision-making in cases of SOM (Figure 3).
Decision-making algorithm of first-line treatment for spheno-orbitary meningiomas, in accordance with the 2016 EANO guidelines [
Despite their common features, SOMs are a heterogeneous group of tumors due to the complex anatomy of the sphenoid bone, which is a part of both the skull base and the orbit. Few attempts have been made to classify SOMs. Roser
Classification of spheno-orbital meningiomas according to their morphology (a), sphenoid wing epicenter (b), and specific extensions (c).
The patient is placed in a supine position with the head rotated 30° to the contralateral side and fixed in a three-pin Mayfield head-holder. The neck is slightly extended to 15°, as is done for a classical pterional approach. Neuronavigation is used to delineate the craniotomy and skin incision. We recommend using millimeter slices of the bone window of the CT scan for registration, to both highlight bone tumor extension and increase the accuracy of this technique [19, 20]. The CT scan is then merged with the MRI, including the gadolinium-enhanced 3D T1-weighted sequence, for intra- and extracranial tumor extensions (Figure 4). A paraumbilical field is prepared and draped to harvest abdominal fat for closure if needed.
The frontotemporal arciform incision starts 1 cm in front of the tragus, with the medial extent adjusted to the size of the surgical target. The scalp is progressively elevated in one layer and reclined forward, preserving the pericranial tissue for dural repair at the time of closure. A standard interfascial dissection is performed over the anterior quarter of the temporal muscle in order to spare the frontotemporal branches of the facial nerve [21, 22]. The orbital rim and zygomatic arch are progressively exposed in a subperiosteal manner. The temporal muscle is incised along the lateral orbital rim, along the superior temporal line, and at its posterior part along the skin incision. Retrograde dissection of the temporal muscle is performed using a cutting spatula from anterior to posterior and from inferior to superior in order to preserve the deep vascularization and innervation of the muscle and thus prevent postoperative atrophy [23]. Tumor-infiltrating of the muscle (1.) temporal fossa extension) must be resected at this stage. If the infratemporal fossa is invaded by the meningioma (2.) infratemporal fossa extension), the zygomatic arch must be cut anteriorly and posteriorly, maintaining its attachment to the masseter muscle, in order to recline the temporal muscle downwards as much as possible. This optional step facilitates resection of the tumor portion located in the infratemporal fossa, with particular attention to the mandibular nerve exiting the foramen ovale. In cases of major invasion of this location, the collaboration of an ear, nose, and throat surgeon is required.
Depending on the extension of the intraosseous portion of the SOM, either a classical pterional craniotomy or a more complex orbitozygomatic approach is performed [24]. Guided by neuronavigation, the tumor-infiltrated bone must be resected as completely as possible using a high-speed drill and rongeurs, without overlooking the craniotomy part. The lateral wall and the roof of the orbit are drilled, initially respecting the periorbita (Figure 5). The intraorbital tumor extension (3.) mostly remains extraconal and can therefore be easily removed once the orbit is correctly opened. Nevertheless, the periorbit must be longitudinally opened and resected in cases of intraconal invasion [25]. If the tumor adheres too much to the cranial nerves, it is recommended to leave a residue in place to avoid postoperative deficits. The drilling continues medially at the level of the greater and lesser wings of the sphenoid bone, opening the SOF (4.), and inferiorly at the level of the floor of the middle cranial fossa, opening the foramens rotundum and ovale if necessary. With the involvement of the ACP (5.) and the invasion of the optic canal (6.), an extradural anterior clinoidectomy, which is carried out under magnification and constant irrigation, must be performed to optimize the decompression of the ON and prevent thermic lesions [26]. This step also allows the surgeon to extradurally split the lateral wall of the CS (7.) when there is a tumor at this level, in order to improve the devascularization of the meningioma.
Intraoperative views of the resection of a left sphenoid-orbital meningioma with invasion of the anterior clinoid process (ACP), optic canal, and orbit. (a) Left pterional approach with drilling of the lesser sphenoid wing (LSW) and lateral wall of the orbit, in order to open the superior orbital fissure (SOF). The orbito-temporal periosteal fold is then identified at the external part of the SOF and divided to optimize the retraction of the frontal and temporal lobes and expose the contours of the ACP. (b) The final step of the extradural resection of the ACP. The LSW, optic strut, and roof of the optic canal were drilled before resecting the bony content inside the ACP. A thin shell of bony contour is preserved in order to remove the clinoid tip en bloc. (c) Once the drilling is completed, the orbit is properly exposed in continuity with the SOF and optic canal which have been opened. (d) The dura mater is opened in an arciform fashion, revealing the intradural portion of the meningioma (asterisk). (e) The dura mater of the optic canal is gently opened with a fine scalpel to remove the tumor fragments compressing the optic nerve at this level. (f) At the end of the procedure, the chiasma and the two optic nerves are correctly exposed. The coagulated portion of the dura mater at the level of the tuberculum sellae can be seen (asterisk; Simpson grade 2 resection).
The dura mater is opened in a curvilinear fashion and the intradural portion of the tumor is progressively resected using conventional microsurgical methods, alternating debulking and peripheral dissection from the brain parenchyma and vessels. An additional dural incision directed medially toward the optic canal may cautiously be performed to complete the extradural anterior clinoidectomy. Once the optic canal has been widely opened intradurally (Figure 5), the tumor fragments at this level can be easily removed using a small blunt hook.
Complete resection is not always possible due to true intracavernous invasion (as opposed to a simple extension to the lateral wall) or excessive tumor adherence in the SOF or optic canal. In such situations, the key is to optimally decompress the ON so that the residual tumor can later be effectively treated with radiation therapy. The radiosensitivity of the ON justifies the creation of a safety zone around it, in order to avoid deleterious iatrogenic irradiation during radiation treatment. It is essential to preserve the function of the cranial nerves as much as possible, as their postoperative recovery is often uncertain.
If the ethmoidal or sphenoidal sinuses are open during the extradural steps, either autologous fat or a temporal muscle graft should be harvested to plug the defect, depending on the size of the opening (for example, the muscle should be used for a small aperture of a pneumatized ACP and fat should be used for a large sinus opening secondary to intranasal tumor invasion). A synthetic fibrin sealant may be used in addition to these measures to prevent postoperative cerebrospinal fluid leakage. The dural and periorbital defects are ideally managed using a vascularized and pedicled pericranial graft that is rotated over the orbit. Alternative solutions include using the temporal fascia or synthetic dura patches. Finally, the remaining dead space left by the tumor removal can be filled with a fat graft.
Bone reconstruction for SOM is often more complex than for other meningiomas due to the extensive bony resection, which sometimes involves the superior and lateral orbital rims. Various options are available to perform cranioplasty and obtain a satisfactory cosmetic result. If the orbital margins are intact, the healthy part of the craniotomy can be replaced using grids that are cut to a suitable shape and serve as anchor points for the reinsertion of the temporal muscle. For larger defects, hydroxyapatite cement can be shaped easily. A custom-made polymethylmethacrylate or polyetheretherketone (PEEK) prosthesis can be ordered before the procedure, especially when the orbital rims are planned to be resected. The design of the prosthesis can also compensate for temporal muscle atrophy by incorporating an increased thickening at the level of the temporal fossa. Trimming of the edges of the prosthesis is often required to perfectly match the craniotomy. The zygomatic osteotomy must be reattached with standard plates before reinserting the temporal muscle and suturing the scalp in layers according to the usual technique.
The first postoperative night is ideally spent in an intensive care unit, so that the patient can be closely monitored, and any respiratory, hemodynamic, or neurological failures can be detected at an early stage, particularly in the event of a surgical site hematoma. Most postoperative complications of SOM are related to the cranial nerves affected by the tumor. In their meta-analysis of retrospective series of operated SOM, Fisher
In most cases, SOM surgery stabilizes or improves visual function. In a large retrospective study of 130 patients, Terrier
Regarding oculomotion, the reporting of results is generally less detailed, but seems to indicate a long-term improvement of the preoperative symptomatology that could reach 96% (although the degree of this improvement was not specified) [12]. Postoperative oculomotor deficits are frequent, varying from 8 to 68% depending on the series, but they recover in the majority of cases and persist in only 0–17% of cases [6, 11, 30, 31].
Proptosis, the most common sign encountered in patients with SOM, may be explained by different, yet interrelated, factors. From a mechanical point of view, the bony involvement of the orbital walls and the intraorbital tumor extension exert a direct mass effect on the eyeball. From a vascular point of view, the meningioma invasion of the SOF is responsible for a decrease in venous drainage and subsequently exacerbates the proptosis by increasing the intraorbital venous engorgement [32, 33]. This multifactorial physiopathology may explain the varied results from retrospective clinical series, which report improvements ranging from 50 to 100% [34, 35, 36, 37, 38, 39]. Thus, if mechanical compression is relieved by surgical opening of the orbit and resection of the intraorbital portion of the tumor, exophthalmos will certainly improve. Nevertheless, it is rare that the proptosis recovers completely, likely due to persistent disturbances of venous drainage and potential trophic disorders of the oculomotor muscles. Removal of the periorbit appears to have a beneficial effect and seems to be a key factor in reducing proptosis [29].
The quality of surgical resection of meningiomas, assessed by Simpson’s grading system, remains an important prognostic factor in the evolution of these tumors, regardless of the histological subtypes considered [40, 41]. Gross total resection, defined as Simpson grade I to III, is achieved in 25–70% of SOM cases depending on the series [34, 42, 43, 44]. Given the complex anatomy of the spheno-orbital region, Simpson grade I or II resections are rarely feasible without risking the induction of cranial nerve deficits, especially at the level of the orbital apex, SOF, and CS [43]. In this context, the current trend is strongly in favor of symptom-oriented surgery rather than radical surgery, targeting optic nerve decompression to improve visual function, and intraorbital tumor resection to reduce proptosis [30, 32].
Histologically, SOMs are commonly World Health Organization (WHO) grade I tumors (77–100%, depending on the series), with the meningothelial subtype being the most frequent [11, 13, 28, 43]. Although much less frequent, WHO grade II (atypical) or III (anaplastic) meningiomas may be encountered, together representing 11% of the cases in the retrospective series presented by Belinsky
The highly variable recurrence rate of SOM in the scientific literature, ranging from 10 to 56%, is likely due to differences in the follow-up duration [34, 47, 48, 49]. Indeed, the risk of recurrence logically increases with the duration of follow-up (6% at 3 years and 46% at 6 years after the intervention) [28].
The role and timing of radiation therapy remain a matter of debate for meningiomas in general and SOM in particular. However, experts (Response Assessment in Neuro-Oncology Committee) agree on the importance of using adjuvant radiotherapy for WHO grade III meningiomas, regardless of the quality of surgical resection [40]. For WHO grade II meningiomas, the European Association of Neuro-Oncology guidelines recommends observation or fractioned radiotherapy in cases of gross total resection and fractioned radiotherapy in cases of subtotal resection [16]. For WHO grade I meningiomas, simple observation is indicated after gross total resection, and stereotactic radiosurgery or fractioned radiotherapy may be proposed after subtotal resection. We suggest radiological monitoring of the tumor residue for subtotal resections of WHO grade I meningiomas initially. Stereotactic radiosurgery is then justified in cases of objective progression. Cases of meningiomas of WHO grade II or III must be discussed in a collegial manner in a multidisciplinary consultation meeting.
Spheno-orbital meningiomas are usually slow-growing skull base tumors revealed by proptosis or visual impairment. They typically present with significant tumoral spheno-orbital hyperostosis and a globoid or
ACP | Anterior clinoid process |
CS | Cavernous sinus |
CT | Computed tomography |
MRI | Magnetic resonance imaging |
OCT | Optical coherence tomography |
ON | Optic nerve |
SOF | Superior orbital fissure |
SOM | Spheno-orbital meningioma |
WHO | World Health Organization |
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On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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