10.14639/0392-100X-suppl.1-41-2021-07
Intracranial complications of sinonasal inflammatory disorders are relatively unusual but can cause significant morbidity and mortality. They often occur in patients with comorbid disorders and immunocompromised but also people without risk factors can be affected. Intracranial complications of acute rhinosinusitis are rare, probably due to oral antibiotics availability, but are less predictable as they often occur in immunocompetent patients without comorbidity. Their management requires a multidisciplinary approach to plan and customize the therapeutic treatment. Intracranial complications of chronic rhinosinusitis are more predictable as they occur often in immunocompromised patient with particularly risk factors. For this reason, a multidisciplinary approach it’s important for treatment and mostly for prevention. The aim of this paper is to present an overview of different multidisciplinary management of intracranial complications of sinonasal inflammatory disorders according to their etiology and severity.
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Ernesto Pasquini
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ACTA Otorhinolaryngologica Italica
nasal endoscopy
When is a multidisciplinary approach required in management of intracranial complications of sinonasal inflammatory disorders?
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Ernesto Pasquini
2021/05/14
10.14639/0392-100X-suppl.1-41-2021-07
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ENT Unit, Surgical Department, AUSL Bologna, Italy
1827-675X
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When is a multidisciplinary approach required in management of intracranial complications of sinonasal inflammatory disorders?
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ACTA OTORHINOLARYNGOLOGICA ITALICA 2021;41(SUPPL.1):S67-S75; doi: 10.14639/0392-100X-suppl.1-41-2021-07




When is a multidisciplinary approach required
in management of intracranial complications
of sinonasal inflammatory disorders?
Quando è richiesto un approccio multidisciplinare nella gestione delle complicanze
intracraniche delle patologie infiammatorie nasosinusali?
Carla De Vita1, Giacomo Sollini1, Matteo Zoli2, Diego Mazzatenta2, Ernesto Pasquini1
1
 ENT Unit, Surgical Department, AUSL Bologna, Italy; 2 Center of Pituitary & Endoscopic Skull Base Surgery IRCCS Neuroscienze di
Bologna, Italy


SUMMARY
Intracranial complications of sinonasal inflammatory disorders are relatively unusual but
can cause significant morbidity and mortality. They often occur in patients with comorbid
disorders and immunocompromised but also people without risk factors can be affected.
Intracranial complications of acute rhinosinusitis are rare, probably due to oral antibiot-
ics availability, but are less predictable as they often occur in immunocompetent patients
without comorbidity. Their management requires a multidisciplinary approach to plan and
customize the therapeutic treatment. Intracranial complications of chronic rhinosinusitis are
more predictable as they occur often in immunocompromised patient with particularly risk
factors. For this reason, a multidisciplinary approach it’s important for treatment and mostly
for prevention. The aim of this paper is to present an overview of different multidisciplinary        Received: November 7, 2020
management of intracranial complications of sinonasal inflammatory disorders according                Accepted: January 31, 2021
to their etiology and severity.
                                                                                                      Correspondence
KEY WORDS: intracranial complications, rhinosinusitis, multidisciplinary management,                  Carla De Vita
nasal endoscopy                                                                                       ENT Unit, Surgical Department, AUSL Bologna,
                                                                                                      Italy
                                                                                                      E-mail: carla.devita@hotmail.it
RIASSUNTO
Le complicanze intracraniche delle patologie infiammatorie nasosinusali sono relativamente            Funding
rare, ma presentano un’elevata mortalità e morbidità. Si verificano in soggetti immunode-             None.
pressi o con diverse comorbidità, ma anche in soggetti immunocompetenti senza particolari
fattori di rischio. Le complicanze intracraniche derivanti da rinosinusite acuta sono rare,           Conflict of interest
verosimilmente per la disponibilità di antibiotici per via orale, ma sono le più imprevedibili,       The Authors declare no conflict of interest.
poiché spesso si verificano in soggetti immunocompetenti e senza particolari comorbidità. Ri-
chiedono una gestione multidisciplinare che coinvolge diversi specialisti per pianificare l’iter        How to cite this article: De Vita C, Sollini G, Zoli
terapeutico che deve essere personalizzato in base alla gravità e all’estensione della patolo-          M, et al. When is a multidisciplinary approach re-
gia. Le complicanze intracraniche derivanti da rinosinusiti croniche sono più prevedibili e si          quired in management of intracranial complications
verificano in pazienti con particolari fattori di rischio. Per tale motivo è importante per gli al-     of sinonasal inflammatory disorders? Acta Otorhi-
tri specialisti riconoscere i primi sintomi per coinvolgere prontamente lo specialista ORL che          nolaryngol Ital 2021;41(SUPPL.1):S67-S75.
ha un ruolo importante per la diagnosi e il trattamento chirurgico. Lo scopo di questo lavoro           https://doi.org/10.14639/0392-100X-sup-
è quello di fornire una panoramica sulla diversa gestione multidisciplinare delle complicanze           pl.1-41-2021-07
intracraniche delle patologie flogistiche nasosinusali in base all’eziologia e alla loro gravità.
                                                                                                      © Società Italiana di Otorinolaringoiatria
PAROLE CHIAVE: complicanze intracraniche, rinosinusite, gestione multidisciplinare,                   e Chirurgia Cervico-Facciale
endoscopia nasale
                                                                                                                     OPEN ACCESS

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Introduction                                                                                          Commercial-NoDerivatives 4.0 International) license. The
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                                                                                                      ning the license, but only for non-commercial purposes and
Sino-nasal inflammatory disorders can potentially spread to any surrounding                           only in the original version. For further information: https://
structures, including orbital and intracranial cavity 1. Orbital complications are                    creativecommons.org/licenses/by-nc-nd/4.0/deed.en




                                                                                                                                                              S67
C. De Vita et al.




more common but intracranial complications of sino-nasal        mechanism described in literature 1,5,9. Direct spread is less
inflammatory disorders (ICSID) are the most serious and         common, it occurs through either a bony defect or infec-
life-threatening.                                               tion of bone lying between the sinuses and the intracranial
ICSID are relatively unusual due to the wide availability       space. The mechanism of indirect spread is thrombophle-
and use nowadays of antibiotics. However these complica-        bitis of the valveless diploic veins that drain the parana-
tion may still occur in the clinical practice and represent a   sal sinuses. Infection then can spread intracranially either
severe condition that can cause significant morbidity and       by propagation of the thrombus or by the release of septic
mortality if not promptly recognized 2-4.                       emboli 10. The indirect spread has been most frequently
ICSID include epidural abscess, subdural abscess, intracer-     reported in immunocompetent, young male patients. This
ebral abscess, meningitis, and cavernous or superior sagit-     predisposition is probably related to their highly vascular-
tal sinus thrombosis 5.                                         ized diploic venous system that allows indirect intracranial
In case of intracranial involvement it is vital to achieve      extension through propagation of septic thrombophlebi-
an urgent diagnosis in order to start as soon as possible a     tis 11. Complications are most often secondary to frontal
proper treatment. The management of these cases requires        sinusitis 7, but they can also occur in odontogenic sinusi-
a multidisciplinary approaches in every single phase 6. Oto-    tis 12. Intracranial complications are relatively rare in pedi-
laryngologist, radiologist and neuroradiologist, infectious     atric populations and mostly affect older children, probably
disease specialist, hematologist, neurologist, neurosurgeon,    because the frontal sinuses are the last paranasal sinuses to
maxillo-facial surgeon/odontologist: all these figures and      develop. They are generally detectable after five years of
others can be involved from the diagnosis to the treatment.     age and are poorly developed until the age of 10 13. Usually,
Otolaryngologist and neurologist are involved in the clinical   polymicrobial infections caused frequently by Streptococ-
diagnosis of ICSID; radiologist and neuroradiologist help to    cus, Staphylococcus, anaerobic gram-positive cocci, and
define and locate the primary site of infection and the type    anaerobic gram-negative bacilli, are responsible for these
of complications; otolaryngologist, neurosurgeon and max-       complications 9,14.
illo-facial surgeon are involved in the surgical management
of the patient while infectious disease specialist, neurolo-    Complications and symptoms
gist, hematologist and clinicians are involved in the medical   Out of the many intracranial complications of ABRS, sub-
management of the infection and patient comorbidities.          dural empyema is the most common one. It occurs as an ex-
There is no universally accepted treatment paradigm for IC-     tension of acute or subacute frontal sinusitis and mostly af-
SID and that’s why the best treatment is probably achieved
                                                                fects healthy adults. If a rapid progression of this infection
via an inter-disciplinary perspective 1. Generally speak-
                                                                occurs, it can lead to increased intracranial pressure and
ing, complications of chronic rhinosinusitis (CRS) are
                                                                subsequent neurologic deficits or death. Epidural abscess is
relatively common but ICSID are typically a complication
                                                                the most common intracranial complication of sinusitis in
of acute bacterial rhinosinusitis (ABRS) rather than CRS
                                                                children, symptoms are similar to those of subdural empy-
and usually involve indirect spread through hematogenous
                                                                ema but less severe 3. Epidural and subdural empyema can
routes rather than direct spread intracranially through bony
                                                                spread to the brain parenchyma and cause cerebritis and
defects 7.
                                                                development of brain abscess. Cavernous venous thrombo-
                                                                sis is known as the V stage of Chandler classification as a
Intracranial complications of ABRS                              result of orbital cellulitis, but it can also be a complication
Intracranial complications include Pott’s puffy tumor, sub-     of sphenoid, ethmoid, frontal or odontogenic sinusitis as
dural empyema, epidural abscess, brain abscess, cerebritis,     a result of indirect spread mechanism and can lead to the
meningitis and cavernous venous thrombosis. They are rare,      other intracranial complications 15.
probably because of the worldwide availability of oral anti-    Symptoms frequently observed are fever, headache and
biotics, and are estimated at 3 cases per million of popula-    mental status changes and are related to increased intrac-
tion 8. Nevertheless, complications continue to occur, par-     ranial pressure, meningeal irritation, and cerebritis 15.
ticularly in children or those individuals who are relatively   Headache is the most common sign of cerebritis, whereas
immunocompromised 7 but can also be seen in adults without      fever and altered mental status are less common. Further
comorbidity.                                                    neurologic deficits may be identified in accordance with
                                                                the affected brain area. Finally, many patients can devel-
Etiologic mechanisms                                            op seizure activity as a result of increasing intracranial
Direct and indirect spread are the two major etiologic          pressure.



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                        When is a multidisciplinary approach required in management of intracranial complications of sinonasal inflammatory disorders?




Multidisciplinary management
Prompt recognition of intracranial complications of ABRS
and multidisciplinary management are extremely impor-
tant. Imaging is mandatory if central nervous system com-
plications are suspected (CT and contrast enhancement
MRI).
Diagnosis and treatment require collaborations between
otolaryngologists, infectious disease specialists and neu-
rosurgeons; when there is an odontogenic sinusitis it also
include maxillo-facial surgeons/odontologist.
Rapid empiric antibiotic therapy and seizure prophylaxis
is indicated:
• penicillins are used to target non-beta lactamase-produc-
    ing, gram-positive aerobes and anaerobes;
• carbapenems are used for beta-lactamase producing or-
    ganisms;
• third generation cephalosporins are commonly adminis-
    tered for aerobic gram-negative organisms;
• metronidazole and chloramphenicol, which both pen-                      Figure 1. MRI showing a huge abscess in the right frontal lobe.
    etrate intracranially, provided coverage against anaer-
    obes 16;
• vancomycin is useful in cases of methicillin-resistant                  ESS as the first treatment as it may not prevent neurosurgical
    Staphylococcus aureus.                                                drainage and as the most accepted treatment of ABRS is an-
In literature the role of neurosurgical treatment with drain-             tibiotic therapy with nasal decongestants. Moreover, as most
age is clear 11,16, both in pediatric and adult patients, and             cases of intracranial complications result from indirect spread,
is required early to decrease mortality rate and to reduce                can happen that surgical drainage of the sinuses does not seem
persistent neurologic deficit especially in larger intracranial           to have a significant immediate result. On the contrary, ESS
abscesses (> 1 cm). Smaller intracranial abscesses (< 1 cm)               is suggested in case of direct spread of the infection from the
can be treated with initial medical management with intra-                sinuses to the intracranial space through a bone defect, espe-
venous antibiotics and serial radiologic evaluation to as-                cially if the defect is near the intracranial abscess 11,20 (Clinical
sess for improvement or progression of disease 11. They can               case reported in Figure 2: Male 3-year-old. Frontal-ethmoidal-
be followed by radiological evaluations after the onset of                maxillary right sinusitis with subdural empyema of right fron-
empiric antibiotic therapy and can be treated with neuro-                 tal lobe. Treated with antibiotic therapy and combined surgery
surgical drainage if there is not a clinical and radiologi-               with craniotomy and ESS; complete clinical and radiological
cal improvement (Clinical case reported in Figure 1: Male                 resolution). Finally, ESS can also be postponed if, despite
16-year-old, frontal sinusitis treated at home with antibiotic            medical therapy, there are still clinical and radiological signs
per OS. Two days after, due to persistent symptoms, was re-               of sinusitis and it is useful to avoid recurrence and mucocele
quired a MRI that showed a huge abscess in the right fron-                (Clinical case of Figure 3: Male 55-year-old, no comorbidity,
tal lobe. A craniotomic drainage of the abscess was carried               hospitalized for fever, headache, rapid deterioration of mental
out via craniotomic route. A long-time antibiotic therapy                 status, coma. At CT acute frontal, ethmoid, maxillary sinus
was performed with complete symptoms resolution and                       sinusitis and ventricular empyema. MRI found out brain ab-
without neurological sequelae. Endoscopic sinus surgery                   scess with edema. Treated with ventricular drainage, antibiotic
not performed).                                                           therapy, seizure prophylaxis, followed with several radiologi-
If intracranial complications are caused by odontogenic si-               cal evaluations, ESS performed 25 days after symptoms on-
nusitis the abscessed teeth should be rapidly extracted and               set to prevent disease recurrence; Clinical case of Figure 4:
the paranasal sinus drained 12.                                           Male 17-year-old, Frontal sinusitis with pneumocephalus and
The role of Endoscopic sinus surgery (ESS) in intracranial                meningitis. Disappearance of meningitis after medical treat-
complications of ABRS in controversial. Some authors sug-                 ment, at radiological follow-up persistent frontal dysventila-
gest ESS as an initial management in order to reduce the num-             tion without cerebrospinal fluid leak and pneumocephalus. In
ber of neurosurgical procedures and in some cases to avoid                a second time performed right frontal sinusotomy with Draf
neurosurgical drainage 17-19. Other studies don’t recommend               IIa procedure: resection of the floor of the frontal sinus from



                                                                                                                                                S69
C. De Vita et al.




Figure 2. (A-B) MRI showing subdural empyema of right frontal lobe; (C-D) CT showing frontal-ethmoidal-maxillary right sinusitis.




Figure 3. (A-B) CT with acute sinusitis (frontal, ethmoid, maxillary sinus; no sphenoid sinus involvement) and ventricular empyema; (C) MRI with brain abscess
and edema.


                                                                                 the nasal septum medially to the lamina papyracea laterally).
                                                                                 In Figure 5 we propose a practical algorithm of management
                                                                                 of Intracranial complications of ABRS.

                                                                                 Intracranial complications of CRS
                                                                                 Mucoceles and fungal rhinosinusitis are responsible for in-
                                                                                 tracranial complications of CRS.

                                                                                 Mucoceles
                                                                                 Sinus Mucoceles are expansile, mucoid-filled, cyst-like le-
                                                                                 sions that grow over time, they can completely opacify the
Figure 4. (A-B) CT with pneumocephalus and frontal sinusitis.                    affected sinus and can deform surrounding structures 7.



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                            When is a multidisciplinary approach required in management of intracranial complications of sinonasal inflammatory disorders?




Figure 5. Management of intracranial complications of ABRS algorithm.


They most frequently originate from the frontal and                           ingitis 24,25. Radiological evaluation with CT and contrast
ethmoid sinuses and tend to be unilateral but can be bi-                      enhancement MRI is mandatory for diagnosis and it is im-
lateral too 8.                                                                portant to plan the surgical treatment.

Etiologic mechanism                                                           Treatment
Mucoceles are caused by trapped mucosal elements in the                       Mucoceles and its complications are treated surgically. Un-
frontal or ethmoid sinuses after obstruction of the normal                    til the 1980s, the only treatment of mucoceles was surgery
pathways of aeration 21. The obliteration of sinus ostium                     using an external route, with large incision and osteoplasty,
can be congenital or acquired, it can be caused by allergic                   but this technique didn’t restore the normal physiological
rhinitis, post-traumatic event, post-inflammation, post-sur-                  aeration. In recent years there has been an improvement in
gery and infective 22. Whether there is an infectious etiol-                  the management of mucoceles with the use of nasal endos-
ogy or if they become secondarily infected, they are termed                   copy which nowadays can be considered the first option
mucopyoceles. They grow slowly and their pressure induce                      treatment for this pathology. The endoscopic technique is
necrosis and release of natural osteolytic factors that lead to               less invasive than the external approach and is successful
the destruction of surrounding bony structures 23. Usually                    as it allows the restoration of sinus drainage. It decreases
they are diagnosed later in their development, only after                     intra and postoperative morbidity, reducing the operative
orbital or cranial invasion has occurred.                                     time, allows a larger view of the lesion and surrounding an-
                                                                              atomical structures, reduces chances of recurrence but the
Complications and symptoms                                                    success rate is strictly linked to the experience of the sur-
Given the proximity of mucoceles to the brain and to the                      geon. Another approach found in literature is the combined
orbit, significant morbidity and potential mortality may re-                  technique (external approach and endoscopy), which can
sult if these are allowed to grow.                                            be used in selected and more complicated cases 26, depend-
In case of an intracranial extension, they can cause facial                   ing on the extension of mucoceles and of its intracranial
pain, headaches, bony erosion of the skull base, leaks of                     complications. In case of infections (mucopyoceles and
cerebrospinal fluid, brain herniation and infections as men-                  meningitis) it is also necessary to administrate antibiotic



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C. De Vita et al.




therapy (in Figure 6 we propose a practical algorithm of                     and hematologic malignancy (40%) account for 90% of
management of intracranial complications of mucoceles).                      the immunosuppression reported in over 800 invasive rhi-
                                                                             nosinusitis patients 31. It is also proved that the extent and
Intracranial complications of fungal rhinosinusitis (FRS)                    duration of immunodeficiency is proportional to the risk of
Between sinonasal fungal infections the ones that can cause                  developing IFRS 32.
intracranial complications are the allergic fungal rhinosi-                  Although less common, there are also case reports describ-
nusitis (AFRS) which are included in the non-invasive vari-                  ing these infections in people with normal immune func-
ant, and the invasive fungal rhinosinusitis (IFRS).                          tion 33.
AFRS occurs in immunocompetent atopic patients with
hypersensitivity to fungal allergens and rarely can cause                    Etiologic mechanism
intracranial involvement. AFRS and bone erosion may be                       In the AFRS the allergic mucin and polyps form a partially
more prevalent in younger male patients, and in individuals                  calcified mass obstructing sinus drainage and tend to in-
of African American descent 27,28.                                           volve multiple sinuses 34. As fungal mucin increases, the
The IFRS can be classified in 3 forms with different                         involved paranasal sinuses begin to resemble a mucocele
clinical and pathologic characteristic depending on the                      and bony remodeling, and decalcification may occur with
progression of the disease and the immune status of the                      subsequent nasal, intraorbital, or intracranial involvement
host 29. They are categorized into acute invasive form with                  mimicking malignancy. Causative agents include dematia-
a course of disease of 4 weeks or less, chronic invasive                     ceous (Bipolaris, Curvularia, and Alternaria) and hyaline
form and the granulomatous form with a development of                        molds (Aspergillus and Fusarium) 35.
more than 12 weeks. These infections occur primarily in                      In the IFRS species most commonly identified are Asper-
immunocompromised patients, with hematologic malig-                          gillus (flavus, fumigatus, terreus, niger) and fungi of the
nancy, bone marrow transplantation, poorly controlled dia-                   order Mucorales (Zygomycetes) 36. Fungal infection begins
betes, acquired immunodeficiency syndrome, immunosup-                        as mucosal inflammation around the middle turbinate and
pressive medications and chemotherapy 30. Diabetes (50%)                     rapidly spreads to the sinuses. Through direct extension or




Figure 6. Management of intracranial complications of mucoceles algorithm. ce = contrast enhancement.



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                              When is a multidisciplinary approach required in management of intracranial complications of sinonasal inflammatory disorders?




                                                                                    Intracranial complications include cavernous sinus throm-
                                                                                    bosis, parenchymal cerebritis or abscess, meningitis, os-
                                                                                    teomyelitis, mycotic aneurysm, stroke, and hematogenous
                                                                                    dissemination 35.

                                                                                    Multidisciplinary management
                                                                                    Diagnosis is made with clinical, radiologic, serologic, and
                                                                                    endoscopic data and it should be proven by histologic and
                                                                                    microbiological examination.
                                                                                    Nasal endoscopy has shown a good reliability and is very im-
Figure 7. (A) CT with pathological tissue in the nasopharynx with invasion of       portant for an early diagnosis in IFRS 38. The endoscopic signs
skull base; (B) CT with contrast enhancement revealed a right brain abscess.        of IFRS are commonly located near the middle turbinate, the
                                                                                    ethmoid or the septum and include mucosal ischemia, plain
                                                                                    necrotic areas with a blackish or grayish color, crusting and
through vascular spread due to their angio-invasive nature
                                                                                    absence of bleeding upon scraping. CT is important to show
it often extends to skull base and brain causing intracra-
                                                                                    bony changes while contrast enhancement MRI evaluates soft
nial complications 37. Hyphal growth into the vessel lumen
causes endothelial dysfunction and thrombosis 35.                                   tissue extension and allows a differentiation from neoplastic
                                                                                    entities (extremely useful in AFRS). Due to their morbidity
Complications and symptoms                                                          and mortality these infections and complications must be ur-
Sinus pain, nasal discharge, low-grade fever, and epistaxis                         gently recognized to avoid treatment delay.
are the most observed symptoms. When orbital symptoms,                              Diagnosis and treatment require collaborations between
neurologic deficits and altered mental status occur, they                           otolaryngologists, infectious disease specialists and neu-
suggest an intracranial involvement (Clinical case of Fig-                          rosurgeons; when patients are immunocompromised for
ure 7: Female 75-year-old with poorly controlled diabetes                           hematologic malignancy and bone marrow transplantation
and blindness of the right eye. She came to hospital with                           it is particularly important that the hematologists promptly
right facial nerve paralysis, impaired right ocular motility                        recognize risk factor and nasal symptoms (Clinical case of
and glycemia 900 mg/dl. CT and MRI with contrast en-                                Figure 8: Male, 52-year-old, immunosuppressive therapy
hancement revealed pathological tissue in the nasopharynx                           for liver transplant. He was hospitalized for mucormycosis
with invasion of skull base and also right brain abscess.                           with invasion of pterygopalatin fossa, huge frontal abscess
Nasal endoscopy with biopsy revealed a fungal infection.                            and orbital cellulitis. Treated with endovenous antimycotic
Treated with endoscopic surgical debridement, ampho-                                therapy, endoscopic surgery with aggressive surgical de-
tericin through endovenous administration and restoring                             bridement of paranasal sinus and pterygopalatin fossa bi-
normal glucose level with complete resolution of the infec-                         laterally with improvement of symptoms. He died 2 months
tious process).                                                                     later for liver failure).




Figure 8. (A) CT with mucormycosis of frontal, ethmoidal and maxillary sinuses; (B) CT with huge frontal abscess; (C) orbital cellulitis.



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C. De Vita et al.




Table I. Treatment and risk factors of intracranial complication of fungal rhinosinusitis.
                                          Allergic fungal rhinosinusitis                       Invasive rhinosinusitis (acute chronic, granuloumatous)
 Risk factors                         History of atopy, allergic rhinitis, asthma         Hematologic malignancy, bone marrow transplantation, poorly controlled
                                                                                           diabetes, acquired immunodeficiency syndrome, immunosuppressive
                                                                                                                medications chemotherapy
 Surgical treatment                  Opening of sinus ostia, polyp and mucin                                     Aggressive debridement
                                                       removal
 Medical treatment                 Oral steroids, topical steroids, antihistamines,                           Systemic antifungal treatment
                                               leukotriene antagonists



In the AFRS it is important to perform a surgical treatment,                          immune system. Each case must be carefully evaluated,
to open sinus ostia and remove polyp and mucin, combined                              the therapeutic approach must be customized, and a mul-
with an anti-inflammatory treatment, which include ster-                              tidisciplinary approach is mandatory as there is not a gold
oids through oral and topic administration, antihistamines                            standard treatment.
and eventually leukotriene antagonists 35.                                            Mucoceles and AFRS rarely cause intracranial complica-
Regular follow up is mandatory to check assessment of na-                             tions and often they are approached with a surgical endo-
sal mucosa and for recurrent endoscopic debridement. Post-                            scopic treatment followed by antibiotic therapy in case of
operative oral steroid therapy is useful to improve symptoms                          infection.
and prevent early recurrences (Tab. I). Extensive AFRS with                           Intracranial complications of IFRS have the worse prog-
intracranial complications are still relatively rare 34.                              nosis as they frequently occur in immunocompromised
The gold standard of IFRS treatment is surgical debride-                              patients with hematologic malignancies or with several
ment and systemic empiric antifungal therapy until the                                comorbidities. A multidisciplinary approach is important
causative fungal species is identified 31,36,38; the most used                        for the treatment and mostly for prevention. The recog-
are amphotericine and voriconazole 26. The angioinvasion,                             nition of first symptoms in patient with risk factors is
thrombosis and resulting tissue necrosis make it difficult                            fundamental to avoid treatment delay and to improve the
for chemotherapeutic agents to penetrate the ischemic tis-                            outcomes.
sues, that’s why surgical debridement of infected and ne-
crotic tissue is considered an essential component of an
optimal management 39 (Tab. I).
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