Encephalopathies are a group of central nervous system (CNS) affection with heterogeneous etiology. Several causes have been recognized including neurodegenerative, vascular, infectious, autoimmune, toxic or allergic affections or secondary to systemic disorders. While 30-50% of acute encephalitis remains without etiological definition, definitive criteria for neurodegenerative diseases are usually unavailable in vivo and possible or probable definitions are used. The Olfactory mucosa (OM) is the part of the nasal mucosa that carries the specialized sensory organ for the modality of smell; the olfactory epithelium is composed of five principal cell types including olfactory receptor neurons. A sample of OM may be collected through a rhinoscopy-guided brushing: it is well-accepted by patients, not-contraindicated in patients with raised intracranial pressure and associated with almost no side-effects. Nasal brushing has recently been proposed for the in vivo diagnosis of Creutzfeldt-Jakob disease (CJD).

Aims of the project are:

1. Training of ear throat and nose (ETN), Infectious disease (ID) and neurology (NEU) specialists in the technique of nasal brushing;
2. Conducting a prospective study comparing the use of nasal brushing with gold-standard criteria in the diagnosis of Encephalopathies;
3. Increasing the diagnostic and prognostic power in the diagnosis of encephalopathies.

A prospective, case control, multicentric study enrolling 400 patients and 100 controls (patients with nasal stenosis undergoing rhinoscopy for clinical reasons). Patients will be diagnosed and followed according to international guidelines and local clinical practice. Cerebrospinal fluid and magnetic resonance imaging will be used, where indicated, for the diagnosis according to the clinical or radiological suspect.

Inclusion criteria for cases:

• age>18 years;
• signing a written informed consent (by the patients or his/her legal representant);
• clinical suspect of encephalopathy (acute or subacute) including acute encephalitis, neurodegenerative disorders and HIV-associated neurocognitive disorders.

Inclusion criteria for controls:

• age>18 years;
• signing a written informed consent (by the patients or his/her legal representant); • clinical indication for rhinoscopy for stenotic disease of nasal sept or turbinates.

Exclusion criteria:

• Nasal anatomical abnormalities precluding the execution of nasal brushing;
• Serious general conditions and/or comorbidities in patients for whom nasal brushing may be a risk factor precipitating their pre-existing condition;
• Anti-coagulant treatment.