Stealth viral encephalopathy is an organic brain disease which can manifest with a wide variety of clinical symptoms and syndromes. Patients with this disease will usually show discernable defects in various brain functions, together with non-neurological signs and symptoms of a systemic viral infection. This review provides general guidelines for the clinical and laboratory assessment of patients with stealth viral encephalopathy. Quantifying the various defects seen in the patients can help in monitoring the efficacy of therapy.

Stealth Viruses

The term stealth refers to cytopathic viruses which avoid confronting the cellular immune system because they lack genes coding for antigens required to evoke effective anti-viral cellular immunity. Consequently, stealth viruses can establish persistent infections in the absence of an inflammatory reaction. While stealth viral infections can cause widespread limited damage throughout many organs of the body, their effects are particularly noticeable when infection involves portions of the brain. As discussed elsewhere, the brain is particularly susceptible to stealth viruses because of the spatial diversity of its functions, such that localized damage can not be compensated by heightened activity elsewhere in the brain.

Clinical Evaluation:

The clinical history should focus on the onset of the patient's illness, the occurrence of illness in family members, friends and household pets and the factors which exacerbate or alleviate symptoms. The prior medical history and a history of family illness should be considered mainly in the context of a predetermined susceptibility of the patient to certain personality changes and specific cognitive impairments. A detailed description of present symptoms is useful in helping to focus the neuropsychological examination. Symptoms that may be present include the following neuropsychological symptoms:

• Alterations in smell, taste, vision, hearing, touch, pain

• Unusual emotional reactions to sensory inputs

• Impaired sleep cycle, unusual vivid dreams,

• Personality changes, blunted affect, depression, attention deficit, agitationaranoid concerns, feelings of vulnerability, changes in feelings about others

• Impaired description and awareness of self

• Absence spells, actual seizures

• Memory loss, word searching and word use difficulty

• Nocturnal urination

• Episodes of unexplained perspiration, palpitations, diarrhea

• Unsteadiness of balance, walking or running

The neurological evaluation is structured to detect objective findings of autonomic, sensory, motor and higher level brain dysfunction. Individual patients will differ in the overall manifestations of their illness and the actual symptoms and signs will also vary over time. The following basic tests should be performed:

Autonomic Nervous System:

• Blood pressure and pulse rate instability comparing supine and standing positions and following brief exercise and the Valsalva maneuver

• Temperature readings outside of normal range, also unstable temperatures taken by the patient at 4 hr. intervals during the day.

• Perspiration or excessive dryness of skin, hair

• Exaggerated "startle reflex"

Sensory Nervous System:

• Pupil abnormalities, uneven, irregular, delayed response to light & accommodation, hippus

• Photophobia with squinting to light

• Diplopia especially with close objects moving to and from the face

• Nystagmus, restricted upward gaze

• Weakened ability to maintain shut eyelids, twitching of eyelids, delayed blink response

• Limited integration of items seen with peripheral vision with and without eye movement

• Impaired hearing of tuning fork ( tinnitus), defective localization of source of soun

• Difficulty with balance (one foot Romberg test), gait

• Reduced peripheral sensation to touch, pain, temperature, vibration and position

Motor Nervous System:

• Motor response slowing, clumsiness, loss of precision of fine motor skills, unsteady gait

• Impaired finger-nose pointing and finger-finger touching especially when unseen

• Muscle tremor, fasciculation or wasting

• Limited control of facial expression

• Uneven chewing and swallowing (also note dry mouth, evidence of crimson crescents)

Higher Level Functions:

• Altered or atonal voice, lessened ability to sing and/or reproduce notes

• Defects in three dimensional reconstruction, e.g., drawing

• Difficulties in word searching, word recognition, calculations, short term memory

Physical Findings Supportive of Viral Infection and/or Immune Activation:

• Lymphadenopathy, salivary gland enlargement

• Gingivitis, crimson crescents in mouth

• Dry eyes, keratitis

• Skin rashes, loss of fingerprints, smooth and/or tight skin, hair loss

• Allergy, sinusitis

• Fibromyalgia tender points, myalgia, arthralgia, joint swelling, nodules

1. Direct evidence of viral infection

• Comprehensive viral cultures including detection of stealth viruses
  (Yellow top tube of blood, CSF, material from vesicular skin lesions)

• Serology for activation of the following viruses

Human and simian cytomegalovirus by immunofluorescence

Human herpesvirus-6 (IgM, IgG and antigen detection by Elisa)

Epstein-Barr virus by Elisa

Varicella-zoster antibody by Elisa

Parvovirus B19 (IgM and-parvovirus by Elisa)

SV40 viral serology

Hepatitis B and C viral antigen and antibodies by Elisa

Poliovirus serology (may be reduced levels)

• Polymerase chain reaction (PCR) for viruses detectable by culture or serology

2. Tests for immune activation

• Flow cytometry of lymphocytes using activation markers

• Natural killer cell assays

• Serum immunoglobulin, C3,C4 C1Q complexes

• Protein electrophoresis

• Immune complex assays, cryoglobulin

• Interferon

3. Tests for endocrine dysfunction

• Thyroid T3, T4, TSH

• Cortisol, DHEA, Melatonin (am and pm )

• Serum and urine glucose, urine osmolarity

4. Tests for liver, kidney, and bowel dysfunction

• Liver function tests, detoxification profiles to acetaminophen challenge

• Cholesterol, homocysteine, albumin

• Serum creatinine

• Steatorrhea, xylose absorption

5. Tests for autoimmunity

• Anti-nuclear panel, ANA, anti-mitochondrial, anti-smooth muscle

• Anti-thyroid microsomal antibodies

• Anti-neuronal antibodies

• Anti-myelin antibodies

• Anti-adrenal antibodies

Dryness

Reddness of fauces, salivary duct openings, gingivitis

Soft palate movement

Gag reflex

Swallowing

Smell    Garlic    Curry    Secondary effects