ENTEROVIRUSES

And Myalgic Encephalomyelitis (M.E.)

INFECTION • IMMUNE RESPONSE • LASTING IMPACT

Enteroviruses:

Coxsackie B
Echovirus
Other numbered enteroviruses
Enterovirus A71
Enterovirus D68
Coxsackie A

BACKGROUND

Patients "misdiagnosed" with Chronic Fatigue Syndrome (CFS) may have preceding illnesses, environmental exposures or co-existing conditions that warrant further investigation. Reported associations include sick building syndrome, mould exposure, prolonged stress, strenuous physical exertion, multiple chemical sensitivity and a history of silicone breast implants.

Co-existing conditions such as Gilbert's syndrome, atopy, endometriosis, asthma, eczema and coeliac disease may also be relevant to the clinical assessment. Gluten sensitivity and associated neurological symptoms warrant consideration where clinically indicated. Episodes of epididymo-orchitis have also been reported preceding prolonged illness in male patients.

ENTEROVIRUSES AND ORGAN INVOLVEMENT

Enteroviruses can affect the nervous system, muscles, and the heart — sometimes all at once.

Early recognition.

Accurate diagnosis.

Specialised care.

Hope for the future.

ASEPTIC MENINGITIS

Inflammation of the meninges surrounding the brain and spinal cord, often causing headache, fever and neck stiffness.

CORTICAL, LIMBIC AND SUBCORTICAL ENCEPHALITIS

Enteroviral inflammation may affect the hippocampus, fornix, cingulate gyrus, hypothalamus, thalamus, basal ganglia and precentral gyrus (primary motor cortex), causing memory impairment and cognitive dysfunction, movement abnormalities, sensory disturbances and autonomic dysfunction.

RHOMBENCEPHALITIS (BRAINSTEM ENCEPHALITIS AND CEREBELLITIS)

Inflammation of the hindbrain, particularly the brainstem and cerebellum, including the medulla, pons, midbrain, cerebellar vermis and dentate nuclei, which may impair cranial nerve function, coordination and autonomic regulation.

MYELITIS (AND POLIO-LIKE SYNDROME)

Spinal cord inflammation affecting anterior horn motor neurons (flaccid weakness/paralysis), posterior horn sensory pathways (pain, numbness) and autonomic pathways (bowel/bladder dysfunction). Radiculitis affects motor and sensory nerve roots.

POST-MORTEM FINDINGS: DORSAL ROOT GANGLIONITIS

Dorsal root ganglionitis (inflammation of sensory nerve-cell ganglia) has been reported in M.E. post-mortem examinations involving Sophia Mirza, Lynn Gilderdale and Merryn Crofts.

“CHRONIC FATIGUE SYNDROME” (CFS) CRITERIA

A patient must have 3-6 months or longer of “persistent or relapsing fatigue” that is:

New or definite in onset (not lifelong).
Associated with a substantial reduction in occupational, educational, social or personal activities.
“UNEXPLAINED FATIGUE” following clinical evaluation (Clinical evaluation involves thorough history-taking, physical examination and tests to exclude other causes of “CHRONIC FATIGUE” and other clinical diagnoses MUST BE RULED OUT).
NOT substantially alleviated by rest.
NOT as a result of ongoing exertion.

A patient must have 4 of 8 of the following symptoms, present concurrently from the blue or pink point lists, for 3–6 months or longer, from the “1994 Fukuda CFS Criteria” column:

1994 Fukuda CFS Criteria

BLUE POINT LIST

Sore throat (pharyngitis) or herpangina (HFMD).
Tender cervical or axillary lymph nodes (lymphadenopathy).
Muscle pain (myalgia) (consider acute viral myositis or polymyositis-like syndrome).
Multi-joint pain without joint swelling or redness (arthralgia).
Headaches of new type, pattern or severity (consider aseptic meningitis or encephalitis).
Impaired short-term memory or concentration (consider encephalitis).
Unrefreshing sleep (non-restorative sleep) or sleep reversals (early hypersomnia to later insomnia) (consider encephalitis).

PINK POINT LIST

It is a proven scientific fact that “Enteroviruses” replicate because they possess an Activity Sense Switch and an Internal Ribosome Entry Site; resulting in “Robbing cell Peter to pay virus Paul”. The end result of which is a sick cell, potentially sick organ(s) and extremely sick patient. It is common sense therefore to rest the patient and only adopt a flexible activity regime when the patient has little or no “Post Exertional Malaise (PEM)” lasting > 24 Hours.

ORTHOSTATIC INTOLERANCE

Orthostatic Intolerance: PoTS (Postural Orthostatic Tachycardia Syndrome), Orthostatic Hypotension (OH), Neurally Mediated Hypotension (NMH), Vasovagal or Orthostatic Syncope (Fainting).

OTHER SYMPTOMS & DIAGNOSES

Fever

Fever (usually low-grade, but may be high during acute aseptic meningitis or encephalitis).

Abortive Poliomyelitis

Fever (usually low-grade), malaise (general feeling of illness), fatigue, tiredness or listlessness, headache, muscle pain/aches (myalgia), loss of appetite (anorexia), sore throat (pharyngitis) or herpangina (HFMD), runny nose (coryza), cough, influenza-like upper respiratory illness, diarrhoea, nausea, vomiting, abdominal pain or stomach ache, abdominal discomfort, constipation, loss of appetite (anorexia), neck stiffness.

Rashes

Maculopapular (Red Spots/Bumps), Vesicular (Blisters), Urticarial (Hives) or occasionally Petechial/Purpuric (Red/Purple Spots), affecting the Face, Trunk (Rubella-like), Limbs, Hands, Feet or Buttocks, with Mouth/Tongue Ulcers (HFMD).

Chills and Night Sweats

Respiratory

Coryza (Cold-like Illness), Laryngitis, Tracheitis, Bronchitis, Bronchiolitis, Pleurisy, Pneumonia, Cough, Wheezing or Shortness of Breath.

Gastrointestinal

Gastritis, Gastroenteritis, Colitis, Terminal Ileitis, Mesenteric Lymphadenitis, Pancreatitis, Hepatitis, Irritable Bowel Syndrome, Food Intolerance or MCAS.

Genitourinary

Orchitis, Epididymitis, Prostatitis, Salpingitis, Interstitial Cystitis or Pelvic Pain.

Chest Pain, Palpitations or Arrhythmias (Tachycardia and Bradycardia)

Bornholm Disease, Pericarditis, Myocarditis, Myopericarditis, Dilated Cardiomyopathy, Costochondritis and Tietze Syndrome.

Vestibular Disorders

Epidemic Vertigo, Vestibular Neuritis and Viral Labyrinthitis.

Primary Thyroid Failure

Hypothyroidism.

DIAGNOSIS

When a patient presents with an infectious disease which does not clear within 14-28 days, and the main symptoms are “FATIGUE” with “POST-EXERTIONAL MALAISE”, further clinical assessment and investigation should be considered.

Emergency hospitalisation if symptoms progress to aseptic meningitis, inpatient services if encephalitis, myalgic encephalomyelitis or AFM.

The doctor should use the John Richardson Research Group M.E. Score Chart and do a full Nervous System (pp. 7-8) and Cardiovascular Assessment.

Consider serology, neutralising antibodies and/or PCR testing for:

ENTEROVIRUS
Epstein-Barr Virus (EBV)
SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2)
Varicella-Zoster Virus (Chickenpox & Shingles)
Cytomegalovirus (CMV)
Human Herpesvirus 6 (HHV-6A & 6B)
Borrelia burgdorferi species

RNA virus infections may trigger reactivation of latent herpesviruses.

GASTROINTESTINAL SYMPTOMS AND ENTEROVIRUS PERSISTENCE

Diarrhoea, nausea or vomiting, abdominal pain and weight loss.

“POST-EXERTIONAL MALAISE” (PEM)

“NON-CYTOLYTIC” PERSISTENT ENTEROVIRUS INFECTION

CARDIAC, CHEST AND ABDOMINAL PAIN

Paroxysmal angina-like chest pain may feel tight, squeezing, heavy or pressure-like, or sharp and stabbing. Coxsackie B enteroviruses can cause myocarditis (tight, squeezing, dull or sometimes sharp chest pain), pericarditis (typically sharp or stabbing pain, worse when breathing deeply or lying flat, often eased by leaning forward), and Bornholm disease (sudden, severe, gripping or spasmodic chest pain). Severe right lower abdominal pain can resemble appendicitis, particularly in the right iliac fossa, and may suggest mesenteric lymphadenitis (mesenteric adenitis), an inflammatory enlargement of abdominal lymph nodes that can accompany viral gastrointestinal infection (appendicitis must be excluded). Episodes of profuse sweating, including nocturnal night sweats, have been reported in enterovirus-associated illness. Autonomic nervous system involvement can also produce tachycardia, palpitations, blood pressure fluctuations and temperature dysregulation.

NEUROLOGICAL AND COGNITIVE MANIFESTATIONS

Enteroviral infection involving the central nervous system can produce encephalitis, encephalomyelitis, rhombencephalitis and poliomyelitis-like neurological syndromes. Cognitive disturbances may include impaired short-term memory, reduced concentration, slowed information processing, word-finding difficulties (anomia) and altered attention. Additional neurological manifestations may include myoclonic jerks, cranial nerve palsies, dysarthria, dysphagia, ataxia, muscle weakness and autonomic disturbances. Persistent or recurrent nocturnal sweating, including episodes of profuse sweating, has been reported in enterovirus-associated postviral illness. Enteroviral infection or persistence may be investigated through tissue biopsy, including VP1 immunohistochemistry and enteroviral RNA detection by RT-PCR. Positive tissue findings provide evidence supporting enteroviral involvement, although further investigation is required to establish ongoing viral replication and its relationship to clinical symptoms. Emotional and behavioural changes may also occur following encephalitis, but should not be presumed to represent a primary psychiatric disorder without appropriate clinical evaluation.

CLINICAL SYMPTOM GROUPS

INITIAL INFECTION

Subclinical infection
Diarrhoea
Nausea (and vomiting)
Abdominal pain and cramps
Hand, foot and mouth disease (HFMD)
Viral labyrinthitis / vestibular neuritis
Rubella-like rash (echovirus)
Aseptic meningitis
Limbic encephalitis / rhombencephalitis
Polymyositis-like illness (infectious myositis)
Bornholm disease (pleurodynia)
Pericarditis / myocarditis / myopericarditis
Hashimoto's thyroiditis
Pancreatitis

MENINGOENCEPHALITIS

Headache
Fever
Neck stiffness and pain
Nausea and vomiting
Photophobia
Altered mental status
Confusion / disorientation
Delirium
Reduced levels of consciousness
Lethargy (somnolence) or drowsiness
Coma (in severe cases)
Seizures
Focal neurological signs (e.g., hemiparesis, hemiplegia, focal motor seizures, aphasia, hyperreflexia)
Extensor plantar response (Babinski sign)
Kernig sign
Brudzinski sign

LIMBIC ENCEPHALITIS

Headache
Lethargy (somnolence) or drowsiness
Confusion / disorientation
Short-term memory loss
Anterograde amnesia
Impaired concentration
Dyslexia
Impaired spatial discrimination
Dysnomia (anomic aphasia)
Aphasia (receptive or expressive)
Reduced levels of consciousness
Seizures
Hypothalamic damage / dysfunction (tertiary adrenal dysfunction)
Central autonomic dysfunction (hypothalamic involvement: temperature dysregulation, sweating abnormalities and impaired heart rate / blood pressure regulation)
Sleep disturbances (e.g., unrefreshing sleep (non-restorative sleep) / sleep reversals)
Emotional lability (reactive depression / frustration / anxiety)
Obsessive-compulsive symptoms
Psychosis (in severe cases)

BRAINSTEM ENCEPHALITIS (RHOMBENCEPHALITIS)

Vertigo (dizziness)
Ataxia (unsteady gait and impaired coordination)
Clumsiness
Tremor
Myoclonic jerks
Nystagmus
Upward gaze palsy (impaired upward gaze / vertical gaze palsy)
Loss of accommodation
Internuclear ophthalmoplegia
Disequilibrium
Hyperacusis, deafness and tinnitus
Cranial nerve palsies and dysfunction (CN III–XII), which may include:
- CN III – Oculomotor nerve: Ptosis, diplopia, ophthalmoplegia, impaired pupillary constriction and abnormal ocular alignment
- CN IV – Trochlear nerve: Vertical diplopia, difficulty looking down and in, and compensatory head tilt
- CN V – Trigeminal nerve: Reduced facial sensation (V1, V2, V3), impaired corneal reflex and weakness of mastication (chewing)
- CN VI – Abducens nerve: Horizontal diplopia, impaired lateral eye movement (abduction), esotropia and strabismus
- CN VII – Facial nerve: Facial droop or weakness, inability to close the eye fully, reduced taste from the anterior two-thirds of the tongue, and altered lacrimation or salivation
- CN VIII – Vestibulocochlear nerve: Sensorineural hearing loss, tinnitus, vertigo, impaired balance and nystagmus
- CN IX – Glossopharyngeal nerve: Dysphagia, impaired gag reflex and reduced taste from the posterior third of the tongue
- CN X – Vagus nerve: Bulbar weakness, dysphagia, dysarthria, dysphonia (hoarse voice), vocal cord paralysis, impaired vagal autonomic function and delayed gastric emptying
- CN XI – Accessory nerve: Weakness turning the head, impaired shoulder elevation and reduced shoulder shrug
- CN XII – Hypoglossal nerve: Tongue weakness, deviation or atrophy, dysarthria and impaired tongue movements
Respiratory dysfunction (medullary failure)
Cardiovascular dysregulation
Baroreflex dysfunction (orthostatic intolerance, neurogenic orthostatic hypotension and impaired heart rate / blood pressure regulation)
Neurogenic pulmonary oedema

AUTONOMIC DYSFUNCTION

Orthostatic intolerance
Postural Orthostatic Tachycardia Syndrome (PoTS)
Heart rate variability
Blood pressure instability (hypertension or hypotension)
Peripheral circulatory dysregulation (impaired vasoconstriction, venous pooling and reduced venous return)
Temperature dysregulation
Sweating abnormalities (profuse)
Gastroparesis
Gastrointestinal dysmotility
Paralytic ileus
Neurogenic bladder
Small fibre polyneuropathy

CARDIAC INVOLVEMENT

Myocarditis
Pericarditis
Myopericarditis
Left-sided diastolic dysfunction
Arrhythmias (sinus tachycardia, sinus bradycardia and cardiac pauses)
Reduced cardiac function
Autoimmune myocarditis
Dilated cardiomyopathy
Cardiac insufficiency
Chest pain (angina-like / pericarditic / Bornholm type)
Preload failure

COMMON CLINICAL SIGNS - MYALGIC ENCEPHALOMYELITIS (M.E.)

Romberg sign (Rombergism): Impaired postural stability and balance, particularly when standing with the eyes closed
Quadriceps muscle jitter: Observable muscle quivering or irregular contractions of the quadriceps during neurological examination
Motor-servo dysfunction (cogwheeling): Intermittent, ratchet-like resistance during passive limb movement, described as cogwheel rigidity
Pronator sign (pronator drift): Involuntary pronation or downward drifting of an outstretched arm
Reverse Argyll Robertson pupil reaction: Preserved pupillary response to light with impaired or absent accommodation (near response)

NIGHTINGALE RESEARCH FOUNDATION DEFINITION

M.E. (also known as enteroviral encephalomyelitis) is described as a debilitating "sudden onset" neurological disease associated with "enteroviral infection", involving "neuroinflammation" and "dysfunction affecting the brain, brainstem, spinal cord" and other organ systems.

Neurological involvement may contribute to cognitive impairment, motor weakness, dysautonomia and spinal cord abnormalities, including anterior horn cell involvement.

The text distinguishes M.E. (also known as Enteroviral Encephalomyelitis) from the “diagnosis of exclusion”, symptom-based CFS criteria centred on “fatigue” and “post-exertional malaise” (PEM), describes a distinct pathophysiology, and emphasises the need for specialist care.