[Abstract] Neuropathology of post-infectious chronic fatigue syndrome, 2009, Cader et al.

[Jonathan Edwards]

I came across this in my filing system and thought it worth a thread if it does not have one.

 

[Jonathan Edwards]

FP03-MO-02

Neuropathology of post-infectious chronic fatigue syndrome

S. Cader1 , D.G. O’Donovan2 , C. Shepherd3, A. Chaudhuri1

1 Neurology,

Queen’s Hospital, Romford, United Kingdom; 2 Neuropathology,

Queen’s Hospital, Romford, United Kingdom; 3 Queen’s Hospital,

Romford, United Kingdom
19th World Congress of Neurology, Free Paper Abstracts / Journal of the Neurological Sciences 285 S1 (2009) S57–S154 S61

Purpose: The pathogenesis of severe and relapsing chronic fatigue after viral or bacterial infection is unknown. Many patients with post-infectious chronic fatigue, which is classified as a neurological disease (G93.3, ICD-10 classification), become disabled and do not recover fully despite symptomatic and rehabilitative therapy.

Method: We report here the histopathological changes in the dorsal root ganglia of three female patients with a diagnosis of chronic fatigue syndrome. All three patients were seen by their local physicians and specialists who had excluded alternative medical cause for their symptoms of disabling fatigue and chronic pain. Due to the nature of death, a full autopsy examination was carried out in each of these cases.

Results: The most remarkable and consistent abnormality was the presence of active inflammation with T8 lymphocytic infiltration in the dorsal root ganglion of one patient and evidence of past inflammation (nodules of Nageotte) in two patients.

Conclusion: Dorsal root ganglion is the gateway for sensory information reaching the central nervous system. Based on the histopathological changes observed in three cases, we propose that inflammation of the dorsal root ganglia may play a key role in the pathogenesis of post-infectious chronic fatigue. Abnormal processing of sensory information secondary to dorsal root ganglionitis could potentially contribute to fatigue due to higher perceived effort and pain because of reduced sensory threshold. This may lead to new treatment options in a group of patients that currently present a significant challenge to neurologists.

 

[Nightsong]

Dr O'Donovan also reported on four cases (three of which seem to overlap with the ones reported here) at a 2010 conference in Australia -

Link

 

[Amadeus]

Sophia Mirza has dorsal root ganglionitis on postmortem. Someone said though it might just be an association rather than cause.

 

[Jonathan Edwards]

There is a paper that James Cox found that notes that lymphocytes in DRG are normal findings. So the question arises as to how abnormal these cases are. They probably are but it would be good to have some quantitative guide.

 

[forestglip]

Sophia Mirza has dorsal root ganglionitis on postmortem. Someone said though it might just be an association rather than cause.

Link to the neuropathology report: https://web.archive.org/web/2026021...phiaandme.org.uk/neuropathologicalreport.html

It says authorized by Dr. O'Donovan.

I copied the microscopy section and added line breaks:

---

"Microscopy
There is some crush artefact of the cervical cord on sections C1 & D2.

Section A5 comprises five pieces: three dorsal root ganglia 2 in transverse section and 1 in logitudinal section and one transvers and one longitudinal section of a root without ganglia.

All three samples of dorsal root ganglia show a mild focal chronic lymphocytic infiltrate. There is loss of ganglion cells and and nodules Nageotte are noted. There is evidence of invasion of some large ganglion cells by lymphocytes. A number of ganglion cells have pale granular eosinophilic cytoplasm and slightly pyknotic nuclei. However, no Cowdry A type nuclear inclusions are identified.

The LFB-CV stain of dorsal root ganglia shows loss of Nissl substance. The nerve roots also show focal loss of myelinated fibres. However, there is no extension of the inflammatory cell infiltrate into the dorsal nerve roots themselves.

Sections of the remainder of the cord show no evidence of inflammation in either ventral or dorsal nerve roots or in the spinal cord grey or spinal white matter columns. In particular there is no evidence of poliomyelitis.

The anterior horn cells appear to be normal in number. Some, however, show loss of Nissl substance and are swollen with granular eosinophilic cytoplasm.

There is no obvious loss of myelinated fibres from the spinal white matter columns. In particular, there is no evidence of B12 deficiency leading to subacute combined degeneration in the spinal cord (SACD). Small numbers of corpora amylacea are noted in the white matter columns and grey matter. There is no evidence of acute purulent meningitis or vasculitis and there is no evidence of neoplasia."

 

[Nightsong]

Expression of lymphocyte, macrophage and class I and II major histocompatibility complex antigens in normal human dorsal root ganglia

Macrophages, lymphocytes and major histocompatibility complex (HLA) class II antigens in adult human sensory and sympathetic ganglia

Persistence of a T Cell Infiltrate in Human Ganglia Years After Herpes Zoster and During Post-herpetic Neuralgia

 

[forestglip]

Dr O'Donovan also reported on four cases (three of which seem to overlap with the ones reported here) at a 2010 conference in Australia -

Link

Quoting the bit about Dr. O'Donovan's talk:

Dominic O’Donovan, (Cambridge,UK) a neuropathologist presented the results of autopsy on 4 patients who had a specialist diagnosis of CFS:

1. A 32 year old male with a 20 year history of CFS, who died of a suicide overdose of medication. Spinal cord and brain at autopsy showed excess corpora amylacea, which was in excess of normal ageing. There were intermediate filaments closely related to glial cells, and maybe within the glia rather than the axons. No evidence of ganglionitis. (EBV negative)

2. A female of 32 with a 5 year history. She had refused any medical help and been bedridden and refused food and water. She finally died of renal failure. The pathology showed a focal chronic inflammatory infiltrate (T8 lymphocyes) in the dorsal root ganglia. (EBV negative).

3. A female of 43 – an assisted suicide in Switzerland with a barbiturate overdose. The brain showed global ischaemia, but this was likely due to the drugs used. Dorsal root ganglia showed mild excess of lymphocytic nodules of nageotte but with no obvious inflammation, but this could represent a subtle chronic inflammatory state.

4. A female of 31 whose death may have been due to opiate ingestion. There was some toxic demyelination with spinal subarachnoid haemorrgae, but she was on warfarin. There was some mild possible chronic ganglionitis.

Differential diagnosis here was discussed and would have included AIDs, Sjorgren’s syndrome, varicella zoster and paraneoplastic disease.

These results have raised the possibility that some cases of CFS may have sensory or autonomic ganglionitis. A specific brain and tissue bank in the UK is proposed.