TGI Friday! Our weekly round-up of recently published research abstracts | 26 December 2014

December 26, 2014

From the eJournal of the European Society of Minimally Invasive Neurological Therapy (full text and illustrations available).

What do lumbar puncture and jugular venoplasty say about a connection between chronic fatigue syndrome and idiopathic intracranial hypertension?

Nicholas Higgins, John D Pickard, Andrew M Lever
Department of Radiology, Box 218, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 0QQ, UK Email:



Similarities between chronic fatigue syndrome and idiopathic intracranial hypertension (IIH) invite speculation that they may be related. Cranial venous outflow obstruction plays a role in the development of IIH. Could it be a factor in chronic fatigue? This paper attempts to evaluate an investigative approach to chronic fatigue syndrome that allows for this possibility.


Since 2007, patients attending a specialist clinic at our institution diagnosed with chronic fatigue syndrome and with prominent headache have been offered CT venography, lumbar puncture and a trial of cerebrospinal fluid withdrawal looking for IIH. Also, if CT venography revealed focal narrowing of the jugular veins, patients were offered catheter cerebral venography and jugular venoplasty attempting to establish their clinical significance.


In the 29 patients investigated to date, the mean cerebrospinal fluid (CSF) pressure was 19 cm H2O (range 12 – 41 cm H2O). Twenty-five patients responded positively to CSF withdrawal and in 5 the CSF pressures were high enough to allow an unequivocal diagnosis of IIH while in the remaining 20, symptoms improved with lumbar puncture even though CSF pressures were within the normal range.

Twenty-one patients had focal narrowing of one or both internal jugular veins on CT venography. Fourteen of these have had jugular venoplasty, all of whom reported an improvement in symptoms afterwards lasting from a few minutes to more than 1 month.


Chronic fatigue syndrome may represent an incomplete form of IIH. Cranial venous outflow obstruction deserves further investigation as a possible aetiological factor.

From Psychosomatics, the Journal of Consultation and Liaison Psychiatry, e-published 16 December 2014.

A Randomized, Placebo-Controlled, Double-Blind, Trial of Duloxetine in the Treatment of General Fatigue in Patients with Chronic Fatigue Syndrome
Lesley M. Arnold, Thomas J. Blom, Jeffrey A. Welge, Elizabeth Mariutto, Alicia Heller
University of Cincinnati Women's Health Research Program



To assess the efficacy and safety of duloxetine in patients with chronic fatigue syndrome.


A 12-week, randomized, double-blind study was designed to compare duloxetine 60-120 mg/day (n=30) with placebo (n=30) for efficacy and safety in the treatment of patients with chronic fatigue syndrome.

The primary outcome measure was the Multidimensional Fatigue Inventory (MFI) general fatigue subscale (range 4–20, with higher scores indicating greater fatigue). Secondary measures were the remaining MFI subscales, Brief Pain Inventory (BPI), Medical Outcomes Study Short Form-36 (SF-36), Hospital Anxiety and Depression Scale (HADS), CDC Symptom Inventory, Patient Global Impression of Improvement (PGI-I), and Clinical Global Impression of Severity (CGI-S).

The primary analysis of efficacy for continuous variables was a longitudinal analysis of the intent-to-treat sample, with treatment-by-time interaction as the measure of effect.


The improvement in the duloxetine group on the MFI general fatigue scores was not significantly greater than the placebo group (P=0.23; estimated difference between groups at week 12 = −1.0 [95% confidence interval −2.8, 0.7]). The duloxetine group was significantly superior to placebo on the MFI mental fatigue score, BPI average pain severity and interference scores, SF-36 bodily pain domain, and CGI-Severity score. Duloxetine was generally well


The primary efficacy measure of general fatigue did not significantly improve with duloxetine compared to placebo. Significant improvement in secondary measures of mental fatigue, pain, and global measure of severity suggests that duloxetine may be efficacious for some CFS symptom domains, but larger, controlled trials are needed to confirm these results.

From Molecular Pain, 15 December 2014.

This article is part of the supplement: Proceedings of the Seventh Scientific Meeting of The TMJ Association

Oral presentation

Small-fiber polyneuropathy (SFPN), a common underlying diagnosis in syndromes involving unexplained chronic pain and multi-system symptoms

Anne Louise Oaklander(1,2*), Heather Downs(1), Zeva Daniela Herzog(1) and Max Klein(1)
1) Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
2) Departments of Pathology (Neuropathology), Massachusetts General Hospital, Boston, MA 02114, USA


Syndromes involving unexplained chronic widespread pain (CWP) and multi-system symptoms are common, with 1-5% prevalence for fibromyalgia alone. They more often affect females and cause disability and high costs [1-3].

Other common syndromes include chronic fatigue, seronegative Lyme, and Gulf War Illness. Fragmentarysyndromes include TMJD, POTS, CRPS, irritable bowel).

These syndromes are particularly devastating in children and young adults, where they interfere with education and development and disrupt entire families [4-6]. SFPN is known to cause CWP and multi-system complaints in older adults.

Unlike the syndromes above, SFPN can be objectively diagnosed by measuring innervation in lower-leg skin biopsies, and autonomic functions testing (AFT) of heart rate, blood pressure and sweating [7]. SFPN has several established causes including diabetes, infections, cancer, and toxins. Many causes are diagnosable, treatable, and sometimes curable [8]. Our work suggests that unrecognized SFPN contributes to several syndromes involving CWP and multi-organ symptoms.


With IRB permission, we retrospectively analyzed the medical records of 41 patients with onset of unexplained CWP and multisymptoms before age 21; most had objective testing for SFPN [9]. We also prospectively studied 27 adult patients with fibromyalgia and 30 healthy volunteers using history, examination, skin biopsies and AFT [10].


Retrospective chart review identified definite (in 59%) and probable SFPN (in 17%) among the young patients with onset before age 21 [9]. We characterized the clinical features, diagnostic, and treatment options for this new early-onset SFPN. Studying children, who lacked the typical causes of late-onset SFPN, implicated autoimmune causality in most.

Among patients treated with immunomodulatory therapies, pain and other symptoms improved in 2/3 [9]. Among adults with fibromyalgia, 41% of skin biopsies from subjects with fibromyalgia vs. 3% of biopsies from controls were diagnostic for SFPN, and symptom and examination scores were higher in fibromyalgia subjects than in controls (all P ≤ 0.001) [10].

All fibromyalgia patients diagnosed with SFPN then had blood tests for all known causes [8]. None had diabetes but 62% had test-results consistent with dysimmunity, and some had genetic causes [10]. Other laboratories have now also linked fibromyalgia to SFPN [11-15].


Some patients with unexplained widespread pain and multi-system syndromes such as fibromyalgia have objectively diagnosable SFPN. SFPN can affect children and young adults, not just older adults.

Multiple lines of evidence suggest that early-onset SFPN has novel causes that can be treated. The prevalence of SFPN among TMJD patients is unstudied.

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