Relationship between fatigue, cognitive dysfunction and small fiber neuropathy. Elske Hoitsma
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1 Relationship between fatigue, cognitive dysfunction and small fiber neuropathy Elske Hoitsma
2 Typical patient 45 year old male, Runs his own busy company, married, 4 young kids. Has always been very energetic and busy. Cough and dyspnoe 2 episodes of high fever Chest radiography and histology consistent with sarcoidosis 6 months prednison, chest radiography, pulmonary function resolved; Severe fatigue, pain and concentration problems persist Not capable for work
3 Pain Nociceptive pain caused by tissue damage Mixed pain Neuropathic pain caused by damage or dysfunction of the nervous system
4 Pain and small fiber neuropathy PainBurning/shooting character, paraesthesias, hypersensitivity of the skin, sheet intolerance Sicca syndrome Flushes Blurry vision Hyperhidrosis / hypohidrosis Micturation disturbances Diarrhea / Constipation Sexual dysfunction Orthostatic intolerance
5 Central nervous system Brain+spinal cord Peripheral nervous system Large (Aβ) nerve fibers Small (Aδ/C) nerve fibers Motor function Sensory function Sensory function Autonomic function muscle control position and movement sensation pain and temp. sensation basal physiology Large fiber neuropathy Polyneuropathy Small fiber neuropathy (SFN)
6 2002 Evidence of small fiber neuropathy in sarcoidosis
7 Fatigue Cognitive impairment: foggy brain Pain hypersensitivity of skin Sweating Tachycardia
8 Infection/inflamm ation Proinflammatory cytokins Acute sickness respons: Fever, pain, fatigue, cognitive decline, depressive mood
9 Fatigue and cognitive impairment Fatigue causes concentration and attention deficits cognitive impairment
10 Mood and the autonomic nervous system
11 The autonomic nervous system and cognition/mood Changes in autonomic nervous system hormones (e.g. cortisol elevation) correlates with fatigue, depression and cognitive impairment* Mood states in young healthy subjects can be estimated from heartrate variability ** Etc etc etc association studies *Thornton, Health psychol 2010; 29: **Park, Auton Res 2011; 21:
12 pain/ small nerve fiber dysfunction inflammation Chicken/ egg? Persisting? fatigue Mood disturbances, cognitive impairment Remission?
13 Acute sickness respons: Fever, pain, fatigue, cognitive decline, depressive mood Monofasic GBS, Lyme, virus sarcoidosis Ongoing MS, sarcoidosis Recovery Persisting fatigue cluster With fatigue cluster Without fatigue cluster
14 Not unique sarcoidosis Lyme disease Post-cancer: the pain, depression, fatigue cluster (PDF) Inflammation and Multiple Sclerosis (MS) Sjögren s syndrome Systemic Lupus cytokines Erythematodes (SLE) Inflammatory Bowel disease Guillain Barre syndrome etc
15 The discovery of by prof Cerami Cerami, J Intern Med 2011; 269: 8-15
16 A crucial role for TNF-α? Neuropathic pain/autonomic dysfunction Fatigue Cognition and depression Continuing TNF release in fatigued sarcoid patients in clinical remission? Anti-TNF therapy relieves only a subset of the patients?
17 Crucial role for damaged small (autonomic) nerve fibers? inflammation SFN Hormonal dysbalance Depression, pain, fatigue, Cogn Impairm.
18 Viral/bacterial infection particles Inflammation genetics Anti-TNF therapy ARA290 Physical activity exercise Dysbalance immune system Pain Fatigue Mood cognitio n Hormonal dysbalance genetics Psychological factors fear Cognitive behavior therapy explain SFN/damage autonomic nerve fibers genetics Anti-TNF, IvIG, ARA290 Stress Relaxation therapy
19 Summary Pain-Depressed cognition-fatigue (PDF) cluster Associations Role for TNF-alpha / autonomic nerve damage / HPA-axis hormones Psycho-neuroimmunology Treatment options: * symptomatic * treat/ prevent SFN: ARA290, IvIG, anti-tnf
20
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