Gluten and CNS Flashcards
Gluten sensitivity definition
A state of heightened immunological responsiveness to ingested gluten in genetically susceptible individuals
Gluten related disorder definition
A group of diseases triggered by the ingestion of gluten that include coealiac disease, dermatitis herpetoformis, gluten allergy, gluten ataxia etc. These conditions are not always associated with enteropathy (disease of the intestine)
Gluten ataxia
- Sporadic otherwise idiopathic ataxia
- Presence of serological markers of sensitivity to gluten (AGA, TCG, TG2, EMA)
- Gluten ataxia (+AGA) - 18% of all ataxias, 47% of all idiopathic sporadic ataxias
- Antibodies released when gluten is digested attack the cerebellum - cerebellar symptoms
- Slowly progressive disease
- Dietary treatment - improvement of ataxia within 1 year of strict gluten-free diet even in those without enteropathy (non-celiac gluten sensitivity)
- MR spectroscopy monitor patients - NAA measure tells you about metabolic activity of the area of interest, the higher the better. Varies patient to patient so require creatine (doesn’t change in health and disease). NAA to creatin ratio detected. NAA well below creatin = abnormal (should be higher).
- Diet improves ratio in all patients who show reduced antibodies
- Diet but still positive antibodies = ratio got worse, need to be very strict with diet
Gluten neuropathy
- 26% of all neuropathies
- Neuropathy in 21% of patients with coeliac disease on GF diet
- CD associated with neuropathy 64 vs. 15 per 100,000 people/year for patients with CD vs. controls
- Two types of neuropathy
1. Sensorimotor axonal symmetrical neuropathy (66%)
2. Sensory ganglionopathy (33%)
symptoms of neuropathy - decreased/lost feeling, difficulty using arms, hands, legs and feet, tingling, numbness/burning in body
Neurophysiological evidence of improved neuropathy within 1 year of adherence to strict GF diet irrespective of enteropathy presence
Gluten encephalopathy
- Episodes often severe/intractable headaches
- White matter abnormalities in MRI
- Headache improves on GF diet
- On GF diet, WM changes do not change
- If no GF diet, can progress to vascular dementia
Neurological dysfunction and Gluten
The frequency of antiglidin antibodies amongst patients with unexplained neurological dysfunction was 57% compared to 12% in blood donors and 5% with defined neurological dysfunction and the frequency of coeliac disease in these patients was 16%.
3 year study looking at whether patients with gastro with classic coeliac disease symptoms have neurological problems. 100 newly diagnosed patients with CD had a neuro exam and imaging. 61% have neuro symptoms (headache/balance/sensory). 46% had abnormal MRI spectroscopy of the cerebellum and 19% had white matter lesions above that expected for their age. 52% who had abnormal MR at baseline (low Naa/cr) repeat scan showed normal MRS at 1 year. 15 pts. showed increased white matter lesions at 1 year and 47% had antibodies at 1 year.
We can conclude that patients with classic presentation of coeliac disease frequently have neurological symptoms and signs unreported or unrecognised due to no linking between the two. TG6 + patients were more likely to have reduced grey matter volume in the thalamus and cerebellum.
Clinical/serological differences between patients with neurological manifestations with or without enteropathy
CD vs. NCGS with neuro dysfunction show no clinical difference and they both respond to a gluten free diet.
Gliadin antibodies react with purkinje cells. serum from patients with GA into ventricle of mouse induced ataxia within 3 hours.
Intracellular enzymes that cross link gliadin
TG2 - autoantigen in CD
TG3 - autoantigen in DH
TG6 - in neurological manifestations
TG6 more prevalent in CD with ND, TG3 and TG6 primarily expressed in locality of tissue involved (skin and brain). TG2 and TG6 antibodies react with neural tissue and can induce ataxia in mice.
