Infection-Associated Neurological Syndromes

Transcription

1 Infection-Associated Neurological Syndromes Anand P, MD PhD Medical Director, BloodCenter of Wisconsin Assistant Professor, Medical College of Wisconsin ASFA Annual Meeting San Antonio, TX, May 8th, 2015

2 No Relevant Conflicts of Interest

3 Infection Associated Neurological Diseases Guillain-Barre Syndrome Acute Disseminated Encephalomyelitis (ADEM) Sydenham s Chorea

4 Pathophysiology Molecular Mimicry Hypothesis: Components of infectious agents are similar in structure to neuronal tissue Antibodies/activated T-cells induced by pathogen crossreact with and damage neuronal myelin

5 1-2/100,000/yr GBS Acute inflammatory demyelinating polyneuropathy of peripheral nervous system Autoimmune etiology Progressive areflexic weakness Mild sensory changes or none

6 GBS AIDP- 90% Acute Motor Axonal Neuropathy- C Jejuni Acute Motor-Sensory Axonal Neuropathy Miller Fisher Syndrome- +Ophthalmoplegia Acute Autonomic Neuropathy

7 GBS 2/3 of patients report preceeding respiratory or GI symptoms C. Jejuni- strongest link Others: M Pneumoniae, H influenza, CMV & EBV. Vaccinations may result in no/very little increased risk AutoAbs to gangliosides: GM1, GD1a, GalNac-GD1a, GD1b, GQ1b, GD3 and GT1a Hughes et al, BMJ 1996; Lasky et al, NEJM 1998

8 Exam: GBS: Diagnosis Ascending, symmetrical motor weakness Diminished myotactic reflexes CSF: Elevated protein, nl WBC Other suggestive signs: Autonomic involvement, CN involvement, mild sensory issues, peak in 2-4 weeks, then plateau/improve Resp failure %

9 Supportive care Management Pain management Corticosteroids not recommended Disease modifying therapy: TPE and IVIg have been used and shown to be effective

10 TPE/IVIG RCT: TPE vs IVIG vs Both All three modalities to be equivalent. There were no differences in the three treatment groups in mean disability improvement nor the time to be able to walk without assistance or d/c from ventilation GBS RCT, Lancet, 1997

11 TPE Other studies have confirmed efficacy of TPE and IVIg in GBS The typical TPE strategy is to exchange ml plasma per kg body weight over days ie. 5-6 one PV exchanges Albumin replacement Early initiation of TPE seems be to associated with treatment efficacy GBS RCT, Ann Neur 1987; van der meche et al, NEJM 1992

12 GBS IVIG cost >2 x TPE Category: I (Initial therapy) III (Poor response to IVIG) Recommendation Grade: 1A (Initial therapy) 2C (Poor response to IVIG) Winters et al BMC Health Serv Res, 2011

13 Acute Disseminated Encephalomyelitis ~ /100,000/yr Monophasic primarily pediatric disease Demyelination White matter dx Multifocal asymmetric lesions

14 ADEM 70-93%: Infection Disease Onset: 2 days-4 weeks after antigenic challenge Often difficult to differentiate from the first episode of Multiple Sclerosis

15 ADEM Typical presentation: Acute encephalopathy : Lethargy to Coma Multifocal neurological deficits: Ataxia Hemiplegia Weakness Dysarthria Seizure Vision loss CN palsies Lasts from 2 4 weeks

16 Alper JCN 2012 ADEM: DIAGNOSIS MRI Characteristic lesions seen on MRI appear as patchy areas of increased signal intensity Involvement of deep cerebral hemispheric and subcortical white matter Periventricular Sparing

17 Treatment Abbreviate the CNS inflammatory reaction High-dose intravenous corticosteroids, such as methylprednisolone considered first-line therapy Prolonged taper TPE/IVIG may be considered for patients with severe ADEM, who respond poorly to steroid treatment

18 TPE: Rationale IgG abs to Myelin Oligodendrocyte glycoprotein (MOG) No Controlled Trials Some suggestion that early initiation in severe cases may be beneficial Probstel et al, Neurology, 2011

19 TPE Schedule Typically 3-6 treatments Albumin replacement; 1 PV, QOD Category II: Disorders for which apheresis is accepted as secondline therapy, either as a standalone treatment or in conjunction with other modes of treatment Grade 2C (Weak recommendation, L/VL quality evidence)

20 ADEM Complete recovery: 57-94% Mortality rare: Hemorrhagic ADEM Some may have some long term cognitive impairment

21 Sydenham s Chorea Chorea is a state of excessive, spontaneous movements, irregularly timed, non-repetitive, randomly distributed and abrupt in character SC is a pediatric post-infectious autoimmune neuropsychiatric disorders Major neurological manifestation of ARF Antibodies produced against GABHS, especially streptococcal M-proteins, cross-react with neurons of the basal ganglia (Anti-GM1, D2 dopam receptor)

22 Wei et al, NEJM 2013

23 Diagnosis Choreoathetoid movements Evidence of GABHS infection through throat culture and/or an elevated or increasing antistreptococcal antibody Other signs of ARF (carditis, arthritis, erythema marginatum) Emotional lability, OCD, anxiety MRI studies demonstrated striatal enlargement and inflammation

24 Sydenham s Chorea Steroids: Not always effective Penicillin tx and long term prophylaxis Haloperidol/valproic acid TPE/IVIg in severe cases

25 TPE Randomized trial of 18 subjects: IVIG vs TPE vs Prednisone Chorea severity scores deceased by 79%, 50% and 29%, respectively at 1 mo f/u Category: I; Recommendation Grade: 1B Garvey et al, J Child Neur 2005

26 Acknowledgments Neurology service at the Medical College of Wisconsin