Stiff-Person Syndrome and Related Disorders: A Comprehensive, Practical Guide

ISBN-13: 9783030430610 / Angielski / Miękka / 2021 / 183 str.

Pichet Termsarasab; Thananan Thammongkolchai; Bashar Katirji

Spis treści

1. Historical background of stiff-person syndrome

• The original description by Moersch and Woltman

• Timeline of discoveries of antibodies

• Treatment advances in the field

2. Clinical phenomenology (including diagnostic criteria) of stiff-person syndrome and stiff-person syndrome variants

• How to differentiate stiffness in stiff-person syndrome from other phenomenologies

o Spasticity/hypertonia

o Dystonia

o Cramps

• Clinical features of classic stiff-person syndrome

o Core features

o Associated features including associated autoimmunity

• Diagnostic criteria of stiff-person syndrome and its limitation

• Clinical features of stiff-person syndrome variants

o Stiff-limb syndrome  (SLS)

o Progressive encephalomyelitis with rigidity and myoclonus (PERM)

o Overlapping syndromes

o Hyperekplexia: A stiff-person syndrome variant or distinguished entity?

o Confusion about terminology in clinical practice

• Clinical pearls and pitfalls in the diagnosis of stiff-person syndrome

3. Differential diagnosis of stiff-person syndrome

• Central hyperexcitability

o Focal spinal cord lesions

o Toxic/parainfectious causes

o Autoimmune causes e.g. LGI-associated faciobrachial dystonic seizures

o Paroxysmal movement disorders

 Paroxysmal kinesigenic dyskinesia (PKD)

 Paroxysmal non-kinesigenic dyskinesia (PNKD)

 Paroxysmal exercise dystonia (PED)

 Secondary paroxysmal kinesigenic dyskinesias

• Paroxysmal tonic spasm in multiple sclerosis

• Other structural spinal cord lesions

 Episodic ataxia

• Peripheral hyperexcitability (overview here with further dedicated information on this subtopic in chapter 14)

o Peripheral nerve hyperexcitability syndromes

o Disorders of skeletal muscle membrane hyperexcitability 

4. Electrophysiology of stiff-person syndromes

• Electrophysiologic techniques in studying stiff-person syndrome

o Needle electromyography vs. surface electromyography

o Special techniques

• Key electrophysiologic findings in stiff-person syndrome

o Continuous motor unit activity (CMUA)

o Loss of vibration-induced inhibition of H-reflex

o Enhanced exteroceptive reflexes including blink reflexes

o Co-contraction of agonist and antagonist muscles

5. Neurochemistry of inhibitory synapses and clinical applications in stiff-person syndromes

• GABA-ergic synapses

• Antigenic targets of GABA-ergic synapses in stiff-person syndrome

o Glutamic acid decarboxylase (GAD)

o Amphiphysin 

o GABAA receptor (GABA AR)

o GABAA receptor-associated protein (GABARAP)

• Glycinergic synapses

• Antigenic targets of glycinergic synapses in stiff-person syndrome

o Glycine receptor

o Glycine transporter 2 (GlyT2)

o Gephyrin

6. Immunopathogenesis of stiff-person syndromes

• GAD-65 vs. GAD-67

In each subtopic below, we will discuss the controversies and current supporting and arguing evidence.

• Is GAD-65 pathogenic or epiphenomenon?

• Cell-mediated immunity vs. humoral immune response

• Role of T-cell vs. B-cell

• Future directions of research in stiff-person syndromes

7. Antibodies in stiff-person syndrome and their correlations with clinical phenotypes

• Eight main antibodies: anti-GAD, anti-amphiphysin, anti- GABA AR, anti-GABARAP, anti-glycine, anti-GlyT2, anti-gephyrin, anti-dipeptidylpeptidase (anti-DPPX)

• Prevalence of these antibodies in stiff-person syndrome and its variants

• Complex correlations between clinical phenotypes and immunophenotypes

• Oncological association/Paraneoplastic stiff-person syndrome

8. Anti-glutamic acid decarboxylase 65 (GAD65)-associated syndromes

• Phenotypic Spectrum of anti-GAD65 antibody syndromes

o Anti-GAD65-associated stiff-person syndrome

o Anti-GAD65 and diabetes mellitus

o Anti-GAD65-associated ataxia

o Anti-GAD65-associated epilepsy

o Other neurologic syndromes associated with anti-GAD65

• Laboratory aspects of anti-GAD65

o Positive high vs. positive low titer

o An issue and caveat about non-unity of reported units

o Laboratory techniques

 Radio-immunoassay (RIA)

 Enzyme-linked immunoassay (ELISA)

 Western blot

 Immunofluorescence

• Oncological association of anti-GAD-65 antibodies: Is paraneoplastic work-up required?

• Treatment response and prognosis

9. Progressive encephalomyelitis with rigidity and myoclonus (PERM) syndrome

• Brief history (already discussed in detail in chapter 1)

• Clinical features

• Electrodiagnostic findings

• Associated antibodies

o Anti-glycine

o Anti-DPPX 

• Prognosis and treatment responses

10. Emergencies in stiff-person syndrome 

In each topic below, we will discuss clinical features, how to recognize and treatment.  These features, if not recognized and treated promptly and appropriately, can lead to morbidity and mortality. This topic is particularly important to clinicians managing stiff-person syndrome in the inpatient setting.

• Paroxysmal dysautonomia

• Respiratory issues

• Status spasticus

• Treatment-related emergencies: Baclofen withdrawal syndrome

11. Diagnostic approach in stiff-person syndrome and its variants

• Complexity between immunophenotypes and antibodies

• Targeted approach vs. shotgun approach

o Pros and cons

o Current status of antibody testing

o Issues with existing diagnostic algorithms

• Proposed diagnostic algorithm

• Future directions

12. Treatment of stiff-person syndrome

For each treatment modality, we will review current evidence in the literature including clinical trials (if any), discuss our experience and provide a practical guide in clinical practice.  Doses and routes of administration will also be provided, likely in a tabulated form.

• Symptomatic therapies

o Benzodiazepines

o Baclofen

o Other medications

• Immunotherapies

o Steroids

o Intravenous immunoglobulins (IVIg)

 Randomized controlled trial 

o Plasma exchange (PLEX)

o Rituximab

 Randomized controlled trial 

o Other immunomodulatory agents including azathioprine, mycophenolate mofetil

o Proposed treatment algorithm

o Future directions

13. Pediatric stiff-person syndrome

• Prevalence

• Reported cases in the literature

• Clinical features

• Difference between pediatric vs. adult stiff-person syndrome

• Treatment outcome 

• Caveats in management of pediatric stiff-person syndrome

14. Peripheral hyperexcitability syndromes

Clinical features, differential diagnoses, how to distinguish from the stiff-person syndrome, investigations and brief discussion about treatment of each entiity will be discussed in this chapter.

• Peripheral nerve hyperexcitability syndromes

o Neuromyotonia including Isaac and Morvan syndromes

o Cramp-fasciculation syndrome

• Disorders of skeletal muscle membrane hyperexcitability

o Myotonic dystrophies

o Myotonia congenita

o Paramyotonia congenita

o Myotonia in periodic paralysis 

o Schwartz-Jampel syndrome

o Rippling muscle disease

15. Hyperekplexia

• Clinical features

• How to distinguish from stiff-person syndromes and other startle syndromes

o Culture-specific startle syndromes e.g. Latah, Jumping Frenchmen, Miryachit

• Genetic basis of hereditary hyperekplexia

• Investigations

• Treatment

O autorze

Pichet Termsarasab, MD

Faculty of Medicine Ramathibodi Hospital

Mahidol University

Bangkok, Thailand

 

Thananan Thammongkolchai, MD

Faculty of Medicine Ramathibodi Hospital

Mahidol University

Bangkok, Thailand

Bashar Katirji, MD

Academic affiliation: Professor of Neurology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA. 

bashar.katirji@uhhospitals.org

Phone number: (216) 844-4854

Blurb

This comprehensive title covers all of the broad aspects of stiff-person spectrum disorders (SPSD), ranging from clinical features and laboratory investigations to the basic scientific roles of neuroimmunology and genetics that aid clinicians in understanding the pathogenesis of this disorder.

Organized across 15 chapters, this highly practical book begins with a thorough account of the history and clinical phenomenology of SPSD.  Subsequent chapters then delve into the differential diagnoses of the disorder, as well as its electrophysiology, immunopathogenesis, and neurochemistry. Following this is an analysis of each subtype of SPSD including classic stiff-person syndrome and its variants, correlations between clinical phenotypes and antibodies, as well as SPSD in the pediatric population. Finally, the book concludes with an examination of the various SPSD diagnostic approaches, treatments, and potential emergencies seen in clinical practice.

Developed by a renowned multidisciplinary authorship, Stiff-Person Syndrome and Related Disorders is an indispensable contribution to the clinical literature and will be of great interest to both clinicians and basic science researchers.