Seizures and Neuromuscular Diseases in Children: Understanding and Management |

1. Agnes Herczegfalvi Seizures, convulsions andNeuromusculardiseases Semmelweis University II. PediatricClinic, Dep. of. Neurology e-mail:herczegfalvi.agnes@med.Semmelweis-univ.hu Budapest, Oct-2017

2. Agnes Herczegfalvi Seizures, convulsions andNeuromusculardiseases Semmelweis University II. PediatricClinic, Dep. of. Neurology e-mail:herczegfalvi.agnes@med.Semmelweis-univ.hu Budapest, Oct-2017

3. Topic • Seizures • Convulsions • Nonepileptic paroxysmal events (NEPE) • Neuromuscular diseases

4. Seizure • is defined as an abnormal, disorderlydischarging of the brain's nerve cells, resulting in a temporary disturbanceof motor sensory, or mental function

5. Types of seizures • Febrile seizures are the most common type of seizure seen in children • 2-5% of children have a febrile seizureduring their childhood • The causeoccurs when a child have infection accompanied by fever. • 1/100 children hasepilepsy -recurring seizures <15y

6. ILAE 2017 Basic Classification of Seizure Seizures are firstcategorized by type of onset Epilepsia, 58(4):531–542, 2017

7. Basic Classification of Seizure by type • Focal-onset seizuresaredefined as » “originating within networks limited to onehemisphere. » Focal seizures may originate in subcortical structures.” • Generalized from onset seizures are defined as » “originating at some point within, and rapidly engaging, bilaterally distributed networks. ” • A seizure of unknownonset may still evidence certain defining » motor (e.g., tonic–clonic) or » nonmotor (e.g., behavior arrest) characteristics

8. Epilepsia, 58(4):531–542, 2017

9. Generalized seizures • involve a much larger portion of the brain • 2 types: convulsive (muscle jerking) and nonconvulsive with several subgroups. • Convulsive seizures are noted by uncontrollable muscle jerking lasting for a few minutes-usually < 5 min. followed by a period of drowsiness that is called the postictalperiod. child should return to his or her normal self except for fatigue/(15’) Often the child may have incontinence and it is normal for the child not to remember the seizure. Sometimes the jerking can cause injury, (from asmall bite on the tongue to abrokenbone • Tonic seizuresresult in continuous muscle contraction and rigidity, • tonic-clonic seizures involve alternating tonic activity with rhythmic jerking of muscle groups.

10. Generalized seizures tonic-clonic seizures

11. Status epilepticus • is either a seizure lasting longer than 30 minutes or • repeated seizures without a return to normal in between them • It is most common in children < 2 years, and most of these children have generalized tonic-clonic seizures.

12. Status epilepticus

13. Infantile spasms • commonly occur in children < 18 months • They are often associated with mental retardation • consist of sudden spasms of muscle groups, causing the child to assume a flexed stature. • They are frequent upon awakening. • Absence seizures, also known as petit mal seizures, are short episodes during which the child stares or eye blinks, with no apparent awareness of their surroundings • these episodes usually do not last longer then a few seconds and start and stop abruptly • but the child does not remember the event at all • these are sometimes discovered after the child's teacher reports daydreaming, if the child loses his or her place while reading or misses instructions for assignments.

14. Infantile spasms

15. Nonepilepticparoxysmalevents (NEPE) • NEPEfchildhoodconstitute a complexconditionincluding recurrentintermittent motor movements, behavioralchangesand somaticsymptoms • Characteristicfotthemovements: suddenonset and ending, whichlastforsecondsorminutes, mayoccuratanyageand most importantly may be misdiagnosedasepilepsy and treatedunnecessarily • Innonepilepticparoxysmaleventsthere is no changes of electroencephalogram (EEG) observedduringtheevent • NEPE’smay be associatedwithdifferentsigns and symptoms: fainting, loss of consciousness, headache, vomiting, dizziness, abdominalpain, irregularbreathing, sleepdisorders, and emotional and psychiatricproblems

16. Commonnon-epilepticparoxysmaleventsbyage

17. Non epileptic paroxysmal events and the epileptic conditions that they imitate Nepe: Non epileptic paroxysmal events Non epileptic paroxysmal events and the epileptic conditions that they imitate Nepe: Non epileptic paroxysmal events

18. Benign sleep myoclonus • Benign sleep myoclonus is characterized by repetitive, high-frequency myoclonic jerks in the arms and legs, which last for seconds or minutes, especially while falling asleep following feeding in the neonatal period • Appear in morning and maybe triggereded by a chnge in posture or by febrile illness • Its differential diagnosis with myoclonic seizures and focal seizures is important. It may be symmetric or generalized, or myoclonic episodes involving a single extremity may be observed. • the most important feature is that it is not observed outside of sleep.

19. Benign sleep myoclonus

20. Jitteriness • is an involuntary movement that is particularly frequent in the newborn • Its hallmark is tremor • The pathogenesis is poorly understood • Jitteriness is often accompanied by other signs of central nervous system excitation, such as hypermotility, hypertonicity, pre-peri-or postnatal events • It must be differentiated from myoclonus and seizure, although they may coexist

21. Jitteriness

22. Infancy and school-age period • Breath-holding spells • Breath-holding spells occur between the ages of 6 months and 5 years in children. • Its frequency is 5% • The spells are clinically observed in two forms as cyanotic form and pallid form. • The frequency of the episodes is variable; they may occur a few times a day or every 3–4 months • Pallid breath-holding spells; the child screams briefly, usually following minor injuries, seeing blood or drawing of blood and painful stimuli (falling, hitting the head) • Afterwards, hypotonia, loss of consciousness, and pale skin occur • The episodes usually last for a period < 60 seconds

23. Cyanotic breath-holding spells • 65% of breath-holding spells are cyanotic • A stimulant factor (pain, anger or fear) may trigger the episode. • Prolongation of expiration during crying may result in apnea • At the time of breath-holding, the skin color starts to change • This period may result in inspiration or cyanosis may deepen • and secondary hypoxia may be added • Loss of tonus and rarely myoclonic jerks may accompany • A postictal period may be observed depending on the severity of the episode

24. Breath-holding spells cyanotic type Pallid type

25. Shuddering attacks • Shuddering attack is an NEPE that initiates with rapid tremor of the head and shapes with continuance of this movement in the shoulder and trunk • The attacks last only for 1–2 seconds and they are benign movements that recur frequently (sometimes 100 times a day) • Stereotypes • are recurrent, simple movement groups (clapping, shaking arms, and head) that can be stopped voluntarily may be unilateral or bilateral and usually concentrated in the upper extremities and do not occur in the lower extremities these ritual movements including clapping, shaking arms, and shaking the head do not involve complex movement series and complex motor movements • most commonly occur in patients with mental retardation, autism.

26. Shuddering attacks

27. Stereotypes

28. Benign paroxysmal vertigo • Benign paroxysmal vertigo comprises episodes of dizziness that occur suddenly and last for a few minutes with an onset during infancinfancy • The attacks usually occur at ages of 1–2 years after the child starts walking, and may last up to the age of 6 years • Nausea, vomiting, and paleness may be prominent. The child is awake, suddenly becomes panicked, as if frightened, and does not want to move until the event ends. • If the child is urged to walk during this period, he/she is unbalanced.

29. Benign paroxysmal torticollis • is a movement disorder characterized by recurrent episodes with an onset at the age of 2–8 months in infancy. • Typically, it disappears at the age of 3–5 years. Episodes may last for 1–2 hours or for days • The child keeps his/her head turned to one direction; vomiting and paleness may accompany. It is notable that the period and frequency of the episodes decrease as the age gets older.

30. Adolescence • Syncope • Paroxysmal consciousness disorders with vascular, cardiac or neurologic origin characterized by sudden loss of consciousness, loss of tonus, falling, and spontaneous recovery in a short time are called syncope. • The frequency in the first two decades is about 15% • Vasovagal syncope • is the most common form of syncope in children • It constitutes approximately half of syncope attacks • The mechanism involves sudden loss of vasomotor tonus and as a result, systemic hypotension, bradycardia, and asystole Hypotension and paradoxical bradycardia are present

31. Neuromuscular disorders

32. Main disorders of the motor unit ANTERIOR HORN AXON NM JUNCTION MUSCLE FIBER DYSTROPHIES Duchenne / Becker Limb girdle (LGMD) sarcoglycanopathies Emery-Dreifuss / FSH MYOTONIC Sd Steinert / Thomsen MISCELLANEOUS Mitochondrial Congenital Metabolic Myositis SPINAL MUSCULAR ATROPHIES (SMA)Types 1-4 (Werdnig-Hoffman) Fried-Emery (SMAII) (Kugelberg-Welander) A.L.S. NEUROPATHIES H.S.M.N. (Charcot- Marie-Tooth, Déjerine-Sotas, others) H.M.N. H.N.A. MYASTHENIAS Myasthenia gravis Congenital myasthenic syndromes

33. Proteins of muscle mebrane R. Cohn & K.P. Campell, Muscle Nerve, 2000 Dystrophin protein (427 kDa), in muscle associated with an oligomeric protein complex (DPC) link between the extracellular matrix and the subsarcolemmal cytoskeleton mechanicalprotection

34. Mode of inheritance & NMD X-linked recessive (XL) DMD : Duchenne Muscular Dystrophy BMD : Becker Muscular Dystrophy XL-EDMD : XL-Emery-Dreifuss muscular dystrophy Autosomal Recessive (AR) sarcoglycanopathies (a, b,g, d) Congenital Muscular Dystrophies (CMD) Spinal Muscular Atrophies (SMA) Charcot-Marie-Tooth (& Déjerine-Sottas) Autosomal Dominant (AD) LGMD 1A, 1B, 1C, 1D, 1E FSHD : Facioscapulohumeral Muscular Dystrophy AD-EDMD: AD-Emery-Dreifuss MD Central Core disease Nemaline myopathy Thomsen myotonia Myotonic dystrophy (DM1)

35. Clinical features relevant to NMD • Gowers’ manoeuver • waddling gait • scapula alata • contractures • facial weakness • ophtalmoplegia, ptosis • myotonia, blepharospasm • macroglossia • respiratory involvement

36. Duchenne/Becker muscular dystrophy (DMD/BMD) • DMD and BMD are allelic forms of Xp21 linked rec.dis. • Birth prevalence of DMD: 1 in 3500 • BMD: 1 in 30000 males • BMD: clinical picture is milder(onset,severity,progress.) • Gene:2.5 Mb,79 exons, several tissue specific promoters • Dystrophin protein (427 kDa), in muscle associated with an oligomeric protein complex (DPC)link between the extracellular matrix and the subsarcolemmal cytoskeleton mechanical protection • In DMD patients dystrophin is missing; BMD patients have10-40% of normal dystrophin or molecules are truncated • Genetic defect: partial deletions in several exons in 60% of patients, 5% duplications, 35%point mutations, 1/3 de novo cases, in-frame (BMD) and out of frame mutations (DMD)

37. big calves = pseudohypertrophy BMD DMD non-specific but suggestive of a dystrophic process…

38. Scapula alata – scapular winging suggestive of FSHD when asymmetrical but occurs in LGMD, DMD, others…

39. Macroglossia Open your patient’s mouth! arched palate ? macroglossia? fasciculations? teeth deformities? suggestive but non-specific of a dystrophic process

40. Heart involvement and neuromuscular diseases DMD, BMD +++ Myotonic dystrophy +++ Kearns-Sayre ++ Desminopathies ++ Sarcoglycan deficiencies +/- distinguish between left ventricular dysfunction and conduction defects

41. Thank you