Presentation on neuromuscular junction and its disorders.

1. Neuromuscular junction

2. Myasthenia gravis
• Autoimmune disorder- Ab to postjunctional Ach receptors
• Fatigue in affected muscle groups with activity that is
restored after rest
• Incidence: < 10/100.000,more in women, associated with
thymic tumor, thyrotoxicosis, RS, DLE

3. Presentation:
• Otherwise healthy pt with laryngeal
weakness, varying dysphonia and
dysphagia, difficulty in breathing
• Involvement of ocular muscles- ptosis ,
diplopia
• General fatigue
• Vocalis and cricothyroideus- fatigue
quickly with lowering of pitch after few
seconds
• Palatal musculature-Rhinolalia, nasal
regurgitation of food
• examination of larynx and palate reveals
fatigue with repetitive movements

4. Diagnosis
• Edrophonium ( Tensilon)- most commonly used
diagnostic test, improvement in muscular strength
• EMG- decreased amplitude and no of motor unit potentials
with repetitive use, which will normalise with edrophonium
• Most are +ve for Ab against Ach receptor
Treatment
Anticholinesterase drugs(pyridostigmine),
corticoteroids, azathioprine, plasmapheresis, IV
Ig, other immune modulating medications

5. Myasthenic syndrome/ Lambert-Eaten
Syndrome
• Association with underlying neoplasm,
autoimmune disease, occasionally no
cause
• In paraneoplastic disorder- Ab against tm
Ag cross-react with voltage-gated Ca 2+
involved in Ach release, leading to
disturbance of neuromuscular
transmission
• Power steadily increases if contraction is
maintained

6. Botulism
• Paralytic disease by poisoning with toxin of anaerobic, spore-
forming, g+ rod Clostridium botulinum.
• Most commonly-ingestion of improperly home-canned food
• Fulminating weakness , after 12-72 hours manifests as- diplopia,
ptosis, facial weakness, dysphagia, rhinolalia, respiratory failure
• Weakness in limbs last to appear
• Anticholinergic symptoms- blurry vision, dry mouth, paralytic
ileus, postural hypotension
Treatment
• Antitoxin is available
• Guanidine hydrochloride-facilitates release of Ach from
nerve endings, improves muscle strength
• Supportive treatment-mainstay

7. Botox mechanism
Disease caused by:
• Inoculation of wound with local proliferation of bacterium
and systemic spread of toxin
• Ingestion of spores in improperly cooked food, with
germination and growth in gut and absorption of toxin
• Ingestion of preformed toxin in improperly cooked foods
with systemic absorption
Toxin is heat labile, inactivated by boiling for several minutes

8. • 7 serotypes(A-G)
• Inhibit exocytotic release of Ach at NM junction
• May have inhibitory activity in afferent
transmission of pain by preventing release of
substance P, CGRP, glutamate or neurokinin A
• Heavy chain- neuron specific binding and
internalisation
• Light chain- protease that cleaves one of fusion
proteins responsible for vesicle docking,
preventing NT exocytosis
• A, E→ SNAP-25 →3 months
• B,D,F,G→ synaptobrevin →2 months
• C → syntaxin

9. 1 unit of BOTOX (botulinum toxin A-Allergen)
• Amount of toxin required to kill 50% of a batch of Swiss-Webster
mice
Lethal dose=3500 U
Ab render resistant to one paralytic effect of one serotype
Intitally, axon responds by creating sprouts to establish new
junctions
New junctions allow weak stimulation at about 1 month
At 90 days, original terminals regain activity, results in
regression of sprouts

10. Aminoglycoside
antibiotics
• Large doses can produce clinical syndrome like botulism
owing to prevention of Ach release from nerve endings.
• Ca 2+ channel blockade likely
• Symptoms resolve on discontinuation
• Best avoided in patients with disturbances of neuromuscular
transmission, Myasthenia gravis

11. Myopathic Disorders

12. Muscular dystrophies
• Group of inherited myopathic
disorders characterised by
progressive muscle weakness
and wasting
• Most forms- limb and girdle
musculature, ocular and
oropharyngeal with autosomal
dominant inheritance
• Myotonia is an abnormality of
muscle fibre membrane that
leads to muscle stiffness owing
to marked delay before affected
muscles can relax after
contraction

13. Polymyositis and dermatomyositis
• Inflammatory myopathies associated with lung carcinoma,
autoimmune disorders or polio
• Muscle pain, tenderness, dysphagia, respiratory difficulties
• Dermatomyositis- heliotrope rash

14. Hyperfuctional disorders

15. Dystonia
• Chronic neurologic disorder
of central motor processing
within basal ganglia
(extrapyramidal system)
• Task-specific, involuntarily
sustained muscle contractions
causing twisting and
repetitive movements or
abnormal postures
• Anxiety aggravates
movements, sedatives may
mitigate them and posturing
characteristically disappears
during sleep

16. Dystonia
• Focal-spasmodic dysphonia, writer’s cramp
• Regional-cervical dystonia
• Generalised
• Idiopathic
• Secondary- hereditary syndromes(DYT1 gene locus),
stroke, trauma, drugs

17. Spasmodic dysphonia
• Focal laryngeal dystonia in which spasmodic
contractions of intrinsic laryngeal musculature occur
• Adductor spasmodic dysphonia- harsh, strained and
strangled quality with voice breaks
1871 Traube first described a
female having “spastic form of
nervous hoarseness”
Cause unknown, autopsy studies-
altered NT in caudate, putamen,
globus pallidus, dentate nuclei

18. • Adult onset, female predominance
• 83%-AddSD, 17% ABdSD, rare mixed and breathing
dystonia cases
• 30%- assoc essential tremor, 14%- other dystonia,
blepharospam, writer’s cramp
• 23%- family history
•Contractions are task specific, usually affect speaking, sparing
breathing, singing, swallowing, coughing, character speech,
yelling
•Strangled feeling when trying to speak, difficulty in getting
words out
•More- speaking over telephone, public speaking, stress
•Alcohol or sedatives reduce voice breaks
•Speech normal during sleep

19. AddSD
• Strangled breaks in
connected speech
• More in words that
begin with vowels
• Eliciting phrases-
counting 80 to 90, “we
eat eggs everyday”
• Hyperadduction of
vocal cords with
hyperfunction of
supraglottis
AbdSD
•Breathy breaks in connected
speech
•Especially vowels following a
voiceless consonant
•Eliciting phrases-”puppy bit the
tape”, “Harry had a hard head”
•Delayed onset of phonation
after p, t, h
•Parting of vocal folds with
“arytenoid hanging” correlating
with a breathy voice break

20. Diagnosis-
• History, vocal characteristics, fiberoptic laryngeal
examination across multiple speech tasks
• Symptoms may be suppressed with sensory trick
(geste antagonist) such as voicing while chewing,
biting tongue, holding finger in the corner of the
mouth
• Insertion of fiberoptic scope may diminish
involuntary contractions
• Neurologic consultation, neuroimaging, selective
serologic testing( serum ceruloplasm, syphilis, B12,
folate)

21. Treatment
• Botulinum toxin injection into affected muscles
• AddSD- thyroarytenoid-lateral cricoarytenoid muscle complex
• AbdSD- posterior cricoarytenoid
• Dose is titrated
• Transorally or transcutaneously, EMG guidance for proper
placement in active location
Complications-
• excessive glottal weakness and breathiness with TA-LCA
• Stridor with PCA
• Dysphagia if toxin diffuses to adjacent constrictors
Surgery
Rhizotomy, myomectomy or denervation and reinnervation
with a branch of ansa
RLN section- global paralysis, high degree of dystoni recidivism
Speech therapy

22. Essential Tremor
• Intention tremor affecting adult female
patients more than male
• 30%- vocal involvement
• Oscillatory shaking of hands and rhythmic head titubation
are most common
• Vocal symptoms- tremor in muscles of larynx, pharynx, soft
palate, strap muscles of neck
• Aggravated by-Anxiety, public speaking, telephone use
• Mitigated by –sedatives
• Differs by rhythmicity and presence across all speech tasks
• Injections of botulinum toxin may decrease amplitude of
tremor by weakening affected musculature, does not
eliminate

23. Tic disorders
• Sudden, recurrent, quick, abnormal movements or
vocalizations that abruptly interrupt normal activity
• Can be temporarily suppressed
• Aggravated by stress, anger, excitement
• Decrease with relaxation, sleep
• Clinical diagnosis, good response to medical therapy
• Gilles de la Tourette syndrome- childhood onset tic
disorder , behavioral abnormalities, 10-20%:
signature coprolalia

24. Myoclonus
• Oculopalatolaryngopharyngeal myoclonus
• Twitchlike, rhythmic contractions of soft palate, pharynx, larynx :1-2/s
• Can be part of seizure disorder, posttraumatic or viral, toxic or
metabolic encephalopathy, with changes in olivary nuclei
• Speech may be choppy with intermittent hypernasality from palatal
dysfunction
• Often c/c- persistent clicking in ear
Treatment:
• Botulinum toxin injected to palate, vocal folds to decrease severity of
contractions
• Eustachian tube dysfunction and velopharyngeal insufficiency are
important limitations
• Systemic medications

25. Miscellaneous voice disorders
• Several disorders occur without clear anatomic or
neurologic dysfunction of larynx
• Caused by abnormal laryngeal posturing and
often occur as compensation for temporary
laryngeal functional deficiency(laryngitis)
• abnormal laryngeal posturing persists despite
resolution of original insult
• May reflect physical manifestation of
psychosocial issues
• Do not represent true neurologic disease but are
often present in d/d

26. Functional aphonia
• Emotionally labile females, 15-30
• Severe or complete loss of voice, despite neurologically intact larynx
• Communicates with whisper
• Laryngeal examination- normal laryngeal responses to nonspeech maneuvers
(e.g. sniffing, coughing, humming)
• When phonation attempted- complete incoordination of respiratory system and
laryngeal system
• Treatment of comorbid medical conditions
• Voice therapy trial

27. Muscle tension dysphonia
• Patients posture their vocal cords using intrinsic and extrinsic laryngeal
muscles in hyperfunctional manner
• Causes tightness and dysphonia with harshness , breathiness, choppy vocal
production
• Examination- hyperadduction of vocal cords with sustained contraction of
supraglottis
Primary-
•In vocal enthusiasts or who have excessive
vocal demands
•Often following upper respiratory infection
or significant laryngopharyngeal reflux disease
Secondary
In compensation for underlying glottal
incompetence

28. • Treatment- addressing underlying glottal pathology (vocal cord
paresis or paralysis, atrophy, mucosal lesion) and voice therapy

29. motion disorder
(episodic paroxysmal
laryngospasm)• Larynx exhibits paradoxical vocal cord adduction during
inspiration
• Poorly defined disorder in which clinical diagnosis relies on
exclusion of other disorders with similar symptoms(asthma,
subglottic or tracheal pathology)
• Attenuation of inspiratory component of flow-volume loop,
indicating a variable extrathoracic airway obstruction may be
seen when symptomatic

30. • Most common- individuals 10-40 years who are
considered high achievers, educated and competitive in
their career or athletic forum
• Adults- predominantly in women, not dramatic gender
difference in children and adolescents
• 60%- coexistent asthma, further complicates diagnosis
and treatment

31. Symptoms
• Coughing, wheezing, dyspnea, hoarseness, throat tightness and stridor
• h/o recurrent respiratory failure, requiring intubation or tracheotomy and
extensive evaluations unrevealing of appropriate causative pathology
• Difficulty breathing in-PVFMD
• Difficulty breathing out- asthma
• Choking sensation at level of larynx or chronic throat constriction with
associated dysphonia
Treatment
• Aggressive treatment of comorbidity-LPR, allergies, asthma with voice therapy
• Heliox and positive airway pressure , with anxiolytics and reassurance may help
to alleviate respiratory distress during an acute attack
• Voice therapy- focus on exhalation and abdominal breathing techniques with
panting and sniffing to encourage vocal fold abduction
• Laryngoscopic biofeedback

32. Dysphonia Plica Ventricularis
(Ventricular Dysphonia)
• Voice is produced by ventricular folds (false cords) which have taken over the
function of true cords.
• Voice is rough, low-pitched and unpleasant.
• Ventricular voice may be secondary to impaired function of the true cord such as
paralysis, fixation, surgical excision, or tumours.
Ventricular bands in these situations try to compensate or assume phonatory
function of true cords.
•
Functional type of ventricular dysphonia occurs in normal larynx . Here cause is
psychogenic.
voice begins normally but soon becomes rough when false cords usurp the
function of true cords.
• Diagnosis is made on indirect laryngoscopy; the false cords are seen to
approximate partially or completely and obscure the view of true cords on
phonation.
• Ventricular dysphonia secondary to laryngeal disorders is difficult to treat but
the function al type can be helped through voice therapy and psychological
counselling.