approach to Dystonia and myoclonus movement disorders

1. DYSTONIA CLINICAL APPROACH
Osama A. Ragab
Neurology MD

2. DYSTONIA
• Dystonia is a movement disorder characterized by sustained or intermittent
muscle contractions causing abnormal, often repetitive, movements, postures, or
both. Dystonic movements are typically patterned, twisting, and may be
tremulous. Dystonia is often initiated or worsened by voluntary action and
associated with overflow muscle activation.

3. DYSTONIA

4. • Several conditions resulting in abnormal movements, postures, or spasm, which
may mimic dystonia, which are also called “pseudo-dystonias.”
DYSTONIA

5. DYSTONIA

6. AXIS I. CLINICAL CHARACTERISTICS

7.  Infancy (birth to 2 years);
 Childhood (3–12 years);
 Adolescence (13–20 years);
 Early adulthood (21–40 years);
 Late adulthood (>40 years).
AGE AT ONSET

8. • Focal. Only one body region is affected. Typical examples of focal forms are
blepharospasm, oromandibular dystonia, cervical dystonia, laryngeal dystonia, and writer's
cramp.
• Segmental. Two or more contiguous body regions are affected. Typical examples of
segmental forms are: cranial dystonia (blepharospasm with lower facial and jaw or tongue
involvement) or bi-brachial dystonia.
• Multifocal. Two noncontiguous or more (contiguous or not) body regions are involved.
• Generalized. The trunk and at least 2 other sites are involved. Generalized forms with leg
involvement are distinguished from those without leg involvement.
• Hemidystonia. More body regions restricted to one body side are involved.
BODY DISTRIBUTION

9. • Persistent. Dystonia that persists to approximately the same extent throughout the
day.
• Action-specific. Dystonia that occurs only during a particular activity or task.
• Diurnal fluctuations. Dystonia fluctuates during the day, with recognizable circadian
variations in occurrence, severity and phenomenology.
• Paroxysmal. Sudden self-limited episodes of dystonia usually induced by a trigger
with return to preexisting neurological state.
TEMPORAL PATTERN

10. Isolated Dystonia or Combined with Another Movement Disorder
• Isolated dystonia. Dystonia is the only motor feature, with the exception of tremor.
• Combined dystonia. Dystonia is combined with other movement disorders (such as
myoclonus, parkinsonism, etc.).
ASSOCIATED FEATURES

11.  The presence or absence of other neurologic or systemic features is a vital
component for characterizing dystonia syndromes.
 Non-motor features have been recently described in cases of dystonia with different
etiologies, cognitive decline is typically observed in degenerative or progressive
dystonia syndromes.
 Wilson disease is a disorder where dystonia is typically combined with other
neurological or psychiatric symptoms and liver disease.
OCCURRENCE OF OTHER NEUROLOGICAL OR
SYSTEMIC MANIFESTATIONS

12. AXIS II. ETIOLOGY

13. AXIS II. ETIOLOGY
Evidence of degeneration, either at the gross, microscopic, or molecular
level, provides a useful means to discriminate subgroups of dystonia into
degenerative and nondegenerative forms:
• Degeneration (progressive structural abnormality, such as neuronal
loss);
• Static lesions (non-progressive neurodevelopmental anomalies or
acquired lesions);
• No evidence of degeneration or structural lesion.

14.  Inherited (dystonia forms of proven genetic origin).
 • Autosomal dominant. Several autosomal dominant forms are listed under this heading, such as
DYT1 .
 • Autosomal recessive. The list of autosomal recessive forms of inherited dystonia is continuously
growing. Notable forms encompass Wilson disease and NBIA.
 • X-linked recessive. Inherited dystonia with X-linked transmission encompass forms such as Lubag,
Lesch-Nyhan syndrome
 • Mitochondrial. Mitochondrial forms, such as Leigh syndrome or Leber optic atrophy and dystonia.
INHERITED OR ACQUIRED

15.  Acquired (dystonia due to a known specific cause).
 • Perinatal brain injury: dystonic cerebral palsy.
 • Infection: viral encephalitis, subacute sclerosing panencephalitis, human immunodeficiency virus.
 • Drug: levodopa and dopamine agonists, neuroleptics .
 • Toxic: manganese, cobalt, carbon disulfide, cyanide, methanol.
 • Vascular: ischemia, hemorrhage.
 • Neoplastic: brain tumor, and paraneoplastic encephalitis.
 • Brain injury: head trauma, brain surgery (including stereotactic ablations), and electrical injury.
 • Psychogenic (functional).
INHERITED OR ACQUIRED

16.  Idiopathic (unknown cause).
 • Sporadic;
 • Familial.
 Many cases of focal or segmental isolated dystonia with onset in adulthood fall in
this category.
 Idiopathic forms may be reclassified as inherited, as new dystonia genes are
recognized.
INHERITED OR ACQUIRED

20. MYOCLONUS DIAGNOSTIC APPROACH

21. • Myoclonus is a complex hyperkinetic movement disorder characterized
by sudden, brief, involuntary jerks of a single muscle or a
group of muscles.
MYOCLONUS DIAGNOSTIC APPROACH

22. • Three approaches to the classification and diagnosis of myoclonus exist:
clinical, aetiological and anatomical.
• The clinical classification is based on clinical signs, including the
distribution and temporal pattern and relationship to motor activity.
• The aetiological classification is divided into four subgroups:
physiological myoclonus, essential myoclonus, epileptic myoclonus, and
symptomatic myoclonus.
• The anatomical classification. Myoclonus can be generated in the
cortex, in subcortical areas, in the spinal cord, or in the peripheral
nerves.
MYOCLONUS DIAGNOSTIC APPROACH

23. MYOCLONUSDIAGNOSTIC
APPROACH

24. • Myoclonus (positive myoclonus) or (negative myoclonus).
• Three types of negative myoclonus have been described:
• Asterixis in patients with a toxic–metabolic encephalopathy.
• Negative myoclonus involving the axial muscles and lower limbs,
which results in a wobbling gait and sudden falls.
• Epileptic negative myoclonus. Epileptic negative myoclonus is defined
as an interruption of muscle activity time-locked to an epileptic EEG
abnormality, without evidence of antecedent positive myoclonus.
STEP 1: IS THE SYMPTOM REALLY
MYOCLONUS?

25. STEP 1: IS THE
SYMPTOM REALLY
MYOCLONUS?

26. STEP 2: ANATOMICAL
SUBSTRATES OF
MYOCLONUS

27. • Cortical and subcortical myoclonus have a broad differential diagnosis.
In general, acute or subacute onset and/or fast progression of
myoclonus are important clues for an acquired cause.
• Spinal or peripheral myoclonus.
• History and clinical examination can differentiate between spinal and
peripheral nerve lesion.
• Nerve conduction study and EMG.Spinal cord imaging.
STEP 3: DEFINING THE AETIOLOGY

28. STEP 4: ARE MEDICATIONS
OR TOXIC AGENTS
INVOLVED?

29. Laboratory assessment for Acute or chronic renal failure, acute or
chronic hepatic failure, chronic respiratory failure with hypercapnia,
disturbances of glucose homeostasis, hyperthyroidism, and metabolic
alkalosis or acidosis.
Careful evaluation of a potential infectious or immune-mediated cause
for myoclonus is warranted.
CSF analysis to test for immune-mediated disorders and to identify
infectious agents. Immune-mediated disorders, such as (anti-NMDAR)
encephalitis, stiff-person syndrome ,progressive encephalomyelitis with
rigidity and myoclonus.
STEP 5: ROUTINE LABORATORY TESTS

30. Abnormalities seen on brain MRI can also indicate a genetic cause,
such as neurodegeneration with brain iron accumulation (NBIA)
disorders, leukodystrophy, or mitochondrial disorders.
 The recommended MRI protocol comprises T1-weighted and T2-
weighted imaging, fluid-attenuated inversion recovery, and diffusion-
weighted imaging (DWI), with administration of gadolinium contrast.
 Diagnosticians should also consider susceptibility-weighted imaging
to assess iron accumulation.
STEP 6: BRAIN MRI

31. Mitochondrial disorders
one must be aware of mitochondrial disorders caused by mutations in
mitochondrial DNA (mtDNA), which are associated with myoclonus
including MERRF syndrome, Leigh syndrome, and MELAS syndrome.
Clinical clues for a mitochondrial disorder are multiorgan
involvement, ophthalmoplegia, muscle involvement, neuropathy, ataxia,
deafness, specific MRI brain findings, and maternal inheritance.
STEP 7: MITOCHONDRIAL OR
NEURODEGENERATIVE?

32. Late-onset neurodegenerative disorders
Late-onset neurodegenerative disorders that are often accompanied by
myoclonus include Alzheimer disease, Parkinson disease (PD), multiple
system atrophy (MSA) and less commonly dementia with Lewy bodies,
Huntington disease, and corticobasal degeneration.
Myoclonus in PD and MSA usually manifests as irregular, small-
amplitude, often stimulus-sensitive myoclonic jerks of the fingers
during muscle activation (cortical polyminimyoclonus).
STEP 7: MITOCHONDRIAL OR
NEURODEGENERATIVE?

33. If the previous diagnostic steps have not revealed the cause of the
myoclonus, the next step is NGS, which comprises several massively
parallel sequencing techniques, including whole-genome sequencing
(WGS), whole-exome sequencing (WES), and targeted resequencing
(TRS).
STEP 8: NEXT-GENERATION SEQUENCING