The Northern Neuroscience Centre Chiangmai University
NNC MU Movement disorder tutorial Surat Tanprawate, MD, MSc (London), FRCP(T) Division of Neurology, Chaingmai University
Neurological symptoms • Conscious and cognitive functions
• alteration of conscious • higher cortical function disorder
• dementia • Cranial nerve functions • anosmia, visual loss,
diplopia, CN V dysfunction, facial weakness, hearing loss, tinnitus, dysphagia, tongue weakness
• Dysfunction of motor system • weakness • ataxia • movement disorder • Dysfunction of sensory system • numbness • pain • Autonomic dysfunction • Episodic disorder
Neurological diseases • Congenital • Trauma • Tumor • Infection/inflammation • Degeneration • Demyelination
• Vascular • Metabolic/Toxic/Drugs • Genetic • Cryptogenic • Idiopathic
What is movement disorder? • The term : movement disorders: originally refer to basal ganglia or extrapyramidal diseases
• slowness or poverty of movement
(bradykinesia or hypokinesia (e.g. parkinsonian disorders)
• abnormal involuntary movements
(hyperkinesias) such as tremor, dystonia, athetosis, chorea, ballism, tics, myoclonus, restless legs syndrome, stereotypies, akathisias, and other dyskinesias
What is movement disorder? • Some may similar movement disorder • abnormalities in muscle tone (e.g.rigidity, spasticity, and stiff man syndrome),
• incoordination (cerebellar ataxia) • apraxia • seizure
Anatomy of movement control
Direct and Indirect pathway of movement control
Step approach 3 question should be asked
1.Is it hypokinetic or hyperkinetic movement disorder?
2.What is the pattern of movement disorder?
3.What is the classification of such movement disorder?
Movement disorder Hypokinetic Hyperkinetic rigid syndrome Hypokinetic rigid syndrome
Hyperkinetic Pattern of movement disorder Classify by anatomy, distribution, cause, age
Hyperkinetic movement disorder • Rhythmic, sustained, intermittent, speed, suppressibility, complex movement
• Tremor, Chorea, athetosis, dystonia, myoclonus, ballism, tic
Chorea = dance irregular, nonrhythmic, unsustained involuntary movement that flows from one part of the body to another “motor impersistence”
Dancing lady
Dystonia syndrome of sustained muscle contractions, frequently causing twisting, repetitive movements, or abnormal postures “sustained contractions, consistent directional or patterned character (predictable), and exacerbation during voluntary movements” “sensory trick”
Generalised dystonia
Myoclonus sudden, brief, jerky, and shock-like involuntary movements involving face, trunk, and extremities
“positive myoclonus” “negative myoclonus”
Generalised myoclonus
Tremor a rhythmic oscillation of a body part produced by alternating or synchronous contraction of opposing muscles
other movement clinical symptoms can be act like tremor: dystonic tremor, myoclonic tremor
Tremor
Tics repetitive, stereotyped, involuntary, sudden, inopportune, non-propositional, and irresistible movement “unpleasant feeling “not absolutely clear as patients can exert some control on the movement” “can be simple or complex”
He have had tic since he was 10 y.o.
Ballism=dacing involuntary, flinging motions of the extremities, the movement are often violent and have wide amplitude of motion, continuous and random, can involve proximal or distal
Athetosis = without fixed position involuntary, convoluted, writhing, slow movements of the arms, fingers and legs
“Pseudoathetosis” in a patient with severe axonal polyneuropathy
Common movement disorder
Tremor
Step approach- MDS consensus
1.Inspection the tremor 2.Specific examination for assessment of signs related to tremor
3.Syndrome classification of tremor
Terminology for tremor and the hierarchical relation of the terms as indicated by the numbers
Inspection • Frequency • Low (<4 Hz) • Medium (4-7 Hz) • High (>7 Hz)
• Location •
Head: chin, face, tongue, palate
•
Upper extremity: shoulder, elbow, wrist, fingers
• •
Trunk Lower extremity: hip, knee, ankle joint, toes
Specific examination for assessment of: • Akinesia/bradykinesia tone (including Froment’s sign for the upper • Muscle and lower extremity and coactivation sign for psychogenic tremor)
• Postural abnormalities • Dystonia • Cerebellar signs • Pyramidal signs • Neuropathic signs • Systemic signs (thyrotoxicosis and so forth) • Gait and stance (orthostatic tremor)
Syndrome classification of tremor Syndrome
Activity
Specific S/S
Cause
Physiologic tremor
Postural
No
Physiologic response
Enhance physiologic tremor
Postural, Kinetic
Hyperthyroid, tachycardia
Hyperthyroid, drugs
Essential tremor
Postural, Kinetic
No
No
Parkinsonian tremor
Rest
Bradykinesia, postural instability, rigidity
Neuro-degeneration
Cerebellar tremor
Postural, kinetic, intention
Ataxia
Various cause affected cerebellar pathway
Syndrome classification of tremor Tremor description (activated by, location, frequency) + Specific s/s
Characteristics of Essential Tremor and Parkinsonian Tremor
Essential tremor Core criteria for identifying ET
•
Bilateral action tremor of the hands and forearms
•
Absence of other neurological signs, with the exception of the cogwheel phenomenon
•
May have isolated head tremor with no abnormal posture
Essential tremor Secondary criteria for identifying ET
• •
Long duration (>3 years)
•
Beneficial response to ethanol
Family history: reported in > 50% of the patients
Essential Tremor
Achimedes spiral
Achimedes spiral
Treatment ET • First line • Propranolol start at 10 mg x 3 => 240-320 mg/d • Primidone
• Second line • Gabapentin, topiramate, clozapine, long acting benzodiazepine (clonazepam)
Holme’s tremor • “midbrain tremor” “rubral tremor” “thalamic tremor”
• predominately proximal limb (<4.5 Hz) during postural in nature
• Upper brain stem, thalamus,
cerebellum, interrupting pathways in the midbrain tegmentum
Wing Beating Tremor in Wilson’s disease
Dystonic tremor
Parkinson’s disease
James Parkinson, London (1755 – 1824)
An Essay on the Shaking Palsy(1817) Shaking Palsy(Paralysis agitans)
He identified 6 cases, 3 of whom he personally examined; 3 he observed on the streets of London J Neuropsychiatry Clin Neurosci 2002;14:223–36
Parkinsonism
• clinical syndrome of bradykinesia, resting tremor, cogwheel rigidity, and postural instability
Parkinson’s disease
• clinical syndrome of asymmetrical parkinsonism,
usually with rest tremor, in association with the specific pathological findings of depigmentation of the SN as a result of loss of melanin-laden dopaminergic neurons containing eosinophilic cytoplasmic inclusions(Lewy bodies)
Epidemiology • Community based series • prevalence 360 per 100,000 and an
incidence of 18 per 100,000 per year
• PD is an age-related disease • gradually increase after age 50 years, and disease before age 30 years is rare
• Female: Male=1:1 de Lau and Breteler. Lancet Neurol 2006; 5: 525-535
Pathophysiology •
•
Structural change
•
Loss of pigmented neurons in the SNc and other pigmented neuron
•
Histopathology: Lewy bodies
Neurotransmitter change
•
Depletion of dopamine containing cells in the substantia nigra leads to decreased dopamine n the striatal
Pathology •
Gross: loss of pigmented cell in substantial nigra(SN) and other pigmented nuclei(locus ceruleus(LC), dorsal motor nucleus of the vagus)
http://www.babraham.ac.uk/images/research/SAS/emson/fig1.jpg
http://www.uhmc.sunysb.edu/pathology/neuropath
Pathology Normal substantia nigra
Surviving neuron contains a Lewy body Extensive loss of pigmented neurons
Group of Parkinsonism •
Primary or idiopathic parkinsonism
• •
hydrocephalus, vascular parkinsonism, encephalitis
Parkinson plus syndrome
• •
Parkinson’s disease
Secondary parkinsonism
• •
TYPICAL OR CLASSIC
Progressive supranuclear palsy(PSP), corticobasal degeneration(CBD), multiple system atrophy(MSA)
Hereditary parkinsonism
•
ATYPICAL
Wilson’s disease, Dopa-responseive dystonia, Huntington’s disease(HD)
United Kingdom Parkinson's Disease Society(UKPDS) Brain Bank Diagnostic Criteria for PD
• •
Step 1: Diagnosis of Parkinsonism
•
Step 3: Features that support a diagnosis of Parkinson’s disease (three or more required for diagnosis of definite Parkinson’s disease)
Step 2: Features tending to exclude Parkinson’s disease as the cause of Parkinsonism
Diagnostic accuracy to 82%
Hughes AJ, Daniel SE, Kilford L, Lees AJ. JNNP 1992 Mar;55(3):181-4
Step 1: Diagnosis of Parkinsonism • Bradykinesia and at least one of the following:
• Muscular rigidity • 4–6 Hz resting tremor • Postural instability not caused by primary visual, vestibular, cerebellar or proprioceptive dysfunction
Pill rolling tremor
Finger tapping
Bradykinesia
Micrographia
Micrographia
Step 2: Features tending to exclude Parkinson’s disease as the cause of Parkinsonism
•
History of repeated strokes with stepwise progression of parkinsonian features
•
History of repeated head injury
• •
History of definite encephalitis
• • •
Neuroleptic treatment at onset of symptoms >1 affected relatives Sustained remission Strictly unilateral features after 3 years
• • • •
Supranuclear gaze palsy
• •
Babinski's sign
•
Negative response to large doses of levodopa (if malabsorption excluded)
•
MPTP exposure
Cerebellar signs Early severe autonomic involvement Early severe dementia with disturbances of memory, language and praxis
Presence of a cerebral tumour or communicating hydrocephalus on computed tomography scan
Step 3: Features that support a diagnosis of PD (three or more required)
• • • • • • • •
Unilateral onset Rest tremor present Progressive disorder Persistent asymmetry affecting the side of onset most Excellent (70–100%) response to levodopa Severe levodopa-induced chorea Levodopa response for 5 years Clinical course of 10 years
Non-motor symptoms • Loss of sense of smell, constipation • REM behavior disorder (a sleep disorder)
• Mood disorders • Orthostatic hypotension (low blood pressure when standing up)
Diagnostic studies
• MRI/CT brain: using for exclude other cause of parkinsonism
• In PD, the MRI brain usually reveals normal
PD disease progressiontreatment response
Modality of treatment
• Symptoms based treatment • Pharmacologic vs Non-pharmacologic • Motor vs Non-motor symptoms
• Neuro-protection • Prevention
Motor symptoms of Parkinson’s disease
Dopamine
Acetylcholine
Symptomatic based treatment • Enhance dopaminergic transmission • L-dopa, dopamine agonist, drug that decrease dopamine destruction
• Drug manipulating other neurotransmitter
• Anti-cholinergic drug
Dose of the preparations of Sinemet and Madopar
Levodopa + DDI Madopar (levodopa+benserazide) Sinemet (levodopa+carbidopa) Madopar HBS Sinemet CR
As the disease progress, the Therapeutic window narrow symptoms and side effects occur as the levodopa therapeutic window diminishes
Dyskinesia threshold
Efficacy threshold
• •
Smooth, extend response Absent or infrequent dyskinesia
• •
Diminished duration Increased incidence of dykinesia
• •
Short, unpredictable response on time is associared with dyskinesia 39
Parkinson Plus Syndrome
Parkinson-plus syndrome • Multiple system atrophy • cerebellar sign + ve, autonomic dysfunction • Progressive supranuclear palsy • vertical gaze palsy • Corticobasal degeneration • limb apraxia • Dementia with lewy bodies • Vivid visual hallucination with dementia
PSP described by Richardson
Dystonia
Dystonia classification • Age of onset • early-onset: age < 26 year • late-onset: age > 26 year
• Distribution • focal (single body reion) • segmental (contiguous region) • multifocal (eg. hemidystonia) • Generalized
Dystonia classification-by etiology Primary dystonia
• AD: early-onset limb dystonia (DYT1), Mixed dystonias
(DYT6, DYT13), Late-onset craniocervical dystonia (DYT7)
• Idiopathic (cervical dystonia, writer cramp, generalised dystonia etc)
Secondary dystonia
• Dystonia-plus: Dopa-responsive dystonia(DRD), rapid onset dystonia parkinsonism (RDP), Myoclonus-dystonia(M-D)
• Heredodegerative dystonias: AD (HD, SCA,3, DRPLA), AR (Wilson’s disease, MLD)
• Acquired cause: drug induced, basal ganglia lesions • From other degenerative disorder (PD, PSP etc.)
Classification of dystonia by distribution
• 5 categories: focal, segmental, multifoacl, hemi-, generalized
• Focal dystonia: 2/3 of dystonic patients • Focal dystonia: cervical dystonia(most common), oromandibular dystonia, blemphalospasm, laryngeal dystonia, limb dystonia
Cervical dystonia • patterned, repetitive, clonic (spasmodic), or tonic (sustained) muscle contractions resulting in abnormal movements and postures of the the head and neck
• Symptoms: pain,
headache, abnormal posture, tremor, orthopedic or neurological complications
2 พี่น้อง cervical dystonia
Blephalospasm+oromandibular dystonia= Meige’s syndrome
Treatment • Levodopar should be tried to exclude DRD
• Anti-cholinergic: • Clonazepam, baclofen,
benzodiazepine, carbamazepine, tizanidine
• Botulinum toxin infection
Myoclonus
Classification • Etiology • physiological, essential,
• •
epileptic, symptomatic
• Anatomical distribution • focal, segmental,
multifocal, generalize
• Provocative factor • spontaneous, reflex, action
Contraction pattern
•
rhythmic, arrhythmic, oscillaroty
Clinical neurophysiology testing
•
cortical, corticalsubcortical, subcorticalsupraspinal, spinal, peripheral
Step • Describe distribution of myoclonusfocal, generalize
• Anatomical localization: cortical, subcortical, spinal, peripheral
• Describe type - negative vs positive • Look for other neurological vs physical sign
• Identify cause
Negative myoclonus (flapping tremor or asterixis) in patient with hepatic encephalopathy
Post hypoxic myoclonus - cortical myoclonus
Hemifacial spasm
Most common peripheral myoclonus
Chorea “the dancing”
Chorea irregular, nonrhythmic, unsustained involuntary movement that flows from one part of the body to another
step to identify chorea - Most important Identify body part of chorea - focal, hemibody: structural lesion in the brain - generalized: diffuse brain lesion (acquire vs congenital) or Toxic/Metabolic/Drug
Acute right side chorea in acute basal ganglia infarction
A Parkinson’s disease patient with motor dyskinesia (chorea) during “on” L-dopa “On”
“Off”
Conclusion • Movement disorder: hypo-hyperkinetic • Each type of hyper kinetic - description the movement disorder pattern
• Identify distribution, associated neurological finding and possible cause (for work up)
• Very common movement disorder you should know :
Parkinson’s disease, essential tremor, structural lesion in the brain (mostly cause focal, hemi-body movement disorder), Generalised movement disorder (look for metabolic/drug)
• Some may have genetic cause (ask for the family members)
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