1. Assoc. Prof. Ales BARTOS, MD, PhD
Movement disorders (Extrapyramidal and cerebellar syndromes) (seminar, teaching unit 60)
Assoc. Prof. Ales BARTOS, MD, PhD
Department of Neurology, Charles University in Prague

2. The questions for the oral state exam in neurobehavioral sciences :
Parkinson´s disease and syndromes: causes, symptoms, diagnosis, treatment (a neurology part)
Disturbances of motor functions, including drug-induced syndromes
Vascular dementia: clinical signs and symptoms, classification, differential diagnosis, treatment and prevention
Dementia: clinical signs and symptoms, classification, differenial diagnosis

3. The questions for the oral state exam in neurobehavioral sciences :
Hydrocephalus: types, causes, symptoms, diagnosis, treatment. CSF hypotension
Nervous system disorders in metabolic and autoimmune diseases, CO toxicity: causes, symptoms, diagnosis, treatment, complications

4. Outline movement disorders in general
case history and examination focused on movement disorders
the Parkinsonian syndrome
Parkinson´s disease
secondary parkinsonian syndromes
and a surprise in the end: questions and quizzes …

5. 2 categories - syndromes:
Movement disorders
observed during the interview („one look is worth a thousand words“)
abnormal involuntary movements are exaggerated with anxiety and diminished during sleep
2 categories - syndromes:
1) Akinetic-rigid – paucity of spontaneous movement, increased tone (rigidity) examples: Parkinson´s disease, vascular encephalopathy / dementia
2) Hyperkinetic-hypotonic – irregular involuntary movements, often at varying sites, diminished muscle tone at rest (chorea, athetosis, ballism, dystonias)
example: Huntington´s disease

6. Types of abnormal movements
Tremor = involuntary, rhythmic movement across a joint:
1) rest – at rest
2) static, postural – only with a specific posture
3) intention – only with motion
Chorea = sudden movement usually involving the extremities and the face
Athetosis = a slow, sinuous movement
(the distinction is sometimes unclear – choreoathetosis)

7. Types of abnormal movements
(Hemi-)ballism = irregular, sudden, large-amplitude movements of an entire limb or limbs
Myoclonus = spontaneous, shocklike contractions of one or more muscles across a joint (the jerk-like movements during falling asleep in dogs, cats and man)
Tics = irregular, stereotyped movements, often in the face
Dystonia = a sustained abnormal or inappropriate posture

8. History of the patient with a movement disorder
symmetry, exacerbating or alleviating factors (stress, sleep, alcohol)
family history – many movement disorders
drug history (!) – neuroleptics → parkinsonism, tardive dyskinesias; antiemetics ! → dystonia, dyskinesia
alcohol history → cerebellar degeneration / dysfunction, Wernicke encephalopathy, alleviate essential tremor
medical history – hyperthyroidism → tremor, liver disease → asterixis

9. Neurologic examination
have the patient draw a spiral or connect dots as a permanent record of the motor dysfunction; later this can be used to monitor the efficacy of treatment
muscle tone: hypertonia – a passive movement of the arm
abnormal postures – during station and gait testing

10. The Parkinsonian SYNDROME (parkinsonism)
= movement abnormalities mainly characterized by: 1) bradykinesia, hypokinesia, 2) rigidity and 3) resting tremor, 4) postural abnormalities (stance and gait)
based on pathology in basal ganglia and their connections

11. The Parkinsonian syndrome
BRADYKINESIA, HYPOKINESIA („slow movements“):
slowness of walking, other movements (and mental processes), delayed responses physically and mentally
difficulty in initiating movements
slow and smaller handwriting
reduced facial reactions („masked face“)

12. The Parkinsonian syndrome
RIGIDITY (increased tone):
passively move the extremities
increased tone as increased resistance (cogwheel phenomenon)
!! (versus spasticity)

13. The Parkinsonian syndrome
TREMOR:
at rest
most commonly in hands and fingers (a „pill rolling“ motion)
often begins unilaterally and distally
spreads proximally and to the other side over months or years
usually asymmetric

14. The Parkinsonian syndrome
POSTURAL CHANGES during station and gait :
slight flexion of back
the first steps are slow and small
difficult turning
imbalance
falls

15. The Parkinsonian syndrome
OTHER FEATURES:
micrographia
dysarthria
cognitive slowing
mood lability
dementia

16. Causes of parkinsonism
the problem to distinguish in a patient with parkinsonism:
1) Idiopathic Parkinson´s disease (80 %)
2) Secondary parkinsonian syndromes (20 %)
vascular parkinsonism
rarer causes:
drug-induced (dopamin receptor blockers: neuroleptics, antiemetics)
Wilson´s disease
normal pressure hydrocephalus
carbon monoxide poisoning
trauma
post-encephalitic parkinsonism (in the past)
parkinson plus syndromes (corticobasal syndrome, progressive supranucelar palsy, Lewy body disease)

17. Parkinson´s DISEASE (vs. syndrome)
chronic, slowly progressive, degenerative and usually sporadic disease
a) loss of dopaminergic neurons pars compacta substantiae nigrae – lack of dopamin
b) Lewy bodies – deposits of alfa-synuclein (synucleinopathy)
in old age over 50 years, prevalence rises with age
the lecture on Parkinson´s disease:

18. Parkinson´s disease in pictures

19. Parkinson´s disease – clinical features
the parkinsonian syndrome – „everything is hypo- (reduced)“:
upper limbs – hypokinesia and rigidity, micrographia, reduced synkinesias during gait
gait disorders – steps: too small, too slow, freezing, difficult turning
face – hypomimia
speech – hypofonia, dysarthria

20. Parkinson´s disease – other clinical features
rest tremor – very typical, not in all patients
depression
cognitive disturbances (attention, executive functions), dementia in late phases

21. Parkinson´s disease – diagnosis
the diagnosis is based on clinical evaluation in 3 steps:
1) the presence of hypokinetic-rigid syndrome and other features typical for Parkinson´s disease
2) red flags – suspect an alternative diagnosis – features for secondary parkinsonism: repeated strokes and step-wise onset, neuroleptics, supranuclear gaze palsy, cerebellar syndromes, early severe dementia, Babinski sign, brain tumor or hydrocephalus on CT scanning, absence of dopa responsiveness
3) the response to dopaminergic treatment

22. Parkinson´s disease – treatment

23. Parkinson´s disease – treatment
a replacement of decreased dopamine concentration:
levodopa – is the most effective treatment, most patients have a remarkable response to levodopa, commonly used if patients have Parkinson´s disease
and / or
dopaminergic agonists (bromocriptine, pregolide, ropinirole, cabergoline, pramipexole) – usually a weaker effect and more peripheral adverse effects (blood pressure fluctuations, arrhythmias, nausea, vomiting)
„start low, go slow“
deep brain stimulation (neuropacemaker)

24. Break

25. Secondary parkinsonian syndromes
frontal type of gait (lower body parkinsonism) – symmetrical involvement of lower limbs, more than relatively spared upper limbs:
vascular parkinsonian syndrome – multiple, repeated strokes in basal ganglias (postsynaptic damage, sometimes effective levodopa) – step-wise progression, Babinski +, axial phenomena, pseudobulbar syndrome, cognitive deficit, dementia
normal pressure hydrocephalus – triad:
1) gait disorder, 2) cognitive deficit, 3) urine incontinence
treatable condition !

26. Vascular parkinsonian syndrome
bilateral lesions!

27. Normal pressure hydrocephalus

28. Drug-induced secondary parkinsonism (contraindicated in Parkinson´s disease)
dopamine receptor blockers:
typical neuroleptics (fenothiazines – chlorpromazine, butyrophenons – haloperidole)
antiemetics (neuroleptics) – metoclopramid
calcium channel blockers – flunarizine, cinnarizine
 treatment of delirium in Parkinson´s patients with ATYPICAL antipsychotic drugs - tiapride

29. Wilson´s disease (=hepatolenticular degeneration)
a genetic autosomal recessive disorder of copper metabolism
„parkinsonism in the young“
progressive, „wing-beating“ tremor, rigidity, dysarthria, mental changes, hepatic dysfunction, corneal Kayser-Fleischer ring
less commonly tremor
treatment: penicillamine, zinc sulfate

30. Wilson´s disease (=hepatolenticular degeneration)

31. Wilson disease in a 14-year-old girl with dysarthria
Wilson disease in a 14-year-old girl with dysarthria.A, Initial T2-weighted axial MR image shows increased signal intensity in both caudate nuclei (arrowheads) and putamen (arrows).B, Follow-up T2-weighted axial MR image obtained after 3 years shows complet...
Wilson disease in a 14-year-old girl with dysarthria.A, Initial T2-weighted axial MR image shows increased signal intensity in both caudate nuclei (arrowheads) and putamen (arrows).B, Follow-up T2-weighted axial MR image obtained after 3 years shows complete resolution of the lesions. Patient’s neurologic symptoms were also improved.
Kim T et al. AJNR Am J Neuroradiol 2006;27:
©2006 by American Society of Neuroradiology

32. Treatment of secondary parkinsonian syndromes
vascular parkinsonism – controlling vascular risk factors, rehabilitation
rarer causes:
normal pressure hydrocephalus – ventriculo-peritoneal shunt
drugs (neuroleptics, antiemetics) – anticholinergic agents, atypical antipsychotics
Wilson´s disease – penicillamine, zinc
post-traumatic, carbon monoxide poisoning - rehabilitation

33. Treatment differences in two parkinsonian syndromes
idiopathic Parkinson´s disease
presynaptic disease
low dopamine concentrations
dopaminergic responsiveness
vascular parkinsonism
postsynaptic (presynaptic ?) disease
normal dopamine concetrations
no effect of dopaminergic drugs

34. Movement disorders in broader sense
Chorea = sudden movement usually involving the extremities and the face
Ataxia = an impairment of coordination in the absence of significant weakness
1) limb
2) truncal
= cerebellar disorders

35. Chorea
irregular, asymmetric, sudden, brief, shooting involuntary movements
in distal segments of the extremities
grimacing and lip-smacking

36. Huntington´s disease autosomal dominant inheritance
expanded CAG repeat on the chromosome 4
longer CAG repeat – earlier age of onset
age: years
presymptomatic diagnosis by genetic testing
very poor prognosis: death after years from the diagnosis
no etiologic treatment, symptomatic management

37. Hemiballism
„ballistic“ movements of high amplitude involving multiple segments of a limb
cause: stroke in the subthalamic nucleus
neuroleptics, but usually resolves spontaneously in a few weeks

38. Cerebellar disorders syndromes:
neocerebellar (limb ataxia, intention tremor, dysdiadochokinesia)
palleocerebellar (truncal ataxia, unstable stance in the Romberg test, unstable, broad-based gait, dyssynergy)
mixed (global)
an important neuroanatomical association of the cerebellum with the rest of the brain

40. Causes of cerebellar disorders
VINDICATE:
Vascular (stroke)
Inflammatory (encephalitis)
Neoplastic (tumors – meningeoma, gliomas –oligodendroglioma, astrocytoma)
Degenerative (spinocerebellar ataxias, paraneoplastic syndromes)
Intoxication (alcohol, Wernicke´s encephalopathy, antiepileptics, lithium)
Congenital – Arnold-Chiari, agenesis
Autoimmune (multiple sclerosis, paraneoplastic cerebellar degeneration in ovarian cancer)
Traumatic (contusion, sub- / epi- dural hematomas)
Endocrine (metabolic – see intoxication)

41. Wernicke´s encephalopathy
conditons due to thiamin deficiency
even in nonalcoholics, e.g. in patients vomiting, poor nutrition
oculomotor disturbances (abducent palsy, nystagmus, gaze palsy)
ataxia (more truncal than limb, unable to stand or walk)
antero- and retrograde amnesis + confabulations
brain MR: lesions in periaqueductal region and adjacent to the third ventricle (demyelination, small foci of hemorrhage)
treatment: thiamin
glucose solutions after thiamin has been given, otherwise it may induce acute worsening of Wernicke´s encephalopathy
early treatment – regression, often residual deficits

42. Wernicke´s encephalopathy

43. Figure. Rapid clearing of MRI signals in Wernicke encephalopathy.
Figure. Rapid clearing of MRI signals in Wernicke encephalopathy. T2-weighted MR images at the time of admission show abnormal hyperintense signal (arrows) in the periaqueductal gray region (A, axial view) and dorsomedial thalami (B, coronal view), which cleared after 5 days of thiamine (100 mg IV) treatment (C, D).
Watson W et al. Neurology 2003;61:527
© 2013 American Academy of Neurology

44. Let us verify your knowledge….

45. Quizzes distinguish different types of tremor
identify the type of abnormal movements

46. Quiz question No 1
The most common cause of the parkinsonian syndrome is:
a) repeated and multiple strokes
b) drug abuse
c) neuroleptics
d) Parkinson´s disease
e) carbon monoxide poisoning

47. Quiz question No 2
Dopaminergic transmission is impaired in Parkinson´s disease due to:
a) blockage of dopamin receptors
b) decreased presynaptic uptake
c) presynaptic degeneration and loss of dopaminergic neurons
d) degeneration of nigrostriatal pathway
e) postsynaptic degeneration and loss of dopaminergic neurons in striatum

48. Quiz question No 3
Parkinsonism prevailing in the upper part of the body:
a) may indicate a treatable condition – normal pressure hydrocephalus
b) is typical for Parkinson´s disease
c) may be found in vascular encephalopathy

49. Quiz question No 4 The onset of the parkinsonian syndrome:
a) under the age of 45 years is impossible
b) in the 7th and 8th decade is usual for Parkinson´s disease
c) between 50 and 60 years is typical for vascular encphalopathy
d) under the age of 45 may be caused by rare disease – which one?

50. Quiz question No 5
A response to levodopa or dopaminergic agonists (motor improvement):
a) is found almost exclusively in Parkinson´s disease
b) is profound in the vascular parkinsonian syndrome
c) is supportive for the diagnosis of Parkinson´s disease
d) is typical for all parkinsonian syndromes
(Why?)

51. Quiz question No 6
Parkinsonian features prevail in lower part of the body. Which statement is true?
a) dopaminergic treatment will be probably effective
b) it is typical in early Parkinson´s disease
c) clinical evaluation is insufficient, brain neuroimaging is not necessary
d) it suggests an alternative diagnosis
(Why?)

53. Overlapping features of various types of tremor
Parkinson´s syndrome
Essential tremor
Cerebellar tremor
Rest tremor ++ +
Postural / static tremor
0 / +
Intentional tremor
Increased tone
Postural abnormality
Incoordination