(Extrapyramidal and cerebellar syndromes) http://vyuka.lf3.cuni.cz
(seminar, teaching unit 60)
1

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
2

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
3

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 … 
4

• 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
5

• 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)
6

• (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
7

• 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
8

• 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
9

= 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
10

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“)
11

RIGIDITY (increased tone):
– passively move the extremities
– increased tone as increased resistance
(cogwheel phenomenon)
– !! (versus spasticity)
12

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
13

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

OTHER FEATURES:
– micrographia
– dysarthria
– cognitive slowing
– mood lability
– dementia
15

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)
16

(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: http://www.youtube.com/watch?v=xRbdzgKFl10

18

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
19

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

• 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
21

22

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)
23

24

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 !
25

bilateral lesions!
26

27

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
28

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
29

Wilson ´s disease
(=hepatolenticular degeneration)
30

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...
Kim T et al. AJNR Am J Neuroradiol 2006;27:1373-1378
©2006 by American Society of Neuroradiology

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
32

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
33

• 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
34

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

• autosomal dominant inheritance
• expanded CAG repeat on the chromosome 4
• longer CAG repeat – earlier age of onset
• age: 30-50 years
• presymptomatic diagnosis by genetic testing
• very poor prognosis: death after 10-15 years from the diagnosis
• no etiologic treatment, symptomatic management
36

• „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
37

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
38

39

VINDICATE:
• V ascular ( stroke )
• I nflammatory (encephalitis)
• N eoplastic ( tumors – meningeoma, gliomas – oligodendroglioma, astrocytoma)
• D egenerative (spinocerebellar ataxias, paraneoplastic syndromes)
• I ntoxication (alcohol, Wernicke ´s encephalopathy, antiepileptics, lithium)
• C ongenital – Arnold-Chiari, agenesis
• A utoimmune ( multiple sclerosis , paraneoplastic cerebellar degeneration in ovarian cancer)
• T raumatic (contusion, sub- / epi- dural hematomas)
• E ndocrine (metabolic – see intoxication)
40

• 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
41

42

Figure. Rapid clearing of MRI signals in Wernicke encephalopathy.
© 2013 American Academy of Neurology
Watson W et al. Neurology 2003;61:527

44

• distinguish different types of tremor
• identify the type of abnormal movements
45

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
46

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
47

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
48

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?
49

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?)
50

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
51
(Why?)

52

Feature Parkinson ´s Essential Cerebellar syndrome tremor tremor
Rest tremor ++ + 0
Postural / static tremor
Intentional tremor
Increased tone
Postural abnormality
Incoordination
+
0
+
+
0
++
+
0
0
0
0 / +
++
0
+
+
53