Assoc. Prof. Ales BARTOS, MD, PhD Movement disorders (Extrapyramidal and cerebellar syndromes) http://vyuka.lf3.cuni.cz (seminar, teaching unit 60) Assoc. Prof. Ales BARTOS, MD, PhD Department of Neurology, Charles University in Prague

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

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

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 …

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

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)

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

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

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

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

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“)

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

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

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

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

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)

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

Parkinson´s disease in pictures

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

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

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

Parkinson´s disease – treatment

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)

Break

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 !

Vascular parkinsonian syndrome bilateral lesions!

Normal pressure hydrocephalus

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

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

Wilson´s disease (=hepatolenticular degeneration)

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;27:1373-1378 ©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

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

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

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

Huntington´s disease 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

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

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

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)

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

Wernicke´s encephalopathy

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

Let us verify your knowledge….

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

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

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

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

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?

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?)

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?)

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