Md abnornal involuntary movements

MD - abnornal involuntary movements

• MD - abnornal involuntary movements

• dysfunction of basal ganglia (anatomically)

• dysfunction of extrapyramidal motor system (functionally)

The Basal Ganglia include the:

• The Basal Ganglia include the:

• Striatum (caudate nucleus and putamen)
• Globus pallidus int. and ext.
• Subthalamic nucleus
• Substantia nigra (pars reticulata, pars compacta)
• Intralaminar nuclei of thalamus

• Akinetic-rigid syndrome:

• reduction of spontaneous activity, increase of muscle tone, (akinesia/hypo/bradykinesia, rigidity)

• Hyperkinetic syndromes:

• involuntary and irregular movements

• (tremor, chorea, balismus, dystonia, myoclonus, tic)

• functional balance

• cooperation of direct and indirect nigro-striatal pathways

Parkinsonism - clinical syndrome, caused by lesion in the basal ganglia

• Parkinsonism - clinical syndrome, caused by lesion in the basal ganglia

• Hypokinesia, bradykinesia
• rigidity
• rest tremor
• postural disturbance

Primary (idiopathic) Parkinson s Disease (PD). PD makes up approximately 80% of cases of parkinsonism

• Primary (idiopathic) Parkinson s Disease (PD). PD makes up approximately 80% of cases of parkinsonism

• Secondary parkinsonism (associated with infectious agents, drugs, toxins, vascular disease, trauma, brain neoplasm)

• Neurodegenerative disorders -„Parkinson-plus“ syndromes (MSA, PSP)

The condition was first described by James Parkinson in 1817 (paralysis agitans)

• The condition was first described by James Parkinson in 1817 (paralysis agitans)

• Most cases of PD start between 50-70 y. (peak age of onset in the 6. decade, young onset before 40y.)

• Prevalence: 160 cases per 100,000 population,

• (increase with age)

progresive degeneration (loss) of dopaminergic neurons in substantia nigra, projecting to the striatum

• progresive degeneration (loss) of dopaminergic neurons in substantia nigra, projecting to the striatum

• resulting in decreased level of dopamine (inbalance in the neurotransmitter mechanism)

• symptomes of PD appear when about 70% of nigrostriate dopamine neurones are lost

• presynaptic lesion !

• postsynaptic dopaminergic receptors D2 are intact

• response to dopaminergic therapy - levodopa - is preserved

Early symptoms may be so mild, that a clinacal diagnosis is not possible.

• Early symptoms may be so mild, that a clinacal diagnosis is not possible.

• Cardinal signs:

• resting tremor

• rigidity

• bradykinesia, hypokinesia

Resting tremor – worse in a rest and decrease during movement

• Resting tremor – worse in a rest and decrease during movement

• Rigidity – resistance to passive movement about a joint, (cogwheel)

• Bradykinesia – refers to slowness of movement and decrease amplitude of movement

• Postural instability - refers to inbalance (freezing, propulsion and festination)

• Other motor signs:

• micrographia, masked facies, absence of associated movements (lack of armswing), quiet and monotonous speech,

Non-motor signs:

• Non-motor signs:

• Autonomic dysfunction (obstipation, urinary, sexual, orthostatic hypotension, seborrheic dermatitis, increased sweating, drooling)
• Sleep disturbances
• Mental and psychiatric problems (depression, cognitive dysfunction, demetia)

The diagnosis is based on the presence of cardinal clinical signs and the response to dopaminergic therapy

• The diagnosis is based on the presence of cardinal clinical signs and the response to dopaminergic therapy

• The best clinical predictors of dg. PD are:

• Asymmetry (symptoms begin on one side of the body (unilateral)
• Presence of at least 2 of 3 major signs
• Absence of a secondary cause
• Good response to dopamine replacement therapy !

Motor fluctuations („off-time“, „on-time“)

• Motor fluctuations („off-time“, „on-time“)

• Dyskinesias (uncontroled movements, chorea)

• Psychiatric symptoms (visual hallucinations)

Basic symptomatic therapy:

• Basic symptomatic therapy:

• L-DOPA (natural precursor of dopamine),
• Dopamine agonists (ropinirol, pramipexol, rotigotin)

• Additional symptomatic therapy:

• COMT inhibitors (entacapon)
• MAO-B inhibitors (Selegiline)
• (Anticholinergics)
• Amantadine

• Surgical therapy

• Deep brain stimulation (DBS)

Levodopa – standard of symptomatic treatment

• Levodopa – standard of symptomatic treatment

• provides the greatest antiparkinsonian benefit

• Dopamine agonists can be used as:

• initial symptomatic therapy in early disease - provide good benefit but lack sufficient efficacy to control signs in later disease
• may control late onset complications (significat effect on the reduction of dyskinesias)

COMT inhibitors – (entacapon) prolong the effectiveness of a dose of levodopa by preventing its breakdown

• COMT inhibitors – (entacapon) prolong the effectiveness of a dose of levodopa by preventing its breakdown

• to decrease the duration of „off-time“

• MAO-B inhibitors (selegilin)– slow the breakdown of dopamin in the brain

Secondary parkinsonism

• Secondary parkinsonism

• drugs- induced

• multiinfarct encephalopathy

• normotension hydrocephalus

• Neurodegenerative disorders

• Atypical parkinsonism - „Parkinson-plus“

• syndromes

• Multisystem atrophy (MSA)

• Progressive supranuclear palsy (PSP)

mechanisms

• mechanisms

• DA receptor blockade in the striatum

• Classical neuroleptics

• (haloperidole, chlorpromazine, levopromazine, prochlorperazine, perfenazine, etc., all depot neuroleptics)

• metoclopramide (Cerucal, Degan, Paspertin)

Subcortical arteriosclerotic encephalopathy

• Subcortical arteriosclerotic encephalopathy

• - white matter lesions (WML)

• - periventricular lesions

• cause typical

• phenotypes of VP

Predominant involvment of the legs = („lower-body parkinsonism“)

• Predominant involvment of the legs = („lower-body parkinsonism“)

• gait and balance disorder (frontal type gait, apraxia of gate, shuffling, short steps)
• tremor is usually absent

• No response to levodopa

• usually additional features: pseudobulbar palsy, pyramidal signs, cognitive disturbances

rest tremor

• rest tremor

• Parkinson‘s disease

• postural tremor

• physiologic tremor
• enhanced physiologic tremor
• essential tremor !!

• kinetic tremor

• cerebellar tremor
• Wilson’s disease
• Holmes’ ("rubral“) tremor

Definition:

• Definition:

• irregular, random movements of body parts, usually quick, twisting, with distal predominance

• Structural involvement:

• striatum (ncl. caudatus, putamen)

• Pharmacological mechanism:

• hyperdopaminergic

• Standard pharmacological treatment:

• neuroleptics

can occur in a variety of conditions and disorders

• can occur in a variety of conditions and disorders

• primary feature of Huntington s disease, other progressive neurological disorders

• may be caused:

• by drugs (levodopa, anti-psychotics)

• by metabolic disorders, endocrine disorders, vascular leasions

Definition:

• Definition:

• sustained muscle contractions producing twisting and repetitive movements or abnormal postures of affected body parts

• Structural involvement:

• striatum, pallidum, thalamus, their connections

• Pharmacological mechanism:

• hypercholinergic

• hypodopaminergic (DRD)

• Standard pharmacological treatment:

• anticholinergics

Definition:

• Definition:

• short synchronous monophasic muscle jerks (agonists and antagonists in the same region), of irregular frequency and amplitude

• Classification:

• epileptic - non-epileptic
• according to distribution of signs:
• focal
• segmentary
• generalised
• according to source:
• cortical
• subcortical (reticular, brain-stem)
• spinal (propriospinal)

• Gilles de la Tourette syndrome

• prevalence  50/100 000 (with associated behav. disorders, up to 1/100)
• combination of motor and vocal tics
• beginning in childhood (95% before 12 yrs), M:F 3-4:1
• associated behavioral disorders (attention deficit hyperactivity disorder, obsessive-compulsive disorder and impulsiveness)
• genetic predisposition + environmental factors

• Transient tic disorder

• prevalence up to 24/100 school children
• duration  12 months